Effects of antihypertensive treatment on endpoints in the diabetic patients randomized in the Systolic Hypertension in Europe (Syst-Eur) trial

In this review we attempt to determine the role of calcium channel blockers in preventing cardiovascular sequela in patients with both hypertension and diabetes mellitus. The data have been collected from three sources: post hoc analyses of subgroups of diabetic patients in placebo-controlled hypertension trials (SHEP, Syst-Eur, Syst-China); a stepped care blood pressure oriented trial (HOT); and comparative trials primarily focussing on metabolic aspects and intermediate endpoints (ABCD, FACET). On balance, the data seem to indicate that long-acting calcium channel blockers score remarkably well in preventing cardiovascular complications in diabetic hypertensive patients.     

Endothelial function and outdoor temperature

Studies within populations consistently showed that cardiovascular mortality increases with hot weather. However, the biological mechanisms underlying this association remain largely unknown. Endothelial function plays a pivotal role in the pathogenesis of cardiovascular disease. Therefore, we investigated the association between endothelial function and outdoor temperature. We measured flow-mediated vasodilatation (FMD) as index of endothelial function in 274 randomly recruited subjects (50% women, mean age 40.6 year). Both before (partial r = −0.14, p = 0.017) and after adjustment (partial r = −0.17, p = 0.006) for sex, age, body mass index, brachial artery diameter and current smoking, FMD was negatively associated with mean daily temperature. The odds of endothelial dysfunction increased by 58% (95% CI: 4–141%; p = 0.03) for each 10 °C increment in mean daily temperature during the week before the examination. Our findings suggest that endothelial dysfunction might contribute to the increase in cardiovascular morbidity and mortality associated with hot weather.     

Effect of chronic diuretic treatment on the plasma renin-angiotensin-aldosterone system in essential hypertension.

1 Chronic treatment with a constant dose of hydrochlorothiazide or tienilic acid increases plasma renin activity (PRA) acutely to reach a maximum within the first week. 2 During chronic diuretic therapy from 1 month to 1 year, PRA remained elevated at a rather constant level, though this was somewhat lower than the maximum level reached after 1 week. 3 A significant (P less than 0.01) correlation (r = 0.74) between changes in plasma angiotensin II and renin activity provoked by chronic treatment for 3 months with hydrochlorothiazide and tienilic acid was found. 4 The increase in plasma aldosterone during chronic treatment with hydrochlorothiazide and tienilic acid (1000 mg) is related (r = 0.68; P less than 0.01) to the rise in plasma angiotensin II.     

Blood pressure and dementia

Hypertension has proven to be a major predisposing factor for the development of both vascular and degenerative (Alzheimer's) dementias, either following stroke or gradually through more insidious microcerebrovascular processes. In the latter case the interval between the respective manifestations of hypertension and dementia may vary between a few years and several decades. The temporal relationships may become complicated by the finding that blood pressure tends to fall shortly before the onset of overt Alzheimers' disease. Whether or not timely antihypertensive regimens may delay or even prevent the development of dementias later in life is still an 'educated' guess, as long there has been no comprehensive trial comparing the potential of the different antihypertensive drug classes in this regard. Until then, the class of dihydropyridine calcium antagonists (exemplified by nitrendipine in the Syst-Eur trial) is the only category having statistically been proven to be of substantial value for prevention of Alzheimer's disease.     

Results of the pilot study for the Hypertension in the Very Elderly Trial

BACKGROUND: The risks and benefits of treating hypertension in individuals older than 80 years are uncertain. A meta-analysis has suggested that a reduction in stroke events of 36% may have to be balanced against a 14% increase in total mortality. OBJECTIVES: To report the results of the pilot study of the Hypertension in the Very Elderly Trial (HYVET), which is in progress to address these issues. METHODS: The HYVET-Pilot was a multicentre international open pilot trial. In 10 European countries, 1283 patients older than 80 years and with a sustained blood pressure of 160-219/90-109 mmHg were allocated randomly to one of three treatments: a diuretic-based regimen (usually bendroflumethiazide; n = 426), an angiotensin-converting enzyme inhibitor regimen (usually lisinopril; n = 431) or no treatment (n = 426). The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment. Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months. RESULTS: In the combined actively treated groups, the reduction in stroke events relative hazard rate (RHR) was 0.47 [95% confidence interval (CI) 0.24 to 0.93] and the reduction in stroke mortality RHR was 0.57 (95% CI 0.25 to 1.32). However, the estimate of total mortality supported the possibility of excess deaths with active treatment (RHR 1.23, 95% CI 0.75 to 2.01). CONCLUSIONS: The preliminary results support the need for the continuing main HYVET trial. It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 (nine non-fatal), but may be associated with 20 extra non-stroke deaths.     

Task Force I: methodological aspects of blood pressure measurement

OBJECTIVE: To reach a consensus on important methodological aspects of blood pressure measurement. METHODS: A Task Force on the methodological aspects of blood pressure measurement wrote this review after the Eighth International Consensus Conference on Blood Pressure Monitoring, in Sendai, Japan (28-31 October 2001). This consensus paper is based on the papers presented by Task Force I and on the discussion sessions, and is therefore representative of a broad spectrum of expert opinion. POINTS OF CONSENSUS: Consensus was reached on the following five issues: (1) there is an urgent need for a simplified protocol for the validation of blood pressure measuring devices; (2) there is a need for a means of updating the "state of the market" for validated devices so that users can have easy access to this information; (3) new devices must be validated independently, and existing devices that have not been validated must be reappraised; (4) manufacturers should confirm when new models use algorithms which have been validated previously; (5) the Food and Drug Administration now accepts that when ambulatory blood pressure measurement is used in clinical short-term trials in which side-effects are not being assessed, a placebo arm is not required.     

Cerebral complications of hypertension

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.     

Treatment of diabetic patients with hypertension

This review attempts to highlight the potential of calciumchannel blockers in the prevention of sequelae of diabetes mellitus and hypertension in patients who have both disorders. Evidence-based medicine is driven by the results of randomized, clinical trials. Major contributions were therefore derived from post hoc analyses of the diabetic patients enrolled in placebo-controlled trials, such as Systolic Hypertension in the Elderly Program (SHEP), Systolic Hypertension in Europe (Syst-Eur), and Systolic Hypertension in China (Syst-China), and stepped-care blood-pressure-oriented trials, such as the Hypertension Optimal Treatment (HOT) and United Kingdom Prospective Diabetes Study (UKPDS). Several studies, such as the Fosiniprl; versus Amlodipine Cardiovascular Events Trial (FACET) and Appropriate Blood Pressure Control in Diabetes (ABCD) Trial, have compared the relative merits of angiotensin-converting enzyme and calcium-channel blockers in preserving renal function and metabolic balance in diabetic patients with hypertension, but their publications focused on cardiovascular disorders, which were only secondary end points. On balance, the articles reviewed prove that dihydropyridine calcium-channel blockers score particularly well in the prevention of cardiovascular complications in diabetic patients with hypertension.     

Benefit of Antihypertensive Treatment in the diabetic patients enrolled in the Systolic Hypertension in Europe (Syst-Eur) Trial

In this review we attempt to determine the role of calcium channel blockers in preventing cardiovascular sequelae in patients with both hypertension and diabetes mellitus. The data have been collected from three sources: post-hoc analyses of subgroups of diabetic patients in placebo-controlled hypertension trials (SHEP, Syst-Eur, Syst-China); stepped-care blood pressure-oriented trials (HOT, UKPDS); and comparative trials focusing primarily on metabolic aspects and intermediate endpoints (ABCD, FACET).On balance, the data seem to indicate that long-acting calcium channel blockers score remarkably well in preventing cardiovascular complications in diabetic hypertensive patients.