[Cycle ergometer stress testing for identification of significant coronary artery disease: improved accuracy by the use of chronotropic reserve adjustment of ST-segment depression]. / Accuratezza diagnostica del test al cicloergometro: superiorità dell'indicizzazione del sottoslivellamento del tratto ST per la riserva cronotropa nell'identificare una coronaropatia emodinamicamente significativa.

BACKGROUND: Diagnostic reliability of indexations of peak exercise ST-segment depression (deltaST) for heart rate reserve (HRi) or chronotropic reserve (CR) to identify significant coronary artery disease (CAD) by bicycle exercise testing has not been evaluated previously. METHODS: Upright bicycle exercise testing (25 W increment every 3 min) was performed in consecutive patients in primary prevention with at least one of the following criteria: history of exercise-induced chest discomfort and cardiovascular risk factors; overt peripheral arterial disease; type 2 diabetes associated with two or more additional cardiovascular risk factors. Coronary angiography was performed to define significant CAD (stenosis > or = 70% of the main coronary arteries or of their major branches, or isolated left main stenosis > or = 50%, or two or more stenoses 50-69%). Duke angina index was used to grade exercise-induced chest pain; deltaST, ST/HRi and ST/CR were calculated at peak exercise; three different criteria for the definition of inducible myocardial ischemia were tested versus significant CAD: peak deltaST > or =100 microV, ST/HRi > 1.69 microV/b/min or ST/CR > 1.76 microV/%. RESULTS: Of the study sample (n = 46), 40% had typical angina; during stress test 80% showed deltaST > or = 100 microV; 76% had ST/HRi > 1.69 microV/b/min; 62% had ST/CR >1.76 microV/%. Diagnostic accuracy of deltaST > or = 100 microV, of ST/HRi > 1.69 micro5V/b/min, and of ST/CR > 1.76 microV/% were 78%, 72%, and 89% respectively (p < 0.001 for the difference in diagnostic performance). ST/CR > 1.76 microV/% showed the highest diagnostic accuracy both in patients with submaximal exercise (96%) and in women (92%). Similarly, ST/CR >1.76 microV/% was associated with the highest diagnostic accuracy both in patients with maximal exercise (78%) and in men (88%). Analyses of the ROC curve revealed that ST/CR was associated with the greatest area under the curve, and a population-specific cut-off of 1.77 microV/% was associated with a sensitivity of 88% and a specificity of 90%. CONCLUSIONS: Our pilot study suggests that in patients undergoing bicycle stress testing for differential diagnosis or screening of significant CAD, and with moderate-to-high pre-test probability, the use of ST/CR > 1.76 microV/% may provide elevated sensitivity and specificity, and the best diagnostic accuracy, which was consistent in patients with submaximal exercise test and in women.

Chronotropic incompetence, beta-blockers, and functional capacity in advanced congestive heart failure: time to pace?

BACKGROUND: Chronotropic incompetence (CI) is often seen in subjects with chronic congestive heart failure (CHF). The prevalence of CI, its mechanisms and association with beta-blocker use as well as exercise capacity have not been clearly defined. METHODS AND RESULTS: Cardiopulmonary exercise tolerance testing data for 278 consecutive patients with systolic CHF was analyzed. CI, defined as the inability to reach 80% of maximally predicted heart rate was present in 128 of 278 subjects (46%). The prevalence of CI was highest in those with most impaired exercise capacity (72, 48, and 24% for subjects with a VO(2) of <14.0, 14.0-20.0, and >20.0 ml/kg/min respectively; p=0.001). While subjects with CI had lower peak exercise heart rate (114 vs. 152 bpm), and lower peak VO(2) (15.4 vs. 19.9 ml/kg/min), they were equally likely to be on chronic beta-blocker therapy (74% vs. 71%; p=0.51). Heart rate and norepinephrine (NE) levels were measured during exercise in a separate cohort of 24 subjects with CHF. There was no difference in beta-blocker dose between subjects with and without CI, however, exercise induced NE release and Chronotropic Responsiveness Index, a measure of post-synaptic beta-receptor sensitivity to NE, were lower in subjects with CI (1687+/-911 vs. 2593+/-1451 pg/ml p=0.08; CRI 12.7+/-5.7 vs. 22.1+/-4.7, p=0.002). CONCLUSIONS: CI occurs in >70% of subjects with advanced systolic CHF irrespective of beta-blocker use and is associated with a trend toward impaired NE release, post-synaptic beta-receptor desensitization and reduced exercise capacity.

Cycle-ergometry stress testing and use of chronotropic reserve adjustment of ST depression for identification of significant coronary artery disease in clinical practice.

Diagnostic reliability of indexations of peak exercise ST segment depression (DeltaST) for heart rate reserve (HRi) or chronotropic reserve (CR) to identify significant coronary artery disease (CAD) by cycle-ergometer exercise testing has not been evaluated previously. Exercise testing by upright cycle-ergometer (25 W/3 min) were performed in consecutive patients in primary prevention with history of exercise-related chest discomfort and cardiovascular risk factors, or with overt peripheral artery disease, with or type-2 diabetes associated with two or more additional cardiovascular risk factors. Coronary angiography was performed after the test to assess significant CAD. Three different criteria for definition of inducible myocardial ischemia were tested versus significant CAD: peak DeltaST>or=100 microV, ST/HRi>1.69 microV/bpm or ST/CR>1.76 microV/%. Diagnostic accuracy vs. CAD of DeltaST>or=100 microV, of ST/HRi>1.69 microV/bpm, and of ST/CR>1.76 microV/% were 78%, 72%, and 89% respectively; sensitivity and specificity of the three criteria were 91% and 50%, 84% and 43%, 88% and 93%, respectively. Abnormal ST/CR predicted CAD independent of risk factors, pre-test probability, and more strongly than DeltaST. Combination of ST/HRi and ST/CR criteria did not improve CAD prediction. In conclusions, in clinical setting in patients in primary prevention but with moderate-to-high pre-test probability of CAD, exercise testing by cycle-ergometry and use of ST/CR>1.76 microV/% showed elevated sensitivity and specificity, and the best accuracy for diagnosis of significant CAD.

Isolated left ventricular diastolic dysfunction: implications for exercise left ventricular performance in patients without congestive heart failure.

OBJECTIVE: Clinical relevance of left ventricular (LV) diastolic dysfunction in the absence of congestive heart failure (CHF) and LV systolic dysfunction is not fully established. METHODS: Asymptomatic outpatients, sedentary, with cardiovascular risk factors but no history of cardiovascular events, underwent echocardiographic evaluation of LV structure and function by standard Doppler, color M-mode, and Doppler tissue methods, and exercise testing with simultaneous noninvasive assessment of LV stroke index and cardiac index. LV ejection fraction less than 50% and significant valvular disease or stress test suggestive of coronary disease were additional exclusion criteria. RESULTS: In 70 patients selected (40 +/- 10 years old, 63% men, 34% hypertensive, 34% diabetic, 4% diabetic and hypertensive, 11% with LV hypertrophy), LV diastolic dysfunction was detected in 26%, which was associated with hypertension, higher LV mass index, lower systolic function, lower peak exercise heart rate, and chronotropic reserve (all P < .05), and with lower peak exercise stroke index and cardiac index (both covariates adjusted P < .05), but not with lower peak exercise metabolic equivalents (P > .5). Abnormal LV relaxation was independently correlated with lower peak exercise cardiac index and stroke index (both P < .05). Peak exercise systolic and cardiac indices were comparable between patients with CHF risk factors (74%) versus those without. CONCLUSIONS: Isolated LV diastolic dysfunction was independently associated with lower peak exercise LV systolic performance in patients without CHF. Its diagnosis may provide a target for aggressive CHF risk management.

Association between post-ischemic forearm blood flow and blood pressure response to maximal exercise in well trained healthy young men.

BACKGROUND: The relationship between peripheral circulation and blood pressure (BP) response to maximal exercise is an intriguing and not yet well defined topic. AIMS: Aims of the present study were to investigate in well trained young healthy males the possible relationships between the endothelial or the smooth muscle component of the peripheral circulation and 1) the BP response to physical exercise on treadmill 2) the body mass composition. SUBJECTS AND METHODS: Fifteen subjects (18-36 years), regularly performing physical activity 3 times weekly underwent the following examinations: body composition by bioelectrical impedance analysis; measurement of the forearm blood flow (FBF) at rest and during post-ischemic hyperemia by strain-gauge plethysmography at the upper arm; measurement of brachial artery diameter (BAD) at rest and after 4-min ischemia by echography; BP response to maximal exercise on treadmill with the determination of maximal oxygen consumption and the measurement of lactic acid serum concentration. RESULTS: BAD was significantly increased during post-ischemic hyperemia up to the 4th minute of observation with a peak at 60 s (+8.5%); FBF increased at 30 s after ischemia (+210%) and returned to baseline levels at the 2nd minute. In the linear correlation analysis, systolic BP increase at the end of the maximal exercise was significantly and inversely related to the increase in FBF (r=-0.663, p<0.01) and to the early FMD (r=0.503, p<0.05). In the multiple regression analysis, however, only FBF independently affected SBP increase during exercise (t=-3.268, p<0.02). Systolic BP increase at the end of the maximal exercise was significantly related to the increase in FBF but not to that of BAD. Among parameters of body composition, fat-free mass was closely related to changes only in BAD. CONCLUSIONS: These data indicate that FBF, which depends on the smooth muscle component of the peripheral circulation, is closely related to BP response to exercise while the endothelial function, which has been determined as changes in BAD, is related to the fat-free mass of the body, possibly through the peripheral insulin sensitivity.

Relations of longitudinal left ventricular systolic function to left ventricular mass, load, and Doppler stroke volume.

AIMS: To evaluate whether the peak systolic velocities of the displacement of the lateral mitral anulus (Sa) and of the mid-portion of the interventricular septal wall (Sm) correlate with measures of left ventricular load, left ventricular mass, and Doppler stroke volume in normotensive and hypertensive subjects without clinically overt cardiovascular disease. METHODS AND RESULTS: Tissue Doppler imaging was used to evaluate Sa and Sm in apical 4-chamber view; standard echocardiographic procedures were used to assess left ventricular structure and traditional parameters of systolic function (ejection fraction, stress-corrected midwall shortening, meridional and circumferential end-systolic stress); pulsed Doppler was employed to evaluate stroke volume. In 87 subjects meeting inclusion criteria, Sa and Sm were not significantly correlated either with left ventricular end-diastolic volume and end-systolic stress, or with stroke volume; in contrast, endocardial and midwall fractional shortening were lower with higher afterload, as expected. Fractional shortening at endocardium and midwall, and Sm were lower with higher left ventricular mass. Mean Sa and Sm values were lower in subjects with low vs. those with normal stress-corrected midwall shortening, but low Sa was not associated with lower stress-corrected midwall shortening in our study sample. CONCLUSIONS: While Sa and Sm might be indices of longitudinal left ventricular systolic mechanics, they should not be considered as measures of left ventricular contractility alternative to well-established parameters of systolic function, such as stress-corrected midwall shortening, in subjects at rest without overt heart disease.

Individuals' cardiovascular risk profile projected by family doctors and individuals' knowledge of cardiovascular risk factors: a challenge for primary prevention. The cardiovascular risk prevention project "Help Your Heart Stay Young".

BACKGROUND: Whether the practice of family doctors of assessing individuals' cardiovascular risk profile improves individuals' knowledge of risk factors in primary prevention has not been established. Accordingly, we evaluated patients' knowledge of cardiovascular risk factors and lifestyle in healthy subjects whose family doctors provided individual cardiovascular risk score. METHODS: Subjects who visited their family doctor in a time frame of 3 months, who accepted to fill-in a simple questionnaire measuring their knowledge of cardiovascular risk factors and of non-pharmacological interventions able to reduce cardiovascular risk were evaluated. RESULTS: Fifty-one family doctors were involved. The study sample comprised 4239 subjects (mean age 56 +/- 9 years, 62% women) in primary prevention. They were classified by their family doctors, based on the Framingham algorithm, as being at low (< 10%; 45.7% of subjects), medium (10-20%; 38.7% of subjects) or moderate-to-high (> 20%; 15.6% of subjects) cardiovascular risk. The prevalence of obese subjects (40, 48, and 49%, respectively) and of heavy smokers (> or = 20 cigarettes/day; 26, 30, and 34%) increased from the low to the moderate-to-high risk group (both p < 0.05). The proportion of subjects unaware of personal history of arterial hypertension (5, 6, and 9%) and that of subjects who were unaware of history of elevated cholesterol levels (10, 11, and 12%, both p < 0.01) increased with higher cardiovascular risk score. The proportion of subjects self-reporting blood pressure > 135/85 mmHg, but self-reporting being normotensive (30, 50, and 52%), and the proportion of subjects who referred cholesterol levels > 200 mg/dl among those who self-referred not to have elevated cholesterol levels (13, 25, and 31%) increased both with cardiovascular risk category (p < 0.001). The proportion of subjects who were unaware of their personal history of diabetes was similar in the cardiovascular risk groups. The prevalence of low educational level was higher (56, 58, and 62%, p < 0.01) and the level of knowledge of non-pharmacological remedies to cardiovascular risk factors (63, 61, and 59%, p < 0.01) was lower in higher cardiovascular risk score group. Subjects aged < 55 years showed similar lack of knowledge about cardiovascular risk factors and the proportion of heavy smoking was as high as in the group of older participants. CONCLUSIONS: In cardiovascular primary prevention, the projection of higher individuals' risk profile by family doctors was not paralleled by an increase in individual's knowledge of major cardiovascular risk factors and of lifestyle interventions able to reduce the cardiovascular risk.

Aerobic exercise performance correlates with post-ischemic flow-mediated dilation of the brachial artery in young healthy men.

In older healthy men, aerobic exercise capacity is related to postischemic flow-mediated dilation of the brachial artery (FMD), but corresponding data in a younger population is not available. In addition, whether submaximal aerobic exercise performance also correlates with this kind of vasomotor reactivity is not known. Therefore, in 15 nonsmoking young healthy men [age 27 (5) years; body mass index: 24 (2) kg/m(2); mean (SD)] with different levels of ordinary physical activity, but not performing upper-extremity training, we measured FMD at 1 min after reactive hyperemia, and pulmonary oxygen uptake (VO(2)) at ventilatory anaerobic threshold (VO(2)AT) and at peak effort (peak VO(2)) during an incremental exercise on a treadmill. In our participants, FMD was 9.1 (3.4)%, VO(2)AT was 40.72 (5.92) ml/kg per min, and peak VO(2) was 52.95 (8.13) ml/kg per min. Using bivariate Pearson's correlation, and in separate multivariate regression analyses, VO(2)AT and peak VO(2) showed a significant and reasonably good correlation with FMD (r = 0.84, P < 0.001 and r = 0.77, P = 0.001, respectively), independent of age, body mass index and serum total cholesterol (beta = 0.77, P < 0.001, R(2) of the overall model = 0.79 and beta = 0.70, P < 0.005, R(2) of the overall model = 0.69, respectively). Our data provide evidence suggesting that in young healthy men a higher submaximal and maximal aerobic exercise performance is associated with a greater FMD of peripheral conduit arteries.

Inter- and intra-study reproducibility of contrast echocardiography for assessment of interventricular septal wall perfusion rate in humans.

AIMS: To assess inter- and intra-study reproducibility of myocardial contrast echocardiography (MCE) imaging for quantitative measurement of myocardial perfusion rate in humans in ambulatory setting. METHODS AND RESULTS: In 20 subjects, we performed 2 MCE tests 20-40 min apart on the same day under the same standardized protocol, and evaluated single-reader between-study and between-reading reproducibility of assessment of indicators of myocardial perfusion rate, such as the slope of video-intensity change k, and the factors A (peak video-intensity) and B (background video-intensity after bubble destruction) and the product k X A. The region of interest was placed at the mid-posterior interventricular septal wall visualized in apical 4-chamber view. In a sub-analysis, we evaluated indicators of myocardial perfusion rate comparing subjects with normal vs. those with subnormal ejection fraction (EF). Inter-study reproducibility of assessment of k was relatively low (intraclass correlation coefficient = 0.36), whereas intra-study reproducibility was fair (intraclass correlation coefficient = 0.61). The parameters k X A and B showed higher reproducibility than the k (inter- and intra-study intraclass correlation coefficients 0.64 and 0.75, 0.74 and 0.91, respectively). For reference, reproducibility data of the depth of the region of interest, of EF and CO were excellent. k and k X A were lower in subjects with low vs. those with normal EF. Only k and k X A were lower in subjects with subnormal than in those with normal EF. CONCLUSIONS: The MCE-derived indicator of myocardial perfusion rate k X A showed fairly good between-study and between-reading reproducibility.

Peak exercise oxygen uptake and left ventricular systolic and diastolic function and arterial mechanics in healthy young men.

Echocardiography can be used to estimate myocardial contractility by the assessment of the circumferential end-systolic stress-corrected left ventricular (LV) fractional shortening measured at midwall level (stress-corrected MWS). Whether stress-corrected MWS at rest predicts exercise peak oxygen uptake (peak VO(2)) is unknown. Also, it is not known whether the propagation rate of the early LV filling wave (E wave propagation rate, V(p)), a new pre-load insensitive index of LV diastolic function, and echocardiographically assessed indices of arterial stiffness correlate to peak VO(2). Accordingly, we performed echocardiographic studies and exercise tests with respiratory gas analysis in 15 young healthy male subjects (mean age 27 years, range 18-36). Neither stress-corrected-MWS ( r=0.20, P=NS) nor ejection fraction ( r=-0.05, P=NS) correlated significantly with peak VO(2). Adjustment for age and resting heart rate had no effect on the results. In separate multiple regression models adjusting for standard covariates (age, LV size and heart rate), peak VO(2) correlated with V(p) (beta=0.98, P<0.01), as well as with E/A (beta=0.85, P<0.01), and with the isovolumic relaxation time (indicator of LV relaxation) (beta=-0.59, P<0.05). Arterial stiffness indices showed no significant relation to peak VO(2). We conclude that in young healthy male subjects, resting myocardial contractility and arterial stiffness are not significant correlates of peak VO(2), whereas LV diastolic function, and in particular V(p), influences the variability of peak VO(2).

Cardiovascular secondary prevention: patients' knowledge of cardiovascular risk factors and their attitude to reduce the risk burden, and the practice of family doctors. The "Help Your Heart Stay Young" study.

BACKGROUND: Whether the practice of family doctors of assessing the global cardiovascular risk profile improves the knowledge of cardiovascular risk factors and the attitude to lifestyle change in patients' secondary cardiovascular prevention is unknown. METHODS: We evaluated subjects who visited their family doctors and those with self-reported cardiovascular disease in the urban area of Naples, Italy. Patients self-administered a simple standard questionnaire to evaluate their knowledge of cardiovascular risk factors and of simple lifestyle modifications to reduce the cardiovascular risk burden. For each participant, family doctors, blinded to the information provided by patients, had to provide a global coronary risk based on the risk factors recorded in their electronic database, or report the missing information. RESULTS: The study sample comprised 560 subjects, 61% male, with mean age 60 +/- 9 years. Angina pectoris (49%) and myocardial infarction (40.9%) were the most frequently self-reported cardiovascular diseases in the study sample. The self-reported data revealed that 46% of the sample was overweight and an additional 20% overtly obese. Among those who self-reported arterial hypertension, approximately 11% admitted that they were unaware of their blood pressure, and 26% believed that they were normotensive but reported a recently detected blood pressure > 140/90 mmHg. Approximately 8% were not aware of whether they had high cholesterol levels, and among those who declared having normal cholesterol levels, 9% referred levels > 200 mg/dl. Of the sample, 22% self-reported diabetes, but 7% did not know whether they were diabetic or not. Thirty percent of the sample were smokers and among these, 40% smoked > 20 cigarettes/day. A low level of education was reported in 66% of the study sample. Women were more frequently obese, more often reported high cholesterol levels, had a low level of education and achieved a lower score from the questionnaire on knowledge of cardiovascular risk factors than men. Patients > 55 years more often reported an elevated blood pressure among those who defined themselves as normotensive, and achieved a lower score from the questionnaire on knowledge of cardiovascular risk factors than younger patients. CONCLUSIONS: With regard to secondary cardiovascular prevention, the study population was found to have insufficient knowledge of cardiovascular risk factors and of the correct approach to reduce their global risk despite the fact that the attitude of their family doctors in detecting and recording risk factors was above average.

Interstudy reproducibility of parameters of left ventricular diastolic function: a Doppler echocardiography study.

BACKGROUND AND METHODS: Interstudy reproducibility of echocardiography for the assessment of parameters of left ventricular (LV) diastolic function is disputed. Therefore, we evaluated the reproducibility of echocardiography for assessment of LV diastolic Doppler parameters in 40 consecutive patients (age range: 19-77 years), who underwent 2 echocardiographic examinations by trained sonographers following a standard protocol, in conditions in which intrapatient sources of variability were minimized. RESULTS: Interstudy reproducibility of measurements of the ratio of early (E) to late (A) peak velocities of transmitral flow (E/A) at tips of the mitral valve leaflets was found to be very good and substantially greater than analogous measurement obtained at mitral annulus level. Reproducibility of measurement of atrial filling fraction was good both at tips of mitral leaflets and at annular level. Interstudy reproducibility of isovolumic relaxation time and E-wave deceleration time was moderate. Measurements of E-wave propagation rate and the ratio of early (E') to late (A') peak velocities of diastolic excursion of lateral mitral annulus (E'/A') by Doppler tissue were found highly reproducible. Intrastudy between-reading reproducibility of Doppler parameters of LV diastolic function were overall very good, except for E-wave deceleration time. However, 80% confidence interval of absolute between-study differences of diastolic parameters were relatively large, and ranged from -0.11 to +0.19 for E/A at tips of mitral valve; -5 to +9 cm/s for E-wave propagation rate; and -0.69 to +0.19 for Doppler tissue-derived E'/A'. CONCLUSIONS: Under a standardized echocardiographic protocol and sonographers' training program, echocardiography can be a reproducible method for serial assessment of Doppler parameters of LV diastolic function, especially in cohort studies.

Gender differences in left ventricular chamber and midwall systolic function in normotensive and hypertensive adults.

OBJECTIVE: Whether left ventricular (LV) systolic function differs between healthy men and women independent of afterload, LV geometry, age, heart rate and body size is disputed. METHODS: We studied 517 clinically healthy adults without history of cardiovascular or endocrinal disease (age range 20-70, 274 with essential arterial hypertension). Echocardiography was used to assess LV geometry and systolic function both at endocardial and midwall levels. RESULTS: Normotensive and hypertensive women had higher LV systolic function at endocardial and midwall levels independent of afterload. After adjustment for age, body surface area, heart rate and LV geometry, LV systolic function remained higher in women than in men in hypertensive and normotensive subjects. In a second set of multivariate analyses adjusting for age, body mass index, LV geometry and heart rate, women had significantly higher LV systolic function than men, both among normotensive and hypertensive subjects. In a reference group of 95 subjects with optimal blood pressure and normal body mass index (mean age 34 +/- 10; 32 men) extracted from the study sample, lower limits (5th percentile) of parameters of LV systolic function were higher in women than in men. Use of gender-specific partition values revealed that subnormal LV chamber function was uncommon in overweight, normotensive subjects as well as in hypertensive subjects; vice versa, stress-corrected midwall dysfunction was frequently subnormal in both normotensive, overweight (14%, mostly women) and in hypertensive subjects (18%, mostly men). At the opposite end of the spectrum, gender-specific supranormal, stress-corrected LV systolic chamber function (> 95th percentile of the distribution in the reference group) was relatively frequent in both overweight, normotensive (14%) and in hypertensive subjects (27%). CONCLUSIONS: Clinically healthy hypertensive and normotensive women have higher LV chamber and midwall systolic function than men, independent of left ventricular geometry, body size, age and heart rate. Use of gender-specific partition values to define subnormal and supranormal LV systolic function revealed that, both in hypertensive and overweight normotensive subjects, subnormal LV chamber function was uncommon, whereas stress-corrected LV chamber systolic function was frequently supranormal. Vice versa, myocardial contractility was subnormal in approximately one-sixth of asymptomatic, normotensive overweight and of hypertensive subjects, with potentially unfavorable prognostic impact.

Effects of the fixed combination of manidipine plus delapril in the treatment of hypertension inadequately controlled by monotherapy with either component: a phase III, multicenter, open-label, clinical trial.

BACKGROUND: Failure to achieve good blood pressure (BP) control is probably the most important reason for high rates of morbidity and mortality in patients with hypertension. Combination therapy has been shown to increase the percentage of patients in whom BP control is achieved. One combination is a calcium channel blocker (CCB) and an angiotensin-converting enzyme inhibitor (ACE-I). OBJECTIVE: The aim of this study was to assess the effects of the fixed combination of the CCB manidipine and the ACE-I delapril in the treatment of hypertensive patients already given monotherapy with either component but with poor results (ie, insufficient BP control or adverse events [AEs]). METHODS: In this Phase III, multicenter, open-label, clinical trial, patients with mild to moderate hypertension were assigned to 1 of 2 groups. Group 1 comprised patients whose diastolic BP (DBP) was >90 mm Hg or who experienced AEs with manidipine 20 mg once daily. Group 2 comprised patients who had a DBP >90 mm Hg or who experienced AEs with delapril 30 mg BID. In both groups, patients aged <65 years were to be treated with a fixed combination of manidipine 10 mg plus delapril 30 mg once daily for 12 weeks, whereas patients aged ≥65 years were to be treated with manidipine 5 mg plus delapril 15 mg once daily for 2 weeks and then manidipine 10 mg plus delapril 30 mg once daily for 10 weeks. Patients were assessed at baseline and at 2, 4, 8, and 12 weeks of treatment. At each visit, systolic blood pressure (SBP), DBP, and heart rate were measured 24 hours after dosing, and AEs were recorded. RESULTS: Group 1 included 154 patients (80 men, 74 women; mean [SD] age, 55 [6] years); group 2 included 158 patients (79 men, 79 women; mean [SD] age, 56 [5] years). Mean BP decreased significantly in both groups (P<0.01). Compared with baseline values, mean SBP/DBP decreased 16.2 (3.8)/10.1 (1.9) mm Hg in group 1 and 15.8 (3.1)/11.0 (1.5) mm Hg in group 2 at the last visit. The success rate-rate of normalized DBP (≤90 mm Hg) and responder rate (DBP reduction ≥10 mm Hg)-was 79% in group 1 and 82% in group 2. The rates of treatment-related AEs were 11% in group 1 and 8% in group 2. In group 1, heart rate significantly increased from baseline only at 2 weeks (P<0.05); in group 2, at each visit (P<0.05) except at week 12. However, none of these differences were clinically significant. CONCLUSION: In this study population of patients whose BP was not adequately controlled by monotherapy, the fixed combination of manidipine 10 mg plus delapril 30 mg, once daily, was effective and well tolerated.

Relations of pulse pressure and other components of blood pressure to preclinical echocardiographic abnormalities.

OBJECTIVE: To evaluate the extent to which pulse pressure (PP) is associated with echocardiographic abnormalities, and in particular to whether PP is related to LV hypertrophy taking into account other blood pressure (BP) components. DESIGN: Cross-sectional. SETTING: University hospital, hypertension outpatient unit. PARTICIPANTS: A total of 275 adults (mean age 47 years, range 19-69, 3% aged > or = 65) with essential hypertension. Overt coronary artery disease, valvular disease and secondary hypertension were exclusion criteria. Subjects were divided in two groups with PP < or = 50 or PP > 50 mmHg. OUTCOME MEASURES: Left ventricular (LV) mass, hypertrophy, LV systolic dysfunction. RESULTS: Prevalence of LV hypertrophy was higher in subjects with clinic PP > 50 mmHg. Subjects with PP > 50 mmHg had higher clinic and ambulatory systolic than subjects with PP < or = 50 mmHg while diastolic BP did not differ between groups. PP and systolic BP, either clinic or ambulatory, showed similar correlation to LV hypertrophy in separate logistic multivariate models. Using different methodologies, PP was not related to LV mass index or hypertrophy when the effect of its component systolic BP was taken into account. In separate analyses, PP was not significantly related to ejection fraction or midwall mechanics. CONCLUSION: Middle-aged clinically healthy hypertensives with PP > 50 mmHg had two-fold higher prevalence of LV hypertrophy than those with PP < or = 50 mmHg, which may contribute to the higher cardiovascular risk in subjects with higher PP. However, in our sample, PP was not related to LV hypertrophy independently of systolic BP, suggesting that systolic BP is the explanatory link of the relation between PP and LV hypertrophy.