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Long-term effects of incident diabetes mellitus on cardiovascular outcomes in people treated for hypertension: the ALLHAT Diabetes Extension Study.

ABSTRACT: Thiazide-type diuretics are associated with an increased incidence of diabetes compared with other antihypertensive medications. In this study, we determined the long-term cardiovascular disease (CVD) consequences of incident diuretic-associated diabetes compared with the effects of incident diabetes associated with calcium channel blocker and angiotensin-converting enzyme inhibitor use.A total of 22 418 participants from the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with baseline diabetes, incident diabetes (7.5% with chlorthalidone, 5.6% with amlodipine, and 4.3% with lisinopril), or no diabetes at 2 years of in-trial follow-up were followed for a mean total of 6.9 years (2.9 years in-trial and 4 additional years posttrial) through the use of national databases. The primary outcome was CVD mortality (death from coronary heart disease [CHD], stroke, heart failure, or other CVD). Among other outcomes were all-cause mortality, non-CVD mortality, and CHD (nonfatal myocardial infarction or fatal CHD). Participants on chlorthalidone with incident diabetes versus no diabetes had consistently lower, nonsignificant risk for CVD mortality (hazard ratio [HR], 1.04; 95% CI, 0.74-1.47), all-cause mortality (HR, 1.04; 95% CI, 0.82-1.30), and non-CVD mortality (HR, 1.05; 95% CI, 0.77-1.42) than participants on amlodipine or lisinopril with incident diabetes (HR range, 1.22-1.53). Participants with incident diabetes had elevated CHD risk compared with those with no diabetes (HR, 1.46; 95% CI, 1.09-1.96), but those on chlorthalidone had significantly lower risk than those on lisinopril (HR, 1.18 versus 2.57; P=0.04 for interaction).The findings suggest that thiazide-related incident diabetes has less adverse long-term CVD impact than incident diabetes that develops while on other antihypertensive medications.

SUBMITTER: Barzilay JI

PROVIDER: S-EPMC3359874 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Long-term effects of incident diabetes mellitus on cardiovascular outcomes in people treated for hypertension: the ALLHAT Diabetes Extension Study.

Barzilay Joshua I JI Davis Barry R BR Pressel Sara L SL Cutler Jeffrey A JA Einhorn Paula T PT Black Henry R HR Cushman William C WC Ford Charles E CE Margolis Karen L KL Moloo Jamaluddin J Oparil Suzanne S Piller Linda B LB Simmons Debra L DL Sweeney Mary Ellen ME Whelton Paul K PK Wong Nathan D ND Wright Jackson T JT

Circulation. Cardiovascular quality and outcomes 20120306 2

<h4>Background</h4>Thiazide-type diuretics are associated with an increased incidence of diabetes compared with other antihypertensive medications. In this study, we determined the long-term cardiovascular disease (CVD) consequences of incident diuretic-associated diabetes compared with the effects of incident diabetes associated with calcium channel blocker and angiotensin-converting enzyme inhibitor use.<h4>Methods and results</h4>A total of 22 418 participants from the ALLHAT (Antihypertensiv ...[more]

PMID: 22396585

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Project description:BackgroundType 2 diabetes mellitus (T2D) confers a two- to three-fold increased risk of cardiovascular disease (CVD). However, the mechanisms underlying increased CVD risk among people with T2D are only partially understood. We hypothesized that a genetic association study among people with T2D at risk for developing incident cardiovascular complications could provide insights into molecular genetic aspects underlying CVD.MethodsFrom 16 studies of the Cohorts for Heart & Aging Research in Genomic Epidemiology (CHARGE) Consortium, we conducted a multi-ancestry time-to-event genome-wide association study (GWAS) for incident CVD among people with T2D using Cox proportional hazards models. Incident CVD was defined based on a composite of coronary artery disease (CAD), stroke, and cardiovascular death that occurred at least one year after the diagnosis of T2D. Cohort-level estimated effect sizes were combined using inverse variance weighted fixed effects meta-analysis. We also tested 204 known CAD variants for association with incident CVD among patients with T2D.ResultsA total of 49,230 participants with T2D were included in the analyses (31,118 European ancestries and 18,112 non-European ancestries) which consisted of 8,956 incident CVD cases over a range of mean follow-up duration between 3.2 and 33.7 years (event rate 18.2%). We identified three novel, distinct genetic loci for incident CVD among individuals with T2D that reached the threshold for genome-wide significance (P<5.0×10-8): rs147138607 (intergenic variant between CACNA1E and ZNF648) with a hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.15 - 1.32, P=3.6×10-9, rs11444867 (intergenic variant near HS3ST1) with HR 1.89, 95% CI 1.52 - 2.35, P=9.9×10-9, and rs335407 (intergenic variant between TFB1M and NOX3) HR 1.25, 95% CI 1.16 - 1.35, P=1.5×10-8. Among 204 known CAD loci, 32 were associated with incident CVD in people with T2D with P<0.05, and 5 were significant after Bonferroni correction (P<0.00024, 0.05/204). A polygenic score of these 204 variants was significantly associated with incident CVD with HR 1.14 (95% CI 1.12 - 1.16) per 1 standard deviation increase (P=1.0×10-16).ConclusionsThe data point to novel and known genomic regions associated with incident CVD among individuals with T2D.

Project description:BackgroundEvidence is limited regarding the impact of healthy lifestyle practices on the risk of subsequent cardiovascular events among patients with diabetes.ObjectivesThe purpose of this study was to examine the associations of an overall healthy lifestyle, defined by eating a high-quality diet (top two-fifths of Alternative Healthy Eating Index), nonsmoking, engaging in moderate- to vigorous-intensity physical activity (≥150 min/week), and drinking alcohol in moderation (5 to 15 g/day for women and 5 to 30 g/day for men), with the risk of developing cardiovascular disease (CVD) and CVD mortality among adults with type 2 diabetes (T2D).MethodsThis prospective analysis included 11,527 participants with T2D diagnosed during follow-up (8,970 women from the Nurses' Health Study and 2,557 men from the Health Professionals Follow-Up Study), who were free of CVD and cancer at the time of diabetes diagnosis. Diet and lifestyle factors before and after T2D diagnosis were repeatedly assessed every 2 to 4 years.ResultsThere were 2,311 incident CVD cases and 858 CVD deaths during an average of 13.3 years of follow-up. After multivariate adjustment of covariates, the low-risk lifestyle factors after diabetes diagnosis were each associated with a lower risk of CVD incidence and CVD mortality. The multivariate-adjusted hazard ratios for participants with 3 or more low-risk lifestyle factors compared with 0 were 0.48 (95% confidence interval [CI]: 0.40 to 0.59) for total CVD incidence, 0.53 (95% CI: 0.42 to 0.66) for incidence of coronary heart disease, 0.33 (95% CI: 0.21 to 0.51) for stroke incidence, and 0.32 (95% CI: 0.22 to 0.47) for CVD mortality (all p trend <0.001). The population-attributable risk for poor adherence to the overall healthy lifestyle (<3 low-risk factors) was 40.9% (95% CI: 28.5% to 52.0%) for CVD mortality. In addition, greater improvements in healthy lifestyle factors from pre-diabetes to post-diabetes diagnosis were also significantly associated with a lower risk of CVD incidence and CVD mortality. For each number increment in low-risk lifestyle factors there was a 14% lower risk of incident total CVD, a 12% lower risk of coronary heart disease, a 21% lower risk of stroke, and a 27% lower risk of CVD mortality (all p < 0.001). Similar results were observed when analyses were stratified by diabetes duration, sex/cohort, body mass index at diabetes diagnosis, smoking status, and lifestyle factors before diabetes diagnosis.ConclusionsGreater adherence to an overall healthy lifestyle is associated with a substantially lower risk of CVD incidence and CVD mortality among adults with T2D. These findings further support the tremendous benefits of adopting a healthy lifestyle in reducing the subsequent burden of cardiovascular complications in patients with T2D.

Project description:AimsThis study aims to assess differences in severity of short-term (<1 year) and long-term (≥1 year) adverse CV outcomes after PCI in insulin-treated vs. non-insulin-treated diabetes mellitus (DM) patients.MethodsA systematic search on Pubmed and Embase led to the incorporation of 29 studies that compared post-percutaneous coronary interventional outcomes in insulin-treated and non-insulin-treated diabetes mellitus. Diabetes mellitus (type 2) was defined as fasting blood glucose (FBG) level of >7.0 mmol/L or with an oral glucose tolerance test (OGTT) level of >11.1 mmol/L at least on two separate occasions. Adverse CV outcomes were assessed in insulin-treated and non-insulin-treated DM after the PCI procedure considered for the analyses were mortality, MACE, TLR, TVR, MI, stent thrombosis, target lesion failure (TLF), and need for-post PCI CABG. Data were pooled and analyzed using Review Manager 5.3, and risk ratios (RR) with respective 95% confidence intervals (CI) were calculated.The statistical analyses were carried out by Review Manager v.5.3, and the data were pooled using a random-effects model. Risk ratios (RRs) with 95% confidence intervals (CI) were reported along with forest plots. The chi-square test was performed to assess for differences between the subgroups. Heterogeneity across studies was evaluated using Higgins I2 statistics. Visual inspection of the funnel plot and Begg's regression test were used to assess publication bias.ResultsA total of 40,527 patients (11742 in the Insulin-treated diabetes mellitus group and 28785 in the non-insulin-treated DM group) who underwent PCI were included. The pooled analysis of short-term follow up outcomes preceding PCI demonstrated a significantly higher risk of mortality (RR = 1.75 [1.24,2.47]; p = 0.002), MI (RR = 1.81[1.14,2.87]; p = 0.01], stent thrombosis (RR = 1.63[1.13, 2.35]; p = 0.009) and target lesion revascularization (TLR) (RR = 1.29[1.02,1.63]; p = 0.03) in insulin-treated DM patients. Similarly, analysis of long-term follow-up studies depicted a significantly higher risk mortality (RR = 1.55 [1.22, 1.97]; p = 0.0003), MI (RR = 1.63 [1.35, 1.97]; p=<0.00001), MACE (R = 1.47 [1.31, 1.65]; p=<0.00001), stent thrombosis (RR = 1.54 [1.19,1.99]; p = 0.001), TLR (RR = 1.40 [1.18, 1.66]; p = 0.0001), target vessel revascularization (TVR) (RR = 1.35 [1.11, 1.64]; p = 0.003) in insulin-treated DM group after PCI versus non-insulin-treated DM patients.ConclusionDespite a tremendous technical success rate of multi-vessel stenting, people living with diabetes who were being treated with insulin had higher long-term, and short-term mortality rates, MI, TLR, TVR, and stroke compared to people living with diabetes who were being treated with means other than insulin and are more prone to detrimental cardiovascular outcomes.

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Long-term effects of incident diabetes mellitus on cardiovascular outcomes in people treated for hypertension: the ALLHAT Diabetes Extension Study.

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Long-term effects of incident diabetes mellitus on cardiovascular outcomes in people treated for hypertension: the ALLHAT Diabetes Extension Study.

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