Objective

To examine use of complementary and alternative medicine (CAM) among individuals with radiographic confirmed osteoarthritis (OA) of the knee

Methods

We included 2,679 participants of the Osteoarthritis Initiative with radiographic tibiofemoral knee OA in at least one knee at baseline. Trained interviewers asked a series of specific questions relating to current OA treatments including CAM therapies (7 categories—alternative medical systems, mind-body interventions, manipulation and body-based methods, energy therapies, and 3 types of biologically based therapies) and conventional medications. Participants were classified as: 1) conventional medication users only, 2) CAM users only; 3) users of both; and 4) users of neither. Polytomous logistic regression identified correlates of treatment approaches including sociodemographics and clinical/functional correlates.

Results

CAM use was prevalent (47%), with 24% reporting use of both CAM and conventional medication approaches. Multi-joint OA was correlated with all treatments (adjusted Odds Ratio (aOR) conventional medications: 1.62; CAM only: 1.37 and both: 2.16). X-ray evidence of severe narrowing (OARSI grade 3) was associated with use of glucosamine/chondroitin (aOR: 2.20) and use of both (aOR: 1.98). The WOMAC-Pain Score was correlated with conventional medication use, either alone (aOR: 1.28) or in combination with CAM (aOR: 1.41 per one standard deviation change). KOOS-QOL and SF-12 Physical Scale scores were inversely related to all treatments.

Conclusion

CAM is commonly used to treat joint and arthritis pain among persons with knee OA. The extent to which these treatments are effective in managing symptoms and slowing disease progression remains to be proven.

Objective

Osteoarthritis (OA) clinical practice guidelines identify a substantial therapeutic role for physical activity but objective information about the physical activity of this population is lacking. We objectively measured physical activity levels of adults with knee OA and report the prevalence of meeting public health physical activity guidelines.

Methods

Cross-sectional accelerometer data from 1111 adults with radiographic knee OA aged 49 to 84 years participating in Osteoarthritis Initiative accelerometer monitoring ancillary study were assessed for meeting the aerobic component of the 2008 Physical Activity Guidelines for Americans (≥150 minutes/week in episodes≥10 minutes). Quantile regression was used to test median gender differences in physical activity levels.

Results

Aerobic physical activity guidelines were met by 12.9% of men and 7.7% of women with knee OA. A substantial 40.1% of men and 56.5% of women were inactive, doing no moderate-to-vigorous (MV) activity over 7 days that lasted 10 minutes or more. Although men engaged in significantly more MV intensity activity (20.7 vs. 12.3 average daily minutes) they also spent more time in no or very light intensity activity (608.2 vs. 585.8 average daily minutes) than women.

Conclusion

Despite substantial health benefits from physical activity, adults with knee OA were particularly inactive based on objective accelerometer monitoring. The percentages of men and women who met public health physical activity guidelines were substantially less than previous reports based on self-reported activity in arthritis populations. These findings support intensified public health efforts to increase physical activity levels among persons with knee OA.

The food frequency questionnaire approach to dietary assessment is ubiquitous in nutritional epidemiology research. Food records and recalls provide approaches that may also be adaptable for use in large epidemiologic cohorts, if warranted by better measurement properties. The authors collected (2007–2009) a 4-day food record, three 24-hour dietary recalls, and a food frequency questionnaire from 450 postmenopausal women in the Women’s Health Initiative prospective cohort study (enrollment, 1994–1998), along with biomarkers of energy and protein consumption. Through comparison with biomarkers, the food record is shown to provide a stronger estimate of energy and protein than does the food frequency questionnaire, with 24-hour recalls mostly intermediate. Differences were smaller and nonsignificant for protein density. Food frequencies, records, and recalls were, respectively, able to “explain” 3.8%, 7.8%, and 2.8% of biomarker variation for energy; 8.4%, 22.6%, and 16.2% of biomarker variation for protein; and 6.5%, 11.0%, and 7.0% of biomarker variation for protein density. However, calibration equations that include body mass index, age, and ethnicity substantially improve these numbers to 41.7%, 44.7%, and 42.1% for energy; 20.3%, 32.7%, and 28.4% for protein; and 8.7%, 14.4%, and 10.4% for protein density. Calibration equations using any of the assessment procedures may yield suitable consumption estimates for epidemiologic study purposes.

Objective

The relationship between arthritis and fracture was examined in the Women’s Health Initiative (WHI).

Methods

Women were classified into three self-reported groups at baseline: no arthritis (n=83,295), osteoarthritis (OA) (n=63,402), and rheumatoid arthritis (RA) (n=960). Incident fractures were self-reported throughout follow-up. Age-adjusted fracture rates by arthritis category were generated, and Cox-proportional hazards model was used to test the association between arthritis and fracture.

Results

After an average of 7.80 years, 24,137 total fractures were reported including 2,559 self-reported spinal fractures and 1,698 adjudicated hip fractures. For each fracture type, age-adjusted fracture rates were highest in the RA group and lowest in the non-arthritic group. After adjustment for several covariates, report of arthritis was associated with increased risk for spine, hip, and any clinical fractures. Compared to the non-arthritis group, the risk [HR (95% CI)] of sustaining any clinical fracture in the OA group was 1.09 (1.05, 1.13) (p<0.001) and 1.49 (1.26, 1.75) (p<0.001) in the RA group. The risk of sustaining a hip fracture was not statistically increased in the OA group [1.11 (0.98, 1.25)] (p=0.122) compared to the non-arthritis group; however the risk of hip fracture significantly increased [3.03 (2.03, 4.51)] (p<0.001) in the RA group compared to the non-arthritis group.

Conclusion

The increase in fracture risk found in this study confirms the importance of fracture prevention in patients with both RA and OA.

Background

The extent to which racial differences exist in use of treatments for osteoarthritis (OA) is debatable. The purpose of this study was to describe the differences between African Americans (AA) and Caucasian Americans (CA) in using treatment approaches to manage symptoms among individuals with radiographic-confirmed knee OA.

Methods

A cross-sectional study was conducted. Using data from the Osteoarthritis Initiative, we identified 508 AA and 2,075 CA with radiographic tibiofemoral OA in at least one knee. Trained interviewers asked questions relating to current OA treatments including seven CAM therapy categories—alternative medical systems, mind-body interventions, manipulation and body-based methods, energy therapies, and three types of biologically based therapies, as well as conventional medications. We categorized participants as: conventional medication only users, CAM only users, users of both and users of neither. Multinomial logistic regression models adjusting for sociodemographics and clinical/functional factors provided estimates of the association between race and treatment use.

Results

Overall, 16.5% of AA and 24.2% of CA exclusively used CAM to treat OA, 25.0% of AA and 23.8% of CA used CAM in conjunction with conventional medications, and 24.8% of AA and 14.6% of CA exclusively used conventional medications. After control for sociodemographic and clinical factors, AA were less likely than CA to use CAM therapies alone (adjusted odds ratio (OR) of using CAM alone relative to no CAM or conventional treatments: 0.68, 95% confidence interval (CI): 0.48–0.96) or with conventional medications (adjusted OR relative to no CAM or conventional treatments: 0.59, 95%CI: 0.42–0.83). However, no differences in use of conventional medications alone were observed after adjustment of covariates.

Conclusion

CAM use is common among people with knee OA, but is less likely to be used by AA relative to CA. For effective CAM therapies, targeted outreach to underserved populations including education about benefits of various CAM treatments and providing accessible care may attenuate observed disparities in effective CAM use by race.

Social isolation confers increased risk for coronary heart disease (CHD) events and mortality. In two recent studies, low levels of social integration among older adults were related to higher levels of C-reactive protein (CRP), a marker of inflammation, suggesting a possible biological link between social isolation and CHD. The current study examined relationships among social isolation, CRP, and 15-year CHD death in a community sample of US adults aged 40 years and older without a prior history of myocardial infarction. A nested case-cohort study was conducted from a parent cohort of community-dwelling adults from the southeastern New England region of the United States (N = 2,321) who were interviewed in 1989 and 1990. CRP levels were measured from stored sera provided by the nested case-cohort (n = 370), which included all cases of CHD death observed through 2005 (n = 48), and a random sample of non-cases. We found that the most socially isolated individuals had two-and-a-half times the odds of elevated CRP levels compared to the most socially integrated. In separate logistic regression models, both social isolation and CRP predicted later CHD death. The most socially isolated continued to have more than twice the odds of CHD death compared to the most socially integrated in a model adjusting for CRP and more traditional CHD risk factors. The current findings support social isolation as an independent risk factor of both high levels of CRP and CHD death in middle-aged adults without a prior history of myocardial infarction. Prospective study of inflammatory pathways related to social isolation and mortality are needed to fully delineate whether and how CRP or other inflammatory markers contribute to mechanisms linking social isolation to CVD health.

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.

Background.

Examine the independent and joint effects of geriatric syndromes (GS) and cardiometabolic diseases (CMDs) on functional impairment.

Methods.

Cross-sectional analysis of baseline data from the Women's Health Initiative, including 62,829 women aged 65 years or older. GS (urinary incontinence, falls, and depression measured by the shortened Center for Epidemiological Studies-Depression scale/Diagnostic Interview Schedule screening instrument) and CMD (coronary artery disease, coronary heart failure, and diabetes) were self-reported. Physical and social functioning and general health subscales of the Short Form-36 dichotomized at the median for the study sample were used to assess functional impairment. Additive interaction between burden of GS and CMD was assessed using logistic regression models.

Results.

Forty-three percent of women had at least one GS; 14.1% had at least one CMD; and 6.9% had at least one of each. Compared with women with no GS or CMD, women with one or more GS but no CMD were as likely to have physical functioning impairments (odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.73, 1.86) as those with CMD alone (OR = 1.97; CI = 1.84, 2.10). The association with social functioning was stronger for GS alone (OR = 2.10; CI = 2.02, 2.18) compared with CMD (OR = 1.60; CI = 1.50, 1.71). The association with general health was stronger for CMD alone (OR = 2.15; CI = 2.01, 2.29) compared with GS (OR = 1.68; CI = 1.62, 1.74). Significant interactions between GS and CMD were observed for all functional measures with 20%–30% of observed ORs attributable to additive interaction.

Conclusion.

GSs alone are associated with functional impairment in older women; the association is stronger in the presence of even one CMD.

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 adult US population: non-wear (a period the monitor was removed) is based on zero activity exceeding 60 minutes; a valid day of monitoring is based on wear time evidence exceeding 10 hours.

Methods

We examined the influence of non-wear thresholds ranging from 20 to 300 minutes of zero activity on 1) mean daily activity minutes (counts>0), 2) mean daily activity counts, and 3) mean daily moderate to vigorous physical activity (MVPA) 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 3536 days’ accelerometer data from 519 persons with knee OA showed mean daily activity minutes increased with the non-wear threshold until stabilizing at 463 minutes per day, corresponding to the 90-minute non-wear threshold. Similar patterns were observed for mean daily activity counts. Varying the non-wear threshold had no effect on mean daily MVPA minutes. Choosing the 90-minute non-wear threshold and a minimum of 10 wear hours to constitute a valid day provided 94% data retention.

Conclusion

Data supported applying the 90-minute non-wear threshold to the knee OA population instead of the general population 60-minute threshold, while retaining the 10-hour valid day threshold.

African Americans have the highest rate of mortality due to coronary heart disease (CHD). Although multiple loci have been identified influencing CHD risk in European-Americans using a genome-wide association (GWAS) approach, no GWAS of incident CHD has been reported for African Americans. We performed a GWAS for incident CHD events collected during 19 years of follow-up in 2,905 African Americans from the Atherosclerosis Risk in Communities (ARIC) study. We identified a genome-wide significant SNP (rs1859023, MAF = 31%) located at 7q21 near the PFTK1 gene (HR = 0.57, 95% CI 0.46 to 0.69, p = 1.86×10−08), which replicated in an independent sample of over 8,000 African American women from the Women's Health Initiative (WHI) (HR = 0.81, 95% CI 0.70 to 0.93, p = 0.005). PFTK1 encodes a serine/threonine-protein kinase, PFTAIRE-1, that acts as a cyclin-dependent kinase regulating cell cycle progression and cell proliferation. This is the first finding of incident CHD locus identified by GWAS in African Americans.

Author Summary

In the United States, African Americans are at high risk for coronary heart disease (CHD). Although environmental and social factors have a role, genetic factors also contribute to CHD risk and mortality. Research to identify genetic factors for CHD susceptibility has been carried out mostly in Europeans and European Americans and little has been done in African Americans. Genome wide association studies (GWAS) provide a means to identify susceptibility loci without any a priori assumptions about the functional importance of a gene. In this study, we used GWAS to identify a novel genomic region associated with incident CHD events in African Americans from the ARIC study and replicated this finding in a large sample of African American women. This region contains several genes, including PFTK1, that regulate cell cycle progression and cell proliferation. This is the first report of a susceptibility locus for incident CHD identified by GWAS in African Americans.

Background

The putative effects of postmenopausal hormone therapy on the association between particulate matter (PM) air pollution and venous thromboembolism (VTE) have not been assessed in a randomized trial of hormone therapy, despite its widespread use among postmenopausal women.

Objective

In this study, we examined whether hormone therapy modifies the association of PM with VTE risk.

Methods

Postmenopausal women 50–79 years of age (n = 26,450) who did not have a history of VTE and who were not taking anticoagulants were enrolled in the Women’s Health Initiative Hormone Therapy trials at 40 geographically diverse U.S. clinical centers. The women were randomized to treatment with estrogen versus placebo (E trial) or to estrogen plus progestin versus placebo (E + P trial). We used age-stratified Cox proportional hazard models to examine the association between time to incident, centrally adjudicated VTE, and daily mean PM concentrations spatially interpolated at geocoded addresses of the participants and averaged over 1, 7, 30, and 365 days.

Results

During the follow-up period (mean, 7.7 years), 508 participants (2.0%) had VTEs at a rate of 2.6 events per 1,000 person-years. Unadjusted and covariate-adjusted VTE risk was not associated with concentrations of PM < 2.5 μm (PM2.5) or < 10 μm (PM10)] in aerodynamic diameter and PM × active treatment interactions were not statistically significant (p > 0.05) regardless of PM averaging period, either before or after combining data from both trials [e.g., combined trial-adjusted hazard ratios (95% confidence intervals) per 10 μg/m3 increase in annual mean PM2.5 and PM10, were 0.93 (0.54–1.60) and 1.05 (0.72–1.53), respectively]. Findings were insensitive to alternative exposure metrics, outcome definitions, time scales, analytic methods, and censoring dates.

Conclusions

In contrast to prior research, our findings provide little evidence of an association between short-term or long-term PM exposure and VTE, or clinically important modification by randomized exposure to exogenous estrogens among postmenopausal women.

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.

INTRODUCTION:

Based on recent analyses, the measures of short-term responsiveness of MRI derived cartilage morphometry may not be as large as earlier studies had suggested. We examined if by selecting regions of interest with denuded cartilage, if the remaining cartilage within this region of interest was susceptible to greater rates of cartilage loss.

METHODS:

Subjects included for this analysis are a subset of the approximately 4700 participants in the Osteoarthritis Initiative (OAI) Study. Bilateral radiographs and 3T MRI (Siemens Trio) of the knees and clinical data are obtained at baseline and annually in all participants.150 subjects from the OAI Progression subcohort all of whom had both frequent symptoms and, in the same knee, radiographic osteoarthritis (ROA defined as definite tibio-femoral osteophytes on x-ray) based on a screening reading done at the OAI clinics. One knee from each subject was selected for analysis. Using sagittal 3D DESSwe MR images from the baseline and 12 follow-up month visit, a segmentation algorithm was applied to the cartilage plates of the index knee to compute the cartilage volume, normalized cartilage volume (Volume normalized to bone surface interface area), and percent denuded area (Total Cartilage Bone Interface area denuded of cartilage). Summary statistics of the changes (absolute and percentage) from baseline at one year and the standardized response mean (SRM), i.e. mean change divided by the standard deviation of that change were calculated. Analyses are stratified into three groups according to baseline assessment of denuded area: those with no denuded area in the region of interest at baseline, and then 2 groups (intermediate denuded area (≤median) and severe (> median) denuded area) of equal sample size.

RESULTS:

On average the subjects were 60.9 years of age and obese with a mean BMI of 30.3 kg/m2. For the combined central medial femur and tibia the mean volume change for the whole sample was −48.2 (SD 159.8) mm3, which gives an SRM of−0.30. In the subsample of knees with no denuded area the SRM was −0.25, in the knees with intermediate denuded area the SRM was −0.30, and in knees with severe denuded area the SRM was -1.00. For normalized volume of the central medial femur in the subsample of knees with no denuded area the SRM was −0.22, in the knees with intermediate denuded area the SRM was −0.26, and in knees with severe denuded area (n=23) the SRM was −0.71. The magnitude of the SRMs was generally smaller in participants with no denuded area. In contrast, the SRMs in participants with denuded area were larger. CONCLUSION: By selecting participants with the presence of cartilage regions with denuded area the ability to demonstrate change in cartilage loss in that specific location is markedly improved compared to persons without a full thickness lesion in that cartilage plate. This option for screening during recruitment in clinical trials could facilitate the detection of participants at greater risk of subsequent cartilage loss.

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).

Purpose

To evaluate whether previously unmeasured biological markers of inflammation or endothelial dysregulation confound the observed association between cardiovascular disease risk perceptions and cardiovascular disease outcomes;

Methods

We conducted a nested case-cohort study among community-dwelling men from Southeastern New England (USA) who were interviewed between 1989 and 1990 as part of the Pawtucket Heart Health Program. We measured C-reactive protein (CRP) and Vascular Endothelial Growth Factor (VEGF) levels from stored sera for a random sample of the parent cohort (control sample, n = 127) and all cases of cardiovascular death observed through 2005 (case sample, n = 44). We evaluated potential confounding using stratified analyses and logistic regression modeling.

Results

Optimistic ratings of risk associated with lower odds of dying from cardiovascular causes among men (OR = 0.39, 95% CI = 0.17, 0.91). Neither CRP nor VEGF confounded these findings.

Conclusions

The strong cardio-protective association between optimistic ratings of cardiovascular disease risk and lower rates of cardiovascular mortality among men is not confounded by baseline biomarkers of systemic inflammation or endothelial dysfunction.

Background

Evidence is mixed regarding how familial predisposition to breast cancer affects the relation between hormone replacement therapy and risk of postmenopausal breast cancer. We investigated whether the risk difference for invasive breast cancer attributable to estrogen plus progesterone replacement therapy is greater among women with a first-degree family history of the disease.

Methods

This study is a longitudinal follow-up of 16,608 postmenopausal women aged 50–79 years who were enrolled between 1993 and 2002 in the Women’s Health Initiative randomized trial of estrogen plus progesterone replacement therapy versus placebo.

Results

Three hundred forty-nine cases of invasive breast cancer occurred during a mean follow-up period of 5.6 years. The invasive breast cancer risk difference attributable to the hormone therapy was 0.007 among women with first-degree family history and 0.005 among the others, resulting in a negligible interaction contrast (IC = 0.002; 95% confidence interval = −0.014 to 0.018). The interaction contrast restricted to estrogen-receptor-positive invasive breast cancers was also negligible (IC = −0.006; 95% CI = −0.021 to 0.008).

Conclusion

Family history and estrogen plus progesterone replacement therapy have independent and noninteracting effects on the risk of invasive breast cancer among participants in the Women’s Health Initiative randomized trial.

Objective

Surgical menopause has been associated with an increased risk of coronary heart disease events. In this study, we aimed to determine the associations between coronary artery calcium (CAC) and hysterectomy, oophorectomy, and hormone therapy use with a focus on the duration of menopause for which there was no hormone therapy use.

Design

In a substudy of the Women’s Health Initiative placebo-controlled trial of conjugated equine estrogens (0.625 mg/d), we measured CAC by computed tomography 1.3 years after the trial was stopped. Participants included 1,064 women with previous hysterectomy, aged 50 to 59 years at baseline. The mean trial period was 7.4 years. Imaging was performed at a mean of 1.3 years after the trial was stopped.

Results

Mean age was 55.1 years at randomization and 64.8 years at CAC measurement. In the overall cohort, there were no significant associations between bilateral oophorectomy, years since hysterectomy, years since hysterectomy without taking hormone therapy (HT), years since bilateral oophorectomy, and years of HT use before Women’s Health Initiative enrollment and the presence of CAC. However, there was a significant interaction between bilateral oophorectomy and prerandomization HT use for the presence of any CAC (P = 0.05). When multivariable analyses were restricted to women who reported no previous HT use, those with bilateral oophorectomy had an odds ratio of 2.0 (95% CI: 1.2–3.4) for any CAC compared with women with no history of oophorectomy, whereas among women with unilateral or partial oophorectomy, the odds of any CAC was 1.7 (95% CI: 1.0–2.8). Among women with bilateral oophorectomy, HT use within 5 years of oophorectomy was associated with a lower prevalence of CAC.

Conclusions

Among women with previous hysterectomy, subclinical coronary artery disease was more prevalent among those with oophorectomy and no prerandomization HT use, independent of traditional cardiovascular disease risk factors. The results suggest that factors related to oophorectomy and the absence of estrogen treatment in oophorectomized women may be related to coronary heart disease.

BACKGROUND

Language barriers among some Latinos may contribute to the lower rates of colorectal cancer (CRC) screening between Latinos and non-Latino Whites. The purpose of this study was to examine the relationship between language and receipt of colorectal cancer screening tests among Latinos and non-Latinos using a geographically diverse, population-based sample of adults.

METHODS

Cross-sectional analysis of the Behavioral Risk Factor Surveillance System (BRFSS) survey. Analysis included adults 50 years of age and older, who completed the 2006 BRFSS in a state that recorded data from English and Spanish-speaking participants.

RESULTS

The primary outcome measure was receipt of colorectal screening tests (fecal occult blood testing within prior 12 months and/or lower endoscopy within 10 years). Of the 99,895 respondents included in the study populations, 33% of Latinos responding-in-Spanish reported having had CRC testing, while 51% of Latinos responding-in-English and 62% of English-speaking non-Latinos reported test receipt. In multivariable analysis, compared to non-Latinos, Latinos responding-in-English were 16% less likely (OR,0.84, 95 % CI, 0.73-0.98), and Latinos responding-in-Spanish were 43% less likely to have received colorectal cancer testing (OR,0.57, 95% CI, 0.44-0.74). Additionally, compared to Latinos responding-in-English, Latinos responding-in-Spanish were 36% less likely to have received CRC testing (OR, 0.64; 95% CI, 0.48-0.84)

CONCLUSION

Latinos responding to the 2006 BRFSS survey in Spanish had a significantly lower likelihood of receiving CRC screening tests compared to non-Latinos and to Latinos responding-in-English. Based on this analysis, Spanish language use is negatively associated with CRC screening and may contribute to disparities in CRC screening.

Objective

Fast low angle shot (FLASH) and double echo steady state (DESS) MRI sequences were recently cross-calibrated for quantification of cartilage morphology at 3 Tesla. In this pilot study for the Osteoarthritis Initiative we compare their test-retest precision and sensitivity to longitudinal change.

Method

9 participants with mild to moderate clinical OA were imaged at baseline, year 1 and year 2. Coronal 1.5mm FLASH and sagittal 0.7mm DESS sequences were acquired; 1.5mm coronal multiplanar reformats (MPR) were obtained from the DESS. Patellar, femoral and tibial cartilage plates were quantified in paired fashion, with blinding to time point.

Results

In the weight-bearing femorotibial joint, average precision errors across plates were 1.8% for FLASH, 2.6% for DESS, and 3.0% for MPR-DESS. Volume loss at year 1 was not significant; at year 2 the average change across the femorotibial cartilage plates was −1.7% for FLASH, −2.8% for DESS, and −0.3% for MPR-DESS. Volume change in the lateral tibia (−5.5%; p<0.03), and in the medial (−2.9%; p<0.04) and lateral femorotibial compartment (−3.8%; p<0.03) were significant for DESS.

Conclusion

FLASH, MPR-DESS and DESS all displayed adequate test-retest precision. Although the comparison between protocols is limited by the small number of participants and by the relatively small longitudinal change in cartilage morphology in this pilot study, the data suggest that significant change can be detected with MRI in a small sample of OA subjects over 2 years.

Recent meta-analyses of European ancestry subjects show strong evidence for association between smoking quantity and multiple genetic variants on chromosome 15q25. This meta-analysis extends the examination of association between distinct genes in the CHRNA5-CHRNA3-CHRNB4 region and smoking quantity to Asian and African American populations to confirm and refine specific reported associations.

Association results for a dichotomized cigarettes smoked per day (CPD) phenotype in 27 datasets (European ancestry (N=14,786), Asian (N=6,889), and African American (N=10,912) for a total of 32,587 smokers) were meta-analyzed by population and results were compared across all three populations.

We demonstrate association between smoking quantity and markers in the chromosome 15q25 region across all three populations, and narrow the region of association. Of the variants tested, only rs16969968 is associated with smoking (p < 0.01) in each of these three populations (OR=1.33, 95%C.I.=1.25–1.42, p=1.1×10−17 in meta-analysis across all population samples). Additional variants displayed a consistent signal in both European ancestry and Asian datasets, but not in African Americans.

The observed consistent association of rs16969968 with heavy smoking across multiple populations, combined with its known biological significance, suggests rs16969968 is most likely a functional variant that alters risk for heavy smoking. We interpret additional association results that differ across populations as providing evidence for additional functional variants, but we are unable to further localize the source of this association. Using the cross-population study paradigm provides valuable insights to narrow regions of interest and inform future biological experiments.

Anterior cruciate ligament (ACL) tears are known to be a risk factor for incident knee osteoarthritis (OA). At the present time, it is unknown whether an incidental ACL tear in those with established knee OA alters the pattern of synovial joint damage. Therefore, our aim was to assess whether ACL tears in persons with knee OA are associated with specific patterns of cartilage loss, meniscal degeneration, and bone marrow lesion (BML) location. We included 160 participants from the progression subcohort of the Osteoarthritis Initiative (OAI) Study, an ongoing 4-year, multicenter study, focusing on knee OA. Regional cartilage morphometry measures including cartilage volume (mm3), denuded area, normalized cartilage volume, bone surface area, as well as location of meniscal pathology and BMLs in index knees on the same side were compared between those with and without ACL tears. Of the 160 subjects (51% women, age 62.1 (±9.9), BMI 30.3 (±4.7) kg/m2), 14.4% had an ACL tear. After adjusting for age, BMI and gender participants with ACL tears had significantly greater cartilage volume in the posterior lateral femur (P = 0.04) and the central medial tibia (0.001) compared to those without ACL tears. Normalized cartilage volume was not different between those with and without ACL tears. In addition, individuals with ACL tears had significantly larger bone surface areas in the medial tibia (P = 0,006), the central medial tibia (P = 0.008), the posterior lateral femur (P = 0.004), and the posterior medial femur (P = 0.04). Furthermore, participants with ACL tears showed significantly more meniscal derangement in the lateral posterior horn (P = 0.019) and significantly more BMLs in the lateral femur (P = 0.0025). We found clear evidence of predominant lateral tibiofemoral involvement, with OA-associated findings on MRI, including increased denuded area and bone surface area, BMLs, and meniscal derangement in knees of individuals with ACL tears compared to those without.

The Metabochip is a custom genotyping array designed for replication and fine mapping of metabolic, cardiovascular, and anthropometric trait loci and includes low frequency variation content identified from the 1000 Genomes Project. It has 196,725 SNPs concentrated in 257 genomic regions. We evaluated the Metabochip in 5,863 African Americans; 89% of all SNPs passed rigorous quality control with a call rate of 99.9%. Two examples illustrate the value of fine mapping with the Metabochip in African-ancestry populations. At CELSR2/PSRC1/SORT1, we found the strongest associated SNP for LDL-C to be rs12740374 (p = 3.5×10−11), a SNP indistinguishable from multiple SNPs in European ancestry samples due to high correlation. Its distinct signal supports functional studies elsewhere suggesting a causal role in LDL-C. At CETP we found rs17231520, with risk allele frequency 0.07 in African Americans, to be associated with HDL-C (p = 7.2×10−36). This variant is very rare in Europeans and not tagged in common GWAS arrays, but was identified as associated with HDL-C in African Americans in a single-gene study. Our results, one narrowing the risk interval and the other revealing an associated variant not found in Europeans, demonstrate the advantages of high-density genotyping of common and rare variation for fine mapping of trait loci in African American samples.

To explore colorectal cancer risk perceptions among Latinos. Focus groups discussions among Spanish-speaking Latinos conducted between February and July 2007 with 37 men and women who were age-eligible for colorectal cancer screening. Predominant themes of perceived colorectal cancer risk included: general cancer risks, risks related to nutrition and the digestive tract, and risks related to sexual practices. Participants frequently referred to the role of diet in keeping the colon “clean,” suggesting that retained feces increase colorectal cancer risk. Among both men and women, rectal sex was commonly associated with increased colorectal cancer risk. Some Latinos may hold misperceptions about colorectal cancer risks, including an association between rectal sex and colon cancer, that may impact their screening behaviors. Clinicians and public health officials should consider these potential risk misperceptions and explore for other risk misperceptions when counseling and educating patients about colorectal cancer screening.

Objective

To compare two semiquantitative scoring systems for assessing the prevalence and severity of morphologic cartilage lesions, meniscal damage and bone marrow lesions from MRIs of knees with OA.

Methods

From participants in the Osteoarthritis Initiative, a sample of 115 knees with radiographic OA at high risk of cartilage loss, were selected based on risk factors for progression. Knee MRIs were read separately using both WORMS and BLOKS, and a subset was fed back to readers for reliability. Baseline readings were used for comparison of the two methods for inter-reader reliability as well as agreement on presence/absence and severity of MRI features at both the compartment level and finer anatomical subregion levels.

Results

Both methods had high inter-reader agreement for all features studied (kappa for WORMS 0.69 to 1.0 and for BLOKS 0.65 to 1.0). . Although the methods agreed well on presence and severity of morphological cartilage lesions (inter-method kappas from 0.66 to 0.95), BLOKS was more sensitive for full thickness defects. The two methods gave equivalent results for extent (kappa 0.74 to 0.80) and number (Spearman’s Rho = 0.85) of BMLs, and little extra information was obtained using the more complex BLOKS BML scoring. Similar results were also obtained for the common types of meniscal damage and extrusion (inter-method kappa 0.85 to 0.94), but the inclusion in BLOKS of meniscal signal abnormality and uncommon types of tear may be an advantage if these prove clinically meaningful.

In conclusion, both WORMS and BLOKS had high reliability. The two methods gave similar results in this sample for prevalence and severity of cartilage loss, bone marrow lesions and meniscal damage. Selecting between, or combining, the two methods should be based on factors such as reader effort, appropriateness for the goals of a study, and longitudinal performance.

Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived “null” variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P<2.5×10−8). The lead SNP (rs9131) on chromosome 4q13 is located in the CXCL2 gene, which encodes a chemotactic cytokine for polymorphonuclear leukocytes. Independent evidence of the novel CXCL2 association with WBC was present in 3,551 Hispanic Americans, 14,767 Japanese, and 19,509 European Americans. The index SNP (rs12149261) on chromosome 16q22 associated with WBC count is located in a large inter-chromosomal segmental duplication encompassing part of the hydrocephalus inducing homolog (HYDIN) gene. We demonstrate that the chromosome 16q22 association finding is most likely due to a genotyping artifact as a consequence of sequence similarity between duplicated regions on chromosomes 16q22 and 1q21. Among the WBC loci recently identified in European or Japanese populations, replication was observed in our African-American meta-analysis for rs445 of CDK6 on chromosome 7q21 and rs4065321 of PSMD3-CSF3 region on chromosome 17q21. In summary, the CXCL2, CDK6, and PSMD3-CSF3 regions are associated with WBC count in African American and other populations. We also demonstrate that large inter-chromosomal duplications can result in false positive associations in GWAS.

Author Summary

Although recent genome-wide association studies have identified common genetic variants associated with total white blood cell (WBC) and WBC sub-type counts in European and Japanese ancestry populations, whether these or other loci account for differences in WBC count among African Americans is unknown. By examining >16,000 African Americans, we show that, in addition to the previously identified Duffy Antigen Receptor for Chemokines (DARC) locus on chromosome 1, another variant, rs9131, and other nearby variants on human chromosome 4 are associated with total WBC count in African Americans. The variants span the CXCL2 gene, which encodes an inflammatory mediator involved in WBC production and migration. We show that the association is not restricted to African Americans but is also present in independent samples of European Americans, Hispanic Americans, and Japanese. This finding is potentially important because WBC mediate or have altered counts in a variety of acute and chronic disorders.