OLD WISDOM NEW DISCOVERIES

July 21, 2009 (Brisbane, Australia) — The first study to evaluate the effects of a low-salt diet in patients with resistant hypertension has shown that this strategy reduced blood pressure far beyond expectations, suggesting that such patients are extremely sensitive to the BP-lowering effects of sodium reduction [1].

The findings indicate "that in patients with resistant hypertension, a low-salt diet may be more effective than increasing the number of antihypertensive medications," lead author Dr Eduardo Pimenta (Princess Alexandra Hospital, Brisbane, Australia) told heartwire . Pimenta and colleagues report the study in Hypertension.

As a result, patients with resistant hypertension should, if possible, be counselled by a dietician, Pimenta said, and "as 75% of sodium comes from prepared foods, restaurant meals, etc, public-health strategies are needed to reduce sodium content."

In an accompanying editorial commentary [2], Dr Lawrence J Appel (Johns Hopkins University, Baltimore, MD) congratulates Pimenta and coauthors on the implementation of a "challenging but informative and likely influential study" that demonstrated "striking" results. However, the study was small--with only 12 participants--and there was only one week per feeding period, so "replication of the study is clearly warranted," says Appel.

Nevertheless, the research indicates that a "renewed and aggressive emphasis on lifestyle modification, specifically sodium reduction, is warranted in patients with resistant hypertension and uncontrolled BP," he states.

Logistical Difficulties Overcome

Pimenta explains that resistant hypertension--defined as patients with uncontrolled BP despite taking three or more medications--is a common problem, affecting an estimated 20% to 30% of those with hypertension, and its prevalence is increasing.

The effects of reducing dietary sodium on mild-to-moderate hypertension are well documented, and have shown a small BP reduction with a low-salt diet, he adds. But according to Pimenta there have been no previous studies evaluating the role of dietary salt in those with resistant hypertension.

He and his colleagues conducted a two-period, randomized, crossover feeding study that compared two levels of sodium intake--250 mmol (5700 mg) per day versus 50 mmol (1150 mg) per day--in 12 patients with resistant hypertension referred to the University of Alabama Hypertension Clinic, where Pimenta was a postdoctoral research fellow. The aim was to determine the effects of dietary sodium restriction on office and 24-hour ambulatory BP, and each feeding period lasted one week.

At baseline, the participants–-half of whom were black and 67% of whom were female--had a mean body mass index of 32.9 kg/m² and a mean office BP of 145.8/83.9 mm Hg on an average of 3.4 antihypertensive medications.

In his commentary, Appel observes that "one cannot overestimate the logistical difficulties of recruiting interested and eligible participants, feeding them every meal over an extended period, and collecting a plethora of measurements."

Results Extend the Role of Sodium Reduction to Resistant Hypertension

Compared with the higher level of sodium intake, the lower level reduced mean office systolic BP by 22.7 mm Hg and office diastolic BP by 9.1 mm Hg. Reductions in daytime, nighttime, and 24-hour ambulatory BP were virtually identical to reductions in office BP.

Importantly, says Appel, "the extent of BP reduction vastly exceeds corresponding levels of BP reduction observed in [salt-reducing] trials of hypertensive individuals not on medication," for example, the participants with untreated hypertension in the Dietary Approaches to Stop Hypertension (DASH)-sodium study.

"In the context of other human research on dietary sodium intake and BP, which has focused almost exclusively on individuals who were on no or few antihypertensive medications, these results extend the role of sodium reduction to an important but understudied population," he states.

And he admits to being "surprised by the extent of the BP reduction," which he describes as "huge . . . roughly equivalent to adding two antihypertensive medications."

HCTZ Not the Best Choice of Diuretic for Resistant Hypertension

All of the participants were taking the diuretic hydrochlorothiazide (HCTZ), and both Appel and Pimenta say that in this setting, one might have expected an attenuated effect from dietary salt reduction, given that the patients were already on volume-reducing therapy.

But the pattern of findings suggests a volume-expanded state on conventional doses of HCTZ, indicating that the diuretic type and dose recommended by general hypertension guidelines "may not be as effective in patients with resistant hypertension [as in] mild-to-moderate hypertensives," Pimenta says.

He suggests that chlorthalidone, "which reduces BP more effectively and has a longer duration of action than HCTZ," should be used in resistant hypertension patients, and Appel concurs.

A Clear Target for Intervention

"Another remarkable, perhaps expected, finding was the high baseline sodium intake" of the participants, "measured when [they] were eating food that they prepared or selected," notes Appel. The mean 24-hour dietary sodium excretion at baseline--194.7 mmol (4470 mg) per day--was nearly double the recommended upper limit of daily sodium for the general population, and nearly triple the corresponding daily limit for people with hypertension, he observes.

"Although one might be discouraged by the excessive levels of sodium intake in this high-risk population, such levels also provide a clear opportunity for intervention," he stresses. But a "critical issue" is how to accomplish this. A combination of individual-based counselling (eg, from a dietician) and public-health strategies to reduce the sodium content of the food supply at a population level are needed, he believes.

"It will be impossible to reach an intake of 50 mmol per day without a major reduction in the sodium content of commercially prepared foods. Outside the arcane environment of the feeding study, a sodium intake of around 50 mmol per day is rare in the US," where, even with intensive behavioral counselling focusing exclusively on sodium reduction, mean achieved levels of sodium intake are typically about 100 mmol (2300 mg) per day, he observes.

In the meantime, doctors managing patients with resistant hypertension should use chlorthalidone rather than HCTZ, should reinforce key messages related to the reduction of dietary sodium intake, and should refer the patient, if possible, to a dietician. In addition, physicians need to "advocate for policy changes that lead to a reduced sodium content of commercially prepared foods," Appel concludes.