Low-salt diet offers key to treating stubborn high blood pressure

Medical Tribune September 2009 P9

David Brill

Cutting down on salt can dramatically lower blood pressure (BP) in patients with resistant hypertension and could offer a genuine alternative to ramping up medications, a study suggests.

American researchers found that BP dropped by 22.7/9.1 mmHg after a week of a low-salt diet compared to a high-salt diet – a magnitude roughly equivalent to adding two more drugs.

This drop came on a background of heavy medication: patients in the study were already taking an average of 3.4 antihypertensive drugs per day.

Although small – just 12 patients took part – the study has been greeted enthusiastically by experts, who are calling for a renewed focus on salt reduction for patients whose BP remains uncontrolled.

Leading hypertension expert Dr. Lawrence Appel described the results as “striking,” particularly given that all study patients were taking hydrochlorothiazide. This volume-reducing therapy might have been expected to attenuate the effects of a low-salt diet, he wrote in an accompanying editorial. [Hypertension 2009 Jul 20; Epub ahead of print]

“The data presented … strongly suggest that persons with resistant hypertension are extremely sensitive to the BP-lowering effects of sodium reduction. The observed reductions in BP were huge – roughly equivalent to adding 2 antihypertensive medications,” wrote Appel, a Professor of Medicine at Johns Hopkins University, Baltimore, US.

“Although clinicians commonly focus on the next drug (e.g. aldosterone blocking therapy) and sometimes a device (e.g. Rheos systems that stimulate carotid baroreceptors), a renewed and aggressive emphasis on lifestyle modification, specifically sodium reduction, is warranted in patients with resistant hypertension and uncontrolled BP.”

Dr. Low Lip Ping, chairman emeritus of the Singapore Heart Foundation and founding president of the Singapore Hypertension Society, said: “This small but interesting study showed that among patients with medication-resistant hypertension, salt restriction has a substantial impact on lowering blood pressure by reducing intravascular fluid retention and improving vascular function.”

“Dietary salt restriction, ideally to less than 100 mEq of sodium/24 hours, should be recommended for all patients with resistant hypertension. With a low-salt diet these patients could have their blood pressure controlled with fewer medications,” said Low, also a private practitioner at the Low Cardiology Clinic, Mount Elizabeth Medical Center.

The study is the first to demonstrate that the benefits of salt reduction extend beyond patients with just mild or moderate hypertension, according to lead author Dr. Eduardo Pimenta.

“A low-salt diet is beneficial for all patients with hypertension but in patients with resistant hypertension the effect is stronger. Before prescribing another antihypertensive medication, doctors should spend more time with their patients explaining about low-salt diets and, if possible, refer the patient to a nutritionist,” said Pimenta, now a clinical research fellow at the Endocrine Hypertension Research Center, University of Queensland School of Medicine, Brisbane, Australia. The study itself was undertaken at the University of Alabama at Birmingham, US.

Study subjects had a mean office BP of 145.8/83.9 mmHg at baseline. All were randomized to either a high- or low-salt diet for 1 week, then a 2-week washout period, followed by a final week of the opposite diet. The low- and high-salt diets provided 50 and 250 mmol of sodium per day, respectively. [Hypertension 2009 Jul 20; Epub ahead of print]

All measures of BP were reduced by the low-salt diet as compared to the high-salt diet: systolic and diastolic; office and ambulatory; and daytime, nighttime and 24-hour.

The Singapore Heart Foundation and Hypertension Society have already been promoting the message about salt reduction – especially in light of National Nutrition Survey data suggesting that nine out of 10 Singaporeans exceed the recommended sodium intake of 2,000 mg/day.

In a joint statement to mark World Hypertension Day in May this year, the societies urged “all residents in Singapore to reduce their salt intake to reduce their risk of hypertension and hypertension-related diseases.” They also called on chefs and restaurants to lower the salt content of foods, and to avoid routinely providing soy sauce unless requested by the customer.

No benefit to excessive BP lowering, study says

Medical Tribune September 2009 P14
David Brill

Lower is not necessarily better when it comes to blood pressure (BP), a recent systematic review has found.

The analysis of seven randomized trials concluded that there was no clinical benefit to lowering BP beyond a currently recommended target of 140/90 to 160/100 mmHg.

Patients treated to lower targets did achieve significantly lower BPs (-4/-3 mmHg), but there were no differences in total mortality, major cardiovascular events, myocardial infarction or stroke rates compared to those treated to standard targets.

The review included data from a total of 22,089 patients, who had taken part in trials targeting various different diastolic BPs below 85 mmHg. No suitable trials of low systolic BP targets were identified. [Cochrane Database Syst Rev 2009;(3):CD004349]

“At present there is no evidence from randomized trials to support aiming for a BP target lower than 140/90 in the general population of patients with elevated blood pressure,” said lead author Dr. Jose Arguedas, of the University of Costa Rica, Costa Rica.

“Our research included patients with diabetes or chronic renal disease, and the evidence was slightly less robust for those subgroups of patients. We intend to carry out separate systematic reviews for those subgroups, especially because guidelines recommend even lower blood pressure targets for them,” he added.

There were also no significant differences in the incidence of congestive heart failure (relative risk [RR] 0.88, 95% CI 0.59 – 1.32) and end-stage renal disease (RR 1.01, 95% CI 0.81 – 1.27) between patients treated to low, as compared to standard, targets.

The full picture remains unclear with regard to safety, the authors note, since six of the seven trials did not provide complete information on serious adverse events and withdrawals.

Excessive BP lowering could cause unnecessary cost and inconvenience to patients, as well exposing them to a potential increased risk of adverse events if the number of antihypertensive medications is increased, they add.

Hypertension study named ‘Trial of the Year’

Medical Tribune July 2009 P9

David Brill

The Hypertension in the Very Elderly Trial (HYVET) has been named as 2008’s Trial of the Year, reflecting its potential to change healthcare and “improve the lot of mankind.”

The study found that antihypertensive treatment reduced the risk of cardiovascular events, death from stroke, and death from any cause in over-80s.

The largest clinical trial of its kind, HYVET was carried out against a backdrop of uncertainty about the benefits of blood pressure (BP) lowering in the very elderly.

The award was bestowed recently by the Society for Clinical Trials (SCT) and Project ImpACT (Important Achievements of Clinical Trials). HYVET was also voted Medscape’s most important clinical trial of the year, and named in the American Heart Association’s top 10 advances in stroke and heart disease research for 2008.

“The results of HYVET will have important implications for the generation of future guidelines and mean that very elderly individuals with sustained systolic BPs of 160 mmHg or more should now be appropriately assessed and treated in accordance with these findings,” said trial coordinator Dr. Nigel Beckett, from the Care of the Elderly group at Imperial College London, UK.

Dr. Deepak Bhatt, director of the Integrated Interventional Cardiovascular Program at Brigham and Women’s Hospital, US, added: “HYVET is a landmark study that challenges current paradigms which question the risk to benefit of treating hypertension in patients older than 80 years of age. The results of this study should encourage practitioners to treat elevated systolic BP in the very elderly.”

HYVET involved 3,845 patients from 13 centers in Europe, China, Tunisia and Australasia, who had a sustained systolic BP of 160mmHg or more. They were randomized to placebo or sustained release indapamide (1.5 mg), with perindopril (2 or 4mg) to be added if the BP target of 150/80 mmHg could not be reached. [N Engl J Med 2008 May 1;358(18):1887-98]

After a median of 1.8 years of follow-up, treatment reduced the risk of death from stroke by 39 percent (unadjusted hazard ratio [HR] 0.61; P=0.046), death from any cause by 21 percent (unadjusted HR 0.79; P=0.02), risk of any cardiovascular event by 34 percent (unadjusted HR 0.66; P<0.001)>

There were also non-significant risk reductions for outcomes of any stroke (unadjusted HR 0.70; P=0.06) and death from cardiovascular cause (unadjusted HR 0.77; P=0.06) in the treatment group.

The SCT / Project ImpACT awards are given to trials which are deemed, among other criteria, to “have improved the lot of mankind,” and “provided the basis for a substantial, beneficial change in health care.”

Office BP not prognostic for resistant hypertension

Medical Tribune January 2009 P16
David Brill

Office-based blood pressure (BP) measurements offer “no prognostic value” for patients with resistant hypertension, a recent study has concluded.


Ambulatory BPs – both systolic and diastolic – were predictors of future cardiovascular morbidity and mortality whereas neither measurement was a significant indicator when recorded in the office, the researchers found.

The study, which followed up 556 outpatients for a median of 4.8 years, also showed that nighttime ambulatory BP was superior to daytime as a prognostic indicator, suggesting that these time periods should be analyzed seperately to give the best assessment of a patient’s cardiovascular risk.

It is only the second prospective study to assess the different BP monitoring strategies in resistant hypertensive patients, according to the researchers, who are based at the Federal University of Rio de Janeiro, Brazil. They note that the superiority of ambulatory BP “is not generally accepted,” despite several studies showing that it offers better cardiovascular risk prediction than office BP in various other patient populations. [Arch Intern Med 2008 Nov 24;168(21):2340-6]

Dr. Chai Ping, a Singapore-based specialist, said that the study should encourage physicians to use ambulatory BP more often for patients with resistant hypertension.

“In the initial evaluation of a patient with elevated office BP despite three or more medications, ambulatory BP monitoring should be performed to confirm that the BP is truly elevated and not a ‘white-coat’ effect,” he said.

“This paper also tells us that suboptimal BP control, as has been known for more than 4 decades now, confers a worse prognosis for hypertensive patients, so every effort must be made to control BP to the targets as recommended by current clinical practice guidelines,” added Chai, who is clinical director of the noninvasive cardiac laboratory at the National University Heart Centre Singapore (NUHCS).

The patients included in the study met standard criteria for resistant hypertension. The mean hypertension duration at enrollment was 18 years. Some patients were followed up for as long as 9 years.

A total of 109 patients (19.6 percent) reached the study’s primary endpoint – a composite of fatal and non-fatal cardiovascular events.

Patients with a one standard deviation increase in nighttime systolic BP at baseline had a 38 percent increased risk of reaching this endpoint following multivariate adjustment (hazard ratio [HR] 1.38), while an equivalent increase in nighttime diastolic BP yielded a 36 percent increase in risk (adjusted HR 1.36; P<0.05 for both).

The only significant predictor of death was a so-called “true” diagnosis of resistant hypertension, based on ambulatory BP monitoring rather than office-based measurement. This diagnosis was associated with a twofold increase in the risk of all-cause mortality (adjusted HR 2.00; P<0.05).

Chai estimates that up to a quarter of patients being followed up at the NUHCS have resistant hypertension. He said that he presently uses both forms of BP measurement but noted that not all hypertensive patients require ambulatory BP monitoring.

The results of the study cannot be generalized to all patients with hypertension, he added.