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Rationale: Decreasing medication overuse represents an opportunity to avoid harm and costs in the era of value-based purchasing. Studies of inhaled corticosteroids (ICS) overuse in chronic obstructive pulmonary disease (COPD) have examined prevalent use. Understanding initiation of low-value ICS among complex patients with COPD may help shape deadoption efforts. Objectives: Examine ICS initiation among a cohort with low exacerbation risk COPD and test for associations with markers of patient and health system complexity. Methods: Between 2012 and 2016, we identified veterans with COPD from 21 centers. Our primary outcome was first prescription of ICS. We used the care assessment needs (CAN) score to assess patient-level complexity as the primary exposure. We used a time-to-event model with time-varying exposures over 1-year follow-up. We tested for effect modification using selected measures of health system complexity. Results: We identified 8,497 patients with COPD without an indication for ICS and did not have baseline use (inception cohort). Follow-up time was four quarters. Patient complexity by a continuous CAN score was associated with new dispensing of ICS (hazard ratio = 1.17 per 10-unit change; 95% confidence interval = 1.13-1.21). This association demonstrated a dose-response when examining quartiles of CAN score. Markers of health system complexity did not modify the association between patient complexity and first use of low-value ICS. Conclusions: Patient complexity may represent a symptom burden that clinicians are attempting to mitigate by initiating ICS. Lack of effect modification by health system complexity may reflect the paucity of structural support and low prioritization for COPD care.

Background: Electronic health data are routinely used to conduct studies of cardiovascular disease in the setting of the Veterans Health Administration (VA). Previous studies have estimated the positive predictive value (PPV) of International Classification of Disease, Ninth Revision (ICD-9) codes for acute myocardial infarction (MI), but the sensitivity of these codes for all true events and the accuracy of coding algorithms for prevalent disease status at baseline are largely unknown., Methods: We randomly sampled 180 Veterans from the VA Puget Sound Health Care System who initiated diabetes treatment. The full electronic medical record was reviewed to identify prevalent conditions at baseline and acute MI events during follow-up. The accuracy of various coding algorithms was assessed., Results: Algorithms for previous acute events at baseline had high PPV (previous MI: 97%; previous stroke: 81%) but low sensitivity (previous MI: 38%; previous stroke: 52%). Algorithms for chronic conditions at baseline had high PPV (heart failure: 72%; coronary heart disease [CHD]: 85%) and high sensitivity (heart failure: 90%, CHD: 84%). For current smoking status at baseline, ICD-9 codes with pharmacy data had a PPV of 77% and sensitivity of 73%. The coding algorithm for acute MI events during follow-up had high PPV (80%) and sensitivity (89%)., Conclusions: ICD-9 codes for acute MI events during follow-up had high PPV and sensitivity. The sensitivity of ICD-9 codes for previous acute events at baseline was low, but a composite variable for baseline CHD had good accuracy., (Copyright © 2015 John Wiley & Sons, Ltd.)

We conducted a population-based case-control study to assess the myocardial infarction (MI) and stroke risks associated with sulphonylureas and insulin when used in combination with metformin. Cases had type 2 diabetes and used metformin + insulin or metformin + sulphonylureas at the time of a first MI or first stroke between 1995 and 2010; controls used the same treatment combinations and were randomly sampled from the same population. MI and stroke diagnoses and potential confounders were validated by medical record reviews. Compared with metformin + sulphonylurea, metformin + insulin was associated with similar risks of MI or stroke [odds ratio 0.98 (95% confidence interval 0.63-1.52)]. Meta-analysis with another observational study improved the precision of the risk estimate [relative risk 0.92 (95% confidence interval 0.69-1.24)]. Current evidence suggests that there may not be large differences in cardiovascular risk associated with the use of insulin or sulphonylureas when used in combination with metformin., (© 2015 John Wiley & Sons Ltd.)

Background: Postpartum venous thromboembolism (VTE) is a potentially fatal and preventable event leading to substantial short- and long-term morbidity. We sought to evaluate whether the delivery of term newborns of low or high birth weight was associated with greater risks of VTE., Methods and Results: In a population-based case-control study conducted in Washington State from 1987 through 2011, cases of hospitalized VTE within 3 months of delivery were identified by using selected International Classification of Diseases, Ninth Revision, Clinical Modification codes. Controls were randomly selected postpartum women without VTE, matched on birth year. Birth weight and other maternal and pregnancy characteristics were extracted from birth certificate data. Among term live singleton deliveries, we compared the risk of VTE for mothers of newborns of low and high birth weights (<2500 g and >4000 g, respectively) versus mothers of newborns of normal birth weight (2500-4000 g). Logistic regression models were adjusted for maternal age, race, education, body mass index, parity, delivery methods, gestational length, smoking, gestational diabetes mellitus, and preeclampsia. Patients with VTE (n=547) were older, had a higher body mass index, and experienced more pregnancy-related complications than controls (n=9482). In comparison with mothers of newborns with normal birth weight, mothers of newborns with low birth weight had a 3-fold increased risk of VTE, which persisted after multivariable adjustment (odds ratio, 2.98; 95% confidence interval, 1.80-4.93). Mothers of newborns with high birth weight had only a slightly increased risk of VTE, which was attenuated after multivariable adjustment (odds ratio, 1.26; 95% confidence interval, 0.99-1.61)., Conclusions: The delivery of a newborn with low birth weight is associated with a 3-fold increased risk of maternal postpartum VTE. This should be considered when assessing VTE risk at delivery., (© 2015 American Heart Association, Inc.)

Background: Venous thromboembolism (VTE) is a major contributor of maternal morbidity and mortality. Whether maternal race/ethnicity is associated with the risk of postpartum VTE remains unclear., Methods and Results: We conducted a population-based, case-control study in Washington State, from 1987 through 2011. Cases comprised all women with selected International Classification of Diseases, Ninth Edition, Clinical Modification codes for hospitalized VTE within 3 months post-delivery. Controls were randomly selected postpartum women who did not experience a VTE. Characteristics of women and their deliveries were abstracted from birth certificates. Using logistic regression models, we compared the risk of postpartum VTE in black, Asian, and Hispanic women with that in non-Hispanic white women, after adjustment for maternal characteristics (age, body mass index, parity, education), pregnancy complications, and delivery methods., Results: Our study comprised 688 cases and 10 246 controls. Among controls, the mean age and body mass index were 27.5 years and 26.3 kg m(-2) , respectively. Compared with white women, black and Asian women had a greater and lower risk of postpartum VTE (adjusted odds ratio [OR] 1.50, 95% confidence interval [CI] 1.10-2.04 and OR 0.67, 95%CI 0.48-0.94, respectively). A lower risk was present in Hispanic women (adjusted OR 0.80, 95% CI 0.61-1.06) but was not statistically significant. In subgroup analyses, we observed an increased risk for black compared with white women among women who delivered via cesarean section (OR 2.03, 95% CI 1.34-3.07) but not among vaginal deliveries (OR 1.03, 95% CI 0.61-1.74)., Conclusions: Maternal race/ethnicity is associated with the risk of postpartum VTE, independently of other risk factors, and should be considered when assessing the use of thromboprophylaxis after delivery., (© 2014 International Society on Thrombosis and Haemostasis.)

Now celebrating its 26th year of existence, the Vietnam Era Twin Registry continues to be one of the largest national samples of adult twins in the United States. The Registry twin member population is composed of 7,369 US male-male twin pair Veterans (14,738 total individuals) who served on active duty in the military during the Vietnam conflict (1964-1975). The Registry also maintains a register, data repository, and a biospecimen repository. Details on the operations of the Registry are described, as well as an overview of specific studies. Registry maintenance activities are also described, including the updating of contact information and vital status. Future plans include expanding the biospecimen repository and obtaining input from twins about study methods and diseases and conditions they would like to see investigated.

Background: After an initial episode of atrial fibrillation (AF), AF may recur and become permanent. AF progression is associated with higher morbidity and mortality. Understanding the risk factors for permanent AF could help identify people who would benefit most from interventions., Objective: To determine whether body mass index (BMI), diabetes, hypertension, and blood pressure levels are associated with permanent AF among people whose initial AF episode terminated., Design: Population-based inception cohort study., Participants: Enrollees in Group Health, an integrated health care system, aged 30-84 with newly diagnosed AF in 2001-2004, whose initial AF terminated within 6 months and who had at least 6 months of subsequent follow-up (N = 1,385)., Main Measures: Clinical characteristics were determined from medical records. Permanent AF was determined from medical records and ECG and administrative databases. Permanent AF was defined as AF present on two separate occasions 6-36 months apart, without any documented sinus rhythm between the two occasions. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs)., Key Results: Five-year cumulative incidence of permanent AF was 24 %. Compared with normal BMI (18.5-24.9 kg/m(2)), BMI levels of 25.0-29.9 (overweight), 30.0-34.9 (obese 1), 35.0-39.9 (obese 2), and ≥ 40.0 kg/m(2) (obese 3) were associated with HRs of permanent AF of 1.26 (95 % CI: 0.92, 1.72); 1.35 (0.96, 1.91); 1.50 (0.97, 2.33); and 1.79 (1.13, 2.84), adjusted for age, sex, diabetes, hypertension, blood pressure, coronary heart disease, valvular heart disease, heart failure, and prior stroke. Diabetes, hypertension, and blood pressure were not associated with permanent AF., Conclusions: For people whose initial AF episode terminates, benefits of having lower BMI may include a lower risk of permanent AF. Risk of permanent AF was similar for people with and without diabetes or hypertension and across blood pressure levels.

Purpose: To assess the validity of a Geographic Information Systems (GIS) measure, the Normalized Difference Vegetation Index (NDVI), as a measure of neighborhood greenness for epidemiologic research., Methods: Using remote-sensing spectral data, NDVI was calculated for a 100-m radial distance around 124 residences in greater Seattle. The criterion standard was rating of greenness for corresponding residential areas by 3 environmental psychologists. Pearson correlations and regression models were used to assess the association between the psychologists' ratings of greenness and NDVI. Analyses were also stratified by residential density to assess whether the correlations differed between low and high density., Results: The mean NDVI among this sample of residences was 0.27 (standard deviation [SD], 0.11; range, -0.04 to 0.54), and the mean psychologist rating of greenness was 2.84 (SD, 0.98; range, 1-5). The correlation between NDVI and expert ratings of greenness was high (r = 0.69). The correlation was equivalently strong within each strata of residential density., Conclusions: NDVI is a useful measure of neighborhood greenness. In addition to showing a strong correlation with expert ratings, this measure has practical advantages, including availability of data and ease of application to various boundaries, which would aid in replication and comparability across studies., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Automated pharmacy databases are increasingly available for assessing medication use, but research on the validity of these data is incomplete. This study aimed to measure agreement on warfarin and aspirin use between medical records and automated pharmacy data among patients with newly detected atrial fibrillation (AF)., Methods: Patients with newly detected AF (n = 1953) were previously identified in a cohort study at Group Health (GH) in Washington State. Medical records were reviewed for information on risk factors and medication use, as well as clinical care during the 6 months after AF onset. Medication data were also obtained from the GH pharmacy database. We determined the sensitivity, specificity, and positive predictive value (PPV) as measures of the validity of the GH pharmacy database as compared with medical records for warfarin and aspirin use during the first 6 and 3 months after AF onset. We also calculated the κ statistic., Results: For warfarin use, in comparison with the medical record review, the sensitivity, specificity, and PPV for the GH pharmacy database were excellent, and agreement was almost perfect in the 3- and 6-month periods after AF onset (κ = 0.92 and 0.93, respectively). For aspirin use, the GH pharmacy database had low sensitivity but high specificity, and agreement was only fair for these two periods (κ = 0.28 and 0.31, respectively)., Conclusions: The GH pharmacy database is a valuable source of data for pharmacoepidemiologic research on warfarin use among patients with AF. However, the database cannot be recommended for assessment of aspirin use. Copyright © 2010 John Wiley & Sons, Ltd., (Copyright © 2010 John Wiley & Sons, Ltd.)

Background: Atrial fibrillation (AF) is a common arrhythmia that affects more than 2 million people in the United States. We sought to determine whether the risk of incident AF among patients treated for hypertension differs by the degree of blood pressure control., Methods: A population-based, case-control study of 433 patients with verified incident AF and 899 controls was conducted to investigate the relationship between average achieved systolic (SBP) and diastolic (DBP) blood pressure and risk of AF. All patients were members of an integrated health-care delivery system and were pharmacologically treated for hypertension. Medical records were reviewed to confirm the diagnosis of new onset AF and to collect information on medical conditions, health behaviors, and measured blood pressures. Average achieved SBP and DBP were calculated from the three most recent outpatient blood pressure measurements., Results: Compared with the reference level of 120-129 mm Hg, for categories of average achieved SBP of <120, 130-139, 140-149, 150-159, 160-169, and > or =170 mm Hg, the odds ratios (ORs; 95% confidence interval (CI)) for incident AF were 1.99 (1.10, 3.62), 1.19 (0.78, 1.81), 1.40 (0.93, 2.09), 2.02 (1.30, 3.15), 2.27 (1.31, 3.93), and 1.84 (0.89, 3.80), respectively. Based on the population attributable fraction, we estimated that, among patients with treated hypertension, 17.2% (95% CI 4.3%, 28.3%) of incident AF was attributable to an average achieved SBP > or =140 mm Hg., Conclusion: Among patients treated for hypertension, uncontrolled elevated SBP and SBP <120 mm Hg were associated with an increased risk of incident AF.

We hypothesized that neighborhood socioeconomic context would be most strongly associated with risk of myocardial infarction (MI) for smaller "neighborhood" definitions. We used data on 487 non-fatal, incident MI cases and 1873 controls from a case-control study in Washington State. Census data on income, home ownership, and education were used to estimate socioeconomic context across four neighborhood definitions: 1 km buffer, block group, census tract, and ZIP code. No neighborhood definition led to consistently stronger associations with MI. Although we confirmed the association between neighborhood socioeconomic measures and risk of MI, we did not find these associations sensitive to neighborhood definition.

Variations in candidate genes participating in oxidative stress, inflammation, and their interactions are potentially associated with diseases of atherosclerotic origin. We investigated independent and joint associations of variations in cholesterol ester transfer protein (CETP), interleukin-8 (IL8), peroxisome proliferator activator receptor-alpha (PPARA), and Toll-like receptor 4 (TLR4) genes with incident nonfatal myocardial infarction (MI) or ischemic stroke. In a population-based case-control study, patients (848 with MI and 368 with ischemic stroke) and controls (2,682) were recruited from postmenopausal women and hypertensive men/women who were members of Group Health in western Washington State. Common tag single-nucleotide polymorphisms (SNPs; n=34) representing gene-wide variations were selected from gene sequencing data using pairwise linkage disequilibrium. Haplotypes were inferred using a modified expectation maximization algorithm. Multivariate logistic regression evaluated individual haplotype and SNP-disease associations in log-additive models. Global haplotype tests assessed overall gene-disease associations. Logic regression was used to evaluate gene-gene interactions. False discovery rates and permutation tests were used for multiple testing adjustment in evaluating independent associations and interactions, respectively. Overall, gene-wide variations in PPARA and TLR4 genes were associated with MI. The minor allele of the PPARA SNP, rs4253623, was associated with a higher risk of MI (odds ratio 1.25, 95% confidence interval 1.08 to 1.46), whereas the minor allele of the TLR4 SNP, rs1927911, was associated with a lower risk of MI (odds ratio 0.88, 95% confidence interval 0.77 to 0.99). No within-gene or gene-gene interaction was associated with MI or ischemic stroke risk. In conclusion, potential SNP-disease associations identified in the present study are novel and need further investigation.

Background: Obesity is associated with increased risk of atrial fibrillation (AF), but it is unknown whether the association differs by duration or persistence of AF. It is also unknown to what extent cardiovascular risk factors may mediate this association., Methods: This population-based case-control study included 425 subjects with new-onset AF and 707 controls. The AF cases were identified through International Classification of Diseases, Ninth Revision codes for inpatient and outpatient visits and verified by medical record review. Medical records provided data on height, weight, and cardiovascular risk factors., Results: On average, AF risk was 3% higher (95% confidence interval [CI], 1%-5%) per unit increment in body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared). For sustained AF (duration > or =6 months), risk was higher by 7% (95% CI, 3%-11%) per unit BMI increment; for intermittent AF (duration > or =8 days or recurrent), 4% (95% CI, 1%-6%); and for transitory AF (duration <8 days), 1% (95% CI, -1% to +4%). Compared with those with normal BMI, the odds ratios for overweight and obese subjects were as follows: overweight, 0.97 (95% CI, 0.68-1.38); obese class 1, 1.18 (95% CI, 0.80-1.73); obese class 2, 1.34 (95% CI, 0.82-2.18); and obese class 3, 2.31 (95% CI, 1.36-3.91) (P = .002 for trend). When diabetes mellitus, a possible mediator, was added to the model, the odds ratio per unit increment of BMI decreased from 1.034 to 1.028. Adjustment for other cardiovascular risk factors including hyperlipidemia and blood pressure did not attenuate the BMI-AF association., Conclusions: The association with BMI was stronger for sustained AF than for transitory or intermittent AF. The obesity-AF association appears to be partially mediated by diabetes mellitus but minimally through other cardiovascular risk factors.

Background: Although cholesterol is an important risk factor for coronary heart disease (CHD) among hypertensives, the burden of CHD among hypertensives that may be due to elevated cholesterol has not been well documented. This study aimed to estimate the proportion of incident myocardial infarction (MI) among hypertensives that may be attributable to elevated total cholesterol, and to investigate how well the National Cholesterol Education Program Adult Treatment Panel III (ATP III) classification method represents risk of MI among hypertensives., Methods: A population-based, case-control study of patients aged 30 to 79 years enrolled in a health maintenance organization, treated pharmacologically for hypertension, and who were not using lipid-lowering medication. Cases were diagnosed with an incident fatal or nonfatal MI between 1986 and 2000 (n = 1535). Controls were randomly sampled and frequency-matched to cases by sex, 10-year age category, and year of event (n = 3743). Subjects' most recent total cholesterol values were categorized according to ATP III guidelines., Results: Overall, 31% (95% confidence interval: 23-39) of incident MIs among hypertensives could be explained by total cholesterol level above the optimal level of 200 mg/dL. Among participants in the highest ATP III risk stratum, 41% (95% confidence interval: 9-62) of the incident MIs were attributable to total cholesterol levels >160 mg/dL, but total cholesterol >or=200 mg/dL accounted for the majority of these excess events., Conclusions: The ATP III risk stratification approach improves detection of the CHD burden due to elevated total cholesterol among hypertensives at highest risk. A strategy to improve cholesterol control in hypertensive patients might prevent a substantial part of the burden of morbidity and mortality from MI.

Background: There is little information about the risk of stroke in relation to time since initiation of hormone therapy and in relation to estrogen dose., Methods: We conducted a population-based case-control study at Group Health Cooperative (GHC), a health maintenance organization in the greater Seattle (Wash) area, to assess the association of hormone replacement therapy with the risks of incident ischemic and hemorrhagic stroke. Cases were all postmenopausal women with incident stroke at GHC during July 1989 through December 1998 (726 ischemic strokes and 213 hemorrhagic strokes). Controls were randomly selected from GHC enrollees and frequency matched to cases on age and calendar year (n = 2525). Hormone use was assessed from computerized pharmacy data. We reviewed the medical record to confirm eligibility and assess other risk factors., Results: After risk factor adjustment, ischemic stroke was not associated with current use of estrogen with progestin (odds ratio [95% confidence interval]: 0.97 [0.69-1.37]) or without (0.94 [0.72-1.23]) compared with never use. Similarly, hemorrhagic stroke was not associated with current use of estrogen with progestin (0.74 [0.43-1.28]) or without (1.06 [0.71-1.56]). However, the risks of ischemic stroke and hemorrhagic stroke were increased 2-fold during the first 6 months of hormone use (ischemic stroke: 2.16 [1.04-4.49], hemorrhagic stroke: 2.20 [0.83-5.81]). Risk of ischemic stroke also increased with estrogen dose (P for trend =.03)., Conclusion: The transitory increase in risks of ischemic stroke and hemorrhagic stroke associated with initiation of hormone replacement therapy merits further investigation.

This study provides data on post-hospitalization medication treatment trends for unstable angina between 1990 and 1995. We conducted an observational cohort study at the Veterans Affairs Puget Sound Health Care System (VAPSHCS). Computerized records of hospital discharges and cardiac catheterizations were used to identify unstable angina diagnoses among veterans between 1990 and 1995. Discharge medications issued within 90 days after discharge were ascertained from computerized outpatient pharmacy records. Of the 1,100 veterans discharged with unstable angina, 885 (80%) filled a prescription through the VAPSHCS within 90 days after discharge. Neither use of aspirin nor use of beta blockers increased between 1990 and 1995: overall use averaged 76% for aspirin (78% of those without potential contraindications) and 32% for beta blockers (36% of those without potential contraindications). Use of non-dihydropyridine calcium antagonists--primarily diltiazem--decreased from 57% to 40% (p <0.01), whereas use of dihydropyridine calcium antagonists increased from 12% to 26% (p <0.01). Thus, pharmacy records indicated that aspirin use was high although it was lower than expected, possibly due to ready availability outside the VAPSHCS pharmacy. The low frequency of beta-blocker use and the increasing reliance on dihydropyridine calcium antagonists through 1995 to treat unstable angina may be an opportunity to improve veteran care according to Agency for Health Care Policy Research recommendations.

Objective: We compared long-term health outcomes associated with beta-adrenergic blocking agents and diltiazem treatment for unstable angina., Background: No long-term data have been published comparing these two antianginal treatments in this setting., Methods: Eligible veterans were discharged from the Veterans Affairs Puget Sound Health Care System (VAPSHCS), Seattle Division, between October 1989 and September 1995 with an unstable angina diagnosis and were prescribed monotherapy beta-blocker or diltiazem treatment at discharge. Medication data were collected from medical records and computerized VAPSHCS outpatient pharmacy files. Follow-up death and coronary artery disease rehospitalization data were collected through 1996. Proportional hazards regression compared survival among diltiazem and beta-blocker users, controlling for patient characteristics with propensity scores., Results: Two hundred forty-seven veterans (24% on beta-blockers, 76% on diltiazem) were included in this study. There were 54 (22%) deaths during an average follow-up of 51 months. After propensity score adjustment, there was no difference in risk of death comparing diltiazem to beta-blocker treatment (hazards ratios [HR] 1.1; 95% confidence interval [CI] 0.49 to 2.4). Among Washington residents (n=207), there were 146 (71%) coronary artery disease rehospitalizations or deaths during follow-up. After adjustment, there was a nonsignificant increase in risk of rehospitalization or death associated with diltiazem use (HR 1.4; 95% CI 0.80 to 2.4). For both analyses, similar risks were found among veterans without relative contraindications to beta-blockers., Conclusions: We found no survival benefit of diltiazem over beta-blocker treatment for unstable angina in this cohort of veterans.