What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling

Nutr Metab Cardiovasc Dis. 2022 Jul;32(7):1651-1660. doi: 10.1016/j.numecd.2022.03.028. Epub 2022 Apr 5.

Abstract

Background and aims: Familial hypercholesterolemia (FH) is a genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of premature coronary heart disease (CHD). Cholesterol-lowering therapy (statins) reduces CHD risk, but have been available only in the last 25 years, thus, elderly FH patients have been exposed to elevated LDL-C levels most of their life. Surprisingly, some of these have never experienced any CHD event, raising the question whether they present CHD resistant characteristics. Identifying possible cardioprotective biomarkers could contribute to future CHD preventive treatment, therefore, we aimed to identify metabolic markers in event-free elderly FH subjects.

Methods and results: We used a high-throughput nuclear magnetic resonance (NMR) spectroscopy platform to quantify a large number of metabolites in serum samples from 83 FH patients ≥65 years, and analyze differences between subjects with (n = 39) and without (n = 44) CHD. Mean age was 70 years in both groups (57% and 38% female in the event-free group and CHD group, respectively). The event-free group had significantly higher levels of large and extra-large high-density lipoprotein (HDL) particles, and higher concentration of Apolipoprotein A1 (ApoA1) and cholesterol in HDL and HDL2 particles, compared to the CHD group (p ≤ 0.05 for all).

Conclusion: CHD resistant elderly FH patients have higher levels of large HDL particles. The mechanisms behind the event-free survival among these patients remain unclear; hence, a deeper understanding of the metabolic profile in event-free elderly FH subjects may lead to development of novel preventive therapies.

Keywords: Coronary heart disease; Elderly; Familial hyper-cholesterolemia; High-density lipoprotein; Metabolic profiling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cholesterol / metabolism
  • Cholesterol, LDL
  • Coronary Disease* / diagnosis
  • Coronary Disease* / epidemiology
  • Coronary Disease* / prevention & control
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Hyperlipoproteinemia Type II* / diagnosis
  • Hyperlipoproteinemia Type II* / drug therapy
  • Hyperlipoproteinemia Type II* / genetics
  • Male

Substances

  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol