Intima-media thickness after pravastatin stabilizes also in patients with moderate to no reduction in LDL-cholesterol levels: the carotid atherosclerosis Italian ultrasound study.

The Carotid Atherosclerosis Italian Ultrasound study (CAIUS), a multicenter, double-blind clinical trial, performed in 305 asymptomatic, moderately hypercholesterolemic patients, clearly demonstrated beneficial effects of pravastatin on the carotid intima-media thickness (IMT) progression. The database of the CAIUS study was examined in order to investigate the presence of a relationship, if any, between the activity of pravastatin on IMT progression rate and its hypocholesterolemic effect. Quantitative B-mode ultrasound imaging was used to quantify the individual mean maximum IMT progression rate in 3 years. In the overall group of patients (placebo and pravastatin) covariance analysis showed that while the variable 'treatment' (0 = placebo, 1 = pravastatin) was significantly related to the reduction of IMT progression (F= 6.6, P = 0.01), the IMT progression did not correlate with the extent of LDL-C lowering (F= 0.00, P = 0.98). To further investigate this issue. the pravastatin treated group was stratified into quartiles of LDL-C reduction. In contrast to what was observed in the placebo group, in which a positive mean IMT progression rate was observed, independent of the extent of LDL-C reduction, no IMT progressionwas observed in any subgroup treated with pravastatin. No significant difference was found among quartiles and no trend could be identified. In conclusion, the effect of pravastatin treatment on carotid IMT progression rate is beneficial; however the CAIUS study demonstrated that lowering LDL-C by itself, does not explain the variability of beneficial changes in IMT.

Systolic and pulse blood pressures (but not diastolic blood pressure and serum cholesterol) are associated with alterations in carotid intima-media thickness in the moderately hypercholesterolaemic hypertensive patients of the Plaque Hypertension Lipid Lowering Italian Study. PHYLLIS study group.

OBJECTIVE: The Plaque Hypertension Lipid Lowering Italian Study (PHYLLIS), is the first study in patients with hypertension (diastolic blood pressure (DBP) 95-115 mmHg; systolic blood pressure (SBP) 150-210 mmHg), moderate hypercholesterolaemia (LDL-cholesterol 4.14-5.17 mmol/l (160-200 mg/dl) and initial carotid artery alterations (maximum intima-media thickness (IMT) Tmax > or = 1.3 mm). The primary objective of PHYLLIS is investigating whether in these patients administration of an angiotensin converting enzyme inhibitor, fosinopril, and a statin, pravastatin, is more effective than administration of a diuretic and a lipid-lowering diet in retarding or regressing alterations in carotid IMT. While the study is in progress, baseline data are here reported to clarify the association of various risk factors with carotid IMT in these medium-high risk hypertensive patients. METHODS: Patients numbering 508 have been randomized to PHYLLIS by 13 peripheral units, in Italy. Age was (mean +/- SD) 58.4 +/- 6.7 years, males were 40.2%, current smokers 16.5%, means +/- SD of serum total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol and triglycerides concentrations were 6.79 +/- 0.67, 4.69 +/- 0.51, 1.37 +/- 0.38, 1.59 +/- 0.64 mmol/l (262.4 +/- 25.8, 181.3 +/- 19.8, 53.0 +/- 14.6, 141.0 +/- 56.7 mg/ dl). Means +/- SD of clinic sitting SBP/DBP were 159.8 +/- 9.0/98.3 +/- 4.2 mmHg. 483 of the 508 patients also had 24 h ambulatory BP monitoring, edited and read at a centralized unit (mean +/- SD 24 h SBP/DBP averages 136.3 +/- 14.1/84.0 +/- 10.0 mmHg). Quantitative B-mode ultrasound (Biosound 2000 II 5A, Biosound, Indianapolis, Indiana, USA) recordings of carotid arteries were taken by certified sonographers in the peripheral units and tracings were all read at a central unit. CBMmax (mean IMT of eight sites at common carotids and bifurcations) was 1.21 +/- 0.17; Mmax (mean of 12 sites also including internal carotids) 1.16 +/- 0.17, and Tmax (single maximum) 1.85 +/- 0.48 mm. RESULTS: Ambulatory SBP and pulse pressure (PP) (24 h, daytime, night-time averages) and their variability indices (24 h SD) were always significantly correlated with CBMmax and Mmax (P0.01 -0.001), and the correlations remained significant after adjustment for age, gender and smoking. No measurement of DBP was ever associated with any IMT measurement. Likewise, no lipid variable was found associated with any IMT measurement. CONCLUSIONS: Baseline data from PHYLLIS indicate that in this population of hypertensive patients with moderate hypercholesterolaemia, SBP and PP are with age among the most significant factors associated with carotid artery alterations. However, the narrow range of inclusion LDL-cholesterol and DBP values may have obscured an additional role of these variables.

An effective approach for treating elderly patients with isolated systolic hypertension: results of an Italian multicenter study with fosinopril.

Cardiovascular diseases are the most common causes of mortality, and hypertension is the most common cardiovascular disease in all ages. The Systolic Hypertension in the Elderly Program (SHEP) trial has shown that the pharmacologic reduction of isolated systolic hypertension can significantly reduce the incidence of cardiovascular complications. The aim of the Italian multicenter study reported here is to compare the efficacy, safety, and tolerability of fosinopril, a novel angiotensin converting enzyme (ACE) inhibitor with a dual route of excretion, with chlorthalidone, the diuretic administered in the SHEP study, in 312 elderly patients with isolated systolic hypertension. Our results show that fosinopril and chlorthalidone produce identical and statistically significant reductions in systolic blood pressure (-23.9 +/- 11.6 mm Hg and -23.7 +/- 10.9 mm Hg, respectively) and, to a lesser extent, in diastolic blood pressure (-7.1 +/- 3.1 mm Hg and -5.2 +/- 2.3 mm Hg, respectively). Only chlorthalidone caused a statistically significant change in uric acid, total cholesterol, blood urea, and serum potassium concentrations. Fosinopril was also somewhat better tolerated than chlorthalidone. In conclusion, the novel ACE inhibitor fosinopril is an effective and well-tolerated antihypertensive agent for use in elderly patients with isolated systolic hypertension and appears to be a suitable alternative for the treatment of isolated systolic hypertension.

Post acute myocardial infarction: the Fosinopril in Acute Myocardial Infarction Study (FAMIS).

Many studies have clearly documented the beneficial effects of angiotensin converting enzyme (ACE) inhibitors in patients with acute myocardial infarction (AMI). The Fosinopril in Acute Myocardial Infarction Study (FAMIS) was a 2-year randomized, double-blind, placebo-controlled multicenter study investigating the hemodynamic and clinical effects of early (< 9 h from onset of symptoms) administration of fosinopril in 285 patients with anterior AMI undergoing thrombolysis within 6 h of symptom onset. The objective of the study was twofold: 1) to estimate changes in left ventricular (LV) volumes and function over 3 months by a series of echocardiographic evaluations, and 2) to clinically assess mortality and the occurrence of congestive heart failure (CHF) over 2 years. LV volumes measured at baseline (24 to 48 h from symptom onset) were within the normal range in over two-thirds of randomized patients, and the changes in volume were comparable after 3 months of treatment with either fosinopril or placebo. However, fosinopril-treated patients showed a 30% reduction in the 2-year incidence of death or moderate-to-severe CHF (P = .04) despite having a worst prognostic profile at baseline. This benefit of fosinopril was confirmed in the subgroup of patients without CHF on admission, who showed a 34.1% reduction in the 2-year occurrence of CHF (P = .05) and a 29.1% reduction in death or CHF (P = .04). The results of the FAMIS study suggest that early treatment with fosinopril, in conjunction with thrombolysis, can significantly delay the development of CHF in patients with AMI, acting through mechanisms independent of fosinopril's impact on LV remodeling.

[Efficacy and tolerability of a preconstituted combination of captopril 50 mg + hydrochlorothiazide 25 mg in aged subjects with isolated systolic hypertension]. / Efficacia e tollerabilità dell'associazione precostituita captopril 50 mg + idroclorotiazide 25 mg in soggetti anziani con ipertensione sistolica isolata.

In this study we evaluated in open the efficacy and tolerability of the preconstituted association Captopril 50 mg + Hydrochlorothiazide 25 mg, for a six-month period, in a population of 201 aged patients affected by isolated systolic hypertension. The results showed a good antihypertensive efficacy of the association Captopril-Hydrochlorothiazide 25 mg and also an optimal safety of use.

Evaluation of regression of left ventricular hypertrophy in hypertensive patients treated with captopril as assessed by magnetic resonance imaging.

Magnetic resonance imaging (MRI) was used to assess left ventricular mass (LVM) in 20 mild to moderate essential hypertensive patients with left ventricular hypertrophy (LVH) (LVM > 120 g/m2), treated with captopril alone or combined with hydrochlorothiazide. MRI examination was performed at the beginning (T0) and after 3 months (T3) of active treatment, by using a Philips Gyroscan S15 superconducting system, operating at 1.5 Tesla. We used a multislice-multiphase spin-echo sequence on the short-axis and transverse plane (TE = 30 ms; TR = 80-90% RR). End-diastolic thickness of interventricular septum (IVST) and lateral wall (LWT) were measured. LVM was calculated according to Simpson's rule. The results were: IVST 12.2 mm +/- 0.7 vs 10.9 mm +/- 0.5 (p < 0.001); LWT 11.5 mm +/- 0.9 vs 10.5 mm +/- 0.9 (p < 0.001); LVM 160 (g/m2) +/- 5.5 vs 138.4 g/m2 +/- 6 (p < 0.001), at T0 and T3, respectively. Our study demonstrates a significant regression of LVH in hypertensive patients after 3 months of treatment with captopril and a high accuracy of MRI as a noninvasive technique of measuring the LVM reduction.

Short- and long-term effects of early fosinopril administration in patients with acute anterior myocardial infarction undergoing intravenous thrombolysis: results from the Fosinopril in Acute Myocardial Infarction Study. FAMIS Working Party.

BACKGROUND: Angiotensin-converting enzyme inhibitors are used in patients who have myocardial infarction with left ventricular (LV) dysfunction. Few data are available in patients whose LV function is within the normal range. METHODS AND RESULTS: The Fosinopril in Acute Myocardial Infarction Study was a 2-year, randomized, double-blind, placebo-controlled, multicenter study of 285 patients with anterior acute myocardial infarction and was designed to investigate the effects of the early (<9 hours) administration of fosinopril and thrombolysis on (1) changes in echocardiographically evaluated LV volumes at 3 months and (2) long-term occurrence of death and congestive heart failure. LV volumes were normal at baseline in more than 70% of patients and were comparable between groups both at baseline and after 3 months of treatment. Fosinopril-treated patients showed a 30% reduction in the 2-year combined prevalence of death or moderate-to-severe congestive heart failure (New York Heart Association class III-IV) despite having a worse clinical profile at baseline. The benefit of fosinopril was confirmed both in patients without congestive heart failure at admission and in those with ejection fraction >40% at baseline. Moreover, the incidence of significant ventricular arrhythmias was lower in the fosinopril group (0.8% vs 6.0%, p < 0.02). CONCLUSIONS: The results of the Fosinopril in Acute Myocardial Infarction Study suggest that early treatment with fosinopril can benefit patients with acute myocardial infarction in addition to a prevention of LV remodeling.

Optimizing the assessment of the elderly patient with borderline hypertension: the Hypertension and Ambulatory Recording in the OLD (HAROLD) study.

This article describes the objectives and protocol of the HAROLD study, a trial designed to assess whether home blood pressure (BP), 24-hour ambulatory BP, left ventricular structure and function, and albumin excretion rate are more accurate predictors of outcome than traditional sphygmomanometric BP in elderly subjects with borderline hypertension. Development of sustained hypertension (BP > or = 160/95 mmHg) and incidence of morbid events over a 5-year follow-up are considered soft and hard endpoints, respectively. Patients with blood pressure values between 140/90 and 159/94 mmHg after three months of observation and who have never been treated, are eligible for the study; these subjects must be 60 to 79 years old, and free from other important risk factors for atherosclerosis. Baseline exams, which include plasma renin and insulin, 24-hour urine collection for detection of microalbuminuria, and echo-doppler cardiac examination are repeated after three and five years follow-up, or when subjects develop sustained hypertension. To recruit a large enough number of subjects to allow a sufficient number of endpoints (over 1000 subjects), the study is conducted as a multicenter trial. Ninety Italian Hospital Centers have agreed to participate in the study.

Effect of the HMG-CoA reductase inhibitors on blood pressure in patients with essential hypertension and primary hypercholesterolemia.

Certain hydroxymethylglutaryl coenzyme A reductase inhibitors, ie, statins, may cause vasodilation by restoring the endothelial dysfunction that frequently accompanies hypertension and hypercholesterolemia. Several studies have found that a blood pressure reduction is associated with the use of statins, but conclusive evidence from controlled trials is lacking. After an 8-week placebo and diet run-in period, 30 persons with moderate hypercholesterolemia and untreated hypertension (total cholesterol 6.29+/-0.52 mmol/L, systolic and diastolic blood pressure 149+/-6 and 97+/-2 mm Hg) were randomized in a double-blind manner to placebo or pravastatin (20 to 40 mg/d) in a crossover design. In 25 participants who completed the 32-week trial, pravastatin decreased total and LDL cholesterol (both -1.09 mmol/L, P=0.001), systolic and diastolic blood pressure (-8 and -5 mm Hg, both P=0.001), and pulse pressure (-3 mm Hg, P=0.011) and blunted the blood pressure increase caused by the cold pressor test (-4 mm Hg, P=0.005) compared with placebo. It also reduced the level of circulating endothelin-1 (P=0.001). The blood pressure results were virtually unchanged in stratified analyses according to gender and age and in intention-to-treat analyses that included the 5 patients who dropped out of the study. When the participants were taking either placebo or pravastatin, blood pressure was not significantly correlated with total or LDL cholesterol or with circulating endothelin-1. Pravastatin decreases systolic, diastolic, and pulse pressures in persons with moderate hypercholesterolemia and hypertension. This antihypertensive effect may contribute to the documented health benefits of certain statins.