Dyslipidemia

Dyslipidemia is an important risk factor for coronary artery disease and stroke. ^[1] Dyslipidemia, especially elevated low-density lipoprotein cholesterol (LDL-C), is a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD), and it remains underdiagnosed and undertreated. ^[2] The 2026 ACC/AHA multisociety Guideline on the Management of Dyslipidemia, which replaces the 2018 blood cholesterol guideline, covers high blood cholesterol, hypertriglyceridemia and elevated lipoprotein(a). ^{[3] [4]} In the metabolic syndrome definition, dyslipidemia refers to raised triglycerides and lowered high-density lipoprotein cholesterol. ^[5] Familial hypercholesterolemia (FH) is a distinct, inherited disorder: a common genetic disorder of autosomal inheritance associated with elevated LDL-C, estimated to affect 1:250 individuals in the general population. ^[6] Population-scale genetic testing in the USA has estimated FH prevalence at at least one in 220, making FH the most common genetic cause of premature coronary artery disease. ^[7] Human genetics distinguishes conventional monogenic FH from polygenic FH, caused by the accumulation of common single nucleotide variants associated with elevated LDL cholesterol, and from oligogenic FH with multiple deleterious variants. ^[8]

Common risk factors for dyslipidaemia include genetic factors, obesity, lack of physical activity, alcohol abuse and poorly controlled glucose levels. ^[9] Typical diabetic dyslipidaemia combines low HDL cholesterol, high triglycerides and mildly increased or even normal LDL, an attenuated LDL rise attributed to more atherogenic small dense LDL particles. ^[9] Atherogenic dyslipidemia is a component of the metabolic syndrome, whose major drivers are excess energy intake and concomitant obesity. ^[10] FH is caused by deleterious mutations in the LDL receptor or its associated genes, and FH genetic testing should include the genes encoding the LDL receptor (LDLR), apolipoprotein B (APOB) and PCSK9. ^[8]

Lipid-lowering therapy should be considered, in addition to lifestyle interventions, for persons at moderate to high risk for ASCVD based on validated risk equations. ^[1] The 2021 Canadian Cardiovascular Society (CCS) guidelines recommend measuring lipoprotein(a) once in a patient's lifetime, as part of initial lipid screening to assess cardiovascular risk. ^[15] For any patient with triglycerides above 1.5 mmol/L, the 2021 CCS guidelines prefer non-HDL cholesterol or apolipoprotein B over LDL-C as the lipid parameter for screening. ^[15] The 2021 CCS guidelines also update the role of coronary artery calcium scoring as a clinical decision tool to aid the decision to initiate statin therapy. ^[15] As summarized in a recent practical review, the 2025 Focused Update of the 2019 ESC/EAS dyslipidaemia guidelines leaves LDL-C

All persons with dyslipidemia should be advised on lifestyle interventions, including regular aerobic exercise, a healthy diet, maintenance of a healthy weight and abstinence from smoking. ^[1] Statins remain the first-line drug treatment, with ezetimibe, bempedoic acid and PCSK9 inhibitors as additional options alone or in combination. ^{[2] [1]} The 2021 CCS guidelines continue to recommend statin therapy in patients with clinical atherosclerosis, abdominal aortic aneurysm, most patients with diabetes or chronic kidney disease, and those with LDL-C of 5 mmol/L or higher, and introduce lipid or lipoprotein thresholds for intensifying therapy with nonstatin agents. ^[15] A key new recommendation of the 2025 ESC/EAS focused update is potent early combination lipid-lowering therapy after an acute coronary syndrome. ^[2]