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Does Vitamin D Have a Role in Reducing the Risk of Peripheral Artery Disease?

  • Luca Mascitelli
    Affiliations
    Comando Brigata Alpina “Julia”, Udine, Italy
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  • Mark R. Goldstein
    Affiliations
    Fountain Medical Court, Bonita Springs, FL
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  • Author Footnotes
    1 Dr Grant receives or has received funding from the UV Foundation (McLean, VA), the Sunlight Research Forum (Veldhoven), Bio-Tech-Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), and the Danish Sunbed Federation.
    William B. Grant
    Footnotes
    1 Dr Grant receives or has received funding from the UV Foundation (McLean, VA), the Sunlight Research Forum (Veldhoven), Bio-Tech-Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), and the Danish Sunbed Federation.
    Affiliations
    Sunlight, Nutrition, and Health Research Center (SUNARC), San Francisco, CA
    Search for articles by this author
  • Author Footnotes
    1 Dr Grant receives or has received funding from the UV Foundation (McLean, VA), the Sunlight Research Forum (Veldhoven), Bio-Tech-Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), and the Danish Sunbed Federation.
      To the Editor: In their otherwise excellent review, Olin and Sealove
      • Olin JW
      • Sealove BA
      Peripheral artery disease: current insight into the disease and its diagnosis and management.
      did not consider the role of vitamin D status in the development of peripheral artery disease (PAD).
      Vitamin D deficiency is highly prevalent in the United States and worldwide. In particular, a recent study reported that vitamin D levels were independently associated with PAD among 4839 participants of the National Health and Nutrition Examination Survey 2001 to 2004.
      • Melamed ML
      • Muntner P
      • Michos ED
      • et al.
      Serum 25-hydroxyvitamin D levels and the prevalence of peripheral arterial disease: results from NHANES 2001 to 2004.
      For each decrease of 10 ng/mL in the 25-hydroxyvitamin D level, the multivariable-adjusted prevalence ratio of PAD was 1.35 (95% confidence interval, 1.15-1.59).
      • Melamed ML
      • Muntner P
      • Michos ED
      • et al.
      Serum 25-hydroxyvitamin D levels and the prevalence of peripheral arterial disease: results from NHANES 2001 to 2004.
      Furthermore, racial differences in vitamin D concentrations could explain nearly one-third of the excess risk of PAD in black adults, above and beyond differences in established and novel risk factors for cardiovascular disease.
      • Reis JP
      • Michos ED
      • von Mühlen D
      • Miller III, ER
      Differences in vitamin D status as a possible contributor to the racial disparity in peripheral arterial disease.
      Several mechanisms may explain the association of vitamin D deficiency with PAD. Low vitamin D status is associated with obesity, diabetes, and hypertension, all of which increase the risk of PAD. However, the inverse relationship between vitamin D status and PAD remained after adjustment for these risk factors, suggesting additional explanatory mechanisms.
      • Reis JP
      • Michos ED
      • von Mühlen D
      • Miller III, ER
      Differences in vitamin D status as a possible contributor to the racial disparity in peripheral arterial disease.
      Vitamin D receptors have a broad distribution that includes vascular smooth cells, macrophages, and lymphocytes. Directly or indirectly, 1,25-dihydroxyvitamin D (the active form of vitamin D) regulates the expression of a number of proteins relevant to the arterial wall, such as vascular endothelial growth factor, matrix metalloproteinase type 9, myosin, elastin, and type I collagen.
      • Norman PE
      • Powell JT
      Vitamin D, shedding light on the development of disease in peripheral arteries.
      PAD manifestations, including claudication, rest pain, and tissue loss, are not related to arterial hemodynamics alone. Indeed, increasing evidence suggests that a myopathy is present, contributes to, and (to a certain extent) determines the pathogenesis of PAD. A state of repetitive cycles of exercise-induced ischemia followed by reperfusion at rest in patients with PAD may mediate a large number of structural and metabolic changes in the muscle, resulting in reduced strength and function. In this setting, vitamin D may exert a fundamental role. Vitamin D status is significantly associated with muscle strength, and a lack of vitamin D can cause myopathy, which tends to be more marked in the proximal muscles. Vitamin D is reported to mediate protein synthesis and cellular adenosine triphosphate accumulation, increase troponin C, and increase actin and sarcoplasmic protein expression in striated muscles.
      • Gilsanz V
      • Kremer A
      • Mo AO
      • Wren TA
      • Kremer R
      Vitamin D status and its relation to muscle mass and muscle fat in young women.
      Thus, vitamin D may have a fundamental role in reducing the risk of PAD, and studies of vitamin D supplementation for patients with PAD are urgently needed. In the meantime, adequate outdoor activity and sun exposure, along with vitamin D supplementation (to reach serum 25-hydroxyvitamin D levels of at least 30 ng/mL), should be considered for both the prevention and the treatment of PAD.

      REFERENCES

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        • Sealove BA
        Peripheral artery disease: current insight into the disease and its diagnosis and management.
        Mayo Clin Proc. 2010; 85: 678-692
        • Melamed ML
        • Muntner P
        • Michos ED
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        Serum 25-hydroxyvitamin D levels and the prevalence of peripheral arterial disease: results from NHANES 2001 to 2004.
        Arterioscler Thromb Vasc Biol. 2008; 28: 1179-1185
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        Differences in vitamin D status as a possible contributor to the racial disparity in peripheral arterial disease.
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        • Powell JT
        Vitamin D, shedding light on the development of disease in peripheral arteries.
        Arterioscler Thromb Vasc Biol. 2005; 25: 39-46
        • Gilsanz V
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        • Mo AO
        • Wren TA
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        Vitamin D status and its relation to muscle mass and muscle fat in young women.
        J Clin Endocrinol Metab. 2010; 95: 1595-1601

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