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First comprehensive paper on statins' adverse effects released
January 27, 2009Provides evidence for reported side effects including muscle and cognitive problems
A paper co-authored by Beatrice Golomb, MD, PhD, associate professor of medicine at the University of California, San Diego School of Medicine and director of UC San Diego's Statin Study group cites nearly 900 studies on the adverse effects of HMG-CoA reductase inhibitors (statins), a class of drugs widely used to treat high cholesterol.
The result is a review paper, currently published in the on-line edition of American Journal of Cardiovascular Drugs, that provides the most complete picture to date of reported side effects of statins, showing the state of evidence for each. The paper also helps explain why certain individuals have an increased risk for such adverse effects.
"Muscle problems are the best known of statin drugs' adverse side effects," said Golomb. "But cognitive problems and peripheral neuropathy, or pain or numbness in the extremities like fingers and toes, are also widely reported." A spectrum of other problems, ranging from blood glucose elevations to tendon problems, can also occur as side effects from statins.
The paper cites clear evidence that higher statin doses or more powerful statins - those with a stronger ability to lower cholesterol - as well as certain genetic conditions, are linked to greater risk of developing side effects.
"Physician awareness of such side effects is reportedly low," Golomb said. "Being vigilant for adverse effects in their patients is necessary in order for doctors to provide informed treatment decisions and improved patient care."
The paper also summarizes powerful evidence that statin-induced injury to the function of the body's energy-producing cells, called mitochondria, underlies many of the adverse effects that occur to patients taking statin drugs.
Mitochondria produce most of the oxygen free radicals in the body, harmful compounds that "antioxidants" seek to protect against. When mitochondrial function is impaired, the body produces less energy and more "free radicals" are produced. Coenzyme Q10 ("Q10") is a compound central to the process of making energy within mitochondria and quenching free radicals. However, statins lower Q10 levels because they work by blocking the pathway involved in cholesterol production - the same pathway by which Q10 is produced. Statins also reduce the blood cholesterol that transports Q10 and other fat-soluble antioxidants.
"The loss of Q10 leads to loss of cell energy and increased free radicals which, in turn, can further damage mitochondrial DNA," said Golomb, who explained that loss of Q10 may lead to a greater likelihood of symptoms arising from statins in patients with existing mitochondrial damage - since these people especially rely on ample Q10 to help bypass this damage. Because statins may cause more mitochondrial problems over time - and as these energy powerhouses tend to weaken with age-new adverse effects can also develop the longer a patient takes statin drugs.
"The risk of adverse effects goes up as age goes up, and this helps explain why," said Golomb. "This also helps explain why statins' benefits have not been found to exceed their risks in those over 70 or 75 years old, even those with heart disease." High blood pressure and diabetes are linked to higher rates of mitochondrial problems, so these conditions are also clearly linked to a higher risk of statin complications, according to Golomb and co-author Marcella A. Evans, of UC San Diego and UC Irvine Schools of Medicine.
The connection between statins' antioxidant properties and mitochondrial risk helps explain a complicated finding that statins can protect against the very same problems, in some people, to which they may predispose others - problems such as muscle and kidney function or heart arrhythmia.
University of California - San Diego
"Muscle problems are the best known of statin drugs' adverse side effects," said Golomb. "But cognitive problems and peripheral neuropathy, or pain or numbness in the extremities like fingers and toes, are also widely reported." A spectrum of other problems, ranging from blood glucose elevations to tendon problems, can also occur as side effects from statins.
The paper cites clear evidence that higher statin doses or more powerful statins - those with a stronger ability to lower cholesterol - as well as certain genetic conditions, are linked to greater risk of developing side effects.
"Physician awareness of such side effects is reportedly low," Golomb said. "Being vigilant for adverse effects in their patients is necessary in order for doctors to provide informed treatment decisions and improved patient care."
The paper also summarizes powerful evidence that statin-induced injury to the function of the body's energy-producing cells, called mitochondria, underlies many of the adverse effects that occur to patients taking statin drugs.
Mitochondria produce most of the oxygen free radicals in the body, harmful compounds that "antioxidants" seek to protect against. When mitochondrial function is impaired, the body produces less energy and more "free radicals" are produced. Coenzyme Q10 ("Q10") is a compound central to the process of making energy within mitochondria and quenching free radicals. However, statins lower Q10 levels because they work by blocking the pathway involved in cholesterol production - the same pathway by which Q10 is produced. Statins also reduce the blood cholesterol that transports Q10 and other fat-soluble antioxidants.
"The loss of Q10 leads to loss of cell energy and increased free radicals which, in turn, can further damage mitochondrial DNA," said Golomb, who explained that loss of Q10 may lead to a greater likelihood of symptoms arising from statins in patients with existing mitochondrial damage - since these people especially rely on ample Q10 to help bypass this damage. Because statins may cause more mitochondrial problems over time - and as these energy powerhouses tend to weaken with age-new adverse effects can also develop the longer a patient takes statin drugs.
"The risk of adverse effects goes up as age goes up, and this helps explain why," said Golomb. "This also helps explain why statins' benefits have not been found to exceed their risks in those over 70 or 75 years old, even those with heart disease." High blood pressure and diabetes are linked to higher rates of mitochondrial problems, so these conditions are also clearly linked to a higher risk of statin complications, according to Golomb and co-author Marcella A. Evans, of UC San Diego and UC Irvine Schools of Medicine.
The connection between statins' antioxidant properties and mitochondrial risk helps explain a complicated finding that statins can protect against the very same problems, in some people, to which they may predispose others - problems such as muscle and kidney function or heart arrhythmia.
University of California - San Diego
Statins Current Events and Statins News RSSWidely used cholesterol-lowering drug may prevent progression
Simvastatin, a commonly used, cholesterol-lowering drug, may prevent Parkinson's disease from progressing further. Neurological researchers at Rush University Medical Center conducted a study examining the use of the FDA-approved medication in mice with Parkinson's disease and found that the drug successfully reverses the biochemical, cellular and anatomical changes caused by the disease.
Statins show dramatic drug and cell dependent effects in the brain
Besides their tremendous value in treating high cholesterol and lowering the risk of heart disease, statins have also been reported to potentially lower the risks of other diseases, such as dementia.
Cholesterol-lowering medicines may be effective against cancer
Statins lower cholesterol by blocking certain enzymes involved in our metabolism.
Adding ezetimibe to atorvastatin improves lipid control
Adding ezetimibe to atorvastatin significantly boosted the attainment of lipid targets as specified by both Canadian and European guidelines in elderly patients aged 65 and older and the combination produced superior results than simply increasing the dose of atorvastatin alone.
Use of statins favors the wealthy, creating new social disparities in cholesterol
Since the introduction of statins to treat high cholesterol, the decline in lipid levels experienced by the wealthy has been double that experienced by the poor.
Women with Atrial Fibrillation Are at Significantly Higher Risk of Stroke and Death Compared to Men and Receive Less Attention
Even though the incidence of atrial fibrillation is higher in men than women, a review of past studies and medical literature completed by cardiac experts at Rush University Medical Center shows that women are more likely than men to experience symptomatic attacks, a higher frequency of recurrences, and significantly higher heart rates during atrial fibrillation, which increases the risk of stroke.
Pre-hospital organization: The first links in the chain of survival for heart attack patients
Mortality rate following a heart attack has fallen by more than 50% in Europe over the past 25 years. However, because only minor advances in the medical treatment of AMI are expected over the next decade, it is through organisational changes in the pre-hospital phase that mortality rate will continue this decline to below 5%.
Fatostatin' is a turnoff for fat genes
A small molecule earlier found to have both anti-fat and anti-cancer abilities works as a literal turnoff for fat-making genes, according to a new report in the August 28th issue of the journal Chemistry and Biology, a Cell Press journal.
Study reveals mounting evidence of fish oil's heart health benefits
There is mounting evidence that omega-3 fatty acids from fish or fish oil supplements not only help prevent cardiovascular diseases in healthy individuals, but also reduce the incidence of cardiac events and mortality in patients with existing heart disease.
New tool finds best heart disease and stroke treatments for patients with diabetes
Researchers from North Carolina State University and Mayo Clinic have developed a computer model that medical doctors can use to determine the best time to begin using statin therapy in diabetes patients to help prevent heart disease and stroke.
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