scholarly journals Cluster Analysis of Cardiovascular Phenotypes in Patients With Type 2 Diabetes and Established Atherosclerotic Cardiovascular Disease: A Potential Approach to Precision Medicine

2021 ◽  
Author(s):  
Abhinav Sharma ◽  
Yinggan Zheng ◽  
Justin A. Ezekowitz ◽  
Cynthia M. Westerhout ◽  
Jacob A. Udell ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cluster Analysis ◽  
Proportional Hazards ◽  
Cardiovascular Death ◽  
Cox Proportional Hazards ◽  
Machine Learning Algorithms ◽  
Atherosclerotic Cardiovascular Disease ◽  
Asian Patients

<b>Objective:</b> Phenotypic heterogeneity among patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) is ill defined.<b> </b>We used cluster analysis machine learning algorithms to identify phenotypes among trial participants with T2DM and ASCVD. <p><b>Research Design and Methods:</b><i> </i>We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n=14,671), a cardiovascular outcome safety trial comparing sitagliptin with placebo in patients with T2DM and ASCVD (median follow-up 3.0 years). Cluster analysis using 40 baseline variables was conducted, with associations between clusters and the primary composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina) assessed by Cox proportional hazards models. We replicated the results using the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial.</p> <p><b>Results:</b><i> </i>Four distinct phenotypes were identified: cluster I included Caucasian men with a high prevalence of coronary artery disease; cluster II included Asian patients with a low body mass index; cluster III included women with non-coronary ASCVD disease; and cluster IV included patients with heart failure and kidney dysfunction. The primary outcome occurred respectively in 11.6%, 8.6%, 10.3%, and 16.8% of patients in clusters I to IV. The crude difference in cardiovascular risk for the highest versus lowest risk cluster (cluster IV vs. II) was statistically significant (HR, 2.74; 95% CI, 2.29-3.29). Similar phenotypes and outcomes were identified in EXSCEL. </p> <p><b>Conclusions:</b><i> </i>In patients with T2DM and ASCVD, cluster analysis identified four clinically distinct groups. Further cardiovascular phenotyping is warranted to inform patient care and optimize clinical trial designs.</p>

scholarly journals Cluster Analysis of Cardiovascular Phenotypes in Patients With Type 2 Diabetes and Established Atherosclerotic Cardiovascular Disease: A Potential Approach to Precision Medicine

2021 ◽  
Author(s):  
Abhinav Sharma ◽  
Yinggan Zheng ◽  
Justin A. Ezekowitz ◽  
Cynthia M. Westerhout ◽  
Jacob A. Udell ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cluster Analysis ◽  
Proportional Hazards ◽  
Cardiovascular Death ◽  
Cox Proportional Hazards ◽  
Machine Learning Algorithms ◽  
Atherosclerotic Cardiovascular Disease ◽  
Asian Patients

<b>Objective:</b> Phenotypic heterogeneity among patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) is ill defined.<b> </b>We used cluster analysis machine learning algorithms to identify phenotypes among trial participants with T2DM and ASCVD. <p><b>Research Design and Methods:</b><i> </i>We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n=14,671), a cardiovascular outcome safety trial comparing sitagliptin with placebo in patients with T2DM and ASCVD (median follow-up 3.0 years). Cluster analysis using 40 baseline variables was conducted, with associations between clusters and the primary composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina) assessed by Cox proportional hazards models. We replicated the results using the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial.</p> <p><b>Results:</b><i> </i>Four distinct phenotypes were identified: cluster I included Caucasian men with a high prevalence of coronary artery disease; cluster II included Asian patients with a low body mass index; cluster III included women with non-coronary ASCVD disease; and cluster IV included patients with heart failure and kidney dysfunction. The primary outcome occurred respectively in 11.6%, 8.6%, 10.3%, and 16.8% of patients in clusters I to IV. The crude difference in cardiovascular risk for the highest versus lowest risk cluster (cluster IV vs. II) was statistically significant (HR, 2.74; 95% CI, 2.29-3.29). Similar phenotypes and outcomes were identified in EXSCEL. </p> <p><b>Conclusions:</b><i> </i>In patients with T2DM and ASCVD, cluster analysis identified four clinically distinct groups. Further cardiovascular phenotyping is warranted to inform patient care and optimize clinical trial designs.</p>

scholarly journals Association Between Change in Accelerometer-Measured and Self-Reported Physical Activity and Cardiovascular Disease in the Look AHEAD Trial

2022 ◽  
Author(s):  
John M. Jakicic ◽  
Robert I. Berkowitz ◽  
Paula Bolin ◽  
George A. Bray ◽  
Jeanne M. Clark ◽  
...  
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Proportional Hazards ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Self Report ◽  
Look Ahead ◽  
The Look

OBJECTIVE: To conduct <i>post-hoc</i> secondary analysis examining the association between change in physical activity (PA), measured with self-report and accelerometry, from baseline to 1 and 4 years and cardiovascular disease (CVD) outcomes in the Look AHEAD Trial. <p>RESEARCH DESIGN AND METHODS: Participants were adults with overweight/obesity and type 2 diabetes with PA data at baseline and year 1 or 4 (n = 1,978). Participants were randomized to diabetes support and education or intensive lifestyle intervention. Measures included accelerometry-measured moderate-to-vigorous PA (MVPA), self-reported PA, and composite (morbidity and mortality) CVD outcomes.</p> <p>RESULTS: In pooled analyses of all participants, using Cox proportional hazards models, each 100 MET-min/wk increase in accelerometry-measured MVPA from baseline to 4 years was associated with decreased risk of the subsequent primary composite outcome of CVD. Results were consistent for changes in total MVPA [HR=0.97 (95% CI: 0.95, 0.99)] and MVPA accumulated in <u>></u>10-minute bouts [HR=0.95 (95% CI: 0.91, 0.98)], with a similar pattern for secondary CVD outcomes. Change in accelerometry-measured MVPA at 1 year and self-reported change in PA at 1 and 4 years were not associated with CVD outcomes.</p> <p>CONCLUSIONS: Increased accelerometry-measured MVPA from baseline to year 4 is associated with decreased risk of CVD outcomes. This suggests the need for long-term engagement in MVPA to reduce the risk of CVD in adults with overweight/obesity and type 2 diabetes.</p>

scholarly journals Empagliflozin and Cardiovascular and Kidney Outcomes across KDIGO Risk Categories

2020 ◽  
Vol 15 (10) ◽  
pp. 1433-1444 ◽  
Author(s):  
Adeera Levin ◽  
Vlado Perkovic ◽  
David C. Wheeler ◽  
Stefan Hantel ◽  
Jyothis T. George ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Standard Of Care ◽  
Cardiovascular Death ◽  
Outcome Data ◽  
Atherosclerotic Cardiovascular Disease ◽  
Clinical Trial Registry ◽  
Treatment Benefit ◽  
Risk Categories

Background and objectivesIn the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG Outcome), empagliflozin, in addition to standard of care, significantly reduced risk of cardiovascular death by 38%, hospitalization for heart failure by 35%, and incident or worsening nephropathy by 39% compared with placebo in patients with type 2 diabetes and established cardiovascular disease. Using EMPA-REG Outcome data, we assessed whether the Kidney Disease Improving Global Outcomes (KDIGO) CKD classification had an influence on the treatment effect of empagliflozin.Design, setting, participants, & measurementsPatients with type 2 diabetes, established atherosclerotic cardiovascular disease, and eGFR≥30 ml/min per 1.73 m2 at screening were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily in addition to standard of care. Post hoc, we analyzed cardiovascular and kidney outcomes, and safety, using the two-dimensional KDIGO classification framework.ResultsOf 6952 patients with baseline eGFR and urinary albumin-creatinine ratio values, 47%, 29%, 15%, and 8% were classified into low, moderately increased, high, and very high KDIGO risk categories, respectively. Empagliflozin showed consistent risk reductions across KDIGO categories for cardiovascular outcomes (P values for treatment by subgroup interactions ranged from 0.26 to 0.85) and kidney outcomes (P values for treatment by subgroup interactions ranged from 0.16 to 0.60). In all KDIGO risk categories, placebo and empagliflozin had similar adverse event rates, the notable exception being genital infection events, which were more common with empagliflozin for each category.ConclusionsThe observed effects of empagliflozin versus placebo on cardiovascular and kidney outcomes were consistent across the KDIGO risk categories, indicating that the effect of treatment benefit of empagliflozin was unaffected by baseline CKD status.Clinical Trial registry name and registration number:EMPA-REG OUTCOME, NCT01131676

scholarly journals Association Between Change in Accelerometer-Measured and Self-Reported Physical Activity and Cardiovascular Disease in the Look AHEAD Trial

2022 ◽  
Author(s):  
John M. Jakicic ◽  
Robert I. Berkowitz ◽  
Paula Bolin ◽  
George A. Bray ◽  
Jeanne M. Clark ◽  
...  
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Proportional Hazards ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Self Report ◽  
Look Ahead ◽  
The Look

OBJECTIVE: To conduct <i>post-hoc</i> secondary analysis examining the association between change in physical activity (PA), measured with self-report and accelerometry, from baseline to 1 and 4 years and cardiovascular disease (CVD) outcomes in the Look AHEAD Trial. <p>RESEARCH DESIGN AND METHODS: Participants were adults with overweight/obesity and type 2 diabetes with PA data at baseline and year 1 or 4 (n = 1,978). Participants were randomized to diabetes support and education or intensive lifestyle intervention. Measures included accelerometry-measured moderate-to-vigorous PA (MVPA), self-reported PA, and composite (morbidity and mortality) CVD outcomes.</p> <p>RESULTS: In pooled analyses of all participants, using Cox proportional hazards models, each 100 MET-min/wk increase in accelerometry-measured MVPA from baseline to 4 years was associated with decreased risk of the subsequent primary composite outcome of CVD. Results were consistent for changes in total MVPA [HR=0.97 (95% CI: 0.95, 0.99)] and MVPA accumulated in <u>></u>10-minute bouts [HR=0.95 (95% CI: 0.91, 0.98)], with a similar pattern for secondary CVD outcomes. Change in accelerometry-measured MVPA at 1 year and self-reported change in PA at 1 and 4 years were not associated with CVD outcomes.</p> <p>CONCLUSIONS: Increased accelerometry-measured MVPA from baseline to year 4 is associated with decreased risk of CVD outcomes. This suggests the need for long-term engagement in MVPA to reduce the risk of CVD in adults with overweight/obesity and type 2 diabetes.</p>

Abstract MP35: Discordant Visceral and Liver Fat Phenotypes are Differentially Associated With Incident Cardiovascular Disease and Type 2 Diabetes

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Sanaa Tejani
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Health Outcomes ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Liver Fat ◽  
Cardiometabolic Health ◽  
Study Cohort ◽  
Incident Cardiovascular Disease

Background: Visceral adipose tissue (VAT) and ectopic liver fat (ELF) are linked with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) but little is known about their joint associations when they are discordant in an individual. Objective and Hypothesis: This study aims to evaluate cardiometabolic health outcomes associated with discordant VAT-ELF phenotypes in a multi-ethnic, population-based cohort of adults. We hypothesized that high VAT-low ELF, but not low VAT-high ELF, would be associated with incident cardiovascular disease, but both would be associated with incident T2DM. Methods: Participants of the Dallas Heart Study with no history of CVD or T2DM had assessments of VAT and ELF by MRI and MRS, respectively, between 2000 and 2002 and were followed for a median (IQR) of 12.0 (11.5-12.7) years for the incidence of CVD or T2DM. Associations between VAT-ELF phenotypes (high/low based on sex- and race-specific median values) and outcomes were evaluated using multivariable adjusted Cox proportional hazards and logistic regression models, as appropriate. Results: The study cohort included 1731 participants (mean age 43, 54% female, 44% black, 18% Hispanic, 41% obese). 128 (7.4%) participants had incident CVD and 95 (5.5%) had incident T2DM during follow-up. In unadjusted models, those with high VAT-low ELF had the highest hazard for CVD ( Table ), but associations were attenuated after multivariable adjustment. In both unadjusted and adjusted models, high VAT and/or high ELF phenotypes were associated with T2DM, with the high VAT-high ELF phenotype demonstrating the highest odds for T2DM ( Table ). Conclusions: In conclusion, we found that the heterogeneous manifestations of abdominal obesity impact cardiometabolic health outcomes. Elevated liver fat in the presence of low or normal VAT is associated with incident T2DM but not CVD.

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