New research funded by the NIH National Heart, Lung, Blood Institute (NHLBI) has identified a combination of biomarkers that can predict a woman’s risk of developing cardiovascular disease over the next 30 years. The study, presented as late-breaking research at the European Society of Cardiology Congress 2024 and published in the New England Journal of Medicine, details how combining analysis of C-reactive protein (CRP), a measure of inflammation and two measures of lipids can help head off cardiovascular health problems decades in advance.
For their research, led by Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, the investigators collected blood samples and medical data from 27,939 female healthcare professionals in U.S. who are participants in the Women’s Health Study. Starting between 1992 and 1995, these women were tracked for 30 years, during which 3,662 of those participating had significant cardiovascular events such as heart attacks, strokes, or cardiovascular-related deaths.
Researchers focused on how three biomarkers—high-sensitivity CRP, low-density lipoprotein (LDL) cholesterol and lipoprotein(a), or Lp(a), a lipid partly made of LDL—singularly and collectively predicted these cardiovascular events. Participants were grouped into five categories, based on the levels of these biomarker identified from the blood tests, from highest levels to lowest levels. Women with the highest levels of LDL had a 36% higher risk of developing heart disease compared with those with the lowest levels. Women with the highest levels of Lp(a) showed a 33% higher risk, and those with the highest levels of CRP showed a 70% higher risk.
But the best predictive power was found when all three measures were combined to develop a more accurate risk profile. Participants with the highest levels of the biomarkers showed more than one-and-a-half times increased risk for stroke and more than three times associated risk for coronary heart disease compared with women with the lowest levels.
While their study was confined to only women, the researchers said they would expect to find similar risk profile among men.
Emphasizing the importance of these findings, Ridker said: “We can’t treat what we don’t measure, and we hope these findings move the field closer to identifying even earlier ways to detect and prevent heart disease.”
The researchers noted that measuring these three levels could help inform early prevention efforts including exercise, a heart-healthy diet, managing stress, and smoking cessation to help mitigate cardiovascular disease risks. For those with heightened risk, interventions may include medication to lower cholesterol or reduce inflammation. Prior research has shown that steps people take earlier in life to support their heart and vascular health can add up over time and correlate with better health outcomes years and even decades later.
The role of inflammation in cardiovascular disease has been an important avenue of research in recent years. The immune system’s reaction to the accumulation of extra cholesterol in cells or the buildup of plaque leads to inflammation. In some cases, this can cause a hyperinflammatory environment whereby plaque can form, build up, or rupture, causing cardiovascular events.
Ahmed A.K. Hasan, MD, PhD, a medical officer and program director at NHLBI, noted: “We’ve learned more about how increased levels of inflammation can interact with lipids to compound cardiovascular disease risks. This helps explain why lower levels are often better.”
While LDL cholesterol measurements have become routine screening for cardiovascular risk in the U.S., the use of Lp(a) and CRP measurements for screening vary widely.
Some countries’ guidelines recommend Lp(a) screening since elevated levels are often tied to hereditary risk. Some therapies are available to those who show elevated levels of Lp(a) and researchers are also testing new approaches to improve treatment options.
CRP screening also varies and often depends on a person’s underlying risks and is at the discretion of clinicians. Colchicine, an anti-inflammatory therapy previously approved for gout, was later approved by the FDA in 2023 to offset risks for cardiovascular disease among people with atherosclerosis. Additional anti-inflammatory therapies and approaches are being studied.
