“Interventional lipidology”: tomographic plaque imaging and aggressive treatment of metabolic disorders

T magnitude of the medical and financial burdens inflicted on our society by coronary artery disease (CAD) mandates a more direct approach to risk stratification, and to aggressive intervention in those at high risk, than currently employed. To meet this need, the new field of “Interventional Lipidology” has emerged. In primary prevention, treatment goals are based upon risk assessment by noninvasive measurement of subclinical atherosclerosis, followed by identification and aggressive treatment of all contributing metabolic abnormalities, as well as traditional risk factors, and reevaluation by imaging of the effects of treatment (Table 1). In secondary prevention, it is based upon aggressive therapy directed toward treatment of all identifiable metabolic disorders; imaging to assess treatment will be increasingly used. Several modalities have been considered for the noninvasive evaluation of subclinical atherosclerosis. Abnormal ankle-brachial index measurements are often associated with CAD, but are present only in advanced peripheral vascular disease and have limited reproducibility. Stress testing identifies only obstructive CAD, limiting its utility to identify patients with significant nonobstructive atherosclerosis. Carotid intima-media thickening has great epidemiologic potential, but is a surrogate for atherosclerosis, and is hampered by the difficulty of performing the procedure in an accurate, reproducible fashion, thereby restricting its use to a handful of institutions. Tomographic calcified plaque imaging currently appears to be the most suitable modality, because it directly identifies CAD in its earlier stages. Electron beam tomography (EBT) is supported by a wealth of data demonstrating its prognostic power and reproducibility; multislice computed tomography is increasingly being used. It is reasonable to assume that most clinical events in the primary prevention trials occurred in patients with subclinical CAD that placed them at higher risk, i.e., with calcified plaque on entry into the study. This is strongly supported by the very low ( 6%) incidence of zero calcium scores by EBT in patients who have acute cardiac events, and by the extremely low likelihood (0.11%/year) of clinical events in the setting of a zero score, despite the possibility of exclusively soft, noncalcified plaque. The incidence of zero or trivial scores in the West of Scotland trial (average low-density lipoprotein [LDL] cholesterol 190 mg/dl) and the Air Force/Texas Coronary Atherosclerosis Study (AFCAPS/TexCAPS) (average LDL cholesterol 150 mg/dl) is unknown. However, their inclusion is strongly suggested by the work of Hecht et al, who showed that 33% and 50% of primary prevention patients with LDL cholesterol 160 and 160 mg/dl, respectively, have zero scores. Thus, the National Cholesterol Education Program drug treatment recommendations are based upon studies involving patients with varying levels of subclinical CAD, and widely disparate risk. Therefore, there is no evidence based medicine that supports treatment in a patient with a zero calcium score, who is at low risk (0.11%/year event rate), irrespective of treatment. Similarly, there are no data supporting the withholding of drug therapy from patients with high-risk calcium scores (2.1% to 4.8%/year event rate), whose LDL cholesterol levels and Framingham risk score do not qualify them for drug treatment. Approximately 50% of asymptomatic patients with LDL cholesterol 130 mg/dl have significant calcified plaque with attendant high risk, but would not be treated by current guidelines. Moreover, the Heart Protection Study suggests that patients with LDL cholesterol 130 mg/dl, and even 100 mg/dl, benefit from statin therapy to the same degree as those with higher levels. Postmenopausal women with and without plaque have similar lipid profiles and Framingham risk scores, but vastly different EBT-determined prognoses; 50% of those with plaque would not be treated by current criteria. Logic suggests that secondary prevention treatment goals and drug therapy initiation levels be applied to patients who have significant plaque burdens, irrespective of their LDL cholesterol levels. However, in the absence of an evidence-based study demonstrating the beneficial effect on outcomes of treating patients solely on the basis of their calcium scores, this paradigm is subject to the same criticism that can be directed to the treatment of patients with zero scores with statins, solely on the basis of lipid levels and risk factors. It is clear that the required evidenced-based studies to support either viewpoint will be quite difficult to implement. Nonetheless, a solution to this problem would seem prudent to complement current clinical decision making. From the Princeton Longevity Center, Princeton, New Jersey. Manuscript received February 4, 2002; revised manuscript received and accepted April 8, 2002. Address for reprints: Harvey S. Hecht, MD, Princeton Longevity Center, 50 Vreeland Drive, Princeton, New Jersey 08858. E-mail: hhecht@aol.com.