Paul R. Conlin

Videos in Clinical Medicine from The New England Journal of Medicine — Blood-Pressure Measurement

High salt intake contributes to the risk of hypertension, and this effect is in part mediated by the physiologic action of aldosterone on renal mineralocorticoid receptors. However, the actions of aldosterone are not restricted to the kidneys, because aldosterone can bind to mineralocorticoid receptors in the heart, vasculature, and brain to produce structural and functional changes that lead to target organ damage. Experimental and clinical studies show that, in the setting of high salt intake, blocking aldosterone at the mineralocorticoid receptor reduces progression to target organ damage and preserves vascular function. In many cases, these benefits are independent of changes in blood pressure. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have short-term effects on reducing aldosterone levels, but frequently aldosterone levels return to pretreatment levels during long-term therapy. Aldosterone blockade may be more completely achieved with mineralocorticoid receptor antagonists. Spironolactone has been shown to have substantial and significant benefits in experimental and clinical studies of cardiac dysfunction. Eplerenone is a selective aldosterone blocker with a greater binding affinity for mineralocorticoid receptors than for androgen and progesterone receptors. Eplerenone has similarly demonstrated significant benefits in experimental animals and in patients with left ventricular dysfunction after myocardial infarction. Thus, aldosterone blockade with mineralocorticoid receptor antagonists offers target organ protection and may blunt some of the adverse effects of chronic high salt intake.

Antihypertensive efficacy must be redefined beyond blood pressure (BP) lowering per se to include reducing the cardiovascular complications of hypertension. Treatment decisions should be based on results from large clinical trials with relevant clinical outcomes. Several recent morbidity and mortality trials with angiotensin II receptor antagonists (AIIAs) provide an evidence-based rationale for the use of AIIAs in patients with hypertension. Studies with AIIAs in comparison to conventional antihypertensive agents showed improved morbidity and mortality outcomes in patients with hypertension and left ventricular hypertrophy (losartan) and diabetes mellitus (losartan and irbesartan). Trials with some members of the AIIA class (candesartan and valsartan) have not demonstrated such benefits in comparison to conventional agents, possibly due to differences in BP control during the trials. The results of these AIIA outcome trials have impacted on recently issued clinical guidelines for management of hypertension.

The Dietary Approaches to Stop Hypertension (DASH) diet, which emphasizes fruits, vegetables, and low fat dairy products, significantly lowers blood pressure (BP). We conducted a clinical trial to assess the BP response to the DASH diet with an antihypertensive medication, losartan, in participants with essential hypertension. A total of 55 hypertensive participants were randomly assigned to 8 weeks of controlled feeding with either a control diet or the DASH diet. Within each diet arm, participants received losartan 50 mg daily or placebo for 4 weeks each, in double blind, randomized, cross-over fashion. Twenty-four-hour ambulatory BP (ABP) was measured at the end of a 2-week run-in period (baseline) and after each 4-week intervention period. There was no significant change in ABP during the placebo period on the control diet (n = 28) (-2.3 +/- 1.5/-1.6 +/- 1.0 mm Hg), but there was a significant reduction in systolic ABP (-5.3 +/- 1.5 mm Hg, P <.05) and no change in DBP (-2.5 +/- 1.0 mm Hg) on the DASH diet (n = 27). Losartan significantly reduced ABP on the control diet (-6.7 +/- 1.5/-3.7 +/- 1.0 mm Hg, P <.05) and to a greater extent on the DASH diet (-11.7 +/- 1.5/-6.9 +/- 1.0 mm Hg, P <.05 versus basal and control diet) particularly in African Americans. On the DASH diet, DeltaSBP on losartan was inversely related to basal plasma renin activity (n = -0.53, P =.004). The DASH diet enhances the ABP response to losartan in essential hypertension. This effect is particularly marked in African Americans.

Journal of Human Hypertension is exclusively concerned with all clinical aspects of human hypertension. The journal publishes fully refereed original research papers from around the world.

It is through blood pressure lowering that reductions in cardiovascular morbidity and mortality are achieved. The treatment of hypertension patients should also focus on prevention and management of cardiovascular complications, not merely on achieving a target level of blood pressure. In making treatment decisions it is appropriate to assess patients for the presence or absence of risk factors and/or clinical cardiovascular disease. Clinicians should strive to use the least intrusive means possible to achieve goal blood pressure and the treatment regiment should be individualized for each patient. The review has illustrated specific clinical conditions where the use of an hypertensive agent that inhibits the renin-angiotensin system may offer added benefit to the patient while producing the needed anti-hypertensive effects.

Several recently published clinical trials and epidemiological studies have added significant new data to our understanding of the impact of dietary modifications on blood pressure. Such studies confirm the blood pressure-lowering effects of sodium restriction, the consumption of diets that are low in fat and enriched in fruits and vegetables, and the sustained effects of weight reduction. This reaffirms the role of lifestyle modifications as both preventative and adjunctive means to lower blood pressure.

We disagree with Doctors Meredith and Trenkwalder that the results of our meta-analysis1 are misleading or inconsistent with the broad, clinical experience with