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............................................................................................................................................................................. conventional CVD risk factors, although data in women are still underpowered compared to men. • Information on whether female-specific conditions improve risk classification. • There are insufficient data to draw conclusions on a possible increased risk of hypertension or DM with premature menopause. • Studies on the specificities of CVD disease in the transgender population are scarce. Erectile dysfunction • The benefit of routine screening for ED and the most effective tool to assess it are still unclear. • The benefit of assessment of subclinical vascular disease in men with ED and low-to-intermediate CVD risk is unclear. Risk factors and interventions at the individual level Physical activity and exercise • Knowledge of the relative importance of the various characteristics of aerobic PA and resistance exercise, or their combination, on all-cause mortality, CV incidence, and mortality. • Understanding how sex, age, weight, race/ethnicity, occupation, and socioeconomic status may modify associations between PA and health outcomes. • Implementation of strategies to achieve long-term adherence to PA. • Evaluation of the effects of eHealth tools in promoting PA. Nutrition • Effective strategies to encourage people to change their diet and to enjoy and maintain a healthy diet. Body weight • Knowledge and implementation of effective lifestyle and medication-assisted strategies to achieve weight loss and maintain a long-term healthy weight. Mental healthcare and psychosocial interventions • The effectiveness of mental healthcare for the prevention of major CVD events. • How to implement effective CVD prevention measures in this high-risk population of patients with mental disorders. Smoking intervention • A better understanding of how to incorporate effective smoking cessation into clinical practice. Lipids • Direct empirical evidence for the stepwise approach to treatment intensification from RCTs. The feasibility and effects of reaching LDL-C levels <1.4 mmol/L (55 mg/dL) needs further investigation, especially in primary care. • Particularly among people at low-to-moderate CVD risk, older people, and for newer interventions, more evidence of the effects of lipid-modifying treatments on overall mortality is needed in the form of long-term post-trial follow-up in RCTs. • The cost-effectiveness of using lifetime CVD risk and more precise CVD risk scores to target interventions needs further investigation. • The value of triglycerides or HDL-C values as a target for therapy. • Whether lipoprotein(a) lowering against background statin, ezetimibe and PCSK9i therapy can reduce the risk of ASCVD. • Whether functional foods and food supplements with a lipidlowering effect can safely reduce the risk of CVD. Blood pressure • What is the incremental benefit, over CVD risk calculators, of measures of HMOD in reclassifying the CV risk of patients with hypertension? • Direct empirical evidence for the stepwise approach to treatment intensification from RCTs. • What are the benefits of BP treatment for patients with BP in the high-normal range? • More data on the benefits of BP treatment in very old people and the influence of frailty. • Effect of single-pill vs. multidrug treatment strategies on adherence to treatment, BP control, and clinical outcomes. • Effectiveness of antihypertensive treatment in preventing cognitive dysfunction or dementia. • Efficacy and cost-effectiveness of invasive procedures and devices for the treatment of hypertension. • Sex-specific BP treatment thresholds for men and women. Diabetes mellitus • More work is needed to develop risk scores for both MACE and HF in type 2 DM. • Whether combined SGLT2 inhibitor and GLP-1RA treatments lower MACE or other outcomes beyond either drug alone requires testing. • Longer-term safety of newer classes of drug is required. Antithrombotic therapy • The role of antithrombotic therapy in primary prevention in (very) high-risk individuals remains to be established. Cardiac rehabilitation and prevention programmes • The effect and the optimal delivery of EBCR in women, older/ frail patients, patients with cardiac implantable electronic devices, after heart transplantation or valve replacement, and in patients with AF, stroke, HFpEF, LEAD, or multiple comorbidities. • Alternative and cost-effective models of CR need to ensure participation globally, including low- and middle-income countries. • Large RCTs investigating the long-term effects of home-based telerehabilitation and mHealth are needed. Environment, air pollution, and climate change • Individual-level exposure studies are needed to better specify the effect of mitigating measures. Risk management of disease-specific cardiovascular disease Coronary artery disease Downloaded from academic.oup.com/eurheartj/article/42/34/3227/6358713 by guest on 07 October 2026