Predicting Cardiovascular Disease in Patients Without Risk Factors with Matthew Budoff, MD

At the 9th Annual Heart in Diabetes Conference in Philadelphia, PA, Matthew Budoff, MD, professor of medicine and director of Cardiac CT at UCLA School of Medicine, presented the results of a recent study investigating cardiovascular disease risk via serum lipoproteins in patients who present without conventional risk factors.1

According to recent studies, conventional risk factors such as diabetes mellitus, family history, tobacco use, obesity, physical inactivity, elevated LDL cholesterol, low HDL cholesterol, and hypertension only explain roughly 66% of all cardiac events. A substantial number of atherosclerosis cases are experienced by patients with no prior indications of risk and are therefore missed by clinicians.2

However, Budoff indicated that these cases are often identifiable by skewed serum lipoproteins. Lipoprotein (a), apolipoprotein B (ApoB), and non-HDL cholesterol are all indicators of plaque, which in turn exhibits increased chances of cardiac events. All these measures are increased during atherosclerosis; to that end, Budoff suggests diagnosing and treating atherosclerosis itself to find otherwise symptomless coronary artery disease (CAD) instead of relying on conventional factors.1

“So overall, in the US, about 20% of patients who have heart attacks have no cardiovascular risk factors,” Budoff told HCPLive. “I think we have to look more carefully at LP(a), at C-reactive protein, at coronary calcium, as adjunctive ways of identifying this population that do have heart attacks but are not picked up by our population-based risk factors.”

Budoff’s study examined a meta-analysis of all patients looked at in a set of population-based studies, including the Miami Heart Study and the Multi-Ethnic Study of Atherosclerosis. Among these, Budoff and colleagues noted that Lp(a) was the most consistent predictor of atherosclerosis.

“It just reinforces what we’re learning; this is Lp(a) being elevated in the setting of normal LDL, no diabetes, no hypertension, no smoking,” Budoff said.

Budoff also stated that traditional population-based risk factors may be insufficient for diagnosing heart disease altogether. He posited that such broad categories miss patients outside of the typical conditions.

“I’ve always been somewhat against just using the traditional population-based risk factors, because it’s very impersonalized and a lot of patients don’t fit into those algorithms of care, where they might not have the right age or diabetes background or LDL to qualify as high risk, y et they really do have significant underlying atherosclerosis.” Budoff said. “And again, 20% of all heart attacks that occur in the United States occur in patients who don’t have any of these known modifiable risk factors.”

Budoff advised clinicians interpreting these results to begin conducting larger studies with broader scopes to better understand seemingly asymptomatic CAD and to better help patients in need.

“I think we need to do larger studies on patients who appear healthy, maybe earlier in life, to identify these patients who, long term, are not going to be so healthy and may put a significant burden on healthcare, but also not survive to their normal life expectancy,” Budoff said. “We’re not focusing on these lower risk individuals, but hopefully there will be enough of the population in these trials to start forming some good evidence.”

Budoff reports the following disclosures: AstraZeneca, Amarin, Merck, Novo Nordisk, Regeneron, and others.

References

1. Budoff M. Serum Lipoproteins & Coronary Atherosclerosis in Asymptomatic U.S. Adults Without Traditional Risk Factors. Presented at the 9th Annual Heart in Diabetes conference in Philadelphia, PA, June 6-8, 2025.

2. Khot UN, Khot MB, Bajzer CT, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA. 2003;290(7):898-904. doi:10.1001/jama.290.7.898