ClinicalTrials.gov Identifier: NCT00240318.

Italy called Limone sul Garda live approximately 40 carriers with a naturally occurring variant of apolipoprotein A-I known as ApoA-I Milano. Individuals with ApoA-I Milano are characterized by very low levels of highdensity lipoprotein cholesterol (HDL-C) (10-30 mg/dL [0.25-0.78 mmol/L]), apparent longevity, 1 and much less atherosclerosis than expected for their HDL-C levels. 2 The ApoA-I Milano protein differs from native ApoA-I in that cysteine is substituted at position 173 for arginine allowing disulfide-linked dimer formation. Recombinant ApoA-I Milano has been formulated in a complex with a naturally occurring phospho-lipid to mimic the properties of nascent HDL (ETC-216, Esperion Therapeutics, Ann Arbor, Mich). Studies in mice and rabbits with experimental ath-Author Affiliations and Financial Disclosures are listed at the end of this article.

Background-Atherosclerotic plaque stability is related to histological composition. However, current diagnostic tools do not allow adequate in vivo identification and characterization of plaques. Spectral analysis of backscattered intravascular ultrasound (IVUS) data has potential for real-time in vivo plaque classification. Methods and Results-Eighty-eight plaques from 51 left anterior descending coronary arteries were imaged ex vivo at physiological pressure with the use of 30-MHz IVUS transducers. After IVUS imaging, the arteries were pressure-fixed and corresponding histology was collected in matched images. Regions of interest, selected from histology, were 101 fibrous, 56 fibrolipidic, 50 calcified, and 70 calcified-necrotic regions. Classification schemes for model building were computed for autoregressive and classic Fourier spectra by using 75% of the data. The remaining data were used for validation. Autoregressive classification schemes performed better than those from classic Fourier spectra with accuracies of 90.4% for fibrous, 92.8% for fibrolipidic, 90.9% for calcified, and 89.5% for calcified-necrotic regions in the training data set and 79.7%, 81.2%, 92.8%, and 85.5% in the test data, respectively. Tissue maps were reconstructed with the use of accurate predictions of plaque composition from the autoregressive classification scheme. Conclusions-Coronary plaque composition can be predicted through the use of IVUS radiofrequency data analysis.Autoregressive classification schemes performed better than classic Fourier methods. These techniques allow real-time analysis of IVUS data, enabling in vivo plaque characterization. (Circulation. 2002;106:2200-2206.)

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For patients with coronary artery disease, the reduced rate of progression of atherosclerosis associated with intensive statin treatment, as compared with moderate statin treatment, is significantly related to greater reductions in the levels of both atherogenic lipoproteins and CRP.

LARGE BODY OF EVIDENCE supports a central role for lowering levels of low-density lipoprotein cholesterol (LDL-C) in the prevention of atherosclerotic cardiovascular disease. Randomized controlled trialshaveestablishedthatstatin-mediated reductions in LDL-C have a favorable effect on the incidence of cardiovascular events. 1-6 As a result, LDL-C lowering has become an integral component of therapeutic strategies in the prevention of cardiovascular disease. 7 In particular, the use of statins has become widespread. Recent studies have reported that highdosestatintherapyresultsinanincrementalbenefitcomparedwithamoderatelipidlowering strategy. 8-11 Some investigators havesuggestedthatstatinsalsohavepleiotropic properties, such as modulation of inflammationwithinthearterialwall,that maycontributetotheirbeneficialeffect. 12-14 Accordingly,mostauthoritiesandcurrent national guidelines emphasize reduction in LDL-C as the primary target for lipidlowering therapy.

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Positive remodeling and larger plaque areas were associated with unstable clinical presentation, whereas negative remodeling was more common in patients with stable clinical presentation. This association between the extent of remodeling and clinical presentation may reflect a greater tendency of plaques with positive remodeling to cause unstable coronary syndromes.