Effect of Vitamin D Supplementation on Arterial Stiffness and Central Blood Pressure Indexes: Demystifying the Evidence
2017; Wiley; Volume: 6; Issue: 10 Linguagem: Inglês
10.1161/jaha.117.007466
ISSN2047-9980
Autores Tópico(s)Blood Pressure and Hypertension Studies
ResumoHomeJournal of the American Heart AssociationVol. 6, No. 10Effect of Vitamin D Supplementation on Arterial Stiffness and Central Blood Pressure Indexes: Demystifying the Evidence Open AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toOpen AccessEditorialPDF/EPUBEffect of Vitamin D Supplementation on Arterial Stiffness and Central Blood Pressure Indexes: Demystifying the Evidence Pankaj Arora, and MD Thomas J. WangMD Pankaj AroraPankaj Arora Division of Cardiovascular Disease, Department of Medicine, University of Alabama, Birmingham, AL Cardiology Service, Birmingham Veterans Affairs Medical Center, Birmingham, AL , and Thomas J. WangThomas J. Wang Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN Originally published24 Oct 2017https://doi.org/10.1161/JAHA.117.007466Journal of the American Heart Association. ;6:e007466IntroductionVitamin D deficiency is highly prevalent, with potentially significant consequences for human health.1 Numerous epidemiological studies have associated vitamin D deficiency with cardiovascular disease and hypertension.2 However, randomized controlled studies have shown no effect of vitamin D supplementation on blood pressure (BP).3, 4 Prior studies assessed BP using a peripheral cuff over the brachial artery, either at a single time point or over 24 hours. Newer measures of central BP and arterial stiffness are more potent predictors of adverse cardiovascular outcomes than brachial BP.5, 6 Thus, could the prior vitamin D–BP trials have used the wrong BP end points?Arterial stiffness is defined as restricted expansion of the arterial wall because of structural and functional changes within the vessel. Pulse‐wave velocity (PWV), measured noninvasively, is a standard measure of arterial stiffness.7 Central BP is the aortic systolic pressure that the left ventricle meets during systole and is influenced by peripheral vascular resistance, arterial stiffness, and magnitude of pressure wave reflections. Clinical trial data exist that support the use of central aortic BP and PWV as targets of antihypertensive therapy.8, 9Data about the effects of vitamin D supplementation on PWV and central BP have been limited.10, 11 Two studies in this issue of JAHA address this need, by examining the potential benefits of vitamin D supplementation on arterial stiffness and central BP.12, 13 In BEST‐D (Biochemical Efficacy and Safety Trial of Vitamin D), 305 community‐dwelling older adults living in the United Kingdom were randomized to receive vitamin D 4000 IU, vitamin D 2000 IU, or placebo for 12 months. The primary end point in BEST‐D was plasma 25‐hydroxyvitamin D, and the main findings have been published previously.14 Tomson et al,12 in this issue of JAHA, examine the effects of vitamin D supplementation on a set of prespecified secondary outcomes related to BP. As in prior studies, they found that vitamin D supplementation in BEST‐D had no effect on systolic BP measured using a peripheral BP cuff. At the end of 12 months, PWV was significantly higher in the 4000 IU vitamin D arm (10.1 m/s) compared with the placebo arm (9.6 m/s), but these values did not differ from baseline values (10.0 and 9.7 m/s, respectively). The authors did not directly report changes in central BP, but augmentation index, a measure of enhanced wave reflection, did not change with vitamin D supplementation. In a randomly selected subset of 177 participants (n=117 in the vitamin D arm, and n=60 in the placebo arm), echocardiographic measures of systolic and diastolic function and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) were assessed. There were no differences in any of the aforementioned parameters after 12 months of vitamin D supplementation between the groups.Another trial, ViDA (Vitamin D Assessment Study),15 randomized 5108 participants to monthly vitamin D supplementation (100 000 IU) versus placebo. The median follow‐up was 3.3 years. In the main trial, there was no significant difference in the incidence of cardiovascular events (hazard ratio, 1.02; 95% confidence interval, 0.87–1.20).15 In the ViDA substudy13 reported in this issue of JAHA, Sluyter et al noted no effect of monthly high‐dose vitamin D (100 000 IU) supplementation on brachial or central BP parameters, measured in a random subset of 517 participants (≈10% of the overall trial population). Median follow up was 1.1 years. In addition, no effect was noted on PWV or augmentation index. However, the authors conducted a further subgroup analysis involving 150 vitamin D–deficient participants (n=71 in the vitamin D arm, and n=79 in the placebo arm). The authors reported modest reductions in PWV (P=0.02), augmentation index (P=0.03), and central systolic BP (P=0.03) in this subgroup. Furthermore, there was a moderate negative correlation of PWV (−0.29), augmentation index (−0.23), and central systolic BP (−0.25) with change in 25‐hydroxyvitamin D levels.These data are interesting, and the positive findings were based on a clinically relevant subgroup (eg, those with established vitamin D deficiency), for whom supplementation would be expected to have the most benefit. On the other hand, the limitations of subgroup analyses are well known.16, 17 False‐positive findings are common, particularly in post hoc analyses of randomized controlled trials that were negative overall.18 The present data are based on a subgroup of a subgroup, further suggesting the need for cautious interpretation. A different question relates to the approach for measuring arterial stiffness. Noninvasive methods using oscillometric methods to capture PWV and central BP have limitations, as described.19 Use of applanation tonometry with application of a generalized transfer function has been suggested as a reliable alternative.19In conclusion, there is no clear evidence that high‐dose vitamin D supplementation improves PWV, augmentation index, and/or central BP. These negative findings are in line with larger trials that focused on traditional BP. The present studies represent important contributions to the existing literature,10 adding to the growing evidence that vitamin D supplementation does not influence BP or related measures. Future trials of vitamin D supplementation should include vitamin D–deficient participants and focus on different aspects of cardiovascular disease, such as metabolism and inflammation, considering the evidence supporting immunomodulatory roles of vitamin D supplementation.20DisclosuresWang has received assay support from Diasorin, Inc. Arora has no relationships to disclose.Footnotes*Correspondence to: Pankaj Arora, MD, Division of Cardiovascular Disease, 1670 University Blvd, Volker Hall B140, University of Alabama at Birmingham, Birmingham, AL 35294‐0019. E‐mail: [email protected]eduThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.References1 Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008; 87:1080S–1086S.CrossrefMedlineGoogle Scholar2 Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D'Agostino RB, Wolf M, Vasan RS. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008; 117:503–511.LinkGoogle Scholar3 Arora P, Song Y, Dusek J, Plotnikoff G, Sabatine MS, Cheng S, Valcour A, Swales H, Taylor B, Carney E, Guanaga D, Young JR, Karol C, Torre M, Azzahir A, Strachan SM, O'Neill DC, Wolf M, Harrell F, Newton‐Cheh C, Wang TJ. Vitamin D therapy in individuals with prehypertension or hypertension: the DAYLIGHT trial. Circulation. 2015; 131:254–262.LinkGoogle Scholar4 Beveridge LA, Struthers AD, Khan F, Jorde R, Scragg R, Macdonald HM, Alvarez JA, Boxer RS, Dalbeni A, Gepner AD, Isbel NM, Larsen T, Nagpal J, Petchey WG, Stricker H, Strobel F, Tangpricha V, Toxqui L, Vaquero MP, Wamberg L, Zittermann A, Witham MD; D‐PRESSURE Collaboration . Effect of vitamin D supplementation on blood pressure: a systematic review and meta‐analysis incorporating individual patient data. JAMA Intern Med. 2015; 175:745–754.CrossrefMedlineGoogle Scholar5 Jankowski P, Kawecka‐Jaszcz K, Czarnecka D, Brzozowska‐Kiszka M, Styczkiewicz K, Loster M, Kloch‐Badelek M, Wilinski J, Curylo AM, Dudek D; Aortic Blood Pressure and Survival Study Group . Pulsatile but not steady component of blood pressure predicts cardiovascular events in coronary patients. 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Dis Markers. 2015; 2015:918968.CrossrefMedlineGoogle Scholar12 Tomson J, Hin H, Emberson J, Kurien R, Lay M, Cox J, Hill M, Arnold L, Leeson P, Armitage J, Clarke R. Effects of vitamin D on blood pressure, arterial stiffness, and cardiac function in older people after 1 year: BEST‐D (Biochemical Efficacy and Safety Trial of Vitamin D). J Am Heart Assoc. 2017; 6:e005707. DOI: 10.1161/JAHA.117.005707.LinkGoogle Scholar13 Sluyter JD, Camargo CA, Stewart AW, Waayer D, Lawes CMM, Toop L, Khaw KT, Thom SAM, Hametner B, Wassertheurer S, Parker KH, Hughes AD, Scragg R. Effect of monthly, high‐dose, long‐term vitamin D supplementation on central blood pressure parameters: a randomized controlled trial substudy. J Am Heart Assoc. 2017; 6:e006802. DOI: 10.1161/JAHA.117.006802.LinkGoogle Scholar14 Hin H, Tomson J, Newman C, Kurien R, Lay M, Cox J, Sayer J, Hill M, Emberson J, Armitage J, Clarke R. Optimum dose of vitamin D for disease prevention in older people: BEST‐D trial of vitamin D in primary care. Osteoporos Int. 2017; 28:841–851.CrossrefMedlineGoogle Scholar15 Scragg R, Stewart AW, Waayer D, Lawes CMM, Toop L, Sluyter J, Murphy J, Khaw KT, Camargo CA. Effect of monthly high‐dose vitamin D supplementation on cardiovascular disease in the vitamin D assessment study: a randomized clinical trial. JAMA Cardiol. 2017; 2:608–616.CrossrefMedlineGoogle Scholar16 Wang R, Lagakos SW, Ware JH, Hunter DJ, Drazen JM. Statistics in medicine: reporting of subgroup analyses in clinical trials. N Engl J Med. 2007; 357:2189–2194.CrossrefMedlineGoogle Scholar17 Feinstein AR. The problem of cogent subgroups: a clinicostatistical tragedy. J Clin Epidemiol. 1998; 51:297–299.CrossrefMedlineGoogle Scholar18 Pocock SJ, Stone GW. The primary outcome fails: what next?N Engl J Med. 2016; 375:861–870.CrossrefMedlineGoogle Scholar19 O'Brien E, Waeber B, Parati G, Staessen J, Myers MG. Blood pressure measuring devices: recommendations of the European Society of Hypertension. BMJ. 2001; 322:531–536.CrossrefMedlineGoogle Scholar20 Konijeti GG, Arora P, Boylan MR, Song Y, Huang S, Harrell F, Newton‐Cheh C, O'Neill D, Korzenik J, Wang TJ, Chan AT. Vitamin D supplementation modulates T cell‐mediated immunity in humans: results from a randomized control trial. J Clin Endocrinol Metab. 2016; 101:533–538.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails October 11, 2017Vol 6, Issue 10Article InformationMetrics Download: 110 © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.https://doi.org/10.1161/JAHA.117.007466PMID: 29066449 Originally publishedOctober 24, 2017 Keywordspulse‐wave velocityvitamin Darterial stiffnessEditorialsPDF download SubjectsHypertensionCardiovascular Disease
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