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CVD varies widely and should be considered.81 It is evident that patients with a recent ACS or progressive vascular disease, and patients with DM and vascular disease, are all at exceptionally high risk for recurrent CVD events. For other patients with established ASCVD, the residual risk may be less evident and could be estimated based on clinical criteria such as age, (change in) risk factor levels, and risk modifiers, or by calculation of residual CVD risk with a calculator. The risk of recurrent CVD is influenced mainly by classical risk factors, vascular disease site, and kidney function. Risk stratification tools for secondary prevention include the SMART (Secondary Manifestations of Arterial Disease) risk score (available in the ESC CVD Risk app) for estimating 10-year residual CVD risk in patients with stable ASCVD, defined as CAD, PAD, or cerebrovascular disease,81 and the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) risk model, which estimates 2-year risk of recurrent CVD in patients with stable CAD.82 Occasionally, recurrent CVD risk is very high despite maximum (tolerated) conventional treatments. In such cases, novel but less well-established preventive treatments such as dual antithrombotic pathway inhibition,83 icosapent ethyl,84 or anti-inflammatory therapy with colchicine (see section 4.10)85,86 may be considered.

3.2.3.8 Risk estimation and risk factor treatment in persons with type 2 diabetes mellitus Most adults with type 2 DM are at high or very high risk for future CVD, particularly from middle age onwards. On average, type 2 DM doubles CVD risk and reduces life expectancy by 4 - 6 years, with absolute risks highest in those with any target organ damage (TOD). Type 2 DM also increases the risk for cardiorenal outcomes, in particular HF and CKD. Relative risks (RRs) for CVD in type 2 DM are higher at younger ages of onset and are modestly higher in women compared with men.87 Smoking cessation and adoption of a healthy lifestyle are recommended for all people with type 2 DM, and risk factor treatment should be considered in all people with DM, at least those above the age of 40 years (see sections 4.6 and 4.7). Still, there is a wide range in individual risk for CVD events, especially after initial risk factor management.88 Persons with DM with severe TOD (for definition: see Table 4) can be considered to be at very high CVD risk, similar to people with established CVD (see Table 4). Most others with DM are considered to be at high ASCVD risk.64 However, an exception can be made for patients with well-controlled short-standing DM (e.g. <10 years), no evidence of TOD, and no additional ASCVD risk factors, who may be considered as being at moderate CVD risk. In addition to the semi-quantitative division into three risk categories described above, DM-specific risk models may refine risk estimates and illustrate the impact of treatments. These models generally include duration of DM, glycated haemoglobin (HbA1c) level, and presence of TOD. Examples are the ADVANCE (Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation) risk score, which predicts 10-year CVD risk, and the UKPDS (UK Prospective Diabetes Study) risk engine, which predicts fatal and non-fatal CVD risk and is available for use in the UK. However, we recommend cautious use of these calculators, since both are based on older cohort data89,90 (Figure 8). Recommendations for CVD risk estimation

Recommendations Classa Levelb

In apparently healthy people <70 years without established ASCVD, DM, CKD, genetic/rarer lipid or BP disorders, estimation of 10-year fatal and non-fatal CVD risk with SCORE2 is recommended.68 I B In apparently healthy people >_70 years without established ASCVD, DM, CKD, genetic/rarer lipid or BP disorders, estimation of 10-year fatal and non-fatal CVD risk with SCORE2-OP is recommended.72 I B In apparently healthy people, after estimation of 10-year fatal and non-fatal CVD risk, lifetime risk and treatment benefit, risk modifiers, frailty, polypharmacy, and patient preferences should be considered. IIa C Patients with established ASCVD and/or DM and/or moderate-to-severe renal disease and/or genetic/rarer lipid or BP disorders are to be considered at high or very high CVD risk.75,77,81,8890 I A A stepwise treatment-intensification approach aiming at intensive risk factor treatment is recommended for apparently healthy people at high or very high CVD risk, as well as patients with established ASCVD and/or DM, with consideration of CVD risk, treatment benefit of risk factors, risk modifiers, comorbidities, and patient preferences.66,67 I B Treatment of ASCVD risk factors is recommended in apparently healthy people without DM, CKD, genetic/rarer lipid, or BP disorders who are at very high CVD risk (SCORE2 >_7.5% for age under 50; SCORE2 >_10% for age 5069; SCORE2-OP >_15% for age >_70 years).68,72 I C Treatment of ASCVD risk factors should be considered in apparently healthy people without DM, CKD, genetic/rarer lipid, or BP disorders who are at high CVD risk (SCORE2

2.5 to <7.5% for age under 50; SCORE2 5 to <10% for age 5069; SCORE2-OP 7.5 to

<15% for age >_70 years), taking CVD risk modifiers, lifetime risk and treatment benefit, and patient preferences into account. IIa C

ASCVD = atherosclerotic cardiovascular disease; BP = blood pressure; CKD = chronic kidney disease (see definition in Table 4); DM = diabetes mellitus; SCORE2 = Systemic Coronary Risk Estimation 2; SCORE2-OP = Systemic Coronary Risk Estimation 2-Older Persons. aClass of recommendation. bLevel of evidence. ESC 2021

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