Cardiovascular Disease

Cardiovascular disease is a major cause of mortality worldwide, and a better understanding of the mechanisms underlying it is key to better management or prevention. ^[1] Dysfunction of the endothelial lining of lesion-prone areas of the arterial vasculature is an important contributor to the pathobiology of atherosclerotic cardiovascular disease and to atherosclerotic lesion initiation and progression. ^[2] The term encompasses several clinical manifestations, including coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. ^{[3] [4]}

Oxidative stress has been strongly implicated in the pathogenesis of cardiovascular disease, with reactive oxygen species reducing nitric oxide bioavailability and driving endothelial cell dysfunction. ^[1] Chronic, low-grade systemic inflammation can lead to cardiovascular disease, and clonal haematopoiesis of indeterminate potential links ageing and inflammation to an increased risk of atherosclerotic cardiovascular disease. ^{[5] [6]} Insulin resistance and attendant hyperinsulinaemia promote cardiovascular disease in part by increasing vascular stiffness and reducing nitric oxide bioavailability in the vasculature. ^[7] Because cholesterol can only enter the arterial wall within apoB-containing particles, apoB more accurately measures the atherogenic risk driving cardiovascular disease than does LDL cholesterol or non-HDL cholesterol ^[8].

Over 65 years, the Framingham Heart Study has provided substantial insight into the epidemiology and risk factors of cardiovascular disease since examining its first volunteer in 1948. ^[9] Early-onset atherosclerotic cardiovascular disease, defined in men younger than 55 years and women younger than 65 years, is increasing, underscoring that the disease process begins early in life. ^[10] 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 such as statins and aspirin. ^[11] Emerging tools such as polygenic risk scores and coronary artery calcium scans show potential for earlier detection of cardiovascular disease risk in younger individuals. ^[10] Traditional blood lipid profiles are routinely used in clinical practice to estimate the risk of cardiovascular disease such as atherosclerotic cardiovascular disease, making the lipid panel a first-line tool for risk assessment and treatment targeting ^[12]

Meta-analysis of blood-pressure-lowering randomized controlled trials shows a benefit almost identical to that predicted from blood pressure risk relationships in cohort studies, and preventing age-related increases in blood pressure would reduce much of the population burden of cardiovascular disease. ^[3] Cigarette smoking contributes to atherosclerotic cardiovascular disease through endothelial dysfunction, inflammation, and thrombosis, highlighting the need for smoking cessation to protect cardiovascular health. ^[13] Regular exercise is a low-cost, drug-free intervention with preventive and therapeutic benefits for cardiovascular disease that are similar to or greater than those of a pharmacological polypill. ^[14] The Mediterranean diet is an effective intervention for both primary and secondary prevention of cardiovascular disease, reducing the incidence of major adverse cardiovascular events, myocardial infarction, stroke, and cardiovascular-related mortality ^[15].