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      Elevated levels of adiponectin associated with major adverse cardiovascular and cerebrovascular events and mortality risk in ischemic stroke

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          Abstract

          Background

          Adiponectin plays role in multiple metabolic pathways. Previous studies in cardiovascular disease evaluated the association between adiponectin and clinical outcomes, yielding conflicting results. The aim of this study was to investigate the association of adiponectin with major adverse cardiovascular and cerebrovascular events (MACCE) and mortality in Chinese patients with first-ever acute ischemic stroke (AIS).

          Methods

          This was a prospective, multicenter cohort study. From September 2009 through October 2015, all patients with AIS from 3 stroke centers in Shandong were included. Serum levels of adiponectin at admission were tested. The prognostic role of adiponectin to predict the MACCE and mortality within 3 years was evaluated by multivariable-adjusted Cox proportional hazards models.

          Results

          This study included 4274 patients (median age 68 years [interquartile ranges {IQR}: 61–76]; 53.2% men). There were 794 deaths and 899 MACCE events. Higher serum levels of adiponectin on admission were found in patients with MACCE events and nonsurvivors (P < 0.001 and P < 0.001). In multivariable models adjusted for factors that confirmed in the univariate model, elevated serum levels of adiponectin were associated with a higher risk of MACCE (Quartile[Q]4 vs. Q1, Hazard ratio[HR] = 4.95 [95% confidence interval {CI}: 3.03–7.06]) and mortality (Q4 vs. Q1, HR = 5.63 [95% CI 3.15–7.99]). Adiponectin improved the prognostic value of the National Institutes of Health Stroke Scale (NIHSS) to predict MACCE (combined areas under the curve [AUC], 0.76; 95% CI 0.68–0.88; P = 0.001) and mortality (0.78[0.69–0.91]; P < 0.01). Subgroups analysis indicated that the prognostic role of adiponectin was more pronounced in women and patients with high levels of N-terminal-pro B-type natriuretic peptide(NT-pro BNP) (P < 0.001 and P < 0.001).

          Conclusions

          Elevated serum levels of adiponectin were associated with a higher risk of MACCE and mortality independent of traditional risk factors in ischemic stroke patients.

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          Most cited references49

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          Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure.

          Recent studies have suggested that higher body mass index (BMI) is associated with improved prognosis in chronic heart failure (CHF). The adipocytokine adiponectin is inversely associated with BMI, and in healthy subjects, low adiponectin is a predictor of mortality. In a prospective study, we therefore evaluated the association between plasma adiponectin levels and mortality among patients with CHF. In 195 CHF patients (age 69.3+/-10.2 years, BMI 27.3+/-5.2 kg/m2, left ventricular ejection fraction 30+/-8.9%, mean+/-SD), plasma adiponectin and N-terminal pro brain natriuretic peptide (NT-proBNP) were measured at baseline. Adiponectin was positively associated with NT-proBNP (beta=0.47, P<0.001), and both biomarkers were negatively associated with BMI (beta=-0.43, P<0.001 for adiponectin and beta=-0.38, P<0.001 for NT-proBNP, respectively) During a median follow-up of 2.6 years, 46 (23.5%) of the patients died. After adjustment for clinical variables associated with CHF severity (age, systolic blood pressure, left ventricular ejection fraction <25%, duration of CHF, and creatinine clearance) and for NT-proBNP, the hazard ratio of mortality for values in the 2 upper tertiles relative to the lowest tertile of adiponectin was 3.23 (P=0.032). BMI predicted mortality independently of clinical parameters of CHF severity (hazard ratio=0.63, P=0.012), but this association became insignificant after additional adjustment for NT-proBNP (hazard ratio=0.74, P=0.13). A high adiponectin level was a predictor of mortality, independent of risk markers of CHF severity, presumably because of its role as a marker for wasting. BMI was also associated with mortality, but a part of this relation may be mediated by adiponectin and NT-proBNP levels.
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            Adiponectin and coronary heart disease: a prospective study and meta-analysis.

            There is uncertainty about the association between circulating concentrations of adiponectin and coronary heart disease (CHD) risk. We report new data from a prospective study in the context of a meta-analysis of previously published prospective studies. We measured baseline adiponectin levels in stored serum samples of 589 men with fatal CHD or nonfatal myocardial infarction and in 1231 controls nested within a prospective study of 5661 men (aged 40 to 59 years) recruited during 1978-1980, as well as in paired samples obtained 4 years apart from 221 of these participants. Baseline adiponectin concentrations correlated (P < 0.0001) positively with HDL cholesterol (r = 0.33) and inversely with C-reactive protein (r = -0.11) and BMI (r = -0.21), and the year-to-year consistency of adiponectin values was comparable to those of blood pressure and total cholesterol levels. No significant difference between median adiponectin levels at baseline was observed between cases and controls (10.2 versus 10.8 microg/mL; P = 0.5), despite the fact that body mass index, HDL, and C-reactive protein were all significant predictors of events in this cohort. The odds ratio for CHD was 0.89 (95% CI, 0.67 to 1.18) in a comparison of men in the top third of adiponectin concentrations compared with those in the bottom third, similar to a meta-analysis (including the present study) of 7 prospective studies involving a total of 1318 CHD cases (odds ratio, 0.84 [95% CI, 0.70 to 1.01]). In contrast to the strong associations previously reported between adiponectin levels and risk of type 2 diabetes, any association with CHD risk is comparatively moderate and requires further investigation.
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              Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure.

              We investigated the functional relationship between natriuretic peptides and adiponectin by performing both experimental and clinical studies. Natriuretic peptides are promising candidates for the treatment of congestive heart failure (CHF) because of their wide range of beneficial effects on the cardiovascular system. Adiponectin is a cytokine derived from adipose tissue with various cardiovascular-protective effects that has been reported to show a positive association with plasma brain natriuretic peptide (BNP) levels in patients with heart failure. The expression of adiponectin messenger ribonucleic acid (mRNA) and its secretion were examined after atrial natriuretic peptide (ANP) or BNP was added to primary cultures of human adipocytes in the presence or absence of HS142-1 (a functional type A guanylyl cyclase receptor antagonist). Changes of the plasma adiponectin level were determined in 30 patients with CHF who were randomized to receive intravenous ANP (0.025 microg/kg/min human ANP for 3 days, n = 15) or saline (n = 15). Both ANP and BNP dose-dependently enhanced the expression of adiponectin mRNA and its secretion, whereas such enhancement was inhibited by pre-treatment with HS142-1. The plasma adiponectin level was increased at 4 days after administration of human ANP compared with the baseline value (from 6.56 +/- 0.40 microg/ml to 7.34 +/- 0.47 microg/ml, p < 0.05), whereas there was no change of adiponectin in the saline group (from 6.53 +/- 0.57 microg/ml to 6.55 +/- 0.56 microg/ml). Natriuretic peptides enhance adiponectin production by human adipocytes in vitro and even in patients with CHF, which might have a beneficial effect on cardiomyocytes in patients receiving recombinant natriuretic peptide therapy for heart failure.
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                Author and article information

                Contributors
                wfzwxin@126.com
                zhaojz205@163.com
                Journal
                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central (London )
                1475-2840
                8 August 2020
                8 August 2020
                2020
                : 19
                : 125
                Affiliations
                [1 ]GRID grid.24696.3f, ISNI 0000 0004 0369 153X, Department of Neurosurgery, Beijing Tiantan Hospital, , Capital Medical University, ; No. 119, South Four Ring West Road, Beijing, 100070 People’s Republic of China
                [2 ]GRID grid.452402.5, Department of Neurosurgery, , Qilu Hospital of Shandong University, ; No. 107 Wenhua West Road, Jinan, 250012 Shandong People’s Republic of China
                [3 ]Institute of Radiation Medicine, China Academy of Medical Science & Peking Union Medical College, Tianjin, China
                [4 ]GRID grid.411617.4, ISNI 0000 0004 0642 1244, China National Clinical Research Center for Neurological Diseases, ; Beijing, China
                [5 ]GRID grid.24696.3f, ISNI 0000 0004 0369 153X, Center of Stroke, , Beijing Institute for Brain Disorders, ; Beijing, China
                [6 ]Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
                Article
                1096
                10.1186/s12933-020-01096-3
                7415178
                32771014
                d343b112-1bb5-4433-bcc9-a41d5ed3a5d0
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 12 March 2020
                : 25 July 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81671175
                Award Recipient :
                Funded by: Beijing Science and Technology Supporting Plan
                Award ID: D16110000381605
                Award Recipient :
                Funded by: China Postdoctoral Science Foundation funded project
                Award ID: 2019M660921
                Award Recipient :
                Funded by: Science Foundation for Post Doctorate Research of the Beijing
                Award ID: 2017-ZZ-123
                Award Recipient :
                Categories
                Original Investigation
                Custom metadata
                © The Author(s) 2020

                Endocrinology & Diabetes
                adiponectin,ischemic stroke,mortality,major adverse cardiovascular and cerebrovascular events,chinese

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