ACE inhibitor use and risk of cataract: a case–control analysis

Background/AimUse of ACE inhibitors (ACEIs) has been associated with an increased risk of cataract in a previous observational study in humans. In contrast, ACEIs were associated with beneficial effects on cataract development in experimental studies. We assessed the risk of cataract in relation to exposure to ACEI and other antihypertensive drugs.MethodsThis is a case-control study based on data from the UK-based Clinical Practice Research Datalink (CPRD). We included first-time cataract patients aged ≥40 years between 1995 and 2015 and an equal number of cataract-free controls. We matched the controls to cases on age, sex, general practice, date of first cataract (ie, index date) and years of history in the CPRD prior to the index date. We assessed the number of prescriptions for ACEI and other antihypertensive drugs in detail and explored the use of single ACEI substances. We performed conditional logistic regression and conducted various sensitivity analyses to test the robustness of our findings. We calculated the risk of cataract associated with previous exposure to ACEI, measured as OR with 95% CIs, and adjusted the multivariable model for body mass index, smoking, diabetes, hypertension, prescriptions of systemic corticosteroids and other antihypertensive drugs.ResultsWe identified 206 931 cataract cases and the same number of matched controls. Use of ACEI was not associated with a materially altered risk of cataract compared with non-use of ACEI, neither in the main analysis (OR 1.06, 95% CI 1.04 to 1.08) nor in any of the sensitivity or stratified analyses.ConclusionIn our large observational study, use of ACEI was not associated with an altered risk of cataract.

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Risk of osteoporosis and fragility fractures in asthma due to oral and inhaled corticosteroids: two population-based nested case-control studies

Thorax ◽

10.1136/thoraxjnl-2020-215664 ◽

2020 ◽

Vol 76 (1) ◽

pp. 21-28 ◽

Cited By ~ 1

Author(s):

Christos V Chalitsios ◽

Dominick E Shaw ◽

Tricia M McKeever

Keyword(s):

Cumulative Dose ◽

Inhaled Corticosteroids ◽

Conditional Logistic Regression ◽

Fragility Fractures ◽

Case Control ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Case Control Studies ◽

Increased Risk ◽

Nested Case Control

BackgroundInhaled (ICS) and oral (OCS) corticosteroids are used widely in asthma; however, the risk of osteoporosis and fragility fracture (FF) due to corticosteroids in asthma is not well-established.MethodsWe conducted two nested case-control studies using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Using an asthma cohort, we separately identified patients with osteoporosis or FF and gender-, age- and practice-matched controls. Conditional logistic regression was used to determine the association between ICS and OCS exposure, and the risk of osteoporosis or FF. The prevalence of patients receiving at least one bisphosphonate was also calculated.ResultsThere was a dose–response relationship between both cumulative dose and number of OCS/ICS prescriptions within the previous year, and risk of osteoporosis or FF. After adjusting for confounders, people receiving more OCS prescriptions (≥9 vs 0) had a 4.50 (95% CI 3.21 to 6.11) and 2.16 (95% CI 1.56 to 3.32) increased risk of osteoporosis and FF, respectively. For ICS (≥11 vs 0) the ORs were 1.60 (95% CI 1.22 to 2.10) and 1.31 (95% CI 1.02 to 1.68). The cumulative dose had a similar impact, with those receiving more OCS or ICS being at greater risk. The prevalence of patients taking ≥9 OCS and at least one bisphosphonate prescription was just 50.6% and 48.4% for osteoporosis and FF, respectively.ConclusionsThe findings suggest that exposure to OCS or ICS is an independent risk factors for bone health in patients with asthma. Steroid administration at the lowest possible level to maintain asthma control is recommended.

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Antihypertensive Medications and COVID-19 Diagnosis and Mortality: Population-based Case-Control Analysis in the United Kingdom

10.1101/2020.09.25.20201731 ◽

2020 ◽

Cited By ~ 1

Author(s):

Emma Rezel-Potts ◽

Abdel Douiri ◽

Phil J Chowienczyk ◽

Martin C Gulliford

Keyword(s):

Antihypertensive Therapy ◽

Population Based ◽

Case Control ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Control Analysis ◽

Antihypertensive Medications ◽

Lower Odds ◽

Healthcare Seeking ◽

Increased Risk

Objectives: To evaluate antihypertensive medications and COVID-19 diagnosis and mortality, accounting for healthcare seeking behaviour. Design: A population-based case control study with additional cohort analysis. Setting: Primary care patients from the UK Clinical Practice Research Datalink (CPRD). Participants: 16 866 patients with COVID-19 events in the CPRD from 29th January to June 25th 2020 and 70 137 matched controls. Main outcome measures: We explored associations between COVID-19 diagnosis and prescriptions for angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (B), calcium-channel blockers (C), thiazide diuretics (D) and other antihypertensive drugs (O). We evaluated all-cause mortality among COVID-19 cases. Analyses were adjusted for covariates and consultation frequency. Results: In covariate adjusted analyses, ACEIs were associated with lower odds of COVID-19 diagnosis (0.82, 95% confidence interval 0.77 to 0.88) as were ARBs, 0.87 (0.80 to 0.95) with little attenuation from adjustment for consultation frequency. In fully adjusted analyses, C and D were also associated with lower odds of COVID-19. Increased odds of COVID-19 for B (1.19, 1.12 to 1.26), were attenuated after adjustment for consultation frequency (1.01, 0.95 to 1.08). In adjusted analyses, patients treated with ACEIs or ARBs had similar mortality to patients treated with classes B, C, D or O (1.00, 0.83 to 1.20) or patients receiving no antihypertensive therapy (0.99, 0.83 to 1.18). Conclusions: Associations were sensitive to adjustment for confounding and healthcare seeking, but there was no evidence that antihypertensive therapy is associated with increased risk of COVID-19 diagnosis or mortality; most classes of antihypertensive therapy showed negative associations with COVID-19 diagnosis.

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Depression in individuals who subsequently develop inflammatory bowel disease: a population-based nested case–control study

Gut ◽

10.1136/gutjnl-2020-322308 ◽

2020 ◽

pp. gutjnl-2020-322308 ◽

Cited By ~ 1

Author(s):

Jonathan Blackwell ◽

Sonia Saxena ◽

Irene Petersen ◽

Matthew Hotopf ◽

Hanna Creese ◽

...

Keyword(s):

Case Control Study ◽

Conditional Logistic Regression ◽

Subsequent Development ◽

Case Control ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Gi Symptoms ◽

Nested Case Control ◽

Incident Cases ◽

Control Study

ObjectiveDepression is a potential risk factor for developing IBD. This association may be related to GI symptoms occurring before diagnosis. We aimed to determine whether depression, adjusted for pre-existing GI symptoms, is associated with subsequent IBD.DesignWe conducted a nested case–control study using the Clinical Practice Research Datalink identifying incident cases of UC and Crohn’s disease (CD) from 1998 to 2016. Controls without IBD were matched for age and sex. We measured exposure to prevalent depression 4.5–5.5 years before IBD diagnosis. We created two sub-groups with prevalent depression based on whether individuals had reported GI symptoms before the onset of depression. We used conditional logistic regression to derive ORs for the risk of IBD depending on depression status.ResultsWe identified 10 829 UC cases, 4531 CD cases and 15 360 controls. There was an excess of prevalent depression 5 years before IBD diagnosis relative to controls (UC: 3.7% vs 2.7%, CD 3.7% vs 2.9%). Individuals with GI symptoms prior to the diagnosis of depression had increased adjusted risks of developing UC and CD compared with those without depression (UC: OR 1.47, 95% CI 1.21 to 1.79; CD: OR 1.41, 95% CI 1.04 to 1.92). Individuals with depression alone had similar risks of UC and CD to those without depression (UC: OR 1.13, 95% CI 0.99 to 1.29; CD: OR 1.12, 95% CI 0.91 to 1.38).ConclusionsDepression, in the absence of prior GI symptoms, is not associated with subsequent development of IBD. However, depression with GI symptoms should prompt investigation for IBD.

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Drug interactions and risk of acute bleeding leading to hospitalisation or death in patients with chronic atrial fibrillation treated with warfarin

Thrombosis and Haemostasis ◽

10.1160/th05-03-0166 ◽

2005 ◽

Vol 94 (09) ◽

pp. 537-543 ◽

Cited By ~ 38

Author(s):

Jennifer Hollowell ◽

Christoph R. Meier ◽

Walter E. Haefeli ◽

Christiane Gasse

Keyword(s):

Atrial Fibrillation ◽

Drug Interactions ◽

Conditional Logistic Regression ◽

General Practice Research Database ◽

Practice Research ◽

Control Analysis ◽

Research Database ◽

Nonvalvular Atrial Fibrillation ◽

Increased Risk

SummaryAlthough drug interactions with warfarin are an important cause of excessive anticoagulation, their impact on the risk of serious bleeding is unknown. We therefore performed a cohort study and a nested case-control analysis to determine the risk of serious bleeding in 4152 patients (aged 40–84 years) with nonvalvular atrial fibrillation (AF) taking long-term warfarin (>3 months). The study population was drawn from the UK General Practice Research Database. More than half (58%) of eligible patients used potentially interacting drugs during continuous warfarin treatment. Among 45 identified cases of incident idiopathic bleeds (resulting in hospitalisation within 30 days or death within 7 days) and 143 matched controls, more cases than controls took ≥1 potentially interacting drug within the preceding 30 days (62.2% vs. 35.7%) and used >4 drugs (polypharmacy) within the preceding 90 days (80.0% vs. 66.4%). Conditional logistic regression analysis yielded an odds ratio (OR) of 3.4 (95% confidence interval [CI]: 1.4–8.5) for the risk of serious bleeding in patients treated with warfarin and ≥1 drugs potentially increasing the effect of warfarin vs. warfarin alone adjusted for polypharmacy, diabetes, hypertension, heart failure, and thyroid disease; the adjusted OR for the combined use of warfarin and aspirin vs. warfarin alone was 4.5 (95% CI: 1.1–18.1). We conclude that concurrent use of potentially interacting drugs with warfarin is associated with a 3 to 4.5-fold increased risk of serious bleeding in long-term warfarin users.

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Degree of serotonin reuptake inhibition of antidepressants and ischemic risk

Neurology ◽

10.1212/wnl.0000000000008060 ◽

2019 ◽

Vol 93 (10) ◽

pp. e1010-e1020 ◽

Cited By ~ 7

Author(s):

Antonios Douros ◽

Sophie Dell'Aniello ◽

Golsa Dehghan ◽

Jean-François Boivin ◽

Christel Renoux

Keyword(s):

Ischemic Stroke ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Conditional Logistic Regression ◽

Large Population ◽

Sensitivity Analyses ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Third Generation

ObjectiveTo assess whether use of antidepressants with strong inhibition of serotonin reuptake is associated with a decreased incidence of ischemic stroke and myocardial infarction (MI).MethodsWe conducted a cohort study using the UK Clinical Practice Research Datalink and considering new users of selective serotonin reuptake inhibitors (SSRIs) or third-generation antidepressants who were ≥18 years of age between 1995 and 2014. Using a nested case-control approach, we matched each case of a first ischemic stroke or MI identified during follow-up with up to 30 controls on age, sex, calendar time, and duration of follow-up. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) of each outcome associated with current use of strong compared with weak inhibitors of serotonin reuptake using conditional logistic regression.ResultsThe cohort included 938,388 incident users of SSRIs (n = 868,755) or third-generation antidepressants (n = 69,633). Mean age at cohort entry was 46 years (64% women). During follow-up, 15,860 cases of ischemic stroke and 8,626 cases of MI were identified and matched to 473,712 and 258,022 controls, respectively. Compared with current use of weak inhibitors of serotonin reuptake, current use of strong inhibitors was associated with a decreased rate of ischemic stroke (RR 0.88, 95% CI 0.80–0.97), but the effect size was smaller in some sensitivity analyses. The rate of MI was similar between strong and weak inhibitors (RR 1.00, 95% CI 0.87–1.15).ConclusionOur large population-based study suggests that antidepressants strongly inhibiting serotonin reuptake may be associated with a small decrease in the rate of ischemic stroke.

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Predictors of Over-Anticoagulation in Warfarin Users in the UK General Population: A Nested Case–Control Study in a Primary Health Care Database

Thrombosis and Haemostasis ◽

10.1055/s-0038-1676519 ◽

2018 ◽

Vol 119 (01) ◽

pp. 066-076 ◽

Cited By ~ 5

Author(s):

Mar Martín-Pérez ◽

David Gaist ◽

Francisco de Abajo ◽

Luis García Rodríguez

Keyword(s):

Index Date ◽

Case Control ◽

Adverse Outcomes ◽

Sensitivity Analyses ◽

Patient Specific ◽

Health Improvement ◽

Chronic Obstructive ◽

Control Analysis ◽

Nested Case Control ◽

Care Database

Background Many patients on warfarin therapy often present with supratherapeutic international normalized ratio (INR) levels, resulting from the influence of several patient-specific factors, which have been associated with adverse outcomes. Objective This article aims to identify risk factors for over-anticoagulation (INR levels ≥4) in a cohort of patients taking warfarin. Methods A cohort of warfarin users aged 18 to 85 years from January 2005 to April 2013 was identified in The Health Improvement Network U.K. primary care database (N = 12,506). A random date was assigned to all patients within their eligible person-time (index date), and a nested case–control analysis was performed with individuals presenting a first episode of INR level ≥4 after the index date used as cases (N = 699) and patients with non-supratherapeutic INR values (≤3) as controls (N = 9,798). Using unconditional logistic regression models, odds ratios with 95% confidence intervals were calculated adjusted for potential confounders. Two sensitivity analyses were performed with alternative definitions of over-anticoagulation (INR levels ≥5 or > 3). Results Among the factors examined, the strongest predictors of over-anticoagulation were warfarin indication (in particular, valvular atrial fibrillation and valve replacement), renal failure (with the risk increasing steeply with decreasing estimated glomerular filtration rate), cancer, anaemia, respiratory infections treated with antibiotics, chronic obstructive pulmonary disease treated with β2-agonists, polypharmacy (≥10 medications), low socio-economic status and residency in rural areas. Similar results were obtained when supratherapeutic levels were defined as INR ≥5 or, alternatively, as INR > 3. Conclusion Predictors of supratherapeutic INR levels found in this study might help physicians identify patients where closer INR monitoring is warranted.

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Comparative effect of statins on the risk of incident Alzheimer disease

Neurology ◽

10.1212/wnl.0000000000004818 ◽

2017 ◽

Vol 90 (3) ◽

pp. e179-e187 ◽

Cited By ~ 16

Author(s):

Liliya Sinyavskaya ◽

Serge Gauthier ◽

Christel Renoux ◽

Sophie Dell'Aniello ◽

Samy Suissa ◽

...

Keyword(s):

Clinical Practice ◽

Alzheimer Disease ◽

Proportional Hazards ◽

Neuroprotective Effect ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Increased Risk

ObjectiveTo investigate whether fungus-derived statins are associated with a lower risk of incident Alzheimer disease (AD) compared with synthetic statins using real-world clinical practice data.MethodsWe identified a population-based retrospective cohort of patients aged ≥60 years newly prescribed a statin between January 1, 1994, and December 31, 2012, and followed until March 31, 2015, using the UK Clinical Practice Research Datalink. Statins were consecutively classified according to their type, lipophilicity, and potency. For each group, we calculated the crude AD incidence rates per 1,000 person-years. Time-dependent Cox proportional hazards models adjusted for propensity score deciles were used to estimate hazard ratios (HRs) with 95% confidence interval (CIs) of incident AD associated with different statin categories.ResultsOver the 18-year study period, we identified 465,085 statin users, including 7,669 patients who developed AD during 2,891,268 person-years of follow-up (incidence rate 2.65 [95% CI 2.59–2.71] per 1,000 person-years). Compared to synthetic, fungus-derived statins were associated with an increased risk of AD (HR 1.09, 95% CI 1.03–1.15). Lipophilic statins also were associated with higher AD risk (HR 1.18, 95% CI 1.09–1.27) compared to hydrophilic statins, while statin potency did not modify the risk of AD (adjusted HR 1.03, 95% CI 0.98–1.08). The risk was further reduced in sensitivity analyses.ConclusionFungus-derived and lipophilic statins were not associated with decreased incidence of AD compared to synthetic and hydrophilic statins. The modest variations in the risk of incident AD observed between statin characteristics needs to be evaluated in future studies on their possible heterogeneous neuroprotective effect.

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Association between malignancies and Marfan syndrome: a population-based, nested case–control study in Taiwan

BMJ Open ◽

10.1136/bmjopen-2017-017243 ◽

2017 ◽

Vol 7 (10) ◽

pp. e017243 ◽

Cited By ~ 1

Author(s):

Chin-Wang Hsu ◽

Jen-Chun Wang ◽

Wen-I Liao ◽

Wu-Chien Chien ◽

Chi-Hsiang Chung ◽

...

Keyword(s):

Marfan Syndrome ◽

Transforming Growth Factor ◽

Conditional Logistic Regression ◽

Case Control ◽

Signalling Pathway ◽

Claim Database ◽

Control Analysis ◽

Research Database ◽

Increased Risk ◽

Nested Case Control

ObjectiveMarfan syndrome (MFS) involves a deficiency of the structural extracellular matrix component fibrillin-1 and overactivation of the transforming growth factor-β (TGF-β) signalling pathway. The TGF-β signalling pathway also actively participates in malignant transformation. Although anecdotal case reports have suggested associations between MFS/MFS-like conditions and several haematological and solid malignancies, such associations have not been thoroughly evaluated in large-scale studies. We sought to use a nationwide healthcare insurance claim database to evaluate whether patients with MFS are at increased risk of malignancy.Patients and methodsWe conducted a nested case–control analysis using a database extracted from Taiwan’s National Health Insurance Research Database. All medical conditions for each case and control were categorised using the International Classification of Diseases, 9th Revision classifications. ORs and 95% CIs for associations between MFS and malignancies were estimated using conditional logistic regression and adjusted for comorbidities.ResultsOur analyses included 1 153 137 cancer cases and 1 153 137 propensity score-matched controls. Relative to other subjects, patients with MFS had a significantly higher risk of having a malignancy (adjusted OR 3.991) and hypertension (adjusted OR 1.964) and were significantly more likely to be men. Malignancies originating from the head and neck and the urinary tract were significantly more frequent among patients with MFS than among subjects without MFS.ConclusionPatients with MFS are at increased risk of developing various malignancies. Healthcare professionals should be aware of this risk when treating such patients, and increased cancer surveillance may be necessary for these patients.

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Assessing the relationship between serum potassium variability and the risk of hyperkalaemia and adverse clinical outcomes

European Heart Journal ◽

10.1093/ehjci/ehaa946.2830 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

P McEwan ◽

K Badora ◽

D Sugrue ◽

G James ◽

M Hurst ◽

...

Keyword(s):

Serum Potassium ◽

Index Date ◽

Adverse Outcomes ◽

Practice Research ◽

Major Adverse Cardiovascular Events ◽

Clinical Practice Research Datalink ◽

Funding Source ◽

Private Company ◽

Increased Risk

Abstract Background Serum potassium (SK+) is a vital electrolyte, which level is maintained by adjusting renal K+ excretion. Variability in SK+ has been linked to increased risk of mortality and other adverse clinical events in patients in intensive care and/or receiving haemodialysis, prompting a similar investigation in cardiovascular patients. Purpose To examine the effect of SK+ variability on all-cause mortality (ACM) and the incidence of major adverse cardiovascular events (MACE), comprising arrhythmia, [subsequent records of] HF, myocardial infarction, or stroke, in patients with heart failure (HF) or resistant hypertension (RHTN). Methods Patients aged ≥18 years with HF or RHTN were identified from the UK Clinical Practice Research Datalink (CPRD, primary care data) and linked Hospital Episode Statistics (HES, secondary care data). HF and RHTN were defined through READ codes recorded during the study period (2008-June 2018) or the five-year look-back period (2003–2007). Index date was set to 1st January 2008 or initial diagnosis; whichever occurred later. Mean SK+ and variability of measurements (quantified as standard deviation [SD] and each patient categorised as low or highly variable based on the median SD of the cohort), and crude incidence rates of ACM and MACE were estimated over a follow-up period from index date to event or end of follow-up (death, loss to follow-up or end of study, whichever was earlier). Results The eligible population included 317,135 RHTN patients and 84,210 HF patients with a mean follow-up of 6.37 (SD 3.06) and 5.01 (SD 3.20) years, respectively. In both cohorts, higher mean SK+ ≥5.0 mmol/L was associated with increased rates of ACM and MACE relative to a mean SK+ of 3.5–5 mmol/L (Table 1). High SK+ variability was associated with increased incidence of adverse outcomes, with rates consistently higher in the high SK+ variability group compared to low-variability patients with the same diagnosis and mean SK+ category (Table 1); all comparisons were statistically significant except for ACM in HF patients with mean SK+ ≥5 mmol/L. Conclusion Independently of mean SK+, increased variability in SK+ levels was associated with an increased rate of mortality and MACE in patients with RHTN or HF. Careful SK+ monitoring and management to maintain SK+ concentrations may improve the outcomes of patients with RHTN and HF. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): AstraZeneca

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