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.

Cognitive rehab shows promise for stroke patients

Medical Tribune September 2009 SFI
David Brill

A cognitive rehabilitation program used after traumatic brain injuries could also help stroke patients to overcome lingering attention deficits, a new study shows.

Stroke survivors who received Attention Process Training (APT) within 4 weeks were better able to concentrate on visual and auditory tasks 6 months later, New Zealand researchers reported in the journal Stroke.

It is the first study to test APT in an important but neglected area of stroke rehabilitation, the researchers say. Concentration problems are very common in stroke patients – affecting quality of life and contributing to poor functional outcomes – yet specific interventions remain largely unstudied.

Singapore stroke expert Dr. Nagaendran Kandiah, a consultant neurologist at the National Neuroscience Institute (NNI), said that APT could be a useful tool for local patients but that equivalent programs would need to be tailored to the language and culture. Researchers at the NNI are already “actively working on this”, he said.

Further research is also needed to better establish the local prevalence of post-stroke attention deficits, he added. Preliminary data from NNI suggest that about 15 to 20 percent of patients have cognitive difficulties, including poor attention, following a stroke.

“There is a significant amount of literature that shows that cognitive training is useful for post-stroke patients. The awareness that attention deficits and other cognitive deficits are common and can be potentially treated needs to be emphasized both to the public and medical community,” said Nagaendran.

The Stroke study researchers randomized 78 stroke patients to receive standard care alone or standard care plus up to 30 hours of APT (mean 13.5 hours). [2009 Jul 23; Epub ahead of print]

APT patients scored significantly better on the Integrated Visual Auditory Continuous Performance Test (IVA-CPT) Full-Scale Attention Quotient (FSAQ), at 5 weeks and 6 months after randomization. The test measures reaction times to auditory and visual stimuli, and can distinguish between genuine attention to the task and impulsive responding.

There were however no significant differences between the groups in other cognitive performance indicators, or broader outcome measures such as the Physical Component Score.

Lead author Dr. Suzanne Barker-Collo, a clinical psychologist and senior lecturer at the University of Auckland, said that she was disappointed that the intervention did not show benefit across other domains but was pleasantly surprised at the magnitude of effect on the primary outcome.

“We were expecting maybe half a standard deviation difference between the groups, and the effect we found was about four times that,” she said.

There are several cognitive rehabilitation packages available but very little evidence on how best to use them in stroke patients, added Barker-Collo, whose ongoing research seeks to better delineate the profile and time course of cognitive deficits after stroke. She is also reviewing the data from the present study to identify factors that could predict which patients will respond best to APT.

“I think cognition after stroke in general has been ignored to some degree,” she said. “A lot of rehabilitation time is spent on more physical tasks like walking, bathing and dressing – it’s very practical but very often the time spent on that means that not as much time is spent on other things like attention and memory, which are a bit less obvious but can still impact on other functional outcomes. Attention deficit in particular is a very, very common problem.”

Questions raised over vertebroplasty for osteo fractures

Medical Tribune September 2009 P12
David Brill

Vertebroplasty performs no better than a placebo procedure for treating painful osteoporotic fractures, two major new studies have found.

Despite its widespread usage and recommendation in guidelines, vertebroplasty did not relieve pain, alleviate disability or improve quality of life compared to sham interventions, US and Australian researchers reported.

The studies are the first true randomized controlled trials to assess a procedure which has become a firmly established treatment for osteoporotic fractures. The number of vertebroplasties performed in the US, for example, almost doubled from 2001 to 2005. [JAMA 2007 Oct 17;298(15):1760-2]

The jury is still out as to how the findings will influence practice, according to an orthopedics expert whose editorial accompanies the papers in the New England Journal of Medicine. [2009 Aug 6;361(6):619-21]

“Although the trials by Kallmes et al. and Buchbinder et al. provide the best available scientific evidence for an informed choice, it remains to be seen whether there will be a paradigm shift in the treatment of vertebral compression fractures with vertebroplasty or similar procedures,” wrote Dr. James Weinstein, chair of the department of orthopedic surgery at Dartmouth-Hitchcock Medical Center, US.

Given the rise in the number of vertebroplasties and the questionable risk-benefit ratio, it is now essential that patients be well informed about the procedure, added Weinstein.

“When faced with several choices for which the evidence is less than clear, patients and doctors must thoroughly review the options together. Informed choice helps to educate patients about treatment options and allows them to recognize that a decision can be based on their values and preferences,” he wrote.

The larger of the two trials, led by Dr. David Kallmes of the Mayo Clinic, Rochester, US, followed 131 patients with osteoporotic vertebral compression fractures. They received either vertebroplasty or a simulation procedure in which cement was not injected into vertebrae. [N Engl J Med 2009;361:569-79.]

At 1 month there was no difference between groups on a pain scale ranking intensity from 0 to 10 (difference 0.7; 95% CI -0.3 to 1.7; P=0.19) or on the Roland-Morris Disability Questionnaire (difference 0.7; 95% CI -1.3 to 2.8; P=0.49). There was however a non-significant trend for more patients in the vertebroplasty group to report clinically meaningful improvements in pain (64 percent versus 48 percent; P=0.06).

Patients were subsequently allowed to cross over and receive the other intervention – still unaware of which they had already received. At 3 months, this option had been taken up by more control patients than vertebroplasty patients (43 percent versus 12 percent), but all patients who crossed over reported comparable or worse outcomes than those who received only the first intervention.

The second trial, led by Dr. Rachelle Buchbinder of Monash University, Australia, reported 6-month follow-up of 35 vertebroplasties and 36 placebo interventions. [N Engl J Med 2009 Aug 6;361(6):557-68]

Both interventions did relieve pain but to a comparable extent: at 3 months, the mean reductions (also measured on a 10-point scale) were 2.6 in the vertebroplasty group and 1.9 in the control group (adjusted between-group difference 0.6; 95% CI -0.7 to 1.8). This difference was also not significant at 1 week or 1 or 6 months; nor was there anything nothing to choose between groups on a range of secondary outcomes, including physical functioning and quality of life.

“It has been argued that performing a randomized, placebo-controlled trial of vertebroplasty is unnecessary and unethical in view of the published results of numerous studies that suggest a benefit of vertebroplasty. Our results show – not for the first time – the hazards of relying on the results of uncontrolled or poorly controlled studies to assess treatment efficacy,” the authors wrote.

Bacteria eradication holds hope for stomach cancer prevention

Medical Tribune September 2009 P14

David Brill

A new study has renewed hopes for reducing the incidence of gastric cancer – a leading cause of death worldwide and a particular burden for Asia.

The link between Helicobacter pylori infection and gastric cancer is well known, but Italian researchers now provide some of the strongest evidence yet that eradicating the bacteria can actually reduce cancer risk.

In a meta-analysis of data from 6,695 participants, they report that H. pylori eradication reduced the relative risk of gastric cancer to 0.65 (95 percent CI 0.43 – 0.98) over up to 10 years of follow-up. [Ann Intern Med 2009;151:121-8]

The findings lend support to a recent Asia-Pacific consensus statement calling for H. pylori screening and eradication in high-risk populations.

Japan and China have the world’s highest rates of gastric cancer, with age-standardized incidences of 62.1 and 41.4, respectively, per 100,000 males and 26.1 and 19.2 per 100,000 females. [CA Cancer J Clin 2005;55:74-108]

Dr. Lorenzo Fuccio, lead author of the meta-analysis, stressed that the cancer risk reduction with H. pylori eradication was only marginally significant, but could prove vital in countries such as these.

“Even a small reduction in risk and incidence achieved with H. pylori treatment will probably give a huge advantage in terms of social health, especially in high-risk areas,” said Fuccio, of the department of internal medicine and gastroenterology at the University of Bologna, Italy.

“Furthermore, H. pylori eradication provides several other benefits: it reduces the risk of peptic ulcer development, it can resolve dyspeptic symptoms and it can resolve gastritis. Once H. pylori is detected, especially in high-risk areas, eradication is always advisable.”

Asia-Pacific experts released their consensus statement on gastric cancer prevention last year, concluding that “there is a definite causal link between H. pylori infection and gastric cancer, and it has come time to try and intervene to prevent this cancer at the population level.” [J Gastroenterol Hepatol 2008;23:351-65]

Lead author Professor Fock Kwong Ming said that H. pylori screening and treatment should be a complement to, not a replacement for, existing cancer surveillance strategies in high-risk countries.

Research is still ongoing to establish exactly who to screen in intermediate-risk countries such as Singapore and Malaysia, said Fock, a senior consultant gastroenterologist at Changi General Hospital (CGH), Singapore. The highest-risk group in Singapore appears to be Chinese males aged 45 to 50, he said.

Previous work showed that gastric cancer risk correlated with H. pylori infection in Chinese and Malay individuals but not Indians. Gastric cancer rates are known to be lower in the latter two groups. [J Gastroenterol Hepatol 2005 Oct;20(10):1603-9]

Two studies are currently underway in Singapore to identify risk factors for gastric cancer development.

The first – a 5-year, S$25 million project conducted across several institutions in the Singapore Gastric Cancer Consortium – will correlate endoscopy and biopsy findings to gastric cancer outcomes, with a view to understanding how cancer develops and improving early detection rates. The second study takes place at CGH, and involves narrow-band endoscopy – a more specialized technique which may be better able to detect precancerous lesions.

Fuccio noted that randomized, multicenter trials are needed to fully understand the impact of H. pylori eradication on cancer prevention, but that such studies would present considerable ethical, logistical and financial challenges. Achieving statistical power would require thousands of participants and decades of follow-up, he said.

He added that gastric cancer results from a complex combination of genetic and environmental factors, and that eradicating H. pylori does not completely abolish risk.

H. pylori eradication is typically achieved using two antibiotics combined with a proton-pump inhibitor.

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.

Sunken treasure

Medical Tribune September 2009 P18
David Brill

If Subic Bay seems unremarkable you may be looking in the wrong place. David Brill finds that attraction lies beneath the surface.

Looking out over Subic Bay, you could be forgiven for thinking you’d booked the wrong trip. Tankers float out at sea, cranes loom over the shoreline, and litter washes up at your feet. Far from the glorious beaches of Boracay or Palawan, Subic does not at first glance appear an obvious destination for visitors to the Philippines.

A look below the water, however, tells a different story. An entire fleet of shipwrecks sits silently at the bottom of the sea, oblivious to the trivial goings-on at the surface. Anemones sprout on deck, while lionfish lurk in twisted metal crannies below. Barracudas swim down gun turrets, emerging in ghostly loading chambers long disused and overgrown with rust. Subic is a sunken goldmine – entry only for those with a diving license.

Back on land, Subic Bay was home to a US naval base until forces withdrew in 1992. The area of the base remains enclosed as the Subic Bay Freeport Zone – the shipyards making way for hotels, restaurants and casinos. International access is via Clark airport, some 2 hours drive southeast of Subic, or from Manila, a further 3 or so hours south of Clark, depending on traffic.

Some of Subic’s shipwrecks date back to the Spanish-American war of 1898, but the majority sank during the years of World War II. Twenty-five ships from Japan alone are claimed to have gone down during the war but with salvage operations undertaken in the 1950s, no one is quite sure how many wrecks remain in the bay. Best guesses suggest that there are some 20 wrecks in still waters – 10 or so of which are suitable for recreational diving.

The main attraction at Subic Bay is the USS New York. Launched in 1891, she played a key role in the Spanish-American war before returning to action in World War I as the USS Saratoga. She was eventually decommissioned in the Philippines in the 1930s and remained moored at Subic Bay until 1941, when she was deliberately scuttled by retreating US forces to prevent her from falling into the hands of the Japanese.

The navy’s loss proved to be scuba divers’ gain, as the 120-meter-long USS New York came to rest on its side with its topmost point just 17 meters from the surface. This depth leaves the top of the wreck accessible for novice divers, with the inside and lower decks offering a variety of options for those seeking more challenging, technical dives. The engine rooms lie at the very bottom of the ship and remain largely unexplored.

Visibility was mediocre during a trip in late July but the wreck is eerily impressive nonetheless. Its sheer, hulking size is enough to leave you feeling insignificant by comparison, while the sight of its three giant gun barrels emerging ominously from the gloom offers another reminder of the vast power the ship once wielded. A variety of wildlife circulates the site: dive instructors list barracuda, rays, octopi, lobsters and spotted sweetlips among the wreck’s inhabitants, although not all were seen on our trip.

Other wrecks at Subic Bay include El Capitan, a shallow site which is easily accessible for all comers. Even fairly novice divers can swim through the hold, and poke their head up into a pocket of trapped, ancient air (attempting to breathe it is strongly not advised). Also of note is the infamous Oryoku Maru – a Japanese cruise liner used for transportation of prisoners of war from Manila to Japan. Later dubbed ‘The Hell Ship’ for the nightmarish conditions in which prisoners were kept, she was bombed and sunk at Subic by US navy planes in 1944. Several other vessels are accessible – including a largely intact Japanese patrol boat – along with various sites of debris, scattered metal, and even a few coral reefs.

Beyond the diving, a few activities are available at Subic, including horse riding, watersports, go-karting and, of course, gambling. Much of the area, however, feels run-down and seedy, and considerable regeneration will likely be needed if tourists are to come in large numbers. In the meantime, however, Subic offers an enjoyable and convenient weekend for divers, especially given the proximity of the wrecks to the shore and the relative ease of transport from abroad. Don’t be fooled by the cranes and tankers – Subic Bay is to be judged on what lies below.

Fears allayed over menopausal memory loss

Medical Tribune August 2009 P8

David Brill

Women who experience memory loss as they approach the menopause can be reassured that the problem is only temporary, say US researchers.

In a recent study of over 2,000 women, they found that verbal memory and processing speed appear to drop during perimenopause, but typically return to normal upon reaching postmenopause.

The findings confirm a problem which is reported by up to 60 percent of women but has been addressed by very few quantitative studies, say the authors. [Neurology 2009;72:1850-7]

Lead author of the Study of Women’s Health Across the Nation (SWAN) report, Dr. Gail Greendale, said that physicians can now use the findings to reassure concerned women and “validate their experience.”

“Women who are experiencing memory difficulties during the menopause transition often find this experience frightening. They do not know what to expect and worry that their memory will worsen over time,” said Greendale, of the David Geffen School of Medicine at the University of California, Los Angeles, US.

“The SWAN results provide women with a frame of reference … and show that the memory problems are temporary. Also, if women are having memory problems of a greater degree than that which we observed, then their physician should not ascribe the problem to menopause and should dig deeper,” she said.

The SWAN study involved 2,362 women with a mean age of 45.9. They were classified as premenopausal, perimenopausal or postmenopausal, and followed for 4 years with regular testing in domains of processing speed, verbal memory and working memory.

The decline in cognition over the menopause transition was particularly marked for processing speed: pre- and postmenopausal women showed significant improvements with repeated testing, whereas late perimenopausal women scored worse over time. A similar effect was seen for verbal memory, but there was no difference in working memory between groups.

The paper also points to cognitive benefits of early initiation of hormone therapy: women who had already begun therapy before their final menstruation scored 4 to 6 percent higher on tests than those with no prior therapy.

Estrogen has a range of effects on the brain and is thought to influence mood, higher cognitive function and motor skills. Estrogen receptor density is particularly high in the prefrontal cortex and hippocampus – hence it has been postulated that the fluctuation in estrogen levels during perimenopause could adversely influence brain function. [J Appl Physiol 2001;91:2785-801]

Only two previous longitudinal studies however have measured cognitive performance over the menopause transition, according to Greendale and colleagues. The more recent of the two, a study of 694 women from a rural community in Taiwan, found that verbal memory declined during the menopause transition. The other study found no cognitive effects of the transition on working memory or perceptual speed. [Maturitas 2006;53:447-53; Neurology 2003;61:801-6]