Biomedical subjects

Yves Lacourcière

Publications and source records attributed to Yves Lacourcière.

At least 19 recordsLinked to original sources

PubMed2006

A multicenter, 14-week study of telmisartan and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure monitoring.

BACKGROUND: Blood pressure (BP) has a circadian pattern with a morning surge that is associated with an increased risk of acute coronary and cerebrovascular events. In a prospective, randomized, open-label, blinded-endpoint, parallel-group, multicenter, forced-titration study of telmisartan and ramipril, the efficacy of both drugs on mean ambulatory diastolic BP (DBP) and systolic BP (SBP) during the last 6 h of a 24-h dosing interval was evaluated. METHODS: After screening and a single-blind run-in phase, 812 adults with mild-to-moderate hypertension (defined as a mean seated DBP > or =95 mm Hg and < or =109 mm Hg and a 24-h ABPM mean DBP 7 > or = 85 mm Hg) were randomized to the open-label, 14-week, forced-titration, active-treatment phase as follows: telmisartan 40 mg/80 mg/80 mg (n = 405) or ramipril 2.5 mg/5 mg/10 mg (n = 407), once daily in the morning. The primary efficacy variable was change from baseline in the last 6-h mean DBP and SBP at 8 and 14 weeks as assessed by ambulatory BP monitoring (ABPM). Secondary efficacy variables were changes from baseline in BP control during each of the 24-h periods and in-clinic trough cuff BP. RESULTS: Telmisartan 80 mg was superior to ramipril 5 mg and 10 mg in change from baseline in the last 6-h ABPM mean DBP and SBP at both 8 and 14 weeks (both P < .0001), respectively. At 14 weeks, the adjusted mean change from baseline in DBP for telmisartan 80 mg was -8.8 mm Hg compared with that for ramipril 10 mg of -5.4 mm Hg (P < .0001). For SBP, the adjusted mean change from baseline for telmisartan 80 mg was -12.7 mm Hg compared with that for ramipril 10 mg of -7.9 mm Hg (P < .0001). At 14 weeks, telmisartan 80 mg also yielded superior reductions from baseline in trough cuff BP compared with ramipril 10 mg (DBP: -11.0 mm Hg v -7.8 mm Hg, respectively; SBP: -14.3 mm Hg v -9.1 mm Hg, respectively; both P < .0001). Measures of 24-h BP control favored telmisartan 80 mg versus ramipril 10 mg (P < .0001), as did other secondary ABPM endpoints during the daytime, night-time, and morning periods. Treatment-related adverse events were uncommon; patients treated with ramipril had a higher incidence of cough than those treated with telmisartan (10.1% v 1.5%, respectively). CONCLUSIONS: Telmisartan 80 mg was consistently more effective than ramipril 10 mg in reducing both DBP and SBP during the last 6 h of the dosing interval, a measure of the early morning period when patients are at greatest risk of life-threatening cardiovascular and cerebrovascular events. Telmisartan 80 mg was also more effective than ramipril 10 mg in reducing BP throughout the entire 24-h dosing interval. Both drugs were well tolerated.

Adult↗

PubMed2006

Noninvasive detection of silent coronary artery disease in patients with essential hypertension, alone or associated with type 2 diabetes mellitus, using dipyridamole stress 99mtechnetium-sestamibi myocardial perfusion imaging.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of morbidity and mortality in hypertensive and diabetic patients. Early diagnosis of CAD and identification of high-risk subgroups, followed by appropriate therapy, may therefore enhance survival. OBJECTIVES: To prospectively establish the prevalence of silent CAD in asymptomatic patients with essential hypertension (EH), and to establish to what extent type 2 diabetes mellitus (DM) modifies the prevalence and severity of silent CAD in these patients. METHODS: The study population consisted of 543 patients 45 years of age and older with EH (n=321) or EH with type 2 DM (n=222), without typical angina or known CAD, selected according to criteria defined by the American Diabetes Association. All patients underwent dipyridamole stress and rest 99mtechnetium sestamibi myocardial single-photon emission computed tomography imaging. The stress and rest myocardial images were divided into 20 segments and blindly scored by two experienced observers. The summed stress score and summed rest score were obtained by adding the scores of the 20 segments of the stress and rest sestamibi images, respectively. The difference between the summed stress score and the summed rest score was defined as the summed difference score, representing reversible ischemia. RESULTS: There was a significant difference (P=0.001) between the percentage of EH patients with (41.4%) and without (27.7%) DM, with regard to abnormal summed stress scores. Moreover, hypertensive, diabetic patients had a significantly greater incidence of moderate to severe ischemia (P=0.011). In addition, a significantly greater proportion of hypertensive patients with DM showed reversible ischemia compared with EH patients without DM (39.6% versus 24.6%; P<0.0001). Proteinuria and dyspnea were significant predictors of silent ischemia in EH patients with DM. CONCLUSIONS: In this high-risk population screened according to the American Diabetes Association criteria with dipyridamole sestamibi myocardial single-photon emission computed tomography imaging, the prevalence of silent ischemia was 28% in EH patients. It is noteworthy that the prevalence (41%) and severity of silent ischemia were significantly greater in EH patients with DM.

Aged↗

PubMed2005

Changes in aortic stiffness and augmentation index after acute converting enzyme or vasopeptidase inhibition.

Augmentation index (AI), a measure of enhanced wave reflection, has been proposed as a bedside measure of aortic stiffness. However, because AI is potentially sensitive to various factors other than vessel wall stiffness, the utility of AI as a stiffness indicator may be limited. To assess relations between AI and vascular properties, we used arterial tonometry and aortic Doppler flow to evaluate trough (24 hours) and peak (4 hours) pulsatile hemodynamics and pulse wave velocity in 159 individuals with systolic hypertension at the completion of a 12-week period of monotherapy with the vasopeptidase inhibitor omapatrilat (80 mg; n=75) or the converting enzyme inhibitor enalapril (40 mg; n=84). Characteristic impedance (Zc) was calculated from the ratio of change in carotid pressure and aortic flow in early systole. Systolic ejection period (SEP), timing of wave reflection, and AI were assessed from the carotid waveform. Comparable acute reductions in mean pressure were associated with greater reductions in peripheral resistance with enalapril, whereas neither drug had an acute effect on Zc. Both drugs reduced AI, but neither drug altered the timing of wave reflection. Both drugs increased heart rate and shortened SEP. Multiple regression analysis demonstrated that the acute reduction in AI was most affected by reductions in SEP and peripheral resistance. Change in AI was inversely related to change in Zc and pulse wave velocity did not enter the model. Our findings indicate that AI is a complex surrogate marker that is inversely related to changes in proximal aortic stiffness in systolic hypertension.

Adult↗

PubMed2005

Effects of circadian rhythms, posture, and medication on renin-aldosterone interrelations in essential hypertensives.

BACKGROUND: The aldosterone-to-renin ratio (ARR) is frequently used to screen primary hyperaldosteronism. This study, part of a clinical trial, was designed to measure the influence of circadian rhythms, antihypertensive drugs, and body posture on plasma renin, on aldosterone, and on their interrelation. METHODS: In a prospective, randomized, open-label, parallel-designed protocol, 57 essential hypertensives (41 men, 16 women) were randomized to a morning dose of telmisartan (80 mg), ramipril (10 mg), or amlodipine (10 mg) for 8 weeks. At baseline and after 8 weeks of therapy, blood pressure (BP), plasma renin (in nanograms per liter), and plasma aldosterone (in picomoles per liter) concentrations were assessed in the supine position every 4 h for 24 h and after 10 min of standing at 9 am. RESULTS: There was no significant association between renin, aldosterone, the ARR and demographic factors, or BP. Circadian variations of plasma renin and aldosterone were clearly present. Aldosterone variations were of greater relative amplitude with earlier-occurring peaks than renin. The ARR exhibited statistically and clinically significant circadian variations with the low and peak values averaging 55.9 +/- 32.3 and 161.84 +/- 85.4 pmol/L/ng/dL, respectively. Telmisartan, ramipril, and amlodipine significantly decreased the ARR. Telmisartan had the greatest influence on the ARR. Posture had a clinically significant but statistically nonsignificant effect on the ARR. CONCLUSIONS: Renin, aldosterone, and their interrelation are influenced by circadian rhythms, telmisartan, ramipril, and amlodipine in patients with essential hypertension. Telmisartan has a greater impact on these parameters than ramipril and amlodipine. Measurement of the ARR in treated hypertensive patients should take these influences into account.

Adult↗

PubMed2005

Antihypertensive efficacy and tolerability of two fixed-dose combinations of valsartan and hydrochlorothiazide compared with valsartan monotherapy in patients with stage 2 or 3 systolic hypertension: an 8-week, randomized, double-blind, parallel-group trial.

BACKGROUND: Combination therapy with at least 2 antihypertensive agents is usually needed to achieve appropriate blood pressure (BP) control in patients with isolated or predominant systolic hypertension. A currently recommended combination is a diuretic added to an angiotensin-receptor blocker. OBJECTIVE: This was a study of the effects on sitting systolic BP (SBP)of 2 combinations of valsartan and hydrochlorothiazide (HCTZ) compared with valsartan monotherapy in patients with stage 2 or 3 systolic hypertension (SBP > or =160 mm Hg and < or =200 mm Hg) with or without other cardiovascular risk factors. METHODS: After a placebo run-in period, patients were randomized to receive double-blind treatment with either valsartan 80 mg OD(monotherapy group) or valsartan 160 mg OD (combination-therapy groups) for 4 weeks, followed by forced titration to valsartan 160 mg OD (V160), valsartan 160 mg plus HCTZ 12.5 mg OD (V160 +HCTZ12.5), or valsartan 160 mg plus HCTZ 25 mg OD (V160 +HCTZ25) for an additional 4 weeks. End points were the change in SBP between the groups receiving combination therapy and the monotherapy group, between-group changes in diastolic BP (DBP), responder rates (SBP <140 mm Hg or a reduction in SBP of > or =20 mm Hg), and tolerability. RESULTS: A total of 774 patients were randomized to treatment: 261 to V160, 258 to V160+HCTZ12.5, and 255 to V160 +HCTZ25. The intent-to-treat population consisted of 767 patients (411 men, 356 women; mean age, 60 years; mean weight, 84 kg; clinic mean [SD] baseline BP, 167.5 [8.1]/93.4 [9.1] mm Hg). All treatments produced significant reductions in SBP from baseline (mean [SD] reduction, 20.7 [15.7] mm Hg with V160, 27.9 [13.8] mm Hg with V160 +HCTZ12.5, and 28.3 [13.1] mm Hg with V160+HCTZ25; all, P < 0.05). DBP was reduced by 6.6 (8.9) mm Hg in the V160 group and by 10.2 (7.7) and 10.1 (7.8) mm Hg in the V160+HCTZ12.5 and V160 +HCTZ25 groups, respectively (all, P < 0.05). The additional reductions in BP with V160+HCTZ25 did not reach statistical significance compared with V160+HCTZ12.5. Responder rates were 56.9% in the V160 group, 74.4% in the V160+HCTZ12.5 group, and 75.0% in the V160 +HCTZ25 group P < 0.05, combination therapy vs monotherapy). Adverse events were reported by 27.5% of patients in the monotherapy group, compared with 28.6% and 34.0% in the groups that received V160+HCTZ12.5 and V160+HCTZ25, respectively; the differences were not significant between treatment groups. CONCLUSIONS: Monotherapy with V160 was effective in these patients with stage 2 or 3 systolic hypertension. Significant additional reductions in SBP and DBP and an increase in responder rates were achieved with the addition to V160 of HCTZ12.5 and HCTZ25, with no significant effect on tolerability.

Antihypertensive Agents↗

PubMed2005

Comparison of fixed-dose combinations of telmisartan/hydrochlorothiazide 40/12.5 mg and 80/12.5 mg and a fixed-dose combination of losartan/hydrochlorothiazide 50/12.5 mg in mild to moderate essential hypertension: pooled analysis of two multicenter, prospective, randomized, open-label, blinded-end point (PROBE) trials.

BACKGROUND: High incidences of cardiovascular events coincide with a surge in blood pressure (BP) that occurs in the early morning hours at the time of arousal. Thus, control of BP at this time of day, using oral fixed-dose combinations (FDCs) as required, is important in reducing cardiovascular risk in hypertensive patients. OBJECTIVE: The aim of this analysis was to compare the antihypertensive efficacy in the early morning hours and tolerability of oral FDCs of telmisartan/hydrochlorothiazide (HCTZ) (40/12.5 mg [T40/H12.5] and 80/12.5 mg [T80/H12.5]) versus a low-dose FDC of losartan 50 mg/HCTZ 12.5 mg (L50/H12.5). METHODS: Data from 2 similarly designed prospective, randomized, open-label, blinded-end point (PROBE) studies were pooled and analyzed. The studies were conducted at 72 centers across the United States, and 70 centers in Canada, Europe (9 countries), and the Philippines. Adult male and female patients with mild to moderate essential hypertension (24-hour mean ambulatory diastolic BP [DBP], > or =85 mm Hg; seated cuff DBP, 90-109 mm Hg) were enrolled. Patients were randomly assigned to receive T40/H12.5, L50/H12.5, or T80/H12.5, QD (morning) for 6 weeks. Antihypertensive efficacy was assessed using 24-hour ambulatory BP monitoring (ABPM) and cuff sphygmomanometry at trough, performed at baseline and on completion of active treatment. The primary end point was the reduction from baseline in mean ambulatory DBP over the last 6 hours of the dosing interval. Secondary end points included other ABPM- and clinic-derived changes in DBP and systolic BP (SBP), and control and response rates (SBP response defined as 24-hour mean SBP <130 mm Hg and/or reduction from baseline > or =10 mm Hg; DBP response defined as 24-hour mean DBP <85 mm Hg or reduction from baseline > or =10 mm Hg; DBP control defined as 24-hour mean DBP <85 mm Hg). Tolerability was assessed using patient interview, spontaneous reporting, and clinical evaluation. RESULTS: A total of 1402 patients were enrolled(876 men, 525 women; mean [SD] age, 53.1 [9.9] years) (T40/H12.5, n = 517; L50/H12.5, n = 518; and T80/H12.5, n = 367). With T40/H12.5, the mean reduction in last-6-hour mean ambulatory DBP was 1.8 mm Hg greater compared with that achieved with L50/H12.5 (-11.3 [0.4] vs -9.4 [0.4] mm Hg; P < 0.001), and with T80/H12.5, the mean reduction was 2.6 mm Hg greater compared with that achieved with L50/H12.5 (-12.0 [0.4] vs -9.4 [0.4] mm Hg; P < 0.001). Analysis of secondary end points found that greater BP reduction occurred with T40/H12.5 and T80/H12.5 compared with L50/H12.5. ABPM SBP control and response rates were similar between the 3 groups, but the ABPM DBP control and response rates were significantly higher with T80/H12.5 compared with L50/H12.5 (46.6% vs 34.0% [P < 0.002] and 69.4% vs 55.0% [P < 0.001], respectively). Clinic SBP and DBP control and response rates were higher with T40/H12.5 and T80/H12.5 compared with L50/H12.5 (SBP response, 80.4% and 80.8% vs 68.5% [both, P < 0.001]; DBP response, 66.1% and 67.4% vs 54.4% [both, P < 0.001]; DBP control, 56.5% and 56.4% vs 44.1% [both, P < 0.001] ). The 2 most commonly recorded adverse events (AEs) were headache (T40/H12.5, 2.9%; L50/H12.5, 3.3%; and T80/H12.5, 3.0%) and dizziness (1.2%, 2.1%, and 3.0%, respectively). Most AEs were mild to moderate. CONCLUSIONS: The results of this pooled analysis of2 PROBE studies in adult patients with mild to moderate essential hypertension suggest that T40/H12.5 and T80/H12.5 conferred greater DBP and SBP control compared with low-dose L50/H12.5, including during the last 6 hours of the dosing interval. All 3 treatments were well tolerated.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

Results of the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial by geographical region.

OBJECTIVE: To examine regional differences in the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial. DESIGN: Double-blind, randomized, international clinical trial. SETTING: Six hundred and sixty-one clinical centers in 15 countries. PATIENTS: Hypertensive volunteers (n = 16,602) with > or =1 additional cardiovascular risk factor, grouped into four regions: USA (n = 8144), Canada (n = 3405), Western Europe (Spain, UK, Italy, Sweden, Germany; n = 2048) or 'other' (Bulgaria, Israel, Mexico, Czech Republic, Hungary, Poland, Slovakia, Brazil; n = 2879); subgroupings included country and state/province within the USA and Canada. INTERVENTIONS: Randomized to COER-verapamil or the investigator's choice of either atenolol or hydrochlorothiazide, titrated and additional drugs added as required. MAIN OUTCOME MEASURES: Baseline characteristics; blood pressure control, medication adherence and lost-to-follow-up at 2 years; and composite primary endpoint (stroke, myocardial infarction, cardiovascular death) by regional groupings. RESULTS: Regional differences were found at baseline for age, gender, blood pressure, percentage receiving antihypertensive drug therapy, initial choice of atenolol or hydrochlorothiazide, and risk factor profile. Blood pressure control rates increased markedly during follow-up in all regions, but varied significantly by region. Blood pressure control, medication adherence and lost-to-follow-up rates were poorest in the USA. After adjustment for baseline differences, the primary-event rate for each region was significantly lower than for the USA. Although baseline factors, blood pressure control and event rates varied by region, treatment differences did not. CONCLUSION: Despite differences in baseline and follow-up measures across geographical regions, the absence of treatment differences by region suggests that the overall findings of CONVINCE are robust.

Aged↗

PubMed2005

Effect of the renin-angiotensin system or calcium channel blockade on the circadian variation of heart rate variability, blood pressure and circulating catecholamines in hypertensive patients.

OBJECTIVE: To determine the effects of 8 weeks of therapy with amlodipine, ramipril or telmisartan on the autonomic system over 24 h in hypertensives. METHODS: After a placebo run-in, 57 patients were included in a prospective randomized open-label design protocol for therapy with amlodipine (5 mg for 4 weeks followed by 10 mg for 4 weeks, n = 22), or ramipril (2.5 mg for 1 week, 5.0 mg for 3 weeks and 10 mg for 4 weeks, n = 17) or telmisartan (80 mg for 8 weeks, n = 18). Autonomic functions were assessed by norepinephrine (NE) and epinephrine (E), as well as by the spectral analysis of heart rate variability (HRV). RESULTS: The 24-h ambulatory blood pressure, plasma NE and HRV demonstrated the characteristic day-night circadian rhythm in hypertensives. Higher values for SBP and DBP and for NE levels, as well as for spectral analysis components - low frequency band (LF) and low frequency/high frequency (LF/HF) ratio - were found during the day, whereas the HF was higher during the night. In patients treated with amlodipine, the HF decreased significantly during the night, while the LF and the LF/HF ratio increased during the day in association with the rise in NE. The therapy with telmisartan did increase the HF during the night and the day, while ramipril did not influence all HRV components during the night but significantly increased the HF, and decreased the LF/HF ratio during the day. No changes were observed in plasma NE with telmisartan or ramipril, but a 50% increase in NE levels throughout the 24-h period was found in amlodipine-treated patients. CONCLUSION: These data suggest a sympathetic activation during the day and a decrease in parasympathetic activity during the night after therapy with amlodipine, correlated with increases in plasma NE. In contrast, the therapy with telmisartan significantly increased parasympathetic activity without changes in NE during the night and day. The therapy with ramipril increased the parasympathetic activity only during the day.

Aged↗

PubMed2004

Sustained antihypertensive activity of telmisartan compared with valsartan.

BACKGROUND: Early morning blood pressure (BP) surge and 24 h mean BP are linked to target-organ damage and cardiovascular events. Antihypertensive agents should sustain BP control, particularly in the last 6 h of the dosing interval or if dosing is missed. The efficacies of the long half-life telmisartan compared with shorter half-life valsartan in the last 6 h of the dosing interval following active treatment and during 24 h after a missed dose were compared. METHODS: In two identically designed multinational, randomized, double-blind, forced-titration studies, hypertensive patients (seated diastolic blood pressure (DBP), 95-109 mm Hg, 24 h mean ambulatory DBP, > or = 85 mm Hg) received once-daily telmisartan (40- 80 mg) or valsartan (80-160 mg) for a total of 8 weeks; uptitration occurred after 2 weeks low-dose treatment. After 4 weeks high-dose treatment, patients were given either 1 days double-blind active therapy or placebo (that is, missed dose). Following a further 2 weeks active treatment, a cross-over was performed: patients who had previously received 1 days placebo received active therapy and vice versa. At baseline and after the two active or missed doses, 24 h ambulatory BP monitoring was performed. Data from the studies were pooled, as prospectively planned and analyzed using the intent-to-treat population. RESULTS: After active therapy, last 6 h mean DBP was reduced by 7.6+/-7.9 mm Hg with telmisartan (n=447) compared with 5.8+/-7.8 mm Hg with valsartan (n=430) (P=0.0044). Last 6 h mean systolic blood pressure (SBP) was reduced by 11.1 mm Hg with telmisartan compared with 9.1 mm Hg with valsartan (P=0.0066). After a missed dose, 24 h mean DBP was reduced by 7.2+/-6.5 mm Hg with telmisartan (n=437) compared with 5.5+/-6.2 mm Hg with valsartan (n=431) (P=0.0004). The reduction in 24 h mean SBP after a missed dose was 10.7 mm Hg with telmisartan and 8.7 mm Hg with valsartan (P=0.0024). Absence of treatment-by-study interaction indicated that pooling of studies was appropriate. All 24 hourly mean reductions in DBP and SBP were greater for telmisartan than valsartan. Both treatments were well tolerated. CONCLUSIONS: Due to its longer half-life, telmisartan offers more sustained BP control, especially at the end of the dosing period and provides sustained efficacy in poorly compliant patients in the event of a missed dose with a statistical superiority compared with valsartan.

Adult↗

PubMed2004

A comparison of the efficacy and duration of action of telmisartan, amlodipine and ramipril in patients with confirmed ambulatory hypertension.

OBJECTIVES: The aim of the study was to compare the antihypertensive effects and the duration of action of telmisartan, amlodipine and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure (ABP) monitoring. METHODS: After a 2-4-week single-blind, placebo run-in period, qualifying patients were randomized to receive telmisartan 80 mg (n=18); amlodipine 5 mg (n=22); titrated to 10 mg after 4 weeks; or ramipril 2.5 mg (n=17); titrated to 5 mg and 10 mg after 1 and 3 weeks, respectively, administered once daily in the morning (0700 h). Ambulatory blood pressure monitoring was performed at baseline and at the end of the 8-week treatment period. Plasma renin activity was measured over 24 h at the same time points. RESULTS: Telmisartan and amlodipine provided significant reductions from baseline (P<0.0001) and not statistically different reductions between treatments in ABP during daytime (9.3/6.0 and 14.7/9.4 mmHg, respectively) and night-time (12.4/7.7 and 13.3/8.6 mmHg, respectively) at the end of 8 weeks' treatment. In contrast, although ramipril provided significant reductions in ambulatory systolic and diastolic BP from 2-6 h post dose (peak effect), it failed to induce significant reductions in mean daytime (4.5/1.6 mmHg) and night-time (1.8/0.1 mmHg) ambulatory BP. In addition, the greater reductions in ABP with telmisartan and amlodipine were associated with a significant rise in plasma renin activity whereas ramipril only increased renin during the first 4 h of the administration interval. CONCLUSION: The results of the present study confirm the efficacy of both telmisartan and amlodipine in reducing ABP during each period of the 24-h interval. Because ABP reduction with ramipril was restricted to its peak effect, the present data do not support the use of this agent when administered once daily in the morning.

Aged↗

PubMed2004

Effects of perindopril on elastic and structural properties of large arteries in essential hypertension.

BACKGROUND: Perindopril, an angiotensin-converting enzyme (ACE) inhibitor, is a well-recognized antihypertensive drug. Its ability to protect against cardiovascular events in hypertension has also been demonstrated. It decreases the stiffness of the larger arteries; questions remain as to the mechanisms involved and whether it is blood pressure (BP) control-dependent. OBJECTIVES: To correlate the BP response to ACE inhibition therapy with changes in arterial stiffness as evaluated by pulse wave velocity (PWV), and to correlate these changes in arterial stiffness with alterations in indicators of vascular collagen metabolism serum levels of metalloproteinase (MMP)-1 and tissue inhibitor of MMP-1 (TIMP-1). METHODS: A total of 162 patients aged 18 to 70 years with stage 1 and 2 essential hypertension (diastolic BP 95 mmHg to 114 mmHg) were enrolled to receive six months (M6) of therapy with the ACE inhibitor, perindopril. Patients were either treatment-naïve or had not received any antihypertensive treatment for at least six months before the study. RESULTS: Mean BP was significantly reduced after two months (M2) of therapy (P=0.00001) and remained stable thereafter. In addition to the significant mean changes in PWV observed at M2 (P=0.00001), further reductions in PWV were noted at M6 (P=0.007). The change in PWV between baseline (M0) and M2 was significantly correlated to all BP parameters at M0 (correlation coefficient at M2 was 0.189 or greater). However, no correlation was seen regarding BP parameters at M2 and further M2 to M6 changes in PWV, suggesting a decrease of arterial stiffness independent of BP reduction. The expression of TIMP-1 and MMP-1 was highly variable and demonstrated no correlation with BP or PWV. CONCLUSIONS: Reductions in BP and PWV appear to be correlated during the first two months of perindopril therapy. After six months, PWV continues to decrease independently of any further reduction in BP, suggesting the occurrence of a pressure-independent pharmacological remodelling of the arterial wall. A long-term, double-blind, randomized trial could be required to confirm that the observed increase in vascular distensibility induced by perindopril is related to a mechanism of action other than a reduction in BP.

Adolescent↗

PubMed2003

Effects of intense and prolonged exercise on insulin sensitivity and glycogen metabolism in hypertensive subjects.

BACKGROUND: The information that insulin sensitivity and glycogen synthesis are reduced in hypertension arises primarily from studies using insulin infusions. Whether glycogen metabolism is actually altered in a physiological condition, such as during and after prolonged exercise, is currently unknown. METHODS AND RESULTS: To examine this issue, 9 hypertensive and 11 normotensive subjects were evaluated on a rest day and after intense and prolonged exercise on a separate day. Insulin sensitivity and hemodynamic variables were measured on both days. On the exercise day, whole-body substrate utilization was assessed and muscle biopsies were taken in the leg at baseline, immediately after exercise, and 2.5 and 4 hours after exercise. Insulin sensitivity at rest was lower in hypertensive than normotensive subjects (P<0.05) and increased after exercise in normotensive (P<0.01) but not in hypertensive (P=NS) subjects. Leg blood flow increased after exercise in both groups but to a lesser extent in hypertensive than normotensive subjects. Baseline glycogen content and maximal glycogen synthase activity were higher in hypertensive than normotensive subjects (P<0.001). Glycogen concentration decreased relatively less (-35 versus -66%) and returned to baseline levels faster in hypertensive subjects after exercise. Hypertensive subjects used approximately 40% less carbohydrates during exercise (P<0.001) at the expense of greater free fatty acid oxidation. CONCLUSIONS: It is concluded that increased intramuscular glycogen storage and resynthesis in hypertension are independent of blood flow and may represent compensatory mechanisms for the reduced insulin sensitivity and carbohydrate metabolism in this condition.

Adult↗

PubMed2003

Determinants of elevated pulse pressure in middle-aged and older subjects with uncomplicated systolic hypertension: the role of proximal aortic diameter and the aortic pressure-flow relationship.

BACKGROUND: Elevated pulse pressure (PP) is associated with increased cardiovascular risk and is thought to be secondary to elastin fragmentation with secondary collagen deposition and stiffening of the aortic wall, leading to a dilated, noncompliant vasculature. METHODS AND RESULTS: By use of calibrated tonometry and pulsed Doppler, arterial stiffness and pulsatile hemodynamics were assessed in 128 subjects with uncomplicated systolic hypertension (supine systolic pressure > or =140 mm Hg off medication) and 30 normotensive control subjects of comparable age and gender. Pulse-wave velocity was assessed from tonometry and body surface measurements. Characteristic impedance (Zc) was calculated from the ratio of change in carotid pressure and aortic flow in early systole. Effective aortic diameter was assessed by use of the water hammer equation. Hypertensives were heavier (P<0.001) and had higher PP (P<0.001), which was attributable primarily to higher Zc (P<0.001), especially in women. Pulse-wave velocity was higher in hypertensives (P=0.001); however, this difference was not significant after adjustment for differences in mean arterial pressure (MAP) (P>0.153), whereas increased Zc remained highly significant (P<0.001). Increased Zc in women and in hypertensive men was attributable to decreased effective aortic diameter, with no difference in wall stiffness at comparable MAP and body weight. CONCLUSIONS: Elevated PP in systolic hypertension was independent of MAP and was attributable primarily to elevated Zc and reduced effective diameter of the proximal aorta. These findings are not consistent with the hypothesis of secondary aortic degeneration, dilation, and wall stiffening but rather suggest that aortic function may play an active role in the pathophysiology of systolic hypertension.

Adult↗

PubMed2003

Antihypertensive effects of two fixed-dose combinations of losartan and hydrochlorothiazide versus hydrochlorothiazide monotherapy in subjects with ambulatory systolic hypertension.

BACKGROUND: The efficacy of losartan (L) in combination with hydrochlorothiazide (HCTZ) has been demonstrated to reduce blood pressure. However, there are limited data on the effects of L/HCTZ combinations versus HCTZ monotherapies in reducing ambulatory systolic blood pressure. The aim of this study was to compare the effects of these treatment approaches in patients with ambulatory systolic hypertension. METHODS: Patients were randomized to receive L 50 mg (n = 60) or HCTZ 12.5 mg (n = 60) for 6 weeks. Patients were then force-titrated to L 50/HCTZ 12.5 mg and to L 100/HCTZ 25 mg or were sham-titrated to HCTZ 12.5 mg and force-titrated to HCTZ 25 mg, respectively. Clinic and 24-h ambulatory blood pressure (ABP) were measured at baseline and after each 6-week treatment period. RESULTS: We found that L 50 and HCTZ 12.5 induced significant and similar decreases in clinic and ABP. The combinations of L 50/HCTZ 12.5 and L 100/HCTZ 25 provided significantly greater decreases in clinic and ABP than did HCTZ monotherapies. The L 50/HCTZ 12.5 and L 100/HCTZ 25 combinations provided significant additional decreases in systolic/diastolic ABP during daytime (-5.3/-2.0 mm Hg; P <.001 and -5.8/-3.4 mm Hg; P <.001) and the other periods of the 24-h interval compared with the levels achieved by the previous treatment, indicating a clear dose-response relationship. However, increasing the dose of HCTZ from 12.5 mg to 25 mg was not associated with additional ABP reductions. CONCLUSIONS: Combinations of L 50/HCTZ 12.5 and L 100/HCTZ 25 provided greater reductions in clinic and ABP than HCTZ monotherapies, with a clear dose-response relationship with regard to ABP. These results support the use of ABP monitoring when assessing the efficacy of antihypertensive therapies.

Aged↗

PubMed2003

Long-term safety and efficacy of the selective aldosterone blocker eplerenone in patients with essential hypertension.

BACKGROUND: Even within the normal range, aldosterone levels are linked to end-organ toxicity and mortality in patients with hypertension. Treatment with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers does not sufficiently reduce plasma aldosterone levels. OBJECTIVE: This study was conducted to assess the long-term safety profile and efficacy of the selective aldosterone blocker eplerenone. METHODS: This was a multicenter, open-label, uncontrolled trial in patients with mild to moderate essential hypertension. After a 1-week washout of previous antihypertensive medications, eplerenone was initiated at 50 mg once daily; the dose was titrated to a maximum of 200 mg/d to achieve a diastolic blood pressure <90 mm Hg and a systolic blood pressure <140 mm Hg. Thereafter, another antihypertensive agent could be added and titrated once, or another agent could be substituted for eplerenone. Eplerenone treatment was continued for up to 14 months in a subset of patients. RESULTS: Five hundred eighty-six patients were enrolled in the study. Their adjusted mean blood pressure (BP) at baseline was 150/96 mm Hg. The majority (80.4%) were white; 51.5% were male and 48.5% were female; 62.3% were between the ages of 45 and 64 years and 21.7% were aged >64 years. Three hundred eighty-five patients (65.7%) completed the study; 98 (16.7%) were withdrawn due to treatment failure (only 4.8% of them after month 4), and 40 (6.8%) were withdrawn due to treatment-emergent adverse events. Four hundred thirty-three of 582 (74.4%) patients in the intent-to-treat population achieved BP control during eplerenone treatment: 261 (44.8%) received eplerenone monotherapy and 172 (30.0%) received eplerenone plus another antihypertensive agent. CONCLUSIONS: Eplerenone therapy was effective in the treatment of mild to moderate hypertension over a 14-month period, either as monotherapy or in combination with another antihypertensive agent. Use of eplerenone was well tolerated in the population studied.

Adolescent↗

PubMed2003

Prospective, randomized, open-label, blinded-endpoint (PROBE) designed trials yield the same results as double-blind, placebo-controlled trials with respect to ABPM measurements.

OBJECTIVE: This meta-analysis aimed to determine whether ambulatory blood pressure monitoring (ABPM) results from double-blind, placebo-controlled (DBPC) and prospective, randomized, open-label, blinded-endpoint (PROBE) hypertension trials are statistically comparable. METHODS: Two DBPC and three PROBE parallel-group studies were selected from an angiotensin II receptor blocker clinical programme. These were fixed-dose studies involving similar mild to moderate hypertensive patient populations. All used SpaceLabs 90207 ABPM devices, and each comprised a 4-week placebo period and a 4-8-week treatment period. Data from patients receiving telmisartan 80 mg were used to compare the results of DBPC (126 patients) and PROBE (734 patients) trials. The analysis had approximately 87% power to show equivalence between the two design types in terms of ruling out differences of >or= 3 mmHg in SBP and >or= 2 mmHg in DBP. Office blood pressure was also compared. RESULTS: The change from baseline in mean 24-h ambulatory SBP was -12.2 mmHg in DBPC trials and -12.3 mmHg in PROBE trials, a rounded difference of 0.2 mmHg [95% confidence interval (CI): -1.8, 2.1]. The change from baseline in mean 24-h ambulatory DBP was -7.7 mmHg in DBPC trials versus -7.9 mmHg in PROBE trials, a difference of 0.2 mmHg (95% CI: -1.1, 1.5). Ambulatory pulse pressure results were identical. CONCLUSIONS: Thus, changes in mean 24-h ambulatory blood pressure from the DBPC and PROBE trials in this meta-analysis are statistically equivalent in terms of ruling out a difference of >or= 3 mmHg in SBP and >or= 2 mmHg in DBP. This supports the validity of the PROBE design in assessing antihypertensive efficacy based on blinded ABPM measurements.

Antihypertensive Agents↗

PubMed2002

Omapatrilat reduces pulse pressure and proximal aortic stiffness in patients with systolic hypertension: results of the conduit hemodynamics of omapatrilat international research study.

BACKGROUND: Increased pulse pressure, an indicator of conduit vessel stiffness, is a strong independent predictor of cardiovascular events in hypertensive cohorts, which suggests that reduction of conduit vessel stiffness may be desirable in hypertension. METHODS AND RESULTS: We assessed changes in pulse pressure and conduit vessel stiffness in a 12-week double-blind, randomized clinical trial that compared monotherapy with the ACE inhibitor enalapril 40 mg daily (n=87) versus the vasopeptidase (dual ACE and neutral endopeptidase) inhibitor omapatrilat 80 mg daily (n=80) in patients with systolic hypertension. Patients were withdrawn from antihypertensive medications 1 to 2 weeks before enrollment, and systolic pressure was confirmed to be > or =160 mm Hg. With the use of calibrated tonometry and pulsed Doppler, pulsatile hemodynamics were assessed before randomization and at 12 weeks. Characteristic impedance (Z(c)), a direct measure of the stiffness of the central aorta, was calculated from the ratio of changes in carotid pressure and aortic flow in early systole. Omapatrilat compared with enalapril produced greater reductions in peripheral (-8.2+/-12.2 versus -4.0+/-12.2 mm Hg, P<0.05) and central (-10.2+/-16.2 versus -3.2+/-16.9 mm Hg, P<0.01) pulse pressures and Z(c) (237+/-83 to 208+/-70 versus 225+/-87 to 231+/-94 dyne x s/cm(5), P<0.001); the latter remained significant (P<0.05) after adjusting for change in mean pressure. CONCLUSIONS: Greater reductions in pulse pressure and Z(c) in hypertensive subjects treated with omapatrilat compared with enalapril suggest that aortic stiffness is maintained by specific, partially reversible mechanisms and underscore a potential role for pharmacological modulation of natriuretic peptides in the treatment of hypertension.

Adult↗

PubMed2002

Effects of mild exercise on insulin sensitivity in hypertensive subjects.

Physical exercise increases insulin sensitivity in conditions associated with insulin resistance, such as obesity and diabetes, but little is known in this regard in hypertension. Whether postexercise changes in hemodynamics and/or changes in insulin-induced vasodilatation could contribute to a postexercise increase in insulin sensitivity in hypertensive subjects is unknown. We investigated the effects of acute physical exercise on insulin sensitivity in 10 hypertensive and 10 normotensive subjects during a control evaluation (CTRL), during lower body negative pressure (LBNP), after 30 minutes of mild bicycle exercise (POSTEX), and during LBNP after exercise (POSTEX+LBNP). Insulin-induced vasodilatation was assessed from peak forearm blood flow during the intravenous glucose tolerance test. Cardiac output (4.9+/-0.3 versus 5.3+/-0.4 L/min, mean+/-SEM) and insulin sensitivity (the glucose disappearance rate over insulin area under the curve: 0.91+/-0.07 versus 1.38+/-0.25 min(-1)/[pmol. L(-1)]. minute) were lower (both P<0.05) in hypertensive than in normotensive subjects, respectively. Cardiac output decreased during LBNP, increased during POSTEX, and was similar to control during POSTEX+LBNP in both groups. Insulin sensitivity was unchanged during LBNP, increased during POSTEX, and remained elevated during POSTEX+LBNP in hypertensive subjects, whereas it remained unchanged in normotensives. Peak forearm blood flow was significantly lower in hypertensive than in normotensive subjects, despite higher insulin levels in hypertensives, and was not modified by LBNP or exercise. In conclusion, insulin sensitivity increases after exercise in hypertensive subjects, and the increase in cardiac output does not contribute to this effect. Endogenous insulin-induced vasodilatation is reduced in hypertensive subjects, and this insulin action is not affected by physical exercise.

Blood Flow Velocity↗