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Zhang K, Ma X, Zhou X, Qiu G, Zhang C. Machine learning based association between inflammation indicators (NLR, PLR, NPAR, SII, SIRI, and AISI) and all-cause mortality in arthritis patients with hypertension: NHANES 1999-2018. Front Public Health 2025; 13:1559603. [PMID: 40255373 PMCID: PMC12007114 DOI: 10.3389/fpubh.2025.1559603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 03/20/2025] [Indexed: 04/22/2025] Open
Abstract
Background This study aimed to evaluate the relationship between CBC-derived inflammatory markers (NLR, PLR, NPAR, SII, SIRI, and AISI) and all-cause mortality (ACM) risk in arthritis (AR) patients with hypertensive (HTN) using data from the NHANES. Methods We employed weighted multivariable logistic regression and WQS regression to explore the relationship between inflammatory markers and ACM in AR patients, as well as to determine the weights of different markers. Kaplan-Meier curves, restricted cubic splines (RCS) and ROC curves were utilized to monitor cumulative survival differences, non-linear relationships and diagnostic utility of the markers for ACM risk, respectively. Key markers were selected using XGBoost and LASSO regression machine learning methods, and a nomogram prognostic model was constructed and evaluated through calibration curves and decision curve analysis (DCA). Results The study included 4,058 AR patients with HTN, with 1,064 deaths over a median 89-month follow-up. All six inflammatory markers were significantly higher in the deceased group (p < 0.001). Weighted multivariable logistic regression showed these markers' elevated levels significantly correlated with increased ACM risk in hypertensive AR patients across all models (p < 0.001). Kaplan-Meier analysis linked higher marker scores to lower survival rates in AR patients with HTN (p < 0.001). WQS models found a positive correlation between the markers and hypertensive AR patients (p < 0.001), with NPAR having the greatest impact (70.02%) and SIRI next (29.01%). ROC analysis showed SIRI had the highest AUC (0.624) for ACM risk prediction, closely followed by NPAR (AUC = 0.618). XGBoost and LASSO regression identified NPAR and SIRI as the most influential markers, with higher LASSO-based risk scores correlating to increased mortality risk (HR, 2.07; 95% CI, 1.83-2.35; p < 0.01). RCS models revealed non-linear correlations between NPAR (Pnon-linear<0.01) and SIRI (Pnon-linear<0.01) with ACM risk, showing a sharp mortality risk increase when NPAR >148.56 and SIRI >1.51. A prognostic model using NPAR and SIRI optimally predicted overall survival. Conclusion These results underscore the necessity of monitoring and managing NPAR and SIRI indicators in clinical settings for AR patients with HTN, potentially improving patient survival outcomes.
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Cacciatore S, Andaloro S, Bernardi M, Oterino Manzanas A, Spadafora L, Figliozzi S, Asher E, Rana JS, Ecarnot F, Gragnano F, Calabrò P, Gallo A, Andò G, Manzo-Silberman S, Roeters van Lennep J, Tosato M, Landi F, Biondi-Zoccai G, Marzetti E, Sabouret P. Chronic Inflammatory Diseases and Cardiovascular Risk: Current Insights and Future Strategies for Optimal Management. Int J Mol Sci 2025; 26:3071. [PMID: 40243756 PMCID: PMC11989023 DOI: 10.3390/ijms26073071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 03/24/2025] [Accepted: 03/24/2025] [Indexed: 04/18/2025] Open
Abstract
Chronic inflammation is a pivotal driver in the progression of atherosclerosis, significantly contributing to the burden of cardiovascular disease (CVD). Patients with chronic inflammatory diseases, such as inflammatory bowel diseases (IBDs) (e.g., ulcerative colitis and Crohn's disease), rheumatological disorders, as well as individuals with auto-immune diseases (such as systemic lupus erythematosus), present a higher risk of major adverse cardiac events (MACEs). Despite their elevated CVD risk, these populations remain underrepresented in cardiovascular research, leading to a critical underestimation of their cardiovascular risk (CVR) in clinical practice. Furthermore, even recent CVR scores poorly predict the risk of events in these specific populations. This narrative review examines the physiopathological mechanisms linking chronic inflammation, immunomodulation, atherosclerosis, thrombosis and cardiovascular events. We review data from epidemiological studies and clinical trials to explore the potential cardiovascular benefits of anti-inflammatory and immunomodulatory therapies. Despite existing evidence, significant gaps in knowledge remain. Future research is mandatory, focusing on innovative strategies for risk stratification and optimization, including lipidomics, proteomics, advanced inflammatory markers, microbiota profiling, and cardiovascular imaging. Addressing these unmet needs will enhance understanding of cardiovascular risk in chronic inflammatory diseases, enabling tailored interventions and better outcomes.
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Affiliation(s)
- Stefano Cacciatore
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy;
- Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy;
| | - Silvia Andaloro
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy;
| | - Marco Bernardi
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy; (M.B.); (L.S.); (G.B.-Z.)
| | - Armando Oterino Manzanas
- Department of Cardiology, Hospital Universitario de Salamanca-IBSAL, Paseo de San Vicente, 58-182, 37007 Salamanca, Spain;
| | - Luigi Spadafora
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy; (M.B.); (L.S.); (G.B.-Z.)
| | - Stefano Figliozzi
- IRCCS Humanitas Research Hospital, Via Alessandro Manzoni, 56, Rozzano, 20089 Milano, Italy;
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, 4, Pieve Emanuele, 20090 Milano, Italy
| | - Elad Asher
- Jesselson Integrated Heart Center, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Shmuel (Hans) Beyth St. 12, Jerusalem 9103102, Israel;
| | - Jamal S. Rana
- Division of Cardiology, Kaiser Permanente Northern California, 1 Kaiser Plaza, Oakland, CA 94612, USA;
- Division of Research, Kaiser Permanente Northern California, 1 Kaiser Plaza, Oakland, CA 94612, USA
| | - Fiona Ecarnot
- Department of Cardiology, University Hospital, Boulevard Fleming, 25000 Besançon, France;
- SINERGIES Unit, University Marie & Louis Pasteur, 19 Rue Ambroise Paré, 25000 Besançon, France
| | - Felice Gragnano
- Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, Via Leonardo Bianchi, Ospedale Monaldi, 80131 Naples, Italy; (F.G.); (P.C.)
- Division of Cardiology, A.O.R.N. “Sant’Anna e San Sebastiano”, Via Ferdinando Palasciano, 81100 Caserta, Italy
| | - Paolo Calabrò
- Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, Via Leonardo Bianchi, Ospedale Monaldi, 80131 Naples, Italy; (F.G.); (P.C.)
- Division of Cardiology, A.O.R.N. “Sant’Anna e San Sebastiano”, Via Ferdinando Palasciano, 81100 Caserta, Italy
| | - Antonio Gallo
- INSERM UMR1166, IHU ICAN, Lipidology and Cardiovascular Prevention Unit, Department of Nutrition, Pitié-Salpêtrière Hospital, Sorbonne University, AP-HP, 47–83 Bd de l’Hôpital, 75013 Paris, France;
| | - Giuseppe Andò
- Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico “Gaetano Martino”, Via Consolare Valeria, 1, 98124 Messina, Italy;
| | - Stephane Manzo-Silberman
- ACTION Study Group, Inserm UMRS1166, Heart Institute, Pitié-Salpetriere Hospital, Sorbonne University, 47-83 Bd de l’Hôpital, 75013 Paris, France; (S.M.-S.); (P.S.)
| | - Jeanine Roeters van Lennep
- Department of Internal Medicine, Cardiovascular Institute, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands;
| | - Matteo Tosato
- Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy;
| | - Francesco Landi
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy;
- Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy;
| | - Giuseppe Biondi-Zoccai
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy; (M.B.); (L.S.); (G.B.-Z.)
- Maria Cecilia Hospital, GVM Care & Research, Via Corriera, 1, 48033 Cotignola, Italy
| | - Emanuele Marzetti
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy;
- Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy;
| | - Pierre Sabouret
- ACTION Study Group, Inserm UMRS1166, Heart Institute, Pitié-Salpetriere Hospital, Sorbonne University, 47-83 Bd de l’Hôpital, 75013 Paris, France; (S.M.-S.); (P.S.)
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Shoghli M, Sinisalo J, Lokki AI, Lääperi M, Lokki ML, Hilvo M, Jylhä A, Tuomilehto J, Laaksonen R. Association of ceramide risk scores with rheumatoid arthritis: a FINRISK population-based cohort study. BMJ Open 2025; 15:e090486. [PMID: 40074276 PMCID: PMC11911702 DOI: 10.1136/bmjopen-2024-090486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 01/06/2025] [Indexed: 03/14/2025] Open
Abstract
OBJECTIVES This study aimed to explore the association between lipid-based Cardiovascular Event Risk Tests (CERT1 and CERT2), including ceramides (Cer) and phosphatidylcholine (PC) lipid species, and rheumatoid arthritis (RA), an inflammatory disease that can increase the risk of cardiovascular diseases. DESIGN Prospective population-based cohort study. SETTING Primary care centres across five geographical areas in Finland. METHODS The study included 7702 individuals (selected from the FINRISK cohort) who were assessed for the prevalence and incidence of RA. At baseline, the cohort included 7518 RA-free individuals, among whom 329 developed RA during the study, and 184 had a history of RA at baseline. Serum levels of ceramides and PC were measured using mass spectrometry, and CERT scores were calculated. MAIN OUTCOME MEASURES Prevalence and incidence of RA, CERT scores, and serum lipid levels. RESULTS CERT scores were associated with prevalent RA but not with incident RA in the full cohort. Adjusted ORs and 95% CI for prevalent RA were 1.24 (95% CI 1.05 to 1.46) for CERT1 and 1.42 (95% CI 1.20 to 1.68) for CERT2. Stratified analyses showed that these associations were consistent among individuals over 50 years of age and across both sexes. The Cer (d18:1/16:0)/PC (16:0/22:5) ratio was significantly associated with RA in younger individuals (OR 1.66; 95% CI (1.26 to 2.18)). Overall, the association between lipids and RA was stronger in women than men. CONCLUSIONS The study shows a significant association between prevalent RA and bioactive lipid species used for cardiovascular risk assessment. These findings emphasise the importance of considering residual inflammatory risks, such as RA, in cardiovascular risk evaluations in clinical settings.
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Affiliation(s)
- Mohammadreza Shoghli
- Population Health, University of Helsinki Faculty of Medicine, Helsinki, Finland
| | - Juha Sinisalo
- Heart and Lung Center, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland
| | - A Inkeri Lokki
- Heart and Lung Center, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland
- Department of Bacteriology and Immunology, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
| | | | | | - Mika Hilvo
- VTT Technical Research Centre of Finland Ltd, Espoo, Finland
| | | | - Jaakko Tuomilehto
- Population Health Unit, Finnish Institute for Health and Welfare, University of Helsinki, Helsinki, Finland
- Department of Public Health, University of Helsinki, Helsinki, Finland
- Department of International Health, Instituto de Salud Carlos III, Madrid, Spain
| | - Reijo Laaksonen
- Zora Biosciences Oy, Espoo, Finland
- Finnish Cardiovascular Research Centre, University of Tampere, Tampere University Hospital, Tampere, Finland
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Moreno RA, Ayala Ugarte C, Hernández EA, Sánchez Olivan E, Leal Villanueva DI, Flores Serrano F, Rojas de León DL, Zaragoza Pérez AF, Reyes Loaiza AP, Velázquez Domínguez FJ, Ibarra Hernández CE, Flores Reséndiz MDLL, Castillo JL, Flores Valdés JR. Unmasking Subclinical Atherosclerosis: The Impact of Carotid Ultrasound on the Evaluation of Patients With Rheumatoid Arthritis. Cureus 2025; 17:e80525. [PMID: 40225433 PMCID: PMC11993276 DOI: 10.7759/cureus.80525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/13/2025] [Indexed: 04/15/2025] Open
Abstract
Rheumatoid arthritis (RA) is the most prevalent autoimmune disease, characterized by chronic joint inflammation and systemic symptoms, particularly affecting cardiovascular health through atherosclerosis development. This study investigates the role of carotid ultrasound in detecting atherosclerosis in RA patients by measuring carotid intima-media thickness (CIMT). We conducted a comprehensive review of studies published from 2017 to 2024, sourced from PubMed, focusing specifically on CIMT measurements in RA patients. Our analysis included eight studies involving a total of 1,242 participants. The results demonstrate that increased CIMT measurements in RA patients are associated with a higher risk of subclinical atherosclerosis. Notably, most studies (N = 7) reported statistically significant increases in CIMT, while only one study found no significant difference. These findings suggest that CIMT is a valuable tool for assessing cardiovascular risk in RA patients, advocating for the more frequent use of carotid ultrasound as a noninvasive clinical assessment method for this population. However, further multicentric randomized controlled trials and enhanced training for healthcare providers are necessary to ensure accurate CIMT measurements in routine practice.
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Affiliation(s)
- Ramiro A Moreno
- Cardiology, Autonomous University of Nuevo León, Monterrey, MEX
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Ma J, Cai J, Chen H, Feng Z, Yang G. Cardiovascular Adverse Events Associated with Tumor Necrosis Factor-Alpha Inhibitors: A Real-World Pharmacovigilance Analysis. J Atheroscler Thromb 2024; 31:1733-1747. [PMID: 38866553 PMCID: PMC11620835 DOI: 10.5551/jat.64767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 04/29/2024] [Indexed: 06/14/2024] Open
Abstract
AIM Evidence regarding the association between various tumor necrosis factor-α (TNF-α) inhibitors and cardiovascular adverse events (AEs) is both limited and contradictory. METHODS A retrospective pharmacovigilance study was conducted using the FDA Adverse Event Reporting System (FAERS) database. Cardiovascular AEs associated with TNF-α inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab) were evaluated using a disproportionality analysis. To reduce potential confounders, adjusted ROR and subgroup analyses were performed. RESULTS After excluding duplicates, 9,817 cardiovascular reports were associated with the five TNF-α inhibitors. Only adalimumab had positive signals for myocardial infarction (ROR=1.58, 95%CI=1.51-1.64) and arterial thrombosis (ROR=1.54, 95%CI=1.49-1.58). The remaining four TNF-α inhibitors did not show a risk association with any type of cardiovascular event. Further analyses of specific indication subgroups and after adjusting for any confounding factors demonstrated that adalimumab was still significantly associated with cardiovascular events, especially in patients with psoriasis (adjusted ROR=2.16, 95%CI=1.95-2.39). CONCLUSIONS This study revealed that adalimumab was the only TNF-α inhibitor associated with an elevated risk of thrombotic cardiovascular AEs, whereas the other four TNF-α inhibitors did not show any risk effect. However, given the limitations of such pharmacovigilance studies, it is necessary to validate these findings in prospective studies in the future.
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Affiliation(s)
- Junlong Ma
- Center of Clinical Pharmacology, Th ird Xiangya Hospital, Central South University, Hunan, China
- Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital, Hubei University of Medicine, Hubei, China
| | - Jiangfan Cai
- Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital, Hubei University of Medicine, Hubei, China
| | - Heng Chen
- Department of Pharmacy, The First Hospital of Changsha, Hunan, China
| | - Zeying Feng
- Center of Clinical Pharmacology, Th ird Xiangya Hospital, Central South University, Hunan, China
| | - Guoping Yang
- Center of Clinical Pharmacology, Th ird Xiangya Hospital, Central South University, Hunan, China
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Lovering E, Kodishala C, George RJ, Kumar R, Crowson CS, Lennon RJ, Davis JM, Myasoedova E. The impact of cardiovascular and cerebrovascular disease on the risk of dementia in rheumatoid arthritis: A mediation analysis. Semin Arthritis Rheum 2024; 69:152570. [PMID: 39413451 PMCID: PMC11606767 DOI: 10.1016/j.semarthrit.2024.152570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 09/20/2024] [Accepted: 10/09/2024] [Indexed: 10/18/2024]
Abstract
OBJECTIVE To examine the role of cardiovascular disease (CVD) as a mediator in the pathway between rheumatoid arthritis (RA) and Alzheimer's disease and related dementias (ADRD). METHODS This retrospective population-based study included patients over 50 years of age with incident RA, who met the 1987 ACR criteria in 1980-2014. This cohort was matched 1:1 on age, sex and index year to comparators without RA. Information on CVD events was manually extracted from electronic health records. The relationships between RA, CVD and ADRD were examined using Cox proportional hazard models. Time dependent mediation analysis was used to examine the role of CVD as a mediator between RA and ADRD. RESULTS 1754 individuals were included (877 persons with RA and 877 comparators without RA). During follow-up, 105 patients with RA and 102 individuals without RA developed ADRD; 444 patients with RA and 375 individuals without RA developed CVD. There was a non-significant association between RA and ADRD both without (aHR 1.27, 95 % CI 0.96, 1.69) and with (aHR 1.27, 95 % CI 0.95,1.68) CVD as a time dependent mediator. The mediation effect of any CVD on ADRD risk was not significant (p = 0.84). We found a significant interaction between RA and CVD on the risk of ADRD (aHR 1.95, 95 % CI 1.11, 3.42; p = 0.021). CONCLUSIONS The risk of ADRD in RA appears to be increased mainly in the presence of CVD. CVD was not a significant mediator on the risk of ADRD in RA. There was a significant synergistic effect of RA and CVD on ADRD risk.
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Affiliation(s)
| | | | | | - Rakesh Kumar
- Division of Rheumatology, Mayo Clinic, Rochester, MN, USA
| | - Cynthia S Crowson
- Division of Rheumatology, Mayo Clinic, Rochester, MN, USA; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Ryan J Lennon
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - John M Davis
- Division of Rheumatology, Mayo Clinic, Rochester, MN, USA
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Drosos AA, Venetsanopoulou AA, Pelechas E, Voulgari PV. Exploring Cardiovascular Risk Factors and Atherosclerosis in Rheumatoid Arthritis. Eur J Intern Med 2024; 128:1-9. [PMID: 39048336 DOI: 10.1016/j.ejim.2024.07.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 07/11/2024] [Accepted: 07/12/2024] [Indexed: 07/27/2024]
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly affecting the peripheral diarthrodial joints symmetrically and also presenting many extra-articular manifestations. Morbidity and mortality in RA patients are higher compared to the general population. Cardiovascular (CV) disease is one of the most common causes of death in these patients. Classical or traditional risk factors for atherosclerosis development occur more frequently in RA patients compared to those without this condition. Studies have showed that RA patients often present comorbidities such as hypertension, dyslipidemia, diabetes mellitus and obesity. However, the high incidence of CV events occurring in RA patients is not explained by the presence of traditional risk factors. Systemic inflammation, as it is expressed with the presence of proinflammatory cytokines and increased acute phase reactants, may contribute to the development of premature atherosclerosis in these patients. In this review, we explore the risk factors for CV disease, the generation of dyslipidemia, the lipid paradox and the role of systemic inflammation in the atherosclerotic process in RA. We discuss also the role of early therapeutic intervention that suppresses inflammation which may have beneficial effects on CV disease in RA patients.
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Affiliation(s)
- Alexandros A Drosos
- Department of Rheumatology, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece.
| | - Aliki A Venetsanopoulou
- Department of Rheumatology, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Eleftherios Pelechas
- Department of Rheumatology, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Paraskevi V Voulgari
- Department of Rheumatology, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece
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Fatima J, Shukla V, Siddiqi Z, Shamsi MZ, Mateen S, Jabbar AA, Usmani Z. Cardiovascular risk markers (computed tomography‑coronary artery calcium and carotid intima‑media thickness) in patients with rheumatoid arthritis and controls. MEDICINE INTERNATIONAL 2024; 4:52. [PMID: 39070004 PMCID: PMC11273241 DOI: 10.3892/mi.2024.176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 06/19/2024] [Indexed: 07/30/2024]
Abstract
Chronic inflammatory diseases, such as arthritis have been linked to a higher risk of developing cardiovascular disease. The present study examined the association between carotid intima-media thickness (CIMT) and coronary artery calcium (CAC), as well as the cardiovascular risk in patients with rheumatoid arthritis (RA). Additionally, the present study used 28 measures to calculate the disease activity score (DAS). To compare healthy controls with patients with RA, a case-control study was conducted that assessed CAC and CIMT in patients with the disease. A total of 45 healthy individuals and 45 patients with a diagnosis of RA were included in the study. With an average age of 50.66±12.35 years, the ages of the participants varied from 24 to 80 years. In both the control and RA patient groups, the sex ratio was 60%. The RA patient group had 53.3% female participants. There were significant variations in the levels of serum urea, potassium, magnesium, serum alkaline phosphatase, serum glutamic pyruvic transaminase, total leucocyte count, erythrocyte sedimentation rate, C-reactive protein (CRP) and lipids [apart from triglycerides and very low-density lipoprotein (VLDL)]. There was a substantial difference in the scores between patients with RA and the controls as regards CAC. A mild-severe risk of coronary artery disease was observed in 55.6% of RA cases and 4.4% of the controls (all mild). Both CIMT thickness and the CAC score exhibited a significant correlation with CRP, serum cholesterol, serum triglycerides, serum low-density lipids and serum VLDL. The DAS of patients ranged between 4.4 and 8.2 (mean, 5.81±0.91). A moderate disease activity was noted in the remaining patients, whereas 66.7% exhibited a high disease activity (DAS >5.2). On the whole, the present study demonstrates that conventional risk factors for cardiovascular disease, such as dyslipidemia, are consistent with both CIMT and CAC. The risk of developing atherosclerosis may be substantially increased by chronic inflammation, as the DAS score corresponds with CIMT and CAC.
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Affiliation(s)
- Jalees Fatima
- Department of Medicine, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh 226003, India
| | - Vaibhav Shukla
- Department of Medicine, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh 226003, India
| | - Zeba Siddiqi
- Department of Medicine, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh 226003, India
| | - Mohammad Zakariya Shamsi
- Department of Cardiology, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan 302022, India
| | - Saboor Mateen
- Department of Medicine, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh 226003, India
| | - Aaliya Abdul Jabbar
- Department of Medicine, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh 226003, India
| | - Zeenat Usmani
- Department of Medicine, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh 226003, India
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Janak JC, Ross RD, Brady BL, Palmer L, Howard JT, Baker JF. Prevalence of Cardiovascular and Cancer Risk Factors Among Rheumatoid Arthritis Patients Prescribed JAK Inhibitors and Tumor Necrosis Factor Inhibitors: A Cross-Sectional Study. Arthritis Care Res (Hoboken) 2024; 76:1287-1293. [PMID: 38682605 DOI: 10.1002/acr.25356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 03/18/2024] [Accepted: 04/26/2024] [Indexed: 05/01/2024]
Abstract
OBJECTIVE The study was to determine the prevalence of baseline risk factors for cardiovascular outcomes and cancer among commercially-insured patients with rheumatoid arthritis (RA) during their first dispensed treatment for either tumor necrosis factor inhibitors (TNFi) or JAK inhibitors (JAKi). METHODS Patients with RA from August 16, 2019 to March 31, 2022 were identified in the Merative MarketScan Commercial and Medicare databases. The first date that a TNFi or JAKi was dispensed was the index date, and baseline risk factors were assessed among patients continuously eligible for 12 months before the index date. Patients who had the following were stratified into an elevated risk category: age ≥65 years, smoking, or a history of a major adverse cardiovascular event, venous thromboembolism, or cancer. The prevalence of modifiable risk factors was also reported: hypertension, hyperlipidemia, obesity, and diabetes. The crude prevalence and prevalence difference (PD) were reported. RESULTS A total of 12,673 patients (TNFi [n = 7,748; 61%] and JAKi [n = 4,925; 39%]) met inclusion criteria. The prevalence of elevated risk was the same for all patients using TNFi (n = 2,051; 26%) and JAKi (n = 1,262; 26%). Compared with patients having low risk, patients with an elevated risk also had a higher prevalence of at least one primary modifiable risk factor for both patients using JAKi (79% vs 58%; PD 21%, 95% confidence interval [CI] 18%-24%) and TNFi (81% vs 60%; PD 21%, 95% CI 19%-23%). CONCLUSION In recent years, JAKi and TNFi were used in similar proportions to treat RA among commercially-insured patients at elevated cardiovascular and cancer risk. Because uncontrolled disease, modifiable comorbidities, and treatment with JAKi are associated with these adverse events, future studies evaluating how practice patterns may be affected by the emergence of safety data will be of value.
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Affiliation(s)
| | | | | | | | | | - Joshua F Baker
- Corporal Michael J. Crescenz VA Medical Center and Perelman School of Medicine, University of Pennsylvania, Philadelphia
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Corrao S, Calvo L, Giardina A, Cangemi I, Falcone F, Argano C. Rheumatoid arthritis, cardiometabolic comorbidities, and related conditions: need to take action. Front Med (Lausanne) 2024; 11:1421328. [PMID: 39114820 PMCID: PMC11303151 DOI: 10.3389/fmed.2024.1421328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 07/03/2024] [Indexed: 08/10/2024] Open
Abstract
Rheumatoid Arthritis (RA) is associated with an increased risk of cardiovascular disease and mortality, however, traditional cardiovascular risk factors do not fully explain this relationship. This high risk of cardiovascular morbidity and mortality in RA has been increasingly acknowledged in past decades, with accumulating evidence that RA is an independent cardiovascular risk factor; RA is also associated with metabolic syndrome, which correlates with disease activity, contributing to the increased prevalence of coronary heart disease in RA patients. Moreover, multimorbidity, including the presence of long-term conditions, impacts adverse clinical outcomes in RA patients, emphasizing the need for holistic management that requires an understanding of shared pathophysiological mechanisms, such as systemic inflammation and immune dysregulation. For all these reasons, the management of RA patients with cardiometabolic comorbidities is a complex endeavor that requires a patient-centered, multidisciplinary approach. In this sense, there is a need to re-evaluate the approach toward a proactive model of care, moving away from a reactive medical paradigm to a multidimensional integrated management model, including aggressive screening, preventive strategies, and tailored therapeutic interventions. The aim of this review was to thoroughly review the literature on cardiometabolic comorbidities and related conditions linked to RA to enable us to identify the necessary actions required to effectively tackle the increasing burden of illness from a fully comprehensive perspective.
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Affiliation(s)
- Salvatore Corrao
- Department of Clinical Medicine, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties [PROMISE], University of Palermo, Palermo, Italy
| | - Luigi Calvo
- Department of Clinical Medicine, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy
| | - Annarita Giardina
- Department of Clinical Medicine, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy
| | - Ignazio Cangemi
- Department of Clinical Medicine, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy
| | - Fabio Falcone
- Department of Clinical Medicine, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties [PROMISE], University of Palermo, Palermo, Italy
| | - Christiano Argano
- Department of Clinical Medicine, Internal Medicine Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, Palermo, Italy
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Sasso EH, Mabey B, Flake DD, Hitraya E, Chin CL, Ben-Shachar R, Gutin A, Lanchbury JS, Curtis JR. External validation of a multi-biomarker-based score for predicting risk of cardiovascular disease in patients with rheumatoid arthritis. PLoS One 2024; 19:e0296459. [PMID: 38709770 PMCID: PMC11073667 DOI: 10.1371/journal.pone.0296459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 12/13/2023] [Indexed: 05/08/2024] Open
Abstract
BACKGROUND A multi-biomarker disease activity (MBDA)-based cardiovascular disease (CVD) risk score was developed and internally validated in a Medicare cohort to predict 3-year risk for myocardial infarction (MI), stroke or CVD death in patients with rheumatoid arthritis (RA). It combines the MBDA score, leptin, MMP-3, TNF-R1, age and four clinical variables. We are now externally validating it in a younger RA cohort. METHODS Claims data from a private aggregator were linked to MBDA test data to create a cohort of RA patients ≥18 years old. A univariable Cox proportional hazards regression model was fit using the MBDA-based CVD risk score as sole predictor of time-to-a-CVD event (hospitalized MI or stroke). Hazard ratio (HR) estimate was determined for all patients and for clinically relevant subgroups. A multivariable Cox model evaluated whether the MBDA-based CVD risk score adds predictive information to clinical data. RESULTS 49,028 RA patients (340 CVD events) were studied. Mean age was 52.3 years; 18.3% were male. HR for predicting 3-year risk of a CVD event by the MBDA-based CVD risk score in the full cohort was 3.99 (95% CI: 3.51-4.49, p = 5.0×10-95). HR were also significant for subgroups based on age, comorbidities, disease activity, and drug use. In a multivariable model, the MBDA-based CVD risk score added significant information to hypertension, diabetes, tobacco use, history of CVD, age, sex and CRP (HR = 2.27, p = 1.7×10-7). CONCLUSION The MBDA-based CVD risk score has been externally validated in an RA cohort that is younger than and independent of the Medicare cohort that was used for development and internal validation.
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Affiliation(s)
- Eric H. Sasso
- Medical and Scientific Affairs, Crescendo Bioscience, South San Francisco, CA, United States of America
- Myriad Genetics Laboratories, Myriad, Salt Lake City, UT, United States of America
| | - Brent Mabey
- Myriad Genetics Laboratories, Myriad, Salt Lake City, UT, United States of America
| | - Darl D. Flake
- Myriad Genetics Laboratories, Myriad, Salt Lake City, UT, United States of America
| | - Elena Hitraya
- Medical and Scientific Affairs, Crescendo Bioscience, South San Francisco, CA, United States of America
- Myriad Genetics Laboratories, Myriad, Salt Lake City, UT, United States of America
| | - Cheryl L. Chin
- Medical and Scientific Affairs, Crescendo Bioscience, South San Francisco, CA, United States of America
- Myriad Genetics Laboratories, Myriad, Salt Lake City, UT, United States of America
| | - Rotem Ben-Shachar
- Myriad Genetics Laboratories, Myriad, Salt Lake City, UT, United States of America
| | - Alexander Gutin
- Myriad Genetics Laboratories, Myriad, Salt Lake City, UT, United States of America
| | - Jerry S. Lanchbury
- Myriad Genetics Laboratories, Myriad, Salt Lake City, UT, United States of America
| | - Jeffrey R. Curtis
- Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, United States of America
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Gasparotto M, Di Pierro G, Toffoli B, Grillo A, Bressan M, Fiorentin M, Di Luozzo L, Fischetti F, Zen M, Fabris B, Bernardi S, Tomietto P. Preliminary Study on Pulse Wave Changes in Patients with Inflammatory Arthropathies Treated with bDMARDs. J Clin Med 2024; 13:2684. [PMID: 38731213 PMCID: PMC11084438 DOI: 10.3390/jcm13092684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 04/23/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024] Open
Abstract
Background: Patients with inflammatory arthropathies exhibit an increased cardiovascular disease (CVD) risk as compared to the general population, which is not fully quantified by the conventional CVD risk scores. Biotechnological disease-modifying drugs (bDMARDs) have proved beneficial to reduce the overall CVD risk in these patients, although CVD remains a major cause of increased mortality. Since it has been shown that pulse wave parameters and in particular carotid-femoral pulse wave velocity (cfPWV) are predictors of CVD risk, the aim of this study was to evaluate their changes in patients with inflammatory arthropathies before and after bDMARD therapy. Methods: Pulse wave parameters were evaluated with applanation tonometry in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and rheumatoid arthritis (RA), before and after two years of bDMARD therapy. Results: At baseline, cfPWV was significantly associated with age (p < 0.001) and, among pulse wave parameters, the subendocardial viability ratio was negatively associated with C-reactive protein (CRP) (p = 0.04) and the HAQ-disability index (p = 0.03). At baseline, PsA patients showed a higher percentage of male subjects, higher CRP, and the highest cfPWV values (p = 0.048). After two years, pulse wave parameters improved in the AS and RA groups, but not in the PsA group. Conclusions: Our data confirm that pulse wave parameters are potentially reversible after bDMARD therapy, as they improved in AS and RA patients. In PsA patients, there were no changes, which may be due to the higher percentage of male subjects and higher baseline cfPWV values.
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Affiliation(s)
- Michela Gasparotto
- UCO Medicina Clinica, ASUGI, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (M.G.); (A.G.); (F.F.) (B.F.); (P.T.)
- Department of Medicine, Padua University Hospital, University of Padua, 35122 Padova, Italy;
| | - Giuliano Di Pierro
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Barbara Toffoli
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Andrea Grillo
- UCO Medicina Clinica, ASUGI, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (M.G.); (A.G.); (F.F.) (B.F.); (P.T.)
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Marco Bressan
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Marco Fiorentin
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Lorenzo Di Luozzo
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Fabio Fischetti
- UCO Medicina Clinica, ASUGI, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (M.G.); (A.G.); (F.F.) (B.F.); (P.T.)
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Margherita Zen
- Department of Medicine, Padua University Hospital, University of Padua, 35122 Padova, Italy;
| | - Bruno Fabris
- UCO Medicina Clinica, ASUGI, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (M.G.); (A.G.); (F.F.) (B.F.); (P.T.)
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Stella Bernardi
- UCO Medicina Clinica, ASUGI, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (M.G.); (A.G.); (F.F.) (B.F.); (P.T.)
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Paola Tomietto
- UCO Medicina Clinica, ASUGI, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (M.G.); (A.G.); (F.F.) (B.F.); (P.T.)
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Huang YC, Lai ECC, Liao TC, Weng MY. Evaluating the risk of ischemic stroke at a young age in patients with autoimmune inflammatory rheumatic diseases: a population-based cohort study in Taiwan. Front Immunol 2024; 15:1272557. [PMID: 38404587 PMCID: PMC10884215 DOI: 10.3389/fimmu.2024.1272557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 01/22/2024] [Indexed: 02/27/2024] Open
Abstract
Background Recent studies have demonstrated an increased incidence of ischemic stroke among patients with certain autoimmune inflammatory rheumatic diseases (AIIRDs). However, the associations between young stroke and AIIRDs have not been fully investigated. This study aimed to evaluate the risk of ischemic stroke among young patients with AIIRDs. Methods The National Health Insurance Research Database in Taiwan was utilized to establish cohorts of patients with AIIRDs diagnosed between 2004 and 2015, who were compared with 1,000,000 control participants. Cox proportional hazards regression models were used to calculate the hazard ratio of ischemic stroke and young ischemic stroke for individual AIIRDs after adjustment for relative risk factors. Results During the study period, a total of 64,120 patients with AIIRDss and 1,000,000 control patients were identified. The overall mean follow-up time was 5.33 years. There were 223 (0.8%) and 1,923 (0.3%) young ischemic stroke-related hospitalizations among patients with AIIRDs and controls, respectively. The incidence rate of young ischemic stroke was 0.08 in patients with rheumatoid arthritis, 0.08 in patients with Sjögren's syndrome, 0.26 in patients with systemic lupus erythematosus, 0.17 in patients with idiopathic inflammatory myositis, 0.24 in patients with systemic sclerosis, 0.05 in patients with Behçet's disease, and 0.44 in patients with systemic vasculitis, versus 0.05 per 100 person-years in the general population. The adjusted hazard ratios for young ischemic stroke were 1.07 (95% CI 0.70-1.43) for rheumatoid arthritis, 1.39 (95% CI 0.94-2.06) for Sjögren's syndrome, 5.79 (95% CI 4.68-7.17) for systemic lupus erythematosus, 2.07 for idiopathic inflammatory myositis (95% CI 0.98-4.38), 2.79 for systemic sclerosis (95% CI 1.38-5.63), 0.82 for Behçet's disease (95% CI 0.26-2.55), and 4.15 (95% CI 1.96-8.82) for systemic vasculitis. Conclusions Patients younger than 50 years with systemic lupus erythematosus, systemic sclerosis, or systemic vasculitis have a significantly elevated risk of developing ischemic stroke. Further research is needed to elucidate the pathogenesis of accelerated atherosclerosis in these AIIRDs.
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Affiliation(s)
- Ya-Chun Huang
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Edward Chia-Cheng Lai
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Tzu-Chi Liao
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Meng-Yu Weng
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Asenjo-Lobos C, González L, Bulnes JF, Roque M, Muñoz Venturelli P, Rodríguez GM. Cardiovascular events risk in patients with systemic autoimmune diseases: a prognostic systematic review and meta-analysis. Clin Res Cardiol 2024; 113:246-259. [PMID: 37650912 DOI: 10.1007/s00392-023-02291-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 08/21/2023] [Indexed: 09/01/2023]
Abstract
BACKGROUND Chronic inflammation is considered a risk factor for the development of atherosclerosis and cardiovascular (CV) events. We seek to assess the risk of CV events in patients with Systemic autoimmune diseases (SAD), such as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Psoriasis (Ps) and Ankylosing Spondylitis (AS), compared with the general population. METHODS AND RESULTS A systematic search of MEDLINE from inception up to May 2021 was performed. Observational studies including individuals with and without autoimmune diseases (SLE, RA, Ps, AS), which reported a measure of association and variability for the effect of SAD on CV events, were included. The random effects meta-analysis was performed using the Hartung-Knapp-Sidik-Jonkman approach to obtain the pooled estimates. Cardiovascular Events including CV mortality, non-fatal myocardial infarction (MI), non-fatal stroke and coronary revascularization were the main outcomes evaluated. Fifty-four studies were selected, with a total of 24,107,072 participants. The presence of SAD was associated with an increased risk of CV mortality (HR 1.49 [95% CI 1.10-2.03]), non-fatal MI (HR 1.42 [95% CI 1.23-1.62]), and non-fatal stroke (HR 1.47 [95% CI 1.28-1.70]). RA, SLE, and Ps (particularly with arthritis) were significantly associated with a higher risk of MI and stroke. SAD was also associated with an increased risk of Major Adverse Cardiovascular Events (MACE) (HR 1.45 [95% CI 1.16-1.83]). CONCLUSION Patients with SAD present an increased risk of CV morbidity and mortality, which should be considered when establishing therapeutic strategies. These findings support the role of systemic inflammation in the development of atherosclerosis-driven disease.
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Affiliation(s)
- Claudia Asenjo-Lobos
- Centro de Estudios Clínicos, Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina Clínica Alemana Universidad de Desarrollo, Santiago, Chile
| | - Leticia González
- Centro de Imágenes Biomédicas, Departamento de Radiología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Instituto Milenio de Ingeniería e Inteligencia Artificial para la Salud, iHEALTH, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Francisco Bulnes
- División de Enfermedades Cardiovasculares, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Marta Roque
- Iberoamerican Cochrane Centre, Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain
| | - Paula Muñoz Venturelli
- Centro de Estudios Clínicos, Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina Clínica Alemana Universidad de Desarrollo, Santiago, Chile
- Faculty of Medicine, The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia
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Al-Ewaidat OA, Naffaa MM. Stroke risk in rheumatoid arthritis patients: exploring connections and implications for patient care. Clin Exp Med 2024; 24:30. [PMID: 38294723 PMCID: PMC10830780 DOI: 10.1007/s10238-023-01288-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Accepted: 11/04/2023] [Indexed: 02/01/2024]
Abstract
Rheumatoid arthritis (RA) can independently increase the risk of stroke, affecting both young and adult RA patients. Recent attention has been drawn to the association between stroke and RA, supported by mounting evidence. Given that stroke is a significant and an urgent public health concern, this review aims to highlight the relationship between stroke and RA, covering mechanisms, underlying risk factors, early detection tools, and treatment implications. By uncovering the connection that links RA to stroke, we can pave the way for targeted healthcare practices and the development of preventive strategies for individuals with RA. Therefore, further research is imperative to deepen our understanding of this association and, ideally, guide treatment decisions for individuals at risk of both RA and stroke.
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Affiliation(s)
- Ola A Al-Ewaidat
- Department of Internal Medicine, Ascension Saint Francis Hospital, Evanston, IL, 60202, USA
| | - Moawiah M Naffaa
- Department of Psychology and Neuroscience, Duke University, Durham, NC, 27708, USA.
- Department of Cell Biology, Duke University School of Medicine, Durham, NC, 27710, USA.
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Zaręba W, Krawiec P, Banaszkiewicz M, Batko K, Gołąb A, Plicner D, Żuber Z, Batko B. Newly developed cardiovascular risk factors in rheumatoid arthritis patients initiating biologic treatment. Reumatologia 2024; 61:424-431. [PMID: 38322099 PMCID: PMC10839918 DOI: 10.5114/reum/176554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 12/07/2023] [Indexed: 02/08/2024] Open
Abstract
Introduction Rheumatoid arthritis (RA) is a risk factor (RF) for cardiovascular (CV) disease, a leading cause of mortality in RA patients. Material and methods Consecutive records of RA patients with high disease activity screened upon biologic therapy initiation were reviewed between January 2001 and 2018. Patients with at least 6-month follow-up and baseline disease activity scores were enrolled (n = 353) and stratified into manifest CV disorder ("overt CVD"), any traditional CV risk factor ("atCVrisk") and no CV risk factor ("vlCVrisk") groups. Results Overall, mean (SD) patient age was 51.4 (±12.2) years, and 291 (82.4%) subjects were female. Median follow-up was 41.9 (IQR 18.6, 80) months. Overall, 89 (25.2%) individuals developed at least one new CV RF, of which 65 (18.4%) acquired one and 24 (6.8%) two or more. Incident lipid disorders (42, 11.9%), followed by hypertension (14, 4%), atrial fibrillation (17, 4.8%) and venous thromboembolism (VTE) (16, 4.5%), were common. Incident major adverse cardiac events (MACE) were not reported in the vlCVrisk group, in contrast to atCVrisk (n = 8, 4.2%) or overt CVD (n = 4, 18.2%). Age was a significant predictor of incident CV risk factor (HR 1.04, 95% CI: 1.02-1.07; p < 0.01). In age-adjusted analyses, only baseline body mass index (BMI) (HR 1.11, 95% CI: 1.04-1.18; p < 0.01), but not ever smoking (p = 0.93), male sex (p = 0.26), positive RF (p = 0.24), positive ACPA (p = 0.90), or baseline disease activity (p = 0.19), were independent predictor of incident CV risk factors. Conclusions Patients with RA initiating biologics should be screened for cardiometabolic risk factors, especially at an older age. The presence of at least one risk factor may be linked to a worse long-term prognosis.
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Affiliation(s)
- Wojciech Zaręba
- Department of Cardiology, Jozef Dietl Specialist Hospital, Krakow, Poland
| | - Piotr Krawiec
- Department of Rheumatology and Immunology, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski University, Krakow, Poland
- Department of Research and Development, Medicine Economy Law Science Foundation (MELS), Krakow, Poland
| | - Małgorzata Banaszkiewicz
- Department of Nephrology and Transplantology, Jagiellonian University Medical College, Krakow, Poland
| | - Krzysztof Batko
- Department of Research and Development, Medicine Economy Law Science Foundation (MELS), Krakow, Poland
- Department of Nephrology and Transplantology, Jagiellonian University Medical College, Krakow, Poland
| | - Aleksandra Gołąb
- Faculty of Medicine and Dentistry, Pomeranian Medical University in Szczecin, Poland
| | - Dariusz Plicner
- Unit of Experimental Cardiology and Cardiac Surgery, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski University, Krakow, Poland
- Department of Cardiovascular Surgery and Transplantation, John Paul II Hospital, Krakow, Poland
| | - Zbigniew Żuber
- Department of Research and Development, Medicine Economy Law Science Foundation (MELS), Krakow, Poland
- Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski University, Krakow, Poland
| | - Bogdan Batko
- Department of Rheumatology and Immunology, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski University, Krakow, Poland
- Department of Research and Development, Medicine Economy Law Science Foundation (MELS), Krakow, Poland
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Fares J, Summer R, Loizidis G. Low utilization of statins in patients with dermatomyositis/polymyositis and hyperlipidemia: a multicenter USA-based study (2013-2023). Clin Rheumatol 2024; 43:325-338. [PMID: 37930595 DOI: 10.1007/s10067-023-06801-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 10/19/2023] [Accepted: 10/20/2023] [Indexed: 11/07/2023]
Abstract
OBJECTIVE While the cardioprotective benefits of statins for rheumatoid arthritis (RA) patients are well-established, there might be a hesitation in recommending them for dermatomyositis/polymyositis (DM/PM) patients with hyperlipidemia (HLD), particularly with myopathy. We sought to contrast statin prescription patterns between DM/PM-HLD and RA-HLD patients and delve into the mortality variations among DM/PM-HLD statin users and non-users. METHODS We examined a decade's worth of anonymized US health data from the TriNetX database. Inclusion criteria were a subsequent HLD diagnosis after an initial DM/PM or RA diagnosis. We compared statin initiation rates and mortality outcomes, adjusting for demographics and cardiovascular risks through propensity score matching. RESULTS The analysis comprised 33,000 RA-HLD and 1079 DM/PM-HLD patients. RA-HLD patients exhibited higher statin initiation (27.4%) than DM/PM-HLD patients (17.91%, p < 0.0001). Notably, DM/PM-HLD statin users (n = 311) presented a reduced mortality rate (75 deaths/1000/year) compared to non-users (n = 661) with 147 deaths/1000/year (p = 0.0273, HR = 0.515, CI 0.28-0.93). CONCLUSION There is a marked disparity in statin initiation between DM/PM-HLD and RA-HLD patients, accompanied by elevated mortality in DM/PM-HLD non-users. It is imperative for further research to elucidate this discrepancy and formulate patient-centric cardiovascular guidelines for DM/PM-HLD patients. Key Points • Statin initiation among patients with DM/PM-HLD is significantly lower than that with RA-HLD. • Mortality rates within the statin initiator DM/PM-HLD were significantly lower compared to non-statin DM/PM-HLD initiators, spanning multiple time intervals.
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Affiliation(s)
- Joseph Fares
- Division of Pulmonary and Critical Care, Department of Medicine, The Jane and Leonard Korman Respiratory Institute, Thomas Jefferson University, Philadelphia, PA, USA
| | - Ross Summer
- Division of Pulmonary and Critical Care, Department of Medicine, The Jane and Leonard Korman Respiratory Institute, Thomas Jefferson University, Philadelphia, PA, USA
| | - Giorgos Loizidis
- Division of Rheumatology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
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Shand G, Fuller DT, Lufkin L, Lovelett C, Pal N, Mondal S, Sur S. A stronger association of depression with rheumatoid arthritis in presence of obesity and hypertriglyceridemia. FRONTIERS IN EPIDEMIOLOGY 2023; 3:1216497. [PMID: 38455932 PMCID: PMC10910964 DOI: 10.3389/fepid.2023.1216497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 11/29/2023] [Indexed: 03/09/2024]
Abstract
Background Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic and systemic inflammation. Recent research underscores the role of chronic inflammation in multiple common RA comorbidities such as depression, obesity, and cardiovascular diseases (CVDs), suggesting a potential overlap of the pathogenic mechanisms for RA. However, it is not well understood how the coexistence of these comorbid conditions impacts the risk of RA and whether any such association relates to body's inflammatory state. Methods We used data from the 2007-2010 United States National Health and Nutrition Examination Survey (NHANES) database and compared RA prevalence between subsamples with the presence of any two conditions among depression, obesity, and hypertriglyceridemia (HTG). Each subsample was further divided into three categories based on the serum level of the inflammatory marker C-reactive protein (CRP) and analyzed for statistically significant differences using three-way χ2 tests of independence. Results The study was conducted on 4,136 patients who fulfilled the inclusion criteria (representing 163,540,241 individuals after adjustment for sampling weights). Rates of depression, obesity, and HTG were found to be significantly higher (P < 0.001) among the subjects with RA compared with the control population with no arthritis. The presence of depression along with obesity or HTG showed a noticeably higher RA prevalence but such an association was not observed for the combination of obesity and HTG. The synergistic effect of HTG with depression was found to be most prominent at a medium CRP level (1-3 mg/L), while for obesity, the effect was observed across all CRP levels examined. These findings were further confirmed by the three-way χ2 test for independence. Conclusions The presence of obesity or HTG in subjects suffering from depression might pose an increased risk of RA. Inflammatory mechanisms potentially play an important underlying role as suggested by the strong dependency of the association to CRP level. Identification of synergistic associations between RA risk conditions could provide useful information to predict the development and progress of RA.
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Affiliation(s)
- Grayden Shand
- David D. Reh School of Business, Clarkson University, Potsdam, NY, United States
| | - Daniel T. Fuller
- Department of Mathematics, Clarkson University, Potsdam, NY, United States
| | - Leon Lufkin
- The Clarkson School, Clarkson University, Potsdam, NY, United States
- Department of Statistics and Data Science, Yale University, New Haven, CT, United States
| | - Carly Lovelett
- Saint Lawrence Health, Canton Potsdam Hospital, Potsdam, NY, United States
| | - Nabendu Pal
- Department of Mathematics, University of Louisiana at Lafayette, Lafayette, LA, United States
| | - Sumona Mondal
- Department of Mathematics, Clarkson University, Potsdam, NY, United States
| | - Shantanu Sur
- Department of Biology, Clarkson University, Potsdam, NY, United States
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19
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Alduraibi FK, Singh JA. How to Use Janus Kinase Inhibitors in the Treatment of Rheumatoid Arthritis? A Clinical Assessment of Risks and Benefits. Curr Rheumatol Rep 2023; 25:295-306. [PMID: 38102522 DOI: 10.1007/s11926-023-01122-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/04/2023] [Indexed: 12/17/2023]
Abstract
PURPOSE OF REVIEW To provide an updated understanding of risks and benefits of Janus kinase inhibitors (JAKi) versus biologic disease-modifying antirheumatic drugs (bDMARDs) in the management of rheumatoid arthritis (RA). RECENT FINDINGS Shared decision-making is needed in choosing between JAKi and bDMARDs. Cardiovascular disease, malignancy, and thromboembolic events guide this choice. In patients with active RA despite methotrexate use, tumor necrosis factor inhibitor is conditionally favored over JAKi for low-cardiovascular-risk patients and strongly favored in those with pre-existing cardiovascular disease or multiple cardiovascular risk factors. Suboptimal treatment of treatment-refractory RA patients may pose a greater absolute cardiovascular risk than with JAKi use. Use of aspirin and statin may be considered to reduce cardiovascular risk. New safety data on JAKi has redefined the treatment approach in RA. JAKi remains an important oral medication option in active RA despite treatment with bDMARDs, especially in those with low cardiovascular risk.
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Affiliation(s)
- Fatima K Alduraibi
- Division of Clinical Immunology and Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
- Division of Clinical Immunology and Rheumatology, Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Jasvinder A Singh
- Division of Clinical Immunology and Rheumatology, Department of Medicine, Musculoskeletal Outcomes Research, University of Alabama at Birmingham, Birmingham, AL, USA.
- Birmingham Veterans Affairs Medical, Birmingham, AL, USA.
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20
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Karpouzas GA, Szekanecz Z, Baecklund E, Mikuls TR, Bhatt DL, Wang C, Sawyerr GA, Chen Y, Menon S, Connell CA, Ytterberg SR, Mortezavi M. Rheumatoid arthritis disease activity and adverse events in patients receiving tofacitinib or tumor necrosis factor inhibitors: a post hoc analysis of ORAL Surveillance. Ther Adv Musculoskelet Dis 2023; 15:1759720X231201047. [PMID: 37942277 PMCID: PMC10629315 DOI: 10.1177/1759720x231201047] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 08/25/2023] [Indexed: 11/10/2023] Open
Abstract
Background In patients with rheumatoid arthritis (RA), persistent inflammation and increasing disease activity are associated with increased risk of adverse events (AEs). Objectives To assess relationships between RA disease activity and AEs of interest in patients treated with tofacitinib or tumor necrosis factor inhibitors (TNFi). Design This was a post hoc analysis of a long-term, postauthorization safety endpoint trial of tofacitinib versus TNFi. Methods In ORAL Surveillance, 4362 patients aged ⩾50 years with active RA despite methotrexate, and ⩾1 additional cardiovascular (CV) risk factor, were randomized 1:1:1 to tofacitinib 5 or 10 mg twice daily or TNFi for up to 72 months. Post hoc time-dependent multivariable Cox analysis evaluated the relationships between disease activity [Clinical Disease Activity Index (CDAI)], inflammation [C-reactive protein (CRP)], and AEs of interest. The AEs included major adverse CV events (MACE), malignancies excluding nonmelanoma skin cancer (NMSC), venous thromboembolism (VTE), serious infections, herpes zoster (HZ), nonserious infections excluding HZ (NSI), and death. Results Across treatments, risk for NSI was higher when patients had CDAI-defined active disease versus remission; MACE and VTE risks trended higher, but did not reach significance. Hazard ratios for MACE, malignancies excluding NMSC, VTE, infections, and death rose by 2-9% for each 5-mg/L increment in serum CRP. The interaction terms evaluating the impact of treatment assignment on the relationship between disease activity and AEs were all p > 0.05. Conclusion In ORAL Surveillance, higher NSI risk was observed in the presence of active RA versus remission. The risk of MACE and VTE directionally increased in active disease versus remission, although statistical power was limited due to small event numbers in these categories. The relationship between active disease and AEs was not impacted by treatment with tofacitinib versus TNFi. Registration NCT02092467.
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Affiliation(s)
- George A. Karpouzas
- Division of Rheumatology, Harbor-UCLA Medical Center, and the Lundquist Institute, Torrance, CA, USA
| | - Zoltán Szekanecz
- Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Eva Baecklund
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Ted R. Mikuls
- Division of Rheumatology, University of Nebraska Medical Center and VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA
| | - Deepak L. Bhatt
- Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Health System, New York, NY, USA
| | - Cunshan Wang
- Inflammation and Immunology, Pfizer Inc, Groton, CT, USA
| | | | - Yan Chen
- Inflammation and Immunology, Pfizer Inc, Collegeville, PA, USA
| | - Sujatha Menon
- Inflammation and Immunology, Pfizer Inc, Groton, CT, USA
| | | | | | - Mahta Mortezavi
- Inflammation and Immunology, Pfizer Inc, 66 Hudson Boulevard, New York, NY 10001, USA
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21
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Montes D, Hulshizer CA, Myasoedova E, Davis JM, Hanson AC, Duarte-Garcia A, Figueroa-Parra G, Chevet B, Crowson CS. Utilisation of cardiovascular preventive services in a rheumatoid arthritis population-based cohort. RMD Open 2023; 9:e003318. [PMID: 37945289 PMCID: PMC10649903 DOI: 10.1136/rmdopen-2023-003318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 10/10/2023] [Indexed: 11/12/2023] Open
Abstract
OBJECTIVES The objective is to examine utilisation of cardiovascular preventive services in patients with rheumatoid arthritis (RA), compared with a non-RA population, and to examine cardiovascular disease (CVD) screening rates among RA patients without diabetes mellitus (DM), hypertension or hyperlipidaemia to non-RA patients with one of these diagnoses. METHODS All ≥18-year-old patients with an RA diagnosis living in one of eight Minnesota counties on 1 January 2015 were included and matched (1:1) by sex, age and county to non-RA comparators. Rates of screening for CVD risk factors, including DM (ie, glucose), hypertension (ie, blood pressure) and hyperlipidaemia (ie, lipids), were compared between groups using Cox models. RESULTS The study included 1614 patients with RA and 1599 non-RA comparators. DM screening was more common among patients with RA (HR: 1.10, 95% CI: 1.01 to 1.19), as was hypertension screening (HR: 1.37, 95% CI: 1.24 to 1.52). Hyperlipidaemia screening in RA was similar to comparators (HR: 0.99, 95% CI: 0.89 to 1.10). Conversely, patients with RA and no CVD risk factors had a lower probability of undergoing diabetes (HR: 0.67, 95% CI: 0.57 to 0.78) and hyperlipidaemia screening (HR: 0.65, 95% CI: 0.54 to 0.79) than non-RA patients with only one CVD risk factor diagnosis. Hypertension screening was similar between both groups. CONCLUSIONS RA patients undergo CVD preventive screening at rates at least comparable to the general population. However, patients with RA as their sole CVD risk factor were less likely to undergo screenings, despite an equivalent-to-higher risk as the traditional CVD risk factors. These findings demonstrate opportunities for improvement of RA patient care.
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Affiliation(s)
- Daniel Montes
- Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Elena Myasoedova
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
- Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA
| | - John M Davis
- Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Andrew C Hanson
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | - Baptiste Chevet
- Spécialité de Rhumatologie, Centre Hospitalier Universitaire de Brest, Brest, France
| | - Cynthia S Crowson
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
- Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA
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22
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Barkhane Z, Zaree A, Zulfiqar S, Qudoos A, Vaidhyula S, Jaiprada F, Dar S, Ali N. Comparison of Cardiovascular Outcomes in Patients With and Without Rheumatoid Arthritis: A Meta-Analysis of Observational Studies. Cureus 2023; 15:e40348. [PMID: 37456442 PMCID: PMC10339149 DOI: 10.7759/cureus.40348] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/13/2023] [Indexed: 07/18/2023] Open
Abstract
The aim of this meta-analysis was to determine the risk of incident cardiovascular disease (CVD) in patients with rheumatoid arthritis compared to patients without rheumatoid arthritis. We conducted a thorough search of online databases, including PubMed, EMBASE, and Web of Science, to identify English-language publications examining cardiovascular outcomes in patients with rheumatoid arthritis from January 1, 2005, to May 15, 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was performed using relevant keywords such as "rheumatoid arthritis," "cardiovascular diseases," and "risk," along with their synonyms. Medical subject heading (MeSH) terms and Boolean operators (AND, OR) were employed to optimize the search. Outcomes assessed in this study included composite cardiovascular events (as defined by individual studies), myocardial infarction, and stroke (including ischemic and hemorrhagic stroke). Overall, 14 studies met the inclusion criteria and were included in the present meta-analysis. We found that the risk of composite CVD was higher in patients with rheumatoid arthritis compared to patients without rheumatoid arthritis. We also found a higher risk of myocardial infarction and stroke in rheumatoid arthritis patients compared to their counterparts. This study demonstrates the elevated risk of CVD in patients with rheumatoid arthritis and highlights the importance of incorporating cardiovascular management and assessment into the care of these patients.
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Affiliation(s)
- Zineb Barkhane
- Medicine and Pharmacy, University of Hassan II Casablanca, Casablanca, MAR
| | - Amna Zaree
- Medicine, Shalimar Medical and Dental College, Lahore, PAK
| | - Sualeha Zulfiqar
- Internal Medicine, Rawalpindi Medical University, Rawalpindi, PAK
| | - Ahmed Qudoos
- Medicine, Liaquat University of Medical and Health Sciences, Hyderabad, PAK
| | - Santhoshi Vaidhyula
- Medicine, Dr. Nandamuri Taraka Rama Rao (NTR) University of Health Sciences, Vijayawada, IND
| | - Fnu Jaiprada
- Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Saleha Dar
- Adult Medicine, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Neelum Ali
- Internal Medicine, University of Health Sciences, Lahore, PAK
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23
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Lee GY, Yao C, Hwang SJ, Ma J, Joehanes R, Lee DH, Ellison RC, Moore LL, Liu C, Levy D. Integrative Mendelian randomization reveals the soluble receptor for advanced glycation end products as protective in relation to rheumatoid arthritis. Sci Rep 2023; 13:8002. [PMID: 37198231 PMCID: PMC10192300 DOI: 10.1038/s41598-023-35098-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 05/12/2023] [Indexed: 05/19/2023] Open
Abstract
Rheumatoid arthritis (RA) is a risk factor for atherosclerotic cardiovascular diseases (CVD). Given the critical roles of the immune system and inflammatory signals in the pathogenesis of CVD, we hypothesized that interrogation of CVD-related proteins using integrative genomics might provide new insights into the pathophysiology of RA. We utilized two-sample Mendelian randomization (MR) for causal inference between circulating protein levels and RA by incorporating genetic variants, followed by colocalization to characterize the causal associations. Genetic variants from three sources were obtained: those associated with 71 CVD-related proteins measured in nearly 7000 Framingham Heart Study participants, a published genome-wide association study (GWAS) of RA (19 234 cases, 61 565 controls), and GWAS of rheumatoid factor (RF) levels from the UK Biobank (n = 30 565). We identified the soluble receptor for advanced glycation end products (sRAGE), a critical inflammatory pathway protein, as putatively causal and protective for both RA (odds ratio per 1-standard deviation increment in inverse-rank normalized sRAGE level = 0.364; 95% confidence interval 0.342-0.385; P = 6.40 × 10-241) and RF levels (β [change in RF level per sRAGE increment] = - 1.318; SE = 0.434; P = 0.002). Using an integrative genomic approach, we highlight the AGER/RAGE axis as a putatively causal and promising therapeutic target for RA.
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Affiliation(s)
- Gha Young Lee
- Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
- Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA
| | - Chen Yao
- Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
- Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA
| | - Shih-Jen Hwang
- Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
- Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA
| | - Jiantao Ma
- Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA
- School of Nutrition Science and Policy, Tufts University, Boston, USA
| | - Roby Joehanes
- Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
- Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA
| | - Dong Heon Lee
- Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
- Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA
| | - R Curtis Ellison
- Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA
- Boston University School of Medicine, Boston, MA, USA
| | - Lynn L Moore
- Boston University School of Medicine, Boston, MA, USA
| | - Chunyu Liu
- Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA
- School of Public Health, Boston University, Boston, MA, USA
| | - Daniel Levy
- Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
- Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA.
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24
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Atzeni F, Maiani S, Corda M, Rodríguez-Carrio J. Diagnosis and management of cardiovascular risk in rheumatoid arthritis: main challenges and research agenda. Expert Rev Clin Immunol 2023; 19:279-292. [PMID: 36651086 DOI: 10.1080/1744666x.2023.2170351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
INTRODUCTION Rheumatoid arthritis (RA) exhibit a cardiovascular (CV) risk that is 1.5-2.0 times higher compared to the general population. This CV risk excess is likely caused by the involvement of chronic inflammation and immune dysregulation. Therefore, conventional algorithms and imaging techniques fail to fully account for this risk excess and provide a suboptimal risk stratification, hence limiting clinical management in this setting. AREAS COVERED Compelling evidence has suggested a role for adaptations of conventional algorithms (Framingham, SCORE, AHA, etc) or the development of RA-specific algorithms, as well as the use of a number of several, noninvasive imaging techniques to improve CV risk assessment in RA populations. Similarly, in-depth analyses of atherosclerosis pathogenesis in RA patients have shed new light into a plethora of soluble biomarkers (such as inflammatory cytokines, vascular remodeling mediators or autoantibodies) that may provide incremental value for CV risk stratification. EXPERT OPINION Extensive research has demonstrated a lack of performance of chart adaptations in capturing real CV risk in RA population, as well as for RA-specific algorithms. Similarly, limitations have been detected in the use of soluble mediators. The development of a novel, RA-specific algorithm including classical and non-traditional risk factors may be advisable.
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Affiliation(s)
- Fabiola Atzeni
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, Messina, Italy
| | - Silvia Maiani
- Clinical Cardiology, Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
| | - Marco Corda
- S.C. Cardiologia UTIC, ARNAS, G.Brotzu, Cagliari, Italy
| | - Javier Rodríguez-Carrio
- Area of Immunology, Department of Functional Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.,Area of Metabolism, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
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25
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Association of soluble cell adhesion molecules and lipid levels in rheumatoid arthritis patients. Clin Rheumatol 2023; 42:731-739. [PMID: 36192664 DOI: 10.1007/s10067-022-06395-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 09/07/2022] [Accepted: 09/23/2022] [Indexed: 11/03/2022]
Abstract
OBJECTIVES To evaluate the relationship between soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), and lipid levels in rheumatoid arthritis (RA) patients with and without carotid plaque (CP). METHODS Cross-sectional study nested of a RA cohort. RA patients without a previous cardiovascular event or statins' therapy, aged 40-75 years were recruited at an outpatient cardio-rheumatology clinic. Carotid ultrasound was performed in all study subjects. RA patients with CP were included and matched to RA patients without CP by age, gender, and traditional cardiovascular risk factors. Blood samples were drawn at the time of recruitment to measure sVCAM-1, sICAM-1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lipid levels. Correlations between cell adhesion molecules, disease activity indexes, ESR and CRP with lipid levels were assessed with Spearman's correlation coefficient (rs). RESULTS We included 71 RA patients, 37 with CP and 34 without CP. RA (n = 71) patients had a moderate negative correlation of sVCAM-1 with total cholesterol (TC) (rs = - 0.366, p = 0.002) and low-density lipoprotein (LDL) (rs = - 0.316, p = 0.007), and a small negative correlation with high-density lipoprotein (rs = - 0.250, p = 0.036). ESR showed a small negative correlation with LDL (rs = - 0.247, p = 0.038). Patients with CP had a moderate negative correlation between sVCAM and TC (rs = - 0.405, p = 0.013). Patients without CP showed a moderate negative correlation between sVCAM with TC (rs = - 0.364, p = 0.034) and LDL (rs = - 0.352, p = 0.041), and sICAM with VLDL (rs = - 0.343, p = 0.047). CONCLUSIONS RA patients showed an inverse association of sVCAM-1 and lipid levels. More studies are needed to define the precise role of sVCAM-1 in the lipid paradox of RA.
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Li Z, Wang XQ. Clinical effect and biological mechanism of exercise for rheumatoid arthritis: A mini review. Front Immunol 2023; 13:1089621. [PMID: 36685485 PMCID: PMC9852831 DOI: 10.3389/fimmu.2022.1089621] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 12/16/2022] [Indexed: 01/09/2023] Open
Abstract
Rheumatoid arthritis (RA) is a common systematic, chronic inflammatory, autoimmune, and polyarticular disease, causing a range of clinical manifestations, including joint swelling, redness, pain, stiffness, fatigue, decreased quality of life, progressive disability, cardiovascular problems, and other comorbidities. Strong evidence has shown that exercise is effective for RA treatment in various clinical domains. Exercise training for relatively longer periods (e.g., ≥ 12 weeks) can decrease disease activity of RA. However, the mechanism underlying the effectiveness of exercise in reducing RA disease activity remains unclear. This review first summarizes and highlights the effectiveness of exercise in RA treatment. Then, we integrate current evidence and propose biological mechanisms responsible for the potential effects of exercise on immune cells and immunity, inflammatory response, matrix metalloproteinases, oxidative stress, and epigenetic regulation. However, a large body of evidence was obtained from the non-RA populations. Future studies are needed to further examine the proposed biological mechanisms responsible for the effectiveness of exercise in decreasing disease activity in RA populations. Such knowledge will contribute to the basic science and strengthen the scientific basis of the prescription of exercise therapy for RA in the clinical routine.
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Affiliation(s)
- Zongpan Li
- Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, China
- Department of Sport Rehabilitation Medicine, Shanghai Shangti Orthopaedic Hospital, Shanghai, China
| | - Xue-Qiang Wang
- Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, China
- Department of Sport Rehabilitation Medicine, Shanghai Shangti Orthopaedic Hospital, Shanghai, China
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27
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Efficacy of Siwan Traditional Therapy on Erythrocyte Sedimentation Rate, Lipid Profile, and Atherogenic Index as Cardiac Risk Factors Related to Rheumatoid Arthritis. MEDICINA (KAUNAS, LITHUANIA) 2022; 59:medicina59010054. [PMID: 36676677 PMCID: PMC9861765 DOI: 10.3390/medicina59010054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 12/15/2022] [Accepted: 12/22/2022] [Indexed: 12/29/2022]
Abstract
Background and Objectives: The most frequent cause of mortality in rheumatoid arthritis (RA) patients is cardiovascular disease (CVD). Inflammation, dyslipidemia, and decreased physical activity are some of the main risk factors for CVD. Siwan sand therapy is a type of traditional therapy used in Egypt to treat RA. The approach of this therapy depends on the experience of the healers. The aim of the current study was to compare the effects of three sessions of Siwan traditional therapy to five sessions on common CVD risk factors and physical function in rheumatoid arthritis patients. Materials and Methods: Thirty patients (9 male and 21 female) were assigned into two groups of equal size: group (A) received three sessions of Siwan traditional therapy in the form of a sand bath. Group (B) received the same form of therapy for five days. Erythrocyte sedimentation rate (ESR), lipid profile, atherogenic index of plasma (AIP), and a health assessment questionnaire (HAQ) were measured before and after treatment. Results: There was a significant increase above normal within group (A) for ESR (p = 0.001), triglycerides (TG; p = 0.015), total cholesterol (Tot-Chol; p = 0.0001), and low-density lipoprotein (LDL; p = 0.0001). However, there were no considerable differences in high-density lipoprotein (HDL; p = 0.106), very low-density lipoprotein (VLDL; p = 0.213), AIP (p = 0.648), and HAQ (p = 0.875). For the second group, there were significant changes within group B only in Tot-Chol (p = 0.0001), HDL (p = 0.0001), VLDL (p = 0.0001), AIP (p = 0.008), and HAQ (p = 0.014). There was a significant difference between both groups regarding HDL (p = 0.027), LDL (p = 0.005), AIP (p = 0.029), ESR (p = 0.016), and HAQ (p = 0.036). Conclusions: For RA patients, five days of Siwan traditional therapy caused significant changes regarding inflammation, Tot-Chol, LDL, HDL, AIP, and functional activity when compared to three days of Siwan hot sand therapy.
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28
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Lee EH, Kim H, Koh JH, Cha KH, Lee KK, Kim WU, Pan CH, Lee YH. Dysbiotic but nonpathogenic shift in the fecal mycobiota of patients with rheumatoid arthritis. Gut Microbes 2022; 14:2149020. [PMID: 36472468 PMCID: PMC9728469 DOI: 10.1080/19490976.2022.2149020] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Rheumatoid arthritis (RA) is closely associated with the oral and gut microbiomes. Fungal cell wall components initiate inflammatory arthritis in mouse models. However, little is known regarding the role of the fungal community in the pathogenesis of RA. To evaluate the association between RA and the gut microbiome, investigations of bacterial and fungal communities in patients with RA are necessary. Therefore, we investigated the compositions and associations of fecal bacterial and fungal communities in 30 healthy controls and 99 patients with RA. The relative abundances of Bifidobacterium and Blautia decreased, whereas the relative abundance of Streptococcus increased, in patients with RA. The relative abundance of Candida in the fecal fungal community was higher in patients with RA than in healthy controls, while the relative abundance of Aspergillus was higher in healthy controls than in patients with RA. Candida species-specific gene amplification showed that C. albicans was the most abundant species of Candida. Ordination analysis and random forest classification models supported the findings of structural changes in bacterial and fungal communities. Aspergillus was the core fecal fungal genus in healthy controls, although Saccharomyces spp. are typically predominant in Western cohorts. In addition, bacterial-fungal association analyses showed that the hub node had shifted from fungi to bacteria in patients with RA. The finding of fungal dysbiosis in patients with RA suggests that fungi play critical roles in the fecal microbial communities and pathogenesis of RA.
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Affiliation(s)
- Eun Ha Lee
- Natural Product Informatics Research Center, KIST Gangneung Institute of Natural Products, Gangneung, Korea,Interdisciplinary Program in Agricultural Genomics, Seoul National University, Seoul, Korea
| | - Hyun Kim
- Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea
| | - Jung Hee Koh
- Division of Rheumatology, Department of Internal Medicine, College of Medicine, the Catholic University of Korea, Seoul, Korea,Center for Integrative Rheumatoid Transcriptomics and Dynamics, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea
| | - Kwang Hyun Cha
- Natural Product Informatics Research Center, KIST Gangneung Institute of Natural Products, Gangneung, Korea
| | - Kiseok Keith Lee
- Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea
| | - Wan-Uk Kim
- Division of Rheumatology, Department of Internal Medicine, College of Medicine, the Catholic University of Korea, Seoul, Korea,Center for Integrative Rheumatoid Transcriptomics and Dynamics, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea,CONTACT Wan-Uk Kim Division of Rheumatology, Department of Internal Medicine, College of Medicine, the Catholic University of Korea, Seoul, Korea; Cheol-Ho Pan Natural Product Informatics Research Center, KIST Gangneung Institute of Natural Products, Gangneung, Korea; Yong-Hwan Lee Interdisciplinary Program in Agricultural Genomics, Seoul National University, Seoul, Korea
| | - Cheol-Ho Pan
- Natural Product Informatics Research Center, KIST Gangneung Institute of Natural Products, Gangneung, Korea
| | - Yong-Hwan Lee
- Interdisciplinary Program in Agricultural Genomics, Seoul National University, Seoul, Korea,Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea,Center for Plant Microbiome Research, Seoul National University, Seoul, Korea,Plant Immunity Research Center, Seoul National University, Seoul, Korea,Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Korea
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Kang S, Han K, Jung JH, Eun Y, Kim IY, Hwang J, Koh EM, Lee S, Cha HS, Kim H, Lee J. Associations between Cardiovascular Outcomes and Rheumatoid Arthritis: A Nationwide Population-Based Cohort Study. J Clin Med 2022; 11:jcm11226812. [PMID: 36431290 PMCID: PMC9695475 DOI: 10.3390/jcm11226812] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/10/2022] [Accepted: 11/12/2022] [Indexed: 11/19/2022] Open
Abstract
Despite a growing burden posed by cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients, large-scale studies on the association between the characteristics of RA patients and CVD risks and studies adjusted for various confounding factors are lacking. In this large-scale nationwide cohort study, we aimed to investigate the association between CVD risk and RA and factors that may increase CVD risk using a dataset provided by the Korean National Health Insurance Service (NHIS). We enrolled 136,469 patients with RA who participated in national health examinations within two years of RA diagnosis between 2010 and 2017 and non-RA controls matched by age and sex (n = 682,345). The outcome was the occurrence of myocardial infarction (MI) or stroke. MI was defined as one hospitalization or two outpatient visits with ICD-10-CM codes I21 or I22. Stroke was defined as one hospitalization with ICD-10-CM codes I63 or I64 and a claim for brain imaging (CT or MRI). The Cox proportional hazard model and Kaplan-Meier curve were used for analysis. The mean follow-up duration was 4.7 years, and the incidence rate of CVD was higher in the RA group than the control group (MI: 3.20 vs. 2.08; stroke: 2.84 vs. 2.33 per 1000 person-years). The risk of MI and stroke was about 50% and 20% higher, respectively, in RA patients. The association between RA and CVD was prominent in females after adjusting for confounding variables. The association between RA and risk of MI was significant in individuals without DM. Therefore, appropriate screening for CVD is important in all RA patients including females and younger patients.
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Affiliation(s)
- Seonyoung Kang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul 06978, Republic of Korea
| | - Jin-Hyung Jung
- Department of Medical Statistics, College of Medicine, Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Yeonghee Eun
- Division of Rheumatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea
| | - In Young Kim
- Department of Medicine, National Police Hospital, Seoul 05715, Republic of Korea
| | - Jiwon Hwang
- Division of Rheumatology, Department of Internal Medicine, Sungkyunkwan University Samsung Changwon Hospital, Changwon 51353, Republic of Korea
| | - Eun-Mi Koh
- Korean Health Insurance Review and Assessment Service, Seoul 06653, Republic of Korea
| | - Seulkee Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
| | - Hoon-Suk Cha
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
| | - Hyungjin Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
- Department of Medical Humanities, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
- Correspondence: (H.K.); (J.L.); Tel.: +82-2-3410-1879 (H.K.); +82-2-3410-3439 (J.L.); Fax: +82-2-3410-6983 (H.K.); +82-2-3410-0231 (J.L.)
| | - Jaejoon Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
- Correspondence: (H.K.); (J.L.); Tel.: +82-2-3410-1879 (H.K.); +82-2-3410-3439 (J.L.); Fax: +82-2-3410-6983 (H.K.); +82-2-3410-0231 (J.L.)
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Ngo ATP, Gollomp K. Building a better
NET
: Neutrophil extracellular trap targeted therapeutics in the treatment of infectious and inflammatory disorders. Res Pract Thromb Haemost 2022. [DOI: 10.1002/rth2.12808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Affiliation(s)
- Anh T. P. Ngo
- Division of Hematology Children's Hospital of Philadelphia Philadelphia Pennsylvania USA
| | - Kandace Gollomp
- Division of Hematology Children's Hospital of Philadelphia Philadelphia Pennsylvania USA
- Department of Pediatrics, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA
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31
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Jain K, Laila D, Nandagudi A, Bharadwaj A. Long-term outcomes in Rheumatoid Arthritis: Review of data from the ‘Basildon Inflammatory Arthritis Cohort’. Rheumatol Adv Pract 2022; 6:rkac075. [PMID: 36176320 PMCID: PMC9514795 DOI: 10.1093/rap/rkac075] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 08/17/2022] [Indexed: 11/24/2022] Open
Abstract
Objective The aim was to determine outcomes in RA with long-term analysis of a real-world inception cohort. Methods We carried out a retrospective cohort analysis of 184 patients with a new diagnosis of RA (ACR/EULAR 2010 criteria) between 2009 and 2013. Measured parameters included patient demographics, serological markers, disease activity (DAS28-CRP), treatment regimen, development of new co-morbidities and all-cause mortality. Results Complete data were available for analysis in 171 patients, 60 men and 111 women, with a median age of 57 years and median follow-up time of 7.5 years. DAS-28 remission was achieved in 73%, with the majority continuing to require pharmacological therapy. Drug-free remission was achieved in 11.7%, whereas 3.5% remained refractory to treatment. Analysis of new co-morbidities revealed malignancy in 12.9% (n = 22), with lung cancer having the highest incidence (n = 9). Cardiovascular, pulmonary and cerebrovascular disease developed in 11.1% (n = 19), 5.8% (n = 10) and 5.3% (n = 9), respectively. The crude mortality rate was 19.3% (33 of 171), incidence mortality rate 174 per 10 000 person-years of follow-up and standardized mortality ratio 1.57 (95% CI 1.10, 2.17). More deaths were recorded from underlying malignancy [7.6% (n = 13)] than with cardiovascular disease [4.7% (n = 8)]. The majority of deaths occurred ≥5 years after initial diagnosis (67%). Conclusion Long-term analysis reveals that mortality in RA remains significantly elevated compared with the general population. Additionally, this real-world study underlines malignancy as the predominant cause of morbidity and mortality in RA.
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Affiliation(s)
- Kanishk Jain
- Department of Rheumatology, Mid & South Essex Foundation Trust, Basildon University Hospital , Basildon, UK
| | - Deena Laila
- Department of Rheumatology, Mid & South Essex Foundation Trust, Basildon University Hospital , Basildon, UK
| | - Anupama Nandagudi
- Department of Rheumatology, Mid & South Essex Foundation Trust, Basildon University Hospital , Basildon, UK
| | - Anurag Bharadwaj
- Department of Rheumatology, Mid & South Essex Foundation Trust, Basildon University Hospital , Basildon, UK
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Suwal A, Shrestha B, Setyono D, Poudel B, Donato A. Outcomes of the First Episode of STEMI in Rheumatoid Arthritis Patients from the National Inpatient Sample Database, 2016-2019. Curr Probl Cardiol 2022; 47:101310. [PMID: 35810846 DOI: 10.1016/j.cpcardiol.2022.101310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 07/01/2022] [Indexed: 12/06/2022]
Abstract
BACKGROUND Patients with Rheumatoid arthritis (RA) have a higher burden of cardiovascular diseases (CVDs), but conflicting results were seen regarding in-hospital outcomes of STEMI in patients with RA compared to patients without RA. OBJECTIVES To compare in-hospital outcomes of the first episode of STEMI between patients with and without RA. METHODS The NIS database was used to conduct a retrospective study of U.S. hospitalizations with a primary diagnosis of first-time STEMI from 2016 to 2019. We divided our study population into two cohorts, with diagnosis codes for RA and those without RA and compared baseline demographics, comorbidities, and in-hospital outcomes and finally performed a multivariate logistic regression analysis after adjusting for baseline factors. RESULTS Our analysis revealed that patients with RA were statistically more likely to be older, white, and female and had more hypertension, cardiomyopathy, CKD stage 3 or greater and heart failure. However, after adjusting for potential confounders, we found lower inpatient mortality in the first STEMI with RA cohort (adjusted OR: 0.70, 95% CI of 0.56-0.87, p <0.002) compared to the patients without RA. However, there was no statistically significant difference between the two groups in rates of in-hospital complications, including repeat MI, acute heart failure, arrhythmias, cardiac arrest, cardiogenic shock, and stroke. CONCLUSION In this study, patients with RA with first STEMI had lower inpatient mortality than those without RA. However, further patient-level studies are needed to understand better the impact of newer biologics and the effect of risk factor modification on this patient subset.
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Affiliation(s)
- Amar Suwal
- Department of Medicine, Reading Hospital, Tower Health, Reading, PA.
| | - Biraj Shrestha
- Department of Medicine, Reading Hospital, Tower Health, Reading, PA
| | | | - Bidhya Poudel
- Department of Medicine, AMITA Health Saint Francis Hospital, Evanston, IL, United States of America
| | - Anthony Donato
- Department of Medicine, Reading Hospital, Tower Health, Reading, PA
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Sewell J, Hussain SM, Wang Y, Wluka AE, Lim YZ, Carrington MJ, Samaras K, Cicuttini FM. Association between arthritis and cardiovascular risk factors in community-based adults: an opportunity to target cardiovascular risk. BMC Cardiovasc Disord 2022; 22:232. [PMID: 35590252 PMCID: PMC9118727 DOI: 10.1186/s12872-022-02674-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 05/13/2022] [Indexed: 11/12/2022] Open
Abstract
Background Undertreated risk factors are major contributors to the burden of cardiovascular disease (CVD). Those with arthritis have an increased prevalence of CVD risk factors. CVD risk factors are often asymptomatic, which may be a barrier their treatment. Arthritis causes pain and immobility, and is a common reason for individuals to seek healthcare. Our aims were to (1) examine the relationship between arthritis and CVD risk factors in Australian adults, and (2) calculate the proportion of CVD risk factors that could be reduced if individuals with arthritis were targeted.
Methods This cross-sectional study uses data from the 2017–18 Australian National Health Survey which included 13,776 participants, categorised into young (18–39 years), middle aged (40–64 years) and older (≥ 65 years) adults. Hypertension, height and weight were measured. Arthritis, dyslipidemia and diabetes were self-reported. The associations between arthritis and CVD risk factors were examined using logistic regression, and the population attributable fraction (PAF) of arthritis for each CVD risk factor was calculated. Results Arthritis was reported by 4.0% of young adults, 28.8% of middle-aged adults and 54.5% of older adults. Those with arthritis were at increased odds of obesity (2.07 fold in young, 1.75 fold in middle-aged and 1.89 fold in older adults), increased odds of diabetes (5.70 fold in young, 1.64 fold in middle-aged and 1.37 fold in older adults), increased odds of hypertension (2.72 fold in young, 1.78 fold in middle-aged and 1.48 fold in older adults) and an increased odds of dyslipidaemia (4.64 fold in young, 2.14 fold in middle-aged and 1.22 fold in older adults) compared to those without arthritis. This elevated chance remained significant even after adjusting for obesity, with the exception of diabetes in the older population. This elevated chance remained significant even after adjusting for obesity, with the exception of diabetes in the older population. The PAF of the presence of arthritis for having at least one CVD risk factor was 30.7% in middle-aged adults and 70.4% in older adults. Conclusion Australian adults of all ages with arthritis are at increased odds of having CVD risk factors. For young and middle-aged adults, this increased odds remains significant even when adjusted for obesity. Presentation to healthcare practitioners with arthritis is an opportunity to screen for asymptomatic CVD risk factors with the potential of improving outcomes for both diseases. By adopting an approach of managing arthritis and CVD risk factors in parallel, rather than in silos, we could reduce the burden of CVD risk factors by 20–30%.
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Affiliation(s)
- Julia Sewell
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC, 3004, Australia
| | - Sultana Monira Hussain
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC, 3004, Australia
| | - Yuanyuan Wang
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC, 3004, Australia
| | - Anita E Wluka
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC, 3004, Australia
| | - Yuan Z Lim
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC, 3004, Australia
| | - Melinda J Carrington
- Pre-Clinical Disease and Prevention, Baker Heart and Diabetes Institute, 75 Commercial Rd, Melbourne, VIC, 3004, Australia
| | - Katherine Samaras
- Clinical Obesity, Nutrition and Adipose Biology Laboratory, Healthy Ageing, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, NSW, 2010, Australia.,Department of Endocrinology, St Vincent's Hospital, Victoria St, Darlinghurst, NSW, 2010, Australia.,St Vincent's Clinnical School, University of New South Wales Sydney, Victoria St, Darlinghurst, NSW, 2010, Australia
| | - Flavia M Cicuttini
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC, 3004, Australia.
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Low-Density Lipoprotein Cholesterol and the Risk of Rheumatoid Arthritis: A Prospective Study in a Chinese Cohort. Nutrients 2022; 14:nu14061240. [PMID: 35334896 PMCID: PMC8954206 DOI: 10.3390/nu14061240] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 02/28/2022] [Accepted: 03/08/2022] [Indexed: 11/17/2022] Open
Abstract
Objective: This study aimed to investigate whether low-density lipoprotein cholesterol (LDL-C) concentration was associated with the risk of rheumatoid arthritis (RA) in Chinese adults. Methods: The study included the 97,411 participants in the Kailuan Study without RA, with complete baseline LDL-C data, and who did not use lipid-lowering medications at baseline or during follow-up. We used Cox proportional hazards modeling to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of RA according to baseline LDL-C tertiles, adjusting for age, sex, body mass index, HDL-C, triglycerides, diabetes, hypertension, alcohol consumption, and smoking. We also calculated the HR and 95% CI of RA using updated LDL-C measurements prior to the end of follow-up, adjusting for covariates. Results: We identified 97 incident RA cases between 2006 and 2018. After adjusting for potential confounders, updated LDL-C concentration—rather than baseline LDL-C—was inversely associated with RA risk. The adjusted HR of RA was 0.64 (95% CI: 0.38, 1.09; p-trend = 0.10) comparing the two extreme baseline LDL-C tertiles, and 0.38 (95% CI: 0.22, 0.64; p-trend < 0.01) comparing the two extreme tertiles of the updated LDL-C concentrations. Conclusions: In this prospective study, high LDL-C concentrations, when measured closest to RA diagnosis or the end of follow-up, were associated with a low risk of RA. These findings highlight the changes in LDL-C prior to RA diagnosis, and the importance of including lipid analyses into studies of the pathogenesis of RA.
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35
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The association between rheumatoid arthritis and cardiovascular disease among adults in the United States during 1999-2018, and age-related effect modification in relative and absolute scales. Ann Epidemiol 2022; 71:23-30. [PMID: 35301105 DOI: 10.1016/j.annepidem.2022.03.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 03/03/2022] [Accepted: 03/09/2022] [Indexed: 11/21/2022]
Abstract
PURPOSE To explore the rheumatoid arthritis (RA)-cardiovascular diseases (CVD) association in relative and absolute risk scales among US adults aged ≥20 years over time and the effect modification of the association by age. METHODS We analyzed aggregated data from all ten continuous National Health and Nutrition Examination Survey cycles. A sample of 43,184 complete-case subjects was considered. The design-based regressions were used to investigate the associations in relative and absolute scales. RESULTS In relative scale, the CVD odds ratio was 2.32, 2.19, and 1.97 among adults with RA than no arthritis in 1999-2006, 2007-2012, and 2013-2018 cycles, respectively. This time trend was not statistically significant. The absolute risk estimates were 11, 10, and 9 per 100 CVD events. We also observed a significant effect modification by age; the higher relative risk among younger adults (<50 years) with RA and higher absolute risk in older adults (≥80 years) with RA were consistent across survey cycles. CONCLUSIONS There is a significant association between RA and CVD among US adults in both relative and absolute risks. Moreover, age is a significant effect modifier for this association; but with opposing age-related trends in relative and absolute scales.
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36
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Alsing CL, Nystad TW, Igland J, Gjesdal CG, Midtbø H, Tell GS, Fevang BT. Trends in the occurrence of ischaemic heart disease over time in rheumatoid arthritis: 1821 patients from 1972 to 2017. Scand J Rheumatol 2022; 52:233-242. [PMID: 35272584 DOI: 10.1080/03009742.2022.2040116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
OBJECTIVE To evaluate trends of acute myocardial infarction (AMI) and ischaemic heart disease (IHD) in rheumatoid arthritis (RA) patients compared with the general population over time. METHOD We performed a retrospective cohort study of 1821 RA patients diagnosed from 1972 to 2013. Aggregated counts of the total population of the same county (Hordaland, Norway) and period were used for comparison. Information on AMI and IHD events was obtained from hospital patient administrative systems or cardiovascular registries. We estimated incidence rates and excess of events [standardized event ratio (SER) with 95% confidence interval (CI)] compared with the general population by Poisson regression. RESULTS There was an average annual decline of 1.6% in age- and gender-adjusted AMI incidence rates from 1972 to 2017 (p < 0.035). The difference in events (excess events) in RA patients compared with the general population declined on average by 1.3% per year for AMI and by 2.3% for IHD from 1972 to 2014. There were no significant excess AMI (SER 1.05, 95% CI 0.82-1.35) or IHD events (SER 1.02, 95% CI 0.89-1.16) for RA patients diagnosed after 1998 compared with the general population. CONCLUSION Incidence rates and excess events of AMI and IHD in RA patients declined from 1972 to 2017. There were no excess AMI or IHD events in RA patients diagnosed after 1998 compared with the general population.
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Affiliation(s)
- C L Alsing
- Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.,Department of Clinical Science, University of Bergen, Bergen, Norway
| | - T W Nystad
- Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
| | - J Igland
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.,Department of Health and Social Science, Centre for Evidence-Based Practice, Western Norway University of Applied Science, Bergen, Norway
| | - C G Gjesdal
- Department of Clinical Science, University of Bergen, Bergen, Norway.,Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
| | - H Midtbø
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
| | - G S Tell
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.,Division of Mental and Physical Health, Norwegian Institute of Public Health, Bergen, Norway
| | - B T Fevang
- Department of Clinical Science, University of Bergen, Bergen, Norway.,Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
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Heluany CS, Scharf P, Schneider AH, Donate PB, Dos Reis Pedreira Filho W, de Oliveira TF, Cunha FQ, Farsky SHP. Toxic mechanisms of cigarette smoke and heat-not-burn tobacco vapor inhalation on rheumatoid arthritis. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 809:151097. [PMID: 34695477 DOI: 10.1016/j.scitotenv.2021.151097] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 09/24/2021] [Accepted: 10/16/2021] [Indexed: 06/13/2023]
Abstract
Tobacco combustion exposure worsens rheumatoid arthritis (RA). Non-combustible tobacco devices, as heat-not-burn tobacco (HNBT), are emerging as harm reduction to smokers by releasing nicotine and lower combustible tobacco products. Nevertheless, HNBT toxicity remains unclear. Hence, here we investigated the impacts of the tobacco combustible product (cigarette smoke; CS) or HNBT vapor exposures on antigen-induced arthritis (AIA) in C57BL/6 mice. Animals were exposed to airflow, HNBT vapor, or CS during 1 h/twice a day, under the Health Canada Intense (HCI) smoking regime, between days 14 to 20 after the first immunization. At day 21, 16 h after the last exposures, mice were i.a. challenged and the AIA effects were evaluated 24 h later. CS- or HNBT-exposed mice presented equivalent blood nicotine levels. CS exposure worsened articular symptoms, pulmonary inflammation, and expression of lung metallothioneins. Nevertheless, CS or HNBT exposures reduced lymphoid organs' cellularity, splenocyte proliferation and IL-2 secretion. Additional in vitro CS or HNBT exposures confirmed the harmful effects on splenocytes, which were partially mediated by the activation of nicotine/α7nAchR pathway. Associated, data demonstrate the toxic mechanisms of CS or HNBT inhalation at HCI regime on RA, and highlight that further investigations are fundamental to assure the toxicity of emerging tobacco products on the immune system during specific challenges.
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Affiliation(s)
- Cintia Scucuglia Heluany
- Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, SP, Brazil
| | - Pablo Scharf
- Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, SP, Brazil
| | | | - Paula Barbim Donate
- Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil
| | | | - Tiago Franco de Oliveira
- Department of Pharmacosciences, Federal University of Health Sciences of Porto Alegre, Porto Alegre, RS, Brazil
| | - Fernando Queiroz Cunha
- Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil
| | - Sandra Helena Poliselli Farsky
- Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, SP, Brazil.
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Chen X, Wang K, Lu T, Wang J, Zhou T, Tian J, Zhou B, Long L, Zhou Q. Adiponectin is negatively associated with disease activity and Sharp score in treatment-naïve Han Chinese rheumatoid arthritis patients. Sci Rep 2022; 12:2092. [PMID: 35136158 PMCID: PMC8826401 DOI: 10.1038/s41598-022-06115-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 01/25/2022] [Indexed: 12/26/2022] Open
Abstract
The association and potential role of the protein hormone adiponectin in autoimmune diseases causing musculoskeletal disorders, including rheumatoid arthritis (RA), are controversial. Conflicting results may arise from the influences of confounding factors linked to genetic backgrounds, disease stage, disease-modifying anti-rheumatic drugs and patients' metabolic characteristics. Here, we examined serum level of adiponectin and its relationship with disease activity score 28 with erythrocytes sedimentation rate (DAS28[ESR]) and Sharp score in a treatment-naïve Han Chinese RA population. This cross-sectional study enrolled 125 RA patients. Serum level of total adiponectin was assessed by enzyme-linked immunosorbent assay (ELISA). Other important clinical and laboratory parameters were collected from the hospital database. DAS28(ESR) was calculated according to the equation previously published. Sharp score was evaluated based on hands radiographs by an independent radiologist. The correlation between serum adiponectin level and DAS28(ESR) or the Sharp score was investigated by univariate and multivariable linear regression analyses, respectively. Multiple imputation by chained equations was used to account for missing data. Univariate analyses showed a significant positive correlation between DAS28(ESR) and age or C-reactive protein (CRP) (both p = 0.003), while serum adiponectin level was negatively correlated with DAS28(ESR) (p = 0.015). The negative correlation between adiponectin level and DAS28(ESR) remained true in multivariable analyses adjusted for confounders. In addition, the univariate analyses revealed positive correlations of Sharp score to disease duration (p < 0.001), CRP (p = 0.023) and ESR (p < 0.001). In the multivariable model adjusted for confounders, adiponectin was negatively correlated with Sharp score (p = 0.013). In this single-institution cross-sectional study, serum adiponectin level in treatment-naive RA patients is negatively correlated with DAS28(ESR) and the Sharp score after adjustment for prominent identified confounders. Serum adiponectin may be potentially useful for assessing disease activity and radiographic progression of RA.
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Affiliation(s)
- Xixi Chen
- Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Kaiwen Wang
- School of Medicine, The University of Leeds, Leeds, UK
| | - Tao Lu
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
- Department of Radiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Jiajia Wang
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
- Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Ting Zhou
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
- Department of Geriatrics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Juan Tian
- The First People's Hospital of Tianmen City, Tianmen, Hubei, China
| | - Bin Zhou
- Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Li Long
- Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China.
| | - Qiao Zhou
- Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China.
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Almalki ZS, AlOmari BA, Alshammari T, Alshlowi A, Khan MF, Hazazi A, Alruwaily M, Alsubaie S, Alanazi F, Aldossary N, Albahkali R. Uncontrolled blood pressure among hypertensive adults with rheumatoid arthritis in Saudi Arabia: A cross-sectional study. Medicine (Baltimore) 2022; 101:e28763. [PMID: 35089255 PMCID: PMC8797535 DOI: 10.1097/md.0000000000028763] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Revised: 11/04/2021] [Accepted: 01/15/2022] [Indexed: 01/05/2023] Open
Abstract
ABSTRACT Despite the availability and advancement of diagnostic and treatments with demonstrated benefits in minimizing cardiovascular morbidity and mortality, hypertension control rates remain suboptimal. Therefore, this research aimed to determine the prevalence of uncontrolled BP in rheumatoid arthritis (RA) patients and understand all potential risk factors for uncontrolled BP.We conducted a cross-sectional study on RA patients in 2 rheumatology clinics in 2 public hospitals in Riyadh. Patients' information such as demographics, comorbidities, drug use, and other clinical data were captured through a review of medical records and supplemented by patient interviews. Multivariate logistic regression was utilized for the analysis to identify the significant factors of uncontrolled BP (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg).In total, 834 subjects with RA and concomitant BP were involved in this cross-sectional study. The prevalence of uncontrolled BP was found to be 31.65% among all the study population. Multivariate analysis showed that males, subjects above 60 years of age, and smokers had a distinctly higher occurrence of uncontrolled BP. Among the patients with comorbid conditions, those with obesity, hyperlipidemia, diabetes, anemia, cancer, and reflex or gastroesophageal reflux disease also showed a significantly higher risk of uncontrolled BP (P < .05).The rate of uncontrolled BP was found to be alarmingly high in the study population. Age, gender, smoking, diabetes, obesity, hyperlipidemia, cancer, gastroesophageal reflux disease, and osteoporosis are independently linked with lack of BP control.
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Affiliation(s)
- Ziyad S. Almalki
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Riyadh, Saudi Arabia
| | - Bedor Abdullah AlOmari
- Internal Medicine and Rheumatology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | | | - Areej Alshlowi
- Clinical Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia
| | - Mohd Faiyaz Khan
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Riyadh, Saudi Arabia
| | - Ali Hazazi
- College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Riyadh, Saudi Arabia
| | - Maha Alruwaily
- Clinical Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia
| | - Sarah Alsubaie
- Clinical Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia
| | - Faten Alanazi
- Clinical Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia
| | - Norah Aldossary
- Clinical Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia
| | - Raseel Albahkali
- Clinical Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia
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Lai ECC, Huang YC, Liao TC, Weng MY. Premature coronary artery disease in patients with immune-mediated inflammatory disease: a population-based study. RMD Open 2022; 8:rmdopen-2021-001993. [PMID: 35064093 PMCID: PMC8785203 DOI: 10.1136/rmdopen-2021-001993] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 12/23/2021] [Indexed: 12/22/2022] Open
Abstract
Background The associations between premature atherosclerosis and immune-mediated inflammatory diseases (IMIDs) are not fully investigated. To determine whether IMIDs are associated with premature atherosclerosis, we examined the risk of incident coronary artery disease (CAD) in men less than 45 years old and women less than 50 years old with various forms of IMIDs compared with general population. Methods A population-based cohort was established and included patients with IMID, who were followed until the development of CAD, withdrawal from the insurance system, death, or 31 December 2016, whichever point came first. Patients with IMID included rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjogren’s syndrome (SjS), idiopathic inflammatory myositis, systemic sclerosis (SSc), Behcet’s disease (BD), and systemic vasculitis (SV). The comparison group was 1 000 000 beneficiaries sampled at random from the whole population as matched control participants. The Kaplan-Meier method was used to compare the cumulative incidences of CAD in patients with and without IMID. Results Among 58 862 patients with IMID, 2139 (3.6%) developed CAD and 346 (1.3%) developed premature CAD. Relative to the comparison cohorts, the adjusted HRs for premature CAD were 1.43 (95% CI 1.09 to 1.86) for primary SjS, 2.85 (95% CI 2.63 to 3.43) for SLE, 3.18 (95% CI 1.99 to 5.09) for SSc and 2.27 (95% CI 1.01 to 5.07) for SV. Conclusions Primary Sjogren’s syndrome, SLE, SSc and SV are associated with an increased risk of premature CAD. Our findings will support essential efforts to improve awareness of IMID impacting young adults.
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Affiliation(s)
- Edward Chia-Cheng Lai
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ya-Chun Huang
- Department of Internal Medicine, Division of Allergy, Immunology, and Rheumatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Tzu-Chi Liao
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Meng-Yu Weng
- Department of Internal Medicine, Division of Allergy, Immunology, and Rheumatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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The role of neutrophils in rheumatic disease-associated vascular inflammation. Nat Rev Rheumatol 2022; 18:158-170. [PMID: 35039664 DOI: 10.1038/s41584-021-00738-4] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/10/2021] [Indexed: 12/13/2022]
Abstract
Vascular pathologies underpin and intertwine autoimmune rheumatic diseases and cardiovascular conditions, and atherosclerosis is increasingly recognized as the leading cause of morbidity in conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis and antineutrophil cytoplasmic antibody-associated vasculitis. Neutrophils, important cells in the innate immune system, exert their functional effects in tissues via a variety of mechanisms, including the generation of neutrophil extracellular traps and the production of reactive oxygen species. Neutrophils have been implicated in the pathogenesis of several rheumatic diseases, and can also intimately interact with the vascular system, either through modulating endothelial barriers at the blood-vessel interface, or through associations with platelets. Emerging data suggest that neutrophils also have an important role maintaining homeostasis in individual organs and can protect the vascular system. Furthermore, studies using high-dimensional omics technologies have advanced our understanding of neutrophil diversity, and immature neutrophils are receiving new attention in rheumatic diseases including SLE and systemic vasculitis. Developments in genomic, imaging and organoid technologies are beginning to enable more in-depth investigations into the pathophysiology of vascular inflammation in rheumatic diseases, making now a good time to re-examine the full scope of roles of neutrophils in these processes.
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Edigin E, Ojemolon PE, Eseaton PO, Shaka H, Akuna E, Asemota IR, Manadan A. Rheumatoid Arthritis Patients Have Better Outcomes Than Non-Rheumatoid Arthritis Patients When Hospitalized for Ischemic Stroke: Analysis of the National Inpatient Sample. J Clin Rheumatol 2022; 28:e13-e17. [PMID: 32925445 DOI: 10.1097/rhu.0000000000001563] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVES The aims of this study were to compare the outcomes of patients primarily admitted for ischemic stroke with and without a secondary diagnosis of RA. METHODS Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 database. The NIS was searched for hospitalizations for adult patients with ischemic stroke as principal diagnosis with and without RA as secondary diagnosis using International Classification of Diseases, 10th Revision codes. The primary outcome was inpatient mortality. Hospital length of stay (LOS), total hospital charges, odds of receiving tissue plasminogen activator, and mechanical thrombectomy were secondary outcomes of interest. Multivariate logistic and linear regression analyses were used accordingly to adjust for confounders. RESULTS There were more than 71 million discharges included in the combined 2016 and 2017 NIS database. Of 525,570 patients with ischemic stroke, 8670 (1.7%) had RA. Hospitalizations for ischemic stroke with RA had less inpatient mortality (4.7% vs. 5.5%; adjusted odds ratio, 0.66; 95% confidence interval, 0.52-0.85; p = 0.001), shorter LOS (5.1 vs 5.7 days, p < 0.0001), lower mean total hospital charges ($61,626 vs. $70,345, p < 0.0001), and less odds of undergoing mechanical thrombectomy (3.9% vs. 5.1%; adjusted odds ratio, 0.55; 95% confidence interval, 0.42-0.72; p < 0.0001) compared with those without RA. CONCLUSIONS Hospitalizations for ischemic stroke with RA had less inpatient mortality, shorter LOS, lower total hospital charges, and less likelihood of undergoing mechanical thrombectomy compared with those without RA. However, the odds of receiving tissue plasminogen activator were similar between both groups. Further studies to understand its mechanism would be helpful.
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Affiliation(s)
- Ehizogie Edigin
- From the Department of Internal Medicine, John H Stroger Jr. Hospital of Cook County, Chicago IL
| | | | | | - Hafeez Shaka
- From the Department of Internal Medicine, John H Stroger Jr. Hospital of Cook County, Chicago IL
| | - Emmanuel Akuna
- From the Department of Internal Medicine, John H Stroger Jr. Hospital of Cook County, Chicago IL
| | | | - Augustine Manadan
- Division of Rheumatology, Rush University Medical Center, Chicago IL
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Malmberg M, Palomäki A, Sipilä JOT, Rautava P, Gunn J, Kytö V. Long-term outcomes after coronary artery bypass surgery in patients with rheumatoid arthritis. Ann Med 2021; 53:1512-1519. [PMID: 34461789 PMCID: PMC8409967 DOI: 10.1080/07853890.2021.1969591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 08/12/2021] [Indexed: 11/30/2022] Open
Abstract
OBJECTIVE To investigate the long-term outcomes of coronary artery bypass grafting surgery (CABG) in patients with rheumatoid arthritis (RA). METHODS Patients with RA (n = 378) were retrospectively compared to patients without RA (n = 7560), all treated with CABG in a multicentre, population-based cohort register study in Finland. The outcomes were studied with propensity score-matching adjustment for baseline features. The median follow-up was 9.7 years. RESULTS Diagnosis of RA was associated with an increased risk of mortality after CABG compared to patients without RA (HR 1.50; CI 1.28-1.77; p < .0001). In addition, patients with RA were in higher risk of myocardial infarction during the follow-up period (HR 1.61; CI 1.28-2.04; p < .0001). Cumulative rate of repeated revascularization after CABG was 14.4% in RA patients and 12.0% in control patients (p = .060). Duration of RA before CABG (p = .011) and preoperative corticosteroid usage in RA (p = .041) were independently associated with higher mortality after CABG. There were no differences between the study groups in 30-d mortality or in the post-operative usage of cardiovascular medications. CONCLUSIONS RA is independently associated with worse prognosis in coronary artery disease treated with CABG. Preoperative corticosteroid use and longer RA disease duration are additional risk factors for mortality.Key messagesPatients with rheumatoid arthritis (RA) have impaired long-term outcomes after coronary artery bypass surgery (CABG).Glucocorticoid use before CABG and duration of RA are associated with higher mortality.Special attention should be paid in secondary prevention of cardiovascular disease in RA patients after CABG.
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Affiliation(s)
- Markus Malmberg
- Heart Center, Turku University Hospital and University of Turku, Turku, Finland
| | - Antti Palomäki
- Centre of Rheumatology and Clinical Immunology, Division of Medicine, Turku University Hospital, Turku, Finland
- Department of Medicine, University of Turku, Turku, Finland
- Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland
| | - Jussi O. T. Sipilä
- Department of Neurology, North Karelia Central Hospital, Siun Sote, Joensuu, Finland
- Clinical Neurosciences, University of Turku, Turku, Finland
| | - Päivi Rautava
- Department of Public Health, University of Turku, Turku, Finland
- Turku Clinical Research Centre, Turku University Hospital, Turku, Finland
| | - Jarmo Gunn
- Heart Center, Turku University Hospital and University of Turku, Turku, Finland
| | - Ville Kytö
- Heart Center, Turku University Hospital and University of Turku, Turku, Finland
- Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
- Center for Population Health Research, Turku University Hospital and University of Turku, Turku, Finland
- Administrative Center, Hospital District of Southwest Finland, Turku, Finland
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Argnani L, Zanetti A, Carrara G, Silvagni E, Guerrini G, Zambon A, Scirè CA. Rheumatoid Arthritis and Cardiovascular Risk: Retrospective Matched-Cohort Analysis Based on the RECORD Study of the Italian Society for Rheumatology. Front Med (Lausanne) 2021; 8:745601. [PMID: 34676228 PMCID: PMC8523847 DOI: 10.3389/fmed.2021.745601] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 09/06/2021] [Indexed: 12/28/2022] Open
Abstract
Background: Rheumatoid arthritis (RA) is associated with an increase in cardiovascular (CV) risk. This issue maybe not only explained by a genetic component, as well as by the traditional CV risk factors, but also by an underestimation and undertreatment of concomitant CV comorbidities. Method: This was a retrospective matched-cohort analysis in the Italian RA real-world population based on the healthcare-administrative databases to assess the CV risk factors and incidence of CV events in comparison with the general population. Persistence and adherence to the CV therapy were also evaluated in both groups. Results: In a RA cohort (N = 21,201), there was a greater prevalence of hypertension and diabetes with respect to the non-RA subjects (N = 249,156) (36.9 vs. 33.4% and 10.2 vs. 9.6%, respectively), while dyslipidemia was more frequent in the non-RA group (15.4 vs. 16.5%). Compared with a non-RA cohort, the patients with RA had a higher incidence of atrial fibrillation (incidence rate ratio, IRR 1.28), heart failure (IRR 1.53), stroke (IRR 1.19), and myocardial infarction (IRR 1.48). The patients with RA presented a significantly lower persistence rate to glucose-lowering and lipid-lowering therapies than the controls (odds ratio, OR 0.73 [95% CI 0.6–0.8] and OR 0.82 [0.8–0.9], respectively). The difference in the adherence to glucose-lowering therapy was significant (OR 0.7 [0.6–0.8]), conversely no statistically significant differences emerged regarding the adherence to lipid-lowering therapy (OR 0.89 [95% CI 0.8–1.0]) and anti-hypertensive therapy (OR 0.96 [95% CI 0.9–1.0]). Conclusion: The patients with RA have a higher risk of developing CV events compared with the general population, partially explained by the excess and undertreatment of CV risk factors.
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Affiliation(s)
- Lisa Argnani
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Anna Zanetti
- Epidemiology Unit, Italian Society for Rheumatology, Milan, Italy.,Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy
| | - Greta Carrara
- Epidemiology Unit, Italian Society for Rheumatology, Milan, Italy
| | - Ettore Silvagni
- Rheumatology Unit, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliero-Universitaria S.Anna, Cona, Italy
| | - Giulio Guerrini
- Biomedical and Biotechnological Science at Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.,Internal Medicine, State Hospital, Borgo Maggiore, San Marino
| | - Antonella Zambon
- Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy
| | - Carlo Alberto Scirè
- Epidemiology Unit, Italian Society for Rheumatology, Milan, Italy.,School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
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Lufkin L, Budišić M, Mondal S, Sur S. A Bayesian Model to Analyze the Association of Rheumatoid Arthritis With Risk Factors and Their Interactions. Front Public Health 2021; 9:693830. [PMID: 34485224 PMCID: PMC8415718 DOI: 10.3389/fpubh.2021.693830] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 07/19/2021] [Indexed: 12/01/2022] Open
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disorder that commonly manifests as destructive joint inflammation but also affects multiple other organ systems. The pathogenesis of RA is complex where a variety of factors including comorbidities, demographic, and socioeconomic variables are known to associate with RA and influence the progress of the disease. In this work, we used a Bayesian logistic regression model to quantitatively assess how these factors influence the risk of RA, individually and through their interactions. Using cross-sectional data from the National Health and Nutrition Examination Survey (NHANES), a set of 11 well-known RA risk factors such as age, gender, ethnicity, body mass index (BMI), and depression were selected to predict RA. We considered up to third-order interactions between the risk factors and implemented factor analysis of mixed data (FAMD) to account for both the continuous and categorical natures of these variables. The model was further optimized over the area under the receiver operating characteristic curve (AUC) using a genetic algorithm (GA) with the optimal predictive model having a smoothed AUC of 0.826 (95% CI: 0.801–0.850) on a validation dataset and 0.805 (95% CI: 0.781–0.829) on a holdout test dataset. Apart from corroborating the influence of individual risk factors on RA, our model identified a strong association of RA with multiple second- and third-order interactions, many of which involve age or BMI as one of the factors. This observation suggests a potential role of risk-factor interactions in RA disease mechanism. Furthermore, our findings on the contribution of RA risk factors and their interactions to disease prediction could be useful in developing strategies for early diagnosis of RA.
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Affiliation(s)
- Leon Lufkin
- The Clarkson School, Clarkson University, Potsdam, NY, United States
| | - Marko Budišić
- Department of Mathematics, Clarkson University, Potsdam, NY, United States
| | - Sumona Mondal
- Department of Mathematics, Clarkson University, Potsdam, NY, United States
| | - Shantanu Sur
- Department of Biology, Clarkson University, Potsdam, NY, United States
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Myasoedova E, Davis JM, Roger VL, Achenbach SJ, Crowson CS. Improved Incidence of Cardiovascular Disease in Patients With Incident Rheumatoid Arthritis in the 2000s: A Population-based Cohort Study. J Rheumatol 2021; 48:1379-1387. [PMID: 33589553 PMCID: PMC8364571 DOI: 10.3899/jrheum.200842] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/29/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To assess trends in incidence of cardiovascular disease (CVD) and mortality following incident CVD events in patients with rheumatoid arthritis (RA) onset in 1980-2009 vs non-RA subjects. METHODS We studied Olmsted County, Minnesota residents with incident RA (aged > 18 yrs, 1987 American College of Rheumatology criteria met in 1980-2009) and non-RA subjects from the same source population with similar age, sex, and calendar year of index. All subjects were followed until death, migration, or December 31, 2016. Incident CVD events included myocardial infarction and stroke. Patients with CVD before RA incidence/index date were excluded. Cox models were used to compare incident CVD events by decade, adjusting for age, sex, and CVD risk factors. RESULTS The study included 905 patients with RA and 904 non-RA subjects. Cumulative incidence of any CVD event was lower in patients with incident RA in the 2000s vs the 1980s. The HR for any incident CVD in the 2000s vs 1980s was 0.53 (95% CI 0.31-0.93). The strength of association attenuated after adjustment for anti-rheumatic medication use (HR 0.64, 95% CI 0.34-1.22). Patients with RA in the 2000s had no excess in CVD over non-RA subjects (HR 0.71, 95% CI 0.42-1.19). Risk of death after a CVD event was somewhat lower in patients with RA after the 1980s with an HR of 0.54 (95% CI 0.33-0.90) in the 1990s vs 1980s and 0.68 (95% CI 0.33-1.41) in the 2000s vs 1980s. CONCLUSION The incidence of major CVD events in RA has declined in recent decades. The gap in CVD occurrence between patients with RA and the general population is closing. Mortality after CVD events in RA may be improving.
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Affiliation(s)
- Elena Myasoedova
- E. Myasoedova, MD, PhD, Division of Rheumatology, Department of Internal Medicine, and Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic;
| | - John M Davis
- J.M. Davis III, MD, MS, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic
| | - Veronique L Roger
- V.L. Roger, MD, MPH, Division of Epidemiology, Department of Health Sciences Research, and Division of Circulatory Failure, Department of Cardiovascular Disease, Mayo Clinic
| | - Sara J Achenbach
- S.J. Achenbach, MS, Division of Medical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic
| | - Cynthia S Crowson
- C.S. Crowson, PhD, Division of Rheumatology, Department of Internal Medicine, and Division of Medical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
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47
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Yafasova A, Diederichsen LP, Schou M, Sun G, Torp-Pedersen C, Gislason GH, Fosbøl EL, Køber L, Butt JH. Increased long-term risk of heart failure and other adverse cardiac outcomes in dermatomyositis and polymyositis: Insights from a nationwide cohort. J Intern Med 2021; 290:704-714. [PMID: 34080737 DOI: 10.1111/joim.13309] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 04/11/2021] [Accepted: 04/28/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Mounting evidence suggests that dermatomyositis/polymyositis (DM/PM) are associated with increased risk of atherosclerotic events and venous thromboembolism. However, data on the association between DM/PM and other cardiac outcomes, especially heart failure (HF), are scarce. OBJECTIVES To examine the long-term risk and prognosis associated with adverse cardiac outcomes in patients with DM/PM. METHODS Using Danish administrative registries, we included all patients ≥18 years with newly diagnosed DM/PM (1996-2018). Risks of incident outcomes were compared with non-DM/PM controls from the background population (matched 1:4 by age, sex, and comorbidity). In a secondary analysis, we compared mortality following HF diagnosis between DM/PM patients with HF and non-DM/PM patients with HF (matched 1:4 by age and sex). RESULTS The study population included 936 DM/PM patients (median age 58.5 years, 59.0% women) and 3744 matched non-DM/PM controls. The median follow-up was 6.9 years. Absolute 10-year risks of incident outcomes for DM/PM patients vs matched controls were as follows: HF, 6.98% (CI, 5.16-9.16%) vs 4.58% (3.79-5.47%) (P = 0.002); atrial fibrillation, 10.17% (7.94-12.71%) vs 7.07% (6.09-8.15%) (P = 0.005); the composite of ICD implantation/ventricular arrhythmias/cardiac arrest, 1.99% (1.12-3.27%) vs 0.64% (0.40-0.98%) (P = 0.02); and all-cause mortality, 35.42% (31.64-39.21%) vs 16.57% (15.10-18.10%) (P < 0.0001). DM/PM with subsequent HF was associated with higher mortality compared with HF without DM/PM (adjusted hazard ratio 1.58 [CI, 1.01-2.47]). CONCLUSION Patients with DM/PM had a higher associated risk of HF and other adverse cardiac outcomes compared with matched controls. Among patients developing HF, a history of DM/PM was associated with higher mortality.
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Affiliation(s)
- A Yafasova
- From the, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - L P Diederichsen
- Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - M Schou
- Department of Cardiology, Herlev and Gentofte University Hospital, Herlev, Denmark
| | - G Sun
- From the, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - C Torp-Pedersen
- Department of Cardiology, Nordsjaellands Hospital, Hillerød, Denmark
| | - G H Gislason
- Department of Cardiology, Herlev and Gentofte University Hospital, Herlev, Denmark.,The National Institute of Public Health, University of Southern Denmark, Odense, Denmark.,The Danish Heart Foundation, Copenhagen, Denmark
| | - E L Fosbøl
- From the, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - L Køber
- From the, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - J H Butt
- From the, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
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Márquez AB, van der Vorst EPC, Maas SL. Key Chemokine Pathways in Atherosclerosis and Their Therapeutic Potential. J Clin Med 2021; 10:3825. [PMID: 34501271 PMCID: PMC8432216 DOI: 10.3390/jcm10173825] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 08/20/2021] [Accepted: 08/20/2021] [Indexed: 12/24/2022] Open
Abstract
The search to improve therapies to prevent or treat cardiovascular diseases (CVDs) rages on, as CVDs remain a leading cause of death worldwide. Here, the main cause of CVDs, atherosclerosis, and its prevention, take center stage. Chemokines and their receptors have long been known to play an important role in the pathophysiological development of atherosclerosis. Their role extends from the initiation to the progression, and even the potential regression of atherosclerotic lesions. These important regulators in atherosclerosis are therefore an obvious target in the development of therapeutic strategies. A plethora of preclinical studies have assessed various possibilities for targeting chemokine signaling via various approaches, including competitive ligands and microRNAs, which have shown promising results in ameliorating atherosclerosis. Developments in the field also include detailed imaging with tracers that target specific chemokine receptors. Lastly, clinical trials revealed the potential of various therapies but still require further investigation before commencing clinical use. Although there is still a lot to be learned and investigated, it is clear that chemokines and their receptors present attractive yet extremely complex therapeutic targets. Therefore, this review will serve to provide a general overview of the connection between various chemokines and their receptors with atherosclerosis. The different developments, including mouse models and clinical trials that tackle this complex interplay will also be explored.
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Affiliation(s)
- Andrea Bonnin Márquez
- Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany;
- Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, Germany
- Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, 6229 ER Maastricht, The Netherlands
| | - Emiel P. C. van der Vorst
- Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany;
- Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, Germany
- Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, 6229 ER Maastricht, The Netherlands
- Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, 80336 Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, 80336 Munich, Germany
| | - Sanne L. Maas
- Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany;
- Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, Germany
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Ebina K. Drug efficacy and safety of biologics and Janus kinase inhibitors in elderly patients with rheumatoid arthritis. Mod Rheumatol 2021; 32:256-262. [PMID: 34894239 DOI: 10.1093/mr/roab003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 04/21/2021] [Accepted: 05/24/2021] [Indexed: 11/14/2022]
Abstract
Elderly patients with rheumatoid arthritis (RA) are frequently associated with higher disease activity and impaired physical function, although they show intolerance for conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate, because of their comorbidities. However, the present treatment recommendation based on randomized controlled trials is not distinguished by age or comorbidities. Therefore, this review aimed to investigate the efficacy and safety of biological DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi) in elderly patients. Present bDMARDs, including tumor necrosis factor inhibitors (TNFi), cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (abatacept), interleukin (IL)-6 receptor antibody (tocilizumab and salirumab), and anti-CD20 antibody (rituximab), may be similarly or slightly less effective or safe in elderly patients compared with younger patients. Oral glucocorticoid use, prolonged disease duration, and very old patients appear to be associated with an increased risk of adverse events, such as serious infection. Some recent cohort studies demonstrated that non-TNFi showed better retention than TNFi in elderly patients. Both TNFi and non-TNFi agents may not strongly influence the risk of adverse events such as cardiovascular events and malignancy in elderly patients. Regarding JAKi, the efficacy appears to be similar, although the safety (particularly for serious infections, including herpes zoster) may be attenuated by aging.
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Affiliation(s)
- Kosuke Ebina
- Department of Musculoskeletal Regenerative Medicine, Osaka University, Graduate School of Medicine, Osaka 565-0871, Japan
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Guo X, Zhao B, Chen T, Hao B, Yang T, Xu H. Multimorbidity in the elderly in China based on the China Health and Retirement Longitudinal Study. PLoS One 2021; 16:e0255908. [PMID: 34352011 PMCID: PMC8341534 DOI: 10.1371/journal.pone.0255908] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 07/26/2021] [Indexed: 11/19/2022] Open
Abstract
This study aimed to investigate the spatial distribution and patterns of multimorbidity among the elderly in China. Data on the occurrence of 14 chronic diseases were collected for 9710 elderly participants in the 2015 waves of the China Health and Retirement Longitudinal Study (CHARLS). Web graph, Apriori algorithm, age-adjusted Charlson comorbidity index (AAC), and Spatial autocorrelation were used to perform the multimorbidity analysis. The multimorbidity prevalence rate was estimated as 49.64% in the elderly in China. Three major multimorbidity patterns were identified: [Asthma/Chronic lungs diseases]: (Support (S) = 6.17%, Confidence (C) = 63.77%, Lift (L) = 5.15); [Asthma, Arthritis, or rheumatism/ Chronic lungs diseases]: (S = 3.12%, C = 64.03%, L = 5.17); [Dyslipidemia, Hypertension, Arthritis or rheumatism/Heart attack]: (S = 3.96%, C = 51.56, L = 2.69). Results of the AAC analysis showed that the more chronic diseases an elderly has, the lower is the 10-year survival rate (P < 0.001). Global spatial autocorrelation showed a positive spatial correlation distribution for the prevalence of the third multimorbidity pattern in China (P = 0.032). The status of chronic diseases and multimorbidity among the elderly with a spatial correlation is a significant health issue in China.
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Affiliation(s)
- Xiaorong Guo
- Department of Vascular Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Benhua Zhao
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnosis, School of Public Health, Xiamen University, Xiamen, Fujian, China
| | - Tianmu Chen
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnosis, School of Public Health, Xiamen University, Xiamen, Fujian, China
| | - Bin Hao
- Department of Vascular Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Tao Yang
- Department of Vascular Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Huimin Xu
- Department of Vascular Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
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