Current approaches in modifiable and nonmodifiable risk factors for ASCVD
As the leading cause of morbidity and mortality globally, atherosclerotic cardiovascular disease (ASCVD) represents a labyrinth of modifiable and nonmodifiable risk factors, including medical, socioeconomic and systemic triggers.
The underpinnings of ASCVD were the focus of the Saturday session, “Shifting Paradigms in Lipid Management for ASCVD Risk,” which promised to deliver current science in managing the condition as well as a case-based discussion of a patient with mixed hyperlipidemia, elevated lipoprotein(a) and ASCVD.
Session panelist Carl E. Orringer, MD, FACC, FNLA, director of preventive cardiology at the Rooney Heart Institute Naples Comprehensive Health System’s Rooney Heart Institute in Florida, said diet and lifestyle changes can be a powerful tool in reducing modifiable ASCVD risk.
“I tell my patients, I’m not looking for perfect — I’m looking for better,” he said. “Even small changes matter. Lifestyle is the most important therapy in the management of hypertriglyceridemia, and when it fails, we have tools to help.”
With a focus on managing elevated triglycerides and their impact on atherosclerosis, Orringer’s presentation was designed to equip clinicians with practical strategies to manage lipid disorders in the context of ASCVD.
Orringer said triglyceride-rich lipoproteins carry cholesterol into the arterial wall, where it’s difficult to remove and leads to inflammation, especially when LDL cholesterol is also elevated.
For patients with triglyceride levels of 150-499 mg/dL, the first step is ruling out secondary causes such as diabetes, chronic kidney disease or medications that may elevate triglycerides. From there, the focus shifts to:
• Dietary changes: Reducing simple carbohydrates, added sugars, alcohol and saturated fats.
• Physical activity: At least 150 minutes of moderate intensity, or 75 minutes of high-intensity, aerobic activity weekly, plus resistance training.
• Weight loss: A 5% to 10% reduction in body weight, which can significantly lower triglyceride levels.
• Icosapent ethyl: Shown in the REDUCE-IT trial to lower cardiovascular risk in statin-treated patients with ASCVD or diabetes and additional risk factors.
Orringer linked the rise in hypertriglyceridemia directly to the obesity epidemic.
“The more patients we have who are overweight and obese, the more hypertriglyceridemia we’re going to see,” he said. “That’s why it’s critical for clinicians to be aware of evidence-based treatment approaches.”
For patients struggling with weight loss, Orringer said clinicians should consider prescribing GLP-1 receptor agonists such as semaglutide or tirzepatide. But he warned these are not direct triglyceride-lowering agents.
In patients with severe hypertriglyceridemia (greater than or equal to 500 mg/dL), especially above 1,000 mg/dL, the risk of pancreatitis becomes a concern. Orringer recommends:
• Maximally tolerated statins as the first-line therapy.
• Triglyceride-lowering drugs
such as fenofibrate or prescription omega-3 fatty acids for patients unresponsive to lifestyle and statins.
He noted, however, that the pill burden, for those taking prescription omega-3 — four capsules daily — can be a barrier for many patients.
Orringer also provided information on two recent clinical trials on inhibitors of apolipoprotein C-3 that have reported favorable results and a good safety profile in patients with mild to moderate hypertriglyceridemia.
Also at the session, panelist Michelle O’Donoghue, MD, MPH, an associate professor of medicine at Harvard Medical School in Boston, addressed challenges in the management of a risk factor that is primarily genetically determined.
Her presentation — “Lipoprotein(a) and ASCVD: What Does the Causal Link Mean for Risk Reduction?” —explored Lp(a), a genetic independent risk factor for ASCVD.
O’Donoghue’s presentation was designed to raise awareness and prepare clinicians for the next wave of lipid management strategies, offering hope for patients with elevated Lp(a) and emphasizing a renewed focus on precision cardiovascular care. Although current treatment options for elevated Lp(a) levels remain limited, O’Donoghue said there are promising new therapies on the horizon.
“Many of these emerging treatments utilize RNA interference to prevent Lp(a) synthesis in the liver, with some showing reductions of over 80% in clinical trials,” she said. “These therapies, mostly injectables, are now in phase 3 trials, with first results expected in early 2026.”
Until these therapies become available, O’Donoghue urges clinicians to focus on aggressive risk factor modification.
“Most current strategies don’t reduce Lp(a) levels directly,” O’Donoghue noted, “but they can help attenuate the risk of heart disease and other complications.”
She said the urgency of addressing Lp(a) is underscored by its genetic nature. Unlike traditional cholesterol, Lp(a) levels are not significantly influenced by lifestyle changes.
“It’s been very challenging for patients with elevated levels,” O’Donoghue said. “They often feel helpless because diet and exercise don’t seem to make a difference.”
She encourages clinicians to begin testing for Lp(a) levels, even in the absence of targeted therapies.
“Ignorance is not bliss in this regard,” she said. “Knowing a patient’s Lp(a) status can guide how aggressively other risk factors should be managed and prepare them for future treatment options.”
