Regular Alcohol Consumption Is Associated With Impaired Atrial Mechanical Function in the Atrial Fibrillation Population: A Cross-Sectional MRI-Based Study.

OBJECTIVES: This study sought to determine the impact of regular alcohol consumption on left atrial (LA) mechanical and reservoir function. BACKGROUND: Earlier studies suggest that regular alcohol intake is associated with increased atrial fibrillation (AF) and LA dilatation. METHODS: This study prospectively enrolled 160 patients with paroxysmal or persistent AF to undergo 3-T cardiac magnetic resonance (CMR) imaging in sinus rhythm. Patients self-reported alcohol consumption in standard drinks (∼12 g alcohol) per week over the preceding 12 months and were categorized into 4 groups: 1) lifelong nondrinkers; 2) mild drinkers (3 to 10 standard drinks/week); 3) moderate drinkers (11 to 20 standard drinks/week); 4) heavy drinkers (>20 standard drinks/week). Permanent AF and cardiomyopathy were excluded. On CMR, maximum LA volume (LAmax) and minimum LA volume (LAmin), global LA emptying fraction (LAEF) as (LAmax - LAmin) / LAmax, and LA reservoir function as (LAmax - LAmin) / LAmin were calculated. RESULTS: Regular alcohol consumption (mean 15.8 ± 6.9 standard drinks/week, n = 120) was associated with larger LA size (LA volume index 50 ± 13 ml/m2 vs. 43 ± 12 ml/m2; p = 0.005), reduction in LAEF (40 ± 14% vs. 52 ± 15%; p < 0.001), and reduction in reservoir function (77 ± 48% vs. 119 ± 63%; p < 0.001) compared with lifelong nondrinkers (n = 40). There were progressive dose-related impairments in LAEF (mild 45.4 ± 13.5% vs. moderate 39.1 ± 14.7% vs. heavy drinkers 35.6 ± 12.6%; p < 0.01) and reservoir function (mild 95.8 ± 55.6% vs. moderate 74.8 ± 47.1% vs. heavy drinkers 61.7 ± 34.4%; p < 0.01). Predictors of atrial mechanical dysfunction included weekly alcohol intake (p = 0.001), older age (p = 0.018), and persistent AF (p = 0.016), but not binge drinking or beverage type. CONCLUSIONS: In patients with AF, habitual alcohol consumption is associated with significantly increased LA size and atrial mechanical dysfunction compared with nondrinkers.

New Glucose-Lowering Agents for Diabetic Kidney Disease.

The prevalence of diabetes mellitus is increasing and is associated with a range of complications including nephropathy. New antidiabetic agents are sought which also have positive effects to diminish diabetic complications. Examples of promising new classes of such agents are glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter 2 inhibitors. In addition to cardiovascular protective effects such as weight loss and decreased blood pressure of some of these agents, there is evidence for renoprotective effects with these agents. This review elaborates on the main results of renoprotective effects of these 3 treatment classes. In conclusion, currently available trials have demonstrated renoprotective effects for certain glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, and the sodium-glucose cotransporter 2 inhibitors, empagliflozin and canagliflozin. Dipeptidyl peptidase-4 inhibitors did not show a significant renoprotective effect. Nevertheless, larger studies with respect to renoprotective effects of these 3 drug classes are currently being performed, and thus, no conclusions for all of these agents can yet be made.

Association of Epicardial Adipose Tissue and High-Risk Plaque Characteristics: A Systematic Review and Meta-Analysis.

BACKGROUND: Epicardial adipose tissue (EAT) is hypothesized to alter atherosclerotic plaque composition, with potential development of high-risk plaque (HRP). EAT can be measured by volumetric assessment (EAT-v) or linear thickness (EAT-t). We performed a systematic review and random-effects meta-analysis to assess the association of EAT with HRP and whether this association is dependent on the measurement method used. METHODS AND RESULTS: Electronic databases were systematically searched up to October 2016. Studies reporting HRP by computed tomography or intracoronary imaging and studies measuring EAT-v or EAT-t were included. Odds ratios were extracted from multivariable models reporting the association of EAT with HRP and described as pooled estimates with 95% confidence intervals (CIs). Analysis was stratified by EAT measurement method. Nine studies (n=3772 patients) were included with 7 measuring EAT-v and 2 measuring EAT-t. Increasing EAT was significantly associated with the presence of HRP (odds ratio: 1.26 [95% CI, 1.11-1.43]; P<0.001). Patients with HRP had higher EAT-v than those without (weighted mean difference: 28.3 mL [95% CI, 18.8-37.8 mL]; P<0.001). EAT-v was associated with HRP (odds ratio: 1.19 [95% CI, 1.06-1.33]; P<0.001); however, EAT-t was not (odds ratio: 3.09 [95% CI, 0.56-17]; P=0.2). Estimates remained significant when adjusted for small-study effect bias (odds ratio: 1.13 [95% CI, 1.03-1.28]; P=0.04). CONCLUSIONS: Increasing EAT is associated with the presence of HRP, and patients with HRP have higher quantified EAT-v. The association of EAT-v with HRP is significant compared with EAT-t; however, a larger scale study is still required, and further evaluation is needed to assess whether EAT may be a potential therapeutic target for novel pharmaceutical agents. CLINICAL TRIAL REGISTRATION: URL: https://www.crd.york.ac.uk/. Unique identifier: CRD42017055473.

NADPH Oxidase Nox5 Accelerates Renal Injury in Diabetic Nephropathy.

NADPH oxidase-derived excessive production of reactive oxygen species (ROS) in the kidney plays a key role in mediating renal injury in diabetes. Pathological changes in diabetes include mesangial expansion and accumulation of extracellular matrix (ECM) leading to glomerulosclerosis. There is a paucity of data about the role of the Nox5 isoform of NADPH oxidase in animal models of diabetic nephropathy since Nox5 is absent in the mouse genome. Thus, we examined the role of Nox5 in human diabetic nephropathy in human mesangial cells and in an inducible human Nox5 transgenic mouse exposed to streptozotocin-induced diabetes. In human kidney biopsies, Nox5 was identified to be expressed in glomeruli, which appeared to be increased in diabetes. Colocalization demonstrated Nox5 expression in mesangial cells. In vitro, silencing of Nox5 in human mesangial cells was associated with attenuation of the hyperglycemia and TGF-ß1-induced enhanced ROS production, increased expression of profibrotic and proinflammatory mediators, and increased TRPC6, PKC-α, and PKC-ß expression. In vivo, vascular smooth muscle cell/mesangial cell-specific overexpression of Nox5 in a mouse model of diabetic nephropathy showed enhanced glomerular ROS production, accelerated glomerulosclerosis, mesangial expansion, and ECM protein (collagen IV and fibronectin) accumulation as well as increased macrophage infiltration and expression of the proinflammatory chemokine MCP-1. Collectively, this study provides evidence of a role for Nox5 and its derived ROS in promoting progression of diabetic nephropathy.