Graham A. MacGregor

Fruit and vegetable consumption and stroke: meta-analysis of cohort studies

BACKGROUND Increased consumption of fruit and vegetables has been shown to be associated with a reduced risk of stroke in most epidemiological studies, although the extent of the association is uncertain. We quantitatively assessed the relation between fruit and vegetable intake and incidence of stroke in a meta-analysis of cohort studies. METHODS We searched MEDLINE, EMBASE, the Cochrane Library, and bibliographies of retrieved articles. Studies were included if they reported relative risks and corresponding 95% CIs of stroke with respect to frequency of fruit and vegetable intake. FINDINGS Eight studies, consisting of nine independent cohorts, met the inclusion criteria. These groups included 257,551 individuals (4917 stroke events) with an average follow-up of 13 years. Compared with individuals who had less than three servings of fruit and vegetables per day, the pooled relative risk of stroke was 0.89 (95% CI 0.83-0.97) for those with three to five servings per day, and 0.74 (0.69-0.79) for those with more than five servings per day. Subgroup analyses showed that fruit and vegetables had a significant protective effect on both ischaemic and haemorrhagic stroke. INTERPRETATION Increased fruit and vegetable intake in the range commonly consumed is associated with a reduced risk of stroke. Our results provide strong support for the recommendations to consume more than five servings of fruit and vegetables per day, which is likely to cause a major reduction in strokes.

A comprehensive review on salt and health and current experience of worldwide salt reduction programmes

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Raised blood pressure (BP), cholesterol and smoking, are the major risk factors. Among these, raised BP is the most important cause, accounting for 62% of strokes and 49% of coronary heart disease. Importantly, the risk is throughout the range of BP, starting at systolic 115 mm Hg. There is strong evidence that our current consumption of salt is the major factor increasing BP and thereby CVD. Furthermore, a high salt diet may have direct harmful effects independent of its effect on BP, for example, increasing the risk of stroke, left ventricular hypertrophy and renal disease. Increasing evidence also suggests that salt intake is related to obesity through soft drink consumption, associated with renal stones and osteoporosis and is probably a major cause of stomach cancer. In most developed countries, a reduction in salt intake can be achieved by a gradual and sustained reduction in the amount of salt added to food by the food industry. In other countries where most of the salt consumed comes from salt added during cooking or from sauces, a public health campaign is needed to encourage consumers to use less salt. Several countries have already reduced salt intake, for example, Japan (1960–1970), Finland (1975 onwards) and now the United Kingdom. The challenge is to spread this out to all other countries. A modest reduction in population salt intake worldwide will result in a major improvement in public health.

Effect of modest salt reduction on blood pressure: a meta-analysis of randomized trials. Implications for public health

Two recent meta-analyses of randomised salt reduction trials have concluded that there is little purpose in reducing salt intake in the general population. However, the authors, as with other previous meta-analyses, included trials of very short duration (eg 1 week or less) and trials of acute salt loading followed by abrupt reductions to very low salt intake (eg from 20 to less than 1 g of salt/day). These acute salt loading and salt depletion experiments are known to increase sympathetic tone, and with salt depletion cause a rise in renin release and, thereby, plasma angiotensin II. These trials are not appropriate, therefore, for helping to inform public health policy, which is for a more modest reduction in salt intake, ie, from a usual intake of ≈10 to ≈5 g of salt per day over a more prolonged period of time. We carried out a meta-analysis to assess the effect of a modest salt reduction on blood pressure. Our data sources were MEDLINE, EMBASE, Cochrane library, CINAHL, and the reference lists of original and review articles. We included randomised trials with a modest reduction in salt intake and a duration of 4 or more weeks. Meta-analysis, meta-regression, and funnel plots were performed. A total of 17 trials in hypertensives (n=734) and 11 trials in normotensives (n=2220) were included in our study. The median reduction in 24-h urinary sodium excretion was 78 mmol (equivalent to 4.6 g of salt/day) in hypertensives and 74 mmol in normotensives. The pooled estimates of blood pressure fall were 4.96/2.73±0.40/0.24 mmHg in hypertensives (P<0.001 for both systolic and diastolic) and 2.03/0.97±0.27/0.21 mmHg in normotensives (P<0.001 for both systolic and diastolic). Weighted linear regression analyses showed a dose response between the change in urinary sodium and blood pressure. A reduction of 100 mmol/day (6 g of salt) in salt intake predicted a fall in blood pressure of 7.11/3.88 mmHg (P<0.001 for both systolic and diastolic) in hypertensives and 3.57/1.66 mmHg in normotensive individuals (systolic: P<0.001; diastolic: P<0.05). Our results demonstrate that a modest reduction in salt intake for a duration of 4 or more weeks does have a significant and, from a population viewpoint, important effect on blood pressure in both hypertensive and normotensive individuals. This meta-analysis strongly supports other evidence for a modest and long-term reduction in population salt intake, and would be predicted to reduce stroke deaths immediately by ≈14% and coronary deaths by ≈9% in hypertensives, and reduce stroke and coronary deaths by ≈6 and ≈4%, in normotensives, respectively.

Increased consumption of fruit and vegetables is related to a reduced risk of coronary heart disease: meta-analysis of cohort studies

Increased consumption of fruit and vegetables has been shown to be associated with a reduced risk of coronary heart disease (CHD) in many epidemiological studies, however, the extent of the association is uncertain. We quantitatively assessed the relation between fruit and vegetable intake and incidence of CHD by carrying out a meta-analysis of cohort studies. Studies were included if they reported relative risks (RRs) and corresponding 95% confidence interval (CI) of CHD with respect to frequency of fruit and vegetable intake. Twelve studies, consisting of 13 independent cohorts, met the inclusion criteria. There were 278 459 individuals (9143 CHD events) with a median follow-up of 11 years. Compared with individuals who had less than 3 servings/day of fruit and vegetables, the pooled RR of CHD was 0.93 (95% CI: 0.86–1.00, P=0.06) for those with 3–5 servings/day and 0.83 (0.77–0.89, P<0.0001) for those with more than 5 servings/day. Subgroup analyses showed that both fruits and vegetables had a significant protective effect on CHD. Our meta-analysis of prospective cohort studies demonstrates that increased consumption of fruit and vegetables from less than 3 to more than 5 servings/day is related to a 17% reduction in CHD risk, whereas increased intake to 3–5 servings/day is associated with a smaller and borderline significant reduction in CHD risk. These results provide strong support for the recommendations to consume more than 5 servings/day of fruit and vegetables.

Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials

Objective To determine the effects of longer term modest salt reduction on blood pressure, hormones, and lipids. Design Systematic review and meta-analysis. Data sources Medline, Embase, Cochrane Hypertension Group Specialised Register, Cochrane Central Register of Controlled Trials, and reference list of relevant articles. Inclusion criteria Randomised trials with a modest reduction in salt intake and duration of at least four weeks. Data extraction and analysis Data were extracted independently by two reviewers. Random effects meta-analyses, subgroup analyses, and meta-regression were performed. Results Thirty four trials (3230 participants) were included. Meta-analysis showed that the mean change in urinary sodium (reduced salt v usual salt) was −75 mmol/24 h (equivalent to a reduction of 4.4 g/day salt), and with this reduction in salt intake, the mean change in blood pressure was −4.18 mm Hg (95% confidence interval −5.18 to −3.18, I2=75%) for systolic blood pressure and −2.06 mm Hg (−2.67 to −1.45, I2=68%) for diastolic blood pressure. Meta-regression showed that age, ethnic group, blood pressure status (hypertensive or normotensive), and the change in 24 hour urinary sodium were all significantly associated with the fall in systolic blood pressure, explaining 68% of the variance between studies. A 100 mmol reduction in 24 hour urinary sodium (6 g/day salt) was associated with a fall in systolic blood pressure of 5.8 mm Hg (2.5 to 9.2, P=0.001) after adjustment for age, ethnic group, and blood pressure status. For diastolic blood pressure, age, ethnic group, blood pressure status, and the change in 24 hour urinary sodium explained 41% of the variance between studies. Meta-analysis by subgroup showed that in people with hypertension the mean effect was −5.39 mm Hg (−6.62 to −4.15, I2=61%) for systolic blood pressure and −2.82 mm Hg (−3.54 to −2.11, I2=52%) for diastolic blood pressure. In normotensive people, the figures were −2.42 mm Hg (−3.56 to −1.29, I2=66%) and −1.00 mm Hg (−1.85 to −0.15, I2=66%), respectively. Further subgroup analysis showed that the decrease in systolic blood pressure was significant in both white and black people and in men and women. Meta-analysis of data on hormones and lipids showed that the mean change was 0.26 ng/mL/h (0.17 to 0.36, I2=70%) for plasma renin activity, 73.20 pmol/L (44.92 to 101.48, I2=62%) for aldosterone, 187 pmol/L (39 to 336, I2=5%) for noradrenaline (norepinephrine), 37 pmol/L (−1 to 74, I2=12%) for adrenaline (epinephrine), 0.05 mmol/L (−0.02 to 0.11, I2=0%) for total cholesterol, 0.05 mmol/L (−0.01 to 0.12, I2=0%) for low density lipoprotein cholesterol, −0.02 mmol/L (−0.06 to 0.01, I2=16%) for high density lipoprotein cholesterol, and 0.04 mmol/L (−0.02 to 0.09, I2=0%) for triglycerides. Conclusions A modest reduction in salt intake for four or more weeks causes significant and, from a population viewpoint, important falls in blood pressure in both hypertensive and normotensive individuals, irrespective of sex and ethnic group. Salt reduction is associated with a small physiological increase in plasma renin activity, aldosterone, and noradrenaline and no significant change in lipid concentrations. These results support a reduction in population salt intake, which will lower population blood pressure and thereby reduce cardiovascular disease. The observed significant association between the reduction in 24 hour urinary sodium and the fall in systolic blood pressure, indicates that larger reductions in salt intake will lead to larger falls in systolic blood pressure. The current recommendations to reduce salt intake from 9-12 to 5-6 g/day will have a major effect on blood pressure, but a further reduction to 3 g/day will have a greater effect and should become the long term target for population salt intake.

Reducing Population Salt Intake Worldwide: From Evidence to Implementation

Raised blood pressure is a major cause of cardiovascular disease, responsible for 62% of stroke and 49% of coronary heart disease. There is overwhelming evidence that dietary salt is the major cause of raised blood pressure and that a reduction in salt intake lowers blood pressure, thereby, reducing blood pressure-related diseases. Several lines of evidence including ecological, population, and prospective cohort studies, as well as outcome trials, demonstrate that a reduction in salt intake is related to a lower risk of cardiovascular disease. Increasing evidence also suggests that a high salt intake may directly increase the risk of stroke, left ventricular hypertrophy, and renal disease; is associated with obesity through soft drink consumption; is related to renal stones and osteoporosis; is linked to the severity of asthma; and is probably a major cause of stomach cancer. In most developed countries, a reduction in salt intake can be achieved by a gradual and sustained reduction in the amount of salt added to foods by the food industry. In other countries where most of the salt consumed comes from salt added during cooking or from sauces, a public health campaign is needed to encourage consumers to use less salt. Several countries have already reduced salt intake. The challenge now is to spread this out to all other countries. A modest reduction in population salt intake worldwide will result in a major improvement in public health.

How Far Should Salt Intake Be Reduced

Abstract—The current public health recommendations are to reduce salt intake from 9 to 12 g/d to 5 to 6 g/d. However, these values are based on what is feasible rather than the maximum effect of salt reduction. In a meta-analysis of longer-term trials, we looked at the dose response between salt reduction and fall in blood pressure and compared this with 2 well-controlled studies of 3 different salt intakes. All 3 studies demonstrated a consistent dose response to salt reduction within the range of 12 to 3 g/d. A reduction of 3 g/d predicts a fall in blood pressure of 3.6 to 5.6/1.9 to 3.2 mm Hg (systolic/diastolic) in hypertensives and 1.8 to 3.5/0.8 to 1.8 mm Hg in normotensives. The effect would be doubled with a 6 g/d reduction and tripled with a 9 g/d reduction. A conservative estimate indicates that a reduction of 3 g/d would reduce strokes by 13% and ischemic heart disease (IHD) by 10%. The effects would be almost doubled with a 6 g/d reduction and tripled with a 9 g/d reduction. Reducing salt intake by 9 g/d (eg, from 12 to 3 g/d) would reduce strokes by approximately one third and IHD by one quarter, and this would prevent ≈20 500 stroke deaths and 31 400 IHD deaths a year in the United Kingdom. The current recommendations to reduce salt intake from 9 to 12 g/d to 5 to 6 g/d will have a major effect on blood pressure and cardiovascular disease but are not ideal. A further reduction to 3 g/d will have a much greater effect and should now become the long-term target for population salt intake worldwide.

Plasma sodium stiffens vascular endothelium and reduces nitric oxide release

Dietary salt plays a major role in the regulation of blood pressure, and the mineralocorticoid hormone aldosterone controls salt homeostasis and extracellular volume. Recent observations suggest that a small increase in plasma sodium concentration may contribute to the pressor response of dietary salt. Because endothelial cells are (i) sensitive to aldosterone, (ii) in physical contact with plasma sodium, and (iii) crucial regulators of vascular tone, we tested whether acute changes in plasma sodium concentration, within the physiological range, can alter the physical properties of endothelial cells. The tip of an atomic force microscope was used as a nanosensor to measure stiffness of living endothelial cells incubated for 3 days in a culture medium containing aldosterone at a physiological concentration (0.45 nM). Endothelial cell stiffness was unaffected by acute changes in sodium concentration <135 mM but rose steeply between 135 and 145 mM. The increase in stiffness occurred within minutes. Lack of aldosterone in the culture medium or treatment with the epithelial sodium channel inhibitor amiloride prevented this response. Nitric oxide formation was found down-regulated in cells cultured in aldosterone-containing high sodium medium. The results suggest that changes in plasma sodium concentration per se may affect endothelial function and thus control vascular tone.

Importance of Salt in Determining Blood Pressure in Children: Meta-Analysis of Controlled Trials

To assess the effect of reducing salt intake on blood pressure in children, we carried out a meta-analysis of controlled trials. Trials were included if participants were children (≤18 years), and duration of salt reduction must have been for ≥2 weeks. Mean effect size was calculated using a fixed-effect model, because there was no significant heterogeneity. Ten trials of children and adolescents with 966 participants were included (median age: 13 years; range: 8 to 16 years; median duration: 4 weeks; range: 2 weeks to 3 years). Salt intake was reduced by 42% (interquartile range [IQR]: 7% to 58%). There were significant reductions in blood pressure: systolic: −1.17 mm Hg (95% CI: −1.78 to −0.56 mm Hg; P<0.001); diastolic: −1.29 mm Hg (95% CI: −1.94 to −0.65 mm Hg; P<0.0001). Three trials of infants with 551 participants were included (median duration: 20 weeks; range: 8 weeks to 6 months). Salt intake was reduced by 54% (IQR: 51% to 79%). There was a significant reduction in systolic blood pressure: −2.47 mm Hg (95% CI: −4.00 to −0.94 mm Hg; P<0.01). This is the first meta-analysis of salt reduction in children, and it demonstrates that a modest reduction in salt intake causes immediate falls in blood pressure and, if continued, may well lessen the subsequent rise in blood pressure with age. This would result in major reductions in cardiovascular disease. These results in conjunction with other evidence provide strong support for a reduction in salt intake in children.

Does potassium supplementation lower blood pressure ? A meta-analysis of published trials

Both epidemiologic and clinical studies have suggested that an increase in potassium intake may lower blood pressure. However, the results of prospective clinical trials looking at the effect of oral potassium supplements on blood pressure have yielded conflicting results. For this reason, we reviewed 19 clinical trials examining the same end-point and involving a total of 586 participants (412 of whom had essential hypertension). Overall, the results of the trials indicate that oral potassium supplements significantly lower systolic blood pressure [-5.9 mmHg, -6.6 to -5.2 mmHg (mean, 95% confidence interval)] and diastolic blood pressure (-3.4 mmHg, -4.0 to 2.8 mmHg). The magnitude of the blood pressure lowering effect is greater in patients with high blood pressure (-8.2 mmHg, -9.1 to -7.3 mmHg for systolic and -4.5 mmHg, -5.2 to -3.8 mmHg for diastolic blood pressure) and appears to be more pronounced the longer the duration of the supplementation (P less than 0.05 and P less than 0.01 for systolic and diastolic, respectively). Based on this analysis, an increase in potassium intake should be included in the recommendations for a non-pharmacological approach to the control of blood pressure in uncomplicated essential hypertension.