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Objectives This study aimed to assess the clinical impact of immediate versus delayed invasive intervention in patients with non–ST-segment myocardial infarction (NSTEMI). Background Previous studies found conflicting results on the effects of earlier invasive intervention in a heterogeneous population of acute coronary syndromes without ST-segment elevation. Methods We randomized 323 NSTEMI patients to an immediate-intervention group (<2 h after randomization, n = 162) and a delayed-intervention group (2 to 72 h, n = 161).The primary endpoint was the occurrence of death or new myocardial infarction (MI) at 30-day follow-up. Results Median time from randomization to angiography was 1.4 h and 61.0 h in the immediate-intervention group and the delayed-intervention group, respectively (p < 0.001). At 30 days, the primary endpoint was achieved less frequently in patients undergoing immediate intervention (4.3% vs. 13%, hazard ratio: 0.32, 95% confidence interval: 0.13 to 0.74; p = 0.008). At 1 year, this difference persisted (6.8% in the immediate-intervention group vs. 18.8% in delayed-intervention group; hazard ratio: 0.34, 95% confidence interval: 0.17 to 0.67; p = 0.002). The observed results were mainly attributable to the occurrence of new MI in the pre-catheterization period (0 deaths + 0 MIs in the immediate-intervention group vs. 1 death + 10 MIs in the delayed-intervention group). The rate of deaths, new MI, or recurrent ischemia was lower in the immediate-intervention group at both 30 days (6.8% vs. 26.7%; p < 0.001) and 1 year (15.4% vs. 33.1%; p < 0.001). Conclusions Immediate invasive strategy in NSTEMI patients is associated with lower rates of death or new MI compared with the delayed invasive strategy at early and midterm follow-up, mainly due to a decrease in the risk of new MI in the pre-catheterization period. (Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients [RIDDLE-NSTEMI]; NCT02419833 ) [ABSTRACT FROM AUTHOR]

Background Previous randomized controlled trials (RCTs) have produced conflicting results on the effects of early versus delayed invasive strategy in NSTE-ACS patients. Objectives To perform up to date meta-analysis on the pooled data sample comparing early versus delayed invasive strategy, and to explore potential causes for the observed high statistical heterogeneity. Methods MEDLINE via Pubmed, Central, Google Scholar, Clinical Trials Registry, Current controlled study and ClinicalTrials.gov registry and relevant conference proceedings were searched. RCTs were included that directly compared early versus delayed invasive strategy and reported rates of death, new myocardial infarction (MI) and/or recurrent ischemia. Results 10 RCTs with 6089 patients were included. Time to coronary angiography varied from 0.5 to 24 h in the early and from 20.5 to 86 h in the delayed group. Meta-analysis showed no significant difference in mortality (OR = 0.83, 95%CI 0.64–1.08, P = 0.16), and similar new MI rates (OR = 1.02, 95%CI 0.63–1.64, P = 0.94). The rate of recurrent ischemia was reduced in patients undergoing early coronary angiography (OR = 0.56, 95%CI 0.40–0.79, P = 0.001). Subgroup analysis indicated that the rate of new MI tended to depend on the study-specific endpoint definition (p for difference between subgroups 0.11), while a meta-regression revealed association of new MI rates with the within-study delay to coronary angiography (p = 0.05). Conclusion Early invasive strategy appears to reduce the occurrence of recurrent ischemia, but confers no mortality benefit. The true effect on the occurrence of new MI is obscured by the high between-study heterogeneity that stems mainly from non-uniform timing of early intervention and new MI definitions across the trials. [ABSTRACT FROM AUTHOR]

Chromosomal region 9p21.3 is most robustly associated with coronary artery disease (CAD) in western European populations. However, heterogeneity in CAD phenotypes leads to uncertainty whether 9p21.3 is associated with stable and/or acute clinical presentations of CAD. 9p21.3 is rich in regulatory elements, but the underlying mechanisms of its actions in CAD remain unclear. We investigate the association of 9p21.3 two haplotype blocks lead variants (rs10757278 and rs518394) with first-ever non-fatal myocardial infarction (MI) in CAD patients and their association with CDKN2B mRNA expression in peripheral blood mononuclear cells 6 months after the event. We included CAD patients with sustained first MI (n = 523) and controls (n = 583). Gene expression was assessed in 72 patients 6 months after MI and 43 healthy controls. TaqMan® technology was used for the gene expression and genotyping analysis. CDKN2B mRNA was significantly lower in MI patients compared with the controls (p = 0.002) and in patients carrying the rs10757278 G risk allele versus AA homozygotes (p = 0.012) 6 months after the event. While we confirmed the association of rs10757278 with CDKN2B expression in MI patients, we failed to find an association between the investigated variants and MI or disease burden. We suggest a dysregulation of gene expression in the 9p21.3 region six months after acute MI, which is affected by a genetic variant in patients. The rs10757278 rare allele is one factor that might lead to prolonged risk for proatherogenic complications. [ABSTRACT FROM AUTHOR]

The 9p21.3 region is rich in regulatory elements and the variants in this region had been robustly associated with carotid plaque (CP) and coronary artery disease (CAD). Recently, the HACD4 was detected as one of the six 9p21.3 differentially expressed genes associated with accelerated atherosclerosis and greater mean lesion area in the Athsq1 congenic mice. We aimed to investigate association of two potentially regulatory HACD4 variants (rs36212560 I/D, rs2275888 T/C) and their haplotypes with CP occurrence and the level of HACD4 and FOCAD mRNA in human CP tissue. Association study was replicated in CAD patients who suffered the first myocardial infarction. Study included 477 CP patients, 303 healthy controls and replication sample of 224 CAD males from the population of Serbia. Genotypes were determined by polymerase chain reaction (PCR) and real-time PCR using TaqMan® technology. The gene expression was detected with TaqMan® technology. We have found significant and independent association of DT haplotype with CP presence in men (adjusted OR = 1.64 CI = 1.12–2.42, p = 0.011). The result was replicated in CAD males (adjusted OR = 1.84 CI = 1.21–2.80, p = 0.004). We have found significant effect of the HACD4 rs2275888 on FOCAD mRNA level in human CP tissue. Correction for multiple testing was performed. Independent association of HACD4 haplotypes with atherosclerotic phenotypes connotes a further validation and replication in larger cohorts as well as functional studies to enlighten the potential mechanism of its action in pathophysiology of atherosclerosis. [ABSTRACT FROM AUTHOR]