Dataset Information

Dose-dependent oral glucocorticoid cardiovascular risks in people with immune-mediated inflammatory diseases: A population-based cohort study.

ABSTRACT: Background: Glucocorticoids are widely used to reduce disease activity and inflammation in patients with a range of immune-mediated inflammatory diseases. It is uncertain whether or not low to moderate glucocorticoid dose increases cardiovascular risk. We aimed to quantify glucocorticoid dose-dependent cardiovascular risk in people with 6 immune-mediated inflammatory diseases.

Methods and findings: We conducted a population-based cohort analysis of medical records from 389 primary care practices contributing data to the United Kingdom Clinical Practice Research Datalink (CPRD), linked to hospital admissions and deaths in 1998-2017. We estimated time-variant daily and cumulative glucocorticoid prednisolone-equivalent dose-related risks and hazard ratios (HRs) of first all-cause and type-specific cardiovascular diseases (CVDs). There were 87,794 patients with giant cell arteritis and/or polymyalgia rheumatica (n = 25,581), inflammatory bowel disease (n = 27,739), rheumatoid arthritis (n = 25,324), systemic lupus erythematosus (n = 3,951), and/or vasculitis (n = 5,199), and no prior CVD. Mean age was 56 years and 34.1% were men. The median follow-up time was 5.0 years, and the proportions of person-years spent at each level of glucocorticoid daily exposure were 80% for non-use, 6.0% for <5 mg, 11.2% for 5.0-14.9 mg, 1.6% for 15.0-24.9 mg, and 1.2% for ?25.0 mg. Incident CVD occurred in 13,426 (15.3%) people, including 6,013 atrial fibrillation, 7,727 heart failure, and 2,809 acute myocardial infarction events. One-year cumulative risks of all-cause CVD increased from 1.4% in periods of non-use to 8.9% for a daily prednisolone-equivalent dose of ?25.0 mg. Five-year cumulative risks increased from 7.1% to 28.0%, respectively. Compared to periods of non-glucocorticoid use, those with <5.0 mg daily prednisolone-equivalent dose had increased all-cause CVD risk (HR = 1.74; 95% confidence interval [CI] 1.64-1.84; range 1.52 for polymyalgia rheumatica and/or giant cell arteritis to 2.82 for systemic lupus erythematosus). Increased dose-dependent risk ratios were found regardless of disease activity level and for all type-specific CVDs. HRs for type-specific CVDs and <5.0-mg daily dose use were: 1.69 (95% CI 1.54-1.85) for atrial fibrillation, 1.75 (95% CI 1.56-1.97) for heart failure, 1.76 (95% CI 1.51-2.05) for acute myocardial infarction, 1.78 (95% CI 1.53-2.07) for peripheral arterial disease, 1.32 (95% CI 1.15-1.50) for cerebrovascular disease, and 1.93 (95% CI 1.47-2.53) for abdominal aortic aneurysm. The lack of hospital medication records and drug adherence data might have led to underestimation of the dose prescribed when specialists provided care and overestimation of the dose taken during periods of low disease activity. The resulting dose misclassification in some patients is likely to have reduced the size of dose-response estimates.

Conclusions: In this study, we observed an increased risk of CVDs associated with glucocorticoid dose intake even at lower doses (<5 mg) in 6 immune-mediated diseases. These results highlight the importance of prompt and regular monitoring of cardiovascular risk and use of primary prevention treatment at all glucocorticoid doses.

SUBMITTER: Pujades-Rodriguez M

PROVIDER: S-EPMC7714202 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dose-dependent oral glucocorticoid cardiovascular risks in people with immune-mediated inflammatory diseases: A population-based cohort study.

Pujades-Rodriguez Mar M Morgan Ann W AW Cubbon Richard M RM Wu Jianhua J

PLoS medicine 20201203 12

<h4>Background</h4>Glucocorticoids are widely used to reduce disease activity and inflammation in patients with a range of immune-mediated inflammatory diseases. It is uncertain whether or not low to moderate glucocorticoid dose increases cardiovascular risk. We aimed to quantify glucocorticoid dose-dependent cardiovascular risk in people with 6 immune-mediated inflammatory diseases.<h4>Methods and findings</h4>We conducted a population-based cohort analysis of medical records from 389 primary c ...[more]

PMID: 33270649

Similar Datasets

Project description:ObjectivesWe studied oral glucocorticoids and osteonecrosis, a rare but serious bone disease, in individuals with various chronic inflammatory diseases. We hypothesised that we would find stronger associations in adults versus children and in people with autoimmune diseases.DesignRetrospective cohort study.SettingPopulation-representative data (1994-2013) from general practices in the UK.ParticipantsChildren and adults diagnosed with asthma; inflammatory bowel disease; juvenile, psoriatic or rheumatoid arthritis; psoriasis; or systemic lupus.ExposuresOral glucocorticoid patterns.Primary and secondary outcome measuresDiagnosed osteonecrosis (primary) and osteonecrosis plus clinical features (eg, symptoms, pain medication, surgical repair) (secondary). Discrete time failure models estimated the adjusted hazard ratio (aHR) of incident osteonecrosis following oral glucocorticoid exposure. Hypothesis testing was one sided (with corresponding 90% CI) since glucocorticoids were unlikely protective.ResultsAfter adjusting for demographic, disease-related and health utilisation factors, glucocorticoid exposure was associated with osteonecrosis in adults (ages 18-49, aHR 2.1 (90% CI 1.5 to 2.9); ages ≥50, aHR 1.3 (90% CI 1.01 to 1.7)). However, low-dose glucocorticoids, corresponding to average doses <7.5 mg prednisolone daily and maximum doses <30 mg daily, were not associated with osteonecrosis in adults. Furthermore, even at high glucocorticoid doses, there was no evidence of increased osteonecrosis among glucocorticoid-exposed children (p=0.04 for interaction by age) (any glucocorticoid exposure, ages 2-9: aHR 1.1 (90% CI 0.7 to 1.7); ages 10-17: aHR 0.6 (90% CI 0.3 to 1.6)). Arthritis, inflammatory bowel disease and lupus were independently associated with osteonecrosis, but there was a similar dose relationship between glucocorticoids and osteonecrosis among adults with low-risk and high-risk diseases.ConclusionsGlucocorticoid use was clearly associated with osteonecrosis in a dose-related fashion in adults, especially young adults, but this risk was not detectable in children. The absolute risk of glucocorticoid-associated osteonecrosis in the general paediatric population and in adults taking low glucocorticoid doses is at most extremely small.

Project description:ImportanceImmune regulation is important for carcinogenesis; however, the cancer risk profiles associated with immune-mediated diseases need further characterization.ObjectiveTo assess the prospective association of 48 immune-mediated diseases with the risk of total and individual cancers and the prospective association of organ-specific immune-mediated diseases with the risk of local and extralocal cancers.Design, setting, and participantsThis prospective cohort study used data from the UK Biobank cohort study on adults aged 37 to 73 years who were recruited at 22 assessment centers throughout the UK between January 1, 2006, and December 31, 2010, with follow-up through February 28, 2019.ExposuresImmune-mediated diseases.Main outcomes and measuresThe association of immune-mediated diseases with risk of cancer was assessed with multivariable hazard ratios (HRs) and 95% CIs after adjusting for various potential confounders using time-varying Cox proportional hazards regression. Heterogeneity in the associations of organ-specific immune-mediated diseases with local and extralocal cancers was assessed using the contrast test method.ResultsA total of 478 753 participants (mean [SD] age, 56.4 [8.1] years; 54% female) were included in the study. During 4 600 460 person-years of follow-up, a total of 2834 cases of cancer were documented in 61 496 patients with immune-mediated diseases and 26 817 cases of cancer in 417 257 patients without any immune-mediated diseases (multivariable HR, 1.08; 95% CI, 1.04-1.12). Five of the organ-specific immune-mediated diseases were significantly associated with higher risk of local but not extralocal cancers: asthma (HR, 1.34; 95% CI, 1.14-1.56), celiac disease (HR, 6.89; 95% CI, 2.18-21.75), idiopathic thrombocytopenic purpura (HR, 6.94; 95% CI, 3.94-12.25), primary biliary cholangitis (HR, 42.12; 95% CI, 20.76-85.44), and autoimmune hepatitis (HR, 21.26; 95% CI, 6.79-66.61) (P < .002 for heterogeneity). Nine immune-mediated diseases were associated with an increased risk of cancers in the involved organs (eg, asthma with lung cancer [HR, 1.34; 95% CI, 1.14-1.57; P < .001] and celiac disease with small intestine cancer [HR, 6.89; 95% CI, 2.18-21.75; P = .001]); 13 immune-mediated diseases were associated with an increased risk of cancer in the near organs (eg, Crohn disease with liver cancer: [HR, 4.01; 95% CI, 1.65-9.72; P = .002]) or distant organs (eg, autoimmune hepatitis with tongue cancer [HR, 27.75; 95% CI, 3.82-199.91; P = .001]) or in different systems (eg, idiopathic thrombocytopenic purpura with liver cancer [HR, 11.96; 95% CI, 3.82-37.42; P < .001]).Conclusions and relevanceIn this cohort study, immune-mediated diseases were associated with an increased risk of total cancer. Organ-specific immune-mediated diseases had stronger associations with risk of local cancers than extralocal cancers. The associations for individual immune-mediated diseases were largely organ specific but were also observed for some cancers in the near and distant organs or different systems. Our findings support the role of local and systemic immunoregulation in cancer development.

Project description:Unhealthy diet is a significant risk factor for cardiovascular diseases (CVD). Therefore, this umbrella review aims to comprehensively review the effects of dietary factors, including dietary patterns, food groups, and nutrients on CVD risks. Medline and Scopus databases were searched through March 2020. Systematic reviews with meta-analyses (SRMA) of randomized controlled trials (RCTs) or observational studies measuring the effects of dietary factors on CVD risks were eligible. Fifty-four SRMAs, including 35 SRMAs of observational studies, 10 SRMAs of RCTs, and 9 SRMAs of combined RCT and observational studies, were included for review. Findings from the SRMAs of RCTs suggest the significant benefit of Mediterranean and high-quality diets for lowering CVD risk, with pooled risk ratios (RRs) ranging from 0.55 (95%CI: 0.39-0.76) to 0.64 (95%CI: 0.53-0.79) and 0.70 (95%CI: 0.57-0.87), respectively. For food nutrients, two SRMAs of RCTs found that high intake of n-3 polyunsaturated fatty acid (PUFA) significantly reduced CVD risks, with pooled RRs ranging from 0.89 (95%CI: 0.82, 0.98) to 0.90 (95%CI: 0.85-0.96), while evidence of efficacy of n-6 PUFA and combined n-3 and n-6 PUFA were inconsistent. Moreover, results from the SRMAs of RCTs did not find a significant benefit of a low-salt diet and low total fat intake for CVD prevention. For food groups, results from the SRMAs of cohort studies suggest that high intakes of legumes, nuts, and chocolate, as well as a vegetarian diet significantly reduced the risk of coronary heart disease, with pooled RRs of 0.90 (95%CI: 0.84-0.97), 0.68 (95%CI: 0.59-0.78), 0.90 (95%CI: 0.82-0.97), and 0.71 (95%CI: 0.57-0.87), respectively. Healthy dietary patterns had a significant benefit for CVD prevention. With the substitutional and synergistic interactions between different food groups and nutrients, dietary recommendations for CVD prevention should be focused more on healthy dietary patterns than single food groups or nutrients.

Project description:BackgroundThe contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease.MethodsWe used linked primary care, hospital admission, disease registry, and death certificate records from the CALIBER programme, which links data for people in England recorded in four electronic health data sources. We included people who were (or turned) 30 years or older between Jan 1, 1998, to March 25, 2010, who were free from cardiovascular disease at baseline. The primary endpoint was the first record of one of 12 cardiovascular presentations in any of the data sources. We compared cumulative incidence curves for the initial presentation of cardiovascular disease and used Cox models to estimate cause-specific hazard ratios (HRs). This study is registered at ClinicalTrials.gov (NCT01804439).FindingsOur cohort consisted of 1 921 260 individuals, of whom 1 887 062 (98·2%) did not have diabetes and 34 198 (1·8%) had type 2 diabetes. We observed 113 638 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1-10·1). Of people with type 2 diabetes, 6137 (17·9%) had a first cardiovascular presentation, the most common of which were peripheral arterial disease (reported in 992 [16·2%] of 6137 patients) and heart failure (866 [14·1%] of 6137 patients). Type 2 diabetes was positively associated with peripheral arterial disease (adjusted HR 2·98 [95% CI 2·76-3·22]), ischaemic stroke (1·72 [1·52-1·95]), stable angina (1·62 [1·49-1·77]), heart failure (1·56 [1·45-1·69]), and non-fatal myocardial infarction (1·54 [1·42-1·67]), but was inversely associated with abdominal aortic aneurysm (0·46 [0·35-0·59]) and subarachnoid haemorrhage (0·48 [0·26-0.89]), and not associated with arrhythmia or sudden cardiac death (0·95 [0·76-1·19]).InterpretationHeart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The differences between relative risks of different cardiovascular diseases in patients with type 2 diabetes have implications for clinical risk assessment and trial design.FundingWellcome Trust, National Institute for Health Research, and Medical Research Council.

Dataset Information

Dose-dependent oral glucocorticoid cardiovascular risks in people with immune-mediated inflammatory diseases: A population-based cohort study.

Publications

Dose-dependent oral glucocorticoid cardiovascular risks in people with immune-mediated inflammatory diseases: A population-based cohort study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets