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Adiponectin and risk of stroke: prospective study and meta-analysis
Maria Arregui1, Brian Buijsse, Andreas Fritsche
1From the Departments of Epidemiology (M.A., B.B., R.d.G., H.B., C.W.) and Molecular Epidemiology (M.B.S.), German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Nuthetal, Germany; Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany (A.F.); Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany (S.W., B.I.); and Institute of Social Medicine, Epidemiology, and Health Economics, Charité University Medical Center, Berlin, Germany (C.W.).
Background And Purpose:
The favorable cardiovascular effects attributed to adiponectin may lower risk of stroke. We investigated this in a prospective study and meta-analysis.
Methods:
A case-cohort study nested within the Potsdam cohort of the European Prospective Investigation into Cancer was performed, with 170 incident cases of ischemic stroke and a randomly selected subcohort of 2155 participants without major cardiovascular disease at baseline. A random-effects dose-response meta-analysis was performed on prospective studies reporting on adiponectin and incident stroke in healthy populations up to April 2013, identified through MEDLINE and EMBASE.
Results:
In European Prospective Investigation into Cancer-Potsdam, after adjustment for cardiovascular risk factors, the hazard ratio of ischemic stroke per 5-µg/mL higher total-adiponectin was 1.10 (95% confidence interval, 0.89-1.37). Participants with higher total-adiponectin had higher high-density lipoprotein-cholesterol and lower high-sensitivity C-reactive protein and triglyceride levels, and had less often diabetes mellitus. Additional adjustment for these putative mediators yielded a hazard ratio of 1.31 (95% confidence interval, 1.04-1.64). Nine studies (19,259 participants, 2960 cases), including European Prospective Investigation into Cancer-Potsdam, were meta-analyzed. Pooling relative risks adjusted for cardiovascular risk factors not including putative mediators indicated moderate between-study heterogeneity (I2=52.2%). This was explained by the smallest study, and the pooled relative risk (95% confidence interval) before and after its exclusion was 1.03 (0.98-1.08) and 0.99 (0.96-1.01) per 5 µg/mL, respectively. The pooled relative risk (95% confidence interval) additionally adjusted for potential mediators was 1.08 (1.01-1.15) and 1.05 (1.00-1.11) before and after excluding the same study, respectively.
Conclusions:
Adiponectin is not associated with risk of stroke. If anything, adiponectin relates directly to stroke risk after controlling for risk factors that favorably correlate with adiponectin.
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