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Biomedical subjects

A Zanchetti

Publications and source records attributed to A Zanchetti.

At least 91 records · Page 5Linked to original sources
PubMed1998

Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group.

BACKGROUND: Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension. METHODS: 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85 mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo. FINDINGS: Diastolic blood pressure was reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or =85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0.001). INTERPRETATION: Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common.

Aged↗
PubMed1998

Rationale and design for the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial.

The Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial is a randomized, prospective, double-blind, parallel-group, two-arm, actively controlled, multicenter, international 5-year clinical trial involving 15,000 patients. CONVINCE will compare the incidence of fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, or cardiovascular-disease-related death in two antihypertensive treatment regimens. One treatment arm begins with controlled onset-extended release (COER)-verapamil, which has its major antihypertensive effect 6-12 hours after administration. The other arm (standard of care (SOC)) begins with either hydrochlorothiazide (HCTZ) or atenolol, one of which is preselected by the investigator for an individual patient prior to randomization. Secondary objectives include comparisons of the regimens for each of the components of the primary endpoint (separately), death or hospitalization related to cardiovascular disease, efficacy in lowering blood pressure to goal, primary events occurring between 6 am and noon, all-cause mortality, withdrawals from blinded therapy, cancer, and hospitalizations due to bleeding. Patients may be enrolled if they are hypertensive and at least 55 years of age and have an established second risk factor for cardiovascular disease. Initial medications include COER-verapamil (180 mg/d), HCTZ (12.5 mg/d), or atenolol (50 mg/d). Initial doses are doubled if blood pressure (BP) does not reach goal (systolic BP < 140 mm and diastolic BP < 90 mm Hg). If BP is not controlled by the higher dose of the initial medication, HCTZ is added to COER-verapamil, or the SOC choice not initially selected is added in the SOC arm. An ACE-inhibitor is recommended (although nearly any open-label medication is allowed) as the third step for patients whose BP is not adequately controlled or who have a contraindication to one of the two SOC medications. Patients take two sets of tablets daily, one in the morning and one in the evening. Although most patients switch from an established antihypertensive medication to randomized treatment, untreated patients with stages I-III hypertension (SBP between 140 and 190 or DBP between 90 and 110 mm Hg) are eligible. Outcomes are monitored by an independent Data and Safety Monitoring Board. Enrollment began during the third quarter of 1996, and follow-up is to be completed in the third quarter of 2002.

Aged↗
PubMed1998

Postischemic left ventricular dysfunction is abolished by alpha-adrenergic blocking agents.

OBJECTIVES: We sought to evaluate the efficacy of alpha-adrenergic blocking agents in counteracting left ventricular (LV) dysfunction occurring after transient ischemia in humans. BACKGROUND: The mechanisms underlying postischemic LV dysfunction are largely unknown. METHODS: Percutaneous transluminal coronary angioplasty (PTCA) provides a clinical model of ischemia and reperfusion. In 50 patients undergoing coronary stenting for 77+/-5% stenosis, LV function was monitored by transesophageal echocardiography during and 30-min after PTCA. Fifteen minutes after stenting, 15 patients received 12 microg/kg body weight of the alpha-blocker phentolamine intracoronarily, 15 patients received 600 microg/kg of the alpha1-blocker urapidil intravenously, 10 patients received the combination of phentolamine and 1.2 mg of propranolol intracoronarily, and 10 patients received saline. RESULTS: Fifteen minutes after successful coronary dilation, significant contractile dysfunction occurred in previously ischemic and nonischemic myocardium. LV dysfunction was accompanied by an increase in coronary resistance and diffuse vasoconstriction. Alpha-blockers counteracted LV dysfunction and coronary resistance and the increase in vasoconstriction. Phentolamine and urapidil increased global LV shortening from 34+/-9% to 45+/-8% and to 49+/-8%, respectively (p < 0.05). After the administration of propranolol combined with phentolamine, LV dysfunction remained unchanged (34+/-6%), as in control subjects. CONCLUSIONS: LV dysfunction occurs after PTCA, as described in animal models after ischemia. Alpha-blockers abolished LV, macrocirculatory and microcirculatory dysfunction, whereas the alpha-blocker effect was prevented by combining alpha- and beta-blockers. The evidence of diffuse rather than regional dysfunction, together with the opposite effects of alpha- and beta-blockade, supports the hypothesis of neural mechanisms eliciting postischemic LV dysfunction.

Adrenergic alpha-Antagonists↗
PubMed1998

Prevalence of episodes of ST-segment depression among mild-to-moderate hypertensive patients in northern Italy: the Cardioscreening Study.

OBJECTIVES: To assess the prevalence of episodes of ST-segment depression in a population of consecutive patients with mild-to-moderate essential hypertension who are free of clinical signs of coronary artery disease. METHODS: The study involved 28 Italian centers that enrolled 414 hypertensive patients (aged 50-70 years; diastolic blood pressure > or = 95-115 mmHg or systolic blood pressure > or = 150-220 mmHg, or both, 10 days after withdrawal of medications). Silent myocardial ischemia was assessed by means of exercise stress testing and 48 h Holter monitoring. An ischemic episode was defined as a horizontal or downward sloping ST-segment depression > or = 100 microV, occurring 80 ms after the J point, and lasting for at least 1 min. RESULTS: Of the 414 patients enrolled, 411 completed the exercise stress test. During the test significant ST-segment depression occurred for 25 patients (6.1%) and all episodes but one were asymptomatic and not associated with arrhythmias. Of the 396 patients for whom we analyzed a 48 h Holter recording, 43 (10.9%) had at least one episode of ST-segment depression and seven of these had also had one during the exercise stress test The median number of episodes per patient was five (range 1-19), median duration was 9 min (range 1-20 min), and the mean amplitude of the ST-segment depression was 190 +/- 180 microV. None of these episodes was associated with symptoms and all of them occurred under resting condition. Patients with (n = 61) and without (n = 335) ST-segment depression during Holter monitoring or exercise stress testing had similar ages (59 +/- 6 versus 58 +/- 6 years) and did not differ for tobacco smoking, plasma lipid levels, blood pressure values and prevalence of echocardiographic left ventricular hypertrophy (57% of patients had left ventricular mass indexes > or = 134 g/m2 for men and > or = 110 g/m2 for women in both groups). Women had a higher prevalence of ST-segment depression than did men during Holter monitoring [32 of 183 (17.5%) versus 11 of 213 (5.2%)], whereas the prevalences of ischemia during the exercise stress test were similar. Female sex was the only significant factor associated with the occurrence of silent myocardial ischemia [odds ratio 2.56 (95% confidence interval 1.40-4.71)]. CONCLUSIONS: Our results show that 15% of patients with mild-to-moderate hypertension, who are free of clinical signs of coronary artery disease, experience episodes of ST-segment depression during Holter monitoring or exercise stress testing. Most of these episodes are asymptomatic and are not associated with the severity of hypertension, the presence of left ventricular hypertrophy, and other risk factors for coronary artery disease. Episodes of ST-segment depression are more common for women than they are for men, particularly during Holter monitoring. The early detection of silent myocardial ischemia by Holter monitoring or by the exercise stress test might be useful for the identification of hypertensive patients who should be investigated further and administered a more specific treatment.

Age Factors↗
PubMed1998

Risk factors associated with alterations in carotid intima-media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis.

BACKGROUND: The possibility that calcium antagonists exert an anti-atherosclerotic action at least partly independently of the blood-pressure-lowering effect is supported by results of a large number of experimental studies and can now be investigated by quantitative B-mode ultrasound imagining of the carotid artery walls. DESIGN: The European Lacidipine Study on Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multinational trial comparing effects of 4-year treatment based on the long-acting, highly lipophilic calcium antagonist lacidipine with those of treatment based on the beta-blocker atenolol on the development of carotid artery wall alterations in patients (aged 45-75 years) with mild-to-moderate hypertension (systolic blood pressure 150-210 mmHg and diastolic blood pressure 95-115 mmHg). While the intervention study is progressing, this article summarizes baseline data obtained from the whole cohort of 2259 patients randomly allocated to treatment. METHODS: Baseline ultrasound data were obtained from two replicate examinations performed shortly before random allocation to treatment by certified sonographers at 23 referral centres and read at the ultrasound coordinating centre at the Wake Forest University School of Medicine. Intima-media thickness was measured at up to 12 different sites in the carotid artery tree and expressed as the mean of the maxima at these sites (Mmax), the mean of the maxima at four sites in the distal common carotid artery and bifurcation (CBMmax) and the maximum intima-media thickness (Tmax). Baseline demographic and clinical measurements were performed by investigators in 410 peripheral clinical units and 24 h ambulatory blood pressure monitorings read and validated by members of a centralized unit at the University of Milan. The statistical analysis centre at the Technische Universität München received and analysed all baseline data, by calculating means +/- SD, medians and ranges and performing correlation (Spearman correlation coefficients) and multiple regression analyses. RESULTS: Prevalence of carotid artery wall alterations among the hypertensive patients randomly allocated to treatment in the ELSA was very high: 82% had Tmax > or = 1.3 mm ('plaques' according to protocol) and 17% had Tmax > or = 1.0 and < 1.3 mm ('thickening'), with a median of two plaques per patient. We found significant correlations between ultrasound measurements and the following demographic and clinical variables: age, sex, systolic blood pressure and pulse pressure (both clinic and ambulatory), concentrations of total, high-density lipoprotein and low-density lipoprotein cholesterol and triglycerides, smoking habit and duration of hypertension. We found no significant correlation to diastolic blood pressure and glucose concentration. A multiple regression analysis indicated significant variables in the following rank order: age, 24 h ambulatory pulse pressure, sex, low-density lipoprotein cholesterol concentration, triglyceride concentration, smoking and clinic systolic blood pressure. CONCLUSIONS: Analysis of baseline data from the ELSA has shown that there is an extremely marked prevalence of carotid artery wall alterations among mild-to-moderate, middle-aged hypertensive patients. In addition to age, systolic blood pressure and pulse pressure, particularly if they are accurately measured by ambulatory monitoring, play a major role, somewhat greater than those of sex, low-density lipoprotein cholesterol concentration and smoking, in influencing intima-media thickness.

Adrenergic beta-Antagonists↗
PubMed1998

Seasonal variations in home and ambulatory blood pressure in the PAMELA population. Pressione Arteriose Monitorate E Loro Associazioni.

OBJECTIVE: Clinic blood pressure values are known to change according to seasonal influences. We therefore examined home and 24 h ambulatory blood pressure values to determine whether these measurements are also affected by the seasons. DESIGN AND METHODS: In 2051 subjects of the Pressione Arteriose Monitorate E Loro Associazioni (PAMELA) study, we measured clinic (sphygmomanometric measurements), home (semi-automatic device) and ambulatory (Spacelabs 90207) systolic blood pressure, diastolic blood pressure and heart rate. Because the overall sample was evenly distributed over each month (except August), we were able to make a cross-sectional determination of whether the values differed between seasons. The corresponding heart rates were also evaluated. RESULTS: As expected, summer was associated with the lowest clinic blood pressure and winter with the highest, and this was the case also for home and 24 h average blood pressure, although seasonal differences in the latter were less pronounced. Seasonal clinic, home and ambulatory blood pressure patterns were similar for normotensive subjects (n = 1152), untreated hypertensives (n = 540) and treated hypertensives (n = 359). Heart rate values did not differ by season. CONCLUSIONS: Seasonal influences on blood pressure are not limited to conventional measurements but characterize daily values as well. These effects are visible in both normal and elevated blood pressure values, regardless of the effect of antihypertensive drugs. This has implications both for the clinician and for studies aimed at evaluating the effects of antihypertensive treatment.

Adult↗
PubMed1998

The Verapamil in Hypertension and Atherosclerosis Study (VHAS): results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness.

BACKGROUND: It is unclear whether the carotid intima-media thickness can be influenced by antihypertensive treatment and whether some antihypertensive agents, such as calcium antagonists, may have a greater effect on this parameter than others, such as diuretics. The present paper reports the principal results of the ultrasound substudy of the randomized, prospective, controlled, Verapamil in Hypertension and Atherosclerosis Study (VHAS). DESIGN AND METHODS: In 498 hypertensive patients in eight Italian centres, randomized to either verapamil (240 mg once a day) or chlorthalidone (25 mg once a day), a B-mode ultrasound scan was performed according to a standardized procedure at baseline and after 3, 12, 24, 36 and 48 months of treatment. The maximum intima-media thicknesses of the far walls of common, bifurcation and internal carotid arteries were measured bilaterally, and the following indices calculated: the mean thickness at the six measured sites, the mean thickness at the common and bifurcation sites and the single maximum thickness. The primary endpoint for treatment efficacy was the slope of the change over 4 years (rate of change, mm/year), corrected by using the initial mean over the six sites (baseline + 3 months) as a covariate (mm/year per mm). The patients were also classified into three strata according to their baseline single maximum thickness: those with normal carotid arteries (single maximum ( 1 mm), those with thickened carotid arteries (single maximum > 1 and < or = 1.5 mm and those with carotid plaques (single maximum > 1.5 mm). RESULTS: Among the 456 patients with satisfactory baseline ultrasound readings, 33% were classified with normal carotid arteries, 27% with thickened carotid arteries and 40% with plaques. In the intention-to-treat population (377 patients with ultrasound measurements taken on at least three different occasions over a period of at least 2 years), the rate of change in the mean thickness at the six sites measured was rather small (0.015 mm/year), but significantly (P < 0.05) smaller in patients with plaques (0.003 mm/year) than in patients with thickened or with normal carotids (0.023 and 0.025 mm/year, respectively). When related to initial values, the rate of change in the mean thickness at the six sites had a negative slope (-0.059 mm/year per mm, P < 0.01). Although rates of change in the carotid intima-media thickness in unstratified patients were not different in those treated with verapamil or with chlorthalidone, when changes in the mean thickness of six sites were related to the initial value, the slope of this relationship was significantly different in the two treatment groups (verapamil -0.082 versus chlorthalidone -0.037 mm/year per mm, P < 0.02). The blood pressure-lowering effect of the two randomized treatments was similar. Taking fatal and nonfatal, major and minor cardiovascular events together, there were 19 events in the verapamil group and 35 in the chlorthalidone group, with a significantly (P < 0.01) greater incidence in patients with plaques, and among patients with plaques in those who were randomized to chlorthalidone (P < 0.05). CONCLUSIONS: In accord with evidence from animal models of atherosclerosis, the calcium antagonist verapamil was more effective than the diuretic chlorthalidone in promoting regression of thicker carotid lesions. Changes in the carotid intima-media thickness were small in both groups, and the differences between the changes under the two treatments were consequently small, but the observation that these small differences in carotid wall changes were paralleled by differences in the incidence of cardiovascular events (better intima-media thickness regression with verapamil paralleled by a lower cardiovascular event rate) suggests that even small effects on carotid plaques may have clinical and prognostic relevance.

Adult↗
PubMed1998

Antihypertensive efficacy of lercanidipine at 2.5, 5 and 10 mg in mild to moderate essential hypertensives assessed by clinic and ambulatory blood pressure measurements. Multicenter Study Investigators.

OBJECTIVE: To evaluate the antihypertensive effect of lercanidipine once a day at three different doses (2.5, 5 and 10 mg) by clinic and ambulatory blood pressure. METHODS: After 3 weeks of a placebo run-in, 243 mild to moderate essential hypertensives (mean+/-SD age 51+/-8 years) were randomly allocated to lercanidipine at 2.5, 5 or 10 mg or a placebo for 4 weeks, in a double-blind parallel-group design. At the end of each period, supine clinic blood pressure (standard sphygmomanometry) and 24 h ambulatory blood pressure (Spacelabs 90207) were measured. The duration and homogeneity of the antihypertensive effect of the active drug compared with placebo over 24 h was evaluated by calculating the smoothness index, the ratio of the mean of the 24 hourly blood pressure changes to the corresponding SD. The higher the smoothness index, the greater and the smoother is the antihypertensive effect of a drug over the 24 h. RESULTS: In 211 patients with valid clinic blood pressure data at the end of treatment, larger systolic/diastolic blood pressure reductions were found in the 5 mg (10+/-12/8+/-6 mmHg; P< 0.05 versus placebo, diastolic blood pressure only) and the 10 mg (12+/-11/9+/-7 mmHg; P < 0.05 versus placebo, both pressures) lercanidipine groups than in the placebo (5+/-11/4+/-8 mmHg) and 2.5 mg lercanidipine (7+/-12/6 +/-7 mmHg) groups. In 105 patients with complete 24 h ambulatory blood pressure recordings, there were significantly (P< 0.05 versus placebo) larger reductions in the 10 mg (9+/-7/7+/-5 mmHg) than the 2.5 mg (1+/-10/1+/-6 mmHg) and placebo (2+/-6/1+/-4 mmHg) groups. The reduction in 24 h blood pressure with 5 mg lercanidipine (6+/-7/4+/-5 mmHg) was significantly greater compared with placebo for diastolic pressure only, and when hourly average blood pressure changes were considered, this reduction did not extend to the final hours of the dosing interval. No significant changes in the clinic or 24 h heart rate were induced by placebo or lercanidipine. The smoothness index was significantly (P< 0.05) lower for 2.5 mg lercanidipine and placebo (0.2+/-0.5 and 0.3+/-0.7 for systolic and 0.1+/-0.4 and 0.2+/-0.7 for diastolic blood pressure) than for the 5 and 10 mg doses (0.7+/-1 and 1+/-0.7 for systolic and 0.7+/-1 and 1+/-0.9 for diastolic blood pressure). CONCLUSIONS: At a dose of 10 mg, lercanidipine had a significant and durable antihypertensive effect over 24 h, but at 5 mg, the effect was less consistent and did not last 24 h. There was no clinically relevant reduction in clinic or ambulatory blood pressure with 2.5 mg lercanidipine, and the effect was superimposable on that of placebo.

Antihypertensive Agents↗
PubMed1998

Chronobiology in cardiovascular disease. Proceedings from the European Society of Cardiology.

Clinical research in the field of cardiovascular chronobiology has been quite productive during the past decade and results have stimulated new areas of investigation in a field of clinical pharmacology known as chronotherapeutics. Chronotherapeutics is a term that has been used when the delivery of a drug is linked to known biologic rhythms in a disease state. This approach is relatively new to practicing phyusicians in that conventional wisdom has been to administer drugs in a homeostatic fashion.

Journal Article↗
PubMed1998

Clinical advantages of lipophilic dihydropyridines.

Lipophilic dihydropyridines have many theoretical and practical clinical advantages owing to their long permanence at the cell membrane. They have a greater chance of smoothly and permanently reducing blood pressure over 24 h than other dihydropyridines, a feature that may have positive prognostic implications since 24-h blood pressure is more closely related to the end-organ damage of hypertension. They may avoid the sympathetic activation consequent to an excessive early-dose hypotension, which is responsible for an increase in 24-h blood-pressure variability and reflex tachycardia, two phenomena that may worsen the prognosis of hypertensive patients. A further advantage which has been shown in experimental and clinical settings is the possibility of reducing the extension and progression of atherogenic lesions in blood vessels, which are responsible for cardiovascular complications in hypertension. Some of these features have been shown by the novel lipophilic dihydropyridine lercanidipine. In particular, clinical studies have shown that (i) this drug is effective in homogeneously reducing blood pressure over 24 h, (ii) its antihypertensive effect is similar to that of some common antihypertensive drugs, and (iii) the rate of adverse events experienced with lercanidipine is no greater than that observed with other antihypertensive drugs, with special reference to non-lipophilic calcium antagonists. In particular, studies performed so far have shown that lercanidipine does not exert a dangerous reflex tachycardia.

Adolescent↗
PubMed1997

Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.

BACKGROUND: Isolated systolic hypertension occurs in about 15% of people aged 60 years or older. In 1989, the European Working Party on High Blood Pressure in the Elderly investigated whether active treatment could reduce cardiovascular complications of isolated systolic hypertension. Fatal and non-fatal stroke combined was the primary endpoint. METHODS: All patients (> 60 years) were initially started on masked placebo. At three run-in visits 1 month apart, their average sitting systolic blood pressure was 160-219 mm Hg with a diastolic blood pressure lower than 95 mm Hg. After stratification for centre, sex, and previous cardiovascular complications, 4695 patients were randomly assigned to nitrendipine 10-40 mg daily, with the possible addition of enalapril 5-20 mg daily and hydrochlorothiazide 12.5-25.0 mg daily, or matching placebos. Patients withdrawing from double-blind treatment were still followed up. We compared occurrence of major endpoints by intention to treat. FINDINGS: At a median of 2 years' follow-up, sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group (n = 2297) and by 23 mm Hg and 7 mm Hg in the active treatment group (n = 2398). The between-group differences were systolic 10.1 mm Hg (95% CI 8.8-11.4) and diastolic, 4.5 mm Hg (3.9-5.1). Active treatment reduced the total rate of stroke from 13.7 to 7.9 endpoints per 1000 patient-years (42% reduction; p = 0.003). Non-fatal stroke decreased by 44% (p = 0.007). In the active treatment group, all fatal and non-fatal cardiac endpoints, including sudden death, declined by 26% (p = 0.03). Non-fatal cardiac endpoints decreased by 33% (p = 0.03) and all fatal and non-fatal cardiovascular endpoints by 31% (p < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, p = 0.07), but all-cause mortality was not influenced (-14%; p = 0.22). INTERPRETATION: Among elderly patients with isolated systolic hypertension, antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications. Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints.

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