HDL anti-inflammatory capacity and residual cardiovascular risk: A prospective cohort study

Protection against vascular inflammation in endothelial cells represents a pivotal atheroprotective attribute of high-density lipoproteins (HDL).

The present study sought to assess the predictive value of the HDL anti-inflammatory property for major adverse cardiovascular events (MACE).

The anti-inflammatory property of HDL was evaluated by its ability to suppress vascular cell adhesion molecule-1 mRNA expression stimulated by tumor necrosis factor α in endothelial cells in a prospective study of patients with coronary artery disease from South China (n = 466, median follow-up of 2.3 years). The primary endpoint was MACE, encompassing nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death.

Within the study population (mean age 64.0 years, 77.9% male), 12.7% experienced recurrent MACE. After multivariable adjustment, higher HDL anti-inflammatory property was independently linked to lower residual cardiovascular risk (adjusted hazard ratio [aHR]: 0.96, 95% CI: 0.92-0.99; P = .022), with a linear inverse relationship (P for nonlinearity = .128). When divided into tertiles, patients with the highest HDL anti-inflammatory property showed significantly reduced MACE risk compared with the reference group in the multivariable-adjusted model (aHR: 0.48, 95% CI: 0.24-0.97; P = .040). Mediation analysis revealed that estimated glomerular filtration rate mediated 36.6% (P < .001) of the observed association. Moreover, subgroup analysis revealed a stronger protective effect in female patients (aHR: 0.73, 95% CI: 0.55-0.97).

Our findings indicate that better HDL anti-inflammatory function was linked to reduced recurrent MACE risk, independent of HDL cholesterol levels and statin treatment. Kidney function partially mediated this association. These findings underscore the prognostic relevance of HDL functional assessment in secondary cardiovascular prevention.