Top

European Journal of Nutrition

Published in:

01-10-2018 | Original Contribution

Associations between serum calcium, phosphorus and mortality among patients with coronary heart disease

Authors: Qian Chen, Yuan Zhang, Ding Ding, Dan Li, Yunou Yang, Qing Li, Xuechen Chen, Gang Hu, Wenhua Ling

Published in: European Journal of Nutrition | Issue 7/2018

Abstract

Purpose

Serum calcium and phosphorus abnormalities are associated with cardiovascular disorders in general population, but evidence among patients with established coronary heart disease (CHD) is limited and controversial. This study aimed to investigate the associations of baseline serum calcium and phosphorus levels with long-term mortality risk among patients with CHD.

Methods

We conducted a prospective cohort study among 3187 patients with CHD from October 2008 and December 2011 in China. Cox proportional hazards model was used to assess the associations of serum calcium and phosphorus at baseline with the risk of death.

Results

During follow-up (mean, 4.9 years), 295 patients died, 193 of which resulted from cardiovascular causes. Multivariable-adjusted hazard ratios (HR) for each 1 mmol/L increase in serum calcium at baseline were 0.27 (95% confidence interval (CI) 0.14–0.51) for all-cause mortality and 0.26 (95% CI 0.12–0.54) for cardiovascular mortality. Patients in the highest compared to the lowest quartile of serum calcium were at lower risk of all-cause mortality (HR, 95% CI 0.57, 0.40–0.82) and cardiovascular mortality (0.50, 0.32–0.79) (both P _trend < 0.001). This inverse association between serum calcium and the risk of mortality did not change when participants were stratified by sex, age groups, level of overweight, types of CHD, and history of diabetes. We also observed a graded positive association between baseline serum phosphorus and the risks of mortality.

Conclusions

The present study is the first to report that lower serum calcium at baseline is associated with an increased risk of all-cause and cardiovascular mortality in a Chinese coronary heart disease cohort. Further studies are required to investigate the causal relationship and actual mechanisms.

World Health Organization (2014) Global status report on noncommunicable diseases 2014

Ford ES, Ajani UA, Croft JB, Critchley JA, Labarthe DR, Kottke TE, Giles WH, Capewell S (2007) Explaining the decrease in U.S. deaths from coronary disease, 1980–2000. N Engl J Med 356(23):2388–2398. doi:10.1056/NEJMsa053935 CrossRefPubMed

Critchley J, Liu J, Zhao D, Wei W, Capewell S (2004) Explaining the increase in coronary heart disease mortality in Beijing between 1984 and 1999. Circulation 110(10):1236–1244CrossRef

Giachelli CM (2004) Vascular calcification mechanisms. J Am Soc Nephrol 15(12):2959–2964. doi:10.1097/01.ASN.0000145894.57533.C4 CrossRefPubMed

Martin M, Valls J, Betriu A, Fernandez E, Valdivielso JM (2015) Association of serum phosphorus with subclinical atherosclerosis in chronic kidney disease. Sex makes a difference. Atherosclerosis 241(1):264–270. doi:10.1016/j.atherosclerosis.2015.02.048 CrossRefPubMed

Ruan L, Chen W, Srinivasan SR, Xu J, Toprak A, Berenson GS (2010) Relation of serum phosphorus levels to carotid intima–media thickness in asymptomatic young adults (from the Bogalusa Heart Study). Am J Cardiol 106(6):793–797CrossRef

Sabanayagam C, Shankar A (2011) Serum calcium levels and hypertension among U.S. adults. J Clin Hypertens (Greenwich) 13(10):716–721. doi:10.1111/j.1751-7176.2011.00503.x CrossRef

Ix JH, De Boer IH, Peralta CA, Adeney KL, Duprez DA, Jenny NS, Siscovick DS, Kestenbaum BR (2009) Serum phosphorus concentrations and arterial stiffness among individuals with normal kidney function to moderate kidney disease in MESA. Clin J Am Soc Nephrol 4(3):609–615. doi:10.2215/cjn.04100808 CrossRefPubMedPubMedCentral

Schwarz S, Trivedi BK, Kalantar-Zadeh K, Kovesdy CP (2006) Association of disorders in mineral metabolism with progression of chronic kidney disease. Clin J Am Soc Nephrol 1(4):825–831. doi:10.2215/CJN.02101205 CrossRefPubMed

10.

Larsson TE, Olauson H, Hagstrom E, Ingelsson E, Arnlov J, Lind L, Sundstrom J (2010) Conjoint effects of serum calcium and phosphate on risk of total, cardiovascular, and noncardiovascular mortality in the community. Arterioscler Thromb Vasc Biol 30(2):333–339. doi:10.1161/ATVBAHA.109.196675 CrossRefPubMed

11.

Yoo KD, Kang S, Choi Y, Yang SH, Heo NJ, Chin HJ, Oh KH, Joo KW, Kim YS, Lee H (2016) Sex, age, and the association of serum phosphorus with all-cause mortality in adults with normal kidney function. Am J Kidney Dis 67(1):79–88. doi:10.1053/j.ajkd.2015.06.027 CrossRefPubMed

12.

Wang Y, Ma H, Hao X, Yang J, Chen Q, Lu L, Zhang R (2016) Low serum calcium is associated with left ventricular systolic dysfunction in a Chinese population with coronary artery disease. Sci Rep 6:22283. doi:10.1038/srep22283 CrossRefPubMedPubMedCentral

13.

Ding D, Qiu J, Li X, Li D, Xia M, Li Z, Su D, Wang Y, Zhang Y, Zhang J, Lv X, Xiao Y, Hu G, Ling W (2014) Hyperglycemia and mortality among patients with coronary artery disease. Diabetes Care 37(2):546–554. doi:10.2337/dc13-1387 CrossRefPubMed

14.

Chen Q, Zhang Y, Ding D, Li D, Xia M, Li X, Yang Y, Li Q, Hu G, Ling W (2016) Metabolic syndrome and its individual components with mortality among patients with coronary heart disease. Int J Cardiol 224:8–14. doi:10.1016/j.ijcard.2016.08.324 CrossRefPubMed

15.

Gibbons RJ, Chatterjee K, Daley J, Douglas JS, Fihn SD, Gardin JM, Grunwald MA, Levy D, Lytle BW, O’Rourke RA, Schafer WP, Williams SV (1999) ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: executive summary and recommendations. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Chronic Stable Angina). Circulation 99(21):2829–2848CrossRef

16.

Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, Pepine CJ, Schaeffer JW, Smith EE 3rd, Steward DE, Theroux P, Gibbons RJ, Alpert JS, Eagle KA, Faxon DP, Fuster V, Gardner TJ, Gregoratos G, Russell RO, Smith SC Jr (2000) ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: executive summary and recommendations. A report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee on the management of patients with unstable angina). Circulation 102(10):1193–1209CrossRef

17.

WHO Monica Project Principal Investigators (1988) The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease): a major international collaboration. J Clin Epidemiol 41(2):105–114CrossRef

18.

Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F (2006) Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145(4):247–254CrossRef

19.

Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, Young EW, Akizawa T, Akiba T, Pisoni RL, Robinson BM, Port FK (2008) Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 52(3):519–530. doi:10.1053/j.ajkd.2008.03.020 CrossRefPubMed

20.

Palmer SC, Hayen A, Macaskill P, Pellegrini F, Craig JC, Elder GJ, Strippoli GF (2011) Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis. JAMA 305(11):1119–1127. doi:10.1001/jama.2011.308 CrossRefPubMed

21.

Cherry RA, Bradburn E, Carney DE, Shaffer ML, Gabbay RA, Cooney RN (2006) Do early ionized calcium levels really matter in trauma patients? J Trauma 61(4):774–779. doi:10.1097/01.ta.0000239516.49799.63 CrossRefPubMed

22.

Sauter TC, Lindner G, Ahmad SS, Leichtle AB, Fiedler GM, Exadaktylos AK, Haider DG (2015) Calcium disorders in the emergency department: independent risk factors for mortality. PLoS One 10(7):e0132788. doi:10.1371/journal.pone.0132788 CrossRefPubMedPubMedCentral

23.

Miller JE, Kovesdy CP, Norris KC, Mehrotra R, Nissenson AR, Kopple JD, Kalantar-Zadeh K (2010) Association of cumulatively low or high serum calcium levels with mortality in long-term hemodialysis patients. Am J Nephrol 32(5):403–413. doi:10.1159/000319861 CrossRefPubMedPubMedCentral

24.

Narang R, Ridout D, Nonis C, Kooner JS (1997) Serum calcium, phosphorus and albumin levels in relation to the angiographic severity of coronary artery disease. Int J Cardiol 60(1):73–79CrossRef

25.

Lim LM, Kuo HT, Kuo MC, Chiu YW, Lee JJ, Hwang SJ, Tsai JC, Hung CC, Chen HC (2014) Low serum calcium is associated with poor renal outcomes in chronic kidney disease stages 3–4 patients. BMC Nephrol 15:183. doi:10.1186/1471-2369-15-183 CrossRefPubMedPubMedCentral

26.

Ising H, Gunther T, Bertschat F, Ibe K, Stoboy V, Heldman E (1987) Alterations of electrolytes in serum and erythrocytes after myocardial infarction. Magnesium 6(4):192–200PubMed

27.

Varga-Szabo D, Braun A, Nieswandt B (2009) Calcium signaling in platelets. J Thromb Haemost 7(7):1057–1066. doi:10.1111/j.1538-7836.2009.03455.x CrossRefPubMed

28.

Tantry US, Bliden KP, Suarez TA, Kreutz RP, Dichiara J, Gurbel PA (2010) Hypercoagulability, platelet function, inflammation and coronary artery disease acuity: results of the Thrombotic RIsk Progression (TRIP) study. Platelets 21(5):360–367. doi:10.3109/09537100903548903 CrossRefPubMed

29.

Bilezikian JP, Khan A, Potts JT Jr, Brandi ML, Clarke BL, Shoback D, Juppner H, D’Amour P, Fox J, Rejnmark L, Mosekilde L, Rubin MR, Dempster D, Gafni R, Collins MT, Sliney J, Sanders J (2011) Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research. J Bone Miner Res 26(10):2317–2337. doi:10.1002/jbmr.483 CrossRefPubMedPubMedCentral

30.

Parker BD, Schurgers LJ, Brandenburg VM, Christenson RH, Vermeer C, Ketteler M, Shlipak MG, Whooley MA, Ix JH (2010) The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: the Heart and Soul Study. Ann Intern Med 152(10):640–648. doi:10.7326/0003-4819-152-10-201005180-00004 CrossRefPubMedPubMedCentral

31.

Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm BO, Weihrauch G, Maerz W (2008) Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med 168(12):1340–1349. doi:10.1001/archinte.168.12.1340 CrossRefPubMed

32.

Bellasi A, Mandreoli M, Baldrati L, Corradini M, Di Nicolo P, Malmusi G, Santoro A (2011) Chronic kidney disease progression and outcome according to serum phosphorus in mild-to-moderate kidney dysfunction. Clin J Am Soc Nephrol 6(4):883–891. doi:10.2215/cjn.07810910 CrossRefPubMedPubMedCentral

33.

Scialla JJ, Parekh RS, Eustace JA, Astor BC, Plantinga L, Jaar BG, Shafi T, Coresh J, Powe NR, Melamed ML (2015) Race, mineral homeostasis and mortality in patients with end-stage renal disease on dialysis. Am J Nephrol 42(1):25–34. doi:10.1159/000438999 CrossRefPubMedPubMedCentral

34.

Kendrick J, Ix JH, Targher G, Smits G, Chonchol M (2010) Relation of serum phosphorus levels to ankle brachial pressure index (from the Third National Health and Nutrition Examination Survey). Am J Cardiol 106(4):564–568. doi:10.1016/j.amjcard.2010.03.070 CrossRefPubMedPubMedCentral

35.

Lau WL, Pai A, Moe SM, Giachelli CM (2011) Direct effects of phosphate on vascular cell function. Adv Chronic Kidney Dis 18(2):105–112. doi:10.1053/j.ackd.2010.12.002 CrossRefPubMedPubMedCentral

36.

Shuto E, Taketani Y, Tanaka R, Harada N, Isshiki M, Sato M, Nashiki K, Amo K, Yamamoto H, Higashi Y, Nakaya Y, Takeda E (2009) Dietary phosphorus acutely impairs endothelial function. J Am Soc Nephrol 20(7):1504–1512. doi:10.1681/asn.2008101106 CrossRefPubMedPubMedCentral

37.

Foley RN, Collins AJ, Herzog CA, Ishani A, Kalra PA (2009) Serum phosphorus levels associate with coronary atherosclerosis in young adults. J Am Soc Nephrol 20(2):397–404. doi:10.1681/asn.2008020141 CrossRefPubMedPubMedCentral

38.

Burke AP, Taylor A, Farb A, Malcom GT, Virmani R (2000) Coronary calcification: insights from sudden coronary death victims. Z Kardiol 89(Suppl 2):49–53CrossRef

39.

Sangiorgi G, Rumberger JA, Severson A, Edwards WD, Gregoire J, Fitzpatrick LA, Schwartz RS (1998) Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using nondecalcifying methodology. J Am Coll Cardiol 31(1):126–133CrossRef

40.

Onufrak SJ, Bellasi A, Cardarelli F, Vaccarino V, Muntner P, Shaw LJ, Raggi P (2009) Investigation of gender heterogeneity in the associations of serum phosphorus with incident coronary artery disease and all-cause mortality. Am J Epidemiol 169(1):67–77. doi:10.1093/aje/kwn285 CrossRefPubMed

41.

Cirillo M, Ciacci C, De Santo NG (2008) Age, renal tubular phosphate reabsorption, and serum phosphate levels in adults. N Engl J Med 359(8):864–866. doi:10.1056/NEJMc0800696 CrossRefPubMed

Title: Associations between serum calcium, phosphorus and mortality among patients with coronary heart disease
Authors: Qian Chen
Yuan Zhang
Ding Ding
Dan Li
Yunou Yang
Qing Li
Xuechen Chen
Gang Hu
Wenhua Ling
Publication date: 01-10-2018
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nutrition / Issue 7/2018
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-017-1518-8

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Associations between serum calcium, phosphorus and mortality among patients with coronary heart disease

Abstract

Purpose

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 7/2018

Large artery stiffness is associated with salt intake in young healthy black but not white adults: the African-PREDICT study

Effect of barley supplementation on the fecal microbiota, caecal biochemistry, and key biomarkers of obesity and inflammation in obese db/db mice

Review of earlier evidence on dietary glycemic index and load and depression needs further attention

Consumption of extra virgin olive oil improves body composition and blood pressure in women with excess body fat: a randomized, double-blinded, placebo-controlled clinical trial

Supplement intervention associated with nutritional deficiencies in autism spectrum disorders: a systematic review

Zinc deficiency as a mediator of toxic effects of alcohol abuse

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page