Showing papers in "Journal of Human Hypertension in 2000"

Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension.

Abstract: Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan losartan > irbesartan valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5–4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60–80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40–50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95–100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). Plasma elimination half-life is short for candesartan cilexetil and losartan (1–4 h), intermediate for eprosartan and valsartan (5–10 h), and longer for candesartan, irbesartan and telmisartan (11–38 h); the active metabolite of losartan has a longer half-life than for the parent drug. The drugs and their active metabolites do not accumulate to a significant extent after repeated dosing, except for telmisartan (100%). Most of the orally administered dose of ARBs is excreted via bile into the faeces; from 2% (telmisartan) to 33% (candesartan) of the oral dose is excreted in the urine. In most cases, changes in pharmacokinetic parameters due to aging, mild to moderate renal disease and heart failure do not require dosage modification; dosage has to be individualised for eprosartan, losartan, telmisartan and valsartan in patients with hepatic disease. In general, pharmacokinetic drug–drug interactions are rare, with the exception of combination of digoxin and telmisartan. The ARBs are an important treatment option for hypertension, being relatively safe and efficacious. The beneficial effects of the ARB therapy go beyond blood pressure control. They may prove to have beneficial haemodynamic and neurohormonal effects in heart failure and provide renoprotection in diabetic nephropathy. Journal of Human Hypertension

Hypertension and stroke in Asia: prevalence, control and strategies in developing countries for prevention.

Abstract: Reliable statistics related to the prevalence, incidence and mortality of hypertension and stroke are not available from Asia. The data may be in national or institutional reports or journals published in the local language only. The mortality rate for stroke has been on the decline since the mid 1960s in the developed countries of Asia, such as Australia, New Zealand, and Japan, with some improvement in Singapore, Taiwan and Hong Kong, some areas of China and Malaysia about 15 years later. In India, China, Phillippines, Thailand, Sri Lanka, Iran, Pakistan, Nepal, there has been a rapid increase in stroke mortality and prevalence of hypertension. The prevalence of hypertension according to new criteria (>140/90 mm Hg) varies between 15–35% in urban adult populations of Asia. In rural populations, the prevalence is two to three times lower than in urban subjects. Hypertension and stroke occur at a relatively younger age in Asians and the risk of hypertension increases at lower levels of body mass index of 23–25 kg/m2. Overweight, sedentary behaviour, alcohol, higher social class, salt intake, diabetes mellitus and smoking are risk factors for hypertension in most of the countries of Asia. In Australia, New Zealand and Japan, lower social class is a risk factor for hypertension and stroke. Population-based long-term follow-up studies are urgently needed to demonstrate the association of risk factors with hypertension in Asia. However prevention programmes should be started based on cross-sectional surveys and case studies without waiting for the cohort studies.

High prevalence of primary aldosteronism in the Tayside hypertension clinic population.

Abstract: Primary aldosteronism (PA) was thought to be rare but recent evidence from Australia suggests that it may be more common As this has important implications in terms of hypertension management, we undertook to screen for this treatable condition in our hypertension clinic We obtained blood samples in sequential patients referred for assessment in our hypertension clinic in Tayside for plasma renin activity (PRA) and aldosterone The aldosterone to PRA ratio (ARR) was used as an initial screening test to identify potential patients with PA Those patients with an elevated ratio (> or =750) were admitted for the salt loading and fludrocortisone suppression test These patients also underwent adrenal CT scanning, and in selected patients, adrenal scintigraphy Between May 1995 and January 1997 (21 months), we screened a total of 495 patients ARR was available in 465 (939%) patients Out of that number, 77 (16 6%) had an elevated ratio of > or =750, five of whom had an adrenal adenoma (one had previous adrenalectomy) Forty-five of these patients were admitted for the salt loading and fludrocortisone suppression test with 41 positive test results suggesting PA One patient with a negative salt loading test result however had an adenoma proven on histology A total of 43 cases of PA were identified, giving a minimum prevalence of 92% (43/465) Potentially the prevalence may be up to 15% assuming that the ARR has a sensitivity of 93% (42/45) in predicting PA In conclusion, about one in 10 patients attending a hypertension clinic may have PA This suggests that the prevalence of PA in Tayside is as high as that in the Australian hypertensive population, and this is likely to be true elsewhere, with obvious important implications for hypertension management

Antihypertensive effect of Valyl-Tyrosine, a short chain peptide derived from sardine muscle hydrolyzate, on mild hypertensive subjects

Abstract: The present study was conducted to determine whether Valyl-Tyrosine (VY) has an antihypertensive effect on high-normal blood pressure and mild essential hypertension, as well as spontaneous hypertensive rats (SHR). A randomised double-blind placebo-controlled study was carried out on 29 volunteers. A 100-ml drink containing 3 mg of VY and a 100-ml placebo drink were prepared. The subjects were grouped as VY(16M/1F, 45.5 +/- 3.2 years, 146.4 +/- 2.3/90.5 +/- 1.8 mm Hg) and the placebo (P) (11 M/1F, 48.8 +/- 3.0 years, 145.5 +/- 2.4/92.3 +/- 1.8 mm Hg). At 3 weeks of the control (C) period, a VY- or P-drink was administered twice a day for 4 weeks in the experimental (E) period and during the 4-week recovery period, neither drink was given to either group. Blood pressure (BP) was measured every week in the morning in the sitting position. Blood specimens were taken on the last day of the C and E periods. In the VY-group, reduction in systolic (S) and diastolic (D) BP was 9.7 and 5.3 mm Hg (P < 0. 001) at 1 week, and 9.3 and 5.2 mm Hg (P < 0.001) at 4 weeks, following the start of the E period, respectively. Neither SBP nor DBP changed in the P-group. BP in the VY-group increased gradually by the end of the recovery period. Plasma angiotensin (Ang) I and VY concentrations significantly increased while Ang II and aldosterone significantly decreased after VY administration in the VY-group. VY appeared to have a significant antihypertensive effect on mild hypertensive subjects via Ang I-converting enzyme inhibition, as well as SHR, but no adverse effects could be detected at all.

Fifty years of Framingham Study contributions to understanding hypertension.

Abstract: The Framingham Study established hypertension as a major cardiovascular risk factor and quantified its atherogenic cardiovascular disease potential. An historical perspective is presented on the epidemiological insights about hypertension derived from 50 years of Framingham Study research into the prevalence, incidence, determinants and hazards of hypertension. Existing misconceptions about the presence of critical levels of blood pressure, the impact of the systolic and diastolic components of blood pressure, the hazard 'mild' hypertension, the impact in advanced age and the hazard of left ventricular hypertrophy. The importance of isolated systolic hypertension and the pulse pressure were demonstrated. It has been demonstrated that hypertension seldom occurs in isolation of other atherogenic risk factors, with which it tends to cluster. This clustering with other metabolically linked risk factors has been shown to reflect insulin resistance promoted by weight gain and abdominal obesity. Obesity was shown to be one of the major determinants of hypertension in the general population. Left ventricular hypertrophy was shown to be an ominous harbinger of cardiovascular disease rather than an incidental compensatory phenomenon. Multivariate risk profiles for coronary disease, stroke, peripheral artery disease and heart failure have been devised to facilitate incorporation of elevated blood pressure in a global, multivariate cardiovascular risk assessment.

An epidemiological study of hypertension and its determinants in a population in transition: the THUSA study.

Abstract: Background: Many black persons in South Africa have been subjected to urbanisation and urbanisation has led to a significant increase in diseases of lifestyle. The determinants of hypertension in a population in transition have not been well-defined and there is a pressing need for observational epidemiological studies as well as randomised-controlled trials in populations from Africa. The aim of this study was to investigate the association between blood pressure and factors known to contribute to hypertension. Methods: The study sample consisted mainly of Setswana speaking people, divided into different levels (strata) of urbanisation, namely stratum 1 (rural) to stratum 5 (urbanised). A total of 1821 black subjects, which included 1040 woman, were recruited and randomly selected from 37 sites from the four geographical quarters of the North West Province of South Africa. The following questionnaires were used: demographic, anthropometric, quantitative food frequency, physical activity and scales to measure psychosocial variables. Biochemical analysis (standardised methods) were done on the serum and plasma of the subjects and the blood pressure was measured with a sphygmo- manometer. Results: Of the total sample, 22.8% of the subjects had systolic and 20.7% diastolic blood pressures above 140/90 mm Hg. Males and females from stratum 3 showed the highest rate of hypertension (32.9% systolic and 25.1% diastolic) and stratum 5 the lowest. Blood pressure correlated positively with age, level of urbanisation, WHR (waist:hip ratio) and smoking. In the woman the diastolic blood pressure correlated the best with body mass index (BMI), serum triglycerides, total serum cholesterol, low-density lipoprotein (LDL) cholesterol and s-GGT. Coping strategies, experience of social support, cultural aspects and affect balance are related to blood pressure, especially in the case of women. Conclusions: It seems that factors associated with urbanisation are related to the manifestation of hypertension in black people of the North West Province, given the highest mean blood pressure in people living in informal settlements, where most newcomers to the urban areas live.

Ambulatory blood pressure monitoring: which arm?

Abstract: To determine the effects of routinely selecting the nondominant arm for ambulatory blood pressure monitoring (ABPM) on estimates of patients' blood pressure (BP) and to evaluate the practise of using manual BP from one arm and ambulatory BP from the other on the estimation of white coat effect (WCE), an observational study was conducted in 10 volunteers, exhibiting an interarm resting clinic systolic BP (SBP) difference > or =10 mm Hg. The main outcome measures were: (i) average ambulatory SBP measured on right and left arm simultaneously during 24 h, and (ii) estimate of WCE derived, by current practise, as the difference between the referral clinic BP (the higher of the manual readings from both arms) and ambulatory non-dominant arm BP, contrasted with the WCE calculated as the difference between clinic and ambulatory readings from the same arm (the arm with the higher manual readings). The supine referral clinic SBP was 16+/-6 mm Hg higher in the right compared with the left arm. Average 24 h ambulatory SBP was 6+/-7 mm Hg higher in the right arm (range +17 to -3 mm Hg), P = 0.025. Diastolic BP measurements mirrored the systolic findings. One-third of the WCE, estimated by current practise, could be attributed to inconsistency in the choice of arm for BP measurement. Thus, inconsistency in the selection of arms for BP measurement, by different techniques, may confound estimation of patients' cardiovascular morbidity risk.

The effects of exercise duration on post-exercise hypotension.

Abstract: Study 1: Thirteen normotensive participants with average baseline blood pressure of 126/71 mm Hg participated in the study. Participants performed bouts of cycle ergometry for 15, 30 and 45 min at 70% VO2 Peak. Blood pressure was monitored by the Finapres method with 2 min windows recorded at rest, 5, 10, 15, 30, 45 and 60 min post-exercise. Following exercise, systolic blood pressure (SBP) was similar between the three trials and was reduced from pre-exercise values at 5 through 60 min of measurement. Diastolic blood pressure (DBP) was also unaffected by the duration of exercise and was lower than before exercise at 30 through 45 min post-exercise. Study 2: Eight borderline hypertensive participants with average baseline blood pressure of 133/79 mm Hg participated in the study. Subjects performed bouts of cycle ergometry for 10 and 30 min at 70% VO2 Peak. Following exercise, blood pressure was monitored as in study 1. SBP was similar between both trials and was reduced from baseline at 5 through 60 min post-exercise. The largest decrement of SBP was 14 mm Hg and occurred 15 min post-exercise. DBP was also unaffected by the duration of exercise and was lower than pre-exercise levels at 5 min and again at 15 through 45 min post-exercise. Mean arterial pressure (MAP) also showed significant decrements throughout the entire 1 h post-exercise period by a maximum of 9 mm Hg at 15 min post-exercise, irrespective of exercise duration. We conclude that moderately intense exercise may be as brief as 10 min in duration in order to elicit a decrease in resting blood pressure and may have potential benefits as a non-pharmacological aid to hypertension.

Decreased endogenous antioxidant enzymatic status in essential hypertension.

Abstract: Several lines of evidence suggest that patients with essential hypertension have impaired endothelial nitric oxide activity and increased superoxide anion production. However, the mechanisms underlying these abnormalities remain unknown. We measured enzymatic superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities in erythrocytes and whole blood, respectively, in 30 newly-diagnosed, normolipidaemic untreated mild hypertensive patients and in 164 age-matched healthy controls. SOD and GPX activities in hypertensive patients (806 +/- 225 U/Hb.g and 5491 +/- 2073 U/L, respectively) were significantly lower than in the control group (931 +/- 202 U/Hb.g and 6669 +/- 1560 U/L, respectively) (P < 0.005). No significant association was found between these antioxidant enzyme activities and blood pressure in normotensive controls. In the hypertensives, only log-transformed SOD activity showed a significant negative correlation with systolic and diastolic blood pressure (r = 0.37, P < 0.05; r = 0.64, P < 0.0001, respectively). The low endogenous antioxidant enzyme activities observed may in turn result in decreased superoxide anion removal leading to nitric oxide inactivation. Journal of Human Hypertension (2000) 14, 343-345

Twenty-four hour, ambulatory blood pressure responses following acute exercise: impact of exercise intensity.

Abstract: Twenty-four hour, ambulatory blood pressure responses following acute exercise: impact of exercise intensity

Blood pressure patterns and cardiovascular risk factors in rural and urban Gambian communities.

Abstract: Hypertension is emerging as an important public health problem in sub-Saharan Africa. We studied blood pressure (BP) patterns, hypertension and other cardiovascular risk factors in a rural and an urban area of The Gambia. A total of 5389 adults (> or =15 years) were selected by cluster sampling in the capital Banjul and a rural area around Farafenni. A questionnaire was completed, BP, pulse rate, height and weight were recorded. Glucose was measured 2 h after a 75 g glucose load among participants > or =35 years (n = 2301); total cholesterol, triglycerides, creatinine and uric acid were measured among a stratified subsample (n = 1075). A total of 7.1% of the study participants had a BP > or =160/95 mm Hg; 18.4% of them had a BP > or =140/90 mm Hg. BP was significantly higher in the urban area. BP increased with age in both sexes in both areas. Increasing age was the major independent risk factor for hypertension. Related cardiovascular risk factors (obesity, diabetes and hyperlipidaemia) were significantly more prevalent in the urban area and among hypertensives; 17% of measured hypertensives were aware of this, 73% of people who reported to have been diagnosed as hypertensive before had discontinued treatment; 56% of those who reported being on treatment were normotensive. We conclude that hypertension is no longer rare in either urban or rural Gambians. In the urban site hypertension and related cardiovascular risk factors were more prevalent. Compliance with treatment was low. Interventions aimed at modifying risk factors at the population level, and at improving control of diagnosed hypertension are essential to prevent future increases of cardiovascular morbidity and mortality. In view of limited resources and feasibility of intervention in rural Gambia, these could initially be directed towards urbanised populations.

Hypertension in a black population: prevalence and biosocial determinants of high blood pressure in a group of urban Nigerians.

Abstract: Aims: To define the prevalence of hypertension, a major cause of morbidity and mortality in blacks, and related biosocial factors in an urban African population group. Methods: The setting was that of a civil service population in Ibadan, a major city in Southwestern Nigeria. Nine hundred and ninety-eight civil servants selected by multistage sampling participated in the survey. Biosocial data including smoking history, alcohol use and level of physical activity; anthropometry, blood pressure and plasma glucose measurements were obtained. Diagnosis of hypertension was based on blood pressure of ≥160/95 mm Hg or known hypertensive on treatment. Results: The overall prevalence rate of hypertension was 10.3% (Cl, 8.4%, 12.2%), rates of 13.9% and 5.3% were obtained in men and women respectively in spite of a much higher rate of generalised obesity in the latter. Hypertension was associated with higher salary grade level, but there was no relationship found with regular exercise, smoking and alcohol. Obesity (body mass index (BMI) ≥30 kg/m 2 ) was associated with hypertension only in women. A two-sided t-test demonstrated age, waist circumference, waist to hip ratio (WHR) and plasma glucose level as significant variables. In multivariate ANOVA models of systolic blood pressures, age, male sex and BMI were highly significant factors (P < 0.0001) and plasma glucose was also significant (P < 0.016); the same variables (except plasma glucose) were associated with diastolic blood pressures. In logistic regression models the variables which predicted hypertension were WHR, plasma glucose, age, sex and family history of diabetes. Conclusions: Prevalence of hypertension in the study was comparable to recently reported rates in urban Nigeria and similar populations in Africa. The biosocial determinants of hypertension in the urban black population were age, male gender, higher socio-economic status, BMI, plasma glucose, generalised and central adiposity. Regional fat distribution was a stronger predictor of hypertension than generalised obesity in the population.

Hypertension and the heart.

Abstract: It has been clearly demonstrated that left ventricular (LV) hypertrophy is a strong blood pressure independent risk factor for cardiovascular morbidity and mortality in the general population, in primary and secondary hypertension and in cardiac patients. LV hypertrophy in arterial hypertension develops in response to an increased afterload, but underlying pathophysiological mechanisms include a variety of non-haemodynamic factors. Due to the prognostic importance of LV hypertrophy, normalisation of LV mass emerged as a desirable goal of antihypertensive treatment. Indeed, several prospective studies now indicate that regression of LV hypertrophy reduced cardiovascular complications. As a consequence, the question was raised whether certain antihypertensive drugs differ in their ability to reduce LV mass. Several comparative studies and meta-analyses have been carried out to resolve this issue. The available data seem to indicate that angiotensin-converting enzyme (ACE)-inhibitors and calcium channel blockers were more potent than beta-blockers in their ability to reduce LV hypertrophy, with diuretics in the intermediate range. The role of new antihypertensive agents such as angiotensin II AT1-receptor blockers appears similar to the one of ACE-inhibitors, since in some studies angiotensin II AT1-receptor blockers were superior to beta-blockers and diuretics. Various aspects of LV hypertrophy including its prevalence, determinants, prognosis and regression are discussed in this article.

Hypertension in developing nations in sub-Saharan Africa.

Abstract: There is a rapid development of the ‘second wave epidemic’ of cardiovascular disease that is now flowing through developing countries and the former socialist republics. It is now evident from WHO data that coronary heart disease and cerebrovascular disease are increasing so rapidly that they will rank No. 1 and No. 5 respectively as causes of global burden by the year 2020. In spite of the current low prevalence of hypertensive subjects in some countries, the total number of hypertensive subjects in the developing world is high, and a cost-analysis of possible antihypertensive drug treatment indicates that developing countries cannot afford the same treatment as developed countries. Control of hypertension in the USA is only 20% (blood pressure <140/90 mm hg). in africa only 5–10% have a blood pressure control of hypertension of <140/90 mm hg. there are varying responses to antihypertensive therapy in black hypertensive patients. black patients respond well to thiazide diuretics, calcium channel blockers vasodilators like α-blockers, hydralazine, reserpine and poorly to β-blockers, angiotensin-converting enzyme inhibitors and aii receptor antagonists unless they are combined with a diuretic. a comprehensive cardiovascular disease (cvd) programme in africa is necessary. there are social, economic, cultural factors which impair control of hypertension in developing countries. hypertension control is ideally suited to the initial component on an integrated cvd control programme which has to be implemented. primary prevention, through a population-based lifestyle linked programme, as well as cost-effective methods of detection and management are synergistically linked. the existing health care infrastructure needs to be orientated to meet the emerging challenge of cvd, while empowering the community through health education.

The effects of exercising muscle mass on post exercise hypotension.

Abstract: Nine recreationally active, borderline hypertensive subjects completed 30 min of arm ergometry (ARM) at 65% VO2 peak and 30 min of leg ergometry (LEG) at 70% VO2 Peak (randomised order). Blood pressure was monitored before and for 1 h after exercise using the Finapres method. Systolic, diastolic and mean blood pressures were significantly reduced for the entire 1 h post exercise. This reduction was independent of exercise modality, but there was an indication for the duration of the effect to be prolonged following the leg exercise. We conclude that the mass of the working muscle does not directly effect the magnitude of post-exercise hypotension (PEH) but may influence the duration of the response. These results suggest that a central mechanism or decreased vascular responsiveness is responsible for PEH.

Epidemiology of hypertension in China and Japan.

Abstract: Hypertension is a major risk factor for cardiovascular disease in Chinese and Japanese with a low to moderate serum cholesterol level. The prevalence of hypertension is diverse in Chinese populations with different geographic region, lifestyles and cultures. The same diversity was observed in Japan in the past, but recently the regional difference has become smaller. The large decline in stroke mortality in Japan was followed by a reduction in the prevalence of hypertension and the lowering level of blood pressure. This is partly explained by various community-based hypertension control programmes. Chinese populations are now showing similar patterns as those observed in Japan. These populations still have high proportions of undetected hypertensives and untreated patients in China. In both Chinese and Japanese, high salt consumption is one of the most important risk factors for hypertension. In addition to this, the increase in body weight, smoking and alcohol consumption in Chinese people seems to be the major factors for the increasing trends in hypertension. Control of hypertension and lowering blood pressure in the population level should be the important strategies for the prevention of cardiovascular disease in Chinese and Japanese.

The mercury sphygmomanometer should be abandoned before it is proscribed.

Abstract: Both in clinical practice and medical research, blood pressure is still largely measured by auscultation using a mercury sphygmomanometer. Blood pressure is the most important predictor of life expectancy. Treatment of high blood pressure reduces strokes, heart attack and heart failure. Accurate measurement is therefore essential. At a large London teaching hospital, just under 500 mercury sphygmomanometers and their associated cuffs were examined. More than half had serious problems that would have rendered them inaccurate in measuring blood pressure. At the same time, assessment of the technical knowledge needed to measure blood pressure by the ausculatory technique was also carried out amongst medical and nursing staff. This showed a considerable level of ignorance. These results inevitably lead to inaccurate measurement of blood pressure with serious consequences. In addition mercury is a non-degradable pollutant, eventually accumulating on the sea bed. The use of mercury in sphygmomanometers is already in the process of being eliminated in Scandinavia and Holland and other countries are likely to follow. Our results suggest that mercury sphygmomanometers are not adequately maintained and require expertise that is not available for accurate measurement of blood pressure. Their use should be dispensed with on these grounds before a ban for other and, perhaps less justifiable reasons. Validated automatic devices, which are less liable to measurement and observer error should be used instead. At the same time a concerted effort is needed to instruct health care professionals on the importance of more accurate measurement of blood pressure. Journal of Human Hypertension (2000) 14, 31-36.

Blood pressure levels and hypertension status among ethnic groups in England.

Abstract: The prevalence of cardiovascular disease and hypertension show wide variability among different ethnic groups in the UK. We combined data collected annually between 1991-1996 in the Health Surveys for England--nationwide surveys that provide information on the health status in a representative sample of the population living in England, to compare blood pressure (BP) levels, hypertension rates (systolic BP > or = 160 mm Hg or diastolic BP > or = 95 mm Hg, or those on antihypertensive medication), hypertension treatment and control rates in people of white, black (combining black-Caribbean, black-African and black-other), and South Asian origin (combining Indians, Pakistanis and Bangladeshis). Analyses were stratified into two age groups, 16-39 (younger) and > or = 40 years (older), but were focused on older adults (30,619 whites, 295 blacks and 529 South Asians). Age-adjusted mean BP levels and hypertension rates of older adults were highest among blacks, while South Asian men showed BP levels and hypertension rates similar to black men and South Asian women had mean BP levels and hypertension rates similar to white women. After controlling for age, BMI, smoking, alcohol consumption, and social class the odds ratio (OR) of being hypertensive among older adults was higher in black men (OR 2.0; 95% CI 1.4, 2.9; P < 0.001); black women (OR 1.7; 95% CI 1.2, 2.5; P < 0.01); and South Asian men (1.9; CI 1.4, 2.4; P < 0.001), than in their white counterparts. Among those studied with hypertension, treatment rates were highest among black men and women. Among those on antihypertensive medication, the odds of having BP controlled (SBP < 160 mm Hg and DBP < 95 mm Hg) did not differ among the three groups of older men but was reduced in older South Asian women, compared with white women.

Angiotensin II can induce and potentiate shape change in human platelets: effect of losartan.

Abstract: Platelet shape change (PSC) is an early phase of platelet activation that precedes platelet aggregation. This phase of platelet activation is essentially aspirin resistant. PSC was monitored, by measuring the median platelet volume (MPV) using a high resolution channelyser. Angiotensin (Ang) II, added in vitro, caused a significant (P = 0.004) increase in MPV in platelet rich plasma prepared from healthy subjects (n = 14). This increase in MPV was marked (>0.40 fl) in 57% (n = 8) of these subjects and was significantly inhibited (P<0.008) by losartan (a selective Ang II antagonist) at concentrations similar to those achieved in the circulation during treatment. Ang II also significantly enhanced sub-maximal PSC induced by ADP and serotonin in all subjects tested. Losartan significantly (n = 9; P<0.001) inhibited U46619 (a thromboxane A2 analogue)-induced PSC. These findings suggest that losartan, in addition to its blood pressure lowering action, has antiplatelet activity. This property may be clinically relevant because of the increased risk of vascular events in hypertensive patients.

Hypertension in women.

Abstract: Cardiovascular disease remains the most common cause of death in women worldwide, with hypertension being the most common modifiable risk factor for cardiovascular disease in both sexes. Further, obesity plays a critical role in the development and management of hypertension with a disproportionate effect on minority women. Overall, gender specific differences in the pathogenesis and response to treatment of hypertension exist, and must be taken into consideration.

Hypertension and the prothrombotic state.

Abstract: The basic underlying pathophysiological processes underlying the major complications of hypertension (that is, heart attacks and strokes) are thrombogenesis and atherogenesis. Indeed, despite the blood vessels being exposed to high pressures in hypertension, the complications of hypertension are paradoxically thrombotic in nature rather than haemorrhagic. The evidence suggests that hypertension appears to confer a prothrombotic or hypercoagulable state, which can be related to conventional risk factors, target organ damage, complications and long-term prognosis, as well as different antihypertensive treatments. Further work is needed to examine the mechanisms leading to this phenomenon, the potential prognostic and treatment implications, and the possible value of measuring these parameters in routine clinical practice.

Antihypertensive treatment modulates the association between the D/I ACE gene polymorphism and left ventricular hypertrophy: a meta-analysis

Abstract: Antihypertensive treatment modulates the association between the D/I ACE gene polymorphism and left ventricular hypertrophy: a meta-analysis

Working under pressure: the vascular endothelium in arterial hypertension.

Abstract: The vascular endothelium synthesizes and releases a spectrum of vasoactive substances like nitric oxide (NO) and endothelin (ET). In hypertension, the delicate balance of endothelium-derived factors is disturbed. ET acts as the natural counterpart to endothelium-derived NO, which exerts vasodilating, antithrombotic, and antiproliferative effects, and inhibits leukocyte-adhesion to the vascular wall. Besides its blood pressure rising effect also in man, ET induces vascular and myocardial hypertrophy, which are independent risk factors for cardiovascular morbidity and mortality. The derangement of endothelial function in hypertension is likely to be caused in part by genetic factors, but also due to elevated blood pressure itself. Due to its position between blood pressure and smooth muscle cells responsible for peripheral resistance, the endothelium is thought to be both target and mediator of arterial hypertension. Oxidative stress plays an important role in the pathogenesis of hypertension. Superoxide anions, ie, oxygen radicals produced in part by angiotensin II-activated NAD(P)H oxidase, can scavenge NO to form peroxynitrite, which can nitrosylate membrane proteins and oxidize lipids. Another source of superoxide is cyclooxygenase. Paradoxically, dysfunctional endothelial NO synthase may also be a source of superoxide anions. Surprisingly and in contrast to animal experiments, not all antihypertensive treatments consistently restore endothelium-dependent vasodilation in patients with arterial hypertension. Endothelial dysfunction in hypertension is crucial both for the development of the disease process in the vasculature and an important therapeutic target.

Favourable effects on arterial wave reflection and pulse pressure amplification of adding angiotensin II receptor blockade in resistant hypertension

Abstract: Objective: Angiotensin-converting enzyme (ACE) inhibitors have beneficial effects on arterial compliance and distensibility and favourably modify the arterial pressure waveform in hypertensive patients. The objective of our study was to explore the possible effects of adding an ATII AT1 receptor antagonist to an ACE inhibitor on augmentation pressure, a measure of arterial stiffness, and pulse pressure amplification in patients with poorly controlled essential hypertension. Design and methods: We studied a group of 18 patients with poorly controlled hypertension, despite at least three antihypertensive drugs including an ACE inhibitor, before, at 2 h and 2 weeks following the administration of 80 mg of valsartan, an ATII AT1 receptor antagonist. Haemodynamic responses were measured by cuff sphygmomanometry, arterial pulse-wave analysis and the pulse pressure gradient was calculated as the difference between the brachial pulse pressure (cuff sphygmomanometry) and derived aortic pulse pressure (arterial pulse wave analysis). Results: Blood pressure decreased significantly (P < 0.001) and the effect was more pronounced on central (aortic) pulse pressure than peripheral (brachial) pulse pressure. the pulse pressure amplification increased significantly (from 8 ± 3 at baseline vs 12 ± 7 at 2 h to 14 ± 5 mm Hg at 2 weeks, P < 0.01) and the augmentation pressure decreased from a baseline value of 21 ± 8 to 11 ± 7 at 2 h and 10 ± 5 at 2 weeks, (P < 0.01) following valsartan. Conclusion: The results of our study show that in a group of poorly controlled hypertensives, combining an ATII AT1 receptor blocker to an ACE inhibitor induced a significant fall in blood pressure. The decrease in blood pressure was accompanied by a decrease in augmentation pressure in the ascending aorta with a greater decrease in the central pulse pressure than in the peripheral, favourably increasing pulse pressure amplification between central and peripheral arteries. This effect on arterial stiffness and amplification suggests that combined angiotensin II blockade by adding an AT1 receptor blocker to an ACE inhibitor may have more beneficial effects on the blood pressure curve than simple blood pressure reduction.

Cerebral complications of hypertension.

Abstract: Ischaemic and degenerative brain diseases are a major health problem leading to a devastating loss of autonomy. Hypertension has been shown to carry an increased risk not only for cerebrovascular morbidity and mortality but also for cognitive impairment and dementia. Although diastolic blood pressure is considered an important risk factor, it is now clear that isolated systolic hypertension and elevated pulse pressure also play an important role in the development of brain complications. Therefore the treatment of these conditions must urgently become a widespread tool of prevention. All the randomised placebo-controlled trials completed for the last 30 years have shown a reduction in fatal and/or non-fatal strokes. In the most recent trials in isolated systolic hypertension in older patients, the benefit was even greater because of the higher risk in these populations. The new classes of drugs, in particular, calcium-channels blockers and angiotensin-converting enzyme inhibitors, have been shown to be as effective as the originally used diuretics and beta-blockers. Active treatment in the Syst-Eur trial based on nitrendipine as first step, possibly associated with enalapril and/or hydrochlorthiazide reduced not only stroke and cardiovascular complications but also the incidence of dementia including Alzheimer's disease. This important finding must be confirmed by further trials specifically focusing on the prevention of dementia. In addition, the importance of pulse pressure as a risk factor, underlines the need for new drugs which could increase aortic distensibility and decrease systolic blood pressure without greatly reducing diastolic pressure. Improving the management of hypertension offers new opportunities to reduce age-related disease in older people and to promote healthy aging.

Familial aggregation of blood pressure: a population-based family study in eastern Finland.

Abstract: Blood pressure (BP) levels in the Finnish population are amongst the highest in the world, despite favourable changes at the national level in the past two decades. The study evaluates the familial aggregation of BP and the association of some environmental factors to the familial aggregation of BP as a primary epidemiological approach of the genetics of hypertension in a sample of families with young offspring from eastern Finland. Offspring aged 15 years were examined between 1996 and 1997 and their biological parents were examined between 1993 and 1994. A total of 224 children were invited, 184 families participated, from which 144 were included in the analysis with complete data. Systolic (SBP), diastolic (DBP) and mean (MAP) arterial BPs were the main outcome measurements. After the offspring’s gender and body mass index (BMI) and the parent’s age and BMI were controlled for, the mother/offspring correlation of SBP and the father/offspring correlation of MAP were statistically significant (r = 0.18, P = 0.039, n = 134 and r = 0.20, P = 0.048, n = 99, respectively). The additional adjustment for the parent’s education and family history of acute myocardial infarction did not change these results. There was a higher proportion of offspring in the highest quartile of SBP and MAP when the mother had a history of hypertension (OR = 3.4, 95% CI = 1.4–8.5, n = 139, and OR = 2.6, 95% CI = 1.0–6.5, n = 139, respectively). The study confirmed the familial aggregation of BP. The consistent BP association between the mother and the offspring may indicate the key role of the mother in the primary prevention of hypertension.

Effects of nicotinic acid on insulin sensitivity and blood pressure in healthy subjects.

Abstract: Insulin resistance and hyperinsulinaemia are associated with hypertension although a causative relationship has not been established. The aim of this study was to determine whether a short term reduction in insulin sensitivity induced by nicotinic acid treatment (NA) would alter blood pressure. The study was a double-blind randomised placebo-controlled cross-over study. Seven healthy volunteers, three males and four females were randomised to placebo or NA 500 mg daily for 7 days then 1 g daily for a further 7 days. Hyperinsulinaemic euglycaemic clamp, indirect calorimetry, 24-h ambulatory blood pressure monitoring (ABPM) and forearm blood flow measurement (FABF) were performed at day 14 of each treatment phase. NA significantly reduced the glucose infusion rate required to maintain euglycaemia in all subjects (placebo vs NA; 31.5+/-4.2 vs. 26.2+/-4.6 micromol/kg/min, P = 0.002) associated with a decrease in non-oxidative glucose disposal. NA did not significantly alter 24-h mean systolic or diastolic blood pressure. Fasting glucose, insulin and non-esterified free fatty acid (NEFA) levels remained unchanged, energy expenditure and substrate oxidation were not altered by NA. These results suggest a short term reduction in insulin sensitivity with NA is not accompanied by a change in blood pressure. This may relate to the short duration of treatment, to a dissociation between insulin resistance and hypertension or to other homeostatic mechanisms which prevent blood pressure rising in subjects not predisposed to hypertension.

Dopamine: a role in the pathogenesis and treatment of hypertension.

Abstract: The catecholamine dopamine (DA), activates two distinct classes of DA-specific receptors in the cardiovascular system and kidney—each capable of influencing systemic blood pressure. D1 receptors on vascular smooth muscle cells mediate vasodilation, while on renal tubular cells they modulate sodium excretion. D2 receptors on pre-synaptic nerve terminals influence noradrenaline release and, consequently, heart rate and vascular resistance. Activation of both, by low dose DA lowers blood pressure. While DA also binds to alpha- and beta-adrenoceptors, selective agonists at both DA receptor classes have been studied in the treatment of hypertension. An unfavourable side-effect profile (largely nausea and orthostasis) have precluded wide use of D2 agonists. In contrast, the D1 selective agonist fenoldopam has been licensed for the parenteral treatment of severe hypertension. Apart from inducing systemic vasodilation it induces a diuresis and natriuresis, enhanced renal blood flow, and a small increment in glomerular filtration rate. Evidence is emerging that abnormalities in DA production, or in signal transduction of the D1 receptor in renal proximal tubules, may result in salt retention and high blood pressure in some humans and in several animal models of hypertension.

Induction of insulin resistance by beta-blockade but not ACE-inhibition: long-term treatment with atenolol or trandolapril.

Abstract: The effects on glucose metabolism by the beta-blocker atenolol and the angiotensin-converting enzyme (ACE)-inhibitor trandolapril were investigated in a randomised double-blind parallel group study of patients with primary hypertension. Twenty-six patients were treated with 50-100 mg atenolol and 27 patients with 2-4 mg trandolapril o.d. Intravenous glucose tolerance tests, euglycaemic hyperinsulinaemic clamps and serum lipid measurements were performed after 8 and 48 weeks of active treatment. After 48 weeks insulin sensitivity was reduced by 23% by atenolol while it remained unchanged during trandolapril treatment (+0.5%, P = 0.0010 for difference between treatments, ANCOVA). The effect on triglycerides (+22% vs -8.5%) and high-density lipoprotein cholesterol (-13% vs +0.7%) also differed significantly between atenolol and trandolapril. Results after 8 weeks were similar. Glucose tolerance was not affected by either drug. Atenolol reduced diastolic blood pressure (DBP) better than trandolapril (-15.3 mm Hg vs -6.6 mm Hg for supine DBP after 48 weeks, P = 0.012). The difference in effect on insulin sensitivity between the drugs corresponded to 25% of the baseline values of insulin sensitivity, and persisted over 48 weeks of treatment. The choice of antihypertensive treatment could influence the risk of diabetes associated with treated hypertension. Journal of Human Hypertension (2000) 14, 175-180.

Arterial stiffness, hypertension and diabetes mellitus.

Abstract: Hypertension is a major risk factor for the development of cardiovascular disease and the benefits of reducing blood pressure in this condition are now well established. An important feature of hypertension is increased peripheral resistance, and considerable research has, therefore, focused on the structure and function of peripheral arterioles. The role of the larger arteries in the genesis and maintenance of hypertension has been largely ignored. Indeed, until recently large arteries were thought to function predominantly as passive conduits and to have little influence on blood pressure. However, mounting evidence suggests that pulse pressure, rather than systolic or diastolic pressure alone, is the most important predictor of cardiovascular risk. Pulse pressure is a surrogate measure of arterial stiffness and this has focused attention away from peripheral resistance and towards arterial stiffness, and in particular the interactions between the heart and the arterial tree. Indeed, aortic stiffness is correlated with the severity of coronary artery disease at angiography. Aging is associated with arterial stiffening, as are a number of cardiovascular risk factors which cause premature vascular stiffening, including hypertension. Type 2 diabetes mellitus is an important cardiovascular risk factor and is commonly associated with hypertension. The benefits of aggressive blood pressure reduction in preventing both microand macro-vascular disease in patients with type 2 diabetes have been demonstrated in the recent UKPDS Study. Patients with type 2 diabetes also have increased left ventricular mass, itself an important and independent predictor of outcome, compared with non-diabetic patients, even after correction for peripheral blood pressure. Increased stiffness, augmenting central systolic pressure may explain this finding, and may provide one potential mechanism