Rheumatoid arthritis, disease-modifying antirheumatic drugs and risk of major osteoporotic fracture: prospective data from the HUNT Study, Norway.

OBJECTIVES: Rheumatoid arthritis has been associated with increased fracture risk. New treatments have improved the course of the disease substantially, but it is not clear if this influences fracture risk. We examined if rheumatoid arthritis, overall and according to disease-modifying antirheumatic drugs (DMARDs), is associated with a risk of major osteoporotic fractures. METHODS: Overall, 92 285 participants in the population-based Nord-Trndelag Health Study (HUNT), Norway were included and linked with hospital records for a validated rheumatoid arthritis diagnosis (n=605), type of DMARD treatment and fracture diagnosis. Participants were followed up until the first major osteoporotic fracture, death, emigration or end of follow-up. Cox regression was used to estimate HRs for fractures among individuals with rheumatoid arthritis, overall and by DMARD treatment, compared with participants without rheumatoid arthritis. RESULTS: A total of 9670 fractures were observed during follow-up, of which 88 were among those with rheumatoid arthritis. Compared with the reference group of participants without rheumatoid arthritis, those with the disease had an HR of fracture of 1.41 (95% CI 1.13 to 1.74). The association was largely similar for users of csDMARDs (HR 1.44; 95% CI 1.15 to 1.81), whereas the association for bDMARD users was weaker and less precise (HR 1.19; 95% CI 0.64 to 2.21). CONCLUSION: Participants with rheumatoid arthritis had a 40% higher risk of fracture than participants without the disease. A similar fracture risk was observed for conventional synthetic DMARD use, whereas there was weak evidence that the use of biological DMARDs may be associated with a somewhat lower fracture risk.

The HUNT study: Association of comorbidity clusters with long-term survival and incidence of exacerbation in a population-based Norwegian COPD cohort.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease often viewed as part of a multimorbidity complex. There is a need for better phenotyping of the disease, characterization of its interplay with other comorbidities and its association with long-term outcomes. This study aims to examine how clusters of comorbidities are associated with severe exacerbations and mortality in COPD. METHODS: Participants with potential COPD were recruited from the second (1995-1997) and third (2006-2008) survey of the HUNT Study and followed up until April 2020. Ten objectively identified comorbidities were clustered using self-organizing maps. Severe COPD exacerbations requiring hospitalization were assessed using hospital data. All-cause mortality was collected from national registries. Multivariable Cox regression was used to calculate hazard ratios (HRs) with 95% CIs for the association between comorbidity clusters and all-cause mortality. Poisson regression was used to calculate incidence rate ratios (IRRs) with 95% CI for the cumulative number of severe exacerbations for each cluster. RESULTS: Five distinct clusters were identified, including 'less comorbidity', 'psychological', 'cardiovascular', 'metabolic' and 'cachectic' clusters. Using the less comorbidity cluster as reference, the psychological and cachectic clusters were associated with all-cause mortality (HR 1.23 [1.04-1.45] and HR 1.83 [1.52-2.20], adjusted for age and sex). The same clusters also had increased risk of exacerbations (unadjusted IRR of 1.24 [95% CI 1.04-1.48] and 1.50 [95% CI 1.23-1.83], respectively). CONCLUSION: During 25 years of follow-up, individuals in the psychological and cachectic clusters had increased mortality. Furthermore, these clusters were associated with increased risk of severe COPD exacerbations.

Association between pelvic floor disorders and bone mineral density: Findings from the HUNT study.

OBJECTIVES: To examine the association between pelvic floor disorders (pelvic organ prolapse, urinary incontinence and anal incontinence) and bone mineral density (BMD). STUDY DESIGN: A cross-sectional study of 6809 women who participated in the third survey of the population-based Norwegian HUNT study was undertaken. BMD was measured by dual-energy X-ray absorptiometry. Information on BMD and self-reported pelvic floor disorders from the HUNT study was linked with hospital-derived data on diagnosis and surgical treatment of pelvic floor disorders. BMD was categorized according to the World Health Organization criteria (normal, osteopenia and osteoporosis). Multi-variate logistic regression models were used to estimate odds ratios (OR) with 95% confidence intervals (CI) for the association between pelvic floor disorders and BMD. RESULTS: Women with a hospital diagnosis of stress urinary incontinence (SUI) were less likely to have osteopenia (OR 0.66, 95% CI 0.50-0.87) or osteoporosis (OR 0.66, 95% CI 0.34-1.30) compared with women without a diagnosis of SUI. In women with self-reported information on pelvic floor disorders, women with a history of SUI had lower odds for osteopenia (OR 0.88, 95% CI 0.75-1.02) or osteoporosis (OR 0.69, 95% CI 0.46-1.01), while no association was found between anal incontinence, self-reported surgery for pelvic organ prolapse, and osteopenia or osteoporosis. CONCLUSION: Pelvic organ prolapse was not associated with BMD. The reasons underlying the observed association between SUI and BMD require further investigation.

Spirometric phenotypes from early childhood to young adulthood: a Chronic Airway Disease Early Stratification study.

BACKGROUND: The prevalences of obstructive and restrictive spirometric phenotypes, and their relation to early-life risk factors from childhood to young adulthood remain poorly understood. The aim was to explore these phenotypes and associations with well-known respiratory risk factors across ages and populations in European cohorts. METHODS: We studied 49 334 participants from 14 population-based cohorts in different age groups (≤10, >10-15, >15-20, >20-25 years, and overall, 5-25 years). The obstructive phenotype was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) z-score less than the lower limit of normal (LLN), whereas the restrictive phenotype was defined as FEV1/FVC z-score ≥LLN, and FVC z-score

Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2015 and GOLD 2019 staging: a pooled analysis of individual patient data.

In 2019, The Global Initiative for Chronic Obstructive Lung Disease (GOLD) modified the grading system for patients with COPD, creating 16 subgroups (1A-4D). As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aim to compare the mortality prediction of the 2015 and 2019 COPD GOLD staging systems. We studied 17 139 COPD patients from the 3CIA study, selecting those with complete data. Patients were classified by the 2015 and 2019 GOLD ABCD systems, and we compared the predictive ability for 5-year mortality of both classifications. In total, 17 139 patients with COPD were enrolled in 22 cohorts from 11 countries between 2003 and 2017; 8823 of them had complete data and were analysed. Mean±sd age was 63.9±9.8 years and 62.9% were male. GOLD 2019 classified the patients in milder degrees of COPD. For both classifications, group D had higher mortality. 5-year mortality did not differ between groups B and C in GOLD 2015; in GOLD 2019, mortality was greater for group B than C. Patients classified as group A and B had better sensitivity and positive predictive value with the GOLD 2019 classification than GOLD 2015. GOLD 2015 had better sensitivity for group C and D than GOLD 2019. The area under the curve values for 5-year mortality were only 0.67 (95% CI 0.66-0.68) for GOLD 2015 and 0.65 (95% CI 0.63-0.66) for GOLD 2019. The new GOLD 2019 classification does not predict mortality better than the previous GOLD 2015 system.

The association of anxiety and depression with mortality in a COPD cohort. The HUNT study, Norway.

BACKGROUND: Anxiety and depression are prevalent among individuals with chronic obstructive pulmonary disease (COPD), but the impact of these comorbidities on long-term mortality is unknown. AIMS: This study aims to compare mortality in individuals with COPD who had or did not have symptoms of anxiety or depression as well as the impact of a change in these symptoms on mortality. METHODS: Individuals with COPD according to the Global Lung Initiative (GLI) LLN criteria (n = 2076) were recruited from the second (1995-97) and third (2006-08) surveys of the HUNT Study and followed until January 2019 for mortality. We assessed baseline status of anxiety or depression using the Hospital Anxiety and Depression Scale (HADS), and probable cases were defined by a score ≥8. We used Cox regression to calculate hazard ratios (HR) with 95% confidence intervals (CI). Change in HADS score over time was assessed using joint models. RESULTS: Among the individuals with COPD, 16.2% had symptoms of anxiety and 15.9% had symptoms of depression. Compared to those with HADS-A and -D score <8, symptoms of anxiety or depression increased mortality by 21% (95% CI 05-47%) and 21% (2-44%), respectively. Over the approximately 11-year period between surveys, change of HADS-A from ≥8 to <8 was associated with a decrease in mortality (HR 0.97 [95% CI 0.94-1.00]), but not in HADS-D (0.97 [95% CI 0.93-1.18]). CONCLUSIONS: Individuals with COPD and symptoms of anxiety or depression have increased mortality, and improved HADS-A score with time is associated with lower mortality.

The Association of Bone Mineral Density with Mortality in a COPD Cohort. The HUNT Study, Norway.

In individuals with chronic obstructive pulmonary disease (COPD), the presence of comorbidities is associated with increased mortality risk. We wanted to study the association between bone mineral density (BMD) and mortality among individuals with COPD in a population-based cohort study. Participants were recruited from the second (1995-1997) and third (2006-2008) surveys of the HUNT Study and followed until February 2019. Hip and forearm BMD were included as continuous T-scores or categorized according to WHO criteria (normal, osteopenia, and osteoporosis). Hazard ratios with 95% confidence intervals were estimated by multivariable Cox regression models. In total, 2076 and 3239 participants were identified as having COPD by FEV1/FVC below lower limit of normal (LLN) or <0.70, respectively, according to Global Lung Initiative (GLI) and Global Initiative for Chronic Obstructive Lung Disease (GOLD). The prevalence of osteoporosis was 15.7% vs. 16.6% in the GLI-COPD vs. GOLD-COPD cohorts. Mean follow-up was 12.7 and 11.9 years. Lower T-scores were associated with a 5% (95% confidence interval (CI) 1.01-1.09) increased mortality in the GLI-COPD and GOLD-COPD cohorts, respectively. However, the presence of osteoporosis (T < -2.5), compared to normal BMD, was not associated with mortality in neither GLI-COPD (HR 1.13, 95% CI 0.91-1.41) nor GOLD-COPD cohorts (HR 1.22, 95% CI 0.99-1.51). Thus, a small positive association was found between decreasing BMD T-score and mortality in both GLI-COPD and GOLD-COPD. However, osteoporosis as defined by WHO was not associated with mortality, probably due to loss of power upon categorization.