A sex-related analysis on the influence of lipoprotein(a) on primary cardiovascular disease prevention and its interplay with traditional lipid markers: results from a 20-year cohort study

Abstract Introduction Elevated lipoprotein(a) [Lp(a)] levels is an established risk factor mediating cardiovascular disease. Purpose The relationship between Lp(a) and the first fatal/non-fatal CVD incident over a 20-year period in males and females without CVD was assessed. Methods A longitudinal prospective study was conducted during 2002–2022. In 2002, a total of 3,042 CVD-free adults (1,514 males and 1,528 females) were enrolled. A follow-up was carried out after 20 years, in 2022, which included 2,169 participants. Out of these, 1,988 had comprehensive data for the occurrence of CVD. The recommended threshold of 50mg/dL was used to define abnormal Lp(a) status (≥50mg/dL). Results During the 2002-2022 period, 718 (i.e. 36%) of participants had a fatal or non-fatal CVD event. Twenty-year CVD-event rate was 35.8% and 40.0% in participants with normal and abnormal Lp(a) levels, respectively. For every mg/dL increase in Lp(a), the odds of having a CVD event within 20 years increases by approximately 0.36% (Hazard ratio (HR) = 1.0036, 95% confidence interval (CI) 1.001,1.007, p=0.048). When stratified by sex the relationship remained significant only in females (HR= 1.006, 95% confidence interval (CI) 1.001,1.011, p=0.023). In the multivariate analysis, significance was lost after adjusting for low- and high-density lipoprotein (LDL-C, HDL-C) and triglycerides (HR= 1.0017, 95% confidence interval (CI) 0.998,1.005, p=0.348). Conclusion Elevated Lp(a) levels are linked to higher CVD risk, particularly in females. Despite growing efforts to clarify Lp(a) as a risk-predicting marker in CVD, clinical guidelines still require definitive evidence, particularly from a sex-focused perspective.