Matthew J. Budoff, MD

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.

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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.

Future Directions for the Treatment of ASCVD and Hypercholesterolemia

 Christie, you mentioned the pipeline. What do we have emerging as new therapies in the pipeline?

 There’s the whole field of PCSK9. You mentioned cholesterin and siRNA [small interfering RNA] every 6 months. There’s also oral PCSK9. Those data were presented at the AHA [American Heart Association Scientific Sessions], giving over 60% reduction. There’s some cool technology: cyclic peptide and enhanced susceptibility with it. We’ve got the LP(a) [lipoprotein (a)], ASO [antisense oligonucleotide], and siRNA. The HORIZON trial is fully recruited. The siRNA is in the pipeline. ANGPTL3 is still alive. There are some data at this meeting that ASO doesn’t work, but siRNA is cruising along.

 That’s the ASO. It hasn’t been presented, but the program is over.

 LFTs [liver function tests] have increased—liver fat—significantly. It reduced LDL [low-density lipoprotein] and A-Fib [atrial fibrillation] and everything, but there was a significant increase in hepatic fat.

 In the dose responses, it didn’t work the way it was expected. It was surprising, but there will be another siRNA on LP(a) presented at this meeting. It looks exciting. You mentioned anti-inflammatory. There’s a trial, CKD [chronic kidney disease], anti–IL-6 with it. There are other programs that target the inflammasome. They’re earlier stage with it. There’s even a CRISPR gene editing that’s going to be phase 1 this year.

 There’s a lot of cool stuff going on. How will it all pan out? I don’t know, but there are going to be even more things.

 Anything emerging that you’re involved in?

 Christie mentioned several things I’m excited about. I have many patients with elevated lipoprotein(a). I check it a lot now, especially in patients who don’t seem to have the LDL response with statins. We don’t have a lot of good therapy for those patients. PCSK9 has some effects. Pelacaren is the agent. With the ASO against we can lower lipoprotein(a) by about 90%. The question is how much does that translate to reduction in events? We’ll see that with the HORIZON trial.

Getting back to patients with FH [familial hypercholesterolemia], we have evolocumab and an ANGPTL3 inhibitor for homozygous FH. Because its mechanism is independent of the LDL receptor, this is for extremely high-risk patients. There are some other agents in that population as well.

 We mentioned ANGPTL3, but the APL-C3s are moving along nicely. There’s an ASO and an siRNA. They’re extremely effective for high triglycerides, even working with FCS [familial chylomicronemia syndrome]. The prior 1 had some adverse effects on platelets, and we’re not seeing that anymore. We’ll have other things in the future. Even for that group that’s still hard to treat, we’ll have something for them.

 The GLP-1, GIP dual inhibition for diabetes may have some cardiovascular benefits. There may be a tolerability issue. We’ll have to see how that pans out, but those large trials are ongoing as well. We’ve seen this great interaction between GLP-1 receptor agonists and cardiovascular event reduction, so this might extend that even further.

 Don’t forget, maybe the hardest and most disappointing 1 over the last 30 years has been the increase in obesity. We’ve got outcomes trials in the pipeline with semaglutide, and these data are very impressive.

 The data remind us of the fenfluramine-phentermine of the time, of the 15% to 20% weight reduction. I’m applauding them for willing to take outcome trial, which everybody was fearful to do in this early disease group of people. It will be superior, I have no doubt.

 We have this outcome trial for patients who are obese or overweight, who don’t have diabetes, looking at GLP-1 receptor agonists and subcutaneous. There’s also cardiovascular outcome trial that’s powered to be a trial for an oral semaglutide, because the prior trial was not. That is another potential option.

 GLP-1 is in the studies. What do you guys think of this revival of CETP inhibitor?

 People forget that the…study, was short of reduction in events, all driven by LDL. But they had low LDLs to go in. When they had the long-term follow-up, curves were still growing apart. This new CETP inhibitor is very effective for lowering LDL. We know that CETP inhibitors don’t work by raising HDL [high-density lipoprotein]; those studies are done. But could this be an easy way to lower LDL another 50%? We’ll see. There are also other approaches toward PCSK9 besides the ones that I mentioned. There’s a scaffolding approach, where some data showed about a 70% reduction instead of doing the monoclonal.

Experts in endocrinology and cardiology review novel agents in the pipeline for the management of hypercholesterolemia and ASCVD.

Matthew J. Budoff, MD

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