Unlocking the Link: Elevated Lp(a) Levels and ASCVD Risk in Patients with Diabetes

"The heightened risk with Lp(a) was observed in women and men, in non-Black and Black participants, and in those at low-intermediate and high risk for cardiovascular disease (CVD) over more than 20 years of follow-up," the researchers reported. Among patients with diabetes mellitus, increases in Lp(a) were linked to an even greater risk of CV events.

ASCVD, characterized by the buildup of plaque in arterial walls, stands as a leading cause of mortality and morbidity worldwide. Individuals with diabetes face a disproportionately higher risk of ASCVD, compounding the already formidable challenges posed by their underlying condition. Against this backdrop, understanding the role of Lp(a) assumes paramount importance.

Lp(a), a unique lipoprotein subclass, has garnered attention for its potential role in atherogenesis. Its structure, consisting of an LDL-like particle linked to apolipoprotein(a), sets it apart from traditional lipid markers.

As noted above, Lp[a] is a causal genetic risk factor for atherosclerotic cardiovascular disease. However, long-term follow-up data from large U.S. population cohorts are limited. Considering this, Nathan D. Wong, Division of Cardiology, University of California—Irvine, Irvine, California, USA, and colleagues aimed to examine the relationship of Lp(a) with ASCVD outcomes in a large, pooled, multi-ethnic U.S. cohort.

The study included data on Lp(a) and ASCVD outcomes from 5 U.S. prospective studies: ARIC (Atherosclerosis Risk In Communities), FHS-OS (Framingham Heart Study-Offspring), JHS (Jackson Heart Study), CARDIA (Coronary Artery Risk Development in Young Adults), and MESA (Multi-Ethnic Study of Atherosclerosis).

Lp(a) levels were classified based on cohort-specific percentiles. Multivariable Cox regression related lipoprotein (a) with composite incident ASCVD events by risk group and diabetes status.

27,756 persons without previous ASCVD who were aged 20 to 79 years were included in the study, including 55.0% women, 35.6% Black participants, and 7.6% patients with diabetes, with a mean follow-up of 21.1 years.

The study led to the following findings:

• 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, 1.18, and 1.46, 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, with HRs for Lp(a) levels ≥90th percentile of 1.92 and 1.41, respectively.
• Lp(a) also individually predicted revascularization, myocardial infarction, stroke, and coronary heart disease death, but not total mortality.

These new data indicate that Lp(a) is an “equal opportunity risk factor across several demographic and clinical categories,” Gregory G. Schwartz, University of Colorado School of Medicine, Aurora, wrote an accompanying editorial.

Regarding the guidelines, Schwartz also believes the US approach of Lp(a) measurement only in select patients might be too restrictive, including the recommendation only to screen in women with hypercholesterolemia. “Current Canadian and European guidelines that recommend testing in most adults would appear to be supported by the current findings,” he states.

Reference:

Wong ND, Fan W, Hu X, et al. Lipoprotein(a) and long-term cardiovascular risk in a multiethnic pooled prospective cohort. J Am Coll Cardiol. 2024;83:1511-1525.