Genetics
Quantifying LPA KIV-2 repeat number by qPCR better predicts 5-year MACE than measured Lp(a) alone, particularly in women (Rev Cardiovasc Med 2024)
Original title: Advantages of using Genetically Elevated Lipoprotein(a) Levels in Predicting 5-Year Major Adverse Cardiovascular Events Relating to Coronary Artery Disease in Women
In 216 patients (120 women, 96 men) hospitalised with unstable angina class IIB coronary artery disease, the relative risk of a 5-year major adverse cardiovascular event (cardiovascular death, non-fatal myocardial infarction, or stroke) was 2.0 (95% CI 1.04-3.87) for the highest Lp(a) quartile (48 mg/dL or above) versus the lowest (6 mg/dL or below), an effect driven mainly by men (relative risk 2.6, 95% CI 1.10-6.16) rather than women (relative risk 1.4, 95% CI 0.50-3.92, not significant). In contrast, quantifying kringle IV type 2 (KIV-2) repeat number in the LPA gene by quantitative PCR, which inversely correlated with Lp(a) level, predicted 5-year MACE risk more consistently across both sexes: relative risk 3.0 for all patients, 3.0 in men, and 3.3 in women when comparing lowest versus highest KIV-2 repeat quartiles (all statistically significant). Directly quantifying LPA KIV-2 copy number captures cardiovascular risk in women with coronary artery disease that measured Lp(a) concentration alone misses.
Original 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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.