Correspondence

Hypercholesterolemia in Primary Biliary Cirrhosis

N Engl J Med 2007; 357:1561-1562October 11, 2007

Article

To the Editor:

Hypercholesterolemia in patients with primary biliary cirrhosis is not consistently associated with preclinical carotid atherosclerosis.1 Although hypercholesterolemia has been documented worldwide as a major risk factor for illness and death from atherosclerotic disease, the mechanistic explanation for the absence of an increased risk of atherosclerotic disease among patients who have hypercholesterolemia and primary biliary cirrhosis remains largely unknown.1,2

We previously showed that patients with primary biliary cirrhosis and extreme hypercholesterolemia (total cholesterol level, >25.86 mmol per liter) had a substantial proportion of circulating lipoprotein X.3 Further in vitro studies revealed that lipoprotein X reduces the atherogenicity of low-density lipoprotein (LDL) cholesterol by preventing LDL oxidation, which suggests that lipoprotein X may protect the integrity of endothelial cells in the presence of hypercholesterolemia.3

To confirm these preliminary findings, from October 2003 to February 2005, we recruited 13 patients with primary biliary cirrhosis and matched them on the basis of age with 71 patients with hypercholesterolemia in order to evaluate the relationship between LDL-oxidation status and the presence or absence of preclinical carotid atherosclerosis. We assessed carotid end-organ disease by measuring the maximal intima–media thickness of the common carotid artery and determining plaque scores for the extracranial carotid artery, as described previously.4 We obtained two bilateral measurements of maximal intima–media thickness of the common carotid artery 0 to 20 mm proximal to the carotid bifurcation, which we used to calculate the mean intima–media thickness.

The procedure for preparation and oxidation of LDL was modified from the method used by Esterbauer et al.5 Oxidation was triggered by the addition of 50 μmol of copper sulfate to the LDL cholesterol solution. Diene conjugation was monitored according to changes in absorbance at 234 nm with the use of a Beckman DU-640 spectrophotometer at 15-minute intervals. We determined the susceptibility of LDL to oxidation by measuring the lag time of the oxidation curve.

Our results showed a prolonged LDL-oxidation lag time in the group with primary biliary cirrhosis (Table 1Table 1Oxidation of Low-Density Lipoprotein (LDL) Cholesterol, Intima–Media Thickness, and Plaque Scores for the Extracranial Carotid Artery in Patients with Primary Biliary Cirrhosis and in Those with Hypercholesterolemia.). Of the 13 patients in the group, 3 underwent liver transplantation. Before liver transplantation, the LDL-oxidation lag time was markedly prolonged (>300 minutes). However, the lag time was no longer prolonged after liver transplantation (100 to 150 minutes). Levels of total cholesterol and LDL cholesterol were higher in the group with primary biliary cirrhosis than in the group with hypercholesterolemia. However, the intima–media thickness of the common carotid artery and plaque scores for the extracranial carotid artery were similar in the two groups (Table 1). These findings support the hypothesis that reduced LDL oxidation may be associated with no significant increase in atherosclerosis in patients with primary biliary cirrhosis, even in those with severe hypercholesterolemia.

Ta-Chen Su, M.D., Ph.D.
Juey-Jen Hwang, M.D., Ph.D.
Jia-Horng Kao, M.D., Ph.D.
National Taiwan University Hospital, Taipei 100, Taiwan
jueyhwang@ntu.edu.tw

5 References

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   Allocca M, Crosignani A, Gritti A, et al. Hypercholesterolaemia is not associated with early atherosclerotic lesions in primary biliary cirrhosis. Gut 2006;55:1795-1800
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   Sorokin A, Brown JL, Thompson PD. Primary biliary cirrhosis, hyperlipidemia, and atherosclerotic risk: a systematic review. Atherosclerosis (in press).
   

3. 3

   Chang PY, Lu SC, Su TC, et al. Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation. J Lipid Res 2004;45:2116-2122
   CrossRef | Web of Science | Medline

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   Su TC, Jeng JS, Chien KL, Sung FC, Hsu HC, Lee YT. Hypertension status is the major determinant of carotid atherosclerosis: a community-based study in Taiwan. Stroke 2001;32:2265-2271
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   Esterbauer H, Striegl G, Puhl H, Rotheneder M. Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Radic Res Commun 1989;6:7-75
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Citing Articles (6)

Citing Articles

1. 1

   Emmanouil Sinakos, Ghulam Abbas, Roberta A. Jorgensen, Keith D. Lindor. (2012) Serum lipids in primary sclerosing cholangitis. Digestive and Liver Disease 44:1, 44-48
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2. 2

   Yi-song XIONG, Ren-qian ZHONG. (2010) Non-elevated cardiovascular risk in patients with primary biliary cirrhosis and hypercholesterolemia. Academic Journal of Second Military Medical University 30:8, 904-906
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3. 3

   M. L. Griffith, B. N. Savani, J. B. Boord. (2010) Dyslipidemia after allogeneic hematopoietic stem cell transplantation: evaluation and management. Blood 116:8, 1197-1204
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4. 4

   Christophe Corpechot, Yves Chrétien, Olivier Chazouillères, Raoul Poupon. (2010) Demographic, lifestyle, medical and familial factors associated with primary biliary cirrhosis. Journal of Hepatology 53:1, 162-169
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5. 5

   Tatjana Stojakovic, Thierry Claudel, Csilla Putz-Bankuti, Günter Fauler, Hubert Scharnagl, Martin Wagner, Harald Sourij, Rudolf E. Stauber, Karl Winkler, Winfried März, Thomas C. Wascher, Michael Trauner. (2010) Low-dose atorvastatin improves dyslipidemia and vascular function in patients with primary biliary cirrhosis after one year of treatment. Atherosclerosis 209:1, 178-183
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6. 6

   Simon Hohenester, Ronald P. J. Oude-Elferink, Ulrich Beuers. (2009) Primary biliary cirrhosis. Seminars in Immunopathology 31:3, 283-307
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