Analysis of variability and reproducibility of echocardiography measurements in valvular aortic valve stenosis.

BACKGROUND: Doppler echocardiography is the most frequent method for detecting and evaluating the severity of valvular aortic stenosis. The aim of this study was to assess the variability and reproducibility of echocardiographic parameters including aortic valve area (AVA), peak aortic jet velocity (V(max)), velocity ratio (V(LVOT)/V(max)), peak gradient (G(max)) and mean gradient (G(mean)) in aortic stenosis (AS) patients. METHODS: Doppler echocardiograms were obtained from 150 randomly selected patients (56.7% male; mean age 73 +/- 9 years) with asymptomatic moderate aortic valve stenosis. The echocardiographic measurements were performed by two independent level III (expert) blinded observers. To assess intra-observer variability, we evaluated parameters of AS progression at two different times (mean of two weeks after the first examination). RESULTS: For intra-observer variability (observer 1), the variation and reproducibility coefficients were, respectively, 1.88% and 0.16 m/s for V(max), 2.08% and 0.14 for V(LVOT)/V(max) 2.05% and 0.18 cm2 for AVA, 3.89% and 5.18 mmHg for G(max) and 7.87% and 6.30 mmHg for G(mean). For inter-observer variability, the variation and reproducibility coefficients were, respectively, 2.00% and 0.14 m/s for V(max), 2.91% and 0.14 for V(LVOT)/V(max), 7.67% and 0.16 cm2 for AVA, 8.53% and 7.06 mmHg for G(mean) and 3.90% and 5.58 mmHg for G(max). Both intra- and inter-observer studies showed excellent intraclass correlation coefficients (ICC) for all echocardiographic parameters (ICC ranged from 0.943 to 0.990 for intra-observer variability and from 0.955 to 0.992 for interobserver variability). CONCLUSION: Doppler echocardiographic measurements of AVA, V(max), G(max) and G(mean) are highly reproducible when performed by expert observers. Of all echocardiographic parameters, V(max) and V(LVOT)/V(max) showed the best variability and reproducibility, and thus constitute reliable tools for clinical and research purposes in aortic stenosis diagnosis and follow-up.

[Bicuspid aortic valve and aortic disease: past, present and future]. / Válvula aórtica bicúspide e aortopatia: o passado, o presente e o futuro [121].

Bicuspid Aortic Valve is the most common cardiac congenital abnormality occurring in 1% to 2% of the general population. The acquired bicuspid valve has been considered by some authors to be a rheumatic disease consequence. Meanwhile, some recent experimental studies where atrioventricular valves have been studied for the presence of rheumatic stigmata have excluded this hypothesis. There are some theories that can explain the genesis of this disease but actually Bicuspid Aortic Valve is often considered a benign lesion early in life, but its valvular and vascular complications result in considerable morbidity and mortality later in life. Beside beta-blockers, there are some drugs that are being study and may be used in a nearly future for slower disease progression, although the definitive treatment still is the cardiac valve replacement surgery.

Medical therapy for rheumatic heart disease: is it time to be proactive rather than reactive?

Rheumatic Heart Disease (RHD) is well known to be an active inflammatory process which develops progressive calcification and leaflet thickening over time. The potential for statin therapy in slowing the progression of valvular heart disease is still controversial. Retrospective studies have shown that medical therapy is beneficial for patients with calcific aortic stenosis and recently for rheumatic valve disease. However, the prospective randomized clinical trials have been negative to date. This article discusses the epidemiologic risk factors, basic science, retrospective and prospective studies in valvular heart disease and a future clinical trial to target RHD with statin therapy to slow the progression of this disease. Recent epidemiological studies have revealed the risk factors associated with valvular disease include male gender, smoking, hypertension and elevated serum cholesterol and are similar to the risk factors for vascular atherosclerosis. An increasing number of models of experimental hypercholesterolemia demonstrate features of atherosclerosis in the aortic valve (AV), which are similar to the early stages of vascular atherosclerotic lesions. Calcification, the end stage process of the disease, must be understood as a prognostic indicator in the modification of this cellular process before it is too late. This is important in calcific aortic stenosis as well as in rheumatic valve disease. There are a growing number of studies that describe similar pathophysiologic molecular markers in the development of rheumatic valve disease as in calcific aortic stenosis. In summary, these findings suggest that medical therapies may have a potential role in patients in the early stages of this disease process to slow the progression of RHD affecting the valves. This review will summarize the potential for statin therapy for this patient population.

I-123-MIBG cardiac uptake imaging, in familial dilated cardiomyopathy.

UNLABELLED: The pathological significance of myocardial adrenergic activity in patients with heart failure is well documented. No previous study has assessed the usefulness of I123-metaiodobenzylguanidine (123I-MIBG) cardiac uptake imaging for the evaluation of familial dilated cardiomyopathy (DCM). OBJECTIVE: To evaluate cardiac adrenergic activity, using 123I-MIBG cardiac uptake imaging, in members of a genotyped family with DCM. METHODS: Clinical evaluation, 12-lead ECG, 2D echocardiogram, heart rate variability analysis by 24h Holter, plasma B-type natriuretic peptide (BNP) measurements and 123I-MIBG cardiac imaging were performed in all participants. Anterior projection planar images and single photon emission computed tomographies of the thorax were obtained 20 min and 4 hours after the intravenous administration of 370 MBq of 123I-MIBG (early and late images). Heart/mediastinal (H/M) ratio and myocardial washout (MW) rate were obtained based on the anterior planar images. In polar maps, segmental uptake of 123I-MIBG was evaluated using a 4-grade visual score: grade 1 - uptake > 75% of maximum myocardial uptake (MMU); grade 2 - uptake 51-75% of MMU; grade 3 - uptake 26-50% of MMU; grade 4 - uptake < or = 25% of MMU. RESULTS: Eleven adults were included: 4 with DCM, 4 with isolated left ventricular enlargement (LVE), and 3 with normal echocardiogram. Patients with DCM and LVE presented higher MW rates, lower H/M ratios and higher visual score grades than those with normal 2D echocardiograms. One patient with a normal echocardiogram but carrying the disease locus also presented an abnormal MIBG cardiac scintigram. CONCLUSION: Patients with the phenotypic expression of the disease (DCM and LVE) and even carriers of the DCM gene with normal echocardiograms may present an abnormal MIBG cardiac scintigram, probably reflecting cardiac adrenergic hyperactivity. If confirmed in larger numbers, this method may be useful for the evaluation of DCM families.

New understanding about calcific aortic stenosis and opportunities for pharmacologic intervention.

PURPOSE OF REVIEW: This review article will discuss aortic stenosis, the evolving studies defining the cellular mechanisms and the potential for medical therapies for the treatment of this disease. RECENT FINDINGS: Currently, the only therapy for these patients is surgical valve replacement. In the past decade there has been a change in the paradigm towards our understanding of the cellular biology of this disease process. Studies in laboratories across the world have demonstrated that this disease has an active biology and that this biology may be targeted with medical therapies similar to that of vascular atherosclerosis. SUMMARY: Calcific aortic stenosis is the third most common form of cardiovascular disease in the USA. It has replaced rheumatic heart disease in prevalence in western countries due to improved access to healthcare and the widespread use of antibiotics.

Familial dilated cardiomyopathy with troponin T K210del mutation.

BACKGROUND: It has been estimated that more than 30% of patients with idiopathic dilated cardiomyopathy have a familial form of the disease. The most frequent pattern of inheritance is autosomal dominant and several genes or loci have been implicated, coding for sarcomeric or cytoskeleton proteins. Most of the genotype-phenotype correlations are still under study, but a particular mutation, K210del in the troponin T gene, has been identified in four different families with severe forms of DCM. The pathogenesis of this mutation has been inferred by functional studies but its transmission has not been demonstrated, perhaps due to the high mortality of the affected family members. The aim of this work was to investigate the prevalence of the K210del mutation in Portuguese and Mozambican families with dilated cardiomyopathy. METHODS: We evaluated 27 probands with familial DCM. Forty idiopathic (sporadic) DCM patients and 100 non-related healthy individuals were used as controls. Mutational analysis was performed by amplification of exon 13 of the troponin T gene by the polymerase chain reaction (PCR), determination of molecular weight of PCR products and further sequencing. RESULTS: The K210del mutation in the cardiac troponin T gene was identified in one of the DCM families which presented an aggressive form of the disease, with a high incidence of sudden death, and need for heart transplant at young age. One affected member had sustained left ventricular function recovery after diagnosis. CONCLUSIONS: These results reinforce previous work by others, indicating that this mutation is a bad prognostic factor in familial forms of DCM. The K210del mutation in the troponin T gene, like other mutations in the troponin complex, seems to be especially prevalent in families with rapidly progressive DCM or sudden cardiac death at young age.

Circadian heart rate and blood pressure variability in autonomic failure.

Autonomic failure (AF) induces disabling orthostatic symptoms. Short-term heart rate (HR) and blood pressure (BP) orthostatic patterns are well characterized in these patients but data on long-term blood pressure and heart rate monitoring is lacking. The aim of this study was to assess circadian HR and BP variation in AF patients. We studied 8 patients with severe AF (7 with TTRmet30+ familial amyloidotic polyneuropathy and 1 with pure autonomic fairure)--Group A, and 2 control groups (8 asymptomatic TTRmet30+ patients--Group B, and 16 normal aged-matched controls--Group C). All groups underwent 24h HR and BP monitoring. Twenty-four-hour systolic (SBP) and diastolic BP (DBP) were similar in all groups (114.5+/-10.6 and 73.2+/-6.7; 123.0+/-6.2 and 79.0+/-9.5; 118.6+/-10.1 and 71.4+/-9.4 mmHg for groups A, B and C respectively). BP dipping was attenuated or even inverted (p < 0.01) in AF patients (SBP and DBP differences between day and night: -1.6+/-11.6 and 3.3+/-6.3; 10.0+/-1.0 and 11.7+/-1.5; 15.6+/-7.9 and 16.2+/-5.8 mmHg for groups A, B and C respectively; p < 0.01). Although mean 24h HR was similar between patients and controls (80.9+/-14.0, 87.0+/-4.6 and 80.7+/-5.2 bpm for groups A, B and C respectively), there were striking differences in heart rate variability between groups (max-min 24h HR difference: 46+/-16, 89+/-11 and 91+/-9 bpm; pNN50: 0+/-0, 6+/-2 and 12+/-6%; SDRR 68+/-24, 128+/-10 and 148+/-32 ms for groups A, BB and C; p < 0.01). There were significant differences between normal controls and asymptomatic TTRmet30+ controls in mean HR, diastolic blood pressure dipping and pNN50; p < 0.05. Autonomic failure can be suspected by simple 24h blood pressure evaluation and heart rate monitoring. Asymptomatic TTRmet30+ patients may already show some degree of autonomic impairment, particularly early vagal dysfunction.

Neurohormonal behavior during prolonged orthostatic stress in normotensive subjects.

Prolonged orthostatic stress induces major changes in hemodynamic and autonomic nervous system function. The neurohormonal response to acute and prolonged orthostatic stress that may trigger neurocardiogenic syncope is not clear. The goal of this study was to assess neurohormonal changes during acute and prolonged orthostatic stress. In fifteen normotensive subjects without medication blood was sampled at supine rest (S), during early passive orthostatic stress (after first 10 min.) (T1) and after prolonged (>40 min.) orthostatic stress (T2). We measured atrial and brain natriuretic peptides (ANP and BNP) and catecholamines [norepinephrine (NOR), epinephrine (EPI) and dopamine (DOP)]. ANP was 7.0 +/- 4.3 pmol/l during S, 7.3 +/- 5.1 during T1 and 4.6 +/- 2.8 during T2 (NS and p < 0.05). BNP was 1.9 +/- 1.6 pmol/l during S, 1.7 +/- 1.5 during T1 and 1.4 +/- 1.3 during T2 (p < 0.05 and p < 0.05). NOR was 172 +/- 92 pg/ml during S, 378 +/-_216 during T1 and 402 +/- 183 during T2 (p < 0.01 and NS). EPI was 10.4 +/- 3.8 pg/ml during S, 22.2 +/- 9.3 during T1 and 44.4 +/- 26.0 during T2 (p < 0.01 and p < 0.01). DOP was 7.8 +/- 4.8 pg/ml, 7.6 +/- 2.1 during T1 and 7.0 +/- 2.3 during T2 (NS and NS), Neurohormonal responses to orthostatic stress varied. Natriuretic peptides (ANP and BNP) decreased with prolonged orthostatic stress, probably due to the progressive hypovolemia it induced. Dopamine levels did not change, whereas norepinephrine and epinephrine showed a considerable rise following acute orthostatic stress, with epinephrine rising still further with prolonged orthostatic stress. Neurohormonal responses to prolonged orthostatic stress could help to clarify the pathophysiology of neurocardiogenic syncope.

Pericardial involvement in human immunodeficiency virus infection.

STUDY OBJECTIVES: Previous studies have showed that the pericardium is frequently involved in HIV infection. However, the characteristics and etiology of the pericardial abnormalities that have been found remained poorly defined. We analyzed the features of pericardial involvement in these patients and investigated the clinical variables associated with moderate and severe effusions. DESIGN: Prospective, clinical, and echocardiographic study. SETTING: The service of infectious diseases of a university hospital. PATIENTS: 181 consecutive patients at all stages of HIV infection. RESULTS: Only one patient (0.55%) had acute pericarditis. Seventy-five patients (41%) had an asymptomatic pericardial effusion; in 23 patients (13% of all patients), the effusion was either moderate or severe. Ten cases (5.5% of all patients) of moderate or severe effusions resulted in right atrium diastolic compression, and three of these cases (1.6% of all patients) required pericardiocentesis for the management of tamponade. Six patients (3%) presented with echogenic pericardial masses of undetermined etiology. A moderate or severe effusion was present in a greater number of patients with symptomatic HIV infection than was present in asymptomatic HIV-infected patients, respectively: 17 vs 2% (p = 0.015). The following are variables independently associated with moderate or severe pericardial effusions: heart failure (odds ratio, 20.3; p = 0.0001); Kaposi's sarcoma (odds ratio, 8.6; p = 0.01), tuberculosis (TB; odds ratio, 47.2; p = 0.0006); and other pulmonary infections (odds ratio,15.0; p = 0.02). CONCLUSIONS: Most of these moderate or severe effusions are clinically unsuspected, but they can lead to life-threatening tamponade. This fact seems to justify echocardiographic surveillance in HIV-infected patients, especially in those with heart failure, Kaposi's sarcoma, TB, or other pulmonary infections.

Predictors of myocardial dysfunction in human immunodeficiency virus-infected patients.

BACKGROUND: Some of the most frequent manifestations of heart involvement in human immunodeficiency virus (HIV) infection include right and left ventricular dysfunction. The pathogenesis remains obscure. METHODS AND RESULTS: This prospective clinical and echocardiographic study involved 181 patients at all stages of HIV infection. We tested a set of clinical variables using a backward logistic regression model to assess their ability to independently predict the presence of ventricular dysfunction. The presence of pulmonary infections (all etiologies mixed) was the only variable independently associated with isolated right ventricular dysfunction (odds ratio = 4.08; P = .02). Signs suggestive of pulmonary arterial hypertension were present in 71% of the patients with right ventricular dilation. History of previous opportunistic infections (all etiologies mixed) (odds ratio = 10.9; P = .0026) and time since the diagnosis of acquired immunodeficiency syndrome more than 12 months (odds ratio = 6.6; P = .03) were the only two independent predictors of left ventricular dysfunction. CONCLUSIONS: Isolated right ventricular dysfunction may be secondary to pulmonary hypertension caused by repetitive pulmonary infections and not to primary myocardial disease. The aggressive treatment of opportunistic infections may become an important element of heart failure prophylaxis in HIV infection because they may be associated with left ventricular dysfunction.

Left ventricular dysfunction in human immunodeficiency virus (HIV)-infected patients.

We evaluated left ventricular function by echocardiography in a prospective study that included 98 consecutive human immunodeficiency virus (HIV)-infected patients and 40 HIV-seronegative normal controls. When compared with controls, HIV patients showed increased isovolumic relaxation time (101+/-18 ms versus 71+/-10 ms; p<0.0001) and left ventricular diastolic diameters (51+/-6 mm versus 47+/-3 mm; p<0.0005), and decreased fractional shortening (31+/-6% versus 37+/-2%; p<0.0001). Diastolic dysfunction was the most frequent finding (63% of the patients). We found depressed ejection fraction in 31 (32%) patients. Only 8 (8%) patients had symptomatic congestive heart failure. Left ventricular dysfunction was not attributable to intravenous drug abuse or to therapy. It was less severe in earlier stages of the infection (fractional shortening: acquired immunodeficiency syndrome=30%+/-6%, asymptomatic HIV-seropositives 34%+/-5%; p<0.005) and in HIV-2-infected patients. Patients with opportunistic infections (all aetiologies mixed) had more frequent congestive heart failure than those without infections (16% of the patients with versus 4% of the patients without infections; p<0.05). The fact that even asymptomatic HIV-seropositives had signs of left ventricular dysfunction (fractional shortening: asymptomatic HIV-seropositives=34%+/-5%; controls=37%+/-2%; p<0.05) favours the hypothesis of the HIV being one of the causes of these abnormalities.

Inhalatory pentamidine therapy and the duration of the QT interval in HIV-infected patients.

We evaluated the effect of chronic Pneumocystis carinii pneumonia (PCP) prophylaxis, with a once a month dose of 300 mg of inhalatory pentamidine isethionate, on QT interval duration. We included 22 human immunodeficiency virus (HIV)-infected patients: 11 were on this medication and 11 were not. The two groups were matched for age, sex and HIV infection stage. No patient had any clinical condition or was under any medication known to affect the duration of the QT interval. The heart rate-corrected QT (QTc) was obtained by averaging the observations of three independent observers. QTc duration was similar in both groups. The time separating pentamidine administration and the performance of the ECG did not influence the results, neither did the duration of inhalatory pentamidine therapy. Our results suggest that inhalatory pentamidine does not prolong the QT interval duration and so, as opposed to what has been reported concerning intravenous pentamidine therapy, does not seem to induce an increased risk of torsades de pointes.

[Essential arterial hypertension: psychopathology, compliance, and quality of life]. / Hipertensão arterial essencial: psicopatologia, compliance e qualidade de vida.

OBJECTIVE: To evaluate the influence of psychological and psychopathological factors and quality of life on hypertension, its treatment and patient compliance. DESIGN: Case-control study. SETTING: Primary Health Care Center in Oporto. PATIENTS OR PARTICIPANTS: Forty nine patients (pts) with essential hypertension (HT), 35 female and 14 male, mean ages: 52 +/- 11 yrs and 59 +/- 10 yrs, respectively, and 39 normotensive controls (NT)--18 female and 21 male, mean ages: 37 +/- 15 yrs and 42 +/- 15 yrs, respectively, were recruited from the same General Practice. METHODS: Hypertension was classified according to the Joint National Committee criteria. The following psychometric evaluations were used: the Beck Depression Inventory, the Hopkins Symptom Distress Checklist, the Psychological General Well-Being Schedule and the Eysenck Personality Inventory. RESULTS: 1. The hypertensive pts differed from the normotensive pts as they scored significantly higher in somatization (p = 0.07), aggression/hostility (p = 0.036), index of psychological distress (p = 0.08) and, neuroticism (p = 0.09); 2. the hypertensive pts showed lower scores of quality of life (p = 0.019); 3. the biochemical parameters studied (uric acid, urea, creatinine, glicose, total cholesterol, HDL cholesterol, trigliceride, transaminases and gammaglutamil transferase) did not show statistically significant correlation with the psychological variables and quality of life items studied; 4. the electrocardiographic and echocardiographic alterations, corresponding to the severity of the clinical situation, were not associated with statistically significant differences in depression and quality of life; 5. the angiotensin converting enzyme inhibitor, the calcium antagonist and the beta-blockers showed no statistically significant influence on the psychological scores studied. However, pts receiving diuretics showed higher scores of somatization (p = 0.0008) and obsession/ compulsion (p = 0.02) and, lower scores of quality of life (p = 0.04); 6. a better compliance was associated with better psychological scores, and somatization scored with statistical significance (p = 0.03). CONCLUSIONS: The hypertensive pts differed from the normotensive pts as they scored significantly higher in aggression/hostility and lower in quality of life. No statistically significant differences were found among the psychological variables in the pts with cardiac involvement. A better compliance was associated with better psychological scores. The results of this study lead us to suggest that when treating pts with HT, the most appropriate therapeutic attitude should attempt to avoid both therapeutic withdrawal and lack of medical control.

Dysrhythmic profile of human immunodeficiency virus infected patients.

We prospectively studied, with 24-h Holter monitoring, 21 consecutive human immunodeficiency virus (HIV) infected patients, at all stages of the infection, in order to assess their dysrhythmic profile. Three (14.3%) patients presented one isolated run of supraventricular tachycardia, with < 10 beats, that was considered clinically irrelevant. No patient presented other clinically relevant supraventricular or ventricular tachy or bradydysrhythmias. One (4.8%) patient presented intermittent Mobitz type I second-degree AV block, two (9.5%) patients paroxistic 2:1 AV block and one (4.8%) patient presented a bifascicular block on the 12-lead ECG that persisted during the ambulatory recording. This study suggests that clinically relevant cardiac tachydysrhythmias are rare in our population of HIV infected patients. On the other hand we found an unexpectedly high incidence of cardiac impulse conduction disturbances.

[Compliance to therapy -- its importance in research and clinical practice]. / Aderência à terapêutica--sua importância na investigação e na prática clínica.

Compliance, defined as patients behaviour to treatment schedule over time, specially in chronic diseases, is an important parameter to be measured in clinical trials. Compliance to a specific drug may compromise the final efficacy expected result assumed by phase I II and III studies. The medication events monitors systems (MEMS) appeared to get a more specific and sensitive measurement than the classic counting pills and drug or markers levels to analyses of compliance. The authors made a revision of literature in order to evaluate the benefits of compliance measurement in trials (specially hypertension as a paradigm of chronic disease) and clinical practice. Partial compliance with antihypertensive treatment could be an obstacle to an effective control or to demonstrate long term efficacy on decreasing morbidity and mortality. A short discussion is made about the possible benefits of using MEMS on clinical trials to evaluate patient's quality of life and behaviour to long term treatment for chronic diseases.

Isradipine in the treatment of mild-to-moderate hypertension in geriatric patients.

A number of studies have shown the benefit of hypertensive treatment even though the most common forms of the disease are mild-to-moderate in severity. Considering the overall aging of the world's population, it is of particular interest to study hypertension and its treatment in geriatric patients. A short-term study of isradipine was conducted to assess its effectiveness and tolerability in patients with mild-to-moderate hypertension. The study was carried out by general practitioners and involved 3343 patients, aged > or = 18 years, with diastolic blood pressures (DBPs) ranging from 95 to 114 mm Hg. A 4-week wash-out and placebo run-in phase was followed by a 12-week active treatment period with isradipine at 1.25 or 2.5 mg/day, depending on the blood pressure response. Posttreatment results in a subgroup of 1092 patients (444 men and 648 women), aged > or = 60 years, showed decreases in systolic blood pressure (SBP) from 173.1 to 149.2 mm Hg (mean decrease, 20.9 mm Hg) and, in DBP, from 102.0 to 85.0 mm Hg (mean decrease, 16.9 mm Hg). The majority (84.6%) of these patients showed DBP reductions of > 10 mm Hg, and 82.3% achieved normalization (DBP < 90 mm Hg) at the end of treatment. The mean dosage was 1.74 +/- 0.69 mg twice daily, and 37% of patients doubled their initial 1.25 mg twice daily dosages. There were no significant changes in either heart rate or major metabolic parameters. Adverse events were reported by 3.1% of the patients, and 90% of both patients and physicians expressed satisfaction with the therapy. There were no differences between men and women with regard to adverse events or efficacy, nor were the results in patients > or = 60 years different from those in younger patients. Thus, isradipine was effective and well tolerated in these geriatric patients.

[Variability of heart rate: a perspective]. / Variabilidade da frequência cardíaca: uma perspectiva.

The present work is an attempt to provide a general overview on the current methods and applications of heart rate variability (HRV), starting from the underlying mechanisms of cardiac rhythmic automaticity and the influence on heart rate of biological modulators, namely autonomous nervous system. Different evaluation methods for HRV are compared in what concerns the duration of the records under analysis and the mathematical approach (spectral/non-spectral). Finally, clinical applications of HRV are mentioned, some of them the Department is particularly interested in, namely coronary heart disease, heart failure and diabetic neuropathy. The authors conclude, minding some aspects susceptible of discussion in the future of this technique.

Isradipine in the treatment of mild-to-moderate hypertension in Portugal.

A short-term trial of isradipine was conducted to assess its effectiveness and tolerability in the treatment of mild-to-moderate hypertension. The study was carried out by general practitioners and involved 2,702 patients, aged 18-70 years, who had diastolic blood pressures (DBP) of 95-114 mm Hg. Patients completed a pretreatment phase of up to 4 weeks for antihypertensive drug washout and placebo run-in, before entering a 12-week active-treatment phase with 1.25 mg of isradipine twice daily, which was increased after 4 weeks to 2.5 mg twice daily, depending on the blood pressure response. At the end of 12 weeks, the mean systolic blood pressure (SBP) and DBP were 148.1 and 86.7 mm Hg compared with 169.0 and 103.0 mm Hg after placebo, respectively. The majority of patients (89.6%) had a DBP reduction greater than 10 mm Hg, and 86.2% had normalized DBP (less than or equal to 90 mm Hg) at the end of treatment. Adverse events were reported by 2.8% of patients, and 90% of patients and general practitioners reported satisfaction with the treatment. Thus, our results indicate that isradipine is effective and well tolerated, and may deserve a place as first-line treatment in mild-to-moderate hypertension.