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) $\ge$ 48 mg/dL versus quartile 1 (Q1) $\le$ 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: CAD; LPA kringle IV type 2 genetic polymorphism; MACE; lipoprotein(a); qPCR; sex differences.

Fig. 1.

Risk of MACEs by quartiles of lipoprotein(a) (Lp(a)) in all patients (A), and men (B)and women (C) separately. Q1, Q2–3, Q4, quartiles of Lp(a); RR, relative risk; MACE, major adverse cardiovascular event.

Fig. 2.

Risk of MACEs by quartiles for 2^{-Δ⁢Δ⁢𝐂𝐭}* (number of KIV-2 repeats) in all patients (A) and men (B) and women (C) separately. Q1, Q2–3, Q4, quartiles of 2^{-Δ⁢Δ⁢Ct}* from quantitative real-time polymerase chain reaction (qPCR), as a genetic score for lipoprotein(a) concentration, associated with apolipoprotein(a) isoform size and LPA KIV-2 number of repeats. RR, relative risk; MACE, major adverse cardiovascular event; KIV-2, kringle IV type 2.