Long-term reduction of C-reactive protein concentration by regular LDL apheresis


      Backround: Increased C-reactive protein (CRP) concentration is an independent risk predictor for coronary heart disease (CHD). A therapeutic reduction of CRP might, therefore, reduce the risk of cardiovascular events. A single LDL apheresis lowers LDL cholesterol by 45–70%, and CRP by 20–65%, however, less is known about the long-term effects of LDL apheresis on CRP levels. Methods: We investigated 34 CHD patients (20 males, 14 females, 52±10 years) on statin therapy who were regularly treated by LDL apheresis because of drug-resistant hypercholesterolemia. Measurements of CRP (ultrasensitive nephelometric assay) were performed before the first apheresis, before a current apheresis (1 or 2 weeks after the last apheresis), and after a current apheresis (treatment period: 5.3±4.2 years, range: 0.25–12.5 years). LDL apheresis was performed by immunoadsorption (n=6), dextran sulfate adsorption (n=13), heparin-induced extracorporal LDL precipitation (HELP, n=9), or direct adsorption of lipoproteins (DALI, n=6). Results: CRP was significantly lower before a current apheresis (median: 0.75 mg/l, range: 0.16–4.33 mg/l) compared to before the first apheresis (median: 0.85 mg/l, range: 0.16–7.02 mg/l; P<0.05). As expected, total and LDL cholesterol were lower before a current apheresis compared to before the initial apheresis while fibrinogen concentration did not differ significantly. Conclusion: Over the period of more than 5 years LDL apheresis slightly, but significantly reduced CRP concentrations in patients with CHD on statin therapy, which may contribute to the stabilization of atherosclerosis in hypercholesterolemic patients treated with LDL apheresis. These results are even more impressive when the known age-related increase in CRP over the treatment period is taken into account.


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        • Ridker P.M.
        • Cushman M.
        • Stampfer M.J.
        • Tracy R.P.
        • Hennekens C.H.
        Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men.
        N. Engl. J. Med. 1997; 336: 973-979
        • Haverkate F.
        • Thompson S.G.
        • Pyke S.D.M.
        • Gallimore J.R.
        • Pepys M.B.
        for the European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Production of C-reactive protein and risk of coronary events in stable and unstable angina.
        Lancet. 1997; 349: 462-466
        • Ross R.
        Atherosclerosis—an inflammatory disease.
        N. Engl. J. Med. 1999; 340: 115-116
        • Pasceri V.
        • Willerson J.T.
        • Yeh E.T.
        Direct proinflammatory effect of C-reactive protein on human endothelial cells.
        Circulation. 2000; 102: 2165-2168
        • Otto C.
        • Schwandt P.
        C-reactive protein concentration is reduced by different types of LDL apheresis.
        Atherosclerosis Suppl. 2001; 2: 81-82
        • Wieland E.
        • Schettler V.
        • Armstrong V.W.
        Highly effective reduction of C-reactive protein in patients with coronary heart disease by extracorporeal low-density lipoprotein apheresis.
        Atherosclerosis. 2002; 162: 187-191
        • Moriarty P.M.
        • Gibson C.A.
        • Shih J.
        • Matias M.S.
        C-reactive protein and other markers of inflammation among patients undergoing HELP LDL apheresis.
        Atherosclerosis. 2001; 158: 495-498
        • Dräger L.J.
        • Julius U.
        • Kraenzle K.
        • et al.
        DALI—the first human whole blood LDL and Lp(a) apheresis system in clinical use: procedure and clinical results.
        Eur. J. Clin. Invest. 1998; 28: 994-1002
        • Richter W.O.
        • Donner M.G.
        • Schwandt P.
        Short- and long-term effects on serum lipoproteins by three different techniques of apheresis.
        Artif. Organs. 1996; 20: 311-317
        • Rifai N.
        • Tracy R.P.
        • Ridker P.M.
        Clinical efficacy of an automated high-sensitivity C-reactive protein assay.
        Clin. Chem. 1999; 45: 2136-2141
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without the use of preparative ultracentrifugation.
        Clin. Chem. 1972; 18: 499-502
        • Ridker P.M.
        • Glynn R.J.
        • Hennekens C.H.
        C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction.
        Circulation. 1998; 97: 2007-2011
        • Ridker P.M.
        • Rifai N.
        • Rose L.
        • Buring J.E.
        • Cook N.R.
        Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events.
        N. Engl. J. Med. 2002; 347: 1557-1565
        • Schuff-Werner P.
        • Gohlke H.
        • Bartmann U.
        • et al.
        The HELP-LDL-apheresis multicentre study, an angiographically assessed trial on the role of LDL-apheresis in the secondary prevention of coronary heart disease. II. Final evaluation of the effect of regular treatment on LDL-cholesterol plasma concentrations and the course of coronary heart disease. The HELP-Study Group. Heparin-induced extra-corporeal LDL-precipitation.
        Eur. J. Clin. Invest. 1994; 24: 724-732
        • Kroon A.A.
        • Aengevaeren W.R.
        • van der Werf T.
        • et al.
        LDL-Apheresis Atherosclerosis Regression Study (LAARS). Effect of aggressive versus conventional lipid lowering treatment on coronary atherosclerosis.
        Circulation. 1996; 93: 1826-1835
        • Mabuchi H.
        • Koizumi J.
        • Shimizu M.
        • et al.
        Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. Hokuriku-FH-LDL-Apheresis Study Group.
        Am. J. Cardiol. 1998; 82: 1489-1495
        • Hutchinson W.L.
        • Koenig W.
        • Fröhlich M.
        • Sund M.
        • Lowe G.D.O.
        Immunoradiometric assay of circulating C-reactive protein: age-related values in the adult general population.
        Clin. Chem. 2000; 46: 934-938
        • Kojima S.
        • Shida M.
        • Yokoyama H.
        Changes in C-reactive protein plasma levels during low-density lipoprotein apheresis.
        Ther. Apheresis. 2003; 7: 431-434
        • Li J.J.
        • Chen M.Z.
        • Chen X.
        • Fang C.H.
        Rapid effects of simvastatin on lipid profile and C-reactive protein in patients with hypercholesterolemia.
        Clin. Cardiol. 2003; 26: 472-476
        • Danesh J.
        • Collins R.
        • Appleby P.
        • Peto R.
        Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies.
        J. Am. Med. Assoc. 1998; 279: 1477-1482