Vitamin D may modulate vascular inflammation, vascular smooth muscle cell proliferation, the renin-angiotensin system, and cardiomyocyte proliferation, myocardial fibrosis, and proliferation. These mechanisms may play a role on arterial stiffness and left ventricle hypertrophy (LVH) in hypertensive patients. We aimed to evaluate the association between serum vitamin D with arterial stiffness and LVH in patients with hypertension.
Methods
We studied 133 patients with newly diagnosed hypertension [mean (SD) age, 62.9 (10.6) years]. Pulse wave velocity (PWV), which reflects arterial stiffness, was calculated using the single-point method via the Mobil-O-Graph ARCsolver algorithm. Left ventricular mass index (LVMI) was determined according to Deverux formula. The patients were divided into the following 2 groups according to serum vitamin D level: vitamin Dlow group with less than 20 ng/mL and vitamin Dhigh group with greater than or equal to 20 ng/mL.
Results
The highest PWV, high-sensitivity C reactive protein, and LVMI values were observed in vitamin Dlow group compared with vitamin Dhigh group. Multiple linear regression analysis showed that vitamin D level was independently associated with LVMI (β = −0.235, P = 0.002) and PWV (β = −0.432, P < 0.001). Adjustment for age, sex, parathyroid hormone level, body surface area, and mean blood pressure did not modify these associations. Vitamin D level was also independently associated with high-sensitivity C reactive protein (β = −0.143, P = 0.047). However, adjustment for parathyroid hormone level or body surface area and mean blood pressure attenuate this association.
Conclusions
Serum 25-hyroxyvitamin D is independently related with arterial stiffness, LVH, and inflammation. Vitamin D may play a role on pathogenesis of arterial stiffness and LVH in patient with newly diagnosed hypertension.
HolickMF.Vitamin D deficiency. N Engl J Med. 2007; 357: 266–281.
2.
ZehnderD, BlandR, ChanaRS, . 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.
3.
BurgazA, OrsiniN, LarssonS, . Blood 25-hydroxyvitamin D concentration and hypertension: a meta-analysis. J Hypertens. 2011; 29: 636–645.
4.
LiYC.Vitamin D regulation of the renin-angiotensin system. J Cell Biochem. 2003; 88: 327–331.
5.
WeberT, AuerJ, O'RourkeMF, . Arterial stiffness, wave reflections, and the risk of coronary artery disease. Circulation. 2004; 109: 184–189.
6.
GurM, YilmazR, DemirbagR, . Relationship between impaired elastic properties of aorta with left ventricle geometric patterns and left ventricle diastolic functions in patients with newly diagnosed essential hypertension. Int J Clin Pract. 2006; 60: 1357–1363.
7.
QuyyumiAA, PatelRS.Endothelial dysfunction and hypertension: cause or effect?Hypertension. 2010; 55: 1092–1094.
8.
LaurentS, BoutouyrieP, AsmarR, . Aortic stiffness is an independent predictor of all cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001; 37: 1236–1241.
9.
Al MheidI, PatelR, MurrowJ, . Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol. 2011; 58: 186–192.
10.
LeeJI, OhSJ, HaWC, . Serum 25-hydroxyvitamin D concentration and arterial stiffness among type 2 diabetes. Diabetes Res Clin Pract. 2012; 95: 42–47.
11.
GiallauriaF, MilaneschiY, TanakaT, . Arterial stiffness and vitamin D levels: the Baltimore longitudinal study of aging. J Clin Endocrinol Metab. 2012; 97: 3717–3123.
12.
ReynoldsJA, HaqueS, BerryJL, . 25-Hydroxyvitamin D deficiency is associated with increased aortic stiffness in patients with systemic lupus erythematosus. Rheumatology. 2012; 51: 544–551.
13.
PatangeAR, ValentiniRP, DuW, . Vitamin D deficiency and arterial wall stiffness in children with chronic kidney disease. Pediatr Cardiol. 2012; 33: 122–128.
14.
PatangeAR, ValentiniRP, GotheMP, . Vitamin D deficiency is associated with increased left ventricular mass and diastolic dysfunction in children with chronic kidney disease. Pediatr Cardiol. 2013; 34: 536–542.
15.
WHO Scientific Group on the Prevention and Management of Osteoporosis. Prevention and Management of Osteoporosis: Report of a WHO Scientific Group. Geneva, Switzerland: WHO; 2003.
16.
Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press; 2011.
17.
LangRM, BierigM, DevereuxRB, . Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005; 18: 1440–1463.
18.
SchillerNB, ShahPM, CrawfordM, . Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989; 2: 358–367.
19.
DevereuxRB, ReichekN.Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation. 1977; 55: 613–618.
20.
ZittermannA, SchleithoffSS, TenderichG, . Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure?J Am Coll Cardiol. 2003; 41: 105–112.
21.
PooleKE, LoveridgeN, BarkerPJ, . Reduced vitamin D in acute stroke. Stroke. 2006; 37: 243–245.
22.
ScraggR, JacksonR, HoldawayIM, . Myocardial infarction is inversely associated with plasma 25-hydroxyvitamin D3 levels: a community-based study. Int J Epidemiol. 1990; 19: 559–563.
23.
WangTJ, PencinaMJ, BoothSL, . Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008; 117: 503–511.
24.
AkinF, AyçaB, KöseN, . Serum vitamin D levels are independently associated with severity of coronary artery disease. J Investig Med. 2012; 60: 869–873.
25.
RaymondMA, DésormeauxA, LabelleA, . Endothelial stress induces the release of vitamin D-binding protein, a novel growth factor. Biochem Biophys Res Commun. 2005; 338: 1374–1382.
26.
Wu-WongJR, NakaneM, MaJ, . Effects of vitamin D analogs on gene expression profiling in human coronary artery smooth muscle cells. Atherosclerosis. 2006; 186: 20–28.
27.
ZehnderD, BlandR, ChanaRS, . 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.
28.
LiYC, KongJ, WeiM, . 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002; 110: 229–238.
29.
McEnieryCM, McDonnellBJ, SoA, . Aortic calcification is associated with aortic stiffness and isolated systolic hypertension in healthy individuals. Hypertension. 2009; 53: 524–531.
30.
DaoH, EssalihiR, BouvetC, . Evolution and modulation of age-related medial elastocalcinosis: impact on large artery stiffness and isolated systolic hypertension. Cardiovasc Res. 2005; 66: 307–317.
31.
HutchinsonMS, GrimnesG, JoakimsenRM, . Low serum 25-hydroxyvitamin D levels are associated with increased all-cause mortality risk in a general population: the Tromsø study. Eur J Endocrinol. 2010: 162: 935–942.
32.
ParkerJ, HashmiO, DuttonD, . Levels of vitamin D and cardiometabolic disorders: systematic review and meta-analysis. Maturitas. 2010; 65: 225–236.
33.
GiallauriaF, LingSM, SchreiberC, . Arterial stiffness and bone demineralization: the Baltimore longitudinal study of aging. Am J Hypertens. 2011; 24: 970–975.
AikawaE, AikawaM, LibbyP, . Arterial and aortic valve calcification abolished by elastolytic cathepsin S deficiency in chronic renal disease. Circulation. 2009; 119: 1785–1794.
36.
HofbauerLC, BrueckCC, ShanahanCM, . Vascular calcification and osteoporosis–from clinical observation towards molecular understanding. Osteoporos Int. 2007; 18: 251–259.
37.
CirilloM, CiacciC, De SantoNG.Age, renal tubular phosphate reabsorption, and serum phosphate levels in adults. N Engl J Med. 2008; 359: 864–866.
38.
FaroquiS, LeviM, SoleimaniM, . Estrogen downregulates the proximal tubule type IIa sodium phosphate cotransporter causing phosphate wasting and hypophosphatemia. Kidney Int. 2008; 73: 1141–1150.
39.
FoleyRN, CollinsAJ, HerzogCA, . Serum phosphorus levels associate with coronary atherosclerosis in young adults. J Am Soc Nephrol. 2009; 20: 397–404.
40.
IxJH, De BoerIH, PeraltaCA, . Serum phosphorus concentrations and arterial stiffness among individuals with normal kidney function to moderate kidney disease in MESA. Clin J Am Soc Nephrol. 2009; 4: 609–615.
41.
VermeerschSJ, RietzschelER, De BuyzereML, . Age and gender related patterns in carotid-femoral PWV and carotid and femoral stiffness in a large healthy, middle-aged population. J Hypertens. 2008; 26: 1411–1419.
42.
ArtazaJN, MehrotraR, NorrisKC.Vitamin D and the cardiovascular system. Clin J Am Soc Nephrol. 2009; 4: 1515–1522.
43.
O'ConnellTD, BerryJE, JarvisAK, . 1,25-Dihydroxyvitamin D3 regulation of cardiac myocyte proliferation and hypertrophy. Am J Physiol. 1997; 272: H1751–H1758.
44.
ChenS, LawCS, GrigsbyCL, . Cardiomyocyte-specific deletion of the vitamin D receptor gene results in cardiac hypertrophy. Circulation. 2011; 124: 1838–1847.
45.
MancusoP, RahmanA, HersheySD, . 1,25-Dihydroxyvitamin-D3 treatment reduces cardiac hypertrophy and left ventricular diameter in spontaneously hypertensive heart failure-prone (cp/+) rats independent of changes in serum leptin. J Cardiovasc Pharmacol. 2008; 51: 559–564.
46.
MatiasPJ, JorgeC, FerreiraC, . Cholecalciferol supplementation in hemodialysis patients: effects on mineral metabolism, inflammation, and cardiac dimension parameters. Clin J Am Soc Nephrol. 2010; 5: 905–911.
47.
WuJ, GaramiM, ChengT, . 1,25(OH)2- vitamin D3 and retinoic acid antagonize endothelin-stimulated- hypertrophy of neonatal rat cardiac myocytes. J Clin Invest. 1996; 97: 1577–1588.
48.
AmeriP, CanepaM, MilaneschiY, . Relationship between vitamin D status and left ventricular geometry in a healthy population: results from the Baltimore Longitudinal Study of Aging. J Intern Med. 2013; 273: 253–262.
49.
GuillotX, SemeranoL, Saidenberg-Kermanac'hN, . Vitamin D and inflammation. Joint Bone Spine. 2010; 77: 552–557.
50.
OhJ, WengS, FeltonSK, . 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.
51.
KittaY, ObataJE, NakamuraT, . Persistent impairment of endothelial vasomotor function has a negative impact on outcome in patients with coronary artery disease. J Am Coll Cardiol. 2009; 53: 323–330.
52.
RubinshteinR, KuvinJT, SofflerM, . Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J. 2010; 31: 1142–1148.
53.
OudshoornC, van der CammenTJ, McMurdoME, . Ageing and vitamin D deficiency: effects on calcium homeostasis and considerations for vitamin D supplementation. Br J Nutr. 2009; 101: 1597–1606.
