pulmonary hypertension in left heart disease

Elevated left ventricular filling pressures are a general feature and hallmark of heart failure resulting from cardiac dysfunctions, essentially arising from and affecting the left ventricle [1, 2]. These disorders include heart failure due to diastolic and/or systolic malfunctions, as such heart failure with preserved (HFpEF) and without preserved; reduced (HFrEF) ejection fraction; valvular diseases; congenital cardiomyopathies; and congenital and acquired afflictions of left heart inflow and/or outflow tract [2, 3]. Thereby, the pressure of the left atrium will be elevated, either subsequently due to the increased LV-filling pressure [1, 4] or even initially, primarily in case of mitral stenosis [5]. In any case, left heart disease (LHD) is generally characterized by elevated left-sided filling pressures [4, 6]. The left-sided filling pressures are transmitted backwards, downstream, thereby causing an increase in pulmonary venous pressures [1, 5–7], a condition "of passive or congestive nature" as associated with pulmonary venous congestion [6]. In the literature this issue has in the past been called pulmonary venous hypertension (PvH) [8], or post-capillary pulmonary hypertension [9] or passive pulmonary hypertension [10]. Consequently, with the rise in pulmonary venous pressure, pulmonary artery pressure (PAP) also increases [11]

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Intercoronary communication in chronic total occlusion: In search of recognition

Intercoronary communications (ICC) or open-ended coronary circulation is rare. We describe intercoronary communication in a case of chronic total occlusion, and discuss the pathophysiological and clinical significance of these rare entities. The present case also demonstrates the anatomical presence of ICC despite angiographic absence for the first time using CT coronary angiography

Absent right coronary artery: A case of single coronary artery or congenital ostial atresia?

Atresia of the right coronary artery ostium is a rare anatomic variant of the coronary circulation. It is often difficult to differentiate from single coronary artery. Its presence unassociated with any other anomaly has never been described in an adult individual. We report this unusual anomaly and discuss its anatomical and pathophysiological significance and possible ways to differentiate from single coronary artery

Tumor necrosis factor-alpha −308G/A gene polymorphism and novel biomarker profiles in patients with Takayasu arteritis

Background: Takayasu arteritis (TA) is an idiopathic chronic inflammatory disease of the aorta and its branches, leading to stenosis, occlusion, and aneurysmal dilatation. Tumor necrosis factor-alpha (TNF-α) is a cytokine with pleomorphic actions and plays a pivotal role in inflammation; the serum level of TNF-α is genetically determined. However, the literature lacks adequate information on the association of TNF-α polymorphisms with TA. Hence, the present study investigates the contribution of TNF-α polymorphism toward the complex etiology of TA. Methods: A cross-sectional study was performed in 87 patients with TA and 90 controls. A promoter region polymorphism of TNF-α, rs1800629 G/A, or −308G/A was genotyped in all the study subjects followed by a case–control association study. Furthermore, to understand the biomarker profile, levels of specific markers such as erythrocyte sedimentation rate, serum high-sensitivity C-reactive protein, interleukin-18, interleukin-6, and TNF-α were measured in all the study subjects. Results: All the inflammatory markers were significantly higher in the TA patients than in the controls. The genetic study (available for 57 TA patients and 36 controls) revealed that the TNF-α −308A allele was overrepresented in the TA patients (12% vs 7%). The TNF-α −308A allele correlated with the increased TNF-α levels, but it could not attain significance because of a small sample size. Conclusion: The TNF-α −308G/A polymorphism is associated with TNF-α levels in Indian population, which might have implications for clinical risk stratification and treatment. The different TNF-α gene promoter polymorphism might contribute to the molecular pathogenesis of TA. However, further study of the underlying mechanism is warranted. Keywords: Takayasu arteritis, Biomarkers, Tumor necrosis factor-alpha, Gene polymorphis

β-T594M epithelial sodium channel gene polymorphism and essential hypertension in individuals of Indo-Aryan ancestry in Northern India

Background: The T594M variant of the β-subunit of the sodium epithelial channel (ENaC) gene may contribute to hypertension in individuals of Indo-Aryan origin. Methods: Present study was performed to assess the role of the ENaC gene variant as an independent risk factor for hypertension in subjects of Indo-Aryan ancestry. A total of 150 patients of recently detected essential hypertension and 150 matched controls were genotyped for the T594M polymorphism of the ENaC gene by PCR–RFLP method. Results: β-T594M mutation was found to be non-polymorphic. There was major genotype call in both the groups i.e. cases and controls. Other phenotypic parameters like age, sex and body mass index were also similar among hypertensive patients and controls (P > 0.05). Hypertensive patients had significantly higher total cholesterol and triglycerides compared with controls (P < 0.0001). Conclusion: These results do not suggest an important role for the T594M variant of the ENaC gene contributing to either the development or severity of hypertension in subjects of Indo-Aryan ancestry

Psychosocial stress and well-being in patients presenting with acute myocardial infarction in a tertiary care center

Background: Psychosocial factors such as stress have been previously implicated as a risk factor for cardiovascular diseases (CVDs). There is little evidence regarding the prevalence of stress among patients with acute myocardial infarction (AMI). Methods: A total of 903 patients with AMI enrolled in the North Indian ST-Segment Elevation Myocardial Infarction (NORIN-STEMI) registry were included in this study. Perceived stress in these subjects was evaluated using the Perceived Stress Scale-10 questionnaire while the World health Organization (WHO-5) Well-being Index was used to evaluate psychological well-being. All these patients were followed up for one month and major adverse cardiac events (MACE) were determined. Results: A majority of patients with AMI had either severe (478 [52.9%]) or moderate stress (347 [38.4%]) while low stress levels were observed in 78 [8.6%] patients. Additionally, most of the patients with AMI (478 [53%]) had WHO-5 well-being index <50%. Subjects with severe stress were younger (50.86 ± 13.31; P < 0.0001), more likely to be males (403 [84.30%]; P = 0.027), were less likely to have optimal level of physical activity (P < 0.0001) and had lower WHO-5 well-being score (45.54 ± 1.94%; P < 0.0001) as compared to those with low and moderate stress levels. On 30-days follow-up, subjects with moderate/severe stress had higher MACE however, the difference was non-significant (2.1% vs 1.04%; P = 0.42). Conclusion: A high prevalence of perceived stress and low well-being index was observed in patients presenting with AMI in India

Role of ApoE gene polymorphism and nonconventional biochemical risk factors among very young individuals (aged less than 35 years) presenting with acute myocardial infarctionKey messages

Background: Incidence rate of acute myocardial infarction (MI) has increased in younger population over the years. The young patients have a different risk profile, presentation, and prognosis than the elderly. Hence, it is essential to understand the risk factors in young patients for proper treatment. Methods: Apolipoprotein E (ApoE) polymorphism and biochemicals such as total cholesterol, serum triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein(a), insulin, interleukin-6, homocysteine, fibrinogen, and highly sensitive C-reactive protein were investigated in very young MI (yMI patients; age ≤ 35 years; n = 125), in old MI (oMI patients; age >35 and  0.05 in yMI patients versus oMI patients). No significant pattern of ApoE polymorphisms was observed. Conclusion: The lower level of HDL-C and ApoA1 and higher ratios of total cholesterol:HDL-C, LDL-C:HDL-C, and ApoB:ApoA1 are risk factors for MI in young patients. Keywords: Myocardial infarction, Cardiovascular disease, ApoE, Genetic polymorphism, Correlatio