Matthew J. Budoff, MD

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

 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 

 risk via serum lipoproteins in patients who present without conventional risk factors.

According to recent studies, conventional risk factors such as 

, 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.

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.

“So overall, in the US, about 20% of patients who have heart attacks have no cardiovascular risk factors,” Budoff told 

. “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.

Budoff M. Serum Lipoproteins & Coronary Atherosclerosis in Asymptomatic U.S. Adults Without Traditional Risk Factors. Presented at the 9

 Annual Heart in Diabetes conference in Philadelphia, PA, June 6-8, 2025.

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

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Budoff suggests monitoring serum lipoproteins like Lp(a) and ApoB to predict cardiovascular disease risk in patients with no conventional indicators.

Matthew J. Budoff, MD: Examining the Interplay of Coronary Artery Calcium and Osteoporosis

22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC)

, Matthew Budoff, MD, a professor of medicine at the David Geffen School of Medicine at UCLA and an investigator at The Lundquist Institute, discussed the intersection of 

 and osteoporosis, emphasizing how these conditions share overlapping pathophysiology as diseases of aging.

Budoff highlighted findings from studies, including the Multi-Ethnic Study of Atherosclerosis, showing that elevated CAC scores not only predicted cardiovascular events but also correlated with lower bone density and increased fracture risk. Importantly, this relationship is bidirectional—osteoporosis independently increases the risk of atherosclerosis, myocardial infarction, stroke, and cardiovascular mortality. Leveraging advanced imaging techniques, clinicians have developed algorithms to measure bone density from coronary calcium scans or routine CT imaging, allowing simultaneous diagnosis of atherosclerosis and osteoporosis. Budoff indicated this approach could bridge the diagnostic gap, as only 8% of Medicare beneficiaries currently receive bone density testing despite the high osteoporosis prevalence.

The conversation also addressed high-risk populations, including older adults, smokers, Caucasians, and those undergoing significant weight loss due to obesity medications, which exacerbate osteoporosis risk. Budoff urged clinicians to prioritize bone density screening for postmenopausal women and men over 65, using existing CT imaging when DEXA scans are unavailable. By recognizing the dual risk of cardiovascular disease and osteoporosis, Budoff suggested healthcare providers can implement earlier interventions to improve patient outcomes.

Relevant disclosures for Budoff include AstraZeneca, Amarin, Merck, Novo Nordisk, Regeneron, and others.

Budoff MJ. CAC in ASCVD Relation to Bone Density & Osteoporosis. Presented at the 22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC). Los Angeles, California. December 12-14, 2024.

Matthew J. Budoff, MD describes bridging the gap between atherosclerosis and osteoporosis through advanced Imaging techniques.

Matthew J. Budoff, MD: Examining the Interplay of Coronary Calcium and Osteoporosis

Matthew J. Budoff, MD: Impact of Obesity on Cardiometabolic Health in T1D

, Matthew Budoff, MD, a professor of medicine at the David Geffen School of Medicine at UCLA and an investigator at The Lundquist Institute, highlighted the rising prevalence of obesity among patients with 

 and its implications for cardiovascular health.

Traditionally considered a disease of lean individuals, T1D now frequently overlaps with obesity and associated cardiometabolic complications, including hypertension, dyslipidemia, and increased risks of myocardial infarction and stroke. This shift parallels the broader obesity epidemic, with projections indicating that 50% of U.S. adults will be obese by 2030.

Budoff emphasized the need for a paradigm shift in managing T1D to address obesity and its cardiovascular consequences. With current treatment largely revolving around insulin, which may exacerbate atherosclerosis, new therapies like sodium-glucose co-transporter (SGLT) 1/2 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists offer promise. Although GLP-1 receptor agonists are not yet approved for glucose control in T1D, Budoff indicated their significant benefits in weight reduction and cardiovascular risk mitigation could transform care. Notably, the early use of calcium scoring or CT angiography in patients with T1D is recommended to identify subclinical atherosclerosis and guide aggressive preventive strategies.

Budoff identified the "obesity revolution" as the year's most significant cardiology breakthrough, highlighting the expanding evidence supporting GLP-1 receptor agonists, demonstrating efficacy across a spectrum of indications—from weight loss to cardiovascular risk reduction and heart failure with preserved ejection fraction (HFpEF). He noted this versatility underscores their role as a game-changing therapeutic class poised to address the complex interplay between obesity, diabetes, and cardiovascular health.

Budoff MJ. Contemporary T1D- Obesity and Cardiometabolic Complications. Presented at the 22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC). Los Angeles, California. December 12-14, 2024.

Matthew J. Budoff, MD discusses the effects of obesity and cardiometabolic complications in the contemporary management of type 1 diabetes.

 We’ve covered a lot of stuff, so we should end this discussion. I’d like to thank everybody for being active in participating and showing your knowledge, which is immense. Can you give us a closing statement? Paul?

 I don’t know if it’s a closing statement, but because there was a great deal of discussion about LDL [low-density lipoprotein] lowering, targets, and goals, I want to remind everyone about 2 groups of patients who, in my opinion, need particular attention to LDL lowering but aren’t getting it. One is the patient with diabetic dyslipidemia, or metabolic syndrome, whose triglycerides are elevated and HDL [high-density lipoproteins] is low. For those patients, as we heard a few times, when their triglyceride levels exceed 90 mg/dL, their LDL becomes more atherogenic. When the triglycerides are 130 or 140 mg/dL, they’re more atherogenic. Yet we use the same LDL targets for those patients if they have much more atherogenic LDL.

I suggest that we overtreat, in a sense—or treat much more aggressively—patients who have high triglycerides, low HDL, insulin resistance, and metabolic syndrome to LDL levels lower than we might think in traditional bracketing of LDL, because their LDL is much more atherogenic. If I have an LDL goal of 70 mg/dL for such a patient, I will say that this atherogenic profile is an LDL of 85 or 90 mg/dL, but I’m going to drive it down lower.

The second group of patients where we need to be more aggressive in lowering LDL are those with elevated LP(a) [lipoprotein (a)], which I measure frequently and is 1 of the hottest topics. We have no agents that effectively lower it very much. The only treatment for this is aggressive lowering of LDL. In the presence of an elevated LP(a), my LDL goal is even lower than the guidelines. Not so much in the second group, but in the first patient group with the diabetic dyslipidemia, I will use an APOB to guide me much more than a LDL because that tells me more about total particle size and atherogenic burden.

 A couple of comments getting back to duration. I like to think of it like pack-years of smoking. We have LDL years about durations. We need to get lower for longer. I want to emphasize the burden in women, because women continue to be undertreated for cholesterol and don’t have less achievement of guideline-directed recommendations compared with men. Also FH [familial hypercholesterolemia] is in 1 of 250 individuals. It’s very common, but people aren’t looking for it. Women in particular are undertreated, especially during their reproductive years. We do women a disservice because there’s no female advantage with FH. The onset of ASCVD [atherosclerotic cardiovascular disease] is the same in men and women. We cannot miss FH, and we must ensure that we’re treating our female patients appropriately.

 Don’t forget the mammogram of the heart. We can do a coronary calcium scan and find early heart disease like we use mammography to find early breast cancer.

 By the way, they’ve shown that in mammography, some classification, you can predict heart disease too.

 Breast or arterial calcification may also be a good predictor. The mammogram of the mammogram might be the mammogram of the heart. Identifying this disease early will help us. Remember, you can’t make an asymptomatic person feel better. You have to convince them that they need to be on these therapies. Even with slight adverse effects, patients taking a pill every day feel worse sometimes. If they feel compelled to be treated for high cholesterol because they also have atherosclerosis, that’s going to make your life a lot easier and your discussion with the patients a lot shorter to get them to comply with these therapies that we’re advocating.

 The biggest causes of premature pain, suffering, and death in our society are cardiovascular disease and cancer. We know how to prevent cardiovascular disease. If we implement these things, we could prevent 80% of this. A very simple aspect is that all the guidelines and the intensity of therapy are dependent upon the risk of the patient. What is the risk of that individual short and long term? Then we can reduce it. There are many things to do, but treating lipids is the easiest. Of all these things that we’ve talked about, it’s hard to change lifestyle and diet. But by controlling someone’s lipids with a little extra effort and attention in the modification of our approach, we can get people to very low levels and at least make a big part of reduction of their risk.

 We hope that we all agree and that we look at the goal, as Erin said. We can use combination therapy, and we can get them to go early on; the earlier, the better. With that, I’d like to thank you for watching this 

. If you enjoyed the content, please subscribe to the e-newsletter to receive more information about other great content sessions like this 1 in your in-box. Thank you. I appreciate you being with us.

Drs Paul S. Jellinger, Erin D. Michos, Matthew J. Budoff, Christie Ballantyne, and Yehuda Handelsman share closing thoughts and advice for the management of ASCVD and hypercholesterolemia.

Matthew J. Budoff, MD

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