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Lipoprotein(a) and recurrent atherosclerotic cardiovascular events: the US Family Heart Database
Diane E MacDougall1, Anne Tybjærg-Hansen2,3, Joshua W Knowles4
1Department of Research, Family Heart Foundation, 5548 First Coast Hwy, Fernandina Beach, FL 32034, USA.
Insights
Higher lipoprotein(a) levels increase the risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events in all individuals. However, potent LDL cholesterol-lowering therapies may reduce this elevated risk, particularly for those with high lipoprotein(a) levels.
Area of Science:
- Cardiology
- Genetics
- Public Health
Background:
- Elevated lipoprotein(a) is a known risk factor for atherosclerotic cardiovascular disease (ASCVD).
- The association between lipoprotein(a) and recurrent ASCVD events requires further investigation.
- The potential mitigating effect of LDL cholesterol-lowering therapy on this association is not fully understood.
Purpose of the Study:
- To determine if higher lipoprotein(a) levels are associated with an increased risk of recurrent ASCVD events.
- To assess whether this association differs across sex and race/ethnicity groups.
- To evaluate if LDL cholesterol-lowering therapy can mitigate the risk associated with elevated lipoprotein(a) levels.
Main Methods:
- Analysis of US medical claims data from 2012-2022, including 273,770 individuals with diagnosed ASCVD and measured lipoprotein(a) levels.
- Inclusion of diverse populations: women (43%), men (57%), Black (8%), Hispanic (9%), and White (59%) individuals.
- Median follow-up of 5.4 years to ascertain recurrent ASCVD events.
Main Results:
- Higher lipoprotein(a) levels were consistently associated with a continuously increasing risk of recurrent ASCVD events.
- This association was observed across various subgroups, including sex, race/ethnicity, baseline ASCVD, and diabetes status.
- High-impact LDL cholesterol-lowering therapy, especially PCSK9 inhibitors, appeared to mitigate the deleterious effect of high lipoprotein(a) levels (≥180 nmol/L).
Conclusions:
- Elevated lipoprotein(a) levels significantly increase the risk of recurrent ASCVD events, irrespective of sex and race/ethnicity.
- High-impact LDL cholesterol-lowering therapy demonstrates a potential to partially mitigate this increased risk.
- These findings underscore the importance of managing lipoprotein(a) levels in ASCVD prevention and treatment strategies.
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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