Articles15 February 1998
    Author, Article, and Disclosure Information

    Abstract

    Background:

    Carotid arterial intima-media thickness is used as a noninvasive surrogate end point to measure progression of atherosclerosis, but its relation to coronary events has not been fully explored.

    Objective:

    To determine whether carotid arterial intima-media thickness predicts coronary events.

    Design:

    Long-term follow-up (average, 8.8 years) of a previously assembled cohort of persons who completed the 2-year Cholesterol Lowering Atherosclerosis Study, a randomized arterial imaging trial designed to study the effects of lipid lowering on progression of atherosclerosis.

    Setting:

    University-based ultrasonography laboratory.

    Patients:

    146 men 40 to 59 years of age who had previously had coronary artery bypass graft surgery.

    Measurements:

    Preintrusive atherosclerosis in the common carotid artery was evaluated every 6 months with B-mode ultrasonography, and intrusive atherosclerosis in the coronary arteries was evaluated at baseline and at 2 years with quantitative coronary angiography. After the trial, the incidences of coronary events (nonfatal acute myocardial infarction, coronary death, and coronary artery revascularization) were documented.

    Results:

    For each 0.03-mm increase per year in carotid arterial intima-media thickness, the relative risk for non-fatal myocardial infarction or coronary death was 2.2 (95% CI, 1.4 to 3.6) and the relative risk for any coronary event was 3.1 (CI, 2.1 to 4.5) (P < 0.001). Absolute intima-media thickness was also related to risk for clinical coronary events (P < 0.02). Absolute thickness and progression in thickness predicted risk for coronary events beyond that predicted by coronary arterial measures of atherosclerosis and lipid measurements (P < 0.001).

    Conclusion:

    Noninvasive B-mode ultrasonographic measurement of progression of intima-media thickness in the distal common carotid artery is a useful surrogate end point for clinical coronary events.

    References

    • 1. Blankenhorn DH, Hodis HN. George Lyman Duff Memorial Lecture. Arterial imaging and atherosclerosis reversal. Arterioscler Thromb. 1994; 14:177-92. Google Scholar
    • 2. Hodis HN, Mack WJ. Risk factor assessment, treatment strategy and prevention of coronary artery disease: the need for a more rational approach [Editorial]. J Intern Med. 1994; 236:111-3. Google Scholar
    • 3. Mack WJ, Selzer RH, Hodis HN, Erickson JK, Liu CR, Liu CH, et al. One-year reduction and longitudinal analysis of carotid intima-media thickness associated with colestipol/niacin therapy. Stroke. 1993; 24:1779-83. Google Scholar
    • 4. Azen SP, Mack WJ, Cashin-Hemphill L, LaBree L, Shircore AM, Selzer RH, et al. Progression of coronary artery disease predicts clinical coronary events. Long-term follow-up from the Cholesterol Lowering Atherosclerosis Study (CLAS). Circulation. 1996; 93:34-41. Google Scholar
    • 5. Buchwald H, Matts JP, Fitch LL, Campos CT, Sanmarco ME, Amplatz K, et al. Changes in sequential coronary arteriograms and subsequent coronary events. Surgical Control of the Hyperlipidemias (POSCH) Group. JAMA. 1992; 268:1429-33. Google Scholar
    • 6. Waters D, Craven TE, Lesperance J. Prognostic significance of progression of coronary atherosclerosis. Circulation. 1993; 87:1067-75. Google Scholar
    • 7. Mitchell JR, Schwartz CJ. Relationship between arterial disease at different sites. Br Med J. 1962; 1:1293-301. Google Scholar
    • 8. Persson J, Formgren J, Israelsson B, Berglund G. Ultrasound-determined intima-media thickness and atherosclerosis. Direct and indirect validation. Arterioscler Thromb. 1994; 14:261-4. Google Scholar
    • 9. Geroulakos G, O'Gorman D, Nicolaides A, Sheridan D, Elkeles R, Shaper AG. Carotid intima-media thickness: correlation with the British Regional Heart Study risk score. J Intern Med. 1994; 235:431-3. Google Scholar
    • 10. Geroulakos G, O'Gorman DJ, Kalodiki E, Sheridan DJ, Nicolaides AN. The carotid intima-media thickness as a marker of the presence of severe symptomatic coronary artery disease. Eur Heart J. 1994; 15:781-5. Google Scholar
    • 11. Crouse JR 3d, Craven TE, Hagaman AP, Bond MG. Association of coronary disease with segment-specific intimal-medial thickening of the extracranial carotid artery. Circulation. 1995; 92:1141-7. Google Scholar
    • 12. Blankenhorn DH, Johnson RL, Nessim SA, Azen SP, Sanmarco ME, Selzer RH. The Cholesterol Lowering Atherosclerosis Study (CLAS): design, methods, and baseline results. Controlled Clin Trials. 1987; 8:354-87. Google Scholar
    • 13. Blankenhorn DH, Nessim SA, Johnson RL, Sanmarco ME, Azen SP, Cashin-Hemphill L. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA. 1987; 257:3233-40. Google Scholar
    • 14. Cashin-Hemphill L, Mack WJ, Pogoda JM, Sanmarco ME, Azen SP, Blankenhorn DH. Beneficial effects of colestipol-niacin on coronary atherosclerosis. A 4-year follow-up. JAMA. 1990; 264:3013-7. Google Scholar
    • 15. Blankenhorn DH, Azen SP, Crawford DW, Nessim SA, Sanmarco ME, Selzer RH, et al. Effects of colestipol-niacin therapy on human femoral atherosclerosis. Circulation. 1991; 83:438-47. Google Scholar
    • 16. Blankenhorn DH, Selzer RH, Crawford DW, Barth JD, Liu CR, Liu CH, et al. Beneficial effects of colestipol-niacin therapy on the common carotid artery. Two- and four-year reduction of intima-media thickness measured by ultrasound. Circulation. 1993; 88:20-8. Google Scholar
    • 17. Selzer RH, Hagerty C, Azen SP, Siebes M, Lee P, Shircore A, et al. Precision and reproducibility of quantitative coronary angiography with applications to controlled clinical trials. A sampling study. J Clin Invest. 1989; 83:520-6. Google Scholar
    • 18. Selzer RH, Hodis HN, Kwong-Fu H, Mack WJ, Lee PL, Liu CR, et al. Evaluation of computerized edge tracking for quantifying intima-media thickness of the common carotid artery from B-mode ultrasound images. Atherosclerosis. 1994; 111:1-11. Google Scholar
    • 19. Salonen JT, Salonen R. Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb. 1991; 11:1245-9. Google Scholar
    • 20. Belcaro G, Nicolaides AN, Laurora G, Cesarone MR, De Sanctis M, Incandela L, et al. Ultrasound morphology classification of the arterial wall and cardiovascular events in a 6-year follow up study. Arterioscler Thromb Vasc Biol. 1996; 16:851-6. Google Scholar
    • 21. Blankenhorn DH, Alaupovic P, Wickham E, Chin HP, Azen SP. Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts. Lipid and nonlipid factors. Circulation. 1990; 81:470-6. Google Scholar
    • 22. Hodis HN, Mack WJ, LaBree L, Selzer RH, Liu C, Liu C, et al. Reduction in carotid arterial wall thickness using lovastatin and dietary therapy: a randomized, controlled clinical trial. Ann Intern Med. 1996; 124:548-56. Google Scholar
    • 23. Blankenhorn DH, Azen SP, Kramsch DM, Mack WJ, Cashin-Hemphill L, Hodis HN, et al. Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS). The MARS Research Group. Ann Intern Med. 1993; 119:969-76. Google Scholar
    • 24. Hodis HN, Mack WJ, Azen SP, Alaupovic P, Pogoda JM, LaBree L, et al. Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin. Circulation. 1994; 90:42-9. Google Scholar
    • 25. Natural history of aortic and coronary atherosclerotic lesions in youth. Findings from the PDAY Study. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb. 1993; 13:1291-8. Google Scholar
    • 26. Mcisaac WJ, Naylor CD, Basinski A. Mismatch of coronary risk and treatment intensity under the National Cholesterol Education Program guidelines. J Gen Intern Med. 1991; 6:518-23. Google Scholar
    • 27. Castelli WP. The fact and fiction of lowering cholesterol concentrations in the primary prevention of coronary heart disease. Br Heart J. 1993; 69:S70-3. Google Scholar