A new long-term analysis from the Women's Health Study provides important clarity on how lipoprotein(a) levels relate to cardiovascular risk in otherwise healthy women and at what levels that risk becomes clinically meaningful.
For the study, published in JAMA Cardiology, corresponding author Ask Tybjærg Nordestgaard, MD, of the Division of Preventive Medicine at Brigham and Women's Hospital in Boston, and colleagues followed 27,748 female health professionals who were free of cardiovascular disease, cancer, and major chronic illness at baseline. The researchers also analyzed 23,279 women of European ancestry with genetic data for a variant known to influence lipoprotein(a) (Lp[a]) levels. Participants had their Lp(a) levels measured in the early 1990s and were then followed for nearly 28 years, with health outcomes tracked through January 2023. During follow-up, researchers documented 3,707 major cardiovascular events among women with Lp(a) measurements and 3,165 events among those with genotype data.
Women with Lp(a) levels greater than 30 mg/dL—roughly the 75th percentile—had a higher 30-year risk of major cardiovascular events and coronary heart disease, even after adjusting for traditional risk factors. The most clinically significant findings were seen in women with Lp(a) levels equal to or greater than 120 mg/dL, corresponding to the top 1% of the population. Compared with women with Lp(a) less than 10 mg/dL, those in this highest category had a 54% higher risk of major cardiovascular events, 80% higher risk of coronary heart disease, and 63% higher risk of cardiovascular death. The association with ischemic stroke was elevated at 41% but did not reach statistical significance.
When analyzed by percentiles, women above the 99th percentile (equal to or greater than 131 mg/dL) showed similar or stronger associations: 74% higher risk of major cardiovascular events, more than double the risk of coronary heart disease, 85% higher risk of ischemic stroke, and 86% higher risk of cardiovascular death.
Among women with genetic data, carriers of the rs3798220 minor allele, a variant known to raise Lp(a), had a 27% higher risk of major cardiovascular events compared with noncarriers, reinforcing the contribution of genetically driven Lp(a) elevation to lifetime risk.
The researchers noted that the findings may not apply to patients of non-European ancestry and that the results should also be confirmed in men.
"We believe our findings for 30-year cardiovascular risk support the case for screening for elevated [Lp(a)] among healthy [patients], as recommended in some guidelines," they wrote. "Most importantly, such screening could help identify [patients] with very high [Lp(a)] levels, as these [patients] may benefit from primary preventive efforts, including possible future [Lp(a)]-lowering therapies."
The Women's Health Study was supported by grants from the National Heart, Lung, and Blood Institute and the National Cancer Institute.
Dr. Nordestgaard reported grants from The Independent Research Fund Denmark during the conduct of the study.
Source: JAMA Cardiology
