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

Context: Some studies have surprisingly indicated that serum adiponectin level 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. Methods: MEDLINE, Web of Science, CINHAL, Cochrane Library, and Scopus databases were searched from their inception dates through June 2018 for English-language prospective studies reporting the association between adiponectin and all-cause or cardiovascular mortality. 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. Pooled hazard ratios (HRs) and 95% CIs were derived using fixed-or random-effects models when appropriate, and results were expressed to a 1-SD increment of adiponectin. Results: We identified 55 studies (n = 61,676 subjects) with all-cause mortality data and 28 (n = 43,979 subjects) studies with cardiovascular mortality data. 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 for high-molecular-weight adiponectin. When meta-analyses were restricted to studies reporting data on natriuretic peptides, reductions of 43% and 28% on a log scale of these respective associations were observed after adjusting for natriuretic peptides. Conclusions: Our results point strongly to a paradoxical association between high adiponectin levels and increased mortality rate, which is partly modulated by natriuretic peptides.