Plasma Coenzyme Q10 Predicts Lipid-lowering Response to High-Dose Atorvastatin

Abstract

Background: Coenzyme Q10 (CoQ10) is a provitamin synthesized via the HMG-CoA reductase pathway, and thus may serve as a potential marker of intrinsic HMG-CoA reductase activity. HMG-CoA reductase inhibitors (statins) decrease CoQ10, although it is unclear whether this is due to reductions in lipoproteins, which transport CoQ10.

Objectives: We evaluated whether baseline plasma CoQ10 concentrations predict the lipid-lowering response to high-dose atorvastatin, and to what extent CoQ10 changes following atorvastatin therapy depend on lipoprotein changes.

Methods: Individuals without dyslipidemia or known cardiovascular disease (n=84) received atorvastatin 80 mg daily for 16 weeks. Blood samples collected at baseline and after 4, 8, and 16 weeks of treatment were assayed for CoQ10.

Results: Individuals with higher baseline CoQ10:LDL-C ratios displayed diminished absolute and percent LDL-C reductions at 8 and 16 weeks of atorvastatin treatment (P<0.001 to 0.01). After 16 weeks of atorvastatin, plasma CoQ10 decreased 45% from 762+/-301 ng/ml to 374+/-150 ng/ml (P<0.001). CoQ10 changes were correlated with LDL-C and apolipoprotein B changes (r=0.27-0.38, P=0.001-0.02), but remained significant when normalized to all lipoproteins. CoQ10 changes were not associated with adverse drug reactions.

Conclusion: Baseline CoQ10:LDL-C ratio was associated with the degree of LDL-C response to atorvastatin. Atorvastatin decreased CoQ10 concentrations in a manner that was not completely dependent on lipoprotein changes. The utility of CoQ10 as a predictor of atorvastatin response should be further explored in patients with dyslipidemia.

Keywords: Coenzyme Q10; HMG CoA-reductase inhibitors; biomarkers; lipids; pharmacology.

Figure 1

CoQ10 Biosynthetic Pathway.

Figure 2. Overview of Data Flow for Study Duration

Abbreviations: LFT, liver function test; ULN, upper limit of normal; CK, creatine kinase; d/c, discontinuation

Figure 3. Changes in CoQ10 Concentrations After 4, 8, and 16 Weeks of Atorvastatin

Each dot represents an individual study participant and the lines represent the mean values. Absolute values of CoQ10 concentrations are shown in panel A. The reduction in CoQ10 relative to baseline is shown in panel B.

Figure 4. Percent (panels A and B) and Absolute (panels C and D) Changes in LDL-C After 8, and 16 Weeks of Atorvastatin According to Baseline CoQ10:LDL-C Ratio

LDL-C values are expressed in mg/dL.

Figure 5. Correlation Between Percent and Absolute Change in CoQ10 Concentrations and LDL-C Concentrations (panels A and C) and Apolipoprotein B Concentrations (panels B and D) at 16 weeks

CoQ10 concentrations expressed as ng/mL, apo-/lipoprotein concentrations expressed as mg/dL.

Figure 6. Normalized CoQ10 Changes in Response to Atorvastatin 80 mg

The ratio of CoQ10 to apo-/lipoprotein concentrations are depicted for each time point (baseline, 8 weeks, and 16 weeks). Percentages reflect the mean of individual percent changes in the normalized CoQ10 concentration from baseline to 16 weeks.