Temporal trends in validated ischaemic stroke hospitalizations in the USA

Background: Accurate assessment of the burden of stroke, a major cause of disability and death, is crucial. We aimed to estimate rates of validated ischaemic stroke hospitalizations in the USA during 1998-2011. Methods: We used the Atherosclerosis Risk in Communities (ARIC) study cohort's adjudicated stroke data for participants aged ≥55 years, to construct validation models for each International Classification of Diseases (ICD)-code group and patient covariates. These models were applied to the Nationwide Inpatient Sample (NIS) data to estimate the probability of validated ischaemic stroke for each eligible hospitalization. Rates and trends in NIS using ICD codes vs estimates of validated ischaemic stroke were compared. Results: After applying validation models, the estimated annual average rate of validated ischaemic stroke hospitalizations in the USA during 1998-2011 was 3.37 [95% confidence interval (CI): 3.31, 3.43) per 1000 person-years. Validated rates declined during 1998-2011 from 4.7/1000 to 2.9/1000; however, the decline was limited to 1998-2007, with no further decline subsequently through 2011. Validation models showed that the false-positive (∼23% of strokes) and false-negative rates of ICD-9-CM codes in primary position for ischaemic stroke approximately cancel. Therefore, estimates of ischaemic stroke hospitalizations did not substantially change after applying validation models. Conclusions: Overall, ischaemic stroke hospitalization rates in the USA have declined during 1998-2007, but no further decline was observed from 2007 to 2011. Validated ischaemic stroke hospitalizations estimates were similar to published estimates of hospitalizations with ischaemic stroke ICD codes in primary position. Validation of national discharge data using prospective chart review data is important to estimate the accuracy of reported burden of stroke

BNP and obesity in acute decompensated heart failure with preserved vs. reduced ejection fraction: The Atherosclerosis Risk in Communities Surveillance Study

Background Levels of B-type natriuretic peptide (BNP), a prognostic marker in patients with heart failure (HF), are lower among HF patients with obesity or preserved Left Ventricular Ejection Fraction (LVEF). We examined the distribution and prognostic value of BNP across BMI categories in acute decompensated heart failure (ADHF) patients with preserved vs. reduced LVEF. Methods We analyzed data from the Atherosclerosis Risk in Communities (ARIC) HF surveillance study which sampled and adjudicated ADHF hospitalizations in patients aged ≥ 55 years from 4 US communities (2005–2009). We examined 5 BMI categories: underweight (< 18.5 kg/m2), normal weight (18.5–<25), overweight (25–<30), obese (30–<40) and morbidly obese (≥ 40) in HF with preserved LVEF (HFpEF) and reduced LVEF (HFrEF). The outcome was 1-year mortality from admission. We used ANCOVA to model log BNP and logistic regression for 1-year mortality, both adjusted for demographics and clinical characteristics. Results The cohort included 9820 weighted ADHF hospitalizations (58% HFrEF; 42% HFpEF). BNP levels were lower in HFpEF compared to HFrEF (p < 0.001) and decreased as BMI increased within the LVEF groups (p < 0.001). After adjustment for covariates, log10 BNP independently predicted 1-year mortality (adjusted OR 1.62 (95% CI 1.17–2.24)) with no significant interaction by BMI or LVEF groups. Conclusions BNP levels correlated inversely with BMI, and were higher in HFrEF compared to HFpEF. Obese patients with HFpEF and ADHF had a significant proportion with BNP levels below clinically accepted thresholds. Nevertheless, BNP was a predictor of mortality in ADHF across groups of BMI in HFpEF and HFrEF

Bronchodilator Responsiveness in Tobacco-Exposed People With or Without COPD

Background: Bronchodilator responsiveness (BDR) in obstructive lung disease varies over time and may be associated with distinct clinical features. Research Question: Is consistent BDR over time (always present) differentially associated with obstructive lung disease features relative to inconsistent (sometimes present) or never (never present) BDR in tobacco-exposed people with or without COPD? Study Design and Methods: We retrospectively analyzed data from 2,269 tobacco-exposed participants in the Subpopulations and Intermediate Outcome Measures in COPD Study with or without COPD. We used various BDR definitions: change of ≥ 200 mL and ≥ 12% in FEV1 (FEV1-BDR), change in FVC (FVC-BDR), and change in in FEV1, FVC or both (ATS-BDR). Using generalized linear models adjusted for demographics, smoking history, FEV1 % predicted after bronchodilator administration, and number of visits that the participant completed, we assessed the association of BDR group: (1) consistent BDR, (2) inconsistent BDR, and (3) never BDR with asthma, CT scan features, blood eosinophil levels, and FEV1 decline in participants without COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 0) and the entire cohort (participants with or without COPD). Results: Both consistent and inconsistent ATS-BDR were associated with asthma history and greater small airways disease (%parametric response mapping functional small airways disease) relative to never ATS-BDR in participants with GOLD stage 0 disease and the entire cohort. We observed similar findings using FEV1-BDR and FVC-BDR definitions. Eosinophils did not vary consistently among BDR groups. Consistent BDR was associated with FEV1 decline over time relative to never BDR in the entire cohort. In participants with GOLD stage 0 disease, both the inconsistent ATS-BDR group (OR, 3.20; 95% CI, 2.21-4.66; P &lt; .001) and consistent ATS-BDR group (OR, 9.48; 95% CI, 3.77-29.12; P &lt; .001) were associated with progression to COPD relative to the never ATS-BDR group. Interpretation: Demonstration of BDR, even once, describes an obstructive lung disease phenotype with a history of asthma and greater small airways disease. Consistent demonstration of BDR indicated a high risk of lung function decline over time in the entire cohort and was associated with higher risk of progression to COPD in patients with GOLD stage 0 disease

Drug-gene interactions of antihypertensive medications and risk of incident cardiovascular disease: A pharmacogenomics study from the CHARGE consortium

Background Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals. Methods Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk ofmajor cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regressionmodels to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases). Results Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0×10-8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genom

Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort

Background Present treatment strategies to stratify exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) rely on a history of two or more events in the previous year. We aimed to understand year to year variability in exacerbations and factors associated with consistent exacerbations over time. Methods In this longitudinal, prospective analysis of exacerbations in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort, we analysed patients aged 40–80 years with COPD for whom 3 years of prospective data were available, identified through various means including care at academic and non-academic medical centres, word of mouth, and existing patient registries. Participants were enrolled in the study between Nov 12, 2010, and July 31, 2015. We classified patients according to yearly exacerbation frequency: no exacerbations in any year; one exacerbation in every year during 3 years of follow-up; and those with inconsistent exacerbations (individuals who had both years with exacerbations and years without during the 3 years of follow-up). Participants were characterised by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric category (1–4) on the basis of post-bronchodilator FEV1. Stepwise logistic regression was used to compare factors associated with one or more acute exacerbations of COPD every year for 3 years versus no exacerbations in the same timeframe. Additionally, a stepwise zero-inflated negative binomial model was used to assess predictors of exacerbation count during follow-up in all patients with available data. Baseline symptom burden was assessed with the COPD assessment test. This trial is registered with ClinicalTrials.gov, number NCT01969344. Findings 2981 patients were enrolled during the study. 1843 patients had COPD, of which 1105 patients had 3 years of complete, prospective follow-up data. 538 (49%) of 1105 patients had at least one acute exacerbation during the 3 years of follow-up, whereas 567 (51%) had none. 82 (7%) of 1105 patients had at least one acute exacerbation each year, whereas only 23 (2%) had two or more acute exacerbations in each year. An inconsistent pattern (both years with and without acute exacerbations) was common (456 [41%] of the group), particularly among GOLD stages 3 and 4 patients (256 [56%] of 456). In logistic regression, consistent acute exacerbations (≥1 event per year for 3 years) were associated with higher baseline symptom burden, previous exacerbations, greater evidence of small airway abnormality on CT, lower interleukin-15 concentrations, and higher interleukin-8 concentrations, than were no acute exacerbations. Interpretation Although acute exacerbations are common, the exacerbation status of most individuals varies markedly from year to year. Among patients who had any acute exacerbation over 3 years, very few repeatedly had two or more events per year. In addition to symptoms and history of exacerbations in the year before study enrolment, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, and interleukin-15 and interleukin-8 concentrations. Funding National Institutes of Health, and National Heart, Lung, and Blood Institute

Human vibrotactile frequency discriminative capacity after adaptation to 25 Hz or 200 Hz stimulation

A two-interval forced-choice (2-IFC) tracking procedure was used to evaluate the effects of a 15-s pre-exposure to either 25 Hz or 200 Hz stimulation (“25 Hz or 200 Hz adaptation”) on human vibrotactile frequency discrimination threshold (frequency DL/Weber fraction). Three subjects were studied. All stimuli (standard and comparison) were delivered to a central location on the thenar eminence of the hand. The frequency DL/Weber fraction was determined for each subject under the following conditions: (1) no recent prior exposure to vibrotactile stimulation (“unadapted”); (2) after 15 s adaptation to 25 Hz stimulation; and (3) after 15 s adaptation to 200 Hz stimulation. The results demonstrate that the effects of frequency of adaptation on frequency discriminative capacity when the standard stimulus is 25 Hz are not the same as when the standard stimulus is 200 Hz. The differential changes in the capacity of subjects to discriminate frequency of cutaneous flutter (10–50 Hz) or vibratory (>200 Hz) stimulation that occur subsequent to a 15-s exposure of the thenar to 25 Hz or 200 Hz stimulation are proposed to reflect frequency-specific, adaptation-induced modification of the response of contralateral primary somatosensory cortex (SI and SII) to skin mechanoreceptor afferent drive

Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium

Pathophysiology, epidemiology and therapy of agein