Circulating adiponectin levels are paradoxically associated with mortality rate. A systematic review and...

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.

To summarize evidence about direction, strength and modulators of this controversial association.

MEDLINE, Web of Science, CINHAL, Cochrane Library and Scopus from inception through June 2018.

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, 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.

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.

Our results strongly points to a paradoxical association between high adiponectin levels and increased mortality rate, which is partly modulated by natriuretic peptides.