The pleiotropic effects of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in rheumatologic disorders: a comprehensive review

Abstract

The hydroxy-methyl-glutaryl-CoA reductase inhibitors (statins) are used extensively in the treatment for hyperlipidemia. They have also demonstrated a benefit in a variety of other disease processes, including a wide range of rheumatologic disorders. These secondary actions are known as pleiotropic effects. Our paper serves as a focused and updated discussion on the pleiotropic effects of statins in rheumatologic disorders and emphasizes the importance of randomized, placebo-controlled trials to further elucidate this interesting phenomenon.

Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

“…Statin-induced myopathy affects large muscle groups and is usually bilateral, symmetrical and may be worsened by exercise [20]. Joint pain, often mistaken for myalgia is a very unusual side effect of statin use and another etiology should be sought [168][169][170]. Muscle symptoms that appear only after a few days is more unusual for statin-related symptoms as true statin-related symptoms most commonly appear weeks to months after initiation of therapy or increase in dose (75% in the first 12 weeks) and are more common in patients on high dose therapy and/or who are also taking other medication [19].…”

“…Moreover, anti-inflammatory properties of statins can positively affect the course of systemic disease, such as rheumatoid arthritis and osteoporosis without an increase in any AEs [168,169]. In a large cross-sectional study among 5170 participants without arthritis, the unadjusted prevalence of musculoskeletal pain was significantly higher for statin users reporting pain in any region (23% among statin users, compared with 18% among those not using statins, p = 0.02) and in the lower extremities (12 vs. 8%, p = 0.02).…”

The pleiotropic effects of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in renal disease

“…3 These cholesterol-independent, or "pleiotropic" effects of statins, provide benefits in a wide range of disease processes, including cardiovascular disorders, malignancies, central nervous system disorders, infection, sepsis, and rheumatologic disorders. [3][4][5][6][7][8][9][10][11][12] Statins achieve their main effect via the inhibition of the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase, decreasing the synthesis of cholesterol and isoprenoids, and upregulating the production of endothelial nitric oxide synthase. 13,14 There is also decreased production of nicotinamide dinucleotide phosphate oxidase that results in fewer free oxygen radicals in the systemic circulation.…”

Expanding the pleiotropic effects of statins: attenuation of air pollution-induced inflammatory response

“…For ambient-induced adverse effects, the accumulating evidence suggests the first option. In Miyata et al's article (12), lovastatin was administered during 4 wk previous to PM 10 exposure showing a reduction on the systemic inflammatory response (12). The lovastatin anti-inflammatory effect was much less when the pretreatment period was shortened.…”

“…They play a pivotal role in the primary and secondary prevention of atherosclerotic heart disease and stroke and due to their pleiotropic effects (independent of their non-lipidlowering properties) that have shown potential benefits for a variety of other cardiovascular (11) and noncardiovascular diseases, including cancer (2), rheumatological (10), and neurological disorders (15). Potential reasons for their pleiotropic effects, are among others, the inhibition of isoprenoid intermediates implicated in oxidative stress, inhibition of the cellular proliferation and migration (6), and inhibition of L-type Ca 2ϩ current (1).…”