Gregory O. von Mering

Abnormal Coronary Vasomotion as a Prognostic Indicator of Cardiovascular Events in Women Results From the National Heart, Lung, and Blood Institute–Sponsored Women’s Ischemia Syndrome Evaluation (WISE)

Background—Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiovascular outcomes in men, but these relationships have not been firmly established in women. Methods and Results—As part of the Women’s Ischemia Syndrome Evaluation (WISE) sponsored by the National Heart, Lung, and Blood Institute, 163 women referred for clinically indicated coronary angiography underwent coronary reactivity assessment with quantitative coronary angiography and intracoronary Doppler flow before and after intracoronary administration of acetylcholine, adenosine, and nitroglycerin and were then followed up for clinical outcomes. History of hypertension was present in 61%, dyslipidemia in 54%, diabetes in 26%, and current tobacco use in 21% of women enrolled. Seventy-five percent had no or only mild epicardial coronary artery disease (CAD). Over a median follow-up of 48 months, events occurred in 58 women. On bivariate analysis, women with an event had significantly less change in coronary cross-sectional area (&Dgr;CSA) in response to acetylcholine (P =0.0006) and nitroglycerin (P =0.04). In addition, women with abnormal coronary dilator response to acetylcholine had less time free from cardiovascular events (P =0.004). In multivariable analysis, after controlling for age, hypertension, diabetes, dyslipidemia, tobacco use, and CAD severity, %&Dgr;CSA with acetylcholine (P =0.001) independently predicted events. When the outcome was restricted to only death, myocardial infarction, congestive heart failure, and stroke, %&Dgr;CSA with acetylcholine remained a significant predictor (P =0.006). Conclusions—In women in this study, impaired coronary vasomotor response to acetylcholine was independently linked to adverse cardiovascular outcomes regardless of CAD severity.

Comparison of type iii fc receptors associated with group c and group g streptococci

The type III Fc receptors present on or secreted by a series of group C and G streptococcal strains were studied. All strains capable of binding radiolabeled human IgG were shown to do so via an antigenically related Fc receptor. Treatment of any of the bacterial strains with papain or trypsin resulted in solubilization of Fc receptor activity. The pattern of Fc receptor activity recovered following enzyme treatment was not uniform. Differences were observed both between group C and G strains as well as within group C and G strains. Analysis of secreted Fc receptors indicated the presence of five molecular forms of Fc receptor. Each form was present at some level in the supernatant of every group C and G strain studied. The relative concn of each form of receptor secreted varied from strain to strain. The Fc receptor activity secreted by each strain demonstrated a similar affinity for the Fc region of human IgG and all were antigenically related. These results suggest that there is a family of closely related Fc receptors associated with group C and G streptococcal strains.

Pulse pressure and adverse outcomes in women: a report from the Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND Recent data suggest that brachial pulse pressure (PP) may be a better predictor of outcome than systolic or diastolic blood pressure (SBP/DBP). We sought to investigate the relative contributions of these indices to risk for adverse outcomes in women with suspected coronary artery disease (CAD) and myocardial ischemia. METHODS Among 857 women referred for angiography for suspected myocardial ischemia, baseline evaluations were performed, and the women were followed for clinical outcome. Relationships between baseline characteristics, blood pressure components, and outcomes were evaluated. Separate multivariate stepwise Cox regression models for PP and SBP (expressed in 10 mm Hg increments) were constructed and included covariates significantly associated with adverse outcomes. RESULTS After 5.2 years (mean), univariate testing identified higher PP associated with higher risk for cardiovascular (CV) mortality and adverse CV outcomes than SBP, DBP, or mean arterial pressure (MAP). Multivariate modeling identified both PP and SBP associated with adverse CV outcomes, but only PP was significantly associated with higher CV mortality. When both PP and SBP were included in the model, only PP remained an independent predictor of adverse outcomes for CV events. CONCLUSIONS In women with suspected CAD and myocardial ischemia, PP is a stronger predictor of adverse outcomes than SBP, DBP, or MAP with an 18% excess mortality risk for every 10 mm Hg increase in PP. Further investigations into pathophysiologic mechanisms and specific pharmacologic approaches to modifying this novel target are warranted.