Preprocedural statin use is associated with a reduced hazard of postprocedural myonecrosis in patients undergoing rotational atherectomy--a propensity-adjusted analysis.

Incidence of myonecrosis in patients undergoing rotational atherectomy was evaluated by preprocedural statin use. The incidence of any myonecrosis (24.1% vs 52.3%, P < .001) or significant myonecrosis (7.5% vs 21.8%, P < .001) was significantly lower among patients pretreated with statins. This difference remained significant after multivariable and propensity adjustment.

Ischemic and bleeding outcomes in women treated with bivalirudin during percutaneous coronary intervention: a subgroup analysis of the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial.

BACKGROUND: Outcomes in women undergoing percutaneous coronary intervention (PCI) in the contemporary era are poorly defined. The REPLACE-2 trial demonstrated that bivalirudin with provisional glycoprotein IIb/IIIa (GpIIb-IIIa) blockade is noninferior to heparin with planned GpIIb-IIIa blockade during PCI, with regard to ischemic and bleeding end points. OBJECTIVES: The aim of this study was to define sex-based clinical ischemic and bleeding outcomes from the REPLACE-2 trial. METHODS: A retrospective sex-based subgroup analysis of the REPLACE-2 trial comparing clinical ischemic and inhospital bleeding end points was conducted. RESULTS: Compared with men in REPLACE-2, women were older, had more diabetes, congestive heart failure and hypertension, and less prior revascularization and myocardial infarction. Female sex was a univariate predictor of death and bleeding complications. Among women treated with either bivalirudin or heparin, there was no significant difference in the individual or composite ischemic end points of death, myocardial infarction, or urgent revascularization at 30 days or 6 months. Protocol-defined major bleeding, minor bleeding, and access site bleeding were less frequent with bivalirudin compared with heparin. Multivariable modeling found no significant interactions between sexes, with the composite ischemic end point, major bleeding, or 1-year mortality. CONCLUSIONS: Women remain at higher risk for poorer outcomes with contemporary PCI, likely because of comorbidities. Bivalirudin with provisional GpIIb-IIIa confers similar protection against ischemic end points compared with heparin and planned GpIIb-IIIa blockade and significantly reduces the inherent bleeding risk of women undergoing contemporary PCI.

Increased tissue factor expression predicts development of cardiac allograft vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) limits the long-term success of cardiac transplantation. The incidence of CAV is increased in patients with elevated plasma levels of oxidized lipids or fibrin deposition within right heart biopsy (RHB) specimens. The present study investigated whether tissue factor (TF), the expression of which is regulated by oxidized lipids, is upregulated in patients with CAV. METHODS AND RESULTS: A TF score was developed to quantify TF expression in RHB specimens from 63 consecutive patients undergoing routine annual posttransplantation RHB and coronary angiography. In patients >2 years (3.0+/-0.8 years) posttransplantation (n=35), a high TF score was observed with greater frequency (75% versus 26%, P<0.004) in patients with CAV than those without CAV. In patients <2 years (0.87+/-0.48 years) posttransplantation (n=28) without evidence of CAV, the TF score was determined and patients were followed up prospectively. A high TF score had a positive predictive value of 78.6% for the development of CAV, and a low TF score had a negative predictive value of 100%. CONCLUSIONS: These data demonstrate that early TF expression predicts subsequent development of CAV. Increased TF expression could link the elevated levels of oxidized LDL and fibrin deposition known to precede CAV. These findings suggest that TF may play a role in the pathophysiology of CAV and could offer a potential prognostic tool and a novel target for the prevention of CAV, possibly with antioxidants or inhibitors of the TF pathway.

Symptomatic patients have similar outcomes compared with asymptomatic patients after carotid artery stenting with emboli protection.

In a single-center cohort of 174 consecutive patients, we sought to evaluate whether the use of emboli protection devices (EPDs) results in equivalent rates of adverse events in symptomatic and asymptomatic patients after carotid artery stenting (CAS) with EPDs. Death or stroke occurred in 3.3% in the symptomatic group and in 3.5% of the asymptomatic group at 30 days (p = NS). At 6 months, there was also no significant difference in the rate of stroke or death between the groups. Unlike surgical revascularization, symptomatic patients did not have a greater risk for stroke and death compared with asymptomatic patients after CAS with EPDs.

Menin controls growth of pancreatic beta-cells in pregnant mice and promotes gestational diabetes mellitus.

During pregnancy, maternal pancreatic islets grow to match dynamic physiological demands, but the mechanisms regulating adaptive islet growth in this setting are poorly understood. Here we show that menin, a protein previously characterized as an endocrine tumor suppressor and transcriptional regulator, controls islet growth in pregnant mice. Pregnancy stimulated proliferation of maternal pancreatic islet beta-cells that was accompanied by reduced islet levels of menin and its targets. Transgenic expression of menin in maternal beta-cells prevented islet expansion and led to hyperglycemia and impaired glucose tolerance, hallmark features of gestational diabetes. Prolactin, a hormonal regulator of pregnancy, repressed islet menin levels and stimulated beta-cell proliferation. These results expand our understanding of mechanisms underlying diabetes pathogenesis and reveal potential targets for therapy in diabetes.

Induction of CD4 T cell changes in murine AIDS is dependent on costimulation and involves a dysregulation of homeostasis.

Strong CD4 T cell activation and proliferation are seen in susceptible mice infected with the murine retroviral inoculum, LP-BM5, which produces an immunodeficiency syndrome called murine AIDS (MAIDS). We developed a short term adoptive transfer model of MAIDS to examine the requirements for the CD4 T cell response. Naive CD4 T cells from uninfected donors responded quickly after adoptive transfer into MAIDS-infected hosts, becoming activated and proliferating within several days. Using blocking mAbs to costimulatory ligands and CD4 T cells deficient in expression of their receptors, we found that the CD4 T cell response requires CD28:B7.1/B7.2 interactions, but not CTLA4 or CD40-CD40 ligand interactions. Naive CD4 T cells did not respond in H-2M-deficient mice with MAIDS, suggesting that disease requires recognition of self peptide-MHC complexes. The self MHC-dependent division and accumulation of large numbers of CD4 T cells suggest that MAIDS involves a disruption of the balance of homeostatic signals. Supporting this hypothesis, CD4 T cells from mice with MAIDS failed to regulate the homeostatic division of naive CD4 T cells in a cotransfer model. Thus, a combination of up-regulation of costimulatory ligands and disruption of homeostatic control may be responsible for CD4 lymphoproliferation in MAIDS.