Association between serum vitamin D levels and subclinical coronary atherosclerosis and plaque burden/composition in young adult population
Evidence suggests that low 25-OH vitamin D 25(OH)D concentrations may increase the risk of several cardiovascular diseases such as hypertension, peripheral vascular disease, diabetes mellitus, obesity, myocardial infarction, heart failure and cardiovascular mortality. Recent studies suggested a possible relationship between vitamin D deficiency and increased carotid intima-media wall thickness and vascular calcification. We hypothesized that low 25(OH)D may be associated with coronary atherosclerosis and coronary plaque burden and composition, and investigated the relationship between serum vitamin D levels and coronary atherosclerosis, plaque burden or structure, in young adult patients by using dual-source 128x2 slice coronary computed tomography angiography (CCTA). We included 98 patients with coronary atherosclerosis and 110, age and gender matched, subjects with normal findings on CCTA examinations. Patients with subclinical atherosclerosis had significantly higher serum total cholesterol, triglycerides, hs-CRP, uric acid, HbA1c and creatinine levels and lower serum 25(OH)D levels in comparison with controls. There was no significant correlation between 25(OH)D and plaque morphology. There was also a positive relationship between 25(OH)D and plaque burden of coronary atherosclerosis. In multivariate analysis, coronary atherosclerosis was associated high hs-CRP (adjusted OR: 2.832), uric acid (adjusted OR: 3.671) and low 25(OH)D (adjusted OR: 0.689). Low levels of 25(OH)D were associated with coronary atherosclerosis and plaque burden, but there was no significant correlation between 25(OH)D and plaque morphology.
Melamed ML, Muntner P, Michos ED, Uribarri J, Weber C, Sharma J, et al. 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.
Siasos G, Tousoulis D, Oikonomou E, Maniatis K, Kioufis S, Kokkou E, et al. Vitamin D serum levels are associated with cardiovascular outcome in coronary artery disease. Int J Cardiol. 2013; 168(4): 4445-7.
Schierbeck LL, Jensen TS, Bang U, Jensen G, Køber L, Jensen JE. Parathyroid hormone and vitamin D-markers for cardiovascular and all cause mortality in heart failure. Eur J Heart Fail. 2011; 13: 626-632.
Akin F, Ayça B, Köse N, Duran M, Sari M, Uysal OK, et al. Serum vitamin D levels are independently associated with severity of coronary artery disease. J Investig Med. 2012; 60(6): 869-73.
Lai H, Fishman EK, Gerstenblith G, Brinker JA, Tong W, Bhatia S, et al. Vitamin D deficiency is associated with significant coronary stenoses in asymptomatic African American chronic cocaine users. Int J Cardiol. 2012; 158(2): 211-6
Yiu YF, Yiu KH, Siu CW, Chan YH, Li SW, Wong LY, et al. Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes. Atherosclerosis. 2013; 227(1): 140-6.
Tarcin O, Yavuz DG, Ozben B, Telli A, Ogunc AV, Yuksel M, et al. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab. 2009; 94: 4023-4030.
Reis JP, von Mühlen D, Michos ED, Miller ER, Appel LJ, Araneta MR, et al. Serum vitamin D, parathyroid hormone levels, and carotid atherosclerosis. Atherosclerosis. 2009; 207: 585-590.
Watson KE, Abrolat ML, Malone LL, Hoeg JM, Doherty T, Detrano R, et al. Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation. 1997; 96: 1755-1760.
Lee MJ, Shin DH, Kim SJ, Oh HJ, Yoo DE, Ko KI, et al. Progression of aortic arch calcification over 1 year is an independent predictor of mortality in incident peritoneal dialysis patients. PLoS One. 2012;7(11):e48793. doi: 10.1371/journal.pone.0048793. Epub 2012 Nov 7. PMID: 23144974
Austen WG, Edwards JE, Frye RL, Gensini GG, Gott VL, Griffith LS, et al. A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc committee for grading of coronary artery disease, council on cardiovascular surgery, American heart association. Circulation 1975; 51(4): 5–40.
Leber AW, Becker A, Knez A, von Ziegler F, Sirol M, Nikolaou K, et al. Accuracy of 64-slice computed tomography to classify and quantify plaque volumes in the proximal coronary system: a comparative study using intravascular ultrasound. J Am Coll Cardiol 2006; 47(3): 672–677.
Blondon M, Sachs M, Hoofnagle AN, Ix JH, Michos ED, Korcarz C, et al. 25-Hydroxyvitamin D and Parathyroid Hormone Are Not Associated With Carotid Intima-Media Thickness or Plaque in the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol 2013; 33(11): 2639-45.
Lim S, Shin H, Kim MJ, Ahn HY, Kang SM, Yoon JW, et al. Vitamin D inadequacy is associated with significant coronary artery stenosis in a community-based elderly cohort: the Korean Longitudinal Study on Health and Aging. J Clin Endocrinol Metab. 2012; 97(1): 169-78.
Carthy EP, Yamashita W, Hsu A, Ooi BS. 1,25-Dihydroxyvitamin D3 and rat vascular smooth muscle cell growth. Hypertension.1989; 13: 954-959.
Shioi A, Katagi M, Okuno Y, Mori K, Jono S, Koyama H, Nishizawa Y. Induction of bone-type alkaline phosphatase in human vascular smooth muscle cells: roles of tumor necrosis factor-alpha and oncostatin M derived from macrophages. Circ Res. 2002; 91(1):9-16.
Nibbelink KA, Tishkoff DX, Hershey SD, Rahman A, Simpson RU. 1,25(OH)2-vitamin D3 actions on cell proliferation, size, gene expression, and receptor localization, in the HL-1 cardiac myocyte. J Steroid Biochem Mol Biol. 2007; 103: 533-537.
Merke J, Milde P, Lewicka S, Hügel U, Klaus G, Mangelsdorf DJ, et al. Identification and regulation of 1,25-dihydroxyvitamin D3 receptor activity and biosynthesis of 1,25-dihydroxyvitamin D3. Studies in cultured bovine aortic endothelial cells and human dermal capillaries. J Clin Invest. 1989; 83: 1903-1915.
Rigby WF, Stacy T, Fanger MW. Inhibition of T lymphocyte mitogenesis by 1,25 dihydroxyvitamin D3 (calcitriol). J Clin Invest. 1984; 74: 1451-1455.
Wakasugi M, Noguchi T, Inoue M, Kazama Y, Tawata M, Kanemaru Y, et al. Vitamin D3 stimulates the production of prostacyclin by vascular smooth muscle cells. Prostaglandins. 1991; 42: 127-136.
Zehnder D, Bland R, Chana RS, Wheeler DC, Howie AJ, Williams MC,et al. Synthesis of 1,25-dihydroxyvitamin D(3) by human endothelial cells is regulated by inflammatory cytokines: a novel autocrine determinant of vascular cell adhesion. J Am Soc Nephrol. 2002; 13: 621-629.
Al Mheid I, Patel R, Murrow J, Morris A, Rahman A, Fike L, et al. Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol. 2011; 58: 186-192.
Pittas AG, Lau J, Hu FB, Dowson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007; 92: 2017-2029.
Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002; 110: 229-238.
Oh J, Weng S, Felton SK, Bhandare S, Riek A, Butler B, et al. 1,25(OH)2 vitamin d inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus. Circulation. 2009; 120: 687-698.
Libby P. Inflammation in atherosclerosis. Nature 2002; 420: 868–874
Murr C, Pilz S, Grammer TB, Kleber ME, Meinitzer A, Boehm BO, et al. Vitamin D deficiency parallels inflammation and immune activation, the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Clin Chem Lab Med. 2012; 50(12): 2205-12.
Shea MK, Booth SL, Massaro JM, Jacques PF, D'Agostino RB Sr, Dawson-Hughes B, et al. Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study. Am J Epidemiol. 2008; 167: 313-320.
Tuzcu EM, Kapadia SR, Tutar E, Ziada KM, Hobbs RE, McCarthy PM, et al. High prevalence of coronary atherosclerosis in asymptomatic teenagers and young adults: evidence from intravascular ultrasound. Circulation 2001; 103(22): 2705-10
Kwang Nam Jin, Eun Ju Chun, Chang-Hoon Lee, Jeong A. Kim, Min Su Lee, et al. Subclinical coronary atherosclerosis in young adults: prevalence, characteristics, predictors with coronary computed tomography angiography. Int J Cardiovasc Imaging 2012; 28: 93–100
Berry JD, Liu K, Folsom AR, Lewis CE, Carr JJ, Polak JF, et al. Prevalence and progression of subclinical atherosclerosis in younger adults with low short-term but high lifetime estimated risk for cardiovascular disease: the coronary artery risk development in young adults study and multi-ethnic study of atherosclerosis. Circulation 2009; 119: 382-9
Celik O, Cakmak HA, Satilmis S, Gungor B, Akin F, Ozturk D, et al. The relationship between gamma-glutamyl transferase levels and coronary plaque burdens and plaque structures in young adults with coronary atherosclerosis. Clin Cardiol. 2014; 37(9): 552-557.
Kanbay M, Segal M, Afsar B, Kang DH, Rodriguez-Iturbe B, Johnson RJ. The role of uric acid in the pathogenesis of human cardiovascular disease. Heart. 2013; 99(11): 759-66.
Kaya EB, Yorgun H, Canpolat U, Hazırolan T, Sunman H, Ülgen A, et al. Serum uric acid levels predict the severity and morphology of coronary atherosclerosis detected by multidetector computed tomography. Atherosclerosis. 2010; 213(1): 178-83.
Oikonen M, Wendelin-Saarenhovi M, Lyytikäinen LP, Siitonen N, Loo BM, Jula A, et al. Associations between serum uric acid and markers of subclinical atherosclerosis in young adults. The cardiovascular risk in Young Finns study. Atherosclerosis. 2012; 223(2): 497-503