Neither plasma coenzyme Q10 concentration, nor its decline during pravastatin therapy, is linked to recurrent cardiovascular disease events: A prospective case–control study from the LIPID study


      Statins decrease LDL cholesterol and the risk of atherosclerotic cardiovascular disease (CVD). They also decrease coenzyme Q10 (CoQ10), an effect that may negate some of the statin benefit on CVD. We examined the relationship between plasma CoQ10 concentration and CVD in a prospective case–control study of the effect of pravastatin. Plasma samples from 250 LIPID trial patients who over 6 years suffered a recurrent CVD event (CVD death, nonfatal MI or stroke) and 250 matched controls who remained event-free for the same duration of follow-up were assayed for CoQ10 and lipids (cholesterol and cholesterylesters). Mean plasma CoQ10 concentrations were significantly lower in pravastatin-treated patients than in those assigned placebo (0.51 versus 0.60 μmol/L, P = 0.006), and there was a moderate correlation between CoQ10 and common cholesterylesters (Pearson correlation coefficients in patients randomised to placebo, range r = 0.42–0.63). Univariate conditional logistic regression did not suggest any relationship between plasma CoQ10 and the risk of future CVD events (odds ratio 1.18; 95% CI 0.74–1.87; P = 0.49). Instead, we observed a reduction in the rate of recurrent CVD events with increasing ratio of plasma cholesterylarachidonate to cholesteryllinoleate. This study confirms that pravastatin lowers plasma CoQ10 concentrations, but this does not appear to predict the risk of recurrent CVD events.


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


        • Scandinavian Simvastatin Survival Study Group
        Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).
        Lancet. 1994; 344: 1383-1389
        • The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group
        Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels.
        New Engl J Med. 1998; 339: 1349-1357
        • Heart Protection Study Collaborative Group
        MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial.
        Lancet. 2002; 360: 7-22
        • Wascher T.C.
        Long-term statin safety and efficacy in secondary prevention: can combination therapy improve outcomes?.
        Atheroscler Suppl. 2003; 4: 11-16
        • Liao J.K.
        Beyond lipid lowering: the role of statins in vascular protection.
        Int J Cardiol. 2002; 86: 5-18
        • Dallner G.
        • Stocker R.
        Coenzyme Q10.
        in: Coates P. Blackman M.R. Cragg G. Levine M. Moss J. White P. Encyclopedia of Dietary Supplements. Marcel Dekker, New York2005: 121-131
        • Grünler J.
        • Ericsson J.
        • Dallner G.
        Branch-point reactions in the biosynthesis of cholesterol, dolichol, ubiquinone and prenylated proteins.
        Biochim Biophys Acta. 1994; 1212: 259-277
        • Witting P.K.
        • Pettersson K.
        • Letters J.
        • et al.
        Anti-atherogenic effect of coenzyme Q10 in apolipoprotein E gene knockout mice.
        Free Radic Biol Med. 2000; 29: 295-305
        • Hodgson J.M.
        • Watts G.F.
        • Playford D.A.
        • et al.
        Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes.
        Eur J Clin Nutr. 2002; 56: 1137-1142
        • Watts G.F.
        • Playford D.A.
        • Croft K.D.
        • et al.
        Coenzyme Q10 improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus.
        Diabetologia. 2002; 45: 420-426
        • Raitakari O.T.
        • McCredie R.J.
        • Witting P.
        • et al.
        Coenzyme Q improves LDL resistance to ex vivo oxidation but does not enhance endothelial function in hypercholesterolemic young adults.
        Free Radic Biol Med. 2000; 28: 1100-1105
        • Bellosta S.
        • Paoletti R.
        • Corsini A.
        Safety of statins: focus on clinical pharmacokinetics and drug interactions.
        Circulation. 2004; 109: III50-III57
        • Folkers K.
        • Langsjoen P.
        • Willis R.
        • et al.
        Lovastatin decreases coenzyme Q levels in humans.
        Proc Natl Acad Sci USA. 1990; 87: 8931-8934
        • Ghirlanda G.
        • Oradei A.
        • Manto A.
        • et al.
        Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study.
        J Clin Pharmacol. 1993; 33: 226-229
        • Watts G.F.
        • Castelluccio C.
        • Rice-Evans C.
        • et al.
        Plasma coenzyme Q (ubiquinone) concentrations in patients treated with simvastatin.
        J Clin Pathol. 1993; 46: 1055-1057
        • The LIPID Study Group
        Design features and baseline characteristics of the LIPID (long-term intervention with pravastatin in ischemic disease) study: a randomized trial in patients with previous acute myocardial infarction and/or unstable angina pectoris.
        Am J Cardiol. 1995; 76: 474-479
        • LIPID Study Group
        Long-term effectiveness and safety of pravastatin in 9014 patients with coronary heart disease and average cholesterol concentrations: the LIPID trial follow-up.
        Lancet. 2002; 359: 1379-1387
        • Gay C.A.
        • Stocker R.
        Simultaneous determination of coenzyme Q10, cholesterol, and major cholesterylesters in human blood plasma.
        Methods Enzymol. 2004; 378: 162-169
        • Marschner I.C.
        • Colquhoun D.
        • Simes R.J.
        • et al.
        • LIPID Study Investigators
        Long-term risk stratification for survivors of acute coronary syndromes. Results from the long-term intervention with pravastatin in ischemic disease (LIPID) study.
        J Am Coll Cardiol. 2001; 38: 56-63
        • Tomasetti M.
        • Alleva R.
        • Solenghi M.D.
        • et al.
        Distribution of antioxidants among blood components and lipoproteins: significance of lipids/CoQ10 ratio as a possible marker of increased risk for atherosclerosis.
        Biofactors. 1999; 9: 231-240
        • Simes J.R.
        • Marschner I.C.
        • Hunt D.M.
        • et al.
        Relationship between lipid levels and clinical outcomes in the long-term intervention with pravastatin in ischemic disease (LIPID) trial: to what extent is the reduction in coronary events with pravastatin explained by on-study lipid levels?.
        Circulation. 2002; 105: 1162-1169
        • Sinzinger H.
        • Wolfram R.
        • Peskar B.A.
        Muscular side effects of statins.
        J Cardiovasc Pharmacol. 2002; 40: 163-171
        • Nakahara K.
        • Kuriyama M.
        • Sonoda Y.
        • et al.
        Myopathy induced by HMG-CoA reductase inhibitors in rabbits: a pathological, electrophysiological, and biochemical study.
        Toxicol Appl Pharmacol. 1998; 152: 99-106
        • Thompson P.D.
        • Clarkson P.
        • Karas R.H.
        Statin-associated myopathy.
        JAMA. 2003; 289: 1681-1690
        • Paiva H.
        • Thelen K.M.
        • Coster R.V.
        • et al.
        High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial.
        Clinical Pharmacol Ther. 2005; 78: 60-68
        • Sacks F.M.
        • Pfeffer M.A.
        • Moye L.A.
        • et al.
        The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and recurrent events trial investigators.
        New Engl J Med. 1996; 335: 1001-1009
        • Silver M.A.
        • Langsjoen P.H.
        • Szabo S.
        • et al.
        Effect of atorvastatin on left ventricular diastolic function and ability of coenzyme Q10 to reverse that dysfunction.
        Am J Cardiol. 2004; 94: 1306-1310
        • Mortensen S.A.
        Overview on coenzyme Q10 as adjunctive therapy in chronic heart failure. Rationale, design and end-points of “Q-symbio”—a multinational trial.
        Biofactors. 2003; 18: 79-89
        • Stocker R.
        • Keaney Jr., J.F.
        The role of oxidative modifications in atherosclerosis.
        Physiol Rev. 2004; 84: 1381-1478
        • Colquhoun D.M.
        • Jackson R.
        • Walters M.
        • et al.
        Effects of simvastatin on blood lipids, vitamin E, coenzyme Q10 levels and left ventricular function in humans.
        Eur J Clin Invest. 2005; 35: 251-258
        • Stocker R.
        • Bowry V.W.
        • Frei B.
        Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does α-tocopherol.
        Proc Natl Acad Sci USA. 1991; 88: 1646-1650
        • Dwight J.F.
        • Mendes Ribeiro A.C.
        • Hendry B.M.
        Effects of HMG-CoA reductase inhibition on erythrocyte membrane cholesterol and acyl chain composition.
        Clin Chim Acta. 1996; 256: 53-63
        • Hrboticky N.
        • Tang L.
        • Zimmer B.
        • et al.
        Lovastatin increases arachidonic acid levels and stimulates thromboxane synthesis in human liver and monocytic cell lines.
        J Clin Invest. 1994; 93: 195-203
        • Rise P.
        • Marangoni F.
        • Galli C.
        Regulation of PUFA metabolism: pharmacological and toxicological aspects.
        Prostaglandins Leukot Essent Fatty Acids. 2002; 67: 85-89
        • Ohrvall M.
        • Berglund L.
        • Salminen I.
        • et al.
        The serum cholesterol ester fatty acid composition but not the serum concentration of alpha tocopherol predicts the development of myocardial infarction in 50-year-old men: 19 years follow-up.
        Atherosclerosis. 1996; 127: 65-71
        • De Lorgeril M.
        • Salen P.
        Fish and N-3 fatty acids for the prevention and treatment of coronary heart disease: nutrition is not pharmacology.
        Am J Med. 2002; 112: 316-319