Cardiologists and primary care doctors frequently encounter patients with unexplained cardiovascular risk despite optimal cholesterol management, and lipoprotein(a)—a genetically driven particle—often lurks behind these cases without clear screening guidance. 
The Women’s Health Study, tracking female health professionals prospectively from 1993 to 2023, delivers compelling 30-year data to inform decisions. 
Researchers studied 27,748 initially healthy women free of cardiovascular disease, cancer, or major illnesses at baseline, collecting blood for lipoprotein(a) measurements, alongside 23,279 of European ancestry with LPA rs3798220 genotype data. Median age reached 53 years (IQR 49-60), yielding 3,707 major cardiovascular events over a median 27.8-year follow-up (IQR 22.8-29.4). Age- and multivariable-adjusted The results were published in the JAMA: Cardiology. 
Thresholds Define Risk Across Outcomes
Lipoprotein(a) exceeding 30 mg/dL or the 75th percentile (31 mg/dL) linked to higher 30-year risks of major cardiovascular events and coronary heart disease, helping identify moderate-risk women for aggressive lifestyle or statin therapy early. Extremely elevated levels above 120 mg/dL or the 99th percentile (131 mg/dL) signaled greater threats for ischemic stroke and cardiovascular death. Multivariable hazard ratios comparing levels over 120 mg/dL to below 10 mg/dL showed 1.54 (95% CI 1.24-1.92) for major events, 1.80 (95% CI 1.36-2.37) for coronary heart disease, 1.41 (95% CI 0.93-2.15) for stroke, and 1.63 (95% CI 1.16-2.28) for cardiovascular death. Percentile contrasts above the 99th versus below the 50th (11 mg/dL) yielded 1.74 for events, 2.06 for coronary disease, 1.85 for stroke, and 1.86 for death.
Genetics Reinforce Measurement Utility
Women carrying the rs3798220 minor allele faced elevated major event risk, confirming lipoprotein(a) as a heritable factor independent of traditional lipids and bolstering calls for targeted testing in families with premature disease.
Practical Screening in Everyday Practice
This robust female cohort highlights lipoprotein(a) testing for midlife women with strong family history, early relatives’ events, or recalcitrant risk despite LDL control, as silent elevation compounds dramatically over decades. Consider one-time screening for such patients, escalating to PCSK9 inhibitors or novel agents when levels top 120 mg/dL alongside standard care.
Guidelines May Shift Toward Testing
Prospective data spanning nearly three decades support broader screening debates, especially with improving assay access, positioning lipoprotein(a) as a key primary prevention tool.