Population specific risk thresholds for lipoprotein(a): implications from angiographic data in Central Asia

Lipoprotein(a) [Lp(a)] is an established, genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD), but population-specific thresholds for cardiovascular risk remain uncertain. Data from Central Asia are particularly limited. We aimed to evaluate the relationship between Lp(a) concentrations and coronary artery disease (CAD) severity in a Kazakhstani cohort and to determine an Lp(a) threshold associated with obstructive coronary disease.

In this single-center observational study, 238 adults (mean age 65.1 ± 0.6 years; 60% male) referred for elective coronary angiography were enrolled. Fasting venous blood samples were obtained for a full lipid panel and Lp(a) assessment. Lp(a) levels were quantified in nmol/L using an immunoturbidimetric method. CAD severity was categorized as no significant stenosis, 1-vessel, 2-vessel, or ≥3-vessel disease. Between-group comparisons were performed using t-tests and ANOVA. Receiver operating characteristic (ROC) analysis identified an optimal Lp(a) cut-off for predicting significant CAD (≥50% stenosis in ≥1 vessel), with the Youden index determining the threshold.

Significant CAD was present in 185 patients (78%), while 53 (22%) had no obstructive disease. Lp(a) levels increased stepwise with CAD severity: 36.5 ± 9.4 nmol/L (no stenosis), 45.3 ± 9.0 nmol/L (1-vessel), 76.7 ± 14.6 nmol/L (2-vessel), and 97.2 ± 15.8 nmol/L (≥3-vessel disease) (p < 0.05 for trend). Patients with prior myocardial infarction had significantly higher Lp(a) than those without (78.9 ± 11.9 vs. 51.9 ± 6.6 nmol/L, p = 0.04), whereas traditional lipid parameters did not differ by MI status or CAD extent. ROC analysis identified 37 nmol/L as the optimal threshold for predicting obstructive CAD. Patients with Lp(a) ≥ 37 nmol/L had markedly higher odds of significant stenosis (90% vs. 71%, OR 3.4, 95% CI 1.6-7.6, p < 0.001).

In this Kazakhstani cohort, Lp(a) was strongly associated with both the presence and angiographic severity of coronary atherosclerosis, whereas LDL-C and other lipid parameters showed no such relationship. Clinically meaningful risk occurred at substantially lower Lp(a) levels than commonly used Western thresholds. These findings highlight the need for population-specific Lp(a) cut-offs in Central Asia and support routine Lp(a) measurement to improve cardiovascular risk stratification. Larger studies are warranted to refine regional thresholds and assess the value of emerging Lp(a)-lowering therapies.