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moderate risk. Recent studies have provided important new evidence regarding the clinical risk associated with subclinical atherosclerosis documented on coronary or peripheral arterial imaging in persons without clinical ASCVD.19 While there are no randomized trials showing that the use of coronary artery calcium (CAC) to classify CV risk and guide therapeutic management improves CV outcomes, nevertheless consideration of CAC improves both discrimination and reclassification.20 An elevated CAC score has been associated in a graded fashion with a higher risk of adverse CV events in persons without clinical ASCVD (primary prevention);21–23 at markedly elevated CAC values (e.g. CAC score >300), the risk was similar or even higher than the risk of patients with known clinical ASCVD (secondary prevention).24,25 Conversely, a CAC score of zero has been associated with a lower risk of ASCVD events and mortality in persons at low to moderate estimated CV risk.26 Consideration of CAC improves the accuracy of predicted CVD risk by means of the SCORE2 algorithm.27 While the presence of significant (typically, obstructive) plaque on invasive or computed tomography (CT)-based coronary angiography was defined as a feature of very high CV risk in the 2019 ESC/EAS Guidelines,1 the presence of less advanced coronary atherosclerosis with non-obstructive plaques was more recently shown to be associated with an increased risk of subsequent MI.28 Against this background, while coronary imaging or CAC measurement are not indicated as broad screening tests for the purpose of CV risk estimation, this Focused Update includes a new recommendation that the presence of subclinical atherosclerosis by imaging or increased CAC score, if measured, should be considered as risk modifiers in individuals at moderate risk or individuals around treatment decision thresholds (Recommendation Table 1). It should be noted, however, that statin therapy may lead to a decrease in lipid-rich plaque and an increase in calcification, indicating plaque stabilization;29,30

therefore, CAC score should be interpreted with caution in statintreated patients. For patients with type 2 diabetes mellitus (T2DM) without ASCVD, the 2023 ESC Guidelines for CVD management in patients with diabetes recommend the use of the SCORE2-Diabetes algorithm to estimate 10 year CVD risk.31,32 It is important to note that the LDL-C treatment goals (Figure 1) and therapeutic guidance (Table 4) for persons in each risk category have not changed from the 2019 ESC/EAS Guidelines.1 The intensity of the recommended LDL-C lowering continues to be determined by a person’s level of risk. Previous studies indicated potential underestimation of CV risk based on the SCORE2 and SCORE2-OP,18 and undertreatment with lipid-lowering therapy in primary prevention if statins were to be recommended only for persons at very high risk.33 Importantly, however, as outlined in the 2019 ESC/EAS Guidelines,1 the recommendation to initiate pharmacological LDL-C-lowering therapy in primary prevention is not restricted to persons at very high risk, but depends on both the estimated CV risk and the baseline (untreated) LDL-C levels (Table 4). This concept was previously illustrated in

• Patients with ASCVD who experience recurrent vascular events while taking maximally tolerated statin-based therapy • Patients with polyvascular (e.g. coronary and peripheral) arterial disease

Treatment goal

for LDL-C

Class IIb

Class IIa

Class I

Class Ia

Class IIb & ≥50% reduction

from baseline

aClass IIa for individuals in primary prevention with FH at very high risk CV Risk

SCORE2/SCORE2-OP <2%

• SCORE2/SCORE2-OP ≥2% and <10% • Young patients (T1DM <35 years; T2DM <50 years) with DM duration <10 years without other risk factors • SCORE2/SCORE2-OP ≥10% and <20% • Markedly elevated single risk factors, in particular TC >8 mmol/L (310 mg/dL) or LDL-C >4.9 mmol/L  (190 mg/dL) or BP ≥180/110 mmHg • FH without other major risk factors • Moderate CKD (eGFR 30–59 mL/min/1.73 m2) • DM w/o target organ damage, with DM duration ≥10 years or other additional risk factor

• ASCVD (clinical/imaging) • SCORE2/SCORE2-OP ≥20% • FH with ASCVD or with another major risk factor • Severe CKD (eGFR <30 mL/min/1.73 m2) • DM & target organ damage: ≥3 major risk factors; or early onset of T1DM of long duration (>20 years)

 

   


 

 

  
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Figure 1 Treatment goals for low-density lipoprotein cholesterol across categories of total cardiovascular risk. ASCVD, atherosclerotic cardiovascular disease; BP, blood pressure; CKD, chronic kidney disease; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; FH, familial hypercholesterolaemia; LDL-C, low-density lipoprotein cholesterol; SCORE2, Systematic Coronary Risk Evaluation 2; SCORE2-OP, Systematic Coronary Risk Evaluation 2-Older Persons; T1DM, type 1 DM; T2DM, type 2 DM; TC, total cholesterol. Downloaded from academic.oup.com/eurheartj/article/46/42/4359/8234482 by guest on 07 October 2026