URL: https://www.crd.york.ac.uk/prospero . Unique identifier: CRD42016048257.

Background — Present therapies for acute coronary syndromes aim toward limiting platelet–platelet adhesion and aggregation processes. However, platelet–leukocyte interactions may contribute importantly to disease progression in the arterial wall. Recent studies suggest that prevention of platelet–leukocyte binding via P-selectin glycoprotein ligand-1 (PSGL-1) may be beneficial in animal models of vascular injury. Methods and Results — P-selectin–PSGL-1 interactions were found to account for most platelet–monocyte binding observed in peripheral blood samples from healthy donors. However, a significant component of observed adhesion was calcium independent, involving neither PSGL-1 nor P-selectin. Platelet–monocyte interactions were examined in 52 patients admitted within 14 hours of symptom onset, with acute coronary syndromes defined as unstable angina (n=12) and acute myocardial infarction (n=13) or noncardiac chest pain (n=27). When compared with patients with noncardiac chest pain, significantly elevated levels of platelet–monocyte binding were found in patients with acute myocardial infarction (70.1±15.4% versus 45.4±23.3%; P <0.01) and unstable angina (67.4±12.9% versus 45.4±23.3%; P >0.01). Calcium-independent platelet–monocyte binding was significantly elevated in myocardial infarction patients alone (14.7±7.7% versus 6.1±5.96%; P <0.001). Conclusions — There is evidence for a significant P-selectin–independent molecular component to the platelet–monocyte conjugation observed in peripheral blood. Patients with myocardial infarction and unstable angina demonstrate increased total binding of platelets to monocytes. Additionally, calcium-independent adhesion was significantly elevated in patients with evidence of myocardial infarction. These findings demonstrate that novel cation-independent adhesion mechanisms may mediate platelet–monocyte binding, representing a new therapeutic target after vascular injury associated with myocardial infarction.

BackgroundUnlike most noninvasive imaging modalities, coronary computed tomography angiography can characterize subtypes of atherosclerotic plaque.ObjectivesThe purpose of this study was to investigate the prognostic implications of adverse coronary plaque characteristics in patients with suspected coronary artery disease.MethodsIn this SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) post hoc analysis, the presence of adverse plaque (positive remodeling or low attenuation plaque), obstructive disease, and coronary artery calcification within 15 coronary segments was assessed on coronary computed tomography angiography of 1,769 patients who were followed-up for 5 years.ResultsAmong study participants (mean age 58 ± 10 years; 56% male), 608 (34%) patients had 1 or more adverse plaque features. Coronary heart disease death or nonfatal myocardial infarction was 3 times more frequent in patients with adverse plaque (n = 25 of 608 [4.1%] vs. n = 16 of 1,161 [1.4%]; p < 0.001; hazard ratio [HR]: 3.01; 95% confidence interval (CI): 1.61 to 5.63; p = 0.001) and was twice as frequent in those with obstructive disease (n = 22 of 452 [4.9%] vs. n = 16 of 671 [2.4%]; p = 0.024; HR: 1.99; 95% CI: 1.05 to 3.79; p = 0.036). Patients with both obstructive disease and adverse plaque had the highest event rate, with a 10-fold increase in coronary heart disease death or nonfatal myocardial infarction compared with patients with normal coronary arteries (HR: 11.50; 95% CI: 3.39 to 39.04; p < 0.001). However, these associations were not independent of coronary artery calcium score, a surrogate measure of coronary plaque burden.ConclusionsAdverse coronary plaque characteristics and overall calcified plaque burden confer an increased risk of coronary heart disease death or nonfatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590)