Statins stimulate atherosclerosis and heart failure: pharmacological mechansisms (Okuyama H, et al.)
In contrast to the current belief that cholesterol reduction with statins decreases atherosclerosis, a Japanese group of researchers revealed in Expert Review of Clinical Pharmacology that statins might in fact be detrimental to heart health for a number of reasons, including inhibiting Vitamin K2 synthesis.
Statins are a class of medications called 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. These drugs block a critical step in the production of LDL cholesterol in the liver, thereby reducing the blood levels of LDL cholesterol. Aside from lowering LDL, statins reduce inflammation and promote health of the lining of the blood vessels. Currently, the statin class of drugs is collectively the most commonly prescribed class of medication used to treat high LDL cholesterol. In general, statins were recognized as safe and well tolerated.
The researchers present a perspective that statins may be causative in coronary artery calcification and can function as mitochondrial toxins that impair muscle function in the heart and blood vessels through the depletion of coenzyme Q10 and ‘heme A’, and thereby ATP generation. Further, statins inhibit the synthesis of vitamin K2, the cofactor for matrix Gla-protein activation, which in turn protects arteries from calcification. In addition, statins inhibit the biosynthesis of selenium-containing proteins, one of which is glutathione peroxidase serving to suppress peroxidative stress. An impairment of selenoprotein biosynthesis may be a factor in congestive heart failure, reminiscent of the dilated cardiomyopathies seen with selenium deficiency.
“Thus, the epidemic of heart failure and atherosclerosis that plagues the modern world may paradoxically be aggravated by the pervasive use of statin drugs,” the researchers wrote. “We propose that current statin treatment guidelines be critically reevaluated.”
“For any prescription drug, the potential benefits to health must be balanced against potential risks,” commented Dr. Katarzyna Maresz, president of the International Science and Health Foundation, explaining that in addition to observational data suggesting a strong link between menaquinone (MK, vitamin K2) intake and cardiovascular (CV) health, but not phylloquinone (vitamin K1), a recently published three-year clinical study by Knapen et al. showed that long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness. “By inhibiting vitamin K2 synthesis, statins are disabling an important protection for arteries from calcification.
“Understanding these potential risks can help physicians and patients make informed decisions on whether to use a medication.”
Reference: Okuyama H, Langsjoen PH, Hamazaki T, Ogushi Y, Hama R, Kobayashi T, Uchino H. Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms. Expert Rev Clin Pharmacol. 2015 Mar;8(2):189-99.