Coronary Artery Disease Risk Reduced With ANGPTL3 Deficiency

HealthDay News — Angiopoietin-like 3 (ANGPTL3) deficiency is associated with reduced risk of coronary artery disease (CAD), according to a study published online in the Journal of the American College of Cardiology.

Nathan O. Stitziel, MD, PhD, from the Washington University School of Medicine in St. Louis, and colleagues used computed tomography angiography to examine coronary atherosclerotic burden in 3 individuals with complete ANGPTL3 deficiency and 3 wild-type first-degree relatives. In addition, ANGPTL3 loss-of-function (LOF) mutations, defined as nonsense, frameshift, and splice-site variants, along with missense variants, were ascertained in up to 21,980 individuals with CAD and 158,200 controls. In a biomarker study, circulating ANGPTL3 concentration was measured in 1493 individuals presenting with myocardial infarction (MI) and 3232 controls.

The researchers observed no evidence of coronary atherosclerotic plaque in the 3 individuals with complete ANGPTL3 deficiency. Approximately 1 in 309 individuals were heterozygous carriers for an LOF mutation in ANGPTL3 gene sequencing. Heterozygous carriers of ANGPTL3 LOF mutations demonstrated a 17% reduction in circulating triglycerides and a 12% reduction in low-density lipoprotein cholesterol, compared with those without mutations. Carrier status correlated with a reduction in the odds of CAD (odds ratio [OR]: 0.66). Individuals in the lowest vs the highest tertile of circulating ANGPTL3 concentrations had reduced odds of MI (adjusted OR: 0.65).

ANGPTL3 deficiency is associated with protection from CAD,” the authors wrote.

Disclosures: Several authors disclosed financial ties to the pharmaceutical industry.

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  1. Stitziel NO, Khera AV, Wang X, et al. ANGPTL3 deficiency and protection against coronary artery disease [published online March 28, 2017]. J Am Coll Cardiol. doi:10.1016/j.jacc.2017.02.030
  2. Genest J. ANGPTL3. A gene, a protein, a new target? Aye, there’s the rub! [published online March 28, 2017]. J Am Coll Cardiol. doi:10.1016/j.jacc.2017.03.015