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Allam NAT, Abdelsalam ME, Elsharkawy HI, Kandil MM, Mohamed AMM, Ali F, Gebely MA, Nour SY, Sedky D, El-Gawad MEHA, Zaki HM, Al-Gallas N, Aboelmaaty AM, Sobhy MM, Ata NS, Abdel-Hamid MS, Badawy GA. Comprehensive epidemiological evaluation of ruminant brucellosis and associated risk factors in some Egyptian Governorates. Vet World 2024; 17:2780-2796. [PMID: 39897353 PMCID: PMC11784036 DOI: 10.14202/vetworld.2024.2780-2796] [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: 06/20/2024] [Accepted: 10/16/2024] [Indexed: 02/04/2025] Open
Abstract
Background and Aim Brucellosis contributes to significant economic losses due to abortion, weak newborns, infertility, and up to 20% reductions in milk yield in carrier animals. This study aimed to estimate the prevalence of ruminant brucellosis in six Egyptian governorates. This study aimed to estimate the prevalence of ruminant brucellosis and evaluate the risk factors regarding the epidemiological status, highlighting the importance of early carrier detection for the success of control programs. Materials and Methods A total of 3000 ruminants were investigated. Blood and serum samples were collected for routine hemato-biochemical analysis (complete blood picture and metabolic panel). In addition, genotoxicity analysis was performed, whereas tissue samples were collected for histopathological analysis. The buffered acidified plate antigen test (BAPAT), Rose Bengal plate test (RBPT), and complement fixation test (CFT) were used for serological diagnosis of brucellosis. The obtained bacterial colonies were typed using Brucella abortus-, melitensis-, ovis-, and suis-polymerase chain reaction (AMOS-PCR), depending on the variability of the IS711 fragment among Brucella spp. Serum trace elements, oxidative stress, and acute phase proteins were compared according to body condition score (BCS) and clinical condition images within the study population. Results Mastitis and abortion were the key recorded symptoms (9.966%, 299/3000 and 6%, 180/3000, respectively); however, symptomless individuals were predominant (82.9%, 2487/3000). Blood lymphocytosis was prominent even in asymptomatic animals. Nutritional and food conversion conditions were defined as low, moderate, or high BCS. Brucella overall seropositivity by BAPAT, RBPT, and CFT was 6.1% (182/3000), 5.6% (168/3000), and 5.1% (154/3000) in ruminant species within the included governorates, respectively. Upon diagnosis, 154 seropositive cases developed 93 bacterial isolates and a 731-bp PCR fragment whose sequences confirmed Brucella melitensis biovar 3. Serum metabolic and biochemical profiles, acute phase proteins, trace elements, and oxidative stress concentrations were indicative of loss of functionality in the liver and kidneys, malnutrition and malabsorption syndrome, and DNA damage, particularly in the low-BCS groups (p < 0.0001). Granulomatous lesions were most prominent in the lymph nodes, spleen, uterus, and udder of the dams, while placental multifocal necrosis with thrombosis was recorded in aborted fetuses. There were 8 types of chromosomal aberrations detected in peripheral white blood cells. The highest frequency was for dicentric aberrations 0.025% (25/1000), whereas the lowest 0.009% (9/1000) was for acentric, ring, fusion, and polyploidy. The difference between species was significant for BCS; 14.2% in low-BCS cattle and camels and 8.4% in high-BCS buffaloes. Conclusion B. melitensis biovar 3 is prevalent in Egypt. Mixed-rearing systems are the main risk factors for interspecies transmission among ruminants. The difficulty in accurately diagnosing all infected animals, particularly carriers, is a major limitation of eradication and control programs. Different biomarkers could be indicators and/or sensors for performance and/or infectivity conditions in animal herds; however, they require further optimization. Early detection using molecular technologies, highly descriptive, quantitative, sensitive, and specific methods, as alternatives to serological diagnosis (CFT, BAPAT, and RBT), is urgently needed to enhance the efficiency of brucellosis-specific prophylaxis. Such a comprehensive procedure is the World Organization for Animal Health dependent decision.
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Affiliation(s)
- Nesreen Allam Tantawy Allam
- Department of Parasitology and Animal Diseases, Veterinary Research Institute, National Research Centre, 33 El Buhouth Street, Dokki, P.O. Box: 12622, Cairo, Egypt
| | - Mahinour Ezzeldin Abdelsalam
- Department of General Biology, Center of Basic Sciences, Misr University for Science and Technology, Al Motamayez District, 6 of October, Giza, Egypt
| | - Hend I. Elsharkawy
- Brucella Reference Laboratory, Animal Health Research Institute, Agricultural Research Center, P.O. Box 264-Giza, Cairo, 12618, Egypt
| | - Mai Mohamed Kandil
- Department of Microbiology and Immunology, Veterinary Research Institute, National Research Centre, 33 El Buhouth Street, Dokki, P.O. Box: 12622, Cairo, Egypt
| | - Amany Mohamed Mohamed Mohamed
- Department of Parasitology and Animal Diseases, Veterinary Research Institute, National Research Centre, 33 El Buhouth Street, Dokki, P.O. Box: 12622, Cairo, Egypt
| | - Fatma Ali
- Department of Physiology, Faculty of Veterinary Medicine, Aswan University, Egypt
| | - Mohamed A. Gebely
- Department of Parasitology and Animal Diseases, Veterinary Research Institute, National Research Centre, 33 El Buhouth Street, Dokki, P.O. Box: 12622, Cairo, Egypt
| | - Safaa Y. Nour
- Animal Medicine Department, Faculty of Veterinary Medicine, Aswan University, Egypt
| | - Doaa Sedky
- Department of Parasitology and Animal Diseases, Veterinary Research Institute, National Research Centre, 33 El Buhouth Street, Dokki, P.O. Box: 12622, Cairo, Egypt
| | | | - Hoda M. Zaki
- Brucella Reference Laboratory, Animal Health Research Institute, Agricultural Research Center, P.O. Box 264-Giza, Cairo, 12618, Egypt
| | - Nazek Al-Gallas
- Department of Biology, Faculty of Science, University of Hafr Al-Batin, P.O. Box: 1803, Hafr Al-Batin, 31991, Kingdom of Saudi Arabia
- Water and Food Control Lab., National Center of Salmonella, Shigella, Vibrio, E. coli-Enteropathogens, Institute Pasteur de Tunis, Tunis
| | - Amal M. Aboelmaaty
- Department of Reproduction, Veterinary Research Institute, National Research Centre, 33 El Buhouth Street, Dokki, P.O. Box: 12622, Cairo, Egypt
| | - Mona Mohamed Sobhy
- Department of Reproductive Diseases, Animal Reproduction Research Institute, Agricultural Research Center, Al-Haram, Giza, Egypt
| | - Nagwa Sayed Ata
- Department of Microbiology and Immunology, Veterinary Research Institute, National Research Centre, 33 El Buhouth Street, Dokki, P.O. Box: 12622, Cairo, Egypt
| | - Marwa Salah Abdel-Hamid
- Department of Microbial Biotechnology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City
| | - Ghada A. Badawy
- Department of Botany, Faculty of Science, El-Fayoum University, Fayoum, 63514, Egypt
- Department of Biology, Faculty of Science, University of Tabuk, Umluj 46429, Kingdom of Saudi Arabia
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Ma LY, Song JH, Gao PY, Ou YN, Fu Y, Huang LY, Wang ZT, Zhang DD, Cui RP, Mi YC, Tan L. Amyloid pathology mediates the associations between plasma fibrinogen and cognition in non-demented adults. J Neurochem 2024; 168:2532-2542. [PMID: 38533619 DOI: 10.1111/jnc.16105] [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: 01/29/2024] [Revised: 03/08/2024] [Accepted: 03/13/2024] [Indexed: 03/28/2024]
Abstract
Though previous studies revealed the potential associations of elevated levels of plasma fibrinogen with dementia, there is still limited understanding regarding the influence of Alzheimer's disease (AD) biomarkers on these associations. We sought to investigate the interrelationships among fibrinogen, cerebrospinal fluid (CSF) AD biomarkers, and cognition in non-demented adults. We included 1996 non-demented adults from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study and 337 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The associations of fibrinogen with AD biomarkers and cognition were explored using multiple linear regression models. The mediation analyses with 10 000 bootstrapped iterations were conducted to explore the mediating effects of AD biomarkers on cognition. In addition, interaction analyses and subgroup analyses were conducted to assess the influence of covariates on the relationships between fibrinogen and AD biomarkers. Participants exhibiting low Aβ42 were designated as A+, while those demonstrating high phosphorylated tau (P-tau) and total tau (Tau) were labeled as T+ and N+, respectively. Individuals with normal measures of Aβ42 and P-tau were categorized as the A-T- group, and those with abnormal levels of both Aβ42 and P-tau were grouped under A+T+. Fibrinogen was higher in the A+ subgroup compared to that in the A- subgroup (p = 0.026). Fibrinogen was higher in the A+T+ subgroup compared to that in the A-T- subgroup (p = 0.011). Higher fibrinogen was associated with worse cognition and Aβ pathology (all p < 0.05). Additionally, the associations between fibrinogen and cognition were partially mediated by Aβ pathology (mediation proportion range 8%-28%). Interaction analyses and subgroup analyses showed that age and ApoE ε4 affect the relationships between fibrinogen and Aβ pathology. Fibrinogen was associated with both cognition and Aβ pathology. Aβ pathology may be a critical mediator for impacts of fibrinogen on cognition.
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Affiliation(s)
- Li-Yun Ma
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Jing-Hui Song
- Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Pei-Yang Gao
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Ya-Nan Ou
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Yan Fu
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Liang-Yu Huang
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Zuo-Teng Wang
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Dan-Dan Zhang
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Rui-Ping Cui
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Yin-Chu Mi
- Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, China
| | - Lan Tan
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
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Wang Z, Yan X, Fang L, Tang J, Zhang J. Association between lipoprotein(a), fibrinogen and their combination with all-cause, cardiovascular disease and cancer-related mortality: findings from the NHANES. BMC Public Health 2024; 24:1927. [PMID: 39026192 PMCID: PMC11256372 DOI: 10.1186/s12889-024-19443-4] [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: 11/09/2023] [Accepted: 07/10/2024] [Indexed: 07/20/2024] Open
Abstract
BACKGROUND There is evidence indicating that both lipoprotein(a) [Lp(a)] and fibrinogen (FIB) are associated with mortality, However, the impact of their combination on mortality has not been determined. Thus, the aim of this study was to examine the association between the combination of Lp(a) and FIB with all-cause and cause-specific mortality. METHODS This prospective cohort study enrolled 4,730 participants from the third National Health and Nutrition Examination Survey. The exposure variables included Lp(a), FIB and their combination, while the outcome variables consisted of all-cause, cardiovascular disease (CVD) and cancer-related mortality. Multivariate COX regression, subgroup analysis, sensitivity analysis and restricted cubic spline (RCS) were used to investigate the association between Lp(a), FIB and their combination with all-cause, CVD and cancer-related mortality. RESULTS Over a median follow-up period of 235 months, 2,668 individuals died, including 1,051 deaths attributed to CVD and 549 deaths due to cancer. Multivariate Cox regression analyses revealed independent associations between both Lp(a) and FIB with all-cause, CVD, and cancer-related mortality. Compared to participants in the 1st to 50th percentiles of both Lp(a) and FIB, those in the 90th to 100th percentiles exhibited multivariable adjusted HRs of 1.813 (95% CI: 1.419-2.317, P < 0.001), 2.147 (95% CI: 1.483-3.109, P < 0.001) and 2.355 (95% CI: 1.396, 3.973, P = 0.001) for all-cause, CVD and cancer-related mortality, respectively. Subgroup and sensitivity analyses did not substantially attenuate the association between the combination of high Lp(a) and high FIB with the risk of all-cause and CVD-related mortality. Additionally, the RCS analysis showed that the relationship between Lp(a) and the risk of all-cause and cancer-related mortality, as well as the relationship between FIB and the risk of cancer-related mortality, were linear (P for nonlinearity > 0.05). Conversely, the relationship between Lp(a) and the risk of CVD-related mortality, as well as the relationship between FIB and the risk of all-cause and CVD-related mortality, were nonlinear (P for nonlinearity < 0.05). CONCLUSIONS High levels of Lp(a) and FIB together conferred a greater risk of mortality from all-cause, CVD and cancer.
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Grants
- 81900453, 82222007, 82170281, and U2004203 National Natural Science Foundation of China
- 81900453, 82222007, 82170281, and U2004203 National Natural Science Foundation of China
- 81900453, 82222007, 82170281, and U2004203 National Natural Science Foundation of China
- Hohhot Healthcare Medical-2023030 Hohhot Healthcare Science and Technology Programme
- ZYQR201912131 Henan Thousand Talents Program
- 202300410362 Excellent Youth Science Foundation of Henan Province
- 2021-CCA-ACCESS-125 Central Plains Youth Top Talent, Advanced funds
- SBGJ202101012 Henan Province Medical Science and Technology Key Joint Project
- 222102230025 Key Scientific and Technological Research Projects in Henan Province
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Affiliation(s)
- Zhenwei Wang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China
- Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, 450018, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, 450052, China
| | - Xuejiao Yan
- Department of Cardiology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, 213003, China
| | - Lijuan Fang
- Department of Cardiology, The First Hospital of Hohhot, Hohhot, 010030, China.
| | - Junnan Tang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
- Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, 450018, China.
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, 450052, China.
| | - Jinying Zhang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
- Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, 450018, China.
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, 450052, China.
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Wang X, Pan Y, Zhang R, Wang M, Meng X, Li Z, Li H, Wang Y, Zhao X, Wang Y, Liu G. Inflammation and Adverse Outcomes in Patients With Acute Ischemic Stroke With and Without Chronic Kidney Disease. J Am Heart Assoc 2024; 13:e033450. [PMID: 38686855 PMCID: PMC11179914 DOI: 10.1161/jaha.123.033450] [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: 12/15/2023] [Accepted: 03/27/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND Elevated white blood cell count, fibrinogen levels, and lower levels of albumin signify higher systemic inflammatory response, hypercoagulable state, and poorer nutritional status, respectively. However, a consistent conclusion could not be drawn on whether the association between inflammatory markers and cardiovascular disease was affected by the presence of chronic kidney disease (CKD). We aimed to explore the association between inflammation and adverse outcomes in patients with acute ischemic stroke (AIS), as well as whether this association differs due to the presence of CKD. METHODS AND RESULTS This research was based on the Third China National Stroke Registry. The main adverse outcomes were poor functional outcome, stroke recurrence, and combined vascular event after 1 year. Inflammation was defined as the worst quartile of at least 2 of the aforementioned 3 markers. Finally, 8493 patients with AIS were enrolled in this study. The adjusted odds ratios/hazard ratios and 95% CIs of inflammation were 1.58 (1.34-1.86) for poor functional outcomes, 1.25 (1.06-1.47) for stroke recurrence, and 1.25 (1.06-1.46) for combined vascular event. The association between inflammation and adverse outcomes existed only in patients with AIS without CKD, although the interaction between CKD and inflammation was not statistically significant. (P for interaction >0.05). CONCLUSIONS Inflammation, which was defined as a combination of fibrinogen, white blood cell count, and albumin, was associated with all 1-year adverse outcomes among patients with AIS. Routine assessment of these biomarkers could become a potential part of the clinical evaluation for patients with AIS, especially those without CKD, aiding clinicians in risk stratification and treatment decision-making.
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Affiliation(s)
- Xiaoyu Wang
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China
| | - Yuesong Pan
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China
- China National Clinical Research Center for Neurological Diseases Beijing China
| | - Runhua Zhang
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China
- China National Clinical Research Center for Neurological Diseases Beijing China
| | - Mengxing Wang
- China National Clinical Research Center for Neurological Diseases Beijing China
| | - Xia Meng
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China
- China National Clinical Research Center for Neurological Diseases Beijing China
| | - Zixiao Li
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China
- China National Clinical Research Center for Neurological Diseases Beijing China
| | - Hao Li
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China
- China National Clinical Research Center for Neurological Diseases Beijing China
| | - Yilong Wang
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China
- China National Clinical Research Center for Neurological Diseases Beijing China
| | - Xingquan Zhao
- China National Clinical Research Center for Neurological Diseases Beijing China
| | - Yongjun Wang
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China
- China National Clinical Research Center for Neurological Diseases Beijing China
- Advanced Innovation Center for Human Brain Protection Capital Medical University Beijing China
- Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical Sciences Beijing China
- Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences Shanghai China
| | - Gaifen Liu
- Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China
- China National Clinical Research Center for Neurological Diseases Beijing China
- Advanced Innovation Center for Human Brain Protection Capital Medical University Beijing China
- Beijing Office for Cerebrovascular Disease Prevention and Control Beijing China
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Güven B, Can M. Fibrinogen: Structure, abnormalities and laboratory assays. Adv Clin Chem 2024; 120:117-143. [PMID: 38762239 DOI: 10.1016/bs.acc.2024.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/20/2024]
Abstract
Fibrinogen is the primary precursor protein for the fibrin clot, which is the final target of blood clotting. It is also an acute phase reactant that can vary under physiologic and inflammatory conditions. Disorders in fibrinogen concentration and/or function have been variably linked to the risk of bleeding and/or thrombosis. Fibrinogen assays are commonly used in the management of bleeding as well as the treatment of thrombosis. This chapter examines the structure of fibrinogen, its role in hemostasis as well as in bleeding abnormalities and measurement thereof with respect to clinical management.
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Affiliation(s)
- Berrak Güven
- Department of Clinical Biochemistry, Zonguldak Bülent Ecevit University, Zonguldak, Turkey.
| | - Murat Can
- Department of Clinical Biochemistry, Zonguldak Bülent Ecevit University, Zonguldak, Turkey
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Popescu AI, Rata AL, Barac S, Popescu R, Onofrei RR, Vlad C, Vlad D. Narrative Review of Biological Markers in Chronic Limb-Threatening Ischemia. Biomedicines 2024; 12:798. [PMID: 38672153 PMCID: PMC11047884 DOI: 10.3390/biomedicines12040798] [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: 03/10/2024] [Revised: 03/30/2024] [Accepted: 04/01/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND Chronic limb-threatening ischemia (CLTI), the advanced stage of peripheral arterial disease, is diagnosed in the presence of ischemic rest pain, non-healing ulcers, or gangrene. Several studies have demonstrated that inflammation and endothelial dysfunction are some of the main substrates of CLTI. METHODS A narrative review was conducted and reported according to PRISMA guidelines. Three databases were searched-Web of Science, Medline, and EMBASE-for the studies assessing CLTI and the biological markers related to it. RESULTS We included 22 studies, and all the markers identified (C-reactive protein, D-dimers, fibrinogen, cytokines, IL-6, TNF-α, ICAM-1 (Intracellular Adhesion Molecule-1), VCAM-1 (Vascular Cell Adhesion Molecule-1), neutrophile-to-lymphocytes ratio (NLR), IL-8, Pentraxin-3, neutrophil gelatinase-associated lipocalin (NGAL), calprotectin, E-selectin, P-selectin, neopterin, High-Mobility Group Box-1 protein (HGMB-1), Osteoprotegerin (OPG) and Sortilin) were positively associated with advanced CLTI, with major limb or major cardiovascular events in these patients. CONCLUSIONS All the studied markers had increased values in patients with CLTI, especially when associated with diabetes mellitus, proving a very important association between diabetes and major limb or cardiovascular events in these patients. There is a need for more studies to validate these markers in terms of diagnosis or prognosis in CLTI patients and in trying to find new medical strategies that target inflammation or endothelial dysfunction in these patients.
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Affiliation(s)
- Alexandra Ioana Popescu
- Pharmacology Department, Doctoral School, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania;
| | - Andreea Luciana Rata
- Surgical Emergencies Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania;
| | - Sorin Barac
- Vascular Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Roxana Popescu
- Cell and Molecular Biology Department, ”Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania;
| | - Roxana Ramona Onofrei
- Department of Rehabilitation, Physical Medicine and Rheumatology, Research Center for Assessment of Human Motion, Functionality and Disability, ”Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania;
| | - Cristian Vlad
- Pharmacology Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (C.V.); (D.V.)
| | - Daliborca Vlad
- Pharmacology Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (C.V.); (D.V.)
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Wang C, Cui T, Li S, Wang T, Cui J, Zhong L, Jiang S, Zhu Q, Chen M, Yang Y, Wang A, Zhang X, Shang W, Hao Z, Wu B. The Change in Fibrinogen is Associated with Outcome in Patients with Acute Ischemic Stroke Treated with Endovascular Thrombectomy. Neurocrit Care 2024; 40:506-514. [PMID: 37316678 DOI: 10.1007/s12028-023-01768-4] [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] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 05/22/2023] [Indexed: 06/16/2023]
Abstract
BACKGROUND Fibrinogen has been identified as a modulator of the coagulation and inflammatory process. There is uncertainty about the relationship between the dynamic profile of fibrinogen levels and its impact on clinical outcomes in patients with acute ischemic stroke treated with endovascular thrombectomy. METHODS We consecutively enrolled patients with acute ischemic stroke who underwent endovascular thrombectomy. Fibrinogen was measured on admission and during hospitalization. The change in fibrinogen (Δfibrinogen) was calculated as the highest follow-up fibrinogen minus admission fibrinogen, with a positive Δfibrinogen indicating an increase in fibrinogen level. Functional outcome was assessed by the modified Rankin Scale at 3 months. Poor outcome was defined as modified Rankin Scale > 2. RESULTS A total of 346 patients were included (mean age 67.4 ± 13.6 years, 52.31% men). The median fibrinogen on admission was 2.77 g/L (interquartile range 2.30-3.39 g/L). The median Δfibrinogen was 1.38 g/L (interquartile range 0.27-2.79 g/L). Hyperfibrinogenemia (> 4.5 g/L) on admission was associated with an increased risk of poor outcome [odds ratio (OR) 5.93, 95% confidence interval (CI) 1.44-24.41, p = 0.014]. There was a possible U-shaped association of Δfibrinogen with outcomes, with an inflection point of - 0.43 g/L (p = 0.04). When Δfibrinogen was < - 0.43 g/L, a higher decrease in fibrinogen (lower Δfibrinogen value) was associated with a higher risk of poor outcome (OR 0.22, 95% CI 0.02-2.48, p = 0.219). When Δfibrinogen was > - 0.43 g/L, the risk of poor outcome increased with increasing fibrinogen (OR 1.27, 95% CI 1.04-1.54, p = 0.016). CONCLUSIONS In patients with endovascular thrombectomy, hyperfibrinogenemia on admission was associated with poor functional outcomes at 3 months, whereas Δfibrinogen was associated with poor 3-month outcomes in a possible U-shaped manner.
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Affiliation(s)
- Changyi Wang
- Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
- Department of Rehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ting Cui
- Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Shucheng Li
- Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Tiantian Wang
- Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jingyu Cui
- Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Luyao Zhong
- Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Shuai Jiang
- Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Qiange Zhu
- The Second Department of Neurology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China
| | - Mingxi Chen
- Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Yuan Yang
- Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Anmo Wang
- Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xuening Zhang
- Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Wenzuo Shang
- Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Zilong Hao
- Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Bo Wu
- Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
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Galos G, Rabai M, Szabo R, Szalai R, Toth K, Hegyi P, Sandor B. The influence of triglyceride and low-density-lipoprotein target levels on microcirculation: Is there a difference? Heliyon 2024; 10:e27954. [PMID: 38515677 PMCID: PMC10955303 DOI: 10.1016/j.heliyon.2024.e27954] [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: 08/31/2023] [Revised: 01/08/2024] [Accepted: 03/08/2024] [Indexed: 03/23/2024] Open
Abstract
Background and aims This study aimed to validate the role of high low-density lipoprotein cholesterol [LDL-C] and triglyceride [TG] treatment target levels on the microcirculation in a very high and high cardiovascular risk group. Methods 119 patients with high or very high cardiovascular [CV] risk were included. We have registered the main co-morbidities, smoking habits, body mass index [BMI] and the lipid lowering medication. Hematocrit, whole blood viscosity [WBV] and plasma viscosity [PV], red blood cell [RBC] aggregation and deformability and fibrinogen, total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], LDL-C and TG levels were determined. Results The investigation found significantly higher PV values in patients with non-target LDL-C, associated with higher fibrinogen level. Non-target TG was related to deteriorated microcirculatory parameters, as significantly higher RBC aggregation, lower RBC deformability, and higher WBV and PV. The main microcirculatory benefit in diabetes could be gained from target level of TG, in chronic coronary syndrome [CCS] patients it is more advantageous to reach both LDL-C and TG target. Conclusion The results could highlight, that TG should play a role in failing microcirculation and cause potentially life-threatening complications, which would worsen the survival and quality of life of high or very high risk CV patients.
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Affiliation(s)
- Gergely Galos
- Department of Medicine, Division of Preventive Cardiology and Rehabilitation, University of Pecs, School of Medicine, Pecs, Hungary
- Department of Medicine, Szentagothai Research Centre, University of Pecs, Medical School, Pecs, Hungary
| | - Miklos Rabai
- Department of Medicine, Division of Cardiology, University of Pecs, School of Medicine, Pecs, Hungary
| | - Reka Szabo
- Department of Medicine, Division of Preventive Cardiology and Rehabilitation, University of Pecs, School of Medicine, Pecs, Hungary
| | - Rita Szalai
- Department of Medicine, Division of Preventive Cardiology and Rehabilitation, University of Pecs, School of Medicine, Pecs, Hungary
| | - Kalman Toth
- Department of Medicine, Division of Cardiology, University of Pecs, School of Medicine, Pecs, Hungary
| | - Peter Hegyi
- Institute for Translational Medicine, University of Pecs, School of Medicine, Pecs, Hungary
| | - Barbara Sandor
- Department of Medicine, Division of Preventive Cardiology and Rehabilitation, University of Pecs, School of Medicine, Pecs, Hungary
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9
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Xu X, Wu LY, Wang SY, Yan M, Wang YH, Li L, Sun ZL, Zhao JX. Investigating causal associations among gut microbiota, metabolites, and psoriatic arthritis: a Mendelian randomization study. Front Microbiol 2024; 15:1287637. [PMID: 38426052 PMCID: PMC10902440 DOI: 10.3389/fmicb.2024.1287637] [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: 09/02/2023] [Accepted: 01/24/2024] [Indexed: 03/02/2024] Open
Abstract
BACKGROUND Currently, there has been observed a significant alteration in the composition of the gut microbiome (GM) and serum metabolites in patients with psoriatic arthritis (PsA) compared to healthy individuals. However, previous observational studies have shown inconsistent results regarding the alteration of gut microbiota/metabolites. In order to shed light on this matter, we utilized Mendelian randomization to determine the causal effect of GM/metabolites on PsA. METHODS We retrieved summary-level data of GM taxa/metabolites and PsA from publicly available GWAS statistics. Causal relationships between GM/metabolites and PsA were determined using a two-sample MR analysis, with the IVW approach serving as the primary analysis method. To ensure the robustness of our findings, we conducted sensitivity analyses, multivariable MR analysis (MVMR), and additional analysis including replication verification analysis, LDSC regression, and Steiger test analysis. Furthermore, we investigated reverse causality through a reverse MR analysis. Finally, we conducted an analysis of expression quantitative trait loci (eQTLs) involved in the metabolic pathway to explore potential molecular mechanisms of metabolism. RESULTS Our findings reveal that eight GM taxa and twenty-three serum metabolites are causally related to PsA (P < 0.05). Notably, a higher relative abundance of Family Rikenellaceae (ORIVW: 0.622, 95% CI: 0.438-0.883, FDR = 0.045) and elevated serum levels of X-11538 (ORIVW: 0.442, 95% CI: 0.250-0.781, FDR = 0.046) maintain significant causal associations with a reduced risk of PsA, even after adjusting for multiple testing correction and conducting MVMR analysis. These findings suggest that Family Rikenellaceae and X-11538 may have protective effects against PsA. Our sensitivity analysis and additional analysis revealed no significant horizontal pleiotropy, reverse causality, or heterogeneity. The functional enrichment analysis revealed that the eQTLs examined were primarily associated with glycerolipid metabolism and the expression of key metabolic factors influenced by bacterial infections (Vibrio cholerae and Helicobacter pylori) as well as the mTOR signaling pathway. CONCLUSION In conclusion, our study demonstrates that Family Rikenellaceae and X-11538 exhibit a strong and negative causal relationship with PsA. These particular GM taxa and metabolites have the potential to serve as innovative biomarkers, offering valuable insights into the treatment and prevention of PsA. Moreover, bacterial infections and mTOR-mediated activation of metabolic factors may play an important role in this process.
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Affiliation(s)
- Xiao Xu
- Department of Nursing, Nantong Health College of Jiangsu Province, Nantong, China
| | - Lin-yun Wu
- School of Nursing, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shu-yun Wang
- Academic Affair Office, Nantong Vocational University, Nantong, China
| | - Min Yan
- Department of Epidemiology, School of Public Health, Changzhou University, Changzhou, China
- Faculty of Health and Welfare, Satakunta University of Applied Sciences, Pori, Finland
| | - Yuan-Hong Wang
- Department of Rheumatology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Li Li
- Department of Rheumatology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhi-ling Sun
- Department of Epidemiology, School of Public Health, Nanjing University of Chinese Medicine, Nanjing, China
| | - Ji-Xiang Zhao
- Department of Nursing, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
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10
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Ding Y, Qi X, Li Y, Sun Y, Wan J, Luo C, Huang Y, Li Q, Wu G, Zhu X, Xu S. Albumin-to-fibrinogen ratio is an independent prognostic parameter in de novo non-M3 acute myeloid leukemia. Clin Exp Med 2023; 23:4597-4608. [PMID: 37914966 DOI: 10.1007/s10238-023-01241-8] [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: 02/21/2023] [Accepted: 10/26/2023] [Indexed: 11/03/2023]
Abstract
Inflammation and nutrition related proteins participate in the development of acute myeloid leukemia (AML). It has been reported that the albumin-to-fibrinogen ratio (AFR) could serve as a prognostic indicator in patients with malignancy, but the precise relevance of AML is unclear. This study aimed to evaluate the effect of AFR on survival prognosis in patients with AML. We analyzed 227 patients newly diagnosed with non-M3 AML. AFR was calculated as albumin divided by fibrinogen. Based on the cutoff point from X-tile program, patients were divided into AFR-high (38.8%) and AFR-low (61.2%) groups. AFR-low group showed a poorer complete remission rate (P < 0.001) and median time to relapse (P = 0.026), while the mortality was higher (P = 0.009) than AFR-high ones. According to the log-rank test, AFR-low group had shorter OS (P < 0.001) and DFS (P = 0.034). Multivariate analysis identified AFR, ELN risk, bone marrow transplant, and hemoglobin as independent prognostic variables associated with OS. A visualized nomogram for predicting OS was performed. The C-index (0.75), calibration plots, and decision curve analyses of new model showed better discrimination, calibration, and net benefits than the ELN risk model. The time-dependent receiver operating characteristic (ROC) curve of 1-, 2-, and 3-year also functioned well (AUC, 0.81, 0.93 and 0.90, respectively). Our study provided a comprehensive view of AFR which could be an independent prognostic indicator in AML patients. The prognostic model utilized readily available information from ordinary clinical practice to improve predictive performance, identify risks, and assist in therapeutic decision-making.
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Affiliation(s)
- Yaqun Ding
- Center for Hematology, Southwest Hospital, Army Medical University, Third Military Medical University), Chongqing, China
| | - Xiangyu Qi
- Center for Hematology, Southwest Hospital, Army Medical University, Third Military Medical University), Chongqing, China
| | - Yang Li
- Center for Hematology, Southwest Hospital, Army Medical University, Third Military Medical University), Chongqing, China
| | - Yanni Sun
- Center for Hematology, Southwest Hospital, Army Medical University, Third Military Medical University), Chongqing, China
| | - Jia Wan
- Center for Hematology, Southwest Hospital, Army Medical University, Third Military Medical University), Chongqing, China
| | - Chengxin Luo
- Center for Hematology, Southwest Hospital, Army Medical University, Third Military Medical University), Chongqing, China
| | - Yarui Huang
- Center for Hematology, Southwest Hospital, Army Medical University, Third Military Medical University), Chongqing, China
| | - Qingrong Li
- Center for Hematology, Southwest Hospital, Army Medical University, Third Military Medical University), Chongqing, China
| | - Guixian Wu
- Center for Hematology, Southwest Hospital, Army Medical University, Third Military Medical University), Chongqing, China
| | - Xiaoqing Zhu
- Chongqing Medical and Pharmaceutical College, Chongqing, China
- Department of Obstetrics and Gynecology, Southwest Hospital, Army Medical University, Third Military Medical University), Chongqing, China
| | - Shuangnian Xu
- Center for Hematology, Southwest Hospital, Army Medical University, Third Military Medical University), Chongqing, China.
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Şimşek F, Yevgi R. Assessment of fibrinogen albumin ratio in patients with pregnancy-related cerebral venous thrombosis. Acta Neurol Belg 2023; 123:2251-2258. [PMID: 37217742 DOI: 10.1007/s13760-023-02294-y] [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: 02/22/2023] [Accepted: 05/17/2023] [Indexed: 05/24/2023]
Abstract
INTRODUCTION AND OBJECTIVE Cerebral venous thrombosis (CVT) is a cerebrovascular disease observed more commonly in women of childbearing age. There is currently no biomarker used to predict the risk of CVT during the follow-up of pregnant/postpartum patients. In this context, the objective of this study is to investigate the importance of fibrinogen and albumin levels and fibrinogen-to-albumin ratio (FAR) values, which predispose to thromboembolism, in pregnant/postpartum patients. MATERIAL AND METHOD The study sample consisted of 19 pregnant/postpartum patients with a diagnosis of CVT, 20 pregnant/postpartum patients without CVT. Albumin and fibrinogen levels and FAR values were compared between these two groups. RESULTS Fibrinogen level was significantly higher in pregnant/postpartum CVT patients compared to pregnant/postpartum patients without CVT (p = 0.010). On the other hand, albumin level was significantly lower in pregnant/postpartum CVT patients compared to the other group (p = 0.010). Lastly, FAR level was significantly higher in pregnant/postpartum CVT patients compared to the other group (p = 0.011). There was no correlation between FAR values and modified Rankin score. CONCLUSION The study findings indicated that high fibrinogen and low albumin levels and high FAR values are associated with an increased risk of CVT in pregnant/postpartum patients.
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Affiliation(s)
- Fatma Şimşek
- Faculty of Medicine, Department of Neurology, Ataturk University, Erzurum, Turkey.
| | - Recep Yevgi
- Faculty of Medicine, Department of Neurology, Ataturk University, Erzurum, Turkey
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12
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AlGhibiwi HK, Sarawi WS, Alosaimi ME, Alhusaini AM, Assiri MA, Algarzae NK. The Association between Cardiovascular Risk Factors and Carotid Intima-Media Thickness in 42,726 Adults in UK Biobank: A Cross-Sectional Study. J Cardiovasc Dev Dis 2023; 10:358. [PMID: 37754787 PMCID: PMC10532383 DOI: 10.3390/jcdd10090358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 08/14/2023] [Accepted: 08/17/2023] [Indexed: 09/28/2023] Open
Abstract
BACKGROUND Traditional modifiable cardiovascular risk factors, such as high blood pressure, have long been positively correlated with high carotid intima-media thickness (cIMT). However, traditional cardiovascular risk factors made a minor contribution to cIMT variance, meaning that other markers may be regarded as independent markers for increasing cIMT. AIMS To investigate the simple demographic patterns of carotid intima-media thickness (cIMT) in the UK Biobank and to identify which upstream cardiovascular disease (CVD) risk factors are independently associated with cIMT. METHODS AND RESULTS A cross-sectional-based study of healthy middle-aged people recruited in the UK between 2006 and 2010 (n = 42,726). RESULTS This study showed that the cardiovascular risk profile generally worsened across the cIMT quantiles from lowest to highest. The lowest cIMT quartile was defined as having a mean cIMT < 588 µm, while the highest cIMT quartile was defined as having a mean cIMT > 748 µm. Specifically, the highest cIMT quantile group had a worse CVD risk factors profile compared to the lowest cIMT quantile group. It was found that, for every one SD increase in age and systolic blood pressure, the mean cIMT increased by 0.357 SD and 0.115 SD, respectively. CONCLUSION Systolic blood pressure and age were the strongest independent risk factors for a high cIMT value compared to other risk factors.
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Affiliation(s)
- Hanan K. AlGhibiwi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11149, Saudi Arabia; (W.S.S.); (A.M.A.); (M.A.A.)
| | - Wedad S. Sarawi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11149, Saudi Arabia; (W.S.S.); (A.M.A.); (M.A.A.)
| | - Manal E. Alosaimi
- Department of Basic Health Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia;
| | - Ahlam M. Alhusaini
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11149, Saudi Arabia; (W.S.S.); (A.M.A.); (M.A.A.)
| | - Mohammed A. Assiri
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11149, Saudi Arabia; (W.S.S.); (A.M.A.); (M.A.A.)
| | - Norah K. Algarzae
- Department of Physiology, College of Medicine, King Saud University, Riyadh 11149, Saudi Arabia;
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Muacevic A, Adler JR, Mishra B, Guria RT, Kumar A, Birua H, Ray HN, Dungdung A, Kumar D, Maitra S. Association of Fibrinogen With Ischemic Stroke: A Systematic Review and Meta-Analysis. Cureus 2023; 15:e34335. [PMID: 36721710 PMCID: PMC9884496 DOI: 10.7759/cureus.34335] [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: 01/28/2023] [Indexed: 01/30/2023] Open
Abstract
Validation of a risk factor in a multifactorial disease like ischemic stroke is necessary to practice precision medicine. Many risk factors have been attributed to causing ischemic stroke but contribute very little to it. There are many risk factors that need to be validated, and fibrinogen is one such risk factor. Using a meta-analysis technique, we investigated fibrinogen as a risk factor for ischemic stroke. We searched the computerized databases such as PubMed, Google Scholar, and Cochrane to explore articles on ischemic stroke. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random effects model. A total of 10 case-control studies with 6877 cases and 7219 controls were included in the study that match inclusion and exclusion criteria. The Asiatic population was portrayed in four studies, whereas the Caucasian population was portrayed in six studies. Under the recessive model, an elevated level of serum fibrinogen is linked to an increased risk of ischemic stroke as shown by pooled odds ratio (OR: 1.47, 95% CI: 1.19-1.76, I2 = 78.3%, P = 0.000). Our meta-analysis concluded that a high level of fibrinogen is associated with an increased risk of ischemic stroke.
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14
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Curry PDK, Morris AP, Barton A, Bluett J. Do genetics contribute to TNF inhibitor response prediction in Psoriatic Arthritis? THE PHARMACOGENOMICS JOURNAL 2023; 23:1-7. [PMID: 36243888 PMCID: PMC9925377 DOI: 10.1038/s41397-022-00290-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 09/09/2022] [Accepted: 09/22/2022] [Indexed: 02/15/2023]
Abstract
Psoriatic arthritis (PsA) is a heterogeneous chronic musculoskeletal disease, affecting up to 30% of people with psoriasis. Research into PsA pathogenesis has led to the development of targeted therapies, including Tumor Necrosis Factor inhibitors (TNF-i). Good response is only achieved by ~60% of patients leading to 'trial and error' drug management approaches, adverse reactions and increasing healthcare costs. Robust and well-validated biomarker identification, and subsequent development of sensitive and specific assays, would facilitate the implementation of a stratified approach into clinical care. This review will summarise potential genetic biomarkers for TNF-i (adalimumab, etanercept and infliximab) response that have been reported to date. It will also comment upon the importance of managing clinical confounders when understanding drug response prediction. Variants in multiple gene regions including TNF-A, FCGR2A, TNFAIP3, TNFR1/TNFR1A/TNFRSF1A, TRAIL-R1/TNFRSF10A, FCGR3A have been reported to correlate with TNF-i response at various levels of statistical significance in patients with PsA. However, results were often from heterogenous and underpowered cohorts and none are currently implemented into clinical practice. External validation of genetic biomarkers in large, well-documented cohorts is required, and assessment of the predictive value of combining multiple genetic biomarkers with clinical measures is essential to clinically embed pharmacogenomics into PsA drug management.
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Affiliation(s)
- Philippa D K Curry
- Versus Arthritis Centre for Genetics and Genomics, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK
| | - Andrew P Morris
- Versus Arthritis Centre for Genetics and Genomics, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK
| | - Anne Barton
- Versus Arthritis Centre for Genetics and Genomics, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK.,NIHR Manchester Biomedical Research Centre, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - James Bluett
- Versus Arthritis Centre for Genetics and Genomics, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK. .,NIHR Manchester Biomedical Research Centre, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
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15
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Malik K, Diaz-Coto S, de la Asunción Villaverde M, Martinez-Camblor P, Navarro-Rolon A, Pujalte F, De la Sierra A, Almagro P. Impact of Spirometrically Confirmed Chronic Obstructive Pulmonary Disease on Arterial Stiffness and Surfactant Protein D After Percutaneous Coronary Intervention. The CATEPOC Study. Int J Chron Obstruct Pulmon Dis 2022; 17:2577-2587. [PMID: 36267326 PMCID: PMC9578359 DOI: 10.2147/copd.s373853] [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: 05/08/2022] [Accepted: 09/09/2022] [Indexed: 11/23/2022] Open
Abstract
Background Several mechanisms have been proposed to explain why chronic obstructive pulmonary disease (COPD) impairs the prognosis of coronary events. We aimed to explore COPD variables related to a worse prognosis in patients undergoing percutaneous coronary intervention (PCI). Methods Patients with an acute coronary event treated by PCI were prospectively included. One month after discharge, clinical characteristics, comorbidities measured with the Charlson index, and prognostic coronary scales (logistic EuroSCORE; GRACE 2.0) were collected. Post-bronchodilator spirometry, arterial stiffness, and serum inflammatory and myocardial biomarkers were measured. Lung plasmatic biomarkers (Surfactant protein D, desmosine, and Clara cell secretory protein-16) were determined with ELISA. COPD was defined by the fixed ratio (FEV1/FVC <70%). Spirometric values were also analyzed as continuous variables using adjusted and non-adjusted ANCOVA analysis. Finally, we evaluated the presence of a respiratory pattern defined by non-stratified spirometric values and pulmonary biomarkers. Results A total of 164 patients with a mean age of 65 (±10) years (79% males) were included. COPD was diagnosed in 56 (34%) patients (68% previously undiagnosed). COPD patients had a longer smoking history, higher scores on the EuroSCORE (p < 0.0001) and GRACE 2.0 (p < 0.001) scales, and more comorbidities (p = 0.006). Arterial stiffness determined by pulse wave velocity was increased in COPD patients (7.35 m/s vs 6.60 m/s; p = 0.006). Serum values of high sensitive T troponin (p = 0.007) and surfactant protein D (p = 0.003) were also higher in COPD patients. FEV1% remained significantly associated with arterial stiffness and surfactant protein D in the adjusted ANCOVA analysis. In the cluster exploration, 53% of the patients had a respiratory pattern. Conclusion COPD affects one-third of patients with an acute coronary event and frequently remains undiagnosed. Several mechanisms, including arterial stiffness and SPD, were increased in COPD patients. Their relationship with the prognosis should be confirmed with longitudinal follow-up of the cohort.
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Affiliation(s)
- Komal Malik
- Internal Medicine Service, University Hospital Mútua de Terrassa, University of Barcelona, Barcelona, Spain
| | - Susana Diaz-Coto
- Epidemiology Department, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | | | - Pablo Martinez-Camblor
- Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA,Faculty of Health Sciences, Universidad Autonoma de Chile, Providencia, 7500912, Chile
| | - Annie Navarro-Rolon
- Pneumology Service, University Hospital Mútua de Terrassa, University of Barcelona, Barcelona, Spain,Immunology Department, Catlab Laboratory, Barcelona, Spain
| | | | - Alejandro De la Sierra
- Internal Medicine Service, University Hospital Mútua de Terrassa, University of Barcelona, Barcelona, Spain
| | - Pere Almagro
- Internal Medicine Service, University Hospital Mútua de Terrassa, University of Barcelona, Barcelona, Spain,Correspondence: Pere Almagro, Email
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Chai D, Yang X, Wang A, Lu S, Dai Y, Zhou J. Usefulness of Platelet Distribution Width and Fibrinogen in Predicting In-stent Restenosis With Stable Angina and Type 2 Patients With Diabetes Mellitus. Front Cardiovasc Med 2022; 9:710804. [PMID: 35387442 PMCID: PMC8977890 DOI: 10.3389/fcvm.2022.710804] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 01/25/2022] [Indexed: 11/13/2022] Open
Abstract
Aim The purpose of this study was to investigate the predicting value of platelet distribution width (PDW) and fibrinogen for in-stent restenosis (ISR) in patients with stable angina pectoris and type 2 diabetes mellitus (T2DM) after drug-eluting stent (DES) implantation. Methods We enrolled 161 patients who were readmitted with recurrent chest pain and successfully reviewed for coronary angiography and were divided into the ISR and non-ISR groups. We compared the levels of PDW and fibrinogen between the two groups. Logistic regression was used for analyzing independent predictors of ISR. The receiver operating characteristic (ROC) curve analysis was used to determine the optimum cutoff points of PDW and fibrinogen to predict ISR. The Kaplan–Meier survival curves for target lesion failure (TLF) by levels of PDW and fibrinogen. Results The multivariate logistic regression analysis showed that PDW and fibrinogen were independent predictors of ISR [odds ratio (OR) = 1.209, 95% CI: 1.024–1.427, p = 0.025; OR = 1.006, 95% CI: 1.002–1.011, p = 0.010, respectively]. The ROC analyses showed that PDW ≥ 13.15% and fibrinogen ≥ 333.5 mg/dl were predictive of ISR in patients with stable angina pectoris and T2DM after DES implantation. However, the Kaplan–Meier estimate for TLF showed no statistical significance. Conclusion Higher levels of PDW and fibrinogen were associated with the incidence of ISR in patients with stable angina with T2DM after DES implantation, but were not independent predictors of TLF.
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Affiliation(s)
- Dayang Chai
- Department of Cardiology, The First People's Hospital of Taicang, The Affiliated Taicang Hospital of Soochow University, Taicang, China
| | - Xi Yang
- Department of Endocrinology, The First People's Hospital of Taicang, The Affiliated Taicang Hospital of Soochow University, Taicang, China
| | - Aichao Wang
- Department of Cardiology, The First People's Hospital of Taicang, The Affiliated Taicang Hospital of Soochow University, Taicang, China
| | - Shu Lu
- Department of Cardiology, The First People's Hospital of Taicang, The Affiliated Taicang Hospital of Soochow University, Taicang, China
| | - Yuxiang Dai
- Department of Cardiology, Zhongshan Hospital Affiliated of Fudan University, Shanghai, China
| | - Jing Zhou
- Department of Cardiology, The First People's Hospital of Taicang, The Affiliated Taicang Hospital of Soochow University, Taicang, China
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17
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Guzman-Sepulveda JR, Batarseh M, Wu R, DeCampli WM, Dogariu A. Passive high-frequency microrheology of blood. SOFT MATTER 2022; 18:2452-2461. [PMID: 35279707 PMCID: PMC8941587 DOI: 10.1039/d1sm01726h] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/07/2023]
Abstract
Indicative of various pathologies, blood properties are under intense scrutiny. The hemorheological characteristics are traditionally gauged by bulk, low-frequency indicators that average out critical information about the complex, multi-scale, and multi-component structure. In particular, one cannot discriminate between the erythrocytes contribution to global rheology and the impact of plasma. Nevertheless, in their fast stochastic movement, before they encounter each other, the erythrocytes probe the subtle viscoelasticity of their protein-rich environment. Thus, if these short time scales can be resolved experimentally, the plasma properties could be determined without having to separate the blood components; the blood is practically testing itself. This microrheological description of blood plasma provides a direct link between the composition of whole blood and its coagulability status. We present a parametric model for the viscoelasticity of plasma, which is probed by the erythrocytes over frequency ranges of kilohertz in a picoliter-sized volume. The model is validated both in vitro, using artificial hemo-systems where the composition is controlled, as well as on whole blood where continuous measurements provide real-time information. We also discuss the possibility of using this passive microrheology as an in vivo assay for clinically relevant situations where the blood clotting condition must be observed and managed continuously for diagnosis or during therapeutic procedures at different stages of hemostatic and thrombotic processes.
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Affiliation(s)
- Jose Rafael Guzman-Sepulveda
- CREOL, The College of Optics and Photonics, University of Central Florida, 4304 Scorpius, Orlando, Florida, 32816, USA.
| | - Mahed Batarseh
- CREOL, The College of Optics and Photonics, University of Central Florida, 4304 Scorpius, Orlando, Florida, 32816, USA.
| | - Ruitao Wu
- CREOL, The College of Optics and Photonics, University of Central Florida, 4304 Scorpius, Orlando, Florida, 32816, USA.
| | - William M DeCampli
- Pediatric Cardiothoracic Surgery, The Heart Center, Arnold Palmer Hospital for Children, Orlando, Florida, USA
- College of Medicine, University of Central Florida, Orlando, Florida, USA
| | - Aristide Dogariu
- CREOL, The College of Optics and Photonics, University of Central Florida, 4304 Scorpius, Orlando, Florida, 32816, USA.
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DeFilippis AP, Trainor PJ, Thanassoulis G, Brumback LC, Post WS, Tsai MY, Tsimikas S. Atherothrombotic factors and atherosclerotic cardiovascular events: the multi-ethnic study of atherosclerosis. Eur Heart J 2022; 43:971-981. [PMID: 34508626 PMCID: PMC8899529 DOI: 10.1093/eurheartj/ehab600] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 07/09/2021] [Accepted: 08/18/2021] [Indexed: 01/02/2023] Open
Abstract
AIMS Traditional atherosclerotic cardiovascular disease (ASCVD) risk factors fail to address the full spectrum of the complex interplay of atherosclerotic and atherothrombotic factors integral to ASCVD events. This study sought to examine the association between atherothrombotic biomarkers and ASCVD events. METHODS AND RESULTS The association between atherothrombotic biomarkers and 877 ASCVD events with and without adjustment for traditional risk factors was evaluated via Cox proportional hazards models and factor analysis in 5789 Multi-Ethnic Study of Atherosclerosis participants over a median follow-up of 14.7 years. Factor analysis accounted for multidimensional relationship and shared variance among study biomarkers, which identified two new variables: a thrombotic factor (Factor 1), principally defined by shared variance in fibrinogen, plasmin-antiplasmin complex, factor VIII, D-dimer, and lipoprotein(a), and a fibrinolytic factor (Factor 2), principally defined by shared variance of plasminogen and oxidized phospholipids on plasminogen. In a model including both factors, the thrombotic factor was associated with the higher risk of ASCVD events [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.45, 1.70], while the fibrinolytic factor was associated with the lower risk of ASCVD events (HR 0.76, 95% CI 0.70, 0.82), with estimated ASCVD free survival highest for low atherothrombotic Factor 1 and high atherothrombotic Factor 2. CONCLUSION Two atherothrombotic factors, one representative of thrombotic propensity and the other representative of fibrinolytic propensity, were significantly and complementarily associated with incident ASCVD events, remained significantly associated with incident ASCVD after controlling for traditional risk factors, and have promise for identifying patients at high ASCVD event risk specifically due to their atherothrombotic profile.
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Affiliation(s)
- Andrew P DeFilippis
- Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, 1215 21st Avenue South, MCE 5th Floor, North Tower, Nashville, TN 37232, USA
| | - Patrick J Trainor
- Department of Chemistry and Biochemistry, New Mexico State University, 1175 N Horseshoe Dr., Las Cruces, NM 88003, USA
| | - George Thanassoulis
- Department of Medicine, Division of Experimental Medicine, McGill University Health Center, 1001 Decarie Boulevard, Montreal, QC H4A 3J1, Canada
| | - Lyndia C Brumback
- Department of Biostatistics, University of Washington, 1959 NE Pacific Street Seattle, WA 98105, USA
| | - Wendy S Post
- Department of Medicine, Division of Cardiology, Johns Hopkins University, School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA
| | - Michael Y Tsai
- Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware ST SE, Minneapolis, Minnesota 55455, USA
| | - Sotirios Tsimikas
- Division of Cardiology, Department of Medicine, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA
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Olas B, Skalski B. Preparations from Various Organs of Sea Buckthorn ( Elaeagnus rhamnoides (L.) A. Nelson) as Important Regulators of Hemostasis and Their Role in the Treatment and Prevention of Cardiovascular Diseases. Nutrients 2022; 14:991. [PMID: 35267966 PMCID: PMC8912734 DOI: 10.3390/nu14050991] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 02/24/2022] [Accepted: 02/25/2022] [Indexed: 02/01/2023] Open
Abstract
Numerous studies on the chemical composition of various organs of sea buckthorn (Elaeagnus rhamnoides (L.) A. Nelson) have found the plant to be a rich source of vitamins, phenolic compounds, amino acids, fatty acids, and micro- and macro-elements. Furthermore, other studies on preparations from various organs have found them to have significant anti-cancer, anti-ulcer, and hepatoprotective properties, as well as various antibacterial and antiviral activities. This paper reviews the current literature concerning the effect of different sea buckthorn preparations, i.e., extracts and fractions with various chemical contents, on hemostasis, and their positive role in the treatment and prevention of cardiovascular diseases. It also sheds new light on the mechanisms involved in their action on hemostasis both in vivo and in vitro. For these studies, biological materials, including blood platelets, plasma, and blood, were isolated from healthy subjects and those with cardiovascular risk factors. In addition, it describes the cardioprotective potential of commercial products from different organs of sea buckthorn.
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Affiliation(s)
- Beata Olas
- Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236 Łódź, Poland;
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21
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Wang M, Wang R, Li L, Yan Y, Jia S, Jiang H, Du Z. Quantitative proteomics of plasma and liver reveals the mechanism of turmeric in preventing hyperlipidemia in mice. Food Funct 2021; 12:10484-10499. [PMID: 34555841 DOI: 10.1039/d1fo01849c] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hyperlipidemia is manifested by abnormal levels of circulating lipids and may lead to various cardiovascular diseases. Studies have demonstrated that turmeric supplemented in food can effectively prevent hyperlipidemia. The aim of this study is to elucidate the underlying mechanism. 27 male C57BL/6J mice were randomly divided into three groups, which were fed with a standard diet, a high-fat diet and a high-fat diet supplemented with turmeric powder (2.0% w/w), respectively. After eight weeks of feeding, turmeric intervention significantly reduced the plasma TC, TG, and LDL-C levels and the LDL-C/HDL-C ratio of mice compared with high-fat diet fed mice. TMT-based proteomic analysis showed that the expression of 24 proteins in mouse plasma and 76 proteins in mouse liver was significantly altered by turmeric, respectively. Bioinformatics analysis showed that differential proteins in the plasma were mainly involved in complement and coagulation cascades and the cholesterol metabolism pathway. The differential proteins in the liver were mainly involved in arachidonic acid metabolism, steroid hormone biosynthesis and the PPAR signaling pathway. Key differential proteins were successfully validated by western blot analysis. This study is the first to reveal the preventive mechanism of turmeric on hyperlipidemia from proteomics. The results showed that dietary turmeric could prevent hyperlipidemia through regulating the expression of proteins in metabolism pathways.
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Affiliation(s)
- Meiqin Wang
- Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Runjing Wang
- Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Lieyao Li
- Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Yingfei Yan
- Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Shuailong Jia
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Hongliang Jiang
- Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Zhifeng Du
- Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
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22
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Fedorowski A, Siller-Matula JM, Patti G. Thrombosis and fibrinolysis in atherosclerotic cardiovascular disease: it takes two to tango. Eur Heart J 2021; 43:982-984. [PMID: 34686876 DOI: 10.1093/eurheartj/ehab710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- Artur Fedorowski
- Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.,Department of Clinical Sciences, Lund University, Malmö, Sweden
| | - Jolanta M Siller-Matula
- Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Austria.,Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland
| | - Giuseppe Patti
- University of Eastern Piedmont, Department of Thoracic and Cardiovascular Diseases, Maggiore della Carità Hospital, Novara, Italy
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Trikouraki A, Yova D, Pouliakis A, Spathis A, Moulakakis KG, Matsopoulos G. Serum Biomarkers and Classification and Regression Trees Can Discriminate Symptomatic from Asymptomatic Carotid Artery Disease Patients. Artery Res 2021. [DOI: 10.1007/s44200-021-00004-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
Abstract
Objective
To assess biomarkers between symptomatic and asymptomatic patients, and to construct a classification and regression tree (CART) algorithm for their discrimination.
Patients and Methods
136 patients were enrolled. They were symptomatic (high risk) (N = 82, stenosis degree ≥ 50%, proven to be responsible for ischemic stroke the last six months) and asymptomatic (low risk) (N = 54, stenosis degree ≤ 50%). Levels of fibrinogen, matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), soluble intercellular adhesion molecule (SiCAM), soluble vascular cell adhesion molecule (SvCAM), adiponectin and insulin were measured on a Luminex 3D platform and their differences were evaluated; subsequently, a CART model was created and evaluated.
Results
All measured biomarkers, except adiponectin, had significantly higher levels in symptomatic patients. The constructed CART prognostic model had 97.6% discrimination accuracy on symptomatic patients and 79.6% on asymptomatic, while the overall accuracy was 90.4%. Moreover, the population was split into training and test sets for CART validation.
Conclusion
Significant differences were found in the biomarkers between symptomatic and asymptomatic patients. The CART model proved to be a simple decision-making algorithm linked with risk probabilities and provided evidence to identify and, therefore, treat patients being at high risk for cardiovascular disease.
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Shabani M, Bakhshi H, Ostovaneh MR, Ma X, Wu CO, Ambale-Venkatesh B, Blaha MJ, Allison MA, Budoff MJ, Cushman M, Tracy RP, Herrington DM, Szklo M, Cox C, Bluemke DA, Lima JAC. Temporal change in inflammatory biomarkers and risk of cardiovascular events: the Multi-ethnic Study of Atherosclerosis. ESC Heart Fail 2021; 8:3769-3782. [PMID: 34240828 PMCID: PMC8497383 DOI: 10.1002/ehf2.13445] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 05/06/2021] [Accepted: 05/16/2021] [Indexed: 11/30/2022] Open
Abstract
Aims Little is known about the association of temporal changes in inflammatory biomarkers and the risk of death and cardiovascular diseases. We aimed to evaluate the association between temporal changes in C‐reactive protein (CRP), fibrinogen, and interleukin‐6 (IL‐6) and risk of heart failure (HF), cardiovascular disease (CVD), and all‐cause mortality in individuals without a history of prior CVD. Methods and results Participants from the Multi‐Ethnic Study of Atherosclerosis (MESA) cohort with repeated measures of inflammatory biomarkers and no CVD event prior to the second measure were included. Quantitative measures, annual change, and biomarker change categories were used as main predictors in Cox proportional hazard models stratified based on sex and statin use. A total of 2258 subjects (50.6% female, mean age of 62 years) were studied over an average of 8.1 years of follow‐up. The median annual decrease in CRP levels was 0.08 mg/L. Fibrinogen and IL‐6 levels increased by a median of 30 mg/dL and 0.24 pg/mL annually. Temporal changes in CRP were positively associated with HF risk among females (HR: 1.18 per each standard deviation increase, P < 0.001) and other CVD in both female (HR: 1.12, P = 0.004) and male participants (HR: 1.24, P = 0.003). The association of CRP change with HF and other CVD was consistently observed in statin users (HR: 1.23 per SD increase, P = 0.001 for HF and HR: 1.19 per SD increase, P < 0.001 for other CVD). There were no significant associations between temporal changes of fibrinogen or IL‐6 with HF or other CVD. Men with sustained high values of IL‐6 had a 2.3‐fold higher risk of all‐cause mortality (P < 0.001) compared with those with sustained low values. Conclusions Temporal change in CRP is associated with HF only in women and statin users, and other CVD in both women and men, and statin users. Annual changes in fibrinogen and IL‐6 were not predictive of cardiovascular outcomes in either sex.
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Affiliation(s)
- Mahsima Shabani
- Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD, 21287-0409, USA.,Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Hooman Bakhshi
- Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD, 21287-0409, USA.,Inova Heart and Vascular Institute, Falls Church, VA, USA
| | - Mohammad R Ostovaneh
- Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD, 21287-0409, USA.,Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Xiaoyang Ma
- Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USA
| | - Colin O Wu
- Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | | | - Michael J Blaha
- Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD, 21287-0409, USA
| | - Matthew A Allison
- Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA
| | - Matthew J Budoff
- Department of Medicine, Los Angeles Biomedical Research Institute, Torrance, CA, USA
| | - Mary Cushman
- Departments of Medicine and Pathology, University of Vermont, Burlington, VT, USA
| | - Russell P Tracy
- Departments of Pathology & Laboratory Medicine and Biochemistry, Larner College of Medicine at the University of Vermont, Colchester, VT, USA
| | - David M Herrington
- Section on Cardiovascular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Moyses Szklo
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Christopher Cox
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - David A Bluemke
- Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - João A C Lima
- Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD, 21287-0409, USA
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Fibrin(ogen) as a Therapeutic Target: Opportunities and Challenges. Int J Mol Sci 2021; 22:ijms22136916. [PMID: 34203139 PMCID: PMC8268464 DOI: 10.3390/ijms22136916] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 06/23/2021] [Accepted: 06/24/2021] [Indexed: 12/19/2022] Open
Abstract
Fibrinogen is one of the key molecular players in haemostasis. Thrombin-mediated release of fibrinopeptides from fibrinogen converts this soluble protein into a network of fibrin fibres that form a building block for blood clots. Thrombin-activated factor XIII further crosslinks the fibrin fibres and incorporates antifibrinolytic proteins into the network, thus stabilising the clot. The conversion of fibrinogen to fibrin also exposes binding sites for fibrinolytic proteins to limit clot formation and avoid unwanted extension of the fibrin fibres. Altered clot structure and/or incorporation of antifibrinolytic proteins into fibrin networks disturbs the delicate equilibrium between clot formation and lysis, resulting in either unstable clots (predisposing to bleeding events) or persistent clots that are resistant to lysis (increasing risk of thrombosis). In this review, we discuss the factors responsible for alterations in fibrin(ogen) that can modulate clot stability, in turn predisposing to abnormal haemostasis. We also explore the mechanistic pathways that may allow the use of fibrinogen as a potential therapeutic target to treat vascular thrombosis or bleeding disorders. Better understanding of fibrinogen function will help to devise future effective and safe therapies to modulate thrombosis and bleeding risk, while maintaining the fine balance between clot formation and lysis.
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26
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Yarlagadda RD, Johnson J, Vårtun Å, Flo K, Acharya G. Maternal plasma pro-atrial and C-type natriuretic peptide levels and their associations with cardiovascular and renal function in the second half of normal pregnancy: a longitudinal study. BMC Pregnancy Childbirth 2021; 21:358. [PMID: 33952207 PMCID: PMC8097896 DOI: 10.1186/s12884-021-03824-3] [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] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 04/21/2021] [Indexed: 10/31/2022] Open
Abstract
BACKGROUND Physiological adaptation in pregnancy is characterized by remodeling of endocrine, cardiovascular and renal functions leading to fluid retention, volume expansion, altered cardiac loading conditions and hyperdynamic circulation. Natriuretic peptides have been used as biomarkers of cardiovascular function, but their associations with gestational age-related changes in maternal cardiac, endothelial and renal function have not been elucidated. The aim of this study was to establish longitudinal reference values for maternal plasma atrial natriuretic peptide (proANP) and C-type natriuretic peptide (CNP) and investigate their temporal association with cardiovascular and renal function in the second half of pregnancy. METHODS This study was a prospective longitudinal study of 53 low-risk pregnancies. Women were examined every 3-5 weeks during 22-40 weeks of gestation (252 observations). Fasting maternal blood samples were obtained to measure proANP, CNP, creatinine, cystatin C, uric acid, and fibrinogen levels. Cardiac function and systemic hemodynamics were assessed noninvasively by impedance cardiography (ICG) and vascular endothelial function by flow-mediated vasodilation of brachial artery (FMD). RESULTS The plasma proANP (R2adj = 0.79; P = 0.007), CNP (R2adj = 0.54; P = 0.005) decreased between 22 and 40 weeks. The creatinine (R2adj = 0.90; P < 0.001), cystatin C (R2adj = 0.93; P = < 0.001) and uric acid (R2adj = 0.83; P < 0.001) increased significantly, whereas the estimated glomerular filtration rate (R2adj = 0.93; P < 0.001) decreased with gestational age. The FMD did not change significantly but fibrinogen (R2adj = 0.79; P < 0.001) increased with advancing gestation. The maternal systemic vascular resistance index (R2adj = 0.50; P < 0.001) increased, stroke index (R2adj = 0.62; P < 0.001) decreased, whereas the cardiac index (R2adj = 0.62; P = 0.438) and thoracic fluid content (R2adj = 0.72; P = 0.132) did not change significantly with gestation. The proANP was associated with thoracic fluid content (R2adj = 0.74; P < 0.001) and fibrinogen (R2adj = 0.78; P = 0.034) but not with other variables of systemic hemodynamics, endothelial function, or renal function. The CNP was not associated significantly with parameters of cardiovascular or renal function. CONCLUSION Longitudinal reference values for maternal plasma proANP and CNP were established. These natriuretic peptides decreased slightly with advancing gestation, but they did not reflect the temporal physiological changes in maternal systemic hemodynamics, vascular endothelial function and renal function during the second half of pregnancy. The proANP correlated with the thoracic fluid content reflecting volume load in pregnancy.
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Affiliation(s)
- Rima D Yarlagadda
- Department of Clinical Medicine, Women's Health and Perinatology Research Group, UiT-The Arctic University of Norway, Tromsø, Norway
- The University of Virginia, College of Arts and Science, Charlottesville, VA, USA
| | - Jonas Johnson
- Division of Obstetrics and Gynecology, CLINTEC, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Åse Vårtun
- Department of Clinical Medicine, Women's Health and Perinatology Research Group, UiT-The Arctic University of Norway, Tromsø, Norway
| | - Kari Flo
- Department of Clinical Medicine, Women's Health and Perinatology Research Group, UiT-The Arctic University of Norway, Tromsø, Norway
- University Hospital of North Norway, Tromsø, Norway
- Department of Obstetrics and Gynecology, Akershus University Hospital, Lørenskog, Norway
| | - Ganesh Acharya
- Department of Clinical Medicine, Women's Health and Perinatology Research Group, UiT-The Arctic University of Norway, Tromsø, Norway.
- Division of Obstetrics and Gynecology, CLINTEC, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
- University Hospital of North Norway, Tromsø, Norway.
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Liu X, Yu Z, Wen D, Ma L, You C. Prognostic value of albumin-fibrinogen ratio in subarachnoid hemorrhage patients. Medicine (Baltimore) 2021; 100:e25764. [PMID: 33907173 PMCID: PMC8084098 DOI: 10.1097/md.0000000000025764] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 03/30/2021] [Accepted: 04/13/2021] [Indexed: 02/05/2023] Open
Abstract
ABSTRACT Inflammation plays an important role in the pathophysiology of subarachnoid hemorrhage (SAH). Recent studies have indicated that the albumin to fibrinogen ratio (AFR) is a useful biomarker of inflammation.This research aimed to determine the ability of AFR to predict the prognosis of patients with SAH.A total of 440 patients with SAH who had been diagnosed within 72 hours of symptom onset were retrospectively reviewed. Clinical findings and laboratory data were retrieved from the hospital database. Functional outcome was measured according to the modified Rankin scale at 30 days. Logistic regression analysis was used to evaluate the correlation between AFR and the prognosis of patients with SAH. Receiver operating characteristic (ROC) analysis was performed to determine the prognostic ability of AFR at admission to predict the 30-day outcomes.The average age of all 440 patients with SAH was 56.75 ± 11.19 years and 31.4% (138) were male. Of these patients, 161 exhibited unfavorable outcomes at 30 days. According to the multivariate logistic regression analysis, the AFR was positively correlated with the outcome of patients with SAH (odds ratio 0.939, 95% confidence interval 0.885-0.996, P = .038). The ROC analysis revealed an area under the curve of 0.713 for AFR's ability to predict the 30-day outcomes.AFR is independently associated with the outcome of SAH patients. As a parameter that can be easily assessed at admission, AFR could be used to help the decision-making of clinical treatment.
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Deokar K, Meshram S, Chawla G, Kunjir N, Meshram C, Abrol N, Gaikwad P. Obstructive sleep apnea, intermittent hypoxemia and prothrombotic biomarkers. SLEEP SCIENCE (SAO PAULO, BRAZIL) 2021; 13:230-234. [PMID: 33564369 PMCID: PMC7856672 DOI: 10.5935/1984-0063.20190147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Objective To study the serum levels of fibrinogen and d-dimer in patients with obstructive sleep apnea (OSA) and its correlation with apnea hypopnea index (AHI), oxygen desaturation index (ODI), minimal oxygen saturation and arousal index. Methods It was a case control study in which 23 cases of OSA and 23 controls were enrolled. Morning fasting serum fibrinogen and d-dimer were measured in cases of OSA and controls. Results Serum fibrinogen levels among OSA patients (268.47±53.11mg/dl) were elevated as compared to the levels in controls (221.52±65.84mg/dl) (p<0.05). Serum fibrinogen co-related positively with AHI (r=0.6381, p=0.0011) and ODI (r=0.7434, p=0.0000), negatively with minimal oxygen saturation (r=-0.4461, p=0.0329). There was no statistically significant correlation of fibrinogen with arousal index (r=0.2697, p=0.2133). There was no statistically significant difference between mean fasting d-dimer level in cases (0.12mg/L, 0.06±0.18mg/L) and controls (0.12mg/L, 0.02±0.22mg/L) (p=0.8926). Conclusions The observation of elevated fibrinogen levels with the increasing severity of OSA and hypoxemic events makes OSA one of the important risk factor for cardiovascular disorders.
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Affiliation(s)
- Kunal Deokar
- Government medical college, Pulmonary Medicine - Nagpur - Maharashtra - India
| | - Sushant Meshram
- Government medical college, Pulmonary Medicine - Nagpur - Maharashtra - India
| | - Gopal Chawla
- All India Institute of Medical Sciences, Pulmonary Medicine and Sleep Disorders - New Delhi - Delhi - India
| | - Nana Kunjir
- Government medical college, Pulmonary Medicine - Nagpur - Maharashtra - India
| | - Chetna Meshram
- Government medical college, Pharmacology - Nagpur - Maharashtra - India
| | - Nupur Abrol
- All India Institute of Medical Sciences, Anaesthesia - Delhi - Delhi - India
| | - Priyanka Gaikwad
- Bhaktivedanta hospital, Paediatrics - Mumbai - Maharashtra - India
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Atzeni F, Nucera V, Gerratana E, Fiorenza A, Gianturco L, Corda M, Sarzi-Puttini P. Cardiovascular Consequences of Autoimmune Rheumatic Diseases. Curr Vasc Pharmacol 2020; 18:566-579. [PMID: 31985379 DOI: 10.2174/1570161118666200127142936] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 12/23/2019] [Accepted: 12/28/2019] [Indexed: 12/23/2022]
Abstract
The increased risk of cardiovascular disease (CVD) among patients with autoimmune rheumatic diseases such as rheumatoid arthritis, spondyloarthritis and systemic lupus erythematosus has been extensively documented. Sub-clinical atherosclerosis can be assessed using various non-invasive imaging techniques. However, the mechanisms underlying the higher risk of atherosclerotic CVD in patients with autoimmune rheumatic diseases are not fully known, although they seem to include chronic low-grade systemic inflammation leading to prolonged endothelial activation, accompanied by a pro-thrombotic/pro-coagulant and autoantibody state. Furthermore, sub-clinical atherosclerosis is also influenced by other traditional risk factors for CVD. Including the individual components of the metabolic syndrome (MetS: obesity, impaired glucose metabolism, dyslipidemia and high blood pressure), the degree of which is higher in these patients than in controls. The aim of this narrative review is to discuss the CV manifestations and risk factors involved in the increased risk of CVD among patients with autoimmune rheumatic diseases.
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Affiliation(s)
- Fabiola Atzeni
- Rheumatology Unit, University of Messina, Messina, Italy
| | - Valeria Nucera
- Rheumatology Unit, University of Messina, Messina, Italy
| | | | | | - Luigi Gianturco
- Cardiology Unit, Beato Matteo Hospital, GSD Hospitals, Vigevano, Pavia, Italy
| | - Marco Corda
- Cardiology Unit, Brotzu Hospital, Cagliari, Italy
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Liu J, Zhang Y, Lavie CJ, Tabung FK, Xu J, Hu Q, He L, Zhang Y. Associations of C-reactive protein and fibrinogen with mortality from all-causes, cardiovascular disease and cancer among U.S. adults. Prev Med 2020; 139:106044. [PMID: 32097752 DOI: 10.1016/j.ypmed.2020.106044] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 01/22/2020] [Accepted: 02/22/2020] [Indexed: 01/05/2023]
Abstract
C-reactive protein (CRP) and fibrinogen are associated with an increased risk of death with suggested differences by gender, diet quality and race/ethnicity. However, the current evidence is limited. We used data including 8646 men and 9880 women from the National Health and Nutrition Examination Survey (NHANES) Linked Morality cohort (1999-2011) to investigate the associations of CRP and fibrinogen with mortality overall and by gender, race/ethnicity and diet quality. Cox-proportional hazard model was used to quantify the associations. With a median follow-up of 6 years, a strong dose-response relationship was observed between CRP levels and mortality risk in men after multivariable adjustment. For subjects who survived the first two years, the adjusted hazard ratios (HRs) for total mortality across quartiles (from lower to higher) of CRP were 1.97 (95% CI: 0.62-6.33), 1.89 (0.59, 6.06) and 6.34 (2.28-17.7) (P for trend <0.001). For cardiovascular disease (CVD) mortality, its association with CRP varied by diet quality. For cancer mortality, its association differed by history of cancer, and positive associations were observed only among subjects with history of cancer. In contrast, no such association of CRP with mortality was found in women. For fibrinogen, we observed its positive association with total mortality and the HRs across quartiles of fibrinogen (from lower to higher) were 1.21 (0.88, 1.67), 1.49 (1.22, 1.82) and 1.99 (1.56, 2.55). The association with CVD mortality differed by diet quality whereas no association was found with cancer mortality. Our findings suggest that higher levels of CRP and fibrinogen were associated with lower survival from total and CVD; the associations of CRP with mortality were more pronounced in men than women. Diet quality is an effect modifier for the association of CRP and fibrinogen with CVD mortality.
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Affiliation(s)
- Junxiu Liu
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA
| | - Yanan Zhang
- Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA
| | - Carl J Lavie
- John Ochsner Heart and Vascular Institute, Ochsner Clinical School-the University of Queensland School of Medicine, New Orleans, LA 70121, USA
| | - Fred K Tabung
- Division of Medical Oncology, The Ohio State University College of Medicine and Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH 43221, USA
| | - Jiting Xu
- Department of Computer Science and Engineering, University of South Carolina, Columbia, SC 29201, USA
| | - Qingwei Hu
- Department of Public Health Sciences, University of Clemson, Clemson, SC 29631, USA
| | - Lixia He
- Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA
| | - Yunxiang Zhang
- Department of Pathology, Weifang People's Hospital, Weifang, Shandong 261053, China.
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Abstract
Biomarkers are widely used for the diagnosing of diseases, evaluation of their severity, prediction of outcomes, and for monitoring the effectiveness and safety of targeted therapy. This review describes specific cardiac biomarkers approved by FDA (Food and Drug AdministrationбUSA). The list of described biomarkers is not exhaustive. In addition to the general concepts of biomarkers, definitions and classification, this Part I of the review contains data on diagnostic and prognostic biomarkers of cardiovascular diseases associated with atherosclerosis.
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Affiliation(s)
| | - N. G. Gumanova
- National Medical Center for Therapy and Preventive Medicine
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32
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Abstract
Blood viscosity is increased by elevated concentrations of acute phase reactants and hypergammaglobulinemia in inflammation. These increase blood viscosity by increasing plasma viscosity and fostering erythrocyte aggregation. Blood viscosity is also increased by decreased erythrocyte deformability, as occurs in malaria. Increased blood viscosity contributes to the association of acute infections with myocardial infarction (MI), venous thrombosis, and venous thromboembolism. It also increases vascular resistance, which decreases tissue perfusion and activates stretch receptors in the left ventricle, thereby initiating the systemic vascular resistance response. This compensates for the increased vascular resistance by vasodilation, lowering hematocrit, and decreasing intravascular volume. This physiological response causes the anemias associated with malaria, chronic inflammation, and other chronic diseases. Since tissue perfusion is inversely proportional to blood viscosity, anemia may be beneficial as it increases tissue perfusion when erythrocyte aggregating factors or erythrocytes with decreased deformability are present in the blood.
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Affiliation(s)
- Gregory D Sloop
- Pathology, Idaho College of Osteopathic Medicine, Meridian, USA
| | - Quirijn De Mast
- Internal Medicine, Radboud University Medical Center, Nijmegan, NLD
| | - Gheorghe Pop
- Cardiology, Radboud University Medical Center, Nijmegen, NLD
| | | | - John A St Cyr
- Cardiac/Thoracic/Vascular Surgery, Jacqmar, Inc., Minneapolis, USA
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33
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Araújo DM, Rodrigues CEM, Gonçalves NGG, Rabelo-Júnior CN, Lobo MDP, Moreira RDA, Monteiro-Moreira ACDO. Proteins Involved in the Induction of Procoagulant Activity and Autoimmune Response in Patients With Primary Antiphospholipid Syndrome. Clin Appl Thromb Hemost 2020; 26:1076029620905338. [PMID: 32299226 PMCID: PMC7289064 DOI: 10.1177/1076029620905338] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 01/02/2020] [Accepted: 01/15/2020] [Indexed: 12/19/2022] Open
Abstract
The aim of this study was to determine the plasma protein profile of patients with primary antiphospholipid syndrome (PAPS) compared to healthy controls and identify proteins that might be used in the evaluation, diagnosis, and prognosis of this condition. The sample consisted of 14 patients with PAPS and 17 sex- and age-matched controls. Plasma samples were submitted to proteomic analysis (albumin and immunoglobulin G depletion, concentration, digestion, and label-free data-independent mass spectrometry). The software ExpressionE was used to quantify intergroup differences in protein expression. The analysis yielded 65 plasma proteins of which 11 were differentially expressed (9 upregulated and 2 downregulated) in relation to controls. Four of these are known to play a role in pathophysiological mechanisms of thrombosis: fibrinogen α chain, fibrinogen α chain, apolipoprotein C-III, and α-1-glycoprotein-1. Our analysis revealed autoimmune response and the presence of proteins believed to be functionally involved in the induction of procoagulant activity in patients with PAPS. Further studies are necessary to confirm our findings and may eventually lead to the development of significantly more accurate diagnostic tools.
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34
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Sangiorgi G, Biondi-Zoccai G, Pizzuto A, Martelli E. Commentary: Biochemical Markers for Diagnosis and Follow-up of Aortic Diseases: An Endless Search for the Holy Grail. J Endovasc Ther 2019; 26:836-842. [PMID: 31608740 DOI: 10.1177/1526602819879941] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Giuseppe Sangiorgi
- Department of Systemic Medicine, Division of Cardiology, University of Tor Vergata, Rome, Italy
| | - Giuseppe Biondi-Zoccai
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
- Mediterranea Cardiocentro, Napoli, Italy
| | - Alessandra Pizzuto
- Department of Systemic Medicine, Division of Cardiology, University of Tor Vergata, Rome, Italy
| | - Eugenio Martelli
- Department of Medical, Surgical and Experimental Sciences, Division of Vascular Surgery, University of Sassari, Italy
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35
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Sit I, Xu Z, Grassian VH. Plasma protein adsorption on TiO2 nanoparticles: Impact of surface adsorption on temperature-dependent structural changes. Polyhedron 2019. [DOI: 10.1016/j.poly.2019.06.036] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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36
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Smith L, Yang L, Hamer M. Handgrip strength, inflammatory markers, and mortality. Scand J Med Sci Sports 2019; 29:1190-1196. [PMID: 30972827 DOI: 10.1111/sms.13433] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 03/22/2019] [Accepted: 04/04/2019] [Indexed: 12/14/2022]
Abstract
PURPOSE To investigate the extent to which inflammatory markers explain the association between handgrip strength and mortality. METHODS Analyses of data from The English Longitudinal Study of Ageing. Handgrip strength and inflammatory marker data (C-reactive protein and fibrinogen) were collected at baseline (2004/5) and inflammatory marker data at follow-up (2012/13). Participant data were linked with death records. General linear models were used to explore associations between handgrip strength and inflammatory markers at follow-up. Cox proportional hazards regression models were used to examine associations between grip strength and risk of death. Models were estimated with the covariates age, sex, wealth, physical activity, smoking, depressive symptoms, long-standing illness, and adiposity. RESULTS The sample comprised of 5,240 participants (mean age 65.9 (SD 9.4) years; 53.8% female). Over an average 9.7 ± 1.4 years follow-up, there were 650 deaths. Inverse associations were evident between handgrip strength and change in inflammatory markers in women only. There was an association between grip strength and lower risk of mortality in women (hazard ratio = 0.85; 95% CI, 0.74, 0.98) after adjusting for age and wealth. The association was attenuated after adjustment for clinical and behavioral risk factors (0.92; 0.79, 1.07), and further attenuated after adjusting for inflammatory markers (0.95; 0.82, 1.11). CONCLUSION Higher grip strength is associated with lower levels of inflammation at 8-year follow-up, and inflammatory markers partly explained the association between handgrip strength and mortality.
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Affiliation(s)
- Lee Smith
- The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, UK
| | - Lin Yang
- Department of Epidemiology, Medical University of Vienna, Vienna, Austria
| | - Mark Hamer
- School Sport, Exercise Health Sciences, Loughborough University, Loughborough, UK
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37
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Searching for the Genetic Determinants of Peripheral Arterial Disease: A Review of the Literature and Future Directions. Cardiol Rev 2019; 27:145-152. [PMID: 30946061 DOI: 10.1097/crd.0000000000000231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Peripheral arterial disease (PAD) is a significant but under-recognized disease that is poorly understood despite population-scale genetic studies. To address this morbid disease, clinicians need additional tools to identify, prevent, and treat patients at risk for PAD. Genetic studies of coronary artery disease have yielded promising results for clinical application, which have thus far been lacking in PAD. In this article, we review recent findings, discuss limitations, and propose future directions of genomic study and clinical application. However, despite many studies, we still lack definitive genetic markers for PAD. This can be attributed to the heterogeneity of PAD's pathogenesis and clinical manifestations, as well as inconsistencies in study methodologies, limitations of current genetic assessment techniques, incompletely comprehended molecular pathophysiology, and confounding generalized atherosclerotic risk factors. The goals of this review are to evaluate the limitations of our current genetic knowledge of PAD and to propose approaches to expedite the identification of valuable markers of PAD.
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38
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Predilection of Low Protein C-induced Spontaneous Atherothrombosis for the Right Coronary Sinus in Apolipoprotein E deficient mice. Sci Rep 2018; 8:15106. [PMID: 30305662 PMCID: PMC6180072 DOI: 10.1038/s41598-018-32584-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 08/24/2018] [Indexed: 01/31/2023] Open
Abstract
Silencing of anticoagulant protein C using RNA interference (siProc) evokes low incident but spontaneous atherothrombosis in the aortic root of apolipoprotein E–deficient (Apoe−/−) mice. The aims of the current study were (1) to analyze if plaque characteristics or circulating factors could be linked to atherothrombosis susceptibility, (2) to increase the incidence of atherothrombosis by transiently increasing blood pressure, and (3) to direct atherothrombosis to an additional predefined vascular site by applying a semi-constrictive collar around the carotid artery. siProc-driven spontaneous atherothrombosis in the aortic root of Apoe−/− mice was reproduced and occurred at an incidence of 23% (9 out of 39 mice), while the incidence of collar-induced atherothrombosis in the carotid artery was 2.6% (1 out of 39 mice). Treatment with phenylephrine, to transiently increase blood pressure, did not increase atherothrombosis in the aortic root of the Apoe−/− mice nor in the carotid arteries with collars. Plaques in the aortic root with an associated thrombus were lower in collagen and macrophage content, and mice with atherothrombosis had significantly more circulating platelets. Plasma protein C, white blood cell counts, total cholesterol, fibrinogen, serum amyloid A, and IL-6 were not different amongst siProc treated mice with or without thrombosis. Remarkably, our data revealed that thrombus formation preferably occurred on plaques in the right coronary sinus of the aortic root. In conclusion, there is a predilection of low protein C-induced spontaneous atherothrombosis in Apoe−/− mice for the right coronary sinus, a process that is associated with an increase in platelets and plaques lower in collagen and macrophage content.
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39
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Walker GE, Follenzi A, Bruscaggin V, Manfredi M, Bellone S, Marengo E, Maiuri L, Prodam F, Bona G. Fetuin B links vitamin D deficiency and pediatric obesity: Direct negative regulation by vitamin D. J Steroid Biochem Mol Biol 2018; 182:37-49. [PMID: 29684480 PMCID: PMC6092561 DOI: 10.1016/j.jsbmb.2018.04.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Revised: 03/30/2018] [Accepted: 04/17/2018] [Indexed: 12/13/2022]
Abstract
Vitamin D (VD) deficiency (VDD) correlates to obesity, with VD a recognized mediator of metabolic diseases. From a previous proteomic study identifying adiponectin as a link between VDD and pediatric obesity, herein we analysed another protein (SSP2301) increased with VDD. A focused 2D-electrophoretic analysis identified 4 corresponding plasma proteins, with one predicted to be fetuin B (FETUB). FETUB was studied due to its emerging role in metabolic diseases and cytogenetic location (3q27.3) with adiponectin. Results were confirmed in obese children, where plasma FETUB was higher with VDD. A direct effect by 1α,25-(OH)2D3 on hepatocellular FETUB synthesis was observed, with a time and dose dependent reduction. Further, we demonstrated the VD-receptor (VDR) is key, with FETUB "released" with VDR silencing. Finally, VD supplementation (6weeks) to juvenile mice fed a standard diet, reduced plasma FETUB. Only at 22weeks did liver FETUB correspond to plasma FETUB, highlighting the contribution of other VD-responsive tissues. Overall, FETUB is a key protein linking VDD to pediatric obesity. With an emerging role in metabolic diseases, we demonstrate that VD/VDR directly regulate FETUB.
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Affiliation(s)
- Gillian E Walker
- Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy.
| | - Antonia Follenzi
- Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy
| | | | - Marcello Manfredi
- Isalit S.R.L., Department of Science Innovation and Technology, Università del Piemonte Orientale, Novara, Italy
| | - Simonetta Bellone
- Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy; Division of Pediatrics, Università del Piemonte Orientale, Novara, Italy
| | - Emilio Marengo
- Isalit S.R.L., Department of Science Innovation and Technology, Università del Piemonte Orientale, Novara, Italy
| | - Luigi Maiuri
- Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy; Division of Pediatrics, Università del Piemonte Orientale, Novara, Italy
| | - Flavia Prodam
- Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy; Division of Pediatrics, Università del Piemonte Orientale, Novara, Italy
| | - Gianni Bona
- Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy; Division of Pediatrics, Università del Piemonte Orientale, Novara, Italy
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40
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Agu KC. Diabetes mellitus: A review of some of the prognostic markers of response to treatment and management. JOURNAL OF INSULIN RESISTANCE 2018. [DOI: 10.4102/jir.v3i1.36] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
Background: The WHO defined ‘diabetes mellitus’ (DM) as a metabolic disorder characterised by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from the defect in insulin secretion, or inaction, or both. When not identified early and controlled, acute and chronic life-threatening consequences may result. Identifying DM early for treatment and management, as well as clinically monitoring recovery and improvement during treatment, involves the assessments of biomarkers. The types, choice, sensitivity and descriptive information trends of these biomarkers are very important. Aim: Some prognostic biomarkers and parameters that this review identified include glycated haemoglobin, white blood cells, mean neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, total leukocytes and neutrophils, plasma low-density lipoprotein, high-density lipoprotein and very low-density lipoprotein, platelet, fibrinogen, D-dimer and C-reactive proteins. Results: These parameters display increases in DM, while red blood cell, haemoglobin concentration, activated partial thromboplastin time, prothrombin time and partial thromboplastin time are decreased. Conclusion: With sound knowledge of the variations of these markers and parameters, observed reversal during treatment and management of DM and its complications can be better monitored, and guided decisions can be made.
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41
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Lai CL, Xing JP, Liu XH, Qi J, Zhao JQ, Ji YR, Yang WX, Yan PJ, Luo CY, Ruan LF. Relationships of Inflammatory Factors and Risk Factors with Different Target Organ Damage in Essential Hypertension Patients. Chin Med J (Engl) 2018; 130:1296-1302. [PMID: 28524828 PMCID: PMC5455038 DOI: 10.4103/0366-6999.206343] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Atherosclerosis (AS) is an inflammatory disease. Inflammation was considered to play a role in the whole process of AS. This study aimed to analyze the relationships of inflammatory factors and risk factors with different target organ damages (TOD) in essential hypertension (EH) patients and to explore its clinical significance. METHODS A total of 294 EH patients were selected and divided into four groups according to their conditions of TOD. Forty-eight healthy subjects were selected as control. The clinical biochemical parameters, serum amyloid A, serum tryptase, and lipoprotein-associated phospholipase A2 (Lp-PLA2) in each group were detected, and the related risk factors were also statistically analyzed. RESULTS Fibrinogen (Fbg) was the most significant independent risk factor in acute coronary syndrome (ACS) group (odds ratio [OR]: 22.242, 95% confidence interval [CI]: 6.458-76.609, P< 0.001) with the largest absolute value of the standardized partial regression coefficient B' (b': 1.079). Lp-PLA2 was the most significant independent risk factor in stroke group (OR: 13.699, 95% CI: 5.236-35.837, P< 0.001) with b' = 0.708. Uric acid (UA) was the most significant independent risk factor in renal damage group (OR: 15.307, 95% CI: 4.022-58.250, P< 0.001) with b' = 1.026. CONCLUSIONS Fbg, Lp-PLA2, and UA are the strongest independent risk factors toward the occurrence of ACS, ischemic stroke, and renal damage in EH patients, thus exhibiting the greatest impacts on the occurrence of ACS, ischemic stroke, and renal damage in EH patients, respectively.
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Affiliation(s)
- Chun-Lin Lai
- Department of Cardiology, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030012, China
| | - Jin-Ping Xing
- Department of Cardiology, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030012, China
| | - Xiao-Hong Liu
- Department of Cardiology, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030012, China
| | - Jie Qi
- Department of Cardiology, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030012, China
| | - Jian-Qiang Zhao
- Department of Cardiology, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030012, China
| | - You-Rui Ji
- Department of Cardiology, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030012, China
| | - Wu-Xiao Yang
- Department of Cardiology, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030012, China
| | - Pu-Juan Yan
- Postgraduate School of Shanxi Medical University, Taiyuan, Shanxi 030012, China
| | - Chun-Yan Luo
- Postgraduate School of Shanxi Medical University, Taiyuan, Shanxi 030012, China
| | - Lu-Fang Ruan
- Postgraduate School of Shanxi Medical University, Taiyuan, Shanxi 030012, China
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Peck MJ, Sanders EB, Scherer G, Lüdicke F, Weitkunat R. Review of biomarkers to assess the effects of switching from cigarettes to modified risk tobacco products. Biomarkers 2018; 23:213-244. [PMID: 29297706 DOI: 10.1080/1354750x.2017.1419284] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Context: One approach to reducing the harm caused by cigarette smoking, at both individual and population level, is to develop, assess and commercialize modified risk alternatives that adult smokers can switch to. Studies to demonstrate the exposure and risk reduction potential of such products generally involve the measuring of biomarkers, of both exposure and effect, sampled in various biological matrices.Objective: In this review, we detail the pros and cons for using several biomarkers as indicators of effects of changing from conventional cigarettes to modified risk products.Materials and methods: English language publications between 2008 and 2017 were retrieved from PubMed using the same search criteria for each of the 25 assessed biomarkers. Nine exclusion criteria were applied to exclude non-relevant publications.Results: A total of 8876 articles were retrieved (of which 7476 were excluded according to the exclusion criteria). The literature indicates that not all assessed biomarkers return to baseline levels following smoking cessation during the study periods but that nine had potential for use in medium to long-term studies.Discussion and conclusion: In clinical studies, it is important to choose biomarkers that show the biological effect of cessation within the duration of the study.
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Affiliation(s)
| | | | | | - Frank Lüdicke
- Research & Development, Philip Morris International, Neuchâtel, Switzerland
| | - Rolf Weitkunat
- Research & Development, Philip Morris International, Neuchâtel, Switzerland
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44
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Amor AJ, Ortega E, Perea V, Cofán M, Sala-Vila A, Nuñez I, Gilabert R, Ros E. Relationship Between Total Serum Bilirubin Levels and Carotid and Femoral Atherosclerosis in Familial Dyslipidemia. Arterioscler Thromb Vasc Biol 2017; 37:2356-2363. [DOI: 10.1161/atvbaha.117.310071] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Accepted: 10/09/2017] [Indexed: 01/09/2023]
Abstract
Objective—
Bilirubin is a potent antioxidant that has been inversely related to cardiovascular disease. There is little information on serum total bilirubin (TB) in relation to atherosclerosis in familial dyslipidemia. We assessed the association between TB and carotid and femoral atherosclerosis in this high-risk group.
Approach and Results—
We evaluated 464 individuals with familial dyslipidemia (56% men; median age, 48 years), 322 with familial hypercholesterolemia, and 142 with familial combined hyperlipidemia. Carotid and femoral arteries were imaged bilaterally with a standardized ultrasonographic protocol. Mean and maximum intima-media thickness and plaque presence (≥1.2 mm) and height were recorded. Cross-sectional associations between TB and atherosclerosis variables were investigated in multivariable-adjusted models, including lipid values and hypolipidemic drug use. Inflammatory markers (C-reactive protein, total leukocyte count, and lipoprotein[a]) were also determined. Increasing TB levels were associated with decreasing intima-media thickness of all carotid segments (
P
<0.05, all). TB also related to carotid plaque, present in 78% of individuals, and to plaque burden (≥3 plaques), with odds ratios (95% confidence interval) 0.59 (0.36–0.98) and 0.57 (0.34–0.96) for each increase of 0.5 mg in TB, respectively. Findings were confirmed in a validation cohort of 177 subjects with nonfamilial dyslipidemia. Only the familial combined hyperlipidemia group, with higher inflammation-related markers, showed an inverse association between TB and femoral plaque height (β=−0.183;
P
=0.030).
Conclusions—
TB was inversely and independently associated with carotid plaque burden in familial and nonfamilial dyslipidemia. These findings support the use of TB as a biomarker of atherosclerosis in this high-risk group.
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Affiliation(s)
- Antonio J. Amor
- From the Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Service of Endocrinology, Hospital Universitari Mútua de Terrassa, Spain (V.P.); and Vascular Unit, Centre de Diagnòstic per l’Imatge, Institut d’Investigacions Biomèdiques
| | - Emilio Ortega
- From the Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Service of Endocrinology, Hospital Universitari Mútua de Terrassa, Spain (V.P.); and Vascular Unit, Centre de Diagnòstic per l’Imatge, Institut d’Investigacions Biomèdiques
| | - Verónica Perea
- From the Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Service of Endocrinology, Hospital Universitari Mútua de Terrassa, Spain (V.P.); and Vascular Unit, Centre de Diagnòstic per l’Imatge, Institut d’Investigacions Biomèdiques
| | - Montserrat Cofán
- From the Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Service of Endocrinology, Hospital Universitari Mútua de Terrassa, Spain (V.P.); and Vascular Unit, Centre de Diagnòstic per l’Imatge, Institut d’Investigacions Biomèdiques
| | - Aleix Sala-Vila
- From the Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Service of Endocrinology, Hospital Universitari Mútua de Terrassa, Spain (V.P.); and Vascular Unit, Centre de Diagnòstic per l’Imatge, Institut d’Investigacions Biomèdiques
| | - Isabel Nuñez
- From the Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Service of Endocrinology, Hospital Universitari Mútua de Terrassa, Spain (V.P.); and Vascular Unit, Centre de Diagnòstic per l’Imatge, Institut d’Investigacions Biomèdiques
| | - Rosa Gilabert
- From the Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Service of Endocrinology, Hospital Universitari Mútua de Terrassa, Spain (V.P.); and Vascular Unit, Centre de Diagnòstic per l’Imatge, Institut d’Investigacions Biomèdiques
| | - Emilio Ros
- From the Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain (A.J.A., E.O., M.C., A.S.-V., E.R.); Service of Endocrinology, Hospital Universitari Mútua de Terrassa, Spain (V.P.); and Vascular Unit, Centre de Diagnòstic per l’Imatge, Institut d’Investigacions Biomèdiques
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Eddy P, Wertheim EH, Kingsley M, Wright BJ. Associations between the effort-reward imbalance model of workplace stress and indices of cardiovascular health: A systematic review and meta-analysis. Neurosci Biobehav Rev 2017; 83:252-266. [DOI: 10.1016/j.neubiorev.2017.10.025] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Revised: 10/25/2017] [Accepted: 10/26/2017] [Indexed: 01/16/2023]
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Yang C, Kwak L, Ballew SH, Garimella PS, Jaar BG, Folsom AR, Heiss G, Selvin E, Lutsey PL, Coresh J, Matsushita K. Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease. Atherosclerosis 2017; 267:167-174. [PMID: 28992939 PMCID: PMC5705382 DOI: 10.1016/j.atherosclerosis.2017.09.020] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 08/25/2017] [Accepted: 09/19/2017] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIMS Reduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function. METHODS Using data from 12,472 participants at baseline (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus). RESULTS During a median follow-up of 21 years, 471 participants developed incident PAD. Low eGFR was significantly associated with future PAD risk, with slightly stronger relationship when cystatin C was used (adjusted hazard ratio [HR] 6.3-8.3 for eGFR <30 and 2.4-3.5 for eGFR 30-59 vs. eGFR ≥90 mL/min/1.73 m2). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91-3.54] for B2M vs. 1.20 [0.91-1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including kidney function (HR 1.47 [1.11-1.94] in top quartile). CONCLUSIONS Kidney dysfunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond kidney function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD.
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Affiliation(s)
- Chao Yang
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Lucia Kwak
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | | | | | | | - Aaron R Folsom
- University of Minnesota School of Public Health, Minneapolis, MN, USA
| | - Gerardo Heiss
- University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, NC, USA
| | - Elizabeth Selvin
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Pamela L Lutsey
- University of Minnesota School of Public Health, Minneapolis, MN, USA
| | - Josef Coresh
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Johns Hopkins School of Medicine, Baltimore, MD, USA
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Park YA, Kong TH, Seo YJ. A sustained increase of plasma fibrinogen in sudden sensorineural hearing loss predicts worse outcome independently. Am J Otolaryngol 2017; 38:484-487. [PMID: 28502595 DOI: 10.1016/j.amjoto.2017.05.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Revised: 04/26/2017] [Accepted: 05/05/2017] [Indexed: 12/20/2022]
Abstract
OBJECTIVES A number of etiologies of idiopathic sudden sensorineural hearing loss (ISSNHL) have been proposed. Vascular disturbance is one cause of ISSNHL and has been reported to be associated with fibrinogen. We aimed to determine whether hyperfibrinogenemia is associated with poor outcome and whether a serial change in fibrinogen level is associated with outcome. METHODS Twenty-two patients with ISSNHL were enrolled. We compared the levels of fibrinogen in ISSNHL groups classified as improved and non-improved according to improvement of hearing. Blood samples were also collected from patients who visited the emergency room with coronary heart disease (CHD) as the control group. RESULTS Initial fibrinogen level was significantly different between the non-improved and improved ISSNHL group (350.63±87.20 vs. 310.71±81.06. The improved ISSNHL group showed a "surge phenomenon", in which fibrinogen started to decrease at day 5 and increased at day 26. In the non-improved group, fibrinogen remained elevated throughout the course of therapy. CONCLUSION It is important to measure not only the initial fibrinogen level but also to monitor its change throughout the course of therapy in order to predict the outcome of ISSNHL.
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Lim WH, Wong G, Lewis JR, Lok CE, Polkinghorne KR, Hodgson J, Lim EM, Prince RL. Total volume and composition of fluid intake and mortality in older women: a cohort study. BMJ Open 2017; 7:e011720. [PMID: 28341683 PMCID: PMC5372039 DOI: 10.1136/bmjopen-2016-011720] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVES The health benefits of 'drinking at least 8 glasses of water a day" in healthy individuals are largely unproven. We aimed to examine the relationship between total fluid and the sources of fluid consumption, risk of rapid renal decline, cardiovascular disease (CVD) mortality and all-cause mortality in elderly women. DESIGN, SETTING AND PARTICIPANTS We conducted a longitudinal analysis of a population-based cohort study of 1055 women aged ≥70 years residing in Australia. MAIN OUTCOME MEASURES The associations between total daily fluid intake (defined as total volume of beverage excluding alcohol and milk) and the types of fluid (water, black tea, coffee, milk and other fluids) measured as cups per day and rapid renal decline, CVD and all-cause mortality were assessed using adjusted logistic and Cox regression analyses. RESULTS Over a follow-up period of 10 years, 70 (6.6%) experienced rapid renal decline and 362 (34.4%) died, of which 142 (13.5%) deaths were attributed to CVD. The median (IQR) intake of total fluid was 10.4 (8.5-12.5) cups per day, with water (median (IQR) 4 (2-6) cups per day) and black tea (median (IQR) 3 (1-4) cups per day) being the most frequent type of fluid consumed. Every cup per day higher intake of black tea was associated with adjusted HRs of 0.90 (95% CI 0.81 to 0.99) and 0.92 (95% CI 0.86 to 0.98) for CVD mortality and all-cause mortality, respectively. There were no associations between black tea intake and rapid renal decline, or between the quantity or type of other fluids, including water intake, and any clinical outcomes. CONCLUSIONS Habitual higher intake of black tea may potentially improve long-term health outcomes, independent of treating traditional CVD risk factors, but validation of our study findings is essential.
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Affiliation(s)
- Wai H Lim
- Sir Charles Gairdner Hospital Unit, University of Western Australia School of Medicine and Pharmacology, Perth, Western Australia, Australia
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - Germaine Wong
- Centre for Kidney Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia
- School of Public Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
| | - Joshua R Lewis
- Sir Charles Gairdner Hospital Unit, University of Western Australia School of Medicine and Pharmacology, Perth, Western Australia, Australia
- Centre for Kidney Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia
| | - Charmaine E Lok
- Department of Medicine, University of Toronto;Division of Nephrology, Toronto General Hospital, Toronto, Ontario, Canada
| | - Kevan R Polkinghorne
- Department of Nephrology, Monash Medical Centre, Clayton, Melbourne, Australia
- Department of Medicine, Monash University, Clayton, Melbourne, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Prahan, Melbourne, Australia
| | - Jonathan Hodgson
- Sir Charles Gairdner Hospital Unit, University of Western Australia School of Medicine and Pharmacology, Perth, Western Australia, Australia
- School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia
| | - Ee M Lim
- PathWest, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - Richard L Prince
- Sir Charles Gairdner Hospital Unit, University of Western Australia School of Medicine and Pharmacology, Perth, Western Australia, Australia
- Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
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Sedighi M, Bahmani M, Asgary S, Beyranvand F, Rafieian-Kopaei M. A review of plant-based compounds and medicinal plants effective on atherosclerosis. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2017; 22:30. [PMID: 28461816 PMCID: PMC5390544 DOI: 10.4103/1735-1995.202151] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Revised: 11/12/2016] [Accepted: 12/20/2016] [Indexed: 01/09/2023]
Abstract
Atherosclerosis is one of the most important cardiovascular diseases that involve vessels through the development of fatty streaks and plaques. Plant-based compounds can help treat or prevent atherosclerosis through affecting the involved factors. The main purpose of this review article is to investigate and introduce medicinal plants and their potential activities regarding antioxidant properties, effective on lipids level and development of plaque, atherosclerosis, and progression of atherosclerosis as well as the development of cardiovascular disease and ischemia. To search for the relevant articles indexed in Information Sciences Institute, PubMed, Scientific Information Database, IranMedex, and Scopus between 1980 and 2013, with further emphasis on those indexed from 2004 to 2015, we used these search terms: atherosclerosis, antioxidant, cholesterol, inflammation, and the medicinal plants below. Then, the articles with inclusion criteria were used in the final analysis of the findings. Plant-based active compounds, including phenols, flavonoids, and antioxidants, can be effective on atherosclerosis predisposing factors and hence in preventing this disease and associated harmful complications, especially through reducing cholesterol, preventing increase in free radicals, and ultimately decreasing vascular plaque and vascular resistance. Hence, medicinal plants can contribute to treating atherosclerosis and preventing its progression through reducing cholesterolemia, free radicals, inflammation, vascular resistance, and certain enzymes. They, alone or in combination with hypocholesterolemic drugs, can therefore be useful for patients with hyperlipidemia and its complications.
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Affiliation(s)
- Mehrnoosh Sedighi
- Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Mahmoud Bahmani
- Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
- Biotechnology and Medicinal Plants Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Sedigheh Asgary
- Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fatemeh Beyranvand
- Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
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Kearney K, Tomlinson D, Smith K, Ajjan R. Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk. Cardiovasc Diabetol 2017; 16:34. [PMID: 28279217 PMCID: PMC5345237 DOI: 10.1186/s12933-017-0515-9] [Citation(s) in RCA: 88] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Accepted: 02/27/2017] [Indexed: 12/11/2022] Open
Abstract
An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmenting thrombosis risk. Current long-term therapies to prevent arterial occlusion in diabetes are focussed on anti-platelet agents, a strategy that fails to address the contribution of coagulation proteins to the enhanced thrombotic milieu. Moreover, antiplatelet treatment is associated with bleeding complications, particularly with newer agents and more aggressive combination therapies, questioning the safety of this approach. Therefore, to safely control thrombosis risk in diabetes, an alternative approach is required with the fibrin network representing a credible therapeutic target. In the current review, we address diabetes-specific mechanistic pathways responsible for hypofibrinolysis including the role of clot structure, defects in the fibrinolytic system and increased incorporation of anti-fibrinolytic proteins into the clot. Future anti-thrombotic therapeutic options are discussed with special emphasis on the potential advantages of modulating incorporation of the anti-fibrinolytic proteins into fibrin networks. This latter approach carries theoretical advantages, including specificity for diabetes, ability to target a particular protein with a possible favourable risk of bleeding. The development of alternative treatment strategies to better control residual thrombosis risk in diabetes will help to reduce vascular events, which remain the main cause of mortality in this condition.
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Affiliation(s)
- Katherine Kearney
- Division of Cardiovascular & Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, LS2 9JT, UK
| | - Darren Tomlinson
- Biomedical Health Research Centre, Astbury Building, University of Leeds, Leeds, LS2 9JT, UK
| | - Kerrie Smith
- Division of Cardiovascular & Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, LS2 9JT, UK
| | - Ramzi Ajjan
- Division of Cardiovascular & Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, LS2 9JT, UK.
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