Elevated Creatine Kinase Concentrations Research Articles

Interactions Between Statins, Exercise, and Health: A Clinical Update

Interactions Between Statins, Exercise, and Health: A Clinical Update

A common disease masked by complex clinical manifestations: A case report of hypothyroidism

Background: Hypothyroidism is a common disease in elderly people. Although hypothyroidism can theoretically have clinical implications related to nearly all major organs, it is often excluded from diagnostic algorithms for elderly patients with multi-system disease because its symptoms are non-specific. Case summary: A 61-year-old woman presented with dizziness, fatigue, facial swelling, dry cracked skin, and myalgia. She had a 2-year history of impairment of multiple organs and multiple adverse drug events. Blood tests showed abnormal liver and kidney function, an elevated creatine kinase concentration, and hyperlipidaemia. During the last 2 years, she had experienced multiple severe adverse drug events, including eosinophilia and systemic symptoms caused by carbamazepine, acute kidney impairment related to ceftriaxone and cefdinir, exfoliative dermatitis caused by ceftazidime, and intolerance to statins. After visiting several large hospitals, she was finally diagnosed in our clinic with hypothyroidism. At the time of diagnosis, she was extremely ill and unable to walk independently. After taking levothyroxine, all of her symptoms and signs completely resolved. Conclusion: Hypothyroidism might be overlooked in elderly patients, especially those with complex and severe clinical conditions. Keywords: Aged; adverse drug events; multiple organ dysfunction; hypothyroidism.

Caveolin 3 deficiency myopathy associated with dyslipidemia: Treatment challenges and possible pathophysiological association

We report the case of a patient treated at the lipid clinic because of high cholesterol levels with consistently elevated creatine kinase concentrations that precluded statin treatment. Electromyography showed a rippling muscle disease pattern. A muscle biopsy confirmed caveolin 3 deficiency, and a missense mutation in the CAV3 gene was identified. The patient could be properly managed with ezetimibe and cholestyramine, which reduced the low-density lipoprotein cholesterol by 30%. He remains asymptomatic after 10 years of follow-up. Caveolae and caveolins are essential to membrane integrity, and their deficit has been associated with insulin resistance and hypercholesterolemia in animal models. Therefore, a putative pathophysiological association between myopathy and lipid metabolism mediated by functional alterations of membrane receptors is considered.

Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS): a randomised, double-blind, placebo-controlled trial

Delirium in critically ill patients is associated with poor clinical outcomes. Neuroinflammation might be an important mechanism in the pathogenesis of delirium, and since simvastatin has anti-inflammatory properties it might reduce delirium. We aimed to establish whether early treatment with simvastatin would decrease the time that survivors of critical illness spent in delirium or coma. We undertook this randomised, double-blind, placebo-controlled trial in a general adult intensive care unit (ICU) in Watford General Hospital (Watford, UK). We enrolled critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission. We randomly assigned patients (1:1 ratio) to receive either simvastatin 80 mg or placebo daily for up to a maximum of 28 days, irrespective of coma or delirium status. We assessed delirium using the Confusion Assessment Method for the ICU (CAM-ICU). The primary outcome was number of days alive and was assessed as delirium-free and coma-free in the first 14 days after being randomly allocated to receive treatment or placebo. ICU clinical and research staff and patients were masked to treatment. We did intention-to-treat analyses with no extrapolation. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN89079989. Between Feb 1, 2013, and July 29, 2016, 142 patients were randomly assigned to receive simvastatin (n=71) or placebo (n=71), and were included in the final analysis. The mean number of days alive without delirium and without coma at day 14 did not differ significantly between the two groups (5·7 days [SD 5·1] with simvastatin and 6·1 days [5·2] with placebo; mean difference 0·4 days, 95% CI -1·3 to 2·1; p=0·66). The most common adverse event was an elevated creatine kinase concentration to more than ten times the upper limit of normal (eight [11%] in the simvastatin group vs three [4%] in the placebo group p=0·208). No patient had a serious adverse event related to the study drug. These results do not support the hypothesis that simvastatin modifies duration of delirium and coma in critically ill patients. National Institute for Health Research.

Clinical outcome, biochemical and therapeutic follow-up in 14 Austrian patients with Long-Chain 3-Hydroxy Acyl CoA Dehydrogenase Deficiency (LCHADD).

BackgroundLCHADD is a long-fatty acid oxidation disorder with immediate symptoms and long-term complications. We evaluated data on clinical status, biochemical parameters, therapeutic regimens and outcome of Austrian LCHADD patients.Study designClinical and outcome data including history, diagnosis, short- and long-term manifestations, growth, psychomotor development, hospitalizations, therapy of 14 Austrian patients with LCHADD were evaluated. Biochemically, we evaluated creatine kinase (CK) and acyl carnitine profiles.ResultsAll LCHADD patients are homozygous for the common mutation. Three are siblings. Diagnosis was first established biochemically. Nine/14 (64%) were prematures, with IRDS occurring in six. In nine (64%), diagnosis was established through newborn screening, the remaining five (36%) were diagnosed clinically. Four pregnancies were complicated by HELLP syndrome, one by preeclampsia. In two, intrauterine growth retardation and placental insufficiency were reported. Five were diagnosed with hepatopathy at some point, seven with cardiomyopathy and eight with retinopathy, clinically relevant only in one patient. Polyneuropathy is only present in one. Three patients have a PEG, one is regularly fed via NG-tube. Growth is normal in all, as well as psychomotor development, except for two extremely premature girls. In 11 patients, 165 episodes with elevated creatine kinase concentrations were observed with 6-31 (median 14) per patient; three have shown no elevated CK concentrations. Median total carnitine on therapy was 19 μmol/l (range 11-61). For 14 patients, there have been 181 hospitalizations (median 9 per patient), comprising 1337 in-patient-days. All centres adhere to treatment with a fat-defined diet; patients have between 15% and 40% of their energy intake from fat (median 29%), out of which between 20% and 80% are medium-chain triglycerides (MCT) (median 62%). Four patients have been treated with heptanoate (C7).ConclusionOur data show LCHADD outcome can be favourable. Growth and psychomotor development is normal, except in two prematures. Frequency of CK measurements decreases with age, correlating with a decreasing number of hospitalizations. About 50% develop complications affecting different organ systems. There is no relevant difference between the patients treated in the respective centers. Concluding from single case reports, anaplerotic therapy with heptanoate should be further evaluated.

Rhabdomyolysis Following a Short Course of Clarythromycin

A healthy 5-year-old girl developed myalgia and an elevated creatine kinase concentration after 4 days of normal doses of clarithromycin. Myalgias resolved and creatine kinase values returned to normal following discontinuation of clarithromycin. No other precipitating factors or interacting drugs were identified; hence, clarithromycin was suspected as the cause of the rhabdomyolysis.

Methamphetamine Exposures in Young Children

Methamphetamine abuse is reaching epidemic proportions. As this occurs, the likelihood of accidental poisoning in children increases. We sought to evaluate the presentation, treatment, and outcome of pediatric methamphetamine exposures reported to the California Poison Control System. This is a retrospective review of California Poison Control System records for methamphetamine exposure from 2000 through 2004. All charts of patients identified as younger than 6 years were reviewed and abstracted. The charts of 47 children younger than 6 years were identified and reviewed. Three were coded as minor effects, 3 as major effects, and 16 as moderate effects. The remainder of the charts were not evaluated because of no effect (n = 6), unrelated or confirmed nonexposure (n = 3), or unable to follow (n = 16). The most common presenting symptom was agitation (82%), whereas seizures were documented in only 2 cases (9%). Tachycardia was common (mean heart rate, 171 beats/min; confidence interval [CI], 154-187), whereas blood pressure (BP) (mean systolic BP, 120 mm Hg; CI, 104-136; and mean diastolic BP, 70 mm Hg; CI, 51-88) and rectal temperature (mean, 37.4 degrees C; CI, 36.9-37.9) were slightly elevated compared with normal values. Creatinine was documented in 6 cases and noted as normal in all (0.3IU/L; CI, 0.2-0.4), whereas creatine kinase was documented in 3 charts and elevated in all (mean 1984 IU/L; range, 212-4942 IU/L). Most cases (55%) received benzodiazepines as treatment, although only 2 received activated charcoal. Symptoms persisted for an average of 22 hours (CI, 16.3-27.2). No deaths were reported. In this series of children, methamphetamine exposure was strongly associated with agitation that was successfully treated with benzodiazepines. Tachycardia was common, although hypertension and hyperthermia were not. Laboratory studies were not routinely recorded. The clinical significance of elevated creatine kinase concentrations recorded in 3 children is unclear.

A 12-Week, Prospective, Open-Label Analysis of the Effect of Rosuvastatin on Triglyceride-Rich Lipoprotein Metabolism in Patients with Primary Dyslipidemia

Background: Although the effect of statins on lowering low-density lipoprotein cholesterol (LDL-C) has been extensively studied, their hypotriglyceridemic capacity is not fully understood. Objective: The present study examined clinical and laboratory factors potentially associated with the triglyceride (TG)-lowering effect of rosuvastatin. Methods: Eligible patients had primary dyslipidemia and a moderate risk of heart disease. Patients were prescribed rosuvastatin 10 mg/d in an open-label fashion and kept 3-day food diaries. Laboratory measurements, performed at baseline and 12 weeks, included serum lipid parameters (total cholesterol [TC], TGs, LDL-C, high-density lipoprotein cholesterol [HDL-C], and apolipoprotein [apo] levels), non-lipid metabolic variables (including carbohydrate metabolism parameters and renal, liver, and thyroid function tests), and LDL-subfraction profile (by high-resolution 3% polyacrylamide gel electrophoresis). Tolerability was assessed at each visit. Results: Participants were 75 hyperlipidemic patients (39 men and 36 women; mean age, 51.7 years). At 12 weeks, TC levels were reduced by 35.1% ( P < 0.001), TGs by 15.2% ( P < 0.001), LDL-C by 48.5% ( P < 0.001), apoE by 35.4% (P < 0.001), and apoE by 17.3% ( P < 0.001) from baseline, whereas HDL-C and apoA1 levels were not significantly changed. Stepwise linear regression analysis showed that baseline TG levels were most significantly correlated ( R 2 = 42.0%; P < 0.001) with the TG-lowering effect of rosuvastatin, followed by the reduction in apoCIII levels ( R 2 = 13.6%; P < 0.01). Rosuvastatin use was associated with a reduction in cholesterol mass of both large LDL particles (mean [SD], from 150.5 [36.6] to 90.5 [24.3] mg/dL; P < 0.001) and small, dense LDL (sdLDL) particles (from 11.5 [8.4] to 6.6 [4.5] mg/dL; P < 0.001). Rosuvastatin had no effect on cholesterol distribution of the LDL subfractions (mean [SD], large particles, from 90.8% [7.0%] to 91.8% [5.1%]; sdLDL, from 7.1% [4.7%] to 7.5% [4.8%]) or the mean LDL particle size (from 26.5 [4.2] to 26.6 [4.0] rim). A significant increase in mean LDL particle size after rosuvastatin treatment (mean [SD], from 26.4 [0.4] to 26.9 [0.4] rim; P = 0.02) was observed only in patients with baseline TG levels ≥120 mg/dL. No serious adverse events requiring study treatment discontinuation were reported. One patient who presented with headache and 2 patients who presented with fatigue quickly recovered without discontinuing rosuvastatin treatment. A posttreatment elevation in aminotransferase levels <3-fold the upper limit of normal (ULN) was recorded in 5 (6.7%) patients, and 2 (2.7%) patients experienced elevated creatine kinase concentrations <5-fold ULN. Conclusion: Baseline TG levels were the most im- portant independent variable associated with the TG-lowering effect of rosuvastatin.

How Can We Manage Hyperlipidemia and Avoid Rhabdomyolysis in Transplant Patients?

Joseph M Kahwaji, MD, MPH Ryszard R Dudek, MD Case Summary A 25-year-old man with a history of perinuclear antineutrophil cytoplasmic antibodies-associated vasculitis presented to the ambulatory clinic with five days of diffuse myalgias and muscle tenderness. The patient had undergone kidney transplantation three years before presentation and had no post-transplant complications. He was maintained on cyclosporine, prednisone, and mycophenolate mofetil. Simvastatin 20 mg daily was started two months after transplantation for development of post-transplant hyperlipidemia. Three months before presentation, the creatinine concentration was 1.8 mg/dL. Two months before presentation, the simvastatin dosage was increased to 40 mg daily. Results of laboratory studies done at presentation were remarkable for the following: creatine kinase, 25,000 U/L; aspartate aminotransferase, 767 U/L; alanine aminotransferase, 620 U/L; and creatinine, 2.3 mg/dL. Urinalysis revealed 4+ blood and 2+ protein. The cyclosporine concentration, 265 ng/mL, was above the normal range of 100 to 200 ng/mL. A diagnosis of rhabdomyolysis was made on the basis of the symptom of myalgias in the setting of acute renal failure and an elevated creatine kinase concentration. Simvastatin was discontinued, and the patient was instructed to selfhydrate. At one day, five days, and two weeks after initial presentation, follow-up clinical evaluations found that symptoms had eased, and follow-up laboratory studies showed improvement.

Rhabdomyolysis in a Patient Treated with Colchicine and Atorvastatin

To report a case of severe rhabdomyolysis that developed after administration of atorvastatin to a patient receiving regular colchicine treatment. A 45-year-old man with nephrotic syndrome and amyloidosis presented with dyspnea, altered mentation, and severe fatigue. He had been taking colchicine 1.5 mg/day for amyloidosis for 3 years without adverse effects. Atorvastatin 10 mg/day was prescribed for hypercholesterolemia one month prior to admission. After 2 weeks of atorvastatin treatment, he began to experience myalgia and reduced muscle strength. The creatinine and creatine kinase concentrations on admission were 8.1 mg/dL and 9035 U/L, respectively. The patient was diagnosed with rhabdomyolysis with the findings of myoglobinuric, oliguric acute renal failure, and more than 50-fold elevated creatine kinase concentration. His muscle strength improved after withdrawal of atorvastatin and colchicine. However, he died because of nosocomial pneumonia that developed during his hospital stay. The Naranjo probability scale indicated that atorvastatin and colchicine were probable causes of rhabdomyolysis. Atorvastatin and colchicine have well-known myotoxic adverse effects. Despite atorvastatin's proven safety, its use with certain drugs, such as colchicine, makes it a potential myotoxic drug. This might be because concomitant administration of P-glycoprotein substrates, such as statins, and colchicine, which is a P-glycoprotein inhibitor, modifies pharmacokinetics by increasing bioavailability and organ uptake of the substrates, leading to more adverse reactions and toxicities. We recommend checking the creatine kinase level one week after prescribing 2 or more potentially myotoxic drugs concomitantly, after dose increase of a myotoxic drug, or after prescribing a new drug to a patient already using other myotoxic agents.

Muscular dystrophy.

Muscular dystrophy.

Acute myopathy associated with combined use of corticosteroids and neuromuscular blocking agents.

To review the occurrence and pathophysiology of myopathy associated with combined use of neuromuscular blocking agents (NMBAs) and systemic corticosteroids. A MEDLINE search (1985 to July 1995, English language) yielded case reports and clinical studies involving myopathy or weakness associated with the use of NMBAs and/or corticosteroids. References cited in those articles were reviewed. Prolonged muscle weakness has been reported in intubated patients in the intensive care unit (ICU) who were receiving NMBAs and/or corticosteroids. Many cases involved the use of both agents in individuals with no underlying risk factors. The term "blocking agent-corticosteroid myopathy" (BACM) has been used to describe this myopathy when it develops following combined use of these agents. Features common to BACM include prolonged weakness, elevated creatine kinase concentrations, myopathic features on electromyography, normal nerve conduction and sensation, and reduced deep tendon reflexes. Muscle biopsy results vary, but tend to show type 1 and/or 2 fiber atrophy without inflammation. Some recently reported cases revealed thick myosin myofilament loss, which is consistent with findings in denervated rat muscle after exposure to corticosteroids. Two small prospective studies reported that 36-50% of mechanically ventilated patients receiving either one or both drugs developed prolonged weakness. NMBAs and corticosteroids alone have both been reported to cause myopathy in patients in the ICU. When coadministered, these agents appear to confer an even greater risk of myopathy; the exact pathology is not understood. Concomitant use of NMBAs and corticosteroids should be avoided if possible. Guidelines for cautious use and careful monitoring are suggested when combined use is deemed necessary.

Merosin-negative non-Fukuyama-type congenital muscular dystrophy: a case report

We report a female infant with non-Fukuyama-type congenital muscular dystrophy with merosin deficiency. She manifested marked hypotonia and muscle weakness from the neonatal period, with an elevated creatine kinase concentration. Her motor developmental milestones were markedly delayed; however, her intellectual development was normal. Although cranial computed tomography (CT) at 3 months of age was normal, subsequent CT at 16 months of age demonstrated diffuse, abnormal white matter lucencies. Muscle biopsy findings at 16 months of age were compatible with those of congenital muscular dystrophy. In addition, no muscle fibers were immunostained by the merosin antibody. The patient died of pneumonia at 23 months of age. These clinical symptoms and CT findings are similar to those described in patients with merosin-negative congenital muscular dystrophy in European countries.

Changes in plasma enzyme concentrations following intramuscular injections and gastroscopy.

The effects of intramuscular injections on plasma creatine kinase (CK), aspartate amino-transferase, lactate dehydrogenase, and hydroxybutyrate dehydrogenase concentrations were examined in 19 patients given intramuscular premedication for gastroscopy, and 18 patients given other intramuscular injections. Only CK concentrations showed significant increases which were as high as four times the upper limit of normal, and affected a maximum of 51% of patients at 12 hours after the first injection. Elevated CK concentrations persisted for up to 72 hours, and followed injections of diazepam, various antibiotics, and the combination of a narcotic analgesic with atropine. Gastroscopy did not appear to increase plasma enzyme concentrations in six patients who were given intravenous premedication. The significance of these findings to the diagnosis of myocardial infarction is discussed.