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Premature atherosclerosis is associated with hypovitaminosis D and angiotensin-converting enzyme inhibitor non-use in lupus patients.

ABSTRACT: The ultimate goal is to identify and target modifiable risk factors that will reduce major cardiovascular events in African American lupus patients. As a first step toward achieving this goal, this study was designed to explore risk factor models of preclinical atherosclerosis in a predominantly African American group of patients with systemic lupus erythematosus (SLE) using variables historically associated with endothelial function in nonlupus populations. Fifty-one subjects with SLE but without a history of clinical cardiovascular events were enrolled. At entry, a Framingham risk factor history and medication list were recorded. Sera and plasma samples were analyzed for lipids, lupus activity markers and total 25-hydroxyvitamin D (25 OH)D) levels. Carotid ultrasound measurements were performed to determine total plaque area (TPA) in both carotids. Cases had TPA values above age-matched controls from a vascular prevention clinic population. Logistic regression and machine learning analyses were performed to create predictive models. 25(OH)D levels were significantly lower, and SLE disease duration was significantly higher in cases. 25(OH)D levels inversely correlated with age-adjusted TPA. Angiotensin-converting enzyme (ACE) inhibitor nonuse associated with case status. Logistic regression models containing ACE inhibitor use, 25(OH)D levels and low-density lipoprotein levels had a diagnostic accuracy of 84% for predicting accelerated atherosclerosis. Similar results were obtained with machine learning models, but hydroxychlo-roquine use associated with controls in these models. This is the first study to demonstrate an association between atherosclerotic burden and 25(OH)D insufficiency or ACE inhibitor nonuse in lupus patients. These findings provide strong rationale for the study of ACE inhibitors and vitamin D replenishment as preventive therapies in this high-risk population.

SUBMITTER: Ravenell RL

PROVIDER: S-EPMC3323721 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Premature atherosclerosis is associated with hypovitaminosis D and angiotensin-converting enzyme inhibitor non-use in lupus patients.

Ravenell Roneka L RL Kamen Diane L DL Spence J David JD Hollis Bruce W BW Fleury Thomas J TJ Janech Michael G MG Almeida Jonas S JS Shaftman Stephanie R SR Oates Jim C JC

The American journal of the medical sciences 20121001 4

The ultimate goal is to identify and target modifiable risk factors that will reduce major cardiovascular events in African American lupus patients. As a first step toward achieving this goal, this study was designed to explore risk factor models of preclinical atherosclerosis in a predominantly African American group of patients with systemic lupus erythematosus (SLE) using variables historically associated with endothelial function in nonlupus populations. Fifty-one subjects with SLE but witho ...[more]

PMID: 22222338

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Project description:Immunosuppressants decrease circulating dipeptidyl peptidase IV (DPPIV) activity in transplant patients, and decreased DPPIV activity has been associated with angiotensin-converting enzyme (ACE) inhibitor-associated angioedema. One study has reported an increased incidence of ACE inhibitor-associated angioedema among transplant patients compared to published rates, while several case series report angioedema in patients taking specific immunosuppressant agents.To test the hypothesis that transplant patients are at increased risk of ACE inhibitor-associated angioedema.We assessed the proportion of transplant patients in 145 cases with ACE inhibitor-associated angioedema and 280 ACE inhibitor-exposed controls. We measured the relationship between case-control status, transplant status, and immunosuppressant use and circulating DPPIV activity. We also assessed the incidence of angioedema among consecutive patients who underwent renal or cardiac transplant and were treated with an ACE inhibitor.Transplant patients were significantly overrepresented among ACE inhibitor-associated angioedema cases compared to controls (odds ratio 18.5, 95% CI 2.3-147.2, P = 0.0004). Immunosuppressant use, chronic renal failure, seasonal allergies and smoking were also associated with ACE inhibitor-associated angioedema in univariate analysis. The association of transplant status with ACE inhibitor-associated angioedema was no longer significant after inclusion of immunosuppressant therapy in a multivariate analysis. Dipeptidyl peptidase IV activity was significantly decreased in sera from cases compared to ACE inhibitor-exposed controls, as well as in individuals taking immunosuppressants. Two of 47 ACE inhibitor-treated renal transplant patients and one of 36 ACE inhibitor-treated cardiac transplant patients developed angioedema.Transplant patients are at increased risk of ACE inhibitor-associated angioedema possibly because of the effects of immunosuppressants on the activity of DPPIV.

Project description:ImportancePatients with acute kidney injury (AKI) are at an increased long-term risk of death. Effective strategies that improve long-term outcomes in patients with AKI are unknown.ObjectiveTo evaluate whether the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) after hospital discharge is associated with better outcomes in patients with AKI.Design, setting, and participantsThis retrospective cohort study used data from the Alberta Kidney Disease Network population database to evaluate 46 253 adults 18 years or older with an episode of AKI during a hospitalization between July 1, 2008, and March 31, 2015, in Alberta, Canada. All patients who survived to hospital discharge were followed up for a minimum of 2 years.ExposuresUse of an ACEI or ARB within 6 months after hospital discharge.Main outcomes and measuresThe primary outcome was mortality; secondary outcomes included hospitalization for a renal cause, end-stage renal disease (ESRD), and a composite outcome of ESRD or sustained doubling of serum creatinine concentration. An AKI was defined as a 50% increase between prehospital and peak in-hospital serum creatinine concentrations. Propensity scores were used to construct a matched-pairs cohort of patients who did and did not have a prescription for an ACEI or ARB within 6 months after hospital discharge.ResultsThe study evaluated 46 253 adults (mean [SD] age, 68.6 [16.4] years; 24 436 [52.8%] male). Within 6 months of discharge, 22 193 (48.0%) of the participants were prescribed an ACEI or ARB. After adjustment for comorbidities, ACEI or ARB use before admission, demographics, baseline kidney function, other factors related to index hospitalization, and prior health care services, ACEI or ARB use was associated with lower mortality in patients with AKI after 2 years (adjusted hazard ratio, 0.85; 95% CI, 0.81-0.89). However, patients who received an ACEI or ARB had a higher risk of hospitalization for a renal cause (adjusted hazard ratio, 1.28; 95% CI, 1.12-1.46). No association was found between ACEI or ARB use and progression to ESRD.Conclusions and relevanceAmong patients with AKI, ACEI or ARB therapy appeared to be associated with lower mortality but a higher risk of hospitalization for a renal cause. These results suggest a potential benefit of ACEI or ARB use after AKI, but cautious monitoring for renal-specific complications may be warranted.

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Dataset Information

Premature atherosclerosis is associated with hypovitaminosis D and angiotensin-converting enzyme inhibitor non-use in lupus patients.

Publications

Premature atherosclerosis is associated with hypovitaminosis D and angiotensin-converting enzyme inhibitor non-use in lupus patients.

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