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Purpose of Review: High dietary sodium is estimated to be the leading dietary risk for death attributed to 1.8 million deaths in 2019. There are uniform recommendations to reduce sodium consumption based on evidence that increased dietary sodium is responsible for approximately a third of the prevalence of hypertension, and meta-analyses of randomized controlled trials show that sodium reduction lowers blood pressure, cardiovascular disease, and total mortality. Nevertheless, there is a perception that the beneficial effect of reducing dietary sodium is controversial. We provide experiential evidence relating to some sources of the controversy and propose potential solutions., Recent Findings: Inappropriate research methodology, lack of rigor in research, conflicts of interest and commercial bias, questions of professional conduct, and lack of policies to protect public interests are likely to contribute to the controversy about reducing dietary sodium. There is a failure to protect policies to reduce dietary sodium from nonscientific threats. Significant efforts need to be made to ensure the integrity of nutritional research and maintain public trust., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: High sodium intake was an established risk factor for stroke and cardiovascular diseases. The objective of this study was to investigate factors associated with high sodium intake based on 24-h urinary sodium excretion from the MyCoSS study., Methods: The cross-sectional survey was conducted among adults aged 18 years and above in Malaysia. A multi-stage stratified sampling was used to represent nationally. Twenty-four-hour urine was collected from a total of 900 respondents. Indirect ion-selective electrode (ISE) method was used to measure sodium intake. Descriptive and logistic regression analysis was applied to determine factors associated with high sodium intake based on 24-h urinary sodium excretion., Results: A total of 798 respondents (76% response rate) completed the 24-h urine collection process. Logistic regression revealed that high sodium intake associated with obese [aOR 2.611 (95% CI 1.519, 4.488)], male [aOR 2.436 (95% CI 1.473, 4.030)], having a waist circumference of > 90cm for adult males [aOR 2.260 ( 95% CI 1.020, 5.009) and >80cm for adult females [aOR 1.210 (95% CI 0.556, 2.631)], being a young adult [aOR 1.977 (95% CI 1.094, 3.574)], and living in urban areas [aOR 1.701 (95% CI 1.094, 2.645)]., Conclusion: Adults who are obese, have a large waist circumference, of male gender, living in urban areas, and belonging to the young adult age group were found to have higher sodium intake than other demographic groups. Hence, reduction of salt consumption among these high-risk groups should be emphasised to reduce the risk of cardiovascular diseases.

Background: Hypertension is one of the most common risk factors for cardiovascular disease and leading cause of mortality globally. The aims of this study were to assess the prevalence of hypertension and its associated risk factors among Malaysian population using data from the Malaysian Community Salt Study (MyCoSS)., Methods: This study was a cross-sectional study using multi-stage stratified sampling method. Data collection was carried out via face-to-face interview at the respondent's home from October 2017 until March 2018. A total of 1047 respondents aged 18 years and above completed the questionnaires and blood pressure measurement. A person who reported diagnosis of hypertension by a physician and had systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg on three readings was categorised as hypertensive. Risk factors of hypertension were analysed using multiple logistic regression., Results: The prevalence of hypertension in the present study was 49.39% (95% CI 44.27-54.51). There was no statistically significant difference in gender. Age, household income, BMI, and diabetes were significantly associated with hypertension. Hypertension found had inverse association with the level of education. Age was the strongest predictor of hypertension (35-44 years old; OR=2.39, 95% CI=1.39-4.09, 45-54 years old; OR=5.50, 95% CI=3.23-9.38, 55-64 years old OR=13.56, 95% CI=7.77-23.64 and 65 years old and above; OR=25.28, 95% CI=13.33-48.66). Those who had higher BMI more likely to be hypertensive as compared to respondents with normal weight (overweight, OR=1.84; 95% CI=1.18-2.86; obese, OR=4.29% CI=2.56-7.29)., Conclusion: The findings showed that hypertension is prevalent among adults in Malaysia. Those with older age, higher BMI, and diabetes are more likely to have hypertension. Efforts regarding lifestyle modification and education could be important in hypertension management and prevention.

Introduction: The scientific evidence base in support of salt reduction is strong but the data required to translate these insights into reduced population salt intake are mostly absent. The aim of this research project is to develop the evidence base required to formulate and implement a national salt reduction programme for India., Methods and Analysis: The research will comprise three components: a stakeholder analysis involving government, industry, consumers and civil society organisations; a population survey using an age-stratified and sex-stratified random samples drawn from urban (slum and non-slum) and rural areas of North and South India; and a systematic quantitative evaluation of the nutritional components of processed and restaurant foods. The stakeholder interviews will be analysed using qualitative methods to summarise the main themes and define the broad range of factors influencing the food environment in India. The population survey will estimate the mean daily salt consumption through the collection of 24 h urine samples with concurrent dietary surveys identifying the main sources of dietary sodium/salt. The survey of foods will record the nutritional composition of the chief elements of food supply. The findings from this research will be synthesised and proposals for a national salt reduction strategy for India will be developed in collaboration with key stakeholders., Ethics and Dissemination: This study has been approved by the Human Research Ethics Committees of the University of Sydney and the Centre for Chronic Disease Control in New Delhi, and also by the Indian Health Ministry's Screening Committee. The project began fieldwork in February 2014 and will report the main results in 2016. The findings will be targeted primarily at public health policymakers and advocates, but will be disseminated widely through other mechanisms including conference presentations and peer-reviewed publications, as well as to the participating communities., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The United Kingdom has successfully implemented a salt reduction programme. We carried out a comprehensive analysis of the programme with an aim of providing a step-by-step guide of developing and implementing a national salt reduction strategy, which other countries could follow. The key components include (1) setting up an action group with strong leadership and scientific credibility; (2) determining salt intake by measuring 24-h urinary sodium, identifying the sources of salt by dietary record; (3) setting a target for population salt intake and developing a salt reduction strategy; (4) setting progressively lower salt targets for different categories of food, with a clear time frame for the industry to achieve; (5) working with the industry to reformulate food with less salt; (6) engaging and recruiting of ministerial support and potential threat of regulation by the Department of Health (DH); (7) clear nutritional labelling; (8) consumer awareness campaign; and (9) monitoring progress by (a) frequent surveys and media publicity of salt content in food, including naming and shaming, (b) repeated 24-h urinary sodium at 3-5 year intervals. Since the salt reduction programme started in 2003/2004, significant progress has been made as demonstrated by the reductions in salt content in many processed food and a 15% reduction in 24-h urinary sodium over 7 years (from 9.5 to 8.1 g per day, P<0.05). The UK salt reduction programme reduced the population's salt intake by gradual reformulation on a voluntary basis. Several countries are following the United Kingdom's lead. The challenge now is to engage other countries with appropriate local modifications. A reduction in salt intake worldwide will result in major public health improvements and cost savings.

High dietary salt is a major contributor to increased blood pressure, the leading risk for death worldwide. In several countries, national programmes to reduce dietary salt have been implemented with leadership and involvement of hypertension experts. Other hypertension experts may be interested in assisting or leading a national programme to reduce dietary salt, however, may not have the experience or training to do so. The article is based on the experiences of three hypertension experts who have led the development of national dietary salt reduction programmes in the United Kingdom, Australia and Canada. The article advises developing leadership and a coalition, conducting a nation-specific environmental scan of facilitators and barriers, estimating the national health and financial costs of high dietary salt and the benefits of reducing salt intake, obtaining core documents to provide the scientific rational for the programme, developing a policy statement to outline the required actions to be undertaken, engaging government and industry, using media to gain public support, overcoming industry supported opposition and sustaining the effort long term. Resources and potential sources for international collaboration are provided as well as caveats for developing the programme within the specific nations' context and overall effort to improve health. Developing and leading a national salt reduction programme is a major commitment, however, reducing dietary salt is estimated to be one of the most effective strategies to improve a nation's health.

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.

Objectives: Hypertension has been associated with impaired cognition. Diffusion tensor imaging (DTI) and magnetic resonance spectroscopy were applied to assess white matter abnormalities in treated vs untreated hypertension and if these correlated with neuropsychological performance., Methods: Subjects were 40 patients with medically treated hypertension (mean age 69.3 years), 10 patients with untreated hypertension (mean age 57.6 years) and 30 normotensive controls (mean age 68.2 years). Hypertension was defined as a previous diagnosis and taking hypertensive medication, or a resting blood pressure of >140/90 mmHg on the day of assessment., Results: Patients with treated hypertension performed worse on immediate (P = 0.037) as well as delayed memory tasks (P = 0.024) compared with normotensive controls. Cognitive performance was worse in untreated compared with treated hypertension on executive functions (P = 0.041) and psychomotor speed (P = 0.003). There was no significant correlation between cognition and any of the imaging parameters in treated hypertension. However, in untreated hypertension the results revealed a positive correlation between an executive functioning and attention composite score and DTI mean diffusivity values (P = 0.016) and between psychomotor speed and spectroscopy NAA/tCr levels (P = 0.015)., Conclusions: These results suggest there is cognitive impairment in hypertension. Treated hypertension was associated with deficits in memory while untreated hypertension revealed a more 'subcortical' pattern of cognitive impairment.

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.

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.

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.

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.

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.

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.

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.

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.

Background: Several studies in isolated cells have reported that intracellular pH (pHi) in individuals with essential hypertension may be relatively alkaline compared to normotensive individuals. Such an abnormality of pHi in hypertension would be consistent with enhanced sodium-hydrogen exchanger activity and may provide potential mechanisms by which hypertension and its complications could develop., Objectives: To determine in-vivo intracellular pH of skeletal muscle at rest and during recovery from exercise-induced acidosis in hypertensive and normotensive subjects., Methods: Using 31-phosphorus magnetic resonance spectroscopy, pHi of the dominant flexor digitorum superficialis was measured in 20 Caucasian subjects (14 male) with essential hypertension and 20 normotensive controls matched for gender, age, race and body mass index. Measurements were made at rest and during the exercise and recovery periods of a stepped incremental maximal exercise protocol. The rate of pHi recovery from exercise-induced acidosis was calculated by linear regression over the first 210 s of recovery from the pHi time plots of respective subjects., Results: Mean resting pHi in the hypertensive (7.05 +/- 0.04) and normotensive groups (7.06 +/- 0.04) were not significantly different. There was a significant effect of gender on pHi: mean pHi was 7.07 +/- 0.03 in males and 7.02 +/- 0.03 in females, respectively (P < 0.0005). The mean intracellular pH achieved by exercise was 6.74 +/- 0.31 in hypertensive individuals and not significantly different in normotensive individuals (6.68 +/- 0.19; P = 0.4). The mean rate of pHi recovery in the hypertensives was 0.08 +/- 0.03 pH units/min and not significantly different in normotensives (0.08 +/- 0.02; P = 0.4)., Conclusions: These results contrast with previously documented abnormalities in the control of pHi in hypertension and demonstrate the absence of major in-vivo disturbances of pHi in skeletal muscle, both at rest and during recovery from exercise-induced acidosis, in essential hypertension. Therefore, it is possible that previously documented abnormalities of pHi and activity of the exchanger may be either specific to cell type or not present under in-vivo conditions.

Hypertensive (n=93) and normotensive (n=39) white individuals were given a high sodium intake of approximately 350 mmol/d for 5 days followed by a low sodium intake of 10 to 20 mmol/d for 5 days. With this acute and large reduction in salt intake, no significant change was seen in blood pressure in the normotensive individuals, but blood pressure decreased in the hypertensive individuals. Compared with normotensive subjects, hypertensive patients had a 7/7-mm Hg greater fall in blood pressure (P<0.05 for systolic and P<0.01 for diastolic, adjusted for age), with similar changes in urinary sodium excretion. From the high-salt to low-salt diet, plasma renin activity rose from 0.90 to 5.99 ng. mL(-1). h(-1) in normotensives, whereas in hypertensives it rose from 0.73 to only 3.14 ng. mL(-1). h(-1) (P<0.05 between hypertensives and normotensives). Plasma aldosterone rose by 1396 pmol/L in normotensive subjects and by 511 pmol/L in hypertensive patients (P<0.05). Significant inverse correlations were obtained for all subjects between the fall in blood pressure from the high-salt to low-salt diet and the rise in plasma renin activity and aldosterone that occurred in addition to the absolute level on the low-salt diet. These results demonstrate that the larger fall in blood pressure with an acute reduction in salt intake in hypertensives compared with normotensives is, at least in part, due to a less-responsive renin-angiotensin-aldosterone system in the hypertensive patients.

Salt-sensitive hypertension is more common and has more severe consequences in urban black populations than in white populations. Increased renal sodium reabsorption through epithelial sodium channels may underlie the development of high blood pressure in black people. Increased sodium channel activity has been detected in subjects with Liddle's syndrome by nasal potential difference measurements. Nasal potential difference measurements were made in 39 black normotensive, 106 black hypertensive, 51 white normotensive, and 61 white hypertensive subjects. Blood pressure, body mass index, and 24-hour urinary sodium excretion were also measured. Maximum potential difference was significantly higher in black subjects than in white subjects (P=0.009) but was not significantly different between normotensive and hypertensive subjects after adjustment for age, gender, current smoking status, body mass index, and 24-hour urinary sodium excretion (black normotensive, -21.6+/-1.0 mV; black hypertensive, -21.5+/-0.7 mV; white normotensive, -18.5+/-1.0 mV; and white hypertensive subjects, -18.9+/-0.9 mV). Nasal potential difference did not correlate with blood pressure or biochemical variables within ethnic and blood pressure groups. Nasal potential difference, an index of nasal sodium channel activity, is greater in black than in white people but does not differ between normotensive and hypertensive groups. Increased nasal potential difference measurements may reflect generalized upregulation of sodium transport in black people compared with white people, which may help to explain the high prevalence of hypertension in black people but would not explain differences in blood pressure within separate ethnic groups.

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.

Salt-sensitive hypertension is common in people of African origin, and may be caused by increased transepithelial sodium absorption. The pH of nasal secretions is negatively correlated with the difference in Na(+) concentration between nasal secretions and plasma, and may be a marker of transepithelial sodium absorption. Nasal pH was measured using a probe sited under the inferior turbinate. Measurements of nasal pH were reproducible, with a coefficient of variation of 3.3% for repeated measurements on the same day and of 2.7% between measurements on different days. Nasal pH did not correlate with nasal potential difference, a measure of transepithelial sodium absorption. Nasal pH was significantly lower in 89 black individuals (24 normotensive and 65 hypertensive) than in 51 white individuals (26 normotensive and 25 hypertensive) (black normotensive. 6.44+/-0.08; black hypertensive, 6.62+/-0.05; white normotensive, 6.91+/-0.06; white hypertensive, 6.98+/-0.06), after adjustment for age, gender, current smoking status, body mass index and 24 h urinary sodium excretion (P=0.002), but was not significantly different between the normotensive and hypertensive individuals. Nasal pH was more acidic in black than in white individuals, which may represent generalized up-regulation of sodium transport in black people. However, the lack of correlation between nasal pH and potential difference suggests that nasal pH is, at best, only weakly related to transepithelial sodium absorption. Ethnic differences in nasal pH may be of direct relevance in the airways, as many of the functions of airway surface liquid are dependent on pH.

This multicenter study evaluated the efficacy of candesartan cilexetil, an angiotensin II type 1 receptor antagonist, used alone or in combination with amlodipine or in combination with amlodipine and hydrochlorothiazide in the treatment of patients with moderate-to-severe essential hypertension. After a 2-week, single-blind, placebo run-in period, patients entered a 12-week, open-label, dose-titration period. The candesartan cilexetil dose was increased from 8 to 16 mg once daily; amlodipine (5 mg once daily), hydrochlorothiazide (25 mg once daily), and additional medication were also added sequentially if necessary. Patients then entered a final 4-week, parallel-group, double-blind, randomized, placebo-controlled withdrawal period of candesartan alone. A total of 216 patients were recruited. After a 2-week run-in period on placebo tablets, mean sitting blood pressure (BP) was 175/108 mm Hg. At the end of the 12-week dose-titration/maintenance period, mean sitting BP fell to 141/88 mm Hg. In 67 patients who were randomized to placebo and had their candesartan withdrawn, there was a highly significant increase in mean systolic/diastolic BP (13/6 mm Hg) compared with those patients who continued with candesartan (ANCOVA, P:<0.0001). In conclusion, candesartan cilexetil is an effective BP-lowering drug when used alone or in combination with amlodipine or amlodipine plus hydrochlorothiazide in the treatment of moderate-to-severe essential hypertension. The drug was well tolerated throughout the investigation period.

Abnormalities in acid-base regulation have previously been reported both in hypertensive humans and animals and a link between abnormalities in renal sodium handling and acid excretion may be particularly important in black hypertensives. The objectives of this study were to compare indices of urinary acid excretion (urinary pH, ammonium and titratable acid excretion) between normotensives and hypertensive people of African origin. Measurements were carried out in 86 black individuals of African origin in a case-control design (19 normotensive; 67 hypertensive). Of these, 17 normotensive and 17 patients with essential hypertension were matched for age, sex and weight. Group comparisons were carried out by unpaired t-tests or two-way analysis of variance and group values are given as means +/- s.d. Urinary pH was significantly higher in the hypertensives both in the unmatched groups and in the matched groups. In the 17 matched pairs: urinary pH in the hypertensive individuals was 6.36 +/- 0.54 and 5.84 +/- 0. 53 in the normotensives, respectively; P = 0.007. Additionally, urinary titratable acidity was significantly lower in the hypertensives than in the normotensives (25.4 +/- 13.7 vs16.7 +/- 10. 7 mmol/24 h; P = 0.047) but there were no significant differences in urinary ammonium excretion. The mechanisms for the apparent reduction in acid excretion in the hypertensives is not clear but these results highlight the possibility that hypertension in blacks is associated with abnormalities of renal sodium and hydrogen exchange with compensatory increases in renal ammonium production.

Objective: To report on renal artery stenosis presenting as congestive heart failure., Design: Case series., Setting: Tertiary referral centre., Patients: Nine hypertensive subjects (five male, four female) seen in the blood pressure unit, St George's Hospital, between 1991 and 1997 with clinical signs and symptoms of congestive cardiac failure but without overt coronary or valvar heart disease. Mean (SEM) age was 67 (3) years. Eight patients had renal artery revascularisation with percutaneous angioplasty and one had surgery., Results: Renal revascularisation was followed by a large fall in blood pressure from 191/94 (7/3) to 150/75 (8/5) mm Hg two days after intervention (p < 0.01). There was also a large natriuresis and weight reduction. One week after revascularisation there was a mean loss in weight of 3.8 (0.6) kg. The largest fall in weight was seen in those patients with stenosis in a single functioning kidney. Furthermore, plasma atrial natriuretic factor fell from 120 (28) to 48 (9) pg/ml (p < 0.05; n = 6; normal value = 8.6 (0.8) pg/ml), and serum creatinine fell from 200 (37) to 140 (11) micromol/l (p < 0. 025). The clinical signs and symptoms of heart failure resolved and the diuretics were then withdrawn in all patients. On long term follow up, patients remained free from symptoms and signs of heart failure and the blood pressure was better controlled., Conclusions: In hypertensive patients with symptoms and signs of congestive heart failure who do not have obvious ischaemic or valvar heart disease, renal artery stenosis should be considered as a possible underlying cause. Relief of the stenosis can result in resolution of the apparent heart failure.

Aims: Previous studies have reported tight linkage disequilibrium between the T235 and the A(-6) molecular variants of the angiotensinogen gene. This study was designed primarily to ascertain whether a similar relationship exists between the M235 and the G(-6) variants of the gene. We have investigated the degree of agreement between the genotypes of the M235T and the G(-6)A polymorphisms in two ethnic groups., Methods: Subjects were an heterogeneous group of normotensive and hypertensive subjects of Caucasian (n = 77) and Afro-Caribbean (n = 51) origin. DNA was extracted from whole blood and was genotyped for both the M235T and G(-6)A polymorphisms using PCR-based methods., Results: The distribution frequencies of the MM, MT, and TT genotypes were 0.39, 0.42, and 0.20 in white subjects, and 0.09, 0.17, and 0.74 in black subjects, respectively (chi-square, P < 0.0001). The distribution of AA, GA, and GG genotypes also differed between the two groups as follows: 0.22, 0.48, and 0.30 in white subjects, and 0.82 and 0.18 and 0 in black subjects respectively (chi-square, P < 0.0001). The agreement for TT-AA, MT-GA, and MM-GG was 93%, 91%, and 76% respectively in white and 100%, 67% and 0% respectively in black subjects., Conclusions: The results indicate ethnic differences in the distribution of both M235T and G(-6)A genotypes. The trend towards a decrease in the degree of agreement in the order of TT-AA > MT-GA > MM-GG suggests that linkage disequilibrium between the M235 and G-6 variant does not mirror that observed with the T235 and A-6 variants. These observations may have significant implications regarding the associations between the G(-6)A polymorphism and hypertension. However, this needs to be further investigated.

We recently showed that rarefaction of skin capillaries in the dorsum of the fingers of patients with essential hypertension is due to the structural (anatomic) absence of capillaries rather than functional nonperfusion. It is not known whether this rarefaction is primary (ie, antedates the onset of hypertension) or secondary (ie, as a consequence of sustained and prolonged elevation of blood pressure [BP]). The aim of the present investigation was to study skin capillary density in a group of patients with mild borderline hypertension to assess whether rarefaction antedates the onset of sustained elevation of BP. The study group included 18 patients with mild borderline hypertension (mean supine BP, 136/83 mm Hg), 32 normotensive controls (mean BP, 126/77 mm Hg), and 45 patients with established essential hypertension (mean BP, 156/98 mm Hg). The skin of the dorsum of the fingers was examined by intravital capillary videomicroscopy before and after venous congestion at 60 mm Hg for 2 minutes. Patients with borderline essential hypertension had the lowest resting capillary density when compared with normotensive controls and patients with established hypertension. Maximal capillary density with venous congestion in the borderline group remained the lowest. The study confirmed that patients with borderline essential hypertension have skin capillary densities that are equally low as or even lower than patients with established hypertension. Both groups had significantly lower capillary densities than normal controls. One explanation for the results is that capillary rarefaction may be due to an early structural abnormality in essential hypertension.

Intravital capillary video-microscopy is a dynamic method for studying skin capillaries. The technique of direct intravital microscopy (without dyes) depends on the presence of red blood cells inside capillaries for their identification. The aim of the present study was to compare different techniques to try to establish the best method for maximizing the number of visible perfused capillaries during intravital capillary microscopy. We compared the effects of venous congestion with those of post-occlusive reactive hyperaemia (Study 1). We also investigated venous congestion followed first by post-occlusive reactive hyperaemia and then by a core heat load test (Study 2). Finally we investigated venous congestion followed by post-occlusive reactive hyperaemia combined with venous congestion (Study 3). In Study 1, capillary density increased with venous congestion from a baseline value of 74+/-2 (mean+/-S.E.M.) per field to 82+/-3 per field (P<0.0001; analysis of variance). With reactive hyperaemia, there was an apparent decrease in visible capillary density to 69+/-2 per field. In Study 2, baseline capillary density was 69+/-4 per field, and this increased significantly with venous congestion to 74+/-4 per field (P=0.01). With both reactive hyperaemia and core heat load, the apparent density was 62+/-4 per field. In Study 3 the baseline density was 70+/-2 per field, and this increased significantly with venous congestion to 80+/-3 per field (P<0.0001). With reactive hyperaemia combined with venous congestion, the density was 81+/-3 per field (P=0.328 compared with venous congestion alone). The results show that venous congestion at 60 mmHg for 2 min is the most effective method for visualization of the maximal number of perfused skin capillaries during intravital video-microscopy.

Use non-pharmacological measures in all hypertensive and borderline hypertensive people. Initiate antihypertensive drug therapy in people with sustained systolic blood pressures (BP) >/=160 mm Hg or sustained diastolic BP >/=100 mm Hg. Decide on treatment in people with sustained systolic BP between 140 and 159 mm Hg or sustained diastolic BP between 90 and 99 mm Hg according to the presence or absence of target organ damage, cardiovascular disease or a 10-year coronary heart disease (CHD) risk of >/=15% according to the Joint British Societies CHD risk assessment programme/risk chart. In people with diabetes mellitus, initiate antihypertensive drug therapy if systolic BP is sustained >/=140 mm Hg or diastolic BP is sustained >/=90 mm Hg. In non-diabetic hypertensive people, optimal BP treatment targets are: systolic BP <140 mm Hg and diastolic BP <85 mm Hg. The minimum acceptable level of control (Audit Standard) recommended is <150/<90 mm Hg. Despite best practice, these levels will be difficult to achieve in some hypertensive people. In diabetic hypertensive people, optimal BP targets are; systolic BP <140 mm Hg and diastolic BP <80 mm Hg. The minimum acceptable level of control (Audit Standard) recommended is <140/<90 mm Hg. Despite best practice, these levels will be difficult to achieve in some people with diabetes and hypertension. In the absence of contraindications or compelling indications for other antihypertensive agents, low dose thiazide diuretics or beta-blockers are preferred as first-line therapy for the majority of hypertensive people. In the absence of compelling indications for beta-blockade, diuretics or long acting dihydropyridine calcium antagonists are preferred to beta-blockers in older subjects. Compelling indications and contraindications for all antihypertensive drug classes are specified. For most hypertensives, a combination of antihypertensive drugs will be required to achieve the recommended targets for blood pressure control. Other drugs that reduce cardiovascular risk must also be considered. These include aspirin for secondary prevention of cardiovascular disease, and primary prevention in treated hypertensive subjects over the age of 50 years who have a 10-year CHD risk >/=15% and in whom blood pressure is controlled to the audit standard. In accordance with existing British recommendations, statin therapy is recommended for hypertensive people with a total cholesterol >/=5 mmol/L and established vascular disease, or 10-year CHD risk >/=30% estimated from the Joint British Societies CHD risk chart. Glycaemic control should also be optimised in diabetic subjects. Specific advice is given on the management of hypertension in specific patient groups, ie, the elderly, ethnic subgroups, diabetes mellitus, chronic renal disease and in women (pregnancy, oral contraceptive use and hormone replacement therapy). Suggestions for the implementation and audit of these guidelines in primary care are provided.

Increased activity of sodium/hydrogen exchange provides a potentially important mechanism for the development of hypertension. The aims of this study were to compare platelet sodium/hydrogen exchanger activity and renal acid-base excretion in normotensives and hypertensives of Caucasian origin. Platelet intracellular pH (pHi) was measured using the fluorescent dye BCECF to monitor intracellular pH. Sodium/hydrogen exchanger activity was estimated from the recovery of pHi clamped to 6.25 with nigericin. Normotensives had supine blood pressures of < 140 and < 90 mmHg; those with essential hypertension had blood pressures > 150/95 mmHg with no known secondary cause. Measurements of platelet pHi and sodium/hydrogen exchanger activity were made on 26 normotensives (ten female, sixteen male) and 25 hypertensives (five female, twenty male). All subjects were on their usual dietary sodium intake. Statistical analysis was by two-way analysis of variance for gender and blood pressure status. Group values are expressed as means+/-SD and a P value of < 0.05 was taken as being statistically significant. There were no significant differences in platelet pHi between the normotensive (n = 26) and the hypertensive (n = 25) group: pHi 7.21+/-0.14 and 7.18+/-0.16, respectively. The pHi recovery after acidification was sodium-dependent and inhibited by N-hexamethylene amiloride. Comparison of kinetic constants showed no significant differences between the normotensive and the hypertensive groups: values for rate constants and initial velocities were 0.24+/-0.04 s(-1), 0.16+/-0.03 dpHi/s for the normotensives and 0.25+/-0.05 s(-1), 0.16+/-0.03 dpHi/s for the hypertensives, respectively; there were also no significant differences in proton fluxes. The inability to find raised platelet sodium/hydrogen exchanger in the hypertensives contrasts with previous observations using other methods for the measurement of this exchanger in platelets and this raises important methodological issues in the assessment of platelet sodium/hydrogen exchanger activity.

Abnormal renal sodium transport causing excess reabsorption of sodium may be one mechanism that causes high blood pressure. For example, increased activity of epithelial sodium channels in the distal tubule is the cause of high blood pressure in Liddle's syndrome, a rare familial form of hypertension. We have shown that the increase in sodium channel activity can be detected in the nose using transepithelial potential difference measurements in 1 family with Liddle's syndrome. We therefore used nasal potential difference measurements to look for increased sodium channel activity in white patients with essential hypertension. Transnasal potential difference was measured in 42 white hypertensive (HT) subjects and 38 white normotensive (NT) subjects before and after topical application of 10(-4) mol/L of amiloride. There was no difference in maximum potential between HT and NT subjects (HT, -18.8+/-0.9 mV; NT, -18.2+/-1.0 mV) (values mean+/-SEM; lumen-negative with respect to the submucosa). However, the postamiloride potential was significantly higher (HT, -12.6+/-0.7 mV; NT, -10.5+/-0.7 mV; P=0. 015) and the change in potential in response to amiloride significantly lower (HT, 6.2+/-0.5 mV, 33.1+/-2.0%; NT, 7.7+/-0.6 mV, 41.9+/-2.0%; P=0.046 and 0.003, respectively) in HT than in NT subjects. These results suggest that sodium channel activity is not increased in whites with essential hypertension and indicate that sodium channel overactivity similar to that seen in Liddle's syndrome is unlikely to be the cause of high blood pressure in this group. Increased postamiloride potential may reflect increased activity of chloride channels or amiloride-insensitive sodium channels.

A reduction in the density of capillaries (rarefaction) is known to occur in many tissues in patients with essential hypertension. This rarefaction may play a role in increasing peripheral resistance. However, the mechanism underlying this capillary rarefaction is not understood. The aim of this study was to assess the extent of structural versus functional capillary rarefaction in the skin of dorsum of fingers in essential hypertension. The capillary microcirculation was examined with video microscopy before and after maximizing the number of perfused capillaries by venous congestion. The study group comprised 17 patients with essential hypertension (mean supine blood pressure, 155/96 mm Hg) and 17 closely matched normotensive controls (mean blood pressure, 127/77 mm Hg). We used intravital video microscopy with an epi-illuminated microscope to examine the skin of the dorsum of left middle phalanx before and after venous congestion at 60 mm Hg for 2 minutes. A significantly lower mean capillary density occurred at baseline in hypertensive subjects versus normotensive subjects. With venous occlusion, capillary density increased significantly in both groups; however, maximal capillary density remained significantly lower in the hypertensive subjects than in the normotensive subjects. The study strongly suggests that much of the reduction in capillary density in the hypertensive subjects is caused by structural (anatomic) absence of capillaries rather than functional nonperfusion.

Seventy-one white and 33 black patients with essential hypertension were studied while on a high sodium intake of 350 mmol/d for 5 days and low sodium intake of 10 mmol/d for 5 days. The fall in blood pressure on changing from the high sodium to the low sodium diet was 17/6 mm Hg in whites and 22/10 mm Hg in blacks. Compared with whites, black patients had a 7-mm Hg greater fall (P<0.05) in systolic blood pressure and 4-mm Hg greater fall (P=0.068) in diastolic blood pressure (adjusted for age and blood pressure on the normal diet) with similar changes in urinary sodium excretion. With sodium restriction, plasma renin activity rose from 0.65 to 3.03 ng. mL-1. h-1 in whites, whereas in blacks it rose only from 0.3 to 1.28 ng. mL-1. h-1 (P<0.001 between blacks and whites). From the high to the low salt diet, plasma angiotensin II increased by 31 pmol/L in whites and by 12 pmol/L in blacks (P<0.05 compared with whites), and plasma aldosterone rose by 499 pmol/L in whites and by 256 pmol/L in blacks (P<0.01). Significant inverse correlations were obtained for all patients between the fall in systolic blood pressure from the high to low salt diet and the rise in plasma renin activity and angiotensin II, as well as the absolute level on the low salt diet. These results demonstrate that the larger fall in blood pressure with a reduction in salt intake in blacks is due at least in part to a less responsive renin-angiotensin-aldosterone system in blacks.

This study has examined the association between circulating atrial natriuretic peptide (ANP), plasma cyclic GMP and urinary cyclic GMP in relation to hypertension and reduced renal function in 30 normotensives, in 30 patients with essential hypertension and in 22 patients with stable dialysis-independent chronic renal failure (CRF). Plasma ANP was significantly raised (about two-three-fold) in the CRF group compared with the hypertensive and normal groups; plasma cyclic GMP was also significantly raised in the CRF group (median group values: 4.6, 5.8 and 11.0 pmol/ml, respectively, for the normal, hypertensive and CRF groups). There were no significant differences in urinary cyclic GMP between the normotensives and hypertensives but urinary cyclic GMP was significantly reduced in the patients with CRF (median group values: 407.1, 450.9 and 247.8 pmol/min for the normal, hypertensive and CRF groups, respectively, P < 0.001). In the subjects with CRF, the clearance of cyclic GMP was reduced in proportion to the clearance of creatinine, but there was no significant difference in the fractional excretion of cyclic GMP (median group values: 78.1% in the normal group, 78.9% in the hypertensive group and 70.2% in the CRF group). In all groups, there was no association between circulating ANP and urinary cyclic GMP: By contrast, there was a positive association between plasma ANP and plasma cyclic GMP (r = 0.39 P < 0.001) that was independent of blood pressure or renal function. These results demonstrate that while a substantial amount of urinary cyclic GMP originates from the glomerular filtrate, to some extent, raised plasma ANP also contributes to the circulating levels of cyclic GMP. However, plasma cyclic GMP cannot be taken as a direct substitute for plasma ANP.

In Liddle's syndrome, a rare inherited form of hypertension, epithelial sodium channel mutations appear to cause high blood pressure by increasing sodium reabsorption through sodium channels in the renal distal tubule. This increase in channel activity has not been confirmed previously by in vivo measurement. We have made transnasal potential difference measurements (effective in detection of increased sodium channel activity in cystic fibrosis) in three brothers with genetically proven Liddle's syndrome, their unaffected sister, and 40 normotensive controls. Maximum potential difference after 2 wk off treatment in the affected brothers was -30.4+/-1.2 mV (values mean+/-SD, lumen-negative with respect to submucosa) and was significantly more lumen-negative than that of the control group (-18.6+/-6.8 mV, P = 0.0228) or the unaffected sister (-18.25 mV, P < 0.01). The change in potential difference after topical application of 10(-)4 M amiloride was greater in the Liddle's patients, 14.0+/-2.1 mV, than in controls (7.9+/-3.9 mV, P = 0.0126) or the unaffected sister (5.5 mV, P < 0.05). This is the first in vivo demonstration of increased sodium channel activity in Liddle's syndrome. If these results are confirmed in other kindreds with this condition, then nasal potential difference measurements could provide a simple clinical test for Liddle's syndrome.

Background: Liddle's syndrome is a rare inherited form of hypertension in which mutations of the epithelial sodium channel result in increased renal sodium reabsorption. Essential hypertension in black patients also shows clinical features of sodium retention so we screened black people for the T594M mutation, the most commonly identified sodium-channel mutation., Methods: In a case-control study, 206 hypertensive (mean age 48.0 [SD 11.8] years, men:women 80:126) and 142 normotensive (48.7 [7.4] years; 61:81) black people who lived in London, UK, were screened for T594M. Part of the last exon of the epithelial sodium-channel beta subunit from genomic DNA was amplified by PCR. The T594M variant was detected by single-strand conformational polymorphism analysis of PCR products and confirmed by DNA sequencing., Findings: 17 (8.3%) of 206 hypertensive participants compared with three (2.1%) of 142 normotensive participants possessed the T594M variant (odds ratio [OR]=4.17 [95% CI 1.12-18.25], p=0.029). A high proportion of participants with the T594M variant were women (15 of 17 hypertensive participants and all three normotensive participants), whereas women comprised a lower proportion of the individuals screened (61.2% hypertensive, 57.7% normotensive). However, the association between the T594M variant and hypertension persisted after adjustment for sex and body-mass index (Mantel-Haenszel OR=5.52 [1.40-30.61], p=0.012). Plasma renin activity was significantly lower in 13 hypertensive participants with the T594M variant (median=0.19 ng mL(-1) h(-1)) than in 39 untreated hypertensive individuals without the variant (median=0.45 ng mL(-1) h(-1), p=0.009)., Interpretation: Among black London people the T594M sodium-channel beta subunit mutation occurs more frequently in people with hypertension than those without. The T594M variant may increase sodium-channel activity and could raise blood pressure in affected people by increasing renal tubular sodium reabsorption. These findings suggest that the T594M mutation could be the most common secondary cause of essential hypertension in black people identified to date.

Plasma and platelet levels of 5-hydroxytryptamine (5 HT) may be altered in essential hypertension. To establish the determinants and correlates of 5 HT in plasma and platelets, we studied 53 untreated subjects with essential hypertension (26 men; 30 whites; mean supine blood pressure 172/101 mm Hg; mean age 49.3 +/- 1.5 years) and 61 normotensive subjects (37 men; 47 whites; mean supine blood pressure 128/78 mm Hg; mean age 42.8 +/- 1.6 years). Plasma and platelet 5 HT were assayed by reverse-phase high performance liquid chromatography with electrochemical detection. No significant difference was found in platelet-poor plasma or platelet 5 HT levels in hypertensive or normotensive subjects (plasma: 43.0 +/- 4.2 and 39.6 +/- 4.4 nmol/L; platelet: 1.65 +/- 1.22 and 1.70 +/- 1.39 nmol/10(9) cells in hypertensive and normotensive subjects, respectively). No significant correlation was found between plasma or platelet 5 HT and systolic or diastolic blood pressure (plasma: r = 0.01 and 0.01 in normotensive subjects and r = 0.01 and -0.14 in hypertensive subjects; platelet: r = 0.12 and 0.13 in normotensive subjects and r = 0.02 and -0.09 in hypertensive subjects). However, plasma 5 HT was associated with supine and standing pulse rates (supine: r = 0.27, p = 0.05 in normotensive subjects and r = 0.54, p < 0.001 in hypertensive subjects; standing: r = 0.19 and r = 0.46, p < 0.001, respectively). Significant relations were also found between platelet 5 HT levels and supine and standing heart rate in the subjects mentioned above (supine: r = 0.28, p = 0.05 in normotensive subjects and r = 0.64, p < 0.001 in hypertensive subjects; standing: r = 0.24 and r = 0.51, p < 0.001, respectively). These associations were stronger in the hypertensive group as a whole, and they held when adjustment was made for differences in age and total blood cholesterol. The present study showed that plasma and platelet 5 HT are not significantly altered in hypertensive subjects. However, plasma and platelet 5 HT levels showed a significant association with supine and standing pulse rate predominantly in hypertensive subjects. This is consistent with experimental evidence of a positive chronotropic effect of 5 HT on perfused hearts and it suggests a possible role of plasma serotonin in the regulation of heart rate.

Background: Stroke is directly related to blood pressure and treatment trials in older hypertensive individuals show a reduction in strokes. However, the majority of strokes occur in normotensive individuals in whom no attempt is made to lower blood pressure. We compared the effects of modest salt restriction on blood pressure in older hypertensive and normotensive people., Methods: 47 untreated elderly people (24 men, age range 60-78 years; blood-pressure range 123-205 mm Hg systolic and 64-112 mm Hg diastolic) completed a 2-month double-blind randomised placebo-controlled crossover study of modest salt restriction with slow sodium and placebo to give a salt intake of either 10 g (equivalent to the normal amount for the UK population) or 5 g., Findings: On the normal salt intake for the UK population, supine blood pressure was 163/90 (SD 21/10) mm Hg with urinary sodium excretion of 177 (49) mmol/day. With modest sodium restriction, blood pressure fell to 156/87 (22/9) mm Hg (p < 0.001/0.004) with a urinary sodium excretion of 94 (50) mmol/day. A reduction in sodium intake of 83 mmol/day was associated with a reduction of 7.2/3.2 mm Hg. There was no significant difference in the blood-pressure fall between 18 normotensive and 29 hypertensive participants (8.2/3.9 vs 6.6/2.7 mm Hg)., Interpretation: A modest reduction in salt intake leads to a fall in blood pressure in both normotensive and hypertensive older people similar to that in outcome trials of thiazide-based treatment. Since the majority of strokes in older people occur below the current definition of hypertension, our results have important implications for the prevention of stroke.