Abstract
Introduction
Over 8% of adults in the United States are estimated to have moderate (stages 3 and 4) chronic kidney disease (CKD), which is increasingly recognized as one of the independent predictors for cardiovascular (CV) disease and related mortality. Secondary hyperparathyroidism with elevated serum intact parathyroid hormone (iPTH) is associated with increased CV mortality in end-stage renal disease and this relationship is unclear in moderate CKD.
Methods
Medical records of 196 patients at Harry S. Truman Memorial Veterans Hospital with stages 3 and 4 CKD (glomerular filtration rate, GFR 16–59 ml/min/1.73 m2) who had iPTH levels determined from 4/2006 to 9/2007 were reviewed. CV event was defined as occurrence of any of the following during follow-up: myocardial infarction, stroke, coronary/carotid/peripheral artery revascularization, and death due to CV reasons.
Results
During median follow-up of 27.2 months, 48 patients had CV events, while 148 patients did not. iPTH was elevated (156.43 ± 107.49) for patients who had CV events compared with those without (109.12 ± 86.54, P = 0.003). Among the covariates studied in the multivariate analysis including history of vascular disease, 25-OH Vit D, corrected calcium, phosphorus levels, calcium–phosphorus product, and GFR, iPTH level was found to have a positive association with CV events during follow-up period (odds ratio = 1.3 for 50 pg/ml change in iPTH, 95% CI: 1.03–1.55, P = 0.02)). Cardiovascular disease history was the only other significant variable with estimated odds ratio of 5.9 (P = 0.002).
Conclusion
iPTH level in patients with stages 3 and 4 CKD is associated with increased incidence of cardiovascular events independent of calcium–phosphorous level.
Similar content being viewed by others
References
Coresh J et al (2007) Prevalence of chronic kidney disease in the United States. JAMA 298(17):2038–2047
Sarnak MJ et al (2003) Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American heart association councils on kidney in cardiovascular disease, high blood pressure research, clinical cardiology, and epidemiology and prevention. Hypertension 42(5):1050–1065
Daly C (2007) Is early chronic kidney disease an important risk factor for cardiovascular disease? A background paper prepared for the UK consensus conference on early chronic kidney disease. Nephrol Dial Transplant 22(Suppl 9): ix19–ix25
Kimata N et al (2007) Association of mineral metabolism factors with all-cause and cardiovascular mortality in hemodialysis patients: the Japan dialysis outcomes and practice patterns study. Hemodial Int 11(3):340–348
Marco MP et al. (2003) Higher impact of mineral metabolism on cardiovascular mortality in a European hemodialysis population. Kidney Int Suppl(85):S111–S114
Young EW et al (2005) Predictors and consequences of altered mineral metabolism: the dialysis outcomes and practice patterns study. Kidney Int 67(3):1179–1187
Kovesdy CP et al (2008) Secondary hyperparathyroidism is associated with higher mortality in men with moderate to severe chronic kidney disease. Kidney Int 73(11):1296–1302
De Boer IH et al (2002) The severity of secondary hyperparathyroidism in chronic renal insufficiency is GFR-dependent, race-dependent, and associated with cardiovascular disease. J Am Soc Nephrol 13(11):2762–2769
Bhuriya R et al (2009) Plasma parathyroid hormone level and prevalent cardiovascular disease in CKD stages 3 and 4: an analysis from the kidney early evaluation program (KEEP). Am J Kidney Dis 53(4 Suppl 4):S3–S10
Kamycheva E, Sundsfjord J, Jorde R (2004) Serum parathyroid hormone levels predict coronary heart disease: the Tromso study. Eur J Cardiovasc Prev Rehabil 11(1):69–74
Hagstrom E et al (2009) Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation 119(21):2765–2771
Pilz S, Tomaschitz A, Drechsler C et al (2010) Parathyroid hormone level is associated with mortality and cardiovascular events in patients undergoing coronary angiography. Eur Heart J 31(13):1591–1598 Epub 2010 May 2
Llach F (1995) Secondary hyperparathyroidism in renal failure: the trade-off hypothesis revisited. Am J Kidney Dis 25(5):663–679
Schumock GT et al (2009) Association of secondary hyperparathyroidism with CKD progression, health care costs and survival in diabetic predialysis CKD patients. Nephron Clin Pract 113(1):c54–c61
Jassal SK, Chonchol M, Mühlen DV et al (2010) Vitamin D, parathyroid hormone, and cardiovascular mortality in older adults: the Rancho Bernardo study. Am J Med 123(12):1114–1120
Slinin Y, Foley RN, Collins AJ (2005) Calcium, phosphorus, parathyroid hormone, and cardiovascular disease in hemodialysis patients: the USRDS waves 1, 3, and 4 study. J Am Soc Nephrol 16:1788–1793
Covic A et al (2009) Systematic review of the evidence underlying the association between mineral metabolism disturbances and risk of all-cause mortality, cardiovascular mortality and cardiovascular events in chronic kidney disease. Nephrol Dial Transplant 24(5):1506–1523
Usdin TB et al (1996) Distribution of parathyroid hormone-2 receptor messenger ribonucleic acid in rat. Endocrinology 137(10):4285–4297
Smogorzewski M (1995) PTH, chronic renal failure and myocardium. Miner Electrolyte Metab 21(1–3):55–62
Ogino K, Burkhoff D, Bilezikian JP (1995) The hemodynamic basis for the cardiac effects of parathyroid hormone (PTH) and PTH-related protein. Endocrinology 136(7):3024–3030
Schluter KD, Piper HM (1992) Trophic effects of catecholamines and parathyroid hormone on adult ventricular cardiomyocytes. Am J Physiol 263(6 Pt 2):H1739–H1746
Amann K et al (1994) A role of parathyroid hormone for the activation of cardiac fibroblasts in uremia. J Am Soc Nephrol 4(10):1814–1819
Schleiffer R, Pernot F, Jones R (1995) Endothelium is a target organ of parathyroid secretions in genetic hypertensive rats. Horm Metab Res 27(1):16–18
Noda M et al (1997) Increased expression of parathyroid hormone-related peptide gene in blood vessels of spontaneously hypertensive rats. Hypertension 30(5):1284–1288
Ejerblad S, Eriksson I, Johansson H (1979) Uraemic arterial disease. An experimental study with special reference to the effect of parathyroidectomy. Scand J Urol Nephrol 13(2):161–169
Neves KR et al (2007) Vascular calcification: contribution of parathyroid hormone in renal failure. Kidney Int 71(12):1262–1270
Rashid G et al (2007) Parathyroid hormone stimulates endothelial expression of atherosclerotic parameters through protein kinase pathways. Am J Physiol Renal Physiol 292(4):F1215–F1218
Perkovic V et al (2003) Parathyroid hormone has a prosclerotic effect on vascular smooth muscle cells. Kidney Blood Press Res 26(1):27–33
Saleh FN et al (2003) Parathyroid hormone and left ventricular hypertrophy. Eur Heart J 24(22):2054–2060
Harnett JD et al (1988) Left ventricular hypertrophy in end-stage renal disease. Nephron 48(2):107–115
Piovesan A et al (1999) Left ventricular hypertrophy in primary hyperparathyroidism. Effects of successful parathyroidectomy. Clin Endocrinol (Oxf) 50(3):321–328
Hara S et al (1995) Relation between parathyroid hormone and cardiac function in long-term hemodialysis patients. Miner Electrolyte Metab 21(1–3):72–76
Park CW et al (1999) Intravenous calcitriol regresses myocardial hypertrophy in hemodialysis patients with secondary hyperparathyroidism. Am J Kidney Dis 33(1):73–81
Akmal M et al (1985) Role of parathyroid hormone in the glucose intolerance of chronic renal failure. J Clin Invest 75(3):1037–1044
Fadda GZ et al (1991) On the mechanism of impaired insulin secretion in chronic renal failure. J Clin Invest 87(1):255–261
Ogard CG et al (2005) Increased plasma N-terminal pro-B-type natriuretic peptide and markers of inflammation related to atherosclerosis in patients with primary hyperparathyroidism. Clin Endocrinol (Oxf) 63(5):493–498
Delfini E et al (2007) Circulating leptin and adiponectin levels in patients with primary hyperparathyroidism. Metabolism 56(1):30–36
Acknowledgments
VISN 15 Veterans Administration Research award to A Chockalingam.
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lishmanov, A., Dorairajan, S., Pak, Y. et al. Elevated serum parathyroid hormone is a cardiovascular risk factor in moderate chronic kidney disease. Int Urol Nephrol 44, 541–547 (2012). https://doi.org/10.1007/s11255-010-9897-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11255-010-9897-2