Background— Troponin elevation above the upper limit of normal (ULN) is diagnostic of myocardial infarction, but interpretation of "gray-zone" troponin elevations (1 to 1.5x ULN) remains uncertain. Using the CRUSADE database, we explored relationships between sex and treatment and outcomes among patients with troponin 1 to 1.5x ULN.

Methods and Results— We compared treatment and outcomes among women and men using logistic generalized estimating equation method. Overall, 5049 of 85 671 (5.9%) non–ST-segment elevation acute coronary syndromes patients (2156 women, 2893 men) had troponin 1 to 1.5x ULN within 24 hours of presentation. Compared with troponin >1.5x ULN, "gray-zone" patients less often received all guidelines-indicated acute (mean composite score, 63% versus 72%) and discharge therapies (mean composite score, 73% versus 78%), but received them more frequently than patients with troponin <1x ULN (mean composite scores, 58% acute and 67% discharge). Among "gray-zone" patients, acute and discharge therapy use was similar between women and men, except acute aspirin (adjusted odds ratio, 0.80 [95% CI, 0.65 to 0.98]) and discharge angiotensin-converting enzyme inhibitors (adjusted odds ratio, 0.77 [95% CI, 0.67 to 0.88]). "Gray-zone" patients had lower mortality (2.3%) than the >1.5x ULN (4.5%) group but higher than the <1x ULN group (1.1%). Outcomes were similar among "gray-zone" women and men (adjusted odds ratios: death, 0.88 [95% CI, 0.58 to 1.35]; death/myocardial infarction, 0.77 [95% CI, 0.55 to 1.06]; transfusion, 1.04 [95% CI, 0.85 to 1.27]).

Conclusions— Patients with non–ST-segment elevation acute coronary syndromes and low-level troponin elevations had lower overall risk and received less aggressive guidelines-based treatment than those with greater troponin elevations, but treatment patterns were largely similar by sex across troponin elevation groups.

Background— The risks of late stent thrombosis with drug-eluting stents (DES) were intensely debated after the presentation of a number of studies highlighting this issue in September 2006. We evaluated trends in the use of DES for patients with non–ST-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) from 2006 to 2008.

Methods and Results— Temporal patterns of DES use were examined among non–ST-elevation myocardial infarction patients in the Can Rapid risk stratification of Unstable angina patients Supress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE; January 2006 to December 2006) and Acute Coronary Treatment and Intervention Outcomes Network–Get With The Guidelines (ACTION–GWTG; January 2007 to June 2008) registries to determine how practice patterns changed for patients with acute myocardial infarction undergoing PCI. Among the 54 662 patients analyzed, the percentage of patients undergoing PCI by quarter varied from 54% to 58% during the analysis time period. More than 90% of patients undergoing PCI received a DES in the first 3 quarters of 2006 before the public debate about the risks of DES began. Thereafter, the use of DES for PCI patients declined during the fourth quarter of 2006 through the first quarter of 2007 (82% to 67%), gradually declined during quarters 2 to 4 of 2007 (63% to 63% to 59%) but then slightly increased from the first to second quarter of 2008 (58% to 60%). Hospital characteristics did not seem to correlate with temporal changes in DES use, but by the last 2 quarters of the study period, patient characteristics such as white race, hypertension, diabetes mellitus, and private or managed care insurance were more common among patients who received a DES compared with the beginning 2 quarters of the study period.

Conclusions— These findings highlight how rapidly treatment decisions in contemporary practice can be affected by public debate related to scientific presentations and publications.

Physiological fluid shear stress evokes pseudopod retraction in normal leukocytes by a mechanism that involves the formyl peptide receptor (FPR) as mechanosensor. In hypertensives, such as the spontaneously hypertensive rat (SHR), leukocytes lack the normal fluid shear response. The increased activity of matrix metalloproteinases (MMPs, including MMP-9) in SHR plasma is associated with cleavage of several cell membrane receptors. We hypothesize that the attenuated fluid shear response in leukocytes (neutrophils) of the SHR is due to extracellular proteolytic cleavage of the FPR. We show that suspended SHR neutrophils in whole blood sheared in a cone-and-plate device or individual neutrophils adherent to a glass surface and subject to fluid shear exhibited reduced pseudopod retractions compared with neutrophils of control Wistar-Kyoto (WKY) rats. SHR neutrophils and naïve Wistar rat neutrophils exposed to SHR plasma also exhibited impaired fluid shear responses as shown by their inability to project pseudopods with fluid shear. Labeling of extracellular FPR revealed that the FPR density in SHR neutrophils is on average 27% reduced compared with those of the WKY rats. Exposure of Wistar rat neutrophils to the gelatinase MMP-9 (final concentration 5 nM) led to attenuation of fluid shear response and decrease in extracellular FPR density. Chronic treatment of the SHR with a broad-acting MMP inhibitor, doxycycline, significantly improved the fluid shear response and increased the FPR extracellular density of SHR neutrophils. These results suggest that proteolytic cleavage of the FPR may interfere with normal fluid shear-induced pseudopod retractions in SHR neutrophils.