Very High Lipoprotein(a) Levels Linked to Cardiovascular Disease Among Healthy Women

Very high levels of lipoprotein(a) are directly correlated with increased 30-year risk of cardiovascular disease among healthy women, according to a recent cohort study.1

Elevated plasma lipoprotein(a) is a well-known risk factor for cardiovascular disease – lipoprotein(a) levels are predominantly determined genetically and stabilize within the first 2 years of life, which highlights its status as a lifelong independent risk factor for cardiovascular disease. However, few guidelines suggest consistent examination of lipoprotein(a) levels in healthy patients, potentially missing a swath of preventable cardiovascular diseases and deaths.1

“Lifestyle intervention and currently available pharmacological treatment only modestly impact plasma lipoprotein(a) levels, and it remains to be demonstrated that isolated effective lipoprotein(a) lowering reduces risk of cardiovascular disease,” Daniel Chasman, PhD, division of preventive medicine, Brigham and Women’s Hospital, and colleagues wrote. “Consequently, contemporary guidelines do not consistently recommend lipoprotein(a) screening among individuals free from cardiovascular disease.”1

Chasman and colleagues pulled patient data from the Women’s Health Study, an ongoing cohort study of initially healthy women recruited between 1992 and 1995 and followed up prospectively since 1993. The program initially intended to investigate the effects of low-dose aspirin on the risk of stroke, first myocardial infarction, and death from cardiovascular causes. A total of 39,876 initially healthy women aged ≥45 years were included in the Women’s Health Study, who were then monitored for 10 years for a first major cardiovascular event.2

Despite the trial’s conclusion in 2004, patients have been continuously followed up through January 2023. Chasman and colleagues therefore gathered blood samples from 28,345 women within the Women’s Health Study patient population. All women with available baseline lipoprotein(a) measurements were included; plasma lipoprotein(a) levels were measured in all baseline samples at once, and participants were grouped according to the following clinical thresholds and percentiles:

• <10 mg/dL
• 10 to <30 mg/dL
• 30 to <60 mg/dL
• 60 to <90 mg/dL
• 90 to <120 mg/dL
• ≥120 mg/dL

Percentiles were then grouped into the following categories:

• ≤50th percentile (<11 mg/dL)
• 51st to 75th (11 to <33 mg/dL)
• 75th to 90th (33 to <66 mg/dL)
• 91st to 95th (66 to <83 mg/dL)
• 96th to 99th (83 to <131 mg/dL)
• >99th percentile (≥131 mg/dL)1

The trial’s primary outcome was the first occurrence of a major cardiovascular event, including incident myocardial infarctions, coronary revascularizations, incident ischemic stroke, and death from cardiovascular causes. Secondary outcomes included fatal and nonfatal myocardial infarctions and fatal and nonfatal ischemic stroke, among others.1

Of the 28,345 patients sampled, 27,748 patients had baseline lipoprotein(a) measurements and were included in the trial. During a median follow-up duration of 27.8 (interquartile range [IQR], 22.8-29.4) years, Chasman and colleagues noted 3707 incident major cardiovascular events, 1985 fatal or nonfatal coronary events, 1041 fatal or nonfatal ischemic stroke events, and 1543 cardiovascular deaths.1

Investigators found that lipoprotein(a) levels >30 mg/dL or the 75th percentile (31 mg/dL) were associated with substantially increased 30-year risk of major cardiovascular events and coronary heart disease. Levels >120 mg/dL or the 99th percentile versus below the 50th percentile (11 mg/dL) were 1.54 (95% CI, 1.24 to 1.92) and 1.74 (95% CI, 1.35 to 2.25) for major cardiovascular events, 1.8 (95% CI, 1.36 to 2.37) and 2.06 (95% CI, 1.49 to 2.84) for coronary heart disease, 1.41 (95% CI, 0.93 to 2.15) and 1.85 (95% CI, 1.17 to 2.93) for ischemic stroke, and 1.63 (95% CI, 1.16 to 2.28) and 1.86 (95% CI, 1.26 to 2.72) for cardiovascular death.1

“We believe our findings for 30-year cardiovascular risk support the case for screening for elevated lipoprotein(a) among healthy individuals, as recommended in some guidelines,” Chasman and colleagues wrote. “Most importantly, such screening could help identify individuals with very high lipoprotein(a) levels, as these individuals may benefit from primary preventive efforts, including possible future lipoprotein(a)-lowering therapies.”1

References

1. Nordestgaard AT, Chasman DI, Moorthy V, et al. Thirty-year risk of cardiovascular disease among healthy women according to clinical thresholds of lipoprotein(a). JAMA Cardiology. Published online January 7, 2026. doi:10.1001/jamacardio.2025.5043

2. Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005;352(13):1293-1304. doi:10.1056/NEJMoa050613