Background: The purpose of this study was to investigate the association between kidney function and arterial calcification in major vascular beds and to establish whether arterial calcification mediates the relation between kidney function measures and cardiovascular disease (CVD) incidence. Methods and Results: In 2241 participants from the Rotterdam Study (mean age 69 years, 52% female), kidney function was assessed using the estimated glomerular filtration rate and urine albumin-to-creatinine ratio. All participants underwent noncontrast computed tomography to quantify the amount of arterial calcification in the coronary arteries, aortic arch, extracranial, and intracranial internal carotid arteries. We used linear regression models, adjusted for age, sex, and cardiovascular risk factors, to evaluate the association between kidney function and arterial calcification volume in the 4 vessel beds. Incidence rate of CVD was calculated in 3 groups of participants based on their kidney function and presence of arterial calcification. We conducted mediation analysis to evaluate whether arterial calcification mediates this association. We found that in age- and sex-adjusted models, lower estimated glomerular filtration rate and higher albumin-to-creatinine ratio were associated with larger calcification volumes in all 4 vascular beds. Adjusting for cardiovascular risk factors attenuated the effect estimates. CVD incidence was higher in participants with estimated glomerular filtration rate <60 mL/min per 1.73 m2 and presence of arterial calcification compared with individuals with estimated glomerular filtration rate >60 and no calcification. After adjusting for cardiovascular risk factors, arterial calcification did not mediate the association between kidney function measures and CVD incidence. Conclusions: The association of impaired kidney function and larger volumes of arterial calcification is partly explained by cardiovascular risk factors. Arterial calcification does not mediate the association between kidney function and CVD beyond cardiovascular risk factors.
Bibliographical noteFunding Information:
The Rotterdam Study investigators are grateful to the participants and staff from the Rotterdam Study, the participating general practitioners, and the pharmacists. We thank Dr Magda Meester for her assistance.
The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture and Science; the Ministry of Health, Welfare and Sports; the European Commission; and the Municipality of Rotterdam. The research leading to these results has received funding from the European Union Seventh Framework Programma (FP7/2007-2013) under grant agreement no. 601055, VPH-DARE@IT. Oscar H. Franco works in Erasmus-AGE, a center for aging research across the life course funded by NestléNutrition (Nestec Ltd), Metagenics Inc, and AXA. Maryam Kavousi is supported by the VENI grant (91616079) from The Netherlands Organization for Health Research and Development (ZonMw). NestléNutrition (Nestec Ltd), Meta-genics Inc, and AXA had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
© 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
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