Epigenetic age acceleration in surviving versus deceased COVID-19 patients with acute respiratory distress syndrome following hospitalization.

BACKGROUND: Aging has been reported as a major risk factor for severe symptoms and higher mortality rates in COVID-19 patients. Molecular hallmarks such as epigenetic alterations and telomere attenuation reflect the biological process of aging. Epigenetic clocks have been shown to be valuable tools for measuring biological age in various tissues and samples. As such, these epigenetic clocks can determine accelerated biological aging and time-to-mortality across various tissues. Previous reports have shown accelerated biological aging and telomere attrition acceleration following SARS-CoV-2 infection. However, the effect of accelerated epigenetic aging on outcome (death/recovery) in COVID-19 patients with acute respiratory distress syndrome (ARDS) has not been well investigated. RESULTS: In this study, we measured DNA methylation age and telomere attrition in 87 severe COVID-19 cases with ARDS under mechanical ventilation. Furthermore, we compared dynamic changes in epigenetic aging across multiple time points until recovery or death. Epigenetic age was measured using the Horvath, Hannum, DNAm skin and blood, GrimAge, and PhenoAge clocks, whereas telomere length was calculated using the surrogate marker DNAmTL. Our analysis revealed significant accelerated epigenetic aging but no telomere attrition acceleration in severe COVID-19 cases. In addition, we observed epigenetic age deceleration at inclusion versus end of follow-up in recovered but not in deceased COVID-19 cases using certain clocks. When comparing dynamic changes in epigenetic age acceleration (EAA), we detected higher EAA using both the Horvath and PhenoAge clocks in deceased versus recovered patients. The DNAmTL measurements revealed telomere attrition acceleration in deceased COVID-19 patients between inclusion and end of follow-up and a significant change in dynamic telomere attrition acceleration when comparing patients who recovered versus those who died. CONCLUSIONS: EAA and telomere attrition acceleration were associated with treatment outcomes in hospitalized COVID-19 patients with ARDS. A better understanding of the long-term effects of EAA in COVID-19 patients and how they might contribute to long COVID symptoms in recovered individuals is urgently needed.

Overweight and obesity are associated with better survival in STEMI patients with diabetes.

OBJECTIVE: The relationship between obesity and in-hospital outcomes in individuals with type 2 diabetes mellitus (T2DM) who develop an ST-elevation myocardial infarction (STEMI) was assessed. METHODS: Data from the National Inpatient Sample (NIS) from 2008 to 2017 were analyzed. Patients with STEMI and T2DM were classified as being underweight or having normal weight, overweight, obesity, and severe obesity. The temporal trend of those BMI ranges and in-hospital outcomes among different obesity groups were assessed. RESULTS: A total of 74,099 patients with T2DM and STEMI were included in this analysis. In 2008, 35.8% of patients had obesity, and 37.3% had severe obesity. However, patients with obesity accounted for most of the study population in 2017 (57.8%). During the observation period, mortality decreased in underweight patients from 18.1% to 13.2% (p < 0.001). Still, it gradually increased in all other BMI ranges, along with cardiogenic shock, atrial fibrillation, and ventricular fibrillation (p < 0.001 for all). After the combination of all patients during the observation period, mortality was lower in patients with overweight and obesity (adjusted odds ratio = 0.625 [95% CI 0.499-0.784]; 0.606 [95% CI 0.502-0.733], respectively). CONCLUSIONS: A U-shaped association governs the relationship between BMI and mortality in STEMI patients with diabetes, with those having overweight and obesity experiencing better survival.

Type 2 diabetes and in-hospital sudden cardiac arrest in ST-elevation myocardial infarction in the US.

Aims: We aimed to assess the impact of diabetes on sudden cardiac arrest (SCA) in US patients hospitalized for ST-elevation myocardial infarction (STEMI). Methods: We used the National Inpatient Sample (2005-2017) data to identify adult patients with STEMI. The primary outcome was in-hospital SCA. Secondary outcomes included in-hospital mortality, ventricular tachycardia (VT), ventricular fibrillation (VF), cardiogenic shock (CS), acute renal failure (ARF), and the revascularization strategy in SCA patients. Results: SCA significantly increased from 4% in 2005 to 7.6% in 2018 in diabetes patients and from 3% in 2005 to 4.6% in 2018 in non-diabetes ones (p < 0.001 for both). Further, diabetes was associated with an increased risk of SCA [aOR = 1.432 (1.336-1.707)]. In SCA patients with diabetes, the mean age (SD) decreased from 68 (13) to 66 (11) years old, and mortality decreased from 65.7% to 49.3% during the observation period (p < 0.001). Compared to non-diabetes patients, those with T2DM had a higher adjusted risk of mortality, ARF, and CS [aOR = 1.72 (1.62-1.83), 1.52 (1.43-1.63), 1.25 (1.17-1.33); respectively] but not VF or VT. Those patients were more likely to undergo revascularization with CABG [aOR = 1.197 (1.065-1.345)] but less likely to undergo PCI [aOR = 0.708 (0.664-0.754)]. Conclusion: Diabetes is associated with an increased risk of sudden cardiac arrest in ST-elevation myocardial infarction. It is also associated with a higher mortality risk in SCA patients. However, the recent temporal mortality trend in SCA patients shows a steady decline, irrespective of diabetes.

Primary hyperaldosteronism is associated with increased mortality and morbidity in patients with hypertension and diabetes.

Aims: Primary hyperaldosteronism (PA) is a common cause of hypertension. It is more prevalent in patients with diabetes. We assessed the cardiovascular impact of PA in patients with established hypertension and diabetes. Methods: Data from the National Inpatient Sample (2008-2016) was used to identify adults with PA with hypertension and diabetes comorbidities and then compared to non-PA patients. The primary outcome was in-hospital death. Secondary outcomes included ischemic stroke, hemorrhagic stroke, acute renal failure, atrial fibrillation, and acute heart failure. Results: A total of 48,434,503 patients with hypertension and diabetes were included in the analysis, of whom 12,850 (0.03%) were diagnosed with primary hyperaldosteronism (PA). Compared to patients with hypertension and diabetes but no PA, those with PA were more likely to be younger [63(13) vs. 67 (14), male (57.1% vs. 48.3%), and African-Americans (32% vs. 18.5%) (p<0.001 for all). PA was associated with a higher risk of mortality (adjusted OR 1.076 [1.076-1.077]), ischemic stroke [adjusted OR 1.049 (1.049-1.05)], hemorrhagic stroke [adjusted OR 1.05 (1.05-1.051)], acute renal failure [adjusted OR 1.058 (1.058-1.058)], acute heart failure [OR 1.104 (1.104-1.104)], and atrial fibrillation [adjusted OR 1.034 (1.033-1.034)]. As expected, older age and underlying cardiovascular disease were the strongest predictors of mortality. However, the female gender conferred protection [OR 0.889 (0.886-0.892]. Conclusion: Primary hyperaldosteronism in patients with hypertension and diabetes is associated with increased mortality and morbidity.

Burden of cardiovascular disease attributable to particulate matter pollution in the eastern Mediterranean region: analysis of the 1990-2019 global burden of disease.

AIMS: Particulate matter pollution is the most important environmental mediator of global cardiovascular morbidity and mortality. Air pollution evidence from the Eastern Mediterranean Region (EMR) is limited, owing to scarce local studies, and the omission from multinational studies. We sought to investigate trends of particulate matter (PM2.5)-related cardiovascular disease (CVD) burden in the EMR from 1990 to 2019. METHODS AND RESULTS: We used the 1990-2019 global burden of disease methodology to investigate total PM2.5, ambient PM2.5, and household PM2.5-related CVD deaths and disability-adjusted life years (DALYs) and cause-specific CVD mortality in the EMR. The average annual population-weighted PM2.5 exposure in EMR region was 50.3 µg/m3 [95% confidence interval (CI):42.7-59.0] in 2019, which was comparable with 199 048.1 µg/m3 (95% CI: 36.5-65.3). This was despite an 80% reduction in household air pollution (HAP) sources since 1990. In 2019, particulate matter pollution contributed to 25.67% (95% CI: 23.55-27.90%) of total CVD deaths and 28.10% (95% CI: 25.75-30.37%) of DALYs in the region, most of which were due to ischaemic heart disease and stroke. We estimated that 353 071 (95% CI: 304 299-404 591) CVD deaths in EMR were attributable to particulate matter in 2019, including 264 877 (95% CI: 218 472-314 057) and 88 194.07 (95% CI: 60 149-119 949) CVD deaths from ambient PM2.5 pollution and HAP from solid fuels, respectively. DALY's in 2019 from CVD attributable to particulate matter was 28.1% when compared with 26.69% in 1990. The age-standardized death and DALY rates attributable to air pollution was 2122 per 100 000 in EMR in 2019 and was higher in males (2340 per 100 000) than in females (1882 per 100 000). CONCLUSION: The EMR region experiences high PM2.5 levels with high regional heterogeneity and attributable burden of CVD due to air pollution. Despite significant reductions of overall HAP in the past 3 decades, there is continued HAP exposure in this region with rising trend in CVD mortality and DALYs attributable to ambient sources. Given the substantial contrast in disease burden, exposures, socio-economic and geo-political constraints in the EMR region, our analysis suggests substantial opportunities for PM2.5 attributable CVD burden mitigation.

Diabetes outcomes in heart failure patients with hypertrophic cardiomyopathy.

Aims: We aimed to assess diabetes outcomes in heart failure (HF) patients with hypertrophic cardiomyopathy (HCM). Methods: The National Inpatient Sample database was analyzed to identify records from 2005 to 2015 of patients hospitalized for HF with concomitant HCM. We examined the prevalence of diabetes in those patients, assessed the temporal trend of in-hospital mortality, ventricular fibrillation, atrial fibrillation, and cardiogenic shock and compared diabetes patients to their non-diabetes counterparts. Results: Among patients with HF, 0.26% had HCM, of whom 29.3% had diabetes. Diabetes prevalence increased from 24.8% in 2005 to 32.7% in 2015. The mean age of patients with diabetes decreased from 71 ± 13 to 67.6 ± 14.2 (p < 0.01), but the prevalence of cardiovascular risk factors significantly increased. In-hospital mortality decreased from 4.3% to 3.2% between 2005 and 2015. Interestingly, cardiogenic shock, VF, and AF followed an upward trend. Age (OR = 1.04 [1.03-1.05]), female gender (OR = 1.50 [0.72-0.88]), and cardiovascular risk factors were associated with a higher in-hospital mortality risk in diabetes. Compared to non-diabetes patients, the ones with diabetes were younger and had more comorbidities. Unexpectedly, the adjusted risks of in-hospital mortality (aOR = 0.88 [0.76-0.91]), ventricular fibrillation (aOR = 0.79 [0.71-0.88]) and atrial fibrillation (aOR 0.80 [0.76-0.85]) were lower in patients with diabetes, but not cardiogenic shock (aOR 1.01 [0.80-1.27]). However, the length of stay was higher in patients with diabetes, and so were the total charges per stay. Conclusion: In total, we observed a temporal increase in diabetes prevalence among patients with HF and HCM. However, diabetes was paradoxically associated with lower in-hospital mortality and arrhythmias.

Assessing the genetic burden of familial hypercholesterolemia in a large middle eastern biobank.

BACKGROUND: The genetic architecture underlying Familial Hypercholesterolemia (FH) in Middle Eastern Arabs is yet to be fully described, and approaches to assess this from population-wide biobanks are important for public health planning and personalized medicine. METHODS: We evaluate the pilot phase cohort (n = 6,140 adults) of the Qatar Biobank (QBB) for FH using the Dutch Lipid Clinic Network (DLCN) criteria, followed by an in-depth characterization of all genetic alleles in known dominant (LDLR, APOB, and PCSK9) and recessive (LDLRAP1, ABCG5, ABCG8, and LIPA) FH-causing genes derived from whole-genome sequencing (WGS). We also investigate the utility of a globally established 12-SNP polygenic risk score to predict FH individuals in this cohort with Arab ancestry. RESULTS: Using DLCN criteria, we identify eight (0.1%) 'definite', 41 (0.7%) 'probable' and 334 (5.4%) 'possible' FH individuals, estimating a prevalence of 'definite or probable' FH in the Qatari cohort of ~ 1:125. We identify ten previously known pathogenic single-nucleotide variants (SNVs) and 14 putatively novel SNVs, as well as one novel copy number variant in PCSK9. Further, despite the modest sample size, we identify one homozygote for a known pathogenic variant (ABCG8, p. Gly574Arg, global MAF = 4.49E-05) associated with Sitosterolemia 2. Finally, calculation of polygenic risk scores found that individuals with 'definite or probable' FH have a significantly higher LDL-C SNP score than 'unlikely' individuals (p = 0.0003), demonstrating its utility in Arab populations. CONCLUSION: We design and implement a standardized approach to phenotyping a population biobank for FH risk followed by systematically identifying known variants and assessing putative novel variants contributing to FH burden in Qatar. Our results motivate similar studies in population-level biobanks - especially those with globally under-represented ancestries - and highlight the importance of genetic screening programs for early detection and management of individuals with high FH risk in health systems.

DNA methylation predicts the outcome of COVID-19 patients with acute respiratory distress syndrome.

BACKGROUND: COVID-19 infections could be complicated by acute respiratory distress syndrome (ARDS), increasing mortality risk. We sought to assess the methylome of peripheral blood mononuclear cells in COVID-19 with ARDS. METHODS: We recruited 100 COVID-19 patients with ARDS under mechanical ventilation and 33 non-COVID-19 controls between April and July 2020. COVID-19 patients were followed at four time points for 60 days. DNA methylation and immune cell populations were measured at each time point. A multivariate cox proportional risk regression analysis was conducted to identify predictive signatures according to survival. RESULTS: The comparison of COVID-19 to controls at inclusion revealed the presence of a 14.4% difference in promoter-associated CpGs in genes that control immune-related pathways such as interferon-gamma and interferon-alpha responses. On day 60, 24% of patients died. The inter-comparison of baseline DNA methylation to the last recorded time point in both COVID-19 groups or the intra-comparison between inclusion and the end of follow-up in every group showed that most changes occurred as the disease progressed, mainly in the AIM gene, which is associated with an intensified immune response in those who recovered. The multivariate Cox proportional risk regression analysis showed that higher methylation of the "Apoptotic execution Pathway" genes (ROC1, ZNF789, and H1F0) at inclusion increases mortality risk by over twofold. CONCLUSION: We observed an epigenetic signature of immune-related genes in COVID-19 patients with ARDS. Further, Hypermethylation of the apoptotic execution pathway genes predicts the outcome. TRIAL REGISTRATION: IMRPOVIE study, NCT04473131.

Hypoglycemia is associated with a higher risk of mortality and arrhythmias in ST-elevation myocardial infarction, irrespective of diabetes.

Aims: We aimed to assess the impact of hypoglycemia in ST-elevation myocardial infarction (STEMI). Background: Hypoglycemia increases the risk of mortality in patients with diabetes and high cardiovascular risk. Methods: We used the National Inpatient Sample (2005-2017) database to identify adult patients with STEMI as the primary diagnosis. The secondary diagnosis was hypoglycemia. We compared cardiovascular and socio-economic outcomes between STEMI patients with and without hypoglycemia and assessed temporal trends. Results: Hypoglycemia tends to complicate 0.17% of all cases hospitalized for STEMI. The mean age (±SD) of STEMI patients hospitalized with hypoglycemia decreased from 67 ± 15 in 2005 to 63 ± 12 in 2017 (p = 0.046). Mortality was stable with time, but the prevalence of ventricular tachycardia, ventricular fibrillation, acute renal failure, cardiogenic shock, total charges, and length of stay (LOS) increased with time (p < 0.05 for all). Compared to non-hypoglycemic patients, those who developed hypoglycemia were older and more likely to be black; only 6.7% had diabetes compared to 28.5% of STEMI patients (p = 0.001). Cardiovascular events were more likely to occur in hypoglycemia: mortality risk increased by almost 2.5-fold (adjusted OR = 2.625 [2.095-3.289]). There was a higher incidence of cardiogenic shock (adjusted OR = 1.718 [1.387-2.127]), atrial fibrillation (adjusted OR = 1.284 [1.025-1.607]), ventricular fibrillation (adjusted OR = 1.799 [1.406-2.301]), and acute renal failure (adjusted OR = 2.355 [1.902-2.917]). Patients who developed hypoglycemia were less likely to have PCI (OR = 0.596 [0.491-0.722]) but more likely to have CABG (OR = 1.792 [1.391-2.308]). They also had a longer in-hospital stay and higher charges/stay. Conclusion: Hypoglycemia is a rare event in patients hospitalized with STEMI. However, it was found to have higher odds of mortality, arrhythmias, and other comorbidities, irrespective of diabetes.

Trends and Outcomes of Aortic Valve Replacement in Patients With Diabetes in the US.

Aims: We aimed to assess the trend and outcome of aortic valve replacement in patients with diabetes. Background: Diabetes is associated with higher cardiovascular events. Methods: Data from the National Inpatient Sample was analyzed between 2012 and 2017. We compared hospitalizations and in-hospital cardiovascular outcomes in patients with diabetes to those without diabetes, hospitalized for aortic valve replacement. Results: In diabetes patients undergoing TAVR, the mean age of participants decreased from 79.6 ± 8 to 67.8 ± 8, hospitalizations increased from 0.97 to 7.68/100,000 US adults (p < 0.002 for both). There was a significant temporal decrease in mortality, acute renal failure (ARF), and stroke. Compared to non-diabetic patients, those with diabetes had a higher risk of stroke, ARF, and pacemaker requirement [adjusted OR = 1.174 (1.03-1.34), 1.294 (1.24-1.35), 1.153 (1.11-1.20), respectively], but a similar adjusted mortality risk. In diabetes patients undergoing sAVR, the mean age of participants decreased from 70.4 ± 10 to 68 ± 9 (p < 0.001), hospitalizations dropped from 7.72 to 6.63/100,000 US adults (p = 0.025), so did mortality, bleeding, and ARF. When compared to non-diabetes patients, those with diabetes were older and had a higher adjusted risk of mortality, stroke, and ARF [adjusted OR= 1.115 (1.06-1.17), 1.140 (1.05-1.23), 1.217 (1.18-1.26); respectively]. Conclusion: The recent temporal trend of aortic valve replacement in patients with diabetes shows a significant increase in TAVR coupled with a decrease in sAVR. Mortality and other cardiovascular outcomes decreased in both techniques. sAVR, but not TAVR, was associated with higher in-hospital mortality risk.

Altered Circulating microRNAs in Patients with Diabetic Neuropathy and Corneal Nerve Loss: A Pilot Study.

An alteration in circulating miRNAs may have important diagnostic and therapeutic relevance in diabetic neuropathy. Patients with type 2 diabetes mellitus (T2DM) underwent an assessment of neuropathic symptoms using Douleur Neuropathique 4 (DN4), the vibration perception threshold (VPT) using a Neurothesiometer, sudomotor function using the Sudoscan, corneal nerve morphology using corneal confocal microscopy (CCM) and circulating miRNAs using high-throughput miRNA expression profiling. Patients with T2DM, with (n = 9) and without (n = 7) significant corneal nerve loss were comparable in age, gender, diabetes duration, BMI, HbA1c, eGFR, blood pressure, and lipid profile. The VPT was significantly higher (p < 0.05), and electrochemical skin conductance (p < 0.05), corneal nerve fiber density (p = 0.001), corneal nerve branch density (p = 0.013), and corneal nerve fiber length (p < 0.001) were significantly lower in T2DM patients with corneal nerve loss compared to those without corneal nerve loss. Following a q-PCR-based analysis of total plasma microRNAs, we found that miR-92b-3p (p = 0.008) was significantly downregulated, while miR-22-3p (p = 0.0001) was significantly upregulated in T2DM patients with corneal nerve loss. A network analysis revealed that these miRNAs regulate axonal guidance and neuroinflammation genes. These data support the need for more extensive studies to better understand the role of dysregulated miRNAs' in diabetic neuropathy.

Angiogenic content of microparticles in patients with diabetes and coronary artery disease predicts networks of endothelial dysfunction.

BACKGROUND: Elevated endothelial microparticles (EMPs) levels are surrogate markers of vascular dysfunction. We analyzed EMPs with apoptotic characteristics and assessed the angiogenic contents of microparticles in the blood of patients with type 2 diabetes (T2D) according to the presence of coronary artery disease (CAD). METHODS: A total of 80 participants were recruited and equally classified as (1) healthy without T2D, (2) T2D without cardiovascular complications, (3) T2D and chronic coronary artery disease (CAD), and (4) T2D and acute coronary syndrome (ACS). MPs were isolated from the peripheral circulation, and EMPs were characterized using flow cytometry of CD42 and CD31. CD62E was used to determine EMPs' apoptotic/activation state. MPs content was extracted and profiled using an angiogenesis array. RESULTS: Levels of CD42- CD31 + EMPs were significantly increased in T2D with ACS (257.5 ± 35.58) when compared to healthy subjects (105.7 ± 12.96, p < 0.01). There was no significant difference when comparing T2D with and without chronic CAD. The ratio of CD42-CD62 +/CD42-CD31 + EMPs was reduced in all T2D patients, with further reduction in ACS when compared to chronic CAD, reflecting a release by apoptotic endothelial cells. The angiogenic content of the full population of MPs was analyzed. It revealed a significant differential expression of 5 factors in patients with ACS and diabetes, including TGF-ß1, PD-ECGF, platelet factor 4, serpin E1, and thrombospondin 1. Ingenuity Pathway Analysis revealed that those five differentially expressed molecules, mainly TGF-ß1, inhibit key pathways involved in normal endothelial function. Further comparison of the three diabetes groups to healthy controls and diabetes without cardiovascular disease to diabetes with CAD identified networks that inhibit normal endothelial cell function. Interestingly, DDP-IV was the only differentially expressed protein between chronic CAD and ACS in patients with diabetes. CONCLUSION: Our data showed that the release of apoptosis-induced EMPs is increased in diabetes, irrespective of CAD, ACS patients having the highest levels. The protein contents of MPs interact in networks that indicate vascular dysfunction.

Temporal Trends in Outcomes of ST-Elevation Myocardial Infarction Patients With Heart Failure and Diabetes.

AIMS: We aimed to assess temporal trends in outcomes of ST-elevation myocardial infarction (STEMI) patients with diabetes and heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) and compared both groups. METHODS: Data from the National Inpatient Sample was analyzed between 2005 and 2017. We assessed hospitalizations rate and in-hospital mortality, ventricular tachycardia (VT), ventricular fibrillation (VF), atrial fibrillation (AF), cardiogenic shock (CS), ischemic stroke, acute renal failure (ARF), and revascularization strategy. Socio-economic outcomes consisted of the length of stay (LoS) and total charges/stay. RESULTS: Hospitalization rate steadily decreased with time in STEMI patients with diabetes and HFrEF. Mean age (SD) decreased from 71 ± 12 to 67 ± 12 (p < 0.01), while the prevalence of comorbidities increased. Mortality was stable (around 9%). However, VT, VF, AF, CS, ischemic stroke, and ARF significantly increased with time. In STEMI patients with HFpEF and diabetes, the hospitalization rate significantly increased with time while mean age was stable. The prevalence of comorbidities increased, mortality remained stable (around 4%), but VF, ischemic stroke, and ARF increased with time. Compared to patients with HFrEF, HFpEF patients were 2 years older, more likely to be females, suffered from more cardio-metabolic risk factors, and had a higher prevalence of cardiovascular diseases. However, HFpEF patients were less likely to die [adjusted OR = 0.635 (0.601-0.670)] or develop VT [adjusted OR = 0.749 (0.703-0.797)], VF [adjusted OR = 0.866 (0.798-0.940)], ischemic stroke [adjusted OR = 0.871 [0.776-0.977)], and CS [adjusted OR = 0.549 (0.522-0.577)], but more likely to develop AF [adjusted OR = 1.121 (1.078-1.166)]. HFpEF patients were more likely to get PCI but less likely to get thrombolysis or CABG. Total charges per stay increased by at least 2-fold in both groups. There was a slight temporal reduction over the study period in the LoS of the HFpEF. CONCLUSION: While hospitalizations for STEMI in patients with diabetes and HFpEF followed an upward trend, we observed a temporal decrease in those with HFrEF. Mortality was unchanged in both HF groups despite the temporal increase in risk factors. Nevertheless, HFpEF patients had lower in-hospital mortality and cardiovascular events, except for AF.

Atrial fibrillation catheter ablation complications in obese and diabetic patients: Insights from the US Nationwide Inpatient Sample 2005-2013.

BACKGROUND: Obesity and diabetes are risk factors for atrial fibrillation (AF) incidence and recurrence after catheter ablation. However, their impact on post-ablation complications in real-world practice is unknown. OBJECTIVES: We examine annual trends in AF ablations and procedural outcomes in obese and diabetic patients in the US and whether obesity and diabetes are independently associated with adverse outcomes. METHODS: Using the Nationwide Inpatient Sample (2005-2013), we identified obese and diabetic patients admitted for AF ablation. Common complications were identified using ICD-9-CM codes. The primary outcome included the composite of any in-hospital complication or death. Annual trends of the primary outcome, length-of-stay (LOS) and total-inflation adjusted hospital charges were examined. Multivariate analyses studied the association of obesity and diabetes with outcomes. RESULTS: An estimated 106 462 AF ablations were performed in the US from 2005 to 2013. Annual trends revealed a gradual increase in ablations performed in obese and diabetic patients and in complication rates. The overall rate of the primary outcome in obese was 11.7% versus 8.2% in non-obese and 10.7% in diabetic versus 8.2% in non-diabetic patients (p < .001). CONCLUSIONS: Obesity was independently associated with increased complications (adjusted OR, 95% CI:1.39, 1.20-1.62), longer LOS (1.36, 1.23-1.49), and higher charges (1.16, 1.12-1.19). Diabetes was only associated with longer LOS (1.27, 1.16-1.38). Obesity, but not diabetes, in patients undergoing AF ablation is an independent risk factor for immediate post-ablation complications and higher costs. Future studies should investigate whether weight loss prior to ablation reduces complications and costs.

Aortic valve function post-replacement of severe aortic stenosis by transcatheter procedure versus surgery: a systematic review and metanalysis.

Transcatheter aortic valve replacement (TAVR) has shown to reduce mortality compared to surgical aortic valve replacement (sAVR). However, it is unknown which procedure is associated with better post-procedural valvular function. We conducted a meta-analysis of randomized clinical trials that compared TAVR to sAVR for at least 2 years. The primary outcome was post-procedural patient-prosthesis-mismatch (PPM). Secondary outcomes were post-procedural and 2-year: effective orifice area (EOA), paravalvular gradient (PVG) and moderate/severe paravalvular leak (PVL). We identified 6 trials with a total of 7022 participants with severe aortic stenosis. TAVR was associated with 37% (95% CI [0.51-0.78) mean RR reduction of post-procedural PPM, a decrease that was not affected by the surgical risk at inclusion, neither by the transcatheter heart valve system. Postprocedural changes in gradient and EOA were also in favor of TAVR as there was a pooled mean difference decrease of 0.56 (95% CI [0.73-0.38]) in gradient and an increase of 0.47 (95% CI [0.38-0.56]) in EOA. Additionally, self-expandable valves were associated with a higher decrease in gradient than balloon ones (beta = 0.38; 95% CI [0.12-0.64]). However, TAVR was associated with a higher risk of moderate/severe PVL (pooled RR: 9.54, 95% CI [5.53-16.46]). All results were sustainable at 2 years.

Mortality and socio-economic outcomes among patients hospitalized for stroke and diabetes in the US: a recent analysis from the National Inpatient Sample.

The prevalence and incidence of diabetes mellitus (DM) are increasing worldwide. We aim to assess mortality and socio-economic outcomes among patients hospitalized for stroke and diabetes in the US and evaluate their recent trends. We examined: in-hospital mortality, length of stay (LoS), and overall hospital charges in diabetic patients over 18 years old who were hospitalized with a stroke from 2005 to 2014, included in the National Inpatient Sample. In those patients, the mean (SD) age slightly decreased from 70 (13) years to 69 (13) years (p-trend < 0.001). Interestingly, although incident cases of stroke amongst DM patients increased from 17.4 to 20.0 /100,000 US adults (p-trend < 0.001), age-adjusted mortality for those with hemorrhagic strokes decreased from 24.3% to 19.6%, and also decreased from 3.23% to 2.48% for those with ischemic strokes (p-trend < 0.01 for both), but remained unchanged in TIAs patients. As expected, the average total charges per hospital stay almost doubled over the ten-year period, increasing from 15 970 to 31 018 USD/stay (adjusted for inflation). Nonetheless, median (IQR) LoS slightly decreased from 4 (2-6) to 3 (2-6) days (p-trend < 0.001). In total, our data show that, from 2005 to 2014, the incidence of stroke among the diabetes patient population are gradually increasing, in-hospital mortality is steadily decreasing, along with average LoS. Admission costs were up almost twofold during the same period.

Exercise Ventricular Rates, Cardiopulmonary Exercise Performance, and Mortality in Patients With Heart Failure With Atrial Fibrillation.

BACKGROUND: In heart failure (HF) with sinus rhythm, resting and exercise heart rates correlate with exercise capacity and mortality. However, in HF with atrial fibrillation (AF), this correlation is unknown. Our aim is to investigate the association of resting and exercise ventricular rates (VRs) with exercise capacity and mortality in HF with AF. METHODS: We identified 903 patients with HF and AF referred for cardiopulmonary stress testing. AF was defined as history of AF and AF during cardiopulmonary stress testing. We constructed multivariable models to evaluate the association of resting VR, peak exercise VR, VR reserve (peak VR-resting VR), and chronotropic index with (1) peak oxygen consumption (PVO2) ≤18 mL/kg per minute, (2) continuous PVO2, and (3) 10-year all-cause mortality. RESULTS: Median (25th-75th percentile) age was 60 (52-67) years, left ventricular ejection fraction was 25 (15-50)%, and 76.1% were males. Patients with lower (quartile 1) compared with higher (quartile 4) peak VR, VR reserve, and chronotropic index were more likely to have PVO2 ≤18 mL/kg per min (adjusted odds ratio [95% CI]: 14.92 [8.07-27.58], 24.60 [12.36-48.98], and 22.31 [11.24-44.27], respectively), and higher all-cause mortality (adjusted hazard ratio [95% CI]: 2.56 [1.62-4.04], 2.29 [1.47-3.59], and 2.30 [1.51-3.49], respectively). For every 10 beats per minute increase in VR reserve, PVO2 increased by 1.05 mL/kg per minute (B-coefficient [95% CI]: 1.05 [0.94-1.15]) and mortality decreased by 12% (adjusted hazard ratio [95% CI]: 0.88 [0.83-0.94]). Resting VR was associated with PVO2 (B-coefficient [95% CI]: -0.46 [-0.70 to -0.23]) but not mortality (adjusted hazard ratio [95% CI]: 0.97 [0.88-1.06]). CONCLUSIONS: In patients with HF and AF, higher resting VR and lower peak exercise VR, VR reserve, and chronotropic index were all associated with worse peak exercise capacity, but only lower exercise VR parameters were associated with higher mortality. Dedicated studies are needed to gauge whether modulating exercise VR enhances exercise performance and outcomes.

Diabetes-related cardiovascular and economic burden in patients hospitalized for heart failure in the US: a recent temporal trend analysis from the National Inpatient Sample.

We aimed to study the cardiovascular and economic burden of diabetes mellitus (DM) in patients hospitalized for heart failure (HF) in the US and to assess the recent temporal trend. Data from the National Inpatient Sample were analyzed between 2005 and 2014. The prevalence of DM increased from 40.4 to 46.5% in patients hospitalized for HF. In patients with HF and DM, mean (SD) age slightly decreased from 71 (13) to 70 (13) years, in which 47.5% were males in 2005 as compared with 52% in 2014 (p trend < 0.001 for both). Surprisingly, the presence of DM was associated with lower in-hospital mortality risk, even after adjustment for confounders (adjusted OR = 0.844 (95% CI [0.828-0.860]). Crude mortality gradually decreased from 2.7% in 2005 to 2.4% in 2014 but was still lower than that of non-diabetes patients' mortality on a yearly comparison basis. Hospitalization for HF also decreased from 211 to 188/100,000 hospitalizations. However, median (IQR) LoS slightly increased from 4 (2-6) to 4 (3-7) days, so did total charges/stay that jumped from 15,704 to 26,858 USD (adjusted for inflation, p trend < 0.001 for both). In total, the prevalence of DM is gradually increasing in HF. However, the temporal trend shows that hospitalization and in-hospital mortality are on a descending slope at a cost of an increasing yearly expenditure and length of stay, even to a larger extent than in patient without DM.

Vitamin D3 metabolite ratio as an indicator of vitamin D status and its association with diabetes complications.

BACKGROUND: Vitamin D deficiency is diagnosed by total serum 25-hydroxyvitamin D (25(OH)D) concentration and is associated with poor health and increased mortality; however, some populations have low 25(OH) D concentrations without manifestations of vitamin D deficiency. The Vitamin D Metabolite Ratio (VMR) has been suggested as a superior indicator of vitamin D status. Therefore, VMR was determined in a population with type 2 diabetes at high risk for vitamin D deficiency and correlated with diabetic complications. RESEARCH DESIGN AND METHODS: Four hundred sisty patients with type 2 diabetes (T2D) were recruited, all were vitamin D3 supplement naive. Plasma concentration of 25-hydroxyvitamin D3 (25(OH)D3) and its metabolites 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) and its epimer, 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3), were measured by LC-MS/MS analysis. VMR-1 was calculated as a ratio of 24,25(OH)2D3:25(OH)D3; VMR-2 as a ratio of 1,25(OH)2D3:25(OH)D3; VMR-3 was calculated as a ratio of 3-epi-25(OH)D3: 25(OH)D3. RESULTS: An association means that there were significant differences between the ratios found for those with versus those without the various diabetic complications studied. VMR-1 was associated with diabetic retinopathy (p = 0.001) and peripheral artery disease (p = 0.012); VMR-2 associated with hypertension (p < 0.001), dyslipidemia (p < 0.001), diabetic retinopathy (p < 0.001), diabetic neuropathy (p < 0.001), coronary artery disease (p = 0.001) and stroke (p < 0.05). VMR-3 associated with hypertension (p < 0.05), dyslipidemia (p < 0.001) and coronary artery disease (p < 0.05). CONCLUSIONS: In this cross sectional study, whilst not causal, VMR-2 was shown to be the superior predictor of diabetic and cardiovascular complications though not demonstrative of causality in this cross-sectional study population over VMR-1, VMR-3 and the individual vitamin D concentration measurements; VMR-2 associated with both microvascular and cardiovascular indices and therefore may have utility in predicting the development of diabetic complications.

Association of vitamin D3 and its metabolites in patients with and without type 2 diabetes and their relationship to diabetes complications.

BACKGROUND: Epidemiological studies have suggested that vitamin D deficiency is associated with the development of type 2 diabetes (T2DM) and is related to diabetes complications. This study was undertaken to determine the relationship between diabetes complications and cardiovascular risk factors with vitamin D3 and its metabolites: 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 25-hydroxyvitamin D3 (25(OH)D3), 24,25-dihydroxyvitamin D3 (24,25(OH)2D3); and 25-hydroxy-3epi-vitamin D3 (3epi25(OH)D3). METHODS: 750 Qatari subjects, 460 (61.3%) with and 290 (38.7%) without T2DM, who were not taking vitamin D3 supplements, participated in this cross-sectional, observational study. Plasma concentrations of vitamin D3 and its metabolites were measured by liquid chromatography tandem mass spectrometry analysis. RESULTS: T2DM subjects had lower concentrations of all vitamin D3 metabolites (p < 0.001) except 3epi25(OH)D3 (p < 0.071). Males had higher concentrations of all vitamin D3 metabolites (p < 0.001). In the T2DM subjects, lower 25(OH)D3 was associated with retinopathy (p < 0.03) and dyslipidemia (p < 0.04), but not neuropathy or vascular complications; lower 1,25(OH)2D3 was associated with hypertension (p < 0.009), dyslipidemia (p < 0.003) and retinopathy (p < 0.006), and coronary artery disease (p < 0.012), but not neuropathy; lower 24,25(OH)2D3 concentrations were associated with dyslipidemia alone (p < 0.019); 3epi25(OH)D3 associated with diabetic neuropathy alone (p < 0.029). In nondiabetics, 25(OH)D3, 1,25(OH)2D3 and 24,25(OH)2D3 were associated with dyslipidemia (p < 0.001, p < 0.001, p < 0.015, respectively) and lower 1,25(OH)2D3 was associated with hypertension (p < 0.001). Spearman's correlation showed 1,25(OH)2D3 to be negatively correlated to age and diabetes duration. CONCLUSIONS: Different diabetes complications were associated with differing vitamin D parameters, with diabetic retinopathy related to lower 25(OH)D3 and 1,25(OH)2D3 levels, hypertension significantly associated with lower 1,25(OH)2D3, while dyslipidemia was associated with lower 25(OH)D3, 1,25(OH)2D3 and 24,25(OH)2D3. While 25(OH)D metabolites were lower in females, there was not an exaggeration in complications.