Systematic Coronary Risk Evaluation 2-Diabetes (SCORE2-Diabetes)

Clinical background

SCORE2-Diabetes was developed to address a weakness in the ESC's earlier risk stratification for type 2 diabetes. Conventional SCORE2, intended for the general population, treats diabetes as a binary variable and thereby misses the large individual variation in cardiovascular risk within the diabetic group. The risk for a person with type 2 diabetes varies several-fold depending on HbA1c, renal function and the age at onset of diabetes, variation that SCORE2 does not capture [1].

In the 2023 ESC guidelines on diabetes and cardiovascular disease, SCORE2-Diabetes was adopted as the recommended tool for risk estimation in patients with type 2 diabetes from the age of 40 without established atherosclerotic cardiovascular disease and without severe target organ damage [2]. The decision the tool is intended to support is primarily when intensified prevention is warranted: statin treatment, blood pressure targets and the choice of glucose-lowering drugs with documented cardiovascular benefit.

Calculating Systematic Coronary Risk Evaluation 2-Diabetes

SCORE2-Diabetes builds on the core predictors of SCORE2 (age, sex, current smoking, systolic blood pressure, total cholesterol and HDL cholesterol) and adds three diabetes-specific variables: HbA1c, the age at diagnosis of type 2 diabetes and the log of the eGFR. Each of the three diabetes-specific predictors has age interaction terms, meaning that their contribution to the risk estimate varies with age. The model is sex-stratified and adjusted for competing risks.

Formally, the 10-year risk is expressed as:

$$\text{Risk}$${10} = 1 - S{0,r}(10)^{\exp(\eta)}

where $S_{0,r}(10)$ is the region-specific baseline survival at 10 years, calibrated to one of the ESC's four cardiovascular risk regions (low risk, moderate risk, high risk or very high risk), and $\eta$ is the linear predictor:

$$\eta = \eta_{\text{SCORE2}} + \beta_1 \cdot \text{HbA1c} + \beta_2 \cdot \text{age}$${\text{diab}} + \beta_3 \cdot \ln(\text{eGFR}) + \sum{j=1}^{3} \gamma_j \cdot X_j \cdot \text{age}

Here $\eta_{\text{SCORE2}}$ is the SCORE2 linear predictor from the conventional risk factors, $X_j$ are the three diabetes-specific variables and $\gamma_j$ their age interaction coefficients.

The derivation cohort comprised 229,460 participants with type 2 diabetes and no previous cardiovascular disease, from four data sources in seven countries (England, Wales, Scotland, France, Germany, Italy and the USA), with 43,706 cardiovascular events during follow-up [1]. The models were recalibrated to CVD incidence in four European risk regions. External validation was carried out in 217,036 individuals with 38,602 events, from Sweden, Spain, Croatia and Malta [1]. The outcome modelled was non-fatal myocardial infarction, stroke or cardiovascular death within 10 years.

Interpretation in practice

Under the 2023 ESC guidelines, the absolute risk estimate translates into a risk class and a treatment intensity [2,6]:

The classification applies only to patients without established atherosclerotic cardiovascular disease and without severe target organ damage. By the ESC definition, severe target organ damage includes an eGFR below 45 mL/min/1.73 m² irrespective of albuminuria, an eGFR of 45 to 59 with albuminuria of 30 to 300 mg/g, proteinuria above 300 mg/g, or microvascular damage in at least three organ systems [6]. Patients with such damage, or with clinically manifest atherosclerosis, are at very high risk whatever the score and should not be assessed with SCORE2-Diabetes.

The contribution of the score is clear from the example in the derivation study: a 60-year-old man in a moderate risk region, a non-smoker, with average conventional risk factors, an HbA1c of 50 mmol/mol, an eGFR of 90 mL/min/1.73 m² and diabetes diagnosed at the age of 60 has a 10-year risk of 11%, compared with 17% for an otherwise identical man with an HbA1c of 70 mmol/mol, an eGFR of 60 and a diagnosis at the age of 50 [1]. For the equivalent woman the figures were 8% and 13%. The difference illustrates the point of adding HbA1c, eGFR and the age at diagnosis of diabetes to the core SCORE2 variables: the same conventional risk factors give an entirely different absolute risk depending on the diabetes profile.

Validation and performance

In the external validation cohort within the derivation study, SCORE2-Diabetes showed good discrimination and improved predictive performance compared with SCORE2 for the general population, with an increase in C-index of 0.009 to 0.031 [1]. Regional calibration was satisfactory in all four risk regions.

An external validation in a Dutch primary care cohort showed that SCORE2-Diabetes calibrated well for people of Dutch origin but underestimated risk in people of other origins and in patients from lower socioeconomic groups [3]. Overestimation was noted in those of high socioeconomic status. Clinical judgement must therefore take migration and socioeconomic status into account when interpreting the estimate.

A Spanish validation in the CARDIANA cohort compared 18 risk models and found that SCORE2-Diabetes was among the best performing, with good calibration and no need for recalibration [4]. Among the models of comparable performance were ADVANCE and DIAL2, which are simpler to use but lack regional calibration.

A metabolomics study has shown that SCORE2-Diabetes can be improved further by adding metabolic biomarkers, suggesting that the discrimination of the model is not optimal and that there is room for future improvement [5].

Limitations

The tool applies only to adults aged 40 to 69 years with type 2 diabetes. It must not be used for type 1 diabetes and should not be used for patients with established atherosclerotic cardiovascular disease or severe target organ damage, who by definition are at very high risk whatever the score.

The eGFR and HbA1c should be current values, ideally measured within the past year, since changes in these variables rapidly affect the estimate. A patient whose HbA1c rises from 50 to 70 mmol/mol may be moved a whole risk class upwards, and the same applies to a falling eGFR.

In a Romanian cross-sectional study of 70 hospitalised patients in a very high risk region, 87% were classified as very high risk by the 2023 criteria, and half were reclassified compared with the 2021 guidelines, usually into a higher risk class [6]. This reflects the fact that in populations with a high background risk SCORE2-Diabetes can lead to a more conservative risk classification than older category-based systems, which is a strength but also underlines that the score must be interpreted in its regional context.

References

1. SCORE2-Diabetes Working Group and ESC CVD Risk Collaboration. SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe. Eur Heart J. 2023;44(28):2544–56. PMID: 37247330
2. Marx N et al. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J. 2023;44(39):4043–140. PMID: 37622663
3. Alfaraj SA et al. External validation of SCORE2-Diabetes in The Netherlands across various socioeconomic levels in native-Dutch and non-Dutch populations. Eur J Prev Cardiol. 2025;32(7):555–63. PMID: 39485827
4. Enguita-Germán M et al. External validation of cardiovascular risk scores in patients with Type 2 diabetes using the Spanish population-based CARDIANA cohort. Eur J Prev Cardiol. 2026;33(1):111–20. PMID: 40439899
5. Xie R et al. Improving 10-year cardiovascular risk prediction in patients with type 2 diabetes with metabolomics. Cardiovasc Diabetol. 2025;24(1):18. PMID: 39806417
6. Luca SA et al. To What Extent Does Cardiovascular Risk Classification of Patients with Type 2 Diabetes Differ between European Guidelines from 2023, 2021, and 2019? A Cross-Sectional Study. Medicina (Kaunas). 2024;60(2):334. PMID: 38399621