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.............. follow-up period was low (1.54.9%).26 In contrast, the rates of ASCVD and coronary heart disease (CHD) events in individuals with a CAC score >100 Agatston were 18.9 and 12.7 per 1000 personyears, respectively.18 Compared with a strategy of treating all patients, the use of CAC score to guide long-term statin therapy has been shown to be cost-effective.27 Note that CAC score is often very low in patients younger than 45 years of age with severe familial hypercholesterolaemia (FH), including homozygous FH (HoFH), and has low specificity in this population. Assessment of coronary luminal stenosis >50% and plaque composition with coronary CT angiography also provides incremental prognostic value over traditional risk stratification models.28 As a result, in asymptomatic individuals with moderate risk, the presence of a CAC score >100 Agatston, and carotid or femoral plaque burden on ultrasonography, may reclassify them to a higher risk category. Therefore, the use of methods to detect these markers should be of interest in that group (see Recommendations for cardiovascular imaging for risk assessment of atherosclerotic cardiovascular disease below).1416 Overall, CAC score assessment with CT may be considered in individuals at low or moderate risk in whom the respective LDL-C goal is not achieved with lifestyle intervention alone, and pharmacological therapy is an option (see Table 5). The use of imaging techniques to determine the presence and extent of atherosclerotic vascular damage in low-risk individuals not being considered for statin therapy is not justified due to low prognostic yield, and the associated costs and radiation hazards when measuring CAC score, particularly among low-risk women.29 Of note, CAC score is increased following statin treatment; therefore, the CAC scores of statin-treated patients should be interpreted with caution.

4.2.2 Risk-based intervention strategies Table 5 presents suggested intervention strategies as a function of total CV risk and LDL-C level. This graded approach is based on evidence from multiple meta-analyses and individual randomized controlled trials (RCTs), which show a consistent and graded reduction in ASCVD risk in response to reductions in TC and LDL-C levels (see Recommendations for cardiovascular disease risk estimation below).3141 These data are consistent in showing that, since the relative risk reduction is proportional to the absolute reduction in LDL-C and the absolute reduction in LDL-C resulting from a particular drug regimen depends only on baseline LDL-C, at any given level of baseline risk the higher the initial LDL-C level the greater the absolute reduction in risk. Advice on individual drug treatments is given in section 8.

5 Lipids and lipoproteins

5.1 Biological role of lipids and

lipoproteins Lipoproteins in plasma transport lipids to tissues for energy utilization, lipid deposition, steroid hormone production, and bile acid formation. Lipoproteins consist of esterified and unesterified cholesterol, TGs, and phospholipids and protein components named apolipoproteins that act as structural components, ligands for cellular receptor binding, and enzyme activators or inhibitors. There are six major lipoproteins in blood: chylomicrons, very lowdensity lipoprotein (VLDL), intermediate-density lipoprotein (IDL), LDL; Lp(a), and HDL (Table 6 and Supplementary Figure 5).

5.2 Role of lipids and lipoproteins in the

pathophysiology of atherosclerosis All ApoB-containing lipoproteins <70 nm in diameter, including smaller TG-rich lipoproteins and their remnant particles, can cross the endothelial barrier, especially in the presence of endothelial dysfunction, where they can become trapped after interaction with extracellular structures such as proteoglycans.42 ApoB-containing

Recommendations for cardiovascular imaging for risk assessment of atherosclerotic cardiovascular disease

Recommendations Classa Levelb

Arterial (carotid and/or femoral) plaque burden on arterial ultrasonography should be considered as a risk modifier in individuals at low or moderate risk.29,30 IIa B CAC score assessment with CT may be considered as a risk modifier in the CV risk assessment of asymptomatic individuals at low or moderate risk.1416,24,26 IIb B

CAC = coronary artery calcium; CT = computed tomography; CV = cardiovascular. aClass of recommendation. bLevel of evidence. Recommendations for cardiovascular disease risk

estimation

Recommendations Classa Levelb

Total risk estimation using a risk estimation system such as SCORE is recommended for asymptomatic adults >40 years of age without evidence of CVD, DM, CKD, familial hypercholesterolaemia, or LDL-C >4.9 mmol/L (>190 mg/dL). I C It is recommended that high- and very-highrisk individuals are identified on the basis of documented CVD, DM, moderate-to-severe renal disease, very high levels of individual risk factors, FH, or a high SCORE risk. It is recommended that such patients are considered as a priority for advice and management of all risk factors. I C Risk scores developed for the general population are not recommended for CV risk assessment in patients with DM or FH. III C

CKD = chronic kidney disease; CV= cardiovascular; CVD = cardiovascular disease; DM = diabetes mellitus; FH = familial hypercholesterolaemia; LDL-C = lowdensity lipoprotein cholesterol; SCORE = Systematic Coronary Risk Estimation. aClass of recommendation. bLevel of evidence. Downloaded from academic.oup.com/eurheartj/article/41/1/111/5556353 by guest on 07 October 2026