According to the latest American College of Cardiology (ACC) clinical guideline, adherence to certain lifestyle interventions, including regular physical activity and avoidance of tobacco, as well as the use of lipid-lowering medications, are recommended to reduce the risk for atherosclerotic cardiovascular disease (ASCVD) in patients with persistent hypertriglyceridemia. The full report has been published in Journal of the American College of Cardiology.

The guideline provides a broader update to a previous American Heart Association (AHA)/ACC/multisociety guideline issued in 2018, which highlighted the specific patient groups most likely to benefit from statin therapy for ASCVD risk reduction.

In the new guidance statement, the ACC offers clinicians recommendations on the use of statins and triglyceride nonstatin treatments, as well as lifestyle interventions to prevent ASCVD in patients with persistent hypertriglyceridemia who have established risk factors for ASCVD, including diabetes mellitus and severe hypertriglyceridemia.

Recommendations for Lifestyle Interventions

According to the guideline authors, lifestyle interventions represent the first-line approach for managing persistent hypertriglyceridemia. In line with the 2018 AHA/ACC/multisociety cholesterol guideline recommendations, the adults who are 20 years and older with moderate hypertriglyceridemia should receive advice on lifestyle interventions with a focus on weight, diet, physical activity, and alcohol intake.

In patients with increasing levels of triglycerides (fasting triglycerides ≥150 mg/dL or nonfasting triglycerides ≥175 mg/dL), the guideline authors recommend that clinicians first assess non-lifestyle secondary causes as well as specific lifestyle practices and factors (eg, body weight, diet, and physical activity). Following this assessment, clinicians should emphasize the importance of a healthy diet and increased physical activity to their patients through a shared decision-making approach.

In addition to clinical guidance from physicians, the guideline indicates that dietitians be employed in a lifestyle intervention model for ASCVD risk reduction. The guideline authors recommend specific recommendations for sugar and fat intake, alcohol consumption, aerobic activity, and weight loss, all of which are stratified by triglyceride levels.

The guideline authors further explain that decreasing carbohydrate intake can also result in “meaningful reductions in triglycerides,” but emphasizing total fat content should be adjusted based on triglyceride levels at baseline. A full summary of nutrition recommendations has also provided in the guideline update, including recommendations on whether to include certain macronutrients and food groups based on triglyceride levels. The guideline also offers suggestions for replacements of common foods or beverages (ie, sugary beverages and alcohol).

Patients at risk for ASCVD should consume 2 or more servings of fish or other seafood each week to increase their intake of omega-3 fatty acids, as recommended by the ACC guideline. Salmon, tuna, and rainbow trout are recommended for patients with triglyceride levels of 200 to 499 mg/dL and 500 to 999 mg/dL. However, patients who are in the higher-triglyceride range may need to limit their fat intake, and focus on consumption of leaner fish or seafood.

Given that increased triglyceride levels are associated with physical inactivity, the new guideline also emphasizes the importance of aerobic physical activity and endurance training. Performing these exercises may increase “fatty acid oxidative capacity and enhance triglyceride hydrolysis in skeletal muscle, thereby increasing the proportion of energy derived from fatty acid oxidation during exercise.” Daily exercise may also improve carbohydrate and lipid metabolism and attenuate postprandial increase in triglyceride-rich particles.

Therapeutic Recommendations

Maximally tolerated statins have been recommended as the most optimal low-density lipoprotein cholesterol (LDL-C) risk-based therapy for patients with clinical ASCVD and persistent hypertriglyceridemia (fasting triglycerides >150 and <500 mg/dL).

Candidates for additional nonstatin therapies, such as ezetimibe, include patients at very high risk due to recurrent ASCVD events or patients with ASCVD who also have other high-risk conditions. The guideline authors suggest that a proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) inhibitor may be a reasonable option for patients with LDL-C that is persistently 70 mg/dL or higher. Patients with ASCVD who require further reductions in their LDL-C may receive bempedoic acid, a Food and Drug Administration (FDA)-approved adjunct to diet and maximally tolerated statin therapy.

The guideline authors also suggest that clinicians may consider adding icosapent ethyl to the treatment protocol of patients with persistent fasting hypertriglyceridemia 150 mg/dL to 499 mg/dL who are at least 50 years of age and have 1 or more ASCVD high-risk features.

The guideline offers recommendations for a clinical workflow of adult patients 20 years and older with no ASCVD or diabetes and fasting triglycerides of 150 mg/dL and higher or nonfasting triglycerides of 175 mg/dL and higher and lower than 500 mg/dL. For these patients, the guideline authors recommended optimizing diet and lifestyle and performing periodic 10-year ASCVD risk assessment in those with low ASCVD risk (<5%). The 10-year ASCVD risk assessment with the Pooled Cohort Equations can categorize patients as low, borderline, intermediate, or high risk.

Among patients at borderline to intermediate ASCVD risk (5% to <20%), the guideline indicates starting or intensifying statin therapy, based on shared decision-making. In addition, patients at high ASCVD risk (≥20%) should consider either starting or intensifying high-intensity statin therapy.

Future Direction

The current guideline is based on the best evidence available, but the authors suggest future genetic studies may help inform future guidance regarding novel therapeutic targets in atherosclerosis, including apo C-III and ANGPTL3. The authors further state that pending outcomes from current and future trials, research “studies targeting specific proteins in” triglyceride-based atherosclerotic “pathways also have the potential to provide clinicians with multiple options to address triglyceride-based ASCVD risk in patients treated with maximally tolerated statin therapy.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 


Virani SS, Morris PB, Agarwala A, et al. 2021 ACC expert consensus decision pathway on the management of ASCVD risk reduction in patients with persistent hypertriglyceridemia: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. Published online July 28, 2021. doi:10.1016/j.jacc.2021.06.011