Skip to main content

Cardiovascular Calcification in Systemic Diseases

  • Chapter
  • First Online:
Cardiovascular Calcification
  • 787 Accesses

Abstract

Over the last two decades cardiovascular calcification (CVC) evolved from a poorly understood process and largely underestimated issue to one due to complex pathophysiologic mechanisms and posing significant health threats. Many clinical conditions are associated with the development of CVC and in several cases the events leading to its growth have been elucidated. Vascular calcification is not uniformly a marker of atherosclerosis, as extensive medial calcification can occur in patients with chronic kidney disease for example. Research efforts have focused on developing therapies tailored at slowing the progression of CVC in the hope to improve the health of affected subjects. Patients with chronic kidney disease are at particularly high risk of suffering from the consequences of CVC and have therefore been targeted with various inhibitors of calcification. Other rarer disorders associated with CVC also have been the focus of research leading to novel therapeutic advances. In this chapter we review some of the most common conditions associated with CVC and some of the most recent therapeutic advances in each area.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Matsushita K, Sang Y, Ballew SH, et al. Subclinical atherosclerosis measures for cardiovascular prediction in CKD. J Am Soc Nephrol. 2015;26:439–47.

    Article  Google Scholar 

  2. Kramer H, Toto R, Peshock R, et al. Association between chronic kidney disease and coronary artery calcification: the Dallas Heart Study. J Am Soc Nephrol. 2005;16:507–13.

    Article  Google Scholar 

  3. Gorriz JL, Molina P, Cerveron MJ, et al. Vascular calcification in patients with nondialysis CKD over 3 years. Clin J Am Soc Nephrol. 2015;10:654–66.

    Article  CAS  Google Scholar 

  4. Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002;62:245–52.

    Article  CAS  Google Scholar 

  5. Raggi P, Boulay A, Chasan-Taber S, et al. Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease? J Am Coll Cardiol. 2002;39:695–701.

    Article  Google Scholar 

  6. Bellasi A, Veledar E, Ferramosca E, et al. Markers of vascular disease do not differ in black and white hemodialysis patients despite a different risk profile. Atherosclerosis. 2008;197:242–9.

    Article  CAS  Google Scholar 

  7. D’Marco L, Bellasi A, Mazzaferro S, et al. Vascular calcification, bone and mineral metabolism after kidney transplantation. World J Transplant. 2015;5:222–30.

    Article  Google Scholar 

  8. London GM, Guerin AP, Marchais SJ, et al. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant. 2003;18:1731–40.

    Article  Google Scholar 

  9. Safar ME, Blacher J, Pannier B, et al. Central pulse pressure and mortality in end-stage renal disease. Hypertension. 2002;39:735–8.

    Article  CAS  Google Scholar 

  10. Adragao T, Pires A, Lucas C, et al. A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients. Nephrol Dial Transplant. 2004;19:1480–8.

    Article  Google Scholar 

  11. Bellasi A, Ferramosca E, Muntner P, et al. Correlation of simple imaging tests and coronary artery calcium measured by computed tomography in hemodialysis patients. Kidney Int. 2006;70:1623–8.

    Article  CAS  Google Scholar 

  12. Okuno S, Ishimura E, Kitatani K, et al. Presence of abdominal aortic calcification is significantly associated with all-cause and cardiovascular mortality in maintenance hemodialysis patients. Am J Kidney Dis. 2007;49:417–25.

    Article  Google Scholar 

  13. Verbeke F, Van Biesen W, Honkanen E, et al. Prognostic value of aortic stiffness and calcification for cardiovascular events and mortality in dialysis patients: outcome of the Calcification Outcome in Renal Disease (CORD) Study. Clin J Am Soc Nephrol. 2010;6:153–6.

    Article  Google Scholar 

  14. Shantouf R, Budoff MJ, Ahmadi N, et al. Effects of sevelamer and calcium-based phosphate binders on lipid and inflammatory markers in hemodialysis patients. Am J Nephrol. 2008;28:275–9.

    Article  CAS  Google Scholar 

  15. Block GA, Raggi P, Bellasi A, et al. Mortality effect of coronary calcification and phosphate binder choice in incident HD patients. Kidney Int. 2007;71:438–41.

    Article  CAS  Google Scholar 

  16. Chen J, Budoff MJ, Reilly MP, et al. Coronary artery calcification and risk of cardiovascular disease and death among patients with chronic kidney disease. JAMA Cardiol. 2017;2:635–43.

    Article  Google Scholar 

  17. Bellasi A, Raggi P. Vascular calcification in chronic kidney disease: usefulness of a marker of vascular damage. J Nephrol. 2011;24(Suppl 18):S11–5.

    Article  CAS  Google Scholar 

  18. Xie Q, Ge X, Shang D, et al. Coronary artery calcification score as a predictor of all-cause mortality and cardiovascular outcome in peritoneal dialysis patients. Perit Dial Int. 2016;36:163–70.

    Article  Google Scholar 

  19. Bellasi A, Block GA, Ferramosca E, Ratti C, Raggi P. Integration of clinical and imaging data to predict death in hemodialysis patients. Hemodial Int. 2013;17:12–8.

    Article  Google Scholar 

  20. Blacher J, Guerin AP, Pannier B, et al. Impact of aortic stiffness on survival in end-stage renal disease. Circulation. 1999;99:2434–9.

    Article  CAS  Google Scholar 

  21. Blacher J, Guerin AP, Pannier B, et al. Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension. 2001;38:938–42.

    Article  CAS  Google Scholar 

  22. Di Iorio B, Nargi O, Cucciniello E, et al. Coronary artery calcification progression is associated with arterial stiffness and cardiac repolarization deterioration in hemodialysis patients. Kidney Blood Press Res. 2011;34:180–7.

    Article  Google Scholar 

  23. Wang MC, Tsai WC, Chen JY, et al. Stepwise increase in arterial stiffness corresponding with the stages of chronic kidney disease. Am J Kidney Dis. 2005;45:494–501.

    Article  Google Scholar 

  24. Kim CS, Bae EH, Ma SK, et al. Chronic kidney disease-mineral bone disorder in korean patients: a report from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). J Korean Med Sci. 2017;32:240–8.

    Article  Google Scholar 

  25. Raggi P, Bellasi A, Ferramosca E, et al. Association of pulse wave velocity with vascular and valvular calcification in hemodialysis patients. Kidney Int. 2007;71:802–7.

    Article  CAS  Google Scholar 

  26. Pressman GS, Movva R, Topilsky Y, et al. Mitral annular dynamics in mitral annular calcification: a three-dimensional imaging study. J Am Soc Echocardiogr. 2015;28:786–94.

    Article  Google Scholar 

  27. Movva R, Murthy K, Romero-Corral A, et al. Calcification of the mitral valve and annulus: systematic evaluation of effects on valve anatomy and function. J Am Soc Echocardiogr. 2013;26:1135–42.

    Article  Google Scholar 

  28. Raggi P, Bellasi A, Gamboa C, et al. All-cause mortality in hemodialysis patients with heart valve calcification. Clin J Am Soc Nephrol. 2011;6:1990–5.

    Article  Google Scholar 

  29. Bellasi A, Ferramosca E, Ratti C, et al. The density of calcified plaques and the volume of calcium predict mortality in hemodialysis patients. Atherosclerosis. 2016;250:166–71.

    Article  CAS  Google Scholar 

  30. Criqui MH, Denenberg JO, Ix JH, et al. Calcium density of coronary artery plaque and risk of incident cardiovascular events. JAMA. 2014;311:271–8.

    Article  CAS  Google Scholar 

  31. Thompson S, James M, Wiebe N, et al. Cause of death in patients with reduced kidney function. J Am Soc Nephrol. 2015;26:2504–11.

    Article  Google Scholar 

  32. US Renal Data System 2019 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2019 Oct 31. pii: S0272-6386(19)31008-X.

    Google Scholar 

  33. Baigent C, Burbury K, Wheeler D. Premature cardiovascular disease in chronic renal failure. Lancet. 2000 Jul 8;356(9224):147–52.

    Article  CAS  Google Scholar 

  34. Bansal N, Keane M, Delafontaine P, et al. A longitudinal study of left ventricular function and structure from CKD to ESRD: The CRIC Study. Clin J Am Soc Nephrol. 2013;8(3):355–62.

    Article  Google Scholar 

  35. Kooman JP, Kotanko P, Schols AM, et al. Chronic kidney disease and premature ageing. Nat Rev Nephrol. 2014;10:732–42.

    Article  CAS  Google Scholar 

  36. Sigrist M, Bungay P, Taal MW, McIntyre CW. Vascular calcification and cardiovascular function chronic kidney disease. Nephrol Dial Transplant. 2006;21:707–14.

    Article  Google Scholar 

  37. Garland JS, Holden RM, Groome PA, et al. Prevalence and associations of coronary artery calcification in patients with stages 3 to 5 CKD without cardiovascular disease. Am J Kidney Dis. 2008;52:849–58.

    Article  CAS  Google Scholar 

  38. Goodman WG, Goldin J, Kuizon BD, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med. 2000;342:1478–83.

    Article  CAS  Google Scholar 

  39. Moe SM, Chen NX. Pathophysiology of vascular calcification in chronic kidney Disease. Circ Res. 2004;95:560–7.

    Article  CAS  Google Scholar 

  40. McCullough PA, Agrawal V, Danielewicz E, Abela GS. Accelerated atherosclerotic calcification and Mönckeberg’s sclerosis: a continuum of advanced vascular pathology in chronic kidney disease. Clin J Am Soc Nephrol. 2008;3(6):1585–98.

    Article  CAS  Google Scholar 

  41. Sage AP, Tintut Y, Demer LL. Regulatory mechanisms in vascular calcification. Nat Rev Cardiol. 2010;7:528–36.

    Article  CAS  Google Scholar 

  42. Raggi P, Giachelli C, Bellasi A. Interaction of vascular and bone disease in patients with normal renal function and patients undergoing dialysis. Nat Clin Pract Cardiovasc Med. 2007;4:26–33.

    Article  CAS  Google Scholar 

  43. Henaut L, Chillon JM, Kamel S, et al. Updates on the mechanisms and the care of cardiovascular calcification in chronic kidney disease. Semin Nephrol. 2018;38:233–50.

    Article  Google Scholar 

  44. Bellasi A, Di Lullo L, Raggi P. Cardiovascular calcification: the emerging role of micronutrients. Atherosclerosis. 2018;273:119–21.

    Article  CAS  Google Scholar 

  45. Mencke R, Hillebrands JL. NIGRAM consortium. The role of the anti-ageing protein Klotho in vascular physiology and pathophysiology. Ageing Res Rev. 2017;35:124–46.

    Article  CAS  Google Scholar 

  46. Kuro-O M. The Klotho proteins in health and disease. Nat Rev Nephrol. 2019;15:27–44.

    Article  CAS  Google Scholar 

  47. Villa-Bellosta R, Egido J. Phosphate, pyrophosphate, and vascular calcification: a question of balance. Eur Heart J. 2017;38:1801–4.

    CAS  Google Scholar 

  48. O’Neill WC, Lomashvili KA. Recent progress in the treatment of vascular calcification. Kidney Int. 2010 Dec;78(12):1232–9.

    Article  Google Scholar 

  49. Chen Z, Qureshi AR, Parini P, et al. Does statins promote vascular calcification in chronic kidney disease? Eur J Clin Investig. 2017;47:137–48.

    Article  CAS  Google Scholar 

  50. De Vriese AS, Caluwé R, Pyfferoen L, De Bacquer D, De Boeck K, Delanote J, De Surgeloose D, Van Hoenacker P, Van Vlem B, Verbeke F. Multicenter randomized controlled trial of vitamin K antagonist replacement by rivaroxaban with or without vitamin K2 in hemodialysis patients with atrial fibrillation: the Valkyrie Study. J Am Soc Nephrol. 2020;31:186–96.

    Article  Google Scholar 

  51. Krueger T, Schlieper G, Schurgers L, et al. Vitamin K1 to slow vascular calcification in haemodialysis patients (VitaVasK trial): a rationale and study protocol. Nephrol Dial Transplant. 2014;29:1633–8.

    Article  CAS  Google Scholar 

  52. Jono S, McKee MD, Murry CE, et al. Phosphate regulation of vascular smooth muscle cell calcification. Circ Res. 2000;87:E10–7.

    Article  CAS  Google Scholar 

  53. Isakova T, Ix JH, Sprague SM, et al. Rationale and approaches to phosphate and Fibroblast Growth Factor 23 reduction in CKD. J Am Soc Nephrol. 2015;26:2328–39.

    Article  CAS  Google Scholar 

  54. Chertow GM, Burke SK, Raggi P, Treat to Goal Working Group. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002;62:245–52.

    Article  CAS  Google Scholar 

  55. Block GB, Spiegel DM, Ehrlich J, et al. Effects of sevelamer and calcium on coronary artery calcification in patients new to HD. Kidney Int. 2005;68:1815–24.

    Article  CAS  Google Scholar 

  56. Chertow GM, Raggi P, Chasan-Taber S, Bommer J, Holzer H, Burke SK. Determinants of progressive vascular calcification in haemodialysis patients. Nephrol Dial Transplant. 2004;19:1489–96.

    Article  Google Scholar 

  57. Anderson JJ, Kruszka B, Delaney JA, et al. Calcium intake from diet and supplements and the risk of coronary artery calcification and its progression among older adults: 10-year follow-up of the Multi-Ethnic Study of Atherosclerosis (MESA). J Am Heart Assoc. 2016;5(10):e003815.

    Article  Google Scholar 

  58. Hulbert M, Turner ME, Hopman WM, Anastassiades T, Adams MA, Holden RM. Changes in vascular calcification and bone mineral density in calcium supplement users from the Canadian Multi-center Osteoporosis Study (CaMOS). Atherosclerosis. 2020;296:83–90.

    Article  CAS  Google Scholar 

  59. Raggi P, James G, Burke SK, Bommer J, Chasan-Taber S, Holzer H, Braun J, Chertow GM. Decrease in thoracic vertebral bone attenuation with calcium-based phosphate binders in hemodialysis. J Bone Miner Res. 2005;20:764–72.

    Article  CAS  Google Scholar 

  60. Morelli MB, Santulli G, Gambardella J. Calcium supplements: good for the bone, bad for the heart? A systematic updated appraisal. Atherosclerosis. 2020;296:68–73.

    Article  CAS  Google Scholar 

  61. Block GA, Raggi P, Bellasi A, Kooienga L, Spiegel DM. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int. 2007;71:438–41.

    Article  CAS  Google Scholar 

  62. Di Iorio B, Bellasi A, Russo D. Mortality in kidney disease patients treated with phosphate binders: A Randomized Study. Clin J Am Soc Nephrol. 2012;7:487–93.

    Article  Google Scholar 

  63. Di Iorio B, Molony D, Bell C, et al. Sevelamer versus calcium carbonate in incident hemodialysis patients: results of an open-label 24-month randomized clinical trial. Am J Kidney Dis. 2013;62:771–8.

    Article  Google Scholar 

  64. Jamal SA, Vandermeer B, Raggi P, et al. Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis. Lancet. 2013;382:1268–77.

    Article  CAS  Google Scholar 

  65. Ketteler M, Block GA, Evenepoel P, et al. Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: what’s changed and why it matters. Kidney Int. 2017;92:26–36. Kidney Int. 2017;92:1558.

    Google Scholar 

  66. Kircelli F, Peter ME, Sevinc Ok E, et al. Magnesium reduces calcification in bovine vascular smooth muscle cells in a dose-dependent manner. Nephrol Dial Transplant. 2012;27:514–21.

    Article  CAS  Google Scholar 

  67. Louvet L, Buchel J, Steppan S, Passlick-Deetjen J, Massy ZA. Magnesium prevents phosphate-induced calcification in human aortic vascular smooth muscle cells. Nephrol Dial Transplant. 2013;28:869–78.

    Article  CAS  Google Scholar 

  68. Xu J, Bai Y, Jin J, et al. Magnesium modulates the expression levels of calcification-associated factors to inhibit calcification in a time-dependent manner. Exp Ther Med. 2015;9:1028–34.

    Article  CAS  Google Scholar 

  69. Diaz-Tocados JM, Peralta-Ramirez A, Rodriguez-Ortiz ME, et al. Dietary magnesium supplementation prevents and reverses vascular and soft tissue calcifications in uremic rats. Kidney Int. 2017;92:1084–99.

    Article  CAS  Google Scholar 

  70. Spiegel DM, Farmer B. Long-term effects of magnesium carbonate on coronary artery calcification and bone mineral density in hemodialysis patients: a pilot study. Hemodial Int. 2009;13:453–9.

    Article  Google Scholar 

  71. Tzanakis IP, Stamataki EE, Papadaki AN, Giannakis N, Damianakis NE, Oreopoulos DG. Magnesium retards the progress of the arterial calcifications in hemodialysis patients: a pilot study. Int Urol Nephrol. 2014;46:2199–205.

    Article  CAS  Google Scholar 

  72. Bressendorff I, Hansen D, Schou M, et al. Oral magnesium supplementation in chronic kidney disease stages 3 and 4: efficacy, safety, and effect on serum calcification propensity-a prospective randomized double-blinded placebo-controlled clinical trial. Kidney Int Rep. 2017;2:380–9.

    Article  Google Scholar 

  73. Sakaguchi Y, Hamano T, Obi Y, et al. A randomized trial of magnesium oxide and oral carbon adsorbent for coronary artery calcification in predialysis CKD. J Am Soc Nephrol. 2019;30:1073–85.

    Article  CAS  Google Scholar 

  74. Wu M, Rementer C, Giachelli CM. Vascular calcification: an update on mechanisms and challenges in treatment. Calcif Tissue Int. 2013;93:365–73.

    Article  CAS  Google Scholar 

  75. Raggi P, Bellasi A, Bushinsky D, Bover J, Rodriguez M, Ketteler M, Sinha S, Salcedo C, Gillotti K, Padgett C, Garg R, Gold A, Perelló J, Chertow GM. Slowing progression of cardiovascular calcification with SNF472 in patients on hemodialysis: results of a randomized phase 2b study. Circulation. 2020;141(9):728–39.

    Article  CAS  Google Scholar 

  76. Cai Q, Hodgson SF, Kao PC, Lennon VA, Klee GG, Zinsmiester AR, Kumar R. Brief report: inhibition of renal phosphate transport by a tumor product in a patient with oncogenic osteomalacia. N Engl J Med. 1994;330(23):1645–9.

    Article  CAS  Google Scholar 

  77. Brown EM, Gamba G, Riccardi D, et al. Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature. 1993;366:575–80.

    Article  CAS  Google Scholar 

  78. Komaba H, Fukagawa M. FGF23-parathyroid interaction: implications in chronic kidney disease. Kidney Int. 2010 Feb;77(4):292–8.

    Article  CAS  Google Scholar 

  79. Voinescu A, Iqbal NW, Martin KJ. Pathophysiology of chronic kidney disease-mineral and bone disorder. In: Turner N, Lameire N, Goldsmith DJ, Winearls CG, Himmelfarber J, Remuzzi G, editors. Oxford textbook of clinical nephrology. 4th ed. Oxford: Oxford University Press; 2016. p. 934–8.

    Google Scholar 

  80. Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int. 2007;71(1):31–8.

    Article  CAS  Google Scholar 

  81. Marx SJ, Simonds WF, Agarwal SK, et al. Hyperparathyroidism in hereditary syndromes: special expressions and special managements. J Bone Miner Res. 2002;17(Suppl. 2):N37–43.

    CAS  Google Scholar 

  82. Pitt SC, Sippel RS, Chen H. Secondary and tertiary hyperparathyroidism, state of the art surgical management. Surg Clin North Am. 2009;89:1227–39.

    Article  Google Scholar 

  83. Kebebew E, Duh QY, Clark OH. Tertiary hyperparathyroidism: histologic patterns of disease and results of parathyroidectomy. Arch Surg. 2004;139:974–7.

    Article  Google Scholar 

  84. Kerby JD, Rue LW, Blair H, Hudson S, Sellers MT, Diethelm AG. Operative treatment of tertiary hyperparathyroidism: a single-center experience. Ann Surg. 1998;227:878–86.

    Article  CAS  Google Scholar 

  85. Onufrak SJ, Bellasi A, Shaw LJ, Herzog CA, Cardarelli F, Wilson PW, Vaccarino V, Raggi P. Phosphorus levels are associated with subclinical atherosclerosis in the general population. Atherosclerosis. 2008;199:424–31.

    Article  CAS  Google Scholar 

  86. Adeney KL, Siscovick DS, Ix JH, Seliger SL, Shlipak MG, Jenny NS, Kestenbaum BR. Association of serum phosphate with vascular and valvular calcification in moderate CKD. J Am Soc Nephrol. 2009;20:381–7.

    Article  CAS  Google Scholar 

  87. Hagström E, Hellman P, Larsson TE, Ingelsson E, Berglund L, Sundström J, Melhus H, Held C, Lind L, Michaëlsson K, Arnlöv J. Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation. 2009;119:2765–71.

    Article  Google Scholar 

  88. Onufrak SJ, Bellasi A, Cardarelli F, Vaccarino V, Muntner P, Shaw LJ, Raggi P. Investigation of gender heterogeneity in the associations of serum phosphorus with incident coronary artery disease and all-cause mortality. Am J Epidemiol. 2009;169:67–77.

    Article  Google Scholar 

  89. Campos-Obando N, Lahousse L, Brusselle G, Stricker BH, Hofman A, Franco OH, Uitterlinden AG, Zillikens MC. Serum phosphate levels are related to all-cause, cardiovascular and COPD mortality in men. Eur J Epidemiol. 2018;33:859–71.

    Article  CAS  Google Scholar 

  90. Dhingra R, Sullivan LM, Fox CS, Wang TJ, D’Agostino RB Sr, Gaziano JM, Vasan RS. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med. 2007;167:879–85.

    Article  CAS  Google Scholar 

  91. Hagström E, Michaëlsson K, Melhus H, Hansen T, Ahlström H, Johansson L, Ingelsson E, Sundström J, Lind L, Arnlöv J. Plasma-parathyroid hormone is associated with subclinical and clinical atherosclerotic disease in 2 community-based cohorts. Arterioscler Thromb Vasc Biol. 2014;34:1567–73.

    Article  Google Scholar 

  92. Hagström E, Ahlström T, Ärnlöv J, Larsson A, Melhus H, Hellman P, Lind L. Parathyroid hormone and calcium are independently associated with subclinical vascular disease in a community-based cohort. Atherosclerosis. 2015;238:420–6.

    Article  Google Scholar 

  93. Yang B, Lu C, Wu Q, Zhang J, Zhao H, Cao Y. Parathyroid hormone, cardiovascular and all-cause mortality: a meta-analysis. Clin Chim Acta. 2016;455:154–60.

    Article  CAS  Google Scholar 

  94. Wannamethee SG, Welsh P, Papacosta O, Lennon L, Whincup PH, Sattar N. Elevated parathyroid hormone, but not vitamin D deficiency, is associated with increased risk of heart failure in older men with and without cardiovascular disease. Circ Heart Fail. 2014;7:732–9.

    Article  CAS  Google Scholar 

  95. Bansal N, Zelnick L, Robinson-Cohen C, Hoofnagle AN, Ix JH, Lima JA, Shoben AB, Peralta CA, Siscovick DS, Kestenbaum B, de Boer IH. Serum parathyroid hormone and 25-hydroxyvitamin D concentrations and risk of incident heart failure: the Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc. 2014;3:e001278.

    Article  Google Scholar 

  96. Hagström E, Kilander L, Nylander R, Larsson EM, Michaëlsson K, Melhus H, Ahlström H, Johansson L, Lind L, Arnlöv J. Plasma parathyroid hormone is associated with vascular dementia and cerebral hyperintensities in two community-based cohorts. J Clin Endocrinol Metab. 2014;99:4181–9.

    Article  Google Scholar 

  97. Kestenbaum B, Sachs MC, Hoofnagle AN, Siscovick DS, Ix JH, Robinson-Cohen C, Lima JA, Polak JF, Blondon M, Ruzinski J, Rock D, de Boer IH. Fibroblast growth factor-23 and cardiovascular disease in the general population: the Multi-Ethnic Study of Atherosclerosis. Circ Heart Fail. 2014;7:409–17.

    Article  CAS  Google Scholar 

  98. Panwar B, Judd SE, Wadley VG, Jenny NS, Howard VJ, Safford MM, Gutiérrez OM. Association of fibroblast growth factor 23 with risk of incident coronary heart disease in community-living adults. JAMA Cardiol. 2018;3:318–25.

    Article  Google Scholar 

  99. di Giuseppe R, Kühn T, Hirche F, Buijsse B, Dierkes J, Fritsche A, Kaaks R, Boeing H, Stangl GI, Weikert C. Plasma fibroblast growth factor 23 and risk of cardiovascular disease: results from the EPIC-Germany case-cohort study. Eur J Epidemiol. 2015;30:131–41.

    Article  Google Scholar 

  100. Panwar B, Jenny NS, Howard VJ, Wadley VG, Muntner P, Kissela BM, Judd SE, Gutiérrez OM. Fibroblast growth factor 23 and risk of incident stroke in community-living adults. Stroke. 2015;46:322–8.

    Article  CAS  Google Scholar 

  101. Wright CB, Dong C, Stark M, Silverberg S, Rundek T, Elkind MS, Sacco RL, Mendez A, Wolf M. Plasma FGF23 and the risk of stroke: the Northern Manhattan Study (NOMAS). Neurology. 2014;82:1700–6.

    Article  CAS  Google Scholar 

  102. Lind L, Skarfors E, Berglund L, Lithell H, Ljunghall S. Serum calcium: a new, independent, prospective risk factor for myocardial infarction in middle-aged men followed for 18 years. J Clin Epidemiol. 1997;50:967–73.

    Article  CAS  Google Scholar 

  103. Lundgren E, Lind L, Palmer M, et al. Increased cardiovascular mortality and normalized serum calcium in patients with mild hypercalcemia followed up for 25 years. Surgery. 2001;130:978–85.

    Article  CAS  Google Scholar 

  104. Larsson TE, Olauson H, Hagström E, Ingelsson E, Arnlöv J, Lind L, Sundström J. Conjoint effects of serum calcium and phosphate on risk of total, cardiovascular, and noncardiovascular mortality in the community. Arterioscler Thromb Vasc Biol. 2010;30:333–9.

    Article  CAS  Google Scholar 

  105. Akat K, Kaden JJ, Schmitz F, Ewering S, Anton A, Klomfass S, Hoffmann R, Ortlepp JR. Calcium metabolism in adults with severe aortic valve stenosis and preserved renal function. Am J Cardiol. 2010;105:862–4.

    Article  CAS  Google Scholar 

  106. Gutiérrez OM, Wolf M, Taylor EN. Fibroblast growth factor 23, cardiovascular disease risk factors, and phosphorus intake in the health professionals follow-up study. Clin J Am Soc Nephrol. 2011;6:2871–8.

    Article  Google Scholar 

  107. di Giuseppe R, Kühn T, Hirche F, Buijsse B, Dierkes J, Fritsche A, Kaaks R, Boeing H, Stangl GI, Weikert C. Potential predictors of plasma fibroblast growth factor 23 concentrations: cross-sectional analysis in the EPIC-Germany Study. PLoS One. 2015;10(7):e0133580.

    Article  Google Scholar 

  108. Wareham NJ, Byrne CD, Carr C, Day NE, Boucher BJ, Hales CN. Glucose intolerance is associated with altered calcium homeostasis: a possible link between increased serum calcium concentration and cardiovascular disease mortality. Metabolism. 1997;46:1171–7.

    Article  CAS  Google Scholar 

  109. Neves KR, Graciolli FG, dos Reis LM, Graciolli RG, Neves CL, Magalhães AO, Custódio MR, Batista DG, Jorgetti V, Moysés RM. Vascular calcification: contribution of parathyroid hormone in renal failure. Kidney Int. 2007;71:1262–70.

    Article  CAS  Google Scholar 

  110. Graciolli FG, Neves KR, dos Reis LM, Graciolli RG, Noronha IL, Moysés RM, Jorgetti V. Phosphorus overload and PTH induce aortic expression of Runx2 in experimental uraemia. Nephrol Dial Transplant. 2009;24:1416–21.

    Article  CAS  Google Scholar 

  111. Andersson P, Rydberg E, Willenheimer R. Primary hyperparathyroidism and heart disease—a review. Eur Heart J. 2004;25:1776–87.

    Article  CAS  Google Scholar 

  112. Walker MD, Silverberg SJ. Cardiovascular aspects of primary hyperparathyroidism. J Endocrinol Investig. 2008;31:925–31.

    Article  CAS  Google Scholar 

  113. Baykan M, Erem C, Erdoğan T, Hacihasanoğlu A, Gedikli O, Kiriş A, Küçükosmanoğlu M, Ersöz HO, Celik S. Impairment of flow mediated vasodilatation of brachial artery in patients with primary hyperparathyroidism. Int J Cardiovasc Imaging. 2007;23:323–8.

    Article  Google Scholar 

  114. Hulter HN, Melby JC, Peterson JC, Cooke CR. Chronic continuous PTH infusion results in hypertension in normal subjects. J Clin Hypertens. 1986;2:360–70.

    CAS  Google Scholar 

  115. Jorde R, Svartberg J, Sundsfjord J. Serum parathyroid hormone as a predictor of increase in systolic blood pressure in men. J Hypertens. 2005;23:1639–44.

    Article  CAS  Google Scholar 

  116. Saleh FN, Schirmer H, Sundsfjord J, Jorde R. Parathyroid hormone and left ventricular hypertrophy. Eur Heart J. 2003;24:2054–60.

    Article  CAS  Google Scholar 

  117. Ozdemir D, Kalkan GY, Bayram NA, Onal ED, Ersoy R, Bozkurt E, Cakir B. Evaluation of left ventricle functions by tissue Doppler, strain, and strain rate echocardiography in patients with primary hyperparathyroidism. Endocrine. 2014;47:609–17.

    Article  CAS  Google Scholar 

  118. Walker MD, Fleischer JB, Di Tullio MR, Homma S, Rundek T, Stein EM, Zhang C, Taggart T, McMahon DJ, Silverberg SJ. Cardiac structure and diastolic function in mild primary hyperparathyroidism. J Clin Endocrinol Metab. 2010;95:2172–9.

    Article  CAS  Google Scholar 

  119. Längle F, Abela C, Koller-Strametz J, et al. Primary hyperparathyroidism and the heart: cardiac abnormalities correlated to clinical and biochemical data. World J Surg. 1994;18:619–24.

    Article  Google Scholar 

  120. Stefenelli T, Abela C, Frank H, et al. Cardiac abnormalities in patients with primary hyperparathyroidism: implications for follow up. J Clin Endocrinol Metab. 1997;82:106–12.

    Article  CAS  Google Scholar 

  121. Mesquita PN, Dornelas Leão Leite AP, Chagas Crisóstomo SD, Veras Filho E, da Cunha Xavier L, Bandeira F. Evaluation of coronary calcium score in patients with normocalcemic primary hyperparathyroidism. Vasc Health Risk Manag. 2017;13:225–9.

    Article  CAS  Google Scholar 

  122. Kepez A, Harmanci A, Hazirolan T, Isildak M, Kocabas U, Ates A, Ciftci O, Tokgozoglu L, Gürlek A. Evaluation of subclinical coronary atherosclerosis in mild asymptomatic primary hyperparathyroidism patients. Int J Cardiovasc Imaging. 2009;25:187–93.

    Article  Google Scholar 

  123. Streeten EA, Munir K, Hines S, Mohamed A, Mangano C, Ryan KA, Post W. Coronary artery calcification in patients with primary hyperparathyroidism in comparison with control subjects from the multi-ethnic study of atherosclerosis. Endocr Pract. 2008;14:155–61.

    Article  Google Scholar 

  124. Osto E, Fallo F, Pelizzo MR, Maddalozzo A, Sorgato N, Corbetti F, Montisci R, Famoso G, Bellu R, Lüscher TF, Iliceto S, Tona F. Coronary microvascular dysfunction induced by primary hyperparathyroidism is restored after parathyroidectomy. Circulation. 2012;126:1031–9.

    Article  Google Scholar 

  125. Ekmekci A, Abaci N, Colak Ozbey N, Agayev A, Aksakal N, Oflaz H, Erginel-Unaltuna N, Erbil Y. Endothelial function and endothelial nitric oxide synthase intron 4a/b polymorphism in primary hyperparathyroidism. J Endocrinol Investig. 2009;32:611–6.

    Article  CAS  Google Scholar 

  126. Stefenelli T, Mayr H, Bergler-Klein J, et al. Primary hyperparathyroidism: incidence of cardiac abnormalities and partial reversibility after successful parathyroidectomy. Am J Med. 1993;95:197–202.

    Article  CAS  Google Scholar 

  127. Dalberg K, Brodin LAA, Juhlin-Dannfelt A, et al. Cardiac function in primary hyperparathyroidism before and after operation. An echocardiographic study. Eur J Surg. 1996;162:171–6.

    CAS  Google Scholar 

  128. Best CAE, Krishnan R, Malvankar-Mehta MS, MacNeil SD. Echocardiogram changes following parathyroidectomy for primary hyperparathyroidism: a systematic review and meta-analysis. Medicine (Baltimore). 2017;96(43):e7255.

    Article  Google Scholar 

  129. Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol. 2004;15:2208–18.

    Article  CAS  Google Scholar 

  130. Seiler-Mussler S, Limbach AS, Emrich IE, Pickering JW, Roth HJ, Fliser D, Heine GH. Association of nonoxidized parathyroid hormone with cardiovascular and kidney disease outcomes in chronic kidney disease. Clin J Am Soc Nephrol. 2018;13:569–76.

    Article  Google Scholar 

  131. Seiler S, Rogacev KS, Roth HJ, Shafein P, Emrich I, Neuhaus S, Floege J, Fliser D, Heine GH. Associations of FGF-23 and sKlotho with cardiovascular outcomes among patients with CKD stages 2-4. Clin J Am Soc Nephrol. 2014;9:1049–58.

    Article  CAS  Google Scholar 

  132. Scialla JJ, Xie H, Rahman M, Anderson AH, Isakova T, Ojo A, Zhang X, Nessel L, Hamano T, Grunwald JE, Raj DS, Yang W, He J, Lash JP, Go AS, Kusek JW, Feldman H, Wolf M, Chronic Renal Insufficiency Cohort (CRIC) Study Investigators. Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol. 2014;25:349–60.

    Article  CAS  Google Scholar 

  133. Shardlow A, McIntyre NJ, Fluck RJ, McIntyre CW, Taal MW. Associations of fibroblast growth factor 23, vitamin D and parathyroid hormone with 5-year outcomes in a prospective primary care cohort of people with chronic kidney disease stage 3. BMJ Open. 2017;7(8):e016528.

    Article  Google Scholar 

  134. Marthi A, Donovan K, Haynes R, Wheeler DC, Baigent C, Rooney CM, Landray MJ, Moe SM, Yang J, Holland L, di Giuseppe R, Bouma-de Krijger A, Mihaylova B, Herrington WG. Fibroblast growth factor-23 and risks of cardiovascular and noncardiovascular diseases: a meta-analysis. J Am Soc Nephrol. 2018;29:2015–27.

    Article  CAS  Google Scholar 

  135. Fox CS, Larson MG, Vasan RS, Guo CY, Parise H, Levy D, Leip EP, O’Donnell CJ, D’Agostino RB Sr, Benjamin EJ. Cross-sectional association of kidney function with valvular and annular calcification: the Framingham heart study. J Am Soc Nephrol. 2006;17:521–7.

    Article  Google Scholar 

  136. Bellasi A, Ferramosca E, Ratti C, Block G, Raggi P. Cardiac valve calcification is a marker of vascular disease in prevalent hemodialysis patients. J Nephrol. 2012;25:211–8.

    Article  CAS  Google Scholar 

  137. Goodman WG. Vascular calcification in end-stage renal disease. J Nephrol. 2002;15(Suppl 6):S82–5.

    Google Scholar 

  138. Raggi P, Chertow GM, Torres PU, Csiky B, Naso A, Nossuli K, Moustafa M, Goodman WG, Lopez N, Downey G, Dehmel B, Floege J, ADVANCE Study Group. The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis. Nephrol Dial Transplant. 2011;26:1327–39.

    Article  CAS  Google Scholar 

  139. Urena-Torres PA, Floege J, Hawley CM, et al. Protocol adherence and the progression of cardiovascular calcification in the ADVANCE study. Nephrol Dial Transplant. 2013;28:146–52.

    Article  CAS  Google Scholar 

  140. EVOLVE Trial Investigators, Chertow GM, Block GA, Correa-Rotter R, Drüeke TB, Floege J, Goodman WG, Herzog CA, Kubo Y, London GM, Mahaffey KW, Mix TC, Moe SM, Trotman ML, Wheeler DC, Parfrey PS. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012;367:2482–94.

    Google Scholar 

  141. Wheeler DC, London GM, Parfrey PS, Block GA, Correa-Rotter R, Dehmel B, Drüeke TB, Floege J, Kubo Y, Mahaffey KW, Goodman WG, Moe SM, Trotman ML, Abdalla S, Chertow GM, Herzog CA; EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial Investigators. Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial. J Am Heart Assoc. 2014 Nov 17;3(6):e001363. Erratum in: J Am Heart Assoc. 2015 Jan;4(1):e000570.

    Google Scholar 

  142. Bellasi A, Cozzolino M, Russo D, et al. Cinacalcet but not vitamin D use modulates the survival benefit associated with sevelamer in the INDEPENDENT study. Clin Nephrol. 2016;86:113–24.

    Article  CAS  Google Scholar 

  143. Daniel WT, Weber C, Bailey JA, Raggi P, Sharma J. Prospective analysis of coronary calcium in patients on dialysis undergoing a near-total parathyroidectomy. Surgery. 2013;154:1315–21.

    Article  Google Scholar 

  144. Sharma J, Raggi P, Kutner N, Bailey J, Zhang R, Huang Y, Herzog CA, Weber C. Improved long-term survival of dialysis patients after near-total parathyroidectomy. J Am Coll Surg. 2012;214:400–7.

    Article  Google Scholar 

  145. Iwamoto N, Sato N, Nishida M, Hashimoto T, Kobayashi H, Yamasaki S, Ono T, Nishimura M, Tokoro T, Sakoda C, Murakawa M, Okino K, Okamoto Y, Imai R, Adachi N, Ninomiya K, Mabuchi H, Koyama M, Nakanouchi T, Iseki K. Total parathyroidectomy improves survival of hemodialysis patients with secondary hyperparathyroidism. J Nephrol. 2012;25:755–63.

    Article  CAS  Google Scholar 

  146. Iwamoto N, Sato N, Nishida M, Hashimoto T, Kobayashi H, Yamazaki S, Okino K, Nishimura M, Takatani T, Okamoto Y, Nakanouchi T, Koyama M, Adachi N, Ninomiya K, Mabuchi H, Iseki K. Low parathyroid hormone levels after parathyroidectomy reduce cardiovascular mortality in chronic hemodialysis patients. Clin Exp Nephrol. 2016;20:808–14.

    Article  CAS  Google Scholar 

  147. Apetrii M, Goldsmith D, Nistor I, Siriopol D, Voroneanu L, Scripcariu D, Vervloet M, Covic A. Impact of surgical parathyroidectomy on chronic kidney disease-mineral and bone disorder (CKD-MBD) – a systematic review and meta-analysis. PLoS One. 2017;12(11):e0187025.

    Article  Google Scholar 

  148. Shoback D. Clinical practice. Hypoparathyroidism. N Engl J Med. 2008;359:391–403.

    Article  CAS  Google Scholar 

  149. Harada K, Fujikawa T. Intracranial calcification due to hypoparathyroidism. Am J Med. 2018;131(6):e253–4.

    Article  Google Scholar 

  150. Goswami R, Sharma R, Sreenivas V, Gupta N, Ganapathy A, Das S. Prevalence and progression of basal ganglia calcification and its pathogenic mechanism in patients with idiopathic hypoparathyroidism. Clin Endocrinol. 2012;77:200–6.

    Article  CAS  Google Scholar 

  151. Mitchell DM, Regan S, Cooley MR, et al. Long-term follow-up of patients with hypoparathyroidism. J Clin Endocrinol Metab. 2012;97:4507–14.

    Article  CAS  Google Scholar 

  152. Agarwal P, Prakash M, Singhal M, Bhadada SK, Gupta Y, Khandelwal N. To assess vascular calcification in the patients of hypoparathyroidism using multidetector computed tomography scan. Indian J Endocrinol Metab. 2015;19:785–90.

    Article  CAS  Google Scholar 

  153. Tentori F, Wang M, Bieber BA, Karaboyas A, Li Y, Jacobson SH, Andreucci VE, Fukagawa M, Frimat L, Mendelssohn DC, Port FK, Pisoni RL, Robinson BM. Recent changes in therapeutic approaches and association with outcomes among patients with secondary hyperparathyroidism on chronic hemodialysis: the DOPPS study. Clin J Am Soc Nephrol. 2015;10:98–109.

    Article  CAS  Google Scholar 

  154. Merle E, Roth H, London GM, Jean G, Hannedouche T, Bouchet JL, Drüeke T, Fouque D, Daugas E. French Calcium and Phosphate Observatory Low parathyroid hormone status induced by high dialysate calcium is an independent risk factor for cardiovascular death in hemodialysis patients. Kidney Int. 2016;89:666–74.

    Article  CAS  Google Scholar 

  155. Galassi A, Spiegel DM, Bellasi A, Block GA, Raggi P. Accelerated vascular calcification and relative hypoparathyroidism in incident haemodialysis diabetic patients receiving calcium binders. Nephrol Dial Transplant. 2006;21:3215–22.

    Article  CAS  Google Scholar 

  156. Tagawa M, Hamano T, Sueta S, Ogata S, Saito Y. Higher dialysate calcium concentration is associated with incident myocardial infarction among diabetic patients with low bone turnover: a longitudinal study. Sci Rep. 2018;8:10060.

    Article  Google Scholar 

  157. Wada N, Jacobson LP, Cohen M, French A, Phair J, Muñoz A. Cause-specific life expectancies after 35 years of age for human immunodeficiency syndrome-infected and human immunodeficiency syndrome-negative individuals followed simultaneously in long-term cohort studies, 1984-2008. Am J Epidemiol. 2013;177:116–25.

    Article  Google Scholar 

  158. Van Sighem AI, Gras LAJ, Reiss P, Brinkman K, de Wolf F. Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals. AIDS. 2010;24:1527–35.

    Article  Google Scholar 

  159. Mocroft A, Reiss P, Gasiorowski J, Ledergerber B, Kowalska J, Chiesi A, Gatell J, Rakhmanova A, Johnson M, Kirk O, Lundgren J. Serious fatal and nonfatal non-AIDS-defining illnesses in Europe. J Acquir Immune Defic Syndr. 2010;55:262–70.

    Article  Google Scholar 

  160. Freiberg MS, Chang C-CH, Kuller LH, Skanderson M, Lowy E, Kraemer KL, Butt AA, Bidwell Goetz M, Leaf D, Oursler KA, Rimland D, Rodriguez Barradas M, Brown S, Gibert C, McGinnis K, Crothers K, Sico J, Crane H, Warner A, Gottlieb S, Gottdiener J, Tracy RP, Budoff M, Watson C, Armah KA, Doebler D, Bryant K, Justice AC. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013;173:614–22.

    Article  CAS  Google Scholar 

  161. Shahbaz S, Manicardi M, Guaraldi G, Raggi P. Cardiovascular disease in human immunodeficiency virus infected patients: a true or perceived risk? World J Cardiol. 2015;7:633–44.

    Article  Google Scholar 

  162. Savès M, Chêne G, Ducimetière P, Leport C, Le Moal G, Amouyel P, Arveiler D, Ruidavets J-B, Reynes J, Bingham A, Raffi F. Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population. Clin Infect Dis. 2003;37:292–8.

    Article  Google Scholar 

  163. Friis-Moller N, Reiss P, Sabin CA, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007;356:1723–35.3.

    Article  Google Scholar 

  164. Sabin CA, Worm SW, Weber R, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multicohort collaboration. Lancet. 2008;371:1417–26.

    Article  CAS  Google Scholar 

  165. Ryom L, Lundgren JD, El-Sadr W, et al. Cardiovascular disease and use of contemporary protease inhibitors: the D:A:D international prospective multicohort study. Lancet HIV. 2018;5:e291–300.

    Article  Google Scholar 

  166. Deeks SG, Lewin SR, Havlir DV. The end of AIDS: HIV infection as a chronic disease. Lancet. 2013;382:1525–33.

    Article  Google Scholar 

  167. Tawakol A, Lo J, Zanni MV, Marmarelis E, Ihenachor EJ, MacNabb M, Wai B, Hoffmann U, Abbara S, Grinspoon S. Increased arterial inflammation relates to high-risk coronary plaque morphology in HIV-infected patients. J Acquir Immune Defic Syndr. 2014;66:164–71.

    Article  CAS  Google Scholar 

  168. Subramanian S, Tawakol A, Burdo TH, Abbara S, Wei J, Vijayakumar J, Corsini E, Abdelbaky A, Zanni MV, Hoffmann U, Williams KC, Lo J, Grinspoon SK. Arterial inflammation in patients with HIV. JAMA. 2012;308:379–86.

    Article  CAS  Google Scholar 

  169. Raggi P, De Francesco D, Manicardi M, Zona S, Bellasi A, Stentarelli C, Carli F, Beghetto B, Mussini C, Malagoli A, et al. Prediction of hard cardiovascular events in HIV patients. J Antimicrob Chemother. 2016;71:3515–8.

    Article  CAS  Google Scholar 

  170. Hsue PY, Lo JC, Franklin A, Bolger AF, Martin JN, Deeks SG, Waters DD. Progression of atherosclerosis as assessed by carotid intima-media thickness in patients with HIV infection. Circulation. 2004;109:1603–8.

    Article  Google Scholar 

  171. Salmazo PS, Bazan SGZ, Shiraishi FG, Bazan R, Okoshi K, Hueb JC. Frequency of subclinical atherosclerosis in Brazilian HIV-infected patients. Arq Bras Cardiol. 2018 May;110(5):402–10.

    CAS  Google Scholar 

  172. Post WS, Budoff M, Kingsley L, Palella FJ, Witt MD, Li X, George RT, Brown TT, Jacobson LP. Associations between HIV infection and subclinical coronary atherosclerosis. Ann Intern Med. 2014;160:458–67.

    Article  Google Scholar 

  173. Guaraldi G, Zona S, Alexopoulos N, Orlando G, Carli F, Ligabue G, Fiocchi F, Lattanzi A, Rossi R, Modena MG, Esposito R, Palella F, Raggi P. Coronary aging in HIV-infected patients. Clin Infect Dis. 2009;49:1756–62.

    Article  Google Scholar 

  174. Bellasi A, Zona S, Orlando G, Carli F, Ligabue G, Rochira V, Santoro A, Mussini C, Guaraldi G, Raggi P. Inverse correlation between vascular calcification and bone mineral density in human immunodeficiency virus-infected patients. Calcif Tissue Int. 2013;93:413–8.

    Article  CAS  Google Scholar 

  175. Guaraldi G, Stentarelli C, Zona S, Orlando G, Carli F, Ligabue G, Lattanzi A, Zaccherini G, Rossi R, Modena MG, Alexopoulos N, Palella F, Raggi P. Lipodystrophy and anti-retroviral therapy as predictors of sub-clinical atherosclerosis in human immunodeficiency virus infected subjects. Atherosclerosis. 2010;208:222–7.

    Article  CAS  Google Scholar 

  176. Alexopoulos N, Katritsis D, Raggi P. Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis. Atherosclerosis. 2014;233:104–12.

    Article  CAS  Google Scholar 

  177. Lo J, Abbara S, Rocha-Filho JA, Shturman L, Wei J, Grinspoon SK. Increased epicardial adipose tissue volume in HIV-infected men and relationships to body composition and metabolic parameters. AIDS. 2010;24:2127–30.

    Article  CAS  Google Scholar 

  178. Guaraldi G, Scaglioni R, Zona S, Orlando G, Carli F, Ligabue G, Besutti G, Bagni P, Rossi R, Modena MG, Raggi P. Epicardial adipose tissue is an independent marker of cardiovascular risk in HIV-infected patients. AIDS. 2011;25:1199–205.

    Article  Google Scholar 

  179. Zona S, Raggi P, Bagni P, Orlando G, Carli F, Ligabue G, Scaglioni R, Rossi R, Modena MG, Guaraldi G. Parallel increase of subclinical atherosclerosis and epicardial adipose tissue in patients with HIV. Am Heart J. 2012;163:1024–30.

    Article  Google Scholar 

  180. Raggi P, Zona S, Scaglioni R, Stentarelli C, Ligabue G, Besutti G, Menozzi M, Santoro A, Malagoli A, Bellasi A, Guaraldi G. Epicardial adipose tissue and coronary artery calcium predict incident myocardial infarction and death in HIV-infected patients. J Cardiovasc Comput Tomogr. 2015;9:553–8.

    Article  Google Scholar 

  181. Guaraldi G, Zona S, Orlando G, Carli F, Ligabue G, Fiocchi F, Menozzi M, Rossi R, Modena MG, Raggi P. Human immunodeficiency virus infection is associated with accelerated atherosclerosis. J Antimicrob Chemother. 2011;66:1857–60.

    Article  CAS  Google Scholar 

  182. Guaraldi G, Zona S, Orlando G, Carli F, Ligabue G, Fiocchi F, Rossi R, Modena MG, Raggi P. Progression of coronary artery calcium in men affected by human immunodeficiency virus infection. Int J Cardiovasc Imaging. 2012;28:935–41.

    Article  Google Scholar 

  183. Blau M, Nagler W, Bender MA. Fluorine-18: a new isotope for bone scanning. J Nucl Med. 1962;3:332–4.

    CAS  Google Scholar 

  184. Lee JM, Bang JI, Koo BK, Hwang D, Park J, Zhang J, Yaliang T, Suh M, Paeng JC, Shiono Y, Kubo T, Akasaka T. Clinical relevance of (18)F-sodium fluoride positron-emission tomography in noninvasive identification of high-risk plaque in patients with coronary artery disease. Circ Cardiovasc Imaging. 2017;10:e006704.

    Article  Google Scholar 

  185. Joshi NV, Vesey AT, Williams MC, Shah AS, Calvert PA, Craighead FH, Yeoh SE, Wallace W, Salter D, Fletcher AM, van Beek EJ, Flapan AD, Uren NG, Behan MW, Cruden NL, Mills NL, Fox KA, Rudd JH, Dweck MR. Newby DE. 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet. 2014;383:705–13.

    Article  Google Scholar 

  186. Raggi P, Prandini N, Ligabue G, Braglia G, Esposito F, Milic J, Malagoli A, Scaglioni R, Besutti G, Beghetto B, Nardini G, Roncaglia E, Mussini C, Guaraldi G. Molecular imaging of vascular calcification with (18)f-sodium-fluoride in patients infected with human immunodeficiency virus. Int J Mol Sci. 2019;20(5).

    Google Scholar 

  187. Guaraldi G, Milic J, Prandini N, Ligabue G, Esposito F, Ciusa G, Malagoli A, Scaglioni R, Besutti G, Beghetto B, Nardini G, Roncaglia E, Mussini C, Raggi P. (18)Fluoride-based molecular imaging of coronary atherosclerosis in HIV infected patients. Atherosclerosis. 2020;297:127–35.

    Article  CAS  Google Scholar 

  188. Raggi P, Senior P, Shahbaz S, Kaul P, Hung R, Coulden R, Yeung R, Abele J. (18)F-sodium fluoride imaging of coronary atherosclerosis in ambulatory patients with diabetes mellitus. Arterioscler Thromb Vasc Biol. 2019;39:276–84.

    Article  CAS  Google Scholar 

  189. Zanni MV, Toribio M, Robbins GK, Burdo TH, Lu MT, Ishai AE, Feldpausch MN, Martin A, Melbourne K, Triant VA, Suchindran S, Lee H, Hoffmann U, Williams KC, Tawakol A, Grinspoon SK. Effects of antiretroviral therapy on immune function and arterial inflammation in treatment-naive patients with human immunodeficiency virus infection. JAMA Cardiol. 2016;1:474–80.

    Article  Google Scholar 

  190. Li Q, van de Wetering K, Uitto J. Pseudoxanthoma elasticum as a paradigm of heritable ectopic mineralization disorders: pathomechanisms and treatment development. Am J Pathol. 2019;189:216–25.

    Article  Google Scholar 

  191. Germain DP. Pseudoxanthoma elasticum. Orphanet J Rare Dis. 2017;12(1):85.

    Article  Google Scholar 

  192. Kranenburg G, de Jong PA, Mali WP, Attrach M, Visseren FL, Spiering W. Prevalence and severity of arterial calcifications in pseudoxanthoma elasticum (PXE) compared to hospital controls. Novel insights into the vascular phenotype of PXE. Atherosclerosis. 2017;256:7–14.

    Article  CAS  Google Scholar 

  193. Zhao J, Kingman J, Sundberg JP, Uitto J, Li Q. Plasma PPi deficiency is the major, but not the exclusive, cause of ectopic mineralization in an Abcc6(−/−) mouse model of PXE. J Invest Dermatol. 2017;137:2336–43.

    Article  CAS  Google Scholar 

  194. Moe SM, Reslerova M, Ketteler M, O’neill K, Duan D, Koczman J, Westenfeld R, Jahnen-Dechent W, Chen NX. Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD). Kidney Int. 2005;67:2295–304.

    Article  CAS  Google Scholar 

  195. Georgalas I, Tservakis I, Papaconstaninou D, Kardara M, Koutsandrea C, Ladas I. Pseudoxanthoma elasticum, ocular manifestations, complications and treatment. Clin Exp Optom. 2011;94:169–80.

    Article  Google Scholar 

  196. van den Berg JS, Hennekam RC, Cruysberg JR, Steijlen PM, Swart J, Tijmes N, Limburg M. Prevalence of symptomatic intracranial aneurysm and ischaemic stroke in pseudoxanthoma elasticum. Cerebrovasc Dis. 2000;10:315–9.

    Article  Google Scholar 

  197. Kauw F, Kranenburg G, Kappelle LJ, Hendrikse J, Koek HL, Visseren FLJ, Mali WPT, de Jong PA, Spiering W. Cerebral disease in a nationwide Dutch pseudoxanthoma elasticum cohort with a systematic review of the literature. J Neurol Sci. 2017;373:167–72.

    Article  Google Scholar 

  198. Trip MD, Smulders YM, Wegman JJ, Hu X, Boer JM, ten Brink JB, Zwinderman AH, Kastelein JJ, Feskens EJ, Bergen AA. Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease. Circulation. 2002;106:773–5.

    Article  CAS  Google Scholar 

  199. Mitchell GF. Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. J Appl Physiol (1985). 2008 Nov;105(5):1652–60.

    Google Scholar 

  200. Bartstra JW, de Jong PA, Spiering W. Accelerated peripheral vascular aging in pseudoxanthoma elasticum – proof of concept for arterial calcification-induced cardiovascular disease. Aging (Albany NY). 2019;11:1062–1064.

    Google Scholar 

  201. Kranenburg G, de Jong PA, Bartstra JW, Lagerweij SJ, Lam MG, Ossewaarde-van Norel J, Risseeuw S, van Leeuwen R, Imhof SM, Verhaar HJ, de Vries JJ, Slart RHJA, Luurtsema G, den Harder AM, Visseren FLJ, Mali WP, Spiering W. Etidronate for prevention of ectopic mineralization in patients with pseudoxanthoma elasticum. J Am Coll Cardiol. 2018;71:1117–26.

    Article  CAS  Google Scholar 

  202. Schantl AE, Ivarsson ME, Leroux JC. Investigational pharmacological treatments for vascular calcification. Adv Ther. 2018;2:1–16.

    Google Scholar 

  203. Schantl AE, Verhulst A, Neven E, Behets GJ, D’Haese PC, Maillard M, Mordasini D, Phan O, Burnier M, Spaggiari D, Decosterd LA, MacAskill MG, Alcaide-Corral CJ, Tavares AAS, Newby DE, Beindl VC, Maj R, Labarre A, Hegde C, Castagner B, Ivarsson ME, Leroux JC. Inhibition of vascular calcification by inositol phosphates derivatized with ethylene glycol oligomers. Nat Commun. 2020;11:721.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Raggi, P., Garg, R. (2022). Cardiovascular Calcification in Systemic Diseases. In: Henein, M. (eds) Cardiovascular Calcification. Springer, Cham. https://doi.org/10.1007/978-3-030-81515-8_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-81515-8_13

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-81514-1

  • Online ISBN: 978-3-030-81515-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics