Advertisement

Colesevelam HCl reduces LDL particle number and increases LDL size in hypercholesterolemia

  • Robert S. Rosenson
    Correspondence
    Tel.: +1 312 695 0013; fax: +1 312 695 0047.
    Affiliations
    Preventive Cardiology Center, Departments of Medicine and Preventive Medicine, Division of Cardiology, Northwestern University, The Feinberg School of Medicine, Galter Pavilion, Suite 11-120, 201 East Huron Street, Chicago, IL 60611, USA
    Search for articles by this author

      Abstract

      Background

      Although LDL-cholesterol (LDL-C) remains the target of cholesterol-lowering therapy, high levels of LDL particle numbers better differentiate cardiovascular risk than LDL-C concentrations. Colesevelam HCl, a novel bile acid sequestrant, has also been shown to reduce mean LDL-C by 18% with the maximum dose. The effect of colesevelam HCl on LDL particle number and particle size has not been previously published. LDL particle number and particle size were measured by NMR spectroscopy.

      Methods

      In this multi-center, double-blind, placebo-controlled study, 149 patients with moderate hypercholesterolemia (LDL-C > 160 mg/dL [4.14 mmol/L]; triglycerides < 300 mg/dL [3.39 mmol/L]) were randomized to colesevelam HCl (1.5–3.75 g/d) or placebo for 6 weeks.

      Results

      Colesevelam HCl reduced LDL particle number by 6.8% at a dosage of 3.0 g/d (P = 0.031), and 13.7% (P = 0.0002) at a dosage of 3.75 g/d. Baseline levels of triglycerides or LDL size did not influence changes in LDL particle number. Further, mean LDL particle size increased with colesevelam HCl 3.75 g/d (1.1% increase versus baseline, P < 0.05).

      Conclusion

      For patients with moderate hypercholesterolemia, treatment with colesevelam HCl at the recommended starting dose of 3.75 g/d lowered LDL particle number, and increased mean LDL particle size.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Cromwell W.C.
        • Otvos J.D.
        Low-density lipoprotein particle number and risk for cardiovascular disease.
        Curr Atheroscler Rep. 2004; 6: 381-387
        • Blake G.J.
        • Otvos J.D.
        • Rifai N.
        • Ridker P.M.
        Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women.
        Circulation. 2002; 106: 1930-1937
        • Kuller L.
        • Arnold A.
        • Tracy R.
        • et al.
        Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the Cardiovascular Health Study.
        Arterioscler Thromb Vasc Biol. 2002; 22: 1175-1180
        • Otvos J.D.
        • Shalaurova I.
        • Freedman D.S.
        • Rosenson R.S.
        Effects of pravastatin treatment on lipoprotein subclass profiles and particle size in the PLAC-I trial.
        Atherosclerosis. 2002; 160: 41-48
        • Blake G.J.
        • Albert M.A.
        • Rifai N.
        • Ridker P.M.
        Effect of pravastatin on LDL particle concentration as determined by NMR spectroscopy: a substudy of a randomized placebo controlled trial.
        Eur Heart J. 2003; 24: 1843-1847
        • Davidson M.H.
        • Dillon M.A.
        • Gordon B.
        • et al.
        Colesevelam hydrochloride (cholestagel): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects.
        Arch Intern Med. 1999; 159: 1893-1900
        • Zambon A.
        • Hokanson J.E.
        • Brown B.G.
        • Brunzell J.D.
        Evidence for a new pathophysiological mechanism for coronary artery disease regression: hepatic lipase-mediated changes in LDL density.
        Circulation. 1999; 99: 1959-1964
        • Witztum J.L.
        • Schonfeld G.
        • Weidman S.W.
        • Giese W.E.
        • Dillingham M.A.
        Bile sequestrant therapy alters the compositions of low-density and high-density lipoproteins.
        Metabolism. 1979; 28: 221-229
        • Young S.G.
        • Witztum J.L.
        • Carew T.E.
        • Krauss R.W.
        • Lindgren F.T.
        Colestipol-induced changes in LDL composition and metabolism. II. Studies in humans.
        J Lipid Res. 1989; 30: 225-238
        • Vega G.L.
        • Grundy S.M.
        Hypercholesterolemia with cholesterol-enriched LDL and normal levels of LDL-apolipoprotein B. Effects of the step I diet and bile acid sequestrants on the cholesterol content of LDL.
        Arterioscler Thromb Vasc Biol. 1996; 16: 517-522
      1. The lipid research clinics coronary primary prevention trial results. I. Reduction in incidence of coronary heart disease. JAMA 1984;251:351–64.

        • Brown G.
        • Albers J.J.
        • Fisher L.D.
        • et al.
        Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B.
        N Engl J Med. 1990; 323: 1289-1298