Background and purpose
Carotid intima-media thickness (CIMT) is a subclinical marker of cardiovascular disease (CVD). Recent studies suggest that shorter sleep duration is a risk factor for CVD, but there is limited evidence regarding this association using high-quality, objective assessments of sleep. The aim of this study is to determine whether sleep duration is associated with CIMT.
The study used an observational cohort consisting of 617 black and white middle-aged healthy participants (37–52 y; 58% female) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Multivariable-adjusted linear regression analyses were performed. Sleep duration was measured using wrist actigraphy monitors. CIMT was calculated using the average of 20 measurements of the mean common carotid, bulb and internal CIMT, which was assessed using ultrasound images.
After adjusting for covariates, one hour of longer sleep duration was associated with 0.026 mm less CIMT among men (p=0.02, 95% CI -0.047, -0.005), and 0.001 mm less CIMT among women (p=0.91, 95% CI -0.020, 0.022). Segment-specific analyses indicated that the carotid bulb was a key driver of the observed association.
Shorter objectively assessed sleep duration was associated with greater CIMT among men but not women.
Sleep; carotid intima-media thickness; atherosclerosis; cardiovascular disease
Knee osteoarthritis (OA) increases healthcare use and cost. Women have higher pain and lower quality of life measures compared to men even after accounting for differences in age, body mass index (BMI), and radiographic OA severity. Our objective was to describe gender-specific correlates of complementary and alternative medicine (CAM) use among persons with radiographically confirmed knee OA.
Using data from the Osteoarthritis Initiative, 2,679 women and men with radiographic tibiofemoral OA in at least one knee were identified. Treatment approaches were classified as current CAM therapy (alternative medical systems, mind-body interventions, manipulation and body-based methods, energy therapies, and three types of biologically based therapies) or conventional medication use (over-the-counter or prescription). Gender-specific multivariable logistic regression models identified sociodemographic and clinical/functional correlates of CAM use.
CAM use, either alone (23.9% women, 21.9% men) or with conventional medications (27.3% women, 19.0% men), was common. Glucosamine use (27.2% women, 28.2% men) and chondroitin sulfate use (24.8% women; 25.7% men) did not differ by gender. Compared to men, women were more likely to report use of mind-body interventions (14.1% vs. 5.7%), topical agents (16.1% vs. 9.5%), and concurrent CAM strategies (18.0% vs. 9.9%). Higher quality of life measures and physical function indices in women were inversely associated with any therapy, and higher pain scores were positively associated with conventional medication use. History of hip replacement was a strong correlate of conventional medication use in women but not in men.
Women were more likely than men to use CAM alone or concomitantly with conventional medications.
Obesity is associated with knee pain and is an independent predictor of incident knee osteoarthritis (OA); increased pain with movement often leads patients to adopt sedentary lifestyles to avoid pain. Detailed descriptions of pain management strategies by body mass index (BMI) level among OA patients are lacking. The objectives were to describe complementary and alternative medicine (CAM) and conventional medication use by BMI level and identify correlates of CAM use by BMI level.
Using Osteoarthritis Initiative baseline data, 2,675 patients with radiographic tibiofemoral OA in at least one knee were identified. Use of CAM therapies and conventional medications was determined by interviewers. Potential correlates included SF-12, CES-D, Western Ontario and McMaster Universities Osteoarthritis Index, and Knee injury and Osteoarthritis Outcome Score quality of life. Multinomial logistic regression models adjusting for sociodemographic and clinical factors provided estimates of the association between BMI levels and treatment use; binary logistic regression identified correlates of CAM use.
BMI was inversely associated with CAM use (45% users had BMI ≥35 kg/m2; 54% had BMI <25 kg/m2), but positively associated with conventional medication use (54% users had BMI ≥35 kg/m2; 35.1% had BMI <25 kg/m2). Those with BMI ≥30 kg/m2 were less likely to use CAM alone or in combination with conventional medications when compared to patients with BMI <25 kg/m2.
CAM use is common among people with knee OA but is inversely associated with BMI. Understanding ways to further symptom management in OA among overweight and obese patients is warranted.
Knee osteoarthritis; Obesity; Pain; Complementary and alternative medicine
We examine the prospective association of soft drink consumption with radiographic progression of knee osteoarthritis (OA).
Prospective cohort study.
This study used data from the osteoarthritis initiative (OAI).
In OAI, 2149 participants with radiographic knee OA and having dietary data at baseline were followed up to 12, 24, 36 and 48 months.
The soft drink consumption was assessed with a Block Brief Food Frequency Questionnaire completed at baseline. To evaluate knee OA progression, we used quantitative medial tibiofemoral joint space width (JSW) based on plain radiographs. The multivariate linear models for repeated measures were used to test the independent association between soft drink intake and the change in JSW over time, while adjusting for body mass index and other potential confounding factors.
In stratified analyses by gender, we observed a significant dose–response relationship between baseline soft drink intake and adjusted mean change of JSW in men. With increasing levels of soft drink intake (none, ≤1, 2–4 and ≥5 times/week), the mean decreases of JSW were 0.31, 0.39, 0.34 and 0.60 mm, respectively. When we further stratified by obesity, a stronger dose–response relationship was found in non-obese men. In obese men, only the highest soft drink level (≥5 times/week) was associated with increased change in JSW compared with no use. In women, no significant association was observed.
Our results suggest that frequent consumption of soft drinks may be associated with increased OA progression in men. Replication of these novel findings in other studies demonstrating the reduction in soft drink consumption leads to delay in OA progression is needed.
Rheumatology; Nutrition & Dietetics
Chronic obstructive pulmonary disease (COPD) is a progressive, debilitating disease associated with significant clinical burden and is estimated to affect 15 million individuals in the US. Although a large number of individuals are diagnosed with COPD, many individuals still remain undiagnosed due to the slow progression of the disorder and lack of recognition of early symptoms. Not only is there under-diagnosis but there is also evidence of sub-optimal evidence-based treatment of those who have COPD. Despite the development of international COPD guidelines, many primary care physicians who care for the majority of patients with COPD are not translating this evidence into effective clinical practice.
This paper describes the design and rationale for a randomized, cluster design trial (RCT) aimed at translating the COPD evidence-based guidelines into clinical care in primary care practices. During Phase 1, a needs assessment evaluated barriers and facilitators to implementation of COPD guidelines into clinical practice through focus groups of primary care patients and providers. Using formative evaluation and feedback from focus groups, three tools were developed. These include a computerized patient activation tool (an interactive iPad with wireless data transfer to the spirometer); a web-based COPD guideline tool to be used by primary care providers as a decision support tool; and a COPD patient education toolkit to be used by the practice team. During phase II, an RCT will be performed with one year of intervention within 30 primary care practices. The effectiveness of the materials developed in Phase I are being tested in Phase II regarding physician performance of COPD guideline implementation and the improvement in the clinically relevant outcomes (appropriate diagnosis and management of COPD) compared to usual care. We will also examine the use of a patient activation tool - ‘MyLungAge’ - to prompt patients at risk for or who have COPD to request spirometry confirmation and to request support for smoking cessation if a smoker.
Using a multi-modal intervention of patient activation and a technology-supported health care provider team, we are testing the effectiveness of this intervention in activating patients and improving physician performance around COPD guideline implementation.
COPD; Guidelines; Randomized Clinical Trial; Primary care
Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening and the Women’s Health Initiative (WHI). We tested association between 2,474,333 single nucleotide polymorphisms (SNPs) and serum selenium concentrations using linear regression models. In the first stage (PLCO) 41 SNPs clustered in 15 regions had p < 1 × 10−5. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003) in the second stage (WHI). Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11) and had p between 2.62 × 10−7 and 4.04 × 10−7 in the combined analysis (PLCO + WHI). Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations.
selenium; serum; selenoprotein; genome-wide association study; AGA; NEIL3; SLC39A11
To estimate the effect of education and income on incident heart failure (HF) hospitalization among post-menopausal women.
Investigations of socioeconomic status (SES) have focused on outcomes after HF diagnosis, not associations with incident HF. We used data from the Women’s Health Initiative Hormone Trials to examine the association between SES levels and incident HF hospitalization.
We included 26,160 healthy, post-menopausal women. Education and income were self-reported. ANOVA, Chi-square tests, and proportional hazards models were used for statistical analysis, with adjustment for demographics, co-morbid conditions, behavioral factors, and hormone and dietary modification assignments.
Women with household incomes <$20,000/year had higher HF hospitalization incidence (57.3/10,000 person-years) than women with household incomes >$50,000/year (16.7/10,000 person-years; p<0.01). Women with less than a high school education had higher HF hospitalization incidence (51.2/10,000 person-years) than college graduates and above (25.5/10,000 person-years; p<0.01). In multivariable analyses, women with the lowest income levels had 56% higher risk (HR 1.56, 95% CI 1.19 to 2.04) than the highest income women; women with the least amount of education had 21% higher risk for incident HF hospitalization (HR 1.21, 95% CI 0.90 to 1.62) than the most educated women.
Lower income is associated with an increased incidence of HF hospitalization among healthy, post-menopausal women, whereas multivariable adjustment attenuated the association of education with incident HF.
heart failure; socioeconomic status; women
Framingham-based and Reynolds risk scores for cardiovascular disease (CVD) prediction have not been directly compared in an independent validation cohort.
Methods and Results
We selected a case-cohort sample of the multi-ethnic Women’s Health Initiative Observational Cohort, comprising 1722 cases of major CVD (752 MIs, 754 ischemic strokes, and 216 other CVD deaths) and a random subcohort of 1994 women without prior CVD. We estimated risk using the ATP-III score, the Reynolds risk score, and the Framingham CVD model, reweighting to reflect cohort frequencies. Predicted 10-year risk varied widely between models, with 10% or higher risk in 6%, 10%, and 41% of women using the ATP-III, Reynolds, and Framingham CVD models, respectively. Calibration was adequate for the Reynolds model, but the ATP-III and Framingham CVD models over-estimated risk for CHD and major CVD, respectively. After recalibration, the Reynolds model demonstrated improved discrimination over the ATP-III model through a higher c-statistic (0.765 vs. 0.757, p=0.03), positive net reclassification improvement (NRI) (4.9%, p=0.02) and positive integrated discrimination improvement (IDI) (4.1%, p<0.0001) overall, excluding diabetics (NRI=4.2%, p=0.01), and in white (NRI=4.3%, p=0.04) and black (NRI=11.4, p=0.13) women. The Reynolds (NRI=12.9, p<0.0001) and ATP-III (NRI=5.9%, p=0.0001) models demonstrated better discrimination than the Framingham CVD model.
The Reynolds Risk Score was better calibrated than the Framingham-based models in this large external validation cohort. The Reynolds score also showed improved discrimination overall and in black and white women. Large differences in risk estimates exist between models, with clinical implications for statin therapy.
cardiovascular disease risk factors; models; prediction; risk score; statins
Few studies simultaneously investigated lipids and lipoprotein biomarkers as predictors of ischemic stroke. The value of these biomarkers as independent predictors of ischemic stroke remains controversial.
We conducted a prospective nested case-control study among postmenopausal women from the Women’s Health Initiative Observational Study to assess the relationship between fasting lipids (total cholesterol, LDL-C, HDL-C, and triglycerides), lipoproteins (LDL, HDL and VLDL particle number and size, IDL particle number, and lipoprotein [a]) and risk of ischemic stroke. Among women free of stroke at baseline, 774 ischemic stroke patients were matched according to age and race to controls using a 1:1 ratio.
In bivariate analysis, baseline triglycerides (P<0.001), IDL particles (P<0.01), LDL particles (P<0.01), VLDL triglyceride (P<0.001), VLDL particles (P<0.01), VLDL size (P<0.001), LDL size (P=0.03), and total/HDL cholesterol ratio (P<0.01) were significantly higher among women with incident ischemic stroke, while levels of HDL-C (P<0.01) and HDL size (P<0.01) were lower. No significant baseline difference for total cholesterol (P=0.15), LDL-C (P=0.47), and lipoprotein (a) (P=0.11) was observed. In multivariable analysis, triglycerides, (OR for the highest vs lowest quartile, 1.56; 95% CI, 1.13-2.17, P for trend =0.02), VLDL size (OR 1.59, 95% CI, 1.10-2.28, P for trend =0.03) and IDL particle number (OR 1.46, 95% CI, 1.04-2.04, P for trend =0.02) were significantly associated with ischemic stroke.
Among a panel of lipid and lipoprotein biomarkers, baseline triglycerides, VLDL size and IDL particle number were significantly associated with incident ischemic stroke in postmenopausal women.
Lipids; Lipoproteins; Ischemic Stroke; Women; Triglycerides
To examine use of complementary and alternative medicine (CAM) among individuals with radiographic confirmed osteoarthritis (OA) of the knee
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.
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.
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.
knee osteoarthritis; complementary and alternative medicine; conventional medication
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.
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.
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.
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.
bias (epidemiology); biological markers; diet; energy intake; epidemiologic methods; measurement error; nutrition assessment
The relationship between arthritis and fracture was examined in the Women’s Health Initiative (WHI).
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.
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.
The increase in fracture risk found in this study confirms the importance of fracture prevention in patients with both RA and OA.
Arthritis; Epidemiology; Fracture; Postmenopausal Women
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.
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.
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.
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.
Osteoarthritis; Race; Pain; Complementary and alternative medicine
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.
USA; social isolation; social integration; social support; inflammation; C-reactive protein; coronary heart disease; mortality
To test the hypothesis of a significant association between resting heart rate (RHR) and coronary artery calcium (CAC).
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.
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.
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.
Examine the independent and joint effects of geriatric syndromes (GS) and
cardiometabolic diseases (CMDs) on functional impairment.
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
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.
GSs alone are associated with functional impairment in older women; the
association is stronger in the presence of even one CMD.
Geriatric syndromes; Cardiometabolic disease; Physical functioning
Bone marrow lesions (BMLs) are a common magnetic resonance (MR) feature in patients with osteoarthritis, however their pathological basis remains poorly understood and has not been evaluated in vivo. Our aim was to evaluate the trabecular structure associated with the presence and size of BMLs present in the same regions of interest (ROI) using quantitative MR-based trabecular morphometry.
158 participants in the Osteoarthritis Initiative (OAI) were imaged with a coronal 3D FISP sequence for trabecular morphometry in the same session as the OAI 3T MR knee evaluation. The proximal medial tibial subchondral bone in the central weight-bearing ROI on these knee 3D FISP images were quantitatively evaluated for apparent bone volume fraction, trabecular number, spacing, and thickness. BMLs were also evaluated in the subchondral bone immediately adjacent to the articular cartilage. BML volume was also evaluated within the same trabecular morphometry ROI and semi-quantitatively classified as none, small, or large. Kruskal-Wallis test was used to determine if mean apparent bone volume fraction, trabecular number, spacing, or thickness differed by BML score.
Compared to knees with ROIs containing no BMLs, knees with small or large BMLs had statistically higher apparent bone volume fraction (p<0.01), trabecular number (p<0.01), and thickness (p=0.02), and lower trabecular spacing (p<0.01).
Compared to knees with ROIs containing no BMLs, knees with ROIs containing small or large BMLs had higher apparent bone volume fraction, trabecular number and thickness, but lower trabecular spacing. These findings may represent areas of locally increased bone remodeling or compression.
magnetic resonance imaging; osteoarthritis; knee
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.
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.
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.
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.
accelerometer; physical activity; non-wear time; valid day; osteoarthritis
Vitamin D status has been linked to the risk of cardiovascular disease (CVD). However, the optimal 25hydroxy-vitamin D (25(OH)-vitamin D) levels for potential cardiovascular health benefits remain unclear.
Methods and Results
We searched MEDLINE and EMBASE from 1966 through February 2012 for prospective studies that assessed the association of 25(OH)-vitamin D concentrations with CVD risk. A total of 24 articles met our inclusion criteria, from which 19 independent studies with 6,123 CVD cases in 65,994 participants were included for a meta-analysis. Comparing the lowest to the highest 25(OH)-vitamin D categories, the pooled relative risks (RR) was 1.52 (95% CI: 1.30-1.77) for total CVD, 1.42 (95% CI: 1.19-1.71) for CVD mortality, 1.38 (95% CI: 1.21-1.57) for coronary heart disease, and 1.64 (95% CI: 1.27-2.10) for stroke. These associations remained strong and significant when analyses were limited to studies that excluded participants with baseline CVD and had better controlled for season and confounding. We used a fractional polynomial spline regression analysis to assess the linearity of dose-response association between continuous 25(OH)-vitamin D and CVD risk. The CVD risk increased monotonically across decreasing 25(OH)-vitamin D below approximately 60 nmol/L, with a RR of 1.03 (95% CI: 1.00-1.06) per 25 nmol/L decrement in 25(OH)-vitamin D.
This meta-analysis demonstrated a generally linear, inverse association between circulating 25(OH)-vitamin D in the range of 20-60 nmol/L and risk of CVD. Further research is needed to clarify the association of 25(OH)-vitamin D higher than 60 nmol/L with CVD risk and assess causality of the observed associations.
25hydroxy-vitamin D; cardiovascular disease; meta-analysis; prospective study
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.
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.
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.
In this study, we examined whether hormone therapy modifies the association of PM with VTE risk.
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.
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.
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.
air pollution; deep vein thrombosis; particulate matter; pulmonary embolism; women’s health
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.
body weight changes; diabetes mellitus; obesity
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.
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.
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.
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).
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;
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.
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.
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.