Elevated lipoprotein(a) levels associated with risk of cardiovascular disease among healthy women: JAMA

A new study published in the Journal of American Medical Association showed that among healthy women, very high lipoprotein (a) levels were associated with a higher 30-year risk of cardiovascular disease.
Screening recommendations are complicated by the fact that elevated lipoprotein (a) indicates a high risk of cardiovascular disease in a small percentage of healthy persons. Thus, spline models, clinical thresholds, and percentiles of baseline lipoprotein (a) levels were investigated as 30-year predictors of cardiovascular risk in this study.
This cohort research was carried out among female health professionals who were prospectively monitored from 1993 to 2023 as part of the Women’s Health research. Blood samples were obtained at baseline from women who did not have cancer, heart disease, or other serious chronic conditions. Every person having measurements of lipoprotein (a) and/or European ancestry who had genotyping data for the LPA rs3798220 variant was included. Major cardiovascular events, coronary heart disease, ischemic stroke, and cardiovascular mortality were the main outcomes. Hazard ratios for the cardiovascular outcomes were computed using age- and multivariable-adjusted cause-specific Cox models. A total of 23,279 women of European descent with rs3798220 genotype information and 27,748 women with baseline lipoprotein(a) measurements were included (median [IQR] age, 53 [49-60] years). During a median (IQR) follow-up period of 27.8 (22.8-29.4) years, 3707 and 3165 major cardiovascular events, respectively.A higher 30-year risk of major cardiovascular events and coronary heart disease was linked to lipoprotein (a) levels over 30 mg/dL or the 75th percentile (31 mg/dL) among women having lipoprotein (a) measurements. A higher risk of ischemic stroke and cardiovascular mortality was linked to levels over 120 mg/dL or the 99th percentile (131 mg/dL).Multivariable adjusted hazard ratios were 1.54 (95% CI, 1.24-1.92) and 1.74 (95% CI, 1.35-2.25) for major cardiovascular events, 1.41 (95% CI, 0.93-2.15), 1.80 (95% CI, 1.36-2.37) and 2.06 (95% CI, 1.49-2.84) for coronary heart disease and 1.85 (95% CI, 1.17-2.93) for ischemic stroke. Major cardiovascular events were more common in women with genotype information who carried the rs3798220 minor allele.Overall, among healthy women, very high lipoprotein (a) levels were associated with an elevated 30-year risk of cardiovascular disease. It could be necessary to screen the general population for increased lipoprotein (a).
Source:Nordestgaard, A. T., Chasman, D. I., Moorthy, V., Kraaijenhof, J. M., Cook, N. R., Lee, I.-M., Buring, J. E., & Ridker, P. M. (2026). Thirty-year risk of cardiovascular disease among healthy women according to clinical thresholds of lipoprotein(a). JAMA Cardiology. https://doi.org/10.1001/jamacardio.2025.5043