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Putting cardiovascular disease and vitamin D insufficiency into perspective

  • Armin Zittermann (a1), Stefanie S. Schleithoff (a1) and Reiner Koerfer (a1)
Abstract

The aetiology of CVD is still not completely understood. The present review article summarises data supporting the hypothesis that an insufficient vitamin D status may contribute to the worldwide high prevalence of CVD. Human vitamin D status primarily depends on skin exposure to the UVB spectrum of the sunlight. Epidemiological data indicate that geographic latitude, altitude, season, and the place of residence (urban or rural) are associated with CVD mortality. Interestingly, all these factors also have an influence on human UVB exposure and thus on vitamin D status. Several mechanisms might be responsible for a protective role of vitamin D in CVD. These mechanisms include the inhibition of vascular smooth muscle proliferation, the suppression of vascular calcification, the down regulation of pro-inflammatory cytokines, the up regulation of anti-inflammatory cytokines, and the action of vitamin D as a negative endocrine regulator of the renin–angiotensin system. The first intervention trials indicate that vitamin D may suppress cardiovascular risk markers. However, more controlled clinical trials are needed to investigate whether optimal oral vitamin D supplementation is able to reduce CVD morbidity and mortality.

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Corresponding author
*Corresponding author: Dr Armin Zittermann, fax +49 5731 97 2020, email azittermann@hdz-nrw.de
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KS Agarwal , MZ Mughal , P Upadhyay , JL Berry , EB Mawer & JM Puliyel (2002) The impact of atmospheric pollution on vitamin D status of infants and toddlers in Delhi, India. Arch Dis Child 87, 111113.

Anonymous (1992) An epidemiological study of cardiovascular and cardiopulmonary disease risk factors in four populations in the People's Republic of China. Baseline report from the P.R.C.-U.S.A. Collaborative Study. People's Republic of China–United States Cardiovascular and Cardiopulmonary Epidemiology Research Group. Circulation 85, 10831096.

Anonymous (2004) The catastrophic failures of public health. Lancet 363, 745.

S Arunabh , S Pollack , J Yeh & JF Aloia (2003) Body fat content and 25-hydroxyvitamin D levels in healthy women. J Clin Endocrinol Metab 88, 157161.

LM Banks , B Lees , JE MacSweeney & JC Stevenson (1994) Effect of degenerative spinal and aortic calcification on bone density measurements in post-menopausal women: links between osteoporosis and cardiovascular disease? Eur J Clin Invest 24, 813817.

EI Barengolts , M Berman , SC Kukreja , T Kouznetsova , C Lin & EV Chomka (1998) Osteoporosis and coronary atherosclerosis in asymptomatic postmenopausal women. Calcif Tissue Int 62, 209213.

HP Bhattoa , P Bettenbut , S Ganacharya , & Balogh (2004) Prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in community dwelling postmenopausal Hungarian women. Osteoporos Int 15, 447451.

GA Block , TE Hulbert-Shearon , NW Levin & FK Port (1998) Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 31, 607617.

GA Block , KJ Martin , AL de Francisco , (2004) Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 350, 15161525.

MO Canning , K Grotenhuis , H de Wit , C Ruwhof & HA Drexhage (2001) 1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully active immature dendritic cells from monocytes. Eur J Endocrinol 145, 351357.

MC Chapuy , AM Schott , P Garnero , D Hans , PD Delmas & PJ Meunier (1996) Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. EPIDOS Study Group. J Clin Endocrinol Metab 81, 11291133.

VL Crawford , O Sweeney , PV Coyle , IM Halliday & RW Stout (2000) The relationship between elevated fibrinogen and markers of infection: a comparison of seasonal cycles. QJM 93, 745750.

MR Davies & KA Hruska (2001) Pathophysiological mechanisms of vascular calcification in end-stage renal disease. Kidney Int 60, 472479.

PS Davies , CJ Bates , TJ Cole , A Prentice & PC Clarke (1999) Vitamin D: seasonal and regional differences in preschool children in Great Britain. Eur J Clin Nutr 53, 195198.

CE Dent , HE Engelbrecht & RC Godfrey (1968) Osteoporosis of lumbar vertebrae and calcification of abdominal aorta in women living in Durban. Br Med J 4, 7679.

S Docio , JA Riancho , A Perez , JM Olmos , JA Amado & J Gonzalez-Macias (1998) Seasonal deficiency of vitamin D in children: a potential target for osteoporosis-preventing strategies? J Bone Miner Res 13, 544548.

TM Doherty & RC Detrano (1994) Coronary arterial calcification as an active process: a new perspective on an old problem. Calcif Tissue Int 54, 224230.

AS Douglas , MG Dunnigan , TM Allan & JM Rawles (1995) Seasonal variation in coronary heart disease in Scotland. J Epidemiol Commun Health 49, 575582.

F Enquselassie , AJ Dobson , HM Alexander & PL Steele (1993) Seasons, temperature and coronary disease. Int J Epidemiol 22, 632636.

PE Enterline , AE Rikli & HI Sauer (1960) Death rates for coronary heart disease in metropolitan and other areas. Pub Health Rep 75, 759766.

M Frohlich , M Sund , S Russ , A Hoffmeister , HG Fischer , V Hombach & W Koenig (1997) Seasonal variations of rheological and hemostatic parameters and acute-phase reactants in young, healthy subjects. Arterioscler Thromb Vasc Biol 17, 26922697.

T Fujita , Y Okamoto , Y Sakagami , K Ota & M Ohata (1984) Bone changes and aortic calcification in aging inhabitants of mountain versus seacoast communities in the Kii Peninsula. J Am Geriatr Soc 32, 124128.

M Fukagawa & K Kurokawa (2005) Renal failure and secondary hyperparathyreodism. In Vitamin D, 2nd ed. pp. 18211831 [D Feldman , JW Pike and FH Glorieux , editors]. Amsterdam: The Netherlands: Elsevier Academic Press.

MH Gannage-Yared , R Chemali , N Yaacoub & G Halaby (2000) Hypovitaminosis D in a sunny country: relation to lifestyle and bone markers. J Bone Miner Res 15, 18561862.

A Gjonca & M Bobak (1997) Albanian paradox, another example of protective effect of Mediterranean lifestyle? Lancet 350, 18151817.

H Glerup , K Mikkelsen , L Poulsen , E Hass , S Overbeck , J Thomsen , P Charles & EF Eriksen (2000) Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med 247, 260268.

WB Grant (2003) Ecologic studies of solar UV-B radiation and cancer mortality rates. Recent Results Cancer Res 164, 371377.

DS Grimes , E Hindle & T Dyer (1996) Sunlight, cholesterol and coronary heart disease. QJM 89, 579589.

DS Grimes , E Hindle & T Dyer (2000) Respiratory infection and coronary heart disease: progression of a paradigm. QJM 93, 375383.

J Guillemant , HT Le , A Maria , A Allemandou , G Peres & S Guillemant (2001) Wintertime vitamin D deficiency in male adolescents: effect on parathyroid function and response to vitamin D3 supplements. Osteoporos Int 12, 875879.

BP Halloran , P Schaefer , M Lifschitz , M Levens & RS Goldsmith (1984) Plasma vitamin D metabolite concentrations in chronic renal failure: effect of oral administration of 25-hydroxyvitamin D3. J Clin Endocrinol Metab 59, 10631069.

V Hegarty , P Woodhouse & KT Khaw (1994) Seasonal variation in 25-hydroxyvitamin D and parathyroid hormone concentrations in healthy elderly people. Age Ageing 23, 478482.

PC Heinrich , JV Castell & T Andus (1990) Interleukin-6 and the acute phase response. Biochem J 265, 621636.

MF Holick (2002) Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endocrinol Diabetes 9, 8798.

NK Hollenberg , G Martinez , M McCullough , T Meinking , D Passan , M Preston , A Rivera , D Taplin & M Vicaria-Clement (1997) Aging, acculturation, salt intake, and hypertension in the Kuna of Panama. Hypertension 29, 171176.

J Honye , DJ Mahon , A Jain , CJ White , SR Ramee , JB Wallis , A Al-Zarka & JM Tobis (1992) Morphological effects of coronary balloon angioplasty in vivo assessed by intravascular ultrasound imaging. Circulation 85, 10121025.

HN Hultgren (1970) Reduction of systemic arterial blood pressure at high altitude. Adv Cardiol 5, 4955.

E Ishimura , Y Nishizawa , M Inaba , (1999) Serum levels of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, and 25-hydroxyvitamin D in nondialyzed patients with chronic renal failure. Kidney Int 55, 1019–27.

JR Juttmann , CJ Buurman , E DeKam , TJ Visser & JC Birkenhager (1981) Serum concentrations of metabolites of vitamin D in patients with chronic renal failure. Clin Endocrinol 14, 225236.

E Kamycheva , J Sundsfjord & R Jorde (2004) Serum parathyroid hormone levels predict coronary heart disease: the Tromso Study. Eur J Cardiovasc Prev Rehabil 11, 6974.

Y Kimura , M Kawamura , M Owada , T Oshima , M Murooka , T Fujiwara & K Hiramori (1999) Effectiveness of 1,25-dihydroxyvitamin D supplementation on blood pressure reduction in a pseudohypoparathyroidism patient with high renin activity. Intern Med 38, 3135.

R Krause , M Buhring , W Hopfenmuller , MF Holick & AM Sharma (1998) Ultraviolet B and blood pressure. Lancet 352, 709710.

CJ Lamberg-Allardt , TA Outila , MU Karkkainen , HJ Rita & LM Valsta (2001) Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe? J Bone Miner Res 16, 20662073.

M Lehtonen-Veromaa , T Mottonen , K Irjala , M Karkkainen , C Lamberg-Allardt , P Hakola & J Viikari (1999) Vitamin D intake is low and hypovitaminosis D common in healthy 9- to 15-year-old Finnish girls. Eur J Clin Nutr 53, 746751.

YC Li , J Kong , M Wei , ZF Chen , SQ Liu & LP Cao (2002) 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 110, 229238.

L Lind , A Hanni , H Lithell , A Hvarfner , OH Sorensen & S Ljunghall (1995) Vitamin D is related to blood pressure and other cardiovascular risk factors in middle-aged. Am J Hypertens 8, 894901.

P Lips (2005) How to define normal values for serum concentrations of 25-hydroxyvitamin D? In Vitamin D 2nd ed. pp. 10191028 [D Feldman , JW Pike and FH Glorieux , editors]. Amsterdam, The Netherlands: Elsevier Academic Press.

AC Looker , B Dawson-Hughes , MS Calvo , EW Gunter & NR Sahyoun (2002) Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. Bone 30, 771777.

G Luo , P Ducy , MD McKee , GJ Pinero , E Loyer , RR Behringer & G Karsenty (1997) Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386, 7881.

M McKenna (1992) Differences in vitamin D status between countries in young adults and elderly. Am J Med 93, 6977.

Z Mallat , S Besnard , M Duriez , (1999) Protective role of interleukin-10 in atherosclerosis. Circulation Res 85, E17E24.

JR Margolis , JT Chen , Y Kong , RH Peter , VS Behar & JA Kisslo (1980) The diagnostic and prognostic significance of coronary artery calcification. A report of 800 cases. Radiology 137, 609616.

A Mavri , B Guzic-Salobir , B Salobir-Pajnic , I Keber , J Stare & M Stegnar (2001) Seasonal variation of some metabolic and haemostatic risk factors in subjects with and without coronary artery disease. Blood Coagul Fibrinolysis 12, 359365.

C Meier , HW Woitge , K Witte , B Lemmer & MJ Seibel (2004) Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial. J Bone Miner Res 19, 12211230.

MA Mendall , P Patel , M Asante , L Ballam , J Morris , DP Strachan , AJ Camm & TC Northfield (1997) Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease. Heart 78, 273277.

J Moon , B Bandy & AJ Davison (1992) Hypothesis: are imbalances in the calciferol endocrine system implicated? J Am Coll Nutr 11, 567583.

EA Mortimer , RR Monson & B MacMahon (1977) Reduction in mortality from coronary heart disease in men residing at high altitude. N Engl J Med 296, 581585.

K Muller , PM Haahr , M Diamant , K Rieneck , A Kharazmi & K Bendtzen (1992) 1,25-Dihydroxyvitamin D3 inhibits cytokine production by human blood monocytes at the post-transcriptional level. Cytokine 4, 506512.

CJ Murray & AD Lopez (1997) Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet 349, 12691276.

G Passeri , G Pini , L Troiano , R Vescovini , P Sansoni , M Passeri , P Gueresi , R Delsignore , M Pedrazzoni & C Franceschi (2003) Low vitamin D status, high bone turnover, and bone fractures in centenarians. J Clin Endocrinol Metab 88, 51095115.

J Pepe , E Romagnoli , I Nofroni , MT Pacitti , S De Geronimo , C Letizia , G Tonnarini , A Scarpiello , E D'Erasmo & S Minisola (2005) Vitamin D status as the major factor determining the circulating levels of parathyroid hormone: a study in normal subjects. Osteoporos Int 16, 805812.

M Pfeifer , B Begerow , HW Minne , D Nachtigall & C Hansen (2001) Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. J Clin Endocrinol Metab 86, 16331637.

PA Price , SA Faus & MK Williamson (2000) Warfarin-induced artery calcification is accelerated by growth and vitamin D. Arterioscler Thromb Vasc Biol 20, 317327.

K Rajakumar (2003) Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective. Pediatrics 112, E132E135.

S Renaud & M de Lorgeril (1992) Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339, 15231526.

PM Ridker , CH Hennekens , JE Buring & N Rifai (2000) C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 342, 836843.

DS Rigel , EG Rigel & AC Rigel (1999) Effects of altitude and latitude on ambient UVB radiation. J Am Acad Dermatol 40, 114116.

SG Rostand (1997) Ultraviolet light may contribute to geographic and racial blood pressure differences. Hypertension 30, 150156.

SG Rostand & TB Drueke (1999) Parathyroid hormone, vitamin D, and cardiovascular disease in chronic renal failure. Kidney Int 56, 383392.

LJ Schurgers , PE Dissel , HM Spronk , BA Soute , CR Dhore , JP Cleutjens & C Vermmer (2001) Role of vitamin K and vitamin K-dependent proteins in vascular calcification. Z Kardiol 90, Suppl. 3, 5763.

R Scragg (1981) Seasonality of cardiovascular disease mortality and the possible protective effect of ultra-violet radiation. Int J Epidemiol 10, 337341.

R Scragg (1982) Seasonal variation in mortality in Queensland. Community Health Stud 6, 120129.

CM Shanahan & PL Weissberg (1998) Smooth muscle cell heterogeneity: patterns of gene expression in vascular smooth muscle cells in vitro and in vivo. Arterioscler Thrombos Vasc Biol 18, 333338.

T Shoji , K Shinohara , E Kimoto , (2004) Lower risk for cardiovascular mortality in oral 1alpha-hydroxy vitamin D3 users in a haemodialysis population. Nephrol Dial Transplant 19, 179184.

RU Simpson & RE Weishaar (1988) Involvement of 1,25-dihydroxyvitamin D3 in regulating myocardial calcium metabolism: physiological and pathological actions. Cell Calcium 9, 285292.

RB Singh , MA Niaz , S Ghosh , R Beegom , P Agarwal , S Nangia , M Moshiri & ED Janus (1998) Low fat intake and coronary artery disease in a population with higher prevalence of coronary artery disease: the Indian paradox. J Am Coll Nutr 17, 342350.

TD Spiess (1932) Production of nonfatal vascular sclerosis in rabbits by means of viosterol (irradiated ergosterol). Arch Intern Med 50, 443449.

S Takeo , M Anan , K Fujioka , T Kajihara , S Hiraga , K Miyake , K Tanoka , R Minematsu , H Mori & Y Taniguchi (1989) Functional changes of aorta with massive accumulation of calcium. Arteriosclerosis 77, 175181.

V Tangpricha , EN Pearce , TC Chen & MF Holick (2002) Vitamin D insufficiency among free-living healthy young adults. Am J Med 112, 659662.

PM Timms , N Mannan , GA Hitman , K Noonan , PG Mills , D Syndercombe-Court , E Aganna , CP Price & BJ Boucher (2002) Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? QJM 95, 787796.

G van den Berghe , D Van Roosbroeck , P Vanhove , PJ Wouters , L De Pourcq & R Bouillon (2003) Bone turnover in prolonged critical illness: effect of vitamin D. J Clin Endocrinol Metab 88, 46234632.

F Van Lente (2000) Markers of inflammation as predictors in cardiovascular disease. Clin Chim Acta 293, 3152.

R Vieth (2002) Vitamin D ingestion and changes to rat aorta. Cardiovascular Res 56, 323324.

R Vieth , DE Cole , GA Hawker , HM Trang & LA Rubin (2001) Wintertime vitamin D insufficiency is common in young Canadian women, and their vitamin D intake does not prevent it. Eur J Clin Nutr 55, 10911097.

R Vieth , S Kimball , A Hu & PG Walfish (2004) Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients. Nutr J 3, 8.

R Vieth , Y Ladak & PG Walfish (2003) Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. J Clin Endocrinol Metab 88, 185191.

T Vik , K Try & JH Stromme (1980) The vitamin D status of man at 70 degrees north. Scand J Clin Lab Invest 40, 227232.

KE Watson , ML Abroiat , LL Malone , JM Hoed , T Doherty , R Detrano & LL Demer (1997) Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation 96, 17551760.

HW Woitge , A Knothe , K Witte , H Schmidt-Gayk , R Ziegler , B Lemmer & MJ Seibel (2000) Circaannual rhythms and interactions of vitamin D metabolites, parathyroid hormone, and biochemical markers of skeletal homeostasis: a prospective study. J Bone Miner Res 15, 24432450.

WS Yancy Jr, EC Westman , PA French & RM Califf (2003) Diets and clinical coronary events: the truth is out there. Circulation 107, 1016.

JS Yudkin , CS Yajnik , V Mohamed-Ali & K Bulmer (1999) High levels of circulating proinflammatory cytokines and leptin in urban, but not rural, Indians. A potential explanation for increased risk of diabetes and coronary heart disease. Diabetes Care 22, 363364.

A Yusuf , S Reddy , S Ounpuu & S Anand (2001) Global burden of cardiovascular diseases part I: General considerations, the epidemiologic transition, risk factors, and impact or urbanization. Circulation 104, 27462753.

A Zittermann , J Dembinski & P Stehle (2004) Low vitamin D status is associated with low cord blood levels of the immunosuppressive cytokine interleukin-10. Pediatr Allergy Immunol 15, 242246.

A Zittermann , O Sabatschus , S Jantzen , P Platen , A Danz , T Dimitriou , K Scheld , K Klein & P Stehle (2000) Exercise-trained young men have higher calcium absorption rates and plasma calcitriol levels in comparison to age-matched sedentary controls. Calcif Tissue Int 67, 215219.

A Zittermann , K Scheld & P Stehle (1998) Seasonal variations in vitamin D status and calcium absorption do not influence bone turnover in young women. Eur J Clin Nutr 52, 501506.

A Zittermann , Schleithoff S Schulze , G Tenderich , HK Berthold , R Körfer & P Stehle (2003) Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol 41, 105112.

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