Cardiovascular Risk

Assessment of atherosclerotic cardiovascular disease (ASCVD) risk is the cornerstone of primary prevention, enabling aggressive therapy in those most likely to benefit while guiding a conservative approach in those at low risk. ^[1] ASCVD risk assessment begins with a traditional 10-year risk calculator, refined by risk-enhancing factors such as lipoprotein(a) and subclinical atherosclerosis testing such as coronary artery calcium scoring. ^[1] The metabolic syndrome refers to the co-occurrence of several cardiovascular risk factors including insulin resistance, obesity, atherogenic dyslipidemia and hypertension, identifying a subgroup at high risk of developing cardiovascular disease and type 2 diabetes. ^[2]

Endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression, and its severity has prognostic value for cardiovascular events. ^[3] High levels of lipoprotein(a), an apoB100-containing lipoprotein, are an independent and causal risk factor for atherosclerotic cardiovascular disease through increased atherogenesis, inflammation and thrombosis, with about 70% to 90% of interindividual variation being genetically determined. ^[4] Arterial stiffness is a leading marker of risk in hypertension and an index of vascular ageing that predicts outcomes beyond conventional risk factors. ^[5] Clonal haematopoiesis of indeterminate potential, driven by somatic mutations in genes such as TET2, is associated with a doubling of the risk of atherosclerotic cardiovascular disease, linking ageing and inflammation to cardiovascular risk. ^[6]

In a systematic review and meta-analysis of 87 studies including 951,083 patients, the metabolic syndrome was associated with an increased risk of cardiovascular disease with a relative risk of 2.35 and of cardiovascular mortality with a relative risk of 2.40. ^[7] Coronary artery calcium scoring is a widely available, reproducible means of assessing risk for major cardiovascular outcomes, especially useful in asymptomatic people for planning primary prevention interventions such as statins and aspirin. ^[8] American Heart Association projections estimate that among US adults the prevalence of hypertension will increase from 51.2% in 2020 to 61.0% in 2050, with diabetes rising from 16.3% to 26.8% and obesity from 43.1% to 60.6%. ^[9] In a meta-analysis of more than 6.4 million women, preeclampsia was independently associated with an increased risk of future heart failure and a 2-fold increased risk of coronary heart disease, stroke and cardiovascular death. ^[10]

Pathologies affecting the cardiovascular system are the leading cause of global morbidity, disability and mortality, and their prevalence is growing. ^[11] Overweight and obesity are independently associated with increased cardiovascular risk, and the GLP-1 receptor agonist semaglutide reduced the incidence of cardiovascular and cerebrovascular events and cardiovascular death in overweight or obese patients with pre-existing cardiovascular disease but without diabetes. ^[12] The menopausal transition period is associated with an increase in clinical and subclinical cardiovascular risk, with the risk of cardiovascular disease rising notably in the fifth decade of a woman's life. ^{[13] [14]} Because ageing drives cardiovascular risk, targeting molecular hallmarks of cardiovascular ageing such as mitochondrial dysfunction, cell senescence and