Serum levels of 25(OH)D are not associated with venous thromboembolism in the elderly population

Marion Andro; Aurélien Delluc; Marie-Pierre Moineau; Cécile Tromeur; Maelenn Gouillou; Karine Lacut; Jean-Luc Carré; Armelle Gentric; Grégoire Le Gal

doi:10.1160/TH15-02-0148

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2016; 115(01): 169-175
DOI: 10.1160/TH15-02-0148

Stroke, Systemic or Venous Thromboembolism

Schattauer GmbH Schattauer

Serum levels of 25(OH)D are not associated with venous thromboembolism in the elderly population

A case-control study

Marion Andro

¹Université de Bretagne Occidentale, EA 3878, Brest, France

²CHRU Brest, Département de gériatrie, Brest, France

,

Aurélien Delluc

¹Université de Bretagne Occidentale, EA 3878, Brest, France

,

Marie-Pierre Moineau

³CHRU Brest, Département de biochimie, Brest, France

,

Cécile Tromeur

¹Université de Bretagne Occidentale, EA 3878, Brest, France

,

Maelenn Gouillou

⁴INSERM, Centre d’investigation clinique CIC 1412, Brest, France

,

Karine Lacut

¹Université de Bretagne Occidentale, EA 3878, Brest, France

⁴INSERM, Centre d’investigation clinique CIC 1412, Brest, France

,

Jean-Luc Carré

³CHRU Brest, Département de biochimie, Brest, France

,

Armelle Gentric

²CHRU Brest, Département de gériatrie, Brest, France

⁵Université de Bretagne Occidentale, EA 4686, Brest, France

,

Grégoire Le Gal

¹Université de Bretagne Occidentale, EA 3878, Brest, France

⁶Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada

› Author Affiliations

Abstract

Summary

The prevalence of both vitamin D deficiency and venous thromboembolism (VTE) is important in the elderly. Previous studies have provided evidence for a possible association between vitamin D status and the risk of VTE. Thus, we aimed to investigate the association between vitamin D levels and VTE in the population aged 75 and over included in the EDITH case-control study. The association between vitamin D status and VTE was analysed. We also analysed the monthly and seasonal variations of VTE and vitamin D. Between May 2000 and December 2009, 340 elderly patients (mean age 81.5 years, 32 % men) with unprovoked VTE and their controls were included. The univariate and multivariate analysis found no significant association between serum levels of vitamin D and the risk of unprovoked VTE. In the unadjusted analysis, a higher BMI was statistically associated with an increased risk of VTE (OR 1.09; 95 % CI 1.05–1.13) whereas a better walking capacity and living at home were associated with a decreased rate of VTE: OR 0.57; 95 % CI 0.36–0.90 and 0.40; 95 % CI 0.25–0.66, respectively. Although not significant, more VTE events occurred during winter (p=0.09). No seasonal variations of vitamin D levels were found (p=0.11). In conclusion, in contrast with previous reports our findings suggest that vitamin D is not associated with VTE in the elderly population.

Keywords

Vitamin D - venous thromboembolism - aged - risk factors - case-control study

Full Text

References

References
1 Oger E. Incidence of venous thromboembolism: a community-based study in Western France. EPI-GETBP Study Group. Groupe d’Etude de la Thrombose de Bretagne Occidentale. Thromb Haemost 2000; 83: 657-660.
2 Heit JA. Venous thromboembolism: disease burden, outcomes and risk factors. J Thromb Haemost 2005; 03: 1611-1617.
3 Glynn RJ, Rosner B. Comparison of risk factors for the competing risks of coronary heart disease, stroke, and venous thromboembolism. Am J Epidemiol 2005; 162: 975-982.
4 Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999; 353: 1167-1173.
5 Cushman M, Tsai AW, White RH. et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med 2004; 117: 19-25.
6 White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107 (23) (Suppl. 01) I4-8.
7 Holick MF. Bioavailability of vitamin D and its metabolites in black and white adults. N Engl J Med 2013; 369: 2047-2048.
8 Recommendations abstracted from the American Geriatrics Society Consensus Statement on Vitamin D for Prevention of Falls and Their Consequences. J Am Geriat Soc 2014; 62: 147-152.
9 Bischoff-Ferrari HA, Conzelmann M, Dick W. et al. Effect of vitamin D on muscle strength and relevance in regard to osteoporosis prevention. Z Rheumatol 2003; 62: 518-521.
10 Bischoff-Ferrari HA, Dietrich T, Orav EJ. et al. Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or =60 y. Am J Clin Nutr 2004; 80: 752-758.
11 Ginde AA, Scragg R, Schwartz RS. et al. Prospective study of serum 25-hydro-xyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older U. S. adults. J Am Geriatr Soc 2009; 57: 1595-1603.
12 Ma Y, Zhang P, Wang F. et al. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. J Clin Oncol 2011; 29: 3775-3782.
13 Baeke F, Takiishi T, Korf H. et al. Vitamin D: modulator of the immune system. Curr Opin Pharmacol 2010; 10: 482-496.
14 Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metabol 2010; 95: 471-478.
15 Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clinic Proc 2011; 86: 50-60.
16 Koyama T, Shibakura M, Ohsawa M. et al. Anticoagulant effects of 1alpha,25-dihydroxyvitamin D3 on human myelogenous leukemia cells and monocytes. Blood 1998; 92: 160-167.
17 Sun J, Kong J, Duan Y. et al. Increased NF-kappaB activity in fibroblasts lacking the vitamin D receptor. Am J Physiol Endocrinol Metabol 2006; 291: E315-322.
18 Wu-Wong JR, Nakane M, Ma J. Vitamin D analogs modulate the expression of plasminogen activator inhibitor-1, thrombospondin-1 and thrombomodulin in human aortic smooth muscle cells. J Vasc Res 2007; 44: 11-18.
19 Watkins RR, Yamshchikov AV, Lemonovich TL. et al. The role of vitamin D deficiency in sepsis and potential therapeutic implications. J Infection 2011; 63: 321-326.
20 Koyama T, Hirosawa S. Anticoagulant effects of synthetic retinoids and activated vitamin D3. Semin Thromb Hemost 1998; 24: 217-226.
21 Hypponen E, Berry D, Cortina-Borja M. et al. 25-Hydroxyvitamin D and pre-clinical alterations in inflammatory and hemostatic markers: a cross sectional analysis in the 1958 British Birth Cohort. PloS One 2010; 05: e10801.
22 Ngo DT, Sverdlov AL, McNeil JJ. et al. Does vitamin D modulate asymmetric dimethylarginine and C-reactive protein concentrations?. Am J Med 2010; 123: 335-341.
23 Cigolini M, Iagulli MP, Miconi V. et al. Serum 25-hydroxyvitamin D3 concentrations and prevalence of cardiovascular disease among type 2 diabetic patients. Diabetes Care 2006; 29: 722-724.
24 Zittermann A, Frisch S, Berthold HK. et al. Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Am J Clin Nutr 2009; 89: 1321-1327.
25 Topaloglu O, Arslan MS, Karakose M. et al. Is there any association between thrombosis and tissue factor pathway inhibitor levels in patients with vitamin D deficiency?. Clin Appl Thromb Hemost 2015; 21: 428-433.
26 Lindqvist PG, Epstein E, Olsson H. Does an active sun exposure habit lower the risk of venous thrombotic events? A D-lightful hypothesis. J Thromb Haemost 2009; 07: 605-610.
27 Oger E, Lacut K, Le Gal G. et al. Hyperhomocysteinemia and low B vitamin levels are independently associated with venous thromboembolism: results from the EDITH study: a hospital-based case-control study. J Thromb Haemost 2006; 04: 793-799.
28 Cavalier E, Lukas P, Crine Y. et al. Evaluation of automated immunoassays for 25(OH)-vitamin D determination in different critical populations before and after standardisation of the assays. Clin Chim Acta 2014; 431: 60-65.
29 Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet 1998; 351: 805-806.
30 Bischoff-Ferrari HA, Giovannucci E, Willett WC. et al. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 2006; 84: 18-28.
31 Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 2008; 87: 1080S-1086S.
32 Hirani V, Tull K, Ali A. et al. Urgent action needed to improve vitamin D status among older people in England!. Age Ageing 2010; 39: 62-68.
33 Brondum-Jacobsen P, Nordestgaard BG, Schnohr P. et al. 25-hydroxyvitamin D and symptomatic ischemic stroke: an original study and meta-analysis. Ann Neurol 2013; 73: 38-47.
34 Semba RD, Houston DK, Bandinelli S. et al. Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults. Eur J Clin Nutr 2010; 64: 203-209.
35 Oger E, Lacut K, Le Gal G. et al. Is APC resistance a risk factor for venous thromboembolism in patients over 70 years?. Thromb Haemost 2002; 88: 587-591.
36 Brodin E, Lerstad G, Grimnes G. et al. Serum levels of vitamin D are not associated with future risk of venous thromboembolism. The Tromso Study. Thromb Haemost 2013; 109: 885-890.
37 Blondon M, Rodabough RJ, Budrys N. et al. The effect of calcium plus vitamin D supplementation on the risk of venous thromboembolism. From the Women’s Health Initiative Randomized Controlled Trial. Thromb Haemost 2015; 113: 999-1009.
38 Folsom AR, Roetker NS, Rosamond WD. et al. Serum 25-hydroxyvitamin D and risk of venous thromboembolism: the Atherosclerosis Risk in Communities (ARIC) Study. J Thromb Haemost 2014; 12: 1455-1460.
39 Dentali F, Ageno W, Rancan E. et al. Seasonal and monthly variability in the incidence of venous thromboembolism. A systematic review and a meta-analysis of the literature. Thromb Haemost 2011; 106: 439-447.
40 Ribeiro DD, Bucciarelli P, Braekkan SK. et al. Seasonal variation of venous thrombosis: a consecutive case series within studies from Leiden, Milan and Tromso. J Thromb Haemost 2012; 10: 1704-1707.
41 Stein PD, Kayali F, Olson RE. Analysis of occurrence of venous thromboembolic disease in the four seasons. Am J Cardiol 2004; 93: 511-513.
42 Lindqvist PG, Epstein E, Olsson H. The relationship between lifestyle factors and venous thromboembolism among women: a report from the MISS study. Br J Haematol 2009; 144: 234-240.
43 Messenger W, Nielson CM, Li H. et al. Serum and dietary vitamin D and cardiovascular disease risk in elderly men: a prospective cohort study. Nutr Metabol Cardiovasc Dis 2012; 22: 856-863.
44 Heit JA, Silverstein MD, Mohr DN. et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160: 809-815.
45 Wattanakit K, Lutsey PL, Bell EJ. et al. Association between cardiovascular disease risk factors and occurrence of venous thromboembolism. A time-dependent analysis. Thromb Haemost 2012; 108: 508-515.