Frans J. Kok

Influence of Weight Reduction on Blood Pressure A Meta-Analysis of Randomized Controlled Trials

Abstract—Increased body weight is a strong risk factor for hypertension. A meta-analysis of randomized controlled trials was performed to estimate the effect of weight reduction on blood pressure overall and in population subgroups. Twenty-five randomized, controlled trials (comprising 34 strata) published between 1966 and 2002 with a total of 4874 participants were included. A random-effects model was used to account for heterogeneity among trials. A net weight reduction of −5.1 kg (95% confidence interval [CI], −6.03 to −4.25) by means of energy restriction, increased physical activity, or both reduced systolic blood pressure by −4.44 mm Hg (95% CI, −5.93 to −2.95) and diastolic blood pressure by −3.57 mm Hg (95% CI, −4.88 to −2.25). Blood pressure reductions were −1.05 mm Hg (95% CI, −1.43 to −0.66) systolic and −0.92 mm Hg (95% CI, −1.28 to −0.55) diastolic when expressed per kilogram of weight loss. As expected, significantly larger blood pressure reductions were observed in populations with an average weight loss >5 kg than in populations with less weight loss, both for systolic (−6.63 mm Hg [95% CI, −8.43 to −4.82] vs −2.70 mm Hg [95% CI, −4.59 to −0.81]) and diastolic (−5.12 mm Hg [95% CI, −6.48 to −3.75] vs −2.01 mm Hg [95% CI, −3.47 to −0.54]) blood pressure. The effect on diastolic blood pressure was significantly larger in populations taking antihypertensive drugs than in untreated populations (−5.31 mm Hg [95% CI, −6.64 to −3.99] vs −2.91 mm Hg [95% CI, −3.66 to −2.16]). This meta-analysis clearly shows that weight loss is important for the prevention and treatment of hypertension.

Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials

Objective The antihypertensive effect of fish oil was estimated from randomized trials using metaregression analysis. Modification of the blood pressure (BP) effect by age, gender, blood pressure, and body mass index was examined. Methods A total of 90 randomized trials of fish oil and BP were identified through MEDLINE (1966–March 2001). Trials with co-interventions, patient populations, non-placebo controls, or duration of < 2 weeks were excluded. A total of 36 trials (50 strata) were included, 22 of which had a double-blind design. Original reports were retrieved for data collection on sample size, study design, duration, fish oil dose, BP changes and baseline characteristics of trial populations. Pooled BP estimates were obtained by metaregression analysis, weighted for trial sample sizes. Stratified analyses according to population characteristics were performed. Results Intake of fish oil was high in most trials (median dose: 3.7 g/day). Fish oil reduced systolic BP by 2.1 mmHg [95% confidence interval (CI): 1.0, 3.2;P < 0.01] and diastolic BP by 1.6 mmHg (95% CI: 1.0. 2.2;P < 0.01). Restricting the analysis to double-blind trials yielded BP reductions of 1.7 mmHg (95% CI: 0.3, 3.1) and 1.5 mmHg (95% CI: 0.6, 2.3), respectively. BP effects tended to be larger in populations that were older (> 45 years) and in hypertensive populations (BP ⩾ 140/90 mmHg). Conclusions High intake of fish oil may lower BP, especially in older and hypertensive subjects. The antihypertensive effect of lower doses of fish oil (< 0.5 g/day) however, remains to be established.

Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised double blind, controlled trial

BACKGROUND Low folate and raised homocysteine concentrations in blood are associated with poor cognitive performance in the general population. As part of the FACIT trial to assess the effect of folic acid on markers of atherosclerosis in men and women aged 50-70 years with raised plasma total homocysteine and normal serum vitamin B12 at screening, we report here the findings for the secondary endpoint: the effect of folic acid supplementation on cognitive performance. METHODS Our randomised, double blind, placebo controlled study took place between November, 1999, and December, 2004, in the Netherlands. We randomly assigned 818 participants 800 mug daily oral folic acid or placebo for 3 years. The effect on cognitive performance was measured as the difference between the two groups in the 3-year change in performance for memory, sensorimotor speed, complex speed, information processing speed, and word fluency. Analysis was by intention-to-treat. This trial is registered with clinicaltrials.gov with trial number NCT00110604. FINDINGS Serum folate concentrations increased by 576% (95% CI 539 to 614) and plasma total homocysteine concentrations decreased by 26% (24 to 28) in participants taking folic acid compared with those taking placebo. The 3-year change in memory (difference in Z scores 0.132, 95% CI 0.032 to 0.233), information processing speed (0.087, 0.016 to 0.158) and sensorimotor speed (0.064, -0.001 to 0.129) were significantly better in the folic acid group than in the placebo group. INTERPRETATION Folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age.

The role of reducing intakes of saturated fat in the prevention of cardiovascular disease: where does the evidence stand in 2010?

Current dietary recommendations advise reducing the intake of saturated fatty acids (SFAs) to reduce coronary heart disease (CHD) risk, but recent findings question the role of SFAs. This expert panel reviewed the evidence and reached the following conclusions: the evidence from epidemiologic, clinical, and mechanistic studies is consistent in finding that the risk of CHD is reduced when SFAs are replaced with polyunsaturated fatty acids (PUFAs). In populations who consume a Western diet, the replacement of 1% of energy from SFAs with PUFAs lowers LDL cholesterol and is likely to produce a reduction in CHD incidence of ≥2-3%. No clear benefit of substituting carbohydrates for SFAs has been shown, although there might be a benefit if the carbohydrate is unrefined and has a low glycemic index. Insufficient evidence exists to judge the effect on CHD risk of replacing SFAs with MUFAs. No clear association between SFA intake relative to refined carbohydrates and the risk of insulin resistance and diabetes has been shown. The effect of diet on a single biomarker is insufficient evidence to assess CHD risk. The combination of multiple biomarkers and the use of clinical endpoints could help substantiate the effects on CHD. Furthermore, the effect of particular foods on CHD cannot be predicted solely by their content of total SFAs because individual SFAs may have different cardiovascular effects and major SFA food sources contain other constituents that could influence CHD risk. Research is needed to clarify the role of SFAs compared with specific forms of carbohydrates in CHD risk and to compare specific foods with appropriate alternatives.

Blood pressure response to changes in sodium and potassium intake: a metaregression analysis of randomised trials

The objective of the study was to assess the blood pressure response to changes in sodium and potassium intake and examine effect modification by age, gender, blood pressure, body weight and habitual sodium and potassium intake. Randomised trials of sodium reduction or potassium supplementation and blood pressure were identified through reference lists of systematic reviews and an additional MEDLINE search (January 1995–March 2001). A total of 40 sodium trials and 27 potassium trials in adults with a minimum duration of 2 weeks were selected for analysis. Data on changes in electrolyte intake and blood pressure during intervention were collected, as well as data on mean age, gender, body weight, initial electrolyte intake and initial blood pressure of the trial populations. Blood pressure effects of changes in electrolyte intake were assessed by weighted metaregression analysis, overall and in strata of trial population characteristics. Analyses were repeated with adjustment for potential confounders. Sodium reduction (median: −77 mmol/24 h) was associated with a change of −2.54 mmHg (95% CI: −3.16, −1.92) in systolic blood pressure and −1.96 mmHg (−2.41, −1.51) in diastolic blood pressure. Corresponding values for increased potassium intake (median: 44 mmol/24 h) were −2.42 mmHg (−3.75, −1.08) and −1.57 mmHg (–2.65, –0.50). Blood pressure response was larger in hypertensives than normotensives, both for sodium (systolic: −5.24 vs −1.26 mmHg, P<0.001; diastolic: −3.69 vs −1.14 mmHg, P<0.001) and potassium (systolic: −3.51 vs −0.97 mmHg, P=0.089; diastolic: −2.51 vs −0.34 mmHg, P=0.074). In conclusion, reduced intake of sodium and increased intake of potassium could make an important contribution to the prevention of hypertension, especially in populations with elevated blood pressure.

Supplementation with vitamin E but not beta-carotene in vivo protects low density lipoprotein from lipid peroxidation in vitro. Effect of cigarette smoking.

Several lines of evidence suggest that oxidatively modified low density lipoprotein (LDL) is atherogenic and that antioxidants may protect LDL against oxidation. In addition, cigarette smoking is known to induce oxidant stress. We have examined the effect of ingestion of the antioxidants D,L-alpha-tocopherol (vitamin E) and beta-carotene and of smoking on the resistance of LDL against copper-mediated oxidation. Six healthy nonsmoking volunteers ingested 1,000 IU/day D,L-alpha-tocopherol acetate for 7 days. After vitamin E ingestion concentrations of alpha-tocopherol in plasma and LDL increased 3.0- and 2.4-fold, respectively. Simultaneously, the oxidation resistance of LDL was elevated significantly (+41%), and the rate of oxidation was decreased significantly (-19%). The increase in alpha-tocopherol content of LDL and the increase in resistance time were highly correlated (rs = 0.89, p = 0.014). Eight weeks after termination of the vitamin E intake, alpha-tocopherol concentrations in plasma and LDL and oxidation resistance of LDL had returned to baseline values. In smokers (n = 46), plasma levels of vitamin C (-26%) and concentrations of beta-carotene (-44%, -43%) and total carotenoids (-23%, -29%) in plasma and LDL, respectively, were significantly lower compared with nonsmokers (n = 23). No differences were found in alpha-tocopherol content of LDL and the susceptibility of LDL to lipid peroxidation in both groups. Supplementation of a group of smokers in a 14-week randomized, double-blind, placebo-controlled intervention trial with beta-carotene resulted in a 16.6- and 5.0-fold increase of LDL beta-carotene and total carotenoid content, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Fruits and vegetables in the prevention of cancer and cardiovascular disease

OBJECTIVE We quantified the public health benefit of fruits and vegetables on the prevention of cancer and cardiovascular disease (CVD), using currently available human data. DESIGN We reviewed over 250 observational studies on cancer and CVD. Relative risks (RRs) for high versus low intake of fruits and vegetables were obtained. The preventable proportion of chronic diseases, i.e. the per cent of cases attributable to low consumption of fruits and vegetables, was estimated using three scenarios: best guess, optimistic (using stronger RRs) and conservative (using weaker RRs and eliminating the contribution of smoking and/or drinking). The preventable proportion was calculated for increasing average intake from the current 250 g day(-1) to the recommended 400 g day(-1) among the general Dutch population. RESULTS It is estimated that in the Netherlands cancer incidence could be reduced by 19% (12,000 cases annually, best guess), ranging from 6% (conservative) to 28% (optimistic). Cardiovascular deaths could be reduced by 16% (8000 deaths annually, best guess), ranging from 6% to 22%. Evidence is most abundant for gastrointestinal cancers, followed by hormone-related cancers, but limited for other sites and CVD. CONCLUSIONS Increasing consumption of fruits and vegetables carries a large public health potential. Population trials and biological mechanisms should eventually provide scientific proof of their efficacy. The available evidence is sufficient to justify public health education and promotion aimed at a substantial increase in the consumption of fruits and vegetables.

Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials

Purpose Coffee is a widely consumed beverage and small health effects of substances in coffee may have large public health consequences. It has been suggested that caffeine in coffee increases the risk of hypertension. We performed a meta-analysis of randomized controlled trials of coffee or caffeine and blood pressure (BP). Data identification BP trials of coffee or caffeine published between January 1966 and January 2003 were identified through literature databases and manual serach. Study selection A total of 16 studies with a randomized, controlled design and at least 7 days of intervention was selected, comprising 25 strata and 1010 subjects. Data extraction Two persons independently obtained data on sample size, type and duration of intervention, changes in BP and heart rate (HR), and subjects’ characteristics for each trial. Meta-analysis was performed using a random-effects model. Results A significant rise of 2.04 mmHg [95% confidence interval (CI), 1.10–2.99] in systolic BP and 0.73 mmHg (95% CI, 0.14–1.31) in diastolic BP was found after pooling of coffee and caffeine trials. When coffee trials (n = 18, median intake: 725 ml/day) and caffeine trials (n = 7, median dose: 410 mg/day) were analysed separately, BP elevations appeared to be larger for caffeine [systolic: 4.16 mmHg (2.13–6.20); diastolic: 2.41 mmHg (0.98–3.84)] than for coffee [systolic: 1.22 mmHg (0.52–1.92) and diastolic: 0.49 mmHg (−0.06–1.04)]. Effects on HR were negligible. Conclusions Regular caffeine intake increases BP. When ingested through coffee, however, the blood pressure effect of caffeine is small.

Effect of fish oil on cognitive performance in older subjects A randomized, controlled trial

Background: High intake of n-3 polyunsaturated fatty acids may protect against age-related cognitive decline. However, results from epidemiologic studies are inconclusive, and results from randomized trials in elderly subjects without dementia are lacking. Objective: To investigate the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on cognitive performance. Methods: Double-blind, placebo-controlled trial involving 302 cognitively healthy (Mini-Mental State Examination score > 21) individuals aged 65 years or older. Participants were randomly assigned to 1,800 mg/d EPA–DHA, 400 mg/d EPA–DHA, or placebo capsules for 26 weeks. Cognitive performance was assessed using an extensive neuropsychological test battery that included the cognitive domains of attention, sensorimotor speed, memory, and executive function. Results: The mean age of the participants was 70 years, and 55% were male. Plasma concentrations of EPA–DHA increased by 238% in the high-dose and 51% in the low-dose fish oil group compared with placebo, reflecting excellent compliance. Baseline scores on the cognitive tests were comparable in the three groups. Overall, there were no significant differential changes in any of the cognitive domains for either low-dose or high-dose fish oil supplementation compared with placebo. Conclusions: In this randomized, double-blind, placebo-controlled trial, we observed no overall effect of 26 weeks of eicosapentaenoic acid and docosahexaenoic acid supplementation on cognitive performance.

Effect of family style mealtimes on quality of life, physical performance, and body weight of nursing home residents: cluster randomised controlled trial

Abstract Objective To assess the effect of family style mealtimes on quality of life, physical performance, and body weight of nursing home residents without dementia. Design Cluster randomised trial. Setting Five Dutch nursing homes. Participants 178 residents (mean age 77 years). Two wards in each home were randomised to intervention (95 participants) or control groups (83). Intervention During six months the intervention group took their meals family style and the control group received the usual individual pre-plated service. Main outcome measures Quality of life (perceived safety; autonomy; and sensory, physical, and psychosocial functioning), gross and fine motor function, and body weight. Results The difference in change between the groups was significant for overall quality of life (6.1 units, 95% confidence interval 2.1 to 10.3), fine motor function (1.8 units, 0.6 to 3.0), and body weight (1.5 kg, 0.6 to 2.4). Conclusion Family style mealtimes maintain quality of life, physical performance, and body weight of nursing home residents without dementia. Trial registration Clinical trials NCT00114582