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.     

Selective reduction of cardiac mass and central blood pressure on low-dose combination perindopril/indapamide in hypertensive subjects

OBJECTIVE: In hypertension, blockade of the renin-angiotensin system reduces left ventricular mass (LVM) independently of brachial systolic (S), diastolic (D), and mean (M) blood pressure (BP). From central to peripheral arteries, MBP and DBP are practically unchanged, whereas SBP and pulse pressure (PP) increase significantly. The objective was to determine whether changes in LVM under drug treatment was preferentially associated with changes in central or brachial SBP and PP. DESIGN: A substudy of 146 subjects was selected from 469 hypertensive patients submitted to a double-blind randomized trial comparing the combination of perindopril (2 mg; Per) and indapamide (0.625 mg; Ind) with atenolol (50 mg, one tablet per day). MAIN OUTCOME MEASURES: Before and after 1 year of treatment: LVM (echocardiography) in 146 subjects and, in 52 of them, central (carotid) BP and timing of wave reflections (tonometry). RESULTS: LVM changes were significantly associated with antihypertensive treatment, with lower LVM with Per/Ind than with atenolol. Changes in SBP and PP, but not in MBP and DBP, were more significantly associated with Per/Ind than with atenolol, with more pronounced effects using central than brachial measurements, and a longer delay in central return of wave reflections under Per/Ind. In the sampling of 52 patients with tonometry, the change in LVM between the two drug regimens was significantly linked to central, but not brachial, PP change. CONCLUSIONS: This observational study shows a lower LVM under Per/Ind than under atenolol. The greater change in LVM on Per/Ind was linked to central and not brachial blood pressure.     

C-reactive protein elevation predicts pulse pressure reduction in hypertensive subjects

Cross-sectional studies have shown a positive association between increased pulse pressure (PP) and an increased likelihood of a C-reactive protein (CRP) level >3 mg/L. In a retrospective subgroup analysis of the hypertensive subjects of the multicenter double-blind study, REASON (PREterax in Regression of Arterial Stiffness in a ContrOlled Double-BliNd), in which fixed first-line antihypertensive combination therapy with an angiotensin converting enzyme (ACE) inhibitor, perindopril (2 mg), and a diuretic, indapamide (0.625 mg), proved significantly more effective than atenolol in normalizing PP, we sought to determine whether perindopril plus indapamide was also more effective than atenolol in lowering CRP levels and, if so, whether this effect correlated with a preferential reduction in PP. At the final visit (12 months) in the 269 patients studied, the decrease in PP was greater, and the proportion of patients with CRP >3 mg/L lower (17.9% versus 28. 9%, P=0.03; adjusted odds ratio, 1.02 to 4.08, P=0.01), in the perindopril plus indapamide group than in the atenolol group. After adjustment for confounders, patients with a baseline CRP >3 mg/L displaying the greatest decrease in PP were more likely (P=0.04) to have a CRP < or =3 mg/L at 12 months. No such relationship was found with systolic or diastolic blood pressure. Perindopril-indapamide combination therapy is more effective than beta-blockade in lowering elevated CRP in hypertensive subjects. This effect is significantly associated with a more effective PP reduction in patients with baseline CRP >3 mg/L.     

Effect of fixed low dose combination of perindopril and indapamide on processes of cardiovascular remodeling in previously untreated patients with hypertension

AIM: To assess changes of blood pressure (BP) and processes of cardiovascular remodeling during treatment of previously untreated patients with hypertension with fixed low dose combination of perindopril and indapamide. MATERIAL: Patients with untreated hypertension (n=30, mean age 46.7+/-1.8 years, 16 men, 14 women) received low-dose perindopril (2 mg) - indapamide (0.625 mg) combination for 6 months. METHODS: Twenty four-hour BP monitoring, measurement of left ventricular (LV) mass index and wall and interventricular septal thickness, carotid artery intima-media thickness, pulse wave velocity and cerebral blood flow velocity. RESULTS: Target BP level was reached in 83.3% of patients. BP monitoring revealed significant lowering of daytime and nocturnal systolic BP (-13.2%, p<0.0001 and -14.5%, p<0.0001, respectively), daytime and nocturnal diastolic BP (- 14.3%, p<0.0001 and -15.3%, p<0.0001, respectively). Significant reduction of LV mass index (-12%, p=0.0002) was also observed. Both LV posterior wall and interventricular septal thicknesses were reduced as well (-5.1%, p<0,01). This was accompanied by decreases of intima-media thickness of right and left carotid arteries (-5,4%, p=0.04 and -5,3%, p=0.01, respectively), reduction of stiffness of elastic arteries (carotid-femoral pulse wave velocity decreased by 8%, p=0.003), and increase of cerebral blood flow velocity. CONCLUSION: The use of perindopril/indapamide combination in hypertensive patients was associated BP lowering and positive effects on remodeling both of the heart and large and medium arteries.     

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.     

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.     

Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol

OBJECTIVES: The goal of this study was to determine if a low-dose combination of the angiotensin-converting enzyme inhibitor perindopril (Per) and the diuretic indapamide (Ind) reduces central (thoracic aorta, carotid artery) as well as brachial systolic blood pressure (SBP) more than the beta-blocker atenolol and to determine the hemodynamic factors influencing independently brachial and central SBP: pulse wave velocity (PWV) and pattern of wave reflections. BACKGROUND: In high cardiovascular risk populations, angiotensin blockade improves survival without affecting brachial SBP and diastolic blood pressure (DBP). Whether central SBP, which is physiologically lower than brachial SBP, is significantly reduced has never been investigated. METHODS: This study was a double-blind randomized trial for one year in patients with essential hypertension. RESULTS: For a similar DBP reduction, Per/Ind decreased SBP significantly more than atenolol, with a more pronounced reduction for central than for brachial SBP. After one year, the difference between brachial and central SBP was maintained by Per/Ind (8.28 +/- 1.53 mm Hg) and significantly attenuated by atenolol (0.29 +/- 1.61 mm Hg). Under atenolol, the principal factor modulating SBP reduction was mean blood pressure. Under Per/Ind, this parameter played a minor role, and the central SBP reduction implied a major role for disturbed PWV and wave reflections. CONCLUSIONS: Under Per/Ind, but not atenolol, normalization of brachial SBP is achieved with a significantly greater reduction of central SBP. This hemodynamic profile reflects changes of wave reflections issued from distal arterial and arteriolar territory, where Per/Ind, but not atenolol, is known to improve vessel wall structure.     

Left ventricular hypertrophy in patients with autonomic failure

BACKGROUND: In autonomic failure (AF), supine hypertension may predispose patients to end-organ damage. The pathophysiology of hypertensive heart disease in AF is not known. The aim of the present study was to evaluate the prevalence and predisposing factors of left ventricular hypertrophy (LVH) in patients with AF. METHODS: We studied 25 patients with AF (67 +/- 8 years); 80% were being treated for orthostatic hypotension. Twenty patients with essential hypertension (68 +/- 6 years) were considered as the control group. All subjects underwent echocardiography for measurement of left ventricular mass (LVM). The patients with AF underwent a 24-h BP monitoring and long-term blood pressure (BP) variability was calculated as standard deviation (SD) of the average of the half-hour mean values. RESULTS: The LVM is comparable in patients with AF and hypertensive controls (145 +/- 35 g/m2 v 127 +/- 32 g/m2, P = .07). The proportion of patients with LVH is similar in both populations (AF 80%, hypertensive 70%). The patients with AF were divided into two groups, with and without LVH. The SDs are significantly higher in AF patients with LVH than in those with normal LVM (SD 24-h systolic BP: 22 +/- 4 v 14 +/- 1 mm Hg, P = .001). CONCLUSIONS: A high proportion of patients with AF show LVH. The LVM values are comparable with those of patients with essential hypertension. The development of LVH seems to depend on high BP variability, characteristic of AF patients. Detection of LVH may help in the choice of treatment for orthostatic hypotension and in the prevention of heart failure.     

Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: a comparison with atenolol

International guidelines recommend that antihypertensive drug therapy should normalize not only diastolic (DBP) but also systolic blood pressure (SBP). Therapeutic trials based on cardiovascular mortality have recently shown that SBP reduction requires normalization of both large artery stiffness and wave reflections. The aim of the present study was to compare the antihypertensive effects of the very-low-dose combination indapamide (0.625 mg) and perindopril (2 mg) (Per/Ind) with the beta-blocking agent atenolol (50 mg) to determine whether Per/Ind decreases SBP and pulse pressure (PP) more than does atenolol and, if so, whether this decrease is predominantly due to reduction of aortic pulse wave velocity (PWV) (automatic measurements) and reduction of wave reflections (pulse wave analysis, applanation tonometry). In a double-blind randomized study, 471 patients with essential hypertension were followed for 12 months. For the same DBP reduction, Per/Ind decreased brachial SBP (-6.02 mm Hg; 95% confidence interval, -8.90 to -3.14) and PP (-5.57; 95% confidence interval, -7.70 to -3.44) significantly more than did atenolol. This difference was significantly more pronounced for the carotid artery than for the brachial artery. Whereas the 2 antihypertensive agents decreased PWV to a similar degree, only Per/Ind significantly attenuated carotid wave reflections, resulting in a selective decrease in SBP and PP. The very-low-dose combination Per/Ind normalizes SBP, PP, and arterial function to a significantly larger extent than does atenolol, a hemodynamic profile that is known to improve survival in hypertensive populations with high cardiovascular risk.     

Short-term effects of rilmenidine on left ventricular hypertrophy and systolic and diastolic function in patients with essential hypertension: comparison with an angiotensin converting enzyme inhibitor and a calcium antagonist

The short-term (three months) effects of rilmenidine on systemic hypertension induced left ventricular hypertrophy (LVH) and left ventricular systolic and diastolic functions in comparison with those of perindopril and nifedipine-slow release (SR) formulation were studied. The short-term effects of rilmenidine on biochemical parameters and lipid profiles were evaluated. Sixty patients (39 men, 21 women) with a mean age of 59 +/- 14 years and with mild to moderate systemic arterial hypertension were enrolled in three groups. The first group received 1 mg/day of rilmenidine, the second group 4 mg/day of perindopril, and the third group 20 mg/day of nifedipine SR. All drugs induced a similar decrease in systolic and diastolic blood pressure (BP) values. Left ventricular mass (LVM) and LVM index decreased equally in all groups associated with a significant increase in the E/A ratio. The ratio between the reduction in LVM and decrease in mean arterial pressure (LVM/mmHg) was higher in groups 1 and 2. Negative correlations between LVM and LVMI. E/A, and the dv/dt ratio were obtained. Rilmenidine did not change the blood chemistry and lipid profile values. Despite its neutral effect on lipid profile and biochemical parameters. rilmenidine is as effective as perindopril and nifedipine in controlling hypertension and decreasing left ventricular hypertrophy.     

Indapamide SR versus candesartan and amlodipine in hypertension: the X-CELLENT Study

BACKGROUND: Reducing systolic blood pressure (BP) is of major benefit to patients with isolated systolic hypertension, but lowering normal diastolic BP may be harmful in terms of cardiovascular risk. Effects of different drugs on systolic BP, diastolic BP, and pulse pressure are therefore of interest. METHODS: The NatriliX SR versus CandEsartan and amLodipine in the reduction of systoLic blood prEssure in hyperteNsive patienTs study (X-CELLENT) was a randomized, double-blind, placebo-controlled study comparing the effects of three drugs on these BP components. Patients with systolic-diastolic or isolated systolic hypertension (n = 1758) received indapamide (1.5 mg) sustained release (SR), candesartan (8 mg), amlodipine (5 mg), or placebo once daily for 12 weeks. RESULTS: Compared to placebo all active treatments reduced all BP components significantly (P < .001). For the patients with isolated systolic hypertension (n = 388), the three treatments significantly reduced systolic BP, but only indapamide SR did not change diastolic BP and thus reduced pulse pressure significantly relative to placebo (P = .005). In an ancillary study using ambulatory BP monitoring (n = 576), all three treatments significantly reduced BP components during 24 h relative to placebo. Changes in systolic BP and pulse pressure were similar with the three treatments, but the reduction in diastolic BP was significantly smaller, and therefore more favorable, with indapamide SR compared with candesartan (P = .039). In patients with isolated systolic hypertension (n = 106), indapamide SR reduced 24-h systolic BP significantly more than amlodipine (P = .037), and only indapamide SR reduced 24-h pulse pressure significantly relative to placebo (P = .03). All three drugs were well tolerated. CONCLUSIONS: This distinctive BP-lowering profile of indapamide SR seems highly beneficial when compared to the either of candesartan or amlodipine.     

Indices of pulse wave analysis are better predictors of left ventricular mass reduction than cuff pressure

BACKGROUND: Studies have required large numbers of patients to associate regression of left ventricular (LV) mass with a decrease in brachial cuff blood pressure (BP) in the treatment of hypertension. Hence, we prospectively examined potential superiority of pulse wave analysis over conventional BP measurement in predicting treatment-induced LV mass reduction. METHODS: Forty-six untreated patients (mean age, 56 +/- 7 years) with hypertension received standard medical treatment based on international guidelines. Echocardiography and measurements of various LV load indices were made before and after 1 year of treatment. RESULTS: Antihypertensive treatment significantly (P < .05) reduced LV load, manifest by a decrease in measured brachial BP, estimated aortic BP, carotid-femoral pulse wave velocity (PWV(cf)), aortic augmentation index (AI(a)), aortic augmented pressure (AugP), and radial augmentation index (AI(r)). These changes were accompanied by significant reduction in LV mass index (LVMI) and improvements in systolic ejection fraction and diastolic early-to-atrial ratio of transmitral flow velocities. The treatment-induced LVMI change was not correlated with changes in brachial BP or PWV(cf), but was closely correlated with factors influenced by wave reflection - changes in AI(a), AI(r), AugP, and aorta-to-arm pulse pressure amplification. On multivariate analysis, AI(a) change was the strongest determinant of LVMI change, independent of brachial BP and PWV(cf) changes (beta = 0.51, P < .001). Estimated subject numbers required for predicting a significant LVMI reduction were far less when wave reflection-related factors were used rather than conventional bracial BP. CONCLUSIONS: These results suggest that reduction in wave reflection is an important therapeutic strategy for reducing LV mass, which can be predicted with modest subject numbers.     

A new dimension in hypertension management with the amlodipine/perindopril combination

Recent guidelines are consistent in acknowledging that most hypertensive patients need at least two drugs for optimal blood pressure (BP) control. Trial data are available to support the use of a renin-angiotensin system (RAS) blocker (ie, an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker), plus a diuretic, a RAS blocker plus a calcium channel blocker (CCB), and a CCB plus a diuretic. The ACCOMPLISH trial demonstrated somewhat convincingly that an ACE inhibitor/CCB is superior to the same ACE inhibitor plus a thiazide. In the ASCOT trial, amlodipine/perindopril was superior to beta-blocker/thiazide in its effects on all major cardiovascular outcomes and new-onset diabetes. Further substudies of ASCOT provided plausible explanations for the benefits of amlodipine/perindopril strategy. In the CAFE substudy, amlodipine/perindopril was significantly more effective in the reduction of central BP as compared to atenolol/bendroflumethiazide, despite similar brachial BP reduction. More recently, analysis of long-term BP variability provided a further explanation for the reduction of cardiovascular events with amlodipine/perindopril in ASCOT. Thus, the combination of perindopril and amlodipine seems an ideal logical evidence-based pair of antihypertensive agents to select.     

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.     

Enhanced radial late systolic pressure augmentation in hypertensive patients with left ventricular hypertrophy

BACKGROUND: Wave reflection augments central blood pressure (BP) in late systole, thus increasing cardiac afterload. We examined the relationship between late systolic pressure augmentation in the peripheral radial artery pulse wave and the existence of left ventricular hypertrophy (LVH) in hypertension. METHODS: Brachial BP, radial augmentation index (AI(r)), and carotid-femoral pulse wave velocity (PWV(cf)) were determined in 77 untreated hypertensive patients aged 56 +/- 10 years. Cardiac structure and function were assessed by ultrasound, and LVH was defined based on the LV mass index (LVMI). Using multivariate analysis, patient characteristics were compared between those with (+) and without (-) LVH. RESULTS: The LVMI was correlated independently and positively with AI(r) (beta = 0.33, P = .004) and the brachial mean arterial pressure (MAP; beta = 0.25, P = .03). The ratio of early to atrial peak velocities (E/A ratio) of the diastolic transmitral flow tended to be correlated negatively with the AI(r). The LVH (+) group had a significantly higher AI(r) than the LVH (-) group [LVH (+), 97% v LVH (-), 89%, P = .003]; this difference remained significant even after adjustment for age, gender, MAP, and heart rate. The adjusted relative risk of LVH was 1.99 for each 10% AI(r) increase (P = .005). In contrast, LVMI was not correlated with the PWV(cf), and the PWV(cf) was not different between the LVH (+) and LVH (-) groups. Moreover, there was no significant correlation between PWV(cf) and AI(r). CONCLUSIONS: These results suggest that the peripheral AI(r) measurement is clinically useful in predicting LVH. Enhanced wave reflection may be related to the development of LVH in hypertensive patients.     

Pulse wave velocity as endpoint in large-scale intervention trial. The Complior study. Scientific, Quality Control, Coordination and Investigation Committees of the Complior Study

OBJECTIVE: To evaluate the ability of an antihypertensive therapy to improve arterial stiffness as assessed by aortic pulse wave velocity (PWV) in a large population of hypertensive patients. SETTING: Sixty-nine healthcare centres, private and institutional (19 countries). PATIENTS: Subjects aged 18-79 years, with essential hypertension. A total of 2,187 patients were enrolled; 1,703 (52% male) completed the study: mean age = 50 +/- 12 years; mean baseline systolic/diastolic blood pressure (S/D BP) = 158 +/- 15/98 +/- 7 mmHg; mean baseline carotid-femoral PWV = 11.6 +/- 2.4 m/s. INTERVENTIONS: Patients were treated for 6 months, starting with perindopril (angiotensin converting enzyme (ACE) inhibitor) 4 mg once daily (OD), increased to 8 mg OD, and combined to diuretic (indapamide 2.5 mg OD) if BP was uncontrolled (> 140/90 mmHg). RESULTS: It was feasible to measure carotid-femoral PWV using the automatic device Complior at inclusion, 2 and 6 months, along with conventional BP assessments in a population of 1,703 patients. Significant decreases (P < 0.001) in BP (systolic: -23.7 +/- 16.8, diastolic: -14.6 +/- 10 mmHg), and carotid-femoral PWV (-1.1 +/- 1.4 m/s) were obtained at 2 and 6 months. CONCLUSIONS: The Complior Study is the first study to show the feasibility of a large-scale intervention trial using PWV as the endpoint in hypertensive patients. Adequate results may be obtained using an automatic device and rigorous criteria for assessment. A long-term controlled intervention study is needed to confirm the results of the present uncontrolled trial.     

Nurse-recorded and ambulatory blood pressure predicts treatment-induced reduction of left ventricular hypertrophy equally well in hypertension: results from the Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA) study

OBJECTIVE : To compare the relationships of treatment-induced reductions of left ventricular hypertrophy to the changes in clinic and ambulatory blood pressure (BP). DESIGN : Double-blind and randomized treatment with irbesartan or atenolol for 48 weeks. PATIENTS : Patients with hypertension and left ventricular hypertrophy (n = 66) with a seated diastolic BP 90-115 mmHg (average of three measurements one minute apart by nurses). MAIN OUTCOME MEASURES : Registrations of echocardiographic left ventricular (LV) mass. Clinic and ambulatory BP. RESULTS : In the total material, nurse-measured BP was reduced by 23 +/- 15/16 +/- 7.7 mmHg and 24-h ambulatory BP fell 20 +/- 15/14 +/- 8.5 mmHg by treatment. The correlation between the change in nurse-measured BP and LV mass index (LVMI) induced by treatment was r = 0.35, P = 0.004 for systolic BP and r = 0.26, P = 0.03 for diastolic BP. Corresponding values for 24-h ambulatory BP were r = 0.29, P = 0.02 and r = 0.35, P = 0.004, respectively, with similar correlations for day- and night-time ambulatory BP. The nurse-recorded BP was slightly higher than ambulatory BP (systolic clinic - systolic 24-h ambulatory BP = 5 mmHg). Using 130/80 mmHg as a cut-off value for normal 24-h ambulatory BP, eight subjects had normal diastolic or systolic ambulatory BP, or both. Interestingly, these patients also experienced LVMI regression following treatment (low/normal ABP, -13 +/- 21 g/m2; remaining patients, -18 +/- 22 g/m2, P > 0.5). CONCLUSIONS : In patients with hypertension and left ventricular hypertrophy, ambulatory BP is not superior to carefully standardized nurse-recorded seated BP in terms of associations with treatment-induced changes in LV mass.     

Relationship between left ventricular mass and noninvasive monitoring of blood pressure

We studied the relationship between left ventricular mass index (LVMI) and blood pressure (BP) monitored during 24 hours in 35 normotensive and 58 hypertensive patients with no treatment for more than three months. We found a close correlation between LVMI and the average daytime systolic BP (r = 0.68). Other parameters derived from BP monitoring were also correlated with LVMI: daytime diastolic BP (0.54), nighttime systolic and diastolic BP (0.61 and 0.54), pulse pressure (0.58), the average of the five highest systolic and diastolic BP (0.57 both), and the percentage of systolic BP above 140 mm Hg (r = 0.64). However, in a stepwise multiple regression analysis only daytime systolic BP was independently correlated to LVMI. The standard deviation of systolic BP was not significantly correlated to LVMI. The same positive correlation between daytime systolic BP and LVMI was found in normotensive and hypertensive patients, males and females, and patients with and without left ventricular hypertrophy. So, at least regarding the prediction of the degree of left ventricular hypertrophy, the average systolic BP during daytime seems to be the only valuable parameter to look at in ambulatory BP monitorings of untreated hypertensive patients.     

培哚普利及美托洛尔对中心动脉压的作用

目的比较培哚普利和美托洛尔对轻中度高血压病患者中心动脉压与肱动脉压的影响。方法在冠状动脉造影结束后,分别同步测量145例高血压病或(和)冠心病患者升主动脉根部(直接测量法)和肱动脉(袖带加压法)的血压,其中单药降压治疗二周以上的轻中度高血压病患者分为培哚普利组(4mg/d,62例)、美托洛尔组(25mg/d,39例)。结果升主动脉收缩压高于袖带加压法测量的肱动脉收缩压9.6mmHg(P<0.01),升主动脉舒张压低于袖带加压法肱动脉舒张压2.0mmHg(P<0.01),升主动脉脉压较肱动脉脉压大11.6mmHg(P<0.01)。虽然培哚普利组和美托洛尔组袖带加压法测得的肱动脉压相同,但是培哚普利组的升主动脉收缩压低于美托洛尔组(P<0.05)。结论升主动脉压与袖带加压法测得的肱动脉压差异有非常显著意义。虽然培哚普利和美托洛尔降低肱动脉压效果相似,但培哚普利降低升主动脉收缩压较美托洛尔更显著。     

Pulse pressure is the best predictor of future left ventricular mass and change in left ventricular mass: 10 years of follow-up.

BACKGROUND : Ambulatory blood pressure correlates more closely with left ventricular mass (LVM) than casual blood pressure in cross-sectional studies, but prospective evidence is very limited. OBJECTIVE : To evaluate the best predictors of LVM and change in LVM during 10 years of follow-up, in a prospective study. METHODS : At baseline, blood pressure was recorded by casual measurements and 24 h intra-arterial ambulatory monitoring. The study participants were 97 healthy, untreated, 35-45-year-old men (34 normotensive, 29 borderline hypertensive, and 34 mildly hypertensive). At 10-year follow-up, echocardiography was performed in 86 (89%) of the men; echocardiographic data were available both at baseline and at follow-up from 70 (72%) of them. Individuals who were not receiving antihypertensive medication (n = 66) were included in the prediction of LVM index (LVMI), which was analysed as a continuous variable. RESULTS : The blood pressure variables that were best in predicting the LVMI were: 24 h pulse pressure (r = 0.308, P = 0.012), night-time pulse pressure (r = 0.291, P = 0.018), daytime pulse pressure (r = 0.253, P = 0.041), and casual systolic blood pressure (r = 0.212, P = 0.088). The LVMI was best predicted by a model including 24 h pulse pressure, positive family history of hypertension, body mass index, and age (adjusted coefficients of determination (adj.R2) = 0.197; that for the casual blood pressure model was adj.R2 = 0.140). During the follow-up, LVMI increased by +7.5 g/m2 and +23 g/m2 in individuals receiving and not receiving antihypertensive medication, respectively (P = 0.015). The change in LVMI was best predicted by the change in casual pulse pressure and use of antihypertensive medication (adj.R2 = 0.102). CONCLUSIONS : Ambulatory blood pressure improved the prediction of future LVMI compared with that obtained from casual measurements. To our knowledge, this is the longest prospective follow-up to show that pulse pressure is the most significant blood pressure parameter in predicting future LVMI and change in LVMI.