Objective

We examined the association between sleep and odds of developing knee pain, and whether this relationship varied by status of widespread pain (WSP).

Methods

At the 60-month visit of the Multicenter Osteoarthritis Study, sleep quality and restless sleep were each assessed by using a single item from 2 validated questionnaires. Each sleep measure was categorized into 3 levels, with poor/most restless sleep as the reference. WSP was defined as pain above and below the waist on both sides of the body and axially using a standard homunculus, based on the American College of Rheumatology criteria. Outcomes from 60-84 months included (1) knee pain worsening (KPW; defined as minimal clinically important difference in WOMAC pain), (2) prevalent, and (3) incident consistent frequent knee pain. We applied generalized estimating equations in multivariable logistic regression models.

Results

We studied 2329 participants (4658 knees; 67.9 yrs, body mass index 30.9]. We found that WSP modified the relationship between sleep quality and KPW (p = 0.002 for interaction). Among persons with WSP, OR (95% CI) for KPW was 0.53 (0.35-0.78) for those with very good sleep quality (p trend < 0.001); additionally, we found the strongest association of sleep quality in persons with > 8 painful joint sites (p trend < 0.01), but not in those with ≤ 2 painful joint sites. Similar results were observed using restless sleep, in the presence of WSP. The cross-sectional relationship between sleep and prevalence of consistent frequent knee pain was significant.

Conclusion

Better sleep was related to less KPW with coexisting widespread pain.

Background and objectives

To understand the role of premature (defined as ≤ 60 years) cardiovascular disease (CVD) in brain health earlier in life, we examined the associations of premature CVD with midlife cognition and white matter health.

Methods

We studied a prospective cohort in the Coronary Artery Risk Development in Young Adults study, who were 18-30 years at baseline (1985-1986) and followed up to 30 years when 5 cognitive tests measuring different domains were administered. A subset (656 participants) had brain MRI measures of white matter hyperintensity (WMH) and white matter integrity. A premature CVD event was adjudicated based on medical records of coronary heart disease, stroke/TIA, congestive heart failure, carotid artery disease, and peripheral artery disease. We conducted linear regression to determine the associations of nonfatal premature CVD with cognitive performance (z-standardized), cognitive decline, and MRI measures.

Results

Among 3,146 participants, the mean age (57% women and 48% Black) was 55.1 ± 3.6 years, with 5% (n = 147) having premature CVD. Adjusting for demographics, education, literacy, income, depressive symptoms, physical activity, diet, and APOE, premature CVD was associated with lower cognition in 4 of 5 domains: global cognition (-0.22, 95% CI -0.37 to -0.08), verbal memory (-0.28, 95% CI -0.44 to -0.12), processing speed (-0.46, 95% CI -0.62 to -0.31), and executive function (-0.38, 95% CI -0.55 to -0.22). Premature CVD was associated with greater WMH (total, temporal, and parietal lobes) and higher white matter mean diffusivity (total and temporal lobes) after adjustment for covariates. These associations remained significant after adjusting for cardiovascular risk factors (CVRFs) and excluding those with stroke/TIA. Premature CVD was also associated with accelerated cognitive decline over 5 years (adjusted OR 3.07, 95% CI 1.65-5.71).

Discussion

Premature CVD is associated with worse midlife cognition and white matter health, which is not entirely driven by stroke/TIA and even independent of CVRFs. Preventing CVD in early adulthood may delay the onset of cognitive decline and promote brain health over the life course.

Objective

Pain persistence following knee replacement (KR) occurs in ∼20-30% of patients. Although several studies have identified preoperative risk factors for persistent post-KR pain, few have focused on post-KR contributing factors. We sought to determine whether altered nociceptive signaling and other peripheral nociceptive drivers present post-operatively contribute to post-KR pain.

Design

We included participants from the Multicenter Osteoarthritis Study who were evaluated ∼12 months after KR. We evaluated the relation of measures of pain sensitivity [pressure pain threshold (PPT), temporal summation (TS), and conditioned pain modulation (CPM)] and the number of painful body sites to post-KR WOMAC knee pain, and of the number of painful sites to altered nociceptive signaling using linear or logistic regression models, as appropriate.

Results

171 participants (mean age 69 years, 62% female) were included. TS was associated with worse WOMAC pain post-KR (β ​= ​0.77 95% CI:0.19-1.35) and reduced odds of achieving patient acceptable symptom state (aOR ​= ​0.54 95%CI:0.34-0.88). Inefficient CPM was also associated with worse WOMAC pain post-KR (β ​= ​1.43 95% CI:0.15-2.71). In contrast, PPT was not associated with these outcomes. The number of painful body sites present post-KR was associated with TS (β ​= ​0.05, 95% CI:0.01, 0.05).

Conclusions

Post-KR presence of central sensitization and inefficient descending pain modulation was associated with post-KR pain. We also noted that presence of other painful body sites contributes to altered nociceptive signaling, and this may thus also contribute to the experience of knee pain post-KR. Our findings provide novel insights into central pain mechanisms and other peripheral pain sources contributing to post-KR persistent knee pain.

Objective

To determine whether intraarticular glucocorticoid (GC) injections are associated with increased knee osteoarthritis (OA) progression compared to hyaluronic acid (HA) injections, which have been reported to delay OA progression and knee replacement.

Methods

We identified participants from 2 large cohort studies, the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis Study. Study visits were performed at regular intervals and included questionnaires about intraarticular GC or HA injection use in the previous 6 months and incident total knee replacement (TKR). Knee radiographs were obtained at each study visit and interpreted in a similar manner. Outcome measures were radiographic progression based on Kellgren/Lawrence (K/L) grade and joint space narrowing (JSN) for both cohorts and based on medial joint space width for OAI participants, and incident TKR. We compared preinjection and postinjection radiographs to generate rate ratios of progression comparing GC injection with HA injection. A Cox proportional hazards model was used to estimate the rate of TKR for both groups.

Results

We studied 791 participants (980 knees) with knee OA, of whom 629 reported GC injection use and 162 HA injection use. Rate ratios of progression were similar between those receiving GCs and those receiving HA for JSN (1.00 [95% confidence interval (95% CI) 0.83-1.21]), K/L grade (1.03 [95% CI 0.83-1.29]), and medial joint space width (1.03 [95% CI 0.72-1.48]). Hazard of TKR was slightly lower for those receiving intraarticular GC compared to those receiving HA (hazard ratio 0.75 [95% CI 0.51-1.09]).

Conclusion

Intraarticular GC injections are not associated with an increased risk of knee OA progression compared to HA.

Abstract

As the population ages, there is a growing burden owing to musculoskeletal diseases, such as knee osteoarthritis, and subsequent functional decline. In the absence of a cure, there is a need to identify factors amenable to intervention to prevent or slow this process. The Multicenter Osteoarthritis Study cohort was developed for this purpose. In this study, associations between variability in peak knee flexor and extensor torque at baseline and worsening of pain and physical function over the subsequent 60 mos were assessed in a cohort of 2680 participants. The highest quartile of baseline knee flexor torque variability was found to be associated longitudinally with worsening pain (fourth quartile ß estimate, mean ± SE, 0.49 ± 0.19; P = 0.0115; with R2 = 0.28 and P for trend across quartiles = 0.0370) and physical function scores (fourth quartile ß estimate, mean ± SE, 1.39 ± 0.64; P = 0.0296; with R2 = 0.25 and P for trend across quartiles = 0.0371), after adjusting for baseline knee osteoarthritis and maximum knee flexor torque. There were no associations between baseline knee extensor torque and worsening pain or physical function by 60 mos. The presence of greater variability in maximum knee flexor strength may identify patients who may benefit from therapies aimed at preventing worsening knee pain and physical function.

Objective

Whether widespread pain (WSP) affects the risk of developing knee pain or knee osteoarthritis (OA) is unknown and could enhance understanding of pain mechanisms in OA.

Methods

Subjects from the Multicenter OA (MOST) study, a US National Institutes of Health-funded prospective cohort of older adults with or at risk of knee OA, were characterized regarding WSP, defined as pain above and below the waist on both sides of the body and axially using a standard homunculus, excluding knee pain at 60 months (baseline). Followup occurred 2 years later. We assessed the relation of WSP to odds of knee pain worsening (≥ 2-point increase in the Western Ontario and McMaster Universities Arthritis Index pain subscale) using logistic regression, and to odds of incident radiographic knee OA (ROA; Kellgren-Lawrence arthritis scale ≥ grade 2 of either knee among those free of ROA at baseline) and incident consistent frequent knee pain (CFKP; knee pain on most days during the past month among participants free of knee pain at baseline) in 1 or both knees using multinomial regression adjusting for potential confounders.

Results

There were 1752 participants available for analysis [mean age (SD) 67.0 yrs (7.7), body mass index 30.5 kg/m² (5.9), 59% women]. Baseline presence of WSP was not associated with worsened knee pain (adjusted OR 1.15, 95% CI 0.89-1.48, p = 0.30), ROA (adjusted OR 0.86, 95% CI 0.46-1.63, p = 0.65), or incident CFKP (adjusted OR 1.69, 95% CI 0.96-2.96, p = 0.07).

Conclusion

WSP was not significantly associated with worsening knee pain, incident ROA, or CFKP. Development of knee pain and ROA does not appear to be influenced by underlying WSP.

Objective

To examine the relation of knee pain patterns to pain severity and to radiographic osteoarthritis (OA) severity and duration.

Methods

The Multicenter Osteoarthritis Study is a longitudinal cohort of older adults with or at risk of knee OA. Participants' Intermittent and Constant Osteoarthritis Pain (ICOAP) scores were characterized as 1) no intermittent or constant pain, 2) intermittent pain only, 3) constant pain only, and 4) a combination of constant and intermittent pain. Knee pain severity was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale and a visual analog scale (VAS). Radiographic knee OA (ROA) severity was defined as Kellgren/Lawrence grade ≥2, and ROA duration was defined according to the clinic visit at which ROA was first noted. We assessed the relation of ICOAP pain patterns to knee pain severity, ROA severity, and ROA duration using regression models with generalized estimating equations.

Results

There were 2,322 participants (mean age 68.8 years, body mass index 31.0 kg/m² , 60% female). Higher ICOAP pain patterns, i.e., a mix of constant and intermittent pain, were associated with greater WOMAC pain severity compared with those patients without either pain pattern (odds ratio [OR] 43.2 [95% confidence interval (95% CI) 26.4-61.3]). Results were similar for the VAS (OR 71.2 [95% CI 45.7-110.9]). Those patients with more severe and longer duration of ROA were more likely to have a mix of constant and intermittent pain compared with those without either pain (OR 3.7 [95% CI 3.1-4.6] and OR 2.9 [95% CI 2.5-3.5], respectively).

Conclusion

Knee pain patterns are associated with radiographic disease stage and duration, as well as pain severity, highlighting the fact that pain patterns are important for understanding symptomatic disease progression.

Objectives

Insulin resistance is central to the development of non-alcoholic fatty liver disease (NAFLD), and gestational diabetes mellitus (GDM) is an early marker of insulin resistance. We hypothesized that a history of GDM would identify women at higher risk of NAFLD in middle age.

Methods

Women from the multicenter Coronary Artery Risk Development in Young Adults (CARDIA) cohort study who delivered ≥1 birth, were free of diabetes prior to pregnancy(ies), and underwent CT quantification of hepatic steatosis 25 years following cohort entry (Y25: 2010-2011) were included (n=1,115). History of GDM by self-report, validated in a subsample by review of antenatal glucose testing, and metabolic risk factors were assessed prospectively. NAFLD was defined by liver attenuation (LA)≤40 Hounsfield Units on CT scan after exclusion of other causes of hepatic steatosis.

Results

Of 1,115 women meeting selection criteria (57% black, 43% white, median age 25 years at baseline), 124 (11%) reported a history of GDM and 75 (7%) met the CT definition for NAFLD at year 25. The crude risk of NAFLD at the 25-year visit was significantly higher in women with GDM compared to those without (14 vs. 5.8%, OR: 2.56, 95% CI: 1.44-4.55, P<0.01). History of GDM remained associated with NAFLD (OR: 2.29, 95% CI: 1.23-4.27, P=0.01) after adjustment for covariates in multivariable logistic regression. Addition of incident diabetes mellitus (DM) into the final model attenuated the association between GDM and NAFLD (OR: 1.48, 95% CI: 0.73-3.02, P=0.28).

Conclusion

GDM is a risk marker for NAFLD and represents an opportunity to identify women at risk for NAFLD at a young age and may be mediated by the development of incident DM.

Background

While many studies have found the built environment to be associated with walking, most have used cross-sectional research designs and few have examined more distal cardiometabolic outcomes. This study contributes longitudinal evidence based on changes in walking, body mass index (BMI), and cardiometabolic risk following residential relocation.

Methods

We examined 1,079 participants in the CARDIA study who moved residential locations between 2000 and 2006 (ages 32-46 in 2000, 49% white/51% black, 55% female). We created a walkability index from measures of population density, street connectivity, and food and physical activity resources, measured at participants' pre- and post-move residential locations. Outcomes measured before and after the move included walking, BMI, waist circumference, blood pressure, insulin resistance, triglycerides, cholesterol, atherogenic dyslipidemia, and C-reactive protein. Fixed effects (FE) models were used to estimate associations between within-person change in walkability and within-person change in each outcome. These estimates were compared to those from random effects (RE) models to assess the implications of unmeasured confounding.

Results

In FE models, a one-SD increase in walkability was associated with a 0.81 mmHg decrease in systolic blood pressure [95% CI: (-1.55, -0.07)] and a 7.36 percent increase in C-reactive protein [95% CI: (0.60, 14.57)]. Although several significant associations were observed in the RE models, Hausman tests suggested that these estimates were biased for most outcomes. RE estimates were most commonly biased away from the null or in the opposite direction of effect as the FE estimates.

Conclusions

Greater walkability was associated with lower blood pressure and higher C-reactive protein in FE models, potentially reflecting competing health risks and benefits in dense, walkable environments. RE models tended to overstate or otherwise misrepresent the relationship between walkability and health. Approaches that base estimates on variation between individuals may be subject to bias from unmeasured confounding, such as residential self-selection.

Objective

Osteoarthritis (OA) is highly heterogeneous and has both biomechanical and systemic components that may not have the same etiology. We therefore aimed to identify specific knee OA phenotypes that may be more strongly associated with hand OA to refine the criteria used to define multi-joint OA.

Design

We assessed data from the Multicenter Osteoarthritis Study (MOST). We ascertained hand OA from bilateral hand photographs; scores for each joint row were summed to yield an aggregate hand OA score. Knee OA was ascertained from bilateral posteroanterior knee radiographs read for Kellgren-Lawrence grade and individual radiographic features. We tested associations between hand and knee OA with phenotypes including symptomatic OA, hyper- and atrophic knee OA, and one excluding post-traumatic OA. Associations between hand and knee OA were assessed with logistic regression, adjusted for age.

Results

We studied 2493 participants with hand and knee OA measures. Median age was 63 years with 57% women. 55% had an aggregate hand OA score ≥2; frequency of knee OA phenotypes ranged from 8% to 34%. The age-adjusted odds ratio (OR) was 1.14 (95% confidence interval (CI) ​= ​1.04-1.26) for knee OA per standard deviation of the hand OA aggregate score. Hand OA associations with symptomatic knee OA and knee OA excluding post-traumatic knee OA were OR ​= ​1.16 (95% CI ​= ​1.03-1.31) and OR ​= ​1.21 (95% CI ​= ​1.08-1.35), respectively. No other knee OA phenotype reached statistical significance.

Conclusions

Age-adjusted associations between hand and knee OA were modest and were largely similar across knee OA phenotypes.