Measuring three factors can predict women’s 30-year risk for heart disease
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Key takeaways:
- Cardiovascular disease remains underdiagnosed and undertreated in women.
- New research stresses the importance of evaluating lifelong risk beyond traditional shorter-term estimates of risk.
A single combined measure of three modifiable biomarkers in healthy women at midlife was predictive of 30-year risk for future cardiovascular events, according to new research presented at the European Society of Cardiology Congress.
Paul M. Ridker, MD, MPH, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, and colleagues measured baseline levels of high-sensitivity C-reactive protein, LDL cholesterol and lipoprotein(a) in nearly 28,000 initially healthy women in the United States participating in the Women’s Health Study.
The three biomarkers were measured upon enrollment in 1992-1995, when the women had an average age of 55 years.
Over the next 3 decades of follow-up, 3,662 participants experienced a first major adverse CV event, which included myocardial infarction, coronary revascularization, stroke and/or death from CV causes. Ridker and colleagues evaluated how hsCRP, LDL and Lp(a) predicted these events, alone and collectively. The data were simultaneously published in The New England Journal of Medicine.
“We believe the time has probably come for universal screening of three simple modifiable CV risk factors,” Ridker said during a presentation.
Predicting risk over 3 decades
Participants were initially healthy at the time of enrollment in the Women’s Health Study. Twenty-five percent had hypertension, 12% reported current smoking and 2.5% had diabetes. Most women were white (94%) and mean BMI was 25.9 kg/m2.
Women were grouped into five categories by highest to lowest level of each biomarker. The highest quintile for CRP was > 5 mg/dL, the highest quintile for LDL was > 150 mg/dL and the highest quintile for Lp(a) > 44 mg/dL.
“C-reactive protein was the strongest long-term predictor of risk,” Ridker said.
Women in the highest quintile of hsCRP had a 70% increased associated risk for CV events compared with those in the lowest quintile (HR = 1.7; 95% CI, 1.52-1.9). Risk for CV events was increased by 36% for those with the highest vs. lowest levels of LDL (HR = 1.36; 95% CI, 1.23-1.52) and by 33% for those with the highest vs. lowest levels of Lp(a) (HR = 1.33; 95% CI, 1.21-1.47).
Cumulative incidence curves revealed a similar pattern of the highest risk in those with the highest levels of biomarkers.
“We’re quite used to seeing 5- and 10-year survival curves,” Ridker said, noting that by 30 years, the researchers saw major differences emerge. “We’re grossly underestimating the lifelong risk of this disease in women by focusing on such short-term issues.”
The researchers reported similar findings for coronary heart disease and stroke risk. Each biomarker independently predicted overall risk, but the researchers said the greatest impact occurred when all three biomarkers were incorporated together.
“While high-sensitivity CRP was a stronger predictor than LDL or Lp(a), the greatest spread in risk was obtained in models that incorporated all three biomarkers, which were fully independent of each other,” Ridker said.
Shift to modifiable risk markers, longer-term risk prediction
Modifiable biomarkers “can be instrumental for understanding biology, predicting risk and targeting cardiovascular interventions,” Ridker said during the presentation.
High-sensitivity CRP, LDL and Lp(a) were selected because they are independent of one another and each is modifiable with available therapies, he said.
“We have proven data for LDL lowering, proven data for inflammation lowering and we may have proven data for Lp(a) lowering when those trials are completed,” Ridker said. Moreover, low-dose colchicine (Lodoco, Agepha Pharma) was approved by the FDA in 2023 to reduce atherosclerotic events, and other anti-inflammatory strategies are being studied.
“Reflecting both completed and ongoing clinical trials, our guidelines for primary and secondary prevention are slowly shifting to include greater focus on modifiable risk markers, including these three, each of which has been shown to predict short-term risk among individuals taking and not taking statin therapy,” Ridker said. “However, data are quite scarce in the long-term (25- to 30-year) risk associated with these biomarkers, both when used alone and in combination, particularly among women, for whom cardiovascular disease remains underdiagnosed and undertreated.”
The researchers concluded that a single measurement of these three biomarkers could provide greater information on risk than any single biomarker alone.
‘A long-term view’
It is important to take “a long-term view” when it comes to CVD prevention, Roger S. Blumenthal, MD, and Seth S. Martin, MD, MHS, wrote in an accompanying editorial in NEJM.
“This innovative work that provides a long-term view of cardiovascular risk is aligned with the growing focus on cardiovascular-kidney-metabolic health and the emergence of the PREVENT tool for estimating 30-year risk. A long-term view can enable earlier recognition of cardiovascular disease risk in women and proactive preventive efforts to mitigate risk. The best way to avoid cardiovascular disease in the future is to reduce risk factors today, because tomorrow will soon be here,” Blumenthal and Martin wrote.
References:
- Blumenthal RS, et al. N Engl J Med. 2024;doi:10.1056/NEJMe2409080.
- NHLBI. Single blood test predicts 30-year cardiovascular disease risks for women. Published Aug. 31, 2024. Accessed Aug. 31, 2024.
- Ridker PM, et al. N Engl J Med. 2024;doi:10.1056/NEJMoa2405182.
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Ridker PM. Late-breaking science: Highlighted registries, observational and other studies. Presented at: European Society of Cardiology Congress; Aug. 30-Sept. 2, 2024; London (hybrid meeting).
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