NEW evidence shows that lipoprotein(a) can predict cardiovascular disease risk up to 30 years later, highlighting its potential value as an early screening marker among apparently healthy women.
Lipoprotein(a) In Women’s Cardiovascular Health
Cardiovascular disease remains the leading cause of death among women, yet risk assessment often focuses on traditional markers such as cholesterol, blood pressure and smoking status. Lipoprotein(a) is a genetically influenced lipid particle that has historically been underused in routine screening. Interest in lipoprotein(a) has grown as researchers seek more precise tools to identify high risk individuals before clinical disease develops. This large prospective investigation aimed to determine whether baseline lipoprotein(a) levels, measured decades earlier, could reliably predict future cardiovascular outcomes in women who were free of major chronic disease at enrolment. By defining specific clinical thresholds and percentile cutoffs, the study sought to inform clearer guidance for population-based screening strategies.
Lipoprotein(a) Thresholds and Thirty-Year Outcomes
The cohort included 27,748 women with baseline lipoprotein(a) measurements and 23 279 women with genotype information, with a median age of 53 years. Over a median follow up of 27.8 years, 3707 and 3165 major cardiovascular events accrued, respectively. Lipoprotein(a) levels above 30 mg/dL or the 75th percentile of 31 mg/dL were associated with increased 30-year risk of major cardiovascular events and coronary heart disease. Levels above 120 mg/dL or the 99th percentile of 131 mg/dL were associated with increased risk of ischemic stroke and cardiovascular death. Multivariable adjusted hazard ratios for levels above 120 mg/dL versus below 10 mg/dL were 1.54 for major cardiovascular events, 1.80 for coronary heart disease, 1.41 for ischemic stroke and 1.63 for cardiovascular death. Corresponding hazard ratios comparing the 99th percentile with the 50th percentile of 11 mg/dL were 1.74, 2.06, 1.85, and 1.86, respectively. Minor allele carriers of rs3798220 also had higher cardiovascular risk.
Clinical Implications and Future Screening
These findings indicate that very high lipoprotein(a) identifies a subset of women at sustained long term cardiovascular risk despite apparent baseline health. Incorporating lipoprotein(a) testing into primary prevention assessments could allow earlier lifestyle intervention, targeted monitoring, and consideration of emerging lipid lowering therapies.
Reference
Nordestgaard AT et al. Thirty-year risk of cardiovascular disease among healthy women according to clinical thresholds of lipoprotein(a). JAMA Cardiol. 2026;DOI:10.1001/jamacardio.2025.5043
