Lipoprotein(a) and recurrent atherosclerotic cardiovascular events: the US Family Heart Database

Abstract Background and Aims Higher levels of lipoprotein(a) drive increasing risk of atherosclerotic cardiovascular disease (ASCVD) in otherwise healthy individuals regardless of sex and race/ethnicity. This study aimed to evaluate whether this is also true for recurrent ASCVD, and whether LDL cholesterol-lowering therapy possibly mitigates such a relationship. Methods In US medical claims between 2012 and 2022 for 340 million individuals, 273 770 had diagnosed ASCVD and lipoprotein(a) measured in nmol/L. These women (n = 117 269; 43%) and men (n = 156 501; 57%) included Black (n = 22 451; 8%), Hispanic (n = 24 606; 9%), and White (n = 161 165; 59%) individuals. Results Lipoprotein(a) levels were higher in women vs men and in Black vs Hispanic and White individuals. During a median follow-up of 5.4 years, 41 687 individuals (15%) experienced recurrent ASCVD. Higher lipoprotein(a) levels were associated with continuously increasing risk of recurrent ASCVD. Compared to individuals with lipoprotein(a) < 15 nmol/L, the adjusted hazard ratios for recurrent ASCVD events were 1.04 (95% confidence interval 1.01–1.07) for 15–79 nmol/L, 1.15 (1.12–1.19) for 80–179 nmol/L, 1.29 (1.25–1.33) for 180–299 nmol/L, and 1.45 (1.39–1.51) for ≥300 nmol/L. Results were similar for individual ASCVD components, and in sex, race/ethnicity, baseline ASCVD, and diabetes subgroups; however, high impact LDL cholesterol-lowering therapy possibly mitigates the deleterious effect of lipoprotein(a) ≥ 180 nmol/L, most pronounced in those on PCSK9 inhibitors. Interaction on recurrent ASCVD events between lipoprotein(a) categories and sex, race/ethnicity, baseline ASCVD, diabetes, and impact of LDL cholesterol-lowering therapy use had P-values of .61, .06, .33, .91, and 2 × 10−8, respectively. Conclusions In 273 770 individuals with ASCVD, higher lipoprotein(a) levels were associated with continuously increasing risk of recurrent ASCVD events regardless of sex and race/ethnicity that may have been partially mitigated by high impact LDL cholesterol-lowering therapy.