Blood pressure response to treadmill testing among medical graduates: the right time to intervene

BACKGROUND: Longitudinal studies have revealed significant correlation between exaggerated blood pressure response to exercise and higher incidence of developing resting hypertension in future. Normotensive persons at high risk of developing systemic hypertension have greater cardiovascular reactivity to exercise. METHODS AND RESULTS: Our study compared the blood pressure response to treadmill exercise in normotensive offspring of the hypertensive parents (age 22 +/- 1.7 years, n = 50; study group) with those of the normotensive parents (age 22 +/- 1.4 years, n = 50; control group). The morphometric characteristics, resting, exercise (treadmill exercise with Bruce protocol) and recovery blood pressure values of all the subjects were recorded. The analysis showed that the difference in mean peak systolic blood pressure during exercise was the only statistically significant parameter in the study and control groups (188.52 +/- 25.16 mmHg and 178.56 +/- 14.96 mmHg, respectively, p < 0.05). The number of hyperreactors (defined as peak systolic blood pressure > 200 mmHg during exercise) was significantly more in study group compared to control group (10 and 3 respectively). The mean resting systolic blood pressure of hyperreactors (126.46 + 8.49 mmHg) falls in the pre-hypertension category as designated by JNC VII. Also, their resting diastolic blood pressure, recovery blood pressure and body mass index were significantly higher as compared to normoreactors. Conclusions: Our study showed that this response pattern could represent impairment in cardiovascular adjustment to exercise indicating a greater risk for development of resting hypertension in the future. Therefore there is a need for early lifestyle modifications to postpone/prevent development of hypertension.     

Gender-related differences in left ventricular chamber function

OBJECTIVES: While women have lower rates of atherosclerotic disease than men, they are more likely to suffer cardiac failure following infarction or cardiac surgery, despite typically having a greater left ventricular (LV) ejection fraction. We hypothesised that gender differences in systolic chamber function and ventriculo-vascular coupling may contribute to these clinical findings. METHODS: LV chamber function was determined in a cohort of 30 patients (16 women) aged 48-75 years with normal LV function using pressure-volume loops obtained by simultaneous conductance catheter volumetry and micromanometer pressure. End-systolic and end-diastolic pressure volume (ESPVR, EDPVR) and preload recruitable stroke work relations (PRSWR) were derived. Results were analysed according to gender, and the effects of body size and chamber dimensions were examined. RESULTS: The groups were closely matched for age (60+/-6 vs. 60+/-8 years) and co-morbid conditions. Women had higher end-systolic blood pressure (139.7+/-21.1 vs. 123.6+/-12.6 mmHg, P=0.001), and smaller LV cavity volume (end-diastolic volume 96.4+/-30.6 vs. 139+/-30.7 ml, P=0.001). Women had significantly higher LV end-systolic elastance (Ees, 2.65+/-0.10 vs. 1.96+/-0.09 mmHg ml(-1), P<0.002), arterial elastance (2.41+/-1.13 vs. 1.54+/-0.55 mmHg ml(-1), P=0.01) and lower passive LV diastolic compliance (slope EDPVR, 6.12+/-0.37 vs. 10.0+/-0.50 ml mmHg(-1), P<0.001). While there was a strong relationship between end-systolic elastance and chamber volume (r=0.69, P<0.001), gender differences in chamber function all persisted after indexing to body size. Higher LV systolic function in women was also shown in PRSWR analysis (slope, M(SW); 101.4+/-3.8 vs. 90.4+/-2.8 mmHg, P<0.05), which is independent of chamber size. After normalising volumes to resting diastolic volume, the greater systolic and diastolic elastance in women was accounted for. The ratio of end-systolic to arterial elastance, a measure of ventriculo-vascular coupling, was similar in women and men (1.19+/-0.40 vs. 1.54+/-0.30, respectively, P=0.23). CONCLUSIONS: This study demonstrates greater systolic chamber function and lower diastolic compliance in women. Within the range of chamber dimensions seen in patients with normal LV function, a strong relationship was found between cardiac size and end-systolic elastance. While these differences were not accounted for by indexing to body size, the greater ventricular elastance in women was removed after normalising to chamber size. Despite differences in resting ventricular elastance, appropriate ventriculo-vascular coupling was maintained in both genders as the greater end-systolic elastance in women was matched by similarly elevated arterial elastance.     

Early detection of myocardial alterations in mitral insufficiency with the angiotensin test

Left ventricular function was assessed at rest and after increasing systemic arterial resistance by angiotensin in 40 patients with isolated mitral insufficiency. Angiotensin was administered intravenously at a dose of 0,4 micrograms/mn until the systolic blood pressure rose by at least 30 mm Hg. Left ventricular and aortic pressures, cardiac index and left ventriculography in the 30 degree right anterior oblique projection (50 frames per second) were recorded before and during angiotensin infusion. The mean rise in systolic left ventricular pressure was 40 +/- 2,8 mm Hg; the heart rate increased slightly but significantly; left ventricular and diastolic pressure rose from 12,0 +/- 1,0 to 24,0 +/- 1,2 mmHg. The systolic index (Fick's method) was significantly decreased (37 +/- 1,6 ml/m2 to 26 +/- 1,6 ml/m2) though the angiographic systolic index remained unchanged. This is explained by an increase in the regurgitant fraction (51 +/- 2,5% ao 65 +/- 3%). The end diastolic volume index was unchanged; the ejection fraction was significantly decreased. The resting hemodynamic status was only slightly disturbed in 29 patients (mean capillary pressure less than 15 mm Hg, 8,8 +/- 0,52 mmHg). The left ventricular function curves with angiotensin distinguished two groups of patients: Group A (20 patients) with left ventricular dysfunction induced by angiotensin, Group B (9 patients) who maintained the systolic index despite the increase in left ventricular end diastolic pressure. These results suggest that the angiotensin test may be useful for detecting early left ventricular dysfunction in patients with isolated mitral insufficiency and virtually normal resting hemodynamic parameters.     

Decreased exercise capacity in mild essential hypertension: non-invasive indicators of limiting factors.

Available data suggest that exercise capacity is limited in hypertension. The mechanism of this reduced maximal exercise capacity has not been fully elucidated. In this study 22 patients with mild essential hypertension (162 +/- 22 mmHg systolic and 95 +/- 8 mmHg diastolic) and 36 normotensive control subjects (128 +/- 13 mmHg systolic and 80 +/- 7 mmHg diastolic) (P less than 0.01) performed an ergometer test till exhaustion. Body mass index in the two groups did not differ. The maximal oxygen consumption VO2 was lower in the hypertensive group (18 +/- 7 versus 23 +/- 8 ml/kg/min; P less than 0.02) as was the maximal workload (141 +/- 52 vs. 185 +/- 70 Watt; P less than 0.01). Rate pressure product rose only 2.7 fold in hypertensive patients versus 3.5 fold in the control group (P less than 0.001). In hypertensive patients maximal workload decreased with increasing resting systolic blood pressure (P less than 0.05) while in the normotensive subjects maximal workload rose with increasing resting systolic blood pressure (P less than 0.05). In conclusion both high and low blood pressure was associated with a decreased maximal voluntary exercise capacity. Even mild hypertension was accompanied by lower maximal exercise capacity. Hypertensive patients also had a lower maximal VO2 and lower maximal rate pressure product than did normotensive subjects.     

Role of educational intervention in the management of comorbid depression and hypertension

To assess the effect of health education on blood pressure control and depression symptoms, we conducted a prospective study in 272 patients with essential hypertension. Depression symptoms were assessed by the Zung Self-rating Depression Scale (SDS). There was no significant difference in the level of hypertension and SDS scores between the educational (n = 138) and control (n = 134) group before the study (p > 0.05). After 12 months of follow-up, the body mass index (BMI) was reduced in the educational group (23.6 +/- 2.6 vs 21.4 +/- 2.2 kg/m2, p < 0.01), but it remained unchanged in the control group. The average systolic and diastolic blood pressure were reduced in both groups, but the amplitude of systolic blood pressure reduction in the educational group was greater than that of the control group (7.9 +/- 2.3 vs 4.2 +/- 2.0 mmHg, p < 0.01). The incidence of depression (10.9% vs 10.4%) and the average SDS scores (32.4 +/- 6.7 vs 33.2 +/- 6.9) were similar between the two groups (p > 0.05). However, in the depressed patients who received hypertension education, the average systolic (160.2 +/- 12.4 mmHg) and diastolic (89.8 +/- 7.3 mmHg) blood pressure was significantly lower than that of the control group (169.1 +/- 16.8 and 96.8 +/- 13.0 mmHg, respectively, p < 0.01). We conclude that hypertension education does not reduce the incidence or symptoms of depression, but it may facilitate blood pressure management in patients with clinical depression.     

Left ventricular mass index and sports: the influence of different sports activities and arterial blood pressure

BACKGROUND: The mechanisms by which endurance training produces physiological hypertrophy have been thoroughly investigated but not with young athletes. The aim of our study was to investigate arterial blood pressure exercise responses in young athletes who started heavy training by the age of 11, participating in metabolically different sports (cycling, kayaking, and soccer) and to analyse the influence that arterial blood pressure at maximum exercise and VO(2) max could have on the development of cardiac mass in these subjects. SUBJECTS AND METHODS: We studied a group of well trained normotensive male subjects, comprising 37 cyclists, 15 soccer players and 12 canoeists (mean age, 16+/-1 years). Evaluation included a clinical history and physical examination, M-mode and two-dimensional echocardiography, 12-lead resting electrocardiogram and a graded exercise test with direct determination of VO(2) max. Systolic and diastolic blood pressure were measured at rest and maximum exercise. Determination of the left ventricular mass index (LVMI) was performed using Devereux's formula with correction for the body surface area. RESULTS: Cyclists showed values of LVMI in g m(-2) significantly higher than those of other subjects (123 vs. 92 and 113). Canoeists showed the maximal arterial blood pressure at maximum exercise in mmHg (190 vs. 172 and 170) and cyclists showed the maximal VO(2) ml kg(-1) min(-1) uptake (57.6 vs. 48.5 and 53.3). A linear correlation was found between LVMI and VO(2) max (r=0.4727, P<0.001) and this correlation was also significant with systolic blood pressure at maximum exercise (r=0.2909, P<0.01). No differences in LVMI were found when comparing those subjects who presented systolic blood pressure at maximum exercise equal or greater than 195 mmHg with those who presented less than this value. CONCLUSIONS: It can be concluded that VO(2) max is the variable that better correlates with the LVMI. Athletes who reach greater systolic blood pressures at peak exercise have a tendency to develop greater LVMI. In comparison with soccer players and canoeists, cyclists are the sportsmen who develop a greater LVMI and VO(2) max.     

Prevalence of sustained hypertension and obesity in urban and rural school going children in Ludhiana

BACKGROUND: Increasing trend of hypertension is a worldwide phenomenon. The data on sustained hypertension in school going children is scanty in India. The present study was conducted to evaluate the prevalence of sustained hypertension and obesity in apparently healthy school children in rural and urban areas of Ludhiana using standard criteria. METHODS AND RESULTS: A total of 2467 apparently healthy adolescent school children aged between 11-17 years from urban area and 859 students from rural area were taken as subjects. Out of total 3326 students, 189 were found to have sustained hypertension; in urban areas prevalence of sustained hypertension was 6.69% (n=165) and in rural area it was 2.56% (n=24). Males outnumbered females in both rural and urban areas. The mean systolic and diastolic blood pressure of hypertensive population in both urban and rural population was significantly higher than systolic and diastolic blood pressure in their normotensive counterparts (urban normotensive systolic blood pressure:115.48+/-22.74 mmHg, urban hypertensive systolic blood pressure: 137.59+/-11.91 mmHg, rural normotensive systolic blood pressure: 106.31+/-19.86 mmHg, rural hypertensive systolic blood pressure: 131.63+/-10.13 mmHg, urban normotensive diastolic blood pressure: 74.18+/-17.41 mmHg, urban hypertensive diastolic blood pressure: 84.58+/-8.14 mmHg, rural normotensive diastolic blood pressure: 68.84+/-16.96 mmHg, rural hypertensive diastolic blood pressure: 79.15+/-7.41 mmHg). Overweight populationwas significantly higher in urban area. There were 287 (11.63%) overweight students and 58 (2.35%) were obese. In rural population overweight and obese students were 44 (4.7%) and 34 (3.63%) respectively. There was significant increase in prevalence of hypertension in both rural and urban population with increased body mass index in urban students; those with normal body mass index had prevalence of hypertension of 4.52% (n=96), in overweight it was 15.33% (n=44) and in obese it was 43.10% (n=25). In rural area, the overweight students showed prevalence of sustained hypertension in 6.82% (n=3) and in obese group it was 61.76% (n=21). None of the student with normal body mass index in rural area was found to be hypertensive. The mean body mass index of hypertensive population in both rural and urban areas was significantly higher than respective normotensive population (mean body mass index in urban normotensive group: 20.34+/-3.72 kg/m2, hypertensive group: 24.91+/-4.92 kg/m2; mean body mass index in rural normotensive group: 18.41+/-3.41 kg/m2, hypertensive group: 21.37+/-3.71 kg/m2, p<0.01). CONCLUSIONS: Prevalence of sustained hypertension is on the rise in urban area even in younger age groups. Blood pressure is frequently elevated in obese children as compared to lean subjects. This is possibly related to their sedentary lifestyle, altered eating habits, increased fat content of diet and decreased physical activities.     

The impact of hypertension and hypertension-related left ventricle hypertrophy on right ventricle function

AIM: The aim of our study is to determine the effect of hypertension and hypertension-related left ventricle hypertrophy on right ventricle (RV) morphology and function by using RV standard Doppler echocardiographic indices, myocardial Doppler imaging, and strain/strain rate imaging indices. METHODS: We studied 35 patients with arterial hypertension and 30 age- and sex-adjusted control subjects who had no other pathological conditions. Standard transthoracic Doppler echocardiographical measurements, pulsed-wave tissue Doppler from tricuspid anulus (Peak systolic-st, peak early diastolic-et, peak late diastolic velocity-at), reconstructed spectral pulsed-wave tissue Doppler velocities (peak systolic-S, peak early-E, peak late diastolic velocity-A), and strain/strain rate imaging of RV free wall mid region (peak systolic strain-in, peak systolic strain rate-SR) were obtained. RESULTS: Age, body surface area, blood pressure, and heart rate were comparable between two groups. Hypertensive subjects had significantly increased LV end-diastolic septal and posterior wall thickness, left atrial diameter, LV mass, LV mass index, and relative wall thickness during diastole. At the level of right ventricular lateral tricuspid annulus without systolic changes, the majority of diastolic measurements were altered in hypertensives (early diastolic velocity et; 13 +/- 2 vs. 18 +/- 4 m/sec, P < 0.0001, late diastolic velocity at; 20 +/- 4 vs. 14 +/- 3 m/sec, P < 0.0001, early to late diastolic velocity ratio; 0.69 +/- 0.14 vs. 1.32 +/- 0.38, P < 0.0001). The velocity data from two-dimensional color myocardial imaging at the level of RV free wall mid region again showed altered diastolic measurements in hypertensives (E; 8.01 +/- 2.6 vs. 10.4 +/- 3.14 m/sec, P < 0.001, A; 11.5 +/- 2.6 vs. 9.12 +/- 3.7 m/sec, P < 0.0001, E/A ratio; 0.75 +/- 0.41 vs. 1.87 +/- 0.48, P < 0.00). The peak systolic strain of RV free wall mid region was significantly lower in hypertensive individuals than controls (25.666 +/- 5.64 vs. 30.03 +/- 6.78%, P < 0.05). No significant differences were found in other parameters of RV function between hypertensive and control subjects. CONCLUSIONS: The present study demonstrates that besides the manifest morphologic LV adaptations, significant RV functional alterations can be determined by TDI and strain/strain rate imaging in patients arterial hypertension. Both tissue velocities by TDI and strain imaging may be new tools to define and quantitate subtle change in systolic and diastolic function of right ventricular function in arterial hypertension that cannot be determined in standard echocardiographic parameters.     

Low prevalence of microalbuminuria in normotensive patients with insulin-dependent diabetes mellitus

We studied the prevalence of microalbuminuria (urinary albumin excretion rate [UAER] greater than 20 micrograms/min less than or equal to 200 micrograms/min) as determined in a single, timed, overnight urine collection in 156 normotensive (BP less than 140/90), Albustix negative subjects with type 1 diabetes and its association with arterial blood pressure, the duration of diabetes, levels of glycosylated hemoglobin, body mass index, daily insulin dose and serum cholesterol. Nineteen subjects (12.2%) had a UAER in the microalbuminuric range. The microalbuminuric patients had a significantly longer duration of diabetes, 21 +/- 2 vs 15 +/- 1 years (P less than 0.01), higher diastolic blood pressure, 80 +/- 2 vs 76 +/- 1 mmHg (P less than 0.05) and serum cholesterol concentration, 206 +/- 11 vs 186 +/- 3 mg/dl (P less than 0.05) than did the normoalbuminuric subjects. There were no differences between the normoalbuminuric and microalbuminuric subjects in terms of age, systolic blood pressure, body mass index, daily insulin dose or glycosylated hemoglobin levels. These data indicate that the prevalence of microalbuminuria in type 1 diabetes has probably been overestimated in previous studies due to the inclusion of patients with hypertension. Thus, microalbuminuria, rather than being a predictor of the development of diabetic renal disease, may indicate the presence of diabetic nephropathy with rising blood pressure levels. Further investigation is needed to clarify the relationship between microalbuminuria and coronary risk factors such as serum cholesterol and diastolic blood pressure levels.     

A modified ambulatory arterial stiffness index is independently associated with all-cause mortality

Dependence of the ambulatory arterial stiffness index (AASI) on data scattering interferes with its potential clinical relevance. We assessed the correlates and all-cause mortality associations of a modified AASI (s-AASI). AASI was derived from the 24-h diastolic vs. systolic blood pressure linear regression line, whereas s-AASI was derived by symmetric regression (bisecting the line of diastolic vs systolic and systolic vs. diastolic). Of 2918 patients 55% were women; age was 56 +/- 16 years and body mass index was 27.3 +/- 4.5 kg/m(2). Average 24-h ambulatory blood pressure was 138 +/- 16/78 +/- 10 mm Hg. Applying the modified method for calculating AASI yielded a different measure: the negative correlation between AASI and blood pressure dipping (r = -0.304, P < 0.0001) was abolished (r = +0.223, P < 0.0001), s-AASI was more dependent on age (r = 0.266 vs. r = 0.089 for AASI), and prediction of all-cause mortality was enhanced; hazard ratio (95% confidence intervals) 1.17 (1.00-1.36) per 1 s.d. increase in s-AASI in the fully adjusted model as compared with 1.15 (0.97-1.36) for AASI.     

Spectral analysis of 24 h blood pressure monitoring in the assessment of trough: peak ratio. A randomized, placebo-controlled, cross-over comparison of ramipril and enalapril

BACKGROUND: The ratio between the magnitude of blood pressure reduction during the steady-state dosage interval (trough) and the maximum blood pressure reduction (peak) is an integrated in-vivo index both of the pharmacokinetic properties and of pharmacodynamic activity of an antihypertensive drug. Angiotensin converting enzyme inhibitors are often characterized by a low (often lower than 50%) trough: peak ratio but no direct drug comparisons are available. OBJECTIVE: To compare the absolute blood pressure reduction and the trough: peak ratio of daily doses of two angiotensin converting enzyme inhibitors, 5 mg ramipril and 10 mg enalapril. METHOD: After a 1-month wash-out and a 2-week placebo run-in, 25 mild hypertensives aged 47 +/- 4 years (17 men and eight women) were randomly assigned to treatments separated by a 2-week interval. Ambulatory blood pressure monitoring was performed and trough: peak ratio was calculated by the fast Fourier transform analysis of placebo-effect-subtracted data. RESULTS: After 1 month of ramipril treatment, 24 h blood pressure decreased from 139 +/- 10 to 129 +/- 11 mmHg for systolic (P < 0.05) and from 89 +/- 8 to 81 +/- 5 mmHg for diastolic blood pressure (P < 0.01). Also enalapril treatment caused a significant 24 h reduction in blood pressure both for systolic (to 132 +/- 7 mmHg, P < 0.05) and for diastolic blood pressure (to 84 +/- 5 mmHg, P < 0.05). Placebo caused a 24 h reduction in blood pressure (to 136 +/- 8 mmHg for systolic and 87 +/- 5 mmHg for diastolic blood pressure, NS, versus wash-out period). The two drugs were equally effective in reducing ambulatory blood pressure, but ramipril produced a trough: peak ratio significantly higher than that with enalapril both for systolic (48 +/- 11%, range 34-74%, versus 38 +/- 11%, range 21-67%, P < 0.005)and for diastolic blood pressure (47 +/- 11%, range 30-79 %, versus 37 +/- 12%, range 21-68%, P < 0.05). CONCLUSION: The low trough : peak ratios could have been due to the daily pattern of blood pressure of mild hypertensives, many of whom are normotensives at night-time, so that the main antihypertensive effect is exerted during daytime rather than during the night or early morning.     

Regression of left ventricular hypertrophy and improvement of diastolic function in hypertensive patients treated with telmisartan

OBJECTIVES: The study was designed to test whether or not the angiotensin II receptor blocker telmisartan brings about regression of left ventricular (LV) concentric hypertrophy and whether or not these changes are associated with improved diastolic filling. METHODS: An echocardiographic follow-up study was performed in 85 hypertensive patients (systolic blood pressure [SBP] >140 mmHg, diastolic blood pressure [DBP] >90 mmHg) and mild-to-moderate LV hypertrophy (LV mass index related to body surface area [LVMI] 117-150 g/m2 for men and 105-150 g/m2 for women) treated with telmisartan monotherapy 40-80 mg once daily for 1 year. Blood pressure, LVMI, left atrial (LA) volumes, and diastolic function were determined at baseline and after 3, 6, 9, and 12 months of treatment. Blood pressure was also monitored at all visits. Diastolic function was assessed by examination of transmitral inflow and pulmonary vein flow patterns. RESULTS: Telmisartan reduced blood pressure; after 12 months, the mean+/-S.D. SBP and DBP were reduced from 144+/-10 to 126+/-8 mmHg (p<0.001) and from 98+/-8 to 86+/-7 mmHg (p<0.001), respectively. The LVMI was decreased from 119+/-7 to 109+/-3 g/m2 (p<0.001) after 12 months' telmisartan treatment. All patients had diastolic dysfunction at baseline. After 12 months' telmisartan treatment, a normal pattern of transmitral inflow was present in 21% of patients. The regression of LV hypertrophy observed after 12 months was associated with increased peak early diastolic velocity/peak late diastolic velocity ratio from 0.60+/-0.18 to 0.83+/-0.20 (p<0.001), shortened isovolumic relaxation time (IVRT) from 110+/-13 to 105+/-13 ms (p<0.001), and decreased deceleration time from 229+/-30 to 215+/-28 ms (p=0.002). Univariate analysis showed that shortened IVRT was related to a reduction in the LVMI and LA maximal and minimal volumes. In the multivariate analysis, the reduction in LVMI and the reduction in LA maximal and minimal volumes were independently associated with IVRT reduction. CONCLUSIONS: Telmisartan 40-80 mg is effective in LV hypertrophy regression in hypertensive patients. The reduction in LVMI due to telmisartan monotherapy was associated with a significant improvement of diastolic filling parameters and with a significant reduction of LA volumes.     

Haemodynamic effects of nifedipine and propranolol in patients with hypertrophic obstructive cardiomyopathy.

The haemodynamic effects of nifedipine, propranolol, and the combined administration of the two drugs were studied in 12 patients with hypertrophic obstructive cardiomyopathy. The combined administration of nifedipine and propranolol appeared to be superior to that of nifedipine alone. The spontaneous heart rate was reduced in most cases after nifedipine plus propranolol, and at atrial pacing the following results were obtained: left ventricular peak systolic pressure was reduced from 200 +/- 39 to 157 +/- 30 mmHg; a positive correlation was found between the pre-drug left ventricular end-diastolic pressure and the magnitude of reduction in left ventricular end-diastolic pressure; systolic blood pressure was reduced from 125 +/- 31 to 111 +/- 27 mmHg, and total peripheral resistance was reduced from 1403 +/- 307 to 1160 +/- 209 dyne s-1 cm-5. The combined administration reduced the resting left ventricular outflow gradient from 76 +/- 19 to 45 +/- 26 mmHg, while cardiac index was left unchanged. The effects on mean pulmonary arteriolar resistance and mean pulmonary arteriolar resistance and mean pulmonary capillary venous pressure were in most cases slight and insignificant. The results indicate an improved haemodynamic condition in patients with hypertrophic obstructive cardiomyopathy after the combined administration of nifedipine and propranolol: a treatment that might provide a new and useful alternative to already existing medication.     

Hemodynamic and antianginal effects during rest and exercise of intravenous isradipine, a new dihydropyridine calcium antagonist

In an open randomized study, hemodynamic and antianginal effects of nifedipine and the new dihydropyridine derivative isradipine were compared in patients with stable, angiographically confirmed coronary heart disease. Right heart hemodynamics, systemic arterial blood pressure, ECG, and drug plasma concentrations were measured before medication at rest and exercise, after infusions of increasing doses at rest, and again after treatment at rest and exercise. A linear relationship between serum concentrations and cumulated dosages was obtained for both drugs. At rest, both drugs significantly increased cardiac output and heart rate. The reduction of arterial blood pressure was significantly greater after isradipine (systolic from 148 +/- 3 to 104 +/- 3 mmHg; diastolic from 90 +/- 4 to 58 +/- 2 mmHg) than after nifedipine (systolic 149 +/- 6 to 125 +/- 4 mmHg; diastolic 92 +/- 4 to 76 +/- 3 mmHg). The minimal effective plasma level of isradipine regarding blood pressure reduction was estimated at 5 ng/ml (nifedipine: 10-25 ng/ml). During exercise both medications significantly reduced mean pulmonary artery pressure (isradipine: 40 +/- 3 to 20 +/- 1 mmHg, nifedipine: 37 +/- 4 to 22 +/- 1 mmHg), pulmonary artery wedge pressure (isradipine: 23 +/- 3 to 10 +/- 1 mmHg, nifedipine 24 +/- 3 to 14 +/- 1 mmHg), and diastolic arterial pressure (isradipine: 103 +/- 3 to 73 +/- 4 mmHg, nifedipine: 99 +/- 3 to 91 +/- 2 mmHg), whereas systolic pressure was reduced by only isradipine (189 +/- 4 to 147 +/- 5 mmHg). Neither medication significantly changed electrocardiographic ST depression during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exaggerated hypertensive response to exercise in patients with diastolic heart failure

Systolic load elevation during exercise prolongs left ventricular (LV) relaxation, compromises filling, and raises end-diastolic pressure, leading to reduced exercise tolerance. The aim of this study was to test the hypothesis that the hypertensive response to exercise is exaggerated in patients with diastolic heart failure (DHF). Echocardiograms and treadmill testing were performed in patients with DHF (n=20) and age-matched hypertension with LV hypertrophy (HTN; n=20). The Minnesota Living with Heart Failure Questionnaire was used to estimate quality of life (QOL). There were no differences in resting blood pressure or echocardiographic parameters between the groups. The maximum exercise time was significantly shorter in the DHF group than in the HTN group (6.0+/-3.0 vs. 12.5+/-2.5 min), and the peak systolic blood pressure during exercise was significantly higher in the DHF group (212+/-18 vs. 189+/-16 mmHg, p<0.05). After 4 weeks of treatment with candesartan, an angiotensin II receptor blocker (8 mg/d), peak systolic blood pressure during exercise decreased to 191+/-13 mmHg, maximum exercise time increased (10.4+/-3.0 min; p<0.05), and QOL improved in patients with DHF, while there was no change in patients with HTN, despite the similar resting blood pressure. In patients with DHF, systolic blood pressure markedly increased during exercise, and this was accompanied by impaired exercise tolerance and a decreased QOL, both of which were partly suppressed by blocking angiotensin II.     

Regression of hypertrophy following nitrendipine: effect on systolic and diastolic function

The purpose of the present study was to determine whether an antihypertensive treatment with the dihydropyridine nitrendipine can induce regression of severe hypertensive hypertrophy and, whether alterations in systolic and diastolic ventricular function do occur. Eleven patients (age 49 +/- 11 years) with hypertensive hypertrophy were treated with nitrendipine (10-40 mg/day) for 12 months. Before and after therapy left ventricular hypertrophy, systolic, and diastolic function were measured by M-mode, two-dimensional- and digitized M-mode echocardiography. Systolic blood pressure dropped from 185.5 +/- 19.8 to 164.1 +/- 15.6 mm Hg (p less than 0.05). Left ventricular muscle mass was reduced from 234.5 +/- 51.2 to 201.5 +/- 37.9 g/m2 (p less than 0.05). Systolic wall stress (257.2 +/- 50.5 vs 245.2 +/- 44.4 x 10(3) dyn/cm2) and fractional shortening (34.9 +/- 6.1 vs 37.1 +/- 5.4%) remained nearly unchanged. The peak rate of left ventricular internal dimension change during diastole (MLVD), as an index of rapid early diastolic filling was increased (13.1 +/- 3.0 vs 16.5 +/- 3.7 cm/s; p less than 0.01), the relaxation time index, as an index of isovolumic relaxation, remained nearly unchanged (76 +/- 35 vs 64 +/- 24 ms; n.s.). A long-term treatment with nitrendipine regressed hypertensive left ventricular hypertrophy in proportion to blood pressure reduction. While systolic function remained unchanged as a consequence of an unaltered systolic wall stress, i.e. afterload, diastolic filling was markedly improved due to changes in left ventricular geometry through reduction in mass to volume ratio. Since relaxation time index remained nearly unchanged, factors contributing to the phase of isovolumic relaxation were not essentially affected by regression of left ventricular hypertrophy.     

Impaired endothelial and smooth muscle functions and arterial stiffness appear before puberty in obese children and are associated with elevated ambulatory blood pressure.

AIMS: To determine whether impaired brachial endothelial (flow-mediated dilation, FMD) and smooth muscle function (nitroglycerin-mediated dilation, NTGMD), and remodelling of the common carotid artery (CCA) develop before puberty in obese children. METHODS AND RESULTS: Arterial intima-media thickness (IMT), FMD and NTGMD were measured by high-resolution ultrasound in 48 obese and 23 lean pre-pubertal children (8.8 +/- 1.5 years old). We assessed central pulse pressure, incremental elastic modulus (Einc), casual and ambulatory systolic (SBP) and diastolic blood pressure (DBP), and body fatness by DXA. Obese children had significantly lower FMD (4.5 +/- 4.0 vs. 8.3 +/- 1.7%), NTGMD (19.0 +/- 9.0 vs. 25.8 +/- 6.1%), and increased Einc (13.9 +/- 5.2 vs. 10.4 +/- 5.2 mmHg/10(2)), ambulatory SBP (121.3 +/- 12.6 vs. 106.6 +/- 7.1, mmHg), and DBP (69.1 +/- 5.7 vs. 63.7 +/- 4.5) than lean subjects, whereas IMT was not augmented. Ambulatory systolic hypertension was present in 47% of obese subjects. FMD, NTGMD, and Einc were correlated with body fatness, body mass index, and blood pressure (BP). CONCLUSION: Impaired endothelial and smooth muscle functions and altered wall material develop before puberty in obese children, however remodelling of the CCA is not yet present. Arterial dysfunction may be considered as the first marker of atherosclerosis and is associated with elevated BP. Ambulatory blood pressure monitoring may be a potential tool to improve risk stratification in obese children.     

High diastolic blood pressure during exercise is associated with hypercholesterolemia in patients with coronary artery disease

Evaluating blood pressure response during exercise rather than during rest might better detect a subtle impairment in relaxation of the resistance vessel in hypercholesterolemia. We examined the relation between serum cholesterol and blood pressure response during exercise in patients with coronary artery disease. One hundred and forty-eight consecutive patients with coronary artery disease were monitored during symptom-limited incremental exercise testing with a cycle ergometer. Cuff blood pressure was measured every minute during exercise testing with an automatic indirect manometer. Although there were no significant differences in systolic or diastolic blood pressure at rest between the patients with hypercholesterolemia (total cholesterol > or = 220 mg/dL, n = 39) and those without it (n = 109), the former reached a higher diastolic blood pressure at peak exercise (94.8+/-16.0 versus 87.8+/-12.9 mmHg, P = 0.007). The increase in diastolic blood pressure at peak exercise versus the resting value in the patients with hypercholesterolemia was 20.6+/-11.3 mmHg, and this was significantly higher than the increase in patients without hypercholesterolemia (14.8+/-11.8 mmHg, P = 0.009). However, there were no differences in the peak exercise systolic blood pressure and the magnitude of the increase in systolic blood pressure between the two groups. Among the patients with coronary artery disease in our study, we found that those with hypercholesterolemia had significantly higher diastolic blood pressure during exercise than those without hypercholesterolemia, strongly suggesting that patients with hyperlipidemia are at a higher risk of developing hypertensive complications.