The primary goal of antihypertensive therapy is to reduce cardiovascular and renal morbidity and mortality using the least intrusive means possible. Indeed, in clinical trials adequate BP control has been associated with mean reductions of >50% in the incidence of congestive heart failure, >20% in myocardial infarction, and >35% in stroke. Thus, JNC 7 and other national guidelines recommend that all patients with hypertension should have their SBP lowered to below 140 mm Hg and DBP below 90 mm Hg. In patients with hypertension and diabetes or chronic kidney disease, the recommended BP goal is less than 130/80 mm Hg.
Appropriate lifestyle modifications are strongly recommended for all patients with either prehypertension or hypertension. Antihypertensive medications should be started if the BP is >140/90 mm Hg despite an adequate trial of nonpharmacologic treatment. The initiation of two drugs should be strongly considered in all patients with a baseline BP of more than 20/10 mm Hg above goal or stage 2 hypertension. This strategy will increase the likelihood of achieving goal BP within a reasonable time period but should be used cautiously in patients with diabetes and the elderly who are at a higher risk of developing orthostatic hypotension.
JNC 7 recommends weight loss for overweight or obese patients with hypertension, limitation of dietary sodium intake to ≤100 mEq/L/day (ie, 2.4 g of sodium or 6 g of sodium chloride) as part of the Dietary Approaches to Stop Hypertension (DASH) eating plan, and moderate alcohol intake of no more than two drinks per day. Increased physical activity such as brisk walking for at least 30 minutes for about 5 days/week is also advised (Table 41–2). Additionally, smoking cessation is also recommended to improve cardiovascular health. The benefits of these interventions include lowering BP, enhancement of antihypertensive efficacy, and reduction of cardiovascular risks.
Table 41–2. Lifestyle Modifications to Manage Essential Hypertension.1 ||Download (.pdf)
Table 41–2. Lifestyle Modifications to Manage Essential Hypertension.1
Approximate Reduction in Systolic Blood Pressure2
Maintain normal body weight (body mass index 18.5–24.9 kg/m2)
5–20 mm Hg/10 kg
Adopt DASH eating plan
Consume a diet rich in fruits, vegetables, and low-fat dairy products with a reduced content of saturated and total fat
8–14 mm Hg
Dietary sodium reduction
Reduce dietary sodium intake to no more than 100 mmol/day (2.4 g sodium or 6 g sodium chloride)
2–8 mm Hg
Engage in regular aerobic physical activity such as brisk walking (at least 30 minutes/day, most days of the week)
4–9 mm Hg
Moderation of alcohol consumption
Limit consumption to no more than two drinks (eg, 24 oz beer, 10 oz wine, or 3 oz 80-proof whiskey) per day in most men and to no more than one drink per day in women and in lighter-weight persons
2–4 mm Hg
Recent clinical trials have convincingly shown that reduction of BP by most antihypertensive agents will reduce the cardiovascular and renal morbidity and mortality associated with hypertension. The JNC 7 recommends that low-dose thiazide-type diuretics (eg, 12.5–25 mg of chlorthalidone or hydrochlorothiazide) should be used as initial therapy for most patients with hypertension either alone in stage 1 hypertension or in combination with other agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) or β-blockers in stage 2 hypertension. The thiazide-diuretic based regimen has been shown by recent clinical trials including Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) to prevent or reduce the cardiovascular complications of hypertension and is associated with a low rate of metabolic complications. Most patients will need two or more antihypertensive agents to achieve the recommended BP goal. If the low-dose thiazide monotherapy is inadequate to achieve the BP goal an ACE inhibitor or ARB should be added. This combination is synergistic and effective in lowering BP, especially among African-Americans and the elderly. Other antihypertensive agents can be added sequentially or substituted at monthly intervals until the BP goal is reached (Figure 41–1). After the BP goal has been achieved and remains stable, patients can be followed up at 3- to 6-month intervals.
Algorithm for the management of essential hypertension in kidney disease. BP, blood pressure; ACE, angiotensin-converting enzyme; ACEI, ACE inhibitors; ARB, angiotensin receptor blockers; CCB, calcium channel blockers.
Treatment of Specific Clinical Conditions
The general recommendations for initial therapy should be adapted for particular clinical conditions in which specific antihypertensive agents have been shown to be beneficial by outcome data from clinical trials, what JNC 7 refers to as compelling indications. These include the demonstration that renin–angiotensin–aldosterone blockers such as ACE inhibitors or ARBs improve outcome in high-risk settings such as patients with diabetes mellitus, congestive heart failure, myocardial infarction, stroke, chronic kidney disease, or albuminuria and that β-blockers improve survival in patients with systolic heart failure and prior myocardial infarction.
Diabetes and Hypertension
The combination of hypertension and diabetes significantly increases the risk of cardiovascular events and end-stage renal disease than either risk factor alone. Recent clinical outcome trials and guidelines have solidified the role of renal angiotensin aldosterone antagonists such as ACE inhibitors and ARBs in delaying the progression of diabetic nephropathy and reducing cardiovascular events and they are indicated as agents of first choice in all patients with diabetes. Additionally, based on the ALLHAT Trial, thiazide diuretics must be included as part of the drug therapy for most patients with diabetes. Combinations of two or more antihypertensive drugs are usually needed to achieve the recommended goal BP of less than 130/80 mm Hg. If the BP goal is not achieved other drugs such as CCBs and vasodilating β-blockers are added until goal BP is attained.
Congestive Heart Failure (CHF)
Hypertension is a major risk factor for the subsequent development of both systolic and diastolic heart failure. For many patients, LVH is an important intermediate step, resulting in “hypertensive heart disease” with impaired LV filling and increased ventricular stiffness. The BP goal for most patients with CHF is less than 140/90 mm Hg. Asymptomatic patients with “reduced LV function” [left ventricular ejection fraction (LVEF) <40%] improve both their BP and long-term prognosis with an ACEI and β-blocker while patients with symptomatic systolic heart failure will require additional agents such as ARBs, aldosterone antagonists, and loop diuretics. Treatment of hypertension in CHF patients with preserved LV function has not been as well studied. In general, β-blockers or non-dihydropyridine (DHP)-CCBs are recommended to increase diastolic filling time and decrease heart rate, but there are currently no randomized clinical trials with outcome data to demonstrate their long-term efficacy.
Coronary Artery Disease (CAD)
The coexistence of CAD and hypertension is an indication for therapy with multiple antihypertensive drugs to achieve a goal BP of less than 140/90 mm Hg. In patients with hypertension and stable angina, β-blockers are strongly recommended but long-acting CCBs are suitable and effective alternatives based on the results of recent outcome trials such as the International Verapamil/Trandolapril Study in which more than 22,000 patients with hypertension and coronary disease were randomized to either atenolol or verapamil. Patients with acute coronary syndromes or post-myocardial infarction should be initially treated with ACE inhibitors, β-blockers, and aldosterone antagonists. Additional recommendations include intensive treatment of dyslipidemia (to achieve or exceed an LDL-cholesterol target of <100 mg/dL) and antiplatelet therapy with aspirin or dypyridamole.
Left Ventricular Hypertrophy (LVH)
LVH is a well-recognized independent risk factor for cardiovascular events and premature death. It is common in the elderly and is often associated with diastolic dysfunction. Intensive BP management with agents that induce regression of LVH and reduce BP to a goal of less than 140/90 mm Hg is recommended. Recent clinical trials indicate that ARBs are very effective agents for the reduction of LVH but other interventions such as weight loss, exercise, and sodium restriction are also effective.
In acute ischemic stroke, the optimal level of BP is controversial. Acute lowering of the BP may lead to a reduction in blood flow to “watershed” areas of the brain with worsening of the neurologic function. In this setting, control of BP to intermediate levels of 160/100 mm Hg is appropriate. In stable patients, ACE inhibitors and thiazide diuretics are recommended to lower BP to a goal of less than 140/90 mm Hg and reduce recurrence of stroke.
Chronic Kidney Disease (CKD)
A majority of patients with CKD have hypertension and the therapeutic goals are to slow the progression of renal disease and to prevent cardiovascular disease. Optimal BP control to a goal of less than 130/80 mm Hg is strongly recommended. ACE inhibitors and ARBs are recommended for initial therapy because they have been shown to retard the progression of both diabetic and nondiabetic renal disease. An increase of the serum creatinine level by as much as 35% over baseline after initiation of these drugs should not lead to discontinuation because of the long-term benefits of these agents. For increases of serum creatinine larger than 35%, an assessment for concomitant nonsteroidal anti-inflammatory drug (NSAID) use, volume depletion, and/or renovascular hypertension is appropriate. Most patients will require three or more BP drugs to achieve the goal BP and loop diuretics are usually added when the estimated GFR is less than 30 mL/minute/1.73 m2.
In all patients with hypertension, albuminuria or proteinuria is an established risk marker for progression of renal disease and has also emerged as an independent marker of cardiovascular risk. Recent pharmacologic interventions with agents that lower BP and reduce albuminuria have resulted in a significant delay and even an arrest in the progression of microalbuminuria to CKD. Moreover, a reduction in proteinuria of more than 50% from baseline following 6 months of treatment reduces the risk of end-stage renal disease by 72% at 5 years. Recent outcome clinical trial data and current guidelines recommend that patients with hypertension with albuminuria should be started on agents that block the renin–angiotensin–aldosterone system, such as ACE inhibitors or ARBs. It has also been shown that maximal dose combinations of ACE inhibitors and ARBs agents further reduce albuminuria by an additional 30–35% over either agent alone, which correlates with slower kidney disease progression independent of BP. Nondihydropyridine CCBs such as verapamil or diltiazem also reduce proteinuria in patients with hypertension with proteinuric kidney disease, and have additive effects when combined with ACE inhibitors.
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