Cardiovascular disease risk associated with elevated lipoprotein(a) attenuates at low low-density lipoprotein cholesterol levels in a primary prevention setting

Abstract

Lipoprotein(a) (Lp(a)) elevation is a causal risk factor for cardiovascular disease (CVD). It has however been suggested that elevated Lp(a) causes CVD mainly in individuals with high low-density lipoprotein cholesterol (LDL-C) levels. We hypothesized that the risk associated with high Lp(a) levels would largely be attenuated at low LDL-C levels. In 16 654 individuals from the EPIC-Norfolk prospective population study, and in 9448 individuals from the Copenhagen City Heart Study (CCHS) parallel statistical analyses were performed. Individuals were categorized according to their Lp(a) and LDL-C levels. Cut-offs were set at the 80th cohort percentile for Lp(a). Low-density lipoprotein cholesterol cut-offs were set at 2.5, 3.5, 4.5, and 5.5 mmol/L. Low-density lipoprotein cholesterol levels in the primary analyses were corrected for Lp(a)-derived LDL-C (LDL-C_corr). Multivariable-adjusted hazard ratios were calculated for each category. The category with LDL-C_corr corr levels ≥2.5 mmol/L. In contrast, for LDL-C_corr corr and Lp(a) levels on CVD risk in either cohort. Lipoprotein(a) and LDL-C are independently associated with CVD risk. At LDL-C levels below <2.5 mmol/L, the risk associated with elevated Lp(a) attenuates in a primary prevention setting.