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vary considerably according to age and sex. In this Focused Update, a 2× multiplier was used to convert previous SCORE-based thresholds17 into the SCORE2- or SCORE2-OP-based thresholds to define different categories of total CVD risk. Notably, this Task Force continues to emphasize that risk is a continuum and cut-off points that are used in any CVD risk model to define different levels of risk are, in part, arbitrary and based on the risk levels at which benefit is evident in clinical trials. Therefore, the SCORE2- and SCORE2-OP-based thresholds presented in this document (Table 3) reflect this concept. Because existing population-based CVD risk models are relatively crude tools for individual risk prediction,18 attention to additional characteristics that are known to increase CV risk is reasonable in order to refine risk assessment, as already discussed in the 2021 ESC Prevention Guidelines.17 This is particularly relevant for persons around treatment decision thresholds (Recommendation Table 1). Clinical conditions and selected biomarkers that can be considered as risk modifiers are summarized in Box 1. Their presence may support reclassifying an individual to a higher risk category than would be calculated by the SCORE2 or SCORE2-OP algorithm, and may thereby guide decisions about LDL-C goals and lipid-lowering interventions. This Focused Update endorses the Class IIa recommendation of the 2019 ESC/EAS Guidelines1 that arterial (carotid and/or femoral) plaque burden should be considered as a risk modifier in individuals at low or Table 4 Intervention strategies as a function of total cardiovascular risk and untreated low-density lipoprotein cholesterol levels Total CV risk Untreated LDL-C levels <1.4 mmol/L (<55 mg/dL) 1.4 to <1.8 mmol/L (55 to <70 mg/dL) 1.8 to <2.6 mmol/L (70 to <100 mg/dL) 2.6 to <3.0 mmol/L (100 to <116 mg/ dL) 3.0 to <4.9 mmol/L (116 to <190 mg/ dL ≥4.9 mmol/L (≥190 mg/dL)a Low Lifestyle advice Lifestyle advice Lifestyle advice Lifestyle advice Lifestyle modification, consider adding drug if uncontrolled N/Aa Moderate Lifestyle advice Lifestyle advice Lifestyle advice Lifestyle modification, consider adding drug if uncontrolled Lifestyle modification, consider adding drug if uncontrolled N/Aa High Lifestyle advice Lifestyle advice Lifestyle modification, consider adding drug if uncontrolled Lifestyle modification and concomitant drug intervention Lifestyle modification and concomitant drug intervention Lifestyle modification and concomitant drug intervention Very high: primary prevention Lifestyle modification, consider adding drug Lifestyle modification, consider adding drug Lifestyle modification and concomitant drug intervention Lifestyle modification and concomitant drug intervention Lifestyle modification and concomitant drug intervention Lifestyle modification and concomitant drug intervention Very high: secondary prevention Lifestyle modification and concomitant drug intervention Lifestyle modification and concomitant drug intervention Lifestyle modification and concomitant drug intervention Lifestyle modification and concomitant drug intervention Lifestyle modification and concomitant drug intervention Lifestyle modification and concomitant drug intervention © ESC/EAS 2025 CV, cardiovascular; LDL-C, low-density lipoprotein cholesterol; N/A, not applicable. aIn individuals with untreated LDL-C levels ≥4.9 mmol/L, total CV risk is already at least high (Table 3). Box 1 Risk modifiers for consideration beyond the risk estimation based on the SCORE2 and SCORE2-OP algorithms Demographic/clinical conditions • Family history of premature CVD (men: <55 years; women: <60 years) • High-risk ethnicity (e.g. Southern Asian) • Stress symptoms and psychosocial stressors • Social deprivation • Obesity • Physical inactivity • Chronic immune-mediated/inflammatory disorders • Major psychiatric disorders • History of premature menopause • Pre-eclampsia or other hypertensive disorders of pregnancy • Human immunodeficiency virus infection • Obstructive sleep apnoea syndrome Biomarkers • Persistently elevated hs-CRP (>2 mg/L) • Elevated Lp(a) [>50 mg/dL (>105 nmol/L)]. CVD, cardiovascular disease; hs-CRP, high sensitivity C-reactive protein; Lp(a), lipoprotein(a). ESC Guidelines 4365 Downloaded from academic.oup.com/eurheartj/article/46/42/4359/8234482 by guest on 07 October 2026