Showing papers by "Charles B. Eaton published in 2014"

Relation of physical activity time to incident disability in community dwelling adults with or at risk of knee arthritis: prospective cohort study

Abstract: Objective To investigate whether objectively measured time spent in light intensity physical activity is related to incident disability and to disability progression. Design Prospective multisite cohort study from September 2008 to December 2012. Setting Baltimore, Maryland; Columbus, Ohio; Pittsburgh, Pennsylvania; and Pawtucket, Rhode Island, USA. Participants Disability onset cohort of 1680 community dwelling adults aged 49 years or older with knee osteoarthritis or risk factors for knee osteoarthritis; the disability progression cohort included 1814 adults. Main outcome measures Physical activity was measured by accelerometer monitoring. Disability was ascertained from limitations in instrumental and basic activities of daily living at baseline and two years. The primary outcome was incident disability. The secondary outcome was progression of disability defined by a more severe level (no limitations, limitations to instrumental activities only, 1-2 basic activities, or ≥3 basic activities) at two years compared with baseline. Results Greater time spent in light intensity activities had a significant inverse association with incident disability. Less incident disability and less disability progression were each significantly related to increasing quartile categories of daily time spent in light intensity physical activities (hazard ratios for disability onset 1.00, 0.62, 0.47, and 0.58, P for trend=0.007; hazard ratios for progression 1.00, 0.59, 0.50, and 0.53, P for trend=0.003) with control for socioeconomic factors (age, sex, race/ethnicity, education, income) and health factors (comorbidities, depressive symptoms, obesity, smoking, lower extremity pain and function, and knee assessments: osteoarthritis severity, pain, symptoms, prior injury). This finding was independent of time spent in moderate-vigorous activities. Conclusion These prospective data showed an association between greater daily time spent in light intensity physical activities and reduced risk of onset and progression of disability in adults with osteoarthritis of the knee or risk factors for knee osteoarthritis. An increase in daily physical activity time may reduce the risk of disability, even if the intensity of that additional activity is not increased.

Effect of long-chain ω-3 fatty acids and lutein + zeaxanthin supplements on cardiovascular outcomes: results of the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial

Abstract: Importance Dietary supplements have been proposed as a mechanism to improve health and prevent disease. Objective To determine if supplementing diet with long-chain ω-3 polyunsaturated fatty acids or with macular xanthophylls results in a reduced rate of cardiovascular disease (CVD). Design, Setting, and Participants The Cardiovascular Outcome Study (COS) was an ancillary study of the Age-Related Eye Disease Study 2 (AREDS2), a factorial-designed randomized clinical trial of 4203 participants recruited from 82 US academic and community ophthalmology clinics, who were followed up for a median of 4.8 years. Individuals were eligible to participate if they were between the ages of 50 and 85 years, had intermediate or advanced age-related macular degeneration in 1 eye, and were willing to be randomized. Participants with stable, existing CVD (>12 months since initial event) were eligible to participate. Participants, staff, and outcome assessors were masked to intervention. Interventions Daily supplementation with long-chain ω-3 polyunsaturated fatty acids (350-mg docosahexaenoic acid [DHA] + 650-mg eicosapentaenoic acid [EPA]), macular xanthophylls (10-mg lutein + 2-mg zeaxanthin), combination of the two, or matching placebos. These treatments were added to background therapy of the AREDS vitamin and mineral formulation for macular degeneration. Main Outcomes and Measures A composite outcome of myocardial infarction, stroke, and cardiovascular death with 4 prespecified secondary combinations of the primary outcome with hospitalized heart failure, revascularization, or unstable angina. Results Study participants were primarily white, married, and highly educated, with a median age at baseline of 74 years. A total of 602 cardiovascular events were adjudicated, and 459 were found to meet 1 of the study definitions for a CVD outcome. In intention-to-treat analysis, no reduction in the risk of CVD or secondary CVD outcomes was seen for the DHA + EPA (primary outcome: hazard ratio [HR], 0.95; 95% CI, 0.78-1.17) or lutein + zeaxanthin (primary outcome: HR, 0.94; 95% CI, 0.77-1.15) groups. No differences in adverse events or serious adverse event were seen by treatment group. The sample size was sufficient to detect a 25% reduction in CVD events with 80% power. Conclusions and Relevance Dietary supplementation of long-chain ω-3 polyunsaturated fatty acids or macular xanthophylls in addition to daily intake of minerals and vitamins did not reduce the risk of CVD in elderly participants with age-related macular degeneration. Trial Registration clinicaltrials.gov Identifier:NCT00345176

Association of knee injuries with accelerated knee osteoarthritis progression: data from the Osteoarthritis Initiative.

Abstract: While knee osteoarthritis is typically a slowly progressive disorder, it has recently been appreciated that 5 to 17% of knees have a rapid progression of structural damage (e.g. from normal to end-stage disease within 4 years) (1, 2). Characterization of the structural aspects of this phenomenon and its risk factors may provide insights into the nature of osteoarthritis progression and allow us to identify an at-risk subset for intervention. Identification of knee osteoarthritis phenotypes, such as those with accelerated knee osteoarthritis progression, may allow us to refine sampling for clinical studies (2-5) and develop interventions targeted at specific subtypes. Individuals with a history of joint trauma are 3 to 6 times more likely to develop knee osteoarthritis (6, 7) and are diagnosed approximately 10 years earlier than individuals without a history of joint trauma (8). Within 5 years of injury, knees have structural changes reflective of altered joint health (e.g., altered cartilage composition, altered bone structure) (9-12). Knee injuries are a strong risk factor for knee osteoarthritis and may distinguish knees with accelerated knee osteoarthritis from common knee osteoarthritis progression or knees with no knee osteoarthritis. We aimed to evaluate if a recent knee injury was associated with accelerated knee osteoarthritis. Furthermore, we conducted preliminary analyses to determine if participants with accelerated knee osteoarthritis progression, common knee osteoarthritis progression, and no knee osteoarthritis differed based on key baseline characteristics, which we selected a priori. These preliminary analyses helped us verify which variables should be adjusted for in our primary analyses.

Significance of preradiographic magnetic resonance imaging lesions in persons at increased risk of knee osteoarthritis.

Abstract: Objective Little is known about early knee osteoarthritis (OA). The significance of lesions on magnetic resonance imaging (MRI) in older persons without radiographic OA is unclear. Our objectives were to determine the extent of tissue pathology by MRI and evaluate its significance by testing the following hypotheses: cartilage damage, bone marrow lesions, and meniscal damage are associated with prevalent frequent knee symptoms and incident persistent symptoms; bone marrow lesions and meniscal damage are associated with incident tibiofemoral (TF) cartilage damage; and bone marrow lesions are associated with incident patellofemoral (PF) cartilage damage. Methods In a cohort study of 849 Osteoarthritis Initiative (OAI) participants who had a bilateral Kellgren/Lawrence (K/L) score of 0, we assessed cartilage damage, bone marrow lesions, and meniscal damage using the MRI OA Knee Score, as well as prevalent frequent knee symptoms, incident persistent symptoms, and incident cartilage damage. Multiple logistic regression (one knee per person) was used to evaluate associations between MRI lesions and each of these outcomes. Results Of the participants evaluated, 76% had cartilage damage, 61% had bone marrow lesions, 21% had meniscal tears, and 14% had meniscal extrusion. Cartilage damage (any; TF and PF), bone marrow lesions (any; TF and PF), meniscal extrusion, and body mass index (BMI) were associated with prevalent frequent symptoms. Cartilage damage (isolated PF; TF and PF), bone marrow lesions (any; isolated PF; TF and PF), meniscal tears, and BMI were associated with incident persistent symptoms. Hand OA, but no individual lesion type, was associated with incident TF cartilage damage, and bone marrow lesions (any; any PF) with incident PF damage. Having more lesion types was associated with a greater risk of outcomes. Conclusion MRI-detected lesions are not incidental and may represent early disease in persons at increased risk of knee OA.

Vitamin D Deficiency Is Associated with Progression of Knee Osteoarthritis

Abstract: Background: Knee osteoarthritis causes functional limitation and disability in the elderly. Vitamin D has biological functions on multiple knee joint structures and can play important roles in the progression of knee osteoarthritis. The metabolism of vitamin D is regulated by parathyroid hormone (PTH). Objective: The objective was to investigate whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] and PTH, individually and jointly, predict the progression of knee osteoarthritis. Methods: Serum 25(OH)D and PTH were measured at the 30- or 36-mo visit in 418 participants enrolled in the Osteoarthritis Initiative (OAI) who had ≥1 knee with both symptomatic and radiographic osteoarthritis. Progression of knee osteoarthritis was defined as any increase in the radiographic joint space narrowing (JSN) score between the 24- and 48-mo OAI visits. Results: The mean concentrations of serum 25(OH)D and PTH were 26.2 μg/L and 54.5 pg/mL, respectively. Approximately 16% of the population had serum 25(OH)D 2-fold elevated risk of knee osteoarthritis progression compared with those with greater vitamin D concentrations (≥15 μg/L; OR: 2.3; 95% CI: 1.1, 4.5). High serum PTH (≥73 pg/mL) was not associated with a significant increase in JSN score. However, participants with both low vitamin D and high PTH had >3-fold increased risk of progression (OR: 3.2; 95%CI: 1.2, 8.4). Conclusion: Our results suggest that individuals deficient in vitamin D have an increased risk of knee osteoarthritis progression.

Risk of Cardiovascular Disease Among Postmenopausal Women with Prior Pregnancy Loss: The Women’s Health Initiative

Abstract: PURPOSE Metabolic, hormonal, and hemostatic changes associated with pregnancy loss (stillbirth and miscarriage) may contribute to the development of cardiovascular disease (CVD) in adulthood. This study evaluated prospectively the association between a history of pregnancy loss and CVD in a cohort of postmenopausal women. METHODS Postmenopausal women (77,701) were evaluated from 1993–1998. Information on baseline reproductive history, sociodemographic, and CVD risk factors were collected. The associations between 1 or 2 or more miscarriages and 1 or more stillbirths with occurrence of CVD were evaluated using multiple logistic regression. RESULTS Among 77,701 women in the study sample, 23,538 (30.3%) reported a history of miscarriage; 1,670 (2.2%) reported a history of stillbirth; and 1,673 (2.2%) reported a history of both miscarriage and stillbirth. Multivariable-adjusted odds ratio (OR) for coronary heart disease (CHD) for 1 or more stillbirths was 1.27 (95% CI, 1.07–1.51) compared with no stillbirth; for women with a history of 1 miscarriage, the OR = 1.19 (95% CI, 1.08–1.32); and for 2 or more miscarriages the OR = 1.18 (95% CI, 1.04–1.34) compared with no miscarriage. For ischemic stroke, the multivariable odds ratio for stillbirths and miscarriages was not significant. CONCLUSIONS Pregnancy loss was associated with CHD but not ischemic stroke. Women with a history of 1 or more stillbirths or 1 or more miscarriages appear to be at increased risk of future CVD and should be considered candidates for closer surveillance and/or early intervention; research is needed into better understanding the pathophysiologic mechanisms behind the increased risk of CVD associated with pregnancy loss.

Severe obesity, heart disease, and death among white, African American, and Hispanic postmenopausal women.

Abstract: Author(s): McTigue, Kathleen M; Chang, Yue-Fang; Eaton, Charles; Garcia, Lorena; Johnson, Karen C; Lewis, Cora E; Liu, Simin; Mackey, Rachel H; Robinson, Jennifer; Rosal, Milagros C; Snetselaar, Linda; Valoski, Alice; Kuller, Lewis H | Abstract: ObjectiveTo compare mortality, nonfatal coronary heart disease (CHD), and congestive heart failure (CHF) risk across BMI categories in white, African American, and Hispanic women, with a focus on severe obesity (BMI ≥ 40), and examine heterogeneity in weight-related CHD risk.MethodsAmong 156,775 Women's Health Initiative observational study and clinical trial participants (September 1993-12 September 2005), multivariable Cox models estimated relative risk for mortality, CHD, and CHF. CHD incidence was calculated by anthropometry, race, and cardiovascular risk factors (CVRF).ResultsMortality, nonfatal CHD, and CHF incidence generally rose with BMI category. For severe obesity versus normal BMI, hazard ratios (HRs, 95% confidence interval) for mortality were 1.97 (1.77-2.20) in white, 1.55 (1.20-2.00) in African American, and 2.59 (1.55-4.31) in Hispanic women; for CHD, HRs were 2.05 (1.80-2.35), 2.24 (1.57-3.19), and 2.95 (1.60-5.41) respectively; for CHF, HRs were 5.01 (4.33-5.80), 3.60 (2.30-5.62), and 6.05 (2.49-14.69). CVRF variation resulted in substantial variation in CHD rates across BMI categories, even in severe obesity. CHD incidence was similar by race/ethnicity when differences in BMI or CVRF were accounted for.ConclusionsSevere obesity increases mortality, nonfatal CHD, and CHF risk in women of diverse race/ethnicity. CVRF heterogeneity contributes to variation in CHD incidence even in severe obesity.

Residential Proximity to Major Roadways and Prevalent Hypertension Among Postmenopausal Women: Results From the Women's Health Initiative San Diego Cohort

Abstract: Background Living near major roadways has been linked with increased risk of cardiovascular events and worse prognosis. Residential proximity to major roadways may also be associated with increased risk of hypertension, but few studies have evaluated this hypothesis. Methods and Results We examined the cross-sectional association between residential proximity to major roadways and prevalent hypertension among 5401 postmenopausal women enrolled into the San Diego cohort of the Women's Health Initiative. We used modified Poisson regression with robust error variance to estimate the association between prevalence of hypertension and residential distance to nearest major roadway, adjusting for participant demographics, medical history, indicators of individual and neighborhood socioeconomic status, and for local supermarket/grocery and fast food/convenience store density. The adjusted prevalence ratios for hypertension were 1.22 (95% CI: 1.07, 1.39), 1.13 (1.00, 1.27), and 1.05 (0.99, 1.12) for women living ≤100, >100 to 200, and >200 to 1000 versus >1000 m from a major roadway ( P for trend=0.006). In a model treating the natural log of distance to major roadway as a continuous variable, a shift in distance from 1000 to 100 m from a major roadway was associated with a 9% (3%, 16%) higher prevalence of hypertension. Conclusions In this cohort of postmenopausal women, residential proximity to major roadways was positively associated with the prevalence of hypertension. If causal, these results suggest that living close to major roadways may be an important novel risk factor for hypertension.

Milk consumption and progression of medial tibiofemoral knee osteoarthritis: data from the Osteoarthritis Initiative.

Abstract: Objective Milk consumption has long been recognized for its important role in bone health, but its role in the progression of knee osteoarthritis (OA) is unclear. We examined the prospective association of milk consumption with radiographic progression of knee OA. Methods In the Osteoarthritis Initiative, 2,148 participants (3,064 knees) with radiographic knee OA and dietary data at baseline were followed up to 12, 24, 36, and 48 months. Milk consumption was assessed with a Block Brief Food Frequency Questionnaire completed at baseline. To evaluate progression of OA, we used quantitative joint space width (JSW) between the medial femur and tibia of the knee based on plain radiographs. The multivariate linear models for repeated measures were used to test the independent association between milk intake and the decrease in JSW over time, while adjusting for baseline disease severity, body mass index, dietary factors, and other potential confounders. Results We observed a significant dose-response relationship between baseline milk intake and adjusted mean decrease of JSW in women (P = 0.014 for trend). With increasing levels of milk intake (none, ≤3, 4–6, and ≥7 glasses/week), the mean decreases of JSW were 0.38 mm, 0.29 mm, 0.29 mm, and 0.26 mm, respectively. In men, we observed no significant association between milk consumption and the decreases of JSW. Conclusion Our results suggest that frequent milk consumption may be associated with reduced OA progression in women. Replication of these novel findings in other prospective studies demonstrating the increase in milk consumption leads to delay in knee OA progression are needed.

Application of marginal structural models in pharmacoepidemiologic studies: a systematic review.

Abstract: Purpose We systematically reviewed pharmacoepidemiologic studies published in 2012 that used inverse probability weighted (IPW) estimation of marginal structural models (MSM) to estimate the effect from a time-varying treatment. Methods Potential studies were retrieved through a citation search within Web of Science and a keyword search within PubMed. Eligibility of retrieved studies was independently assessed by at least two reviewers. One reviewer performed data extraction, and a senior epidemiologist confirmed the extracted information for all eligible studies. Results Twenty pharmacoepidemiologic studies were eligible for data extraction. The majority of reviewed studies did not report whether the positivity assumption was checked. Six studies performed intention-to-treat analyses, but none of them reported adherence levels after treatment initiation. Eight studies chose an as-treated analytic strategy, but only one of them reported modeling the multiphase of treatment use. Almost all studies performing as-treated analyses chose the most recent treatment status as the functional form of exposure in the outcome model. Nearly half of the studies reported that the IPW estimate was substantially different from the estimate derived from a standard regression model. Conclusions The use of IPW method to control for time-varying confounding is increasing in medical literature. However, reporting of the application of the technique is variable and suboptimal. It may be prudent to develop best practices in reporting complex methods in epidemiologic research. Copyright © 2014 John Wiley & Sons, Ltd.

Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the women's health initiative randomized trials

Abstract: RESULTS During the CEE plus MPA intervention phase, the numbers of CHD cases were 196 for CEE plus MPA vs 159 for placebo (hazard ratio [HR], 1.18; 95% CI, 0.95-1.45) and 206 vs 155, respectively, for invasive breast cancer (HR, 1.24; 95% CI, 1.01-1.53). Other risks included increased stroke, pulmonary embolism, dementia (in women aged65 years), gallbladder disease, and urinary incontinence; benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Most risks and benefits dissipated postintervention, although some elevation in breast cancer risk persisted during cumulative follow-up (434 cases for CEE plus MPA vs 323 for placebo; HR, 1.28 [95% CI, 1.11-1.48]). The risks and benefits were more balanced during the CEE alone intervention with 204 CHD cases for CEE alone vs 222 cases for placebo (HR, 0.94; 95% CI, 0.781.14) and 104 vs 135, respectively, for invasive breast cancer (HR, 0.79; 95% CI, 0.61-1.02); cumulatively, there were 168 vs 216, respectively, cases of breast cancer diagnosed (HR, 0.79; 95% CI, 0.65-0.97). Results for other outcomes were similar to CEE plus MPA. Neither regimen affected all-cause mortality. For CEE alone, younger women (aged 50-59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P < .05 for trend by age). Absolute risks of adverse events (measured by the global index) per 10 000 women annually taking CEE plus MPA ranged from 12 excess cases for ages of 50-59 years to 38 for ages of 70-79 years; for women taking CEE alone, from 19 fewer cases for ages of 50-59 years to 51 excess cases for ages of 70-79 years. Quality-of-life outcomes had mixed results in both trials. CONCLUSIONS AND RELEVANCE Menopausal hormone therapy has a complex pattern of risks and benefits. Findings from the intervention and extended postintervention follow-up of the 2 WHI hormone therapy trials do not support use of this therapy for chronic disease prevention, although it is appropriate for symptom management in some women.

Association analysis of BMD-associated SNPs with knee osteoarthritis

Abstract: Osteoarthritis (OA) risk is widely recognized to be heritable but few loci have been identified. Observational studies have identified higher systemic bone mineral density (BMD) to be associated with an increased risk of radiographic knee osteoarthritis. With this in mind, we sought to evaluate whether well-established genetic loci for variance in BMD are associated with risk for radiographic OA in the Osteoarthritis Initiative (OAI) and the Johnston County Osteoarthritis (JoCo) Project. Cases had at least one knee with definite radiographic OA, defined as the presence of definite osteophytes with or without joint space narrowing (Kellgren-Lawrence [KL] grade ≥ 2) and controls were absent for definite radiographic OA in both knees (KL grade ≤ 1 bilaterally). There were 2014 and 658 Caucasian cases, respectively, in the OAI and JoCo Studies, and 953 and 823 controls. Single nucleotide polymorphisms (SNPs) were identified for association analysis from the literature. Genotyping was carried out on Illumina 2.5M and 1M arrays in Genetic Components of Knee OA (GeCKO) and JoCo, respectively and imputation was done. Association analyses were carried out separately in each cohort with adjustments for age, body mass index (BMI), and sex, and then parameter estimates were combined across the two cohorts by meta-analysis. We identified four SNPs significantly associated with prevalent radiographic knee OA. The strongest signal (p = 0.0009; OR = 1.22; 95% CI, 1.08–1.37) maps to 12q3, which contains a gene coding for SP7. Additional loci map to 7p14.1 (TXNDC3), 11q13.2 (LRP5), and 11p14.1 (LIN7C). For all four loci the allele associated with higher BMD was associated with higher odds of OA. A BMD risk allele score was not significantly associated with OA risk. This meta-analysis demonstrates that several genomewide association studies (GWAS)-identified BMD SNPs are nominally associated with prevalent radiographic knee OA and further supports the hypothesis that BMD, or its determinants, may be a risk factor contributing to OA development. © 2014 American Society for Bone and Mineral Research.

Extending Brauer's Height Zero Conjecture to Blocks with Nonabelian Defect Groups

Abstract: We propose a generalization of Brauer?s Height Zero Conjecture that considers positive heights. We give strong evidence supporting one half of the generalization and obtain some partial results regarding the other half.

Relationship of Meeting Physical Activity Guidelines With Health-Related Utility

Abstract: Objective Health-related utility measures overall health status and quality of life and is commonly incorporated into cost-effectiveness analyses. This study investigates whether attainment of federal physical activity guidelines translates into better health-related utility in adults with or at risk for knee osteoarthritis (OA). Methods Cross-sectional data from 1,908 adults with or at risk for knee OA participating in the accelerometer ancillary study of the Osteoarthritis Initiative were assessed. Physical activity was measured using 7 days of accelerometer monitoring and was classified as 1) meeting guidelines (≥150 bouted moderate-to-vigorous [MV] minutes per week); 2) insufficiently active (≥1 MV bout[s] per week but below guidelines); or 3) inactive (zero MV bouts per week). A Short Form 6D health-related utility score was derived from patient-reported health status. Relationship of physical activity levels to median health-related utility adjusted for socioeconomic and health factors was tested using quantile regression. Results Only 13% of participants met physical activity guidelines, and 45% were inactive. Relative to the inactive group, median health-related utility scores were significantly greater for the meeting guidelines group (0.063; 95% confidence interval [95% CI] 0.055, 0.071) and the insufficiently active group (0.059; 95% CI 0.054, 0.064). These differences showed a statistically significant linear trend and strong cross-sectional relationship with physical activity level even after adjusting for socioeconomic and health factors. Conclusion We found a significant positive relationship between physical activity level and health-related utility. Interventions that encourage adults, including persons with knee OA, to increase physical activity even if recommended levels are not attained may improve their quality of life.

Cardiac risk factors: environmental, sociodemographic, and behavioral cardiovascular risk factors.

Abstract: Several environmental exposures are associated with increased risk of coronary heart disease (CHD). Exposure to secondhand smoke may increase the risk by as much as 25% to 30%. Exposure to third hand smoke, residual components of tobacco smoke that remain in the environment after a cigarette is extinguished, also appears to increase risk. These residual components can remain in rooms and automobiles for up to 30 years and enter the body through the skin or via inhalation or ingestion. Exposure to particulate matter air pollution from automobile emissions, power plants, and other sources is yet another environmental risk factor for CHD, resulting in tens of thousands of deaths annually in the United States. Exposure to other environmental toxins, particularly bisphenol A and phthalates, also has been linked to CHD. There are sociodemographic risks for CHD, with numerous studies showing that lower socioeconomic status is associated with higher risk. Behavioral risk factors include poor diet, such as frequent consumption of fast food and processed meals; sleep disturbance; and psychological stress, particularly related to marital or work issues. Finally, although high alcohol consumption is associated with increased CHD risk, moderate alcohol consumption (ie, less than 1 to 2 drinks/day), particularly of wine and possibly beer, appears to reduce the risk.

Morita equivalence classes of 2-blocks of defect three

Abstract: We give a complete description of the Morita equivalence classes of blocks with elementary abelian defect groups of order 8 and of the derived equivalences between them. A consequence is the verification of Brou\'e's abelian defect group conjecture for these blocks. It also completes the classification of Morita and derived equivalence classes of 2-blocks of defect at most three defined over a suitable field.

Improvement in stroke risk prediction: role of C-reactive protein and lipoprotein-associated phospholipase A2 in the women's health initiative

Abstract: Background Classification of risk of ischemic stroke is important for medical care and public health reasons. Whether addition of biomarkers adds to predictive power of the Framingham Stroke Risk or other traditional risk factors has not been studied in older women. Methods The Hormones and Biomarkers Predicting Stroke Study is a case-control study of blood biomarkers assayed in 972 ischemic stroke cases and 972 controls, nested in the Women's Health Initiative Observational Study of 93 676 postmenopausal women followed for an average of eight-years. We evaluated additive predictive value of two commercially available biomarkers: C-reactive protein and lipoprotein-associated phospholipase A2 to determine if they added to risk prediction by the Framingham Stroke Risk Score or by traditional risk factors, which included lipids and other variables not included in the Framingham Stroke Risk Score. As measures of additive predictive value, we used the C-statistic, net reclassification improvement, category-less net reclassification improvement, and integrated discrimination improvement index. Results Addition of C-reactive protein to Framingham risk models or additional traditional risk factors overall modestly improved prediction of ischemic stroke and resulted in overall net reclassification improvement of 6·3%, (case net reclassification improvement = 3·9%, control net reclassification improvement = 2·4%). In particular, high-sensitivity C-reactive protein was useful in prediction of cardioembolic strokes (net reclassification improvement = 12·0%; 95% confidence interval 4·3–19·6%) and in strokes occurring in less than three-years (net reclassification improvement = 7·9%, 95% confidence interval 0·8–14·9%). Lipoprotein-associated phospholipase A2 was useful in risk prediction of large artery strokes (net reclassification improvement = 19·8%, 95% confidence interval 7·4−32·1%) and in early strokes (net reclassification improvement = 5·8%, 95% confidence interval 0·4–11·2%). Conclusions C-reactive protein and lipoprotein-associated phospholipase A2 can improve prediction of certain subtypes of ischemic stroke in older women, over the Framingham stroke risk model and traditional risk factors, and may help to guide surveillance and treatment of women at risk.

Cardiac risk factors: biomarkers and genetic tests to determine cardiovascular risk.

Abstract: Current guidelines recommend global risk assessment instruments as the primary approach for determining risk of coronary heart disease (CHD). The Framingham Risk Score (FRS) yields a 10-year risk of CHD, whereas the newer Pooled Cohort Equations yield a 10-year risk of stroke or CHD. High-sensitivity C-reactive protein, a biomarker for inflammation, along with family history of CHD, can be added to the parameters of the FRS in the Reynolds Risk Score to yield a more refined 10-year CHD risk. Various other biomarkers also can be used. Patients with elevated urinary albumin have higher rates of CHD events, though the incremental yield of adding urinary albumin provides only minor improvements in risk assessment compared with the FRS. Elevated levels of lipoprotein (a) [Lp(a)] also predict increased risk of CHD, and some guidelines recommend Lp(a) testing for patients with strong family histories of premature CHD. Another biomarker is platelet-activating factor acetylhydrolase (Lp-PLA2). Elevated levels indicate increased risk, and some recommendations suggest a lower goal level for low-density lipoprotein with statin therapy when Lp-PLA2 levels are high. Finally, genome-wide association studies for genetic risk of CHD currently are not recommended, but such tests likely will be useful within the next few years.

Is inflammatory chronic obstructive pulmonary disease a coronary heart disease risk equivalent? A longitudinal analysis of the third National Health and Nutrition Examination Survey (NHANES III), 1988-1994

Abstract: Evidence suggests that there is an association between chronic obstructive pulmonary disease (COPD) and coronary heart disease (CHD). An important etiological link between COPD and CHD may be an underlying systemic inflammatory process. Given that COPD patients are at greater risk of cardiovascular mortality, understanding the burden of CHD on COPD patients could permit future risk attenuation. Longitudinal cohort analyses of the Third National Health and Nutrition Examination Survey from 1988–1994 were performed. 3,681 individuals ≥40 years of age with good quality spirometry data were included. Participants were divided into 5 groups: 1) no COPD, no CHD; 2) COPD without inflammation, no CHD; 3) COPD with inflammation, no CHD; 4) CHD only, and 5) CHD + COPD. A novel “inflammatory” COPD designation included those with COPD and clinical evidence of inflammation (i.e., CRP ≥95.24 nmol/L). The risk for CHD mortality was significant only for the CHD group (HR 5.56, 95% CI 3.24-9.55) and the COPD + CHD group (HR 5.02, 95% CI 2.83-8.90). Similarly, the risk for cardiovascular disease (CVD) mortality was significant only for the CHD group (HR 4.25, 95% CI 2.70-6.69) and the CHD + COPD group (HR 4.12, 95% CI 2.60-6.54) after adjusting for nonmodifiable CHD risk factors (age, gender, race/ethnicity, family history of CHD). After adjusting for modifiable CHD risk factors (diabetes, BMI, physical activity, systolic blood pressure, cholesterol, and smoking), hazard ratios of the two groups remained similar but attenuated. For total mortality, the risk was significant for the four groups: the non-inflammatory COPD group; the COPD with inflammation group, the CHD group, and the COPD + CHD group. Our study did not confirm that inflammatory COPD may be a CHD risk equivalent. However, due to the small size of the “inflammatory” COPD group, further prospective replication and validation is needed. Moreover, given that COPD results from inflammation, the systemic inflammation associated with COPD may have worsened comorbid conditions and may have lead to the increased total mortality found in the COPD with inflammation and COPD + CHD groups which requires further investigation.

Cardiac risk factors: new cholesterol and blood pressure management guidelines.

Abstract: The 2013 American College of Cardiology/American Heart Association cholesterol guidelines depart from low-density lipoprotein (LDL) treatment targets and recommend treating four specific patient groups with statins. Statins are the only cholesterol-lowering drugs with randomized trial evidence of benefit for preventing atherosclerotic cardiovascular disease (ASCVD). The groups are patients with clinical ASCVD; patients ages 40 to 75 years with diabetes and LDL of 70 to 189 mg/dL but no clinical ASCVD; patients 21 years or older with LDL levels of 190 mg/dL or higher; and patients ages 40 to 75 years with LDL of 70 to 189 mg/dL without clinical ASCVD or diabetes but with 10-year ASCVD risk of 7.5% or higher. Ten-year ASCVD risk may be calculated using the Pooled Cohort Equations. The Eighth Joint National Committee (JNC 8) guidelines for blood pressure management recommend a blood pressure goal of less than 140/90 mm Hg for all adults except those 60 years or older. For the latter group, the JNC 8 recommends a systolic blood pressure goal of less than 150 mm Hg. In another notable change from prior guidelines, the JNC 8 recommends relaxing the systolic blood pressure goal for patients with diabetes and chronic kidney disease to less than 140 mm Hg from less than 130 mm Hg.

Validation of quantitative magnetic resonance imaging-based apparent bone volume fraction in peri-articular tibial bone of cadaveric knees

Abstract: In the knee, high-resolution magnetic resonance (MR) imaging has demonstrated that increased apparent bone volume fraction (trabecular bone volume per total volume; BV/TV) in the peri-articular proximal medial tibia is associated with joint space narrowing and the presence of bone marrow lesions. However, despite evidence of construct validity, MR-based apparent BV/TV has not yet been cross-validated in the proximal medial tibia by comparison with a gold standard (e.g., micro-computed tomography [microCT]). In this cadaveric validation study we explored the association between MR-based apparent BV/TV and microCT-based BV/TV in the proximal peri-articular medial tibia. Fresh cadaveric whole knee specimens were obtained from individuals 51 to 80 years of age with no knee pathology other than osteoarthritis. Ten knees were collected from five cadavers within 10 hours of death and underwent a 3-Tesla MR exam including a coronal-oblique 3-dimensional fast imaging with steady state precession (3D FISP) sequence within 36 hours of death. The specimens were placed in a 4% paraformaldehyde in phosphate buffer within 58 hours of death. After preservation, a subchondral region from the tibial plateau was collected and underwent microCT imaging with a voxel size of 9 μm x 9 μm x 9 μm. A single reader analyzed the microCT images in a similar volume of interest as selected in the MR measures. A different reader analyzed the MR-based trabecular morphometry using a custom analysis tool. To analyze the MR-based trabecular morphometry, a rectangular region of interest (ROI) was positioned on the 20 central images in the proximal medial tibial subchondral bone. The primary outcome measures were MR-based and microCT-based trabecular BV/TV in the proximal medial tibia. The MR-based apparent BV/TV was strongly correlated with microCT-based BV/TV (r = 0.83, confidence interval = 0.42 to 0.96), despite the MR-based apparent BV/TV being systematically lower than measured using microCT. MR-based apparent BV/TV in the proximal peri-articular medial tibia has good construct validity and may represent an alternative for CT-based BV/TV.

The Brown Primary Care Initiative Design for Strategies towards Patient- Centered Medical Home Practice Transformation

Abstract: Introduction: Primary care providers are needed who provide cost-effective, comprehensive care that is teambased and patient-centered (i.e., Patient-Centered Medical Homes-PCMH). Although PCMH implementation is underway in a variety of settings across the U.S, adopting the PCMH model can be challenging even in motivated and efficient practices. The purpose of this study was to help facilitate Patient-Centered Medical Home and other practice transformation initiatives in the state of Rhode Island. The objectives of the Brown Primary Care Transformation Initiative were to: train medical students, residents, and faculty/community family physicians in practice transformation; convene a series of Think Tanks with PCMH experts to discuss domains and data collection tools that could be used in the development of a comprehensive and feasible evaluation methodology for identifying how transformation within the practice environment occurs; and helping with practice transformation of 8 primary care practices. Method: This paper describes the development and delivery of a curriculum utilizing PCMH principles to train medical students and residents in practice transformation; convening three Think Tanks with PCMH experts to address theoretical and practical problems associated with PCMH; the transformation of 8 primary care teaching practices; the development of a methodology for measuring transformation and evaluation of curriculum change; and dissemination of the findings. Discussion: This study provides insights into how and why a diverse group of family medicine practices transform and how training of primary care residents and providers prepares them to implement and/or teach the principles of PCMH.

Effect of Dietary Modification on Incident Carotid Artery Disease in Postmenopausal Women Results From the Women’s Health Initiative Dietary Modification Trial

Abstract: Background and Purpose—Because the diagnosis and treatment of carotid artery disease may reduce the rate of stroke, the aim of this study was to determine whether a diet intervention was associated with incident carotid artery disease. Methods—Participants were 48 835 postmenopausal women aged 50 to 79 years who were randomly assigned to either the intervention or comparison group in the Women’s Health Initiative Diet Modification Trial. Incident carotid artery disease was defined as an overnight hospitalization with either symptoms or a surgical intervention to improve flow. Results—After a mean follow-up of 8.3 years from 1994 to 2005, there were 297 (0.61%) incident carotid artery events. In contrast to the comparison group, the risk of incident carotid disease did not differ from those assigned to the intervention group (hazard ratio, 1.08; 95% confidence interval, 0.9–1.4). In secondary analysis, there was no significant effect of the intervention on the risk for incident carotid disease during the 5...