Salt intake and cardiovascular mortality.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
Graham A MacGregor
Publications and source records attributed to Graham A MacGregor.
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 (< or = 18 years), and duration of salt reduction must have been for > or = 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.
Adolescent↗
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.
Cohort Studies↗
The effect of sodium and angiotensin-converting enzyme inhibition on the classic circulating renin-angiotensin system in autosomal-dominant polycystic kidney disease patients.
BACKGROUND: It has been suggested that inappropriate stimulation of the renin-angiotensin system (RAS) is responsible for the increase in blood pressure that occurs in autosomal-dominant polycystic kidney disease (ADPKD) before the development of renal failure. However, the interpretation of previous studies in ADPKD patients is confounded by inadequate matching with control populations for blood pressure and renal function, or failure to control the sodium intake of participants. METHODS: A double-blind, placebo-controlled study of two different sodium intakes (350 and 50 mmol/day for 5 days) in a group of 11 hypertensive ADPKD patients and eight matched control subjects with essential hypertension. In addition, blood pressure and hormonal responses were measured after the administration of the angiotensin-converting enzyme inhibitor enalapril for 3 days. RESULTS: Blood pressure and hormonal responses of the RAS after a reduction in sodium intake and after the administration of enalapril were identical in ADPKD patients and controls. CONCLUSIONS: Activation of the classic circulating RAS is no greater in hypertensive ADPKD patients than in individuals with essential hypertension.
Adult↗
Plasma aldosterone: comparison of a new automated assay with a standard extraction method.
Explore the source record for details and available documents.
Aldosterone↗
Autosomal dominant polycystic kidney disease: role of the renin-angiotensin system in raised blood pressure in progression of renal and cardiovascular disease.
Raised blood pressure (BP) is extremely common in individuals with autosomal dominant polycystic kidney disease (ADPKD) and is almost invariably raised once they develop renal failure. The underlying mechanisms for the rise in BP in individuals with ADPKD are unclear. The progressive number and enlargement of renal cysts, causing structural damage to the kidneys and, thereby, affecting tubular function as well as causing distortion of the glomeruli and renal ischaemia, is likely to be of primary importance. There is some evidence from animal models that there may be over-activity of the intra-renal renin-angiotensin system (RAS) that could account for the rise in BP. Studies in man have shown conflicting results, but a recent more carefully controlled study using both measurements of activity and pharmacological blockade of the RAS clearly demonstrated no evidence of over-activity of the circulating RAS in ADPKD compared to matched individuals with essential hypertension. A more likely explanation for the rise in BP that occurs in ADPKD is retention of sodium and water due to tubular damage. Disappointingly, in spite of good evidence that RAS blocking drugs slow the progression of other renal, particularly glomerular, diseases, there is little evidence to suggest this is true for patients with ADPKD. Nevertheless, there is no doubt that lowering BP in ADPKD is just as important, if not more important, as in essential hypertension to prevent cardiovascular disease and strokes, with a recommended BP target of < 120/80 mmHg.
Animals↗
Modest salt reduction reduces blood pressure and urine protein excretion in black hypertensives: a randomized control trial.
High blood pressure and proteinuria are the major risk factors for cardiovascular and renal disease. In black individuals, there is an increased risk of hypertension, stroke, heart failure, and kidney disease. There are no controlled studies of the effects of reducing salt intake on blood pressure and urine protein excretion in black individuals. Therefore, the aim of our study was to determine the effects of modest salt restriction on blood pressure and urine protein excretion in nondiabetic black hypertensive subjects. The study was randomized, double blind, and placebo controlled. After run-in periods on their usual diet and on reduced salt, participants continued to restrict their salt intake and then received either slow sodium tablets, designed to bring their salt intake back to normal, or placebo tablets for 4 weeks in a randomized, double-blind, crossover study. In the 40 who completed the study, urinary sodium excretion fell on slow sodium to placebo from 169+/-73 to 89+/-52 mmol per 24 hours (P<0.001; approximately 10 to 5 g salt per day). Blood pressure fell from 159/101+/-13/8 to 151/98+/-13/8 mm Hg (P<0.01). Protein excretion fell from 93+/-48 mg to 75+/-30 mg per 24 hours (P<0.008). Thus, reducing salt intake from approximately 10 to 5 g per day reduced blood pressure and urine protein excretion in black hypertensives. In light of these findings, we would recommend that all black individuals with raised blood pressure reduce their salt intake to < or =5 g per day.
Adult↗
Modest salt reduction lowers blood pressure in isolated systolic hypertension and combined hypertension.
Many randomized trials have shown that a reduction in salt intake lowers blood pressure in hypertensive individuals. However, few have looked at the effects according to hypertension category. A recent analysis of the third and fourth National Health and Nutrition Examination Survey suggests that salt intake may not be related to blood pressure in isolated systolic or combined hypertension. To look at this further, we reanalyzed the data of our previous salt reduction trials. Hypertensive individuals were studied in randomized double-blind crossover studies: 1 month of usual salt intake compared with 1 month of reduced salt intake. In isolated systolic hypertension (n=24), blood pressure was reduced from 166+/-19/86+/-7 to 156+/-20/85+/-7 mm Hg (systolic P<0.001; diastolic P=0.459) with a reduction in urinary sodium from 175+/-51 to 87+/-38 mmol per 24-hour period (10.3 to 5.1 g per day of salt). In combined hypertension (n=88), blood pressure was reduced from 161+/-16/100+/-9 to 154+/-17/96+/-9 mm Hg (P<0.001) with a reduction urinary sodium from 176+/-65 to 98+/-51 mmol per 24-hour period (10.4 to 5.8 g per day of salt). These results demonstrate that salt reduction has a significant effect on blood pressure in isolated systolic and combined hypertension. The fall in systolic observed in isolated systolic hypertension would be predicted to reduce stroke by approximately one third, ischemic heart disease by one quarter, and heart failure by one quarter in the population between 60 and 80 years of age, in whom isolated systolic hypertension is the predominate form of hypertension and carries the highest risk. These results provide strong support for universal salt reduction in all hypertensives.
Adult↗
Systematic review of combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade in hypertension.
Some evidence suggests that long-term angiotensin-converting enzyme (ACE) inhibition may become less effective, thereby increasing angiotensin II levels, which could be inhibited by the addition of an angiotensin receptor blocker. We conducted a meta-analysis of randomized trials with searches of MEDLINE, EMBASE, and Cochrane databases. Overall, the combination of an ACE inhibitor and an angiotensin receptor blocker reduced ambulatory blood pressure by 4.7/3.0 mm Hg (95% confidence interval [CI], 2.9 to 6.5/1.6 to 4.3) compared with ACE inhibitor monotherapy and 3.8/2.9 mm Hg (2.4 to 5.3/0.4 to 5.4) compared with angiotensin receptor blocker monotherapy. Clinic blood pressure was reduced by 3.8/2.7 mm Hg (0.9 to 6.7/0.8 to 4.6) and 3.7/2.3 mm Hg (0.4 to 6.9/0.2 to 4.4) compared with ACE inhibitor and angiotensin receptor blocker, respectively. However, the majority of these studies used submaximal doses or once-daily dosing of shorter-acting ACE inhibitors and, when a larger dose of shorter-acting ACE inhibitor was given or a longer-acting ACE inhibitor was used, there was generally no additive effect of the angiotensin receptor blocker on blood pressure. Proteinuria was reduced by the combination compared with ACE inhibitor and angiotensin receptor blocker monotherapy, an effect that was independent of blood pressure in several studies, suggesting that the combination could have benefits in proteinuric nephropathies. None of the studies was of sufficient size and duration to determine whether there may be safety concerns. In conclusion, although there is a small additive effect on blood pressure with an ACE inhibitor-angiotensin receptor blocker combination, the routine use of this combination in uncomplicated hypertension is not recommended until more carefully controlled studies are performed.
Angiotensin II Type 1 Receptor Blockers↗
Effect of short-term supplementation of potassium chloride and potassium citrate on blood pressure in hypertensives.
Randomized trials have shown that increasing potassium intake lowers blood pressure. However, most previous trials used potassium chloride, whereas potassium in fruits and vegetables is not a chloride salt. It is unclear whether a nonchloride salt of potassium has a greater or lesser effect on blood pressure compared with potassium chloride. We performed a randomized crossover trial comparing potassium chloride with potassium citrate (96 mmol/d, each for 1 week) in 14 hypertensive individuals. At baseline, blood pressure was 151+/-16/93+/-7 mm Hg with a 24-hour urinary potassium of 81+/-24 mmol. During the randomized crossover part of the study, blood pressure was 140+/-12/88+/-7 mm Hg with potassium chloride (24-hour urinary potassium: 164+/-36 mmol) and 138+/-12/88+/-6 mm Hg with potassium citrate (24-hour urinary potassium: 160+/-33 mmol). These blood pressures were significantly lower compared with that at baseline; however, there was no significant difference in blood pressure between potassium chloride and potassium citrate, mean difference (95% confidence interval): 1.6 (-2.3 to 5.6) mm Hg for systolic and 0.6 (-2.4 to 3.7) mm Hg for diastolic. Our results, in conjunction with the evidence from many previous trials that potassium chloride has a significant blood pressure-lowering effect, suggest that potassium citrate has a similar effect on blood pressure as potassium chloride. These results support other evidence for an increase in potassium intake and indicate that potassium does not need to be given in the form of chloride to lower blood pressure. Increasing the consumption of foods high in potassium is likely to have the same effect on blood pressure as potassium chloride.
Adult↗
Blood pressure--importance of salt intake.
Explore the source record for details and available documents.
Blood Pressure↗
Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases.
Epidemiological, migration, intervention, and genetic studies in humans and animals provide very strong evidence of a causal link between high salt intake and high blood pressure. The mechanisms by which dietary salt increases arterial pressure are not fully understood, but they seem related to the inability of the kidneys to excrete large amounts of salt. From an evolutionary viewpoint, the human species is adapted to ingest and excrete <1 g of salt per day, at least 10 times less than the average values currently observed in industrialized and urbanized countries. Independent of the rise in blood pressure, dietary salt also increases cardiac left ventricular mass, arterial thickness and stiffness, the incidence of strokes, and the severity of cardiac failure. Thus chronic exposure to a high-salt diet appears to be a major factor involved in the frequent occurrence of hypertension and cardiovascular diseases in human populations.
Animals↗
Plasma sodium: ignored and underestimated.
Salt intake is a major regulator of blood pressure. There is evidence that those who develop high blood pressure have an underlying defect in the ability of the kidney to excrete salt. It has been suggested that this results in a greater tendency to retain sodium and an increased compensatory response that is responsible for the rise in blood pressure. There is also evidence suggesting that small increases in plasma sodium may directly affect blood pressure, independent of the associated expansion in extracellular volume. We reanalyzed 3 types of studies of changing salt intake. (1) An acute and large reduction in salt intake from 350 mmol/d to 10 to 20 mmol/d for 5 days in hypertensives and normotensives was associated with a fall in plasma sodium of approximately 3 mmol/L (P<0.001). (2) Progressive increases in salt intake from 10 to 250 mmol/d by a daily amount of 50 mmol in normotensives caused increases in plasma sodium (P<0.001). (3) Longer-term modest reduction in salt intake in hypertensives was studied in double-blind randomized crossover studies; 1 month of usual salt intake ( approximately 170 mmol/d) compared with reduced salt intake ( approximately 100 mmol/d). There was a decrease in plasma sodium of 0.4+/-0.2 mmol/L (P<0.05), which was weakly but significantly correlated with the fall in systolic blood pressure (r=0.18; P<0.05). These studies demonstrate that an increase or a decrease in salt intake causes changes in plasma sodium. Small changes in plasma sodium alter extracellular volume, which may influence blood pressure. Changes in plasma sodium may also affect blood pressure directly.
Adult↗
Universal salt reduction.
Explore the source record for details and available documents.
Blood Pressure↗
Molecular variants of the sodium/hydrogen exchanger type 3 gene and essential hypertension.
OBJECTIVES: The objectives of this study were to identify polymorphic variants within the gene coding for the sodium/hydrogen exchanger type 3 (NHE3) and to examine their relationship with hypertension and biochemical indices of sodium balance. DESIGN AND METHODS: Case-control comparisons on a total of 691 subjects of which 399 (68% with essential hypertension) were of African or Afro-Caribbean origin (blacks) and 292 (50% with essential hypertension) were of Caucasian origin (whites). RESULTS: Eight exons of the C terminus of the NHE3 gene were screened systematically. A total of six variants were identified: (G1579A, G1709A, G1867A, C1945T, A2041G and C2405T). Further analyses in relation to essential hypertension and phenotypic characteristics were confined to the more frequent A2041G and the C2405T polymorphisms. The genotype frequencies of the A2041G polymorphism were significantly different between the whites and blacks, with the A allele being more frequent in the white population (0.43 for the whites and 0.14 for the blacks, respectively; P < 0.001). In contrast, there was no significant difference in the C2405T polymorphism between whites and blacks (C allele frequency: 0.86 for the whites and 0.88 for the blacks, respectively). In both the white and the black groups, there were no significant associations between these variants and essential hypertension (P > 0.05) or with serum electrolytes, creatinine or plasma renin activity (PRA) (ANOVA P > 0.05). CONCLUSIONS: These results suggest a high degree of structural conservation of the NHE3 gene; however, the lack of association between these polymorphisms and blood pressure status does not necessarily eliminate the participation of this important sodium/hydrogen exchanger in the pathophysiology of essential hypertension, as we cannot exclude the existence of functionally important genetic variants in other sequences within the NEH3 gene.
Adult↗
Plasma sodium and hypertension.
Dietary salt is the major cause of the rise in the blood pressure with age and the development of high blood pressure in populations. However, the mechanisms whereby salt intake raises the blood pressure are not clear. Existing concepts focus on the tendency for an increase in extracellular fluid volume (ECV), but an increased salt intake also induces a small rise in plasma sodium, which increases a transfer of fluid from the intracellular to the extracellular space, and stimulates the thirst center. Accordingly, the rise in plasma sodium is responsible for the tendency for an increase in ECV. Although the change in ECV may have a pressor effect, the associated rise in plasma sodium itself may also cause the blood pressure to rise. There is some evidence in patients with essential hypertension and the spontaneously hypertensive rat (SHR) that plasma sodium may be raised by 1 to 3 mmol/L. An experimental rise in sodium concentration greater than 5 mmol/L induces pressor effects on the brain and on the renin-angiotensin system. Such a rise can also induce changes in cultured vascular tissue similar to those that occur in the vessels of humans and animals on a high sodium diet, independent of the blood pressure. We suggest that a small increase in plasma sodium may be part of the mechanisms whereby dietary salt increases the blood pressure.
Animals↗
Blood pressure in haemodialysis patients: the importance of the relationship between the renin-angiotensin-aldosterone system, salt intake and extracellular volume.
This review outlines the major mechanisms for control of blood pressure (BP) in individuals with renal failure on haemodialysis. Dietary salt stimulates thirst and, thereby, greater fluid intake with excessive fluid gain between dialysis sessions and chronic expansion of extracellular volume. At the same time, this volume expansion often fails to suppress the renin-angiotensin system (RAS) appropriately and this inevitably leads to high BP in the majority of individuals on haemodialysis. A greater understanding of the mechanisms involved leads to more rational treatment and better BP control. This can be achieved by careful measurement of BP before and after dialysis, allowing time for the equilibration of extracellular fluid shifts that occur after dialysis, combined with measurements of plasma renin activity. It is relatively easy to then decide how the high BP should be treated: either by removal of excess volume by gradual ultrafiltration combined with restriction of salt intake to help prevent thirst and excessive fluid gain between dialyses, or by inhibition of the RAS, or by a combination of both. In those individuals who are unable to adequately reduce their dietary salt intake and still continue to gain large amounts of weight between dialysis, and are resistant to reducing their pre-dialysis weight, calcium antagonists may help to lower BP, either alone or in combination with RAS blockade. However, the BP often remains resistant to treatment unless they can be persuaded to reduce their salt intake.
Blood Pressure↗