Analysis of multimodal ultrasound characteristics of statin-related myopathy in elderly patients with hyperlipidemia / 中华老年医学杂志

Objective:To investigate the characteristics of multimodal ultrasound imaging in elderly hyperlipidemia patients with statin-related myopathy and to provide a reference of new method for non-invasive quantitative evaluation on statin myopathy.Methods:We collected 20 elderly hyperlipidemia patients with statin-related myopathy(the statin-related myopathy group), 20 elderly hyperlipidemia patients without statin-related myopathy after taking statins during the same period(the non-statin-related myopathy group), and 20 healthy volunteers who matched the age and sex of the above two groups during the same period(the healthy control group)in our hospital.Two-dimensional ultrasound, shear wave elastography and superb microvascular imaging were used to obtain thickness, echo, pinnation angle and shear wave velocity(SWV)values as well as vascular index(VI)values of the medial gastrocnemius during relaxation, dorsiflexion, and plantar flexion for each group, which were then analyzed.Results:There were no significant differences among the three groups in general conditions such as age, height, weight, and body mass index(all P>0.05). The mean thickness of the medial gastrocnemius in the statin-related myopathy group was about(1.04 ± 0.20)cm, which was less than(1.34 ± 0.16)cm in the non-statin-related myopathy group and(1.35 ± 0.15)cm in the healthy control group( F=22.03, P<0.001). The pinnation angle in the statin-related myopathy group was about(12.50 ± 1.10), which was less than(18.55 ± 1.28)in the non-statin-related myopathy group and(18.60 ± 1.35)in the healthy control group( F=158.03, P<0.001). Compared with the non-statin-related myopathy group and the healthy control group, SWV during resting, dorsiflexion and plantar flexion in the statin-related myopathy group decreased( F=61.71, 111.96 and 8.69, respectively, P<0.01). The average value of VI in the statin-related myopathy group was about(0.43 ± 0.12)%, which was less than that in the non-statin-related myopathy group(0.75 ± 0.20)% and in the healthy control group(0.93 ± 0.17)%( F=48.93, P<0.001). However, there was no significant difference in values from the parameters between the non-statin-related myopathy group and the healthy control group(all P>0.05). Conclusions:Multimodal ultrasound imaging of statin-related myopathy in elderly hyperlipidemia patients shows distinct characteristics and can be used to evaluate muscle damage of statin-related myopathy.

Miopatía por estatinas y vitamina D / Statin-Related Myopathy and Vitamin D

Las estatinas son fármacos habitualmente seguros y bien tolerados, muy eficaces para la prevención de trastornos cardiovasculares. La presencia de mialgias, poco frecuente, pero con incidencia dispar en diversos reportes, es una de las causas de abandono de su uso. También las distintas denominaciones (mialgia, miopatía, rabdomiólisis) y la subjetividad de cada paciente para referirlas han creado confusión en el tema. Se ha comenzado a reportar asociación entre niveles de vitamina D sérica disminuida y mayor riesgo de miopatía, por un lado, y trabajos donde pacientes que las abandonaban a causa de mialgias, con deficiencia de vitamina D, pueden tolerarlas una vez que se suplementa la vitamina hasta valores deseables. La presencia de polimorfismos en genes de enzimas que metabolizan o transportan a las estatinas es otro factor claramente relacionado con miopatía. Es posible que el déficit de vitamina D deba ser considerado un factor de riesgo para desarrollar miopatía por estatinas, como lo serían también la administración simultánea de fármacos que se metabolizan por la misma vía de citocromo P450, o la presencia de los polimorfismos mencionados. En conclusión, el hallazgo de tener deficiencia de vitamina D se asocia a miopatía por estatinas, o que es un factor de riego para desarrollarla, abre nuevas perspectivas para un gran número de pacientes que abandonan este tratamiento debido a esta patología. (AU)

Statins are usually safe and well tolerated drugs, very effective for preventing cardiovascular complications. The rare presence of myalgia, with different incidence as reported by several studies, is one of the causes of lack of drug compliance. Also the different symptoms referred (myalgia, myopathy, rhabdomyolysis) and the lack of objetivity of each patient when referring to the symptoms, have created confusion in this matter. Associations between decreased vitamin D levels and increased risk of myopathy has been reported. Indeed, studies describing patients with vitamin D deficiency who are not compliant due to myalgia show that they become tolerant to the drugs once the vitamin is supplemented to desirable values. The presence of gene polymorphisms for enzymes that metabolize or transport statins is another factor clearly related to myopathy. Therefore, we should consider vitamin D deficiency and other conditions such as the simultaneous administration of drugs that are metabolized by the same cytochrome P450 pathway, or the presence of mentioned polymorphisms as a risk factor for developing myopathy due to statins. In conclusion, the finding that vitamin D deficiency is associated with statin myopathy, or is a risk factor its develpoment, opens new perspectives for a large number of patients who leave this treatment due to this condition. (AU)

Genetic and immunologic susceptibility to statin-related myopathy.

Statin-related myopathy (SRM) undermines drug adherence that is critical for achieving the benefits of lipid-lowering therapy. While the exact mechanism of SRM remains largely unknown, recent evidence supports specific genetic and immunologic influence on the development of intolerance. Genes of interest include those involved in the pharmacokinetics of statin response (i.e. drug metabolism, uptake transporters, and efflux transporters), pharmacodynamics (i.e. drug toxicity and immune-mediated myopathy), and gene expression. We examine the influence of genetic and immunologic variation on the pharmacokinetics, pharmacodynamics, and gene expression of SRM.

Risk identification and possible countermeasures for muscle adverse effects during statin therapy.

The use of statins for cardiovascular disease prevention is clearly supported by clinical evidence. However, in January 2014 the U.S. Food and Drug Administration released an advice on statin risk reporting that "statin benefit is indisputable, but they need to be taken with care and knowledge of their side effects". Among them the by far most common complication is myopathy, ranging from common but clinically benign myalgia to rare but life-threatening rhabdomyolysis. This class side effect appears to be dose dependent, with more lipophilic statin (i.e., simvastatin) carrying a higher overall risk. Hence, to minimize statin-associated myopathy, clinicians should take into consideration a series of factors that potentially increase this risk (i.e., drug-drug interactions, female gender, advanced age, diabetes mellitus, hypothyroidism and vitamin D deficiency). Whenever it is appropriate to stop statin treatment, the recommendations are to stay off statin until resolution of symptoms or normalization of creatine kinase values. Afterwards, clinicians have several options to treat dyslipidemia, including the use of a lower dose of the same statin, intermittent non-daily dosing of statin, initiation of a different statin, alone or in combination with nonstatin lipid-lowering agents, and substitution with red yeast rice.