Journal article
Use of bisphosphonates in chronic kidney disease is associated with cardiovascular death
Clinical nephrology, Vol.103(1), pp.5-11
01/01/2025
DOI: 10.5414/CN111428
PMID: 39545393
Abstract
Chronic kidney disease (CKD) is associated with increased cardiovascular risk, which may be mediated by vascular calcification. Based on evidence that bisphosphonates inhibit vascular calcification, we hypothesized use of bisphosphonates in CKD would be associated with lower incident cardiovascular disease (CVD), CVD-related mortality, and all-cause mortality.BACKGROUND AND OBJECTIVESChronic kidney disease (CKD) is associated with increased cardiovascular risk, which may be mediated by vascular calcification. Based on evidence that bisphosphonates inhibit vascular calcification, we hypothesized use of bisphosphonates in CKD would be associated with lower incident cardiovascular disease (CVD), CVD-related mortality, and all-cause mortality.This was a longitudinal observational study including 2,593 Framingham Offspring participants. We used propensity score-adjusted Cox regression models to determine the association between bisphosphonate use and outcomes: time to incident CVD, time to CVD-related mortality, and time to all-cause mortality. The data were stratified by presence or absence of CKD, defined as estimated glomerular filtration rate < 60 mL/min/1.73m2. The propensity score included age, sex, hypertension, smoking status, diabetes, total cholesterol, high-density lipoprotein, and self-reported history of fracture.MATERIALS AND METHODSThis was a longitudinal observational study including 2,593 Framingham Offspring participants. We used propensity score-adjusted Cox regression models to determine the association between bisphosphonate use and outcomes: time to incident CVD, time to CVD-related mortality, and time to all-cause mortality. The data were stratified by presence or absence of CKD, defined as estimated glomerular filtration rate < 60 mL/min/1.73m2. The propensity score included age, sex, hypertension, smoking status, diabetes, total cholesterol, high-density lipoprotein, and self-reported history of fracture.In unadjusted and propensity score-adjusted analyses, those with CKD using bisphosphonates had a trend toward increased incident CVD risk (adjusted hazard ratio (HR) 1.66 (95% CI, 93 - 2.97)) compared to those with CKD not using bisphosphonates. Those with CKD using bisphosphonates also had increased risk of cardiovascular mortality in the propensity score-adjusted model (adjusted HR 2.20 (95% CI, 1.12 - 4.32)). There was no significant association between bisphosphonate use and all-cause mortality in participants with CKD. Among individuals without CKD, bisphosphonate use was significantly associated with an increase in all-cause mortality in the propensity-score adjusted analysis (adjusted HR 1.59 (95% CI, 1.27 - 1.98)). However, there was no significant association between bisphosphonate use and incident CVD events (adjusted HR 0.85 95% CI, 0.63 - 1.16) or CVD-related death (adjusted HR 0.70 (95% CI 0.36 - 1.37) in those without CKD.RESULTSIn unadjusted and propensity score-adjusted analyses, those with CKD using bisphosphonates had a trend toward increased incident CVD risk (adjusted hazard ratio (HR) 1.66 (95% CI, 93 - 2.97)) compared to those with CKD not using bisphosphonates. Those with CKD using bisphosphonates also had increased risk of cardiovascular mortality in the propensity score-adjusted model (adjusted HR 2.20 (95% CI, 1.12 - 4.32)). There was no significant association between bisphosphonate use and all-cause mortality in participants with CKD. Among individuals without CKD, bisphosphonate use was significantly associated with an increase in all-cause mortality in the propensity-score adjusted analysis (adjusted HR 1.59 (95% CI, 1.27 - 1.98)). However, there was no significant association between bisphosphonate use and incident CVD events (adjusted HR 0.85 95% CI, 0.63 - 1.16) or CVD-related death (adjusted HR 0.70 (95% CI 0.36 - 1.37) in those without CKD.Contrary to our hypothesis, bisphosphonate use was associated with a trend toward increased incident CVD and a two-fold higher risk of CVD mortality in CKD.CONCLUSIONContrary to our hypothesis, bisphosphonate use was associated with a trend toward increased incident CVD and a two-fold higher risk of CVD mortality in CKD.
Details
- Title: Subtitle
- Use of bisphosphonates in chronic kidney disease is associated with cardiovascular death
- Creators
- Kathleen A Borghoff - University of Nebraska Medical CenterAgnes E Ounda - The University of Texas Health Science Center at TylerMelissa L Swee - University of IowaSaket Girotra - The University of Texas Southwestern Medical CenterAmal A Shibli-Rahhal - University of IowaPatrick Ten Eyck - University of IowaDiana I Jalal - University of IowaAnna J Jovanovich - Bozeman Health Deaconess Hospital
- Resource Type
- Journal article
- Publication Details
- Clinical nephrology, Vol.103(1), pp.5-11
- Publisher
- DUSTRI-VERLAG DR KARL FEISTLE
- DOI
- 10.5414/CN111428
- PMID
- 39545393
- ISSN
- 0301-0430
- Grant note
- University of Iowa Clinical and Translational Science Award - NIH: UL1TR002537 VA Merit Award
This study was supported in part by The University of Iowa Clinical and Translational Science Award - NIH (UL1TR002537) . Dr. Jalal is supported by R01HL134738 Dr. Jova-novich by VA Merit Award I01CX001985.
- Language
- English
- Electronic publication date
- 11/15/2024
- Date published
- 01/01/2025
- Academic Unit
- Biostatistics; Cardiovascular Medicine; Nephrology; Medicine Administration; Endocrinology and Metabolism; Internal Medicine; Design Biostat and Ethics
- Record Identifier
- 9984747818802771
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