Primer hiperparatiroidizmle ilişkili hiperkalsemide yaştan bağımsız olarak hipertansiyon ve koroner arter hastalığı sıklığında artış

Abstract

Giriş ve amaç: Primer hiperparatiroidi (PHP)'li hastalarda koroner arter hastalığı (KAH) sıklığında artış olup olmadığı ile ilgili literatürde çelişkili veriler bulunmaktadır. Bu çalışmada PHP'li hastalarda KAH ve hipertansiyon (HT) sıklığının araştırılması planlanmıştır. Material ve metod: Hasta grubu olarak endokrinoloji kliniğine Eylül 2020-Şubat 2023 tarihleri arasında başvuran 18 yaş ve üzeri PHP'li hastalar, kontrol grubu olarak aynı tarihler arasında yaş ve cinsiyet uyumlu tiroid nodülü nedeniyle başvuran bireyler alınmıştır. Çalışmaya uygun PHP'li 114, kontrol grubu olarak da 103 olmak üzere toplamda 217 hasta tespit edildi. Çalışma retrospektif data incelemesi şeklinde yapılmış olup hastaların ve kontrol grubunun laboratuvar ve demografik bilgileri dosyalarından elde edilmiştir. Sonuçlar: Hasta grubu ile kontrol grubunun yaş ve cinsiyet dağılımı benzer idi (sırasıyla; yaş 55.6+12.9 yıl, 53.0+7.2 yıl, p=0.058, kadın/erkek dağlımı; 93/21, 80/23 p=0.48). HT ve KAH sıklığı hasta grubunda daha yüksek iken (sırasıyla; HT; %65.1, %31.0, p<0.001, KAH; %32.0, %3.1, p<0.001), DM sıklığı ise benzerdi (sırasıyla; %18.1, %17.3, p=0.89). Hafif ve şiddetli PHP'si olanlar arasında HT, KAH ve DM sıklıklarının aynı olduğu tespit edildi (sırasıyla; HT; %65.6%, 64.4, p=0.90, KAH; %38.3, %23.3, p=0.14, DM; %19.7, %15.9, p=0.62). KAH üzerine etkili faktörler incelendiğinde yaş (β=0.10, ods oranı [OR];1.11 [%95 güven aralığı (%95GA);1.05-1.17], p<0.001) ve kalsiyum (β=0.67, OR;1.96 [%95 GA;1.10-3.51], p=0.023) düzeylerinin bağımsız etkili faktörler olduğu saptandı. Tartışma: PHP'de artmış kalsiyum düzeyleri yaştan bağımsız KAH için risk oluşturmaktadır. Ayrıca kalsiyum yüksekliği KAH risk faktörü olan HT sıklığını artırmaktadır.

Keywords

• Primer hiperparatiroidi
• hipertansiyon
• koroner arter hastalığı
• hiperkalsemi

Increased frequency of hypertension and coronary artery disease independent of age in primary hyperparathyroidism associated hypercalcaemia

Abstract

Aims: There are conflicting data in the literature regarding whether there is an increased frequency of coronary artery disease (CAD) in patients with primary hyperparathyroidism (PHP). In this study, we planned to investigate the frequency of CAD and hypertension (HT) in patients with PHP. Methods: Patients with PHP aged 18 years and older who were admitted to the endocrinology clinic between September 2020 and February 2023 were included as the patient group, and age- and gender-matched individuals who presented with thyroid nodules between the same dates were included as the control group. A total of 217 patients, 114 with PHP and 103 as control group, were eligible for the study. The study was conducted as a retrospective data analysis and laboratory and demographic information of the patients and the control group were obtained from their files. Results: Age and gender distribution of the patient group and the control group were similar (respectively; age: 55.6+12.9 years, 53.0+7.2 years, p=0.058, female/male distribution: 93/21, 80/23 p=0.48). The prevalence of HT and CAD was higher in the patient group (respectively; HT: 65.1%, 31.0%, p<0.001, CAD: 32.0%, 3.1%, p<0.001), while the prevalence of DM was similar (respectively; 18.1%, 17.3%, p=0.89). The prevalence of HT, CAD and DM was found to be the same among those with mild and severe PHP (respectively; HT: 65.6%, 64.4%, p=0.90, CAD: 38.3%, 23.3%, p=0.14, DM: 19.7%, 15.9%, p=0.62, ). Age (β=0.10, odds ratio [OR];1.11 [95% confidence interval (95% CI);1.05-1.17], p<0.001) and calcium (β=0.67, OR;1.96 [95% CI;1.10-3.51], p=0.023) levels were found to be independent effective factors on CAD. Conclusion: Increased calcium levels in PHP constitute an age-independent risk for CAD. In addition, elevated calcium increases the frequency of HT, which is a CAD risk factor.

Keywords

• Primary hyperparathyroidism
• hypertension
• coronary artery disease
• hypercalcaemia.

References

1. Gopinath P, Mihai R. Hyperparathyroidism. Surgery. 2011; 29:451e8.
2. Bilezikian JP, Brandi ML, Eastell R, et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3561-9. doi:10.1210/jc.2014-1413.
3. Applewhite MK, Schneider DF. Mild primary hyperparathyroidism: a literature review. Oncol. 2014;19(9): 919e29.
4. Bilezikian JP. Primary Hyperparathyroidism. J Clin Endocrinol Metab. 2018;103(11):3993-4004. doi:10.1210/jc.2018-01225.
5. Rosenberg J, Pines M, Hurwitz S. Response of adrenal cells to parathyroid hormone stimulation. J Endocrinol. 1987;112:431–437.
6. Hanley NA, Wester RM, Carr BR, Rainey WE. Parathyroid hormone and parathyroid hormone-related peptide stimulate aldosterone production in the human adrenocortical cell line, NCI-H295. Endocrine J. 1993;1:447–450.
7. Mazzocchi G, Aragona F, Malendowicz LK, Nussdorfer GG. PTH and PTH-related peptide enhance steroid secretion from human adrenocortical cells. Am J Physiol Endocrinol Metab. 2001;280:E209–E213.
8. Vestergaard P, Mosekilde L. Cohort study on effects of parathyroid surgery on multiple outcomes in primary hyperparathyroidism. BMJ. 2003;327:530-534.

9. 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-R308. doi:10.1530/EJE-17-0485.
10. Nelson JA, Alsayed M, Milas M. The role of parathyroidectomy in treating hypertension and other cardiac manifestations of primary hyperparathyroidism. Gland Surg. 2020;9(1):136-141. doi:10.21037/gs.2019.12.12.
11. Maniero C, Fassina A, Seccia TM, et al. Mild hyperparathyroidism:a novel surgically correctable feature of primary aldosteronism. J Hypertens. 2012;30(2):390-5. doi:10.1097/HJH.0b013e32834f0451.
12. Kalla A, Krishnamoorthy P, Gopalakrishnan A, Garg J, Patel NC, Figueredo VM. Primary hyperparathyroidism predicts hypertension:Results from the National Inpatient Sample. Int J Cardiol. 2017;227:335-337. doi:10.1016/j.ijcard.2016.11.080.
13. Kepez A, Harmanci A, Hazirolan T, et al. Evaluation of subclinical coronary atherosclerosis in mild asymptomatic primary hyperparathyroidism patients. Int J Cardiovasc Imaging. 2009 Feb;25(2):187-93. doi:10.1007/s10554-008-9369-2.
14. Bilezikian JP. Primary hyperparathyroidism. In: DeGroot L, ed. www.ENDOTEXT.org (version of. 2017); Singer F, Section Editor. South Dartmouth, MA:MDTEXT.COM, Inc.;2017.
15. Satman I, Omer B, Tutuncu Y, et al. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults. Eur J Epidemiol. 2013;28(2):169-80. doi:10.1007/s10654-013-9771-5.
16. 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-R308. doi:10.1530/EJE-17-0485.
17. Luigi P, Chiara FM, Laura Z, et al. Arterial hypertension, metabolic syndrome and subclinical cardiovascular organ damage in patients with asymptomatic primary hyperparathyroidism before and after parathyroidectomy: preliminary results. Int J Endocrinol. 2012;2012:408295. doi:10.1155/2012/408295.
18. Brunaud L, Germain A, Zarnegar R, et al. Serum aldosterone is correlated positively to parathyroid hormone (PTH) levels in patients with primary hyperparathyroidism. Surgery. 2009;146(6):1035-41. doi:10.1016/j.surg.2009.09.041.
19. Gennari C, Nami R, Gonnelli S. Hypertension and primary hyperparathyroidism: the role of adrenergic and renin– angiotensin–aldosterone systems. Miner Electrolyte Metab. 1995;21:77–81.
20. Heyliger A, Tangpricha V, Weber C, Sharma J. Parathyroidectomy decreases systolic and diastolic blood pressure in hypertensive patients with primary hyperparathyroidism. Surgery. 2009;146(6):1042-1047. doi:10.1016/j.surg.2009.09.024.
21. Graff-Baker AN, Bridges LT, Chen Q, Faries MB, Said M. Parathyroidectomy for patients with primary hyperparathyroidism and associations with hypertension. JAMA Surg. 2020;155(1):32-39. doi:10.1001/jamasurg.2019.3950.
22. Beysel S, Caliskan M, Kizilgul M, et al. Parathyroidectomy improves cardiovascular risk factors in normocalcemic and hypercalcemic primary hyperparathyroidism. BMC Cardiovasc Disord. 2019;19(1):106. doi:10.1186/s12872-019-1093-4.
23. Kosch M, Hausberg M, Vormbrock K, et al. Impaired flow-mediated vasodilation of the brachial artery in patients with primary hyperparathyroidism improves after parathyroidectomy. Cardiovasc Res. 2000;47:813– 818.
24. Vestergaard P, Mollerup CL, Frøkjaer VG, Christiansen P, Blichert-Toft M, Mosekilde L. Cardiovascular events before and after surgery for primary hyperparathyroidism. World J Surg. 2003;27(2):216-22. doi:10.1007/s00268-002-6541-z.
25. Andersson P, Rydberg E, Willenheimer R. Primary hyperparathyroidism and heart disease—a review. Eur Heart J. 2004;25:1776-1787.
26. Fitzpatrick LA, Bilezikian JP & Silverberg SJ. Parathyroid hormone and the cardiovascular system. Curr Osteoporos Rep. 2008;6:77-83.
27. Lundgren E, Lind L, Palmér M, Jakobsson S, Ljunghall S, Rastad J. Increased cardiovascular mortality and normalized serum calcium in patients with mild hypercalcemia followed up for 25 years. Surgery. 2001;130(6):978-85. doi:10.1067/msy.2001.118377.
28. Yakar B, Onalan E, Pirincci E, Kaya MO, Demir M. The effects of secondary hyperparathyroidism on circadian blood pressure in hemodialysis patients. J Coll Physicians Surg Pak. 2021 Nov;31(11):1325-1330. doi:10.29271/jcpsp.2021.11.1325.
29. Wang M, Wen D, Zhang W, et al. Effects of cinacalcet and parathyroidectomy on blood pressure in maintenance hemodialysis patients with secondary hyperparathyroidism. Iran J Kidney Dis. 2022;16(2):135-146.