Sex-specific differences in lipoprotein (a) levels and their shared impact on coronary artery disease extent in ACS

Introduction Women generally exhibit higher lipoprotein(a) [Lp(a)] levels than men, particularly after menopause. However, the influence of sex on the relationship between Lp(a) and the risk of coronary artery disease (CAD) remains controversial. While some studies suggest this association is sex-independent, others indicate that CAD characteristics may differ between men and women with high Lp(a) levels. Objectives Our objective was to analyze potential sex-based differences in Lp(a) levels among patients with acute coronary syndrome (ACS) and to evaluate their association with the extent of CAD. Methods Prospective, observational, single-centre study of a cohort of patients admitted for ACS with angiographicaly proven obstructive coronary lesions by angiography. Fasting lipid profiles including plasma Lp(a) levels were obtained. Variables associated with elevated Lp(a) were analyzed using multivariable linear regression, with the natural logarithm of Lp(a) as the dependent variable. Subsequently, binary logistic regression was used to identify clinical and analytical predictors of extensive CAD (defined as severe three-vessel disease), including a Lp(a)*female sex interaction term. Results The study included 931 patients (mean age 66.6 ± 12.0 years), of whom 24.2% (n=225) were women. Female sex was associated with a higher prevalence of dyslipidemia (70.2% vs. 62.0%; p=0.026), but a lower prevalence of prior smoking (48.4% vs. 74.9%; p=0.004) and prior CAD (16.0% vs. 27.1%; p=0.001). No differences were found in other clinical variables. Women presented higher levels of total cholesterol (164 [138-199] vs. 156 [126-188]; p=0.003), HDL cholesterol (43 [36-54] vs. 37 [32-45]; p<0.001), and Lp(a) (76 [31-204] vs. 59 [25-137]; p=0.002), as well as lower creatinine clearance (67 [48-91] vs. 87 [66-112]; p<0.001). The proportion of patients with Lp(a) >105 nmol/L was 44.0% (n=99) in women vs. 33.0% (n=122) in men (p=0.003). In the multiple linear regression analysis, higher Lp(a) levels were independently associated with female sex, prior CAD, and elevated apolipoprotein B levels (Table 1). In the analysis of independent predictors for extensive CAD, only diabetes mellitus (OR 2.020 [95% CI 1.402–2.911]; p<0.001), creatinine clearance (OR 0.992 [95% CI 0.985–0.999]; p=0.029), and Lp(a) (OR 1.003 [95% CI 1.001–1.005]; p=0.013) reached significance. Neither female sex nor the Lp(a)*female sex interaction showed a statistically significant association with extensive CAD (Table 2). Conclusions In patients with ACS, women have significantly higher Lp(a) levels than men. In this population, extensive CAD is associated with traditional risk factors such as diabetes and reduced creatinine clearance, as well as Lp(a) levels. The association between Lp(a) and the extent of CAD is not influenced by sex.Table 1.Predictors of lipoprotein(a) levels.Table 2.Predictors of extensive CAD