Heart failure (HF) is one of the most common causes of death in Western society. Recent
results underscore the utility of coenzyme Q10 (CoQ10) addition to standard medications in order to reduce mortality and to improve quality
of life and functional capacity in chronic heart failure (CHF). The rationale for
CoQ10 supplementation in CHF is two-fold. One is the well-known role of CoQ10 in myocardial bioenergetics, and the second is its antioxidant property. Redox balance
is also improved by oral supplementation of CoQ10, and this effect contributes to enhanced endothelium-dependent relaxation. Previous
reports have shown that CoQ10 concentration is decreased in myocardial tissue in CHF and by statin therapy, and
the greater the CoQ10 deficiency the more severe is the cardiocirculatory impairment. In patients with
CHF and hypercholesterolaemia being treated with statins, the combination of CoQ10 with a statin may be useful for two reasons: decreasing skeletal muscle injury and
improving myocardial function. Ubiquinol, the active reduced form of CoQ10, presents higher bioavailability than the oxidised form ubiquinone, and should be
the preferred form to be added to a statin. The combination ezetimibe/simvastatin
may have advantages over single statins. Since ezetimibe reduces absorption of cholesterol
and does not affect CoQ10 synthesis in the liver, the impact of this combination on CoQ10 tissue levels will be much less than that of high dose statin monotherapy at any
target low density lipoprotein-cholesterol (LDL-C) level to be reached. This consideration
makes the ezetimibe/statin combination the ideal LDL-lowering agent to be combined
with ubiquinol in CHF patients. However, particular caution is advisable with the
use of strategies of extreme lowering of cholesterol that may negatively impact on
myocardial function. All in all there is a strong case for considering co-administration
of ubiquinol with statin therapy in patients with depressed or borderline myocardial
function.
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 accessOne-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 Heart, Lung and CirculationAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Clinical epidemiology of heart failure.Heart. 2007; 93: 1137-1146
- National and regional trends in heart failure hospitalization and mortality rates for Medicare beneficiaries, 1998–2008.JAMA. 2011; 306: 1669-1678
- Cardiovascular disease in Europe — epidemiological update 2015.Eur Heart J. 2015; 36: 2696-2705
- Hypertension prevalence, awareness, treatment and control in Germany 1998 to 2008-11.J Hum Hypertens. 2015; 29: 247-253
- BNP-guided vs symptom-guided heeart failure therapy: The Trial of intensified vs standard medical therapy in elderly patients with congestive heart failure (TIME-CHF) randomized trial.JAMA. 2009; 301: 383-392
- 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.Eur Heart J. 2016; 37: 2129-22005
- Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.New Engl J Med. 2003; 348: 1309-1321
- Ivabradine and outcomes in chronic heart failure (SHIFT): a randomized placebo-controlled study.Lancet. 2010; 376: 875-885
- Aldosterone receptor antagonists: current perspectives and therapies.Vasc Health Risk Manag. 2013; 9: 321-331
- Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue.J Thorac Cardiovasc Surg. 2005; 129: 25-32
- Deficiency of coenzyme Q10 in human heart disease-part II.Int J Vit Nutr Res. 1972; 42: 413-434
- Regulatory aspects of coenzyme q metabolism.Free Radic Res. 2002; 36: 437-443
- Quinone-responsive multiple respiratory chain dysfunction due to widespread Coenzyme Q10 deficiency.Lancet. 2000; 356: 391-395
- Deficiency of Coenzyme Q10 in human heart disease-part II.Int J Vit Nutr Res. 1972; 42: 413-434
- Assay of coenzyme Q10 in plasma by a single dilution step.Anal Biochem. 2002; 305: 49-54
- Long-term coenzyme Q10 therapy: a major advance in the management of resistant myocardial failure.Drugs Exp Clin Res. 1985; 11: 581-593
- Plasma ubiquinone to ubiquinol ratio in patients with hepatitis, cirrhosis and hepatoma, and in patients treated with percutaneous transluminal coronary reperfusion.Biofactors. 1999; 9: 241-246
- Long-term efficacy and safety of coenzyme Q10 therapy for idiopathic dilated cardiomyopathy.Am J Cardiol. 1990; 65: 521-523
- Overview of the use of CoQ10 in cardiovascular disease.Biofactors. 1999; 9: 273-284
- Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure.J Am Coll Cardiol. 1999; 33: 1549-1552
- The effect of coenzyme Q in patients with congestive heart failure.Ann Int Med. 2000; 132: 636-640
- Lack of effect of coenzyme Q10 on left ventricular function in patients with congestive heart failure.J Am Coll Cardiol. 2000; 35: 816-817
- Coenzyme Q10 and exercise training in chronic heart failure.Eur Heart J. 2006; 27: 2675-2678
- Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis.Am J Clin Nutr. 2013; 97: 268-275
- The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure. Results from Q-SYMBIO: a randomized double-blind trial.JACC Heart Fail. 2014; 2: 641-649
- Effect of coenzyme Q10 in Europeans with chronic heart failure: a sub-group analysis of the Q-SYMBIO randomized double-blind trial.Cardiol J. 2019; 26: 147-156
- Oxidative stress and endothelial dysfunction in heart failure.Congest Heart Fail. 2002; 8: 165-172
- Coenzyme Q versus hypertension: does coenzyme Q10 decrease endothelial superoxide generation?.Med Hypotheses. 1999; 53: 300-304
- Oxidation of ubiquinol by peroxynitrite: implications forprotection of mitochondria against nitrosative damage.J Biochem. 2000; 349: 35-42
- Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure.Circulation. 1998; 98: 2709-2715
- Low intensity exercise training in patients with chronic heart failure.J Am Coll Cardiol. 1995; 26: 975-982
- Effect of coenzyme Q10 administration on endothelial function and extracellular superoxide dismutase in patients with ischemic heart disease.Eur Heart J. 2007; 28: 2249-2255
- Plasma lipophilic antioxidants and malondialdehyde in congestive heart failure patients: relationship to disease severity.Free Radic Biol Med. 2002; 32: 148-152
- Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease.Circulation. 2001; 104: 2673-2678
- A study on the interactions between coenzyme Q10 and superoxide anion. Could ubiquinones mimic superoxide dismutase (SOD)?.Res Chem Intermed. 2000; 26: 269-282
- Extracellular superoxide dismutase and cardiovascular disease.Cardiovasc Res. 2002; 55: 239-249
- Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells.Int J Biochem Cell Biol. 2005; 37: 1208-1218
- Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).Lancet. 1994; 344: 1383-1389
- FDA adverse event reports on statin-associated rhabdomyolysis.Ann Pharmacother. 2002; 36: 288-295
- Statin-associated myopathy.JAMA. 2003; 289: 1681-1690
FDA drug safety communication: new restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury (https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-new-restrictions-contraindications-and-dose-limitations-zocor).
- Lovastatin decreases coenzyme Q levels in humans.Proc Natl Acad Sci USA. 1990; 87: 8931-8934
- Comparison of effects of pitavastatin and atorvastatin on plasma coenzyme Q10 in heterozygous familial hypercholesterolemia: results from a crossover study.Clin Pharmacol Ther. 2008; 83: 73-739
- High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial.Clin Pharmacol Ther. 2005; https://doi.org/10.1016/j.clpt.2005.03.006
- Statin-associated cardiomyopathy responds to statin withdrawal and administration of coenzyme Q10.Perm J. 2019; (Accepted 2019)
- Characterization of mammalian selenoprotein O: a redox-active mitochondrial protein.PLoS One. 2014; 21e95518
- Analysis of oligomerization properties of heme A synthase provides insights into its function in eukaryocytes.J Biol Chem. 2016; 291: 10411-10425
- In vivo and in vitro characterization of skeletal muscle metabolism in patients with statin-induced adverse effects.Arthritis Rheum. 2006; 55 (17): 551-557
- Bioenergetic and antioxidant properties of coenzyme Q10: recent developments.Mol Biotechnol. 2007; 37: 31-37
- Regulatory aspects of coenzyme Q metabolism.Free Radic Res. 2002; 36: 437-443
- Coenzyme Q is an obligatory cofactor for uncoupling protein function.Nature. 2000; 408: 609-613
- Statin adverse effects: a review of the literature and evidence for a mitochondrial mechanism.Am J Cardiovasc Drugs. 2008; 8: 373-418
- Rosuvastatin in older patients with chronic heart failure.N Engl J Med. 2007; 357: 2248-2261
- Why did high-dose rosuvastatin not improve cardiac remodeling in chronic heart failure? Mechanistics insights from the UNIVERSE study.Int J Cardiol. 2011; 146: 404-407
- Ezetimibe added to statin therapy after acute coronary syndromes.N Engl J Med. 2015; 372: 2387-2397
- Efficacy and safety of evolocumab in reducing lipids and cardiovascular events.N Engl J Med. 2015; 372: 1500-1509
- Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.N Engl J Med. 2015; 372: 1489-1499
- Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial.Lancet. 2017; 390: 1962-1971
- Ubiquinol-10 and total peroxyl radical trapping capacity of LDL lipoproteins during aging: the effect of Q10 supplementation.Mol Aspects Med. 1997; : S113-S120
- Association between serum level of ubiquinol and NT-proBNP, a marker of chronic heart failure, in healthy elderly subjects.Biofactors. 2015; 41: 35-43
Article info
Publication history
Published online: September 16, 2019
Accepted:
August 16,
2019
Received in revised form:
July 1,
2019
Received:
October 19,
2017
Identification
Copyright
© 2019 Published by Elsevier B.V. on behalf of Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
