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............................................................................................................................................................................. 3.2.1.4 Diabetes mellitus Type 1 DM, type 2 DM, and prediabetes are independent risk factors for ASCVD, increasing risk of ASCVD by about two-fold, depending on the population and therapeutic control.41 Women with type 2 DM appear to have a particularly higher risk for stroke.42 Patients with type 2 DM are likely to have multiple ASCVD risk factors (including dyslipidaemia and hypertension), each of which mediates an increase in risk of both ASCVD and non-ASCVD.

3.2.1.5 Adiposity Over recent decades, body mass index (BMI)—measured as weight (in kg) divided by squared height (in m2)—has increased substantially worldwide in children, adolescents, and adults.43 Mendelian randomization analyses suggest a linear relation between BMI and mortality in non-smokers and a J-shaped relation in ever-smokers.44 All-cause mortality is lowest at a BMI of 2025 kg/m2 in apparently healthy people, with a J-shaped or U-shaped relation.45,46 In HF patients, there is evidence for an obesity paradox, with lower mortality risk in patients with higher BMI. A meta-analysis concluded that both BMI and waist circumference are similarly, strongly, and continuously associated with ASCVD and type 2 DM.47

3.2.2. Sex and gender and their impact on health The current prevention guidelines recognize the importance of integrating sex, gender, and gender identity considerations into the risk assessment and clinical management of individuals and populations. These guidelines also acknowledge the complexity of the interrelationship between these concepts and CV, as well as psychological, health. There is, at present, no official ESC position on the specific terminology to be used. According to the World Health Organization (WHO), sex ‘refers to the different biological and physiological characteristics of females, males, and intersex persons, such as chromosomes, hormones and reproductive organs’.48 This is to be distinguished from gender, which ‘refers to the characteristics of women, men, girls and boys that are socially constructed. This includes norms, behaviours and roles associated with being a woman, man, girl or boy, as well as relationships with each other. As a social construct, gender varies from society to society and can change over time’.48 The Global Health 50/50 definition further states that gender refers ‘to the socially constructed norms that impose and determine roles, relationships, and positional power for all people across their lifetime’.49 Where evidence exists on the risk modifying effect of sex or where sex-specific clinical conditions and clinical management strategies exist, this has been included in these guidelines.50 The influence of gender on an individual’s experience and access to healthcare is paramount.50 The specific health concerns related to gender are thus also acknowledged in these prevention Guidelines. Epigenetic effects of social constructs appear to condition the translation of biological sex into disease pathophysiology. Furthermore, social constructs can also be determinants of health access, healthcare utilization, disease perception, decision-making, and perhaps therapeutic response,50 including in the field of CVD and ASCVD prevention. Research is ongoing, but gaps in evidence remain and this has also been recognized in the guidelines. Examples of specific topics regarding physiological, pathological, and clinical differences related to sex and gender that have been studied include left ventricular (LV) ejection fraction (LVEF), adverse drug reactions, trends in ASCVD risk factors and awareness, sex disparities in the management of and outcomes after acute coronary syndromes (ACS).5158 Furthermore, CVD health after menopause transition, pregnancy disorders, and gynaecologic conditions have recently been reviewed.59

3.2.3. Cardiovascular disease risk classification The current guidelines on CVD prevention in clinical practice concentrate principally, but not exclusively, on risk and prevention of ASCVD. This includes risk factors, risk prediction, risk modifiers, as well as clinical conditions that often increase the likelihood of ASCVD. Identifying patients who will benefit most from ASCVD risk factor treatment is central to ASCVD prevention efforts. In general, the higher the absolute CVD risk, the higher the absolute benefit of risk factor treatment, and thus the lower the number needed to treat to prevent one CVD event during a period of time.60,61 With this in mind, the estimation of CVD risk remains the cornerstone of these guidelines and thus appears at the forefront of the proposed management schemes, which are summarized in flowcharts. Age is the major driver of CVD risk. Women below 50 years and men below 40 years of age are almost invariably at low 10-year CVD risk, but may have unfavourable modifiable risk factors that sharply increase their longer-term CVD risk. Conversely, men over 65 years and women over 75 years of age are almost always at high 10-year CVD risk. Only between the ages of 55 and 75 years in women and 40 and 65 years in men does the 10-year CVD risk vary around commonly used thresholds for intervention. The age categories <50, 5069, and >_70 years should be used with common sense and flexibility. Different age ranges may be considered for men and women and may differ according to geographic region. Uncertainty around risk estimations should also be considered. CVD risk can also be assessed in patients with type 2 DM and in patients with established ASCVD. The populations or patient groups in whom CVD risk needs to be considered are summarized and presented in Table 4. Lifetime CVD risk estimation is available for various groups of patients, and enables estimation of lifetime benefit from preventive interventions such as smoking cessation (see section 4.5.1), lipid-lowering (see section 4.6.2.1), and BP treatment (see section 4.7.5.2). Lifetime risk and benefit estimation may be used for communication in the shared decision-making process, together with consideration of comorbidities, frailty, patient preferences for initiating (STEP 1) and intensifying (STEP 2) risk factor treatment (Figure 2).

3.2.3.1 A stepwise approach to risk factor treatment and treatment intensification As explained before, targets and goals for LDL-C, BP, and glycaemic control in DM remain as recommended in recent ESC Guidelines.35 These guidelines propose a stepwise approach to treatment intensification as a tool to help physicians and patients pursue these targets in a way that fits patient profiles and preferences. This principle (outlined in Figure 2, using the example of a stepwise approach) is not conceptually novel, but rather reflects routine clinical practice, in which treatment strategies are initiated and then intensified, both as part of a shared decision-making process involving healthcare professionals and patients. Downloaded from academic.oup.com/eurheartj/article/42/34/3227/6358713 by guest on 07 October 2026