Addition of 24‐hour heart rate variability parameters to the Cardiovascular Health Study stroke risk score and prediction of incident stroke: The Cardiovascular Health Study

Background Heart rate variability (HRV) characterizes cardiac autonomic functioning. The association of HRV with stroke is uncertain. We examined whether 24‐hour HRV added predictive value to the Cardiovascular Health Study clinical stroke risk score (CHS‐SCORE), previously developed at the baseline examination. Methods and Results N=884 stroke‐free CHS participants (age 75.3±4.6), with 24‐hour Holters adequate for HRV analysis at the 1994–1995 examination, had 68 strokes over ≤8 year follow‐up (median 7.3 [interquartile range 7.1–7.6] years). The value of adding HRV to the CHS‐SCORE was assessed with stepwise Cox regression analysis. The CHS‐SCORE predicted incident stroke (HR=1.06 per unit increment, P=0.005). Two HRV parameters, decreased coefficient of variance of NN intervals (CV%, P=0.031) and decreased power law slope (SLOPE, P=0.033) also entered the model, but these did not significantly improve the c‐statistic (P=0.47). In a secondary analysis, dichotomization of CV% (LOWCV% ≤12.8%) was found to maximally stratify higher‐risk participants after adjustment for CHS‐SCORE. Similarly, dichotomizing SLOPE (LOWSLOPE <−1.4) maximally stratified higher‐risk participants. When these HRV categories were combined (eg, HIGHCV% with HIGHSLOPE), the c‐statistic for the model with the CHS‐SCORE and combined HRV categories was 0.68, significantly higher than 0.61 for the CHS‐SCORE alone (P=0.02). Conclusions In this sample of older adults, 2 HRV parameters, CV% and power law slope, emerged as significantly associated with incident stroke when added to a validated clinical risk score. After each parameter was dichotomized based on its optimal cut point in this sample, their composite significantly improved prediction of incident stroke during ≤8‐year follow‐up. These findings will require validation in separate, larger cohorts. Keywords: autonomic nervous system, clinical stroke risk model, heart rate variability, prediction, predictors, risk prediction, risk stratification, strok

Accelerated nuclei preparation and methods for analysis of histone modifications in yeast

The continuing identification of new histone post-translational modifications and ongoing discovery of their roles in nuclear processes has increased the demand for quick, efficient, and precise methods for their analysis. In the budding yeast Saccharomyces cerevisiae, a variety of methods exist for the characterization of histone modifications on a global scale. However, a wide gap in preparation time and histone abundance exists between the most widely used extraction methods, a simple whole cell extraction (WCE) and an intensive histone extraction. In this work we evaluate various published WCE buffers for their relative effectiveness in the detection of histone modifications by western blot analysis. We also present a precise, yet time-efficient method for the detection of subtle changes in histone modification levels. Lastly, we present a protocol for the rapid small-scale purification of nuclei that improves the performance of antibodies that do not work efficiently in WCE, and aids in the detection of histone modifications that are low in abundance. These new methods are ideal for the analysis of histone modifications and could be applied to the analysis and improved detection of other nuclear proteins

Bone mineral density and risk of heart failure in older adults: The Cardiovascular Health Study

Background Despite increasing evidence of a common link between bone and heart health, the relationship between bone mineral density ( BMD ) and heart failure ( HF ) risk remains insufficiently studied. Methods and Results We investigated whether BMD measured by dual‐energy x‐ray absorptiometry was associated with incident HF in an older cohort. Cox models were stratified by sex and interactions of BMD with race assessed. BMD was examined at the total hip and femoral neck separately, both continuously and by World Health Organization categories. Of 1250 participants, 442 (55% women) developed HF during the median follow‐up of 10.5 years. In both black and nonblack women, neither total hip nor femoral neck BMD was significantly associated with HF ; there was no significant interaction by race. In black and nonblack men, total hip, but not femoral neck, BMD was significantly associated with HF , with evidence of an interaction by race. In nonblack men, lower total hip BMD was associated with higher HF risk (hazard ratio, 1.13 [95% CI, 1.01–1.26] per 0.1 g/cm 2 decrement), whereas in black men, lower total hip BMD was associated with lower HF risk (hazard ratio, 0.74 [95% CI, 0.59–0.94]). There were no black men with total hip osteoporosis. Among nonblack men, total hip osteoporosis was associated with higher HF risk (hazard ratio, 2.83 [95% CI, 1.39–5.74]) compared with normal BMD . Conclusions Among older adults, lower total hip BMD was associated with higher HF risk in nonblack men but lower risk in black men, with no evidence of an association in women. Further research is needed to replicate these findings and to study potential underlying pathways. </jats:sec

Association of alcohol consumption after development of heart failure with survival among older adults in the Cardiovascular Health Study

Importance: More than 1 million older adults develop heart failure annually. The association of alcohol consumption with survival among these individuals after diagnosis is unknown. Objective: To determine whether alcohol use is associated with increased survival among older adults with incident heart failure. Design, Setting, and Participants: This prospective cohort study included 5888 community-dwelling adults aged 65 years or older who were recruited to participate in the Cardiovascular Health Study between June 12, 1989, and June 1993, from 4 US sites. Of the total participants, 393 individuals had a new diagnosis of heart failure within the first 9 years of follow-up through June 2013. The study analysis was performed between January 19, 2016, and September 22, 2016. Exposures: Alcohol consumption was divided into 4 categories: abstainers (never drinkers), former drinkers, 7 or fewer alcoholic drinks per week, and more than 7 drinks per week. Primary Outcomes and Measures: Participant survival after the diagnosis of incident heart failure. Results: Among the 393 adults diagnosed with incident heart failure, 213 (54.2%) were female, 339 (86.3%) were white, and the mean (SD) age was 78.7 (6.0) years. Alcohol consumption after diagnosis was reported in 129 (32.8%) of the participants. Across alcohol consumption categories of long-term abstainers, former drinkers, consumers of 1-7 drinks weekly and consumers of more than 7 drinks weekly, the percentage of men (32.1%, 49.0%, 58.0%, and 82.4%, respectively; P \u3c .001 for trend), white individuals (78.0%, 92.7%, 92.0%, and 94.1%, respectively, P \u3c. 001 for trend), and high-income participants (22.0%, 43.8%, 47.3%, and 64.7%, respectively; P \u3c .001 for trend) increased with increasing alcohol consumption. Across the 4 categories, participants who consumed more alcohol had more years of education (mean, 12 years [interquartile range (IQR), 8.0-10.0 years], 12 years [IQR, 11.0-14.0 years], 13 years [IQR, 12.0-15.0 years], and 13 years [IQR, 12.0-14.0 years]; P \u3c .001 for trend). Diabetes was less common across the alcohol consumption categories (32.1%, 26.0%, 22.3%, and 5.9%, respectively; P = .01 for trend). Across alcohol consumption categories, there were fewer never smokers (58.3%, 44.8%, 35.7%, and 29.4%, respectively; P \u3c .001 for trend) and more former smokers (34.5%, 38.5%, 50.0%, and 52.9%, respectively; P = .006 for trend). After controlling for other factors, consumption of 7 or fewer alcoholic drinks per week was associated with additional mean survival of 383 days (95% CI, 17-748 days; P = .04) compared with abstinence from alcohol. Although the robustness was limited by the small number of individuals who consumed more than 7 drinks per week, a significant inverted U-shaped association between alcohol consumption and survival was observed. Multivariable model estimates of mean time from heart failure diagnosis to death were 2640 days (95% CI, 1967-3313 days) for never drinkers, 3046 days (95% CI, 2372-3719 days) for consumers of 0 to 7 drinks per week, and 2806 (95% CI, 1879-3734 days) for consumers of more than 7 drinks per week (P = .02). Consumption of 10 drinks per week was associated with the longest survival, a mean of 3381 days (95% CI, 2806-3956 days) after heart failure diagnosis. Conclusions and Relevance: These findings suggest that limited alcohol consumption among older adults with incident heart failure is associated with survival benefit compared with long-term abstinence. These findings suggest that older adults who develop heart failure may not need to abstain from moderate levels of alcohol consumption

Second SNPP Cal/Val Campaign: Environmental Data Retrieval Analysis

Satellite ultraspectral infrared sensors provide key data records essential for weather forecasting and climate change science. The Suomi National Polar-orbiting Partnership (Soumi NPP) satellite Environmental Data Records (EDRs) are retrieved from calibrated ultraspectral radiance or Sensor Data Records (SDRs). Understanding the accuracy of retrieved EDRs is critical. The second Suomi NPP Calibration/Validation field campaign was conducted during March 2015 with flights over Greenland. The NASA high-altitude ER-2 aircraft carrying ultraspectral interferometer sounders such as the National Airborne Sounder Testbed-Interferometer (NAST-I) flew under the Suomi NPP satellite that carries the Crosstrack Infrared Sounder (CrIS) and the Advanced Technology Microwave Sounder (ATMS). Herein we inter-compare the EDRs produced from different retrieval algorithms employed on these satellite and aircraft campaign data. The available radiosonde measurements together with the European Centre for Medium-Range Weather Forecasts (ECMWF) analyses are used to assess atmospheric temperature and moisture retrievals from the aircraft and satellite platforms. Preliminary results of this experiment under a winter, Arctic environment are presented

First SNPP Cal/Val Campaign: Satellite and Aircraft Sounding Retrieval Intercomparison

Satellite ultraspectral infrared sensors provide key data records essential for weather forecasting and climate change science. The Suomi National Polar-orbiting Partnership (SNPP) satellite Environmental Data Record (EDR) is retrieved from calibrated ultraspectral radiance so called Sensor Data Record (SDR). It is critical to understand the accuracy of retrieved EDRs, which mainly depends on SDR accuracy (e.g., instrument random noise and absolute accuracy), an ill-posed retrieval system, and radiative transfer model errors. There are few approaches to validate EDR products, e.g., some common methods are to rely on radiosonde measurements, ground-based measurements, and dedicated aircraft campaign providing in-situ measurements of atmosphere and/or employing similar ultraspectral interferometer sounders. Ultraspectral interferometer sounder aboard aircraft measures SDR to retrieve EDR, which is often used to validate satellite measurements of SDR and EDR. The SNPP Calibration/Validation Campaign was conducted during May 2013. The NASA high-altitude aircraft ER-2 that carried ultraspectral interferometer sounders such as the NASA Atmospheric Sounder Testbed-Interferometer (NAST-I) flew under the SNPP satellite that carries the Cross-track Infrared Sounder (CrIS). Here we inter-compare the EDRs produced with different retrieval algorithms from SDRs measured by the sensors from satellite and aircraft. The available dropsonde and radiosonde measurements together with the European Centre for Medium-Range Weather Forecasts (ECMWF) analysis were also used to draw the conclusion from this experiment

Genetically Elevated Fetuin-A Levels, Fasting Glucose Levels, and Risk of Type 2 Diabetes: The Cardiovascular Health Study*

OBJECTIVE Fetuin-A levels are associated with higher risk of type 2 diabetes, but it is unknown if the association is causal. We investigated common (>5%) genetic variants in the fetuin-A gene (AHSG) fetuin-A levels, fasting glucose, and risk of type 2 diabetes. RESEARCH DESIGN AND METHODS Genetic variation, fetuin-A levels, and fasting glucose were assessed in 2,893 Caucasian and 542 African American community-living individuals 65 years of age or older in 1992–1993. RESULTS Common AHSG variants (rs4917 and rs2248690) were strongly associated with fetuin-A concentrations (P < 0.0001). In analyses of 259 incident cases of type 2 diabetes, the single nucleotide polymorphisms (SNPs) were not associated with diabetes risk during follow-up and similar null associations were observed when 579 prevalent cases were included. As expected, higher fetuin-A levels were associated with higher fasting glucose concentrations (1.9 mg/dL [95% CI, 1.2–2.7] higher per SD in Caucasians), but Mendelian randomization analyses using both SNPs as unbiased proxies for measured fetuin-A did not support an association between genetically predicted fetuin-A levels and fasting glucose (−0.3 mg/dL [95% CI, −1.9 to 1.3] lower per SD in Caucasians). The difference between the associations of fasting glucose with actual and genetically predicted fetuin-A level was statistically significant (P = 0.001). Results among the smaller sample of African Americans trended in similar directions but were statistically insignificant. CONCLUSIONS Common variants in the AHSG gene are strongly associated with plasma fetuin-A concentrations, but not with risk of type 2 diabetes or glucose concentrations, raising the possibility that the association between fetuin-A and type 2 diabetes may not be causal

Barriers to obesity management: a pilot study of primary care clinicians

BACKGROUND: Obesity is an increasing epidemic in both the US and veteran populations, yet it remains largely understudied in the Veteran's Health Administration (VHA) setting. The purpose of our study was to identify barriers to the effective management of obesity in VHA primary care settings. METHODS: Three focus groups of clinicians from a Veteran's Affairs Medical Center (VAMC) and an affiliated Community Based Outpatient Center (CBOC) were conducted to identify potential barriers to obesity management. The focus groups and previously published studies then informed the creation of a 47-item survey that was then disseminated and completed by 55 primary care clinicians. RESULTS: The focus groups identified provider, system, and patient barriers to obesity care. Lack of obesity training during medical school and residency was associated with lower rates of discussing diet and exercise with obese patients (p < 0.05). Clinicians who watched their own diets vigorously were more likely to calculate BMI for obese patients than other clinicians (42% vs. 13%, p < 0.05). Many barriers identified in previous studies (e.g., attitudes toward obese patients, lack of insurance payments for obesity care) were not prevalent barriers in the current study. CONCLUSION: Many VHA clinicians do not routinely provide weight management services for obese patients. The most prevalent barriers to obesity care were poor education during medical school and residency and the lack of information provided by the VHA to both clinicians and patients about available weight management services

Effect of partial portal vein ligation on hepatic regeneration

To evaluate the effect of portal hypertension and diminished portal venous blood flow to the liver on hepatic regeneration, male rats were subjected to partial portal vein ligation and subsequently to a two-thirds partial hepatectomy. The levels of ornithine decarboxylase activity at 6 h after partial hepatectomy were greater (p > 0.001) in the rats with prior partial portal vein ligation than in those without portal hypertension. The rats with prior partial portal vein ligation also had greater (p > 0.005) levels of thymidine kinase activity at 48 h after partial hepatectomy than did those without portal hypertension. Hepatic sex hormone receptor activity was not affected by prior partial portal vein ligation either before or after partial hepatectomy. The reductions in both estrogen and androgen receptor activity observed in the hepatic cytosol after partial hepatectomy were similar to those observed in control animals. These data indicate that animals with portal hypertension having a diminished hepatic portal blood flow have a normal capacity to regenerate hepatic mass following a hepatic resection © 1988 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted