Corticosteroids: do they damage the cardiovascular system?

Maxwell, Scott; Moots, R. J.; Kendall, M. J.

doi:10.1136/pgmj.70.830.863

Cited by 144 publications

(83 citation statements)

References 102 publications

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“…However, we were only able to examine this variable in the incident cases; thus, some caution in the interpretation of these data is in order. Glucocorticoids have been considered to contribute to accelerated atherosclerosis in SLE (36)(37)(38)(39). Although venous and arterial thrombosis may share some clotting abnormalities, atherogenic factors, which are very important in the arterial system, are less important in the venous compartment.…”

Section: Discussionmentioning

confidence: 99%

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients

Calvo‐Alén

Toloza

Fernández

et al. 2005

Arthritis & Rheumatism

127

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Objective. Venous thrombosis is a relatively frequent and serious complication in systemic lupus erythematosus (SLE) that has been associated with the presence of antiphospholipid antibodies (aPL). However, venous thrombotic events can also be seen in patients without aPL, and only a few patients with aPL develop venous thrombosis. This study was carried out to ascertain other factors contributing to the development of venous thrombosis in SLE.Methods. Patients with SLE, ages >16 years with <5 years disease duration and of Hispanic, African American, or Caucasian ethnicity, from LUMINA (LUpus in MInorities, NAture versus nurture), a multiethnic, longitudinal study of outcome, were studied. Selected socioeconomic/demographic, clinical, laboratory, and treatment-exposure variables were compared between patients who developed and those who did not develop venous thrombotic events. Significant and clinically relevant variables were then entered into different multivariable models (Cox proportional hazards and unconditional stepwise logistic regression) to identify independent risk factors associated with the primary outcome. In another model, only patients who developed an event after enrollment (time 0) in the cohort were included.Results. Of 570 LUMINA patients, 51 developed at least 1 venous thrombotic event after SLE diagnosis. In univariable analyses, smoking (P ‫؍‬ 0.020), shorter disease duration at time 0 (P ‫؍‬ 0.017), serum levels of total cholesterol, low-density lipoprotein, and triglycerides (all P < 0.0001), and presence of lupus anticoagulant (LAC) (P ‫؍‬ 0.045) were associated with venous thrombotic events. Survival analyses showed a timedependent significant association of the primary outcome with smoking (P ‫؍‬ 0.008) and a borderline significant association with the presence of LAC (P ‫؍‬ 0.070). Multivariable models showed an independent association with smoking, age at time 0, disease activity over time, LAC, mean dose of glucocorticoids, and shorter disease duration at time 0.Conclusion. Venous thrombotic events occur early in the course of SLE. Our data confirm the association between LAC and venous thrombotic events. Smoking, shorter disease duration, older age, disease activity over

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Section: Discussionmentioning

confidence: 99%

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients

Calvo‐Alén

Toloza

Fernández

et al. 2005

Arthritis & Rheumatism

127

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“…Therefore, it was assumed that only 23% of the plasma total drug enters the cell to bind to their cytosolic receptors. Thus the free drug can be expressed as (4) where D t is the total MPL concentration in the plasma in nM (C t · 1000/374.4; MW of MPL: 374.4), where C t is expressed in terms of ng/ml and D f is the intracellular drug concentration (in nM).…”

Section: Modeling Of Receptor Dynamicsmentioning

confidence: 99%

“…Severe metabolic side effects, including steroid-induced diabetes, muscle atrophy, and disorders in lipid metabolism (3,4), limit their therapeutic usefulness, especially with high-dose and long-term therapy. These actions of CS are predominantly generated by influencing the expression of diverse genes in numerous tissues.…”

Section: Introductionmentioning

confidence: 99%

Assessing the Dynamics of Nuclear Glucocorticoid-Receptor Complex: Adding Flexibility to Gene Expression Modeling

Hazra

DuBois

Almon

et al. 2007

J Pharmacokinet Pharmacodyn

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A retrospective analysis was performed to modify our fourth-generation pharmacodynamic model for glucocorticoid receptor (GR) dynamics with incorporation of more physiological features. This modified model was developed by integrating previously reported free cytosolic GR and GR mRNA data following single (10, 50 mg/kg) and dual (50 mg/kg at 0 and 24 hr) intravenous doses of methylprednisolone (MPL) in adrenalectomized (ADX) male Wistar rats with several in vitro studies describing real-time kinetics of the transfer of rat steroid-receptor complex from the cell cytosol to the nucleus. Additionally, free hepatic cytosolic GR and its mRNA data from a chronic infusion dosing study of MPL (0.1 and 0.3 mg/kg/hr) in male ADX Wistar rats were used to verify the predictability of the model. Incorporation of information regarding in vitro receptor kinetics allowed us to describe the receptor-mediated pharmacogenomic effects of MPL for a larger variety of genes in rat liver from microarray studies. These included early responsive gene like CCAAT/ enhancer binding protein-β (CEBP-β), a transcription factor, as well as the later responsive gene for tyrosine aminotransferase (TAT), a classical biomarker of glucocorticoid (GC) genomic effects. This more mechanistic model of GR dynamics can be applied to characterize profiles for a greater number of genes in liver.

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“…The role of glucocorticoids in the occurrence of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) has been a subject of controversy for decades (1)(2)(3)(4)(5)(6). The undesirable effects of glucocorticoids on blood pressure, insulin resistance, lipid profile, body weight and fat distribution, and coagulation proteins might significantly increase the risk of CVD in RA patients (1,2,4,6).…”

mentioning

confidence: 99%

“…The undesirable effects of glucocorticoids on blood pressure, insulin resistance, lipid profile, body weight and fat distribution, and coagulation proteins might significantly increase the risk of CVD in RA patients (1,2,4,6). Although the literature supports the development of these potentially harmful effects with high-dose glucocorticoid therapy, it has been recognized that there is no firm evidence linking low-dose therapy and CVD in the RA population (7,8).…”

mentioning

confidence: 99%

Glucocorticoids and cardiovascular events in rheumatoid arthritis: A population‐based cohort study

Davis¹,

Kremers²,

Crowson³

et al. 2007

Arthritis & Rheumatism

220

122

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Objective. To determine the relationship between glucocorticoid exposure and cardiovascular (CV) events in patients with rheumatoid arthritis (RA).Methods. A total of 603 adult residents of Rochester, Minnesota with incident RA between 1955 and 1995 were followed up through their medical records for a median of 13 years (total of 9,066 person-years). Glucocorticoid exposure was defined 3 ways: tertiles of cumulative exposure; recent use (<3 months) versus past use (>3 months); and average daily dosage (<7.5 mg/day or >7.5 mg/day). CV events, including myocardial infarction, heart failure, and death from CV causes, were defined according to validated criteria. Cox regression models were adjusted for demographic features, CV risk factors, and RA characteristics.Results. Rheumatoid factor (RF)-negative patients with exposure to glucocorticoids were not at increased risk of CV events, irrespective of the glucocorticoid dosage or timing of use, as compared with the reference group of RF-negative patients who had never been exposed to glucocorticoids. In contrast, RFpositive patients were at increased risk of CV events, particularly with higher cumulative exposure, higher average daily dosage, and recent use of glucocorticoids. RF-positive patients with high cumulative exposure to glucocorticoids had a 3-fold increased risk of CV events (hazard ratio 3.06 [95% confidence interval 1.81-5.18]), whereas RF-negative patients with high cumulative exposure were not at increased risk (hazard ratio 0.85 [95% confidence interval 0.39-1.87]).Conclusion. RF-positive but not RF-negative patients were at increased risk of CV events following exposure to glucocorticoids. These findings suggest that glucocorticoids interact with RF status to modulate the occurrence of CV events in patients with RA. The mechanisms underlying this interaction are unknown and should be the subject of further research.

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Corticosteroids: do they damage the cardiovascular system?

Cited by 144 publications

References 102 publications

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients

Assessing the Dynamics of Nuclear Glucocorticoid-Receptor Complex: Adding Flexibility to Gene Expression Modeling

Glucocorticoids and cardiovascular events in rheumatoid arthritis: A population‐based cohort study

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