Advertisement

Effect of Central Obesity, Low High-Density Lipoprotein Cholesterol and C-Reactive Protein Polymorphisms on C-Reactive Protein Levels During Treatment With Rosuvastatin (10 mg Daily)

      Plasma levels of high-sensitivity C-reactive protein (hsCRP) are an important predictor of cardiovascular disease, and achievement of lower targets of hsCRP with rosuvastatin treatment was associated with improved cardiovascular outcomes. The aim of this study was to examine whether hsCRP levels were related to genetic variants and traditional cardiovascular risk factors in Chinese patients treated with rosuvastatin 10 mg/day. The relations were analyzed between on-treatment plasma hsCRP concentrations and cardiovascular risk factors and 14 single-nucleotide polymorphisms in CRP and other candidate genes. In 281 patients with a median plasma hsCRP level of 0.81 mg/L (interquartile range 0.46 to 1.86), higher hsCRP levels were significantly associated with female gender, greater waist circumference (WC), having diabetes, higher triglycerides, and lower high-density lipoprotein (HDL) cholesterol. Three single-nucleotide polymorphisms (rs1205, 3872G>A and rs2808630, 5237A>G in CRP and rs1169288, I27L in HNF1A) were independently associated with hsCRP levels before and after adjustment for other variables. WC and the CRP rs1205 polymorphism showed the strongest relations with hsCRP, and in multiple regression analysis, gender, WC, diabetes, triglycerides, HDL cholesterol, and the 3 genetic variants explained 35.5% of the variance in hsCRP levels. The 2 CRP polymorphisms, female gender, higher WC, and lower HDL cholesterol were associated with risk for having CRP concentrations ≥1 mg/L. In conclusion, central obesity, low HDL cholesterol, and CRP polymorphisms are major determinants of higher hsCRP levels in Chinese patients receiving treatment with rosuvastatin.
      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 American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ray K.K.
        • Cannon C.P.
        • Cairns R.
        • Morrow D.A.
        • Rifai N.
        • Kirtane A.J.
        • McCabe C.H.
        • Skene A.M.
        • Gibson C.M.
        • Ridker P.M.
        • Braunwald E.
        Relationship between uncontrolled risk factors and C-reactive protein levels in patients receiving standard or intensive statin therapy for acute coronary syndromes in the PROVE IT-TIMI 22 trial.
        J Am Coll Cardiol. 2005; 46: 1417-1424
        • Liem A.H.
        • van de Woestijne A.P.
        • Zwinderman A.H.
        • Visseren F.L.
        • Jukema J.W.
        Determinants of CRP level in statin-treated patients.
        Curr Med Res Opin. 2008; 24: 1065-1068
        • Tomlinson B.
        • Hu M.
        • Lee V.W.
        • Lui S.S.
        • Chu T.T.
        • Poon E.W.
        • Ko G.T.
        • Baum L.
        • Tam L.S.
        • Li E.K.
        ABCG2 polymorphism is associated with the low-density lipoprotein cholesterol response to rosuvastatin.
        Clin Pharmacol Ther. 2010; 87: 558-562
      1. Hu M, Lui SSH, Mak VWL, Chu TTW, Lee VWY, Poon EWM, Tsui TKC, Ko GTC, Baum L, Tam LS, Li EK, Tomlinson B. Pharmacogenetic analysis of lipid responses to rosuvastatin in Chinese patients. Pharmacogenet Genomics. In press.

        • National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
        Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.
        Circulation. 2002; 106: 3143-3421
        • Kathiresan S.
        • Larson M.G.
        • Vasan R.S.
        • Guo C.Y.
        • Gona P.
        • Keaney Jr, J.F.
        • Wilson P.W.
        • Newton-Cheh C.
        • Musone S.L.
        • Camargo A.L.
        • Drake J.A.
        • Levy D.
        • O'Donnell C.J.
        • Hirschhorn J.N.
        • Benjamin E.J.
        Contribution of clinical correlates and 13 C-reactive protein gene polymorphisms to interindividual variability in serum C-reactive protein level.
        Circulation. 2006; 113: 1415-1423
        • Elliott P.
        • Chambers J.C.
        • Zhang W.
        • Clarke R.
        • Hopewell J.C.
        • Peden J.F.
        • Erdmann J.
        • Braund P.
        • Engert J.C.
        • Bennett D.
        • Coin L.
        • Ashby D.
        • Tzoulaki I.
        • Brown I.J.
        • Mt-Isa S.
        • McCarthy M.I.
        • Peltonen L.
        • Freimer N.B.
        • Farrall M.
        • Ruokonen A.
        • Hamsten A.
        • Lim N.
        • Froguel P.
        • Waterworth D.M.
        • Vollenweider P.
        • Waeber G.
        • Jarvelin M.R.
        • Mooser V.
        • Scott J.
        • Hall A.S.
        • Schunkert H.
        • Anand S.S.
        • Collins R.
        • Samani N.J.
        • Watkins H.
        • Kooner J.S.
        Genetic loci associated with C-reactive protein levels and risk of coronary heart disease.
        JAMA. 2009; 302: 37-48
        • Ridker P.M.
        • Pare G.
        • Parker A.
        • Zee R.Y.
        • Danik J.S.
        • Buring J.E.
        • Kwiatkowski D.
        • Cook N.R.
        • Miletich J.P.
        • Chasman D.I.
        Loci related to metabolic-syndrome pathways including LEPR, HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study.
        Am J Hum Genet. 2008; 82: 1185-1192
        • Bailey K.M.
        • Romaine S.P.
        • Jackson B.M.
        • Farrin A.J.
        • Efthymiou M.
        • Barth J.H.
        • Copeland J.
        • McCormack T.
        • Whitehead A.
        • Flather M.D.
        • Samani N.J.
        • Nixon J.
        • Hall A.S.
        • Balmforth A.J.
        Hepatic metabolism and transporter gene variants enhance response to rosuvastatin in patients with acute myocardial infarction: the GEOSTAT-1 study.
        Circ Cardiovasc Genet. 2010; 3: 276-285
        • Lee C.C.
        • You N.C.
        • Song Y.
        • Hsu Y.H.
        • Manson J.
        • Nathan L.
        • Tinker L.
        • Liu S.
        Relation of genetic variation in the gene coding for C-reactive protein with its plasma protein concentrations: findings from the Women's Health Initiative Observational Cohort.
        Clin Chem. 2009; 55: 351-360
        • Teng M.S.
        • Hsu L.A.
        • Wu S.
        • Chang H.H.
        • Chou H.H.
        • Ko Y.L.
        Association between C-reactive protein gene haplotypes and C-reactive protein levels in Taiwanese: interaction with obesity.
        Atherosclerosis. 2009; 204: e64-e69
        • Reiner A.P.
        • Barber M.J.
        • Guan Y.
        • Ridker P.M.
        • Lange L.A.
        • Chasman D.I.
        • Walston J.D.
        • Cooper G.M.
        • Jenny N.S.
        • Rieder M.J.
        • Durda J.P.
        • Smith J.D.
        • Novembre J.
        • Tracy R.P.
        • Rotter J.I.
        • Stephens M.
        • Nickerson D.A.
        • Krauss R.M.
        Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are associated with C-reactive protein.
        Am J Hum Genet. 2008; 82: 1193-1201
        • Eiriksdottir G.
        • Aspelund T.
        • Bjarnadottir K.
        • Olafsdottir E.
        • Gudnason V.
        • Launer L.J.
        • Harris T.B.
        Apolipoprotein E genotype and statins affect CRP levels through independent and different mechanisms: AGES-Reykjavik Study.
        Atherosclerosis. 2006; 186: 222-224
        • Kelley-Hedgepeth A.
        • Lloyd-Jones D.M.
        • Colvin A.
        • Matthews K.A.
        • Johnston J.
        • Sowers M.R.
        • Sternfeld B.
        • Pasternak R.C.
        • Chae C.U.
        Ethnic differences in C-reactive protein concentrations.
        Clin Chem. 2008; 54: 1027-1037
        • Zacho J.
        • Tybjaerg-Hansen A.
        • Jensen J.S.
        • Grande P.
        • Sillesen H.
        • Nordestgaard B.G.
        Genetically elevated C-reactive protein and ischemic vascular disease.
        N Engl J Med. 2008; 359: 1897-1908
        • Nishikawa T.
        • Hagihara K.
        • Serada S.
        • Isobe T.
        • Matsumura A.
        • Song J.
        • Tanaka T.
        • Kawase I.
        • Naka T.
        • Yoshizaki K.
        Transcriptional complex formation of c-Fos, STAT3, and hepatocyte NF-1 alpha is essential for cytokine-driven C-reactive protein gene expression.
        J Immunol. 2008; 180: 3492-3501
        • Armendariz A.D.
        • Krauss R.M.
        Hepatic nuclear factor 1-alpha: inflammation, genetics, and atherosclerosis.
        Curr Opin Lipidol. 2009; 20: 106-111
        • Brooks G.C.
        • Blaha M.J.
        • Blumenthal R.S.
        Relation of C-reactive protein to abdominal adiposity.
        Am J Cardiol. 2010; 106: 56-61
        • Miller D.T.
        • Zee R.Y.
        • Suk Danik J.
        • Kozlowski P.
        • Chasman D.I.
        • Lazarus R.
        • Cook N.R.
        • Ridker P.M.
        • Kwiatkowski D.J.
        Association of common CRP gene variants with CRP levels and cardiovascular events.
        Ann Hum Genet. 2005; 69: 623-638
        • Ridker P.M.
        • Danielson E.
        • Fonseca F.A.
        • Genest J.
        • Gotto Jr, A.M.
        • Kastelein J.J.
        • Koenig W.
        • Libby P.
        • Lorenzatti A.J.
        • Macfadyen J.G.
        • Nordestgaard B.G.
        • Shepherd J.
        • Willerson J.T.
        • Glynn R.J.
        Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial.
        Lancet. 2009; 373: 1175-1182
        • Cushman M.
        • McClure L.A.
        • Lakoski S.G.
        • Jenny N.S.
        Eligibility for statin therapy by the JUPITER trial criteria and subsequent mortality.
        Am J Cardiol. 2010; 105: 77-81