Toward Understanding of Environmental Risk Factors in Systemic Sclerosis

2020 ◽  
pp. 120347542095795
Author(s):  
Lydia Ouchene ◽  
Anastasiya Muntyanu ◽  
Jérôme Lavoué ◽  
Murray Baron ◽  
Ivan V. Litvinov ◽  
...  

Importance Systemic sclerosis (SSc) is a severe, chronic, and incurable autoimmune fibrotic skin disease with significant extracutaneous involvement. Low concordance rate in twin studies and unequal geographic distribution of SSc argues for importance of environment in disease initiation and progression. Objective In this manuscript we provide a summary of all investigated potential external risk factors for SSc. Data sources A literature search in PubMed and EMBASE database was performed for studies published until January 1, 2020 by 2 reviewers (EN and LO) independently. Findings Occupational and/or environmental exposures to silica and organic solvents are associated with increased incidence and severity of SSc. Exposure to epoxy resins, asbestos, and particulate air pollution favors increased risk of SSc, but data are based on limited number of observational studies. There is insufficient evidence to conclude an association between SSc development and other occupational (eg, welding fumes) or personal exposures (eg, smoking, vitamin D deficiency). Association of SSc with silicone breast implants has been disproven. Infectious pathogens (eg, Helicobacter pylori and angiotropic viruses) and dysbiosis seem to play a role in SSc development and severity, but their role remains to be clarified. Conclusions and relevance It may be prudent to counsel our patients with SSc (or those at risk of SSc) to avoid occupations with exposure to silica, organic solvents, asbestos and epoxy resins; restraint from smoking, using cocaine or drugs with pro-fibrotic potential. While the association between low vitamin D and SSc remains to be confirmed, we believe that SSc patients should be encouraged to maintain healthy vitamin D levels as benefits outweigh the risks.

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Chi Chen ◽  
Yi Chen ◽  
Pan Weng ◽  
Fangzhen Xia ◽  
Qin Li ◽  
...  

Abstract Background Low circulating vitamin D levels have been associated with increased risk of metabolic syndrome (MS) and cardiometabolic risk factors in multiple epidemiology studies. However, whether this association is causal is still unclear. We aimed to test whether genetically lowered vitamin D levels were associated with MS and its metabolic traits, using mendelian randomization (MR) methodology. Methods Ten thousand six hundred fifty-five participants were enrolled from the SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. Using four single-nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH) D concentrations, we created a genetic risk score (GRS) as instrumental variable (IV) to estimate the effect of genetically lowered 25(OH) D on MS and cardiometabolic risk factors. MS was defined according to the International Diabetes Federation criteria. Results Lower measured 25(OH)D levels were associated with MS (OR 0.921, 95% CI 0.888, 0.954) after multivariable adjustment. However, the MR-derived odds ratio of genetically determined 25(OH) D for risk of MS was 0.977 (95% CI 0.966, 1.030). The MR-derived estimates for raised fasting plasma glucose was 0.578 (95% CI 0.321, 0.980) per 10 nmol/L GRSsynthesis determined increase of 25(OH) D levels. Conclusions We found no evidence that genetically determined reduction in 25(OH)D conferred an increased risk of MS and its metabolic traits. However, we created our GRS only on the basis of common variants, which represent limited amount of variance in 25(OH)D. MR studies using rare variants, and large-scale well-designed RCTs about the effect of vitamin D supplementation on MS are warranted to further validate the findings.


2017 ◽  
Vol 23 (4) ◽  
pp. 525-533 ◽  
Author(s):  
Susanne Hempel ◽  
Glenn D Graham ◽  
Ning Fu ◽  
Elena Estrada ◽  
Annie Y Chen ◽  
...  

Background: The presenting symptoms and rate of progression of multiple sclerosis (MS) are very heterogeneous. The diverse clinical manifestations and the clinical course of the disease may vary with modifiable risk factors. Objective: To systematically review modifiable risk factors and exposures associated with MS progression. Methods: We searched six databases till March 2015, reference-mined reviews, and consulted with experts (PROSPERO 2015:CRD42015016461). Two reviewers screened and extracted data. We used random meta-analysis models and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess the quality of evidence. Results: In total, 59 studies met inclusion criteria. Lower vitamin D levels were associated with higher Expanded Disability Status Scale (EDSS) scores ( r = −0.22; confidence interval (CI) = −0.32, −0.12; 11 studies; I2 = 66%), smokers had an increased risk of MS progression (hazard ratio (HR) = 1.55; CI = 1.10, 2.19; I2 = 72%; seven studies), and there was no association of MS progression with the use of epidural analgesics during childbirth delivery (three studies). There was insufficient evidence to draw conclusions for 11 risk factors due to conflicting results or use of different predictor and outcome measures. Conclusion: MS progression was consistently associated with low vitamin D levels, and smoking was associated with a more rapid decline in MS disability. Studies used a variety of methods, predictors, and outcomes making it difficult to draw conclusions. Future studies should focus on prospective assessments.


2020 ◽  
Vol 19 (3) ◽  
pp. 250-268 ◽  
Author(s):  
Ioanna Gouni-Berthold ◽  
Heiner K. Berthold

: Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Vitamin D deficiency has been identified as a potential risk factor for a number of diseases unrelated to the classical skeletal pathophysiology, such as cancer and CVD, but the effects of vitamin D supplementation are less clear. Purpose of this narrative review is to discuss the evidence suggesting an association between vitamin D status and CVD as well as the results of supplementation studies. Vitamin D deficiency has been associated with CVD risk factors such as hypertension, dyslipidemia and diabetes mellitus as well as with cardiovascular events such as myocardial infarction, stroke and heart failure. While vitamin D deficiency might contribute to the development of CVD through its association with risk factors, direct effects of vitamin D on the cardiovascular system may also be involved. Vitamin D receptors are expressed in a variety of tissues, including cardiomyocytes, vascular smooth muscle cells and endothelial cells. Moreover, vitamin D has been shown to affect inflammation, cell proliferation and differentiation. While observational studies support an association between low plasma vitamin D levels and increased risk of CVD, Mendelian randomization studies do not support a causal association between the two. At present, high quality randomized trials do not find evidence of significant effects on CVD endpoints and do not support supplementation of vitamin D to decrease CVD events.


2014 ◽  
Vol 32 (31_suppl) ◽  
pp. 247-247
Author(s):  
George A. Dawson ◽  
Anne Greener ◽  
Dalila Reyes-Dawson ◽  
Sheetal Malhotra ◽  
Sarah Weinbrom ◽  
...  

247 Background: In general, men are not routinely screened for bone health. Prostate cancer patients are at an increased risk because of treatment with androgen deprivation therapy (ADT). Unlike other patients diagnosed with a malignancy, they may survive a long time. Some risk factors include inadequate calcium, vitamin D deficiency, tobacco use and alcohol abuse. We implemented a pre-ADT program to mitigate the effects of ADT on bone health. This study evaluates the pre-existing risk factors and bone health by baseline DEXA scans pre-ADT initiation. Methods: We completed a chart review of 182 veterans referred to Radiation Oncology for curative treatment of prostate cancer from 2009 to 2013. Of those, 160 patients underwent baseline DEXA scans. Clinical variables analyzed were demographics, tobacco and alcohol use, vitamin D levels, incidence of AODM (adult onset diabetes mellitus), and calcium or vitamin D intervention. Descriptive statistics and bivariate analysis including Chi Square tests and odds ratios were carried out. Results: The mean age of the study participants was 66.6 years (range 47-82.8 years). Baseline DEXA scans were abnormal in 63% of patients, showing osteoporosis and/or osteopenia. Vitamin D levels were abnormal in 61% of patients- 26% of whom had normal DEXA scans. Twenty percent had a history of alcohol abuse, and 56% used tobacco; 33% had AODM. Smokers with an abnormal Vitamin D level were at increased risk of bone disease as compared to non smokers (OR 3.23, 95% CI 1.35-7.69 p<0.01). Variables significantly impacting bone health were age (OR 1.087, p=0.012, 95% CI 1.018-1.161) and Tobacco use (OR 0.424, p=0.045, 95% CI 0.183-0.980). Almost 90% of the patients in this study had intermediate risk prostate cancer with an expected cancer specific survival of 85 to 90% at 5 to 10 years. Conclusions: Pre-ADT screening confirms the risk of underlying bone disease in this veteran population with an expectation of long term survival. Guidelines for treatment and prevention of bone disease should be implemented in all patients over age of 50. Particular attention should be paid to patients who underwent ADT. This can affect the quality of life in this group of cancer survivors.


Author(s):  
Najlaa Aljefree ◽  
Noha M. Almoraie ◽  
Israa M. Shatwan

Background: Cardiovascular disease (CVD) is a main cause of mortality and disability worldwide. One of the key factors in the soaring prevalence of CVD globally has been nutrition transitions and changes in dietary patterns. Objective: This study investigated the association between two diet scores, namely, a high-fat dietary (HFD) pattern score and a Mediterranean diet (MedDiet) score, and CVD risk factors (obesity, hypertension, total cholesterol, and blood glucose) and serum 25 hydroxy vitamin D (25[OH]D) levels. Methods: Three hundred twenty-one participants were included in this study. Fasting blood tests were collected from all participants for biochemical measurements. Blood pressure and anthropometric measurements were also taken. A validated, semi-quantitative food frequency questionnaire was used to collect data on participants’ dietary intake. Dietary scores for the HFD pattern were calculated based on recommended food groups. MedDiet scores were calculated based on a previously validated method that contains 14 questions related to MedDiet. Both diet scores were classified into tertiles. Linear regression analyses were performed to assess the statistical significance of the tertile groups. Result: A significant association was found between HFD score and obesity when comparing the lowest tertile (27.3±4.6 kg/m2) of HFD scores with the medium tertile (29.2±5.7 kg/m2; P = 0.02). A higher HFD score was significantly associated with lower 25(OH)D levels (P = 0.02). In addition, a significant association was observed between MedDiet scores and 25(OH)D levels, with an increase in MedDiet score resulting in an increase in 25(OH)D levels (P = 0.01). Furthermore, a significant negative association between MedDiet scores and low-density lipoprotein levels was reported only in participants with CVD (P = 0.03). Conclusion: The results of this study revealed that HFD and MedDiet scores might have a role in the development of CVD and vitamin D deficiency among the Saudi Arabian population. Further studies are required using diet scores to assess the quality of dietary patterns and their association with an increased risk of diseases in Saudi Arabians.


2013 ◽  
Vol 22 (04) ◽  
pp. 271-276 ◽  
Author(s):  
P. Farahmand ◽  
J. D. Ringe

SummaryOsteoporosis in men is increasingly recognized as an important public health problem but affected patients are still under-diagnosed and -treated. As in women the diagnostic and therapeutic strategy has to be adapted to the individual case. In the practical management it is very important to detect possible causes of secondary osteoporosis, to explain the possibilities of basic therapy counteracting individual risk factors and communicate that osteoporosis is a chronic disease and adherence to a long-term treatment is crucial. In established severe osteoporosis a careful analgesic therapy is important to avoid further bone loss related to immobility. In elderly men with increased risk of falling insufficient Vitamin D supply or impaired activation of Vitamin D due to renal insufficiency must be taken into consideration. Specific medications available today for the treatment of male osteoporosis comprise among antiresorptive drugs the bis phosphonates alendronate, risedronate and zoledronic acid. Denosumab, the first biological therapy is approved for men with androgen deprivation therapy for prostate cancer. An important advantage of this potent antiresorptive drug is the increased adherence due to the comfortable application by sixmonthly subcutaneous injections. Study results from the 2-year multi-center randomized controlled ADAMO-Study will very soon allow the use of denosumab in all types of male osteoporosis. Teriparatide, the 34 N-terminal amino acid sequence of parathyroid hormone was approved for men with osteoporosis as an anabolic agent based on proven efficacy by different studies. Among drugs with other modes of action the D-hormone pro-drug alfacalcidol can be used in men alone or in combination with the advantage of pleiotropic effects on calcium absorption, parathyroids, bone and muscle. Recently also Strontium-ranelate was approved for male patients with the limitation to exclude men with clinical relevant cardiovascular risk factors. In general the possibilities to treat male osteoporosis have considerably improved during recent years. Today there is a choice of a spectrum of drugs from mild to strong potency with different modes of action on bone turnover to design strategies for individual male patients.


Background: The risk factors for asthma exacerbations are well understood. However, the effect of vitamin D levels on number of asthma exacerbations per year is not clearly studied. The objective of the study was to find out the association of serum vitamin D levels and asthma risk factors on asthma exacerbations. Methods: In this study, ninety-nine subjects from 5 to 15 years of age were recruited at an episode of acute exacerbation. It was a cross sectional study and carried out from 2012 to 2015. Pulmonary function test was done by spirometry. Asthma exacerbation was labeled when forced expiratory volume/ forced vital capacity (FEV1/FVC) ratio was less than 80% (American Thoracic Society). Global Initiative for Asthma (GINA) guidelines were used to classify asthma into mild, moderate and severe persistent asthma. Serum vitamin D levels were measured by chemiluminescence method. Pearson Chi-square test was applied and p value (p<0.05) was considered as statistically significant. Results: Children who had exposure to animal dander had significantly lower asthma exacerbations per year (p-value <0.046). There was no significant association between vitamin D levels and number of exacerbations per years (p-value <0.099). Asthma was prevalent in girls of low socioeconomic status (SES) compared to males. However, there was no significant association between smoke, exercise, home environment, food allergies, weather, pollen and dust with asthma exacerbations. Conclusion: Low levels of vitamin D were not associated with increased number of asthma exacerbations per year. However, children exposed to animal dander had lesser number of exacerbations per year (p-value <0.046). Keywords: Asthma; Vitamin D; Children; Exacerbations, Risk factors.


2021 ◽  
pp. 239719832110340
Author(s):  
Yasser A Radwan ◽  
Reto D Kurmann ◽  
Avneek S Sandhu ◽  
Edward A El-Am ◽  
Cynthia S Crowson ◽  
...  

Objectives: To study the incidence, risk factors, and outcomes of conduction and rhythm disorders in a population-based cohort of patients with systemic sclerosis versus nonsystemic sclerosis comparators. Methods: An incident cohort of patients with systemic sclerosis (1980–2016) from Olmsted County, MN, was compared to age- and sex-matched nonsystemic sclerosis subjects (1:2). Electrocardiograms, Holter electrocardiograms, and a need for cardiac interventions were reviewed to determine the occurrence of any conduction or rhythm abnormalities. Results: Seventy-eight incident systemic sclerosis cases and 156 comparators were identified (mean age 56 years, 91% female). The prevalence of any conduction disorder before systemic sclerosis diagnosis compared to nonsystemic sclerosis subjects was 15% versus 7% ( p = 0.06), and any rhythm disorder was 18% versus 13% ( p = 0.33). During a median follow-up of 10.5 years in patients with systemic sclerosis and 13.0 years in nonsystemic sclerosis comparators, conduction disorders developed in 25 patients with systemic sclerosis with cumulative incidence of 20.5% (95% confidence interval: 12.4%–34.1%) versus 28 nonsystemic sclerosis patients with cumulative incidence of 10.4% (95% confidence interval: 6.2%–17.4%) (hazard ratio: 2.57; 95% confidence interval: 1.48–4.45), while rhythm disorders developed in 27 patients with systemic sclerosis with cumulative incidence of 27.3% (95% confidence interval: 17.9%–41.6%) versus 43 nonsystemic sclerosis patients with cumulative incidence of 18.0% (95% confidence interval: 12.3%–26.4%) (hazard ratio: 1.62; 95% confidence interval: 1.00–2.64). Age, pulmonary hypertension, and smoking were identified as risk factors. Conclusion: Patients with systemic sclerosis have an increased risk of conduction and rhythm disorders both at disease onset and over time, compared to nonsystemic sclerosis patients. These findings warrant increased vigilance and screening for electrocardiogram abnormalities in systemic sclerosis patients with pulmonary hypertension.


2021 ◽  
Vol 36 (3) ◽  
pp. 299-309 ◽  
Author(s):  
Joshua Elliott ◽  
Barbara Bodinier ◽  
Matthew Whitaker ◽  
Cyrille Delpierre ◽  
Roel Vermeulen ◽  
...  

AbstractMost studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK Biobank cohort, we investigate risk factors for COVID-19 mortality in comparison with non-COVID-19 mortality. We investigated demographic, social (education, income, housing, employment), lifestyle (smoking, drinking, body mass index), biological (lipids, cystatin C, vitamin D), medical (comorbidities, medications) and environmental (air pollution) data from UK Biobank (N = 473,550) in relation to 459 COVID-19 and 2626 non-COVID-19 deaths to 21 September 2020. We used univariate, multivariable and penalised regression models. Age (OR = 2.76 [2.18–3.49] per S.D. [8.1 years], p = 2.6 × 10–17), male sex (OR = 1.47 [1.26–1.73], p = 1.3 × 10–6) and Black versus White ethnicity (OR = 1.21 [1.12–1.29], p = 3.0 × 10–7) were independently associated with and jointly explanatory of (area under receiver operating characteristic curve, AUC = 0.79) increased risk of COVID-19 mortality. In multivariable regression, alongside demographic covariates, being a healthcare worker, current smoker, having cardiovascular disease, hypertension, diabetes, autoimmune disease, and oral steroid use at enrolment were independently associated with COVID-19 mortality. Penalised regression models selected income, cardiovascular disease, hypertension, diabetes, cystatin C, and oral steroid use as jointly contributing to COVID-19 mortality risk; Black ethnicity, hypertension and oral steroid use contributed to COVID-19 but not non-COVID-19 mortality. Age, male sex and Black ethnicity, as well as comorbidities and oral steroid use at enrolment were associated with increased risk of COVID-19 death. Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants, renin–angiotensin–aldosterone system inhibitors may be explained by the aforementioned factors.


Sign in / Sign up

Export Citation Format

Share Document