Title: Vitamin D and Stroke: A Comparative Study to Risk Factors and Stroke Type

Authors: Abeer A.Tony, Effat A E.Tony, Emad F. Kholef, Wafaa S Mohammed

 DOI:  https://dx.doi.org/10.18535/jmscr/v5i3.18

Abstract

Background: Stroke remains one of the most devastating neurological diseases, often causing death, or gross physical impairment. Vitamin D deficiency has been reported to contribute to the risk of cardiovascular disease especially stroke. Thus, our study was designed to examine the relationship between serum 25 (OH) D levels and outcomes after stroke either ischemic or hemorrhagic.

Methods: Fifty patients with first–ever acute stroke (25 patients with intracerebal hemorrhage and 25 patients with ischemic infarction). All participants were subjected to full clinical and neurological examination. Brain imaging was performed. Blood samples were drawn for assessment of serum 25-hydroxy vitamin D and parathormone. 

Results: The Majority (84% and 76% respectively) of our studied  patients with acute stroke had insufficient  levels  of vitamin D (˂ 50 nmol/L ) with more reduction in patients with  acute ischemic infarction than hemorrhagic cases (28.72 ± 22.45 versus 38.49 ± 24.68 in group I and group II respectively), but with no statistical significance differences between both groups. There was an association between vitamin D levels, severity of stroke and functional outcome in patients with intracerebral hemorrhage but not in patients with ischemic stroke. In dead patients with intracerebal hemorrhage, an insufficient median vitamin D level was noticeable.

Conclusion: Vitamin D insufficiency may bear an association with acute stroke and its prevalent risk factors with a highest association between low 25(OH)D levels and risk of incident hemorrhagic stroke among people in Upper Egypt.

Keywords: Acute stroke, Scandinavian Stroke Scale (SSS), Modified Rankin Scale (mRS), Serum 25-hydroxyvitamin D, Parathormone (PTH).

References

1.      Pilz S, Tomaschitz A, Drechsler C, Zittermann A, Dekker JM, März W. Vitamin D supplementation: a promising approach for the prevention and treatment of strokes. Curr Drug Targets  2011 ;12:88-96

2.      Wang  L. Song Y, Manson JE, et al. Circulating 25-hydroxyvitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ Cardiovasc Qual Outcomes. 2012;5:819-829.

3.      Anderson JL, May HT, Horne BD,Bair TL, Hall NL,Carlquist JF, Lappé DL, Muhlestein JB. Intermountain Heart Collaborative (IHC) Study Group. Relat-ion of vitamin D deficiency to cardio-vascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol.  2010;106:963-968.

4.      Sun Q, Pan A,  Hu FB, Manson JE, Rexrode KM. 25-hydroxyvitamin D levels and risk of stroke : a prospective study and meta-analysis. Stroke 2012;43: 1470-7 

5.      Wang  Y, Ji  H, Tong Y etal., (2014) Prognostic value of serum 25-hydroxyvitamin D in patients with stroke. Neurochem Res 39:1332-1337

6.      Gupta A, Prabhakar S, Modi M, Bhadada S K,, Lal V, Khurana D. Vitamin D status and risk of ischemic stroke in North Indian patients. Indian Journal of Endocrinology and Metabolism .Sep-Oct 2014; Vol.18, Iss.5:721-5

7.      Mitsuhashi T, Morris RC JR, Ives HE (1991) 1,25-Dihydroxyvitamin D3 modulates growth of vascular smooth muscle cells. J Clin Invest 87: 1889-1895.

8.      Wang TJ, Pencina MJ, Booth SL,etal. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117:503-511.

9.      Rigby WF, Denome S, Fanger MW. Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxyvitamin D3. Specific inhibition at the level of messenger rna. J ClinInvest  1987;79:1659-1664.

10.  Aihara K, Azuma H, Akaike M, Ikeda Y, Yamashita M, Sudo T et al. Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenecity in mice. J BiolChem 2004; 279: 35798-35802.

11.  Michos  ED, and Gottesman RF. Vitamin D for the prevention of stroke incidence and disability: Promising but too early for prime-time. Eur J Neurol. 2013 January; 20 (1):3-4.

12.  Witham MD, Dove FJ, Sugden JA, Doney AS, Struthers AD. The effect of vitamin D replacement on markers of vascular health in stroke  patients- a randomized contro-lled trial. Nutr Metab Cardiovasc Dis 2012;22:864-70.

13.  Pokharel  BR, Kharel G, Thapa LJ, Rana PVS. Vitamin D and other risk factors among stroke patients. Kathmandu Univ Med J 2015;49(1):71-3

14.  Thapa   L, Shrestha A, Pradhan M, Bhandari T R, Shrestha S, Poudel RS, Pokhrel B, Poudel R. Status of vitamin D and its association with stroke risk factors in patients with acute ischemic stroke in a tertiary carte hospital. J Nepal Med Assoc  2014;52(195):935-39.

15.  Kojima  G, Bell C, Abbott RD, Launer L, Chen R, Motonaga H, etal.Low  dietary vitamin D predicts 34-year incident stroke: the Honolulu Heart Program. Stroke 2012; 43:2163-7

16.  Kikkinen  A, Knert P, Aro A, Rissanen H, Marniemi J, Heliövaara M, Impivaara O, Reunanen A. Vitamin D status and the risk of cardiovascular  disease death.  Am J Epidemiol 2009;170:1032-1039.

17.  Chatterjee  K, Mandal SK, Chatterjee S, Sarkar P, Mondal SS, Ganguly J, Sardar D, Mani S, Das B. Assesment of vitamin D in cerebrovascular accident patients in Eastern India. National Journal of Medical Research , vol.4,iss. 4, Oct-Dec 2014;264-269  

18.  Marcén  R, Jimenez S, Fernández-Rodriguez A,Galeano C, Villafruela JJ, Gomis A, etal. Are low levels of 25-hydroxyvitamin D a risk factor for cardiovascular disease or malignancies in renal transplantation. Nephrol Dial Transplant 2012 ; 27(Suppl 4): iv47-52

19.  Kühn T, Kaaks  R, Teucher B, Hirche F, Dierkes J, Weikert C, Katzke V, Boeing H, Stangl GI, Buijsse B  (2013) 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 8:e69080. 

20.  Burgaz A, Orsini N, Larson SC,Wolk A (2011) Bood 25-hydroxyvitamin D concenteration and hypertension: a meta-analysis. J Hypertens29:636-645 

21.  Tamez H and Thadhani RI. Vitamin D and hypertension: an update and review. CurrOpin Nephrol Hypertens 2012; 21:492-9

22.  Scragg  R, Wishart J, Stewart A, Ofanoa  M, Kerse N, Dyall L, etal. No effect of ultraviolet radiation on blood pressure and other  cardiovascular risk factors . J Hypertens  2011;29:1749.

23.  Afzal  S, Bojesen SE, Nordestgaard BG. Low 25-hydroxyvitamin D and risk of type 2 diabetes: a prospective cohort study and meta-analysis. Clin Chem. 2013;59:381-391.

24.  Song  Y, Wang L, Pittas AG, Del Gobbo LC, Zhang C, Manson JE, Hu FB ( 2013) Blood 25-hydroxyvitamin D levels and incident type 2 diabetes: a meta-anlysis of prospective studies. Diabetes Care 36: 1422-1428.

25.  Kazlauskaite  R, Powell LH, Mandapakal C, Cursio JF, Avery EF,Calvin J. Vitamin D is associated with atheroprotective high-density lipoprotein profile in postmenopausal women. J ClinLipidol 2010;4:113-119.

26.  Zittermann A, Gummert JF, Börgermann J. The role of vitamin D in dyslipidemia and cardiovascular disease.Curr Pharm Des 2011; 17: 933-42.

27.  Ponda  MP, Huang X,Odeh MA, Breslow JL, Kaufman HW (2012) Vitamin D may not improve lipid levels: a serial clinical laboratory data study. Circulation 126: 270-277.

28.  Wang H, Xia N, Yang Y, Peng DQ (2012) Influence of vitamin D supplementation on plasma lipid profile: a meta-analysis of randomized controlled trials. Lipids Health Dis 11:42.

29.  van BallegooijenAJ,ReindersI,Visser M, Dekker JM, Nijpels G, Stehouwer CD, Pilz S, Brouwer IA (2013)  Serum parathyroid hormone in relation to all-cause and cardiovascular mortality: the Hoorn study. J ClinEndocinolMetab 98: E638-E645.

30.  vanBallegooijenAJ,ReindersI,Visser M, Brouwer IA (2013 )  Parathyroid hormone and cardiovascular disease events: a systematic review and meta-analysis of prospective studies. Am Heart J 165: 655-664.

31.  Pilz  S, Tomaschitz A, Drechsler C, Dekker JM, März W. Vitamin D deficiency and myocardial diseases. MolNutr Food Res 2010; 54 :1103-13

32.  Pilz S, Gaksch M., O'Hartaigh B, Tomaschitz A, März W. The role of vitamin D deficiency in cardiovascular disease: where do we stand in  2013? Arch Toxicol (2013) 87: 2083-2103.

33.  Park  K Y, Chung PW, Kim YB, Moon HS, Suh BC, Won YS, Kim JM, Youn YC, Kwon OS . Serum vitamin D status as a predictor of prognosis in patients with acute ischemic stroke.Cerebrovasc Dis 2015;40:73-80 

34.  TuWJ,ZhaoSJ,Xu  DJ etal (2014) Serum 25-hydroxyvitamin D predicts the short-term outcomes of Chinese patients with acute ischemic stroke. ClinSci 126(5) :339-346

35.  Daubail  B, Jacquin A, Guiland  JC, Khoumri C, Aboa-Eboulé C, Giroud M, Béjot Y: Association between serum concentration of vitamin D and 1-year mortality in stroke patients. Cerebrovasc Dis 2014 ; 37:364-367

36.  Chaudhuri JR, Mridula KR, Alladi S, Anamika A, Umamahesh M, Balaraju B, Swath A, Bandaru VS. Serum 25-hydroxyvitamin D deficiency in  ischemic stroke and subtypes in Indian patients. J Stroke 2014; 16:44-50 

37.  Bakradze  E, McCullough L, Staff I, Nouh A (2016)Vitamin D deficiency correlates with stroke severity on presentation in intracerebral hemorrhage. Stroke; Feb., Vol.47,Iss. Supp 1

38.  Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S (2012). Vitamin D deificiency and mortality risk in the general population: a meta- analysis of prospective cohort studies. Am J ClinNutr 95:91-100..

39.  GiovannucciE,LiuY,Hollis BW, Rinm EB. 25-hydroxyvitamin D and risk of myocardial  infarction in men. Arch Intern Med. 2008:168:1174-1180.

40.  Allison M, His S, Wassel C, Morgan C,   Joachin H, Wright C, etal. Calcified atherosclerosis in different vascular beds and the risk of mortality. Arterioscler ThrombVascBiol,  2012 ; 32:140-6

41.  Touboul PJ, Grobbee DE, RuijterHD. Assesment of subclinical atherosclerosis by carotid intima media thickness: technical issues. European Journal of preventive Cardiology,  2012;19(2):8-24 

42.  Giri R, Rai R, Verma S, Verma RK .Correlation between vitamin D and carotid artery intima media thickness  in patients with ischemic stroke. Iternational J of Advances in Medicine ,April-june  2016, Vol 3,Issue 2;398-393.

43.  Carreli A L, Walker  M D, Lowe H, McMahon D J, Rundek T, Sacco RL and Silverberg S J. Vitamin D deficiency is associated with subclinical  carotid atherosclerosis: The Northern Manhatten study . Stroke, 2011;42:2240-2245.

44.  Blondon M, Sachs M, Hoofnagle AN, TX JH, Michos ED, KorcarzC,etal. 25-hydroxyvitamin D and parathyroid hormone are not associated with carotid intima- media thickness. Arteioscler Thromb VascBiol, 2013;33 (11):2639-45.

45.  Sachs  MC, Brunzell JD , Cleary PA, Hoofnagle AN, Lachin JM, Molitch ME, Steffes MW, Zinman B,  de Boer IH. Diabetes control and complication Tria/Epidemiology of Diabetes Interven-sions and Complications Study (DCCT/EDIC) Research Group ( 2013 ) Circulating vitamin D metabolites and subclinical atherosclerosis in type ӏ diabetes. Diabetes Care 36:2423-2429.  

46.  Akio Nakashima, Keitaro Yokoyama, Takashi Yokoo, Mitsuyoshi Urashima : Role of vitamin D in diabetes mellitus and chronic kidney disease. World J Diabetes 2016 March 10; 7(5): 89-100.

47.  V Majumdar, P Prabhakar, GB Kulkarni and R Christopher : Vitamin D status, hypertension and ischemic stroke: a clinical perspective.  Journal of Human Hypertension (2015) 29, 669–674.

Corresponding Author

Effat A E.Tony

Internal Medicine, Assuit University