Advantages of using Genetically Elevated Lipoprotein(a) Levels in Predicting 5-Year Major Adverse Cardiovascular Events Relating to Coronary Artery Disease in Women

Abstract

Background: This study aimed to investigate major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD) over 5 years, in general, and depending on sex, lipoprotein(a) level, and number of kringle IV type 2 (KIV-2) repeats in the Lipoprotein(A) (LPA) gene. Methods: This study comprised 216 patients (120 women and 96 men) hospitalized with a diagnosis of “CAD, unstable angina IIB class”. The three-point risk of MACEs was assessed over 5 years: cardiovascular death, non-fatal myocardial infarction, and stroke. The number of KIV-2 repeats in the LPA gene was determined by quantitative real-time polymerase chain reaction (qPCR). Results: The relative risk of MACE in patients with elevated lipoprotein(a) (Lp(a)) was 2.0 (95% CI 1.04–3.87, p < 0.05) for quartile 4 (Q4) ≥48 mg/dL versus quartile 1 (Q1) ≤6 mg/dL. This was mainly attributable to an increase in men—relative risk (RR) 2.6 (95% CI 1.10–6.16, p < 0.05)—but not in women: RR 1.4 (95% CI 0.50–3.92). Mean lipoprotein(a) levels were inversely correlated with 42.5 and 7.5 for Q1 and Q4 KIV-2 repeat numbers, respectively. The relative risks of MACE for Q1 vs. Q4 KIV-2 repeats were as follows: 3.0 (95% CI 1.48–6.08, p < 0.001) for all patients; 3.0 (95% CI 1.20–6.55, p < 0.01) for men; 3.3 (95% CI 1.02–10.4, p < 0.05) for women. Conclusions: Quantifying kringle IV type 2 repeat copy number in the LPA gene using qPCR more accurately reflects the risk of major adverse cardiovascular events within 5 years in women with coronary artery disease.

Keywords

• lipoprotein(a)
• qpcr
• lpa kringle iv type 2 genetic polymorphism
• cad
• mace
• sex differences