Resources

Severe hypertriglyceridemia, or sHTG, is defined by fasting triglyceride levels of 500 milligrams per deciliter and above and is characterized by an increased risk of acute pancreatitis, atherosclerotic cardiovascular disease, metabolic dysfunction-associated liver disease, which can progress to steatohepatitis, and other comorbidities.

The importance of treating triglyceride levels of 500 milligrams per deciliter and above to reduce these risks is outlined in multiple expert guidelines and recommendations on sHTG by the American Heart Association, the American College of Cardiology, the Endocrine Society, and the National Lipid Association.

And while more than 3 million Americans are estimated to have sHTG, the true prevalence may be higher.

This is due to a number of factors. First, there has not historically been an ICD-10 code specifically for sHTG. Second, guidelines call for testing fasting triglyceride levels, whereas patients are in a postprandial state for most of the day, allowing severe elevations to be missed. And finally, lipoprotein lipase becomes saturated at triglyceride levels above 500 milligrams per deciliter, impeding clearance of triglyceride-rich lipoproteins, and contributing to the high variability that makes sHTG difficult to estimate.

In treating patients with sHTG, I commonly saw extreme triglyceride fluctuations, even in patients who were being followed closely.

sHTG is typically caused by a combination of several factors, including lifestyle, certain medications, certain clinical conditions, and genetics, and existing treatment approaches are insufficient to get triglyceride levels to goal.

And because they depend on patient adherence, diet and exercise have proved to be an unreliable means of lowering triglycerides for most.

Commonly prescribed omega-3 fatty acids, fibrates, and statins do not reduce triglyceride levels sufficiently in all patients with sHTG. And none of these treatments have been studied to evaluate their effects on acute pancreatitis risk in patients with sHTG.

Niacin is no longer recommended in adults with sHTG due to its adverse effects.

And GLP-1 agonists have been associated with an increased risk of gastrointestinal adverse events, including acute pancreatitis.

However, despite the limitations of these treatment options, it is critical to treat sHTG aggressively and appropriately because the risks are too great to ignore.

Severe hypertriglyceridemia, or sHTG, is associated with an increased risk of acute pancreatitis. And as triglyceride levels surpass 500 milligrams per deciliter, the risk of acute pancreatitis continues to rise.
In fact, elevated triglyceride levels are the third leading cause of acute pancreatitis.

Acute pancreatitis that’s induced by sHTG can lead to irreversible organ damage— including pancreatic necrosis and beta-cell dysfunction, which, in turn, may lead to pancreatogenic diabetes—and death.

sHTG-induced acute pancreatitis is also associated with a mortality rate as high as 8%, prolonged hospitalization of around 17 days, and healthcare-related costs averaging $100,000 in total mean all-cause costs in the 12 months following the attack.

In people with sHTG, preventing the first episode of acute pancreatitis is critical.

Not just because of the serious risk associated with every episode, but also because each subsequent event after the first increases the risk of another attack.

I saw this firsthand in my patients with sHTG. For those who had pancreatitis, it often recurred.

Studies show that, once someone has had an episode of sHTG-induced acute pancreatitis, their risk of another episode can be as high as 24%.

Therefore, it is critical to reduce triglyceride levels that are 500 milligrams per deciliter or higher.

Severe hypertriglyceridemia, or sHTG, can substantially increase a person’s risk of atherosclerotic cardiovascular disease, or ASCVD.

This is due to the accumulation of atherogenic lipoproteins seen in triglyceride levels of 500 milligrams per deciliter and greater, including very low-density lipoprotein, or VLDL, and cholesterol-rich remnant lipoproteins.

Patients with sHTG are twice as likely to have an ASCVD event compared with patients with normal triglyceride levels less than 150 milligrams per deciliter.

As a result of this increased ASCVD risk, sHTG is independently associated with coronary heart disease, or CHD.

In a real-world study, the rate of CHD events was significantly higher in patients with sHTG compared with those who had normal triglyceride levels at baseline: 16.2% vs 9.5%.

And the rate of new CHD events remained statistically significant at follow-up 11.3 years later.

This is why sHTG demands urgent action to lower triglycerides and reduce the risk of ASCVD.

The primary risks associated with severe hypertriglyceridemia, or sHTG, are well known: acute pancreatitis, or AP, and atherosclerotic cardiovascular disease, or ASCVD.

However, there are additional physical and mental symptoms of sHTG that should be considered when identifying at-risk patients.

In 2 studies of adults with sHTG, respondents reported experiencing physical as well as emotional and cognitive symptoms.

Physical symptoms included gastrointestinal distress, abdominal and back pain, and fatigue.

Emotional and cognitive symptoms included stress, anxiety, depression, brain fog, and difficulty verbalizing thoughts.

Addressing sHTG is important, not only to reduce the risk of potentially life-threatening AP and ASCVD but potentially to improve the overall quality of life for your patients.

sHTG may, in fact, be impacting your patients’ lives more than you know.

Expert organizations underscore the importance of treating severe hypertriglyceridemia, or sHTG.

Guidelines and recommendations by the American Heart Association, the American College of Cardiology, the Endocrine Society, and the National Lipid Association have all highlighted the urgency of reducing fasting triglyceride levels of 500 milligrams per deciliter and above.

Whether through diet, lifestyle interventions, or pharmacotherapy, the primary goal in treating patients with sHTG is to reduce the risks of acute pancreatitis, or AP, and atherosclerotic cardiovascular disease, or ASCVD.

However, your patient’s sHTG and other comorbidities are interconnected, further increasing the risks of AP and ASCVD.

As such, there are important considerations for optimizing your patient’s sHTG treatment.

First, diet and exercise, while important, do not adequately lower triglycerides or reduce AP and ASCVD risk in all patients. Nor do therapies such as omega-3 fatty acids, fibrates, and statins.

Second, it’s important to remember that comorbidities such as obesity, insulin resistance, diabetes, and other metabolic disorders contribute to sHTG and its associated risks.

Therefore, ensuring these comorbidities are controlled is a critical part of an optimized sHTG treatment plan.

In closing, sHTG requires vigilant management and urgent intervention with standard-of-care treatment.