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.

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.

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.