• Monia Garofolo, Giuseppe Penno, Anna Solini, Emanuela Orsi, Martina Vitale, Veronica Resi, Enzo Bonora, Cecilia Fondelli, Roberto Trevisan, Monica Vedovato, Antonio Nicolucci, Giuseppe Pugliese, and Renal Insufficiency And Cardiovascular Events (RIACE) Study Group.
• Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
• Eur. J. Intern. Med. 2024 Oct 1; 128: 536253-62.

AimsTo assess whether and to what extent excess risk of all-cause death is reduced in individuals with type 2 diabetes by achieving optimal control of traditional cardiovascular risk factors.MethodsThis observational, prospective, cohort study enrolled 15,773 Caucasian patients in 19 Italian centres in 2006-2008. Participants were stratified according to the number of the following risk factors outside target: haemoglobin A1c, blood pressure, micro/macroalbuminuria, current smoking, LDL cholesterol, and triglycerides. All-cause mortality was retrieved for 15,656 patients (99.3 %) on 31 October 2015.ResultsAge-adjusted mortality rates and hazard ratios were significantly higher in the whole RIACE cohort (by ∼20 %) and in patients with (by ∼100 %) but not in those without prior cardiovascular disease (CVD), as compared with the coeval Italian general population. In all patients and in those without prior CVD, the relationship with mortality according to the number of risk factors outside target was J-shaped, an effect that was attenuated after either excluding "overtreated " patients, i.e., those with haemoglobin A1c ≤6.0 % on anti-hyperglycaemic agents causing hypoglycaemia and/or systolic blood pressure ≤120 mmHg on anti-hypertensive agents, or adjusting for "overtreatment". Conversely, in patients with prior CVD, mortality remained higher than in the general population in all categories and increased progressively from +70 % to +314 %, without J-effect.ConclusionsIn patients with type 2 diabetes, optimal treatment of traditional cardiovascular risk factors completely eliminated the excess mortality risk versus the general population, provided that they were not "overtreated". However, this effect was observed only in participants without history of CVD.Trial RegistrationClinicalTrials.gov, NCT00715481, retrospectively registered 15 July 2008.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.

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