The PROSPECT study validates that despite having more comorbid risk factors than men, women have less extensive coronary artery disease by both angiographic and IVUS measures, and that lesions in women compared with men have less plaque rupture, less necrotic core and calcium, similar plaque burden, and smaller lumens. TCFA may also be a stronger marker of plaque vulnerability in women than men.

Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies.

Among patients with STEMI undergoing primary percutaneous coronary intervention, adverse events are markedly increased in those with LVEF <40% during the index revascularization procedure. Nevertheless, these high-risk patients experience substantial clinical benefits from bivalirudin and PES.

Peroxisome biogenesis disorders, of which Zellweger syndrome is the most severe, result in severe neurological dysfunction associated with abnormal CNS neuronal migrations due to the lack of functional peroxisomes. The PEX2-/- mouse model for Zellweger syndrome has enabled us to evaluate the role of peroxisomes in the development and functioning of the nervous system. These studies have shown that, in addition to disturbances in neuronal migration in developing cerebral cortex and cerebellum, defects in neuronal differentiation, proliferation and survival may also contribute to the CNS malformations. However, owing to the multiorgan dysfunction in peroxisomal disorders, it has been difficult to clearly define an intrinsic role for the peroxisome in brain cells. The use of several in vitro cell culture assays to evaluate the migration and differentiation of cerebellar neurons demonstrates a persistence of defects in peroxisome-deficient neurons. The absence of potential systemically derived, extrinsic factors in these in vitro systems indicates that CNS intrinsic defects contribute to the pathogenesis of disease in these disorders. However, bile acid treatment also increases the survival and growth of PEX2-/- mice and improves some aspects of cerebellar development, indicating that extrinsic factors also affect the developing peroxisome-deficient brain. Therefore, the final phenotype of nervous system dysfunction in peroxisomal disorders will reflect a combination of both CNS intrinsic and extrinsic factors.