Adipocytokines and risk of ischaemic events in acute coronary syndromes: an age-dependent relationship

Abstract Background Adiponectin plays a key role in glucose metabolism and fatty acid oxidation, exerting acute metabolic effects, while leptin primarily regulates long-term energy homeostasis by influencing adiposity. Deeply implicated in metabolism, adipokines influence cardiovascular risk (1). Adiponectin associate with reduced rate of ischaemic events in individuals free of cardiovascular disease (2), whereas elevated circulating leptin is linked to an increase in ischaemic risk (3). It remains unclear whether similar relationships hold true in the very-high risk population of individuals with established atherosclerotic cardiovascular disease, particularly in those with recent acute coronary syndrome (ACS). Purpose The present study aimed to assess the associations of adiponectin and leptin with major acute cardiovascular events in patients with a recent ACS. Methods We analysed 4’787 ACS patients, with plasma adiponectin and leptin being assessed prior to coronary angiography. The primary endpoint was 1-year major adverse cardiovascular events, defined as a composite measure of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. The secondary endpoint was 1-year mortality. Uni- and multivariable Cox proportional hazard regression models were fit to assess the (independent) associations of adipokine levels with outcomes. In sensitivity analysis, an interaction analysis was performed. Results At baseline, plasma adiponectin correlated negatively with body-mass index and surface area, while a positive association was noted for leptin (Figure 1A-B). In patients with a recent ACS, high plasma adiponectin was linked to an increased risk of 1-year MACE (Figure 1C) (HR, tertile (T)3, 1.75, 95% CI, 1.30-2.34) and 1-year death (HR, 2.59, 1.71-3.93), while plasma leptin was linked to neither of these outcomes (HR, 1.18, 0.89-1.57 and 1.32, 0.90-1.96) (Figure 1D). For both primary and secondary endpoints, similar observations were made in multivariable-adjusted models accounting for established risk factors (adiponectin: HR, 1.59, 1.13-2.20 and 2.12, 1.30-3.45, respectively; leptin: HR 0.91, 0.64-1.31 and 0.84, 0.50-1.43). An interaction analysis identified age as an important modulator of the adiponectin-MACE association (pinteraction=0.004). Indeed, high plasma adiponectin conferred an increased MACE risk in those aged 55 years (HR 2.12, 1.44-3.12), while this association was absent in those aged 55 years (HR 0.45, 0.16-1.25)(Figure 1 E), as it was for leptin (Figure 1F). Conclusions In patients with a recent ACS, plasma adiponectin but not leptin is linked to an increased risk of ischaemic events. This association is pronounced in those aged 55 years but intriguingly absent in patients with premature ACS. While external validation studies are ongoing, these observations suggest an age-dependency of fat tissue derived adipocytokines to determine ischaemic risk in secondary prevention settings.Figure 1