HDL antioxidative capacity and MACE outcomes: A prospective cohort study from Southern China.

Protection of low-density lipoproteins (LDL) from oxidative alteration is a critical antiatherosclerotic capacity of high-density lipoproteins (HDL). The study aimed to evaluate the prognostic significance of the HDL antioxidative capacity for residual cardiovascular risk. The antioxidative property of HDL against native LDL oxidation was evaluated in vitro in a prospective cohort of coronary artery disease patients undergoing percutaneous coronary intervention (PCI) (n = 490, median follow-up 856 days). The study endpoint was a composite of time to non-fatal stroke, unplanned rehospitalization for heart failure, non-fatal myocardial infarction and cardiovascular mortality. Participants were stratified into two groups based on the median value of baseline HDL antioxidative capacity. Among participants (mean age 63.6 years, 75.1 % male), 20.2 % experienced recurrent major adverse cardiovascular events (MACE). After controlling for confounders, patients with higher HDL antioxidative capacity showed significantly increased residual cardiovascular risk compared to the reference group (adjusted HR: 2.35, 95 % CI: 1.36-4.08; P = 0.002). A positive and linear association was observed between antioxidative property of HDL and MACE outcomes (P for nonlinearity = 0.106, P < 0.05). Mediation analysis revealed that estimated glomerular filtration rate (eGFR) mediated 18.9 % (P = 0.003) of the relationship between HDL antioxidative capacity and MACE risk. Moreover, subgroup analysis showed a significant interaction between HDL antioxidative function and sex in relation to recurrent MACE (Pinteraction = 0.010). Our data demonstrated that higher HDL antioxidative capacity was linked to increased residual cardiovascular risk, irrespective of HDL cholesterol and statin therapy. The association of higher HDL antioxidative capacity with MACE is especially pronounced in patients with heightened baseline systemic oxidative stress and chronic inflammation.