Prognostic Importance of Dyspnea for Cardiovascular Outcomes and Mortality in Persons without Prevalent Cardiopulmonary Disease: The Atherosclerosis Risk in Communities Study

The relationship between dyspnea and incident heart failure (HF) and myocardial infarction (MI) among patients without previously diagnosed cardiopulmonary disease is unclear. We studied the prognostic relevance of self-reported dyspnea for cardiovascular outcomes and all-cause mortality in persons without previously diagnosed cardiopulmonary disease

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Gadolinium enhancement in newly diagnosed patients with lumbar disc herniations are associated with inflammatory peridiscal tissue reactions - Evidence of fragment degradation?

Objective: It is debatable whether a local inflammatory tissue response caused by herniated disc material contributes to sciatic pain and/or sensorimotor deficits. The impact of inflammatory changes on local tissue remodelling, the healing process and the clinical course of disease remains unclear. Methods: In this prospective observational study, we included a total of 31 patients with a single-level, unilateral lumbar disc herniation. The diagnosis was confirmed by magnetic resonance imaging (MRI)+/- gadolinium. The presence of peridiscal contrast enhancement was correlated with the extent of inflammatory reactions in the herniated fragments as confirmed by immunohistochemistry; clinical symptoms, including the duration of radicular pain; and the incidence of sensorimotor deficits. Results: Peridiscal contrast enhancement was found in 17 patients (55%) and was encasing the adjacent rootlet in 4 cases. There was no significant correlation between gadolinium uptake and the presence of sensorimotor deficits or the duration of radicular symptoms. Degenerative changes were observed in all 31 disc specimens. Overall, 18 cases exhibited increased cellularity in the marginal areas, which were mostly populated by CD68(+) macrophages and fibroblasts. Additionally, these areas displayed a limited number of CD3(+) T-lymphocytes and different degrees of concomitant neovascularisation, which represented a chronic and unspecific immune response. Peridiscal contrast enhancement on MRI was significantly correlated with the histopathological characteristics of tissue inflammation. However, no correlation was found between the histological evidence and the degree of inflammation and neurological symptoms. Conclusion: Gadolinium-enhanced MRI is a sensitive method to detect unspecific inflammatory reactions in therapy-naive disc herniations. However, the neuroradiological and histological evidence of peridiscal inflammation was not correlated with the severity of pain or sensorimotor deficits in our patients. Additional research is needed because the occurrence of local inflammation may indicate an ongoing degradation of herniated fragments and thus be helpful in therapeutic decision-making. (C) 2014 Elsevier B.V. All rights reserved

Cumulative socioeconomic status and incident type 2 diabetes among African American adults from the Jackson heart study

Background: The cumulative socioeconomic status (SES) model posits that childhood and adult experiences accumulate to influence disease risk. While individual SES indicators such as education and income are independently associated with incident type 2 diabetes (T2D), the association of cumulative SES and incident T2D is unclear, especially in African American adults. Methods: We utilized cohort data of African American participants (n = 3681, mean age 52.6 years) enrolled in the Jackson Heart Study from 2000 to 2013 free of T2D or cardiovascular disease at baseline (2000–2004). Cumulative SES scores at baseline were derived using six SES indicators (education, wealth, income, occupation, employment status, and mother's education) categorized as low, middle, and high. Incident T2D was defined at exam 2 (2005–2008) or exam 3 (2009–2013) based on fasting glucose ≥126 mg/dL, HbA1c ≥ 6.5, reported diabetic medication use, or self-reported physician diagnosis. Proportional hazards regression, allowing for interval censoring, was used to estimate the association between cumulative SES and incident T2D (hazard ratio(HR), 95% confidence interval (CI)) after adjustment for covariates. Sex and age differences were tested using interaction terms. Results: There were 544 incident T2D cases. The association between low (versus high) cumulative SES and incident T2D was not significant (HR 1.04 [95% CI 0.85, 1.28]) and did not differ by sex (p value for interaction>0.05). However, there were differences by (age p value for interaction = 0.0052 for middle-aged adults and 0.0186 for older adults). Low (versus high) cumulative SES was associated a greater hazard of incident T2D among those 20–46 years (HR 1.12 [95% CI 1.03, 1.21]), 47–59 years (HR 1.25 [95% CI 1.06, 1.47]) and those 60–93 years (HR 1.39 [95% CI 1.09, 1.78]) after adjustment for sex and family history of diabetes. Associations attenuated after adding behavioral and lifestyle risk factors. Conclusion: The association of low cumulative SES and incident T2D differed by age, which may suggest interventionist should consider impacts of SES on T2D by age

3D rotational fluoroscopy for intraoperative clip control in patients with intracranial aneurysms – assessment of feasibility and image quality

Background Mobile 3D fluoroscopes have become increasingly available in neurosurgical operating rooms. In this series, the image quality and value of intraoperative 3D fluoroscopy with intravenous contrast agent for the evaluation of aneurysm occlusion and vessel patency after clip placement was assessed in patients who underwent surgery for intracranial aneurysms. Materials and methods Twelve patients were included in this retrospective analysis. Prior to surgery, a 360° rotational fluoroscopy scan was performed without contrast agent followed by another scan with 50 ml of intravenous iodine contrast agent. The image files of both scans were transferred to an Apple PowerMac® workstation, subtracted and reconstructed using OsiriX® free software. The procedure was repeated after clip placement. Both image sets were compared for assessment of aneurysm occlusion and vessel patency. Results Image acquisition and contrast administration caused no adverse effects. Image quality was sufficient to follow the patency of the vessels distal to the clip. Metal artifacts reduce the assessability of the immediate vicinity of the clip. Precise image subtraction and post-processing can reduce metal artifacts and make the clip-site assessable and depict larger neck-remnants. Conclusion This technique quickly supplies images at adequate quality to evaluate distal vessel patency after aneurysm clipping. Significant aneurysm remnants may be depicted as well. As it does not require visual control of all vessels that are supposed to be evaluated intraoperatively, this technique may be complementary to other intraoperative tools like indocyanine green videoangiography and micro-Doppler, especially for the assessment of larger aneurysms. At the momentary state of this technology, it cannot replace postoperative conventional angiography. However, 3D fluoroscopy and image post-processing are young technologies. Further technical developments are likely to result in improved image quality

Cumulative socioeconomic status and incident type 2 diabetes among African American adults from the Jackson heart study.

BackgroundThe cumulative socioeconomic status (SES) model posits that childhood and adult experiences accumulate to influence disease risk. While individual SES indicators such as education and income are independently associated with incident type 2 diabetes (T2D), the association of cumulative SES and incident T2D is unclear, especially in African American adults.MethodsWe utilized cohort data of African American participants (n = 3681, mean age 52.6 years) enrolled in the Jackson Heart Study from 2000 to 2013 free of T2D or cardiovascular disease at baseline (2000-2004). Cumulative SES scores at baseline were derived using six SES indicators (education, wealth, income, occupation, employment status, and mother's education) categorized as low, middle, and high. Incident T2D was defined at exam 2 (2005-2008) or exam 3 (2009-2013) based on fasting glucose ≥126 mg/dL, HbA1c ≥ 6.5, reported diabetic medication use, or self-reported physician diagnosis. Proportional hazards regression, allowing for interval censoring, was used to estimate the association between cumulative SES and incident T2D (hazard ratio(HR), 95% confidence interval (CI)) after adjustment for covariates. Sex and age differences were tested using interaction terms.ResultsThere were 544 incident T2D cases. The association between low (versus high) cumulative SES and incident T2D was not significant (HR 1.04 [95% CI 0.85, 1.28]) and did not differ by sex (p value for interaction>0.05). However, there were differences by (age p value for interaction = 0.0052 for middle-aged adults and 0.0186 for older adults). Low (versus high) cumulative SES was associated a greater hazard of incident T2D among those 20-46 years (HR 1.12 [95% CI 1.03, 1.21]), 47-59 years (HR 1.25 [95% CI 1.06, 1.47]) and those 60-93 years (HR 1.39 [95% CI 1.09, 1.78]) after adjustment for sex and family history of diabetes. Associations attenuated after adding behavioral and lifestyle risk factors.ConclusionThe association of low cumulative SES and incident T2D differed by age, which may suggest interventionist should consider impacts of SES on T2D by age