To assess the association of prevalent cartilage damage and cartilage loss over time with incident bone marrow lesions (BMLs) in the same subregion of the tibiofemoral compartments as detected on magnetic resonance imaging (MRI).
The Multicenter Osteoarthritis Study is an observational study of individuals with or at risk for knee osteoarthritis (OA). Subjects whose baseline and 30-month follow-up MRIs were read for findings of OA were included. MRI was performed with a 1.0T extremity system. Tibiofemoral compartments were divided into 10 subregions. Cartilage morphology was scored from 0 to 6 and BMLs were scored from 0 to 3. Prevalent cartilage damage and cartilage loss over time were considered predictors of incident BMLs. Associations were assessed using logistic regression, with adjustments for potential confounders.
Medially, incident BMLs were associated with baseline cartilage damage (adjusted odds ratio (OR) 3.9 [95% CI 3.0, 5.1]), incident cartilage loss (7.3 [95% CI 5.0, 10.7]) and progression of cartilage loss (7.6 [95% CI 5.1, 11.3]) Laterally, incident BMLs were associated with baseline cartilage damage (4.1 [95% CI 2.6, 6.3]), incident cartilage loss (6.0 [95% CI 3.1, 11.8]), and progression of cartilage loss (11.9 [95% CI 6.2, 23.0]).
Prevalent cartilage damage and cartilage loss over time are strongly associated with incident BMLs in the same subregion, supporting the significance of the close interrelation of the osteochondral unit in the progression of knee OA.
Bone marrow; cartilage; knee; osteoarthritis; magnetic resonance imaging
We investigate how early adult and 20-year changes in modifiable cardiovascular risk factors (MRF) predict left atrial dimension (LAD) at age 43–55 years.
The Coronary Artery Risk Development in Young Adults (CARDIA) study enrolled black and white adults (1985–1986). We included 2903 participants with echocardiography and MRF assessment in follow-up years 5 and 25. At years 5 and 25, LAD was assessed by M-mode echocardiography, then indexed to body surface area (BSA) or height. Blood pressure (BP), body mass index (BMI), heart rate (HR), smoking, alcohol use, diabetes and physical activity were defined as MRF. Associations of MRF with LAD were assessed using multivariable regression adjusted for age, ethnicity, gender and year-5 left atrial (LA) size.
The participants were 30±4 years; 55% white; 44% men. LAD and LAD/height were modest but significantly higher over the follow-up period, but LAD/BSA decreased slightly. Increased baseline and 20-year changes in BP were related to enlargement of LAD and indices. Higher baseline and changes in BMI were also related to higher LAD and LAD/height, but the opposite direction was found for LAD/BSA. Increase in baseline HR was related to lower LAD but not LAD indices, when only baseline covariates were included in the model. However, baseline and 20-year changes in HR were significantly associated to LA size.
In a biracial cohort of young adults, the most robust predictors for LA enlargement over a 20-year follow-up period were higher BP and BMI. However, an inverse direction was found for the relationship between BMI and LAD/BSA. HR showed an inverse relation to LA size.
Knee Osteoarthritis (OA) and pain are assumed to be barriers for meeting physical activity guidelines, but this has not been formally evaluated. The purpose of this study was to determine the proportion of people with and without knee OA and knee pain who met recommended physical activity levels through walking.
Cross-sectional analysis of community dwelling adults who have or who are at high risk of knee OA from The Multicenter Osteoarthritis Study. Participants wore a StepWatch activity monitor to record steps/day over 7 days. The proportion that met the recommended physical activity levels was determined as those accumulating ≥150 minutes/week at ≥100 steps/minute in bouts lasting ≥10 minutes. These proportions were also determined for those with and without knee OA, as classified by radiograph, and by severity of knee pain.
Of the 1788 study participants (age 67 sd 8 yrs, BMI 31 sd 6 kg/m2, 60% female), lower overall percentages of participants with radiographic knee OA and knee pain met recommended physical activity levels. However, these differences were not statistically significant between those with and without knee OA; 7.3% and 10.1% of men (p=0.34), and 6.3% and 7.8% of women (p=0.51), respectively, met recommended physical activity levels. Similarly, for those with moderate/severe pain versus no pain, 12.9% and 10.9% of men (p=0.74) and 6.7% and 11.0% (p=0.40) of women met recommended physical activity levels.
Disease and pain have little impact on achieving recommended physical activity levels among people with or at high risk of knee OA.
To assess risk of cartilage loss in the tibiofemoral joint in relation to baseline damage severity, and to analyze the association of nearby pathologic findings on the risk of subsequent cartilage loss.
The Multicenter Osteoarthritis (MOST) Study is a longitudinal study of individuals with or at high risk for knee osteoarthritis. Magnetic resonance imaging (MRI) examinations were assessed according to the Whole Organ Magnetic Resonance Imaging Score (WORMS). Included were all knees with available baseline and 30 months MRIs. Ordinal logistic regression was used to estimate risk of cartilage loss in each subregion in relation to the number of associated articular features including bone marrow lesions, meniscal damage and extrusion and also in regard to baseline damage severity, respectively.
13524 subregions of 1365 knees were included. 3777 (27.9%) subregions exhibited prevalent cartilage damage at baseline and 1119 (8.3%) subregions showed cartilage loss at 30-month follow-up. Risk of cartilage loss was increased for subregions with associated features (ORs 2.53, 95% confidence interval [CI] 2.03-3.15 for one, 4.32 95% CI 3.42-5.47 for two and 5.30 95% CI 3.95-7.12 for three associated features; p for trend <0.0001). Subregions with prevalent cartilage damage showed increased risk for further cartilage loss compared to subregions with intact cartilage at baseline with small superficial defects exhibiting highest risk.
Risk of cartilage loss is increased for subregions with associated pathology and further increased when more than one type of associated feature is present. In addition, prevalent cartilage damage increases risk for subsequent cartilage loss.
magnetic resonance imaging; osteoarthritis; risk factors; cartilage loss; meniscal damage; mensical extrusion; bone marrow lesions
In order to increase sensitivity to detect longitudinal change, recording of within-grade changes was introduced for cartilage morphology and bone marrow lesion (BML) assessment in semiquantitative magnetic resonance imaging (MRI) scoring of knee osteoarthritis. The aim of this study was to examine the validity provided by within-grade scoring.
The Multicenter Osteoarthritis (MOST) Study is a longitudinal study of subjects with or at risk of knee osteoarthritis. Baseline and 30 months MRIs were read according to the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) system including within-grade changes for cartilage and BMLs. We tested the validity of within-grade changes by whether the 30 month changes in cartilage and bone marrow lesion assessment were predicted by baseline ipsi-compartmental meniscal damage and malalignment, factors known to affect cartilage loss and bone marrow lesions, using ordinal logistic regression.
1867 knees (from 1411 participants) were included. Severe medial meniscal damage predicted partial grade (aOR 4.4, 95%CI 2.2,8.7) but not ≥ full grade (aOR 1.3, 95%CI 0.8,2.2) worsening of cartilage loss and predicted both, partial grade (aOR 9.6, 95%CI 3.6,25.1) and ≥ full grade (aOR 5.1, 95%CI 3.2,8.2) worsening of BMLs. Severe, but not moderate, malalignment predicted ipsicompartmental within-grade (medial cartilage damage: aOR 5.5, 95%CI 2.6,11.6; medial worsening of BMLs: aOR 4.9, 95%CI 2.0,12.3) but not full grade worsening of BMLs and cartilage damage.
Within-grade changes in semiquantitative MRI assessment of cartilage and bone marrow lesions are valid and their use may increase the sensitivity of semiquantitative readings in detecting longitudinal changes in these structures.
osteoarthritis; MRI; semiquantitative scoring; WORMS; within grade; validity
Data supporting physical activity guidelines to prevent long-term weight gain are sparse, particularly during the period when the highest risk of weight gain occurs.
To evaluate the relationship between habitual activity levels and changes in body mass index (BMI) and waist circumference over 20 years.
Design, Setting, and Participants
The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective longitudinal study with 20 years of follow-up, 1985-86 to 2005-06. Habitual activity was defined as maintaining high, moderate, and low activity levels based on sex-specific tertiles of activity scores at baseline. Participants comprised a population-based multi-center cohort (Chicago, Illinois; Birmingham, Alabama; Minneapolis, Minnesota; and Oakland, California) of 3554 men and women aged 18 to 30 years at baseline.
Main Outcome Measures
Average annual changes in BMI and waist circumference
Over 20 years, maintaining high levels of activity was associated with smaller gains in BMI and waist circumference compared with low activity levels after adjustment for race, baseline BMI, age, education, cigarette smoking status, alcohol use, and energy intake. Men maintaining high activity gained 2.6 fewer kilograms (+ 0.15 BMI units per year; 95 % confidence interval [CI] 0.11-0.18 vs +0.20 in the lower activity group; 95% CI, 0.17-0.23) and women maintaining higher activity gained 6.1 fewer kilograms (+0.17 BMI units per year; 95 % CI, 0.12-0.21 vs. +0.30 in the lower activity group; 95 % CI, 0.25-0.34). Men maintaining high activity gained 3.1 fewer centimeters in waist circumference (+0.52 cm per year; 95 % CI, 0.43-0.61 cm vs 0.67 cm in the lower activity group; 95 % CI, 0.60-0.75) and women maintaining higher activity gained 3.8 fewer centimeters (+0.49 cm per year; 95 % CI, 0.39-0.58 vs 0.67 cm in the lower activity group; 95 % CI, 0.60-0.75).
Maintaining high activity levels through young adulthood may lessen weight gain as young adults transition to middle age, particularly in women.
Varus and valgus alignment are associated with progression of knee osteoarthritis, but their role in incident disease is less certain. Radiographic measures of incident knee osteoarthritis may be capturing early progression rather than disease development. We tested the hypothesis: in knees with normal cartilage morphology by MRI, varus is associated with incident medial cartilage damage and valgus with incident lateral damage.
In MOST, a prospective study of persons at risk for or with knee osteoarthritis, baseline full-limb x-rays and baseline and 30-month MRIs were acquired. In knees with normal baseline cartilage morphology in all tibiofemoral subregions, we used logistic regression with GEE to examine the association between alignment and incident cartilage damage adjusting for age, gender, BMI, laxity, meniscal tear, and extrusion.
Of 1881 knees, 293 from 256 persons met criteria. Varus vs. non-varus was associated with incident medial damage (adjusted OR 3.59, 95% CI: 1.59, 8.10), as was varus vs. neutral, with evidence of a dose effect (adjusted OR 1.38/1° varus, 95% CI: 1.19, 1.59). Findings held even excluding knees with medial meniscal damage. Valgus was not associated with incident lateral damage. Varus and valgus were associated with a reduced risk of incident lateral and medial damage, respectively.
In knees with normal cartilage morphology, varus was associated with incident cartilage damage in the medial compartment, and varus and valgus with a reduced risk of incident damage in the less loaded compartment. These results support that varus increases the risk for initial development of knee osteoarthritis.
Slow heart rate recovery (HRR) from a graded exercise treadmill test (GXT) is a marker of impaired parasympathetic reactivation that is associated with elevated mortality. Our objective was to test whether demographic, behavioral or coronary heart disease (CHD) risk factors during young adulthood were associated with the development of slow HRR.
Participants from the Coronary Artery Risk Development in Young Adults study underwent symptom-limited maximal GXT using a modified Balke protocol at baseline (1985–86) and 20-year follow-up (2005–06) examinations. HRR was calculated as the difference between peak heart rate (HR) and HR two-minutes following cessation of the GXT. Slow HRR was defined as 2-minute HRR < 22 beats·min−1.
In 2,730 participants who did not have slow HRR at baseline, mean HRR was 44 beats*min−1 (SD = 11) at baseline and declined to 40 beats·min−1 (SD=12) in 2005–06; slow HRR developed in 5% (n=135) of the sample by 2005–06. Female sex, black race, fewer years of education, obesity, cigarette smoking, higher depressive symptoms, higher fasting glucose, hypertension, metabolic syndrome and physical inactivity and low fitness were each associated with incident slow HRR. In a multivariable model higher BMI, larger waist, low education, fasting glucose and current smoking remained significantly associated with incident slow HRR. Increasing BMI (per SD higher) over follow-up and incident hypertension, diabetes and metabolic syndrome (in the subsets of participants who were free from those conditions at baseline), were each associated with a significantly elevated odds of incident slow HRR.
On average, HRR declines with aging; however, the odds of having slow HRR in early middle age is significantly associated with traditional CHD risk factors.
Epidemiology; Cardiovascular Disease; Exercise; Autonomic Nervous System
Serum phosphorus is associated with cardiovascular disease (CVD) in the general population but may not comprehensively reflect phosphorus homeostasis. Whether urine phosphorus/creatinine ratio (UPi/UCr, a marker of intestinal absorption) or urine fractional excretion of phosphorus (FePi, a marker of urinary phosphorus handling) is associated with risk of mortality or CVD is uncertain.
Prospective observational study.
Setting and Participants
1,325 community-dwelling men aged ≥65 years.
Serum phosphorus, UPi/UCr, and FePi.
All-cause and CVD death.
Mean age was 74±6 years, eGFR was 75±16 ml/min/1.73m2, and serum phosphorus was 3.2±0.4 mg/dL. During 9.3 years median follow-up, there were 364 deaths (120 CVD deaths). After adjustment for demographics, CVD risk factors, and kidney function, the risks of all-cause death in the highest quartiles of serum phosphorus (≥3.6 mg/dL), UPi/UCr, and FePi were 1.63 (95% CI 1.23-2.17), 1.22 (95% CI 0.90-1.65), and 0.88 (95% CI 0.64-1.23), respectively. Results were similar for CVD death. Results were also similar irrespective of eGFR above or below 60 ml/min/1.73m2.
Older, all male cohort. Few had advanced CKD. Specimens were collected in the morning after an overnight fast.
In community-living older men, higher serum phosphorus is associated with all-cause and CVD death. In contrast, UPi/UCr and FePi were not. These findings do not support using UPi/UCr or FePi as adjuvant measures to predict risk of mortality or CVD in the general population.
Phosphorus; urine phosphorus; mortality; cardiovascular disease; kidney disease; geriatrics
The Look AHEAD (Action for Health in Diabetes) Study is a long-term clinical trial that aims to determine the cardiovascular disease (CVD) benefits of an intensive lifestyle intervention (ILI) in obese adults with type 2 diabetes. The study was designed to have 90% statistical power to detect an 18% reduction in the CVD event rate in the ILI Group compared to the Diabetes Support and Education (DSE) Group over 10.5 years of follow-up.
The original power calculations were based on an expected CVD rate of 3.125% per year in the DSE group; however, a much lower-than-expected rate in the first 2 years of follow-up prompted the Data and Safety Monitoring Board (DSMB) to recommend that the Steering Committee undertake a formal blinded evaluation of these design considerations. The Steering Committee created an Endpoint Working Group (EPWG) that consisted of individuals masked to study data to examine relevant issues.
The EPWG considered two primary options: (1) expanding the definition of the primary endpoint and (2) extending follow-up of participants. Ultimately, the EPWG recommended that the Look AHEAD Steering Committee approve both strategies. The DSMB accepted these modifications, rather than recommending that the trial continue with inadequate statistical power.
Trialists sometimes need to modify endpoints after launch. This decision should be well justified and should be made by individuals who are fully masked to interim results that could introduce bias. This article describes this process in the Look AHEAD study and places it in the context of recent articles on endpoint modification and recent trials that reported endpoint modification.
Health care access is associated with improved control of multiple chronic diseases, but the association between health care access and weight change is unclear. This study aims to test the association between health care access and weight change.
The Coronary Artery Risk Development in Young Adults (CARDIA) study is a multi-center population-based prospective study. Weight change was calculated at 3 and 13 years after CARDIA year 7 (1992–1993). Health care access was defined as no barriers or one or more barriers to access (health insurance gap, no usual source of care, not seeking care due to expense). Intermediary variables evaluated included history of dieting, and use of diet pills, meal replacements, or weight control programs.
Four cities in the United States.
Participants were aged 18–30 years at baseline (1985–1986). Analyses include 3922 black and white men and women with relevant data from CARDIA years 7, 10, and 20 (1992–1993, 1995–1996, and 2005–2006, respectively).
Mean weight change was +4.9 pounds by 3 years and +18.7 pounds by 13 years, with no differences by health care access. Being on a weight-reducing diet was not consistently associated with health care access across examinations. Use of diet pills, meal replacements or organized weight control programs was low, and did not vary by health care access.
Weight gain was high irrespective of health care access. Public health and clinical approaches are needed to address weight gain.
health care accessibility; body weight change
While depressive symptoms and knee pain are independently known to impede daily walking in older adults, it is unknown whether positive affect promotes daily walking. This study investigated this association among adults with knee osteoarthritis (OA) and examined whether knee pain modified this association.
Cross-sectional analysis of the Multicenter Osteoarthritis Study. We included 1018 participants (mean age 63.1 ± 7.8 years, 60% female) who had radiographic knee OA and had worn a StepWatch monitor to record steps/day. High- and low- positive affect, and depressive symptoms were based on the Center for Epidemiologic Studies-Depression Scale. Knee pain was categorized as present in respondents who reported pain on most days at both a clinic visit and a telephone screen.
Compared to respondents with low positive affect (27% of respondents), those with high positive affect (63%) walked similar steps/day while those with depressive symptoms (10%) walked less (adjusted beta coefficients = −32.6 [−458.9, 393.8] and −579.1 [−1274.9, 116.7], respectively). There was a statistically significant interaction of positive affect by knee pain (p= 0.0045). Among respondents with knee pain (39%), those with high positive affect walked significantly more steps/day (711.0 [55.1, 1366.9]) than those with low positive affect.
High positive affect was associated with more daily walking among adults with painful knee OA. Positive affect may be an important psychological factor to consider to promote physical activity among people with painful knee OA.
Physical Activity; Positive Affect; Depressive Symptoms; Knee Pain; Walking
Osteoarthritis is the most common form of arthritis, with knee osteoarthritis being the leading cause of lower extremity disability among older adults in the US. There are no treatments available to prevent the structural pathology of osteoarthritis. Because of vitamin K’s role in regulating skeletal mineralization, it has potential to be a preventative option for osteoarthritis. We therefore examined the relation of vitamin K to new-onset radiographic knee osteoarthritis and early osteoarthritis changes on magnetic resonance imaging (MRI).
Subjects from the Multicenter Osteoarthritis (MOST) Study had knee radiographs and MRI scans obtained at baseline and 30 months later, and plasma phylloquinone (vitamin K) measured at baseline. We examined the relationship of subclinical vitamin K deficiency to incident radiographic knee osteoarthritis and MRI-based cartilage lesions and osteophytes, respectively, using log binomial regression with generalized estimating equations, adjusting for potential confounders.
Among 1180 participants (62% women, mean age 62 ± 8 years, mean body mass index 30.1 ± 5.1 kg/m2), subclinical vitamin K deficiency was associated with incident radiographic knee osteoarthritis (risk ratio [RR] 1.56; 95% confidence interval [CI], 1.08–2.25) and cartilage lesions (RR 2.39; 95% CI, 1.05–5.40) compared with no deficiency, but not with osteophytes (RR 2.35; 95% CI, 0.54–10.13). Subclinically vitamin K-deficient subjects were more likely to develop osteoarthritis in one or both knees than neither knee (RR 1.33; 95% CI, 1.01–1.75 and RR 2.12; 95% CI, 1.06-4.24, respectively).
In the first such longitudinal study, subclinical vitamin K deficiency was associated with increased risk of developing radiographic knee osteoarthritis and MRI-based cartilage lesions. Further study of vitamin K is warranted given its therapeutic/prophylactic potential for osteoarthritis.
Incident knee osteoarthritis; MRI cartilage abnormalities; Vitamin K
Intermuscular adipose tissue (IMAT) is associated with metabolic abnormalities similar to those associated with visceral adipose tissue (VAT). Increased IMAT has been found in obese human immunodeficiency virus (HIV)-infected women. We hypothesized that IMAT, like VAT, would be similar or increased in HIV-infected persons compared with healthy controls, despite decreases in subcutaneous adipose tissue (SAT) found in HIV infection. In the second FRAM (Study of Fat Redistribution and Metabolic Change in HIV infection) exam, we studied 425 HIV-infected subjects and 211 controls (from the Coronary Artery Risk Development in Young Adults study) who had regional AT and skeletal muscle (SM) measured by magnetic resonance imaging (MRI). Multivariable linear regression identified factors associated with IMAT and its association with metabolites. Total IMAT was 51% lower in HIV-infected participants compared with controls (P = 0.003). The HIV effect was attenuated after multivariable adjustment (to −28%, P < 0.0001 in men and −3.6%, P = 0.70 in women). Higher quantities of leg SAT, upper-trunk SAT, and VAT were associated with higher IMAT in HIV-infected participants, with weaker associations in controls. Stavudine use was associated with lower IMAT and SAT, but showed little relationship with VAT. In multivariable analyses, regional IMAT was associated with insulin resistance and triglycerides (TGs). Contrary to expectation, IMAT is not increased in HIV infection; after controlling for demographics, lifestyle, VAT, SAT, and SM, HIV+ men have lower IMAT compared with controls, whereas values for women are similar. Stavudine exposure is associated with both decreased IMAT and SAT, suggesting that IMAT shares cellular origins with SAT.
To evaluate the effect of HIV infection on longitudinal changes in kidney function and to identify independent predictors of kidney function changes in HIV-infected individuals.
A prospective cohort.
Cystatin C was measured at baseline and at the 5-year follow-up visit of the Study of Fat Redistribution and Metabolic Change in HIV infection in 554 HIV-infected participants and 230 controls. Control participants were obtained from the Coronary Artery Risk Development in Young Adults study. Glomerular filtration rate (eGFRcys) was estimated using the formula 76.7 × cysC−1.19.
Compared with controls, HIV-infected participants had a greater proportion of clinical decliners (annual decrease in eGFRcys > 3 ml/min per 1.73 m2; 18 versus 13%, P=0.002) and clinical improvers (annual increase in eGFRcys > 3 ml/min per 1.73 m2; 26 versus 6%, P< 0.0001). After multivariable adjustment, HIV infection was associated with higher odds of both clinical decline (odds ratio 2.2; 95% confidence interval 1.3, 3.9, P = 0.004) and clinical improvement (odds ratio 7.3; 95% confidence interval 3.9, 13.6, P ≤ 0.0001). Among HIV-infected participants, a decrease in HIV viral load during follow-up was independently associated with clinical improvement; conversely, higher baseline and an increase in viral load during follow-up were associated with clinical decline. No individual antiretroviral drug or drug class appeared to be substantially associated with clinical decline or improvement.
Compared with controls, HIV-infected persons were more likely both to have clinical decline and clinical improvement in kidney function during 5 years of follow-up. The extent of viremic control had a strong association with longitudinal changes in kidney function.
cystatin C; glomerular filtration rate; HIV; kidney; viral load
Calcium plus vitamin D (CaD) supplementation has a modest but significant effect on slowing loss of femoral bone mass and reducing risk of hip fractures in adherent postmenopausal women. The goal of this study was to determine if CaD supplementation influences hip structural parameters that are associated with fracture risk.
We studied 1,970 postmenopausal women enrolled in the Women’s Health Initiative randomized controlled trial of CaD at one of three bone mineral density (BMD) clinical centers. Hip structural analysis software measured BMD and strength parameters on DXA scans at three regions: femoral narrow neck, intertrochanteric and shaft. Random effects models were used to test the average differences in hip BMD and geometry between intervention and placebo.
There was greater preservation of hip BMD at the narrow neck with CaD relative to placebo across six years of intervention. CaD also altered the underlying cross-sectional geometry at the narrow neck in the direction of greater strength with small increases in cross-sectional area and section modulus, and a decrease in buckling ratio with CaD relative to placebo. While trends at both the intertrochanter and shaft regions were similar to those noted at the narrow neck, no significant intervention effects were evident. There was no significant interaction of CaD and age or baseline calcium levels for hip structural properties.
CaD supplementation is associated with modest beneficial effects on hip structural features at the narrow neck, which may explain some of the benefit of CaD in reducing hip fracture risk.
Calcium and Vitamin D Supplementation; Bone Strength; Postmenopausal Women; Hip Structure
To examine the associations between insulin resistance and changes in body composition in older men without diabetes mellitus.
Longitudinal cohort study of older men participating in the Osteoporotic Fractures in Men (MrOS) study.
Six U.S. clinical centers.
Three thousand one hundred thirty-two ambulatory men aged 65 and older at baseline.
Baseline insulin resistance was calculated for men without diabetes mellitus using the homeostasis model assessment of insulin resistance (HOMA-IR). Total lean, appendicular lean, total fat, and truncal fat mass were measured using dual energy X-ray absorptiometry scans at baseline and 4.6 ± 0.3 years later in 3,132 men with HOMA-IR measurements.
There was greater loss of weight, total lean mass, and appendicular lean mass and less gain in total fat mass and truncal fat mass with increasing quartiles of HOMA-IR (P<.001 for trend). Insulin-resistant men in the highest quartile had higher odds of 5% or more loss of weight (odds ratio (OR) = 1.88, 95% confidence interval (CI) = 1.46–2.43), total lean mass (OR = 2.09, 95% CI = 1.60–2.73) and appendicular lean mass (OR= 1.57, 95% CI = 1.27–1.95) and lower odds of 5% or more gain in total fat mass (OR = 0.56, 95% CI = 0.45–0.68) and truncal fat mass (OR = 0.52, 95% CI = 0.42–0.64) than those in the lowest quartile. These findings remained significant after accounting for age, site, baseline weight, physical activity, and change in physical activity. These associations were also independent of other metabolic syndrome features and medications.
Greater lean mass loss and lower fat mass gain occurred in insulin-resistant men without diabetes mellitus than in insulin-sensitive men. Insulin resistance may accelerate age-related sarcopenia.
older men; lean mass; fat mass; insulin resistance; body composition
Few studies to date have described the prevalence of electrocardiographic (ECG) abnormalities in a biracial middle-aged cohort.
Methods and Results
Participants underwent measurement of traditional risk factors and 12-lead ECGs coded using both Minnesota Code (MC) and Novacode (NC) criteria. Among 2585 participants, of whom 57% were women and 44% were black (mean age 45 years), the prevalence of major and minor abnormalities were significantly higher (all P<0.001) among black men and women compared to whites. These differences were primarily due to higher QRS voltage and ST/T wave abnormalities among blacks. There was also a higher prevalence of Q waves (MC 1-1, 1-2, 1-3) than described by previous studies. These racial differences remained after multivariate adjustment for traditional cardiovascular (CV) risk factors.
Black men and women have a significantly higher prevalence of ECG abnormalities, independent of traditional CV risk factors, than whites in a contemporary cohort middle-aged participants.
The overall goal of this study was to assess the longitudinal changes in bone strength in women reporting rheumatoid arthritis (RA) (n=78) compared to non-arthritic control participants (n=4,779) of the Women's Health Initiative Bone Mineral Density sub-cohort. Hip structural analysis program was applied to archived dual energy X-ray absorptiometry scans (baseline, years 3, 6, and 9) to estimate bone mineral density (BMD) and hip structural geometry parameters in three femoral regions: narrow neck, intertrochanteric and shaft. The association between RA and hip structural geometry was tested using linear regression and random coefficient models (RCM). Compared to the non-arthritic control the RA group had a lower BMD (p=0.061) and significantly lower outer diameter (p=0.017), cross-sectional area (p=0.004), and section modulus (p=0.035) at the narrow neck region in the longitudinal models. No significant associations were seen at the intertrochanteric or shaft regions, and the association was not modified by age, ethnicity, glucocorticoid use, or time. Within the WHI-BMD, women with RA group had reduced BMD and structural geometry at baseline, and this reduction was seen at a fixed rate throughout the nine years of study.
Rheumatoid Arthritis; Hip Structural Geometry; Osteoporosis; Epidemiology
Stress has been proposed as a cause of preterm birth (PTB) and small for gestational age (SGA), but stress does not have the same effects on all women. It may be that a woman’s reaction to stress relates to her pregnancy health, and previous studies indicate higher reactivity is associated with reduced birthweight and gestational age. The objective of the study was to examine the relationship between pre-pregnancy cardiovascular reactivity to stress and pregnancy outcome. The sample included 917 women in the Coronary Artery Risk Development in Young Adults (CARDIA) Study who had cardiovascular reactivity measured in 1987–1988 and at least one subsequent singleton live birth within an 18-year period. Cardiovascular reactivity was measured using a video game, star tracing, and cold pressor test. Gestational age and birthweight were based on the women’s self-report, with PTB defined as birth <37 weeks’ gestation and SGA as weight <10th percentile for gestational age. Linear and poisson regression and generalised estimating equations were used to model the relationship between reactivity to stress and birth outcomes with control for confounders. Few associations were seen between reactivity and pregnancy outcomes. Higher pre-pregnancy diastolic blood pressure (adjusted relative risk, 1.14, 95% confidence interval 0.98–1.34) and mean arterial pressure (MAP) reactivity (1.15, 0.98–1.36) were associated with risk of PTB at first pregnancy, while SGA was associated with lower SBP reactivity (0.76, 0.60–0.95). No associations were seen with other measures of reactivity. Contrary to hypothesis, the association between heart rate reactivity and preterm birth in first pregnancy was stronger in whites (aRRs 1.39, 1.03–1.88) than in blacks (1.00, 0.83–1.20; p for interaction=0.08). Similar results were found for mean arterial pressure. No strong associations were found between higher pre-pregnancy stress reactivity and SGA or PTB, and stress reactivity did not have a stronger association with birth outcomes in blacks than whites.
To evaluate if two different measures of synovial activation, baseline Hoffa-synovitis and effusion-synovitis, assessed by MRI, predict cartilage loss in the tibiofemoral joint at 30 months follow-up in subjects with neither cartilage damage nor tibiofemoral radiographic osteoarthritis (OA) of the knee.
Non-contrast enhanced MRI was performed using proton density-weighted fat-suppressed sequences in the axial and sagittal planes and a STIR sequence in the coronal plane. Hoffa-synovitis, effusion-synovitis and cartilage status were assessed semiquantitatively according to the WORMS scoring system. Included were knees that had neither radiographic OA nor MRI-detected tibio-femoral cartilage damage at the baseline visit. Presence of Hoffa-synovitis was defined as any grade ≥2 (range from 0–3) and effusion-synovitis as any grade ≥2 (range from 0–3). We performed logistic regression to examine the relation of presence of either measure to the risk of cartilage loss at 30 months adjusting for other potential confounders of cartilage loss.
Of 514 knees included in the analysis, prevalence of Hoffa-synovitis and effusion-synovitis at the baseline visit was 8.4% and 10.3%, respectively. In the multivariable analysis, baseline effusion-synovitis was associated with an increased risk for cartilage loss (odds ratio (OR) = 2.7, 95% confidence intervals 1.4–5.1, p=0.002); however, no such an association was observed for baseline Hoffa-synovitis (OR =1.0, 95% confidence intervals 0.5–2.0).
Baseline effusion-synovitis, but not Hoffa-synovitis, predicted cartilage loss. Our findings suggest that effusion-synovitis, a reflection of inflammatory activity including joint effusion and synovitic thickening, may play a role in future development of cartilage lesions in knees without OA.
Osteoarthritis; magnetic resonance imaging; effusion; synovitis; cartilage loss
Type 2 diabetes in normal weight (body mass index [BMI] <25kg/m2) adults is an intriguing representation of the metabolically obese normal weight phenotype with unknown mortality consequences.
To minimize the influence of diabetes duration and voluntary weight loss on mortality, we tested the association of weight status with mortality in adults with new onset diabetes.
Pooled analysis of five longitudinal cohort studies: Atherosclerosis Risk in Communities Study, 1990–2006; Cardiovascular Health Study, 1992–2008; Coronary Artery Risk Development in Young Adults, 1987–2011; Framingham Offspring Study, 1979–2007; Multi-Ethnic Study of Atherosclerosis, 2002–2011. Participants contributed 27,125 person-years of follow-up.
2,625 participants with incident diabetes
Men and women (age>40 years) who developed incident diabetes based on fasting glucose ≥ 126 mg/dL or newly-initiated diabetes medication and who had concurrent measurements of body mass index (BMI). Participants were classified as normal weight if their BMI was 18.5 to 24.99kg/m2 or overweight/obese if BMI≥25 kg/m2.
Main Outcome Measures
Total, cardiovascular, and non-cardiovascular mortality
The proportion of adults who were normal weight at the time of incident diabetes ranged from 9–21% (overall=12%). Over follow-up, 449 participants died, 178 from cardiovascular causes and 253 from non-cardiovascular causes (18 were not classified). The rate of total, cardiovascular and non-cardiovascular mortality was higher in normal weight participants (248.8, 99.8, and 198.1 per 10,000 person-years, respectively) than overweight/obese participants (152.1, 67.8, and 87.9 per 10,000 person-years, respectively). Following adjustment for demographic characteristics and blood pressure, lipids, waist circumference and smoking status, hazard ratios comparing normal weight participants to overweight/obese participants for total, cardiovascular, and non-cardiovascular mortality were 2.08 (95% confidence interval [CI]: 1.52, 2.85), 1.52 (95% CI: 0.89, 2.58) and 2.32 (95% CI: 1.55, 3.48), respectively.
Adults who are normal weight at the time of incident diabetes have higher mortality than adults who are overweight or obese.
type 2 diabetes; obesity; cardiovascular disease; longitudinal studies
To examine longitudinal changes in total and appendicular lean body mass in older men with impaired fasting glucose (IFG) or diabetes and to determine whether these changes differ by diabetes treatment.
RESEARCH DESIGN AND METHODS
A total of 3,752 ambulatory men aged ≥65 years at baseline participated in a multicenter longitudinal cohort study. Baseline glycemic status was categorized as normoglycemia, IFG, undiagnosed/untreated diabetes, or treated diabetes. Insulin sensitizer medication use (metformin and/or thiazolidinediones) was assessed by prescription medication inventory. The change in total lean and appendicular lean mass was derived from dual X-ray absorptiometry scans taken at baseline and 3.5 ± 0.7 years later.
This male cohort included 1,853 individuals with normoglycemia, 1,403 with IFG, 234 with untreated diabetes, 151 with diabetes treated with insulin sensitizers, and 111 with diabetes treated without insulin sensitizers. Men with untreated diabetes, diabetes treated without insulin sensitizers, or IFG had greater percentage loss in total or appendicular lean mass (P ≤ 0.05 in comparison to normoglycemic men). There remained a significantly greater percentage loss in appendicular lean mass for these groups even after adjustment for medical comorbidities or lifestyle factors. In contrast, the percentage loss in total or appendicular lean mass in men with diabetes treated with insulin sensitizers was significantly less than that in normoglycemic men in minimally and fully adjusted models.
Skeletal muscle loss was accelerated in men with IFG and diabetes, except when the latter was treated with insulin sensitizers. These findings suggest that insulin sensitizers may attenuate muscle loss.
To examine the relationship of knee malalignment with occurrence of incident and enlarging bone marrow lesions (BMLs) and regression of BMLs.
Subjects from the Multicenter Osteoarthritis Study aged 50–79 years with or at high risk of knee osteoarthritis were studied. Full-limb radiographs were taken at baseline and hip-knee-ankle mechanical axis was measured. Baseline and 30-month MRI of knees (n=1782) were semiquantitatively assessed for BMLs. Outcome was defined as a change in BML score in femoral/tibial condyle in medial/lateral compartments. Medial compartment in varus alignment and lateral compartment in valgus alignment were combined to form ‘more loaded’ compartment, while lateral compartment in valgus and medial compartment in varus were combined to form ‘less loaded’ compartment. Relative risk (RR) of BML score increase or decrease in relation to malalignment was estimated using a log linear regression model with the Poisson assumption, adjusting for age, gender, body mass index, physical activity scale for the elderly, race and clinic site. Further, results were stratified by ipsilateral meniscal and cartilage status at baseline.
Baseline varus alignment was associated with higher risk of BML score increase from baseline to follow-up in the medial compartment (adjusted RRs [95%CI]: 1.5 [1.2–1.9]) and valgus alignment in the lateral compartment (1.4 [1.0–2.1]). Increase in BML score was more likely in the more loaded compartments (1.7 [1.4–2.0]) in malaligned knees. Regardless of ipsilateral cartilage or meniscus status, adjusted RR for BML score increase was higher in the more loaded compartments of malaligned knees than those with neutral alignment. Decrease in BML score was less likely in the more loaded compartments in malaligned knees (0.8, [0.7–1.0]).
Knee malalignment is associated with increased risk of incident and enlarging BMLs in the more loaded compartments of the tibiofemoral joint.
bone marrow lesion; malalignment; osteoarthritis; knee; MRI