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Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Review Article

Hyperparathyroidism and Peripheral Arterial Disease

Author(s): Pier Luigi Antignani*, Mateja K Jezovnik, Ales Blinc, Dimitri P. Mikhailidis, Panagiotis Anagnostis, Gerit-Holger Schernthaner, Mojca Jensterle, Katica Bajuk Studen, Miso Sabovic and Pavel Poredos

Volume 22, Issue 2, 2024

Published on: 25 January, 2024

Page: [88 - 94] Pages: 7

DOI: 10.2174/0115701611280905231227045826

Price: $65

Open Access Journals Promotions 2
Abstract

Primary hyperparathyroidism (PHPT) is presented in various forms, including classic PHPT, characterised by increased parathyroid hormone (PTH) secretion, normohormonal PHPT, and normocalcaemic PHPT. Secondary hyperparathyroidism is characterised by increased PTH secretion triggered by factors such as vitamin D deficiency and kidney failure. This review aims to discuss the involvement of hyperparathyroidism (HPT) in atherosclerosis, including peripheral arterial disease (PAD).

The increased level of PTH is involved in developing subclinical and overt vascular diseases, encompassing endothelial dysfunction, vascular stiffness, hypertension, and coronary and peripheral arterial diseases. It has been consistently associated with an augmented risk of cardiovascular morbidity and mortality, independent of classical risk factors for atherosclerosis. Chronic hypercalcemia associated with increased levels of PTH contributes to the development of calcification of vessel walls and atherosclerotic plaques. Vascular calcification can occur in the intima or media of the arterial wall and is associated with stiffness of peripheral arteries, which the formation of atherosclerotic plaques and narrowing of the vessel lumen can follow. For treating hyperparathyroidism, particularly SHPT, calcimimetics, novel phosphorus binders and novel vitamin D receptor activators are used. However, they are ineffective in severe PHPT. Therefore, parathyroidectomy remains the primary therapeutic option of PHPT.

Keywords: Parathyroid hormone, chronic hypercalcaemia, vascular calcifications, peripheral arterial disease, parathyroidectomy, hyperparathyroidism.

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[1]
Zhu CY, Sturgeon C, Yeh MW. Diagnosis and management of primary hyperparathyroidism. JAMA 2020; 323(12): 1186-7.
[http://dx.doi.org/10.1001/jama.2020.0538] [PMID: 32031566]
[2]
Dandurand K, Ali DS, Khan AA. Primary hyperparathyroidism: A narrative review of diagnosis and medical management. J Clin Med 2021; 10(8): 1604.
[http://dx.doi.org/10.3390/jcm10081604] [PMID: 33918966]
[3]
Silver J, Levi R. Regulation of PTH synthesis and secretion relevant to the management of secondary hyperparathyroidism in chronic kidney disease. Kidney Int 2005; 67(95): S8-S12.
[http://dx.doi.org/10.1111/j.1523-1755.2005.09501.x] [PMID: 15882315]
[4]
Kukora JS, Zeiger MA, Clark OH, et al. The american association of clinical endocrinologists and the american association of endocrine surgeons position statement on the diagnosis and management of primary hyperparathyroidism. Endocr Pract 2005; 11(1): 49-54.
[http://dx.doi.org/10.4158/EP.11.1.49] [PMID: 16033736]
[5]
Wilhelm SM, Wang TS, Ruan DT, et al. The american association of endocrine surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg 2016; 151(10): 959-68.
[http://dx.doi.org/10.1001/jamasurg.2016.2310] [PMID: 27532368]
[6]
Yeh MW, Ituarte PHG, Zhou HC, et al. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab 2013; 98(3): 1122-9.
[http://dx.doi.org/10.1210/jc.2012-4022] [PMID: 23418315]
[7]
Wang X, Duan Y, Beck T, Seeman E. Varying contributions of growth and ageing to racial and sex differences in femoral neck structure and strength in old age. Bone 2005; 36(6): 978-86.
[http://dx.doi.org/10.1016/j.bone.2004.11.015] [PMID: 15869919]
[8]
Cosman F, Nieves J, Horton J, Shen V, Lindsay R. Effects of estrogen on response to edetic acid infusion in postmenopausal osteoporotic women. J Clin Endocrinol Metab 1994; 78(4): 939-43.
[PMID: 8157725]
[9]
Heath H III, Hodgson SF, Kennedy MA. Primary Hyperparathyroidism. N Engl J Med 1980; 302(4): 189-93.
[http://dx.doi.org/10.1056/NEJM198001243020402] [PMID: 7350459]
[10]
Bilezikian JP, Khan AA, Silverberg SJ, et al. Evaluation and management of primary hyperparathyroidism: Summary statement and guidelines from the fifth international workshop. J Bone Miner Res 2022; 37(11): 2293-314.
[http://dx.doi.org/10.1002/jbmr.4677] [PMID: 36245251]
[11]
Verlinden L, Carmeliet G. Integrated view on the role of vitamin d actions on bone and growth plate homeostasis. JBMR Plus 2021; 5(12): e10577.
[http://dx.doi.org/10.1002/jbm4.10577] [PMID: 34950832]
[12]
Lofrese J, Basit H, Lappin S. Physiology, Parathyroid edited by. StatPearls Publishing 2023.
[13]
Habas E Sr, Eledrisi M, Khan F, Elzouki ANY. Secondary hyperparathyroidism in chronic kidney disease: Pathophysiology and management. Cureus 2021; 13(7): e16388.
[http://dx.doi.org/10.7759/cureus.16388] [PMID: 34408941]
[14]
Garcia de la Torre N, Wass J A H, Turner HE. Parathyroid adenomas and cardiovascular risk. Endocr Relat Cancer 2003; 10(2): 309-22.
[http://dx.doi.org/10.1677/erc.0.0100309] [PMID: 12790792]
[15]
Walker MD, Fleischer J, Rundek T, et al. Carotid vascular abnormalities in primary hyperparathyroidism. J Clin Endocrinol Metab 2009; 94(10): 3849-56.
[http://dx.doi.org/10.1210/jc.2009-1086] [PMID: 19755478]
[16]
Perkovic V, Hewitson TD, Kelynack KJ, Martic M, Tait MG, Becker GJ. Parathyroid hormone has a prosclerotic effect on vascular smooth muscle cells. Kidney Blood Press Res 2003; 26(1): 27-33.
[http://dx.doi.org/10.1159/000069761] [PMID: 12697974]
[17]
Goettsch C, Iwata H, Aikawa E. Parathyroid hormone. Arterioscler Thromb Vasc Biol 2014; 34(7): 1333-5.
[http://dx.doi.org/10.1161/ATVBAHA.114.303637] [PMID: 24951650]
[18]
Rashid G, Bernheim J, Green J, Benchetrit S. Parathyroid hormone stimulates endothelial expression of atherosclerotic parameters through protein kinase pathways. Am J Physiol Renal Physiol 2007; 292(4): F1215-8.
[http://dx.doi.org/10.1152/ajprenal.00406.2006] [PMID: 17190908]
[19]
Baczynski R, Massry SG, Kohan R, Magott M, Saglikes Y, Brautbar N. Effect of parathyroid hormone on myocardial energy metabolism in the rat. Kidney Int 1985; 27(5): 718-25.
[http://dx.doi.org/10.1038/ki.1985.71] [PMID: 3160882]
[20]
Jorde R, Saleh F, Figenschau Y, Kamycheva E, Haug E, Sundsfjord J. Serum parathyroid hormone (PTH) levels in smokers and non-smokers. The fifth Tromsø study. Eur J Endocrinol 2005; 152(1): 39-45.
[http://dx.doi.org/10.1530/eje.1.01816] [PMID: 15762185]
[21]
Kamycheva E, Sundsfjord J, Jorde R. Serum parathyroid hormone level is associated with body mass index. The 5th Tromso study. Eur J Endocrinol 2004; 151(2): 167-72.
[http://dx.doi.org/10.1530/eje.0.1510167] [PMID: 15296470]
[22]
Cheng SP, Liu CL, Liu TP, Hsu YC, Lee JJ. Association between parathyroid hormone levels and inflammatory markers among US adults. Mediators Inflamm 2014; 2014: 1-8.
[http://dx.doi.org/10.1155/2014/709024] [PMID: 24782595]
[23]
Emam AA, Mousa SG, Ahmed KY, Al-Azab AA. Inflammatory biomarkers in patients with asymptomatic primary hyperparathyroidism. Med Princ Pract 2012; 21(3): 249-53.
[http://dx.doi.org/10.1159/000334588] [PMID: 22179481]
[24]
Zemel MB. Calcium modulation of hypertension and obesity: Mechanisms and implications. J Am Coll Nutr 2001; 20(5 suppl): 428S-35S.
[http://dx.doi.org/10.1080/07315724.2001.10719180] [PMID: 11603653]
[25]
Hagström E, Hellman P, Larsson TE, et al. Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation 2009; 119(21): 2765-71.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.108.808733] [PMID: 19451355]
[26]
Ahlström T, Hagström E, Larsson A, Rudberg C, Lind L, Hellman P. Correlation between plasma calcium, parathyroid hormone (PTH) and the metabolic syndrome (MetS) in a community-based cohort of men and women. Clin Endocrinol 2009; 71(5): 673-8.
[http://dx.doi.org/10.1111/j.1365-2265.2009.03558.x] [PMID: 19250270]
[27]
Resnick L. The cellular ionic basis of hypertension and allied clinical conditions. Prog Cardiovasc Dis 1999; 42(1): 1-22.
[http://dx.doi.org/10.1016/S0033-0620(99)70006-X] [PMID: 10505490]
[28]
Baldi S, Natali A, Buzzigoli G, Quiñone Galvan A, Sironi AM, Ferrannini E. In vivo effect of insulin on intracellular calcium concentrations: Relation to insulin resistance. Metabolism 1996; 45(11): 1402-7.
[http://dx.doi.org/10.1016/S0026-0495(96)90122-5] [PMID: 8931646]
[29]
Anagnostis P, Lambrinoudaki I, Stevenson JC, Goulis DG. Menopause-associated risk of cardiovascular disease. Endocr Connect 2022; 11(4): 11.
[http://dx.doi.org/10.1530/EC-21-0537] [PMID: 35258483]
[30]
Stamatelopoulos K, Athanasouli F, Pappa T, et al. Hemodynamic markers and subclinical atherosclerosis in postmenopausal women with primary hyperparathyroidism. J Clin Endocrinol Metab 2014; 99(8): 2704-11.
[http://dx.doi.org/10.1210/jc.2013-4273] [PMID: 24840809]
[31]
Oh YS. Arterial stiffness and hypertension. Clin Hypertens 2018; 24(1): 17.
[http://dx.doi.org/10.1186/s40885-018-0102-8] [PMID: 30519485]
[32]
Safar ME, Asmar R, Benetos A, et al. Interaction between hypertension and arterial stiffness. Hypertension 2018; 72(4): 796-805.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.11212] [PMID: 30354723]
[33]
Rosa J, Raska I Jr, Wichterle D, et al. Pulse wave velocity in primary hyperparathyroidism and effect of surgical therapy. Hypertens Res 2011; 34(3): 296-300.
[http://dx.doi.org/10.1038/hr.2010.232] [PMID: 21107330]
[34]
Zandifar S, Mardanparvar H, Mohammadi S, Dehghan S. Hyperparathyroidism and vessel diseases. Journal of Parathyroid Disease 2023; 11: e11217-7.
[http://dx.doi.org/10.34172/jpd.2023.11217]
[35]
Lazarus JM, Lowrie EG, Hampers CL, Merrill JP. Cardiovascular disease in uremic patients on hemodialysis. Kidney Int Suppl 1975; (2): 167-75.
[PMID: 1099301]
[36]
Gosmanova EO, Chen K, Ketteler M, et al. Risk of cardiovascular conditions in patients with chronic hypoparathyroidism: A retrospective cohort study. Adv Ther 2021; 38(8): 4246-57.
[http://dx.doi.org/10.1007/s12325-021-01787-7] [PMID: 34165700]
[37]
Reid DG, Shanahan CM, Duer MJ, et al. Lipids in biocalcification: Contrasts and similarities between intimal and medial vascular calcification and bone by NMR. J Lipid Res 2012; 53(8): 1569-75.
[http://dx.doi.org/10.1194/jlr.M026088] [PMID: 22651923]
[38]
Wu M, Rementer C, Giachelli CM. Vascular calcification: An update on mechanisms and challenges in treatment. Calcif Tissue Int 2013; 93(4): 365-73.
[http://dx.doi.org/10.1007/s00223-013-9712-z] [PMID: 23456027]
[39]
Lanzer P, Boehm M, Sorribas V, et al. Medial vascular calcification revisited: Review and perspectives. Eur Heart J 2014; 35(23): 1515-25.
[http://dx.doi.org/10.1093/eurheartj/ehu163] [PMID: 24740885]
[40]
Atkinson J. Age-related medial elastocalcinosis in arteries: Mechanisms, animal models, and physiological consequences. J Appl Physiol 2008; 105(5): 1643-51.
[http://dx.doi.org/10.1152/japplphysiol.90476.2008] [PMID: 18772323]
[41]
Rocha-Singh KJ, Zeller T, Jaff MR. Peripheral arterial calcification: Prevalence, mechanism, detection, and clinical implications. Catheter Cardiovasc Interv 2014; 83(6): E212-20.
[http://dx.doi.org/10.1002/ccd.25387] [PMID: 24402839]
[42]
Wu M, Zhang JD, Tang RN, et al. Elevated PTH induces endothelial-to-chondrogenic transition in aortic endothelial cells. Am J Physiol Renal Physiol 2017; 312(3): F436-44.
[http://dx.doi.org/10.1152/ajprenal.00210.2016] [PMID: 27582099]
[43]
Neves KR, Graciolli FG, dos Reis LM, et al. Vascular calcification: Contribution of parathyroid hormone in renal failure. Kidney Int 2007; 71(12): 1262-70.
[http://dx.doi.org/10.1038/sj.ki.5002241] [PMID: 17410101]
[44]
Lee SA, Lee MJ, Ryu GW, et al. Low serum intact parathyroid hormone level is an independent risk factor for overall mortality and major adverse cardiac and cerebrovascular events in incident dialysis patients. Osteoporos Int 2016; 27(9): 2717-26.
[http://dx.doi.org/10.1007/s00198-016-3636-1] [PMID: 27216997]
[45]
Wanner C, Amann K, Shoji T. The heart and vascular system in dialysis. Lancet 2016; 388(10041): 276-84.
[http://dx.doi.org/10.1016/S0140-6736(16)30508-6] [PMID: 27226133]
[46]
Clemens TL, Cormier S, Eichinger A, et al. Parathyroid hormone related protein and its receptors: Nuclear functions and roles in the renal and cardiovascular systems, the placental trophoblasts and the pancreatic islets. Br J Pharmacol 2001; 134(6): 1113-36.
[http://dx.doi.org/10.1038/sj.bjp.0704378] [PMID: 11704631]
[47]
Shao JS, Cheng SL, Sadhu J, Towler DA. Inflammation and the osteogenic regulation of vascular calcification: A review and perspective. Hypertension 2010; 55(3): 579-92.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.134205] [PMID: 20101002]
[48]
Cheng ZY, Ye T, Ling QY, Wu T, Wu GY, Zong GJ. Parathyroid hormone promotes osteoblastic differentiation of endothelial cells via the extracellular signal-regulated protein kinase 1/2 and nuclear factorκB signaling pathways. Exp Ther Med 2018; 15(2): 1754-60.
[PMID: 29434762]
[49]
Chen NX, Moe SM. Vascular calcification: Pathophysiology and risk factors. Curr Hypertens Rep 2012; 14(3): 228-37.
[http://dx.doi.org/10.1007/s11906-012-0265-8] [PMID: 22476974]
[50]
Kang IS, Lee W, Choi BW, et al. Semiquantitative assessment of tibial artery calcification by computed tomography angiography and its ability to predict infrapopliteal angioplasty outcomes. J Vasc Surg 2016; 64(5): 1335-43.
[http://dx.doi.org/10.1016/j.jvs.2016.04.047] [PMID: 27432201]
[51]
Majcen M, Hocevar M. Surgical options in treating patients with primary hyperparathyroidism. Radiol Oncol 2020; 54(1): 22-32.
[http://dx.doi.org/10.2478/raon-2020-0010] [PMID: 32114525]
[52]
Stefenelli T, Mayr H, Bergler-Klein J, Globits S, Woloszczuk W, Niederle B. Primary hyperparathyroidism: Incidence of cardiac abnormalities and partial reversibility after successful parathyroidectomy. Am J Med 1993; 95(2): 197-202.
[http://dx.doi.org/10.1016/0002-9343(93)90260-V] [PMID: 8356983]
[53]
Pepe J, Cipriani C, Sonato C, Raimo O, Biamonte F, Minisola S. Cardiovascular manifestations of primary hyperparathyroidism: a narrative review. Eur J Endocrinol 2017; 177(6): R297-308.
[http://dx.doi.org/10.1530/EJE-17-0485] [PMID: 28864535]
[54]
Best CAE, Krishnan R, Malvankar-Mehta MS, MacNeil SD. Echocardiogram changes following parathyroidectomy for primary hyperparathyroidism. Medicine 2017; 96(43): e7255.
[http://dx.doi.org/10.1097/MD.0000000000007255] [PMID: 29068975]
[55]
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(1): 106-12.
[http://dx.doi.org/10.1210/jcem.82.1.3666] [PMID: 8989242]
[56]
Walker MD, Rundek T, Homma S, et al. Effect of parathyroidectomy on subclinical cardiovascular disease in mild primary hyperparathyroidism. Eur J Endocrinol 2012; 167(2): 277-85.
[http://dx.doi.org/10.1530/EJE-12-0124] [PMID: 22660025]
[57]
Bernardi S, Giudici F, Barbato V, Zanatta L, Grillo A, Fabris B. Meta-analysis on the effect of mild primary hyperparathyroidism and parathyroidectomy upon arterial stiffness. J Clin Endocrinol Metab 2021; 106(6): 1832-43.
[http://dx.doi.org/10.1210/clinem/dgab157] [PMID: 33693666]
[58]
Yavari M, Feizi A, Haghighatdoost F, Ghaffari A, Rezvanian H. The influence of parathyroidectomy on cardiometabolic risk factors in patients with primary hyperparathyroidism: A systematic review and meta-analysis. Endocrine 2021; 72(1): 72-85.
[http://dx.doi.org/10.1007/s12020-020-02519-7] [PMID: 33057988]
[59]
Seib CD, Meng T, Cisco RM, et al. Adverse cardiovascular outcomes among older adults with primary hyperparathyroidism treated with parathyroidectomy versus nonoperative management. Ann Surg 2023; 278(2): e302-8.
[http://dx.doi.org/10.1097/SLA.0000000000005691] [PMID: 36005546]
[60]
Drüeke TB, Massy ZA. Role of vitamin D in vascular calcification: Bad guy or good guy? Nephrol Dial Transplant 2012; 27(5): 1704-7.
[http://dx.doi.org/10.1093/ndt/gfs046] [PMID: 22431706]
[61]
Gluba-Brzózka A, Franczyk B , Ciałkowska-Rysz A , Olszewski R , Rysz J . Impact of vitamin D on the cardiovascular system in advanced chronic kidney disease (CKD) and dialysis patients. Nutrients 2018; 10(6): 709.
[http://dx.doi.org/10.3390/nu10060709] [PMID: 29865146]
[62]
Briese S, Wiesner S, Will JC, et al. Arterial and cardiac disease in young adults with childhood-onset end-stage renal disease—impact of calcium and vitamin D therapy. Nephrol Dial Transplant 2006; 21(7): 1906-14.
[http://dx.doi.org/10.1093/ndt/gfl098] [PMID: 16554325]
[63]
Hernandes FR, Goldenstein P, Custódio MR. Treatment of hyperparathyroidism (SHPT). J Bras Nefrol 2021; 43(4 Suppl. 1): 645-9.
[http://dx.doi.org/10.1590/2175-8239-jbn-2021-s107] [PMID: 34910799]
[64]
Wu CC, Chang JH, Chen CC, et al. Calcitriol treatment attenuates inflammation and oxidative stress in hemodialysis patients with secondary hyperparathyroidism. Tohoku J Exp Med 2011; 223(3): 153-9.
[http://dx.doi.org/10.1620/tjem.223.153] [PMID: 21350317]
[65]
Nana M, Morgan H, Shrikrishnapalasuriyar N, Kalhan A. Primary hyperparathyroidism: Comparing cardiovascular morbidity and mortality in patients treated with parathyroidectomy versus conservative management. J Endocrinol Metab 2019; 9(4): 95-107.
[http://dx.doi.org/10.14740/jem573]
[66]
Hsu YH, Yu HY, Chen HJ, Li TC, Hsu CC, Kao CH. The risk of peripheral arterial disease after parathyroidectomy in patients with end-stage renal disease. PLoS One 2016; 11(6): e0156863.
[http://dx.doi.org/10.1371/journal.pone.0156863] [PMID: 27284924]
[67]
Fahrleitner A, Dobnig H, Obernosterer A, et al. Vitamin D deficiency and secondary hyperparathyroidism are common complications in patients with peripheral arterial disease. J Gen Intern Med 2002; 17(9): 663-9.
[http://dx.doi.org/10.1046/j.1525-1497.2002.11033.x] [PMID: 12220361]
[68]
Poredoš P, Schernthaner GH, Blinc A, et al. Endocrine disorders and peripheral arterial disease: A series of reviews. Curr Vasc Pharmacol 2023; 21(3): 147-8.
[http://dx.doi.org/10.2174/1570161121666230516141319] [PMID: 37194233]

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