M Kyla Shea1, Kathryn Barger1, Sarah L Booth1, Jifan Wang1, Harold I Feldman2, Raymond R Townsend2, Jing Chen3, John Flack4, Jiang He5, Bernard G Jaar6, Mayank Kansal7, Sylvia E Rosas8, Daniel E Weiner9. 1. USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. 2. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. 3. Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA. 4. Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA. 5. Department of Epidemiology, Tulane University School of Medicine, New Orleans, LA, USA. 6. Department of Medicine, Johns Hopkins University, Baltimore, MD, USA. 7. Department of Medicine, University of Illinois-Chicago, Chicago, IL, USA. 8. Joslin Diabetes Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. 9. Division of Nephrology, Tufts Medical Center, Boston, MA, USA.
Abstract
BACKGROUND: Vascular calcification contributes to cardiovascular disease (CVD) and mortality in individuals with chronic kidney disease (CKD). Vitamin K-dependent proteins function as calcification inhibitors in vascular tissue. OBJECTIVES: We sought to determine the association of vitamin K status with mortality and CVD events in adults with CKD. METHODS: Plasma dephospho-uncarboxylated matrix gla protein ((dp)ucMGP), which increases when vitamin K status is low, and plasma phylloquinone (vitamin K1), which decreases when vitamin K status is low, were measured in 3066 Chronic Renal Insufficiency Cohort participants (median age = 61 y, 45% female, 41% non-Hispanic black, median estimated glomerular filtration rate [eGFR] = 41 mL/min/1.73m2). The association of vitamin K status biomarkers with all-cause mortality and atherosclerotic-related CVD was determined using multivariable Cox proportional hazards regression. RESULTS: There were 1122 deaths and 599 atherosclerotic CVD events over the median 12.8 follow-up years. All-cause mortality risk was 21-29% lower among participants with plasma (dp)ucMGP <450 pmol/L (n = 2361) compared with those with plasma (dp)ucMGP ≥450 pmol/L (adjusted HRs [95% CIs]: <300 pmol/L = 0.71 [0.61, 0.83], 300-449 pmol/L = 0.77 [0.66, 0.90]) and 16-19% lower among participants with plasma phylloquinone ≥0.50 nmol/L (n = 2421) compared to those with plasma phylloquinone <0.50 nmol/L (adjusted HRs: 0.50, 0.99 nmol/L = 0.84 [0.72, 0.99], ≥1.00 nmol/L = 0.81 [0.70, 0.95]). The risk of atherosclerotic CVD events did not significantly differ across plasma (dp)ucMGP or phylloquinone categories. CONCLUSIONS: Two biomarkers of vitamin K status were associated with a lower all-cause mortality risk but not atherosclerotic CVD events. Additional studies are needed to clarify the mechanism underlying this association and evaluate the impact of improving vitamin K status in people with CKD.
BACKGROUND: Vascular calcification contributes to cardiovascular disease (CVD) and mortality in individuals with chronic kidney disease (CKD). Vitamin K-dependent proteins function as calcification inhibitors in vascular tissue. OBJECTIVES: We sought to determine the association of vitamin K status with mortality and CVD events in adults with CKD. METHODS: Plasma dephospho-uncarboxylated matrix gla protein ((dp)ucMGP), which increases when vitamin K status is low, and plasma phylloquinone (vitamin K1), which decreases when vitamin K status is low, were measured in 3066 Chronic Renal Insufficiency Cohort participants (median age = 61 y, 45% female, 41% non-Hispanic black, median estimated glomerular filtration rate [eGFR] = 41 mL/min/1.73m2). The association of vitamin K status biomarkers with all-cause mortality and atherosclerotic-related CVD was determined using multivariable Cox proportional hazards regression. RESULTS: There were 1122 deaths and 599 atherosclerotic CVD events over the median 12.8 follow-up years. All-cause mortality risk was 21-29% lower among participants with plasma (dp)ucMGP <450 pmol/L (n = 2361) compared with those with plasma (dp)ucMGP ≥450 pmol/L (adjusted HRs [95% CIs]: <300 pmol/L = 0.71 [0.61, 0.83], 300-449 pmol/L = 0.77 [0.66, 0.90]) and 16-19% lower among participants with plasma phylloquinone ≥0.50 nmol/L (n = 2421) compared to those with plasma phylloquinone <0.50 nmol/L (adjusted HRs: 0.50, 0.99 nmol/L = 0.84 [0.72, 0.99], ≥1.00 nmol/L = 0.81 [0.70, 0.95]). The risk of atherosclerotic CVD events did not significantly differ across plasma (dp)ucMGP or phylloquinone categories. CONCLUSIONS: Two biomarkers of vitamin K status were associated with a lower all-cause mortality risk but not atherosclerotic CVD events. Additional studies are needed to clarify the mechanism underlying this association and evaluate the impact of improving vitamin K status in people with CKD.
Authors: M Kyla Shea; Kathryn Barger; Sarah L Booth; Gregory Matuszek; Mary Cushman; Emelia J Benjamin; Stephen B Kritchevsky; Daniel E Weiner Journal: Am J Clin Nutr Date: 2020-06-01 Impact factor: 7.045
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Authors: Mark J Sarnak; Kerstin Amann; Sripal Bangalore; João L Cavalcante; David M Charytan; Jonathan C Craig; John S Gill; Mark A Hlatky; Alan G Jardine; Ulf Landmesser; L Kristin Newby; Charles A Herzog; Michael Cheung; David C Wheeler; Wolfgang C Winkelmayer; Thomas H Marwick Journal: J Am Coll Cardiol Date: 2019-10-08 Impact factor: 24.094
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Authors: M Kyla Shea; Jifan Wang; Kathryn Barger; Daniel E Weiner; Sarah L Booth; Stephen L Seliger; Amanda H Anderson; Rajat Deo; Harold I Feldman; Alan S Go; Jiang He; Ana C Ricardo; Manjula Kurella Tamura Journal: Curr Dev Nutr Date: 2022-06-24