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Thromb Haemost 2017; 117(01): 158-163
DOI: 10.1160/TH16-07-0551
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

Serum 25-hydroxyvitamin D and the risk of stroke in Hong Kong Chinese

Raymond Y. H. Leung   *
1   Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
2   Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
,
Yi Han   *
1   Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
,
Chor-Wing Sing
1   Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
,
Bernard M. Y. Cheung
2   Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
3   The State Key Laboratory of Pharmaceutical Biotechnology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
,
Ian C. K. Wong
1   Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
5   Research Department of Practice and Policy, UCL School of Pharmacy, London, United Kingdom
,
Kathryn C. B. Tan
2   Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
,
Annie W. C. Kung
2   Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
,
Ching-Lung Cheung
1   Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
3   The State Key Laboratory of Pharmaceutical Biotechnology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
4   Centre for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
› Author Affiliations Financial support: This project was funded by HMRF (HKU-12132451), HKSAR, China.
Further Information

Publication History

Received: 21 July 2016

Accepted after major revision: 30 September 2016

Publication Date:
01 December 2017 (online)

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Summary

Low vitamin D levels have been associated with various cardiovascular diseases; however, whether it is associated with stroke remains inconclusive. We aimed to evaluate the association between serum 25-hydroxyvitamin D and risk of stroke. We conducted a cohort study consisting of 3,458 participants from the Hong Kong Osteoporosis Study aged ≥45 at baseline, examined between 1995 and 2010 and followed up using electronic medical records. Ischaemic and haemorrhagic stroke were defined using the ICD-9 code. In multivariable Cox-proportional hazard regression, quintiles 1 and 4 were significantly associated with increased risk of stroke when compared to the highest quintile (Quintile 1: HR, 1.78; 95 % CI, 1.16–2.74 and quintile 4: HR, 1.61; 95 % CI, 1.07–2.43). A similar association was observed in both men and women. In subgroup analysis, the association was specifically observed for ischaemic stroke, but not haemorrhagic stroke. Using a penalized regression spline, the association between vitamin D and risk of stroke was in a reverse J-shape, with the lowest risk of stroke being observed at 25(OH)D levels between 70 and 80 nmol/l. In conclusion, a low vitamin D level is associated with increased risk of ischaemic stroke; however, whether high vitamin D level is also associated with increased risk of stroke requires further study.

Supplementary Material to this article is available at www.thrombosis-online.com.

Keywords

Stroke - vitamin D - epidemiological studies

* These authors contributed equally.


 

  • References

  • 1 Anderson JL, May HT, Horne BD. et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol 2010; 106: 963-968.
    CrossrefPubMedGoogle Scholar
  • 2 Brøndum-Jacobsen P, Nordestgaard BG, Schnohr P. et al. 25-Hydroxyvitamin D and symptomatic ischaemic stroke: An Original Study and Meta-Analysis. Ann Neurol 2013; 73: 38-47.
    CrossrefPubMedGoogle Scholar
  • 3 Bouillon R, Carmeliet G, Verlinden L. et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocrine Rev 2008; 29: 726-776.
    CrossrefPubMedGoogle Scholar
  • 4 Kilkkinen A, Knekt P, Aro A. et al. Vitamin D status and the risk of cardiovascular disease death. Am J Epidemiol 2009; 170: 1032-1039.
    CrossrefPubMedGoogle Scholar
  • 5 Christakos S, Dhawan P, Verstuyf A. et al. Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. Physiol Rev 2016; 96: 365-408.
    CrossrefPubMedGoogle Scholar
  • 6 Bhan I, Powe CE, Berg AH. et al. Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident haemodialysis patients. Kidney Internat 2012; 82: 84-89.
    CrossrefPubMedGoogle Scholar
  • 7 Forman JP, Giovannucci E, Holmes MD. et al. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension 2007; 49: 1063-1069.
    CrossrefPubMedGoogle Scholar
  • 8 Forouhi NG, Luan Ja, Cooper A. et al. Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance the medical research council ely prospective study 1990-2000. Diabetes 2008; 57: 2619-2625.
    CrossrefPubMedGoogle Scholar
  • 9 Judd SE, Nanes MS, Ziegler TR. et al. Optimal vitamin D status attenuates the age-associated increase in systolic blood pressure in white Americans: results from the third National Health and Nutrition Examination Survey. Am J Clin Nutrition 2008; 87: 136-141.
    PubMedGoogle Scholar
  • 10 Martins D, Wolf M, Pan D. et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Internal Med 2007; 167: 1159-1165.
    CrossrefPubMedGoogle Scholar
  • 11 Melamed ML, Michos ED, Post W. et al. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Internal Med 2008; 168: 1629-1637.
    CrossrefPubMedGoogle Scholar
  • 12 Bouillon R, Carmeliet G, Verlinden L. et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocrine Rev 2008; 29: 726-776.
    CrossrefPubMedGoogle Scholar
  • 13 Li YC. Molecular mechanism of vitamin D in the cardiovascular system. J Invest Med 2011; 59: 868-871.
    CrossrefPubMedGoogle Scholar
  • 14 Buell JS, Dawson-Hughes B. Vitamin D and neurocognitive dysfunction: preventing “D” ecline?. Mol Aspects Med 2008; 29: 415-422.
    CrossrefPubMedGoogle Scholar
  • 15 Kojima G, Bell C, Abbott RD. et al. Low dietary vitamin D predicts 34-year incident stroke the Honolulu heart program. Stroke 2012; 43: 2163-2167.
    CrossrefPubMedGoogle Scholar
  • 16 Sun Q, Pan A, Hu FB. et al. 25-hydroxyvitamin D levels and the risk of stroke a prospective study and meta-analysis. Stroke 2012; 43: 1470-1477.
    CrossrefPubMedGoogle Scholar
  • 17 Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266-281.
    CrossrefPubMedGoogle Scholar
  • 18 Holick MF. Vitamin D Status: Measurement, Interpretation, and Clinical Application. Ann Epidemiol 2009; 19: 73-78.
    CrossrefPubMedGoogle Scholar
  • 19 Kühn T, Kaaks R, Teucher B. et al. Plasma 25-hydroxyvitamin D and its genetic determinants in relation to incident myocardial infarction and stroke in the European prospective investigation into cancer and nutrition (EPIC)-Germany study. PLoS one 2013; 08: e69080.
    CrossrefPubMedGoogle Scholar
  • 20 Gupta A, Prabhakar S, Modi M. et al. Vitamin D status and risk of ischaemic stroke in North Indian patients. Indian J Endocrinol Metabol 2014; 18: 721.
    PubMedGoogle Scholar
  • 21 Marniemi J, Alanen E, Impivaara O. et al. Dietary and serum vitamins and minerals as predictors of myocardial infarction and stroke in elderly subjects. Nutrition Metabol Cardiovasc Dis 2005; 15: 188-197.
    PubMedGoogle Scholar
  • 22 Drechsler C, Pilz S, Obermayer-Pietsch B. et al. Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients. Eur Heart J 2010; 31: 2253-2261.
    CrossrefPubMedGoogle Scholar
  • 23 Michos ED, Reis JP, Post WS. et al. 25-Hydroxyvitamin D deficiency is associated with fatal stroke among whites but not blacks: The NHANES-III linked mortality files. Nutrition 2012; 28: 367-371.
    CrossrefPubMedGoogle Scholar
  • 24 Cheung CL, Tan KC, Bow CH. et al. Low handgrip strength is a predictor of osteoporotic fractures: cross-sectional and prospective evidence from the Hong Kong Osteoporosis Study. Age 2012; 34: 1239-1248.
    CrossrefPubMedGoogle Scholar
  • 25 Sing CW, Cheng VK, Ho DK. et al. Serum calcium and incident diabetes: an observational study and meta-analysis. Osteoporosis Int 2016; 27: 1747-1754.
    CrossrefPubMedGoogle Scholar
  • 26 Cheung CL, Lau KS, Sham PC. et al. Genetic variants in GREM2 are associated with bone mineral density in a southern Chinese population. J Clin Endocrinol Metab 2013; 98: E1557-1561.
    CrossrefPubMedGoogle Scholar
  • 27 Govindarajulu US, Malloy EJ, Ganguli B. et al. The comparison of alternative smoothing methods for fitting non-linear exposure-response relationships with Cox models in a simulation study. Int J Biostatistics 2009 05. Article 2. doi: 10.2202/1557-4679.1104
    PubMedGoogle Scholar
  • 28 Durup D, Jorgensen HL, Christensen J. et al. A Reverse J-Shaped Association Between Serum 25-Hydroxyvitamin D and Cardiovascular Disease Mortality: The CopD Study. J Clin Endocrinol Metab 2015; 100: 2339-2346.
    CrossrefPubMedGoogle Scholar
  • 29 Zittermann A, Kuhn J, Dreier J. et al. Vitamin D status and the risk of major adverse cardiac and cerebrovascular events in cardiac surgery. Eur Heart J 2013; 34: 1358-1364.
    CrossrefPubMedGoogle Scholar
  • 30 Amrein K, Quraishi SA, Litonjua AA. et al. Evidence for a U-shaped relationship between prehospital vitamin D status and mortality: a cohort study. J Clin Endocrinol Metabol 2014; 99: 1461-1469.
    CrossrefPubMedGoogle Scholar
  • 31 Sempos CT, Durazo-Arvizu RA, Dawson-Hughes B. et al. Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the US nationally representative NHANES. J Clin Endocrinol Metabol 2013; 98: 3001-3009.
    CrossrefPubMedGoogle Scholar
  • 32 Lugg ST, Howells PA, Thickett DR. Optimal Vitamin D Supplementation Levels for Cardiovascular Disease Protection. Dis Markers 2015; 2015: 864370.
    PubMedGoogle Scholar
  • 33 Sun Q, Pan A, Hu FB. et al. 25-Hydroxyvitamin D levels and the risk of stroke: a prospective study and meta-analysis. Stroke 2012; 43: 1470.
    CrossrefPubMedGoogle Scholar
  • 34 Hulter H, Melby J, Peterson J. et al. Chronic continuous PTH infusion results in hypertension in normal subjects. J Clin Hypertension 1986; 02: 360-370.
    PubMedGoogle Scholar
  • 35 Gronhoj MH, Gerke O, Mickley H. et al. Associations between calcium-phosphate metabolism and coronary artery calcification; a cross sectional study of a middle-aged general population. Atherosclerosis 2016; 251: 101-108.
    CrossrefPubMedGoogle Scholar
  • 36 Rohrmann S, Garmo H, Malmstrom H. et al. Association between serum calcium concentration and risk of incident and fatal cardiovascular disease in the prospective AMORIS study. Atherosclerosis 2016; 251: 85-93.
    CrossrefPubMedGoogle Scholar
  • 37 Tanko LB, Christiansen C, Cox DA. et al. Relationship between osteoporosis and cardiovascular disease in postmenopausal women. J Bone Mineral Res 2005; 20: 1912-1920.
    CrossrefPubMedGoogle Scholar
  • 38 Jorgensen L, Engstad T, Jacobsen BK. Bone mineral density in acute stroke patients: low bone mineral density may predict first stroke in women. Stroke 2001; 32: 47-51.
    CrossrefPubMedGoogle Scholar
  • 39 Chen YC, Wu JC, Liu L. et al. Hospitalized osteoporotic vertebral fracture increases the risk of stroke: a population-based cohort study. J Bone Mineral Res 2013; 28: 516-523.
    CrossrefPubMedGoogle Scholar
  • 40 Wat WZ, Leung JY, Tam S. et al. Prevalence and impact of vitamin D insufficiency in southern Chinese adults. Ann Nutrition Metabol 2007; 51: 59-64.
    PubMedGoogle Scholar
  • 41 Ford J, Maclennan G, Avenell A. et al. Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis. Am J Clin Nutr 2014; 100: 746-755.
    CrossrefPubMedGoogle Scholar
  • 42 Chan EW, Lau WC, Siu CW. et al. Effect of suboptimal anticoagulation treatment with antiplatelet therapy and warfarin on clinical outcomes in patients with nonvalvular atrial fibrillation: A population-wide cohort study. Heart Rhythm 2016 Epub ahead of print
    PubMedGoogle Scholar
  • 43 Heijboer AC, Blankenstein MA, Kema IP. et al. Accuracy of 6 routine 25-hydroxyvitamin D assays: influence of vitamin D binding protein concentration. Clin Chem 2012; 58: 543-548.
    CrossrefPubMedGoogle Scholar
  • 44 Pradhan AD, Manson JE. Update on the Vitamin D and OmegA-3 trial (VITAL). J Steroid Biochem Mol Biol 2016; 155: 252-256.
    CrossrefPubMedGoogle Scholar
  • 45 Bassuk SS, Manson JE, Lee IM. et al. Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL). Contemp Clin Trials 2016; 47: 235-243.
    CrossrefPubMedGoogle Scholar