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Hypertriglyceridemia

Updated : October 22, 2023





Background

Hypertriglyceridemia is a growing concern, as it has been linked to an increased risk of both cardiovascular disease and pancreatitis. When triglyceride levels are severely elevated, the risk of pancreatitis rises, necessitating a combination of lifestyle changes and pharmacotherapy to lower these levels.

It is also important to address the underlying causes of hypertriglyceridemia. While the use of statin therapy to target low-density lipoprotein cholesterol (LDL-C) has led to improvements in atherosclerotic cardiovascular disease outcomes, residual risk remains.

In the context of this remaining risk for ASCVD, various studies have demonstrated that even mild to moderate hypertriglyceridemia serves as an independent risk factor for cardiovascular disease. However, the available data does not definitively confirm that treating hypertriglyceridemia reduces the risk of cardiovascular disease.

Epidemiology

Hypertriglyceridemia is relatively common, and its prevalence has been increasing in recent years due to changes in lifestyle and dietary habits. It affects a significant portion of the population, with varying degrees of severity. The prevalence of HTG tends to increase with age. It is more common in adults than in children and adolescents. Men are often more affected than women, but this gender difference can vary depending on the population studied.

It is often associated with other health conditions like cardiovascular disease, diabetes, and obesity. People with these comorbidities are at a higher risk of developing HTG. The prevalence can vary by geographic location and ethnicity. Specific populations may be more susceptible to HTG due to genetic predispositions or dietary practices.

Anatomy

Pathophysiology

Triglycerides are a type of fat found in the blood. They are primarily obtained from dietary fats or synthesized in the liver. Triglycerides are stored in adipose tissue and released into the bloodstream when the body needs energy between meals. Inherited genetic factors can predispose individuals to HTG. Certain gene mutations can affect the metabolism of triglycerides and increase their levels in the blood.

In cases of HTG, the liver may overproduce triglycerides, especially when influenced by dietary factors, obesity, or insulin resistance. The body may have difficulty removing triglycerides from the bloodstream due to the reduced activity of enzymes responsible for breaking down triglycerides. Elevated triglycerides are often associated with changes in lipoproteins, including very low-density lipoproteins (VLDL). VLDL particles carry triglycerides from the liver to peripheral tissues and are closely linked to HTG.

Insulin resistance, often seen in obesity and metabolic syndrome, can lead to HTG. Insulin plays a role in triglyceride metabolism, and its resistance can disrupt this process. High triglyceride levels are an established risk factor for atherosclerosis and cardiovascular disease, as they can lead to the formation of fatty deposits in blood vessels. Severely elevated triglyceride levels increase the risk of acute pancreatitis, which can be fatal.

Etiology

Genetics: In some cases, HTG has a genetic basis. Specific genetic mutations can affect the metabolism of triglycerides, leading to familial or hereditary hypertriglyceridemia. Notable examples include familial hypertriglyceridemia, familial combined hyperlipidemia, and familial dysbetalipoproteinemia.

Dietary Habits: Dietary choices can significantly impact triglyceride levels. Consuming a diet high in carbohydrates, particularly simple sugars, and unhealthy fats, such as saturated and trans fats, can increase triglyceride synthesis in the liver. Overconsumption of calories, especially in the form of high-carbohydrate and high-fat meals, contributes to HTG.

Physical Inactivity: A sedentary lifestyle can reduce the body’s ability to metabolize and remove triglycerides from the blood. Regular physical activity helps improve triglyceride metabolism.

Alcohol Consumption: Excessive alcohol intake can lead to HTG. The liver metabolizes alcohol and converts it into triglycerides, contributing to elevated levels in the bloodstream.

Pregnancy: Pregnancy can cause temporary HTG due to hormonal changes and increased fat storage for fetal development.

Genetics

Prognostic Factors

Clinical History

Healthcare providers should conduct assessments to identify potential secondary causes of hypertriglyceridemia. These causes may encompass factors like alcohol consumption, endocrine disorders, metabolic syndrome, and the use of certain medications.

In cases of primary hypertriglyceridemia, it is essential to evaluate patients for additional cardiovascular risk factors, such as hypertension, obesity, diabetes, and tobacco use. Moreover, it is important to inquire about the family history of lipid disorders, including dyslipidemia and cardiovascular disease.

Physical Examination

In patients with familial dysbetalipoproteinemia, characteristic signs include pathognomonic palmar xanthomas, which are yellow-orange deposits along the creases of the palms, as well as eruptive xanthomas on pressure sites like the elbows, buttocks, and knees.

Chylomicronemia syndrome may manifest with symptoms such as epigastric abdominal pain, eruptive xanthomas on the buttocks and upper limb extensor surfaces, hepatosplenomegaly, acute pancreatitis, temporary memory loss, lipemia retinalis, and, in rare instances, focal neurological deficits.

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Lipodystrophy

Acute Pancreatitis

Familial Hypertriglyceridemia

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

The management of hypertriglyceridemia is a multifaceted approach aimed at reducing elevated triglyceride levels and mitigating associated health risks. Lifestyle modifications play a crucial role, emphasizing dietary changes to promote a heart-healthy diet low in saturated fats and sugars, weight management to address obesity and regular physical activity.

Medications, including statins, fibrates, omega-3 fatty acids, niacin, and others, may be prescribed based on the severity of HTG and underlying causes. Treating and managing concurrent conditions like diabetes and metabolic syndrome is also important.

Regular monitoring of triglyceride levels and assessing other cardiovascular risk factors, such as obesity and diabetes, are essential components of effective HTG management. A personalized and comprehensive approach is key to reducing the risk of cardiovascular disease and pancreatitis associated with HTG while improving overall cardiovascular health.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Lifestyle Modifications

  • Dietary Changes: A heart-healthy diet low in saturated fats, trans fats, and refined sugars can help lower triglyceride levels. A focus on complex carbohydrates, lean proteins, and healthy fats is essential. Reducing alcohol intake is also important, particularly for those with alcohol-induced HTG. 
  • Weight Management: Weight loss, particularly for individuals who are overweight or obese, can significantly reduce triglyceride levels. 
  • Physical Activity: Regular physical activity, including aerobic exercise, can help improve triglyceride metabolism. Aim for at least 150 minutes of moderate-intensity exercise per week. 

Administration with pharmaceutical agent

  • Statins: Statins, primarily used to lower LDL cholesterol, can also have a moderate effect on lowering triglycerides. 
  • Fibrates: Fibrate medications, such as fenofibrate and gemfibrozil, are often used to reduce triglyceride levels. They can also raise high-density lipoprotein cholesterol. 
  • Omega-3 Fatty Acids: Prescription-strength omega-3 fatty acid medications, such as icosapent ethyl, can lower triglycerides, especially in patients with very high triglyceride levels. 
  • Niacin: Niacin can help lower triglycerides, but its use is less common today due to potential side effects. 
  • Bile Acid Sequestrants: These medications may lower triglycerides, especially when combined with other lipid-lowering drugs. 
  • Ezetimibe: In some cases, ezetimibe may be prescribed with a statin to lower triglycerides and LDL cholesterol. 

 

Medication

 

atorvastatin 

initial dose:

10 - 20

mg

Tablet

Orally 

every day

maintenance dose:10-80mg orally every day



icosapent 

Indicated for Severe hypertriglyceridemia:

2

g

Capsule

Orally 

Twice a day after meal



icosapent 

Indicated for the Cardiovascular risk reduction with hypertriglyceridemia:

2

g

Capsule

Orally 

Twice a day after meal



gemfibrozil 

600mg orally every 12 hours
Administer 30 mins before morning and night meals



omega 3 carboxylic acids 


Indicated for Hypertriglyceridemia
2-4 gm orally every day
It is recommended as a supplementary treatment along with dietary modifications in patients suffering from severe hypertriglyceridemia (TG ≥500 mg/dL)
Adjust the dose depending on patient response, tolerability



fenofibric acid 

Indicated as a supplement to diet for more than 500mg/dl for severe hypertriglyceridemia
Fibricor- 35-105 mg orally each day
Trilipix- 45-135 mg orally each day



fenofibrate micronized  

Antara: dose is 30-90 mg orally daily
Fenofibrate (micronized): dose is 43-130 mg orally daily, with a maximum limit of 130 mg per day
Lofibra capsules: dose ranges between 67-200 mg orally daily



glandular products 

Take 96 mg orally daily
Thymus extract
Take 120 mg of pure polypeptides daily Pancreas USP extract
Take 500 to 1000 mg orally three times daily



reishi 

In the form of dried mushroom take 1.5 to 9 g orally daily
In the form of powder take 1 to 1.5 g orally daily
In the form of tincture take 1 ml orally daily



bezafibrate 

400 mg orally as a sustained-release tablet once daily
Take with food



ciprofibrate 

It is used in the therapy for Hyperlipidaemia with a recommended dose of 100 mg via oral administration taken per day



Dose Adjustments

Renal dose adjustment
In case of renal impairment, dose of ciprofibrate depends on CrCl. When CrCl falls between 30 and 80 ml/min dose of ciprofibrate reduced to 100 mg every alternate day. If CrCl is less than 30 ml/min, ciprofibrate is contraindicated

 

bezafibrate 

400 mg orally as a sustained-release tablet once daily
Take with food



 

Media Gallary

References

Hypertriglyceridemia

Updated : October 22, 2023




Hypertriglyceridemia is a growing concern, as it has been linked to an increased risk of both cardiovascular disease and pancreatitis. When triglyceride levels are severely elevated, the risk of pancreatitis rises, necessitating a combination of lifestyle changes and pharmacotherapy to lower these levels.

It is also important to address the underlying causes of hypertriglyceridemia. While the use of statin therapy to target low-density lipoprotein cholesterol (LDL-C) has led to improvements in atherosclerotic cardiovascular disease outcomes, residual risk remains.

In the context of this remaining risk for ASCVD, various studies have demonstrated that even mild to moderate hypertriglyceridemia serves as an independent risk factor for cardiovascular disease. However, the available data does not definitively confirm that treating hypertriglyceridemia reduces the risk of cardiovascular disease.

Hypertriglyceridemia is relatively common, and its prevalence has been increasing in recent years due to changes in lifestyle and dietary habits. It affects a significant portion of the population, with varying degrees of severity. The prevalence of HTG tends to increase with age. It is more common in adults than in children and adolescents. Men are often more affected than women, but this gender difference can vary depending on the population studied.

It is often associated with other health conditions like cardiovascular disease, diabetes, and obesity. People with these comorbidities are at a higher risk of developing HTG. The prevalence can vary by geographic location and ethnicity. Specific populations may be more susceptible to HTG due to genetic predispositions or dietary practices.

Triglycerides are a type of fat found in the blood. They are primarily obtained from dietary fats or synthesized in the liver. Triglycerides are stored in adipose tissue and released into the bloodstream when the body needs energy between meals. Inherited genetic factors can predispose individuals to HTG. Certain gene mutations can affect the metabolism of triglycerides and increase their levels in the blood.

In cases of HTG, the liver may overproduce triglycerides, especially when influenced by dietary factors, obesity, or insulin resistance. The body may have difficulty removing triglycerides from the bloodstream due to the reduced activity of enzymes responsible for breaking down triglycerides. Elevated triglycerides are often associated with changes in lipoproteins, including very low-density lipoproteins (VLDL). VLDL particles carry triglycerides from the liver to peripheral tissues and are closely linked to HTG.

Insulin resistance, often seen in obesity and metabolic syndrome, can lead to HTG. Insulin plays a role in triglyceride metabolism, and its resistance can disrupt this process. High triglyceride levels are an established risk factor for atherosclerosis and cardiovascular disease, as they can lead to the formation of fatty deposits in blood vessels. Severely elevated triglyceride levels increase the risk of acute pancreatitis, which can be fatal.

Genetics: In some cases, HTG has a genetic basis. Specific genetic mutations can affect the metabolism of triglycerides, leading to familial or hereditary hypertriglyceridemia. Notable examples include familial hypertriglyceridemia, familial combined hyperlipidemia, and familial dysbetalipoproteinemia.

Dietary Habits: Dietary choices can significantly impact triglyceride levels. Consuming a diet high in carbohydrates, particularly simple sugars, and unhealthy fats, such as saturated and trans fats, can increase triglyceride synthesis in the liver. Overconsumption of calories, especially in the form of high-carbohydrate and high-fat meals, contributes to HTG.

Physical Inactivity: A sedentary lifestyle can reduce the body’s ability to metabolize and remove triglycerides from the blood. Regular physical activity helps improve triglyceride metabolism.

Alcohol Consumption: Excessive alcohol intake can lead to HTG. The liver metabolizes alcohol and converts it into triglycerides, contributing to elevated levels in the bloodstream.

Pregnancy: Pregnancy can cause temporary HTG due to hormonal changes and increased fat storage for fetal development.

Healthcare providers should conduct assessments to identify potential secondary causes of hypertriglyceridemia. These causes may encompass factors like alcohol consumption, endocrine disorders, metabolic syndrome, and the use of certain medications.

In cases of primary hypertriglyceridemia, it is essential to evaluate patients for additional cardiovascular risk factors, such as hypertension, obesity, diabetes, and tobacco use. Moreover, it is important to inquire about the family history of lipid disorders, including dyslipidemia and cardiovascular disease.

In patients with familial dysbetalipoproteinemia, characteristic signs include pathognomonic palmar xanthomas, which are yellow-orange deposits along the creases of the palms, as well as eruptive xanthomas on pressure sites like the elbows, buttocks, and knees.

Chylomicronemia syndrome may manifest with symptoms such as epigastric abdominal pain, eruptive xanthomas on the buttocks and upper limb extensor surfaces, hepatosplenomegaly, acute pancreatitis, temporary memory loss, lipemia retinalis, and, in rare instances, focal neurological deficits.

Lipodystrophy

Acute Pancreatitis

Familial Hypertriglyceridemia

The management of hypertriglyceridemia is a multifaceted approach aimed at reducing elevated triglyceride levels and mitigating associated health risks. Lifestyle modifications play a crucial role, emphasizing dietary changes to promote a heart-healthy diet low in saturated fats and sugars, weight management to address obesity and regular physical activity.

Medications, including statins, fibrates, omega-3 fatty acids, niacin, and others, may be prescribed based on the severity of HTG and underlying causes. Treating and managing concurrent conditions like diabetes and metabolic syndrome is also important.

Regular monitoring of triglyceride levels and assessing other cardiovascular risk factors, such as obesity and diabetes, are essential components of effective HTG management. A personalized and comprehensive approach is key to reducing the risk of cardiovascular disease and pancreatitis associated with HTG while improving overall cardiovascular health.

  • Dietary Changes: A heart-healthy diet low in saturated fats, trans fats, and refined sugars can help lower triglyceride levels. A focus on complex carbohydrates, lean proteins, and healthy fats is essential. Reducing alcohol intake is also important, particularly for those with alcohol-induced HTG. 
  • Weight Management: Weight loss, particularly for individuals who are overweight or obese, can significantly reduce triglyceride levels. 
  • Physical Activity: Regular physical activity, including aerobic exercise, can help improve triglyceride metabolism. Aim for at least 150 minutes of moderate-intensity exercise per week. 

  • Statins: Statins, primarily used to lower LDL cholesterol, can also have a moderate effect on lowering triglycerides. 
  • Fibrates: Fibrate medications, such as fenofibrate and gemfibrozil, are often used to reduce triglyceride levels. They can also raise high-density lipoprotein cholesterol. 
  • Omega-3 Fatty Acids: Prescription-strength omega-3 fatty acid medications, such as icosapent ethyl, can lower triglycerides, especially in patients with very high triglyceride levels. 
  • Niacin: Niacin can help lower triglycerides, but its use is less common today due to potential side effects. 
  • Bile Acid Sequestrants: These medications may lower triglycerides, especially when combined with other lipid-lowering drugs. 
  • Ezetimibe: In some cases, ezetimibe may be prescribed with a statin to lower triglycerides and LDL cholesterol. 

 

atorvastatin 

initial dose:

10 - 20

mg

Tablet

Orally 

every day

maintenance dose:10-80mg orally every day



icosapent 

Indicated for Severe hypertriglyceridemia:

2

g

Capsule

Orally 

Twice a day after meal



icosapent 

Indicated for the Cardiovascular risk reduction with hypertriglyceridemia:

2

g

Capsule

Orally 

Twice a day after meal



gemfibrozil 

600mg orally every 12 hours
Administer 30 mins before morning and night meals



omega 3 carboxylic acids