2111
J Physiol 593.8 (2015) p 2111
LETTER TO THE EDITOR
The Journal of Physiology
Prevention of statin-induced myopathy – do not stop physical activity The deleterious effects of statins might be especially problematic in the elderly, with recent research showing that statin-myalgic elders haved blunted muscle power, increased abdominal adiposity, whole-body and leg insulin resistance and a muscle phenotype indicative of mitochondrial dysfunction and apoptosis (Mallinson et al. 2015). Statins are widely prescribed to counteract the high incidence of hyperlipidaemia among westerners, and the proportion of treated people aged ࣙ45 years is progressively increasing. Yet one of the most prevalent side-effects of statins is myopathy, especially when these drugs (e.g. simvastatin) are administered at high doses or combined with certain other medications which inhibit statin metabolism, such as erythromycin or verapamil. The laboratory and clinical presentation of statin-induced myopathy ranges from asymptomatic elevations in serum creatine kinase, a widely used biomarker of muscle tissue injury, to severe muscle symptoms (myalgia, weakness) and rhabdomyolysis, sometimes accompanied by myoglobinuria and subsequent risk of acute renal failure (Alis et al. 2014). Some genetic variants are strongly associated with higher risk of statin-related myopathy, suggesting the potential of genotype screening to improve the safety and effectiveness of statin therapy (Link et al. 2008). There are phenotype (lifestyle) modulators of the risk of statin-induced myopathy, especially physical exercise habits, which should be also kept in mind. The evidence that regular exercise is associated with lower risk of morbidity and mortality from cardiometabolic diseases
is irrefutable. An active lifestyle should be promoted, and in fact prescribed, by clinicians, especially in high cardiovascular risk populations and elderly people. Unfortunately, regular exercise can have a double edge effect in those taking statins, as it maintains cardiovascular health and muscle function but at the same time increases the likelihood of statin-induced myopathy and its related symptoms (Parker & Thompson, 2012). The muscle discomfort associated with statin-related myopathy over time can lead to cessation not only of treatment, but also of exercise practice in those who are active, thereby eliminating the benefits of two major strategies to maintain cardiovascular health over life. There is thus an urgent need to develop a pharmacological strategy, e.g. xanthine oxidase inhibitors (Alis et al. 2014), to attenuate the harmful effects that statins have at the muscle–tissue level or alternatively a side-effects prognostic test to determine which individuals will benefit from statins (Burgers et al. 2014). Future research might also determine to what extent prescription of regular exercise in the first place can replace, at least partially, the use of statins in certain population groups. This would be especially useful in older people at risk of sarcopenia. Fabian Sanchis-Gomar1 , Helios Pareja-Galeano2 and Alejandro Lucia2 1
Research Institute of Hospital 12 de Octubre (‘i+12’), Avda. de C´ordoba s/n 28041, Madrid, Spain 2 Universidad Europea and Research Institute of Hospital 12 de Octubre (‘i+12’), 28670 Villaviciosa de Od´on, Madrid, Spain
References Alis R, Sanchis-Gomar F, Risso-Ballester J, Perez-Quilis C, Cortell-Ballester J, Romagnoli M, Blesa JR & Emanuele E (2014). Inhibition of xanthine oxidase to prevent statin-induced myalgia and rhabdomiolysis. Atherosclerosis 239, 38–42. Burgers LT, Nauta ST, Deckers JW, Severens JL & Redekop WK (2014). Is it cost-effective to use a test to decide which individuals with an intermediate cardiovascular disease risk would benefit from statin treatment? Int J Cardiol 176, 980–987. Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, Gut I, Lathrop M & Collins R; SEARCH Collaborative Group (2008). SLCO1B1 variants and statin-induced myopathy – a genomewide study. N Engl J Med 359, 789–799. Mallinson JE, Marimuthu K, Murton A, Selby A, Smith K, Constantin-Teodosiu D, Rennie MJ & Greenhaff PL (2015). Statin myalgia is not associated with reduced muscle strength, mass or protein turnover in older male volunteers, but is allied with a slowing of time to reach peak power output, insulin resistance and differential muscle mRNA expression. J Physiol 593, 1239–1257. Parker BA & Thompson PD (2012). Effect of statins on skeletal muscle: exercise, myopathy, and muscle outcomes. Exerc Sport Sci Rev 40, 188–194.
Additional information Competing interests
The authors declare that no conflict of interest exists.
Email: [email protected]
C 2015 The Authors. The Journal of Physiology C 2015 The Physiological Society
DOI: 10.1113/JP270319
J Physiol 593.8 (2015) p 2111
LETTER TO THE EDITOR
The Journal of Physiology
Prevention of statin-induced myopathy – do not stop physical activity The deleterious effects of statins might be especially problematic in the elderly, with recent research showing that statin-myalgic elders haved blunted muscle power, increased abdominal adiposity, whole-body and leg insulin resistance and a muscle phenotype indicative of mitochondrial dysfunction and apoptosis (Mallinson et al. 2015). Statins are widely prescribed to counteract the high incidence of hyperlipidaemia among westerners, and the proportion of treated people aged ࣙ45 years is progressively increasing. Yet one of the most prevalent side-effects of statins is myopathy, especially when these drugs (e.g. simvastatin) are administered at high doses or combined with certain other medications which inhibit statin metabolism, such as erythromycin or verapamil. The laboratory and clinical presentation of statin-induced myopathy ranges from asymptomatic elevations in serum creatine kinase, a widely used biomarker of muscle tissue injury, to severe muscle symptoms (myalgia, weakness) and rhabdomyolysis, sometimes accompanied by myoglobinuria and subsequent risk of acute renal failure (Alis et al. 2014). Some genetic variants are strongly associated with higher risk of statin-related myopathy, suggesting the potential of genotype screening to improve the safety and effectiveness of statin therapy (Link et al. 2008). There are phenotype (lifestyle) modulators of the risk of statin-induced myopathy, especially physical exercise habits, which should be also kept in mind. The evidence that regular exercise is associated with lower risk of morbidity and mortality from cardiometabolic diseases
is irrefutable. An active lifestyle should be promoted, and in fact prescribed, by clinicians, especially in high cardiovascular risk populations and elderly people. Unfortunately, regular exercise can have a double edge effect in those taking statins, as it maintains cardiovascular health and muscle function but at the same time increases the likelihood of statin-induced myopathy and its related symptoms (Parker & Thompson, 2012). The muscle discomfort associated with statin-related myopathy over time can lead to cessation not only of treatment, but also of exercise practice in those who are active, thereby eliminating the benefits of two major strategies to maintain cardiovascular health over life. There is thus an urgent need to develop a pharmacological strategy, e.g. xanthine oxidase inhibitors (Alis et al. 2014), to attenuate the harmful effects that statins have at the muscle–tissue level or alternatively a side-effects prognostic test to determine which individuals will benefit from statins (Burgers et al. 2014). Future research might also determine to what extent prescription of regular exercise in the first place can replace, at least partially, the use of statins in certain population groups. This would be especially useful in older people at risk of sarcopenia. Fabian Sanchis-Gomar1 , Helios Pareja-Galeano2 and Alejandro Lucia2 1
Research Institute of Hospital 12 de Octubre (‘i+12’), Avda. de C´ordoba s/n 28041, Madrid, Spain 2 Universidad Europea and Research Institute of Hospital 12 de Octubre (‘i+12’), 28670 Villaviciosa de Od´on, Madrid, Spain
References Alis R, Sanchis-Gomar F, Risso-Ballester J, Perez-Quilis C, Cortell-Ballester J, Romagnoli M, Blesa JR & Emanuele E (2014). Inhibition of xanthine oxidase to prevent statin-induced myalgia and rhabdomiolysis. Atherosclerosis 239, 38–42. Burgers LT, Nauta ST, Deckers JW, Severens JL & Redekop WK (2014). Is it cost-effective to use a test to decide which individuals with an intermediate cardiovascular disease risk would benefit from statin treatment? Int J Cardiol 176, 980–987. Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, Gut I, Lathrop M & Collins R; SEARCH Collaborative Group (2008). SLCO1B1 variants and statin-induced myopathy – a genomewide study. N Engl J Med 359, 789–799. Mallinson JE, Marimuthu K, Murton A, Selby A, Smith K, Constantin-Teodosiu D, Rennie MJ & Greenhaff PL (2015). Statin myalgia is not associated with reduced muscle strength, mass or protein turnover in older male volunteers, but is allied with a slowing of time to reach peak power output, insulin resistance and differential muscle mRNA expression. J Physiol 593, 1239–1257. Parker BA & Thompson PD (2012). Effect of statins on skeletal muscle: exercise, myopathy, and muscle outcomes. Exerc Sport Sci Rev 40, 188–194.
Additional information Competing interests
The authors declare that no conflict of interest exists.
Email: [email protected]
C 2015 The Authors. The Journal of Physiology C 2015 The Physiological Society
DOI: 10.1113/JP270319
