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Aims: The 2019 and 2021 European Society of Cardiology (ESC) classifications stratified patients with type 2 diabetes into three categories according to the 10-year risk of death from atherosclerotic cardiovascular disease (ASCVD). The very high-risk category included individuals with established ASCVD, target organ damage (TOD), and/or, in the 2019 classification only, ≥ 3 additional ASCVD risk factors. We assessed risk of all-cause mortality according to the two ESC classifications in the Renal Insufficiency And Cardiovascular Events cohort. Methods: Participants (n = 15,773) were stratified based on the presence of ASCVD, TOD, and ASCVD risk factors at baseline (2006–2008). Vital status was retrieved in 2015. Results: Less than 1% of participants fell in the moderate-risk category. According to the 2019 classification, ~ 1/3 fell in the high-risk and ~ 2/3 in the very high-risk category, whereas the opposite occurred with the 2021 classification. Mortality risk increased across categories according to both classifications. Among very high-risk patients, mortality was much lower in those with ≥ 3 additional ASCVD risk factors and almost equal in those with TOD and ASCVD ± TOD, using the 2019 classification, whereas it was much higher in those with ASCVD + TOD and, to a lesser extent, TOD only than in those with ASCVD only, using the 2021 classification. Conclusions: The negligible number of moderate-risk patients suggests that these classifications might overestimate risk of ASCVD death. Downgrading patients with ≥ 3 additional ASCVD risk factors to the high-risk category is consistent with mortality data. Risk of death is very high in the presence of TOD irrespective of established ASCVD. Trial registration: ClinicalTrials.gov, NCT00715481.

Additional file 1: Figure S1. Scatterplot of clamp-derived GDR and eGDR (A) or HOMA-IR (B) in 140 individuals with T2D.

Additional file 2: Table S1. Binary logistic regression analyses of kidney parameters (albuminuria categories, eGFR categories, and DKD phenotypes as dependent variables) with eGDR tertiles as covariate adjusted for confounders*.

Additional file 3. The RIACE Study Group

Additional file 2: Figure S1. Survival analysis by quartiles of triglycerides in males. Figure S2. Survival analysis by quartiles of triglycerides in females. Figure S3. Survival analysis by quartiles of HDL cholesterol in males. Figure S4. Survival analysis by quartiles of HDL cholesterol in females. Figure S5. Survival analysis by quartiles of TG:HDL in males. Figure S6. Survival analysis by quartiles of TG:HDL in females.

Additional file 1: Table S1. Baseline clinical features of study participants by quartiles of triglycerides. Table S2: Baseline clinical features of study participants by quartiles of HDL cholesterol. Table S3: Baseline clinical features of study participants by quartiles of TG:HDL.

Additional file 5: Table S3. Survival analysis by Cox proportional hazards regression according to eGDR tertiles, adjusted for age, gender, albuminuria and eGFR categories (Model 4) or DKD phenotypes (Model 5), plus multiple confounders*.

Additional file 6: Figure S3. Cox proportional hazards regression, unadjusted (A), and adjusted by age and gender (B; model 1), plus albuminuria and eGFR categories (C; model 2) plus multiple confounders* (D; model 4), according to tertiles of eGDR calculated using measured waist circumference. HRs (95% CI) for mortality are shown for each tertile.

Additional file 4: Table S2. Survival analysis by Cox proportional hazards regression according to eGDR tertiles, adjusted for age and gender (Model 1) and for age and gender plus albuminuria and eGFR categories (Model 2) or DKD phenotypes (Model 3).

Additional file 3: Figure S2. Cumulative survival by Kaplan Meier analysis according to eGDR tertiles. Numbers (percentages) of death are shown for each tertile.

Table S2. Baseline clinical features in the RIACE participants with valid information on vital status and resistant hypertension on-target with >â 4 drugs or not on-target with >â 3 drugs according to the 140/90â mmHg BP targets. (DOCX 16 kb)

Figure S1. Cumulative survival by Kaplan Meier analysis according to BP status, based on the 130/80â mmHg (A) and 140/90â mmHg (B) BP targets. Numbers (percentages) of death are shown for each group. NT = normotension; UTHT = untreated hypertension; CHT = controlled hypertension; UCHT = uncontrolled hypertension; RHT = resistant hypertension. (DOC 824 kb)

Figure S3. Cox proportional hazards regression, unadjusted (A) and adjusted for age and gender (B) plus CVD risk factors (C) plus complications/comorbidities (D), according to BP status (based on the 140/90â mmHg BP targets). HRs (95% CI) for mortality are shown for each group. NT = normotension; UTHT = untreated hypertension; CHT = controlled hypertension; UCHT = uncontrolled hypertension; CRHT = controlled resistant hypertension; UCRHT = uncontrolled resistant hypertension. (DOC 1012 kb)

Table S1. Baseline clinical features in the RIACE participants with valid information on vital status, stratified by BP status according to the 140/90â mmHg BP targets. (DOCX 17 kb)

Figure S2. Cox proportional hazards regression, unadjusted (A) and adjusted for age and gender (B) plus CVD risk factors (C) plus complications/comorbidities (D), according to BP status (based on the 140/90â mmHg BP targets). HRs (95% CI) for mortality are shown for each group. NT = normotension; UTHT = untreated hypertension; CHT = controlled hypertension; UCHT = uncontrolled hypertension; RHT = resistant hypertension. (DOC 809 kb)