CORRESPONDENCE Vitamin D Deficiency and PAD: A Close and Often Overlooked Relationship I read with great interest the recent article by Mazur et al.1 A number of vitamin deficiencies besides vitamin B12 deficiency may contribute to PAD. Vitamin D deficiency is an independent risk factor for the development and progression of PAD. Individuals with lower serum vitamin D are more prone to develop PAD. Similarly, one third of the increased risk of PAD in Afro-American populations in comparison to Caucasian populations is explained by the lower vitamin D status observed in Afro-American populations. Not surprisingly, secondary hyperparathyroidism is relatively more common in patients with PAD. Higher amputation rates have been noticed in individuals with lower serum vitamin D in the scenario of underlying PAD.2 Nearly 14% of patients with PAD demonstrate vitamin C levels less than 11.4 mmol/l.3 In fact, a shorter absolute claudication distance is seen in those with low L-ascorbic acid concentration and underlying PAD. The above examples clearly illustrate the importance of vitamin supplementation in patients with PAD and the need to increase awareness about this amongst physicians as well as patients. CONFLICT OF INTEREST None declared. REFERENCES 1 Mazur P, Kozynacka A, Durajski L, Głowacki R, Pfitzner R, Fijorek K, et al. N3-homocysteinyl-lysine isopeptide is associated with progression of peripheral artery disease in patients treated with folic acid. Eur J Vasc Endovasc Surg 2012;43:588e93. 2 Gaddipati VC, Bailey BA, Kuriacose R, Copeland RJ, Manning T, Peiris AN. The relationship of vitamin D status to cardiovascular risk factors and amputation risk in veterans with peripheral arterial disease. J Am Med Dir Assoc 2011;12:58e61. 3 Langlois M, Duprez D, Delanghe J, De Buyzere M, Clement DL. Serum vitamin C concentration is low in peripheral arterial disease and is associated with inflammation and severity of atherosclerosis. Circulation 2001;103:1863e8.
S. Kapoor* 2400 Crossing Street, Mechanicsville, VA, United States *Tel.: þ1 8654565678 (Mobile). Email-address:
[email protected] Available online 29 December 2012 Ó 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejvs.2012.11.020 DOI of original article: http://dx.doi.org/10.1016/ j.ejvs.2012.02.022
Re: ‘Vitamin D Deficiency and PAD: A Close and Often Overlooked Relationship’ Vitamins and Homocysteine Metabolism We thank Dr. Kapoor for his interest in our recent article1 and comments on potential links between vitamin D and peripheral artery disease (PAD). Metabolism of homocysteine (Hcy), derived from dietary methionine (Met), is regulated by transsulfuration to cysteine, catalyzed by vitamin B6 dependent cystathionine b-synthase (CBS), and remethylation to Met, catalyzed by vitamin B12 and 5,10-methylenetetrahydrofolate dependent Met synthase (MS).2 Deficiency in vitamin B12, vitamin B6 or folate is associated with increased plasma total Hcy (tHcy), but it is still unknown to what extent reduced vitamin cofactors alter N3ehomocysteinylelysine (N3eHcyeLys), a degradation product of homocysteinylated proteins. We reported that in PAD patients successfully treated for hyperhomocysteinemia, N3eHcyeLys is still associated with disease progression and higher risk of adverse cardiovascular events.1 Moreover, high intake of vitamins C and E and carotenes is associated with lower tHcy.3 Interestingly, Kapoor pointed to a role of vitamin D deficiency in PAD in the context of hyperhomocysteinemia. An in vitro study revealed a link between Hcy metabolism and vitamin D, which was confirmed by the Longitudinal Aging Study Amsterdam.4 Of note, vitamin D deficiency has been reported to be accompanied by higher plasma asymmetric dimethylarginine (ADMA) concentrations, which also correlate positively with circulating N3eHcyeLys.5,6 To our knowledge, there have been no reports showing any association of vitamin D with N3eHcyeLys. It might be speculated that deficiency in vitamin D contributes to PAD progression in part via disturbed Hcy metabolism. REFERENCES 1 Mazur P, Kozynacka A, Durajski L, Glowacki R, Pfitzner R, Fijorek K, et al. N3-homocysteinyl-lysine isopeptide is associated with progression of peripheral artery disease in patients treated with folic acid. Eur J Vasc Endovasc Surg 2012;43:588e93. 2 Jakubowski H. Molecular basis of homocysteine toxicity in humans. Cell Mol Life Sci 2004;61:470e87. 3 Floegel A, Chung SJ, von Ruesten A, Yang M, Chung CE, Song WO, et al. Antioxidant intake from diet and supplements and elevated serum c-reactive protein and plasma homocysteine concentrations in US adults: a cross-sectional study. Public Health Nutr 2011;14:2055e64. 4 Kriebitzsch C, Verlinden L, Eelen G, van Schoor NM, Swart K, Lips P, et al. 1,25-dihydroxyvitamin D3 influences cellular homocysteine levels in murine preosteoblastic mc3t3-e1 cells by direct regulation of cystathionine beta-synthase. J Bone Miner Res. 2011;26:2991e3000. 5 Bednarek-Skublewska A, Smolen A, Jaroszynski A, Zaluska W, Ksiazek A. Effects of vitamin D3 on selected biochemical parameters of nutritional status, inflammation, and cardiovascular disease in patients undergoing long-term hemodialysis. Pol Arch Med Wewn 2010;120:167e74.
