Analysis of
 Recent Papers in Hypertension

Abstract

Lifestyle modification continues to be an important initial strategy in both the prevention and treatment of hypertension as recommended in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). Clinical trials have documented that weight loss, sodium restriction, alcohol restriction, and increasing physical activity may help prevent, as well as treat, hypertension. While the effects of dietary macronutrients on blood pressure (BP) have not been as well studied, the most effective dietary approach to lowering BP involves a diet rich in fruits, vegetables, and lowfat dairy products, i.e., the Dietary Approaches to Stop Hypertension (DASH) diet. The DASH diet involves a modest increase in dietary animal and vegetable protein. Other clinical trials studying dietary protein intake and reduction in BP have produced conflicting results. He and colleagues conducted a randomized, double-blind, multicenter, controlled trial of a diet rich in soybean protein compared to a complex carbohydrate control diet in 302 adult Chinese subjects with stage 1 hypertension (systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or both) or prehypertension (systolic BP 120 mm Hg-139 mm Hg; diastolic BP 80 mm Hg-89 mm Hg) from three communities in the People's Republic of China. Demographic and dietary characteristics were similar in the three communities and were made up of men and women 35–64 years of age. Trial participants had not been on any antihypertensive medication for at least 2 months and had no underlying cardiovascular or renal disease or diabetes. Of interest, they had restricted their alcohol use to no more than 21 drinks per week. Subjects were randomized to 12 weeks of supplementation with 40 g/d of isolated soybean protein or 40 g of complex carbohydrate from wheat, both given in the form of cookies. The daily nutritional content of the cookies was similar except for their dietary protein content (49 g vs. 12.9 g) and carbohydrate content (64.8 g vs. 95.3 g), soybean and control groups, respectively. The daily portion of the soybean protein cookies contained 76.4 mg of total isoflavone. On entry, average systolic BP was between 130-159 mm Hg (mean 135 mm Hg) and average diastolic BP was between 80-99 mm Hg (mean 84.7 mm Hg) based on an average of nine readings (three observations at each of three screening visits). BP readings were obtained at follow-up visits 6 and 12 weeks after randomization. Trained research staff conducted a 24-hour dietary recall at the screening visit, the 6-week visit, and the 12-week visit. A 24-hour urine specimen was obtained at the same time periods to measure urinary sodium and potassium. Side effects (15 items) were evaluated using a standard questionnaire at the 12-week follow-up visit. The primary outcome was the net difference in change (final follow-up - baseline) of systolic and diastolic BP between the study groups. After 12 weeks, approximately 90% of both study groups completed the study and 92% of both groups adhered to their dietary intervention. Urinary excretion of sodium decreased and urinary excretion of potassium increased to a similar extent in both groups with no significant differences in body weight. There was a significant reduction in both systolic (−4.3 mm Hg) and diastolic (−2.76 mm Hg) BP in subjects on the soy protein supplement. Differences between the treatment groups were greater among subjects with hypertension (−7.88 mm Hg systolic and −5.27 mm Hg diastolic) than among people with prehypertension (−2.34 mm Hg systolic and −1.28 mm Hg diastolic). Favorable effects on BP reduction occurred in both men and women, in younger and older subjects, as well as in obese and nonobese individuals. Rates of adverse effects did not differ between the groups. In this short-term, 12-week study, increased intake of vegetable protein, in the form of soybean supplementation, resulted in reductions in both systolic and diastolic BP. Whether this favorable effect on BP is due to the vegetable protein or isoflavone content in soybeans remains unclear.—He J, Gu D, Wu X, et al. Effect of soybean protein on blood pressure: a randomized, controlled trial. Ann Intern Med. 2005;143:l-9. While observational studies have suggested that soybean protein supplementation lowers BP, several small clinical trials have previously reported inconsistent findings. Most clinical trials that have evaluated the effects of an increased intake of dietary protein on BP have had a small sample size, did not systematically evaluate BP, and did not use changes in BP as the primary outcome of interest. The present study, with the largest sample size and several well-executed measurements of BP, suggests that soybean supplementation reduces both systolic and diastolic BP. This effect was consistent regardless of gender, age, and body weight. The effect noted was greatest in people with hypertension, with less of an effect in prehypertensive individuals. While not powered to evaluate subgroups, this study suggests that soybean protein supplementation is more important for treating hypertension than for preventing it. This was not a forced feeding study like the DASH trial. By using 24-hour dietary recall, the authors found that subjects increased their dietary protein intake by only 26 g, less than the targeted 40 g. It also remains unclear whether the favorable effect on BP reduction is due to soybean protein or isoflavone content: this needs to be evaluated in future trials. In addition, since there has been an association between soy protein and bladder cancer in two cohort studies, this association needs further clarification before we can promote this recommendation. Further research is necessary to determine the mechanistic benefits of soybean protein supplementation on BP reduction. Proposed mechanisms include the vasodilatory protein components of soybean; the soybean associated dietary increase in arginine, the metabolic precursor of NO; or an improvement in insulin sensitivity. Although recommended as first-line therapy in the treatment of hypertension, physicians have remained pessimistic over the ability of lifestyle modification, including nutritional intervention, to effectively prevent as well as treat hypertension. The current findings suggest that increasing consumption of soybean protein may be useful in treating hypertension. As dietary protein in China is mainly derived from plant foods (not from animal foods as in the United States) and with the average dietary protein intake of 69 g/d in this Chinese study (whereas the average dietary protein intake in the United States is 79 g/d [National Health and Nutrition Examination Survey (NHANES III)]), the authors appropriately wonder whether their study findings can directly apply to the US population. Before we recommend increased soybean protein intake as a means of treating and preventing hypertension, further evidence of safety, feasibility, and efficacy in this country is required. At present, we should continue to recommend the DASH diet, providing an increased amount of both animal and vegetable protein in our diet. Ginseng is a commonly used herbal supplement that grows in the temperate regions of Asia and North America. Currently, about 4.5% of Americans use it. Like many supplements, the safety and efficacy of ginseng is not well studied in individuals with hypertension. Ginseng's exact mechanism of action is unknown. Previous reports have suggested that ginseng may increase blood pressure (BP), while other reports have shown a neutral effect. The ginseng currently used is often a blend of several species of ginseng, which vary in their ginsenoside content, the component believed to be responsible for its effect on blood pressure. The two most consumed species in the United States are Panax ginseng and Panax quinquefolius, also known as North American ginseng (NAG). In the current clinical trial, Canadian investigators examined the acute effects of NAG on BP in individuals with hypertension. Nineteen individuals, aged 18-75 years, with hypertension (defined as systolic BP >140 mm Hg or diastolic BP >90 mm Hg) at each of three separate prestudy visits or on antihypertensive medications provided informed consent. Exclusion criteria included secondary hypertension, diabetes mellitus, kidney or liver disease, unstable angina, change in body weight of >2.2 kg between visits, or use of any herbal supplements in the previous 2 months or during the study. Sixteen participants (12 men and 4 women, mean age of 61 years, with a mean BP 132/83 mm Hg) completed the study. Thirteen of the 16 individuals were on antihypertensive therapy on entry. Each participant, serving as their own control, was randomized in a double-blind fashion to six different batches of 3-mg NAG and two identical 3-mg corn starch placebo tablets. The batches of NAG were selected by the Ontario Ginseng Growers Association to represent the spectrum of NAG available on the market; they were carefully examined for quality. Each NAG root batch (or placebo) was ground into a powder and packed into identical capsules by a technician blinded to study allocation. On eight consecutive mornings, participants arrived at the study center in a fasting state, did not take their prescribed antihypertensive medications, and were fitted with an ambulatory BP monitor. Office and ambulatory BP readings (5-minute intervals for 30 minutes using SpaceLabs 90207, SpaceLabs Medical, Inc., Issaquah, Washington) were taken at baseline and 60 minutes after administration of study medication (corresponding to peak plasma concentrations of NAG). For each batch of NAG and placebo, the post-treatment change in systolic BP, diastolic BP, and pulse pressure per individual relative to baseline were calculated at 10-minute intervals and averaged. In addition, each batch of NAG had its ginsenoside content determined by high-performance liquid chromatography. All six NAG samples showed a comparable content of ginsenosides. No significant differences in mean systolic BP, diastolic BP, or pulse pressure at each of the 10-minute intervals or over the entire 160-minute post-treatment period were seen between the six individual NAG and placebo treatments. Taken together, and compared with placebo, the NAG treatments increased systolic and diastolic BP slightly at 140 and 160 minutes, respectively, but decreased diastolic BP slightly at 100 minutes. Overall, there was no significant difference between the average of the NAG batches and placebo on total post-treatment change in systolic BP, diastolic BP, and pulse pressure. The authors conclude that NAG exerts a neutral acute effect on BP in hypertensive individuals.—Stavro PM, Woo M, Heim TF, et al. North American ginseng exerts a neutral effect on blood pressure in individuals with hypertension. Hypertension. 2005;46:406-411. Roughly one third of adults use neutraceuticals, and 15 million Americans use them together with conventional medicines. Their use is of tremendous importance to the hypertension community. A recent prevalence study from the Mayo Clinic found that 61% of people 18 years of age and older had used a neutraceutical over the past year. These “dietary supplements,” defined as a vitamin, mineral, herb, or other botanical, are excluded from the rigorous scientific evaluation that ensures both the safety and the effectiveness required of “drugs” presented before the FDA. These products are often promoted and accepted by the public to positively affect one's health, despite their lack of certainty for benefit. With sales of neutraceutical products increasing 25% per year in the United States, their influence on BP control continues to be of great importance. Nine million American adults use ginseng, and it continues to be popular among patients with hypertension. In many cases, its safety and efficacy is undocumented. One concern has been a lack of standardization of available preparations. In this evaluation, Canadian investigators working with the Ontario Ginseng Growers Association took great trouble to ensure that they were using a sample that represented the spectrum of what is currently available on the market. Even so, the study is limited to only one type of commonly used ginseng root, NAG. The other ginseng root commonly used, Panax ginseng, was not used in this trial, but a previous investigation by the same investigators demonstrated that in steamed form, Panax ginseng caused a modest decline in BP with acute administration. The authors postulate that perhaps the disparate effects on BP between the two species may be due to the presence of ginosenoside Rg3, which is found in Panax ginseng but not in NAG. As opposed to regulated prescription medications, the safety and efficacy of one formulation of an herbal supplement should not necessarily be extrapolated to other formulations that may vary considerably in active ingredient content. While this well-designed, clinical trial using ambulatory BP monitoring describes the acute effects of ginseng on BP, it is limited by its small sample size, low dosage used, lack of concomitant antihypertensive medication administration, and sole focus on the acute BP changes associated with a single dose of ginseng. While the available evidence suggests that patients with hypertension need not avoid either NAG or Panax ginseng due to concerns about acute BP elevation, further investigations will determine its safety and efficacy with chronic administration in hypertensive patients. At present, ginseng should not be recommended for individuals with hypertension.