Circulating Adiponectin Levels Are Paradoxically Associated With Mortality Rate: A Systematic Review and Meta-Analysis

CONTEXT: Some studies have surprisingly indicated that serum adiponectin is positively related to mortality rate, thus casting doubts on its role as a therapeutic target for cardiovascular disease. OBJECTIVE: To summarize evidence about direction, strength and modulators of this controversial association. DATA SOURCES: MEDLINE, Web of Science, CINHAL, Cochrane Library and Scopus from inception through June 2018. STUDY SELECTION: English-language prospective studies reporting the association between adiponectin and all-cause or cardiovascular mortality. DATA EXTRACTION: Two investigators independently extracted data and assessed study quality using standard criteria following the Preferred Reporting Items for Systematic Reviews and Meta-analyses and The Newcastle-Ottawa Scale, respectively. Pooled hazard ratios (HRs) (95% confidence intervals-CIs) were derived using a fixed or random effects models when appropriated and were expressed for one standard deviation (SD) increment of adiponectin. DATA SYNTHESIS: We identified fifty-five (n=61,676 subjects) and twenty-eight (n=43,979 subjects) studies for all-cause and cardiovascular mortality, respectively. Pooled HRs, were 1.24 (1.17-1.31) and 1.28 (1.19-1.37) for all-cause and cardiovascular mortality, respectively. Similar results were obtained also for High Molecular Weight adiponectin. When meta-analyses were restricted to studies reporting data on natriuretic peptides a 43% and 28% reduction on a log scale of these associations were observed after natriuretic peptides adjustment. CONCLUSIONS: Our results strongly points to a paradoxical association between high adiponectin levels and increased mortality rate, which is partly modulated by natriuretic peptides.