enalapril and Stroke

Left ventricular hypertrophy (LVH) is a strong, independent predictor of cardiovascular events and all-cause mortality. Patients with LVH are at increased risk for stroke, coronary heart disease, congestive heart failure, and sudden cardiac death. Hypertension is a major influence on the development of LVH. The prognostic power of LVH is likely multifactorial. LVH represents both a manifestation of the effects of hypertension and other cardiac risk factors over time as well as an intrinsic condition causing pathologic changes in cardiac structure and function. Angiotensin II plays a central role in the development of LVH. Several antihypertensive treatments, especially angiotensin II receptor blockers, can reverse LVH and improve cardiovascular outcomes independent of blood pressure reduction. Further studies are required to determine if these agents should become first-line therapy for all patients with hypertension and LVH.

Topics: Adrenergic Antagonists; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Carbazoles; Carvedilol; Chi-Square Distribution; Cohort Studies; Coronary Disease; Death, Sudden, Cardiac; Diuretics; Drug Therapy, Combination; Echocardiography; Electroencephalography; Enalapril; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Indapamide; Logistic Models; Losartan; Male; Multivariate Analysis; Prognosis; Propanolamines; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Risk Assessment; Risk Factors; Sex Factors; Stroke; Survival Analysis; Telmisartan

For hypertensive patients without a history of stroke or myocardial infarction (MI), the China Stroke Primary Prevention Trial (CSPPT) demonstrated that treatment with enalapril-folic acid reduced the risk of primary stroke compared with enalapril alone. Whether folic acid therapy is an affordable and beneficial treatment strategy for the primary prevention of stroke in hypertensive patients from the Chinese healthcare sector perspective has not been thoroughly explored.. We performed a cost-effectiveness analysis alongside the CSPPT, which randomized 20,702 hypertensive patients. A patient-level microsimulation model based on the 4.5-year period of in-trial data was used to estimate costs, life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) for enalapril-folic acid vs. enalapril over a lifetime horizon from the payer perspective.. During the in-trial follow-up period, patients receiving enalapril-folic acid gained an average of 0.016 QALYs related primarily to reductions in stroke, and the incremental cost was $706.03 (4553.92 RMB). Over a lifetime horizon, enalapril-folic acid treatment was projected to increase quality-adjusted life years by 0.06 QALYs or 0.03 life-year relative to enalapril alone at an incremental cost of $1633.84 (10,538.27 RMB), resulting in an ICER for enalapril-folic acid compared with enalapril alone of $26,066.13 (168,126.54 RMB) per QALY gained and $61,770.73 (398,421.21 RMB) per life-year gained, respectively. A probabilistic sensitivity analysis demonstrated that enalapril-folic acid compared with enalapril would be economically attractive in 74.5% of simulations at a threshold of $37,663 (242,9281 RMB) per QALY (3x current Chinese per capita GDP). Several high-risk subgroups had highly favorable ICERs < $12,554 (80,976 RMB) per QALY (1x GDP).. For both in-trial and over a lifetime, it appears that enalapril-folic acid is a clinically and economically attractive medication compared with enalapril alone. Adding folic acid to enalapril may be a cost-effective strategy for the prevention of primary stroke in hypertensive patients from the Chinese health system perspective.

Topics: Cost-Benefit Analysis; Enalapril; Folic Acid; Humans; Hypertension; Primary Prevention; Quality-Adjusted Life Years; Stroke

The role of serum calcium on the risk of stroke is still uncertain. We aimed to evaluate the effect of serum calcium on first stroke risk, and on the efficacy of folic acid treatment in prevention of first stroke among hypertensive patients.. Our analyses included a total of 19,644 eligible hypertensive adults from the China Stroke Primary Prevention Trial (CSPPT). In the CSPPT, a total of 20,702 hypertensive patients were randomly assigned to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. The primary outcome was a first stroke.. Over a median of 4.5 years, among those not receiving folic acid, a significantly higher risk of first stroke was found in hypertensive males with baseline albumin-corrected serum calcium ≥2.43 mmol/L (median) (vs. <2.43 mmol/L; 6.5% vs. 2.3%; adjusted HR, 2.47; 95% CI: 1.72, 3.55). For those with enalapril and folic acid treatment, compared with the enalapril only group, the risk of first stroke was reduced from 6.5% to 3.0% (adjusted HR, 0.49; 95% CI: 0.35, 0.68) in hypertensive males with baseline albumin-corrected serum calcium ≥2.43 mmol/L, whereas there was no significant effect among hypertensive males with baseline albumin-corrected serum calcium <2.43 mmol/L. However, among hypertensive females, serum calcium did not significantly affect the first stroke risk and the efficacy of folic acid in prevention of first stroke.. Among Chinese hypertensive males, those with elevated serum calcium levels had increased risk of first stroke, and this risk was reduced by 51% with folic acid treatment.

Topics: Antihypertensive Agents; Calcium; Double-Blind Method; Enalapril; Female; Folic Acid; Humans; Hypertension; Male; Middle Aged; Risk Assessment; Serum Albumin; Stroke

Identification of novel risk factors is needed to further lower stroke risk. Data concerning the association between plasma retinol concentrations and the risk of stroke are limited.. We aimed to evaluate the effect of plasma retinol on the risk of first stroke and to examine any possible effect modifiers in hypertensive patients.. The study sample population was drawn from the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, including 620 cases with first stroke and 620 matched controls. In the CSPPT, a total of 20,702 hypertensive patients were randomly assigned to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. The median treatment duration was 4.5 y.. There was a significant inverse association between plasma retinol and the risk of first stroke (per 10-μg/dL increment; OR: 0.92; 95% CI: 0.86, 0.97) and first ischemic stroke (OR: 0.92; 95% CI: 0.86, 0.98). When retinol was assessed as quartiles, significantly lower risks of first stroke (OR: 0.64; 95% CI: 0.46, 0.88) and first ischemic stroke (OR: 0.67; 95% CI: 0.46, 0.96) were found in participants in quartiles 2-4 compared with those in quartile 1. Furthermore, a stronger inverse association between plasma retinol and first stroke was observed in participants with baseline total homocysteine (<10 compared with ≥10 μmol/L; P-interaction = 0.049). However, plasma retinol had no significant effect on first hemorrhagic stroke (per 10-μg/dL increment; OR: 0.98; 95% CI: 0.79, 1.18).. Our data showed a significant inverse association between plasma retinol and the risk of first stroke among Chinese hypertensive adults. This study was registered at clinicaltrials.gov as NCT00794885.

Topics: Aged; Antihypertensive Agents; Brain Ischemia; Case-Control Studies; China; Double-Blind Method; Enalapril; Female; Folic Acid; Hemorrhage; Homocysteine; Humans; Hypertension; Male; Middle Aged; Odds Ratio; Primary Prevention; Risk Factors; Stroke; Vitamin A; Vitamin A Deficiency

Brachial-ankle pulse wave velocity (baPWV), as a marker of arterial stiffness, has been demonstrated to be associated with blood pressure (BP) and onset of hypertension. However, little information is available on the associations between baPWV and BP indices [systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), mean arterial pressure (MAP)] in treated hypertensive patients. We aimed to assess the associations between BP indices and baPWV. In this cross-sectional study, 14,598 hypertensive patients from China Stroke Primary Prevention Trial (CSPPT) at the exit visit of the trial were analyzed. Elevated baPWV was defined as ≥18.3 m/s. Multivariate linear and logistic regression analyses were performed to evaluate the associations of BP indices with baPWV and elevated baPWV. Moreover, the smooth curve fitting (penalized spline method) was conducted. Multivariate linear regression analyses showed that continuous SBP, DBP, PP and MAP were independently and positively associated with baPWV (β = 0.081, 0.084, 0.078 and 0.115, respectively, all P < 0.001). Compared with controlled SBP group (<140 mm Hg), uncontrolled SBP (≥140 mm Hg) was significantly associated with higher baPWV [β = 2.234, 95% confidence interval (CI): 2.137-2.332]. Similarly, compared with controlled DBP group (<90 mm Hg), uncontrolled DBP (≥90 mm Hg) was significantly associated with higher baPWV (β = 1.466, 95%CI: 1.341-1.590). Multiple logistic analyses also showed that SBP, DBP, PP and MAP were significantly and positively associated with elevated baPWV (OR = 1.056, 1.049, 1.052, and 1.075, respectively, all P < 0.001). The fully-adjusted smooth curve fitting presented a linear association between BP indices with baPWV. In conclusion, among treated hypertensive patients, SBP, DBP, PP and MAP levels were independently and positively associated with baPWV and elevated baPWV, suggesting that baPWV might be a way to predict uncontrolled BP.

Topics: Adult; Aged; Ankle Brachial Index; Antihypertensive Agents; Blood Pressure; China; Enalapril; Female; Folic Acid; Humans; Hypertension; Male; Middle Aged; Pulse Wave Analysis; Risk Factors; Stroke; Vascular Stiffness

Previous studies indicated that trace elements may play an important role in cardiovascular diseases. However, data concerning the association between blood copper and the risk of stroke are limited.. The aim of this study was to evaluate the association between plasma copper and the risk of first stroke, and examine any possible effect modifiers in hypertensive patients.. We conducted a nested case-control study, using data from the China Stroke Primary Prevention Trial. Hypertension is defined as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, or taking antihypertensive medication. A total of 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site were included in this study. The crude and adjusted risks of first stroke were estimated by ORs and 95% CIs using conditional logistic regression, without or with adjusting for pertinent covariates, respectively.. There were significant positive associations of plasma copper with risk of first stroke (per SD increment-OR: 1.20; 95% CI: 1.03, 1.39) and first ischemic stroke (OR: 1.26; 95% CI: 1.07, 1.50). When plasma copper was categorized in quartiles, significantly higher risks of first stroke (OR: 1.72; 95% CI: 1.12, 2.65) and first ischemic stroke (OR: 1.91; 95% CI: 1.18, 3.11) were found in participants in quartile 4 (≥ 117.0 μg/dL) than in those in quartile 1 (< 91.2 μg/dL). Furthermore, the plasma copper-first stroke association was significantly stronger in participants with higher BMI (< 25.0 compared with ≥ 25.0 kg/m2, P-interaction = 0.024). However, there was no significant association between plasma copper and first hemorrhagic stroke.. In Chinese hypertensive patients, there was a significant positive association between baseline plasma copper and the risk of first stroke, especially among those with higher BMI.This trial was registered at clinicaltrials.gov as NCT00794885.

Topics: Aged; Antihypertensive Agents; Body Mass Index; Case-Control Studies; China; Copper; Double-Blind Method; Enalapril; Female; Folic Acid; Humans; Hypertension; Male; Middle Aged; Risk Factors; Stroke

We aimed to examine whether the efficacy of folic acid therapy in the primary prevention of stroke is jointly affected by smoking status and baseline folate levels in a male population in a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial).. Eligible participants of the CSPPT were randomly assigned to a double-blind daily treatment of a combined enalapril 10-mg and folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. In total, 8384 male participants of the CSPPT were included in the current analyses. The primary outcome was first stroke.. The median treatment duration was 4.5 years. In the enalapril-alone group, the first stroke risk varied by baseline folate levels and smoking status (never versus ever). Specifically, there was an inverse association between folate levels and first stroke in never smokers (. Baseline folate levels and smoking status can interactively affect the risk of first stroke. Our data suggest that compared with never smokers, ever smokers may require a higher dosage of folic acid to achieve a greater beneficial effect on stroke. Our findings need to be confirmed by future randomized trials.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Topics: Aged; Double-Blind Method; Enalapril; Folic Acid; Humans; Hypertension; Male; Middle Aged; Risk Factors; Smoking; Stroke

Elevated blood homocysteine concentration increases the risk of stroke, especially among hypertensive individuals. Homocysteine is largely affected by the methylenetetrahydrofolate reductase C677T polymorphism and folate status. Among hypertensive patients, we aimed to test the hypothesis that the association between homocysteine and stroke can be modified by the methylenetetrahydrofolate reductase C677T polymorphism and folic acid intervention.. We analyzed the data of 20 424 hypertensive adults enrolled in the China Stroke Primary Prevention Trial. The participants, first stratified by methylenetetrahydrofolate reductase genotype, were randomly assigned to receive double-blind treatments of 10-mg enalapril and 0.8-mg folic acid or 10-mg enalapril only. The participants were followed up for a median of 4.5 years.. In Chinese hypertensive patients, the effect of homocysteine on the first stroke was significantly modified by the methylenetetrahydrofolate reductase C677T genotype and folic acid supplementation. Such information may help to more precisely predict stroke risk and develop folic acid interventions tailored to individual genetic background and nutritional status.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Topics: Aged; Antihypertensive Agents; China; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Folic Acid; Follow-Up Studies; Genotype; Homocysteine; Humans; Hypertension; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Stroke; Treatment Outcome; Vitamin B Complex

To examine whether a change in serum total homocysteine (tHcy) levels is associated with first stroke risk in a post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT).. We analyzed 16,867 participants of the CSPPT with tHcy measurements at both baseline and exit visits. The primary outcome was first stroke. The secondary outcome was a composite of cardiovascular events consisting of cardiovascular death, myocardial infarction, and stroke. The percent decline in tHcy was calculated as [(baseline tHcy - exit tHcy)/baseline tHcy × 100].. Over the median treatment duration of 4.5 years, participants who developed a first stroke had a significantly lower percent decline in tHcy (β = -5.7; 95% confidence interval [CI] -8.8 to -2.6) compared to their counterparts. A 20% tHcy decline was associated with a reduction in stroke risk of 7% (hazard ratio [HR] 0.93; 95% CI 0.90-0.97). When percent decline in tHcy was assessed as tertiles, a significantly lower stroke risk was found in those in tertiles 2-3 (HR 0.79; 95% CI 0.64-0.97) compared with participants in tertile 1. Similar results were observed for the composite of cardiovascular events. The beneficial effect associated with greater tHcy reduction was observed across strata for age, sex, treatment group (with vs without folic acid),. Percent lowering in tHcy was significantly associated with a reduction in first stroke risk in Chinese adults with hypertension, and if further confirmed, may serve as a useful indicator for folic acid treatment efficacy on stroke prevention.. NCT00794885.

Topics: Aged; Antihypertensive Agents; China; Drug Therapy, Combination; Enalapril; Female; Folic Acid; Homocysteine; Humans; Hypertension; Male; Middle Aged; Risk; Stroke; Vitamin B Complex

We aimed to investigate the relationship of time-averaged on-treatment systolic blood pressure (SBP) with the risk of first stroke in the CSPPT (China Stroke Primary Prevention Trial). A post hoc analysis was conducted using data from 17 720 hypertensive adults without cardiovascular disease, diabetes mellitus, and renal function decline from the CSPPT, a randomized double-blind controlled trial. The primary outcome was first stroke. Over a median follow-up duration of 4.5 years, the association between averaged on-treatment SBP and risk for first stoke followed a U-shape curve, with increased risk above and below the reference range of 120 to 130 mm Hg. Compared with participants with time-averaged on-treatment SBP at 120 to 130 mm Hg (mean, 126.2 mm Hg), the risk of first stroke was not only increased in participants with SBP at 130 to 135 mm Hg (mean, 132.6 mm Hg; 1.5% versus 0.8%; hazard ratio, 1.63; 95% confidence interval, 1.01-2.63) or 135 to 140 mm Hg (mean, 137.5 mm Hg; 1.9% versus 0.8%; hazard ratio, 1.85; 95% confidence interval, 1.17-2.93), but also increased in participants with SBP <120 mm Hg (mean, 116.7 mm Hg; 3.1% versus 0.8%; hazard ratio, 4.37; 95% confidence interval, 2.10-9.07). Similar results were found in various subgroups stratified by age, sex, and treatment group. Furthermore, lower diastolic blood pressure was associated with lower risk of stroke, with a plateau at a time-average on-treatment diastolic blood pressure <80 mm Hg. In conclusion, among adults with hypertension and without a history of stroke or myocardial infarction, diabetes mellitus, or renal function decline, a lower SBP goal of 120 to 130 mm Hg, as compared with a target SBP of 130 to 140 mm Hg or <120 mm Hg, resulted in the lowest risk of first stroke.

Topics: Administration, Oral; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; China; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Folic Acid; Follow-Up Studies; Humans; Hypertension; Incidence; Male; Middle Aged; Primary Prevention; Risk Factors; Stroke; Survival Rate; Time Factors; Treatment Outcome; Vitamin B Complex

The aim of the present post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT) was to evaluate the effect of folic acid supplementation on the risk of new-onset diabetes in hypertensive adults in China.. In all, 20 702 hypertensive adults with no history of stroke and/or myocardial infarction (MI) were randomly assigned to receive double-blind daily treatment with tablets containing either: (i) 10 mg enalapril and 0.8 mg folic acid (n = 10 348); or (ii) 10 mg enalapril alone (n = 10 354). New-onset diabetes was defined as either self-reported physician-diagnosed diabetes or the use of glucose-lowering drugs during the follow-up period of the CSPPT.. Over a median treatment duration of 4.5 years, new-onset diabetes occurred in 198 (2.0%) and 214 (2.1%) subjects in the enalapril-folic acid and enalapril groups, respectively (hazard ratio [HR] 0.92; 95% confidence interval [CI] 0.76-1.12). Similar results were observed when analyses were limited to subjects with baseline fasting glucose (FG) <7.0 mmol/L (HR 0.85; 95% CI 0.62-1.14). Furthermore, there was no significant group difference in: (i) the risk of new-onset FG ≥7.0 mmol/L (defined as FG <7.0 at baseline and ≥7.0 mmol/L at the last visit; relative risk [RR] 1.07; 95% CI 0.96-1.20); or (ii) the composite of new-onset diabetes or new-onset FG ≥7.0 mmol/L (RR = 1.06; 95% CI 0.95-1.19).. Among adults with hypertension with no history of stroke and/or MI in China, folic acid supplementation had no significant effect on the risk of new-onset diabetes.

Topics: Aged; Antihypertensive Agents; Asian People; Blood Glucose; Blood Pressure; China; Diabetes Mellitus; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Folic Acid; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Outcome Assessment, Health Care; Proportional Hazards Models; Risk Assessment; Risk Factors; Stroke; Vitamin B Complex

Pulse wave velocity (PWV) has been shown to influence the effects of antihypertensive drugs in the prevention of cardiovascular diseases. Data are limited on whether PWV is an independent predictor of stroke above and beyond hypertension control. This longitudinal analysis examined the independent and joint effect of brachial-ankle PWV (baPWV) with hypertension control on the risk of first stroke. This report included 3310 hypertensive adults, a subset of the China Stroke Primary Prevention Trial (CSPPT) with baseline measurements for baPWV. During a median follow-up of 4.5 years, 111 participants developed first stroke. The risk of stroke was higher among participants with baPWV in the highest quartile than among those in the lower quartiles (6.3% versus 2.4%; hazard ratio, 1.66; 95% confidence interval, 1.06-2.60). Similarly, the participants with inadequate hypertension control had a higher risk of stroke than those with adequate control (5.1% versus 1.8%; hazard ratio, 2.32; 95% confidence interval, 1.49-3.61). When baPWV and hypertension control were examined jointly, participants in the highest baPWV quartile and with inadequate hypertension control had the highest risk of stroke compared with their counterparts (7.5% versus 1.3%; hazard ratio, 3.57; 95% confidence interval, 1.88-6.77). There was a significant and independent effect of high baPWV on stroke as shown among participants with adequate hypertension control (4.2% versus 1.3%; hazard ratio, 2.29, 95% confidence interval, 1.09-4.81). In summary, among hypertensive patients, baPWV and hypertension control were found to independently and jointly affect the risk of first stroke. Participants with high baPWV and inadequate hypertension control had the highest risk of stroke compared with other groups.

Topics: Aged; Ankle Brachial Index; Blood Pressure Determination; China; Confidence Intervals; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Folic Acid; Follow-Up Studies; Humans; Hypertension; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Proportional Hazards Models; Pulse Wave Analysis; Risk Assessment; Stroke; Survival Rate; Treatment Outcome

We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial.. A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. The primary outcome was first stroke.. The median treatment duration was 4.5 years. For participants not receiving folic acid treatment (enalapril-only group), high total cholesterol (≥200 mg/dL) was an independent predictor of first stroke when compared with low total cholesterol (<200 mg/dL; 4.0% versus 2.6%; hazard ratio, 1.52; 95% confidence interval, 1.18-1.97; P=0.001). Folic acid supplementation significantly reduced the risk of first stroke among participants with high total cholesterol (4.0% in the enalapril-only group versus 2.7% in the enalapril-folic acid group; hazard ratio, 0.69; 95% confidence interval, 0.56-0.84; P<0.001; number needed to treat, 78; 95% confidence interval, 52-158), independent of baseline folate levels and other important covariates. By contrast, among participants with low total cholesterol, the risk of stroke was 2.6% in the enalapril-only group versus 2.5% in the enalapril-folic acid group (hazard ratio, 1.00; 95% confidence interval, 0.75-1.30; P=0.982). The effect was greater among participants with elevated total cholesterol (P for interaction=0.024).. Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke. Folic acid supplementation reduced the risk of first stroke associated with elevated total cholesterol by 31% among hypertensive adults without a history of major cardiovascular diseases.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Topics: Aged; Antihypertensive Agents; China; Comorbidity; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Folic Acid; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Outcome Assessment, Health Care; Risk; Stroke; Vitamin B Complex

Uncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data.. To test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension.. The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20,702 adults with hypertension without history of stroke or myocardial infarction (MI) participated in the study.. Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10 mg, and folic acid, 0.8 mg (n = 10,348) or a tablet containing enalapril, 10 mg, alone (n = 10,354).. The primary outcome was first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death.. During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril-folic acid group had a significant risk reduction in first stroke (2.7% of participants in the enalapril-folic acid group vs 3.4% in the enalapril alone group; hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), first ischemic stroke (2.2% with enalapril-folic acid vs 2.8% with enalapril alone; HR, 0.76; 95% CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril-folic acid vs 3.9% with enalapril alone; HR, 0.80; 95% CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95% CI, 0.65-1.34), MI (HR, 1.04; 95% CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95% CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events.. Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels.. clinicaltrials.gov Identifier: NCT00794885.

Topics: Antihypertensive Agents; China; Double-Blind Method; Drug Therapy, Combination; Enalapril; Folic Acid; Humans; Hypertension; Kaplan-Meier Estimate; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Primary Prevention; Risk; Stroke; Vitamin B Complex

To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial by an open-label follow-up study lasting 4 years.. The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160-219 mmHg systolic and below 95 mmHg diastolic. The double-blind trial ended after a median follow-up of 2.0 years (range 1-97 months). Of 4409 patients still alive, 3517 received open-label treatment consisting of nitrendipine (10-40 mg daily) with the possible addition of enalapril (5-20 mg daily), hydrochlorothiazide (12.5-25 mg daily), or both add-on drugs. Non-participants (n = 892) were also followed up.. Median follow-up increased to 6.1 years. Systolic pressure decreased to below 150 mmHg (target level) in 2628 participants (75.0%). During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. These rates were similar to those previously observed in the active-treatment group during the double-blind trial. Considering the total follow-up of 4695 randomized patients, immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P = 0.01) and 15% (P = 0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P < 0.02) were 60, 51 and 38%, respectively.. Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus; Dihydropyridines; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Enalapril; Europe; Female; Follow-Up Studies; Heart Failure; Humans; Hydrochlorothiazide; Hypertension; Incidence; Linear Models; Male; Myocardial Infarction; Nitrendipine; Stroke; Survival Rate; Time Factors; Treatment Outcome

Peripheral arterial disease (PAD) and diabetes are both associated with a high risk of ischemic events, but the role of intensive blood pressure control in PAD has not been established.. The Appropriate Blood Pressure Control in Diabetes study followed 950 subjects with type 2 diabetes for 5 years; 480 of the subjects were normotensive (baseline diastolic blood pressure of 80 to 89 mm Hg). Patients randomized to placebo (moderate blood pressure control) had a mean blood pressure of 137+/-0.7/81+/-0.3 mm Hg over the last 4 years of treatment. In contrast, patients randomized to intensive treatment with enalapril or nisoldipine had a mean 4-year blood pressure of 128+/-0.8/75+/-0.3 mm Hg (P<0.0001 compared with moderate control). PAD, which is defined as an ankle-brachial index <0.90 at the baseline visit, was diagnosed in 53 patients. In patients with PAD, there were 3 cardiovascular events (13.6%) on intensive treatment compared with 12 events (38.7%) on moderate treatment (P=0.046). After adjustment for multiple cardiovascular risk factors, an inverse relationship between ankle-brachial index and cardiovascular events was observed with moderate treatment (P=0.009), but not with intensive treatment (P=0.91). Thus, with intensive blood pressure control, the risk of an event was not increased, even at the lowest ankle-brachial index values, and was the same as in a patient without PAD.. In PAD patients with diabetes, intensive blood pressure lowering to a mean of 128/75 mm Hg resulted in a marked reduction in cardiovascular events.

Topics: Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Cohort Studies; Comorbidity; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Nisoldipine; Odds Ratio; Peripheral Vascular Diseases; Risk Assessment; Stroke; Treatment Outcome

Although several important studies have been performed in hypertensive type 2 diabetic patients, it is not known whether lowering blood pressure in normotensive (BP <140/90 mm Hg) patients offers any beneficial results on vascular complications. The current study evaluated the effect of intensive versus moderate diastolic blood pressure (DBP) control on diabetic vascular complications in 480 normotensive type 2 diabetic patients.. The current study was a prospective, randomized controlled trial in normotensive type 2 diabetic subjects. The subjects were randomized to intensive (10 mm Hg below the baseline DBP) versus moderate (80 to 89 mm Hg) DBP control. Patients in the moderate therapy group were given placebo, while the patients randomized to intensive therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication. The primary end point evaluated was the change in creatinine clearance with the secondary endpoints consisting of change in urinary albumin excretion, progression of retinopathy and neuropathy and the incidence of cardiovascular disease.. The mean follow-up was 5.3 years. Mean BP in the intensive group was 128 +/- 0.8/75 +/- 0.3 mm Hg versus 137 +/- 0.7/81 +/- 0.3 mm Hg in the moderate group, P < 0.0001. Although no difference was demonstrated in creatinine clearance (P = 0.43), a lower percentage of patients in the intensive group progressed from normoalbuminuria to microalbuminuria (P = 0.012) and microalbuminuria to overt albuminuria (P = 0.028). The intensive BP control group also demonstrated less progression of diabetic retinopathy (P = 0.019) and a lower incidence of strokes (P = 0.03). The results were the same whether enalapril or nisoldipine was used as the initial antihypertensive agent.. Over a five-year follow-up period, intensive (approximately 128/75 mm Hg) BP control in normotensive type 2 diabetic patients: (1) slowed the progression to incipient and overt diabetic nephropathy; (2) decreased the progression of diabetic retinopathy; and (3) diminished the incidence of stroke.

Topics: Adult; Aged; Albuminuria; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Disease Progression; Enalapril; Female; Humans; Male; Middle Aged; Nisoldipine; Prospective Studies; Single-Blind Method; Stroke

Previous studies have indicated that selenium (Se) may play an important role in cardio-cerebrovascular disease. However, the relation between circulating selenium and risk of first stroke remains inconclusive.. We conducted a secondary analysis of the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, and aimed to investigate the correlation between Se concentration and first stroke risk in adults with hypertension and examine the potential effect modifiers.. In the CSPPT, a total of 20,702 adults with hypertension were randomly assigned to a double-blind daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. A total of 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site were included in this study.. During a median follow-up duration of 4.5 y (IQR: 4.2-4.6 y), there was a significant inverse association between plasma Se and the risk of first stroke (per SD increment; adjusted OR: 0.81; 95% CI: 0.68, 0.96) and ischemic stroke (per SD increment; adjusted OR: 0.76; 95% CI: 0.62, 0.93). Furthermore, a stronger inverse association between plasma Se and first stroke was observed in participants with higher folate concentrations at baseline [≥7.7 ng/mL (median), adjusted OR: 0.67; 95% CI: 0.54, 0.85, compared with <7.7 ng/mL, adjusted OR: 0.98; 95% CI: 0.80, 1.21; P-interaction = 0.008] and those with higher time-averaged systolic blood pressure (SBP) over the treatment period (≥140 mm Hg, adjusted OR: 0.71; 95% CI: 0.58, 0.86, compared with <140 mm Hg, adjusted OR: 0.96; 95% CI: 0.77, 1.20; P-interaction = 0.023).. There was a significant inverse association between plasma Se and risk of first stroke in Chinese adults with hypertension, especially among those with higher baseline folate concentrations and those with higher time-averaged SBP over the treatment period. This trial was registered at clinicaltrials.gov as NCT00794885.

Topics: Antihypertensive Agents; Asian People; Cardiometabolic Risk Factors; Case-Control Studies; China; Double-Blind Method; Enalapril; Female; Folic Acid; Humans; Hypertension; Male; Middle Aged; Odds Ratio; Primary Prevention; Randomized Controlled Trials as Topic; Selenium; Stroke; Vitamin B Complex

We aimed to test the impact of achieved blood pressure (BP) on first stroke among patients with grade 1 hypertension and without cardiovascular diseases in the China Stroke Primary Prevention Trial.. A total of 3187 patients with uncomplicated grade 1 hypertension were included. The risk of outcomes was assessed according to: (1) the proportion of visits in which BP was reduced to <140/90 mm Hg, and (2) the time-averaged systolic BP (SBP) or diastolic BP levels during the study treatment period. The median antihypertensive treatment duration was 4.6 years. Only 1.5% of the participants discontinued the treatments because of adverse reaction. Overall, the risk of stroke decreased with the increase of the proportion of study visits with BP <140/90 mm Hg (for per 5% increase; hazard ratio, 0.92 [95% CI, 0.87-0.98]). Consistently, compared with patients with time-averaged SBP ≥140 or diastolic BP ≥90 mm Hg, the risk of stroke was lower in patients with time-averaged SBP of 120 to <140 mm Hg (1.1% versus 2.9%; hazard ratio, 0.39 [95% CI, 0.22-0.69]) or diastolic BP <90 mm Hg (1.5% versus 2.7%; hazard ratio, 0.41 [95% CI, 0.17-0.98]). The beneficial results were consistent across age (<60 versus ≥60 years), sex, baseline SBP (<150 versus 150 to <160 mm Hg), study treatment groups (enalapril or enalapril-folic acid), and hypertension subtypes (isolated systolic hypertension or systolic-diastolic hypertension). However, a time-averaged SBP <120 mm Hg (versus 120-140 mm Hg) was associated with an increased risk for stroke. Similar results were observed for composite cardiovascular events or all-cause death.. Achieved BP <140/90 mm Hg was significantly associated with a decreased risk of stroke or all-cause death in patients with uncomplicated grade 1 hypertension.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Cause of Death; China; Double-Blind Method; Enalapril; Female; Folic Acid; Humans; Hypertension; Male; Middle Aged; Mortality; Proportional Hazards Models; Randomized Controlled Trials as Topic; Severity of Illness Index; Stroke; Treatment Outcome; Vitamin B Complex

Topics: Antihypertensive Agents; Enalapril; Folic Acid; Humans; Hypertension; Male; Stroke; Vitamin B Complex

Topics: Antihypertensive Agents; Enalapril; Folic Acid; Humans; Hypertension; Male; Stroke; Vitamin B Complex

Topics: Antihypertensive Agents; Enalapril; Folic Acid; Humans; Hypertension; Male; Stroke; Vitamin B Complex

Topics: Antihypertensive Agents; Enalapril; Folic Acid; Humans; Hypertension; Male; Stroke; Vitamin B Complex

Topics: Antihypertensive Agents; Enalapril; Folic Acid; Humans; Hypertension; Male; Stroke; Vitamin B Complex

Topics: Antihypertensive Agents; Asian People; China; Enalapril; Folic Acid; Genetic Variation; Genotype; Humans; Hypertension; Methylenetetrahydrofolate Reductase (NADPH2); Primary Prevention; Randomized Controlled Trials as Topic; Stroke; Vitamin B Complex

Topics: Albuminuria; Antihypertensive Agents; Blood Pressure; Combined Modality Therapy; Dihydropyridines; Drug Combinations; Enalapril; Humans; Hypertension; Physical Fitness; Stroke

To examine the impact of tissue selectivity of angiotensin-converting enzyme (ACE) inhibitors on mortality and morbidity in patients following acute myocardial infarction (AMI).. A retrospective cohort study using a Medicaid claims database was conducted. Patients hospitalized for an AMI and subsequently filling a prescription for an ACE inhibitor were followed longitudinally for the occurrence of cardiovascular-related hospitalizations and all-cause mortality. A subanalysis was also conducted to account for switching/discontinuation of ACE inhibitor therapy. Stepwise (forward conditional) Cox-proportional hazards models were used to analyze the effect of tissue selectivity on study outcomes.. The final study sample consisted of 689 AMI and the results indicated that tissue-selective ACE inhibitors had a protective effect against hospitalization due to stroke/transient ischemic attack (TIA) (hazard ratio [HR] = 0.265; 95% confidence interval [CI] = 0.101-0.698). A similar lower rate in hospitalizations due to heart failure was observed in the group using tissue-selective ACE inhibitors; however, the results were not statistically significant (HR = 0.681; 95% CI = 0.436-1.063). A protective effect was also observed on the combined outcome of hospitalization due to any cardiovascular condition (HR = 0.712; 95% CI = 0.536-0.945). Hospitalizations due to recurrent AMI, need for coronary revascularization procedures, and mortality were not significantly different between patients using tissue-selective and non-tissue-selective ACE inhibitors. The completer subanalysis provided similar findings regarding the impact of tissue selectivity on study outcomes.. Tissue-selective ACE inhibitors may have a protective effect against hospitalization due to stroke/TIA or heart failure when compared to non-tissue-selective ACE inhibitors for patients following AMI.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Diseases; Comorbidity; Enalapril; Female; Heart Failure; Humans; Lisinopril; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Organ Specificity; Proportional Hazards Models; Ramipril; Retrospective Studies; Secondary Prevention; Stroke; Survival Analysis

The attempts to develop new treatments for acute ischemic stroke have been fraught with costly and spectacularly disappointing failures. Repurposing of safe, older drugs provides a lower risk alternative. Vascular protection is a novel strategy for improving stroke outcome. Promising targets for vascular protection after stroke have been identified, and several of these targets can be approached with "repurposed" old drugs, including statins, angiotensin receptor blockers (ARBs), and minocycline. We tested the vascular protection (ability to reduce hemorrhagic transformation) of three marketed drugs (candesartan, minocycline, and atorvastatin) in the experimental stroke model using three different rat strains [Wistar, spontaneously hypertensive rats (SHR) and type 2 diabetic Goto-Kakizaki (GK) rats]. All agents decreased the infarct size, improved the neurological outcome and decreased bleeding. Mechanisms identified include inhibition of MMP-9, activation of Akt, and increased expression of proangiogenic growth factors. Premorbid vascular damage (presence of either diabetes or hypertension) increased the likelihood of vascular injury after ischemia and reperfusion and improved the response to vascular protection.

Topics: Animals; Anticholesteremic Agents; Antihypertensive Agents; Atorvastatin; Benzimidazoles; Biphenyl Compounds; Brain Infarction; Diabetes Mellitus, Type 2; Disease Models, Animal; Enalapril; Enzyme-Linked Immunosorbent Assay; Functional Laterality; Hemoglobins; Hemorrhage; Heptanoic Acids; Male; Matrix Metalloproteinase 9; Pyrroles; Rats; Rats, Inbred SHR; Rats, Wistar; Reperfusion; Stroke; Tetrazoles; Vascular System Injuries

The current literature supports the immediate use of combinations of antihypertensive drugs in terms of ease of use and adherence, but the key issue whether combination therapy is more effective than monotherapy in the prevention of cardiovascular complications remains unproven.. We analysed the double-blind (median follow-up 2.0 years) and open follow-up (6.0 years) phases of the Systolic Hypertension in Europe trial. Patients were 60 years or more with an entry systolic/diastolic blood pressure (BP) of 160-219/less than 95 mmHg. Antihypertensive treatment started immediately after randomization in the active-treatment group, but only after completion of the double-blind trial in control patients. Treatment consisted of nitrendipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day). We adjusted our analyses for sex, age, history of cardiovascular complications, baseline systolic BP and previous antihypertensive treatment.. During the double-blind trial, adding enalapril to nitrendipine (n = 515), compared with the equivalent combination of placebos (n = 559), decreased systolic BP by a further 9.5 mmHg and reduced all cardiovascular events by 51% (P = 0.0035) and heart failure by 66% (P = 0.032), with similar trends for stroke (-51%; P = 0.066) and cardiac events (-44%; P = 0.075). Over the whole duration of follow-up, combination therapy (n = 871), compared with nitrendipine monotherapy (n = 1552), decreased systolic BP by 3.1 mmHg and reduced total mortality (-32%; P = 0.023), with similar trends for all cardiovascular events (-23%; P = 0.081) and stroke (-42%; P = 0.054).. Despite the limitations of a posthoc analysis, but congruent with the stronger BP reduction, our results suggest that combination therapy with nitrendipine plus enalapril might improve outcome over and beyond the benefits seen with nitrendipine monotherapy.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Double-Blind Method; Drug Therapy, Combination; Enalapril; Europe; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Male; Middle Aged; Nitrendipine; Randomized Controlled Trials as Topic; Retrospective Studies; Stroke; Time Factors; Treatment Outcome

To investigate the cost-utility of eprosartan versus enalapril (primary prevention) and versus nitrendipine (secondary prevention) on the basis of head-to-head evidence from randomized controlled trials.. The HEALTH model (Health Economic Assessment of Life with Teveten for Hypertension) is an object-oriented probabilistic Monte Carlo simulation model. It combines a Framingham-based risk calculation with a systolic blood pressure approach to estimate the relative risk reduction of cardiovascular and cerebrovascular events based on recent meta-analyses. In secondary prevention, an additional risk reduction is modeled for eprosartan according to the results of the MOSES study ("Morbidity and Mortality after Stroke--Eprosartan Compared to Nitrendipine for Secondary Prevention"). Costs and utilities were derived from published estimates considering European country-specific health-care payer perspectives.. Comparing eprosartan to enalapril in a primary prevention setting the mean costs per quality adjusted life year (QALY) gained were highest in Germany (Euro 24,036) followed by Belgium (Euro 17,863), the UK (Euro 16,364), Norway (Euro 13,834), Sweden (Euro 11,691) and Spain (Euro 7918). In a secondary prevention setting (eprosartan vs. nitrendipine) the highest costs per QALY gained have been observed in Germany (Euro 9136) followed by the UK (Euro 6008), Norway (Euro 1695), Sweden (Euro 907), Spain (Euro -2054) and Belgium (Euro -5767).. Considering a Euro 30,000 willingness-to-pay threshold per QALY gained, eprosartan is cost-effective as compared to enalapril in primary prevention (patients >or=50 years old and a systolic blood pressure >or=160 mm Hg) and cost-effective as compared to nitrendipine in secondary prevention (all investigated patients).

Topics: Acrylates; Antihypertensive Agents; Cardiovascular Diseases; Cost-Benefit Analysis; Enalapril; Europe; Geography; Humans; Hypertension; Imidazoles; Male; Meta-Analysis as Topic; Middle Aged; Monte Carlo Method; Nitrendipine; Primary Prevention; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Stroke; Thiophenes

Topics: Age Factors; Aged, 80 and over; Antihypertensive Agents; Drug Combinations; Enalapril; Female; Humans; Hypertension; Myocardial Infarction; Nitrendipine; Risk Factors; Stroke; Systole

Topics: Antihypertensive Agents; Drug Labeling; Drugs, Generic; Enalapril; Humans; Myocardial Infarction; Stroke

Topics: Aged; Antihypertensive Agents; Blood Pressure; Diuretics; Double-Blind Method; Drug Therapy, Combination; Enalapril; Europe; Female; Humans; Hypertension; Male; Middle Aged; Nitrendipine; Randomized Controlled Trials as Topic; Stroke; Systole

The present study examined the levels of Angiotensin II type 1 receptor (AT(1)) and type 2 receptor (AT(2)) in the brain stem and cerebral cortex of the stroke-prone spontaneously hypertensive rat (SHR-sp) after long-term treatment with three types of antihypertensive drugs: valsartan, enalapril, and amlodipine. In both tissues, expression of the AT(1) was decreased by administration of each drug. Expression of the AT(2) was decreased in the cerebral cortex by drug administration, but did not change in the brain stem. This study may contribute to elucidating the relationship between AT(1) and AT(2) expressions and the effect of antihypertensive drugs in SHR-sp brain.

Topics: Amlodipine; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Brain Stem; Calcium Channel Blockers; Cerebral Cortex; Disease Models, Animal; Down-Regulation; Enalapril; Hypertension; Male; Rats; Rats, Inbred SHR; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; RNA, Messenger; Stroke; Tetrazoles; Time Factors; Valine; Valsartan

Recent studies have suggested that the calcium antagonists have an antiatherogenic antioxidant property. The effects of the calcium antagonists on reactive oxygen species (ROS)-related enzymes, however, remain unknown. We hypothesized that the calcium antagonists inhibit oxidative stress in the hearts of stroke-prone spontaneously hypertensive rats (SHRSP) through the ROS-scavenging enzymes known as superoxide dismutases (SODs). Male 12-week-old Wister-Kyoto rats (WKY) and SHRSP were used for the study. SHRSP were randomized and treated for 6 weeks with a vehicle, amlodipine (5 mg/kg/day), or enalapril (10 mg/kg/day). NAD(P)H oxidase activity was measured by a luminescence assay, and SOD activity was measured spectrophotometrically. Protein expressions were analyzed by immunoblots. Both drugs showed equipotent effects on systolic blood pressure, left ventricular hypertrophy and fibrosis, the wall-to-lumen ratio, the manganese SOD activity, ROS, and the endothelial NO synthase expression in the SHRSP hearts. Furthermore, amlodipine significantly restored copper/zinc-containing SOD (Cu/ZnSOD) expression and its activity in SHRSP hearts to a level equal to that of WKY more effectively than did enalapril (p <0.05), whereas enalapril downregulated NAD(P)H oxidase activity more than did amlodipine (p <0.05) in the SHRSP hearts. Furthermore, amlodipine restored Cu/ZnSOD expression and its activity in SHRSP hearts to a level equal to that in WKY hearts, and this restoration was significantly more effective than that by enalapril (p <0.05); on the other hand, enalapril induced a greater downregulation of NAD(P)H oxidase activity in SHRSP hearts than did amlodipine (p <0.05). Thus, amlodipine may inhibit vascular remodeling and oxidative stress in the SHRSP heart by efficiently upregulating Cu/ZnSOD, suggesting that the calcium antagonist may exhibit an antiatherogenic antioxidative action beyond blood-pressure lowering through the restoration of Cu/ZnSOD activity in the heart in cases of hypertension.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Animals; Calcium Channel Blockers; Coronary Vessels; Enalapril; Hypertension; Male; Myocardium; NADPH Oxidases; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Oxidative Stress; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Stroke; Superoxide Dismutase; Up-Regulation

Interpretation of the fields of vision forms a key part of ophthalmic and neurologic examinations. The homonymous hemianopa is a hallmark of a retrochiasmal lesion. Postchiasmal lesions that interrupt the visual pathway may have multiple causes which the circulatory disturbances is one of the most important. The authors present the case of a woman who has an isolated homonymous hemianopa produced by a vascular accident of occipital lobe, dwell upon the only manifestation of the cerebral acute hemorrhagic vascular accident was represented by an visual field defect.

Topics: Aged; Amlodipine; Antihypertensive Agents; Aphakia; Drug Therapy, Combination; Enalapril; Female; Hemianopsia; Humans; Occipital Lobe; Stroke; Treatment Outcome; Visual Field Tests

Topics: Acrylates; Antihypertensive Agents; Coronary Disease; Enalapril; Humans; Hypertension; Imidazoles; Risk Factors; Stroke; Systole; Thiophenes; Treatment Outcome

Topics: Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Diseases; Clinical Trials as Topic; Enalapril; Humans; Perindopril; Protease Inhibitors; Pyridines; Stroke; Thiazepines; Ventricular Dysfunction, Left

This consensus is the result of a recent meeting to establish the ideal approach for thrombolysis in acute stroke patients in Brazil. Some peculiarities concerning the emergency rooms, stroke units, available equipments and stroke teams are considered in order to characterize the stroke centers. Protocols concerning the use of thrombolytic drugs are reviewed. This is the official guideline for thrombolysis in acute stroke of the Brazilian Society of Cerebrovascular Disease.

Topics: Acute Disease; Brain Ischemia; Brazil; Enalapril; Fibrinolytic Agents; Humans; Metoprolol; Stroke; Thrombolytic Therapy

Stroke-prone spontaneously hypertensive rats (SHRSP), subjected to high NaCl, show severe hypertension, organ damage, and early death. Preventive treatment with angiotensin II type 1 (AT1) receptor antagonists is known to be effective. Previously, we found that angiotensin converting enzyme (ACE) inhibition could reduce cerebral edema when treatment was started after manifestation of either proteinuria or cerebral edema. In this study AT1 receptor blockade was started at the same time points to evaluate whether this had an effect superior to ACE inhibition. SHRSP drank 1% NaCl. Group 1 served as controls. Group 2 and 3 rats were started on losartan and enalapril after proteinuria exceeded 40 mg/day. Group 4 and 5 rats were started on losartan and enalapril after the first observation of cerebral edema with T2-weighted magnetic resonance imaging scans. In controls, median survival was 54 days (range, 35 to 80 days) after the start of salt loading. With early-onset losartan and enalapril, survival increased to 305 days (range, 184 to 422 days) and 320 days (range, 134 to 368 days) (both P < .01 v group 1). Cerebral edema formation was prevented in all but two rats, one from each treatment modality. Development of proteinuria was markedly reduced. With late-onset treatment with losartan and enalapril, survival was 290 days (range, 120 to 367 days) and 264 days (range, 154 to 319 days) (both P < .01). Both losartan and enalapril decreased cerebral edema to baseline levels. Ultimately cerebral edema reoccurred, despite continued treatment, in 75% of the rats. Systolic blood pressure did not decrease after losartan treatment, but, similarly to early-onset treatment, decreased transiently after enalapril treatment. Cerebral edema and proteinuria were prevented and reduced in SHRSP treated with either an AT1 receptor antagonist or an ACE inhibitor. Survival was markedly and similarly prolonged by both treatments, whether initiated directly before or after development of cerebral edema. In rats where treatment was initiated after manifestation of cerebral edema, both cerebral edema and proteinuria reappeared despite continued treatment. Apparently, when hypertension is sustained, reappearance of target organ damage may not be entirely dependent on angiotensin.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Brain Edema; Drug Administration Schedule; Enalapril; Genetic Predisposition to Disease; Hypertension; Losartan; Male; Proteinuria; Rats; Rats, Inbred SHR; Stroke; Survival Analysis

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Cardiovascular Diseases; Clinical Trials as Topic; Enalapril; Heart Failure; Humans; Indoles; Isoquinolines; Myocardial Infarction; Perindopril; Prodrugs; Quinapril; Ramipril; Stroke; Stroke Volume; Tetrahydroisoquinolines; Treatment Outcome; Ventricular Dysfunction, Left

Previous studies have shown that angiotensin II (Ang II), by mediating rapid recruitment of collateral circulation, has a protective effect in the setting of acute ischaemia. In an experimental model of acute cerebral ischaemia in the gerbil, Fernandez et al. have reported that the mechanism of the protective effect of Ang 11 is blood pressure (BP)-independent, and that the AT1-receptor antagonist, losartan, but not the ACE inhibitor (ACE-I),enalapril, decreases mortality following unilateral carotid artery ligation. The aim of this study was to examine there producibility of the respective effects of losartan and enalapril, and to verify that these differential effects are drug class-related. Acute cerebral ischaemia was induced in anaesthetised gerbils bv unilateral carotid ligation. The effect of pretreatment with two different ACE-I(enalapril and lisinopril), and two different AT1-receptor antagonists (losartan and candesartan), administered orally or intravenously, on mortality were compared. Kaplan-Meier survival curves at day three were analysed bv a log-rank test. Pretreatment with both enalapril and lisinopril significantly decreased survival at day three compared with controls, while the AT1-receptor antagonists losartan and candesartan, despite similarly lowering BP, did not increase mortality. Coadministration of losartan and enalapril increased mortality to the same extent as enalapril alone. This study confirms that Ang II contributes to protective mechanisms against acute cerebral ischaemia through non AT1-receptor-mediated, BP-independent effects.

Topics: Acute Disease; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Brain Ischemia; Disease Models, Animal; Enalapril; Gerbillinae; Lisinopril; Losartan; Male; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Reproducibility of Results; Stroke; Tetrazoles

Chronic oral administration of l -NAME precipitates stroke in stroke-prone spontaneously hypertensive rats (SHRSP). The present study investigated whether acetazolamide (an acidotic agent) given alone or in combination with an angiotensin blocker (enalapril maleate) offers any protection from NO-deficient stroke in SHRSP. We also examined whether protection from NO-deficient stroke involves activation of K(+)channels. Five-week-old SHRSP drank saline (group I), l -NAME (group II), l -NAME+enalapril (group III), l -NAME+acetazolamide (group IV), and l -NAME+enalapril+acetazolamide (group V). Within a few hours following onset of stroke, rats were attached to a blood pressure recorder. In subsequent experiments, to investigate the involvement of K(+)channels, glibenclamide and BaCl(2)(K(+)channel blockers) were included in the drinking solutions that were given to the SHRSP groups receiving l -NAME, acetazolamide and enalapril. Group I of SHRSP did not develop stroke. Group II, III and IV developed stroke in 12+/-2, 29+/-2 and 20+/-2 days, respectively. SHRSP from group V did not develop stroke. However, they died in 70+/-2 days. The glibenclamide and BaCl(2)administration failed to prevent this protection from stroke. In conclusion, concurrent administration of acetazolamide and enalapril prevents onset of NO-deficient stroke in SHRSP. These stroke-protective effects are independent of reductions in mean or systolic blood pressures and do not involve an activation of K(+)channels.

Topics: Acetazolamide; Angiotensin-Converting Enzyme Inhibitors; Animals; Barium Compounds; Blood Pressure; Carbonic Anhydrase Inhibitors; Chlorides; Drug Interactions; Enalapril; Enzyme Inhibitors; Glyburide; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Potassium Channel Blockers; Potassium Channels; Rats; Rats, Inbred SHR; Stroke

1. The structure of the basilar artery and the relationship of structure to blood pressure and ventricular hypertrophy was examined in genetically hypertensive (GH) rats, their control normotensive (N) Wistar strain, GH given the nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) and GH given L-NAME and either valsartan or enalapril. 2. Systolic blood pressure (SBP; tail-cuff) was measured weekly from age 7-12 weeks. At the end of the experiment at 12 weeks, the basilar artery was fixed by perfusion and embedded in Technovit (Heraeus Kulzer GmbH, Werheim, Germany). Serial sections were cut and stained and stereological analysis applied to quantify the morphology of the vessels. Left ventricular (LV) mass was determined. 3. Both SBP and LV mass were significantly increased in GH compared with N (P < 0.001) and increased further in GH given L-NAME (P < 0.05). The GH L-NAME + valsartan and GH L-NAME + enalapril groups had significantly lower (P < 0.001) SBP and LV mass than the GH L-NAME group. 4. Basilar arteries in GH (which are frankly hypertensive, but have no apparent endothelial defect) showed hypotrophic inward remodelling compared with the N control group with no change in media to lumen ratio. 5. In the GH L-NAME group, further inward remodelling occurred and the media to lumen ratio was increased compared with N (P < 0.01) and GH (P < 0.05). Valsartan treatment in GH L-NAME rats caused eutrophic outward remodelling. Enalapril caused hypertrophic outward remodelling, suggesting that the angiotensin II-stimulated growth was not entirely suppressed with an angiotensin-converting enzyme inhibitor or that there was a bradykinin effect with enalapril. 6. In GH with an endothelial defect induced by treatment with L-NAME, the further remodelling, together with an increased media to lumen ratio and the development of a stroke-like syndrome, indicates the NOS-inhibited GH rat may be a useful model for essential hypertension (where it is known that endothelial abnormalities exist) and where stroke can develop as a consequence of the hypertension.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Basilar Artery; Blood Pressure; Brain; Enalapril; Enzyme Inhibitors; Hypertension; Muscle, Smooth, Vascular; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Rats; Rats, Inbred SHR; Stroke; Tetrazoles; Valine; Valsartan; Ventricular Function, Left