Serum calcium and phosphorus associate with the occurrence and severity of angiographically documented coronary heart disease, possibly through correlation with atherogenic (apo)lipoproteins
-
Mehdi Rasouli
Abstract
The associations of serum calcium and phosphorus concentrations as well as other cardiovascular risk factors were investigated in relation to the existence and severity of coronary heart disease (CHD) in 260 clinically stable, angiographically defined CHD patients aged 40–70years. The subjects were classified as CHD+ cases if one or more coronary arteries had a significant stenosis (≥70%) and CHD− controls if there was no stenosis (≤10%) in any artery. The severity of coronary occlusion was scored on the basis of the number and extent of lesions, as normal, mild, moderate or severe. Fasting serum concentrations of electrolytes, lipids and (apo)lipoproteins were determined. The concentrations of serum total calcium (2.41±0.14 vs. 2.33±0.22mmol/L, p≤0.05), albumin-corrected calcium (2.33±0.25 vs. 2.23±0.25 mmol/L, p≤0.01), phosphorus (1.32±0.21 vs. 1.25±0.17mmol/L, p≤0.007) and the ion product of calcium and phosphorus (3.16±0.58 vs. 2.91±0.50, p≤0.0001) were significantly higher in the CHD+ compared to the CHD− group. Patients with CHD compared with controls had increased serum levels of triglyceride, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), lipoprotein(a) [Lp(a)] and decreased serum levels of high-density lipoprotein (HDL)-C and apoAI. Multiple logistic regression analysis showed strong and significant association between diabetes mellitus (odds ratio, OR=5.24, p≤0.0001), male gender (OR=8.84, p≤0.0001), Lp(a) (OR=1.014, p≤0.006), hypertension (OR=2.61, p≤0.02), apoB (OR=1.031, p≤0.001), age (OR=1.055, p≤0.003), phosphorus (OR=2.438, p≤0.01), albumin-adjusted calcium (OR=1.532, p≤0.05), cholesterol (OR=1.009, p≤0.05) and the occurrence of CHD. On the basis of bivariate correlation analysis, serum-adjusted calcium was positively correlated with the levels of cholesterol (r=0.285, p≤0.0001), LDL-C (r=0.320, p≤0.0001), Lp(a) (r=0.173, p≤0.005), apoB (r=0.237, p≤0.0001), LDL-C/apoB ratio (r=0.180, p≤0.007), apoAI (r=0.181, p≤0.003) and inversely to HDL-C (r=−0.146, p≤0.02) and HDL-C/apoAI ratio (r=−0.263, p≤0.0001). Serum phosphorus concentration was a significant correlate of triglyceride (r=0.199, p≤0.001) and Lp(a) (r=0.129, p≤0.04). The results demonstrated that serum calcium and phosphorus are associated with the prevalence and severity of CHD, probably through correlation with atherogenic lipids and (apo)lipoproteins. Serum calcium and phosphorus and their ion product were also independent risk factors for CHD.
References
1. Baigent C, Burbury K, Wheeler D. Premature cardiovascular disease in chronic renal failure. Lancet 2000; 356:147–52.10.1016/S0140-6736(00)02456-9Search in Google Scholar
2. Raggi P, Boulay A, Chasan-Taber S, Amin N, Dillon M, Burke SK, et al. Cardiac calcification in adult hemodialysis patients, a link between end-stage renal disease and cardiovascular disease? J Am Coll Cardiol 2002; 39;695–701.10.1016/S0735-1097(01)01781-8Search in Google Scholar
3. Schmermund A, Baumgart D, Gorge G, Gronemeyer D, Seibel R, Bailey KR, et al. Measuring the effect of risk factors on coronary atherosclerosis: coronary calcium score versus angiographic disease severity. J Am Coll Cardiol 1998; 31:1267–73.10.1016/S0735-1097(98)00082-5Search in Google Scholar
4. Tolstrup K, Roldan CA, Qualls CR, Crawford MH. Aortic valve sclerosis, mitral annular calcium, and aortic root sclerosis as markers of atherosclerosis in men. Am J Cardiol 2002; 89:1030–4.10.1016/S0002-9149(02)02270-1Search in Google Scholar
5. Nair CK, Sudahkaran C, Aronow WS, Thomson W, Woodruff MP, Sketch MH. Clinical characteristics of patients younger than 60 years with mitral annular calcium: comparison with age- and sex- matched control subjects. Am J Cardiol 1984; 54:1286–7.10.1016/S0002-9149(84)80082-XSearch in Google Scholar
6. Aronow WS, Ahn C, Kronzon I. Association of mitral annular calcium with symptomatic peripheral arterial disease in older persons. Am J Cardiol 2001; 88:333–4.10.1016/S0002-9149(01)01657-5Search in Google Scholar
7. Bostrom K. Insights into the mechanism of vascular calcification. Am J Cardiol 2001; 88:20E–22E.10.1016/S0002-9149(01)01718-0Search in Google Scholar
8. Lind L, Skarfos 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; 50:967–73.10.1016/S0895-4356(97)00104-2Search in Google Scholar
9. Narang R, Ridout D, Nonis C, Kooner JS. Serum calcium, phosphorus and albumin levels in relation to the angio-graphic severity of coronary artery disease. Int J Cardiol 1997; 60:73–9.10.1016/S0167-5273(97)02971-9Search in Google Scholar
10. Pak C. Calcium disorders: hypercalcemia and hypocalcemia. In: Kokko JP, Tannen RL, editors. Fluids and electrolytes, 2nd ed. Philadelphia, PA: WB Saunders, 1990:596–630.Search in Google Scholar
11. Fraser D, Jones G, Kooh SW, Radde IC. Calcium and phosphate metabolism. In: Burtis CA, Ashwood ER, editors. Tietz textbook of clinical biochemistry. Philadelphia, PA: WB Saunders, 1986:722–49.Search in Google Scholar
12. Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000; 18:1478–83.10.1056/NEJM200005183422003Search in Google Scholar PubMed
13. Herrmann G, Hehrmann R, Scholz HC, Atkinson M, Lichtlen P, von zur Muhlen A, et al. Parathyroid hormone in coronary artery disease, results of a prospective study. J Endocrinol Invest 1986; 9:265–71.10.1007/BF03346923Search in Google Scholar
14. Nishizawa Y, Shoji T, Kawagishi T, Morii H. Atherosclerosis in uremia: possible roles of hyperparathyroidism and intermediate density lipoprotein accumulation. Kidney Int 1997; 62:S90–2.Search in Google Scholar
15. de Vinuesa SG, Ortega M, Martinez P, Goicoechea M, Campdera FG, Luno J. Subclinical peripheral arterial disease in patients with chronic kidney disease: prevalence and related risk factors. Kidney Int 2005; 93:S44–7.10.1111/j.1523-1755.2005.09310.xSearch in Google Scholar
16. Braun J, Oldendorf M, Moshage W, Heidler R, Zeitler E, Luft FC. Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients. Am J Kidney Dis 1996; 27:394–401.10.1016/S0272-6386(96)90363-7Search in Google Scholar
17. Wade MR, Chen YJ, Soliman M, Kaptein E, Massry SG, Rahimtoola SH, et al. Myocardial texture and cardiac calcification in uremia. Miner Electrolyte Metab 1993; 19:21–4.Search in Google Scholar
18. Arad Y, Spadaro LA, Roth M, Scordo J, Goodman K, Sherman S, et al. Serum concentration of calcium, 1,25 vitamin D and parathyroid hormone are not correlated with coronary calcifications. An electron beam computed tomography study. Coron Artery Dis 1998; 9:513–8.10.1097/00019501-199809080-00007Search in Google Scholar
19. Staessen J, Sartor F, Roels H, Bulpitt CJ, Claeys F, Ducoffre G, et al. The association between blood pressure, calcium and other divalent cations: a population study. J Hum Hypertens 1991; 5:485–94.Search in Google Scholar
20. Phillips AN, Shaper AG. Serum calcium and blood pressure. J Hum Hypertens 1991; 5:479–84.Search in Google Scholar
21. Fogh-Andersen N, Hedegaard L, Thode J, Siggaard-Andersen O. Sex-dependent relation between ionized calcium in serum and blood pressure. Clin Chem 1984; 30:116–8.10.1093/clinchem/30.1.116Search in Google Scholar
22. Green MS, Jucha E. Interrelationships between blood pressure, serum calcium and other biochemical variables. Int J Epidemiol 1987; 16:532–6.10.1093/ije/16.4.532Search in Google Scholar
23. Hunt SC, McCarron DA, Smith JB, Ash KO, Bristow MR, Williams RR. The relationship of plasma ionized calcium to cardiovascular disease endpoint and family history of hypertension. CIin Exp Hypertens 1984; 6:1397–414.10.3109/10641968409044058Search in Google Scholar
24. Cooper RS, Shamsi N. Ionized serum calcium in black hypertensives: absence of a relationship with blood pressure. J Clin Hypertens 1987; 3:514–9.Search in Google Scholar
25. Gutler JA, Brittain E. Calcium and blood pressure: an epidemiologic perspective. Am J Hypertens 1990; 3:1375–8.Search in Google Scholar
26. Jimenez E, del Nido P, Sarin M, Nakamura H, Feinberg H, Levitsky S. Effects of low extracellular calcium on cytosolic calcium and ischemic contracture. J Surg Res 1990; 49:252–5.10.1016/0022-4804(90)90129-PSearch in Google Scholar
27. Stimpel M, Neyses L, Locher R, Knorr M, Vetter W. High density lipoproteins: modulators of the calcium channel? J Hypertens 1985; 3:S49–S51.Search in Google Scholar
28. Jendryczko A, Parela M. Abnormal effect of sera from patients with atherosclerosis on calcium influx into normal erythrocytes. Cor Vasa 1992; 34:428–33.Search in Google Scholar
29. Fleckenstein-Grun G, Fleckenstein A. Calcium: a neglected key factor in arteriosclerosis. The pathogenic role of arterial calcium overload and its prevention by calcium antagonists. Ann Med 1991; 23:589–99.10.3109/07853899109150522Search in Google Scholar PubMed
30. Nayler WG. Basic mechanisms involved in the protection of the ischaemic myocardium. The role of calciumantagonists. Drugs 1991; 42:21–7.10.2165/00003495-199100422-00005Search in Google Scholar PubMed
31. Lind L, Jakobsson S, Lithell H, Wengle B, Ljunghall S. Relation of serum calcium concentration to metabolic risk factors for cardiovascular disease. Br Med J 1988; 15:960–3.10.1136/bmj.297.6654.960Search in Google Scholar
32. Bacquer DD, Henauw SD, Backer GD, Kornitzer M. Epidemiological evidence for an association between serum calcium and serum lipids. Atherosclerosis 1994; 108:193–200.10.1016/0021-9150(94)90114-7Search in Google Scholar
33. Wilson PW, Garrison RJ, Abbott RD, Castelli WP. Factors associated with lipoprotein cholesterol levels. The Framingham Study. Arteriosclerosis 1983; 3:273–81.10.1161/01.ATV.3.3.273Search in Google Scholar
34. Zemel MB, Shi H, Greer B, Dirienzo D, Zemel PC. Regulation of adiposity by dietary calcium. FASEB J 2000; 14:1132–8.10.1096/fasebj.14.9.1132Search in Google Scholar
35. McCarty MF, Thomas CA. PTH excess may promote weight gain by impeding catecholamine-induced lipolysis-implications for the impact of calcium, vitamin D, and alcohol on body weight. Med Hypotheses 2003; 61:535–42.10.1016/S0306-9877(03)00227-5Search in Google Scholar
36. Lewis GF. Fatty acid regulation of very low density lipoprotein production. Curr Opin Lipidol 1997; 8:146–53.10.1097/00041433-199706000-00004Search in Google Scholar
37. Bjornsson OG, Sparks JD, Sparks CE, Gibbons GF. Prostaglandins suppress VLDL secretion in primary rat hepatocyte cultures: relationships to hepatic calcium metabolism. J Lipid Res 1992; 33:1017–27.10.1016/S0022-2275(20)41417-8Search in Google Scholar
38. Nossen JO, Rustan AC, Drevon CA. Calcium-antagonists inhibit secretion of very-low-density lipoprotein from rat hepatocytes. Biochem J 1987; 247:433–9.10.1042/bj2470433Search in Google Scholar
39. Rasouli M, Trischuk T, Lehner R. Calmodulin antagonist W-7 inhibits de novo synthesis of cholesterol and suppresses secretion of de novo synthesized and preformed lipids from cultured hepatocytes. Biochem Biophys Acta 2004; 1682:92–101.10.1016/j.bbalip.2004.02.002Search in Google Scholar
40. Packard C, Caslake M, Sheperd J. The role of small density lipoprotein (LDL): a new look. Int J Cardiol 2000; 74:S17–22.10.1016/S0167-5273(99)00107-2Search in Google Scholar
©2006 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Where does the evidence come from?
- NASBA: a novel approach to assess hormonal receptors and ERBB2 status in breast cancer
- Plasma cell-free DNA as an indicator of severity of injury in burn patients
- Bivariate statistical approach to evaluate laboratory performance by analysis of standard curves in an External Quality Assurance program for quantitative assays based on real-time PCR with Taq-Man™ probes
- Erythrocyte membrane acetylcholinesterase activity in subjects with MTHFR 677C→T genotype
- Plasma levels of tumor M2-pyruvate kinase should not be used as a tumor marker for hematological malignancies and solid tumors
- APO A-V–1131T→C polymorphism frequency and its association with morbidity in a Brazilian elderly population
- Association study between fibronectin and coronary heart disease
- Serum calcium and phosphorus associate with the occurrence and severity of angiographically documented coronary heart disease, possibly through correlation with atherogenic (apo)lipoproteins
- Urinary calcium excretion in severe preeclampsia and eclampsia
- In vitro re-mineralization of demineralized bone matrix in human serum
- Measurement of serum amyloid A1 (SAA1), a major isotype of acute phase SAA
- Disturbed lipoprotein composition in non-dialyzed, hemodialysis, continuous ambulatory peritoneal dialysis and post-transplant patients with chronic renal failure
- Measurement of serum testosterone using high-performance liquid chromatography/tandem mass spectrometry
- Quantitative bacterial micro-assay for rapid detection of serum phenylalanine on dry blood-spots: application in phenylketonuria screening
- N-Terminal pro-brain natriuretic peptide: normal ranges in the pediatric population including method comparison and interlaboratory variability
- A new quality control model using performance goals based on biological variation in External Quality Assurance Schemes
- Improvement in glycemic control over 11 years in patients monitored for diabetes in one county
- The clinical usefulness of glucose tolerance testing in gestational diabetes to predict early postpartum diabetes mellitus
- Analytical performance of a new two-step ADVIA Centaur® estradiol immunoassay during ovarian stimulation
- EC4 European Syllabus for Post-Graduate Training in Clinical Chemistry and Laboratory Medicine: version 3 – 2005
- POX-Act assay and d-ROMs test – what are the facts?
- External quality control of urinary methyl malonic acid quantification – announcement of a pilot study
Articles in the same Issue
- Where does the evidence come from?
- NASBA: a novel approach to assess hormonal receptors and ERBB2 status in breast cancer
- Plasma cell-free DNA as an indicator of severity of injury in burn patients
- Bivariate statistical approach to evaluate laboratory performance by analysis of standard curves in an External Quality Assurance program for quantitative assays based on real-time PCR with Taq-Man™ probes
- Erythrocyte membrane acetylcholinesterase activity in subjects with MTHFR 677C→T genotype
- Plasma levels of tumor M2-pyruvate kinase should not be used as a tumor marker for hematological malignancies and solid tumors
- APO A-V–1131T→C polymorphism frequency and its association with morbidity in a Brazilian elderly population
- Association study between fibronectin and coronary heart disease
- Serum calcium and phosphorus associate with the occurrence and severity of angiographically documented coronary heart disease, possibly through correlation with atherogenic (apo)lipoproteins
- Urinary calcium excretion in severe preeclampsia and eclampsia
- In vitro re-mineralization of demineralized bone matrix in human serum
- Measurement of serum amyloid A1 (SAA1), a major isotype of acute phase SAA
- Disturbed lipoprotein composition in non-dialyzed, hemodialysis, continuous ambulatory peritoneal dialysis and post-transplant patients with chronic renal failure
- Measurement of serum testosterone using high-performance liquid chromatography/tandem mass spectrometry
- Quantitative bacterial micro-assay for rapid detection of serum phenylalanine on dry blood-spots: application in phenylketonuria screening
- N-Terminal pro-brain natriuretic peptide: normal ranges in the pediatric population including method comparison and interlaboratory variability
- A new quality control model using performance goals based on biological variation in External Quality Assurance Schemes
- Improvement in glycemic control over 11 years in patients monitored for diabetes in one county
- The clinical usefulness of glucose tolerance testing in gestational diabetes to predict early postpartum diabetes mellitus
- Analytical performance of a new two-step ADVIA Centaur® estradiol immunoassay during ovarian stimulation
- EC4 European Syllabus for Post-Graduate Training in Clinical Chemistry and Laboratory Medicine: version 3 – 2005
- POX-Act assay and d-ROMs test – what are the facts?
- External quality control of urinary methyl malonic acid quantification – announcement of a pilot study
