8
Disease Categories
TOP 10 TAKEAWAY MESSAGES:
Obesity and CVD
1. Obesity adversely affects heart and vascular anatomy and
function. CVD and cancer are the most common causes of
mortality among patients with obesity.
2. Obesity increases the risk of CVD both directly (e.g., via the
adiposopathic effects of epicardial fat), and indirectly via
the adiposopathic promotion of major CVD risk factors such
as diabetes mellitus, high blood pressure, dyslipidemia, and
thrombosis.
3. Patients with obesity benefit from global CVD risk reduction (e.g.,
healthful nutrition and physical activity, smoking cessation, as
well as optimal control of blood sugar, blood pressure, and blood
lipids). Additionally in the SELECT trial, semaglutide reduced
MACE from 8% to 6.5% (19% relative risk reduction) over 3 years in
individuals with obesity and established cardiovascular disease
but without diabetes. This is similar to the relative risk reduction
seen with statins.
4. Obesity may increase pericardial (paracardial and epicardial)
fat, intracardial fat, visceral fat, and liver and skeletal muscle
fat. Visceral and epicardial fat share the same mesodermal
embryonic origin, both increase the risk for atherosclerosis, and
both are highly correlated with coronary artery calcification.
5. Epicardial fat accumulation may directly contribute to heart
failure with preserved ejection fraction (HFpEF), atherosclerotic
CVD, dysrhythmias, fatty infiltration of the heart, and increased
coronary calcium. HFpEF (diastolic heart failure) is especially
common among patients with obesity, women, obstructive sleep
apnea, older age, and CVD risk factors.
6. In patients with T2DM, GLP-1 RA have cardiovascular outcome
trial (CVOT) evidence to support reduction in MACE (e.g.,
liraglutide, semaglutide, dulaglutide). Ongoing CVOTs include
oral semaglutide 14 mg per day in patients with T2DM.
Tirzepatide is a dual GLP-1 RA plus GIP receptor agonist being
evaluated as an anti-obesity agent, as well as a treatment for
T2DM and metabolic-associated steatohepatitis (MASH). In a
CVOT, tirzepatide is being compared to dulaglutide on MACE in
patients with type 2 diabetes mellitus (SURPASS-CVOT).
