Researchers at Brigham and Women’s Hospital have linked very high levels of lipoprotein(a) [Lp(a)] with a substantially increased risk of major cardiovascular events over 30 years in women who were considered completely healthy at the start of observation.

The study, published in JAMA Cardiology, is based on one of the longest and most comprehensive follow-ups in this area.

Lipoprotein(a) is a blood particle long recognized as a cardiovascular risk factor. Unlike cholesterol, its level is almost entirely genetically determined, established early in life, and remains relatively stable over decades. This makes a single measurement potentially informative for lifelong risk but also presents a challenge: Lp(a) is minimally affected by lifestyle or most standard medications.

The study used data from the Women’s Health Study. Follow-up began in 1993 and continued until January 2023. The analysis included 27,748 women with a mean age of 53 years, who had no cardiovascular disease, cancer, or other major chronic conditions at baseline. All participants had their Lp(a) levels measured, along with detailed information on health and lifestyle. Genetic analysis was additionally performed in women of European ancestry.

The results showed that risk rises significantly only at very high Lp(a) levels. Risk begins to increase at concentrations of 30 mg/dL and above, but the most pronounced rise occurs at 120–130 mg/dL or higher. In these groups, the relative risk of major cardiovascular events was 54–74% higher than in women with low Lp(a) levels. In absolute terms, this corresponded to approximately a 10% higher lifetime risk.

The strongest association was observed with ischemic heart disease. For stroke and cardiovascular mortality, risk increased only at the most extreme Lp(a) levels. The genetic variant LPA rs3798220, associated with elevated Lp(a), was also linked to an increased 30-year risk.

The authors conclude that widespread screening for moderately elevated Lp(a) levels is unlikely to be justified. However, identifying women with extremely high Lp(a) may have practical value. This group, the researchers suggest, could benefit from closer monitoring and future therapies aimed at lowering Lp(a).