PCSK9 inhibitionLandmark
Lp(a) and recurrent ASCVD in 273,770 US patients: risk rises continuously to a hazard ratio of 1.45 above 300 nmol/L (MacDougall et al., EHJ 2025)
Original title: Lipoprotein(a) and recurrent atherosclerotic cardiovascular events: the US Family Heart Database
In US claims data on 273,770 people with diagnosed ASCVD and an Lp(a) result in nmol/L (43 percent women), recurrent events over 5.4 years rose from a hazard ratio of 1.04 at 15 to 79 nmol/L to 1.15 at 80 to 179, 1.29 at 180 to 299 and 1.45 at 300 nmol/L or more, consistently across sex and race, with high-impact LDL-C lowering (notably PCSK9 inhibitors) partly mitigating the risk at 180 nmol/L and above. The largest secondary-prevention dataset to date, and support for aggressive LDL-C lowering while waiting for specific therapy.
Original 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.
ancestrydiabetesepidemiologyPCSK9 inhibitiontestingwomen
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.