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Effects of the Antianginal Drugs Ranolazine, Nicorandil, and Ivabradine on Coronary Microvascular Function in Patients With Nonobstructive Coronary Artery Disease: A Meta-analysis of Randomized Controlled Trials.
Zhu, H, Xu, X, Fang, X, Zheng, J, Zhao, Q, Chen, T, Huang, J
Clinical therapeutics. 2019;(10):2137-2152.e12
Abstract
PURPOSE The goal of this study was to investigate the effects of the antianginal drugs ranolazine, nicorandil, and ivabradine on coronary microvascular function. METHODS Electronic scientific databases were searched for randomized trials investigating the effects of antianginal drugs on coronary microvascular function. Primary outcomes were changes in the coronary flow reserve (CFR), index of microvascular resistance (IMR), and myocardial perfusion reserve index (MPRI). The secondary outcome was the Seattle Angina Questionnaire scores. The standardized mean difference or weighted mean difference (WMD) (95% CI) served as a summary statistic. FINDINGS The antianginal drugs ranolazine, nicorandil, and ivabradine did not increase the CFR compared with the control drugs (standardized mean difference, 0.39; 95% CI, -0.08 to 0.85; P = 0.10). Ranolazine did not increase the global MPRI compared with the control drugs (weighted mean difference [WMD], 0.11; 95% CI, -0.06 to 0.29; P = 0.21). However, in the subgroups with a baseline CFR <2.5 or a global MPRI <2, ranolazine increased the global MPRI (WMD, 0.19; 95% CI, 0.10 to 0.27; P < 0.0001). In addition, the subendocardial midventricular MPRI (mid-subendocardial MPRI) was improved after ranolazine treatment (WMD, 0.12; 95% CI, 0.03 to 0.20; P = 0.007). Moreover, nicorandil significantly reduced the IMR compared with the control drugs (WMD, -7.63; 95% CI, -11.82 to -3.44; P = 0.0004). In addition, ranolazine and ivabradine improved 3 of the 5 Seattle Angina Questionnaire scores. IMPLICATIONS Ranolazine improved the global MPRI in patients with definite coronary microvascular dysfunction and the mid-subendocardial MPRI with suspicious coronary microvascular dysfunction, and nicorandil reduced the IMR. In addition, ranolazine and ivabradine reduced angina. Moreover, it is possible that the IMR and mid-subendocardial MPRI are more sensitive than the CFR and global MPRI for evaluating coronary microvascular function.
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A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.
Nikpay, M, Goel, A, Won, HH, Hall, LM, Willenborg, C, Kanoni, S, Saleheen, D, Kyriakou, T, Nelson, CP, Hopewell, JC, et al
Nature genetics. 2015;(10):1121-1130
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Abstract
Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
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Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease.
Lu, X, Wang, L, Chen, S, He, L, Yang, X, Shi, Y, Cheng, J, Zhang, L, Gu, CC, Huang, J, et al
Nature genetics. 2012;(8):890-4
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Abstract
We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases and 5,019 controls followed by replication studies in 15,460 cases and 11,472 controls, all of Chinese Han ancestry. We identify four new loci for coronary artery disease that reached the threshold of genome-wide significance (P < 5 × 10(-8)). These loci mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (in or near PHACTR1, TCF21, CDKN2A-CDKN2B and C12orf51). These findings provide new insights into pathways contributing to the susceptibility for coronary artery disease in the Chinese Han population.