Losing excess weight reduces SBP and DBP. The Trials of Hypertension Prevention, phase II (40) studied 2382 prehypertensive patients and achieved an average of 4.4 kg weight loss at 6 months and reduction of SBP and DBP by 3.7 and 2.7 mm Hg, respectively. In a study of patients with established hypertension, weight management associated with an average 7.8 kg weight loss yielded 7 mm Hg SBP and 5 mm Hg DBP reductions in clinic BP (41).

Most trials confirm that BP reduction is directly related to the weight loss achieved. If weight gain recurs, hypertension may return, but the long-term benefits of BP reduction persist. After 7 years of following 181 participants, body weight was similar in the weight loss and control groups, but the odds of developing hypertension in the weight loss group were reduced by 77% (P = .02) (42). Caloric restriction and regular physical activity remain the two basic ingredients for successful weight loss.

Adding physical activity to a weight-loss program accelerates the weight loss and augments BP reduction (43). An addition of even a 20-minute daily walk can reduce the risk of incident hypertension by 29% (44). The precise mechanism likely involves decreases in cardiac output and peripheral resistance as well as modifications in serum norepinephrine levels, insulin sensitivity, electrolyte balance, neural and baroreflex mechanisms, and vascular structure (41,45).

Cardiovascular exercise training is the most effective type of exercise for the prevention and treatment of hypertension. In a review of 39 studies using predominately walking or jogging exercise, lower intensity exercise resulted in greater BP reduction than did high-intensity exercise. Combined random and nonrandom trials showed average reductions in SBP of -13 mm Hg and in DBP of -18 mm Hg in hypertensive patients. Training more than three times per week or for more than 50 minutes per session did not confer added antihypertensive benefit (46). Current recommendations specify that exercise should occur for 20 to 60 minutes, 3 to 5 days per week, at low to moderate intensity (47).

Some of the most dramatic evidence supporting nonpharmacologic therapy has emerged from the Dietary Approaches to Stop Hypertension (DASH) trial (48). The study evaluated 459 adults with prehypertension or stage 1 hypertension (<160/80 to 95 mm Hg) randomized to usual diet or to a diet with
increased fruits and vegetables with or without reduced total and saturated fat intake. During the trial, investigators kept patients’ sodium intake and body weight at constant levels. After 8 weeks, the combined dietary intervention reduced BP by 11.4/5.5 mm Hg versus 7.2/2.8 mm Hg achieved by increasing fruits and vegetables alone (P < .01). Remarkably, 70% of subjects on combination diet—versus 23% on usual diet—were normotensive at the end of 8 weeks (49). Recent data establishes the combination diet as sustainable (50) and particularly effective in groups at highest risk of hypertension-related end-organ damage (African Americans, those with hypertension, and patients over age 50) (51).

The impact of reducing sodium on BP remains controversial, perhaps because salt sensitivity is heterogeneously distributed to a minority. In an unselected, normotensive population, there is insufficient evidence to recommend universal restriction of salt intake (52). In contrast, salt restriction may yield modest antihypertensive benefit among elderly hypertensives (53). Adding extra salt confers no medical value and possible harm. High sodium intake predicted mortality and risk of coronary disease among 2436 adults, independent of other cardiovascular risk factors including BP in a prospective trial (54) and cumulative mortality up to 27 years later (55).

There is consensus about the benefit of salt restriction among hypertensives (9). In the DASH-Sodium trial (56,57), subjects received the DASH diet or a typical U.S. diet and three levels of sodium (50, 100, and 150 mmol per 2100 kcal) for 30 days. Both the DASH diet group and the low-sodium groups had significant reductions in BP, but the greatest effect was seen in the combined groups (58). The benefit of BP reduction was greatest in the oldest subjects and in those with the lowest sodium intake. Moderate salt restriction with a target range of 90 to 130 mmol per day carries no associated adverse effects (52).

Importantly, sodium restriction often allows reduced need for antihypertensive medications, regardless of combination with weight loss (59). In one trial of sodium reduction with or without weight reduction among elderly hypertensives, over one third of patients were able to remain off their hypertensive medication, compared to only 16% who continued on their usual diet (60).

Adjustments in dietary and nondietary calcium supplementation may lower BP. In a meta-analysis of 42 randomized trials, calcium supplementation resulted in a small (about 1 mm Hg) but significant (P < .001) decrease in SBP and DBP (61). Recent data in elderly women demonstrate that adding vitamin D₃ supplementation to calcium may confer additional benefit in lowering BP versus supplementation with calcium alone. During an 8-week trial of 140 women with 25-hydroxycholecalciferol levels below 50 nmol/L, 81% of subjects in the combined vitamin D₃ and calcium group compared with 47% of subjects in the calcium alone group showed a decrease of at least 5 mm Hg SBP (P = .04) (62).

Most other dietary interventions appear to have trivial effects on BP. A randomized controlled intervention studying a low carbohydrate, high-protein, and high-fat diet (e.g., Atkins diet) did not significantly change SBP over 12 months (63). Reflecting a 1966–1996 Medline search, supplementing above the general dietary allowance of potassium and/or magnesium carries no demonstrable benefit in treating hypertension (64). More recently, isolated reports of mild benefit have appeared for potassium supplementation (65).

Alcohol acts as a vasodilator at low doses (1 to 2 drinks per day) and as a pressor at high doses (66). Despite popular attention surrounding potential health benefits of red wine, there is insufficient rigorous evidence to recommend a “therapeutic” daily glass of wine (67). In contrast, among habitual drinkers there is ample evidence to recommend restriction of alcohol intake to two or fewer drinks. For individuals consuming four to six standard drinks a day, the pressor effect lasts throughout a 24-hour period (68). Alcohol may have a BP-lowering effect at 4 hours yet lead to BP elevations 10 hours later (69). Restricting habitual alcohol consumption can reduce BP in normotensive and hypertensive individuals (70). In a trial of hypertensive, alcohol-dependent patients, ethanol abstinence over a 24-hour period was associated with a decrease in mean BP of up to 12.5 mm Hg (71).

Among smokers, smoking cessation is commonly associated with a 3- to 4-kg weight gain and increased incidence of hypertension (72). Nevertheless, smoking cessation dramatically reduces overall cardiovascular risk.

For over 45 years, scientists have explored the relationship between mental stress and cardiovascular disease (73). Currently, insufficient evidence exists to support stress reduction as a principal or sufficient treatment for hypertension. Conflicting data exist as to whether high job stress alone is a predictor of subsequent hypertension or whether the methods used to cope with stress are more determinant (74). In a 5-year study of 292 healthy adult subjects, there was no increased risk among subjects with the highest perceived job stress, although 32% did progress to hypertension during the study period (75).

Although stress reduction programs have unclear impact on BP, device-assisted slow breathing shows promise. In a randomized study of 149 hypertensives, accumulated time spent in slow breathing resulted in significant decreases in BP. The greatest decreases in SBP (-15.0 mm Hg) were seen in subjects who spent more than 180 minutes over 8 weeks in device-assisted slow breathing. Postulated mechanisms involve effects on baroreceptor sensitivity, heart rate variability, and venous return (76). Additional studies of greater size and duration are needed before such BP-lowering techniques gain broad acceptance.

The most comprehensive strategy for selecting antihypertensive therapy is the individualized approach. It takes into account
several key components of each patient: profile of hemodynamics and pathophysiology, cardiovascular risk analysis, concurrent medical conditions and therapies, quality of life analysis, and cost. In essence, the customized approach corresponds to a type of “mosaic” model of treatment, incorporating a large number of variables that differ for each individual (79).

Responding to the projected pathophysiology and hemodynamics, the clinician chooses medications to reverse the underlying circulatory dysregulation, lowering the vascular resistance, if elevated, while preserving cardiac output and maintaining perfusion to critical target organs: at rest, with exercise, and over the entire 24 hours.

Reflecting cardiovascular risk profile analysis, the clinician should avoid medications that likely worsen the known risk profile, such as using high-dose thiazides in a patient with elevated low-density lipoprotein cholesterol (80,81). The clinician should prospectively monitor those regimen-affected factors that impact risk and adjust the regimen to minimize overall risk, whether related to atherosclerosis, arrhythmias, congestive failure, or sudden death (82).

Aware of concurrent medical conditions and therapies, the clinician prescribes the fewest antihypertensive drugs to treat the greatest number of concomitant conditions, such as using β-blockers when the need for coronary prophylaxis and hypertension are present in the absence of limiting bradycardia or bronchospasm. Such therapeutic parsimony facilitates medication adherence by simplifying the overall regimen and minimizes adverse drug reactions and drug–drug interactions.

For regimen adherence, the clinician seeks to optimize the patient’s quality of life by considering physical and mental factors (83). For example, diuretic-based therapy may be more problematic in an older patient with incontinence (84). Similarly, β-blocker therapy has been associated with a small but significant increase in fatigue and sexual dysfunction (85). Such adjustments necessitate ongoing clinician–patient dialogue regarding disease- and treatment-mediated symptoms.

Rising health care expenditures, especially for medications, prompt both clinician and patient to consider cost. Key components include drug acquisition, concomitant treatment (e.g., potassium supplementation) and tests (e.g., monitoring serum potassium and renal function) (86), clinician visits, switching to a new agent after therapeutic failure or adverse event (87), and cost of not treating to goal BPs with attributable morbidity and mortality (88).

The JNC VII recommends thiazide diuretics as the drug of choice for initial monotherapy in the absence of specific contraindications or compelling indications (9). In support, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) comprises the largest randomized trial comparing outcomes with antihypertensive monotherapy. The ALLHAT trial compared a calcium channel blocker, angiotensin-converting enzyme (ACE) inhibitor, and thiazide diuretic among 33,357 hypertensive adults over a mean of 5 years (89). All-cause mortality did not differ among the groups, but the rate of heart failure was lowest in the diuretic group. Similar results have been seen in both black and non-black patients (90,91). In a meta-analysis of 42 trials designed to compare several antihypertensive drugs, low-dose diuretics were the most effective initial treatment for prevention of cardiovascular morbidity and mortality (92). Whereas BP reductions were similar between comparison groups for every outcome studied (coronary heart disease, CHF, stroke, cardiovascular disease events, cardiovascular mortality, and total mortality), no drug was significantly better than low-dose diuretics. When analyzed from a financial perspective, thiazide therapy is the least expensive hypertensive agent available with the atypical exception of vasodilator therapy (86).

Despite concern about links between thiazide use and elevated blood glucose, recent data show that thiazides did not


increase risk of developing diabetes among 12,550 hypertensive adults. In contrast, use of β-blockers was associated with a 28% higher risk of subsequent diabetes (93). Similarly, over a mean 14-year follow-up in the Systolic Hypertension in the Elderly Program (94), diuretic treatment versus placebo or atenolol in diabetics was associated with the most improved long-term outcomes.