Can hydrochlorothiazide (HCTZ) cause hypertriglyceridemia?

From the Guidelines

Yes, hydrochlorothiazide can cause elevated triglyceride levels in some patients. This diuretic medication, commonly prescribed for high blood pressure, has been associated with metabolic side effects including increases in blood lipid levels, as noted in a study published in 2011 1. Typically, hydrochlorothiazide can raise triglycerides by 5-15% in susceptible individuals, though the effect varies from person to person. The mechanism involves the medication's impact on insulin sensitivity and glucose metabolism, which indirectly affects how the body processes fats.

Some key points to consider:

• Hydrochlorothiazide is listed as a medication that can cause elevated triglyceride levels, along with other drugs such as beta blockers, estrogen, and bile acid–binding resins 1.
• The Endocrine Society has released guidelines on the diagnosis and management of hypertriglyceridemia, which includes recommendations for monitoring and treating patients with elevated triglyceride levels 1.
• The American College of Cardiology and American Heart Association have also released guidelines on the management of blood cholesterol, which includes recommendations for reducing triglyceride levels in patients with moderate or severe hypertriglyceridemia 1.
• More recent guidelines, such as the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack, also acknowledge the importance of managing hypertriglyceridemia to reduce the risk of cardiovascular disease 1.

Patients taking hydrochlorothiazide should have their lipid profiles monitored periodically, especially in the first few months after starting treatment. If significant triglyceride elevation occurs, your doctor might consider adjusting the dosage, switching to a different type of blood pressure medication, or adding lipid-lowering therapy. It's essential not to stop taking hydrochlorothiazide without consulting your healthcare provider, as uncontrolled high blood pressure poses greater health risks than moderately elevated triglycerides.

From the Research

Hydrochlorothiazide and Triglycerides

• Hydrochlorothiazide (HCT) may cause an increase in triglycerides in some patients, as seen in a study where 6 out of 10 patients with essential hypertension had higher plasma triglycerides during HCT treatment compared to placebo periods 2.
• Another study found that plasma triglycerides increased by 17% in mildly hypertensive patients treated with hydrochlorothiazide, suggesting a potential adverse effect of the drug on lipid metabolism 3.
• However, it is worth noting that the increase in triglycerides may not be uniform and can vary between individuals, as seen in the study where changes in triglycerides were not related to changes in blood pressure, body weight, or serum potassium 2.

Mechanism and Clinical Implications

• The exact mechanism by which hydrochlorothiazide increases triglycerides is not fully understood, but it may be related to its effects on lipid metabolism and insulin resistance.
• The increase in triglycerides associated with hydrochlorothiazide use may be a concern for patients with pre-existing hypertriglyceridemia or those at risk of cardiovascular disease, as hypertriglyceridemia is a known risk factor for cardiovascular disease 4.
• Alternative antihypertensive agents may be considered in patients with elevated triglycerides or those at risk of cardiovascular disease, as some agents may have more favorable effects on lipid metabolism 3, 5.

Management and Treatment

• Patients taking hydrochlorothiazide should be monitored regularly for changes in lipid profiles, including triglycerides, and managed accordingly.
• A cholesterol-lowering diet may help mitigate the increase in triglycerides associated with hydrochlorothiazide use, as suggested by a study where a cholesterol-lowering diet largely prevented the increase in plasma lipids 3.
• Other lipid-lowering therapies, such as fibrates or statins, may be considered in patients with hypertriglyceridemia, depending on the individual's risk factors and medical history 4, 6.