Effects of once-daily angiotensin-converting enzyme inhibition and calcium channel blockade-based antihypertensive treatment regimens on left ventricular hypertrophy and diastolic filling in hypertension: the prospective randomized enalapril study evaluating regression of ventricular enlargement (preserve) trial.

BACKGROUND: The Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) study was designed to test whether enalapril achieves greater left ventricular (LV) mass reduction than does a nifedipine gastrointestinal treatment system by a prognostically meaningful degree on a population basis (10 g/m(2)). METHODS AND RESULTS: An ethnically diverse population of 303 men and women with essential hypertension and increased LV mass at screening echocardiography were enrolled at clinical centers on 4 continents and studied by echocardiography at baseline and after 6- and 12-month randomized therapy. Clinical examination and blinded echocardiogram readings 48 weeks after study entry in an intention-to-treat analysis of 113 enalapril-treated and 122 nifedipine-treated patients revealed similar reductions in systolic/diastolic pressure (-22/12 versus -21/13 mm Hg) and LV mass index (-15 versus -17g/m(2), both P>0.20). No significant between-treatment difference was detected in population subsets defined by monotherapy treatment, sex, age, race, or severity of baseline hypertrophy. Similarly, there was no between-treatment difference in change in velocities of early diastolic or atrial phase transmitral blood flow. More enalapril-treated than nifedipine-treated patients required supplemental treatment with hydrochlorothiazide (59% versus 34%, P<0.001) but not atenolol (27% versus 22%, NS). CONCLUSIONS: Once-daily antihypertensive treatment with enalapril or long-acting nifedipine, plus adjunctive hydrochlorothiazide and atenolol when needed to control blood pressure, both had moderately beneficial and statistically indistinguishable effects on regression of LV hypertrophy.

Relationship between site of disease and familial occurrence in Crohn's disease.

Concordance in the extent of disease among the family members of patients with Crohn's disease has not been widely investigated. Furthermore, the relationship between the site of the disease and familial occurrence has never been studied. Our aim was to evaluate the familial occurrence of Crohn's disease in the various sites. Nine hundred thirty-four patients with Crohn's disease, observed consecutively in two gastrointestinal departments, were investigated to determine first-degree familial incidence (in both Crohn's disease and ulcerative colitis). Whenever two or more members were attending the same clinic, only one was regarded as a propositus. The analysis, therefore, was carried out on 882 patients. The exact site of the disease was determined in all patients either at diagnosis or during the follow-up by colonoscopy and by small bowel enema. The rate of concordance in the extent of disease and familial occurrence in the various sites was evaluated and the difference was calculated by chi-square test. Sixty-one propositi were identified among all the patients. Forty-nine had familial occurrence for the same disease (concordant patients), whereas 12 had at least one relative with ulcerative colitis (discordant patients). In 44 propositi with only one relative affected, the rates of concordance in the extent of the disease were 84, 68, 18, and 0% respectively, for the ileum, the ileum-right colon, the ileum-total colon, and the colon. The number of propositi in the various sites was as follows: 4 of 162 (2.4%) patients with the disease located in the colon, 1 of 9 (11%) with the jejunum site, 24 of 380 (6.3%) with the ileum site, 16 of 165 (9.7%) with the ileum and right colon site, and 16 of 164 (9.7%) with the ileum and total colon site. The chi-square values of propositi distribution among other sites and the colon was, respectively, as follows: jejunum, 2.2 (N.S.); ileum, 3.4 (P = 0.06); ileum and right colon, 7.4 (P = 0.006); and ileum and total colon, 7.4 (P = 0.006). This study shows a pronounced concordance in the site of the disease for family members with Crohn's disease and suggests that familial occurrence in Crohn's disease is less frequent when the disease is located in the colon rather than elsewhere.

Effects of new fish oil derivative on fatty acid phospholipid-membrane pattern in a group of Crohn's disease patients.

Fish oil has been recently proposed as a possible effective treatment in inflammatory bowel disease (IBD); however, a lot of annoying side effects (ie, belching, halitosis, diarrhea, etc) affect patient compliance. We carried out a study of patient tolerance in a group of Crohn's disease (CD) patients with a new fish oil derivative consisting of 500-mg capsules of eicosapentaenoic-docosahexaenoic (EPA 40%-DHA 20%), a free fatty acid mixture (Purepa), and we also evaluated its incorporation into phospholipids, both in plasma and in red cell membranes. Five groups of 10 CD patients in remission received nine Purepa capsules daily in four different preparations (A: uncoated, B: coated, pH 5.5; C: coated, pH 5.5, 60 min time release; D: coated, pH 6.9) and 12 x 1-g capsules daily of a triglyceride preparation (Max-EPA, EPA 18%-DHA 10%), respectively. We coated three of the four Purepa preparations in order to delay the release of contents in an attempt to minimize the side effects. After six weeks of treatment, the group taking Purepa capsules, coated, pH 5.5, 60 min time release (group C) showed the best incorporation of EPA and DHA in red blood cell phospholipid membranes (EPA from 0.2 to 4.4%, DHA from 3.7 to 6.3%), and no side effects were registered, whereas in all other groups side effects were experienced in 50% or more of subjects. This new preparation will make it possible to treat patients for long periods.

Zinc supplementation restores plasma concentrations of zinc and thymulin in patients with Crohn's disease.

The aim of this work was to evaluate whether oral supplementation with zinc sulphate (ZnSO4) could restore thymic endocrine function in patients with Crohn's disease who showed decreased plasma concentrations of zinc and active thymulin, a zinc-dependent thymic hormone. Twenty-seven patients in clinical remission were randomly assigned to receive, for 3 months, one of the following treatments: 60 mg/day ZnSO4; 200 mg/day ZnSO4 or placebo. Plasma thymulin activity and zinc concentrations significantly increased only in patients treated with 200 mg/day ZnSO4. Lymphocyte subpopulations, within the range of normality before zinc supplementation, were unaffected by any of the administered treatments. In conclusion, low plasma concentrations of zinc and thymulin in Crohn's disease patients were restored by the administration of high doses of zinc.

Noninvasive assessment of hemodynamic changes during therapy with nitrendipine in arterial hypertension.

Changes in hemodynamic variables regulating systolic function were examined by M-mode echocardiography in 14 patients with long-duration primary uncomplicated hypertension treated with nitrendipine once daily (20 mg). At the end of treatment (8th week) blood pressure and peripheral resistance were greatly reduced (p less than 0.0001), while the indices of cardiac function (ejection fraction and cardiac index) showed significant increases (p less than 0.01). The variations in ejection fraction were analyzed by multiple linear regression and were mainly influenced by the decrease in end-systolic stress (contribution: 60%). At baseline, despite no radiographic or clinical signs of heart failure, 6 of the studied patients showed impaired systolic function, likely due to the strength of other variables (age, risk factors); in those patients, systolic function was clearly enhanced at the end of treatment, while no change was found in patients with initial normal pump function. Changes in cardiac output were due to a significant increase in heart rate in patients with normal pump function and to improved stroke volume in the others. Left ventricular mass index was slightly reduced (p less than 0.005), primarily because of the reduction in end-diastolic volume (p less than 0.01). When analyzed by the 2 subgroups (with or without impaired systolic function), the left ventricular mass index appeared to be significantly reduced only in those patients with normal basal pump function. This difference was most likely due to the different effects of treatment on end-diastolic volume.

Slow-release nifedipine versus placebo in the treatment of arterial hypertension. A double blind ergometric evaluation of cardiac workload.

The effects of slow-release nifedipine on blood pressure and cardiac workload have been studied during bicycle exercise testing in a randomized, double blind trial in 20 patients with mild to moderate hypertension. After a fortnight's wash-out, patients were allocated to either slow-release nifedipine (20 mg twice daily) or placebo for a 2-month period. At baseline and at the end of treatment blood pressure and heart rate were measured at rest and during ergometric exercise; cardiac workload was calculated as the product of systolic blood pressure by heart rate. Significant decreases in blood pressure at rest and in cardiac workload on exercise were demonstrated at the end of nifedipine treatment. The reduction of cardiac workload was mainly due to the lower baseline values of resting blood pressure. Heart rate showed a reduction of its increase during ergometric exercise at the end of nifedipine treatment as compared to baseline, likely due to an improvement in stroke volume.

Changes in left ventricular mass during a double-blind study with chlorthalidone and slow-release nifedipine.

The presence of a possible correlation between changes in left ventricular mass of hypertensive patients and the degree of blood pressure reduction with different antihypertensive drugs has been investigated in 40 outpatients by M-mode echocardiography. Ten of these, with blood pressure in normal limits with different antihypertensive treatment had their therapy changed in chlorthalidone 25 mg/day without any run-in (Group A); other 30 patients, with a previously uncontrolled blood pressure, after a 14 day run-in, were randomly allocated to chlorthalidone 25 mg/day (Group B), slow release nifedipine 20 mg/day (Group C) or placebo (Group D). At the end of the eight week treatment period a further decrease in systolic blood pressure was observed in Group A without changes in ventricular mass; an highly significant decrease in both systolic and diastolic blood pressure was observed in B and C but only patients on chlorthalidone changed their ventricular mass; no change in both blood pressure and ventricular mass was observed on placebo. As changes in ventricular mass are not correlated with blood pressure reduction, we conclude that other, not well defined factors, apart from the decrease in duration and degree of left ventricular systolic wall tension, may be responsible for reversal of left ventricular hypertrophy.