A panel at the 83rd Scientific Sessions analyzed the association of hyperlipidemia, hypertension, and glucose levels with macrovascular risk during Current Controversies in the Primary Prevention of Diabetes Macrovascular Complications.

The session can be viewed on-demand by registered meeting participants at ADA2023.org. If you haven’t registered for the 83rd Scientific Sessions, register today to access the valuable meeting content through August 28. 

The panelists framed their discussion around a case study of a 64-year-old Caucasian woman who was recently diagnosed with diabetes and with a history of hypertension.

The patient has never been treated with aspirin, statin, or anti-hypertensive pharmacotherapy. She has no family history of cardiovascular disease (CVD) and walks her dog for 30 minutes each day, but she exhibits elevated blood pressure (136/82 mmHg) and her body mass index (BMI) meets the criteria for obesity. A lipid panel showed her high-density lipoprotein (HDL) cholesterol levels at 52 mg/dL, triglycerides at 130 mg/dL, and low-density lipoprotein (LDL) cholesterol at 152 mg/dL. Her A1C level is 7.1.

“I think we might all agree that one of the first steps we’d take in a clinic visit like this is to perform some assessment of this patient’s risk of a cardiovascular event over the next 10 years,” said Michael J. Wilkinson, MD, Assistant Professor of Medicine, University of California San Diego.

Cardiologist Heather M. Johnson, MD, MS, MMM, Baptist Health South Florida, analyzed the effectiveness of angiotensin-converting enzyme (ACEIs) inhibitors versus angiotensin II receptor blockers (ARBs) for managing hypertension as a risk factor for macrovascular complications in diabetes.

She cited studies from the New England Journal of Medicine and PLOS that found no significant differences in CVD outcomes. The cardiovascular community has moved beyond the question of ACEIs versus ARBs and reframed the discussion to ACEIs or ARBs. Dr. Johnson said she would prescribe either to the case study patient.

“We can start any first-line agent, ACEIs or ARBs. Dihydropyridine-based calcium channel blocker or longer lasting thiazide-type diuretic is also fine,” she said. “We look at our patient in front of us, what other medications are on board, physical exam findings, other concerns, and make a shared decision-making discussion.”

Dr. Wilkinson reviewed the application of moderate versus high-intensity statin therapy and the role of non-statin lipid-lowering therapies in managing LDL cholesterol levels and the risk of CVD.

“Everybody with diabetes, between 40 and 75, should be on some statin to lower their risk of cardiovascular disease,” he said.

A set of multi-society guidelines cited by Dr. Wilkinson instructs clinicians to analyze traditional CVD risk factors and diabetes-specific risk factors, including long duration, albuminuria, and the presence of microvascular complications, to determine whether a patient requires high-intensity statin therapy instead of moderate first-line treatment. He explained that high-intensity statin therapy is usually prescribed when the goal is to reduce a patient’s LDL cholesterol levels by 50% or more.

Non-statin lipid-lowering drugs can enhance the effects of high-intensity statin therapy. 

“There are data that adding ezetimibe in particularly high-risk patients, to further lower their LDL cholesterol, can help to reduce risk,” Dr. Wilkinson said.

He also cited the recently published CLEAR trial, which found that bempedoic acid reduced cardiovascular events in statin-intolerant patients.

Karol E. Watson, MD, PhD, Professor of Medicine, Cardiology, University of California, Los Angeles, investigated whether patients at risk for atherosclerotic cardiovascular disease (ASCVD) should start therapy with sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists instead of metformin. She also scrutinized whether A1C levels should be used to measure the risk of CVD.

“Metformin has been everybody’s favorite first-line therapy,” Dr. Watson stated. “At least, most people are most comfortable with it.”

The 1999 UK Prospective Diabetes Study suggested there was a lower rate of myocardial infarction among patients who were randomized to metformin versus those receiving conventional treatment. However, Dr. Watson questioned the validity of these findings due to a low sample size. She asserted that most cardiologists don’t review a study unless there are at least 20,000 patients; only 342 patients in the UK Prospective Diabetes Study were prescribed metformin.

“It makes me really think that the data on metformin is pretty thin,” Dr. Watson said.

She shared more recent data that concluded SGLT2 inhibitors and GLP-1 receptor agonists led to a reduction in major adverse cardiovascular events and strokes.

“We saw benefits that we never could have dreamed of,” she said. “So, cardiologists need to get comfortable with these drugs.”

Dr. Watson also explained that the long-known association between A1C and CVD was slightly misleading for clinicians and researchers. For many years, they focused on managing glucose levels to factor in cardiovascular risk. Now, it appears that patients benefit more from risk interventions that address a patient’s blood pressure and/or cholesterol than A1C measurements.

“Over time, we realized that it wasn’t really just about the glucose; it was about the whole constellation of risk factors that our patients have,” Dr. Watson said.