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............................................................................................................................................................................. • Management of CVD risk in older people (>85 years) with marked fragility, for whom no data currently exist. • Comparison of different methods for the estimation of lifetime CVD risk and lifetime benefit of risk factor treatment.

Risk modifiers Psychosocial factors

• More evidence that psychosocial factors improve risk prediction beyond the classical risk-factor models. Ethnicity

• Whether recalibration of factors for ethnicity are homogeneous in various European countries. • Risks associated with other ethnic backgrounds. Frailty

• Consensus on a clinically orientated screening tool for frailty to be applied across the spectrum of ASCVD. • Quantitative contribution of frailty to the global CVD riskprediction scheme. • At which degree of frailty treatment of specific risk factors should be less aggressive. Family history

• Disentangle the role and (genetic, socioeconomic, etc.) mechanisms of family history on CVD risk. Genetics

• The potential of polygenic risk scores to complement existing risk scores. Socioeconomic determinants

• More evidence from different risk regions that the inclusion of socioeconomic factors improves risk prediction beyond classical risk factor models in both men and women. Environmental exposure

• Whether air pollution reclassifies risk in individual patients. Biomarkers

• Added value of biomarkers in risk classification. Clinical conditions Chronic kidney disease

• Identification of a good biomarker, besides albuminuria, and perhaps the use of CAC score to subclassify CV risk in CKD. • Early and precise identification of progressive CKD with novel biomarkers that are more sensitive than eGFR and albuminuria. Atrial fibrillation

• Evaluate the effect of interventions aimed at reducing outcomes beyond stroke. • Is AF a causal factor for increased CVD morbidity and mortality? • Stroke risk prediction for low-risk AF patients. • Emerging evidence suggests that stroke can occur in patients with AF even after sinus rhythm is restored.

Heart failure

• It remains unknown whether patients with HFrEF of ischaemic origin should have different target LDL-C levels than those recommended for secondary prevention in individuals without HF. Cancer

• RCTs using preventive therapy to demonstrate a clear effect on prevention of CV events. Chronic obstructive pulmonary disease

• Although common pathophysiological pathways between CVD and COPD are probable, they remain to be clarified. Inflammatory conditions

• The optimal way of integrating information on chronic inflammatory conditions into CVD risk assessment. • The effect of modern anti-inflammatory drugs on CV risk [e.g. anti-tumour necrosis factor (TNF), interleukin (IL)-1, IL-17, IL-23 biologics]. Infections

• Large-scale studies to assess the efficacy of influenza vaccination or periodontitis treatment in preventing CVD. • The association of infection with HIV and total CVD risk. Migraine

• There are no data that allow reliable identification of subgroups of migraineurs at particular high risk (e.g. active migraine, highfrequency auras, young subjects, women). • The role of comorbid factors (e.g. patent foramen ovale, thrombophilic factors) is unclear, and at the moment there is no indication to screen or to manage for these factors.

Sleep disorders

• There is lack of evidence that the inclusion of sleep improves risk prediction. • Trials are needed that target the complex pathways linking sleep disturbances with CVD.

Mental disorders

• The precise mechanism by which mental disorders increase CVD remains uncertain. • How the consideration of mental disorders improves CV risk models.

Non-alcoholic fatty liver disease

• Whether NAFLD increases CV risk beyond traditional risk factors.

Sex-specific conditions

• The degree to which increased CVD risk associated with several of the female-specific conditions occurs independently of Downloaded from academic.oup.com/eurheartj/article/42/34/3227/6358713 by guest on 07 October 2026