Impact of Combined C-Reactive Protein and High-Density Lipoprotein Cholesterol Levels on Long-Term Outcomes in Patients With Coronary Artery Disease After a First Percutaneous Coronary Intervention

Abstract

Cardiovascular risk persists despite intensive low-density lipoprotein cholesterol (LDL-C) reduction using statins. High-density lipoprotein (HDL-C) is inversely associated with coronary artery disease (CAD) that is independent of LDL-C levels. C-reactive protein (CRP) is an established marker of inflammation that can impair the protective function of HDL-C: however, the impact of inflammation on the association between HDL-C and long-term outcomes in patients with CAD under statin therapy remains uncertain. We prospectively enrolled 3,507 consecutive patients with CAD who underwent a first percutaneous coronary intervention (PCI) from 1997 to 2011 at our institution. We stratified 1,682 patients (48%) who had been treated with statin at the time of PCI into 4 groups according to HDL-C levels (cutoffs of 40 and 50 mg/dl for men and women, respectively) and a CRP cutoff of 2 mg/dl: (1) high HDL-C/low CRP, (2) high HDL-C/high CRP, (3) low HDL-C/low CRP, and (4) low HDL-C/high CRP comparing the rates of all-cause death among them. The median follow-up period was 1,985 days (interquartile range 916 to 3,183 days). During this period, 197 patients (11.7%) died because of cardiac death (n = 58), carcinoma (n = 61), stroke (n = 10), and other causes (n = 69). The rates of all-cause death significantly differed among the groups (log-rank test, p <0.0001). In multivariate Cox hazard regression analyses, low HDL-C with high CRP levels remained significantly associated with a higher rate of all-cause death even after adjustment for other co-variates (hazard ratio 2.38, 1.59 to 3.61, p <0.0001). Low HDL-C together with elevated CRP levels is significantly associated with long-term outcomes in patients who received statin therapy after PCI.