RESEARCH - Genetic risk factors for statin myopathy found; coenzyme Q10, carnitine supplements might help

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Genetic risk factors for statin myopathy found; coenzyme Q10, carnitine

supplements might help

Rheumawire

Oct 22, 2004

Janis

San , TX - Statins are increasingly important in rheumatology as

clinicians work out ways to reduce the high risk of cardiovascular

disease associated with rheumatoid arthritis (RA) and other rheumatoid

conditions. Serious myopathies have been reported in only 0.1% to 0.2%

of patients treated with statins, but milder myalgias have been reported

in up to 6% of patients. Presentations at the American College of

Rheumatology 2004 meeting point to several genetic risk factors that may

trigger myopathies in susceptible patients.

Dr Wortmann (University of Oklahoma College of Medicine, Tulsa)

reported that muscle biopsies or tests of blood samples from more than

100 patients who developed statin myopathies showed that such patients

are 11 times more likely to be heterozygous carriers for carnitine

palmitoyltransferase (CPT) II deficiency and 20 times more likely to be

carriers for McArdle's disease (glycogen storage disease type V) and

have 4 times the usual rate of myoadenylate deaminase deficiency [1].

" Patients with statin-induced myopathies are at increased risk for

having underlying metabolic muscle diseases and, in some cases, carrier

status alone appears to contribute to the increased risk, " Wortmann

said.

" We hypothesized that the prevalence of combined or single inherited

metabolic gene defects would be higher among patients who suffer from

statin myopathies than would be expected in the general population.

Furthermore, since manifesting carriers for metabolic myopathies exist,

we expected that symptoms in carriers may also be triggered by statins, "

Wortmann said. " People with these defects are usually asymptomatic until

forced to depend on the metabolic pathway with the defect in it. "

The cholesterol-lowering drugs are thought to cause that type of

metabolic shift. " We think the downstream metabolic changes from

blocking cholesterol may trigger the myopathies in susceptible

individuals because they alter components the cell needs to manage

energy, " Wortmann said.

Wortmann and colleagues analyzed muscle biopsy and/or blood samples from

132 patients who presented with statin myopathies. " Thirty-six percent

of patients had at least 1 genetic abnormality, and 30% had multiple

abnormalities, " Wortmann said. More than half of the muscle biopsies

evaluated for CPT II activity also had a secondary deficiency, 31% had

carnitine abnormalities, and one third had lipid-storage abnormalities.

Although plasma creatine kinase (CK) elevations have been associated

with statin-related problems, Wortmann said that this is not always the

case. He found that 75% of patients with a 10-fold elevation of plasma

CK had evidence for a defined underlying metabolic myopathy but that

some affected individuals had normal plasma CK.

Nearly half of the samples analyzed had coenzyme Q10 (ubiquinone) levels

2 to 4 standard deviations below normal. Statins inhibit the enzyme

HMG-CoA reductase before the final formation of cholesterol in the

mevalonate pathway, and this same pathway is used to synthesize coenzyme

Q10. The result can be a deficit in the amount of coenzyme Q10 needed

for optimal heart and skeletal muscle function.

The link between statin use and reduction in coenzyme Q10 levels has

also been well studied by drug developers, and in fact 2 patents were

issued to Merck in 1990 for combination statin/coenzyme Q10

formulations. One was meant " to counteract

HMG-CoA-reductase-inhibitor-associated skeletal muscle myopathy [2]. The

other was for " counteracting HMG-CoA-reductase-inhibitor-associated

elevated transaminase levels " through " the adjunct administration of an

effective amount of a HMG-CoA-reductase inhibitor and an effective

amount of coenzyme Q10 " [3].

" In addition to coenzyme Q10 supplementation, which has been recommended

for treatment of statin myopathy and which some patients do respond to,

these data provide a rationale for consideration of the use of carnitine

in these patients, " Wortmann said. " For patients who do not respond to

coenzyme Q10, I would suggest the use of carnitine. "

Sources

Vladutiu G, Isackson P, Wortmann R. Metabolic muscle

disorders and cholesterol-lowering drugs. American College of

Rheumatology 2004 meeting, October 16-21, 2004; San , TX;

Abstract 1784.

US Patent 4 933 165. June 12, 1990. Coenzyme Q.sub.10

with HMG-CoA reductase inhibitors. A pharmaceutical composition and

method of counteracting HMG-CoA reductase inhibitor-associated myopathy

is disclosed. The method comprises the adjunct administration of an

effective amount of an HMG-CoA reductase inhibitor and an effective

amount of coenzyme Q.sub.10. Inventors: Brown MS (Dallas, TX). Assignee:

Merck & Co Inc (Rahway, NJ).

US Patent 4 929 437. May 29, 1990. Coenzyme Q sub 10

with HMG-CoA reductase inhibitors. A pharmaceutical composition and

method of counteracting HMG-CoA reductase inhibitor-associated elevated

transaminase levels is disclosed. The method comprises the adjunct

administration of an effective amount of an HMG-CoA reductase inhibitor

and an effective amount of coenzyme Q sub10. Inventors: Tobert JA

(Maplewood, NJ). Assignee: Merck & Co Inc (Rahway, NJ).

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org