gms | German Medical Science

Background: Lipoprotein(a) (Lp[a]) is a low-density lipoprotein (LDL) cholesterol–like particle bound to apolipoprotein(a) [1]. Although the association between Lp(a) and manifest atherosclerotic cardiovascular disease (ASCVD) is well established [2], there is scarce evidence concerning the role of Lp(a) in subclinical carotid atherosclerosis (CA), and a notable lack of knowledge with regard to potential sex differences [3], [4]. This study investigated the relationship of Lp(a) and the presence of subclinical CA among asymptomatic women and men from the general population.

Methods: The Hamburg City Health Study (HCHS) is a large population-based cohort study of 17,000 deeply phenotyped Hamburg residents aged 45-74, investigating risk and prognostic factors for major chronic diseases. Lp(a) was measured in 7482 participants without prevalent ASCVD (defined as coronary heart disease, myocardial infarction, stroke, and peripheral arterial disease). Subclinical CA was assessed via carotid ultrasound and defined as presence of any atherosclerotic plaque. The association between Lp(a) values and the presence of CA was assessed by logistic regression analysis after categorization of the study population according to recently proposed Lp(a) cutoffs (<75, ≥75-<125 and ≥125 nmol/L reflecting low, intermediate and high ASCVD risk respectively), and continuously by mean of cubic spline regression analysis.

Results: Median Lp(a) in this cohort (52.6% female, median age 62 years) was 17.7 (quartiles 7.8, 59.5) nmol/L, and 32.6% had at least one carotid plaque. The prevalence of subclinical increased with higher Lp(a) levels (p = 0.034). When comparing high (≥125 nmol/L) to low (<75nmol/L) Lp(a) categories, a statistically significant association with subclinical CA was observed (Odds Ratio [OR] 1.24, 95% confidence interval [CI] 1.05-1.48) after multivariable adjustment for traditional CV risk factors including LDLLp(a)corrected and lipid-lowering medication. Intermediate Lp(a) concentrations were not found to be associated with higher risk for subclinical CA (OR 1.14, 95% CI 0.91-1.42). Although there was no significant difference in the overall effect between men and women (p for interaction = 0.70), sex-specific differences in the association were observed in the cubic splines, with an earlier increase in risk for men (<75 nmol/L) than women (>85 nmol/L).

Conclusion: The findings from this population-based study suggest that Lp(a) values are independently associated with the presence of subclinical CA in asymptomatic individuals from the general population. The Lp(a)-associated risk might vary by sex and requires further investigation in order to tailor preventive measures.

Competing interests: Die Autorin war Referentin auf der Hyperlipidemia Tagung 2023 des Biotechnologie-Unternehmen Amgen und stellte gegen ein Honorar die Lp(a) Messungen in der Hamburg City Health Study vor.

The authors declare that an ethics committee vote is not required.