Action to Control Cardiovascular Risk in Diabetes (ACCORD) Clinical Trial
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PROVIDER: PRJNA394548 | ENA |
REPOSITORIES: ENA
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Project description:Action to Control Cardiovascular Risk in Diabetes (ACCORD - Imaging)
| PRJNA1079426 | ENA
Project description:Action to Control Cardiovascular Risk in Diabetes (ACCORD - Imaging)
| PRJNA1079425 | ENA
Project description:Action to Control Cardiovascular Risk in Diabetes (ACCORD-BioLINCC)
| PRJNA1075472 | ENA
Project description:<p>The Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial was a randomized, multicenter, double 2 x 2 factorial design study involving 10,251 middle-aged and older participants with type-2 diabetes who are at high risk for CVD events because of existing CVD or additional risk factors. The purpose of ACCORD was to determine if intensive glycemic control, intensive lipid management and intensive blood pressure control could prevent major cardiovascular events (myocardial infarction, stroke or cardiovascular death) in adults with type 2 diabetes mellitus. Secondary hypotheses included treatment differences in other cardiovascular outcomes, total mortality, microvascular outcomes, health-related quality of life and cost-effectiveness.</p> <p>The ACCORD trial failed to show a beneficial effect of intensive blood pressure or lipid therapy on the primary outcome, and intensive glycemia management actually increased mortality. The hypothesis underlying this ancillary study is that the failure of ACCORD to achieve its goal of reducing cardiovascular risk in diabetic patients through intensive management of hyperglycemia, dyslipidemia, and hypertension may be the result of variation in drug response due to genetic variation between individual participants. Benefits of intensive therapy may accrue to subsets of subjects with specific genetic variants predisposing to efficacious responses to particular therapeutic regimens, and harms may accrue to those with other variants predisposing to poor efficacy or adverse events. Identifying these variants could lead to a precision medicine approach to treating diabetes where each patient's genetic profile could identify the most efficacious treatment regimen with the lowest likelihood of adverse events. To test this hypothesis, a genome-wide genetic analysis was undertaken, incorporating both common variants distributed across the genome and rare variants targeted to exonic regions. Associations of genetic variants with short term responses to individual medicines as well as long term outcomes were investigated.</p> <p>The dataset is composed of genetic data from the ~6100 participants who agreed to participate in the ACCORD optional genetic studies and who allowed broad investigator access to their samples and the data derived from those samples, and from whom a DNA sample of sufficient quality was obtained. While a total of 8514 participants consented to the optional genetics studies, not all consented to broad investigator access, and those who did not are not included in this dataset, although they were also genotyped. Access to these additional genotypes can only be obtained by direct collaboration with the investigators of this study. Phenotype data used in the association analyses are derived from the ACCORD public release clinical data set, which has been made available through <a href="https://biolincc.nhlbi.nih.gov/studies/accord/">BioLINCC</a>.</p>
| phs001411 | dbGaP
Project description:Action to Control Cardiovascular Risk in Diabetes (ACCORD) Clinical Trial
| PRJNA394549 | ENA
Project description:ObjectiveIntensive therapy targeting normal blood glucose increased mortality compared with standard treatment in a randomized clinical trial of 10,251 participants with type 2 diabetes at high-risk for cardiovascular disease (CVD) events. We evaluated whether the presence of cardiac autonomic neuropathy (CAN) at baseline modified the effect of intensive compared with standard glycemia treatment on mortality outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants.Research design and methodsCAN was assessed by measures of heart rate variability (HRV) and QT index (QTI) computed from 10-s resting electrocardiograms in 8,135 ACCORD trial participants with valid measurements (mean age 63.0 years, 40% women). Prespecified CAN definitions included a composite of the lowest quartile of HRV and highest QTI quartile in the presence or absence of peripheral neuropathy. Outcomes were all-cause and CVD mortality. Associations between CAN and mortality were evaluated by proportional hazards analysis, adjusting for treatment group allocation, CVD history, and multiple prespecified baseline covariates.ResultsDuring a mean 3.5 years follow-up, there were 329 deaths from all causes. In fully adjusted analyses, participants with baseline CAN were 1.55-2.14 times as likely to die as participants without CAN, depending on the CAN definition used (P < 0.02 for all). The effect of allocation to the intensive group on all-cause and CVD mortality was similar in participants with or without CAN at baseline (P(interaction) > 0.7).ConclusionsWhereas CAN was associated with increased mortality in this high-risk type 2 diabetes cohort, these analyses indicate that participants with CAN at baseline had similar mortality outcomes from intensive compared with standard glycemia treatment in the ACCORD cohort.
| S-EPMC2890362 | biostudies-literature
Project description:BackgroundGreater lipid variability may cause adverse health events among diabetic patients. We aimed to examine the effect of lipid variability on the risk of diabetic microvascular outcomes among type 2 diabetes mellitus patients.MethodsWe assessed the association between visit-to-visit variability (measured by variability independent of mean) in high-density lipoprotein (HDL) cholesterol, low-density lipoprotein-cholesterol (LDL), triglyceride, and remnant cholesterol (RC) measurements among participants involved in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and the risk of incident microvascular outcomes, including nephropathy, neuropathy, and retinopathy. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for potential confounders.ResultsThere were 2400, 2470, and 2468 cases of nephropathy, neuropathy, and retinopathy during a follow-up period of 22 600, 21 542, and 26 701 person-years, respectively. Higher levels of HDL, triglyceride, and RC variability were associated with an increased risk of incident nephropathy and neuropathy. Compared with the lowest quartile, the fully adjusted HRs (95% CI) for the highest quartile of HDL, triglyceride, and RC variability for nephropathy risk were 1.57 (1.22, 2.01), 1.50 (1.18, 1.92), and 1.40 (1.09, 1.80), respectively; and for neuropathy, the corresponding risks were 1.36 (1.05, 1.75), 1.47 (1.14, 1.91), and 1.35 (1.04, 1.74), respectively. Null association was observed between LDL variability and all microvascular complications. Additionally, all associations of variability in the other lipids with retinopathy risk were null.ConclusionAmong individuals with type 2 diabetes mellitus, HDL, triglyceride, and RC variability were associated with increased risks of nephropathy and neuropathy but not retinopathy.Trial registrationClinicalTrials.gov., no. NCT00000620.
| S-EPMC9366577 | biostudies-literature
Project description:Orthostatic hypotension (OH) is associated with hypertension and diabetes mellitus. However, in populations with both hypertension and diabetes mellitus, its prevalence, the effect of intensive versus standard systolic blood pressure (BP) targets on incident OH, and its prognostic significance are unclear. In 4266 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial, seated BP was measured 3×, followed by readings every minute for 3 minutes after standing. Orthostatic BP change, calculated as the minimum standing minus the mean seated systolic BP and diastolic BP, was assessed at baseline, 12 months, and 48 months. The relationship between OH and clinical outcomes (total and cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization or death and the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) was assessed using proportional hazards analysis. Consensus OH, defined by orthostatic decline in systolic BP ?20 mm?Hg or diastolic BP ?10 mm?Hg, occurred at ?1 time point in 20% of participants. Neither age nor systolic BP treatment target (intensive, <120 mm?Hg versus standard, <140 mm?Hg) was related to OH incidence. Over a median follow-up of 46.9 months, OH was associated with increased risk of total death (hazard ratio, 1.61; 95% confidence interval, 1.11-2.36) and heart failure death/hospitalization (hazard ratio, 1.85, 95% confidence interval, 1.17-2.93), but not with the primary outcome or other prespecified outcomes. In patients with type 2 diabetes mellitus and hypertension, OH was common, not associated with intensive versus standard BP treatment goals, and predicted increased mortality and heart failure events.
| S-EPMC5016241 | biostudies-literature
Project description:SPRINT (Systolic Blood Pressure Intervention Trial) and the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial used similar interventions but produced discordant results. We investigated whether differences in systolic blood pressure (SBP) response contributed to the discordant trial results.We evaluated the distributions of SBP response during the first year for the intensive and standard treatment groups of SPRINT and ACCORD using growth mixture models. We assessed whether significant differences existed between trials in the distributions of SBP achieved at 1 year and the treatment-independent relationships of achieved SBP with risks of primary outcomes defined in each trial, heart failure, stroke, and all-cause death. We examined whether visit-to-visit variability was associated with heterogeneous treatment effects. Among the included 9027 SPRINT and 4575 ACCORD participants, the difference in mean SBP achieved between treatment groups was 15.7 mm Hg in SPRINT and 14.2 mm Hg in ACCORD, but SPRINT had significantly less between-group overlap in the achieved SBP (standard deviations of intensive and standard groups, respectively: 6.7 and 5.9 mm Hg in SPRINT versus 8.8 and 8.2 mm Hg in ACCORD; P<0.001). The relationship between achieved SBP and outcomes was consistent across trials except for stroke and all-cause death. Higher visit-to-visit variability was more common in SPRINT but without treatment-effect heterogeneity.SPRINT and ACCORD had different degrees of separation in achieved SBP between treatment groups, even as they had similar mean differences. The greater between-group overlap of achieved SBP may have contributed to the discordant trial results.
| S-EPMC5721802 | biostudies-other
Project description:The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial reported no differences in most cardiovascular disease (CVD) outcomes between intensive and standard blood pressure therapy in individuals with diabetes mellitus (DM) and hypertension. Many such individuals are centrally obese. Here we evaluate whether the trial outcomes varied by the level of central obesity.The cohort included 4,687 people (47.7% women) with DM and hypertension. Mean age was 62.2, and mean follow-up was 4.7 years. Participants were randomly assigned to one of two blood pressure treatment strategies: intensive (systolic <120 mmHg) or standard (systolic <140 mmHg). Sex-specific quartiles of waist-to-height ratio were used as the measure of central obesity. The primary ACCORD outcome (a composite of nonfatal myocardial infarction [MI], nonfatal stroke, or CVD death) and three secondary outcomes (nonfatal MI, fatal or nonfatal stroke, and CVD death) were examined using proportional hazard models.There was no evidence that the effect of intensively lowering blood pressure differed by quartile of waist-to-height ratio for any of the four outcomes (P > 0.25 in all cases). Controlling for waist-to-height quartile had no significant impact on previously published results for intensive blood pressure therapy. Waist-to-height ratio was significantly related to CVD mortality (hazard ratio 2.32 [95% CI 1.40-3.83], P = 0.0009 comparing the heaviest to lightest quartiles), but not to the other outcomes (P > 0.09 in all cases).Intensive lowering of blood pressure versus standard treatment does not ameliorate CVD risk in individuals with DM and hypertension. These results did not vary by quartile of waist-to-height ratio.
| S-EPMC3379577 | biostudies-literature