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162 in patients ⬎⫽ and ⬍65 years and reached statistical significance in the younger patients. The improved clinical outcome in younger and older patients was not associated with any persistent elevations in creatinine kinase. Occurrence of liver function abnormalities was low and comparable in patients ⬎⫽ and ⬍65 years. Conclusions: Intensive lipid-lowering with atorvastatin 80 mg in patients with stable CHD produced reductions in risk of major cardiovascular events in both older (⬎⫽65 years) and younger patients (⬍65 years). Academic Practice Abstract Submissions 301 Cholesterol Crystallization Induces Volume Expansion to Cause Plaque Rupture While Statins or Ethanol Interrupt this Process to Stabilize Plaques George S. Abela, MD, Kusai Aziz, Ewa Danielewicz, Ruiping Huang, Joyce DeJong, Ara K. Pridjian, John D. Talbott, (East Lansing, MI) Synopsis: We recently demonstrated that cholesterol crystallization is strongly associated with plaque rupture and thrombosis in human plaques and in vitro studies. In an autopsy study we demonstrated a significant association between the presence of cholesterol crystals perforating the arterial intima both at and adjacent to the site of rupture. We also demonstrated that statins could interrupt this process. Purpose: Thus, we hypothesized that statins or ethanol could stabilize plaques by actually dissolving cholesterol crystals to prevent volume expansion during crystallization. Methods: Cholesterol crystals were made by two methods: (1) melting cholesterol powder and then allowing crystal formation by cooling at room temperature; (2) retrieving cholesterol crystals formed in a saturated solution of cholesterol in corn oil at 37°C. The various cholesterol crystals were placed on a glass cover slip and then immersed in physiological buffered saline (PBS) with and without simvastatin (10 mg/ml). The same experiment was repeated with pravastatin (10 mg/ml). Also, human coronary (n⫽5) and carotid arteries (n⫽4) with plaque rupture/erosion sites were obtained from patients who either died of coronary artery syndrome or underwent carotid endarterectomy. Plaque segments were cut in half with one half segment placed in PBS and the other was placed in PBS with simvastatin and incubated for 48 hr. Other segments were treated with ethanol as is standard for dehydration during preparation for scanning electron microscopy (SEM). These were compared to half segments that were treated by vacuum dehydration without ethanol. SEM was then performed on the crystals in vitro and post mortem human plaques to determine if there was a direct effect of statins or ethanol on cholesterol crystals. Results: SEM of crystals demonstrated a marked alteration in the crystal morphologies with presence of large clusters of pointed tipped crystals in the PBS incubated crystals and

Journal of Clinical Lipidology, Vol 1, No 2, May 2007 very few to no pointed tipped crystals in the PBS plus statin incubated group. Also, the amount of crystals present in the matched coronary and carotid artery segments by SEM was markedly reduced by incubation with statins. Only 3 of 9 segments had visible crystals and those were markedly dissolved and distorted. Ethanol preparation markedly reduced presence of crystals in adjacent segments compared to their control counterparts (Figure). Conclusions: These data indicated that statins and ethanol may help prevent acute cardiovascular events and plaque rupture by dissolving cholesterol crystals and markedly altering their geometrical configuration. This was demonstrated in vitro as well as in ruptured/eroded human plaques. Cholesterol Crystallization Induces Volume Expansion

Figure: (Left) image of carotid artery plaque with crystals dissolving and thinning down with ethanol (arrow). (Right) image of same carotid plaque with intact crystals (arrow) prepared by vacuum dehydration.

302 Progressive Decrease in Large and Small Artery Elasticity With the Presence of Multiple Components of the Metabolic Syndrome Daniel A. Duprez, MD, Fred M. Wu, Natalia D. Florea, Kathy Jones, Lynn Hoke, Jay N. Cohn, (Minneapolis, MN) Synopsis: There has been considerable controversy surrounding the value of the metabolic syndrome as an independent CVD risk marker beyond that of its individual components. Large (LAE) and small artery elasticity (SAE) have been considered to be early markers of CVD. Purpose: To examine the additive effects of the components of the metabolic syndrome on LAE and SAE in patients who meet the diagnostic criteria for metabolic syndrome and age-matched controls. Methods: A total number of 672 subjects without overt cardiovascular disease underwent determination of the large (LAE or C1) and small artery elasticity (SAE or C2) using radial pulse wave contour analysis. Components of the metabolic syndrome were measured according to NCEP criteria and related to large and small artery elasticity by ANCOVA, correcting for age, gender and body-mass index (BMI). Results: Data are expressed as mean ⫾ SEM in Table 1.