Antihypertensive drugs and lipids

INTRODUCTION — Drug-induced changes in lipid levels may be particularly important in hypertensive patients since up to 45 percent of untreated patients with primary hypertension (formerly called "essential" hypertension) already have lipid abnormalities, such as an elevated low-density lipoprotein (LDL) cholesterol [1]. In addition, genetic studies in humans suggest that a predisposition for the development of both hypertension and dyslipidemia may result from the inheritance of shared genetic risk factors [2].

In general, effects of blood pressure-lowering agents on lipid levels and effects of statins on blood pressure are modest. Blood pressure lowering and lipid lowering provide independent and additive reductions in cardiovascular risk [3,4] and may provide a high absolute benefit in individuals with multiple cardiovascular risk factors [5].

This topic will address the effects of antihypertensive medications on serum lipids and the effects of cholesterol lowering medications on blood pressure. The management of adults with hypertension, a review of established risk factors for cardiovascular disease, and cardiovascular disease risk assessment are discussed elsewhere. (See "Goal blood pressure in adults with hypertension" and "Overview of established risk factors for cardiovascular disease" and "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults: Our approach" and "Cardiovascular disease risk assessment for primary prevention: Risk calculators".)

EFFECTS OF DIFFERENT ANTIHYPERTENSIVE AGENTS — Treatment of hypertension can affect lipid levels. Some antihypertensive drugs, for example, have a neutral or beneficial effect on the lipid profile, while others have an adverse effect; such adverse effects are outweighed by the beneficial clinical effects of blood pressure lowering on cardiovascular risk.

Antihypertensive drugs with adverse effects on plasma lipid levels — Thiazide diuretics and beta blockers may adversely affect lipid levels. However, we would not avoid using these medications (if otherwise indicated) in a patient with dyslipidemia, and, similarly, we would not discontinue these medications in a patient just to improve the lipid profile [6].

Thiazide diuretics — High doses of thiazide diuretics (50 to 100 mg of hydrochlorothiazide or chlorthalidone in one study) produce an initial 5 to 10 percent elevation in total and low-density lipoprotein (LDL) cholesterol and a lesser increase in triglycerides [7]. The hyperlipidemic effect of thiazide diuretics is dose dependent [7,8]; contemporary doses lead to more modest lipid effects. As an example, there is little or no effect on lipid metabolism with hydrochlorothiazide 12.5 mg daily or its equivalent [9], a dose that may have an antihypertensive effect nearly as great as higher doses (see "Use of thiazide diuretics in patients with primary (essential) hypertension"). In addition, in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), chlorthalidone 25 mg produced a slightly higher mean total cholesterol than did lisinopril 40 mg or amlodipine 10 mg at four years, but the mean difference was <2.5 mg/dL [10].

Beta blockers — Beta blockers are a heterogeneous class of antihypertensive medications. The effect of beta blockers on serum lipids varies with their unique pharmacologic characteristics and may be more prominent among smokers [8,11].

Many traditional beta blockers, both cardioselective and noncardioselective (such as atenolol, metoprolol, and propranolol), lead to a fairly modest increase in triglycerides (20 to 40 percent), a decrease in high-density lipoprotein (HDL) cholesterol (approximately 10 percent), and little effect on total cholesterol or LDL cholesterol [8,12]. By contrast, labetalol (a combined alpha and beta blocker) as well as beta blockers with intrinsic sympathomimetic activity (eg, acebutolol and pindolol) have relatively little impact on lipid levels due to a favorable effect on lipoprotein lipase [8].

Vasodilating beta blockers have a more favorable metabolic profile. Carvedilol, a combined nonselective beta and alpha-1 blocker, has less of a deleterious effect on triglyceride levels than metoprolol or atenolol [13,14], and nebivolol appears to have a neutral effect [15]. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Beta blocker'.)

Antihypertensive drugs with neutral or beneficial effects on plasma lipid levels — Other than thiazide diuretics and beta blockers, antihypertensive medications generally have a neutral or beneficial effect on the lipid profile [16]. However, we do not consider these effects when choosing antihypertensive therapy.

Angiotensin-converting enzyme inhibitors — The angiotensin-converting enzyme inhibitors appear to have no significant effect on plasma lipids [8] and may minimize or prevent the rise in lipids induced by diuretic therapy (via an unknown mechanism) [17].

Angiotensin receptor blockers — In most clinical studies, angiotensin receptor blockers had either a neutral or modest beneficial effect on lipid levels [18,19].

Calcium channel blockers — The calcium channel blockers appear to have either a neutral or mildly beneficial effect on the lipid profile [8].

Alpha blockers — The selective alpha-1 blockers, specifically prazosin, doxazosin, and terazosin, improve lipoprotein lipase activity and consistently demonstrate favorable effects on plasma lipids. These drugs lower total cholesterol by approximately 3 to 5 percent, reduce triglyceride levels by 3 to 4 percent, and mildly raise HDL cholesterol; the clinical significance of these changes is unclear [8,20].

Sympathetic blockers — The effect of the centrally acting sympathetic inhibitors, methyldopa, clonidine, and guanabenz, on the lipid profile has not been well studied. Both favorable and detrimental changes have been reported. On average, there is little, if any, change in lipid levels [8].

Effects of combination therapy — The effect of combination therapy in most cases appears to reflect the sum of the effect of the individual drugs [8].

EFFECT OF STATINS ON BLOOD PRESSURE — Treatment of dyslipidemia with statins may independently lower blood pressure, although the effect is modest [21,22]. This was demonstrated in the University of California San Diego (UCSD) Statin Effects Study, which randomly assigned 973 individuals to 20 mg of simvastatin, 40 mg of pravastatin, or placebo [23]. At six months, both statins modestly reduced systolic and diastolic blood pressure by 2.2 and 2.4 mmHg, respectively. Similarly, in a meta-analysis of 49 randomized trials involving over 45,000 participants, mean systolic and diastolic blood pressure was lower by 1.42 mmHg and 0.82 mmHg, respectively, in patients receiving statin therapy when compared with placebo [24]. Nonstatin lipid-lowering medications have not been reported to have any notable effects on blood pressure.

SUMMARY

●Overview – Treatment of hypertension can affect lipid levels, and treatment of dyslipidemia with statins can affect blood pressure. In general, effects of blood pressure-lowering agents on lipid levels and effects of statins on blood pressure are modest. Blood pressure lowering and lipid lowering provide independent and additive reductions in cardiovascular risk.

●Thiazide diuretics and beta blockers – Thiazide diuretics (at doses higher than typically used) and some beta blockers (particularly atenolol, metoprolol, and propranolol) may adversely affect lipid levels. However, we would not discontinue or avoid using these medications in a patient with dyslipidemia, as these effects are outweighed by the beneficial clinical effects of blood pressure lowering on cardiovascular risk. (See 'Antihypertensive drugs with adverse effects on plasma lipid levels' above.)

●Other antihypertensive drugs – Most other antihypertensive medications, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, and alpha blockers, have a neutral or beneficial effect on the lipid profile. However, we do not consider these effects when choosing antihypertensive therapy. (See 'Antihypertensive drugs with neutral or beneficial effects on plasma lipid levels' above.)

●Statins and blood pressure – Treatment of dyslipidemia with statins may independently lower blood pressure, although the effect is modest. (See 'Effect of statins on blood pressure' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Norman M Kaplan, MD, who contributed to an earlier version of this topic review.