Routine Handheld Carotid Ultrasonography for Cardiovascular Risk Stratification and Primary Prevention Treatment Decisions in a Contemporary Middle‐Aged General Population

Nonstandard Abbreviations and Acronyms

CPS

carotid plaque score

SCORE2

Systematic Coronary Risk Evaluation 2

Current European guidelines for primary atherosclerotic cardiovascular disease (ASCVD) prevention recommend treatment decisions to be based on estimating the 10‐year ASCVD risk with the Systematic Coronary Risk Evaluation 2 (SCORE2) model and using age‐dependent cutoffs to define ASCVD risk categories. ¹ Despite the evidence‐based validity of this approach, there is no consideration of factors such as the duration of exposure to a risk factor and relevant drug treatment, or the impact of very high levels of high‐density lipoprotein cholesterol and of risk modifiers. ²

Asymptomatic carotid atherosclerosis has been reported to provide incremental predictive value for ASCVD events over risk factors alone and contributes to considerable ASCVD risk restratification. ² , ³ , ⁴ , ⁵ In a recent study, the degree of carotid atherosclerosis determined by carotid plaque score (CPS) was found to outperform SCORE2 in a head‐to‐head comparison of their prognostic ability. ⁵

The raw data that support the findings of this study are available from the corresponding author upon reasonable request.

This study examined the impact of routine in‐office handheld carotid ultrasonography on detecting asymptomatic carotid atherosclerosis and on treatment decision‐making in a middle‐aged (40–69 years) general population without ASCVD, invited to participate on a voluntary basis in screening programs in 3 municipalities of Attica, Greece, during the period 2023 to 2025. Participants were classified as low‐moderate, high, or very‐high ASCVD risk according to SCORE2 and the guideline‐suggested thresholds as follows: for <50 years old, <2.5%, 2.5 to <7.5%, and ≥7.5%, respectively; for 50 to 69 years old, <5%, 5 to <10%, and ≥10%, respectively. ¹ , ² SCORE2‐Diabetes was used for individuals with diabetes. ¹ , ² Carotid ultrasonography was performed by 2 trained clinicians using a portable device (Lumify Philips Healthcare). Their interobserver variability for 68 carotid intima‐media thickness measurements in 18 individuals was satisfactory: intraclass correlation coefficient 0.84 (95% CI, 0.74–0.90) and absolute difference 0.03 (95% CI, −0.04 to 0.07) mm. CPS was calculated by summing points allocated to the presence of plaques in common carotid artery, carotid bifurcation, and internal carotid artery bilaterally as follows: plaque maximum thickness ≥1.5, ≥2.5, and ≥3.5 mm was given 1, 2, and 3 points, respectively. ⁵ CPS 0 corresponded to low‐moderate ASCVD risk; 1 to 3 to high ASCVD risk; >3 to very‐high ASCVD risk. ⁵ The study protocol was approved by the Sotiria Hospital Scientific Committee and all participants signed informed consent.

Agreement between SCORE2 and CPS in risk classification was assessed using the κ statistic. Multivariable logistic regression was used as a descriptive, incremental modeling approach to identify variables associated with ASCVD risk restratification to a higher category. A base model including variables represented in the SCORE2 equation at their default granularity was used and then additional variables (prediabetes/diabetes, lipoprotein(a), drug therapy, ex‐smoking) were entered one at a time into the base model. Analyses were performed using the R Statistical Software (v4.4.2; R Core Team 2025). Statistical significance was set at the level of P<0.05.

A total of 1070 individuals were analyzed (mean age 57.2±8.0 [SD] years, men 43.3%, body mass index 27.8±4.7 kg/m², smokers 28.4%, diabetes 7.8%, antihypertensive/lipid‐lowering drug treatment 42.3%/46.8% respectively, systolic/diastolic blood pressure 123.8± 14.9/76.8±9.6 mm Hg, SCORE2 5.3±3.5%, CPS 2.4± 2.8). Participants classified as low‐moderate/high/very‐high ASCVD risk were 50.6%/43.5%/5.9% according to SCORE2 and 55.7%/35.8%/8.5% according to CPS (Figure). Applying the ASCVD risk classification thresholds, the agreement between SCORE2 and CPS was 57.5% (κ statistic 0.31, P<0.05) (Figure).

Figure 1. Carotid atherosclerosis and atherosclerotic cardiovascular disease risk reclassification in a middle‐aged population.

A, Sex‐stratified prevalence of ASCVD risk categories according to SCORE2 and CPS. B, Sankey diagrams illustrating reclassification of SCORE2‐based ASCVD risk categories after incorporation of CPS. C, Eligibility for initiation or intensification of antihypertensive and lipid‐lowering treatment among individuals with high ASCVD risk (presence of carotid atherosclerosis). ASCVD indicates atherosclerotic cardiovascular disease; CPS, carotid plaque score; and SCORE2, Systematic Coronary Risk Evaluation 2.

In incremental analyses, significant improvements in model fit for upward ASCVD risk reclassification beyond traditional risk factors were observed for the addition of lipid‐lowering drug treatment (χ² change=11.89, P<0.001), presence of prediabetes and diabetes (7,67, P=0.01), and a trend for antihypertensive treatment (3.82, P=0.05), ex‐smoking (3.58, P=0.06), and lipoprotein(a) ≥50 mg/dL (3.47, P=0.06).

Among individuals not receiving lipid‐lowering treatment (n=569), 33% had carotid atherosclerosis (CPS ≥1) and were eligible for statin initiation. Among individuals not receiving antihypertensive treatment (n=617), 35% had carotid atherosclerosis; 26% of them had blood pressure ≥140/90 mm Hg (systolic or diastolic) and were eligible for antihypertensive therapy. Among individuals with lipid‐lowering treatment 57% had carotid atherosclerosis, and 76% of them had uncontrolled low‐density lipoprotein cholesterol (≥70 mg/dL in high and ≥55 mg/dL in very‐high ASCVD risk according to CPS) (Figure). Among individuals with antihypertensive drug treatment, 57% had carotid atherosclerosis and 47% of them had uncontrolled blood pressure ≥130/80 mm Hg (systolic or diastolic) (Figure).

In this cross‐sectional study, almost half of the screened European middle‐aged population had carotid atherosclerosis. However, only two‐thirds of them were identified by SCORE2 as at least high ASCVD risk. Most important, ASCVD risk factors were poorly controlled, and many individuals were eligible for drug treatment initiation or intensification. These data suggest that the detection of asymptomatic carotid atherosclerosis by clinicians using a handheld ultrasonography device might help in more accurate and timely treatment decisions. Carotid ultrasonography is widely available, easy to perform, and can enhance patients' adherence to drug treatment. ² Current primary prevention guidelines base treatment decisions on ASCVD risk and defined thresholds for drug therapy, whereas detecting subclinical atherosclerosis can reclassify uncertain cases.

The incremental value of drug treatment in risk reclassification probably resulted from the fact that SCORE2 is derived and calibrated in populations untreated for dyslipidemia and does not account for treatment‐related risk attenuation. In this setting, carotid plaque burden appears to capture residual atherosclerotic risk not adequately reflected by SCORE2.

In conclusion, this study showed that standardized routine handheld carotid ultrasonography is feasible and can aid in identifying individuals at high risk for ASCVD at baseline assessment and whose risk might be underestimated based on classic methods.

Sources of Funding

This work was partly supported by research grants from Elpen, Krka, Rafarm, Uni‐Pharma, Velka, Vianex, Viatris through the Special Account for Research Grants, National and Kapodistrian University of Athens.

Disclosures

Anastasios Kollias received lecture/consulting fees by Astra‐Zeneca, Boehringer In, Elpen, Menarini, Pfizer, Rafarm, Servier, Uni‐Pharma, Vianex, Viatris, Winmedica. George S. Stergiou received lecture fees by AstraZeneca, Menarini, Servier, Viatris, WinMedica, consulting fees by AstraZeneca, Menarini, Sanofi‐Aventis, Viatris, and research grants by AstraZeneca, Menarini, Servier, WinMedica. The other authors declared no competing interests.

Supporting information

STROBE Checklist S1