A strong association between hypertension and coronary artery disease (CAD) has been established in epidemiologic studies, but the risk of cardiovascular disease can be greatly reduced with antihypertensive therapy. The American Heart Association (AHA) Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention have released guidelines on the management of hypertension in adults with or at risk of CAD. Table 1 summarizes the main recommendations.

The guidelines are aimed at answering the following questions: (1) What are the appropriate blood pressure targets for patients at a high risk of CAD or those with established CAD? (2) Are the beneficial effects of treatment a result of blood pressure reduction, or do particular classes of drugs have additional benefits? (3) Are there antihypertensive drugs that are particularly effective in the prevention of ischemic heart disease? and (4) Which antihypertensive drugs should be used in patients who have CAD with stable or unstable angina, in those with non–ST-elevation myocardial infarction (MI), and in those with ST-elevation MI? The recommendations are based on the best available evidence; however, consensus recommendations are proposed when data are lacking.

Prevention of CAD in Patients with Hypertension

Ischemic heart disease can be prevented or reversed by achieving aggressive targets for major cardiovascular disease risk factors. In patients with hypertension, dyslipidemia, and diabetes, surrogate end points (i.e., blood pressure, cholesterol, and blood glucose) have been established as diagnostic markers. The effectiveness of therapy is determined by the degree of reduction in the surrogate end point and the therapy's ability to reduce clinical end points (e.g., MI).

BLOOD PRESSURE GOALS

Blood pressure reduction is appropriate for the primary prevention of CAD in patients with hypertension. The consensus goal for blood pressure is less than 140/90 mm Hg in general. There are no clinical trials specifically designed to determine the most appropriate blood pressure target for persons with latent or overt CAD. However, a target of less than 130/80 mm Hg is recommended for patients with CAD or at high risk of CAD (i.e., those with carotid artery disease [carotid bruit or abnormal carotid ultrasound or angiograph findings], peripheral arterial disease, abdominal aortic aneurysm, diabetes, chronic renal disease, or a 10-year Framingham risk score of 10 percent or greater). If ventricular dysfunction is present, lowering the goal to 120/80 mm Hg may be considered.

Many studies show that lowering systolic or diastolic blood pressure decreases overall cardiovascular risk, but there are concerns about the adverse effects of excessive diastolic blood pressure reduction. Although there is uncertainty in the data, when standard medications are used, lowering diastolic blood pressure does not cause problems in most patients with hypertension, including those with wide pulse pressures or overt cardiac disease.

Elevated diastolic blood pressure levels should be lowered slowly in patients with occlusive CAD; caution is advised when the level falls below 60 mm Hg in patients who are older than 60 years or who have diabetes. Lowering systolic blood pressure can cause very low diastolic blood pressure levels in older persons with hypertension; therefore, physicians should carefully assess the patient for untoward signs or symptoms, especially those caused by myocardial ischemia.

NONPHARMACOLOGIC THERAPY

Although hypertension, hypercholesterolemia, cigarette smoking, obesity, and a sedentary lifestyle are potentially modifiable risk factors for ischemic heart disease, lifestyle modification has not been proven to reduce clinical events in individual patients. However, lifestyle modifications (e.g., smoking cessation, weight loss, reduced sodium intake, exercise, healthy diet, moderation of alcohol consumption in those who drink) are recommended to reduce the overall burden of hypertension.

PHARMACOLOGIC THERAPY

Careful blood pressure control is the most important strategy for lowering the burden of atherosclerotic disease. Meta-analyses have shown that the amount of blood pressure reduction is more determinant of the reduction in cardiovascular risk than drug choice, and that combination therapy is usually needed for long-term control, thereby making the choice of drug class less important. However, there is sufficient evidence to recommend an angiotensin-converting enzyme (ACE) inhibitor (or angiotensin receptor blocker [ARB] in those who are intolerant of ACE inhibitors), calcium channel blocker (CCB), or thiazide diuretic as the first-line agent. Another agent should be added if blood pressure is not controlled with monotherapy. However, because two or more agents are usually needed to reach blood pressure targets, two agents are usually used at the outset of treatment.

In patients with a high risk of CAD (e.g., those with ischemic heart disease, chronic kidney disease, or recurrent stroke), not all drug classes have been proven to have optimal benefit. An ACE inhibitor, ARB, CCB, or thiazide diuretic, or a combination of these drugs is recommended in these patients.

Management of Hypertension in Patients With CAD and Stable Angina

Management of hypertension in patients with chronic CAD and chronic stable angina is focused on the prevention of death, MI, and stroke; the reduction of myocardial ischemia; and the improvement of symptoms. This relies on lifestyle modifications and eventual pharmacologic therapy.

The mainstays of angina treatment are beta blockers, CCBs, and nitrates. Patients with a history of MI should receive a beta blocker and thiazide diuretic, and those with diabetes or left ventricular (LV) systolic dysfunction should receive an ACE inhibitor or ARB and a thiazide diuretic. This regimen may also be considered in patients without MI, diabetes, or LV systolic dysfunction. If beta blockers are contraindicated or cause adverse effects and there is no LV systolic dysfunction, a nondihydropyridine CCB may be substituted. If the initial regimen does not control the angina or hypertension, a long-acting dihydropyridine CCB may be added; however, nondihydropyridine CCBs should be used with caution in patients with symptomatic CAD and hypertension.

Management of Hypertension in Patients With Acute Coronary Syndromes

Data are lacking on the impact of anti-hypertensive treatment in patients with acute coronary syndromes, particularly non–ST-elevation MI. However, hypertension increases mortality rates in patients with acute coronary syndromes, and most patients will respond to standard methods of hypertension control. The cornerstone of hypertension management in patients with acute coronary syndromes is the modification of the balance between myocardial oxygen supply and demand plus anticoagulant and platelet inhibitor therapy.

UNSTABLE ANGINA OR NON–ST-ELEVATION MI

Treatment for hypertension in hemodynamically stable patients with unstable angina or non–ST-elevation MI should initially include a short-acting beta₁-selective beta blocker without intrinsic sympathomimetic activity, usually administered intravenously, plus a nitrate for symptom control. Oral beta blockers may be substituted later during hospitalization or considered in initial therapy. An ACE inhibitor or an ARB should be added if the patient has anterior MI, if hypertension persists, if there is evidence of LV dysfunction or heart failure, or if the patient has diabetes. In hemodynamically unstable patients, beta blocker therapy should be delayed until the patient is stable. Diuretics may be added for blood pressure control and management of heart failure.

If beta blockers are contraindicated or cause adverse effects and there is no LV dysfunction, a nondihydropyridine CCB may be substituted. If the initial regimen does not control the angina or hypertension, a long-acting dihydropyridine CCB may be added.

ST-ELEVATION MI

Therapy for hypertension in patients with ST-elevation MI is similar to that in patients with unstable angina or non–ST-elevation MI. Aldosterone antagonists may have an additive blood pressure–lowering effect in patients who have ST-elevation MI with LV dysfunction and heart failure, although serum potassium levels must be monitored. Aldosterone antagonists should be avoided in patients with elevated serum creatinine or potassium levels. CCBs have not been shown to reduce mortality rates in patients with ST-elevation MI; however, a nondihydropyridine CCB may be substituted in patients without LV dysfunction if beta blockers are contraindicated or cause adverse effects. If the initial regimen does not control the angina or hypertension, a long-acting dihydropyridine CCB may be added.

Management of Hypertension in Patients With Heart Failure

In patients with heart failure, hypertension management should include sodium restriction and a closely monitored exercise program. Drugs that have been shown to improve outcomes in patients with heart failure generally also lower blood pressure. Patients should receive thiazide or loop diuretics, ACE inhibitors or ARBs, beta blockers, and aldosterone receptor antagonists. Loop diuretics are less effective than thiazide diuretics in lowering blood pressure, but they should be used in patients with severe heart failure or severe renal impairment. Aldosterone receptor antagonists should be added if there is severe heart failure; however, potassium levels should be monitored carefully. These drugs should be avoided in patients with elevated serum creatinine or potassium levels. In black patients with New York Heart Association class III or IV heart failure, the addition of hydralazine/isosorbide dinitrate (Bidil) should be considered. Several drugs are contraindicated in patients with heart failure, including verapamil (Calan), diltiazem (Cardizem), clonidine (Catapres), and moxonidine (not available in the United States); alpha adrenergic blockers should be used only if other drugs do not effectively control blood pressure.