Showing papers by "Charles B. Eaton published in 2010"

Operative blood loss, blood transfusion, and 30-day mortality in older patients after major noncardiac surgery.

Abstract: Objective:Anemia and operative blood loss are common in the elderly, but evidence is lacking on whether intraoperative blood transfusions can reduce the risk of postoperative death.Methods:We analyzed retrospective data from 239,286 patients 65 years of older who underwent major noncardiac surgery i

Assessing physical activity in persons with knee osteoarthritis using accelerometers: data from the osteoarthritis initiative.

Abstract: Objective Physical activity measured by accelerometers requires basic assumptions to translate the output into meaningful measures. We used accelerometer data from the Osteoarthritis Initiative to investigate in the context of knee osteoarthritis (OA) the following data processing assumptions derived from the general US adult population: nonwear (a period the monitor was removed), based on zero activity exceeding 60 minutes; and a valid day of monitoring, based on wear time evidence exceeding 10 hours. Methods We examined the influence of nonwear thresholds ranging from 20 to 300 minutes of zero activity on mean daily activity minutes (counts >0), mean daily activity counts, and mean daily moderate to vigorous physical activity minutes. The effect of selecting minimums of 8, 10, or 12 wear hours to signify a valid day of monitoring on data retention was examined. Results Our sample of 3,536 days of accelerometer data from 519 persons with knee OA showed that mean daily activity minutes increased with the nonwear threshold until stabilizing at 463 minutes per day, corresponding to the 90-minute nonwear threshold. Similar patterns were observed for mean daily activity counts. Varying the nonwear threshold had no effect on mean daily moderate to vigorous physical activity minutes. Choosing the 90-minute nonwear threshold and a minimum of 10 wear hours to constitute a valid day provided 94% data retention. Conclusion Data supported applying the 90-minute nonwear threshold to the knee OA population instead of the 60-minute threshold for the general population, while retaining the 10-hour valid day threshold.

Frequency of varus and valgus thrust and factors associated with thrust presence in persons with or at higher risk of developing knee osteoarthritis

Abstract: Knee osteoarthritis (OA), a leading cause of functional limitation and disability in older persons, is believed to result from local mechanical factors acting within the context of a systemic susceptibility. Varus thrust is a local mechanical factor shown to be associated with a 4-fold increase in the odds of medial tibiofemoral OA progression over an 18 month follow-up period (1). Varus thrust is visualized during gait as the dynamic worsening or abrupt onset of varus (bow-leg) alignment as the limb accepts weight (stance phase), with a return to less varus and more neutral alignment during lift-off and the non-weightbearing (swing) phase of gait. A varus thrust indicates dynamic instability of the knee in the frontal plane and an acute increase in load transmitted to the medial compartment with each step of walking. Valgus thrust is the worsening or abrupt onset of valgus (knock-knee) alignment visualized during the stance phase, with a return to less valgus (more neutral) alignment during lift-off and the swing phase of gait. In theory, a valgus thrust increases load transmitted to the lateral tibiofemoral compartment, potentially contributing to lateral OA disease onset or progression. While valgus thrust is thought to be less common than varus thrust, the frequency of varus thrust and valgus thrust in persons either with knee OA or at risk to develop it is not known for any racial group. In the Johnston County Osteoarthritis Project, African-Americans were more likely than Caucasians to have lateral joint space narrowing (2), a finding that was not explained by differences in static varus-valgus alignment (3); a greater frequency of valgus thrust in African-Americans could help to explain a predisposition to lateral compartment involvement. The factors associated with varus or valgus thrust presence have not been identified. A thrust is a visible manifestation of excessive motion of one tibiofemoral surface in relation to the other under the dynamic conditions of gait. Thrust presence may represent capsuloligamentous damage and/or insufficient neuromuscular stabilization, conditions that may precede OA or develop or worsen as a result of disease. The capsular changes from static varus-valgus alignment may predispose to thrust development. Knee injury may primarily or secondarily damage stabilizing joint tissues. In theory, greater axial load from obesity may intensify a thrust in knees with compromised frontal-plane stability. Quadriceps weakness or pain-induced quadriceps inhibition may impair mechanisms of neuromuscular stabilization. To address these gaps in knowledge relating to varus and valgus thrust, we undertook an ancillary study to the Osteoarthritis Initiative (OAI) in which thrust was assessed by trained examiners. Here we analyze thrust data from African-Americans and Caucasians, the two largest racial groups in the OAI sample. The objectives of our study were: 1) to determine the frequency of varus thrust and valgus thrust in African-Americans and Caucasians for persons at high risk for but without radiographic OA in either knee and for persons with radiographic OA in one or both knees; and 2) to identify factors associated with the presence of varus and valgus thrust in persons without radiographic OA and with radiographic OA in one or both knees.

Novel proteins associated with risk for coronary heart disease or stroke among postmenopausal women identified by in-depth plasma proteome profiling

Abstract: Coronary heart disease (CHD) and stroke were key outcomes in the Women's Health Initiative (WHI) randomized trials of postmenopausal estrogen and estrogen plus progestin therapy. We recently reported a large number of changes in blood protein concentrations in the first year following randomization in these trials using an in-depth quantitative proteomics approach. However, even though many affected proteins are in pathways relevant to the observed clinical effects, the relationships of these proteins to CHD and stroke risk among postmenopausal women remains substantially unknown. The same in-depth proteomics platform was applied to plasma samples, obtained at enrollment in the WHI Observational Study, from 800 women who developed CHD and 800 women who developed stroke during cohort follow-up, and from 1-1 matched controls. A plasma pooling strategy, followed by extensive fractionation prior to mass spectrometry, was used to identify proteins related to disease incidence, and the overlap of these proteins with those affected by hormone therapy was examined. Replication studies, using enzyme-linked-immunosorbent assay (ELISA), were carried out in the WHI hormone therapy trial cohorts. Case versus control concentration differences were suggested for 37 proteins (nominal P < 0.05) for CHD, with three proteins, beta-2 microglobulin (B2M), alpha-1-acid glycoprotein 1 (ORM1), and insulin-like growth factor binding protein acid labile subunit (IGFALS) having a false discovery rate < 0.05. Corresponding numbers for stroke were 47 proteins with nominal P < 0.05, three of which, apolipoprotein A-II precursor (APOA2), peptidyl-prolyl isomerase A (PPIA), and insulin-like growth factor binding protein 4 (IGFBP4), have a false discovery rate < 0.05. Other proteins involved in insulin-like growth factor signaling were also highly ranked. The associations of B2M with CHD (P < 0.001) and IGFBP4 with stroke (P = 0.005) were confirmed using ELISA in replication studies, and changes in these proteins following the initiation of hormone therapy use were shown to have potential to help explain hormone therapy effects on those diseases. In-depth proteomic discovery analysis of prediagnostic plasma samples identified B2M and IGFBP4 as risk markers for CHD and stroke respectively, and provided a number of candidate markers of disease risk and candidate mediators of hormone therapy effects on CHD and stroke. ClinicalTrials.gov identifier: NCT00000611

Renewing primary care: lessons learned from the Spanish health care system.

Abstract: From 1978 on, Spain rapidly expanded and strengthened its primary health care system, offering a lesson in how to improve health outcomes in a cost-effective manner. The nation moved to a tax-based system of universal access for the entire population and, at the local level, instituted primary care teams coordinating prevention, health promotion, treatment, and community care. Gains included increases in life expectancy and reductions in infant mortality, with outcomes superior to those in the United States. In 2007 Spain spent $2,671 per person, or 8.5 percent of its gross domestic product on health care, versus 16 percent in the United States. Despite concerns familiar to Americans—about future shortages of primary care physicians and relatively low status and pay for these physicians—the principles underlying the Spanish reforms offer lessons for the United States.

Incident Diabetes in Relation to Weight Patterns During Middle Age

Abstract: The authors examined the association between weight patterns during middle age and incident type 2 diabetes mellitus using a subset (n = 1,476) of the Framingham Heart Study original cohort limited-access data set (1948-2003). Participants diagnosed with diabetes before age 50 years were excluded. A functional principal components analysis of body mass index from age 40 years to age 50 years was used to define weight patterns in terms of overall weight status (normal weight, overweight, or obese), weight change (weight loss, stable weight, or weight gain), and weight cycling. Overall overweight and obesity were associated with higher rates of diabetes (for overall overweight, crude hazard ratio (HR) = 3.2, 95% confidence interval (CI): 2.3, 4.6; for overall obesity, crude HR = 8.8, 95% CI: 6.0, 12.8). Weight cycling was also associated with higher rates of diabetes (crude HR = 1.6, 95% CI: 1.2, 2.1). Neither weight loss nor weight gain was associated with incident diabetes. After adjustment for overall weight status, weight cycling was no longer associated with higher rates of diabetes. This study underscores the importance of obesity in diabetes risk and the importance of preventing the development of overweight and obesity earlier in life.

The lack of utility of circulating biomarkers of inflammation and endothelial dysfunction for type 2 diabetes risk prediction among postmenopausal women: the Women's Health Initiative Observational Study.

Abstract: Background Recent studies have linked plasma markers of inflammation and endothelial dysfunction to type 2 diabetes mellitus (DM) development. However, the utility of these novel biomarkers for type 2 DM risk prediction remains uncertain. Methods The Women's Health Initiative Observational Study (WHIOS), a prospective cohort, and a nested case-control study within the WHIOS of 1584 incident type 2 DM cases and 2198 matched controls were used to evaluate the utility of plasma markers of inflammation and endothelial dysfunction for type 2 DM risk prediction. Between September 1994 and December 1998, 93 676 women aged 50 to 79 years were enrolled in the WHIOS. Fasting plasma levels of glucose, insulin, white blood cells, tumor necrosis factor receptor 2, interleukin 6, high-sensitivity C-reactive protein, E-selectin, soluble intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 were measured using blood samples collected at baseline. A series of prediction models including traditional risk factors and novel plasma markers were evaluated on the basis of global model fit, model discrimination, net reclassification improvement, and positive and negative predictive values. Results Although white blood cell count and levels of interleukin 6, high-sensitivity C-reactive protein, and soluble intercellular adhesion molecule 1 significantly enhanced model fit, none of the inflammatory and endothelial dysfunction markers improved the ability of model discrimination (area under the receiver operating characteristic curve, 0.93 vs 0.93), net reclassification, or predictive values (positive, 0.22 vs 0.24; negative, 0.99 vs 0.99 [using 15% 6-year type 2 DM risk as the cutoff]) compared with traditional risk factors. Similar results were obtained in ethnic-specific analyses. Conclusion Beyond traditional risk factors, measurement of plasma markers of systemic inflammation and endothelial dysfunction contribute relatively little additional value in clinical type 2 DM risk prediction in a multiethnic cohort of postmenopausal women.

Differences in Cardiovascular Disease Risk Factor Management in Primary Care by Sex of Physician and Patient

Abstract: PURPOSE The purpose of this study was to evaluate differences in the management of cardiovascular disease (CVD) risk factors based upon the sex of the patient and physician and their interaction in primary care practice. METHODS We evaluated CVD risk factor management in 4,195 patients cared for by 39 male and 16 female primary care physicians in 30 practices in southeastern New England. RESULTS Many of the sex-based differences in CVD risk factor management on crude analysis are lost once adjusted for confounding factors found at the level of the patient, physician, and practice. In multilevel adjusted analyses, styles of CVD risk factor management differed by the sex of the physician, with more female physicians documenting diet and weight loss counseling for hypertension (odds ratio [OR] = 2.22; 95% confidence interval [CI], 1.12–4.40) and obesity (OR = 2.14; 95% CI, 1.30–3.51) and more physical activity counseling for obesity (OR = 2.03; 95% CI, 1.30–3.18) and diabetes (OR = 6.55; 95% CI, 2.01–21.33). Diabetes management differed by the sex of the patient, with fewer women receiving glucose-lowering medications (OR = 0.49; 95% CI, 0.25–0.94), angiotensin-converting enzyme inhibitor therapy (OR = 0.39; 95% CI, 0.22–0.72), and aspirin prophylaxis (OR = 0.30; 95% CI, 0.15–0.58). CONCLUSION Quality of care as measured by patients meeting CVD risk factors treatment goals was similar regardless of the sex of the patient or physician. Selected differences were found in the style of CVD risk factor management by sex of physician and patient.

Evaluation and comparison of the Minnesota Code and Novacode for electrocardiographic Q-ST wave abnormalities for the independent prediction of incident coronary heart disease and total mortality (from the Women's Health Initiative).

Abstract: Electrocardiographic (ECG) Q- and ST-T–wave abnormalities predict coronary heart disease (CHD) and total mortality. No comparison has been made of the classification of these abnormalities by the 2 most widely used ECG coding systems for epidemiologic studies—the Minnesota Code (MC) and Novacode (NC). We evaluated 12-lead electrocardiograms from 64,597 participants (49 to 79 years old, 82% non-Hispanic white) in the Women's Health Initiative clinical trial in 1993 to 1998, with a maximum of 11 years of follow-up. We used MC and NC criteria to identify Q-wave, ST-segment, and T-wave abnormalities for comparison. In total, 3,322 participants (5.1%) died during an average 8-year follow-up, and 1,314 had incident CHD in the baseline cardiovascular disease-free group. Independently, ECG myocardial infarction criteria by the MC or NC were generally equivalent and were strong predictors for CHD death and total mortality (hazard ratio 1.62, 95% confidence interval 1.05 to 2.51 for CHD death; hazard ratio 1.36, 95% confidence interval 1.09 to 1.71 for total mortality) in a multivariable analytic model. Electrocardiograms with major ST-T abnormalities by the MC or NC coding system were stronger in predicting CHD deaths and total mortality than was the presence of Q waves alone. In conclusion, the ECG classification systems for myocardial infarction/ischemia abnormalities from the MC and NC are valuable and useful in clinical trials and epidemiologic studies. ST-T abnormalities are stronger predictors for CHD events and total mortality than isolated Q-wave abnormalities.

Family history of later-onset breast cancer, breast healthy behavior and invasive breast cancer among postmenopausal women: a cohort study

Abstract: Introduction A family history of later-onset breast cancer (FHLBC) may suggest multi-factorial inheritance of breast cancer risk, including unhealthy lifestyle behaviors that may be shared within families. We assessed whether adherence to lifestyle behaviors recommended for breast cancer prevention--including maintaining a healthful body weight, being physically active and limiting alcohol intake--modifies breast cancer risk attributed to FHLBC in postmenopausal women.

Abstract 10904: Resting Heart Rate and Coronary Artery Calcium in Postmenopausal Women

Abstract: OBJECTIVE To test the hypothesis of a significant association between resting heart rate (RHR) and coronary artery calcium (CAC). METHODS This is a cross-sectional study of a subset of women enrolled in the estrogen-alone clinical trial of the Women's Health Initiative (WHI). We used a longitudinal study that enrolled 998 postmenopausal women with a history of hysterectomy between the ages of 50 and 59 at enrollment at 40 different clinical centers. RHR was measured at enrollment and throughout the study, and CAC was determined approximately 7 years after the baseline clinic visit. RESULTS The mean (standard deviation [SD]) age was 55 (2.8) years. With adjustment for age and ethnicity, a 10-unit increment in RHR was significantly associated with CAC (SD 1.18, 95% confidence interval [CI] 1.01-1.38), but this was no longer significant after adjustment for body mass index (BMI), income, education, dyslipidemia, diabetes, smoking, and hypertension (SD 1.06, 95% CI 0.90-1.25). In a fully adjusted multivariable model, however, there was a significant interaction (p=0.03) between baseline RHR and systolic blood pressure (SBP) for the presence of any CAC. Compared to women with an RHR < 80 beats per minute (BPM) and an SBP < 140 mm Hg, those who had an RHR ≥ 80 BPM and an SBP ≥ 140 mm Hg had 2.66-fold higher odds (1.08-6.57) for the presence of any CAC. CONCLUSIONS Compared to those with normal BP and RHR, postmenopausal, hysterectomized women with an elevated SBP and RHR have a significantly higher odds for the presence of calcified coronary artery disease.

Is the association between optimistic cardiovascular risk perceptions and lower rates of cardiovascular disease mortality explained by biomarkers of systemic inflammation or endothelial function? A case-cohort study

Abstract: Background More optimistic perceptions of cardiovascular disease risk are associated with substantively lower rates of cardiovascular death among men. It remains unknown whether this association represents causality (i.e. perception leads to actions/conditions that influence cardiovascular disease occurrence) or residual confounding by unmeasured factors that associate with risk perceptions and with physiological processes that promote cardiovascular disease (i.e. inflammation or endothelial dysfunction).