PMID- 36030198 OWN - NLM STAT- MEDLINE DCOM- 20220830 LR - 20221024 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 21 IP - 1 DP - 2022 Aug 27 TI - Development and validation of a model to predict cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease. PG - 166 LID - 10.1186/s12933-022-01603-8 [doi] LID - 166 AB - BACKGROUND: Among individuals with atherosclerotic cardiovascular disease (ASCVD), type 2 diabetes mellitus (T2DM) is common and confers increased risk for morbidity and mortality. Differentiating risk is key to optimize efficiency of treatment selection. Our objective was to develop and validate a model to predict risk of major adverse cardiovascular events (MACE) comprising the first event of cardiovascular death, myocardial infarction (MI), or stroke for individuals with both T2DM and ASCVD. METHODS: Using data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), we used Cox proportional hazards models to predict MACE among participants with T2DM and ASCVD. All baseline covariates collected in the trial were considered for inclusion, although some were excluded immediately because of large missingness or collinearity. A full model was developed using stepwise selection in each of 25 imputed datasets, and comprised candidate variables selected in 20 of the 25 datasets. A parsimonious model with a maximum of 10 degrees of freedom was created using Cox models with least absolute shrinkage and selection operator (LASSO), where the adjusted R-square was used as criterion for selection. The model was then externally validated among a cohort of participants with similar criteria in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial. Discrimination of both models was assessed using Harrell's C-index and model calibration by the Greenwood-Nam-D'Agostino statistic based on 4-year event rates. RESULTS: Overall, 1491 (10.2%) of 14,671 participants in TECOS and 130 (9.3%) in the ACCORD validation cohort (n = 1404) had MACE over 3 years' median follow-up. The final model included 9 characteristics (prior stroke, age, chronic kidney disease, prior MI, sex, heart failure, insulin use, atrial fibrillation, and microvascular complications). The model had moderate discrimination in both the internal and external validation samples (C-index = 0.65 and 0.61, respectively). The model was well calibrated across the risk spectrum-from a cumulative MACE rate of 6% at 4 years in the lowest risk quintile to 26% in the highest risk quintile. CONCLUSION: Among patients with T2DM and prevalent ASCVD, this 9-factor risk model can quantify the risk of future ASCVD complications and inform decision making for treatments and intensity. CI - (c) 2022. The Author(s). FAU - Stevens, Susanna R AU - Stevens SR AD - Duke Clinical Research Institute, Duke University School of Medicine, P.O. Box 17969, Durham, NC, 27715, USA. Susanna.Stevens@duke.edu. FAU - Segar, Matthew W AU - Segar MW AD - Department of Cardiology, Texas Heart Institute, Houston, TX, USA. FAU - Pandey, Ambarish AU - Pandey A AD - Division of Cardiology, University of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas, TX, USA. FAU - Lokhnygina, Yuliya AU - Lokhnygina Y AD - Duke Clinical Research Institute, Duke University School of Medicine, P.O. Box 17969, Durham, NC, 27715, USA. FAU - Green, Jennifer B AU - Green JB AD - Duke Clinical Research Institute, Duke University School of Medicine, P.O. Box 17969, Durham, NC, 27715, USA. FAU - McGuire, Darren K AU - McGuire DK AD - Division of Cardiology, University of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas, TX, USA. FAU - Standl, Eberhard AU - Standl E AD - Diabetes Research Group e.V. at Munich Helmholtz Center, Munich, Germany. FAU - Peterson, Eric D AU - Peterson ED AD - Duke Clinical Research Institute, Duke University School of Medicine, P.O. Box 17969, Durham, NC, 27715, USA. AD - Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Holman, Rury R AU - Holman RR AD - Diabetes Trials Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220827 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 SB - IM MH - *Atherosclerosis MH - *Cardiovascular Diseases MH - Clinical Trials as Topic MH - *Diabetes Mellitus, Type 2 MH - Humans MH - Models, Statistical MH - *Myocardial Infarction MH - Reproducibility of Results MH - Risk Assessment MH - *Stroke PMC - PMC9420281 OTO - NOTNLM OT - Atherosclerotic cardiovascular disease OT - Major adverse cardiovascular events OT - Risk modeling OT - Type 2 diabetes mellitus COIS- MWS has received personal fees from Merck & Co. YL has received grants from Merck, Janssen Research & Development, AstraZeneca, GlaxoSmithKline, and Bayer HealthCare AG. JBG has received grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Sanofi, and personal fees from AstraZeneca, Merck, Boehringer-Ingelheim, Sanofi/Regeneron, and NovoNordisk. DKM has received honoraria for clinical trial leadership for Lilly US, AstraZeneca, Sanofi, Janssen, Boehringer Ingelheim, Merck & Co, Novo Nordisk, Lexicon, Eisai, GlaxoSmithKline, CSL Behring and Esperion, and for consultancy for Afimmune, AstraZeneca, Sanofi, Lilly US, Boehringer Ingelheim, Merck & Co, Pfizer, Novo Nordisk, Applied Therapeutics, and Metavant. ES reports personal fees from the Oxford Diabetes Trials Unit, AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Menarini, Merck Serono, Excemed, Novartis, NovoNordisk, and Sanofi. EDP has received grant support from Janssen, Merck, Sanofi, AstraZeneca, Genentech, and Amgen; and has had consulting associations with Bayer, Merck, Sanofi, and Janssen. RRH reports research support from AstraZeneca, Bayer and Merck Sharp & Dohme, and personal fees from Anji Pharmacueticals, Bayer, Novartis and Novo Nordisk. All other authors report no disclosures or conflicts of interest. EDAT- 2022/08/28 06:00 MHDA- 2022/08/31 06:00 PMCR- 2022/08/27 CRDT- 2022/08/27 23:12 PHST- 2022/03/04 00:00 [received] PHST- 2022/08/14 00:00 [accepted] PHST- 2022/08/27 23:12 [entrez] PHST- 2022/08/28 06:00 [pubmed] PHST- 2022/08/31 06:00 [medline] PHST- 2022/08/27 00:00 [pmc-release] AID - 10.1186/s12933-022-01603-8 [pii] AID - 1603 [pii] AID - 10.1186/s12933-022-01603-8 [doi] PST - epublish SO - Cardiovasc Diabetol. 2022 Aug 27;21(1):166. doi: 10.1186/s12933-022-01603-8.