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Cardiometabolic comorbidities present a considerable burden for patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA). Both RA and PsA are associated with an increased risk of cardiovascular disease (CVD). PsA more often exhibits an increased risk of metabolically linked comorbidities such as obesity, insulin resistance, type 2 diabetes mellitus and non-alcoholic fatty liver disease. Although both RA and PsA are characterized by a state of chronic inflammation, the mechanisms that contribute to CVD risk in these conditions might not be identical. In RA, systemic inflammation is thought to directly contribute to CVD risk, whereas in PsA, adiposity is thought to contribute to a notable metabolic phenotype that, in turn, contributes to CVD risk. Hence, appropriate management strategies that consider the increased risk of cardiometabolic comorbidities in patients with inflammatory arthropathy are important. In RA, such strategies should focus on the prediction of CVD risk and its management through targeting chronic inflammation and traditional CVD risk factors. In PsA, management strategies should additionally focus on targeting metabolic components, including weight management, which might not only help improve disease activity in the joints, entheses and skin, but also reduce the risk of metabolic comorbidities and improve the quality of life of patients.

Psoriasis is a common inflammatory skin disease that has been reported to be associated with obesity. We aimed to investigate a possible causal relationship between body mass index (BMI) and psoriasis. Following a review of published epidemiological evidence of the association between obesity and psoriasis, mendelian randomization (MR) was used to test for a causal relationship with BMI. We used a genetic instrument comprising 97 single-nucleotide polymorphisms (SNPs) associated with BMI as a proxy for BMI (expected to be much less confounded than measured BMI). One-sample MR was conducted using individual-level data (396,495 individuals) from the UK Biobank and the Nord-Trøndelag Health Study (HUNT), Norway. Two-sample MR was performed with summary-level data (356,926 individuals) from published BMI and psoriasis genome-wide association studies (GWASs). The one-sample and two-sample MR estimates were meta-analysed using a fixed-effect model. To test for a potential reverse causal effect, MR analysis with genetic instruments comprising variants from recent genome-wide analyses for psoriasis were used to test whether genetic risk for this skin disease has a causal effect on BMI. Published observational data showed an association of higher BMI with psoriasis. A mean difference in BMI of 1.26 kg/m2 (95% CI 1.02-1.51) between psoriasis cases and controls was observed in adults, while a 1.55 kg/m2 mean difference (95% CI 1.13-1.98) was observed in children. The observational association was confirmed in UK Biobank and HUNT data sets. Overall, a 1 kg/m2 increase in BMI was associated with 4% higher odds of psoriasis (meta-analysis odds ratio [OR] = 1.04; 95% CI 1.03-1.04; P = 1.73 × 10(-60)). MR analyses provided evidence that higher BMI causally increases the odds of psoriasis (by 9% per 1 unit increase in BMI; OR = 1.09 (1.06-1.12) per 1 kg/m2; P = 4.67 × 10(-9)). In contrast, MR estimates gave little support to a possible causal effect of psoriasis genetic risk on BMI (0.004 kg/m2 change in BMI per doubling odds of psoriasis (-0.003 to 0.011). Limitations of our study include possible misreporting of psoriasis by patients, as well as potential misdiagnosis by clinicians. In addition, there is also limited ethnic variation in the cohorts studied. Our study, using genetic variants as instrumental variables for BMI, provides evidence that higher BMI leads to a higher risk of psoriasis. This supports the prioritization of therapies and lifestyle interventions aimed at controlling weight for the prevention or treatment of this common skin disease. Mechanistic studies are required to improve understanding of this relationship.

ObjectivesWe aimed to investigate demographic, lifestyle, socioeconomic and clinical risk factors for COVID-19, and compared them to risk factors for pneumonia and influenza in UK Biobank.DesignCohort study.SettingUK Biobank.Participants49–83 year olds (in 2020) from a general population study.Main outcome measuresConfirmed COVID-19 infection (positive SARS-CoV-2 test). Incident influenza and pneumonia were obtained from primary care data. Poisson regression was used to study the association of exposure variables with outcomes.ResultsAmong 235 928 participants, 397 had confirmed COVID-19. After multivariable adjustment, modifiable risk factors were higher body mass index and higher glycated haemoglobin (HbA1C) (RR 1.28 and RR 1.14 per SD increase, respectively), smoking (RR 1.39), slow walking pace as a proxy for physical fitness (RR 1.53), and use of blood pressure medications as a proxy for hypertension (RR 1.33). Higher forced expiratory volume in 1 s (FEV1) and high-density lipoprotein (HDL) cholesterol were both associated with lower risk (RR 0.84 and RR 0.83 per SD increase, respectively). Non-modifiable risk factors included male sex (RR 1.72), black ethnicity (RR 2.00), socioeconomic deprivation (RR 1.17 per SD increase in Townsend Index), and high cystatin C (RR 1.13 per SD increase). The risk factors overlapped with pneumonia somewhat, less so for influenza. The associations with modifiable risk factors were generally stronger for COVID-19, than pneumonia or influenza.ConclusionThese findings suggest that modification of lifestyle may help to reduce the risk of COVID-19 and could be a useful adjunct to other interventions, such as social distancing and shielding of high risk.

Background Sarcopenia often co‐occurs with osteoporosis in cross‐sectional studies. However, this association has rarely been studied in prospective studies. This study aimed to investigate the association between sarcopenia categories—along with its individual components—and incident osteoporosis in both middle‐aged and older men and women from the UK Biobank study. Methods A total of 168,682 participants (48.8% women, aged 37 to 70 years at baseline) were included in this prospective study. Categories of sarcopenia (pre‐sarcopenia and sarcopenia), and its individual components, were defined according to the EWGSOP2 criteria (2019). Associations with incident osteoporosis by sex were investigated using Cox‐proportional hazard models adjusted for socio‐demographic, lifestyle and health‐related factors, and morbidity count. Associations between categories of sarcopenia and incident osteoporosis were also investigated by age‐groups and subtype of osteoporosis (with and without pathological fractures). Results After a median follow‐up of 7.4 years, 6296 participants were diagnosed with osteoporosis. When the analyses were adjusted for a range of relevant confounding factors, pre‐sarcopenia was associated with 1.3‐times higher risk of osteoporosis in men (HR: 1.30 [95% CI: 1.03 to 1.63]) but not in women, and sarcopenia was associated with 1.66‐times increased osteoporosis risk in women (HR: 1.66 [95% CI: 1.33 to 2.08]) but not in men compared with people without sarcopenia or pre‐sarcopenia. A similar magnitude of associations was found in osteoporosis without pathological fractures but weaker for those with pathological fractures. Within the individual components, low muscle mass (HRwomen: 1.36 [95% CI: 1.22 to 1.51] and HRmen: 3.07 [95% CI: 1.68 to 5.59]), followed by slow gait speed (HRwomen: 1.30 [95% CI: 1.17 to 1.45] and HRmen: 1.70 [95% CI: 1.43 to 2.02]), were associated with a higher risk of incident osteoporosis in both sexes. Low grip strength was associated with a higher risk of incident osteoporosis in men (HR: 1.38 [95% CI: 1.15 to 1.65]), but not in women. No significant interaction between the exposures and incident osteoporosis by age groups were identified. Conclusions Our findings demonstrated that pre‐sarcopenic men and sarcopenic women had a higher risk of developing osteoporosis even after adjustment for a large range of potential confounders. Considering that sarcopenia could be prevented, health interventions to improve physical capability may delay or prevent the onset of osteoporosis.

IntroductionEarly detection and treatment of diabetes as well as its prevention help lessen longer-term complications. We determined the prevalence of pre-diabetes and undiagnosed diabetes in the UK Biobank and standardized the results to the UK general population.Research design and methodsThis cross-sectional study analyzed baseline UK Biobank data on plasma glycated hemoglobin (HbA1c) to compare the prevalence of pre-diabetes and undiagnosed diabetes mellitus in white, South Asian, black, and Chinese participants. The overall and ethnic-specific results were standardized to the UK general population aged 40–70 years of age.ResultsWithin the UK Biobank, the overall crude prevalence was 3.6% for pre-diabetes, 0.8% for undiagnosed diabetes, and 4.4% for either. Following standardization to the UK general population, the results were similar at 3.8%, 0.8%, and 4.7%, respectively. Crude prevalence was much higher in South Asian (11.0% pre-diabetes; 3.6% undiagnosed diabetes; 14.6% either) or black (13.8% pre-diabetes; 3.0% undiagnosed diabetes; 16.8% either) participants. Only six middle-aged or old-aged South Asian individuals or seven black would need to be tested to identify an HbA1c result that merits action.ConclusionsSingle-stage population screening for pre-diabetes or undiagnosed diabetes in middle-old or old-aged South Asian and black individuals using HbA1c could be efficient and should be considered.

To investigate the associations of objectively measured cardiorespiratory fitness (CRF) and grip strength (GS) with incident heart failure (HF), a clinical syndrome that results in substantial social and economic burden, using UK Biobank data. Of the 502,628 participants recruited into the UK Biobank between April 1, 2007, and December 31, 2010, a total of 374,493 were included in our GS analysis and 57,053 were included in CRF analysis. Associations between CRF and GS and incident HF were investigated using Cox proportional hazard models, with adjustment for known measured confounders. During a mean of 4.1 (range, 2.4-7.1) years, 631 HF events occurred in those with GS data, and 66 HF events occurred in those with CRF data. Higher CRF was associated with 18% lower risk for HF (hazard ratio [HR], 0.82; 95% CI, 0.76-0.88) per 1-metabolic equivalent increment increase and GS was associated with 19% lower incidence of HF risk (HR, 0.81; 95% CI, 0.77-0.86) per 5-kg increment increase. When CRF and GS were standardized, the HR for CRF was 0.50 per 1-SD increment (95% CI, 0.38-0.65), and for GS was 0.65 per 1-SD increment (95% CI, 0.58-0.72). Our data indicate that objective measurements of physical function (GS and CRF) are strongly and independently associated with lower HF incidence. Future studies targeting improving CRF and muscle strength should include HF as an outcome to assess whether these results are causal.

To investigate the associations of objectively measured cardiorespiratory fitness (CRF) and grip strength (GS) with incident heart failure (HF), a clinical syndrome that results in substantial social and economic burden, using UK Biobank data. Of the 502,628 participants recruited into the UK Biobank between April 1, 2007, and December 31, 2010, a total of 374,493 were included in our GS analysis and 57,053 were included in CRF analysis. Associations between CRF and GS and incident HF were investigated using Cox proportional hazard models, with adjustment for known measured confounders. During a mean of 4.1 (range, 2.4-7.1) years, 631 HF events occurred in those with GS data, and 66 HF events occurred in those with CRF data. Higher CRF was associated with 18% lower risk for HF (hazard ratio [HR], 0.82; 95% CI, 0.76-0.88) per 1–metabolic equivalent increment increase and GS was associated with 19% lower incidence of HF risk (HR, 0.81; 95% CI, 0.77-0.86) per 5-kg increment increase. When CRF and GS were standardized, the HR for CRF was 0.50 per 1-SD increment (95% CI, 0.38-0.65), and for GS was 0.65 per 1-SD increment (95% CI, 0.58-0.72). Our data indicate that objective measurements of physical function (GS and CRF) are strongly and independently associated with lower HF incidence. Future studies targeting improving CRF and muscle strength should include HF as an outcome to assess whether these results are causal.

Objective: Psoriasis and eczema are common inflammatory skin diseases that have been reported to be associated with obesity. However, causality has not yet been established. We aimed to investigate the possible causal relationship between body mass index (BMI) and psoriasis or eczema. Methods: Following a review of published epidemiological evidence of the association between obesity and either psoriasis or eczema, Mendelian Randomization (MR) was used to test for a causal relationship between BMI and these inflammatory skin conditions. We used a genetic instrument comprising 97 single nucleotide polymorphisms (SNPs) associated with BMI. One-sample MR was conducted using individual-level data (401,508 individuals) from the UK Biobank and the Nord-Tr ndelag Health Study (HUNT), Norway. Two-sample MR was performed with summary-level data (731,021 individuals) from published BMI, psoriasis and eczema GWAS. The one-sample and two-sample MR estimates were meta-analysed using a fixed effect model. To explore the reverse causal direction, MR analysis with genetic instruments comprising variants from recent genome-wide analyses for psoriasis and eczema were used to test if inflammatory skin disease has a causal effect on BMI. Results: Published observational data show an association of greater BMI with both psoriasis and eczema case status. The observational associations were confirmed in UK Biobank and HUNT datasets. MR analyses provide evidence that higher BMI causally increases the odds of psoriasis (by 53% per 5 units higher BMI; OR= 1.09 (1.06 to 1.12) per 1 kg/m2; P=4.67x10-9) and eczema (by 8% per 5 units higher BMI; OR=1.02 (1.00 to 1.03) per 1 kg/m2; P=0.09). When investigating causality in the opposite direction, MR estimates provide little evidence for an effect of either psoriasis or eczema influencing BMI. Conclusion: Our study, using genetic variants as instrumental variables for BMI, shows that higher BMI leads to a higher risk of inflammatory skin disease. The causal relationship was stronger for psoriasis than eczema. Therapies and life-style interventions aimed at controlling BMI or targeting the mechanisms linking obesity with skin inflammation may offer an opportunity for the prevention or treatment of these common skin diseases.