Key result
Higher Lp(a) is linked to continuously increasing recurrent ASCVD risk, partially mitigated by LDL lowering.
Why the study?
Do higher lipoprotein(a) levels increase the risk of recurrent ASCVD events in patients with established ASCVD?
Cohort (n=273,770)
Yes
Do higher lipoprotein(a) levels increase the risk of recurrent ASCVD events in patients with established ASCVD?
Higher lipoprotein(a) levels are associated with a continuously increasing risk of recurrent ASCVD events in patients with established ASCVD, which may be partially mitigated by intensive LDL-C lowering therapy.
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.
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MacDougall et al. (2025) conducted a cohort in Atherosclerotic cardiovascular disease (ASCVD) (n=273,770). Higher lipoprotein(a) levels (≥300 nmol/L) vs. Lipoprotein(a) < 15 nmol/L was evaluated on Recurrent ASCVD events (HR 1.45, 95% CI 1.39-1.51). Higher lipoprotein(a) levels (≥300 vs <15 nmol/L) were associated with an increased risk of recurrent ASCVD events (HR 1.45; 95% CI 1.39-1.51), which may be mitigated by LDL-lowering therapy.
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