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Biomedical subjects

G A MacGregor

Publications and source records attributed to G A MacGregor.

At least 19 recordsLinked to original sources
PubMed2005

Importance of controlling blood pressure.

Cardiovascular disease is the leading cause of death and disability world-wide. Blood pressure, throughout the range seen in developed countries, is the most important risk factor for cardiovascular disease. Lowering blood pressure within the whole population by lifestyle interventions, such as reducing dietary salt intake and increasing the consumption of fruit and vegetables, will be of great benefit. Blood pressure-lowering trials also demonstrate immense benefits in preventing strokes, heart failure and coronary heart disease. There are no differences in outcome between the different methods used to lower blood pressure and the benefit is proportional to the degree of blood pressure-lowering. Thiazide diuretics are effective in lowering blood pressure and have been the most widely prescribed blood pressure-lowering drugs. They work by causing both sodium and water loss, but also cause potassium loss and a fall in plasma potassium levels. The latter may mitigate the beneficial effects from blood pressure-lowering. Some diuretics, such as spironolactone, affect the distal tubule and do not cause a fall in plasma potassium levels. However, spironolactone has endocrine side-effects associated with the fact that it is not specific for the mineralocorticoid receptor. The development of a more selective aldosterone antagonist without endocrine side-effects could be a major advance as it would be able to oppose the effects of aldosterone, both on sodium retention and potassium loss and the other vascular effects.

Androstenes↗
PubMed2004

Effect of longer-term modest salt reduction on blood pressure.

BACKGROUND: Many randomised trials assessing the effect of salt reduction on blood pressure show reduction in blood pressure in individuals with high blood pressure. However, there is controversy about the magnitude and the clinical significance of the fall in blood pressure in individuals with normal blood pressure. Several meta-analyses of randomised salt reduction trials have been published in the last few years. However, most of these included trials of very short duration (e.g. 5 days) and included trials with salt loading followed by salt deprivation (e.g. from 20 to 1 g/day) over only a few days. These short-term experiments are not appropriate to inform public health policy which is for a modest reduction in salt intake over a prolonged period of time. A meta-analysis by Hooper et al is an important attempt to look at whether advice to achieve a long-term salt reduction (i.e. more than 6 months) in randomised trials causes a fall in blood pressure. However, most trials included in this meta-analysis achieved a small reduction in salt intake; on average, salt intake was reduced by 2 g/day. It is, therefore, not surprising that this analysis showed a small fall in blood pressure, and that a dose-response to salt reduction was not demonstrable. OBJECTIVES: To assess the effect of the currently recommended modest reduction in salt intake (WHO 2003; SACN 2003; Whelton 2002), on blood pressure in individuals with normal and elevated blood pressure. To assess whether the magnitude of the reduction in blood pressure is dependent on the magnitude of the reduction in salt intake. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Cochrane library, CINAHL, and reference list of original and review articles. SELECTION CRITERIA: We included randomised trials with a modest reduction in salt intake and a duration of 4 or more weeks. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two persons. Mean effect sizes were calculated using both fixed and random effect models using Review Manager 4.2.1 software. Weighted linear regression was used to examine the relationship between the change in urinary sodium and the change in blood pressure. We used funnel plots to detect publication and other biases in the meta-analysis. MAIN RESULTS: Seventeen trials in individuals with elevated blood pressure (n=734) and 11 trials in individuals with normal blood pressure (n=2220) were included. In individuals with elevated blood pressure the median reduction in 24-h urinary sodium excretion was 78 mmol (4.6 g/day of salt), the mean reduction in systolic blood pressure was -4.97 mmHg (95%CI:-5.76 to -4.18), and the mean reduction in diastolic blood pressure was -2.74 mmHg (95% CI:-3.22 to -2.26). In individuals with normal blood pressure the median reduction in 24-h urinary sodium excretion was 74 mmol (4.4 g/day of salt), the mean reduction in systolic blood pressure was -2.03 mmHg (95% CI: -2.56 to -1.50) mmHg, and the mean reduction in diastolic blood pressure was -0.99 mmHg (-1.40 to -0.57). Weighted linear regression analyses showed a correlation between the reduction in urinary sodium and the reduction in blood pressure. REVIEWERS' CONCLUSIONS: Our meta-analysis demonstrates that a modest reduction in salt intake for a duration of 4 or more weeks has a significant and, from a population viewpoint, important effect on blood pressure in both individuals with normal and elevated blood pressure. These results support other evidence suggesting that a modest and long-term reduction in population salt intake could reduce strokes, heart attacks, and heart failure. Furthermore, our meta-analysis demonstrates a correlation between the magnitude of salt reduction and the magnitude of blood pressure reduction. Within the daily intake range of 3 to 12 g/day, the lower the salt intake achieved, the lower the blood pressure.

Aldosterone↗
PubMed2003

Better blood pressure control: how to combine drugs.

Prospective comparisons of different drug classes have shown that differences in blood pressure control, rather than differences between drug classes, have the over-riding influence on overall outcome. The same studies have also reinforced the need, in the majority of patients, to use combinations of drugs in order to achieve the target of <140/85 mmHg. By contrast, most patients in routine practice receive single agents and consequently fail to achieve target blood pressure. This failure reflects in part the emphasis in individual studies and subsequent guidelines on comparison of individual drugs. In this article we show how the consistency of both theory and a broad range of evidence permits a didactic approach to combination therapy. Our advice is based on the growing recognition that essential hypertension and its treatment fall into two main categories. Younger Caucasians usually have renin-dependent hypertension that responds well to angiotensin-converting-enzyme inhibition or angiotensin receptor blockade (A) or ss blockade (B). Most other patients have low-renin hypertension that responds better to calcium channel blockade (C) or diuretics (D). These latter drugs activate the renin system rendering patients responsive to the addition of renin suppressive therapy. Coincidence of the initials of these main drug classes with the first four letters of the alphabet permits an AB/CD rule, according to which recommended combinations are one drug from each of the "AB" and "CD" categories of drugs. However, the diabetogenic potential of the older "B" and "D" classes leads us to advise against combining "B" and "D" in older patients, and to recommend "A" + "C" + "D" as standard triple therapy for resistant hypertension.

Antihypertensive Agents↗
PubMed2003

Cost of poor blood pressure control in the UK: 62,000 unnecessary deaths per year.

High blood pressure is the most important risk factor for cardiovascular disease. With the information on systolic blood pressure from the recently published meta-analysis of prospective studies, we calculated the reductions in stroke and ischaemic heart disease with control of all hypertensives to a systolic blood pressure of 140 mmHg. For adults there would be a reduction of 28-44% in stroke and 20-35% in ischaemic heart disease depending on age. In the UK, this would prevent approximately 21,400 stroke deaths and 41,400 ischaemic heart disease deaths each year. Around half of those who suffer a stroke or ischaemic heart disease survive, there would be a proportionate decrease in these people as well. These amount to approximately 42,800 strokes and 82,800 ischaemic heart diseases saved, making a total of 125,600 events saved a year in the UK. This would result in a reduction in disability and major cost savings both to individuals, their families and the Health Service. The blood pressure levels and control of blood pressure in many countries are similar to those in the UK, so the reductions in stroke and ischaemic heart disease worldwide, if the same control of high blood pressure could be obtained, would be immense.

Adult↗
PubMed2003

Rarefaction of skin capillaries in normotensive offspring of individuals with essential hypertension.

BACKGROUND: Rarefaction of skin capillaries in people with intermittent borderline essential hypertension suggests a primary or an early abnormality that may antedate the onset of sustained hypertension. OBJECTIVE: To compare skin capillary density in subjects with and without a family history of essential hypertension. SUBJECTS: 21 normotensive individuals, one or both of whose parents had essential hypertension (mean age 39.3 years; blood pressure 124/79 mm Hg); 21 normotensive controls with no family history of hypertension (age 46.3 years; blood pressure 124/78 mm Hg). METHODS: The skin of the dorsum of the fingers was examined by intravital capillary microscopy before and after venous congestion at 60 mm Hg for two minutes. RESULTS: By analysis of variance, both baseline and maximum skin capillary density were lower in subjects with a family history of essential hypertension than in those with no family history (baseline: 67 v 79 capillaries per field, p = 0.008; maximum: 74 v 93 capillaries per field, p < 0.0005). CONCLUSIONS: Capillary rarefaction in essential hypertension may occur before the increase in blood pressure and could, at least in part, reflect a primary rather than a secondary abnormality.

Adult↗
PubMed2003

Potassium: more beneficial effects.

Over 70 years ago, potassium was found to have a natriuretic effect and was used in patients with heart failure. However, it took many years for its role in the control of blood pressure to be recognized. Recently, epidemiological and clinical studies in man and experimental studies in animals have shown that increasing potassium intake towers blood pressure and that communities with a high potassium intake tend to have lower population blood pressures. Several studies have shown an interaction between salt intake and potassium intake. However, the recent DASH-Sodium (Dietary Approaches to Stop Hypertension) study demonstrates an additive effect of a low salt and high potassium diet on blood pressure. Increasing potassium intake may have other beneficial effects, for example, reducing the risk of stroke and preventing the development of renal disease independent of its effect on blood pressure. A high potassium intake reduces calcium excretion and could play an important role in the management of hypercalciuria and kidney stone formation, as well as bone demineralization. Potassium intake may also play an important role in carbohydrate intolerance. A reduced serum potassium increases the risk of lethal ventricular arrhythmias in those at risk, i.e. patients with ischemic heart disease, heart failure or left ventricular hypertrophy, and increasing potassium intake may prevent this. In this article, we address the evidence for the important role of potassium intake in regulating blood pressure and other beneficial effects of potassium which may be independent of and additional to its effect on blood pressure.

Animals↗
PubMed2002

Harmful effects of dietary salt in addition to hypertension.

In addition to raising the blood pressure dietary salt is responsible for several other harmful effects. The most important are a number which, though independent of the arterial pressure, also harm the cardiovascular system. A high salt intake increases the mass of the left ventricle, thickens and stiffens conduit arteries and thickens and narrows resistance arteries, including the coronary and renal arteries. It also increases the number of strokes, the severity of cardiac failure and the tendency for platelets to aggregate. In renal disease, a high salt intake accelerates the rate of renal functional deterioration. Apart from its effect on the cardiovascular system dietary salt has an effect on calcium and bone metabolism, which underlies the finding that in post-menopausal women salt intake controls bone density of the upper femur and pelvis. Dietary salt controls the incidence of carcinoma of the stomach and there is some evidence which suggests that salt is associated with the severity of asthma in male asthmatic subjects.

Cardiovascular Diseases↗
PubMed2002

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 approximately 10 to approximately 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 approximately 14% and coronary deaths by approximately 9% in hypertensives, and reduce stroke and coronary deaths by approximately 6 and approximately 4%, in normotensives, respectively.

Blood Pressure↗
PubMed2002

Sodium and blood pressure.

The human race is genetically programmed to consume less than 1 g of salt per day. In most human populations, the diet contains 6 to 12 g of salt per day and, in contrast to populations that consume less than 3 g of salt per day, their blood pressure rises with age. Independent of the rise in blood pressure, a high-salt diet also increases left ventricular mass, incidence of strokes, stiffness of conduit arteries, and activity of resistance arteries. In populations with high salt intake, a modest reduction in salt intake lowers blood pressure and diminishes cardiovascular disease and mortality.

Blood Pressure↗
PubMed2002

Percutaneous transluminal renal artery angioplasty: who benefits most?

We set out to assess the long-term benefits of renal percutaneous transluminal angioplasty (PTA) in 107 consecutive hypertensive patients with atheromatous renal artery stenosis. During 12-month follow-up, blood pressure fell to normal levels in 10 (8.8%) patients and improved in 76 (67.3%); renal function improved or remained stable in 74% of patients. In patients with atheromatous disease, renal angioplasty was most successful in those with stenosis in a single functioning kidney, and in nine patients who presented with symptoms and signs of heart failure, in the absence of overt ischaemic or valvular heart disease. In the latter group, renal PTA resulted in a large loss of sodium and water, resolution of the 'apparent' heart failure, and a marked improvement in blood pressure and renal function. It is suggested that all hypertensive patients with haemodynamically significant renal artery stenosis (and/or mild to moderate impairment in renal function), should be considered for renal PTA. Patients with atheromatous stenosis in a single functioning kidney, and those who present with signs of sodium and water retention, are likely to benefit most.

Adult↗
PubMed2001

T594M and G442V polymorphisms of the sodium channel beta subunit and hypertension in a black population.

Polymorphisms of the epithelial sodium channel may raise blood pressure by increasing renal sodium reabsorption. This study examines frequency distributions and associations with hypertension of the T594M and of the G442V polymorphisms of the beta subunit of the epithelial sodium channel in a population-based sample. We studied a stratified random sample of 459 subjects (279 women), aged 40-59 years, of black African origin from general practices' lists within a defined area of South London. All were first generation immigrants. The polymorphic variants were detected using single strand conformational polymorphism technique (SSCP). The prevalence of hypertension (BP > or =160 and/or 95 mm Hg or on drug therapy) was 43%; of these, 76% were on drug therapy. The main analysis was carried out by three ordered blood pressure categories (I to III) according to increasing blood pressure and presence or absence of drug therapy. The frequency of the 594M variant (heterozygotes and homozygotes) was 4.6%; the frequency of the 442V variant was higher (27.0%). The frequency of the 594M variant increased with increasing blood pressure category (P = 0.05) and was more common in hypertensives than normotensives. By contrast the frequency of the 442V variant did not vary across increasing blood pressure categories (P = 0.62). No gender difference was observed. Adjustment for age, sex and body mass index did not alter these findings. These results suggest that the 594M variant may contribute to high blood pressure in black people of African origin whereas the G442V polymorphism is unlikely to influence blood pressure in this population.

Adult↗
PubMed2001

Platelet sodium-hydrogen exchanger activity and left ventricular mass.

INTRODUCTION: The sodium-hydrogen exchanger (NHE) is integral to the processes that facilitate cell growth and may contribute to the development of left ventricular hypertrophy. The aim of this study was to examine the relationship between platelet sodium-hydrogen exchanger activity and left ventricular mass index (LVMI). METHODS: Twenty male untreated Caucasians (mean age +/- s.d.: 48 +/- 13; body mass index: 29 +/- 4 kg/m(2)) with a wide range of blood pressures were studied (mean BP: 152 +/- 22/93 +/- 15 mm Hg; range: 115-190/61-117 mm Hg). Sodium-hydrogen exchanger activity was determined as the rate of sodium-dependent recovery of intracellular pH in isolated platelets loaded with BCECF and acidified to pH 6.25 using nigericin. LVMI was calculated from measurements made by M-mode echocardiography. Associations between continuous variables were examined using parametric tests. RESULTS: The mean rate of pHi recovery was 0.15 +/- 0.03 dpHi/s (range: 0.09-0.21). Mean LVMI was 120 +/- 32 g/m(2) (range: 56-178) and was not significantly correlated with either systolic (r = 0.39, P = 0.09) or diastolic blood pressure (r = 0.27, P = 0.3). Platelet NHE activity was not significantly correlated with LVMI (r = 0.06; P = 0.8). Platelet NHE activity was not significantly different between subjects with (n = 7 with LVMI >131 g/m(2)) and without left ventricular hypertrophy (n = 13). CONCLUSIONS: The results of this study show that platelet NHE activity is not significantly correlated with LVMI. These data contrast with previously described correlations of LVMI with exchanger activity measured in leucocytes and erythrocytes; and indicate that the relationship between LVMI and exchanger activity may be specific to the cell type in which exchanger activity is measured.

Adult↗
PubMed2001

Blood pressure: importance of the kidney and the need to reduce salt intake.

The height of the blood pressure is one of the most important determinants of strokes and heart attacks, the two most common causes of death and disability in the western world. In undeveloped communities that do not have access to salt, blood pressure remains low throughout life in comparison with that in developed countries, where blood pressure is higher and increases inexorably with increasing age. An understanding of why blood pressure increases could lead to better preventive strategies, and thereby to a major reduction in cardiovascular disease. Much evidence suggests that salt intake plays an important role in elevating blood pressure. At the same time, elegant cross-transplantation experiments on inherited hypertension in rats and more circumstantial evidence in humans suggests that an inherited abnormality in the kidney, combined with our high salt intake, is likely to explain the development of high blood pressure in individuals. At the same time, studies now show that modest reductions in salt intake cause large decreases in blood pressure in hypertensive individuals and smaller, but very important from a public health perspective, decreases in blood pressure in normotensive people. A large effort is now required to persuade the salt, soft drink, and food manufacturers to reduce the unnecessarily high salt content of processed food.

Animals↗