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

Diabetes Care ◽  
2021 ◽  
pp. dc202806
Author(s):  
Abhinav Sharma ◽  
Yinggan Zheng ◽  
Justin A. Ezekowitz ◽  
Cynthia M. Westerhout ◽  
Jacob A. Udell ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cluster Analysis ◽  
Precision Medicine ◽  
Atherosclerotic Cardiovascular Disease ◽  
Potential Approach

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>

Abstract 15004: Bariatric Surgery is Associated With Reduced Atherosclerotic Cardiovascular Disease Burden in Obese Patients With Type 2 Diabetes: A Propensity-matched Cohort Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Francesca Watson ◽  
Maddalena Ardissino ◽  
Ravi J Amin ◽  
Chanpreet Arhi ◽  
Peter Collins ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Bariatric Surgery ◽  
Disease Burden ◽  
Atherosclerotic Cardiovascular Disease ◽  
Obese Patients ◽  
Matched Cohort ◽  
All Cause Mortality

Introduction: Obesity is an increasingly prevalent global health issue and has a considerable disease burden, including numerous co-morbidities. Atherosclerotic cardiovascular disease (ASCVD) is one such co-morbidity associated with a high mortality rate and prevalence, especially in patients with obesity and concomitant Type 2 diabetes mellitus (T2DM). Bariatric surgery is an effective intervention for patients with obesity, shown to reduce overall cardiovascular disease risk. However, few studies have quantified the long-term impact of bariatric surgery on ASCVD outcomes in the context of key co-morbidities such as T2DM. Hypothesis: Bariatric surgery will improve long-term ASCVD outcomes in obese patients with T2DM. Methods: A nested, nationwide, propensity-matched cohort study was carried out using the Clinical Practice Research Datalink. The study cohort included 593 patients who underwent bariatric surgery and had no past history of ASCVD. A further 593 patients served as propensity-score matched controls. Patients were followed up for a median time of 47.2 months. The primary composite study endpoint was the incidence of ASCVD defined by a diagnosis of new coronary artery disease (CAD), cerebrovascular disease (CeVD), peripheral arterial disease (PAD), or other miscellaneous atherosclerotic disease. Secondary endpoints included all-cause mortality and the incidence of CAD, CeVD, and PAD individually. Results: Patients who underwent bariatric surgery had significantly lower rates of new ASCVD during follow-up (HR 0.53, CI 0.30-0.95, p=0.032). No significant difference was observed in rates of new CAD (HR 0.69, CI 0.32-1.46, p=0.331), CeVD (HR 0.23, CI 0.00-5.45, p=0.1760) and PAD (HR 0.55, CI 0.21-1.43, p=0.218). The bariatric surgery group also had a lower rate of all-cause mortality (HR 0.36, CI 0.19-0.71, p=0.003) compared to controls. Conclusions: In this study, bariatric surgery was associated with improved ASCVD outcomes, as well as lower all-cause mortality, in patients with obesity and T2DM. These findings support the use of bariatric surgery in treating obesity and reducing the burden of its related comorbidities.

scholarly journals Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Kausik K. Ray ◽  
Stefano Del Prato ◽  
Dirk Müller-Wieland ◽  
Bertrand Cariou ◽  
Helen M. Colhoun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Open Label ◽  
Double Blind ◽  
Mixed Dyslipidemia

Abstract Background Individuals with diabetes often have high levels of atherogenic lipoproteins and cholesterol reflected by elevated low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and LDL particle number (LDL-PN). The presence of atherosclerotic cardiovascular disease (ASCVD) increases the risk of future cardiovascular events. We evaluated the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, among individuals with type 2 diabetes (T2DM), high LDL-C or non-HDL-C, and established ASCVD receiving maximally tolerated statin in ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) and DM-INSULIN (NCT02585778). Methods In DM-DYSLIPIDEMIA, individuals with T2DM and mixed dyslipidemia (non-HDL-C ≥ 100 mg/dL; n = 413) were randomized to open-label alirocumab 75 mg every 2 weeks (Q2W) or usual care (UC) for 24 weeks, with UC options selected before stratified randomization. In DM-INSULIN, insulin-treated individuals with T2DM (LDL-C ≥ 70 mg/dL; n = 441) were randomized in a double-blind fashion to alirocumab 75 mg Q2W or placebo for 24 weeks. Study participants also had a glycated hemoglobin < 9% (DM-DYSLIPIDEMIA) or < 10% (DM-INSULIN). Alirocumab dose was increased to 150 mg Q2W at week 12 if week 8 LDL-C was ≥ 70 mg/dL (DM-INSULIN) or non-HDL-C was ≥ 100 mg/dL (DM-DYSLIPIDEMIA). Lipid reductions and safety were assessed in patients with ASCVD from these studies. Results This analysis included 142 DM-DYSLIPIDEMIA and 177 DM-INSULIN participants with ASCVD, including 95.1% and 86.4% with coronary heart disease, and 32.4% and 49.7% with microvascular diabetes complications, respectively. At week 24, alirocumab significantly reduced LDL-C, non-HDL-C, ApoB, and LDL-PN from baseline versus control. This translated into a greater proportion of individuals achieving non-HDL-C < 100 mg/dL (64.6% alirocumab/23.8% UC [DM-DYSLIPIDEMIA]; 65.4% alirocumab/14.9% placebo [DM-INSULIN]) and ApoB < 80 mg/dL (75.1% alirocumab/35.4% UC and 76.8% alirocumab/24.8% placebo, respectively) versus control at week 24 (all P < 0.0001). In pooling these studies, 66.4% (alirocumab) and 67.0% (control) of individuals reported treatment-emergent adverse events. The adverse event pattern was similar with alirocumab versus controls. Conclusions Among individuals with T2DM and ASCVD who had high non-HDL-C/LDL-C levels despite maximally tolerated statin, alirocumab significantly reduced atherogenic cholesterol and LDL-PN versus control. Alirocumab was generally well tolerated. Trial registration Clinicaltrials.gov. NCT02642159. Registered 30 December 2015 and Clinicaltrials.gov. NCT02585778. Registered 23 October 2015

scholarly journals Metabolic syndrome in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a post hoc analyses of the EMPA-REG OUTCOME trial

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
João Pedro Ferreira ◽  
Subodh Verma ◽  
David Fitchett ◽  
Anne Pernille Ofstad ◽  
Sabine Lauer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Trial Registration ◽  
World Health ◽  
Atherosclerotic Cardiovascular Disease ◽  
Renal Outcomes ◽  
Outcome Trial

Abstract Background Patients with type 2 diabetes (T2D) and metabolic syndrome (MetS) are at greater cardiovascular risk than those with T2D without MetS. In the current report we aim to study the characteristics, cardio-renal outcomes and the effect of empagliflozin in patients with MetS enrolled in the EMPA-REG OUTCOME trial. Methods A total of 7020 patients with T2D and atherosclerotic cardiovascular disease were treated with empagliflozin (10 mg or 25 mg) or placebo for a median of 3.1 years. The World Health Organization MetS criteria could be determined for 6985 (99.5%) patients. We assessed the association between baseline MetS and multiple cardio-renal endpoints using Cox regression models, and we studied the change in the individual component over time of the MetS using mixed effect models. Results MetS at baseline was present in 5740 (82%) patients; these were more often white and had more often albuminuria and heart failure, had lower eGFR and HDL-cholesterol, and higher blood pressure, body mass index, waist circumference, and triglycerides. In the placebo group, patients with MetS had a higher risk of all outcomes including cardiovascular death: HR = 1.73 (95% CI 1.01–2.98), heart failure hospitalization: HR = 2.64 (95% CI 1.22, 5.72), and new or worsening nephropathy: HR = 3.11 (95% CI 2.17–4.46). The beneficial effect of empagliflozin was consistent on all cardio-renal outcomes regardless of presence of MetS. Conclusions A large proportion of the EMPA-REG OUTCOME population fulfills the criteria for MetS. Those with MetS had increased risk of adverse cardio-renal outcomes. Compared with placebo, empagliflozin improved cardio-renal outcomes in patients with and without MetS. Trial registration Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT 01131676

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