A new approach to a routine blood test could predict a 30-year risk of heart disease, research published Saturday in New England Journal of Medicine found.
Doctors have long assessed their patients’ risk of cardiovascular disease by using a blood test to monitor cholesterol levels, focusing particularly on LDL or “bad” cholesterol. But limiting blood tests to only cholesterol misses important — and usually silent — risk factors, experts say.
“We have other biomarkers that tell us about other kinds of biological problems that our patients who are destined to have cardiovascular disease are likely to have,” said lead study author Dr. Paul Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s. Boston Hospital.
Ridker and his team discovered that in addition to LDL cholesterol, there are two other markers — a type of fat in the blood called lipoprotein (a) or Lp (a), and an indicator of inflammation—are important predictors of a person’s risk infarctstroke and coronary heart disease.
The findings were also presented on Saturday at the European Society of Cardiology 2024 Congress in London.
In the study, researchers analyzed data from nearly 30,000 American women who were part of Women’s Health Study. On average, the women were 55 years old when they enrolled between 1992 and 1995. About 13% — about 3,600 participants — had either a heart attack or stroke, had surgery to repair a narrowed or blocked artery, or died of heart disease. for 30 years of follow-up.
Although the research was conducted on women, Ridker said the findings would likely apply to men as well.
Still, the focus on women was intentional, he said. “This is a largely preventable disease, but women tend to be undertreated and underdiagnosed.”
All the women had blood tests done at the start of the study to measure their levels of LDL cholesterol, Lp(a) and C-reactive protein, a marker of inflammation in the body.
These measurements, individually and together, appear to predict a woman’s heart health over the next three decades, the study found.
Women with the highest LDL cholesterol levels had 36% higher risk of heart disease compared to those with the lowest levels. The highest Lp(a) levels indicated a 33% increased risk, and those with the highest CRP levels were 70% more at risk of heart disease.
When the three were examined together, women who had the highest levels were 1.5 times more likely to have a stroke and more than three times more likely to develop coronary heart disease over the next 30 years compared to women with the lowest levels.
All the markers were individually associated with a higher risk of heart disease, but “all three represent different biological processes. They tell us why someone is actually at risk,” Ridker said.
Early intervention
Traditional risk factors for heart disease include: obesity, diabetes, high blood pressure and high cholesterol levels. Testing for Lp(a) and CRP may reveal less obvious risk factors.
“You may not have any traditional risk factors, and just by having Lp(a) that high, you’re at higher risk,” said Dr. Rachel Bond, system director of women’s heart health at Dignity Health in Arizona, who was not involved in the study.
Bond said everyone should get tested for Lp(a) at least once in their life. If they are elevated at any point, they will be for life. There is one caveat: Postmenopausal women can develop high Lp(a) and may want to retest their levels at that time, Bond said.
On the other hand, the level of LDL cholesterol and CRP fluctuates throughout a person’s life. Ridker encourages doctors to perform the three-point blood test when patients are in their 30s or 40s to catch potentially overlooked risk factors early when it’s time to intervene.
Although it’s important to exercise, eat well and not smoke, people with already elevated Lp(a), LDL and CRP levels are likely to need medication, said Dr. Steven Nissen, Chief Academic Officer of the Heart, Vascular and Thoracic Institute. Cleveland Clinic, which was not involved in the study.
“We can’t expect lifestyle interventions to be done by most people on their own,” Nissen said.
The study had several limitations that future research can address, including a lack of racial and ethnic diversity, which plays an important role at risk of heart disease. Almost all participants—94%—were white.
Nissen also noted that the study stopped measuring Lp(a) levels once they crossed a certain threshold.
“The highest levels of lipoprotein(a) in this study were not even high enough to reach the clinical threshold at which the patient would be treated,” he said. “Tends to underestimate the risk of lipoprotein (a).”
Dr. Kunihiro Matsushita, a professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health who specializes in cardiology, said that while inflammation is certainly important, “it doesn’t mean that CRP is the best marker for predicting cardiovascular disease risk.”
“The use of three biomarkers is interesting, but the choice of which biomarkers they are can be explored further,” said Matsushita, who was also not involved in the new research.
He added that testing for inflammation, LDL and Lp(a) is especially important for people traditionally considered to be at low risk of heart disease, including women, young people and people of East Asian descent.
Ridker agreed.
“Doctors won’t treat things they don’t measure,” he said.