Impact of Comorbidities on Atherosclerosis

Yehuda Handelsman, MD: We used to believe that people with type 1 diabetes did not have those lipid abnormalities…but they actually have a very high risk for cardiovascular disease, which starts 10 years after they’ve been diagnosed with diabetes. Christie, you mentioned that you may study some of those atypical people with diabetes and cardiovascular disease, do you want to touch on this?

Christie Ballantyne, MD: One of the things that’s been dramatically different is that, when I was a resident, that was a long time ago, but it was unusual to see young people with type 2 diabetes, and type 1 diabetes was frequently thought of as happening in childhood. What we’re seeing now is very different, there are many young people. There are also more atypical forms of diabetes, where you don’t have loss of all insulin, or late in life diabetes; there’s basically just a lot more diabetes. There has been a tremendous explosion of this, and I think it’s something combined with the lipid abnormalities, the effects on blood vessels, arterial function, and kidney disease—it’s a wave of diabetics. It’s not just COVID-19. If you get diabetes when you’re 20 years old, then 20 years later, they’re 40 and 50, and they’re showing up with infarcts in the CCU [coronary care unit].

Paul S. Jellinger, MD, MACE: To amplify your question regarding the relationship of glucose to ASCVD [atherosclerotic cardiovascular disease], the EDIC trial showed that in the first 3 or 4 years of tight control of type 1 diabetes, if you impart that tight control right at the onset, patients seem to be protected forever; it’s a metabolic memory.

Christie Ballantyne, MD: Glucose is important. But not forever, nothing’s forever.

Erin D. Michos, MD, MHS: I wanted to comment on the impact of the comorbidities of diabetes and kidney disease. Diabetes is a huge problem, 37 million US adults have diabetes, and it’s estimated to be 54 million by 2030, and cardiovascular disease is the leading cause of death in patients with diabetes. Patients with diabetes have a 2-to-4-fold increased risk of heart disease and stroke, a 50% increased risk of cardiovascular death, and they live 8 years less than their counterparts who don’t have diabetes. Then kidney disease; both reduction in EGFR [estimated glomerular filtration rate] and the presence of albuminuria, both independently are associated with increased cardiovascular disease in a dose-dependent fashion. Chronic kidney disease [CKD] is a risk enhancing factor for cardiovascular disease, and if you don’t measure albuminuria, you’ll miss a lot of patients with CKD, and we have new therapies targeted for that. Patients who have diabetes and CKD have an even greater risk of cardiovascular death compared to diabetes or kidney disease alone.

Yehuda Handelsman, MD: Can anybody think of other causes of atherosclerosis beyond CKD, diabetes, smoking, any other contributing factors?

Matthew J. Budoff, MD: More people are learning about Lp(a) [lipoprotein(a)] . What’s on the horizon, Christie?

Christie Ballantyne, MD: In addition to the traditional, there are other genetic factors that are important in the progression of atherosclerosis. We’re just beginning to understand those, and unfortunately the things that are having an impact at the level of the vascular wall or inflammation are difficult to quantitate by our current technologies. We all see patients who end up having severe disease without apparent clinical risk factors. It’s important when you’re treating individual patients to recognize this. However, they still benefit by aggressive treatment of the traditional risk factors, including lipids in particular.

Yehuda Handelsman, MD: It’s interesting that none of you mentioned inflammation. Does anybody want to touch upon inflammation?

Christie Ballantyne, MD: Inflammation is one of those factors. You mentioned those patients who are diabetic and obese, you might talk a little, Erin, about some of the data you’ve done in terms of inflammation and the impact on their prognosis.

Erin D. Michos, MD, MHS: Inflammation is a driver of atherothrombosis, it kind of fuels the fire. There are emerging therapies specifically targeting inflammation, which may be an important role not only for preventing progression of kidney disease, but preventing cardiovascular disease as well.

Yehuda Handelsman, MD: Also, the group of people more at risk for cardiovascular disease, people with rheumatoid arthritis or lupus, for example, we never looked at them that way, but their risk is much higher.

Christie Ballantyne, MD: HIV also.

Yehuda Handelsman, MD: And HIV. But what you said is correct, we need to control the blood pressure, the glucose, and specifically the lipids, which seems to do the job for the majority of the patients.

Transcript Edited for Clarity