Acute pancreatitis risk

What if we could reduce the risk of acute pancreatitis for people with extremely high triglycerides despite standard of care?

Extremely high triglycerides can cause acute pancreatitis

Consistent fasting triglyceride levels >880 mg/dL could be a sign of an underlying genetic disease.

In some people, extremely high triglycerides that do not respond to traditional triglyceride-lowering therapies could be caused by Familial Chylomicronemia Syndrome (FCS), a rare genetic disorder. Other people with extremely high triglycerides that do not respond to traditional triglyceride-lowering therapies may display clinical characteristics similar to FCS, but have no clear genetic cause.

Regardless of the cause, people with extremely high triglycerides that do not respond to traditional triglyceride-lowering therapies face a risk of acute pancreatitis, which is a serious complication that often requires hospitalization and can be fatal.

Expert guidelines support lowering triglycerides below 500 mg/dL to reduce the risk of acute pancreatitis.

What is FCS?

FCS is a rare, autosomal recessive disorder caused by genetic variants that impair lipoprotein lipase (LPL) activity. In unaffected individuals, LPL clears circulating triglycerides and chylomicrons from the blood shortly after a meal. In people with FCS, the loss of LPL activity leads to the accumulation of triglycerides and chylomicrons, resulting in fasting levels at 10x-100x the normal level that do not respond to traditional treatments.

Clinical manifestations of FCS, including treatment resistance and acute pancreatitis, can also have a multifactorial, polygenic cause.

Woman walking looking away from the camera lost in deep thought.
Not an actual patient.

People with triglycerides over 500 mg/dL, like those with FCS, are in an acute pancreatitis risk danger zone.

An increasing risk of acute pancreatitis

Acute pancreatitis caused by high triglycerides is often more severe than acute pancreatitis caused by other factors.

Identifying those at risk of acute pancreatitis caused by high triglycerides is critical—even one acute pancreatitis event can dramatically increase the chance of a future one. Multiple episodes of acute pancreatitis can damage the pancreas, leading to chronic pancreatitis and insulin-dependent diabetes.

Acute Pancreatitis Risk

>1000

~17x

>880–≤1000

~14x

>500-≤880

~3x

People with triglycerides >500 mg/dL are in an established acute pancreatitis risk danger zone.

≥200–≤500

~1.5x

<200

Triglycerides (mg/dL)

Retrospective cohort study annualized incidence rate of acute pancreatitis. Data were obtained from IQVIA’s US Ambulatory Electronic Medical Records Database (N=7,119,195).

Among people with triglycerides >500 mg/dL to ≤880 mg/dL, how much more likely is it for someone to experience an acute pancreatitis event if they’ve had 1 acute pancreatitis event in the past year vs someone who has not?*

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Thank you for your response.

*Data from a national, retrospective study analyzing anonymized outpatient records of ~76 million patient records in the US from 2006-2020.
Illustration of a chart showing an increase as a result of dietary fat.

This chart is for demonstration purposes only.

The risk of unseen spikes in triglyceride levels

Chylomicrons are large triglyceride-rich lipoprotein particles derived mostly from dietary fat. In healthy individuals, chylomicrons are generally cleared from circulation within 3 to 4 hours after a meal.

People with extremely high triglycerides despite standard of care are unable to clear dietary chylomicrons, which causes triglyceride clearance to become saturated. Once clearance is saturated, chylomicrons from additional dietary fats can rapidly and drastically increase overall triglyceride levels.

Just one meal can increase acute pancreatitis risk

Accumulation of chylomicrons (chylomicronaemia) from dietary fat can increase acute pancreatitis risk after just one meal.

Illustration of additional dietary chylomicrons that cannot be cleared by the body due to high triglyceride levels.

Triglycerides clearance can be saturated, and the body may be unable to clear additional dietary chylomicrons.

Illustration of how high levels of chylomicrons are thought to restrict blood flow and induce inflammation in blood vessels.

High levels of chylomicrons are thought to restrict blood flow and induce inflammation.

Illustration of a pancreas.

The pancreas may be particularly vulnerable to ischemic damage caused by high levels of chylomicrons.

Other risk factors that exacerbate high triglyceride levels

In addition to dietary factors, certain medications and clinical conditions can increase triglyceride levels and the risk of complications like acute pancreatitis.

In women, hormonal changes due to pregnancy increase triglycerides and can lead to or exacerbate symptoms of severe hypertriglyceridemia. For women with FCS, estrogen-containing medications such as oral contraceptives may worsen hypertriglyceridemia.

Medications and clinical considerations that may increase triglyceride levels

Medications:

beta blockers, thiazide diuretics, estrogen receptor agonists, and oral contraceptives

Clinical considerations:

pregnancy, puberty, menopause, chronic kidney disease, uncontrolled diabetes, and excessive alcohol intake

The risk of acute pancreatitis

Imagine if we could get more people with extremely high triglycerides to the recommended goal.

Expert guidelines support lowering triglycerides below 500 mg/dL to reduce the risk of acute pancreatitis. For people with FCS or those with a similar clinical presentation, traditional treatments may not consistently keep triglycerides below this important guideline.

A man walking away to the side while carrying a shoulder tote bag wearing jeans and a jean jacket.
Not an actual patient.

There are few options to keep triglycerides in check

For some people, the use of traditional triglyceride-lowering therapies and intensive dieting are not enough to lower levels and reduce acute pancreatitis risk.

See the impact
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Show References Expand Collapse

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