A case-cohort study of the association between adiponectin and mortality in EPIC-Heidelberg: NT-proBNP may explain the adiponectin paradox

Background and aims: NT-proBNP has been hypothesized as a possible explanation for the paradoxical association between adiponectin and cardiovascular and all-cause mortality. We examined the heterogeneities by NT-proBNP, sex, BMI, smoking status, hypertension and dia-betes status in the association between adiponectin and cardiovascular disease risk and mortal-ity.Methods and results: We used a case-cohort design nested within the EPIC-Heidelberg cohort, including 1387 incident cases of myocardial infarction or stroke, 582 deaths from cardiovascular causes and 2352 total deaths. We estimated hazard ratios for the association between 1SD in-crease in log-transformed total adiponectin levels and cardiovascular disease risk, cardiovascular mortality and mortality using Prentice-weighted Cox-proportional hazard models and assessed heterogeneity of the associations across strata of covariates. Overall, adiponectin was signifi-cantly associated with all-cause mortality [HR = 1.09, 95% CI: 1.03-1.16, p = 0.004]. The asso-ciation with cardiovascular mortality did not reach statistical significance [1.10 (0.99-1.37), p = 0.073]. There was significant heterogeneity by NT-proBNP in the association between total adiponectin and all-cause mortality (phet = 0.019) such that significant increase in hazards of mortality were restricted to participants in the highest tertile of NT-proBNP. Among these partic-ipants, adiponectin showed a dose-response relationship with total mortality such that; compared to participants in the lowest quintile, those in the third, fourth and fifth were at 1.22 (0.87-1.70), 1.50 (1.07-2.11), and 1.59 (1.15-2.21) higher hazards of mortality respectively. Conclusions: Significant association between adiponectin and mortality was only observed in the context of high NT-proBNP. Our findings provide further support for hypothesis that NT-proBNP may explain the adiponectin paradox.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study analyzed data from over 4000 participants and found that NT-proBNP is associated heterogeneously with adiponectin, cardiovascular disease risk, and mortality, with a significant association between adiponectin and mortality observed only in the context of high NT-proBNP. These findings provide further support for the hypothesis that NT-proBNP may explain the adiponectin paradox.