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Zhang W, Zhou Q, Yang W, Tan X, Xu Y, Yi Z. Relationship between dietary flavan-3-ols intake and mortality in metabolic syndrome population; a large cohort study. Front Nutr 2025; 12:1572189. [PMID: 40276531 PMCID: PMC12019991 DOI: 10.3389/fnut.2025.1572189] [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: 02/06/2025] [Accepted: 03/27/2025] [Indexed: 04/26/2025] Open
Abstract
Background Metabolic syndrome (MetS) is a global health concern linked to increased mortality. Diets rich in plant-derived compounds, such as polyphenols, have shown potential health benefits for MetS. Among these, flavan-3-ols, a class of commonly occurring polyphenolic compounds, are known for their antioxidant and anti-inflammatory properties. Therefore, we hypothesize that flavan-3-ols intake is negatively associated with mortality risk in MetS population. Methods This study analyzed NHANES data (2007-2008, 2009-2010, and 2017-2018). Flavan-3-ol and monomer intake were obtained from the USDA Flavonoid and FNDDS databases. Associations with mortality were assessed using Cox regression, survival differences were compared using Kaplan-Meier curves, and non-linear trends were examined using restricted cubic splines. Subgroup analyses were conducted to explore potential effect modifications. Results Over a median follow-up period of 114 months, 1,856 participants survived, while 329 deaths were recorded. In Model 3, participants in the highest tertile (T3) of flavan-3-ol intake exhibited a 33% lower risk of all-cause mortality compared to those in the lowest tertile (T1) (HR = 0.67, 95%CI: 0.49-0.92). For monomers, the hazard ratios ranged from 0.55 for higher levels of epigallocatechin to 0.71 for higher levels of gallocatechin. Kaplan-Meier curves indicated significant differences in survival status across dietary flavan-3-ol intake groups. However, no association was found between flavan-3-ol intake and cardiovascular mortality risk. Additionally, restricted cubic spline (RCS) analysis did not reveal any non-linear relationship, and no significant interaction effects were observed in the subgroup analysis. Conclusion Higher dietary intake of flavan-3-ols is negatively associated with mortality risk in MetS population.
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Affiliation(s)
- Wanjia Zhang
- Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Qian Zhou
- Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Weiqing Yang
- Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Xiaoqin Tan
- Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Yin Xu
- Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Zhan Yi
- Xiangxing College, Hunan University of Chinese Medicine, Changsha, Hunan, China
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Oraby MI, Haddad MM, Nasser M, Hussein M. Insulin resistance, metabolic syndrome and micro-RNA-122 serum level in patients with cerebral venous sinus thrombosis: a case-control study. Thromb J 2024; 22:103. [PMID: 39563387 PMCID: PMC11575197 DOI: 10.1186/s12959-024-00654-z] [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: 04/13/2024] [Accepted: 09/12/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND The relationship between venous thromboembolism and both insulin resistance and metabolic syndrome is still a matter of debate. The objective of this work was to investigate the possible association between cerebral venous sinus thrombosis (CVST) and both insulin resistance and metabolic syndrome. We aimed also to assess micro-RNA-122 serum levels in patients with CVST in comparison to controls. METHODS This case-control study was conducted on patients having a clinical and neuroimaging diagnosis of acute CVST (within 1 week from the onset). Patients with inconclusive brain imaging, those with a history of malignancy, diabetic patients, and patients on drugs known to affect the insulin sensitivity or lipid profile were excluded from the study. Metabolic syndrome in the included cases and controls was evaluated by measuring waist circumference and blood pressure in addition to assessment of Triglycerides, HDL, and fasting blood sugar. The state of insulin resistance was established if the Homeostasis model assessment-insulin resistance (HOMA-IR) value > 2.5. Serum micro-RNA-122 serum level was measured for both patients and controls. RESULTS In the present study, 36 cases diagnosed as having CVST and 34 age & sex matched controls were included. There were statistically significant differences between patients with CVST and controls regarding BMI, waist circumference, TG, fasting glucose, fasting insulin & HOMA- IR (P-value = 0.002, 0.001, 0.004, 0.003, 0.021, 0.008 respectively). There was no statistically significant difference between patients with CVST and controls regarding micro-RNA-122 serum level (P-value = 0.376), whereas CVST patients with insulin resistance had a significantly higher micro-RNA-122 serum level in comparison to those without (P-value < 0.001). Patients with CVST had a significantly higher frequency of both metabolic syndrome and insulin resistance in comparison to controls (P-value = 0.008, 0.002 respectively). CONCLUSION There is a significant association between CVST and both insulin resistance and metabolic syndrome.
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Affiliation(s)
| | - Manar M Haddad
- Department of Neurology, Beni-Suef University, Beni-Suef, Egypt
| | - Mona Nasser
- Department of Clinical and Chemical pathology, Beni-Suef University, Beni-Suef, Egypt
| | - Mona Hussein
- Department of Neurology, Beni-Suef University, Beni-Suef, Egypt.
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Gehlot P, Brünnert D, Kaushik V, Yadav A, Bage S, Gaur K, Saini M, Ehrhardt J, Manjunath GK, Kumar A, Kasliwal N, Sharma AK, Zygmunt M, Goyal P. Unconventional localization of PAI-1 in PML bodies: A possible link with cellular growth of endothelial cells. Biochem Biophys Rep 2024; 39:101793. [PMID: 39161580 PMCID: PMC11332193 DOI: 10.1016/j.bbrep.2024.101793] [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: 05/14/2024] [Revised: 07/14/2024] [Accepted: 07/17/2024] [Indexed: 08/21/2024] Open
Abstract
Plasminogen activator inhibitor-1 (PAI-1/Serpin E1) is classically known for its antifibrinolytic activity via inhibiting uPA and tPA of the fibrinolytic pathway. PAI-1 has a paradoxical role in tumor progression, and its molecular functions are poorly understood. PAI-1 is a widely accepted secretory protease inhibitor, however, a study suggested the localization of PAI-1 in the cytoplasm and the nucleus. Besides the plethora of its biological functions as a secretory protein, intracellular localization, and functions of PAI-1 remain unexplored at the molecular level. In this study, using various in silico approaches, we showed that PAI-1 possesses a nuclear export signal. Using the CRM1-specific inhibitor leptomycin B, we demonstrated that PAI-1 has a functional CRM1-dependent NES, indicating the possibility of its nuclear localization. Further, we confirm that PAI-1 is localized in the nucleus of endothelial cells using fluorescence microscopy and immunoprecipitation. Notably, we identified an unconventional distribution of PAI-1 in the PML bodies of the nucleus of normal endothelial cells, while the protein was restricted in the cytoplasm of slow-growing cells. The data showed that the localization of PAI-1 in PML bodies is highly correlated with the growth potential of endothelial cells. This conditional nucleocytoplasmic shuttling of PAI-1 during the aging of cells could impart a strong link to its age-related functions and tumor progression. Together, this study identifies the novel behavior of PAI-1 that might be linked with cell aging and may be able to unveil the elusive role of PAI-1 in tumor progression.
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Affiliation(s)
- Pragya Gehlot
- Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, Bandarsindri, Kishangarh, 305 817, Rajasthan, India
| | - Daniela Brünnert
- University Hospital of Würzburg, Department of Obstetrics and Gynecology, Josef-Schneider-Str. 4, D-97080, Würzburg, Germany
- Department of Obstetrics and Gynecology, University of Greifswald, Ferdinand-Sauerbruchstrasse, D-17489, Greifswald, Germany
| | - Vibha Kaushik
- Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, Bandarsindri, Kishangarh, 305 817, Rajasthan, India
| | - Arpana Yadav
- Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, Bandarsindri, Kishangarh, 305 817, Rajasthan, India
| | - Saloni Bage
- Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, Bandarsindri, Kishangarh, 305 817, Rajasthan, India
| | - Kritika Gaur
- Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, Bandarsindri, Kishangarh, 305 817, Rajasthan, India
| | - Mahesh Saini
- Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, Bandarsindri, Kishangarh, 305 817, Rajasthan, India
| | - Jens Ehrhardt
- Department of Obstetrics and Gynecology, University of Greifswald, Ferdinand-Sauerbruchstrasse, D-17489, Greifswald, Germany
| | - Gowrang Kasaba Manjunath
- Manipal Academy of Higher Education (MAHE), Manipal, 576104, Karnataka, India
- Institute of Bioinformatics, International Technology Park, Bangalore, 560066, Karnataka, India
| | - Abhishek Kumar
- Manipal Academy of Higher Education (MAHE), Manipal, 576104, Karnataka, India
- Institute of Bioinformatics, International Technology Park, Bangalore, 560066, Karnataka, India
| | - Neena Kasliwal
- Department of Pathology, J.L.N. Medical College, Ajmer, 305001, Rajasthan, India
| | - Ajay Kumar Sharma
- Department of Obstetrics and Gynecology, J.L.N. Medical College, Ajmer, 305001, Rajasthan, India
| | - Marek Zygmunt
- Department of Obstetrics and Gynecology, University of Greifswald, Ferdinand-Sauerbruchstrasse, D-17489, Greifswald, Germany
| | - Pankaj Goyal
- Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, Bandarsindri, Kishangarh, 305 817, Rajasthan, India
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Zhang S, Fan T, Wang L, Chen N, Ma L. Impact of the triglyceride-glucose index on 28-day mortality in non-diabetic critically Ill patients with sepsis: a retrospective cohort analysis. BMC Infect Dis 2024; 24:785. [PMID: 39103750 DOI: 10.1186/s12879-024-09711-4] [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: 11/17/2023] [Accepted: 08/02/2024] [Indexed: 08/07/2024] Open
Abstract
INTRODUCTION Sepsis is a life-threatening condition that poses a globally high mortality rate. Identifying risk factors is crucial. Insulin resistance and the TYG index, associated with metabolic disorders, may play a role. This study explores their correlation with mortality in non-diabetic septic patients. METHODS This retrospective cohort study used data from the MIMIC-IV (version 2.1) database, which includes over 50,000 ICU admissions from 2008 to 2019 at Beth Israel Deaconess Medical Center in Boston. We included adult patients with sepsis who were admitted to the intensive care unit in the study. The primary outcome was to evaluate the ability of TYG to predict death at 28-day of hospital admission in patients with sepsis. RESULTS The study included 2213 patients with sepsis, among whom 549 (24.8%) died within 28 days of hospital admission. We observed a non-linear association between TYG and the risk of mortality. Compared to the reference group (lower TYG subgroup), the 28-day mortality increased in the higher TYG subgroup, with a fully adjusted hazard ratio of 2.68 (95% CI: 2.14 to 3.36). The area under the curve (AUC) for TYG was 67.7%, higher than for triglycerides alone (AUC = 64.1%), blood glucose (AUC = 62.4%), and GCS (AUC = 63.6%), and comparable to SOFA (AUC = 69.3%). The final subgroup analysis showed no significant interaction between TYG and each subgroup except for the COPD subgroup (interaction P-values: 0.076-0.548). CONCLUSION In our study, TYG can be used as an independent predictor for all-cause mortality due to sepsis within 28 days of hospitalization.
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Affiliation(s)
- Sen Zhang
- Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan City, 030001, Shanxi Province, China
| | - Tianhua Fan
- Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan City, 030001, Shanxi Province, China
| | - Li Wang
- Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan City, 030001, Shanxi Province, China
| | - Nan Chen
- Department of General Medicine, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China
| | - Liansheng Ma
- Department of Neurology, Second Hospital of Shanxi Medical University, Taiyuan City, 030001, Shanxi Province, China.
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Majumdar S, Jacob JJ, Jude EB. Obesity associated hypogonadism—a growing concern in metabolic syndrome. METABOLIC SYNDROME 2024:293-307. [DOI: 10.1016/b978-0-323-85732-1.00054-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Ahn HJ, Lee SR, Choi EK, Lee SW, Han KD, Kwon S, Oh S, Lip GYH. Metabolic syndrome and ischaemic stroke in non-anticoagulated atrial fibrillation with low CHA 2DS 2-VASc scores. Heart 2023; 110:101-107. [PMID: 36963818 DOI: 10.1136/heartjnl-2022-322143] [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: 11/13/2022] [Accepted: 03/13/2023] [Indexed: 03/26/2023] Open
Abstract
OBJECTIVE Conflicting results have been reported on whether metabolic syndrome (MetS) confers an increased risk of ischaemic stroke in atrial fibrillation (AF). We investigated the risk of ischaemic stroke according to MetS in patients with AF who are not indicated for oral anticoagulants. METHODS A total of 76 015 oral anticoagulant-naïve patients with AF with low Congestive Heart Failure, Hypertension, Age ≥75 years (Doubled), Diabetes Mellitus, Stroke (Doubled), Vascular Disease, Age 65-74 years, Sex Category (Female) (CHA2DS2-VASc) score (0 and 1) were included from the National Health Information Database. The risk of ischaemic stroke was evaluated according to MetS, the number of MetS components (metabolic burden), and individual metabolic components defined by health examination data within 2 years of AF diagnosis. RESULTS MetS was prevalent among 21 570 (28.4%) of the entire study population (mean age 49.8±11.1 years, mean CHA2DS2-VASc score 0.7±0.5). During a mean follow-up of 5.1 years, ischaemic stroke occurred in 1395 (1.84%) patients. MetS was associated with a higher risk of ischaemic stroke (adjusted HR (aHR) 1.19, 95% CI 1.06 to 1.33, p=0.002). Patients with the highest number of MetS components (4 or 5) showed the greatest aHR of 1.38 (95% CI 1.13 to 1.69), whereas those with a single component had a marginal risk of ischaemic stroke (aHR 1.17, 95% CI 0.97 to 1.40). Elevated blood pressure and increased waist circumference were independent components associated with 1.48-fold and 1.15-fold higher risks of ischaemic stroke, respectively. CONCLUSION Among AF patients with CHA2DS2-VASc scores of 0 and 1 with no anticoagulation, MetS is associated with an increased risk of ischaemic stroke. Given the linear incremental association between metabolic burden and ischaemic stroke, the integrated management of metabolic derangements in AF is required.
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Affiliation(s)
- Hyo-Jeong Ahn
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - So-Ryoung Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Eue-Keun Choi
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Seung-Woo Lee
- Department of Medical Statistics, Catholic University of Korea College of Medicine, Seoul, Korea
| | - Kyung-Do Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
| | - Soonil Kwon
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Seil Oh
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, UK
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Miles LA, Bai H, Chakrabarty S, Baik N, Zhang Y, Parmer RJ, Samad F. Overexpression of Plg-R KT protects against adipose dysfunction and dysregulation of glucose homeostasis in diet-induced obese mice. Adipocyte 2023; 12:2252729. [PMID: 37642146 PMCID: PMC10481882 DOI: 10.1080/21623945.2023.2252729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 08/22/2023] [Accepted: 08/24/2023] [Indexed: 08/31/2023] Open
Abstract
The plasminogen receptor, Plg-RKT, is a unique cell surface receptor that is broadly expressed in cells and tissues throughout the body. Plg-RKT localizes plasminogen on cell surfaces and promotes its activation to the broad-spectrum serine protease, plasmin. In this study, we show that overexpression of Plg-RKT protects mice from high fat diet (HFD)-induced adipose and metabolic dysfunction. During the first 10 weeks on the HFD, the body weights of mice that overexpressed Plg-RKT (Plg-RKT-OEX) were lower than those of control mice (CagRosaPlgRKT). After 10 weeks on the HFD, CagRosaPlgRKT and Plg-RKT-OEX mice had similar body weights. However, Plg-RKT-OEX mice showed a more metabolically favourable body composition phenotype. Plg-RKT-OEX mice also showed improved glucose tolerance and increased insulin sensitivity. We found that the improved metabolic functions of Plg-RKT-OEX mice were mechanistically associated with increased energy expenditure and activity, decreased proinflammatory adipose macrophages and decreased inflammation, elevated brown fat thermogenesis, and higher expression of adipose PPARγ and adiponectin. These findings suggest that Plg-RKT signalling promotes healthy adipose function via multiple mechanisms to defend against obesity-associated adverse metabolic phenotypes.
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Affiliation(s)
- Lindsey A. Miles
- Department of Molecular Medicine, Scripps Research, La Jolla, CA, USA
| | - Hongdong Bai
- Department of Medicine, Veterans Administration San Diego Healthcare System, San Diego, CA, USA
| | - Sagarika Chakrabarty
- Department of Cell Biology, San Diego Biomedical Research Institute, San Diego, CA, USA
| | - Nagyung Baik
- Department of Molecular Medicine, Scripps Research, La Jolla, CA, USA
| | - Yuqing Zhang
- Department of Molecular Medicine, Scripps Research, La Jolla, CA, USA
| | - Robert J. Parmer
- Department of Medicine, Veterans Administration San Diego Healthcare System, San Diego, CA, USA
- Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Fahumiya Samad
- Department of Cell Biology, San Diego Biomedical Research Institute, San Diego, CA, USA
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Khalil SK, Khalil SK, Al Refai F, B Yousif Z, Maliyakkal AM, Madani OAA, Musa M. Facial Nerve Palsy in Hypertriglyceridemia-Induced Pancreatitis: A Case Report and Literature Review. Cureus 2023; 15:e46714. [PMID: 38021661 PMCID: PMC10630761 DOI: 10.7759/cureus.46714] [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: 10/09/2023] [Indexed: 12/01/2023] Open
Abstract
Acute pancreatitis is associated with multiple local or systemic complications in response to systemic inflammation that may eventually result in multi-organ failure. Neurological complications are uncommon in acute pancreatitis. Examples include cerebral hemorrhage, infarction, cerebral fat embolism, Wernicke encephalopathy, and cranial nerve (CN) palsy. Facial nerve palsy is a rare event in the setting of acute pancreatitis, with various theories about its etiology and pathophysiology. We report the case of a 46-year-old female who presented with acute pancreatitis secondary to hypertriglyceridemia. She developed right-sided facial palsy on the third day of admission. Her clinical condition improved with standard conservative medical management of acute pancreatitis. Facial nerve palsy improved after a short course of oral glucocorticoids, supportive measures, and physiotherapy. This case demonstrates a rare occurrence of facial nerve palsy in the setting of acute pancreatitis, although the etiopathology behind this manifestation remains unclear.
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Affiliation(s)
| | | | | | | | - Abdul Majeed Maliyakkal
- Medicine, Hamad Medical Corporation, Doha, QAT
- Clinical Medicine, Weill Cornell Medicine, Doha, QAT
- Clinical Medicine, QU Health, Qatar University, Doha, QAT
| | | | - Muzamil Musa
- Internal Medicine, Hamad Medical Corporation, Doha, QAT
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Zhang B, Lei H, Ambler G, Werring DJ, Fang S, Li H, Chen R, Wei J, Chen G, Liu N, Du H. Association between Triglyceride-Glucose Index and Early Neurological Outcomes after Thrombolysis in Patients with Acute Ischemic Stroke. J Clin Med 2023; 12:jcm12103471. [PMID: 37240578 DOI: 10.3390/jcm12103471] [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: 01/05/2023] [Revised: 02/23/2023] [Accepted: 03/09/2023] [Indexed: 05/28/2023] Open
Abstract
BACKGROUND The triglyceride-glucose (TyG) index is a novel biomarker of insulin resistance which might plausibly influence endogenous fibrinolysis and thus early neurological outcomes in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis using recombinant tissue-plasminogen activator. METHODS We included consecutive AIS patients within 4.5 h of symptom onset undergoing intravenous thrombolysis between January 2015 and June 2022 in this multi-center retrospective observational study. Our primary outcome was early neurological deterioration (END), defined as ≥2 (END2) or ≥ 4 (END4) National Institutes of Health Stroke Scale (NIHSS) score worsening compared to the initial NIHSS score within 24 h of intravenous thrombolysis. Our secondary outcome was early neurological improvement (ENI), defined as a lower NIHSS score at discharge. TyG index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2. We evaluated the association of END and ENI with TyG index using a logistic regression model. RESULTS A total of 676 patients with AIS were evaluated. The median age was 68 (Interquartile range, IQR (60-76) years old), and 432 (63.9%) were males. A total of 89 (13.2%) patients developed END2, 61 (9.0%) patients developed END4, and 492 (72.7%) experienced ENI. In multivariable logistic regression analysis, after adjustment for confounding factors, TyG index was significantly associated with increased risks of END2 (categorical variable, vs. lowest tertile, medium tertile odds ratio [OR] 1.05, 95% confidence interval, CI 0.54-2.02, highest tertile OR 2.94, 95%CI 1.64-5.27, overall p < 0.001) and END4 (categorical variable, vs. lowest tertile, medium tertile OR 1.21, 95%CI 0.54-2.74, highest tertile OR 3.80, 95%CI 1.85-7.79, overall p < 0.001), and a lower probability of ENI (categorical variable, vs. lowest tertile, medium tertile OR 1.00, 95%CI 0.63-1.58, highest tertile OR 0.59, 95%CI 0.38-0.93, overall p = 0.022). CONCLUSIONS Increasing TyG index was associated with a higher risk of END and a lower probability of ENI in patients with acute ischemic stroke treated with intravenous thrombolysis.
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Affiliation(s)
- Baixiang Zhang
- Department of Rehabilitation Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan 364099, China
| | - Hanhan Lei
- Stroke Research Center, Department of Neurology, Fujian Medical University Union Hospital, Fuzhou 350001, China
- Institute of Clinical Neurology, Fujian Medical University, Fuzhou 350005, China
| | - Gareth Ambler
- Department of Statistical Science, University College London, London WC1E 6BT, UK
| | - David J Werring
- Department of Brain Repair and Rehabilitation, University College London Queen Square Institute of Neurology, London WC1N 3BG, UK
| | - Shuangfang Fang
- Stroke Research Center, Department of Neurology, Fujian Medical University Union Hospital, Fuzhou 350001, China
- Institute of Clinical Neurology, Fujian Medical University, Fuzhou 350005, China
| | - Hangfeng Li
- Department of Neurology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan 364099, China
| | - Ronghua Chen
- Stroke Research Center, Department of Neurology, Fujian Medical University Union Hospital, Fuzhou 350001, China
- Institute of Clinical Neurology, Fujian Medical University, Fuzhou 350005, China
| | - Jin Wei
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Guangliang Chen
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Nan Liu
- Stroke Research Center, Department of Neurology, Fujian Medical University Union Hospital, Fuzhou 350001, China
- Institute of Clinical Neurology, Fujian Medical University, Fuzhou 350005, China
- Department of Rehabilitation, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Houwei Du
- Stroke Research Center, Department of Neurology, Fujian Medical University Union Hospital, Fuzhou 350001, China
- Institute of Clinical Neurology, Fujian Medical University, Fuzhou 350005, China
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Swanepoel AC, van Reenen M, de Lange-Loots Z, Pieters M. Association of the metabolic syndrome with PAI 1 act and clot lysis time over a 10-year follow up in an African population. Nutr Metab Cardiovasc Dis 2023; 33:592-601. [PMID: 36646603 DOI: 10.1016/j.numecd.2022.12.011] [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: 08/17/2022] [Revised: 11/25/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIMS The association between the metabolic syndrome (MetS) and plasminogen activator inhibitor-1 (PAI-1) has been well established in cross-sectional studies. It is less clear whether this translates into decreased clot lysis rates and very little information is available on non-European populations. Little is known regarding prospective associations and whether clot lysis progressively worsens in MetS individuals over time. We determined the prospective association of MetS with PAI-1 activity (PAI-1act) and clot lysis time (CLT) over a 10-year period. METHODS AND RESULTS As many as 2010 African men and women aged ≥30 years were stratified according to MetS status and number of MetS criteria (0-5). We also determined the contribution of the PAI-1 4G/5G polymorphism to these associations and identified which MetS criteria had the strongest associations with PAI-1act and CLT. Both PAI-1act and CLT remained consistently elevated in individuals with MetS throughout the 10-year period. PAI-1act and CLT did not increase more over time in MetS individuals than in controls. The 4G/5G genotype did not influence the association of PAI-1act or clot lysis with MetS. Increased waist circumference, increased triglycerides and decreased HDL-C were the main predictors of PAI-1act and CLT. CONCLUSIONS Black South Africans with MetS had increased PAI-1act and longer CLTs than individuals without MetS. The inhibited clot lysis in MetS did, however, not deteriorate over time compared to controls. Of the MetS criteria, obesity and altered lipids were the main predictors of PAI-1act and CLT and are thus potential targets for prevention strategies to decrease thrombotic risk.
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Affiliation(s)
- Albe C Swanepoel
- Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa
| | - Mari van Reenen
- Human Metabolomics, North-West University, Potchefstroom, South Africa
| | - Zelda de Lange-Loots
- Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa; Medical Research Council Extramural Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa
| | - Marlien Pieters
- Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa; Medical Research Council Extramural Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa.
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Moneke I, Ogutur ED, Kalbhenn J, Hettich I, Passlick B, Jungraithmayr W, Senbaklavaci O. Independent risk factors for an increased incidence of thromboembolism after lung transplantation. J Thromb Thrombolysis 2023; 55:252-262. [PMID: 36495365 PMCID: PMC10011327 DOI: 10.1007/s11239-022-02748-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/27/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Thromboembolism (TE) after lung transplantation (LTX) is associated with increased morbidity and mortality. The aim of this study is to analyze the incidence and outcome of venous and arterial thromboembolic complications and to identify independent risk factors. PATIENTS AND METHODS We retrospectively analyzed the medical records of 221 patients who underwent LTX at our institution between 2002 and 2021. Statistical analysis was performed using SPSS and GraphPad software. RESULTS 74 LTX recipients (33%) developed TE. The 30-days incidence and 12-months incidence were 12% and 23%, respectively. Nearly half of the patients (48%) developed pulmonary embolism, 10% ischemic stroke. Arterial hypertension (p = 0.006), a body mass index (BMI) > 30 (p = 0.006) and diabetes mellitus (p = 0.041) were independent predictors for TE. Moreover, a BMI of > 25 at the time of transplantation was associated with an increased risk for TE (43% vs. 32%, p = 0.035). At the time of LTX, 65% of the patients were older than 55 years. An age > 55 years also correlated with the incidence of TE (p = 0.037) and these patients had reduced overall post-transplant survival when the event occurred within the first postoperative year (59% vs. 72%, p = 0.028). CONCLUSIONS The incidence of TE after LTX is high, especially in lung transplant recipients with a BMI > 25 and an age > 55 years as well as cardiovascular risk factors closely associated with the metabolic syndrome. As these patients comprise a growing recipient fraction, intensified research should focus on the risks and benefits of regular screening or a prolonged TE prophylaxis in these patients. Trial registration number DKRS: 00021501.
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Affiliation(s)
- Isabelle Moneke
- Department of Thoracic Surgery, Faculty of Medicine, Medical Center, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.
| | - Ecem Deniz Ogutur
- Department of Thoracic Surgery, Faculty of Medicine, Medical Center, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
| | - Johannes Kalbhenn
- Department of Anaesthesiology and Intensive Care Medicine, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
| | - Ina Hettich
- Department of Pneumology, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
| | - Bernward Passlick
- Department of Thoracic Surgery, Faculty of Medicine, Medical Center, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
| | - Wolfgang Jungraithmayr
- Department of Thoracic Surgery, Faculty of Medicine, Medical Center, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
| | - Omer Senbaklavaci
- Department of Thoracic Surgery, Faculty of Medicine, Medical Center, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
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12
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Yap ES, Lijfering WM, Timp JF, Rosendaal FR, Cannegieter SC, Scheres LJJ. Procoagulant factors and future risk of arterial cardiovascular disease in patients with prior venous thrombosis: A cohort study. EJHAEM 2023; 4:3-12. [PMID: 36819164 PMCID: PMC9928659 DOI: 10.1002/jha2.618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 10/31/2022] [Accepted: 11/03/2022] [Indexed: 01/18/2023]
Abstract
Patients with venous thrombosis (VT) are at increased risk of future arterial cardiovascular disease (CVD) (i.e., myocardial infarction, ischemic stroke or peripheral artery disease). We investigated whether shared risk factors for VT and CVD are associated with the levels of procoagulant factors (fibrinogen, factor VIII, and von Willebrand factor), and whether the relationship between these risk factors and subsequent CVD was mediated through these procoagulant factors in patients with VT. In a follow-up study consisting of 4956 patients with VT, 2176 patients (44%) provided blood samples and were linked to the Dutch Hospital registry of Statistics Netherlands to identify hospital admissions or procedures for subsequent CVD. In total, 52 CVD events occurred over a follow-up of 11,124 years, with an incidence rate of 4.7 per 1000 patient years (95% confidence intervals 3.5-6.1). Increasing age, male sex, smoking history, major illnesses, dyslipidemia, and impaired fasting glucose levels were associated with increased CVD risk. Procoagulant factor levels were also associated with CVD risk. When adjusted for these procoagulant factors, the association between the risk factors and CVD attenuated partially. This study provides evidence that procoagulant factors can partially explain the association between increased risks of subsequent CVD in patients with previous VT.
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Affiliation(s)
- Eng Soo Yap
- Department of Clinical EpidemiologyLeiden University Medical CenterLeidenThe Netherlands
- Department of Laboratory MedicineNational University HospitalSingaporeSingapore
| | - Willem M. Lijfering
- Department of Clinical EpidemiologyLeiden University Medical CenterLeidenThe Netherlands
- Kennisinstituut, Federatie Medisch SpecialistenUtrechtThe Netherlands
| | - Jasmijn F. Timp
- Department of Clinical EpidemiologyLeiden University Medical CenterLeidenThe Netherlands
| | - Frits R. Rosendaal
- Department of Clinical EpidemiologyLeiden University Medical CenterLeidenThe Netherlands
- Einthoven Laboratory for Experimental Vascular MedicineLeiden University Medical CenterLeidenThe Netherlands
| | - Suzanne C. Cannegieter
- Department of Clinical EpidemiologyLeiden University Medical CenterLeidenThe Netherlands
- Department of Internal MedicineSection of Thrombosis and HaemostasiasLeiden University Medical CenterLeidenThe Netherlands
| | - Luuk J. J. Scheres
- Department of Clinical EpidemiologyLeiden University Medical CenterLeidenThe Netherlands
- Department of Internal MedicineRadboud University Medical CenterNijmegenThe Netherlands
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13
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Chew NW, Muthiah MD, Sanyal AJ. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: pathophysiology and implications for cardiovascular disease. CARDIOVASCULAR ENDOCRINOLOGY AND METABOLISM 2023:137-173. [DOI: 10.1016/b978-0-323-99991-5.00003-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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14
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Zhang B, Chen X, Liu Y, Chen F, Yang N, Li L. Relationship between bullous pemphigoid and metabolic syndrome: a 12-year case-control study conducted in China. Ther Adv Chronic Dis 2022; 13:20406223221130707. [PMID: 36267486 PMCID: PMC9577067 DOI: 10.1177/20406223221130707] [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: 04/26/2022] [Accepted: 09/16/2022] [Indexed: 11/15/2022] Open
Abstract
Background Hypertension, diabetes, dyslipidemia, and obesity are prevalent in patients with bullous pemphigoid (BP) and are all components of metabolic syndrome (MS). However, the prevalence of MS in patients with BP is unknown. We aimed to evaluate the relationship between MS and BP and to define the clinical and laboratory characteristics of patients with both conditions. Methods This retrospective case-control study was conducted for 12 years at Peking Union Medical College (162 with BP and 162 age and sex-matched controls). The components of MS were analyzed and logistic regression was used to identify independent risk factors for BP. In addition, the clinical and laboratory characteristics of patients with BP ± MS were compared. Results The prevalence of MS in patients with BP was 35.2% and that in controls was 14.8% (p < 0.001). After adjustment for sex and age, multivariate analysis demonstrated a positive correlation between BP and MS [odds ratio (OR) 2.490, 95% confidence interval (CI) 1.040-5.963], diabetes (OR 1.870, 95% CI 1.029-3.396), and overweight or obesity (OR 1.807, 95% CI 1.026-3.182). In the BP group, participants with MS were older (p = 0.006), were less likely to present erythema (p = 0.028), and had higher serum C3 (p = 0.007) and incidence of infection within 1 year of their diagnosis (p = 0.035) than participants without MS. Conclusion MS and its components hyperglycemia and overweight were found to be independently associated with BP. Therefore, clinicians should screen for MS in patients with BP, especially if they are older, present less erythema, or have a high serum C3.
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Affiliation(s)
- Bingjie Zhang
- Department of Dermatology, State Key Laboratory
of Complex Severe and Rare Diseases, Peking Union Medical College Hospital,
Chinese Academy of Medical Science and Peking Union Medical College,
National Clinical Research Center for Dermatologic and Immunologic Diseases,
Beijing, China
| | - Xinyi Chen
- Department of Dermatology, State Key Laboratory
of Complex Severe and Rare Diseases, Peking Union Medical College Hospital,
Chinese Academy of Medical Science and Peking Union Medical College,
National Clinical Research Center for Dermatologic and Immunologic Diseases,
Beijing, China
| | - Yangchun Liu
- Department of Dermatology, State Key Laboratory
of Complex Severe and Rare Diseases, Peking Union Medical College Hospital,
Chinese Academy of Medical Science and Peking Union Medical College,
National Clinical Research Center for Dermatologic and Immunologic Diseases,
Beijing, China
| | - Fangyuan Chen
- Department of Dermatology, State Key Laboratory
of Complex Severe and Rare Diseases, Peking Union Medical College Hospital,
Chinese Academy of Medical Science and Peking Union Medical College,
National Clinical Research Center for Dermatologic and Immunologic Diseases,
Beijing, China
| | - Nan Yang
- Department of Pharmacology, Institute of Basic
Medical Sciences, Chinese Academy of Medical Sciences & School of Basic
Medicine, Peking Union Medical College, Beijing, China
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15
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Ali M, Hussein M, Magdy R, Khamis A, Othman AM, Abdelkareem SA, Osama W. The potential role of insulin resistance in predicting outcome from intravenous thrombolytic therapy. Acta Neurol Belg 2022:10.1007/s13760-022-02060-6. [DOI: 10.1007/s13760-022-02060-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 08/08/2022] [Indexed: 11/30/2022]
Abstract
Abstract
Background
The potential impact of insulin resistance on stroke prognosis after IV thrombolysis is poorly understood. This study aimed to assess the effect of insulin resistance and metabolic syndrome on the outcome of IV thrombolysis in non-diabetic patients with acute ischaemic stroke.
Methods
This prospective observational study was conducted on 70 non-diabetic acute ischaemic stroke patients who received rt-PA within 3 h of stroke onset. Patients were subjected to baseline and follow-up NIHSS measurements at 24 h and 3 months post-treatment. Stroke outcome was assessed after 3 months using the Modified Rankin Scale (mRS). The homeostasis model assessment–insulin resistance (HOMA-IR) was calculated for the included patients at stroke onset.
Results
The mean age of included patients was 57.04 ± 14.39 years. Patients with unfavourable outcome had a significantly higher frequency of insulin resistance and metabolic syndrome, higher values of baseline NIHSS, insulin, HOMA-IR, uric acid and lower levels of HDL than those with favourable outcome (P value = 0.035, 0.007, ≤ 0.001, 0.001, ≤ 0.001, 0.002, 0.033, respectively). Each point increase in NIHSS before rt-PA increased the odds of an unfavourable outcome by 2.06 times (95% CI 1.22 − 3.478). Also, insulin resistance increased the odds of the unfavourable outcome by 11.046 times (95% CI 1.394–87.518). There was a statistically significant improvement in NIHSS 3 months after receiving rt-PA in all patients, significantly higher in patients who did not have insulin resistance or metabolic syndrome.
Conclusion
Insulin resistance and metabolic syndrome were associated with worse functional outcomes in non-diabetic stroke patients after receiving rt-PA.
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16
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DeLeeuw P, Agbim U. Pre-transplant portal vein thrombosis in non-alcoholic fatty liver disease patients-pathogenesis, risk factors, and implications on management. Transl Gastroenterol Hepatol 2022; 7:27. [PMID: 35892050 PMCID: PMC9257532 DOI: 10.21037/tgh-19-361] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 07/20/2020] [Indexed: 02/18/2024] Open
Abstract
Along with the worldwide increase in obesity and metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and its more severe subset, non-alcoholic steatohepatitis (NASH), are on path to become the leading cause of liver transplantation in the United States. NAFLD, as well as obesity, create an inflammatory milieu via the release of adipocytokines. In turn, the inflammatory environment can trigger an increase in prothrombotic factors. Independent of inflammation, the severity of NASH is associated with a graded increase in hypercoagulability such as an increase in factor VIII, increase in plasminogen activator inhibitor-1, and decrease in protein C. Ultimately, this environment creates an increase in thrombotic risk, leading to higher rates of pre-transplant portal vein thrombosis (PVT) in patients with NASH cirrhosis vesus other causes of cirrhosis. Many studies have shown worse outcomes in liver transplant recipients with PVT as it complicates anastomotic reconstruction which can negatively affect portal blood supply needed for adequate liver functioning. Management and treatment of PVT is not standardized, but from a pharmacologic standpoint, multiple classes of anticoagulants have shown to be successful in recanalization of the portal vein and preventing recurrence of clot with minimal bleeding complications. The increasing prevalence of NASH cirrhosis and subsequent increase in PVT require further research for improved outcomes.
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Affiliation(s)
- Peter DeLeeuw
- Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Uchenna Agbim
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA
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17
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Samad F, Bai H, Baik N, Haider P, Zhang Y, Rega-Kaun G, Kaun C, Prager M, Wojta J, Bui Q, Chakrabarty S, Wang J, Parmer RJ, Miles LA. The plasminogen receptor Plg-R KT regulates adipose function and metabolic homeostasis. J Thromb Haemost 2022; 20:742-754. [PMID: 34897983 PMCID: PMC8885904 DOI: 10.1111/jth.15622] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 11/30/2021] [Accepted: 12/10/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Plg-RKT , a unique transmembrane plasminogen receptor, enhances the activation of plasminogen to plasmin, and localizes the proteolytic activity of plasmin on the cell surface. OBJECTIVES We investigated the role of Plg-RKT in adipose function, metabolic homeostasis, and obesity. METHODS We used adipose tissue (AT) sections from bariatric surgery patients and from high fat diet (HFD)-induced obese mice together with immunofluorescence and real-time polymerase chain reaction to study adipose expression of Plg-RKT . Mice genetically deficient in Plg-RKT and littermate controls fed a HFD or control low fat diet (LFD) were used to determine the role of Plg-RKT in insulin resistance, glucose tolerance, type 2 diabetes, and associated mechanisms including adipose inflammation, fibrosis, and ectopic lipid storage. The role of Plg-RKT in adipogenesis was determined using 3T3-L1 preadipocytes and primary cultures established from Plg-RKT -deficient and littermate control mice. RESULTS Plg-RKT was highly expressed in both human and mouse AT, and its levels dramatically increased during adipogenesis. Plg-RKT -deficient mice, when fed a HFD, gained more weight, developed more hepatic steatosis, and were more insulin resistant/glucose intolerant than HFD-fed wild-type littermates. Mechanistically, these metabolic defects were linked with increased AT inflammation, AT macrophage and T-cell accumulation, adipose and hepatic fibrosis, and decreased insulin signaling in the AT and liver. Moreover, Plg-RKT regulated the expression of PPARγ and other adipogenic molecules, suggesting a novel role for Plg-RKT in the adipogenic program. CONCLUSIONS Plg-RKT coordinately regulates multiple aspects of adipose function that are important to maintain efficient metabolic homeostasis.
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Affiliation(s)
- Fahumiya Samad
- Department of Cell Biology, San Diego Biomedical Research Institute, San Diego, CA, USA
| | - Hongdong Bai
- Department of Medicine, Veterans Administration San Diego Healthcare System, San Diego
| | - Nagyung Baik
- Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA
| | - Patrick Haider
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Yuqing Zhang
- Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA
| | - Gersina Rega-Kaun
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
- 5th Department of Internal Medicine for Diabetes and Rheumatology, Wilhelminen Hospital, Vienna, Austria
| | - Christoph Kaun
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Manfred Prager
- Department of Surgery, Hospital Oberwart, Oberwart, Austria
| | - Johann Wojta
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
- Ludwig Boltzmann Institute for Cardiovascular Research, Vienna
| | - Quyen Bui
- Department of Cell Biology, San Diego Biomedical Research Institute, San Diego, CA, USA
| | - Sagarika Chakrabarty
- Department of Cell Biology, San Diego Biomedical Research Institute, San Diego, CA, USA
| | - Jing Wang
- Department of Cell Biology, San Diego Biomedical Research Institute, San Diego, CA, USA
| | - Robert J. Parmer
- Department of Medicine, Veterans Administration San Diego Healthcare System, San Diego
- Department of Medicine, University of California San Diego, La Jolla, CA
| | - Lindsey A. Miles
- Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA
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18
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Kim TH, Yeo SG, Byun JY. Role of Biomarkers as Prognostic Factors in Acute Peripheral Facial Palsy. Int J Mol Sci 2021; 23:307. [PMID: 35008742 PMCID: PMC8745072 DOI: 10.3390/ijms23010307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 12/24/2021] [Accepted: 12/25/2021] [Indexed: 11/25/2022] Open
Abstract
Acute peripheral facial palsy (APFP), including Bell's palsy and Ramsay Hunt syndrome, is a disease that affects daily life through facial motor dysfunction, causing psychological problems. Various tests to evaluate prognosis have been studied; however, there are no validated predictive biomarkers to guide clinical decision making. Therefore, specific biomarkers that respond to treatment are required to understand prognostic outcomes. In this review, we discuss existing literature regarding the role of APFP biomarkers in prognosis and recovery. We searched the PubMed, EMBASE, and Cochrane Library databases for relevant papers. Our screening identified relevant studies and biomarkers correlating with the identification of predictive biomarkers. Only studies published between January 2000 and October 2021 were included. Our search identified 5835 abstracts, of which 35 were selected. All biomarker samples were obtained from blood and were used in the evaluation of disease severity and prognosis associated with recovery. These biomarkers have been effective prognostic or predictive factors under various conditions. Finally, we classified them into five categories. There is no consensus in the literature on the correlation between outcomes and prognostic factors for APFP. Furthermore, the correlation between hematologic laboratory values and APFP prognosis remains unclear. However, it is important to identify new methods for improving the accuracy of facial paralysis prognosis prediction. Therefore, we systematically evaluated prognostic and potentially predictive APFP biomarkers. Unfortunately, a predictive biomarker validating APFP prognosis remains unknown. More prospective studies are required to reveal and identify promising biomarkers providing accurate prognosis.
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Affiliation(s)
| | | | - Jae Yong Byun
- Department of Otorhinolaryngology—Head and Neck Surgery, School of Medicine, Kyung Hee University, Seoul 05278, Korea; (T.H.K.); (S.G.Y.)
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19
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Lee M, Kim CH, Kim Y, Jang MU, Mo HJ, Lee SH, Lim JS, Yu KH, Lee BC, Oh MS. High Triglyceride Glucose Index Is Associated with Poor Outcomes in Ischemic Stroke Patients after Reperfusion Therapy. Cerebrovasc Dis 2021; 50:691-699. [PMID: 34229319 DOI: 10.1159/000516950] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 04/28/2021] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION The triglyceride glucose index (TyG index) is a simple and reliable surrogate marker of insulin resistance (IR) that can predict functional outcomes and mortality after acute ischemic stroke (AIS). However, it is unclear whether the TyG index is associated with functional outcomes in patients with stroke who receive reperfusion therapy. Thus, we aimed to explore the prognostic value of the TyG index for the clinical outcomes of patients with AIS who underwent reperfusion therapy. METHODS We retrospectively assessed patients with AIS, with occlusion of either the middle cerebral artery or internal carotid artery, who were evaluated using multiphase computed tomography angiography (mCTA) and received reperfusion therapy. The TyG index was calculated as "ln [fasting glucose level (mg/dL) × triglyceride level (mg/dL)]/2." Collateral status was evaluated using mCTA based on the University of Calgary Scale. Clinical outcomes included 3-month functional outcomes, early neurological deterioration, recanalization status, and hemorrhagic transformation. RESULTS In all, 183 subjects (age 69.5 ± 12.4 years; men, 59.0%) were enrolled. The median initial National Institutes of Health Stroke Scale score was 15.0 (interquartile range [IQR] 11-18). The median TyG index was 4.8 (IQR, 4.6-5.1), and 158 patients had TyG levels >4.49, which represents the presence of IR. On univariate analysis, a higher TyG index was associated with both early neurological deterioration (18.4 vs. 0.0%, p = 0.041) and a 3-month poor functional outcome (mRS3-6) (61.4 vs. 32.0%, p = 0.011). After adjusting for multiple variables, including age, sex, type of reperfusion therapy, recanalization status, initial stroke severity, type of stroke, and history of hypertension and diabetes, high TyG index remained an independent predictor of a poor 3-month functional outcome (adjusted OR, 5.22; p = 0.014). However, TyG levels were not significantly associated with collateral status (p = 0.756). CONCLUSIONS IR, represented by a high TyG index, may predict poor 3-month functional outcomes in patients with AIS who undergo reperfusion therapy.
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Affiliation(s)
- Minwoo Lee
- Department of Neurology, Hallym University Sacred Heart Hospital, Hallym Neurological Institute, Hallym University College of Medicine, Anyang, Republic of Korea,
| | - Chul-Ho Kim
- Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea
| | - Yerim Kim
- Department of Neurology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Min Uk Jang
- Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Hee Jung Mo
- Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Sang-Hwa Lee
- Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea
| | - Jae-Sung Lim
- Department of Neurology, Asan Medical Center, Ulsan University College of Medicine, Seoul, Republic of Korea
| | - Kyung-Ho Yu
- Department of Neurology, Hallym University Sacred Heart Hospital, Hallym Neurological Institute, Hallym University College of Medicine, Anyang, Republic of Korea
| | - Byung-Chul Lee
- Department of Neurology, Hallym University Sacred Heart Hospital, Hallym Neurological Institute, Hallym University College of Medicine, Anyang, Republic of Korea
| | - Mi Sun Oh
- Department of Neurology, Hallym University Sacred Heart Hospital, Hallym Neurological Institute, Hallym University College of Medicine, Anyang, Republic of Korea
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20
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Stewart LK, Kline JA. Fibrinolytics for the treatment of pulmonary embolism. Transl Res 2020; 225:82-94. [PMID: 32434005 PMCID: PMC7487055 DOI: 10.1016/j.trsl.2020.05.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 04/07/2020] [Accepted: 05/05/2020] [Indexed: 12/15/2022]
Abstract
The use of fibrinolytic agents in acute pulmonary embolism (PE), first described over 50 years ago, hastens the resolution of RV stain, leading to earlier hemodynamic improvement. However, this benefit comes at the increased risk of bleeding. The strongest indication for fibrinolysis is in high-risk PE, or that characterized by sustained hypotension, while its use in patients with intermediate-risk PE remains controversial. Fibrinolysis is generally not recommended for routine use in intermediate-risk PE, although most guidelines advise that it may be considered in patients with signs of acute decompensation and an overall low bleeding risk. The efficacy of fibrinolysis often varies significantly between patients, which may be at least partially explained by several factors found to promote resistance to fibrinolysis. Ultimately, treatment decisions should carefully weigh the risks and benefits of the individual clinical scenario at hand, including the overall severity, the patient's bleeding risk, and the presence of factors known to promote resistance to fibrinolysis. This review aims to further explore the use of fibrinolytic agents in the treatment of PE including specific indications, outcomes, and special considerations.
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Affiliation(s)
- Lauren K Stewart
- Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
| | - Jeffrey A Kline
- Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana
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Sriram K, Insel PA. Inflammation and thrombosis in COVID-19 pathophysiology: proteinase-activated and purinergic receptors as drivers and candidate therapeutic targets. Physiol Rev 2020; 101:545-567. [PMID: 33124941 PMCID: PMC8238137 DOI: 10.1152/physrev.00035.2020] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Evolving information has identified disease mechanisms and dysregulation of host biology that might be targeted therapeutically in coronavirus disease 2019 (COVID-19). Thrombosis and coagulopathy, associated with pulmonary injury and inflammation, are emerging clinical features of COVID-19. We present a framework for mechanisms of thrombosis in COVID-19 that initially derive from interaction of SARS-CoV-2 with ACE2, resulting in dysregulation of angiotensin signaling and subsequent inflammation and tissue injury. These responses result in increased signaling by thrombin (proteinase-activated) and purinergic receptors, which promote platelet activation and exert pathological effects on other cell types (e.g., endothelial cells, epithelial cells, and fibroblasts), further enhancing inflammation and injury. Inhibitors of thrombin and purinergic receptors may, thus, have therapeutic effects by blunting platelet-mediated thromboinflammation and dysfunction in other cell types. Such inhibitors include agents (e.g., anti-platelet drugs) approved for other indications, and that could be repurposed to treat, and potentially improve the outcome of, COVID-19 patients. COVID-19, caused by the SARS-CoV-2 virus, drives dysregulation of angiotensin signaling, which, in turn, increases thrombin-mediated and purinergic-mediated activation of platelets and increase in inflammation. This thromboinflammation impacts the lungs and can also have systemic effects. Inhibitors of receptors that drive platelet activation or inhibitors of the coagulation cascade provide opportunities to treat COVID-19 thromboinflammation.
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Affiliation(s)
- Krishna Sriram
- Department of Pharmacology, University of California San Diego, La Jolla, California
| | - Paul A Insel
- Department of Pharmacology and Medicine, University of California San Diego, La Jolla, California
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22
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Use of the ZDF rat to model dietary fat induced hypercoagulability is limited by progressive and fatal nephropathy. J Pharmacol Toxicol Methods 2020; 107:106933. [PMID: 33122074 DOI: 10.1016/j.vascn.2020.106933] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 08/31/2020] [Accepted: 10/06/2020] [Indexed: 01/22/2023]
Abstract
INTRODUCTION Zucker diabetic fatty (ZDF) rats are used widely as an animal model of metabolic syndrome and insulin resistance. Our study focused on the effects of high versus low dietary fat on the development of Type 2 diabetes in obese male ZDF rats (fa/fa), including biomarkers to detect early signs of hypercoagulability and vascular injury in the absence of overt thrombosis. METHODS In this study, male (5/group) 10-week-old CRL:ZDF370(obese) rats were fed low (LFD, 16.7% fat) or high fat (HFD, 60% fat) diet for 12 or 15 weeks. Cohorts of 5 rats within diet groups were scheduled for sample collection after weeks 12 and 15. RESULTS HFD-fed ZDF rats had oily coats, lower rates of food consumption, more accelerated weight gain and increased serum cholesterol (+15%) and triglyceride concentrations (+75%) vs. LFD-fed ZDF rats. Urinary ketones were observed only in HFD-fed ZDF rats and greater urine glucose and protein concentrations in HFD-fed ZDF vs. LFD-fed ZDF rats were seen. Hemostasis testing showed ~2-fold greater fibrinogen concentration, increased von Willebrand factor concentration, and high thrombin generation in HFD-fed ZDF vs LFD-fed ZDF rats. Increased mortality in the HFD-fed ZDF rat was attributed to exacerbations of altered carbohydrate metabolism as evidenced by ketonuria and nephropathy leading to renal failure. DISCUSSION This characterization shows that the ZDF rat at the age, sex and weight used in this study is highly sensitive to dietary fat content that can exacerbate prothrombotic, metabolic and renal disturbances and increase mortality.
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Ullah H, De Filippis A, Khan H, Xiao J, Daglia M. An overview of the health benefits of Prunus species with special reference to metabolic syndrome risk factors. Food Chem Toxicol 2020; 144:111574. [PMID: 32679287 DOI: 10.1016/j.fct.2020.111574] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 06/24/2020] [Accepted: 06/30/2020] [Indexed: 02/08/2023]
Abstract
Metabolic syndrome is a cluster of pathologies and conditions such as obesity, hyperglycemia, hyperlipidemia and hypertension representing a serious health concern in many countries due to its high rate of mortality and morbidity. Insulin resistance is known to play a central role in the development of metabolic syndrome and several risk factors, including visceral obesity, oxidative stress and chronic inflammation, could trigger insulin resistance. Different strategies are currently in practice to manage metabolic syndrome. Along with dietary components, botanicals contain secondary metabolites, which may play a pivotal role in the maintenance of health by combating chronic disorders. Genus Prunus is classified under family Rosaceae and consists of 400-430 species. This genus contains some important species of fruits and ornamental plants. Prunus species contain important micronutrients such as vitamins and minerals and their consumption could maintain health by nourishing the body with essential and non-essential compounds. Besides nutritional components, they also contain bioactive compounds such as polyphenols, which make them potential alternative therapeutic agents for a number of chronic disorders including dysregulated metabolic conditions. The present review is designed to highlight the evidence-based effects of Prunus species against metabolic syndrome risk factors.
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Affiliation(s)
- Hammad Ullah
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Anna De Filippis
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan, 23200, Pakistan
| | - Jianbo Xiao
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, 212013, China
| | - Maria Daglia
- Department of Pharmacy, University of Naples Federico II, Naples, Italy; International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, 212013, China.
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He X, Fei Q, Sun T. Metabolic syndrome increases risk for perioperative outcomes following posterior lumbar interbody fusion. Medicine (Baltimore) 2020; 99:e21786. [PMID: 32957307 PMCID: PMC7505287 DOI: 10.1097/md.0000000000021786] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
The present study is a retrospective cohort study. Metabolic syndrome (MetS) is a clustering of clinical findings that has been shown to increase the risk of the surgical outcomes. Our study aimed to evaluate whether MetS was a risk factor for increased perioperative outcomes in patients undergoing posterior lumbar interbody fusion (PLIF).We retrospectively analyzed patients over 18 years following elective posterior lumbar spine fusion from January 2014 to December 2018. Emergency procedures, infections, tumor, fracture, and revision surgeries were excluded. Patients were divided into 2 groups with and without MetS. The MetS was defined by having 3 of the following 4 criteria: obesity (body mass index ≥30 kg/m), dyslipidemia, hypertension, and diabetes. The follow-up period lasted up to 30 days after surgery. The outcomes of demographics, comorbidities, perioperative complications, and length of stay were compared between the 2 groups. Multivariate logistic regression analysis was used to identify perioperative outcomes that were independently associated with MetS.The overall prevalence of MetS was 12.5% (360/2880). Patients with MetS was a significantly higher risk factor for perioperative complications, and longer length of stay cmpared with patients without MetS (P < .05). The MetS group had a higher rate of cardiac complications (P = .019), pulmonary complication (P = .035), pneumonia (P = .026), cerebrovascular event (P = .023), urinary tract infection (P = .018), postoperative ICU admission (P = .02), and deep vein thrombosis (P = .029) than non-MetS group. The patients with MetS had longer hospital stays than the patients without MetS (22.16 vs 19.99 days, P < .001). Logistic regression analysis revealed that patients with MetS were more likely to experience perioperative complications (odds ratio [OR] 1.31; 95% confidence interval [CI]: 1.06-2.07; P < .001), and extend the length of stay (OR: 1.69; 95% CI: 1.25-2028; P = .001).The MetS is a significant risk factor for increased perioperative complications, and extend length of stay after PLIF. Strategies to minimize the adverse effect of MetS should be considered for these patients.
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Affiliation(s)
- Xiaoqi He
- Department of Orthopedics, Xianyang Central Hospital, Xianyang, Shaanxi
| | - Qiaoman Fei
- Graduate School of Tianjin Medical University, Tianjin
| | - Tianwei Sun
- Department of Spinal Surgery, Tianjin Union Medical Center, Tianjin, People's Republic of China
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Chocair PR, Neves PDMDM, Pereira LVB, Mohrbacher S, Oliveira ES, Nardotto LL, Bales AM, Sato VAH, Ferreira BMC, Cuvello Neto AL. Covid-19 and Metabolic Syndrome. ACTA ACUST UNITED AC 2020; 66:871-875. [PMID: 32844933 DOI: 10.1590/1806-9282.66.7.871] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Accepted: 05/23/2020] [Indexed: 01/18/2023]
Affiliation(s)
| | | | | | - Sara Mohrbacher
- Serviço de Clínica Médica, Hospital Alemão Oswaldo Cruz, São Paulo, SP, Brasil
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Paczkowska-Abdulsalam M, Niemira M, Bielska A, Szałkowska A, Raczkowska BA, Junttila S, Gyenesei A, Adamska-Patruno E, Maliszewska K, Citko A, Szczerbiński Ł, Krętowski A. Evaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects. Int J Mol Sci 2020; 21:ijms21041455. [PMID: 32093387 PMCID: PMC7073064 DOI: 10.3390/ijms21041455] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 02/17/2020] [Accepted: 02/19/2020] [Indexed: 01/03/2023] Open
Abstract
Multiple mechanisms have been suggested to confer to the pathophysiology of metabolic syndrome (MetS), however despite great interest from the scientific community, the exact contribution of each of MetS risk factors still remains unclear. The present study aimed to investigate molecular signatures in peripheral blood of individuals affected by MetS and different degrees of obesity. Metabolic health of 1204 individuals from 1000PLUS cohort was assessed, and 32 subjects were recruited to four study groups: MetS lean, MetS obese, “healthy obese”, and healthy lean. Whole-blood transcriptome next generation sequencing with functional data analysis were carried out. MetS obese and MetS lean study participants showed the upregulation of genes involved in inflammation and coagulation processes: granulocyte adhesion and diapedesis (p < 0.0001, p = 0.0063), prothrombin activation pathway (p = 0.0032, p = 0.0091), coagulation system (p = 0.0010, p = 0.0155). The results for “healthy obese” indicate enrichment in molecules associated with protein synthesis (p < 0.0001), mitochondrial dysfunction (p < 0.0001), and oxidative phosphorylation (p < 0.0001). Our results suggest that MetS is related to the state of inflammation and vascular system changes independent of excess body weight. Furthermore, “healthy obese”, despite not fulfilling the criteria for MetS diagnosis, seems to display an intermediate state with a lower degree of metabolic abnormalities, before they proceed to a full blown MetS.
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Affiliation(s)
- Magdalena Paczkowska-Abdulsalam
- Clinical Research Centre, Medical University of Białystok, M. Skłodowskiej-Curie 24A, 15-276 Białystok, Poland
- Correspondence: ; Tel.: +48-85-831-81-59
| | - Magdalena Niemira
- Clinical Research Centre, Medical University of Białystok, M. Skłodowskiej-Curie 24A, 15-276 Białystok, Poland
| | - Agnieszka Bielska
- Clinical Research Centre, Medical University of Białystok, M. Skłodowskiej-Curie 24A, 15-276 Białystok, Poland
| | - Anna Szałkowska
- Clinical Research Centre, Medical University of Białystok, M. Skłodowskiej-Curie 24A, 15-276 Białystok, Poland
| | - Beata Anna Raczkowska
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, M. Skłodowskiej-Curie 24A, 15-276 Białystok, Poland
| | - Sini Junttila
- Vienna Biocenter Core Facilities, Dr.-Bohr-Gasse 3, 1030 Vienna, Austria
| | - Attila Gyenesei
- Vienna Biocenter Core Facilities, Dr.-Bohr-Gasse 3, 1030 Vienna, Austria
| | - Edyta Adamska-Patruno
- Clinical Research Centre, Medical University of Białystok, M. Skłodowskiej-Curie 24A, 15-276 Białystok, Poland
| | - Katarzyna Maliszewska
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, M. Skłodowskiej-Curie 24A, 15-276 Białystok, Poland
| | - Anna Citko
- Clinical Research Centre, Medical University of Białystok, M. Skłodowskiej-Curie 24A, 15-276 Białystok, Poland
| | - Łukasz Szczerbiński
- Clinical Research Centre, Medical University of Białystok, M. Skłodowskiej-Curie 24A, 15-276 Białystok, Poland
| | - Adam Krętowski
- Clinical Research Centre, Medical University of Białystok, M. Skłodowskiej-Curie 24A, 15-276 Białystok, Poland
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, M. Skłodowskiej-Curie 24A, 15-276 Białystok, Poland
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Bukhari IA, Habib SS, Alnahedh A, Almutairi F, Alkahtani L, Alareek LA, Assiri GA. Relationship of Body Adiposity with Platelet Function in Obese and Non-obese Individuals. Cureus 2020; 12:e6815. [PMID: 32133271 PMCID: PMC7049893 DOI: 10.7759/cureus.6815] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Background Adiposity is firmly linked to a higher incidence of various cardiovascular and metabolic morbidities, including diabetes, hypertension, and thromboembolism. This research study was aimed to verify the association of increased adiposity and hyperreactivity of platelets in obese and non-obese individuals. Methods This cross-sectional study was conducted on 42 subjects aged 18 years and above. Subjects were divided into obese and non-obese groups based on their body mass index (BMI). The data was collected through self-administered questionnaires. All participants underwent body composition analysis. Blood samples were collected from all subjects and taken to the Pharmacology Department for the preparation of platelet-rich plasma (PRP) and poor platelet plasma (PPP). Platelet aggregation was induced by arachidonic acid and was monitored with a Bio/Data multichannel aggregation profiler (Bio/Data Corp., Horsham, PA, USA). Results Significant differences were observed in most parameters, such as fat mass, body fat percentage, free fat mass (FFM), the percentage of trunk fat, total body water, waist-hip ratio (WHR), and basal metabolic rate (BMR) of obese and non-obese subjects. The average percent of platelet aggregation in obese and non-obese subjects was 56.33 ± 15.62 and 59.38 ± 12.62, respectively. The average area under the curve (AUC) for platelet aggregation for both groups was 339.33 ± 191.55 and 342 ± 146.68, respectively. Platelet function was not significantly different and didn’t positively correlate with most parameters of the body composition, except WHR, which positively correlated with AUC for platelet function. Conclusion There was no significant direct correlation between adiposity and platelet activation in obese subjects. However, a significant positive correlation of AUC for platelet aggregation with WHR was observed (resistance (r)-value: 0.307, p < 0.05). These findings suggest that WHR could be an effective determinant to assess the risk of thromboembolism in obese individuals.
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Affiliation(s)
- Ishfaq A Bukhari
- Pharmacology, College of Medicine, King Saud University, Riyadh, SAU
| | - Syed S Habib
- Physiology Department, College of Medicine and King Saud University Medical City, King Saud University, Riyadh, SAU
| | - Alaa Alnahedh
- Pharmacology Section, College of Medicine and King Saud University Medical City, King Saud University, Riyadh, SAU
| | - Futoon Almutairi
- Pharmacology Section, College of Medicine and King Saud University Medical City, King Saud University, Riyadh, SAU
| | - Lama Alkahtani
- Pharmacology Section, College of Medicine and King Saud University Medical City, King Saud University, Riyadh, SAU
| | - Latefa A Alareek
- Pharmacology Section, College of Medicine and King Saud University Medical City, King Saud University, Riyadh, SAU
| | - Ghadah A Assiri
- Clinical Pharmacology Department, College of Pharmacy, King Saud University, Riyadh, SAU
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Association of Patients' Characteristics with Acupuncture Treatment Outcomes in Treating Bell's Palsy: Results from a Randomised Controlled Trial. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:6073484. [PMID: 31511780 PMCID: PMC6714330 DOI: 10.1155/2019/6073484] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 07/22/2019] [Accepted: 07/29/2019] [Indexed: 11/17/2022]
Abstract
Background Acupuncture has been found to be effective for treating Bell's palsy (BP). However, which class of BP patients will have a better response to acupuncture remains uncertain and requires investigation. Methods We performed a secondary analysis of a multicenter, randomized, controlled trial. BP patients were randomly divided into five acupuncture treatment groups. The degree of facial nerve recovery was assessed according to the House–Brackmann grading system (HB grade). Grade I was defined as complete recovery (CR), and grades II–VI were defined as incomplete recovery (IR). The relevant patient characteristics were collected and compared between CR and IR groups by univariate and logistic regression analyses. Results Eight-hundred twenty-six subjects were analyzed. Among these, 698 (85%) subjects had a good prognosis. No significant difference in the effectiveness of the five treatments was observed (all P > 0.05). The likelihood of IR increased by 2.2% with each one-year increase in age (odds ratio (OR) 1.022, 95% confidence interval (CI) 1.005–1.038; P=0.009). The likelihood of IR increased by 9% with each kg/m2 increase in BMI (OR 1.090, 95% CI 1.019–1.165; P=0.012). The likelihood of IR at the recovery stage was higher than that at the acute stage (OR 7.996, 95% CI 4.570–13.991; P < 0.001), and the likelihood of IR of patients with lesions at or above the chorda tympani was higher than that of patients with lesions below the chorda tympani (OR 1.989, 95% CI 1.256–3.150; P=0.003). The likelihood of IR increased by 281.7% with each unit increase in the HB grade (OR 2.817, 95% CI 2.113–3.756; P < 0.001). Conclusions Younger patients at the acute stage of the disease with low BMIs, low initial HB grades, and lesions below the chorda tympani were more likely to respond to acupuncture.
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Omae T, Koh K, Kumemura M, Sakuraba S, Katsuda Y. Perioperative management of patients with atrial fibrillation receiving anticoagulant therapy. J Anesth 2019; 33:551-561. [PMID: 31069541 DOI: 10.1007/s00540-019-02653-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Accepted: 05/03/2019] [Indexed: 12/16/2022]
Abstract
The number of patients with atrial fibrillation (AF) and the number of patients indicated for anticoagulant therapy have been increasing because AF would affect patient survival due to thromboembolism. Once AF develops, following the disappearance of pulsation, the circumstances within the atrium become prothrombotic and thrombus formation within the left atrium occurs in patients with AF. In recent years, not only warfarin but also new oral anticoagulants were introduced clinically and have become used as oral anticoagulants. In the perioperative period, the risk of major hemorrhage needs to be reduced. On the other hand, the suspension of anticoagulant therapy and neutralization of anticoagulant effects elevate the risk of thrombosis. The perioperative management of patients receiving anticoagulant therapy is different from that of scheduled surgery and emergency surgery. In addition, knowledge of the characteristics of each oral anticoagulant is required at drug cessation and resumption. Unlike warfarin, which has been used in the past five decades, direct oral anticoagulants (DOACs) do not have sensitive indicators such as prothrombin time-international normalized ratio. To avoid major hemorrhages and thromboembolism, quantitative assays can be implemented for DOAC monitoring and for reversal therapies in perioperative settings.
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Affiliation(s)
- Takeshi Omae
- Department of Anesthesiology and Pain Clinic, Juntendo University Shizuoka Hospital, Izunokuni, 1129 Nagaoka, Izunokuni, Shizuoka, 410-2295, Japan.
| | - Keito Koh
- Department of Anesthesiology and Pain Clinic, Juntendo University Shizuoka Hospital, Izunokuni, 1129 Nagaoka, Izunokuni, Shizuoka, 410-2295, Japan
| | - Masateru Kumemura
- Department of Anesthesiology and Pain Clinic, Juntendo University Shizuoka Hospital, Izunokuni, 1129 Nagaoka, Izunokuni, Shizuoka, 410-2295, Japan
| | - Sonoko Sakuraba
- Department of Anesthesiology and Pain Clinic, Juntendo University Shizuoka Hospital, Izunokuni, 1129 Nagaoka, Izunokuni, Shizuoka, 410-2295, Japan
| | - Yosuke Katsuda
- Department of Anesthesiology and Pain Clinic, Juntendo University Shizuoka Hospital, Izunokuni, 1129 Nagaoka, Izunokuni, Shizuoka, 410-2295, Japan
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Mosimah CI, Murray PJ, Simpkins JW. Not all clots are created equal: a review of deficient thrombolysis with tissue plasminogen activator (tPA) in patients with metabolic syndrome. Int J Neurosci 2018; 129:612-618. [PMID: 30465701 DOI: 10.1080/00207454.2018.1550400] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Metabolic syndrome is a cluster of cardiovascular risk factors associated with a prothrombotic, proinflammatory and hypofibrinolysis state. Although resistance to tissue plasminogen activator (tPA) in metabolic syndrome patients has been associated with a defective fibrinolytic system, the factors and mechanisms underlining such resistance is unclear. While there is a great debate on proposed mechanisms, fundamental questions regarding resistance to tPA in metabolic syndrome patients with ischemic stroke remain unanswered. This article reviews articles and documents published between 2001 and 2017, and provides an overview of metabolic syndrome, factors associated with tPA resistance in metabolic syndrome, conflicting evidence of insufficient dosing of tPA in overweight/obese patients and future directions for research.
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Affiliation(s)
- Charles I Mosimah
- a Department of Clinical and Translational Sciences , West Virginia University , Morgantown , WV , USA
| | - Pamela J Murray
- b Department of Pediatrics , West Virginia University , Morgantown , WV , USA
| | - James W Simpkins
- c Department of Physiology Pharmacology & Neuroscience , West Virginia University , Morgantown , WV , USA
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Pedro-Botet J, Ascaso JF, Barrios V, De la Sierra A, Escalada J, Millán J, Mostaza JM, Pérez-Martínez P, Pintó X, Salas-Salvadó J, Valdivielso P. COSMIC project: consensus on the objectives of the metabolic syndrome in clinic. Diabetes Metab Syndr Obes 2018; 11:683-697. [PMID: 30464566 PMCID: PMC6217133 DOI: 10.2147/dmso.s165740] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Metabolic syndrome (MetS), a disorder with a high and growing prevalence, is a recognized risk factor for cardiovascular disease (CVD) and type 2 diabetes. It is a constellation of clinical and metabolic risk factors that include abdominal obesity, dyslipidemia, glucose intolerance, and hypertension. Unfortunately, MetS is typically underrecognized, and there is great heterogeneity in its management, which can hamper clinical decision-making and be a barrier to achieving the therapeutic goals of CVD and diabetes prevention. Although no single treatment for MetS as a whole currently exists, management should be targeted at treating the conditions contributing to it and possibly reversing the risk factors. All this justifies the need to develop recommendations that adapt existing knowledge to clinical practice in our healthcare system. In this regard, professionals from different scientific societies who are involved in the management of the different MetS components reviewed the available scientific evidence focused basically on therapeutic aspects of MetS and developed a consensus document to establish recommendations on therapeutic goals that facilitate their homogenization in clinical decision-making.
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Affiliation(s)
- Juan Pedro-Botet
- Lipids and Vascular Risk Unit, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain,
| | - Juan F Ascaso
- Endocrinology and Nutrition Service, Hospital Clínico, Universitat de Valencia, Valencia, Spain
- INCLIVA Research Institute, Diabetes and Metabolic Diseases Ciber (Networked Biomedical Research Centres - CIBERDEM), Carlos III, Valencia, Spain
| | - Vivencio Barrios
- Cardiology Service, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain
- Department of Medicine, Universidad Católica de Murcia (UCAM), Murcia, Spain
| | - Alejandro De la Sierra
- Internal Medicine Service, Hospital Mutua de Terrassa, Department of Medicine, Universidad de Barcelona, Spain
| | - Javier Escalada
- Department of Endocrinology and Nutrition, Clínica Universitaria de Navarra, IdiSNA
- CIBEROBN "Physiopathology of Obesity and Nutrition", Carlos III Health Institute, Spain
| | - Jesús Millán
- Lipid Unit, Department of Internal Medicine, Hospital Universitario General Gregorio Marañón, Universidad Complutense, Madrid, Spain
| | - Jose M Mostaza
- Lipid and Arteriosclerosis Unit, Internal Medicine Service, Hospital Carlos III, Madrid, Spain
| | - Pablo Pérez-Martínez
- CIBEROBN "Physiopathology of Obesity and Nutrition", Carlos III Health Institute, Spain
- Lipid and Arteriosclerosis Unit, Hospital Universitario Reina Sofía, IMIBIC/University of Cordoba, Cordoba, Spain
| | - Xavier Pintó
- CIBEROBN "Physiopathology of Obesity and Nutrition", Carlos III Health Institute, Spain
- Lipids Unit, Department of Internal Medicine Hospital Universitario de Bellvitge, Universidad de Barcelona, Barcelona, Spain
| | - Jordi Salas-Salvadó
- CIBEROBN "Physiopathology of Obesity and Nutrition", Carlos III Health Institute, Spain
- Nutrition Unit, Hospital Universitari Sant Joan de Reus, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili
| | - Pedro Valdivielso
- Internal Medicine Service, Department of Medicine and Dermatology, Hospital Universitario Virgen de la Victoria, Málaga Biomedicine Institute (IBIMA), Universidad de Málaga, Málaga, Spain
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Jung SY, Jung J, Byun JY, Park MS, Kim SH, Yeo SG. The effect of metabolic syndrome on Bell's palsy recovery rate. Acta Otolaryngol 2018; 138:670-674. [PMID: 29374993 DOI: 10.1080/00016489.2018.1425902] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVE This study investigated the effects metabolic syndrome (MetS) and its factors such as diabetes mellitus (DM), hypertension (HTN), obesity, hypertriglyceridemia (high TG) and low high-density lipoprotein cholesterol (low HDL-C) on the recovery rate of patients with BP. METHODS The medical records of 124 patients with BP were retrospectively reviewed. Patients were divided into a MetS group and a Non-MetS group according to the diagnostic criteria of MetS, and the demographic and clinical characteristics of the two groups at baseline and six months after BP onset were analyzed. RESULTS Age was significantly higher in the MetS group than in the Non-MetS group (p < .05), but there were no significant differences in sex ratio, initial House-Brackmann (H-B) grade, initial electroneurography and initial electromyography (p > .05). The most common comorbidity of BP was high TG, followed by low HDL-C, HTN, obesity and DM. There were no differences in initial H-B grade in patients with and without each component of the MetS (p > .05). The recovery rate of BP was significantly lower in the MetS than in the Non-MetS group and was particularly affected by DM, obesity and high TG. CONCLUSIONS Recovery rate op BP is lower in patients with than without MetS.
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Affiliation(s)
- Su Young Jung
- Department of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, Kyung Hee University, Seoul, South Korea
| | - Junyang Jung
- Department of Anatomy, School of Medicine, Kyung Hee University, Seoul, South Korea
| | - Jae Yong Byun
- Department of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, Kyung Hee University, Seoul, South Korea
| | - Moon Suh Park
- Department of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, Kyung Hee University, Seoul, South Korea
| | - Sang Hoon Kim
- Department of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, Kyung Hee University, Seoul, South Korea
| | - Seung Geun Yeo
- Department of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, Kyung Hee University, Seoul, South Korea
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Homeostasis model assessment of insulin resistance in relation to the poor functional outcomes in nondiabetic patients with ischemic stroke. Biosci Rep 2018; 38:BSR20180330. [PMID: 29588341 PMCID: PMC5938425 DOI: 10.1042/bsr20180330] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Revised: 03/24/2018] [Accepted: 03/26/2018] [Indexed: 12/11/2022] Open
Abstract
Whether insulin resistance (IR) predicts worse functional outcome in ischemic stroke is still a matter of debate. The aim of the present study is to determine the association between IR and risk of poor outcome in 173 Chinese nondiabetic patients with acute ischemic stroke. This is a prospective, population-based cohort study. Insulin sensitivity, expressed by the homeostasis model assessment (HOMA) of insulin sensitivity (HOMA index = (fasting insulin × fasting glucose)/22.5). IR was defined by HOMA-IR index in the top quartile (Q4). Functional impairment was evaluated at discharge using the modified Rankin scale (mRS). The median (interquartile range) HOMA-IR was 2.14 (1.17–2.83), and Q4 was at least 2.83. There was a significantly positive correlation between HOMA-IR and National Institutes of Health Stroke Scale (r = 0.408; P<0.001). In multivariate analyses, patients in IR group were associated with a higher risk of poor functional outcome (odds ratio (OR) = 3.23; 95% confidence interval (CI) = 1.75–5.08; P=0.001). In multivariate models comparing the third and fourth quartiles against the first quartile of the HOMA-IR, levels of HOMA-IR were associated with poor outcome, and the adjusted risk of poor outcome increased by 207% (OR = 3.05 (95% CI 1.70–4.89), P=0.006) and 429% (5.29 (3.05–9.80), P<0.001). In a receiver operating characteristic curve (ROC) analysis of poor outcome, the area under the curve (AUC) increased from 0.80 to 0.84 (95% CI: 0.79–0.88) by adding HOMA-IR to clinical examination variables (P=0.02). High HOMA-IR index is associated with a poor functional outcome in nondiabetic patients with acute ischemic stroke.
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Itzhaki Ben Zadok O, Eisen A. Use of non-vitamin K oral anticoagulants in people with atrial fibrillation and diabetes mellitus. Diabet Med 2018; 35:548-556. [PMID: 29438571 DOI: 10.1111/dme.13600] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/08/2018] [Indexed: 11/30/2022]
Abstract
AIMS To examine the efficacy and safety of non-vitamin K oral anticoagulants in people with both atrial fibrillation and diabetes mellitus. METHODS We reviewed efficacy and safety data from the warfarin-controlled phase III non-vitamin K oral anticoagulants trials (ARISTOTLE, RE-LY, ROCKET-AF, ENGAGE AF-TIMI 48) and their post hoc analyses with regard to diabetes status. We also reviewed the updated literature regarding this population. RESULTS At baseline 20-40% of the participants in the phase III non-vitamin K oral anticoagulants trials had diabetes mellitus at baseline. This population, in comparison with those without diabetes, was more likely to have other comorbidities, such as hypertension and coronary artery disease; thus, their cardiovascular risk was higher. Participants with diabetes had higher rates of stroke and systemic embolism than participants without diabetes. This risk was decreased using non-vitamin K oral anticoagulants, with no significant interaction by diabetic status or the specific drug used. Overall, compared with warfarin, non-vitamin K oral anticoagulants were safe and reduced the incidence of major bleeding in people with atrial fibrillation and diabetes, although the results varied with the different non-vitamin K oral anticoagulants. CONCLUSIONS The efficacy and safety of non-vitamin K oral anticoagulants compared with warfarin generally extend to participants with diabetes mellitus, although dedicated randomized trials or real-world data are lacking.
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Affiliation(s)
- O Itzhaki Ben Zadok
- Department of Cardiology, Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - A Eisen
- Department of Cardiology, Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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35
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Kutluturk F, Ozsoy Z. Effect of Sleeve Gastrectomy on Platelet Counts and Mean Platelet Volumes. Obes Surg 2018; 28:3159-3164. [PMID: 29717406 DOI: 10.1007/s11695-018-3287-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Faruk Kutluturk
- Department of Endocrinology and Metabolism, Faculty of Medicine, Gaziosmanpasa University, School of Medicine, 60100, Tokat, Turkey.
| | - Zeki Ozsoy
- Department of General Surgery, Gaziosmanpasa University, School of Medicine, Tokat, Turkey
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36
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da Rosa Franchi Santos LF, Stadtlober NP, Costa Dall'Aqua LG, Scavuzzi BM, Guimarães PM, Flauzino T, Batisti Lozovoy MA, Mayumi Iriyoda TV, Vissoci Reiche EM, Dichi I, Maes M, Colado Simão A. Increased adhesion molecule levels in systemic lupus erythematosus: relationships with severity of illness, autoimmunity, metabolic syndrome and cortisol levels. Lupus 2018; 27:380-388. [DOI: 10.1177/0961203317723716] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Background This study was performed to assess adhesion molecules in systemic lupus erythematosus (SLE). Methods This case-control study examined 126 SLE patients and 48 healthy individuals. Blood levels of six adhesion molecules, cortisol, nuclear autoantibody (ANA) and anti-double stranded DNA (anti-dsDNA) titers were measured, while disease activity was assessed using the SLE Disease Activity Index (SLEDAI) score. Results Platelet endothelial cell adhesion molecule 1 (PECAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, P-selectin, and plasminogen activator inhibitor type-1 (PAI-1) were significantly higher in SLE patients than in controls. Binary logistic regression analysis showed that PECAM-1 and PAI-1 predicted SLE with a sensitivity of 86.5% and a specificity of 81.3%. ANA titers were significantly and positively associated with PECAM-1, VCAM-1, E-selectin, and PAI-1, whereas there were no associations between anti-dsDNA titers and adhesion molecules. Cortisol was negatively associated with PCAM-1 and ICAM-1. There were significant associations between metabolic syndrome (MetS) and E-selectin and PAI-1. 14.8% of the variance in the SLEDAI score was explained by the regression on PECAM-1 and MetS. Conclusions Our data show that adhesion molecules, especially PECAM-1, are significantly associated with SLE and disease activity, suggesting that they play a role in SLE pathophysiology. While MetS, ANA titers and cortisol levels modulate adhesion molecule levels, these associations do not explain the increased levels of adhesion molecules in SLE. Increased levels of adhesion molecules are new drug targets in SLE.
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Affiliation(s)
| | - N P Stadtlober
- Graduate Program in Pathology, Clinical Analysis and Toxicology, University of Londrina, Brazil
| | - L G Costa Dall'Aqua
- Graduate Program in Pathology, Clinical Analysis and Toxicology, University of Londrina, Brazil
| | - B M Scavuzzi
- Graduate Program in Health Sciences, University of Londrina, Brazil
| | - P M Guimarães
- Graduate Program in Health Sciences, University of Londrina, Brazil
| | - T Flauzino
- Graduate Program in Health Sciences, University of Londrina, Brazil
| | - M A Batisti Lozovoy
- Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Brazil
| | | | - E M Vissoci Reiche
- Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Brazil
| | - I Dichi
- Department of Internal Medicine, University of Londrina, Brazil
| | - M Maes
- IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, VIC, Australia
| | - A Colado Simão
- Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Brazil
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Targher G, Lonardo A, Byrne CD. Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus. Nat Rev Endocrinol 2018; 14:99-114. [PMID: 29286050 DOI: 10.1038/nrendo.2017.173] [Citation(s) in RCA: 292] [Impact Index Per Article: 41.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus are common diseases that often coexist and might act synergistically to increase the risk of hepatic and extra-hepatic clinical outcomes. NAFLD affects up to 70-80% of patients with type 2 diabetes mellitus and up to 30-40% of adults with type 1 diabetes mellitus. The coexistence of NAFLD and diabetes mellitus increases the risk of developing not only the more severe forms of NAFLD but also chronic vascular complications of diabetes mellitus. Indeed, substantial evidence links NAFLD with an increased risk of developing cardiovascular disease and other cardiac and arrhythmic complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus. NAFLD is also associated with an increased risk of developing microvascular diabetic complications, especially chronic kidney disease. This Review focuses on the strong association between NAFLD and the risk of chronic vascular complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus, thereby promoting an increased awareness of the extra-hepatic implications of this increasingly prevalent and burdensome liver disease. We also discuss the putative underlying mechanisms by which NAFLD contributes to vascular diseases, as well as the emerging role of changes in the gut microbiota (dysbiosis) in the pathogenesis of NAFLD and associated vascular diseases.
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Affiliation(s)
- Giovanni Targher
- Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Stefani 1, 37126 Verona, Italy
| | - Amedeo Lonardo
- Azienda Ospedaliera Universitaria di Modena, Ospedale Civile Sant'Agostino Estense, Via Giardini 1355, 41126 Baggiovara, Modena, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, Institute of Developmental Sciences (IDS), MP887, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
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38
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Hayward C. Platelet activation in the pathogenesis of obesity and vascular disease. Thromb Haemost 2017; 106:567-8. [DOI: 10.1160/th11-08-0527] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2011] [Accepted: 08/19/2011] [Indexed: 11/05/2022]
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Alessi MC, Nicaud V, Scroyen I, Lange C, Saut N, Fumeron F, Marre M, Lantieri O, Fontaine-Bisson B, Juhan-Vague I, Balkau B, Tregouet DA, Morange PE. Association of vitronectin and plasminogen activator inhibitor-1 levels with the risk of metabolic syndrome and type 2 diabetes mellitus. Thromb Haemost 2017; 106:416-22. [DOI: 10.1160/th11-03-0179] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2011] [Accepted: 05/26/2011] [Indexed: 11/05/2022]
Abstract
SummaryIt was the objective of this study to investigate the relation between vitronectin and plasminogen activator inhibitor (PAI)-1 plasma levels with nine-year incidences of the metabolic syndrome (MetS) and of type 2 diabetes mellitus (T2DM). Baseline plasma concentrations of vitronectin and PAI-1 were measured in 627 healthy participants from the prospective D.E.S.I.R. cohort who subsequently developed MetS (n=487) and T2DM (n=182) over a nine-year follow-up (42 presented both) and who were matched with two healthy control subjects each by use of a nested case-control design. Parameters composing the MetS explained about 20% of plasma vitronectin levels. An increase of one standard deviation of vitronectin was associated with increased risks of both the MetS (odds ratio [OR] = 1.21 [1.07 – 1.37], p = 0.003) and T2DM (OR = 1.24 [1.01 – 1.53], p = 0.045). Corresponding ORs for PAI-1 levels were 1.46 [1.27 – 1.68] (p < 10−4) and 1.40 [1.14 – 1.72] (p = 0.0012). However, the effects of vitronectin and PAI-1 levels on outcomes were not independent. The vitronectin–MetS association was restricted to individuals with low to modest PAI-1 levels (OR = 1.33 [1.14 – 1.54], p = 0.0003) while no association was observed in individuals with high PAI-1 levels (OR = 0.87 [0.68 – 1.10], p = 0.24), the test for interaction being highly significant (p = 0.0009). In conclusion, baseline plasma vitronectin is a marker of incident MetS at nine years. Its predictive ability for MetS and T2DM should not be assessed independently of PAI-1 levels.
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40
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Lagrange J, Didelot M, Mohamadi A, Walton LA, Bloemen S, de Laat B, Louis H, Thornton SN, Derby B, Sherratt MJ, Fève B, Challande P, Akhtar R, Cruickshank JK, Lacolley P, Regnault V. Implication of Free Fatty Acids in Thrombin Generation and Fibrinolysis in Vascular Inflammation in Zucker Rats and Evolution with Aging. Front Physiol 2017; 8:949. [PMID: 29213245 PMCID: PMC5702631 DOI: 10.3389/fphys.2017.00949] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 11/08/2017] [Indexed: 12/31/2022] Open
Abstract
Background: The metabolic syndrome (MetS) and aging are associated with modifications in blood coagulation factors, vascular inflammation, and increased risk of thrombosis. Objectives: Our aim was to determine concomitant changes in thrombin generation in the blood compartment and at the surface of vascular smooth muscle cells (VSMCs) and its interplay with adipokines, free fatty acids (FFA), and metalloproteinases (MMPs) in obese Zucker rats that share features of the human MetS. Methods: Obese and age-matched lean Zucker rats were compared at 25 and 80 weeks of age. Thrombin generation was assessed by calibrated automated thrombography (CAT). Results: Endogenous thrombin potential (ETP) was increased in obese rats independent of platelets and age. Clot half-lysis time was delayed with obesity and age. Interleukin (IL)-1β and IL-13 were increased with obesity and age respectively. Addition of exogenous fibrinogen, leptin, linoleic, or palmitic acid increased thrombin generation in plasma whereas adiponectin had an opposite effect. ETP was increased at the surface of VSMCs from obese rats and addition of exogenous palmitic acid further enhanced ETP values. Gelatinase activity was increased in aorta at both ages in obese rats and MMP-2 activity was increased in VSMCs from obese rats. Conclusions: Our study demonstrated in MetS an early prothrombotic phenotype of the blood compartment reinforced by procoagulant properties of dedifferentiated and inflammatory VSMCs. Mechanisms involved (1) increased fibrinogen and impaired fibrinolysis and (2) increased saturated fatty acids responsible for additive procoagulant effects. Whether specifically targeting this hypercoagulability using direct thrombin inhibitors would improve outcome in MetS is worth investigating.
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Affiliation(s)
- Jérémy Lagrange
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1116, Vandœuvre-lès-Nancy, France.,Faculté de Médecine, Université de Lorraine, Nancy, France.,Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany
| | - Mélusine Didelot
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1116, Vandœuvre-lès-Nancy, France.,Faculté de Médecine, Université de Lorraine, Nancy, France
| | - Amel Mohamadi
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1116, Vandœuvre-lès-Nancy, France.,Faculté de Médecine, Université de Lorraine, Nancy, France
| | - Lucy A Walton
- Faculty of Medical and Human Sciences, Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom.,Directorate of Radiography, School of Health Sciences, University of Salford, Salford, United Kingdom
| | - Saartje Bloemen
- Synapse Research Institute, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, Netherlands
| | - Bas de Laat
- Synapse Research Institute, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, Netherlands
| | - Huguette Louis
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1116, Vandœuvre-lès-Nancy, France.,Faculté de Médecine, Université de Lorraine, Nancy, France
| | - Simon N Thornton
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1116, Vandœuvre-lès-Nancy, France.,Faculté de Médecine, Université de Lorraine, Nancy, France
| | - Brian Derby
- School of Materials, University of Manchester, Manchester, United Kingdom
| | - Michael J Sherratt
- Faculty of Medical and Human Sciences, Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom
| | - Bruno Fève
- Centre de Recherche Saint-Antoine Institut National de la Santé et de la Recherche Médicale-Université Pierre et Marie Curie, UMR_S 938, Paris, France.,Institut Hospitalo-Universitaire ICAN, Paris, France.,Assistance-Publique des Hôpitaux de Paris, Service d'Endocrinologie, Hôpital Saint-Antoine, Paris, France
| | - Pascal Challande
- UPMC, University of Paris, Paris, France.,Centre National de la Recherche Scientifique, UMR 7190, Paris, France
| | - Riaz Akhtar
- Centre for Materials and Structures, School of Engineering, University of Liverpool, Liverpool, United Kingdom
| | - J Kennedy Cruickshank
- Diabetes & Cardiovascular Medicine, Nutritional Sciences Division, King's College London, London, United Kingdom
| | - Patrick Lacolley
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1116, Vandœuvre-lès-Nancy, France.,Faculté de Médecine, Université de Lorraine, Nancy, France.,CHRU Nancy, Vandœuvre-lès-Nancy, France
| | - Véronique Regnault
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1116, Vandœuvre-lès-Nancy, France.,Faculté de Médecine, Université de Lorraine, Nancy, France.,CHRU Nancy, Vandœuvre-lès-Nancy, France
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Gan YL, Fu JY, Lai OM, Chew BH, Yuen KH, Teng KT, Nesaretnam K, Selvaduray KR, Meganathan P. Effect of palm-based tocotrienols and tocopherol mixture supplementation on platelet aggregation in subjects with metabolic syndrome: a randomised controlled trial. Sci Rep 2017; 7:11542. [PMID: 28912593 PMCID: PMC5599564 DOI: 10.1038/s41598-017-11813-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Accepted: 08/30/2017] [Indexed: 02/08/2023] Open
Abstract
Tocotrienols, the unsaturated form of vitamin E, were reported to modulate platelet aggregation and thrombotic mechanisms in pre-clinical studies. Using a Food and Drug Administration (FDA)-approved cartridge-based measurement system, a randomised, double-blind, crossover and placebo-controlled trial involving 32 metabolic syndrome adults was conducted to investigate the effect of palm-based tocotrienols and tocopherol (PTT) mixture supplementation on platelet aggregation reactivity. The participants were supplemented with 200 mg (69% tocotrienols and 31% α-tocopherol) twice daily of PTT mixture or placebo capsules for 14 days in a random order. After 14 days, each intervention was accompanied by a postprandial study, in which participants consumed 200 mg PTT mixture or placebo capsule after a meal. Blood samples were collected on day 0, day 14 and during postprandial for the measurement of platelet aggregation reactivity. Subjects went through a 15-day washout period before commencement of subsequent intervention. Fasting platelet aggregation reactivity stimulated with adenosine diphosphate (ADP) did not show substantial changes after supplementation with PTT mixture compared to placebo (p = 0.393). Concomitantly, changes in postprandial platelet aggregation reactivity remained similar between PTT mixture and placebo interventions (p = 0.408). The results of this study highlight the lack of inhibitory effect on platelet aggregation after short-term supplementation of PTT mixture in participants with metabolic syndrome.
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Affiliation(s)
- Yee-Lin Gan
- Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Selangor, Malaysia
- Nutrition Unit, Product Development and Advisory Services Division, Malaysian Palm Oil Board, 6, Persiaran Institusi, Bandar Baru Bangi, Kajang, Selangor, Malaysia
| | - Ju-Yen Fu
- Nutrition Unit, Product Development and Advisory Services Division, Malaysian Palm Oil Board, 6, Persiaran Institusi, Bandar Baru Bangi, Kajang, Selangor, Malaysia.
| | - Oi-Ming Lai
- Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Selangor, Malaysia
- Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia
| | - Boon-How Chew
- Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia
| | - Kah-Hay Yuen
- School of Pharmaceuticals Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Kim-Tiu Teng
- Nutrition Unit, Product Development and Advisory Services Division, Malaysian Palm Oil Board, 6, Persiaran Institusi, Bandar Baru Bangi, Kajang, Selangor, Malaysia
| | - Kalanithi Nesaretnam
- Nutrition Unit, Product Development and Advisory Services Division, Malaysian Palm Oil Board, 6, Persiaran Institusi, Bandar Baru Bangi, Kajang, Selangor, Malaysia
| | - Kanga Rani Selvaduray
- Nutrition Unit, Product Development and Advisory Services Division, Malaysian Palm Oil Board, 6, Persiaran Institusi, Bandar Baru Bangi, Kajang, Selangor, Malaysia
| | - Puvaneswari Meganathan
- Nutrition Unit, Product Development and Advisory Services Division, Malaysian Palm Oil Board, 6, Persiaran Institusi, Bandar Baru Bangi, Kajang, Selangor, Malaysia
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Kopec AK, Abrahams SR, Thornton S, Palumbo JS, Mullins ES, Divanovic S, Weiler H, Owens AP, Mackman N, Goss A, van Ryn J, Luyendyk JP, Flick MJ. Thrombin promotes diet-induced obesity through fibrin-driven inflammation. J Clin Invest 2017; 127:3152-3166. [PMID: 28737512 DOI: 10.1172/jci92744] [Citation(s) in RCA: 89] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Accepted: 06/02/2017] [Indexed: 02/06/2023] Open
Abstract
Obesity promotes a chronic inflammatory and hypercoagulable state that drives cardiovascular disease, type 2 diabetes, fatty liver disease, and several cancers. Elevated thrombin activity underlies obesity-linked thromboembolic events, but the mechanistic links between the thrombin/fibrin(ogen) axis and obesity-associated pathologies are incompletely understood. In this work, immunohistochemical studies identified extravascular fibrin deposits within white adipose tissue and liver as distinct features of mice fed a high-fat diet (HFD) as well as obese patients. Fibγ390-396A mice carrying a mutant form of fibrinogen incapable of binding leukocyte αMβ2-integrin were protected from HFD-induced weight gain and elevated adiposity. Fibγ390-396A mice had markedly diminished systemic, adipose, and hepatic inflammation with reduced macrophage counts within white adipose tissue, as well as near-complete protection from development of fatty liver disease and glucose dysmetabolism. Homozygous thrombomodulin-mutant ThbdPro mice, which have elevated thrombin procoagulant function, gained more weight and developed exacerbated fatty liver disease when fed a HFD compared with WT mice. In contrast, treatment with dabigatran, a direct thrombin inhibitor, limited HFD-induced obesity development and suppressed progression of sequelae in mice with established obesity. Collectively, these data provide proof of concept that targeting thrombin or fibrin(ogen) may limit pathologies in obese patients.
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Affiliation(s)
- Anna K Kopec
- Department of Pathobiology and Diagnostic Investigation, Institute for Integrative Toxicology, Michigan State University, East Lansing, Michigan, USA
| | | | | | | | | | - Senad Divanovic
- Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio, USA
| | - Hartmut Weiler
- Department of Physiology, Blood Center of Wisconsin, Milwaukee, Wisconsin, USA
| | - A Phillip Owens
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Nigel Mackman
- Thrombosis and Hemostasis Program, Division of Hematology and Oncology, Department of Medicine, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Ashley Goss
- Department of Cardiometabolic Disease Research, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA
| | - Joanne van Ryn
- Department of Cardiometabolic Disease Research, Boehringer Ingelheim Pharma GmbH, Biberach, Germany
| | - James P Luyendyk
- Department of Pathobiology and Diagnostic Investigation, Institute for Integrative Toxicology, Michigan State University, East Lansing, Michigan, USA
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Akhter MS, Biswas A, Abdullah SM, Behari M, Saxena R. The Role of PAI-1 4G/5G Promoter Polymorphism and Its Levels in the Development of Ischemic Stroke in Young Indian Population. Clin Appl Thromb Hemost 2017; 23:1071-1076. [PMID: 28460568 DOI: 10.1177/1076029617705728] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The plasminogen activator inhibitor-1 (PAI-1) gene has been found to be associated with the pathogenesis and progression of vascular diseases including stroke. A 4G/5G, PAI-1 gene polymorphism has been found to be associated with the plasma PAI-1 levels in different ethnic populations but results are still controversial. The aim of this study was to determine the potential association of 4G/5G polymorphism and plasma PAI-1 levels in the development of ischemic stroke (IS) in young Asian Indians. One hundred patients with IS and an equal number of age- and sex-matched controls were studied. The 4G/5G polymorphism was genotyped in the study population through allele-specific polymerase chain reaction. Plasma PAI-1 levels were evaluated using a commercial kit. The PAI-1 levels were significantly higher in patients when compared to the controls ( P = .03). The variant 4G allele for the PAI-I 4G/5G polymorphism showed both genotypic ( P = .0013, χ2 = 10.303; odds ratio [OR] = 3.75) as well as allelic association ( P = .0004, χ2 = 12.273; OR = 1.99) with IS. The homozygous variant 4G/4G also was found to be associated with the higher PAI-1 levels (0.005). The variant allele 4G of PAI-1 4G/5G polymorphism and higher plasma PAI-1 levels were found to be significantly associated with IS in young Asian Indians.
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Affiliation(s)
- Mohammad Suhail Akhter
- 1 Department of Genetics, College of Applied Medical Sciences, Jazan University, Jizan, Saudi Arabia.,2 Department of Hematology, All India Institute of Medical Sciences, New Delhi, India
| | - Arijit Biswas
- 3 Institute of Experimental Hematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany
| | - Saleh Mohammed Abdullah
- 4 Department of Hematology, College of Applied Medical Sciences, Jazan University, Jizan, Saudi Arabia
| | - Madhuri Behari
- 5 Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
| | - Renu Saxena
- 2 Department of Hematology, All India Institute of Medical Sciences, New Delhi, India
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Jönsson Rylander AC, Lindgren A, Deinum J, Bergström GML, Böttcher G, Kalies I, Wåhlander K. Fibrinolysis inhibitors in plaque stability: a morphological association of PAI-1 and TAFI in advanced carotid plaque. J Thromb Haemost 2017; 15:758-769. [PMID: 28135035 DOI: 10.1111/jth.13641] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Indexed: 11/27/2022]
Abstract
Essentials Fibrinolysis inhibitors are localized in advanced atheroma by immunohistology of endarterectomies. Neovascular endothelium/neocapillaries show thrombin-activatable fibrinolysis inhibitor (TAFI). Macrophage areas show free plasminogen activator inhibitor (PAI-1), notably in the vulnerable part. Free PAI-1 and TAFI stabilize active plaque area by inhibition of fibrinolysis and inflammation. SUMMARY Background Fibrinolysis plays an important role in destabilization of atherosclerotic plaques and is tightly regulated by specific inhibitors. Objective The fibrinolysis inhibitors plasminogen activator inhibitor type-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) were quantified and described in the morphological context of advanced carotid plaques American Heart Association VI-VIII to elucidate their role in plaque stability. Methods Immunohistochemistry in serial sections along the longitudinal axis of endarterectomies from patients with symptomatic carotid stenosis (n = 19) were studied using an antibody specific for free PAI-1 (I205), an antibody with high affinity for TAFI/TAFIa (CP17) and established antibodies for smooth muscle cells (α-actin), endothelial cells (von Willebrand factor [VWF]), macrophages (CD68) and platelets (CD42). Results PAI-1 and TAFI show a specific distribution in these advanced plaques with a maximum corresponding to the internal carotid artery (ICA). Free PAI-1 was mainly detected in macrophages and in intravascular thrombi, and TAFI in endothelial cells (ECs) but also macrophages. The one-way ANOVA analysis with Bonferroni's correction showed a significant increase of macrophages and ECs, TAFI and PAI-1 in areas with high neovascularization in endarterectomy sections corresponding to ICA. High Spearman factors for TAFI, PAI-1 and VWF indicate neovascularization as the main source of plasma proteins, transported by platelets into the atheroma (PAI-1) or expressed by ECs (TAFI). CD68 was highly associated with VWF, PAI-1 and especially TAFI, underlining the role of macrophages in fibrinolytic activity and inflammation. Conclusion The abundance of free PAI-1 and TAFI in the plaque may inhibit plasmin generation and thereby counteract plaque destabilization by fibrinolysis, cell migration and inflammation.
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Affiliation(s)
| | - A Lindgren
- Personalised Healthcare and Biomarkers, AstraZeneca R&D Mölndal, Mölndal, Sweden
| | - J Deinum
- CVMD IMED AstraZeneca R&D Mölndal, Mölndal, Sweden
| | - G M L Bergström
- Sahlgrenska Center for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - G Böttcher
- CSM Pathology Sciences, AstraZeneca R&D Mölndal, Sweden
| | - I Kalies
- CVMD GMed, AstraZeneca R&D Mölndal, Sweden
| | - K Wåhlander
- CVMD Translational Medicine Unit, Early Clinical Development, AstraZeneca R&D Mölndal, Mölndal, Sweden
- Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
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Wong CJ, Koch M, Behling-Kelly EL. Development of a plasminogen activator inhibitor (PAI-1) assay and comparison of plasma PAI-1 activity in hyperlipidemic/dyslipidemic dogs with either hyperadrenocorticism or diabetes mellitus, and healthy dogs. Res Vet Sci 2017; 111:1-8. [DOI: 10.1016/j.rvsc.2016.11.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Revised: 10/19/2016] [Accepted: 11/05/2016] [Indexed: 01/11/2023]
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Barnard SA, Pieters M, Nienaber-Rousseau C, Kruger HS. Degree of obesity influences the relationship of PAI-1 with body fat distribution and metabolic variables in African women. Thromb Res 2016; 146:95-102. [DOI: 10.1016/j.thromres.2016.09.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Revised: 08/19/2016] [Accepted: 09/06/2016] [Indexed: 11/16/2022]
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Nussberger F, Roth B, Metzger T, Kiss B, Thalmann GN, Seiler R. A low or high BMI is a risk factor for renal hematoma after extracorporeal shock wave lithotripsy for kidney stones. Urolithiasis 2016; 45:317-321. [PMID: 27576325 DOI: 10.1007/s00240-016-0915-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2016] [Accepted: 08/22/2016] [Indexed: 10/21/2022]
Abstract
The purpose of this study was to evaluate risk factors for renal hematoma after extracorporeal shock wave lithotripsy (SWL) for kidney stones in a matched case-control analysis of a subgroup of patients recruited from a prospective randomized cohort. Between 06/2010 and 03/2013, 418 patients underwent SWL with the MODULITH®-SLX-F2-lithotripter for kidney stones. In 39/418 patients (9 %), ultrasound at post-treatment day 1 revealed renal hematomas. For 37 of these patients, a matched group without hematoma could be selected according to the following matching criteria: age, gender, number and energy of shock waves, stone burden and localization. Risk factors for renal hematoma after SWL were compared between the two groups. The rates of diabetes, stopped anticoagulant/antiplatelet medications and arterial hypertension were not different between the two groups (p > 0.2). The skin-kidney distance was virtually the same in both groups (p = 0.5). In the hematoma group, significantly more patients had a high (>30: n = 16) as well as a low (<21.5: n = 4) BMI when compared to the control group (n = 4; n = 0; p < 0.001). Importantly, all patients with BMI <21.5 developed renal hematomas after SWL. Patients with a high (>30) or low (<21.5) BMI had a higher risk for renal damage after SWL. Therefore, alternative endoscopic treatment options should be considered in these patients.
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Affiliation(s)
- Fabio Nussberger
- Department of Urology, University of Bern, Freiburgstrasse, 3010, Bern, Switzerland
| | - Beat Roth
- Department of Urology, University of Bern, Freiburgstrasse, 3010, Bern, Switzerland
| | - Tobias Metzger
- Department of Urology, University of Bern, Freiburgstrasse, 3010, Bern, Switzerland
| | - Bernhard Kiss
- Department of Urology, University of Bern, Freiburgstrasse, 3010, Bern, Switzerland
| | - George N Thalmann
- Department of Urology, University of Bern, Freiburgstrasse, 3010, Bern, Switzerland
| | - Roland Seiler
- Department of Urology, University of Bern, Freiburgstrasse, 3010, Bern, Switzerland.
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Barnard SA, Pieters M, De Lange Z. The contribution of different adipose tissue depots to plasma plasminogen activator inhibitor-1 (PAI-1) levels. Blood Rev 2016; 30:421-429. [PMID: 27233154 DOI: 10.1016/j.blre.2016.05.002] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Revised: 04/15/2016] [Accepted: 05/13/2016] [Indexed: 12/31/2022]
Abstract
Increased plasma plasminogen activator inhibitor-1 (PAI-1) level is considered a mechanistic pathway through which obesity contributes to increased cardiovascular disease risk. Abdominal adipose tissue specifically, is a major PAI-1 source with visceral adipose tissue (VAT), an ectopic fat depot, generally considered to produce more PAI-1 than subcutaneous adipose tissue. However, this does not necessarily lead to increased plasma PAI-1 levels. This review provides an overview of studies investigating the association between body fat distribution and plasma PAI-1 levels. It discusses factors that influence this relationship and also considers the contribution of other tissue to plasma PAI-1 levels, placing the relative contribution of adipose tissue into perspective. In conclusion, the relationship between VAT and plasma PAI-1 levels is not fixed but can be modulated by a number of factors such as the size of the subcutaneous adipose tissue depot, ethnicity, possibly genetics and other obesity-related metabolic abnormalities.
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Affiliation(s)
- Sunelle A Barnard
- Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa.
| | - Marlien Pieters
- Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa.
| | - Zelda De Lange
- Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa.
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Dehghani MR, Rezaei Y, Fakour S, Arjmand N. White Blood Cell Count to Mean Platelet Volume Ratio Is a Prognostic Factor in Patients with Non-ST Elevation Acute Coronary Syndrome with or without Metabolic Syndrome. Korean Circ J 2016; 46:229-38. [PMID: 27014354 PMCID: PMC4805568 DOI: 10.4070/kcj.2016.46.2.229] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Revised: 07/14/2015] [Accepted: 08/11/2015] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Leukocyte and platelet have been found to be associated with metabolic syndrome (MetS). We aimed to determine the usefulness of a novel marker named white blood cell count to mean platelet volume ratio (WMR) for predicting outcomes of non-ST elevation acute coronary syndrome (NSTE-ACS) with or without MetS. SUBJECTS AND METHODS A total of 331 NSTE-ACS individuals (60±12.5 years, 57.4% male) were enrolled and followed for a median of 24 months. MetS was identified using the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS Patients were divided into two groups: high WMR (WMR≥720) and low WMR (WMR<720). Major adverse cardiovascular events (MACE) and MetS rates were significantly greater in the higher WMR group compared to those in the low WMR group (MACE: 14.3% vs. 25%, p=0.014; MetS: 50.9% vs. 75%, p<0.001). MetS was diagnosed in 62.2% of patients. MACE incidence in patients with or without MetS was comparable (p=0.737). Among MetS individuals, patients in the high WMR group had more MACE than the low WMR group (11.2% vs. 26.5%, p=0.007). However, MACE was comparable among non-MetS individuals (p=0.681). In multivariable Cox regression analysis, hazard ratios (HR) of MACE incidence for high-WMR in MetS individuals was 2.616 (95% confidence interval: 1.282-5.339, p=0.008). However, HR of MACE incidence for high WMR in non-MetS individuals was not significant. CONCLUSION Among NSTE-ACS patients without revascularization therapy, elevated admission WMR was associated with an increased risk of developing composite MACE in MetS individuals but not in non-MetS patients.
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Affiliation(s)
| | - Yousef Rezaei
- Seyyed-al-Shohada Heart Center, Urmia University of Medical Sciences, Urmia, Iran
| | - Sanam Fakour
- School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Nasim Arjmand
- School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
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Stubblefield WB, Alves NJ, Rondina MT, Kline JA. Variable Resistance to Plasminogen Activator Initiated Fibrinolysis for Intermediate-Risk Pulmonary Embolism. PLoS One 2016; 11:e0148747. [PMID: 26866684 PMCID: PMC4751085 DOI: 10.1371/journal.pone.0148747] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2015] [Accepted: 01/22/2016] [Indexed: 12/23/2022] Open
Abstract
Background We examine the clinical significance and biomarkers of tissue plasminogen activator (tPA)-catalyzed clot lysis time (CLT) in patients with intermediate-risk pulmonary embolism (PE). Methods Platelet-poor, citrated plasma was obtained from patients with PE. Healthy age- and sex-matched patients served as disease-negative controls. Fibrinogen, α2-antiplasmin, plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), plasminogen activator Inhibitor 1 (PAI-1), thrombin time and D-dimer were quantified. Clotting was induced using CaCl2, tissue factor, and phospholipid. Lysis was induced using 60 ng/mL tPA. Time to 50% clot lysis (CLT) was assessed by both thromboelastography (TEG) and turbidimetry (A405). Results Compared with disease-negative controls, patients with PE exhibited significantly longer mean CLT on TEG (+2,580 seconds, 95% CI 1,380 to 3,720 sec). Patients with PE and a short CLT who were treated with tenecteplase had increased risk of bleeding, whereas those with long CLT had significantly worse exercise tolerance and psychometric testing for quality of life at 3 months. A multivariate stepwise removal regression model selected PAI-1 and TAFI as predictive biomarkers of CLT. Conclusion The CLT from TEG predicted increased risk of bleeding and clinical failure with tenecteplase treatment for intermediate-risk PE. Plasmatic PAI-1 and TAFI were independent predictors of CLT.
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Affiliation(s)
| | - Nathan J. Alves
- Indiana University School of Medicine, Indianapolis, United States of America
| | - Matthew T. Rondina
- University of Utah School of Medicine, Salt Lake City, United States of America
| | - Jeffrey A. Kline
- Department of Emergency Medicine, and Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, United States of America
- * E-mail:
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