Lipoprotein(a) concentration, kringle IV-2 repeat copy number, and myocardial infarction risk in Chinese populations: insights from the INTERHEART China study

To elucidate the independent and joint effects of plasma Lipoprotein(a) [Lp(a)] concentration and Kringle IV-2 (KIV-2) repeat copy number in genomic DNA on the risk of acute myocardial infarction (AMI) in a Chinese population, to estimate their population attributable risks (PAR), and to explore interactions with metabolic and psychosocial factors, thereby providing evidence for precise cardiovascular prevention and control. Based on the INTERHEART China subgroup case-control study, 4,479 participants from 26 centers in China were included (2,100 first-onset AMI patients, 2,379 age- and sex-matched controls). Risk factors (lifestyle, metabolic indicators, psychosocial factors) were collected using standardized questionnaires. Lp(a) concentration was measured using an isoform-insensitive immunoassay, and KIV-2 repeat copy number in genomic DNA was quantified using quantitative PCR (qPCR) (represented as ΔCT value, lower values indicate fewer repeats). Multivariable logistic regression models were used to analyze risk associations, restricted cubic splines assessed dose-response relationships, PAR was calculated, and interactions were tested. Elevated Lp(a) concentration (highest vs. lowest quintile; OR = 1.784, 95% CI: 1.402–2.270) and fewer KIV-2 repeats (lowest vs. highest quintile; OR = 2.421, 95% CI: 1.905–3.086) were significantly associated with AMI risk. Dose-response analysis revealed that Lp(a) concentration showed a monotonically increasing relationship with AMI risk, while KIV-2 repeats showed a continuous negative association. Both factors remained independent predictors after mutual adjustment, and were moderately negatively correlated (r=-0.323, P < 0.001). The PAR was 10.3% for the highest Lp(a) quintile (> 17.6 mg/dL) and 10.4% for the lowest KIV-2 repeat quintile (ΔCT < 4.1). No significant interactions were found between Lp(a) or KIV-2 and sex, diabetes, smoking, or psychological factors (P-interaction > 0.00625). In the Chinese population, both Lp(a) concentration and KIV-2 repeat copy number in genomic DNA independently predict AMI risk, with PARs exceeding 10% for both. This study reveals for the first time that KIV-2 repeat copy number may have pathophysiological implications independent of Lp(a) concentration regulation, suggesting the need to incorporate this genetic marker into high-risk screening and to adopt a lower Lp(a) risk threshold of > 18 mg/dL (approximately the 80th percentile) for this population.