April 24, 2024
Journal of the American College of Cardiology
TAKE-HOME MESSAGE
- In a large pooled US cohort involving 27,756 individuals, higher lipoprotein(a) (Lp[a]) levels were significantly associated with an increased risk of atherosclerotic cardiovascular disease events over a mean follow-up period of 21.1 years, especially in those with Lp(a) levels in the highest percentile (≥90th).
- These results suggest that Lp(a) levels may offer value in cardiovascular risk assessment. Prospective studies are needed to further understand the role of Lp(a) levels in guiding targeted interventions in addition to phenotyping the natural history of elevated Lp(a) levels.
Written by Matthew J. Budoff MD, FACC, FAHA
Lipoprotein (a) (Lp[a]) is growing in clinical interest given the potential for treatments being developed for this atherogenic particle.
This study included data on the association of Lp(a) levels with atherosclerotic cardiovascular disease (ASCVD) outcomes from five US prospective studies: Multi-Ethnic Study of Atherosclerosis, Coronary Artery Risk Development in Young Adults, Jackson Heart Study, Framingham Heart Study Offspring, and Atherosclerosis Risk In Communities. The study followed 27,756 individuals without previous ASCVD for a mean follow-up period of 21.1 years. Although elevated Lp(a) levels predicted the rate of incident ASCVD events similarly by risk group, sex, and race or ethnic groups, a stronger association was noted in individuals with diabetes. This study showed, in a large US pooled cohort, that higher Lp(a) levels are associated with an increased ASCVD risk.
As guidelines change and the utility of Lp(a) levels increases in clinical practice, this study demonstrates the strong association of this marker with cardiovascular risk. Measurement of this serum biomarker will allow better risk stratification and permit more aggressive risk-factor modifications. The stronger association with diabetes warrants more research as the use of advanced therapies for diabetes to lower cardiovascular risk may be warranted in individuals with diabetes with elevated Lp(a) levels.
The measurement of Lp(a) levels can be incorporated into patient care plans and hopefully improve outcomes in individuals at risk for CVD.
Abstract
BACKGROUND
Lipoprotein(a) (Lp[a]) is a causal genetic risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited long-term follow-up data from large U.S. population cohorts.
OBJECTIVES
This study examined the relationship of Lp(a) with ASCVD outcomes in a large, pooled, multi-ethnic U.S.
METHODS
The study included data on Lp(a) and ASCVD outcomes from 5 U.S.
PROSPECTIVE STUDIES
MESA (Multi-Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults), JHS (Jackson Heart Study), FHS-OS (Framingham Heart Study-Offspring), and ARIC (Atherosclerosis Risk In Communities). Lp(a) levels were classified on the basis of cohort-specific percentiles. Multivariable Cox regression related Lp(a) with composite incident ASCVD events by risk group and diabetes status.
RESULTS
The study included 27,756 persons without previous ASCVD who were aged 20 to 79 years, including 55.0% women, 35.6% Black participants, and 7.6% patients with diabetes, with mean follow-up of 21.1 years. Compared with Lp(a) levels <50th percentile, Lp(a) levels in the 50th to <75th, 75th to <90th, and ≥90th percentiles had adjusted HRs of 1.06 (95% CI: 0.99-1.14), 1.18 (95% CI: 1.09-1.28), and 1.46 (95% CI: 1.33-1.59), respectively for ASCVD events. Elevated Lp(a) predicted incident ASCVD events similarly by risk group, sex, and race or ethnic groups, but more strongly in patients with vs without diabetes (interaction P = 0.0056), with HRs for Lp(a) levels ≥90th percentile of 1.92 (95% CI: 1.50-2.45) and 1.41 (95% CI: 1.28-1.55), respectively. Lp(a) also individually predicted myocardial infarction, revascularization, stroke, and coronary heart disease death, but not total mortality.
CONCLUSIONS
The study shows, in a large U.S. pooled cohort, that higher Lp(a) levels are associated with an increased ASCVD risk, including in patients with diabetes.