Serum level of HDL particles are independently associated with long-term prognosis in patients with coronary artery disease: The GENES study

Abstract

HDL-Cholesterol (HDL-C) is not an accurate surrogate marker to measure the cardioprotective functions of HDL in coronary artery diseases (CAD) patients. Hence, measurement of other HDL-related parameters may have prognostic superiority over HDL-C. In this work, we examined the predictive value of HDL particles profile for long-term mortality in CAD patients and to compare its informative value to that of HDL-C and apoA-I. HDL particles profiles were measured by nuclear magnetic resonance (NMR) spectroscopy in 214 male participants with stable CAD (45-74 years). Median follow up was 12.5 years with a 36.4% mortality rate. Cardiovascular mortality accounted for 64.5%. Mean concentrations of total HDL particles (HDL-P), small-sized HDL (SHDL-P) and apoA-I were lower in deceased than in surviving patients whereas no difference was observed according to HDL-C and large HDL particles. All NMR-HDL measures were correlated between themselves and with other HDL markers (HDL-C, apoA-I and LpA-I). In a multivariate model adjusted for cardiovascular risk factors and bioclinical variables, HDL-P and SHDL-P displayed the strongest inverse association with all-cause and cardiovascular mortality. Weaker associations were recorded for apoA-I. Based on our results, we conclude that HDL particle profile measured by NMR spectroscopy should be considered to better stratify risk in population at high risk or in the setting of pharmacotherapy.

Figure 1

Relative risk of all-cause and cardiovascular mortality as a function of HDL-C, apoA-I, HDL-P, SHDL-P and LHDL-P. Graphic represents hazard ratios (dots) and corresponding 95% confidence interval (95% CI) for risk of all-cause and cardiovascular mortality per 1 standard deviation increase of HDL-C, apoA-I, HDL-P, SHDL-P or LHDL-P. Among the 78 deceased patients analyzed, the number of CV death was 50. Model 1: adjusted for age, smoking, treatment for dyslipidemia, eGFR, LVEF, duration of CAD and Gensini score. Model 2: adjusted for treatment for dyslipidemia, LVEF, duration of CAD and Gensini score.

Figure 2

Kaplan-Meier survival curves. Survival curves for the follow up period were established as a function of HDL-C (A), apoA-I (B), HDL size (C), HDL-P (D), LHDL-P (E) and SHDL-P (F) tertiles. Tertiles range for HDL-C: ≤36.5, 36.6–42.3, >42.3 g/L; tertiles range for apoA-I: ≤1.1, 1.2–1.26, >1.26 g/L; Tertiles range for HDL size: ≤8.69, 8.70–8.95, >8.95 nm; tertiles range for HDL-P: ≤24.6, 24.7–28.4, >28.4 μmol/L; Tertiles range for LHDL-P: ≤2.3, 2.4–4.3, >4.3 μmol/L; tertile for SHDL-P: ≤21.0, 21.1–24.8, >24.8 μmol/L.