Abstract. Forty patients with uncomplicated essential hypertension were investigated with respect to diurnal variability of arterial pressure (indirect recordings), intra‐arterial pressure, cardiac output, plasma volume, renal plasma flow and glomerular filtration rate. Extracellular volume was estimated in 17, plasma renin concentration in 33 and vector‐cardiograms were recorded in 27 patients. Treatment was discontinued at least a fortnight before and sodium intake was standardized.—Blood pressure varied across a wide range. Variability (lability) of blood pressure was quantified by expressing the difference between highest and lowest automatic blood pressure readings as a percentage of the highest reading. Cardiac output correlated with variability of blood pressure, blood volume and renal blood flow.—Plasma renin concentration was correlated with renal vascular resistance and filtration fraction.— QRS magnitude appeared to be related with the level of arterial pressure.—Haemodynamic variables exhibited a definite relationship with age, deviating in part from distribution according to age in normal populations.
Background To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial by an open-label follow-up study lasting 4 years. Methods The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160–219 mmHg systolic and below 95 mmHg diastolic. The double-blind trial ended after a median follow-up of 2.0 years (range 1–97 months). Of 4409 patients still alive, 3517 received open-label treatment consisting of nitrendipine (10–40 mg daily) with the possible addition of enalapril (5–20 mg daily), hydrochlorothiazide (12.5–25 mg daily), or both add-on drugs. Non-participants (n = 892) were also followed up. Results Median follow-up increased to 6.1 years. Systolic pressure decreased to below 150 mmHg (target level) in 2628 participants (75.0%). During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. These rates were similar to those previously observed in the active-treatment group during the double-blind trial. Considering the total follow-up of 4695 randomized patients, immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P = 0.01) and 15% (P = 0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P< 0.02) were 60, 51 and 38%, respectively. Conclusions Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension.
Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP) are a useful animal model for studying juvenile malignant hypertension. Using M-SHRSP males, the effects of SQ 29,852 { (S)-1-[6-amino-2-[[hydroxy (4-phenylbutyl) phosphinyl]oxy]-1-oxohexyl]- proline; 30-40 mg/kg per day}, captopril (30-40 mg/kg per day), hydralazine hydrochloride (10-15 mg/kg per day) and a 33% fish meal diet on the prevention and therapy of malignant hypertension were examined. Drugs and diet were given separately, beginning at weaning, maturity or adulthood. Observed effects included antihypertension, prolonged life span and prevention and/or reversal of angionecrosis. Each treatment resulted in an antihypertensive effect, but some adult rats seemed treatment-resistant. SQ 29,852 was the most effective treatment for reducing blood pressure. The life span of animals in the treated groups was extended significantly beyond that of the controls. In particular, those rats treated with either captopril or SQ 29,852 lived in excess of 500 days. This included not only those in which treatment resulted in a lowering of blood pressure, but also those whose severe hypertension was not so reduced. Angionecrosis was observed in the organs of many of the non-treated animals, including the brain, heart, kidneys and testes. Both hydralazine and the fish meal diet had a limited effect, if any, on the prevention or reversal of angionecrosis. In contrast, almost none of the rats given either captopril or SQ 29,852 showed cerebrovascular lesions or angionecrosis of the brain, heart and kidneys; angionecrosis in adult M-SHRSP kidneys disappeared within 10 or 18 days after the initiation of SQ 29,852 or captopril, respectively. This data seems to support a possible role for these two drugs not only in prevention, but also in repair, of angionecrosis independent of markedly high blood pressure in M-SHRSP. Based on our overall observations, SQ 29,852 was seen as the most effective of the treatments studied
In 1989, the European Working Party on High Blood Pressure in the Elderly started the double-blind, placebo-controlled, Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension. This report addresses whether the benefit of antihypertensive treatment varied according to sex, previous cardiovascular complications, age, initial blood pressure (BP), and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per-protocol analysis.
Methods
After stratification for center, sex, and cardiovascular complications, 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were randomized. Active treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d) and/or hydrochlorothiazide (12.5-25 mg/d), titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg, to below 150 mm Hg. In the control group, matching placebo tablets were employed similarly.
Results
In the intention-to-treat analysis, male sex, previous cardiovascular complications, older age, higher systolic BP, and smoking at randomization were positively and independently correlated with cardiovascular risk. Furthermore, for total (P=.009) and cardiovascular (P=.09) mortality, the benefit of antihypertensive drug treatment weakened with advancing age; for total mortality (P=.05), the benefit increased with higher systolic BP at entry, while for fatal and nonfatal stroke (P=.01), it was most evident in nonsmokers (92.5% of all patients). In the per-protocol analysis, active treatment reduced total mortality by 24% (P=.05), reduced all fatal and nonfatal cardiovascular end points by 32% (P<.001), reduced all strokes by 44% (P=.004), reduced nonfatal strokes by 48% (P=.005), and reduced all cardiac end points, including sudden death, by 26% (P=.05).
Conclusions
In elderly patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis. The per-protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths, 54 major cardiovascular end points, 29 strokes, or 25 cardiac end points. The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients.
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