Serum concentration of lipoprotein(a) decreases on treatment with hydrosoluble coenzyme Q10 in patients with coronary artery disease: discovery of a new role1

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Abstract

Objective: To examine the effect of coenzyme Q10 supplementation on serum lipoprotein(a) in patients with acute coronary disease. Study Design: Randomized double blind placebo controlled trial. Subjects and Methods: Subjects with clinical diagnosis of acute myocardial infarction, unstable angina, angina pectoris (based on WHO criteria) with moderately raised lipoprotein(a) were randomized to either coenzyme Q10 as Q-Gel (60 mg twice daily) (coenzyme Q10 group, n=25) or placebo (placebo group, n=22) for a period of 28 days. Results: Serum lipoprotein(a) showed significant reduction in the coenzyme Q10 group compared with the placebo group (31.0% vs 8.2% P<0.001) with a net reduction of 22.6% attributed to coenzyme Q10. HDL cholesterol showed a significant increase in the intervention group without affecting total cholesterol, LDL cholesterol, and blood glucose showed a significant reduction in the coenzyme Q10 group. Coenzyme Q10 supplementation was also associated with significant reductions in thiobarbituric acid reactive substances, malon/dialdehyde and diene conjugates, indicating an overall decrease in oxidative stress. Conclusion: Supplementation with hydrosoluble coenzyme Q10 (Q-Gel) decreases lipoprotein(a) concentration in patients with acute coronary disease.

Introduction

Recent studies indicate that lipoprotein(a) is a genetically determined independent risk factor of premature coronary artery disease (CAD) 1, 2, 3, 4, 5. A few studies 6, 7, 8, 9, 10have also shown that lipoprotein(a) concentrations are higher in South Asians and their siblings living in Great Britain than those found in the indigenous population. Several family studies have demonstrated that lipoprotein(a) is inherited through a major monogenic pattern influenced by other genes. Serum levels of lipoprotein(a) have been shown to correlate well with the presence, severity and lesion score on a coronary angiography, as well as with the occurrence and recurrence of myocardial infarction and cardiac death 11, 12. Apolipoprotein(a), which is a constituent protein of lipoprotein(a), has considerable homology with plasminogen and interferes with fibrinolysis and may predispose thrombosis. It is possible that higher levels of lipoprotein(a) may initiate and promote an atherogenic and thrombogenic state in the body which may be responsible for a higher prevalence of premature CAD and the increased mortality observed among Indians 13, 14, 15. Serum lipoprotein(a) is largely unaffected by environmental factors and maximum levels are reached early in infancy which predisposes CAD at a younger age [16]. Niacin, neomycin, Colestipol, N-acetylcysteine and Danazol are effective but have limitations in reducing lipoprotein(a) concentrations 17, 18. Coenzyme Q10, which is a naturally occurring substance in the body which plays an important role in the electron transport system, also has potent antioxidant and cell membrane stabilizing effects 19, 20. It is present predominantly in the low density lipoprotein cholesterol and possibly in the apo lipoprotein(a) fraction [20]. Coenzyme Q10 has been shown to be cardioprotective [21]and can inhibit human vitronectin receptor expression [22]. In the present study, we examined the effect of a new highly bioavailable form of coenzyme Q10 (Q-Gel), on serum lipoprotein(a) levels in patients with CAD.

Section snippets

Patients and methods

Serum concentrations of lipoprotein(a) were obtained in all the patients admitted in the coronary care units of the Medical Hospital and Research Centre in Moradabad during a 4 month period. Patients were screened using the selection criteria as described earlier [19]. Acute myocardial infarction (AMI) was diagnosed in the presence of a symmetric ST segment elevation of 1 mm from the baseline in limb leads and 2 mm in the chest leads. The diagnosis of AMI was also made in the presence of T wave

Results

We randomized 79 patients with acute CAD to intervention group A (n=27) or placebo group B (n=24). Two patients in each group died. The remaining 28 patients with CAD but lower (<20 mg/dl) or very high (<50 mg/dl) lipoprotein(a) levels were excluded from entry to the study. Mean age (mean±SD) 48.4±0.5 vs 47.6±0.3 years, body mass index, male sex and drug therapy showed no significant difference between the two groups (Table 1). The proportion of patients with previous CAD and current smoking

Discussion

This study shows that treatment with coenzyme Q10 as Q Gel in patients with CAD for 4 weeks was associated with a significant reduction in plasma lipoprotein(a). Both the active and the placebo groups had higher plasma lipoprotein(a) concentrations and a higher risk of developing coronary thrombosis due to CAD at baseline. Furthermore, intervention group showed a significant increase in HDL cholesterol without any effect on total and LDL cholesterol.

Lipoprotein(a) is composed of a low density

Acknowledgements

The authors express their appreciation to Mr. Raj Chopra of Tishcon Corp. Westbury, NY for supplying Q-Gel (coenzyme Q10 softsules, 30 mg) used in this study and also for financial support, and to Dr. Hemmi N. Bhagavan of Hoffmann-LaRoche Inc., Nutley, NJ for his discussions. The authors also thank Nancy Staron and Patricia Kosior for their help with the manuscript.

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    Supported in part by: Tishcon Corp., Westbury NY (USA), Sandoz-Novartis Foundation of Gerontologic Research (Australia), Centre of Nutrition Research, Moradabad (India).

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