Lipid Disorder

  • T. Shoji
  • Y. Nishizawa


Epidemiological studies in a cohort of 2,185 male subjects identified a higher serum calcium concentration within the normal range as an independent prospective risk factor for myocardial infarction during 18 years of follow-up [1], This was confirmed by a recent cross-sectional study of 12,865 men and 14,293 women showing that serum calcium was higher in men with a history of myocardial infarction than in those without [2]. Since calcium has diverse effects on cellular functions, extracellular and intracellular abnormalities in calcium may affect the cardiovascular risk factor profile. This chapter summarises the findings regarding the possible relationship between calcium and lipid disorder (Table 10.6). First, we briefly describe human lipoprotein metabolism in normal conditions, then changes in lipid metabolism in chronic renal failure, as a model for the study of the effects of calcium and related factors on lipid disorder (Table 10.7). This chapter also deals with possible lipid abnormalities in primary hyperparathyroidism and other topics.


Chronic Renal Failure Primary Hyperparathyroidism Secondary Hyperparathyroidism Cholesterol Efflux Microsomal Triglyceride Transfer Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lind L, Skarfors 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.PubMedCrossRefGoogle Scholar
  2. 2.
    Jorde R, Sundsfjord J, Fitzgerald P, Bonaa KH. Serum calcium and cardiovascular risk factors and diseases: the Tromso study. Hypertension 1999;34:484–90.PubMedGoogle Scholar
  3. 3.
    Attman PO, Samuelsson O, Alaupovic P. Lipoprotein metabolism and renal failure. Am J Kidney Dis 1993;21:573–92.PubMedGoogle Scholar
  4. 4.
    Shoji T, Nishizawa Y, Kawagishi T, Tanaka M, Kawasaki K, Tabata T et al. Atherogenic lipoprotein changes in the absence of hyperlipidemia in patients with chronic renal failure treated by hemodialysis. Atherosclerosis 1997;131:229–36.PubMedCrossRefGoogle Scholar
  5. 5.
    Savdie E, Gibson JC, Crawford GA, Simons LA, Mahony JF. Impaired plasma triglyceride clearance as a feature of both uremic and post-transplant triglyceridemia. Kidney Int 1980;18:774–82.PubMedCrossRefGoogle Scholar
  6. 6.
    Chan PC, Persaud J, Varghese Z, Kingstone D, Baillod RA, Moorhead JF. Apolipoprotein B turnover in dialysis patients: its relationship to pathogenesis of hyperlipidemia. Clin Nephrol 1989;31:88–95.PubMedGoogle Scholar
  7. 7.
    Horkko S, Huttunen K, Kesaniemi YA. Decreased clearance of low-density lipoprotein in uremic patients under dialysis treatment. Kidney Int 1995;47:1732–40.PubMedCrossRefGoogle Scholar
  8. 8.
    Mordasini R, Frey F, Flury W, Klose G, Greten H. Selective deficiency of hepatic triglyceride lipase in uremic patients. N Engl J Med 1977;297:1362–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Shoji T, Nishizawa Y, Nishitani H, Yamakawa M, Morii H. Impaired metabolism of high density lipoprotein in uremic patients. Kidney Int 1992;41:1653–61.PubMedCrossRefGoogle Scholar
  10. 10.
    Shoji T, Nishizawa Y, Nishitani H, Yamakawa M, Morii H. Roles of hypoalbuminemia and lipoprotein lipase on hyperlipoproteinemia in continuous ambulatory peritoneal dialysis. Metabolism 1991;40:1002–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Nishizawa Y, Shoji T, Nishitani H, Yamakawa M, Konishi T, Kawasaki K et al. Hypertriglyceridemia and lowered apolipoprotein C-II/C-III ratio in uremia: effect of a fibric acid, clinofibrate. Kidney Int 1993;44:1352–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Samuelsson O, Attman PO, Knight-Gibson C, Kron B, Larsson R, Mulec H etal. Lipoprotein abnormalities without hyperlipidaemia in moderate renal insufficiency. Nephrol Dial Transplant 1994;9:1580–5.PubMedGoogle Scholar
  13. 13.
    Akmal M, Kasim SE, Soliman AR, Massry SG. Excess parathyroid hormone adversely affects lipid metabolism in chronic renal failure. Kidney Int 1990;37:854–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Vaziri ND, Liang K. Down-regulation of tissue lipoprotein lipase expression in experimental chronic renal failure. Kidney Int 1996;50:1928–35.PubMedCrossRefGoogle Scholar
  15. 15.
    Akmal M, Perkins S, Kasim SE, Oh HY, Smogorzewski M, Massry SG. Verapamil prevents chronic renal failure-induced abnormalities in lipid metabolism. Am J Kidney Dis 1993;22:158–63.PubMedGoogle Scholar
  16. 16.
    Vaziri ND, Deng G, Liang K. Hepatic HDL receptor, SR-B1 and Apo A-I expression in chronic renal failure. Nephrol Dial Transplant 1999;14:1462–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Shoji T; Nishizawa Y, Koyama H, Hagiwara S, Aratani H, Sasao K etal. High-density lipoprotein metabolism during a very-low-calorie diet. Am J Clin Nutr 1992;56:297S–8S. PubMedGoogle Scholar
  18. 18.
    Shoji T, Nishizawa Y, Kawagishi T, Emoto M, Morii H. Secondary hyperparathyroidism, decreased hepatic triglyceride lipase, elevated intermediate density lipoprotein and atherosclerosis in hemodialysis patients. Nephron 1998;78:121–2.PubMedCrossRefGoogle Scholar
  19. 19.
    Lacour B, Roullet JB, Liagre AM, Jorgetti V, Beyne P, Dubost C etal. Serum lipoprotein disturbances in primary and secondary hyperparathyroidism and effects of parathyroidectomy. Am J Kidney Dis 1986;8:422–9.PubMedGoogle Scholar
  20. 20.
    Khajehdehi P, Ali M, Al-Gebory F, Henry G, Bastani B. The effects of parathyroidectomy on nutritional and biochemical status of hemodialysis patients with severe secondary hyperparathyroidism. J Ren Nutr 1999;9:186–91.PubMedCrossRefGoogle Scholar
  21. 21.
    Lim PS, Hung TS, Yeh CH, Yu MH. Effects of treatment of secondary hyperparathyroidism on the lipid profile in patients on hemodialysis. Blood Purif 1998;16:22–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Burke SK, Slatopolsky EA, Goldberg DI. RenaGel, a novel calcium- and aluminium-free phosphate binder, inhibits phosphate absorption in normal volunteers. Nephrol Dial Transplant 1997;12:1640–4.PubMedCrossRefGoogle Scholar
  23. 23.
    Chertow GM, Burke SK, Lazarus JM, Stenzel KH, Wombolt D, Goldberg D et al. Poly[allylamine hydrochloride] (RenaGel): a noncalcemic phosphate binder for the treatment of hyperphosphatemia in chronic renal failure. Am J Kidney Dis 1997;29:66–71.PubMedCrossRefGoogle Scholar
  24. 24.
    Chertow GM, Burke SK, Dillon MA, Slatopolsky E. Long-term effects of sevelamer hydrochloride on the calcium x phosphate product and lipid profile of haemodialysis patients. Nephrol Dial Transplant 1999;14:2907–14.PubMedCrossRefGoogle Scholar
  25. 25.
    Mak RH. 1,25-Dihydroxyvitamin D3 corrects insulin and lipid abnormalities in uremia. Kidney Int 1998;53:1353–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Navarro JF, Teruel JL, Lasuncion MA, Mora-Fernandez C, Ortuno J. Relationship between serum parathyroid hormone levels and lipid profile in hemodialysis patients. Evolution of lipid parameters after parathyroidectomy. Clin Nephrol 1998;49:303–7. Google Scholar
  27. 27.
    Lindner A, Charra B, Sherrard DJ, Scribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med 1974;290:697–701.PubMedCrossRefGoogle Scholar
  28. 28.
    Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32:S 112–9. CrossRefGoogle Scholar
  29. 29.
    Kawagishi T, Nishizawa Y, Konishi T, Kawasaki K, Emoto M, Shoji T et al. High-resolution B-mode ultrasonography in evaluation of atherosclerosis in uremia. Kidney Int 1995;48:820–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Shoji T, Kawagishi T, Emoto M, Maekawa K, Taniwaki H, Kanda H et al. Additive impacts of diabetes and renal failure on carotid atherosclerosis. Atherosclerosis 2000;153:257–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Shoji T, Nishizawa Y, Kawagishi T, Kawasaki K, Taniwaki H, Tabata T et al. Intermediate-density lipoprotein as an independent risk factor for aortic atherosclerosis in hemodialysis patients. J Am Soc Nephrol 1998;9:1277–84.PubMedGoogle Scholar
  32. 32.
    Kawagishi T, Nishizawa Y, Konishi T, Kawasaki K, Emoto M, Shoji T et al. High-resolution B-mode ultrasonography in evaluation of atherosclerosis in uremia. Kidney Int 1995;48:820–6.PubMedCrossRefGoogle Scholar
  33. 33.
    De Moor P, Creyttens G, Bouillon R, Joossens J. Results obtained in 75 patients operated upon for hyperparathyroidism: low cholesterol levels in overt primary hyperparathyroidism. Ann Endocrinol 1973;34:616–620.Google Scholar
  34. 34.
    Christensson T, Einarsson K. Serum lipids before and after parathyroidectomy in patients with primary hyperparathyroidism. Clin Chim Acta 1977;78:411–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Vaziri ND, Wellikson L, Gwinup G, Byrne C. Lipid fractions in primary hyperparathyroidism before and after surgical cure. Acta Endocrinol (Copenh) 1983;102:539–42.Google Scholar
  36. 36.
    Lundgren E, Ljunghall S, Akerstrom G, Hetta J, Mallmin H, Rastad J. Case-control study on symptoms and signs of asymptomatic primary hyperparathyroidism. Surgery 1998;124:980–5; discussion 985-6. PubMedCrossRefGoogle Scholar
  37. 37.
    Valdemarsson S, Lindblom P, Bergenfelz A. Metabolic abnormalities related to cardiovascular risk in primary hyperparathyroidism: effects of surgical treatment. J Intern Med 1998;244:241–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Bjornsson OG, Bourgeois CS, Gibbons GF. Varying very-low-density lipoprotein secretion of rat hepatocytes by altering cellular levels of calcium and the activity of protein kinase C. Eur J Clin Invest 1998;28:720–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Takahashi Y, Smith JD. Cholesterol efflux to apolipoprotein Al involves endocytosis and resecretion in a calcium-dependent pathway. Proc Natl Acad Sci USA 1999;96:11358–63.PubMedCrossRefGoogle Scholar
  40. 40.
    Bostick RM, Fosdick L, Grandits GA, Grambsch P, Gross M, Louis TA. Effect of calcium supplementation on serum cholesterol and blood pressure. A randomized, double-blind, placebo-controlled, clinical trial. Arch Fam Med 2000;9:31–8. Google Scholar
  41. 41.
    Shahkhalili Y, Murset C, Meirim I, Duruz E, Guinchard S, Cavadini C et al. Calcium supplementation of chocolate: effect on cocoa butter digestibility and blood lipids in humans. Am J Clin Nutr 2001;73:246–52.PubMedGoogle Scholar
  42. 42.
    Lacour B, Basile C, Drueke T, Funck-Brentano JL. Parathyroid function and lipid metabolism in the rat. Miner Electrolyte Metab 1982;7:157–65.PubMedGoogle Scholar
  43. 43.
    Arnadottir M, Nilsson-Ehle P. Parathyroid hormone is not an inhibitor of lipoprotein lipase activity. Nephrol Dial Transplant 1994;9:1586–9.PubMedGoogle Scholar
  44. 44.
    Nishizawa Y, Okui Y, Inaba M, Okuno S, Yukioka K, Miki T et al. Calcium/calmodulin-mediated action of calcitonin on lipid metabolism in rats. J Clin Invest 1988;82:1165–72.PubMedCrossRefGoogle Scholar
  45. 45.
    De Novellis V, Loffreda A, Vitagliano S, Stella L, Lampa E, Filippelli W etal. Effects of dietary vitamin D deficiency on the cardiovascular system. Res Commun Chem Pathol Pharmacol 1994;83:125–44.PubMedGoogle Scholar
  46. 46.
    Heikkinen AM, Tuppurainen MT, Niskanen L, Komulainen M, Penttila I, Saarikoski S. Long-term vitamin D3 supplementation may have adverse effects on serum lipids during postmenopausal hormone replacement therapy. Eur J Endocrinol 1997;137:495–502.PubMedCrossRefGoogle Scholar
  47. 47.
    Mathur SN, Born E, Murthy S, Field FJ. Microsomal triglyceride transfer protein in CaCo-2 cells: characterization and regulation. J Lipid Res 1997;38:61–7.PubMedGoogle Scholar
  48. 48.
    Hayashi K, Gohda M, Matzno S, Kubo Y, Kido H, Yamauchi T etal. Possible mechanism of action of AE0047, a calcium antagonist, on triglyceride metabolism. J Pharmacol Exp Ther 1997;282:882–90.PubMedGoogle Scholar
  49. 49.
    Masuo K, Mikami H, Ogihara T, Tuck ML. Metabolie effects of long-term treatments with nifedipineretard and Captopril in young hypertensive patients. Am J Hypertens 1997;10:600–10.PubMedCrossRefGoogle Scholar
  50. 50.
    Reuter MK, Lorenz H, Verho P, Smith N, Degen A, Verho M. Effects of felodipine ER, a dihydropyridine calcium antagonist, on blood pressure and serum lipids. Curr Med Res Opin 1998;14:97–103.PubMedCrossRefGoogle Scholar
  51. 51.
    Sumiya T, Ikeno A, Kato H, Fujitani B, Masuda Y, Hosoki K et al. Inhibitory effect of monatepil maleate on acyl-CoA:cholesterol acyltransferase activity in the liver of cholesterol-fed Japanese monkeys. Am J Hypertens 1997;10:779–85.PubMedCrossRefGoogle Scholar
  52. 52.
    Ikeno A, Sumiya T, Minato H, Fujitani B, Masuda Y, Hosoki K et al. Effects of monatepil maleate, a new Ca2+ channel antagonist with alpha 1-adrenoceptor antagonistic activity, on cholesterol absorption and catabolism in high cholesterol diet-fed rabbits. Jpn J Pharmacol 1998;78:303–12.PubMedCrossRefGoogle Scholar
  53. 53.
    Matsunaga A, Inoue T, Koga T, Mori K, Kugi M, Sasaki J etal. Effects of monatepil, a novel calcium antagonist with alpha 1-adrenergic blocking activity, on the low-density lipoprotein receptor in human skin fibroblasts. Cardiovasc Drugs Ther 1997;11:747–50. PubMedCrossRefGoogle Scholar
  54. 54.
    Kritz H, Sinzinger H, Fitscha P, O’Grady J. Isradipine lowers human arterial low-density lipoprotein retention in vivo. Prostaglandins Leukot Essent Fatty Acids 1998;59:305–12.PubMedCrossRefGoogle Scholar
  55. 55.
    Hayashi K, Imada T, Yamauchi T, Kido H, Shinyama H, Matzno S et al. Possible mechanism for the anti-atherosclerotic action of the calcium channel blocker AE0047 in cholesterol-fed rabbits. Clin Exp Pharmacol Physiol 1998;25:17–25.PubMedCrossRefGoogle Scholar
  56. 56.
    Inouye M, Mio T, Sumino K. Nilvadipine protects low-density lipoprotein cholesterol from in vivo oxidation in hypertensive patients with risk factors for atherosclerosis. Eur J Clin Pharmacol 2000; 56:35–41.PubMedCrossRefGoogle Scholar
  57. 57.
    Berkels R, Hass U, Klaus W. The calcium antagonist nifedipine inhibits the uptake of acetylated LDL into endothelial cells. Naunyn Schmiedebergs Arch Pharmacol 2000;362:91–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2002

Authors and Affiliations

  • T. Shoji
  • Y. Nishizawa

There are no affiliations available

Personalised recommendations