Follow-up of renal function in treated and untreated older patients with isolated systolic hypertension. Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.

BACKGROUND: In the outcome trials that provided information on renal function in older hypertensive patients, diuretics and beta-blockers were mostly used as first-line drugs. The long-term renal effects of calcium-channel blockers remain unclear. OBJECTIVE: To compare the changes in renal function in 2,258 treated and 2,148 untreated patients with isolated systolic hypertension, of whom 455 had diabetes mellitus and 390 had proteinuria. METHODS: We performed a post-hoc analysis of the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Active treatment was initiated with nitrendipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), or both, titrated or combined to reduce the sitting systolic blood pressure by at least 20 mmHg, to less than 150 mmHg. The main outcome measures were serum creatinine concentration and creatinine clearance calculated by the formula of Cockroft and Gault. RESULTS: Serum creatinine concentration at the time when participants were randomly allocated to study groups was less than 176.8 micromol/l (2.0 mg/dl), averaging 88 micromol/l. At the time of the last serum creatinine measurement, the blood pressure difference (P< 0.001) between the two groups was 11.6/4.1 mmHg. In the intention-to-treat analysis (11,427 patient-years), serum creatinine and the calculated creatinine clearance were not influenced by active treatment. However, in the patients assigned randomly to receive active treatment, the incidence of mild renal dysfunction (serum creatinine at least 176.8 mmol/l) decreased by 64% (P= 0.04) and that of proteinuria by 33% (P= 0.03). Active treatment reduced the risk of proteinuria more in diabetic than in non-diabetic patients: by 71%, compared with 20% (P= 0.04). In non-proteinuric patients, active treatment did not influence serum creatinine, whereas in patients with proteinuria at entry to the study, serum creatinine decreased on active treatment (P< 0.001). Furthermore, in on-randomized treatment comparison stratified for risk at baseline, serum creatinine concentration did not change (P= 0.98) in patients continuing to receive monotherapy with nitrendipine, whereas it increased by 6.73 mmol/l (P < 0.001) in patients who received hydrochlorothiazide alone or in combination with other study medication (P < 0.001 for difference in trends). CONCLUSIONS: In older patients with isolated systolic hypertension, antihypertensive treatment starting with the dihydropyridine calcium-channel blocker, nitrendipine, did not decrease blood pressure at the expense of renal function and prevented the development of proteinuria, especially in diabetic patients.

Calcium channel blockade and cardiovascular prognosis in the European trial on isolated systolic hypertension.

In the double-blind Systolic Hypertension in Europe (Syst-Eur) Trial, active treatment was initiated with nitrendipine (10 to 40 mg/d) with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d) titrated or combined to reduce sitting systolic blood pressure by at least 20 mm Hg to <150 mm Hg. In the control group, matching placebos were used similarly. In view of persistent concerns about the use of calcium channel blockers as first-line antihypertensive drugs, this report explored to what extent nitrendipine, administered alone, prevented cardiovascular complications. Age at randomization averaged 70.2 years and systolic/diastolic blood pressure 173.8/85.5 mm Hg. Of 2398 actively treated patients, 1327 took only nitrendipine (average dose, 23.4 mg/d), and 1042 progressed to other treatments including nitrendipine (n=757; 35.7 mg/d), enalapril (n=783; 13.4 mg/d), and/or hydrochlorothiazide (n=294; 21.0 mg/d). Compared with the whole placebo group (n=2297), patients receiving monotherapy with nitrendipine had 25% (P=0.05) fewer cardiovascular end points, and those progressing to other active treatments showed decreases (P

Prevalence of obesity in Greek hypertensives.

An association of obesity and hypertension is well recognised and there is a direct positive relationship between body weight or body mass index (BMI) and blood pressure (BP), although the mechanisms responsible for weight-related increases of BP are still unknown. Obesity does appear to be an independent risk factor for premature mortality, especially when it is associated with other risk factors such as hyperinsulinemia and glucose intolerance (or diabetes), hyperlipidemia, and hypertension. However, there are differences among racial and ethnic subgroups. The aim of our study was the investigation of the prevalence of obesity and its severity among Greek hypertensive patients in comparison to normotensive controls. We have studied a large enough sample of Greek hypertensives consisting of 1101 patients (504 male/597 female, 23-85 years of age) and 242 normotensive controls (136 male/106 female, 23-75 years of age). In all patients and normotensive controls BMI (ie weight/height in 2mm) was measured, as well as the waist-to-hip (W/H) ratio. A BMI of less than 27 was accepted as normal, a BMI of 27-32 as indicating mild to moderate obesity, a BMI of 32-37 as an index of severe obesity, and a BMI > 37 as a measure of very severe obesity. Obesity in hypertensive patients was more frequent than in normotensive controls (62.5% vs 54.2%, P = 0.024), and hypertensive women were more commonly obese than hypertensive men (67.16% vs 56.8%, P = 0.002). Severe and very severe obesity was more common in hypertensive women than in men (20.7% vs 9.68%, P < 0.001, and 8.1% vs 0.52%, P < 0.0001, respectively), although obesity of severe and very severe degree was equally found in hypertensives and normotensives of both sexes. BMI of all hypertensives was significantly greater in comparison to that of normotensives (30.13 +/- 0.44 vs 26.74 +/- 0.76, mean +/- s.e., P < 0.0001); W/H ratio of hypertensives was significantly greater than that of normotensives, indicating more frequent central obesity in hypertensives. We conclude that obesity in Greek hypertensive patients is more frequent than in normotensive controls, while hypertensive women have more severe obesity than hypertensive men, and are more frequently obese than men.

Frequency of cough during therapy with ACE inhibitors in Greek hypertensives.

Persistent dry cough is one of the most common side-effects during therapy with ACE inhibitors. The frequency of cough ranges widely (from 0.2% to 15%) in different series, being higher in small studies and smaller in retrospective studies with large number of patients. The aim of the present study was to evaluate the true frequency of cough induced by treatment with ACE inhibitors in Greek hypertensives and to determine various possibly correlated parameters, including sex, duration of therapy and kind and dose of ACE inhibitors. All hypertensive patients followed in our Hypertension Clinic and treated with ACE inhibitors participated in the study. A total of 228 patients, 103 males and 125 females, 24-80 years of age, were treated with ACE inhibitors for a period of 1-41 months: 121 with enalapril, 40 with captopril, 39 with lisinopril, 25 with perindopril and 3 with ramipril. During treatment with ACE inhibitors persistent dry cough occurred in 15 patients, 12 women and 3 men, giving a frequency of 6.58%. Eleven patients (4.82%) volunteered the information and three after questioning. The mean age of these 15 patients with cough was significantly higher from that of the group (n = 213) without cough (64.27 +/- 2.5 vs. 57.9 +/- 0.74 years, mean +/- SEM, P = 0.024). The 12 women with cough were significantly older than the 113 without cough (67.77 +/- 2.8 vs. 57.8 +/- 1.04 years, P = 0.032).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of single and combined infusions of angiotensin II and aldosterone on colonic potential difference, blood pressure and renal function, in patients with adrenal deficiency.

1. The effect of single and combined infusions of angiotensin and aldosterone on colonic potential difference, blood pressure and renal function was studied in two normal male subjects and four female patients with adrenal deficiency maintained only on cortisone. 2. Aldosterone had its usual effect on colonic potential difference and it was possible to show that angiotensin had a small but definte effect of its own in the absence of aldosterone. The two hormones produced a summation response when given together. 3. The effects on renal function in two normal young male subjects were similar to those known previously. The response of the patients was different and probably reflected a number of factors, such as age, sex and long-standing adrenal deficiency. 4. Although the numbers were small, both normal subjects and patients showed a significantly greater rise of blood pressure with combined infusions of angiotensin and aldosterone than with angiotensin alone. The plasma concentrations of angiotensin were similar with both types of infusion, and so increased sensitivity to angiotensin in the presence of aldosterone is postulated.