Advertisement

Subclinical impairment of myocardial and endothelial functionality in very early psoriatic and rheumatoid arthritis patients: Association with vitamin D and inflammation

      Highlights

      • Subclinical myocardial dysfunction is found in very early rheumatoid arthritis (RA) and psoriatic arthritis (PsA).
      • Inflammatory burden is associated with altered myocardial function in inflammatory joint diseases (IJD).
      • Speckle-tracking echocardiography may be useful for CV risk stratification in IJD.

      Abstract

      Background and aims

      Cardiovascular (CV) morbidity is increased in inflammatory joint diseases (IJD), as rheumatoid (RA) and psoriatic arthritis (PsA). Whereas increased prevalence of subclinical atherosclerosis has been reported in these conditions, whether an early myocardial functionality is also impaired remains unknown. The aim of this study was to evaluate the myocardial functionality by speckle-tracking echocardiography (STE) in recent onset RA and PsA patients and its potential associations with the levels of circulating CD34 + cells, vitamin D, and with disease activity.

      Methods

      STE was used to assess the myocardial functionality in patients with very early RA (n = 41) and PsA (n = 35) without traditional CV risk factors, and 58 matched healthy controls (HC). Global longitudinal and circumferential strain (GLS and GCS) was estimated. Pulse wave velocity (PWV) and carotid intima-media thickness (cIMT) were measured as surrogate markers of atherosclerosis. Circulating CD34 + counts were evaluated by flow cytometry and vitamin D levels were quantified by HPLC. Disease activity was assessed by Disease Activity Score-28 (DAS28).

      Results

      RA patients exhibited impaired GLS and GCS (both p < 0.001) as compared to HC, GLS being also altered in PsA (p = 0.020 vs. HC). DAS28 was correlated to GLS (r = 0.908, p < 0.001) and GCS (r = 0.868, p < 0.001) in RA, these findings being confirmed by multivariate regression analyses adjusted for confounders and Principal Component Analyses. GLS and GCS were impaired in PsA patients with high disease activity as compared to HC, and GLS was found to be a predictor of cIMT in this condition. On the other hand, vitamin D was negatively associated with cIMT in HC (r = −0.308, p = 0.026) but not in PsA or RA, although decreased levels were observed (both p < 0.001). Vitamin D was an independent predictor of decreased CD34 + levels in PsA and RA. CD34 + counts negatively correlated DAS28, GLS and GCS in RA.

      Conclusions

      Subclinical myocardial dysfunction is observed in IJD patients with preserved left-ventricular function and without traditional CV risk factors. Subclinical myocardial dysfunction was found to be a very early event in IJD. Disease activity was the main predictor of myocardial strain impairment. Interestingly, myocardial function was altered and associated with cIMT also in PsA patients with high disease activity.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Jamnitski A.
        • Visman I.M.
        • Peters M.J.L.
        • Boers M.
        • Dijkmans B.A.C.
        • Nurmohamed M.T.
        Prevalence of cardiovascular diseases in psoriatic arthritis resembles that of rheumatoid arthritis.
        Ann. Rheum. Dis. 2011; 70: 875-876https://doi.org/10.1136/ard.2010.136499
        • Han C.
        • Robinson D.W.
        • V Hackett M.
        • Paramore L.C.
        • Fraeman K.H.
        • V Bala M.
        Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.
        J. Rheumatol. 2006; 33: 2167-2172
        • Bartoloni E.
        • Shoenfeld Y.
        • Gerli R.
        Inflammatory and autoimmune mechanisms in the induction of atherosclerotic damage in systemic rheumatic diseases: two faces of the same coin.
        Arthritis Care Res. 2011; 63: 178-183https://doi.org/10.1002/acr.20322
        • del Rincón I.D.
        • Williams K.
        • Stern M.P.
        • Freeman G.L.
        • Escalante a
        High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors.
        Arthritis Rheum. 2001; 44: 2737-2745https://doi.org/10.1002/1529-0131(200112)44:12<2737::AID-ART460>3.0.CO;2-#
        • Agca R.
        • Heslinga S.C.
        • Rollefstad S.
        • Heslinga M.
        • McInnes I.B.
        • Peters M.J.L.
        • Kvien T.K.
        • Dougados M.
        • Radner H.
        • Atzeni F.
        • Primdahl J.
        • Södergren A.
        • Wallberg Jonsson S.
        • van Rompay J.
        • Zabalan C.
        • Pedersen T.R.
        • Jacobsson L.
        • de Vlam K.
        • Gonzalez-Gay M.A.
        • Semb A.G.
        • Kitas G.D.
        • Smulders Y.M.
        • Szekanecz Z.
        • Sattar N.
        • Symmons D.P.M.
        • Nurmohamed M.T.
        EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update.
        Ann. Rheum. Dis. 2017; 76: 17-28https://doi.org/10.1136/annrheumdis-2016-209775
        • Kristensen S.L.
        • McInnes I.B.
        • Sattar N.
        Psoriasis, psoriatic arthritis and cardiovascular risk: are we closer to a clinical recommendation?.
        Ann. Rheum. Dis. 2015; 74: 321-322https://doi.org/10.1136/annrheumdis-2014-206617
        • Fine N.M.
        • Crowson C.S.
        • Lin G.
        • Oh J.K.
        • Villarraga H.R.
        • Gabriel S.E.
        Evaluation of myocardial function in patients with rheumatoid arthritis using strain imaging by speckle-tracking echocardiography.
        Ann. Rheum. Dis. 2014; 73: 1833-1839https://doi.org/10.1136/annrheumdis-2013-203314
        • Langeland S.
        • D’hooge J.
        • Wouters P.F.
        • Leather H.A.
        • Claus P.
        • Bijnens B.
        • Sutherland G.R.
        Experimental validation of a new ultrasound method for the simultaneous assessment of radial and longitudinal myocardial deformation independent of insonation angle.
        Circulation. 2005; 112: 2157-2162https://doi.org/10.1161/CIRCULATIONAHA.105.554006
        • Shah A.M.
        • Claggett B.
        • Sweitzer N.K.
        • Shah S.J.
        • Anand I.S.
        • Liu L.
        • Pitt B.
        • Pfeffer M.A.
        • Solomon S.D.
        Prognostic importance of impaired systolic function in heart failure with preserved ejection fraction and the impact of spironolactone.
        Circulation. 2015; 132: 402-414https://doi.org/10.1161/CIRCULATIONAHA.115.015884
        • Hung C.-L.
        • Verma A.
        • Uno H.
        • Shin S.-H.
        • Bourgoun M.
        • Hassanein A.H.
        • McMurray J.J.
        • Velazquez E.J.
        • Kober L.
        • Pfeffer M.A.
        • Solomon S.D.
        • VALIANT investigators
        Longitudinal and circumferential strain rate, left ventricular remodeling, and prognosis after myocardial infarction.
        J. Am. Coll. Cardiol. 2010; 56: 1812-1822https://doi.org/10.1016/j.jacc.2010.06.044
        • Santos-Gallego C.G.
        • Vahl T.P.
        • Goliasch G.
        • Picatoste B.
        • Arias T.
        • Ishikawa K.
        • Njerve I.U.
        • Sanz J.
        • Narula J.
        • Sengupta P.P.
        • Hajjar R.J.
        • Fuster V.
        • Badimon J.J.
        Sphingosine-1-Phosphate receptor agonist fingolimod increases myocardial salvage and decreases adverse postinfarction left ventricular remodeling in a porcine model of ischemia/reperfusion.
        Circulation. 2016; 133: 954-966https://doi.org/10.1161/CIRCULATIONAHA.115.012427
        • Haugaa K.H.
        • Edvardsen T.
        Global longitudinal strain: the best biomarker for predicting prognosis in heart failure?.
        Eur. J. Heart Fail. 2016; 18: 1340-1341https://doi.org/10.1002/ejhf.632
        • Shang Q.
        • Tam L.-S.
        • Sanderson J.E.
        • Sun J.-P.
        • Li E.K.-M.
        • Yu C.-M.
        Increase in ventricular-arterial stiffness in patients with psoriatic arthritis.
        Rheumatology. 2012; 51: 2215-2223https://doi.org/10.1093/rheumatology/kes213
        • Abella V.
        • Scotece M.
        • Conde J.
        • López V.
        • Lazzaro V.
        • Pino J.
        • Gómez-Reino J.J.
        • Gualillo O.
        Adipokines, metabolic syndrome and rheumatic diseases.
        J. Immunol. Res. 2014; 2014343746https://doi.org/10.1155/2014/343746
        • Choy E.
        • Ganeshalingam K.
        • Semb A.G.
        • Szekanecz Z.
        • Nurmohamed M.
        Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment.
        Rheumatology. 2014; 53: 2143-2154https://doi.org/10.1093/rheumatology/keu224
        • Ku I.A.
        • Imboden J.B.
        • Hsue P.Y.
        • Ganz P.
        Rheumatoid arthritis: model of systemic inflammation driving atherosclerosis.
        Circ. J. 2009; 73: 977-985
        • Ramonda R.
        • Lo Nigro A.
        • Modesti V.
        • Nalotto L.
        • Musacchio E.
        • Iaccarino L.
        • Punzi L.
        • Doria A.
        Atherosclerosis in psoriatic arthritis.
        Autoimmun. Rev. 2011; 10: 773-778https://doi.org/10.1016/j.autrev.2011.05.022
        • Rodríguez-Carrio J.
        • López P.
        • Suárez A.
        Endothelial Progenitor Cells as mediators of the crosstalk between vascular repair and immunity: lessons from systemic autoimmune diseases.
        Curr. Med. Chem. 2017; https://doi.org/10.2174/0929867324666170428110311
        • Yamaguchi Y.
        • Kuwana M.
        Proangiogenic hematopoietic cells of monocytic origin: roles in vascular regeneration and pathogenic processes of systemic sclerosis.
        Histol. Histopathol. 2013; 28: 175-183https://doi.org/10.14670/HH-28.175
        • Aragona C.O.
        • Imbalzano E.
        • Mamone F.
        • Cairo V.
        • Lo Gullo A.
        • D'Ascola A.
        • Sardo M.A.
        • Scuruchi M.
        • Basile G.
        • Saitta A.
        • Mandraffino G.
        Endothelial progenitor cells for diagnosis and prognosis in cardiovascular disease.
        Stem Cell. Int. 2016; 20168043792https://doi.org/10.1155/2016/8043792
        • Jujo K.
        • Ii M.
        • Losordo D.W.
        Endothelial progenitor cells in neovascularization of infarcted myocardium.
        J. Mol. Cell. Cardiol. 2008; 45: 530-544https://doi.org/10.1016/j.yjmcc.2008.08.003
        • Takahashi T.
        • Kalka C.
        • Masuda H.
        • Chen D.
        • Silver M.
        • Kearney M.
        • Magner M.
        • Isner J.M.
        • Asahara T.
        Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization.
        Nat. Med. 1999; 5: 434-438https://doi.org/10.1038/7434
        • Maltais S.
        • Perrault L.P.
        • Ly H.Q.
        The bone marrow-cardiac axis: role of endothelial progenitor cells in heart failure.
        Eur. J. Cardio. Thorac. Surg. 2011; 39: 368-374https://doi.org/10.1016/j.ejcts.2010.04.022
        • Grundmann M.
        • Haidar M.
        • Placzko S.
        • Niendorf R.
        • Darashchonak N.
        • Hubel C.A.
        • von Versen-Höynck F.
        Vitamin D improves the angiogenic properties of endothelial progenitor cells.
        Am. J. Physiol. Cell Physiol. 2012; 303: C954-C962https://doi.org/10.1152/ajpcell.00030.2012
        • Lo Gullo A.
        • Mandraffino G.
        • Bagnato G.
        • Aragona C.O.
        • Imbalzano E.
        • D'Ascola A.
        • Rotondo F.
        • Cinquegrani A.
        • Mormina E.
        • Saitta C.
        • Versace A.G.
        • Sardo M.A.
        • Lo Gullo R.
        • Loddo S.
        • Saitta A.
        Vitamin D status in rheumatoid arthritis: inflammation, arterial stiffness and circulating progenitor cell number.
        PLoS One. 2015; 10e0134602https://doi.org/10.1371/journal.pone.0134602
        • Assalin H.B.
        • Rafacho B.P.
        • dos Santos P.P.
        • Ardisson L.P.
        • Roscani M.G.
        • Chiuso-Minicucci F.
        • Barbisan L.F.
        • Fernandes A.A.H.
        • Azevedo P.S.
        • Minicucci M.F.
        • Zornoff L.A.
        • de Paiva S.A.R.
        Impact of the length of vitamin D deficiency on cardiac remodeling.
        Circ. Heart Fail. 2013; 6: 809-816https://doi.org/10.1161/CIRCHEARTFAILURE.112.000298
        • Aletaha D.
        • Neogi T.
        • Silman A.J.
        • Funovits J.
        • Felson D.T.
        • Bingham C.O.
        • Birnbaum N.S.
        • Burmester G.R.
        • Bykerk V.P.
        • Cohen M.D.
        • Combe B.
        • Costenbader K.H.
        • Dougados M.
        • Emery P.
        • Ferraccioli G.
        • Hazes J.M.W.
        • Hobbs K.
        • Huizinga T.W.J.
        • Kavanaugh A.
        • Kay J.
        • Kvien T.K.
        • Laing T.
        • Mease P.
        • Ménard H.A.
        • Moreland L.W.
        • Naden R.L.
        • Pincus T.
        • Smolen J.S.
        • Stanislawska-Biernat E.
        • Symmons D.
        • Tak P.P.
        • Upchurch K.S.
        • Vencovský J.
        • Wolfe F.
        • Hawker G.
        2010 Rheumatoid arthritis classification criteria: an american college of rheumatology/European league against rheumatism collaborative initiative.
        Arthritis Rheum. 2010; 62: 2569-2581https://doi.org/10.1002/art.27584
        • Taylor W.
        • Gladman D.
        • Helliwell P.
        • Marchesoni A.
        • Mease P.
        • Mielants H.
        • CASPAR Study Group
        Classification criteria for psoriatic arthritis: development of new criteria from a large international study.
        Arthritis Rheum. 2006; 54: 2665-2673https://doi.org/10.1002/art.21972
        • Mandraffino G.
        • Aragona C.O.
        • Basile G.
        • Cairo V.
        • Mamone F.
        • Morace C.
        • D'Ascola A.
        • Alibrandi A.
        • Lo Gullo A.
        • Loddo S.
        • Saitta A.
        • Imbalzano E.
        CD34+ cell count predicts long lasting life in the oldest old.
        Mech. Ageing Dev. 2017; 164: 139-145https://doi.org/10.1016/j.mad.2017.03.003
        • Fleischmann R.M.
        • van der Heijde D.
        • V Gardiner P.
        • Szumski A.
        • Marshall L.
        • Bananis E.
        DAS28-CRP and DAS28-ESR cut-offs for high disease activity in rheumatoid arthritis are not interchangeable.
        RMD Open. 2017; 3e000382https://doi.org/10.1136/rmdopen-2016-000382
        • Mancia G.
        • De Backer G.
        • Dominiczak A.
        • Cifkova R.
        • Fagard R.
        • Germano G.
        • Grassi G.
        • Heagerty A.M.
        • Kjeldsen S.E.
        • Laurent S.
        • Narkiewicz K.
        • Ruilope L.
        • Rynkiewicz A.
        • Schmieder R.E.
        • Boudier H.A.S.
        • Zanchetti A.
        ESH-ESC task force on the management of arterial hypertension, 2007 ESH-ESC practice guidelines for the management of arterial hypertension: ESH-ESC task force on the management of arterial hypertension.
        J. Hypertens. 2007; 25: 1751-1762https://doi.org/10.1097/HJH.0b013e3282f0580f
        • Castañeda S.
        • Nurmohamed M.T.
        • González-Gay M.A.
        Cardiovascular disease in inflammatory rheumatic diseases.
        Best Pract. Res. Clin. Rheumatol. 2016; 30: 851-869https://doi.org/10.1016/j.berh.2016.10.006
        • Dessein P.H.
        • Joffe B.I.
        • Veller M.G.
        • Stevens B. a
        • Tobias M.
        • Reddi K.
        • Stanwix A.E.
        Traditional and nontraditional cardiovascular risk factors are associated with atherosclerosis in rheumatoid arthritis.
        J. Rheumatol. 2005; 32 (0315162X-32-435 [pii]): 435-442
        • Ikonomidis I.
        • Tzortzis S.
        • Andreadou I.
        • Paraskevaidis I.
        • Katseli C.
        • Katsimbri P.
        • Pavlidis G.
        • Parissis J.
        • Kremastinos D.
        • Anastasiou-Nana M.
        • Lekakis J.
        Increased benefit of interleukin-1 inhibition on vascular function, myocardial deformation, and twisting in patients with coronary artery disease and coexisting rheumatoid arthritis.
        Circ. Cardiovasc. Imaging. 2014; 7: 619-628https://doi.org/10.1161/CIRCIMAGING.113.001193
        • Ikonomidis I.
        • Tzortzis S.
        • Lekakis J.
        • Paraskevaidis I.
        • Andreadou I.
        • Nikolaou M.
        • Kaplanoglou T.
        • Katsimbri P.
        • Skarantavos G.
        • Soucacos P.
        • Kremastinos D.T.
        Lowering interleukin-1 activity with anakinra improves myocardial deformation in rheumatoid arthritis.
        Heart. 2009; 95: 1502-1507https://doi.org/10.1136/hrt.2009.168971
        • Midtbø H.
        • Semb A.G.
        • Matre K.
        • Kvien T.K.
        • Gerdts E.
        Disease activity is associated with reduced left ventricular systolic myocardial function in patients with rheumatoid arthritis.
        Ann. Rheum. Dis. 2017; 76: 371-376https://doi.org/10.1136/annrheumdis-2016-209223
        • Solomon D.H.
        • Reed G.W.
        • Kremer J.M.
        • Curtis J.R.
        • Farkouh M.E.
        • Harrold L.R.
        • Hochberg M.C.
        • Tsao P.
        • Greenberg J.D.
        Disease activity in rheumatoid arthritis and the risk of cardiovascular events.
        Arthritis Rheum. 2015; 67: 1449-1455https://doi.org/10.1002/art.39098
        • Fernández-Gutiérrez B.
        • Perrotti P.P.
        • Gisbert J.P.
        • Domènech E.
        • Fernández-Nebro A.
        • Cañete J.D.
        • Ferrándiz C.
        • Tornero J.
        • García-Sánchez V.
        • Panés J.
        • Fonseca E.
        • Blanco F.
        • Rodríguez-Moreno J.
        • Carreira P.
        • Julià A.
        • Marsal S.
        • Rodriguez-Rodriguez L.
        IMID Consortium, Cardiovascular disease in immune-mediated inflammatory diseases: a cross-sectional analysis of 6 cohorts.
        Medicine (Baltim.). 2017; 96e7308https://doi.org/10.1097/MD.0000000000007308
        • Ikonomidis I.
        • Makavos G.
        • Papadavid E.
        • Varoudi M.
        • Andreadou I.
        • Gravanis K.
        • Theodoropoulos K.
        • Pavlidis G.
        • Triantafyllidi H.
        • Parissis J.
        • Paraskevaidis I.
        • Rigopoulos D.
        • Lekakis J.
        Similarities in coronary function and myocardial deformation between psoriasis and coronary artery disease: the role of oxidative stress and inflammation.
        Can. J. Cardiol. 2015; 31: 287-295https://doi.org/10.1016/j.cjca.2014.11.002
        • Kul S.
        • Kutlu G.A.
        • Guvenc T.S.
        • Kavas M.
        • Demircioglu K.
        • Yilmaz Y.
        • Yakar H.I.
        • Kanbay A.
        • Boga S.
        • Caliskan M.
        Coronary flow reserve is reduced in sarcoidosis.
        Atherosclerosis. 2017; 264: 115-121https://doi.org/10.1016/j.atherosclerosis.2017.05.005
        • Santos-Gallego C.G.
        • Weiss A.J.
        • Sanz J.
        Non-cardiac sarcoid actually affects the heart by reducing coronary flow reserve.
        Atherosclerosis. 2017; 264: 74-76https://doi.org/10.1016/j.atherosclerosis.2017.07.006
        • González-Gay M.A.
        • González-Juanatey C.
        • Llorca J.
        Carotid ultrasound in the cardiovascular risk stratification of patients with rheumatoid arthritis: when and for whom?.
        Ann. Rheum. Dis. 2012; 71: 796-798https://doi.org/10.1136/annrheumdis-2011-201209
        • Fent G.J.
        • Greenwood J.P.
        • Plein S.
        • Buch M.H.
        The role of non-invasive cardiovascular imaging in the assessment of cardiovascular risk in rheumatoid arthritis: where we are and where we need to be.
        Ann. Rheum. Dis. 2017; 76: 1169-1175https://doi.org/10.1136/annrheumdis-2016-209744
        • Gorcsan J.
        • Tanaka H.
        Echocardiographic assessment of myocardial strain.
        J. Am. Coll. Cardiol. 2011; 58: 1401-1413https://doi.org/10.1016/j.jacc.2011.06.038
        • Bellavia D.
        • Pellikka P.A.
        • Abraham T.P.
        • Al-Zahrani G.B.
        • Dispenzieri A.
        • Oh J.K.
        • Bailey K.R.
        • Wood C.M.
        • Lacy M.Q.
        • Miyazaki C.
        • Miller F.A.
        Evidence of impaired left ventricular systolic function by Doppler myocardial imaging in patients with systemic amyloidosis and no evidence of cardiac involvement by standard two-dimensional and Doppler echocardiography.
        Am. J. Cardiol. 2008; 101: 1039-1045https://doi.org/10.1016/j.amjcard.2007.11.047
        • Imbalzano E.
        • Zito C.
        • Carerj S.
        • Oreto G.
        • Mandraffino G.
        • Cusmà-Piccione M.
        • Di Bella G.
        • Saitta C.
        • Saitta A.
        Left ventricular function in hypertension: new insight by speckle tracking echocardiography.
        Echocardiography. 2011; 28: 649-657https://doi.org/10.1111/j.1540-8175.2011.01410.x
        • Ikonomidis I.
        • Athanassopoulos G.
        • Stamatelopoulos K.
        • Lekakis J.
        • Revela I.
        • Venetsanou K.
        • Marinou M.
        • Monaco C.
        • Cokkinos D.V.
        • Nihoyannopoulos P.
        Additive prognostic value of interleukin-6 at peak phase of dobutamine stress echocardiography in patients with coronary artery disease. A 6-year follow-up study.
        Am. Heart J. 2008; 156: 269-276https://doi.org/10.1016/j.ahj.2008.03.020
        • Maradit-Kremers H.
        • Nicola P.J.
        • Crowson C.S.
        • Ballman K.V.
        • Gabriel S.E.
        Cardiovascular death in rheumatoid arthritis: a population-based study.
        Arthritis Rheum. 2005; 52: 722-732https://doi.org/10.1002/art.20878
        • Ikonomidis I.
        • Lekakis J.P.
        • Nikolaou M.
        • Paraskevaidis I.
        • Andreadou I.
        • Kaplanoglou T.
        • Katsimbri P.
        • Skarantavos G.
        • Soucacos P.N.
        • Kremastinos D.T.
        Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis.
        Circulation. 2008; 117: 2662-2669https://doi.org/10.1161/CIRCULATIONAHA.107.731877
        • Frieler R.A.
        • Mortensen R.M.
        Immune cell and other noncardiomyocyte regulation of cardiac hypertrophy and remodeling.
        Circulation. 2015; 131: 1019-1030https://doi.org/10.1161/CIRCULATIONAHA.114.008788
        • Gardner D.G.
        • Chen S.
        • Glenn D.J.
        Vitamin D and the heart.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2013; 305: R969-R977https://doi.org/10.1152/ajpregu.00322.2013
        • Tamez H.
        • Zoccali C.
        • Packham D.
        • Wenger J.
        • Bhan I.
        • Appelbaum E.
        • Pritchett Y.
        • Chang Y.
        • Agarwal R.
        • Wanner C.
        • Lloyd-Jones D.
        • Cannata J.
        • Thompson B.T.
        • Andress D.
        • Zhang W.
        • Singh B.
        • Zehnder D.
        • Pachika A.
        • Manning W.J.
        • Shah A.
        • Solomon S.D.
        • Thadhani R.
        Vitamin D reduces left atrial volume in patients with left ventricular hypertrophy and chronic kidney disease.
        Am. Heart J. 2012; 164 (902–909.e2)https://doi.org/10.1016/j.ahj.2012.09.018
        • Prietl B.
        • Treiber G.
        • Pieber T.R.
        • Amrein K.
        Vitamin D and immune function.
        Nutrients. 2013; 5: 2502-2521https://doi.org/10.3390/nu5072502
        • Norman P.E.
        • Powell J.T.
        Vitamin D and cardiovascular disease.
        Circ. Res. 2014; 114: 379-393https://doi.org/10.1161/CIRCRESAHA.113.301241
        • Gambardella J.
        • Santulli G.
        Integrating diet and inflammation to calculate cardiovascular risk.
        Atherosclerosis. 2016; 253: 258-261https://doi.org/10.1016/j.atherosclerosis.2016.08.041
        • Costa S.P.
        • Beaver T.A.
        • Rollor J.L.
        • Vanichakarn P.
        • Magnus P.C.
        • Palac R.T.
        Quantification of the variability associated with repeat measurements of left ventricular two-dimensional global longitudinal strain in a real-world setting.
        J. Am. Soc. Echocardiogr. 2014; 27: 50-54https://doi.org/10.1016/j.echo.2013.08.021