The rationale behind adiponectin serum level as an independent predictor of mortality after TAVI

Author(s): Jeroen Walpot, Paul van Herck, Caroline M. Van de Heyning, Hein Heidbuchel, Christophe De Block, Johan Bosmans

Transcatheter Aortic Valve Implantation (TAVI) is a suitable treatment for patients with severe symptomatic Aortic Stenosis (AS) ≥ 75 years or with high operative risk. Adiponectin, released by adipose tissue, has been associated with cardio protective properties: Anti-inflammatory and anti-atherosclerotic features, improved insulin sensitivity, and attenuated LV remodeling.

Nevertheless, several studies have reported the counter-intuitive finding that high adiponectin serum levels were associated with poor survival. Situations in which high adiponectin levels do not translate into beneficial insulin sensitivity and health benefits have been coined “the adiponectin paradox” in the medical literature.

A recent study reported that the adiponectin serum concentration before TAVI is an independent predictor of all-cause 5-year mortality after TAVI. Compared to patients with the lowest adiponectin level, patients in the third tertile had a hazards ratio of allcause mortality after TAVI of 4.155 (95% CI: 1.364-12.655) (p=0.004), tested in a multivariable model, including classical clinical operative risk assessment, CT- measured psoas muscle density, and adiponectin serum level. In a supplemental multivariable model including LDL cholesterol serum levels, adiponectin plasma concentration remained an independent predictor of all-cause mortality after TAVI.

The European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort study provided new insight into the adiponectin paradox and may explain these counter-intuitive study results in the TAVI population. A significant heterogeneity by N-Terminal pro B-type Natriuretic Peptide (NT-proBNP) in the association between total adiponectin and all-cause mortality was observed, with a significant increase in hazards of cardiovascular mortality restricted to participants in the highest N-Terminal pro B-type Natriuretic Peptide (NT-proBNP) levels. Among these latter participants, adiponectin showed a dose-response relationship with total mortality. Given the pathophysiological features of severe symptomatic AS and the clinical characteristics of the frail TAVI-candidates population, it is plausible that these latter patients represent a cohort with increased levels of NT-pro-BNP levels.

In this review, we briefly discuss the biological actions of adiponectin, the factors influencing adiponectin levels, the studies examining an association between adiponectin level and AS severity progression, the adiponectin paradox, and adiponectin as a biomarker to predict survival after TAVI.