Association of Vitamin K status with arterial calcification and stiffness in chronic kidney disease: The chronic renal insufficiency cohort

Authors: SHEA, KYLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WANG, JIFAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BARGER, KATHRYN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WEINER, DANIEL - Tufts University; TOWNSEND, RAYMOND - University Of Pennsylvania; FELDMAN, HAROLD - University Of Pennsylvania; ROSAS, SYLVIA - Beth Israel Deaconess Medical Center; CHEN, JING - Tulane University; HE, JIANG - Tulane University; FLACK, JOHN - Southern Illinois University; JAAR, BERNARD - Johns Hopkins University; KANSAL, MAYANK - University Of Illinois; BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Current Developments in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/20/2022
Publication Date: 12/23/2022
Citation: Shea, K., Wang, J., Barger, K., Weiner, D.E., Townsend, R., Feldman, H.I., Rosas, S., Chen, J., He, J., Flack, J., Jaar, B., Kansal, M., Booth, S.L. 2022. Association of Vitamin K status with arterial calcification and stiffness in chronic kidney disease: The chronic renal insufficiency cohort. Current Developments in Nutrition. https://doi.org/10.1016/j.cdnut.2022.100008.
DOI: https://doi.org/10.1016/j.cdnut.2022.100008

Interpretive Summary: Motivated by cross-sectional studies reporting inverse associations between vitamin K status and arterial calcification and stiffness, we evaluated the association of vitamin K status biomarkers with coronary artery calcification and arterial stiffness in a cohort of adults with chronic kidney disease (CKD). Individuals with CKD commonly develop arterial calcification and stiffness, which are both manifestations of poor vascular health. Vitamin K status was estimated using two blood-based biomarkers. Coronary artery calcification and arterial stiffness were measured for up to 4 years of follow-up. In contrast to our hypothesis, we did not detect any consistent associations between vitamin K status with coronary artery calcification or arterial stiffness. Given the burden of poor vascular health in CKD, alternate therapeutic strategies merit investigation.

Technical Abstract: Background: Individuals with chronic kidney disease (CKD) frequently develop arterial calcification and stiffness. Cross-sectionally, higher vitamin K status has been associated with less arterial calcification and stiffness in CKD. Objective: To determine the association of vitamin K status with coronary artery calcium (CAC) and arterial stiffness (pulse wave velocity (PWV)) at baseline and over 2-4 follow-up years in adults with mild to moderate CKD. Methods: Participants (n=2722) were drawn from the well-characterized Chronic Renal Insufficiency Cohort. Two vitamin K status biomarkers, plasma phylloquinone and plasma dephospho-uncarboxylated matrix gla protein ((dp)ucMGP), were measured at baseline. CAC and PWV were measured at baseline and over 2-4 years of follow-up. Differences across vitamin K status categories in CAC prevalence, incidence, and progression (defined as >=100 Agatston Units/year increase) and PWV at baseline and over follow-up were evaluated using multivariable-adjusted generalized linear models. Results: CAC prevalence, incidence and progression did not differ across plasma phylloquinone categories. CAC prevalence and incidence did not differ according to plasma (dp)ucMGP. Compared to participants with the highest (dp)ucMGP (>=450 pmol/L), those in the middle category (300-449 pmol/L) had a 49% lower rate of CAC progression [incidence rate ratio (IRR) (95%CI)=0.51(0.33, 0.78)]. However, CAC progression did not differ between those with the lowest (<300 pmol/L) and those with the highest plasma (dp)ucMGP [IRR(95%CI)=0.82(0.56, 1.19)]. Neither vitamin K status biomarker was associated with PWV at baseline or longitudinally. Conclusions: Vitamin K status was not consistently associated with CAC or PWV in adults with mild to moderate CKD.