Perindopril/indapamide combination more effective than enalapril in reducing blood pressure and left ventricular mass: the PICXEL study

OBJECTIVE: Few data are available comparing the effects of monotherapy and combination therapy on target organ damage. The PICXEL study compared the efficacy of a strategy based on first-line combination with perindopril/indapamide versus monotherapy with enalapril in reducing left ventricular hypertrophy (LVH) in hypertensive patients. METHODS: In this 1-year multicentre randomized double-blind study, patients received an increasing dosage of perindopril/indapamide (n = 284) or enalapril (n = 272). Changes in blood pressure and echocardiographic measures of LVH were assessed from baseline to the end of treatment. Reading of the echocardiograms was central and blinded for therapy, patient and sequence. RESULTS: Systolic and diastolic blood pressure decreased significantly more in the perindopril/indapamide than in the enalapril group (P < 0.0001 and P = 0.003). The left ventricular mass index decreased by 13.6 +/- 23.9 g/m(2) (mean +/- SD) with perindopril/indapamide (P < 0.0001) and 3.9 +/- 23.9 g/m(2) with enalapril (P < 0.005); these decreases were significantly different (P < 0.0001). The left ventricular internal diameter, posterior and interventricular septal wall thickness decreased significantly with perindopril/indapamide (P < or = 0.0001); the interventricular septal wall thickness decreased significantly with enalapril (P < 0.001). Both treatments were well tolerated. CONCLUSION: A strategy based on first-line combination with perindopril/indapamide achieved better blood pressure decrease with a significantly greater degree of LVH reduction than a strategy based on monotherapy with enalapril in hypertensive patients with LVH.     

Regression of left ventricular mass in hypertensive patients treated with perindopril/indapamide as a first-line combination: the REASON echocardiography study

BACKGROUND: Increase in left ventricular mass (LVM) may be linked to morbidity and mortality in hypertensive patients. Arterial stiffness, systolic blood pressure (BP), and pulse pressure (PP) seem to be the main determinants of LVM. The perindopril/indapamide combination normalizes systolic BP, PP, and arterial function to a greater extent than atenolol. The aim of this study was to compare the effects of perindopril (2 mg)/indapamide (0.625 mg) first-line combination with atenolol (50 mg) on LVM reduction in hypertensive patients. METHODS: Two hundred fourteen patients with essential hypertension participating in the PREterax in Regression of Arterial Stiffness in a ContrOlled Double-BliNd (REASON), randomized, double-blind, parallel-group study, underwent M-mode two-dimensional-guided echocardiography. RESULTS: Perindopril/indapamide and atenolol were both effective at brachial BP reduction during the 12-month period. The systolic BP reduction was significantly greater with perindopril/indapamide than with atenolol (-21.2 v -15.3 mm Hg), whereas the reduction in diastolic BP was similar between treatment groups (-12.1 v -11.3 mm Hg). Reduction in LVM was higher with perindopril/indapamide than with atenolol. The between-group difference was significant for LVM (-13.6 v -4.3 g, P = .027), LVM/body surface area (LVMI1, P = .032), and LVM/body height2.7 (LVMI2, P = .013). The 124 patients with LV hypertrophy at baseline showed greatest LVM regression (LVM: -22.5 v -8.9 g, P = .009; LVMI1, P = .031; LVMI2, P = .028). The reduction in LVM adjusted for brachial systolic BP and heart rate was still significantly greater with perindopril/indapamide than with atenolol. CONCLUSIONS: Treatment, based on a first-line perindopril/indapamide combination in hypertensive patients, was more effective than atenolol on regression of echocardiographic indices of LVM and LV hypertrophy.     

Twenty-four-hour ambulatory blood pressure monitoring efficacy of perindopril/indapamide first-line combination in hypertensive patients: the REASON study

BACKGROUND: Circadian blood pressure (BP) measurements provide more information on hypertensive complications than office BP measurements. The purpose of this study was to analyze the efficacy of the first-line combination of perindopril 2 mg plus indapamide 0.625 mg versus atenolol 50 mg on BP parameters and variability over 24 h in patients with hypertension. METHODS: A double-blind, randomized, controlled, 12-month study comparing perindopril/indapamide and atenolol was performed in 201 patients (age 55.0 years) with uncomplicated sustained essential hypertension. Ambulatory BP measurements (ABPM) were done every 15 min over 24 h. RESULTS: After 1 year of treatment, the decrease in systolic BP was significantly greater for perindopril/indapamide than for atenolol during the entire 24-h period (-13.8 v -9.2 mm Hg), the daytime and the nighttime periods (P <.01). Diastolic blood pressure (DBP) variations were comparable for the two groups (-7.2 v -8.3 mm Hg, NS). Pulse pressure (PP) reduction was also significantly greater for perindopril/indapamide than for atenolol (for the whole 24 h, -6.6 v -0.9 mm Hg, P <.001). The through to peak (T/P) BP ratio and the smoothness index were comparable in the two groups for DBP. For systolic blood pressure (SBP), higher values of the T/P ratio (0.80 v 0.59) and the smoothness index (1.45 v 0.98; P <.02) were achieved for the perindopril/indapamide combination than for atenolol. CONCLUSIONS: The perindopril/indapamide first-line combination decreased SBP and PP more effectively than atenolol. Moreover, the BP control effect was smooth and consistent throughout the 24-h dosing interval and BP reduction variability was lower than the one induced by atenolol.     

Obstructive sleep apnea, hypertension, and their interaction on arterial stiffness and heart remodeling

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and hypertension are independently associated with increased stiffness of large arteries that may contribute to left ventricular (LV) remodeling. We sought to investigate the impact of OSA, hypertension, and their association with arterial stiffness and heart structure. DESIGN: We studied 60 middle-aged subjects classified into four groups according to the absence or presence of severe OSA with and without hypertension. All participants were free of other comorbidities. The groups were matched for age, sex, and body mass index. MEASUREMENTS AND RESULTS: Full polysomnography, pulse-wave velocity (PWV), and transthoracic echocardiography were performed in all participants. Compared with normotensive subjects without OSA, PWV, left atrial diameter, interventricular septal thickness, LV posterior wall thickness, LV mass index, and percentage of LV hypertrophy had similar increases in normotensive OSA and patients with hypertension and no OSA (p < 0.05 for all comparisons), with a significant further increase in PWV, LV mass index, and percentage of LV hypertrophy in subjects with OSA and hypertension. Multivariate regression analysis showed that PWV was associated with systolic BP (p < 0.001) and apnea-hypopnea index (p = 0.002). The only independent variable associated with LV mass index was PWV (p < 0.0001). CONCLUSIONS: Severe OSA and hypertension are associated with arterial stiffness and heart structure abnormalities of similar magnitude, with additive effects when both conditions coexist. Increased large arterial stiffness contributes to ventricular afterload and may help to explain heart remodeling in both OSA and hypertension.     

Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER

Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.     

Ambulatory blood pressure, blood pressure variability and the prevalence of carotid artery alteration: the Ohasama study

OBJECTIVES: To investigate the association between ambulatory blood pressure (BP) variables (level, short-term variability, circadian variation and morning pressor surge) and carotid artery alteration in a general population. METHODS: We measured ambulatory BP every 30 min in 775 participants (mean age 66.2 +/- 6.2 years, 68.8% women) from the Japanese general population. Short-term BP variability during the daytime and night-time were estimated as within-subject standard deviation of daytime and night-time BP, respectively. Circadian BP variation was calculated as the percentage decline in nocturnal BP. Morning pressor surge was defined as morning BP minus pre-waking BP. The extent of carotid artery alteration was evaluated as the average of common carotid intima-media thickness (IMT) and the presence of focal carotid plaque. RESULTS: Daytime and night-time BP values were more closely associated with carotid artery alteration than casual BP. With mutual adjustment for daytime and night-time BP, the latter (P < 0.0001) was more closely associated with IMT, which represents diffuse arterial thickening and arteriosclerosis, than daytime BP (P = 0.2). Night-time systolic BP variability was positively associated with carotid plaque (focal atherosclerotic lesions) independently of possible confounding factors, including night-time systolic BP (P = 0.01). A diminished nocturnal decline in systolic BP was associated with a greater IMT after adjustment for confounding factors (P = 0.03). A morning pressor surge was not associated with carotid artery alteration. CONCLUSION: Ambulatory BP levels and BP variability were closely associated with carotid artery alteration, suggesting that these parameters are independent risk factors or predictors of carotid artery alteration.     

Low-dose diuretic and/or dietary sodium restriction when blood pressure is resistant to ACE inhibitor.

AIM: To compare the efficacy of indapamide (1.25 mg daily) and low-salt diet (<100 mmol/day) separately and in combination in essential hypertensive patients with inadequate BP response to perindopril. DESIGN AND METHODS: Randomized double-blind, double-dummy, crossover design. The randomized treatments were indapamide 1.25 mg daily, sodium chloride 80 mmol daily, the combination of indapamide and sodium chloride and placebo. All patients received perindopril 4 mg daily and maintained a low-sodium diet. RESULTS: 19 patients entered and 17 completed the study. Prior to randomization, average clinic sitting blood pressure was 162/101 mm Hg and average 24-h urine sodium excretion was 157 mmol/day. Compared to the phase in which patients received perindopril with sodium repletion, clinic and ambulatory BPs were significantly reduced (p<0.01) in all the other phases. Indapamide had a greater effect on BP than dietary sodium restriction, and in combination their effects were additive. The effect of indapamide on ambulatory BP persisted throughout 24 h, but the effect of the low-salt diet was predominantly observed during waking hours. CONCLUSIONS: In hypertensives with BP resistant to the angiotensin converting enzyme (ACE) inhibitor perindopril, the diuretic indapamide had greater additional efficacy and longer duration of action than dietary sodium restriction. In combination they had additive effects on BP.     

The impact of one or two missed doses on the duration of action of combined perindopril and indapamide

To evaluate the persistence of the antihypertensive effect of perindopril 4 mg+indapamide 1.25 mg once daily for up to 72 h using the 'missed-dose' technique. Hypertensive patients were initially treated with perindopril 2 mg+indapamide 0.625 mg once daily. After 4 weeks, the 135 of 216 patients who still had a diastolic BP> or =85 mm Hg went on to receive perindopril 4 mg+indapamide 1.25 mg daily for a further 8 weeks. During either week 9 or 11, placebo was substituted for perindopril 4 mg+indapamide 1.25 mg on either one or two consecutive days to simulate BP changes, which might occur after one or two missed doses. A 24-h ambulatory BP recording was performed at baseline, after 9 or 11 weeks of perindopril+indapamide therapy and during the simulated missed doses, 24- 48 and 48-72 h after the administration of perindopril 4 mg+indapamide 1.25 mg. Significant (P<0.001) reductions in mean (+/-s.d.) 24-h ambulatory BP (mm Hg) during the first 24 h after perindopril 4 mg+indapamide 1.25 mg therapy versus baseline were noted for patients later randomized to the one missed dose (-15.9+/-10.5/-9.4+/-7.6) or two missed dose (-17.4+/-8.7/-10.3+/-5.1) sub-groups. A significant reduction in BP (P<0.001 versus baseline) was still present on the days when placebo was substituted for perindopril 4 mg+indapamide 1.25 mg with decreases in mean 24-h ambulatory BP from 24 to 48 h and 48 to 72 h after dosing being -11.9+/-10.1/-6.9+/-6.2 and -10.6+/-9.9/-5.8+/-5.7, respectively. Use of the 'missed-dose' technique has demonstrated a prolonged antihypertensive effect for perindopril 4 mg+indapamide 1.25 mg for up to 72 h, supporting the use of this combination as therapy for hypertension.     

The correlation between isolated interventricular septal hypertrophy and 24-h ambulatory blood pressure monitoring in apparently healthy air crew

BACKGROUND: Interventricular septal (IVS) hypertrophy is considered to affect prognosis in hypertensive patients. However, the natural history of isolated septal hypertrophy, identified by echocardiography in otherwise healthy subjects is not well defined. METHODS: The study population included 51 apparently healthy pilots with septal hypertrophy (septal thickness > 11 mm) defined by routine echocardiography, with a calculated normal left ventricular (LV) mass. All pilots underwent casual blood pressure (BP) measurements and a 24-h ambulatory BP monitoring (ABPM). Hypertension (HTN) was defined as a casual measurement of > 140/90 mmHg. RESULTS: The mean age of the pilots was 38 +/- 11 years and the body mass index (BMI) 26.3 kg/m(2). The 17 pilots found to be hypertensive had a higher septal thickness than the 34 counterparts with normal BP measurements (13.8 +/- 2.0 mm versus 12.6 +/- 1.7 mm, P < 0.04, respectively). The mean ambulatory daytime systolic and diastolic BP were higher in comparison to non-hypertensive pilots (142 +/- 6.2 versus 128 +/- 5.0 mmHg, P < 0.0001 for systolic BP and 91 +/- 5.3 versus 78 +/- 4.1 mmHg, P = 0.001 for diastolic BP), respectively. The adjusted relative risk (RR) of a subject with an IVS thickness P > 12 mm to be hypertensive by ABPM was 3.12 (95% confidence interval 1.04-9.37, P < 0.02). CONCLUSIONS: Isolated IVS hypertrophy, even in the presence of normal LV mass is associated with HTN. Screening healthy subjects at risk for hypertension by echocardiography enables one to identify those who should be closely monitored, using among others, ABPM.     

Left ventricular function in patients with obstructive sleep apnoea syndrome before and after treatment with nasal continuous positive airway pressure

BACKGROUND: Previous studies have yielded disparate results regarding the effect of obstructive sleep apnoea (OSA) syndrome on left ventricular (LV) function. OBJECTIVES: In order to clarify this, we performed a prospective study investigating OSA patients with no history of systemic hypertension, coronary artery disease, myocardial, pericardial or valvular problems, asthma or chronic obstructive pulmonary disease before and after treatment with nasal continuous positive airway pressure (nCPAP). METHODS: Fifteen patients (3 women, 12 men) with an apnoea/hypopnoea index >15 (mean +/- SD = 52 +/- 21) were studied with complete polysomnography, ambulatory blood pressure monitoring, M-mode two-dimensional echocardiography and pulsed Doppler echocardiography in two phases, i.e. before and after 12-14 weeks of nCPAP therapy. We measured systolic and diastolic blood pressure (BP) separately in the daytime and night-time, isovolumic relaxation time (IVRT), the ratio of peak early filling velocity (E) to peak late velocity (A) diastolic transmitral flow (E/A), posterior wall thickness (PWT) and septal thickness (IVST). The shortening fraction (SF) was also calculated. Eleven overweight non-apnoeic normal subjects matched for age were used as the control group. RESULTS: Our results showed that the patient group exhibited, before treatment, LV diastolic, but not systolic, dysfunction compared with the normal group (IVRT = 94.3 +/- 11.6 ms, p < 0.05; E/A = 0.94 +/- 0.26, p < 0.02; SF = 39.9 +/- 4.1%, not significant (NS); IVST = 9.9 +/- 1.2 mm, NS; PWT = 8.3 +/- 1.2 mm, NS). Moreover, the patient group developed diastolic hypertension both in the daytime and night-time (BP/diastolic/daytime = 93.3 +/- 9.2 mm Hg, BP/diastolic/night-time = 90.3 +/- 10.7 mm Hg). After 12-14 weeks of nCPAP treatment (no change in body mass index), significant improvement in LV diastolic function and a drop in blood pressure were noticed (IVRT = 85.6 +/- 8.8 ms, p < 0.05; E/A = 1.07 +/- 0.3, p < 0.05; BP/diastolic/daytime = 86.3 +/- 5.5 mm Hg, p < 0.02; BP/diastolic/night-time = 83.9 +/- 8. 6 mm Hg, p < 0.05) in our patient group. CONCLUSIONS: We conclude that repetitive apnoeas/hypopnoeas are very important factors in the development of both LV diastolic dysfunction and diastolic systemic hypertension in patients with OSA syndrome. Treatment with nCPAP leads to significant improvement in both ventricular function and systemic hypertension.     

Relation of extent of nocturnal blood pressure decrease to cardiovascular remodeling in never-treated patients with essential hypertension

The clinical significance of the extent of a decrease in nocturnal blood pressure (BP) and the resulting classification of hypertensives as "dipper" (decrease in BP >10% day BP) or "nondipper" (decrease in BP <10% day BP) has been questioned recently. The aim of our study was to evaluate if the extent of a nocturnal BP decrease, established on the basis of a single 24-hour BP monitoring, is related to cardiovascular remodeling in essential hypertension. We enrolled 253 never-treated essential hypertensives (24-hour BP > or = 140 and/or 90 mm Hg); for each patient we recorded 24-hour BP, left ventricular (LV) echocardiogram, Doppler transmitral flow velocities, and carotid-femoral pulse-wave velocities. A dipper BP profile was found in 161 patients, whereas 92 patients were nondippers. The 2 groups did not differ with regard to age, gender, body mass index, 24-hour and daytime BP, and 24-hour, daytime, and nighttime heart rate. All LV morphologic characteristics LV systolic and diastolic functional parameters, mitral Doppler-derived diastolic indexes, as well as carotid-femoral pulse-wave velocity, and aortic index distensibility were not significantly different between dippers and nondippers. The prevalence of LV hypertrophy and diastolic dysfunction was also similar between the 2 groups. The extent of a decrease in nocturnal BP did not correlate with any cardiovascular parameter. In conclusion, in never-treated hypertensives, the extent of a nocturnal BP decrease is not related to LV morpho-functional characteristics and aortic distensibility; therefore, the nondipping status established on the basis of a single 24-hour BP monitoring does not identify hypertensive patients with greater cardiovascular damage.     

Relation of insulin resistance and left ventricular function and structure in non-diabetic patients with essential hypertension

OBJECTIVE: Both left ventricular hypertrophy and insulin resistance (IR) have often been demonstrated in patients with essential hypertension (EH). Insulin may exert a direct growth-promoting effect on cardiomyocytes. The purpose of this study was to examine the relationship between left ventricular structure, function and IR in patients with EH. METHODS: We enrolled 73 patients (21 men, mean age 51.7 +/- 9.2 years) with untreated hypertension (BP > 140 and/or 90 mm Hg, fasting glycaemia < 110 mg/dl) and 64 healthy subjects without diabetes mellitus and hypertension (21 men, mean age 48.9 +/- 10.6 years) constituted the control group. In all subjects, transthoracic echocardiography was performed and blood samples were taken. Homeostasis model assessment (HOMA) was calculated by the formula: HOMA-index = fasting blood glucose (mg/dl) * immunoreactive insulin (microU/ml)/405 for the assessment of IR. Hypertensive patients were divided in two groups by mean HOMA index values. Each subject was examined for LV end-diastolic diameter, septal and posterior wall thickness, LV mass index (LVMI), fractional shortening (FS), mitral inflow velocity pattern, atrial filling fraction (AFF), left ventricular outflow velocity pattern and the total ejection isovolume index (TEI index). RESULTS: The HOMA index (p < 0.001), LVMI (p < 0.001), AFF (p < 0.0001), peak A velocity (p < 0.028), septal (p < 0.0001) and posterior (p < 0.0001) wall thickness were significantly higher and FS (p < 0.001), E/A ratio (p < 0.0001) were significantly lower in hypertensive patients than healthy controls. LVMI (p < 0.01) and septal wall thickness (p < 0.001) were significantly higher in those hypertensive patients with a higher HOMA index. The HOMA-index was univariately related to the TEI index (r = 0.27, p = 0.01) and septal wall thickness (IVS) (r = 0.29, p = 0.01) by Pearson correlation analysis in hypertensive patients. LVMI, FS and mitral inflow velocity pattern were not related to the HOMA index. The TEI index (R2 = 0.20, p = 0.0001) and IVS (R2 = 0.12, p = 0.002) were significantly related to the HOMA-index as an independent variable by stepwise regression analysis. CONCLUSIONS: These results demonstrated that hypertensive patients had both abnormal cardiac structure and function and higher IR index. In our study group, the effect of hypertension on cardiac structure and function was correlated with IR. Our results suggested that IR might be an important factor causing left ventricular dysfunction and wall thickness in non-diabetic patients with EH.     

Left ventricular apical rotation is related to ambulatory blood pressure and body mass in healthy elderly females

OBJECTIVE: The interaction between left ventricular (LV) apical rotation, blood pressure (BP) and body mass in elderly females may reveal mechanisms involved in the syndrome of diastolic heart failure. METHODS: Thirty-one healthy females, age 69-84 years, were studied with echocardiography, ambulatory BP and an exercise capacity (VO2peak) test. RESULTS: LV apical short-axis loops were eligible for speckle tracking analysis in 27 subjects. Peak apical rotation (PAR) correlated inversely with diastolic BP (r = -0.47, p = 0.01). PAR correlated positively with stroke volume and body weight (p<0.05), but not with VO2peak (n = 19, p = ns). PAR also correlated with peak rotation velocity in systole (r = 0.76, p<0.0001) and in diastole (r = 0.58, p = 0.001). Diastolic peak rotation velocity correlated with mitral E wave peak velocity (r = 0.48, p = 0.01). There was a significant reduction in LV volumes during the 4 years of follow-up. CONCLUSIONS: In healthy elderly females, there seems to be an interaction between LV apical rotation, BP and body mass. Peak apical rotation and peak diastolic rotation velocity correlate with indices of LV filling and ejection, indicating that suction, a crucial element for effective early LV filling, may be preserved in healthy elderly subjects. Suction deteriorates with elevations of the arterial BP. An age- and BP-related reduction in LV end-diastolic volume may represent an additional impediment to LV filling. Both features may contribute to the development of LV diastolic dysfunction and to episodes of diastolic heart failure.     

Relative wall thickness is an independent predictor of left ventricular systolic and diastolic dysfunctions in essential hypertension.

The objective of this study was to elucidate the relationship between left ventricular geometry and left ventricular (LV) function in patients with untreated essential hypertension. We evaluated LV systolic and diastolic functions by M-mode echocardiography in 24 normotensive control subjects (NC) and 129 patients with essential hypertension. Patients were divided into four groups according to the relative wall thickness and LV mass index: a normal left ventricle (n=57), a concentric remodeling (n=7), a concentric hypertrophy (n=31), and an eccentric hypertrophy (n=34) group. LV systolic function as measured by midwall fractional shortening (FS) was significantly decreased in both the concentric remodeling and concentric hypertrophy groups; no differences were observed for endocardial FS. LV diastolic function as measured by isovolumic relaxation time (IRT) was also decreased in both the concentric remodeling and concentric hypertrophy groups. In multivariate analysis, relative wall thickness (p<0.0001), end-systolic wall stress (p<0.0001), and systolic blood pressure (p=0.002) were independently associated (r2=0.72) with midwall FS in a model including age, LV mass index, body mass index, diastolic blood pressure and IRT. In addition, relative wall thickness (p=0.0008) and age (p<0.0001) were independently associated (r2=0.31) with IRT in a model including LV mass index, end-systolic wall stress, body mass index, systolic and diastolic blood pressures and midwall FS. We conclude that LV geometry as evaluated by relative wall thickness may provide a further independent stratification of LV systolic and diastolic functions in essential hypertension.     

Alterations in left ventricular structure and function in young healthy obese women: assessment by echocardiography and tissue Doppler imaging

OBJECTIVES: This study was designed to determine the effects of obesity on left ventricular (LV) structure and function in young obese women. BACKGROUND: Severe prolonged obesity in older adults results in increased plasma volume, eccentric LV hypertrophy, and systolic and diastolic dysfunction. Obese women are at increased risk for the development of heart failure. However, the effects of the obesity on cardiac structure and function in young, otherwise-healthy women are controversial. METHODS: Fifty-one women were evaluated: 20 were obese (body mass index [BMI] > or =30 kg/m(2)) and 31 were non-obese (BMI <30 kg/m(2)). Left ventricular structure and systolic and diastolic function were assessed by two-dimensional echocardiography and tissue Doppler imaging, including the load-independent systolic myocardial velocity (Sm global) and early diastolic myocardial velocity (Em global), respectively. The effects of BMI on LV structure and function were assessed using multivariate regression analyses. RESULTS: Obese women had higher end-diastolic septal and posterior wall thickness, LV mass, and relative wall thickness than non-obese women; BMI values showed significant correlations with these variables (r = 0.58, p < 0.0001; r = 0.50, p < 0.0002; r = 0.52, p < 0.0001, and r = 0.40, p < 0.005, respectively). The Sm global and Em global were lower in obese women, suggesting systolic and diastolic function are decreased; both were negatively correlated with BMI (r = -0.43, p <. 002 and r = -0.61, p < 0.0001, respectively). Multivariate analysis showed BMI was the only independent predictor of relative wall thickness, Sm global, and Em global. CONCLUSIONS: Obesity in young otherwise-healthy women is associated with concentric LV remodeling and decreased systolic and diastolic function. These early abnormalities in LV structure and function may have important implications for explaining the myocardial dysfunction that is associated with increased cardiovascular morbidity and mortality caused by obesity.     

Morning rise, morning surge and daytime variability of blood pressure and cardiovascular target organ damage. A cross-sectional study in 743 subjects.

OBJECTIVE: To evaluate in a large population the relationship between cardiovascular target organ damage and values of the night-to-morning rise of systolic blood pressure (MR-BP), the morning surge of BP at the moment of rising (BP surge) and daytime BP variability (standard deviation [SD] of daytime BP). METHODS: This was a cross-sectional study, evaluating 743 subjects, aged 30-75 years, 416 female, with normal renal function and no previous cardiovascular events. The population included: I-174 patients with type 2 diabetes, II-317 hypertensive patients with ongoing treatment over at least the previous 6 months, III-127 hypertensive patients untreated in the last 6 months, IV-125 healthy normotensive subjects. All underwent 24-hour ambulatory BP monitoring to calculate MR-BP, BP surge and SD of daytime BP. Target organ evaluation included: pulse wave velocity (PWV) (an indicator of aortic stiffness) in 711 subjects, left ventricular mass index (LVMI) in 185 subjects and 24-hour albuminuria in 239 subjects. RESULTS: In the population as a whole, BP surge, MR-BP and SD of daytime BP correlated significantly with PWV (r = 0.434, p < 0.0001; r = 0.126, p < 0.001; 0.337, p < 0.001, respectively), with LVMI (r = 0.447, p < 0.0001; r = 0.307, p < 0.001; 0.162, p < 0.05, respectively) and to a lesser degree with albuminuria (r = 0.126, p < 0.05; r = 0.083, NS; 0.082, NS, respectively). In the upper quintile of distribution of BP surge, the percentage of cases with abnormal PWV (>12 m/s) (21%), cardiac hypertrophy (53 %) and microalbuminuria (47 %) was significantly greater (p < 0.03) than that observed in the lower quintile (1%, 14% and 27%, respectively). BP surge correlated more strongly with indices of target organ damage than did MR-BP or SD of daytime BP, independently of night-time BP and nocturnal BP fall. CONCLUSIONS: In this large population, MR-BP, BP surge and daytime BP variability are strongly correlated with target organ damage severity, and are probably related to organ deterioration. Of the three, morning surge of BP at the moment of rising is more strongly related to organ damage than MR-BP, perhaps because unlike MR-BP, BP surge is independent of night-time BP values.     

Effects of dual blockade of Renin-Angiotensin system on concentric left ventricular hypertrophy in essential hypertension: a randomized, controlled pilot study

BACKGROUND: The renin-angiotensin system (RAS) plays a major role in promoting left ventricular (LV) remodeling in essential hypertension. We designed a controlled, randomized pilot study aimed to test the hypothesis that the dual RAS blockade with angiotensin-converting enzyme (ACE) inhibitor (ACEi) + angiotensin II receptor blocker (ARB) can be more effective in decreasing LV hypertrophy and improving diastolic function than a largely employed association such as ACEi + calcium-antagonist (Ca-A). METHODS: Twenty-four never-treated hypertensive patients with LV concentric hypertrophy were randomized to ramipril + candesartan or ramipril + lercanidipine. Before and after the 6-month treatment they underwent a 24-h blood pressure (BP) monitoring and echocardiographic examination. RESULTS: At baseline, age, body mass index (BMI), 24-h BP, and LV morpho-functional parameters were similar between the two groups. The 6-month treatment induced in both groups a significant decrease of 24-h BP, septal and posterior wall thickness, and LV mass index (LVMi) (ACEi + ARB 155 +/- 19 to 122 +/- 17 g/m(2), P < 0.0001; ACEi + Ca-A 146 +/- 18 to 127 +/- 20 g/m(2), P < 0.0001). Systolic function remained unchanged; LV diastolic parameters increased significantly in both groups. The extent of 24-h BP decrease was similar between the two groups (-13.3/16.3% vs. -12.3/15.8%, P = 0.63/P = 0.71), whereas the decrease of LV mass (-22% vs. -12.8%, P < 0.005) and the improvement of diastolic function were greater in ACEi + ARB group. CONCLUSIONS: In comparison with ACEi + Ca-A, ACEi + ARB treatment showed a greater antiremodeling effect, that can be reasonably ascribed to a BP-independent effect of the dual RAS blockade.     

Nurse-recorded clinic and ambulatory blood pressures correlate equally well with left ventricular mass and carotid intima-media thickness

OBJECTIVE: To assess relationships between noninvasive ambulatory blood pressure (BP), clinic BP (mean value of three readings in the seated position measured by nurses), structural cardiac indices, intima-media thickness of the common carotid artery and several hormones. DESIGN: Cross-sectional study of 75 subjects with hypertension and left ventricular hypertrophy (HTH) according to echocardiography, 35 subjects with hypertension and normal left ventricular dimensions (HT) and 23 normotensive subjects (NT). RESULTS: We found an excellent correlation between mean 24-h ambulatory BP and clinic BP, the r-value for systolic BP being 0.82 and for diastolic levels 0.78 (both P < 0.0001). Clinic and ambulatory BP correlated equally well with left ventricular (LV) mass index (r-values between 0.55 and 0.64, all P < 0.0001) and to intima-media thickness of the carotid artery (r = 0.18-0.34, P < 0.01). The systolic white-coat effect (clinic BP - day-time BP) was higher in the HTH and HT compared with NT and was weakly correlated to LV mass index (r = 0.18, P = 0.04). Nondippers (mean arterial night/day BP ratio of > 0.9) had higher brain (6.1 +/- 7.5 pmol L(-1) vs. 3.7 +/- 3.2 pmol L(-1), P = 0.01) and atrial (14 +/- 3.4 pmol L(-1) vs. 9.3 +/- 5.4 pmol L(-1), P = 0.04) natriuretic peptide levels, and also exhibited a lower ejection fraction (49 +/- 8% vs. 57 +/- 9%, P = 0.006), than dippers. CONCLUSION: Clinic BP recordings performed by nurses as three measurements 1 min apart provide excellent relationship to target organ damage. Nondippers exhibited signs of a more advanced hypertensive organ damage than dippers which corresponds well with the poor prognosis linked to this condition.     

Indapamide retard and enalapril in patients with arterial hypertension: hypotensive effectiveness and effect on endothelial function

AIM: To find out what type of therapy was better for restoration of 24 hour blood pressure (BP) rhythm and impaired function of vascular endothelium, and to determine preferential therapy for patients with severe endothelial dysfunction. METHODS: We performed ambulatory blood pressure monitoring and assessments of endothelial dependent (flow mediated-FM) and endothelial independent (nitroglycerine) dilatation of forearm artery (DFA) in patients with stage I-III essential hypertension. In a randomized comparative cross-over study 76 patients (mean age 49.2 +/- 6.2 years) received indapamide retard 1.5 mg and enalapril 20 mg for 24 weeks. RESULTS: Hypotensive effect of both drugs was identical (indapamide lowered systolic/diastolic BP by 13.6/12.0% and 12.9/9.9%, enalapril lowered BP by 14/14.6% and 13.2/12.9%). BP rhythm was better transformed by treatment with indapamide: nocturnal fall of mean BP increased on indapamide from 8.1 +/- 6.9% at baseline to 12.8 +/- 5.0% after treatment, p=0.007, and on enalapril from 11.8 +/- 7.9% at baseline to 10.4 +/- 6.2% after treatment, p=0.2. Indapamide and enalapril significantly augmented FM DFA (from 4.7 +/- 2.8% to 9.03 +/- 3.47%, p < 0.001, and from 4.6 +/- 2.2% to 10.9 +/- 3.5%, p < 0.001, respectively). All patients were divided into 2 groups: with baseline FM DFA - 2.5% (group I, n=59) and < 2.5% (group II, n=16). In group II indapamide lowered BP more effectively than enalapril ( - 10.2/ - 9.1% and - 5.5/ - 5.2%, p < 0,01/0.01, respectively). CONCLUSION: Both indapamide retard 1.5 mg and enalapril 20 mg exerted normalizing action on endothelium dependent DFA. However indapamide transformed 24 hour BP profile better than enalapril. Hypotensive therapy with indapamide was more effective than therapy with enalapril in patients with more pronouncedly disturbed FM arterial vasodilatation. This can be used in selection of a preparation in patients with impaired FM vasodilatation.     

Effects of surgical septal myectomy on left ventricular wall thickness and diastolic filling

This study was conducted to examine the late effects of surgical myectomy on left ventricular (LV) structure and diastolic function in patients with obstructive hypertrophic cardiomyopathy. Patients with hypertrophic cardiomyopathy who had complete echocardiographic studies before and > or =6 months after myectomy were included in this retrospective analysis of cavity dimension, septal and LV posterior wall thicknesses, and Doppler flow variables. Compared with preoperative measurement, mean septal thickness (23.6 vs 19.5 mm, p <0.001) and LV posterior wall thickness (14.2 vs 12.4 mm, p <0.001) were smaller after myectomy. Likewise, mitral inflow Doppler velocity curves indicated improvement in LV filling, with decreased mitral E velocity (0.95 to 0.87 m/s, p = 0.008). In conclusion, the long-term benefits of this operation may be mediated in part by favorable LV remodeling and changes in LV diastolic filling.