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For decades, the “gold standard” of heart health monitoring has focused on a familiar checklist: blood pressure, smoking status, and LDL cholesterol—the so-called “bad” cholesterol. However, a landmark study spanning nearly 30 years suggests that for a specific group of women, a silent, genetically determined factor called Lipoprotein(a), or Lp(a), may be the most significant predictor of their long-term cardiovascular destiny.
The findings, published recently in JAMA, analyzed data from nearly 28,000 initially healthy participants in the Women’s Health Study. Researchers discovered that women with the highest levels of Lp(a) faced a relative risk of major heart events up to 100% higher than those with the lowest levels. The study is sparking a renewed debate in the medical community: Is it time to make Lp(a) screening a routine part of preventative care?
The Silent Genetic Marker
Lipoprotein(a) is a type of particle in the blood that carries cholesterol, similar to LDL. However, unlike LDL—which fluctuates based on diet and exercise—Lp(a) levels are roughly 90% determined by genetics. Most people are born with a certain level that remains relatively stable throughout their lives.
“I was surprised at the magnitude of risk among those with very high levels,” said Dr. Ask T. Nordestgaard, lead author of the study and a postdoctoral research fellow at Brigham and Women’s Hospital. “The fact that elevated Lp(a) levels are strongly associated with high risk of ischemic stroke and cardiovascular death, and not only coronary heart disease, is significant.”
Key Findings at a Glance
The researchers followed participants recruited between 1992 and 1995, tracking “Major Adverse Cardiovascular Events” (MACE), which include heart attacks, strokes, and cardiovascular-related deaths.
| Lp(a) Level Category | Prevalence in Study | Observed Risk Trend |
| Low/Normal (< 30 mg/dL) | ~75% of women | Baseline risk; no significant elevation. |
| Moderately Elevated (30–120 mg/dL) | ~23-24% of women | Risk begins to rise gradually after 30 mg/dL. |
| Extremely High (≥ 120 mg/dL) | ~1-2% of women | 50% to 100% higher relative risk of major events. |
Unmasking the 30-Year Risk
What makes this study particularly robust is its duration. Because heart disease develops over decades, the 30-year follow-up allowed investigators to see how early-life Lp(a) levels manifested as late-life medical emergencies.
The study found that while most women (about 75%) had low levels that did not impact their health, those in the top 1% to 2% were in a high-danger zone. For these women, the risk wasn’t just limited to clogged arteries (coronary heart disease); it extended significantly to ischemic stroke and cardiovascular death.
“What is relatively unique here is the demonstration that Lp(a) is a strong risk factor even in relatively young women, emphasizing that no one is likely spared by this risk factor,” noted Dr. Steven E. Nissen, Chief Academic Officer at the Cleveland Clinic, who was not involved in the research.
To Screen or Not to Screen?
The medical community is currently divided on whether every adult should be tested for Lp(a). Because current medications like statins—the primary tool for lowering LDL—have a negligible effect on Lp(a), some argue that screening the general population is not yet “clinically worthwhile.”
The Argument Against Universal Screening:
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Low Prevalence: Only a small percentage of the population has the extremely high levels (≥ 120 mg/dL) that drive the most severe risks.
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Limited Treatment: Currently, there are no FDA-approved drugs specifically designed to lower Lp(a) (though several are in late-stage clinical trials).
The Argument For Universal Screening:
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Hidden Risk: Women with high Lp(a) might have perfect blood pressure and low LDL, yet remain at high risk. Screening identifies this “invisible” subgroup.
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Aggressive Management: Knowing a patient has high Lp(a) allows doctors to be much more aggressive in managing other controllable factors, such as blood pressure and lifestyle, to offset the genetic disadvantage.
“The advice to screen more widely is increasingly supported by data from many sources, including the current study,” added Dr. Nissen.
What This Means for You
If you have a strong family history of early heart disease or stroke—especially if those family members had “normal” cholesterol levels—discussing an Lp(a) test with your doctor may be a proactive step.
Why it matters for women:
Heart disease remains the leading cause of death for women globally. Because Lp(a) levels do not typically change with lifestyle, a one-time blood test can provide a “lifetime risk profile.”
“While we cannot yet change our genetics, we can change how we respond to them. Identifying high Lp(a) allows for a personalized ‘prevention-first’ approach that could save lives over a 30-year horizon.”
Study Limitations and Disclosures
While the study is one of the longest of its kind, it focused on the Women’s Health Study cohort, which may not fully represent all demographics. Additionally, while the association between high Lp(a) and CVD is strong, researchers are still working to prove that lowering Lp(a) with medication will definitively reduce that risk.
Conflicts of Interest:
The study was supported by the NIH and the Independent Research Fund Denmark. Several authors reported receiving grants or personal fees from pharmaceutical companies, including Novo Nordisk, Eli Lilly, and Amgen, which are currently developing Lp(a)-lowering therapies.
References
- https://www.medscape.com/viewarticle/study-shows-strong-association-between-long-term-cvd-risk-2026a10000qq
Medical Disclaimer: This article is for informational purposes only and should not be considered medical advice. Always consult with qualified healthcare professionals before making any health-related decisions or changes to your treatment plan. The information presented here is based on current research and expert opinions, which may evolve as new evidence emerges.
