Author + information
- aDepartment of Vascular Surgery, Imperial College, London, United Kingdom
- bDepartment of Surgery, Nicosia Medical School, University of Nicosia, Nicosia, Cyprus
- cCyprus International Institute for Environmental and Public Health in association with the Harvard T.H. Chan School of Public Health, Cyprus University of Technology, Limassol, Cyprus
- ↵∗Reprint requests and correspondence:
Prof. Andrew Nicolaides, Vascular Screening and Diagnostic Center, 2 Kyriacou Matsi Street, 2368 Nicosia, Cyprus.
- atheroclerotic plaques
- common femoral plaques
- computed tomography
- risk stratification
Screening and improved selection of individuals for more effective prevention is now possible because of the following: 1) subclinical atherosclerosis develops slowly over several decades before it becomes clinically manifest; 2) screening methods are now available for detecting the presence and severity of subclinical atherosclerotic plaques; and 3) current primary prevention with aggressive risk factor modification can reduce morbidity and mortality from heart attacks and strokes by 50%.
Two screening methods are currently popular: 1) coronary artery calcium scoring (CACS) using multislice computed tomography scanning; and 2) ultrasonic arterial scanning. Both provide information that can improve the Framingham risk score (FRS).
CACS Using Multislice Computed Tomography Scanning
Prospective studies have shown that CACS is an independent predictor of future coronary events and can be used to reclassify individuals in the intermediate FRS group (10-year FRS 10% to 20%). On the basis of the available data, the American College of Cardiology Foundation and American Heart Association have stated in their guidelines (1) that screening is only recommended in individuals for whom the treatment decision is uncertain after risk estimation (i.e., those at intermediate risk). In these patients, the finding of CACS ≥300 supports reclassification to a higher risk and alters clinical decision making. Individuals with a high FRS (10-year FRS ≥20%) should be treated aggressively according to current guidelines and do not require additional testing.
Disadvantages of CACS include cost and radiation, which do not allow repeated testing, although radiation is low with modern equipment, and lack of information on stroke risk.
Screening With Ultrasound
High-resolution ultrasound can provide images of the arterial wall and plaques at a resolution of 0.2 mm. Although intima-media thickness (IMT) has been used to study the effect of risk factor modification in large groups and has become a validated biomarker (2), it is only marginally better than conventional risk factors in identifying individuals at increased risk and is not recommended in the latest American College of Cardiology Foundation/American Heart Association guidelines (1). However, in a prospective Norwegian study (the Tromsø study ) and a Canadian cohort study (4) with 10- and 5-year follow-up, respectively, total plaque area was strongly associated with first-ever ischemic stroke and myocardial infarction (3) and combined risk of stroke, myocardial infarction, and vascular death (4), with risk increasing with increasing plaque area quartile. Three prospective studies (5–7) demonstrated that the presence of carotid plaques and presence of common femoral bifurcation plaques were both associated with future cardiovascular events, independently of risk factors. In addition, increased plaque burden increased the cardiovascular risk further. The increase in risk for myocardial infarction, cardiovascular mortality, and overall mortality was 52%, 70%, and 45%, respectively, for each increase in the number of plaque-affected arteries (p < 0.001) (6). A recent meta-analysis demonstrated the superiority of plaque compared with IMT in cardiovascular risk prediction (8). Thus, the presence and size of subclinical carotid and femoral plaques are emerging as having a strong association with coronary heart disease and stroke. They can be used to reclassify those in intermediate and low FRS into higher or lower risk. However, in contrast to IMT, the value of subclinical atherosclerotic plaques has not yet been considered in any of the guidelines on cardiovascular risk assessment.
The paper by Laclaustra et al. (9) in this issue of the Journal demonstrates a strong independent association of risk factors, carotid bifurcation plaques, and common femoral bifurcation plaques with CACS, highlighting the possible use of femoral ultrasound in screening and primary prevention. Femoral plaques were more prevalent in this middle-aged occupational male cohort, were more strongly associated with the most common risk factors for cardiovascular disease (i.e., hypertension, dyslipidemia, and smoking), and better predicted a positive CACS than carotid plaques. Importantly, the area under the receiver-operating characteristic curve for prediction of positive CACS increased from 0.665 considering only traditional risk factors to 0.719 when adding both femoral and carotid plaques, with the odds ratio for femoral (2.58) exceeding that for carotid (1.80) for prediction of positive CACS. Another important observation was that prevalence of subclinical atherosclerosis was demonstrated in 21% to 34% for each individual vessel in men with no risk factors. These reports support previous findings of a high prevalence (34%) of carotid plaques in individuals at low FRS and CACS of 0 (10) who could be reclassified at higher risk. Although, keeping in mind that the associations reported by Laclaustra et al. (9) come from a cross-sectional analysis and demonstrate only the association between carotid/femoral plaques and CACS, they highlight the possibility of improving existing risk prediction scores by adding a relatively simple piece of information.
The messages from the previously mentioned studies are clear: 1) subclinical atherosclerotic plaques are common; 2) they are present in 30% to 40% of individuals at low FRS; and 3) the risk is increased with increasing number of carotid or common femoral vessels involved (i.e., increased plaque burden).
Advantages of screening with ultrasound are the relatively low cost and absence of radiation. In addition, scans can be repeated at 6-monthly intervals or annually providing information on plaque progression or regression. Although scrutiny of the significance of subclinical atherosclerotic plaques (not IMT) by the panel of experts on practice guidelines and cost effectiveness studies are needed before population screening can be recommended, a rational plan as currently used by the authors is provided in Table 1.
A final consideration is that ultrasound could prove to be a potent tool in life-style modification, as there is nothing more powerful than asymptomatic individuals experiencing a real-time image of their arteries showing atherosclerotic deposits. Such deposits are the end result of all risk factors, known, genetic, emerging, and others yet unknown.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose. Tasneem Z. Naqvi, MD, served as Guest Editor for this paper.
- American College of Cardiology Foundation
- Goff D.C. Jr..,
- Lloyd-Jones D.M.,
- Bennett G.,
- et al.
- Lorenz M.W.,
- Marcus H.S.,
- Bots M.L.,
- et al.
- Mathiesen E.B.,
- Johnsen S.H.,
- Wilsgaard T.,
- et al.
- Spence J.D.,
- Eliasziw M.,
- DiCicco M.,
- et al.
- Lamina C.,
- Meisinger C.,
- Heid I.M.,
- et al.
- Laclaustra M.,
- Casasnovas J.A.,
- Fernández-Ortiz A.,
- et al.