Coronary Artery Calcium and Carotid Artery Intima Media Thickness and Plaque: Clinical Use in Need of Clarification

Abstract

Atherosclerosis begins in early life and has a long latent period prior to onset of clinical disease. Measures of subclinical atherosclerosis, therefore, may have important implications for research and clinical practice of atherosclerotic cardiovascular disease (ASCVD). In this review, we focus on coronary artery calcium (CAC) and carotid artery intima-media thickness (cIMT) and plaque as many population-based studies have investigated these measures due to their non-invasive features and ease of administration. To date, a vast majority of studies have been conducted in the US and European countries, in which both CAC and cIMT/plaque have been shown to be associated with future risk of ASCVD, independent of conventional risk factors. Furthermore, these measures improve risk prediction when added to a global risk prediction model, such as the Framingham risk score. However, no clinical trial has assessed whether screening with CAC or cIMT/plaque will lead to improved clinical outcomes and healthcare costs. Interestingly, similar levels of CAC or cIMT/plaque among various regions and ethnic groups may in fact be associated with significantly different levels of absolute risk of ASCVD. Therefore, it remains to be determined whether measures of subclinical atherosclerosis improve risk prediction in non-US/European populations. Although CAC and cIMT/plaque are promising surrogates of ASCVD in research, we conclude that their use in clinical practice, especially as screening tools for primary prevention in asymptomatic adults, is premature due to many vagaries that remain to be clarified.

Fig. 1.

A schematic of the theoretical LDL-initiated formation of atherosclerotic plaques in the arterial wall A high concentration of circulating LDL causes damage to the arterial wall and allows for entry and oxidization of LDL in the intimal layer. This leads to the secretion of chemokines and expression of leukocyte adhesion markers by endothelial cells. Monocytes are recruited to the site of injury. Once inside the intima, monocytes differentiate into macrophages and engulf the oxidized LDL. Continual uptake of oxidized LDL (due to prolonged high levels of circulating LDL) causes macrophages to become lipid-laden foam cells. Foam cells remain in the intima, secrete proinflammatory cytokines and chemokines, thus recruiting more monocytes. Dying foam cells lead to the formation of the necrotic core, which may become calcified. Smooth muscle cells migrate to the lipid pool of foam cells in an attempt to stabilize the plaque, however, local macrophages secrete enzymes that degrade the fibrous cap, causing the plaque to be vulnerable to rupture. Once ruptured, thrombosis ensues and may lead to myocardial infarction or stroke.

Fig. 2.

A) CT images of four different individuals with varying degrees of coronary artery calcium (CAC) and B) calculation of CAC score (Agatston method) On CT image, calcification is expressed as a white lesion (≥ 130 Hounsfield Unit (HU). Calcification in the left anterior descending artery is depicted by arrows. Ao = aorta, LA = left atrium.

Fig. 3.

Visualization of the carotid artery A) A simplified diagram of the carotid artery. The layers of the arterial wall are depicted, with the distance from the intima to the media-adventitia interface being intima-media thickness (IMT). IMT measurements of common carotid artery (CCA), bifurcation, and internal carotid artery (ICA) are often included in cIMT. B) An ultrasound image of the CCA, with the distance between arrow heads corresponding to IMT. C) A plaque found in the bifurcation of the carotid artery.

Fig. 4.

Prevalence of CAC scores of 0–9, 10–99, 100–399, ≥ 400 according to number of risk factors in Japanese men in Japan (2006–2008) and Caucasian men in the US (2000–2002), aged 45 to 74 years. (Modified from Am J Epidemiol. 2014; 180 (6): 590–598.) Crude prevalence of each CAC category was shown according to age group (45–54 y, 55–64 y, and 65–74 y) and number of 5 conventional risk factors assessed. Number of participants was given in parenthesis under each bar. Five risk factors: (A) Current smoking; (B) Overweight defined as body mass index ≥ 25 kg/m₂; (C) Diabetes mellitus defined as fasting glucose ≥ 126 mg/dL or medication; (D) Hypertension defined as systolic/diastolic blood pressure ≥ 140/90 mmHg or medication; (E) Dyslipidemia defined as LDL-c ≥ 160 mg/dL or HDL-c <40 mg/dL or medication.