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Oral glucocorticoids and incidence of hypertension in people with chronic inflammatory diseases: a population-based cohort study.

ABSTRACT: BACKGROUND:Only a few population-based studies have examined the association between glucocorticoids and hypertension, with inconsistent results. We aimed to investigate the effect of oral glucocorticoids on incidence of hypertension in adults with chronic inflammatory diseases. METHODS:We analyzed electronic health records from 389 practices in England during 1998-2017 of adults diagnosed with any of 6 chronic inflammatory diseases but with no previous diagnosis of hypertension. We used glucocorticoid prescription data to construct time-variant daily and cumulative variables of prednisolone-equivalent dose (cumulated from 1 year before the start of follow-up) and estimated incidence rates and adjusted hazard ratios (HRs) for hypertension using Cox regression analysis. RESULTS:Among 71 642 patients in the cohort, 24 896 (34.8%) developed hypertension during a median follow-up of 6.6 years. The incidence rate of hypertension was 46.7 (95% confidence interval [CI] 46.0-47.3) per 1000 person-years. Incidence rates increased with higher cumulative glucocorticoid prednisolone-equivalent dose, from 44.4 per 1000 person-years in periods of nonuse to 45.3 per 1000 person-years for periods with between > 0.0 and 959.9 mg (HR 1.14, 95% CI 1.09-1.19), to 49.3 per 1000 person-years for periods with 960-3054.9 mg (HR 1.20, 95% CI 1.14-1.27), and to 55.6 per 1000 person-years for periods with ? 3055 mg (HR 1.30, 95% CI 1.25-1.35). Cumulative effects were seen for the 6 diseases studied, but dose-response effects were not found for daily dose. INTERPRETATION:Cumulative dose of oral glucocorticoids was associated with increased incidence of hypertension, suggesting that blood pressure should be monitored closely in patients routinely treated with these drugs. Given that glucocorticoids are widely prescribed, the associated health burden could be high. Trial registration: ClinicalTrials. gov, no. NCT03760562.

SUBMITTER: Mebrahtu TF

PROVIDER: S-EPMC7101178 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Oral glucocorticoids and incidence of hypertension in people with chronic inflammatory diseases: a population-based cohort study.

Mebrahtu Teumzghi F TF Morgan Ann W AW West Robert M RM Stewart Paul M PM Pujades-Rodriguez Mar M

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20200301 12

<h4>Background</h4>Only a few population-based studies have examined the association between glucocorticoids and hypertension, with inconsistent results. We aimed to investigate the effect of oral glucocorticoids on incidence of hypertension in adults with chronic inflammatory diseases.<h4>Methods</h4>We analyzed electronic health records from 389 practices in England during 1998-2017 of adults diagnosed with any of 6 chronic inflammatory diseases but with no previous diagnosis of hypertension. ...[more]

PMID: 32392512

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Project description:BackgroundGlucocorticoids 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 findingsWe 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.ConclusionsIn 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.

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:ImportanceSeveral studies have linked chronic inflammatory skin diseases (CISDs) with venous thromboembolism (VTE) in a range of data sources with mixed conclusions.ObjectiveTo examine the incidence of VTE in patients with vs without CISD.Design, setting, and participantsA cohort study using commercial insurance claims data from a nationwide US health care database from January 1, 2004, through 2019 was conducted. A total of 158 123 patients with dermatologist-recorded psoriasis, atopic dermatitis, alopecia areata, vitiligo, or hidradenitis suppurativa were included. Risk-set sampling identified patients without a CISD. Patient follow-up lasted until the first of the following occurred: VTE, death, disenrollment, or end of data stream.ExposuresPatients with vs without CISD.Main outcomes and measuresVenous thromboembolism events were identified with validated algorithms. Incidence rates were computed before and after 1:1 propensity-score matching to account for VTE risk factors. Hazard ratios were estimated to compare the incidence of VTE in the CISD vs non-CISD cohorts.ResultsA total of 158 123 patients were identified with CISD: with psoriasis (n = 96 138), atopic dermatitis (n = 30 418), alopecia areata (n = 17 889), vitiligo (n = 7735), or HS (n = 5934); 9 patients had 2 of these conditions. A total of 1 570 387 patients were without a CISD. The median follow-up time was 1.9 years (interquartile range, 0.8-4.0 years) in patients with CISD. The incidence rate (per 1000 person-years) of outpatient or inpatient VTE was 1.57 in psoriasis, 1.83 in atopic dermatitis, 0.94 in alopecia areata, 0.93 in vitiligo, 1.65 in HS and 1.53 in CISD overall, compared with 1.76 in patients without a CISD. Incidence rates increased in patients aged 50 years or older (2.3 per 1000 person-years) and decreased in those aged 18 to 49 years (0.8 per 1000 person-years). After propensity-score matching to patients without a CISD, the hazard ratio (HR) of VTE was 0.86 (95% CI, 0.75-0.99) in psoriasis, 1.19 (95% CI, 0.95-1.48) in atopic dermatitis, 0.97 (95% CI, 0.65-1.46) in alopecia areata, 0.90 (95% CI, 0.49-1.65) in vitiligo, 1.64 (95% CI, 0.82-3.27) in hidradenitis suppurativa, and 0.94 (95% CI, 0.84-1.05) in CISD overall.Conclusions and relevanceIn this large-scale cohort study, CISDs were not associated with an increased incidence of VTE after controlling for relevant VTE risk factors in a representative dermatology patient population.

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Oral glucocorticoids and incidence of hypertension in people with chronic inflammatory diseases: a population-based cohort study.

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Oral glucocorticoids and incidence of hypertension in people with chronic inflammatory diseases: a population-based cohort study.

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