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............................................................................................................................................................................. 3.3.10.3 Assess risk factors and cardiovascular disease risk in persons with obesity Comprehensive CVD risk assessment should be considered in individuals with unfavourable body composition. The main risk-related sequalae of adiposity include hypertension, dyslipidaemia, insulin resistance, systemic inflammation, a prothrombotic state, albuminuria, as well as a decline in estimated glomerular filtration rate (eGFR)171 and the development of type 2 DM, CVD events, as well as HF and AF.

3.4 Clinical conditions

Individual calculated risks of CVD, as evaluated by conventional risk factors in risk scores, are subject to refinement by potential risk modifiers as highlighted in section 3.3. Beyond these potential modifiers, specific clinical conditions can influence CVD risk. These clinical conditions often increase the likelihood of CVD, or are associated with poorer clinical prognosis. The current section reviews some of these conditions, which are not often included in traditional risk scores but may be integrated in some national risk scores. Here we discuss how these conditions increase this risk. Many clinical conditions share common CVD and ASCVD risk factors and therefore treating these allows a synergistic reduction in the overall burden of disease.

3.4.1. Chronic kidney disease Worldwide, the total number of individuals with chronic kidney disease (CKD) who are not treated with kidney replacement therapy was approximately 850 million in 2017.194 This number accounts to a prevalence of 10 - 12% among men and women. CKD is the third fastest growing cause of death globally.195 CKD is defined as abnormalities of kidney structure or function, present for >3 months, with health implications. Criteria and markers of kidney damage, especially kidney disease due to DM, are albuminuria [albumin-to-creatinine ratio (ACR) >30 mg/g in spot urine specimens] and glomerular filtration rate (GFR) <60 mL/min/1.73 m2. GFR can be estimated (eGFR) from calibrated serum creatinine and estimating equations using the CKD-EPI (Chronic Kidney Disease Epidemiology) Collaboration formula. Kidney disease severity is differentiated into stages (categories) according to the level of GFR and albuminuria; a patient with an eGFR <60 mL/min/1.73 m2 is classified as having CKD stage 3a, which represents an advanced kidney function impairment.172 Among persons with CKD, CVD is the leading cause of morbidity and death.196 Even after adjustment for known CAD risk factors, including DM and hypertension, mortality risk progressively increases with worsening CKD.197 As GFR declines below approximately 60- 75 mL/ min/1.73 m2, the probability of developing CAD increases linearly,198 with up to triple the CVD mortality risk when reaching an eGFR of 15 mL/min/1.73 m2. Kidney disease is associated with a very high CVD risk. Among persons with CKD, there is a high prevalence of traditional CAD risk factors, such as DM and hypertension. The use of CAC score to risk stratify patients with CKD might be a promising tool.199203 Furthermore, persons with CKD are also exposed to other nontraditional ASCVD risk factors such as uraemia-related ones, including inflammation, oxidative stress, and promotors of vascular calcification. CKD and kidney failure not only increase the risk of CAD, they also modify its clinical presentation and cardinal symptoms.204 3.4.2. Atrial fibrillation Atrial fibrillation (AF) appears to be associated with an increased risk of death and of CVD and kidney disease.205 Furthermore, AF appears to be a stronger risk factor for CVD in women than in men.206

The prevalence of AF ranges between 2% and 4%, and a 2.3-fold rise is expected, owing in part to ageing of the population and intensified searching for undiagnosed AF, as well as lower CV death.207 The age-adjusted incidence, prevalence, and lifetime risk of AF are lower in women vs. men and in non-white vs. white cohorts.208,209 The lifetime AF risk estimate is now 1 in 3 individuals of European ancestry at an index age of 55 years.210 ASCVD risk factor burden and comorbidities, including lifestyle factors, and age significantly affect the lifetime risk for AF development.211213 The observed effect of clinical ASCVD risk factor burden and multiple comorbidities on the lifetime risk of AF (significantly increasing from 23.4% among individuals with an optimal clinical risk factor profile to 33.4% and 38.4% in those with borderline and elevated clinical risk factors, respectively214) suggests that early intervention and control of modifiable ASCVD risk factors could reduce incident AF. The continuum of unhealthy lifestyle, risk factor(s), and CVDs can contribute to atrial remodelling/cardiomyopathy and development of AF that commonly results from a combined effect of multiple interacting factors (Figure 9).215 Risk factor and CVD management reduces AF burden. Targeted therapy of underlying conditions may significantly improve maintenance of sinus rhythm in patients with persistent AF and HF.216 However, studies addressing isolated management of specific conditions alone (e.g. hypertension) yielded inconsistent findings.217 The overall annual risk of ischaemic stroke in patients with AF is 5%, but varies considerably according to comorbidities.215 Cardioembolic strokes associated with AF are usually more severe, and often recurrent.218 Furthermore, AF appears to be a stronger predictor of stroke in women than in men.215 AF is also associated with impaired cognitive function, ranging from mild cognitive impairment to dementia.219 AF is independently associated with a two-fold increased risk of all-cause mortality in women and a 1.5-fold increased risk in men.220 In one population, the most common causes of death were HF (14.5%), malignancy (23.1%), and infection/sepsis (17.3%), while stroke-related mortality was only 6.5%.221 These data indicate that, in addition to anticoagulation and HF treatment, comorbid conditions need to be actively treated to reduce AF-related mortality and morbidity. Regarding PA, both sedentary lifestyles and very high levels of PA are associated with development of AF (U-shaped association), through different mechanisms. Furthermore, when AF develops in athletes it is not associated with the same increased risk of stroke.

3.4.3. Heart failure Heart failure (HF) of ischaemic origin constitutes a severe clinical manifestation of ASCVD. Conversely, HF itself (predominantly of ischaemic aetiology) increases the risk of CVD events (myocardial infarction, arrhythmias, ischaemic stroke, CV death). Asymptomatic LV dysfunction (systolic or/and diastolic dysfunction) as well as overt symptomatic HF [across the spectrum of LVEF, i.e. HF with reduced ejection fraction (HFrEF), HF with mid-range ejection fraction,222 and HF with preserved ejection fraction (HFpEF)] increases the risk of urgent CV hospitalizations (including hospitalizations due to HF worsening) and CV and all-cause deaths. Downloaded from academic.oup.com/eurheartj/article/42/34/3227/6358713 by guest on 07 October 2026