Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-BioLINCC)
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PROVIDER: PRJNA1250173 | ENA |
REPOSITORIES: ENA
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Project description:Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-BioLINCC)
| PRJNA1250172 | ENA
Project description:To unravel antihypertensive drug-induced gene expression changes that are potentially related to the amelioration of end-organ damages, we performed in vivo phenotypic evaluation and transcriptomic analysis on the heart and the kidney, with administration of antihypertensive drugs to two inbred strains of (i.e., hypertensive and normotensive) rats. We chose to use six antihypertensive classes: enalapril (angiotensin converting enzyme inhibitor), candesartan (angiotensin receptor blocker), hydrochlorothiazide (diuretics), amlodipine (calcium-channel blocker), carvedilol (vasodilating beta-blocker) and hydralazine. In the tested rat strains, four of six drugs, including two renin-angiotensin system (RAS) inhibitors, were effective for BP lowering, whereas the remaining two drugs were not. Besides BP lowering, there appeared to be some inter-drug heterogeneity in phenotypic changes, such as suppressed body weight (Bw) gain and Bw-adjusted heart weight reduction. For the transcriptomic response, a considerable number of genes showed prominent mRNA expression changes either in a BP-dependent or BP-independent manner with substantial diversity between the target organs. Noticeable changes of mRNA expression were induced particularly by RAS blockade, e.g., for genes in the natriuretic peptide system (Nppb and Corin) in the heart and for those in the RAS/ kallikrein-kinin system (Ren and rat Klk1 paralogs) and those related to calcium ion binding (Calb1 and Slc8a1) in the kidney. This submission includes the kidney data.
2022-04-15 | E-MTAB-10672 | biostudies-arrayexpress
Project description:To unravel antihypertensive drug-induced gene expression changes that are potentially related to the amelioration of end-organ damages, we performed in vivo phenotypic evaluation and transcriptomic analysis on the heart and the kidney, with administration of antihypertensive drugs to two inbred strains of (i.e., hypertensive and normotensive) rats. We chose to use six antihypertensive classes: enalapril (angiotensin converting enzyme inhibitor), candesartan (angiotensin receptor blocker), hydrochlorothiazide (diuretics), amlodipine (calcium-channel blocker), carvedilol (vasodilating -blocker) and hydralazine. In the tested rat strains, four of six drugs, including two renin-angiotensin system (RAS) inhibitors, were effective for BP lowering, whereas the remaining two drugs were not. Besides BP lowering, there appeared to be some inter-drug heterogeneity in phenotypic changes, such as suppressed body weight (Bw) gain and Bw-adjusted heart weight reduction. For the transcriptomic response, a considerable number of genes showed prominent mRNA expression changes either in a BP-dependent or BP-independent manner with substantial diversity between the target organs. Noticeable changes of mRNA expression were induced particularly by RAS blockade, e.g., for genes in the natriuretic peptide system (Nppb and Corin) in the heart and for those in the RAS/ kallikrein-kinin system (Ren and rat Klk1 paralogs) and those related to calcium ion binding (Calb1 and Slc8a1) in the kidney. The heart data comprises of this submission and part of E-MTAB-9244.
2022-04-15 | E-MTAB-10667 | biostudies-arrayexpress
Project description:To unravel antihypertensive drug-induced gene expression changes that are potentially related to the amelioration of end-organ damages, we performed in vivo phenotypic evaluation and transcriptomic analysis on the heart and the kidney, with administration of antihypertensive drugs to two inbred strains of (i.e., hypertensive and normotensive) rats. We chose to use six antihypertensive classes: enalapril (angiotensin converting enzyme inhibitor), candesartan (angiotensin receptor blocker), hydrochlorothiazide (diuretics), amlodipine (calcium-channel blocker), carvedilol (vasodilating beta-blocker) and hydralazine. In the tested rat strains, four of six drugs, including two renin-angiotensin system (RAS) inhibitors, were effective for BP lowering, whereas the remaining two drugs were not. Besides BP lowering, there appeared to be some inter-drug heterogeneity in phenotypic changes, such as suppressed body weight (Bw) gain and Bw-adjusted heart weight reduction. For the transcriptomic response, a considerable number of genes showed prominent mRNA expression changes either in a BP-dependent or BP-independent manner with substantial diversity between the target organs. Noticeable changes of mRNA expression were induced particularly by RAS blockade, e.g., for genes in the natriuretic peptide system (Nppb and Corin) in the heart and for those in the RAS/ kallikrein-kinin system (Ren and rat Klk1 paralogs) and those related to calcium ion binding (Calb1 and Slc8a1) in the kidney. This submission includes the kidney data.
2022-04-15 | GSE188349 | GEO
Project description:To unravel antihypertensive drug-induced gene expression changes that are potentially related to the amelioration of end-organ damages, we performed in vivo phenotypic evaluation and transcriptomic analysis on the heart and the kidney, with administration of antihypertensive drugs to two inbred strains of (i.e., hypertensive and normotensive) rats. We chose to use six antihypertensive classes: enalapril (angiotensin converting enzyme inhibitor), candesartan (angiotensin receptor blocker), hydrochlorothiazide (diuretics), amlodipine (calcium-channel blocker), carvedilol (vasodilating beta-blocker) and hydralazine. In the tested rat strains, four of six drugs, including two renin-angiotensin system (RAS) inhibitors, were effective for BP lowering, whereas the remaining two drugs were not. Besides BP lowering, there appeared to be some inter-drug heterogeneity in phenotypic changes, such as suppressed body weight (Bw) gain and Bw-adjusted heart weight reduction. For the transcriptomic response, a considerable number of genes showed prominent mRNA expression changes either in a BP-dependent or BP-independent manner with substantial diversity between the target organs. Noticeable changes of mRNA expression were induced particularly by RAS blockade, e.g., for genes in the natriuretic peptide system (Nppb and Corin) in the heart and for those in the RAS/ kallikrein-kinin system (Ren and rat Klk1 paralogs) and those related to calcium ion binding (Calb1 and Slc8a1) in the kidney. The heart data comprises of this submission and part of ArrayExpress E-MTAB-9244.
2022-04-15 | GSE188348 | GEO
Project description:A randomized, double-blind, active-controlled, multicenter trial assigned 32,804 participants aged 55 years and older with hypertension and ≥ 1 other coronary heart disease risk factors to receive chlorthalidone (n=15,002), amlodipine (n=8898), or lisinopril (n=8904) for 4 to 8 years, when double-blinded therapy was discontinued. Passive surveillance continued for a total follow-up of 8 to 13 years using national administrative databases to ascertain deaths and hospitalizations. During the post-trial period, fatal outcomes and nonfatal outcomes were available for 98% and 65% of participants, respectively, due to lack of access to administrative databases for the remainder. This paper assesses whether mortality and morbidity differences persisted or new differences developed during the extended follow-up. Primary outcome was cardiovascular mortality and secondary outcomes were mortality, stroke, coronary heart disease, heart failure, cardiovascular disease, and end-stage renal disease. For the post-trial period, data are not available on medications or blood pressure levels. No significant differences (P<.05) appeared in cardiovascular mortality for amlodipine (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.93-1.06) or lisinopril (HR, 0.97; CI, 0.90-1.03), each compared with chlorthalidone. The only significant differences in secondary outcomes were for heart failure, which was higher with amlodipine (HR, 1.12; CI, 1.02-1.22), and stroke mortality, which was higher with lisinopril (HR, 1.20; CI, 1.01-1.41), each compared with chlorthalidone. Similar to the previously reported in-trial result, there was a significant treatment-by-race interaction for cardiovascular disease for lisinopril vs chlorthalidone. Black participants had higher risk than non-black participants taking lisinopril compared with chlorthalidone. After accounting for multiple comparisons, none of these results were significant. These findings suggest that neither calcium channel blockers nor angiotensin-converting enzyme inhibitors are superior to diuretics for the long-term prevention of major cardiovascular complications of hypertension.
| S-EPMC3261592 | biostudies-literature
Project description:Left ventricular hypertrophy (LVH) predicts cardiovascular risk in hypertensive patients. We analyzed baseline/follow-up electrocardiographies in 26,376 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to amlodipine (A), lisinopril (L), or chlorthalidone (C). Prevalent/incident LVH was examined using continuous and categorical classifications of Cornell voltage. At 2 and 4 years, prevalence of LVH in the C group (5.57%; 6.14%) was not statistically different from A group (2 years: 5.47%; P = .806, 4 years: 6.54%; P = .857) or L group (2 years: 5.64%; P = .857, 4 years: 6.50%; P = .430). Incident LVH followed similarly, with no difference at 2 years for C (2.99%) compared to A (2.57%; P = .173) or L (3.16%; P = .605) and at 4 years (C = 3.52%, A = 3.29%, L = 3.71%; P = .521 C vs. A, P = .618 C vs. L). Mean Cornell voltage decreased comparably across treatment groups (Δ baseline, 2 years = +3 to -27 μV, analysis of variance P = .8612; 4 years = +10 to -17 μV, analysis of variance P = .9692). We conclude that risk reductions associated with C treatment in secondary end points of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial cannot be attributed to differential improvements in electrocardiography LVH.
| S-EPMC5161112 | biostudies-literature
Project description:ObjectivesGout is a common complication of blood pressure management and a frequently cited cause of medication nonadherence. Little trial evidence exists to inform antihypertensive selection with regard to gout risk.MethodsThe Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized clinical trial on the effects of first-step hypertension therapy with amlodipine, chlorthalidone, or lisinopril on fatal coronary heart disease or nonfatal myocardial infarction (1994-2002). Trial participants were linked to CMS and VA gout claims (ICD9 274.XX). We determined the effect of drug assignment on gout with Cox regression models. We also determined the adjusted association of self-reported atenolol use (ascertained at the 1-month visit for indications other than hypertension) with gout.ResultsClaims were linked to 23 964 participants (mean age 69.8 ± 6.8 years, 45% women, 31% black). Atenolol use was reported by 928 participants at the 1-month visit. Over a mean follow-up of 4.9 years, we documented 597 gout claims. Amlodipine reduced the risk of gout by 37% (hazard ratio 0.63; 95% CI 0.51--0.78) compared with chlorthalidone and by 26% (hazard ratio 0.74; 95% CI 0.58--0.94) compared with lisinopril. Lisinopril nonsignificantly lowered gout risk compared with chlorthalidone (hazard ratio 0.85; 95% CI 0.70--1.03). Atenolol use was not associated with gout risk (adjusted hazard ratio 1.18; 95% CI 0.78--1.80). Gout risk reduction was primarily observed after 1 year of follow-up.ConclusionAmlodipine lowered long-term gout risk compared with lisinopril or chlorthalidone. This finding may be useful in cases where gout risk is a principal concern among patients being treated for hypertension.This trial is registered at clinicaltrials.gov, number: NCT00000542.
| S-EPMC7244334 | biostudies-literature
Project description:To determine whether an angiotensin-converting enzyme inhibitor (lisinopril) or calcium channel blocker (amlodipine) is superior to a diuretic (chlorthalidone) in reducing cardiovascular disease incidence in sex subgroups, we carried out a prespecified subgroup analysis of 15 638 women and 17 719 men in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Total follow-up (active treatment + passive surveillance using national administrative databases to ascertain deaths and hospitalizations) was 8 to 13 years. The primary outcome was fatal coronary heart disease or nonfatal myocardial infarction. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (coronary heart disease death, nonfatal myocardial infarction, stroke, angina, coronary revascularization, heart failure [HF], or peripheral vascular disease), and end-stage renal disease. In-trial rates of HF, stroke, and combined cardiovascular disease were significantly higher for lisinopril compared with chlorthalidone, and rates of HF were significantly higher for amlodipine compared with chlorthalidone in both men and women. There were no significant treatment sex interactions. These findings did not persist through the extension period with the exception of the HF result for amlodipine versus chlorthalidone, which did not differ significantly by sex. For both women and men, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary coronary heart disease outcome or any other cardiovascular disease outcome, and chlorthalidone-based treatment resulted in the lowest risk of HF. Neither lisinopril nor amlodipine is superior to chlorthalidone for initial treatment of hypertension in either women or men. Clinical Trial Registration- clinicaltrials.gov; Identifier: NCT00000542.
| S-EPMC4114223 | biostudies-literature
Project description:Thiazide-type diuretics have been recommended for initial treatment of hypertension in most patients, but should this recommendation differ for patients with and without coronary heart disease (CHD)? The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind hypertension treatment trial in 42,418 participants with high risk of combined cardiovascular disease (CVD) (25% with preexisting CHD). This post hoc analysis compares long-term major clinical outcomes in those assigned amlodipine (n = 9048) or lisinopril (n = 9,054) with those assigned chlorthalidone (n = 15,255), stratified by CHD status. After 4 to 8 years, randomized treatment was discontinued. Total follow-up (active treatment + passive surveillance using national databases for deaths and hospitalizations) was 8 to 13 years. For most CVD outcomes, end-stage renal disease, and total mortality, there were no differences across randomized treatment arms regardless of baseline CHD status. In-trial rates of CVD were significantly higher for lisinopril compared with chlorthalidone, and rates of heart failure were significantly higher for amlodipine compared with chlorthalidone in those with and without CHD (overall hazard ratios [HRs] 1.10, p <0.001, and 1.38, p <0.001, respectively). During extended follow-up, significant outcomes according to CHD status interactions (p = 0.012) were noted in amlodipine versus chlorthalidone comparison for CVD and CHD mortality (HR 0.88, p = 0.04, and 0.84, p = 0.04, respectively) in those with CHD at baseline (HR 1.06, p = 0.15, and 1.08, p = 0.17) and in those without. The results of the overall increased stroke mortality in lisinopril compared with chlorthalidone (HR 1.2; p = 0.03) and hospitalized heart failure in amlodipine compared with chlorthalidone (HR 1.12; p = 0.01) during extended follow-up did not differ by baseline CHD status. In conclusion, these results provide no reason to alter our previous recommendation to include a properly dosed diuretic (such as chlorthalidone 12.5 to 25 mg/day) in the initial antihypertensive regimen for most hypertensive patients.
| S-EPMC4690772 | biostudies-literature