Crosstalk between the hepatologist and the cardiologist: A future place for the lithocholic acid as a coronary atheroma risk factor?

Authors

  • Henri Duboc M.D.,

    1. University Paris Diderot, Sorbonne Paris Cité, AP-HP, Louis Mourier Hospital, Department of Gastroenterology and Hepatology, Paris, France
    2. University Pierre and Marie Curie, ERL INSERM U 1057/UMR 7203, AP-HP, Saint-Antoine Hospital, Paris, France
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    • Henri Duboc, M.D., and Hélène Aelion, M.D. contributed equally.

      Language was improved by CardioScript international, Salt Lake city, UT, USA.

  • Hélène Aelion M.D.,

    1. University Paris Descartes, AP-HP, Cochin Hospital, Department of Cardiology, Paris, France
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    • Henri Duboc, M.D., and Hélène Aelion, M.D. contributed equally.

      Language was improved by CardioScript international, Salt Lake city, UT, USA.

  • Dominique Rainteau Ph.D.,

    1. University Pierre and Marie Curie, ERL INSERM U 1057/UMR 7203, AP-HP, Saint-Antoine Hospital, Paris, France
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  • Sylvie Rajca M.D.,

    1. University Pierre and Marie Curie, ERL INSERM U 1057/UMR 7203, AP-HP, Saint-Antoine Hospital, Paris, France
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  • Harry Sokol M.D., Ph.D.,

    1. University Pierre and Marie Curie, ERL INSERM U 1057/UMR 7203, AP-HP, Saint-Antoine Hospital, Paris, France
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  • Lydie Humbert,

    1. University Pierre and Marie Curie, ERL INSERM U 1057/UMR 7203, AP-HP, Saint-Antoine Hospital, Paris, France
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  • Dominique Farabos,

    1. University Pierre and Marie Curie, ERL INSERM U 1057/UMR 7203, AP-HP, Saint-Antoine Hospital, Paris, France
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  • Benoit Coffin M.D., Ph.D.,

    1. University Paris Diderot, Sorbonne Paris Cité, AP-HP, Louis Mourier Hospital, Department of Gastroenterology and Hepatology, Paris, France
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  • Simon Weber M.D.,

    1. University Paris Descartes, AP-HP, Cochin Hospital, Department of Cardiology, Paris, France
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    • Henri Duboc, M.D., and Hélène Aelion, M.D. contributed equally.

      Language was improved by CardioScript international, Salt Lake city, UT, USA.

  • Raphaël Porcher Ph.D.,

    1. University Paris Diderot, Sorbonne Paris Cité, UMR-S 717, APHP, Saint Louis Hospital, Biostatistic and Medical Informatics Department, Paris, France
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  • Olivier Varenne M.D., Ph.D.,

    1. University Paris Descartes, AP-HP, Cochin Hospital, Department of Cardiology, Paris, France
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  • Denis Duboc M.D.

    1. University Paris Descartes, AP-HP, Cochin Hospital, Department of Cardiology, Paris, France
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  • Potential conflict of interest: Dr. Varenne has receive funding from Abbott laboratories.

To the Editor:

Although low-density lipoprotein (LDL) cholesterol, synthesized by liver, is one of the main risk factors of coronary atheroma in humans, clinical practice has taught us that meetings between our 2 specialties are not about this subject, except maybe when discussing the opportunity of a liver transplantation in patients with severe coronary disease. Recent works demonstrating a strong protective effect of the bile acids receptor FXR and TGR5 in a mice models of atheroma1, 2 could change this old rule in the not so distant future, but so far no evidences exists in humans. The level of activation of these receptors depends on the type of bile acids that activate them.3 We designed a pilot prospective and observational study conducted between June 2010 and September 2010 to search for variations in the bile acid pool composition between 2 populations: patients with or without coronary atheroma. We determined the serum concentrations of cholic, chenodeoxycholic, deoxycholic, and lithocholic acids in a fasting blood sample in all consecutive patients undergoing coronary angiograms in the cathlab unit of Cochin Hospital. Applying very restrictive exclusions criteria to avoid artificial variations of the bile acid pool (post-cardiac arrest; nonfasting states; hepatic disease; treatment with antimicrobials, corticosteroids, statins, or fibrates) of 393 screened patients, 44 met the criteria and were divided between 27 with (group A) and 17 without (group B) angiographically visible coronary atheromas.

Except for more males in group A, the groups were comparable. The serum lithocholic acid (LCA) concentration was significantly lower in group A (median 0.03 μmol/L; interquartile range 0.02–0.05) than in group B (0.08 μmol/L; interquartile range 0.05–0.11; P = 0.015) (Fig. 1). In the multivariate analysis, LCA was the only predictor of coronary atheroma independently of patient gender (odds ratio 2.41 per 0.05 decrease; 95% confidence interval 1.11-5.25; P = 0.027).

Figure 1.

(A) Box and whisker plots showing the median, and 25th and 75th percentiles of the distribution (box) and whiskers extending to the most extreme data point, which is no more than 1.5 times the interquartile range from the box. (B) Receiver operating characteristics curve. The area under the curve (AUC) is presented with its 95% confidence interval (95% CI). LCA, lithocholic acid.

Although the populations were small, we believe this observation connecting LCA and coronary atheroma is a field worth investigating further, as LCA is the most powerful activator of TGR5.3 A study targeting the proinflammatory mechanism acting in atheroma plaque evidenced that the activation of the TGR5 receptor significantly limits the formation of plaques in LDL−/− mice by decreasing the inflammation inside the plaque and the proinflammatory cytokines secretion by macrophages. This raises the hypothesis that lowering the most prominent activator of TGR5 is likely to lower the protection against plaque development in humans. Further studies are needed to confirm this observation, to better understand the origin and the extent to which a decrease in LCA is implicated in the development of coronary atheromatous plaques, and to maybe put us hepatologists and cardiologists more often around the same table.

Henri Duboc M.D.† ‡, Hélène Aelion M.D.*, Dominique Rainteau Ph.D.‡, Sylvie Rajca M.D.‡, Harry Sokol M.D., Ph.D.‡, Lydie Humbert‡, Dominique Farabos‡, Benoit Coffin M.D., Ph.D.†, Simon Weber M.D.*, Raphaël Porcher Ph.D.§, Olivier Varenne M.D., Ph.D.*, Denis Duboc M.D.*, * University Paris Descartes, AP-HP, Cochin Hospital, Department of Cardiology, Paris, France, † University Paris Diderot, Sorbonne Paris Cité, AP-HP, Louis Mourier Hospital, Department of Gastroenterology and Hepatology, Paris, France, ‡ University Pierre and Marie Curie, ERL INSERM U 1057/UMR 7203, AP-HP, Saint-Antoine Hospital, Paris, France, § University Paris Diderot, Sorbonne Paris Cité, UMR-S 717, APHP, Saint Louis Hospital, Biostatistic and Medical Informatics Department, Paris, France.

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