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64 Chapter 2 Figure 7. Birefringent and calcium crystals in human carotid atherosclerotic plaques and coronary artery aspirate. (A, B) Crystalloids are seen in atherosclerotic plaque using phase contrast microscopy. (C) Calcium phosphate crystals (black arrow) intertwined with cholesterol crystals (white arrow) are present in aspirate retrieved from culprit coronary artery from patient during acute myocardial infarction. (D) Energy-dispersive X-ray spectroscopy of sample in “C” demonstrates high calcium and phosphate content as well as carbon and oxygen consistent with cholesterol. Courtesy of George Abela. THERAPEUTIC IMPLICATIONS OF THE ROLE OF EXTRACELLULAR CRYSTALS IN ATHEROSCLEROSIS The strongest support for the central role of CCs in the atherosclerotic process comes from clinical trials, which demonstrate that agents that either effectively lower low-density lipoprotein cholesterol or specifically inhibit aspects of crystal- induced inflammation both significantly and independently reduce CV risk. 1,3,4,76, 77, 78 Despite the benefits of these therapies, future efforts to reduce CV risk may need to be directed at the potential to alter the evolutionary pathway of CCs, by altering the transition of metastable structures to their final flat plate morphology in the