Author + information
- Received June 26, 2018
- Revision received September 7, 2018
- Accepted October 14, 2018
- Published online January 21, 2019.
- Georgios Vavilis, MDa,b,c,∗ (, )
- Magnus Bäck, MD, PhDb,d,
- Giuseppe Occhino, MSce,f,
- Marco Trevisan, MSce,
- Rino Bellocco, ScDe,f,
- Marie Evans, MD, PhDg,
- Bengt Lindholm, MD, PhDg,
- Karolina Szummer, MD, PhDa,b,∗@karolinskainst and
- Juan Jesus Carrero, PhDe,∗
- aDepartment of Medicine, Karolinska Institute, Huddinge, Stockholm, Sweden
- bTheme of Heart and Vessels, Division of Coronary and Valvular Heart Disease, Karolinska University Hospital, Stockholm, Sweden
- cFunctional Area of Emergency Medicine, Karolinska University Hospital, Huddinge, Stockholm, Sweden
- dDepartment of Medicine, Karolinska Institute, Solna, Stockholm, Sweden
- eDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
- fDepartment of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy
- gDepartment of Clinical Science, Intervention, and Technology, Karolinska Institute, Stockholm, Sweden
- ↵∗Address for correspondence:
Dr. Georgios Vavilis, Theme of Heart and Vessels, Division of Coronary and Valvular Heart Disease, Karolinska University Hospital, Hälsovägen 1-3, Stockholm 14186, Sweden.
Background Chronic kidney disease (CKD) and aortic stenosis (AS) share many risk factors.
Objectives This study sought to evaluate whether kidney dysfunction is associated with the development of AS in the community.
Methods The study included 1,121,875 Stockholm citizens without a prior diagnosis of AS from the SCREAM (Stockholm CREAtinine Measurements) project. Estimated glomerular filtration rate (eGFR) (ml/min/1.73 m2) was calculated from serum creatinine. AS incidence during follow-up was ascertained by clinical diagnostic codes. The association between eGFR and AS incidence was estimated with multivariable Cox proportional hazards models. Sensitivity analyses included analysis of possible reverse causation bias by excluding the first 6 months to 2 years after enrollment and excluding individuals with comorbid heart failure.
Results The median age was 50 years (interquartile range [IQR]: 36 to 64 years), and 54% of participants were women. Median eGFR was 96 ml/min/1.73 m2 (IQR: 82 to 109 ml/min/1.73 m2), and 66,949 (6.0%) participants had CKD (eGFR <60 ml/min/1.73 m2). During a median follow-up of 5.1 years (IQR: 3.3 to 6.1 years), 5,858 (0.5%) individuals developed AS (incidence rate [IR] 1.13/1,000 person-years). Compared with eGFR >90 (IR 0.34/1,000 person-years), lower eGFR strata were associated with higher hazards of AS: eGFR 60 to 90 ml/min/1.73 m2; IR: 1.88; hazard ratio (HR): 1.14; 95% confidence interval (CI): 1.05 to 1.25; eGFR 45 to 59 ml/min/1.73 m2; IR: 4.61; HR: 1.17; 95% CI: 1.05 to 1.30; eGFR 30 to 44 ml/min/1.73 m2; IR: 6.62; HR: 1.22; 95% CI: 1.07 to 1.39; and eGFR 30 ml/min/1.73 m2; IR: 8.27; HR: 1.56; 95% CI: 1.29 to 1.87. Sensitivity analysis attenuated only slightly the magnitude of the association; individuals with eGFR ≤44 ml/min/1.73 m2 remained at an approximate 20% risk of AS both when excluding events within the 2 years after baseline (HR: 1.22; 95% CI: 1.06 to 1.42) and when excluding participants with heart failure (HR: 1.20; 95% CI: 1.03 to 1.39).
Conclusions CKD, even in moderate to severe stages, is associated with an increased risk of AS.
↵∗ Drs. Szummer and Carrero contributed equally to this work.
Baxter Novum is the result of a grant from Baxter Healthcare to Karolinska Institute. The SCREAM project is funded by Stockholm County Council and the Swedish Heart and Lung Foundation. Dr. Bäck has received grant support from the Swedish Research Council (2014-2312), the Swedish Heart and Lung Foundation (20150600 and 20150683), and the Stockholm County Council (20150869 and 20170365). Dr. Evans has received financial support from the Stockholm County Council (post doc appointment). Dr. Lindholm is employed by Baxter Healthcare. Dr. Szummer has received financial support from the Stockholm County Council (clinical research appointment) and the Swedish Medical association (Svenska Läkarsällskapet); and has received payment for lectures from AstraZeneca and Vifor. Dr. Carrero has reported funding from the Stockholm County Council and the Swedish Heart and Lung Foundation; has received institutional grants from AstraZeneca, ViforPharma, Astellas, Merck, and Novartis; and has been a speaker or consultant for Abbott, Baxter Healthcare, Astellas, and ViforPharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received June 26, 2018.
- Revision received September 7, 2018.
- Accepted October 14, 2018.
- 2019 American College of Cardiology Foundation
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