Diabetes and Lipid Clinic of Alaska

 

 


Using Carotid Intima-Media Thickness Measurements To Improve Cardiovascular Risk Prediction

Measurement of carotid intima-media thickness (CIMT) with B-mode ultrasound is a noninvasive and highly reproducible technique for quantifying atherosclerotic burden. Although it is a well-validated research technique, until recently it has not been used widely as a clinical tool, even though the AHA Prevention Conference V concluded that CIMT could be used clinically "for further clarification of coronary heart disease (CHD) risk assessment" (1). We have demonstrated that measurement of CIMT is feasible in a clinical setting and that the age component of Framingham CHD risk assessment can be modified by incorporating "vascular age," an assessment of current atherosclerotic burden derived from measurement of CIMT (2).

Why look at the neck when you are interested in the heart?

The carotid arteries provide a "window" to the coronary arteries. Not only do they have similar risk factors - more importantly, the relationship between the atherosclerotic burden in a carotid artery and a coronary artery is the same as between any two coronary arteries (3). Thus, carotid atherosclerosis provides a window to the degree of coronary atherosclerosis in an individual. By examining the carotid artery wall rather than the lumen, risk prediction with carotid ultrasound identifies an earlier stage of atherosclerosis than standard Duplex carotid imaging. Using a high-resolution B-mode ultrasound transducer, the common carotid, the carotid bulb, and the internal carotid artery can be interrogated to identify the presence of non-occlusive plaques and specifically to measure CIMT, the combined thicknesses of the intimal and medial layers of carotid walls. CIMT is an independent predictor of future cardiovascular events, including heart attacks, cardiac death, and stroke (1).

Why use CIMT measurements clinically?

There are several advantages to using CIMT measurements in a clinical setting. It is completely noninvasive, does not involve radiation, and has no known adverse biological effects. It also identifies both minor and major stenoses, corresponding to both early and late vascular disease. A major advantage to using CIMT to predict risk is that normal values are known, which is an advantage over many other imaging modalities. Large, prospective epidemiological trials that included large numbers of men and women, individuals of many races, and a wide range of ages permit the delineation of percentiles so patients and health care professionals can know which values are "normal," "high," or "low" (2,4,5). CIMT values not only predict future myocardial infarction and strokes, they also provide incremental predictive power in addition to standard risk factors (6-11). In recognition of this rich database, the American Heart Association Prevention Conference V recommended CIMT scanning for patients who are over 45 years old who require further clarification of their coronary heart disease risk (1).

Evidence for Use of CIMT in Clinical Risk Prediction

Several studies have demonstrated that CIMT values predict future cardiovascular events (1,6-11). The Atherosclerosis Risk in Communities (ARIC) study is an excellent example (6,7). The ARIC study included 15,792 men and women who were 45-64 years old. In the ARIC study, increasing CIMT identified prevalent cardiovascular disease, including angina, myocardial infarction, stroke, transient ischemic attack, or peripheral vascular disease (13). More important, the presence of increased CIMT predicted future coronary heart disease events, both for men and women (6). As the walls of the carotid arteries became thicker, the age and gender adjusted incidence rates for cardiac death or myocardial infarction increased in a stepwise fashion. CIMT also predicts strokes, and after seven years of followup in ARIC, increased CIMT predicted cerebrovascular events both in men and women (7). In multivariate analysis, after adjusting for CHD risk factors such as cholesterol levels, blood pressure, and tobacco use, the ability of CIMT to predict future cardiovascular events remained statistically significant and had incremental predictive power both in women and in men (6,7). Five studies, all of which had over 1,000 patients, have demonstrated the predictive power of CIMT measurement (6-10).

Rationale for Using CIMT-Derived "Vascular Age" in Clinical Practice

Current guidelines recommend that if a patient has two or more risk factors for CHD, the Framingham Risk algorithm should be used to determine 10-year risk of heart attack or cardiac death (14). One of the limitations of using the Framingham Risk algorithm is that it assigns the same number of points to every patient at a given age regardless of their atherosclerotic burden, which ignores great variation in plaque burden at any chronological age (15). The rich database from the many clinical trials that used CIMT provides an opportunity to adjust a patient's chronological age for their atherosclerotic burden, a concept that we call "vascular age" (2,16). Vascular age reflects atherosclerotic burden, which varies between individuals with the same chronological age, despite similar CHD risk profiles. Vascular age can be used to modify population-based risk estimates (2,16).

Determination of Vascular Age

Based on data from the ARIC study, models were constructed for each of the CIMT percentile functions specifically created for each of six carotid arterial segments, by sex, race, and age (2,4). Composite CIMT values were used to determine vascular age, defined as the age at which the composite CIMT value for an individual of a given race and sex would represent the median value in the ARIC study. Specifically, the linear 50th percentile function by chronological age, sex, and race was used to project the age of each subject based on their composite CIMT value. If each of a given subject's segmental CIMT values were at the 50th percentile for their chronological age, sex, and race, then their composite CIMT would be at the 50th percentile and their vascular age would be equal to their chronological age. For example, a 45-year black female with a composite CIMT of 0.593 mm would have a CIMT percentile of 50% and a vascular age of 45 years; however, a 45-year black female with a composite CIMT of 0.678 mm would have a CIMT percentile of 71% and a vascular age of 55 years, representing the age at which a composite CIMT value of 0.678 mm represents the 50 th percentile. Vascular age was substituted for chronological age in the Framingham CHD risk prediction model, resulting in a modified CHD risk estimate (2). Biases in projected CIMT values resulting from application of linear and non-linear functions were <5% for composite CIMT values for all ages, sexes, and races represented by the data. Because the biases in projected CIMT estimates at the 50th percentile were very small and both clinically and statistically insignificant for both linear and nonlinear functions, linear estimates are used in our laboratory (mean bias 1.37 ± 0.36%, p=0.324) (2). We also have created vascular age nomograms for individuals < 40 years old using data from the Bogalusa Heart Study (5).

Summary

Measurement of CIMT is feasible in a clinical setting. Determining vascular age is a powerful clinical strategy by which a noninvasive estimate of an individual's current atherosclerotic burden can be integrated into global CHD risk assessment models to alter CHD risk prediction. Measuring CIMT can help identify previously unrecognized high-risk individuals and help clinicians better tailor primary prevention strategies to an individual patient's cardiovascular risk.


References

  1. Greenland P, Abrams J, Aurigemma GP, Bond MG, Clark LT, Criqui MH, et al. Prevention Conference V: Beyond secondary prevention: identifying the high-risk patient for primary prevention: noninvasive tests of atherosclerotic burden: Writing Group III. Circulation 2000;101:E16-E22.
  2. Stein JH, Fraizer MC, Aeschlimann SE, Nelson-Worel J, McBride PE, Douglas PS. Vascular age: Integrating carotid intima-media thickness measurements with global coronary risk assessment. Clinical Cardiology 2004; 27:388-392.
  3. Young W, Gofman J, Tandy R, Malamud N, Waters E. The quantitation of atherosclerosis III. The extent of correlation of degrees of atherosclerosis with and between the coronary and cerebral vascular beds. Am J Cardiol 1960;8:300-8.
  4. Howard G, Sharrett A, Heiss G, Evans G, Chambless L, Riley W, et al. Carotid artery intimal-medial thickness distribution in general populations as evaluated by B-mode ultrasound. Stroke 1993;24:1297-1304.
  5. Stein JH , Douglas PS, Srinivasan SR, Bond MG, Tang R, Chen W, Berenson GS. Distribution and cross-sectional age-related increases of carotid artery intima-media thickness in young adults: The Bogalusa Heart Study. Stroke 2004; 12:2782-2787 (correction Stroke 2005; 36:414).
  6. Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M, Sharrett AR, et al. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993. Am J Epidemiol 1997;146:483-94.
  7. Chambless LE, Folsom AR, Clegg LX, Sharrett AR, Shahar E, Nieto FJ, et al. Carotid wall thickness is predictive of incident clinical stroke: the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol 2000;151:478-87.
  8. O'Leary D, Polak J, Kronmal R, Manolio T, Burke G, Wolfson S Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults: Cardiovascular Health Study. N Engl J Med 1999;340:14-22.
  9. 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;96:1432-7.
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