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Atherosclerosis imaging--how and whom?

Coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral artery disease (PAD) cause significant mortality and morbidity. Clinical management in the symptomatic patient is aimed at treatment, while primary prevention requires early identification of asymptomatic individuals. The role of imaging is discussed.

Atherosclerosis

Atherosclerosis is a disease of the arterial wall. Arterial walls consist of three layers: intima, media and adventitia. When low-density lipoprotein (LDL) cholesterol infiltrates the subendothelial space and becomes oxidised, a complex inflammatory process is triggered. Plaques with large lipid cores and thin fibrous caps are vulnerable to rupture, resulting in thrombus formation and possible arterial occlusion. In early atherosclerosis there is thickening of the arterial wall. Narrowing of the lumen occurs late. There is a long subclinical period. Clinical presentation may be acute, with sudden death, myocardial infarct or stroke (occlusion) or chronic, with effort-induced stable angina pectoris or claudication (narrowing).

Risk factors

Large epidemiological studies have identified atherosclerosis risk factors including age, male gender, [up arrow] LDLC, [up arrow] triglyceride, [down arrow] HDLC, hypertension, diabetes and smoking. Guidelines stratify management according to CAD risk, calculated in primary prevention settings using the Framingham risk score (FRS) (USA) or Systemic Coronary Risk Evaluation (SCORE) (Europe).

Imaging modalities

Angiography

Conventional angiography (catheterisation), CT angiography (CTA) and MR angiography (MRA) allow imaging of the lumen. Although conventional angiography is invasive, angioplasty and stent placement is possible. Both conventional and CT angiography expose the patient to ionising radiation and involve the use of contrast. CTA and MRA are non-invasive. However, CTA and MRA of the coronary arteries are technically difficult due to movement, small diameter (3 - 4 mm) and tortuousness of the arteries. The use of beta-blockers to slow the heart rate and ECG gating to allow imaging in mid-diastole may be needed to reduce motion artefacts.1 In selected patients with stable disease and normal cardiac rhythm multidetector CT (MDCT) has sensitivity of 96% and specificity of 74% for detection of significant coronary artery stenoses (>50% narrowing). (2)

It is not possible to identify early atherosclerosis or vulnerable plaque on an angiogram. Angiography is used in the evaluation of symptomatic patients and in clinical trials. It is not used in epidemiological studies or screening.

Ultrasound

Brightness mode (B-mode) ultrasound images the artery wall and is used to detect plaque in the carotid artery and peripheral arteries. Coronary arteries are too small and tortuous and are located deep within the chest cavity. Doppler studies are used to assess flow and quantify obstruction. (3) Ultrasound is safe, non-invasive and without radiation exposure. Ultrasound is used in symptomatic patients and for evaluating the asymptomatic bruit. Doppler is not used in epidemiological studies as flow increases once disease is advanced.

Intima-media thickness (IMT)

B-mode images of the carotid and femoral arteries are analysed using computer software. The average distance between the lumen-intima and the media-adventitia interfaces is measured over a segment of arterial wall. Far wall IMT is more accurate and common carotid IMT more reproducible than bulb or internal carotid measurements. There is good agreement with histology. (4) In the Atherosclerosis Risk in Communities study (ARIC), the 75th percentile was 0.65 mm in men 35-45 years; 1.2 mm in men >65 years; 0.6 mm in women 35-45 years and 1.1 mm in women >65 years. (3) Common carotid IMT increases by approximately 0.010-0.012 mm/year. (5) IMT is associated with risk for CAD and stroke. (6) In a meta-analysis of eight studies relative risk of MI per 1 SD in common carotid IMT was 1.26 (95% CI 1.21-1.3) and per 0.1 mm difference 1.15 (05% CI 1.12-1.17). Relative risk of stroke per 1 SD in common carotid IMT was 1.32 (95% CI 1.27-1.38) and per 0.1 mm difference 1.18 (05% CI 1.16-1.21). (7)

Advantages of IMT are that it is a noninvasive, focused study with few incidental findings.3 Potential problems are that it is difficult to establish age--and gender-adjusted norms, because laboratories use different protocols. Methods also need to be standardised. (3)

IMT is used in epidemiological studies, and as surrogate endpoint in statin and antihypertensive trials. It has a possible use in individual patients to help quantify risk.

Intravascular ultrasound (IVUS)

IVUS uses a miniature ultrasound probe inside a coronary artery catheter. Images of the arterial wall are acquired during cardiac catheterisation and allow measurement of plaque volume and characterisation of plaque. The disadvantage of IVUS is that it is invasive.

It is used in research, but is not suitable for epidemiological studies or screening. (8)

Coronary artery calcium score (CAC)

The measurement of calcium in coronary arteries by rapid CT scan (CAC score) correlates well with histological findings and is predictive of CAD. (9) Non-stenotic lesions may display calcification, resulting in high sensitivity but poor specificity for the detection of significant stenoses. (10) Although CAC score has a poor positive predictive value for near-term events,9 patients with calcified plaques are more likely to have non-calcified plaques that may rupture. A meta-analysis of studies of CAD risk in 27 622 asymptomatic individuals and CAC found a summary relative risk ratio of 4.3 (95% CI 3.5 -5.2) for any measurable coronary calcium compared with CAC score of 0 (p<0.0001). (10)

Advantages of CAC are good spatial resolution, fast image acquisition and sensitive calcium detection. (11) Disadvantages include ionising radiation and incidental findings such as pulmonary nodules.

CAC is useful in asymptomatic individuals with intermediate FRS (10-20%) to discriminate higher risk, but not in patients with risk > 20% or <10%. It is also not recommended in symptomatic patient (nonspecific for obstructive coronary disease) (10) or for routine screening. (12)

MRI

MRI using the 'black-blood' technique (wall shows up as white structure) allows non-invasive imaging of the arterial wall, characterisation of plaque and fibrous cap and can be used to study plaque progression and regression. (13) Measurements of wall thickness, wall area and total plaque volume are highly reproducible, with little error in wall area measurement (aorta 2.6%; carotids 3.5%). (11)

Advantages of MRI are that it is noninvasive, there is no radiation, and it does not require contrast. It also has good resolution. It is used to study carotid arteries in epidemiological studies and clinical trials, but is difficult to use in coronary arteries.

Conclusion

In conclusion, imaging techniques are becoming increasingly sophisticated. Atherosclerosis can be imaged using different modalities--some are used in clinical practice and others only for research purposes. Factors such as availability, cost, radiation dose, possible nephrotoxic effects of contrast and the specific vascular bed to be imaged, need to be considered.

References

(1.) Flice R, Lima JA, Bluemke DA. Subclinical disease detection: advanced imaging applications. Top Magn Reson Imaging 2007; 18(5): 339-348.

(2.) Sanz J, Fayad ZA. Imaging of atherosclerotic cardiovascular disease. Nature 2008; 451(7181): 953-957.

(3.) Redberg RF, Vogel RA, Criqui MH, Herrington DM, Lima JA, Roman MJ. 34th Bethesda Conference: Task force #3--What is the spectrum of current and emerging techniques for the noninvasive measurement of atherosclerosis? J Am Coll Cardiol 2003; 41(11): 1886-1898.

(4.) Schulte-Altedorneburg G, Droste DW, Felszeghy S, et al. Accuracy of in vivo carotid B-mode ultrasound compared with pathological analysis: intima-media thickening, lumen diameter, and cross-sectional area. Stroke 2001; 32(7): 1520-1524.

(5.) Howard G, Burke GL, Evans GW, et al. Relations of intimal-medial thickness among sites within the carotid artery as evaluated by B-mode ultrasound. ARIC Investigators. Atherosclerosis Risk in Communities. Stroke 1994; 25(8): 1581-1587.

(6.) Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation 1997; 96(5): 1432-1437.

(7.) Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 2007; 115(4): 459-467.

(8.) Toth PP. Subclinical atherosclerosis: what it is, what it means and what we can do about it. Int J Clin Pract 2008; 62(8): 1246-1254.

(9.) Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study. Circulation 1995; 92(8): 2157-2162.

(10.) Greenland P, Bonow RO, Brundage BH, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography). Circulation 2007; 115(3): 402-426.

(11.) Rudd JH, Myers KS, Sanz J, Fayad ZA. Multimodality imaging of atherosclerosis (magnetic resonance imaging/computed tomography/positron emission tomography-computed tomography). Top Magn Reson Imaging 2007; 18(5): 379-388.

(12.) Greenland P, Lloyd-Jones D. Defining a rational approach to screening for cardiovascular risk in asymptomatic patients. J Am Coll Cardiol 2008; 52(5): 330-332.

(13.) Yuan C, Oikawa M, Miller Z, Hatsukami T. MRI of carotid atherosclerosis. J Nucl Cardiol 2008; 15(2): 266-275.

K H WOLMARANS, MB ChB

Medical Officer, Lipid Clinic, Groote Schuur Hospital and Lipid Laboratory, University of Cape Town Health Science Faculty
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Title Annotation:More about... Dyslipidaemia
Author:Wolmarans, K.H.
Publication:CME: Your SA Journal of CPD
Article Type:Report
Geographic Code:6SOUT
Date:Mar 1, 2009
Words:1544
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