Statin-induced rhabdomyolysis in a 60-year-old woman with decompensated type 2 diabetes: a case report

Rhabdomyolysis is a very rare and most severe form of statin-induced muscle adverse event characterized by muscle pain, muscle necrosis with myoglobinemia and/or myoglobinuria with a very high risk of acute kidney injury and death. The article presents a case report of developing rhabdomyolysis in a middleaged female patient with hypertension, decompensated type 2 diabetes and albuminuria. A 60-year-old woman was admitted to the hospital for emergency indications with complaints of severe muscle weakness that began in the neck, which spread over several days to the upper and lower extremities, with a symptoms progression up to paresis. According to the appointment of a primary care physician, three months before hospitalization, the patient was switched from therapy with European generic brand-name rosuvastatin 20 mg to the Russian generic unbranded atorvastatin in the same dose (20 mg), which is not comparable in lipid-lowering effect. In a laboratory study, an increase in creatine phosphokinase level by 348 times (50462 U/L) of upper normal limit in combination with severe hypokalemia 1б7 mmol/L in the absence of renal dysfunction was recorded. Cancellation of statin, metformin and empagliflozin, intensive infusion therapy and treating electrolyte imbalance made it possible to prevent the development of acute renal damage, life-threatening arrhythmias and completely stop muscle complaints within a few days. The patient was discharged from the hospital on the 23rd day with reference clinical and laboratory values, including creatine phosphokinase.This case emphasizes the importance of maintaining clinical suspicion regarding rhabdomyolysis in patients receiving statin therapy in the presence of risk factors (in this case, female sex, hyperglycemia, chronic kidney disease, concomitant therapy), as well as the relevance of timely diagnosis and treatment of this condition

Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes : Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration

Background: The potential for global collaborations to better inform public health policy regarding major non-hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide. Methods: The EAS FHSC will maximise the potential exploitation of currently available and future FH data (retrospective and prospective) by bringing together regional/national/international data sources with access to individuals with a clinical and/or genetic diagnosis of heterozygous or homozygous FH. A novel bespoke electronic platform and FH Data Warehouse will be developed to allow secure data sharing, validation, cleaning, pooling, harmonisation and analysis irrespective of the source or format. Standard statistical procedures will allow us to investigate cross-sectional associations, patterns of real-world practice, trends over time, and analyse risk and outcomes (e.g. cardiovascular outcomes, all-cause death), accounting for potential confounders and subgroup effects. Conclusions: The EAS FHSC represents an excellent opportunity to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH patients. (C) 2016 Elsevier Ireland Ltd.Peer reviewe

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Current approaches to the treatment of dyslipidemia: from scholarly disputes to the individual patient

Lipid metabolism, and especially increased plasma levels of low-density lipoprotein cholesterol (LDLC), are positively correlated with the incidence and number of cardiovascular events - heart attacks and ischemic strokes. [1--7] Randomized trials of statins and a series of meta-analyses of statin trials - Cholesterol Treatment Trialists' (STT) Collaboration 2005, 2010, 2012 - demonstrated a close relationship between decrease in the "bad" cholesterol level on statin therapy and decrease in the number of cardiovascular (CV) complications. [8, 9] In the Russian Federation, despite advances in preventive cardiology in recent years, cardiovascular and total mortality rates remain high. Circulatory system diseases cause death of more than 1 million people in Russia annually; CS diseases account for more than 50% in the structure of total mortality. [5--7] Compared with other developed and developing countries, life expectancy in the Russian Federation, according to the WHO, remains low equalling an average of 66 years. Specifically in 2013, according to the WHO, average life expectancy of Russian people was low equalling an average of 66.05 in general, 59.1 years for men and 73 years for women. We are on the 129th place in the total list of countries, between Guyana and the Bahamas (Slide 1). One of the most challenging tasks in reducing CV mortality in this country is adequate monitoring of the key CV risk factors (diabetes, smoking, hypertension and dyslipidemia

Low density lipoprotein cholesterol (H-LDL) and remnant non-HDL cholesterol: any reason to change the order when assessing cardiovascular risk?

The paper reviews the relevance of various types of cholesterol as factors of cardiovascular risks. According to recent recommendations, apart from the routinely evaluated low-density lipoprotein cholesterol (LDL-H), clinicians now look at non-HDL (high-density lipoprotein) cholesterol. The paper questions, whether there is enough clinical and scientific evidence to change priorities in the lipid assessment of cardiovascular risk: measurement and monitoring of non-HDL cholesterol vs. routine lipid markers - LDL cholesterol and plasma HDL cholesterol

Statins at the equator of decades. 40 years since the study of 4S

Interview with MD, leading researcher at clinical lipidology laboratory of the atherosclerosis unit, Russian Cardiology Research and Production Complex of the Ministry of Health of the Russian Federation, member of EAS/IAS/NLA/HEARTUK/ACC/AHA//CGAB/IAS Lipid Guidelines Committee/WCCL Advisory Board А.V. Suseko

Statin therapy and atherosclerosis regression

Various clinical forms and complications of atherosclerosis remain the leading causes of morbidity and mortality in both developed and developing countries. HMG-CoA reductase inhibitors (statins) are the key components of pharmaceutical treatment in patients with dyslipidemia (DLP) and atherosclerosis. Statins have been thoroughly studied not only in randomised clinical trials with “hard” end-points, but also in the so called regression studies. The latter tested the hypothesis of qualitative and quantitative changes in coronary arteries (CA) due to aggressive reduction (-40-50% from baseline) of low-density lipoprotein (LDL) cholesterol levels. The results of the first regression studies justified the increase of statin doses in clinical practice, as well as led to large randomised clinical trials of statin therapy. In current regression studies, vascular atherosclerosis is monitored using such methods as intima-media thickness assessment, magnetic resonance imaging, and intravascular ultrasound. Reduced progression of carotid atherosclerosis (METEOR Study, rosuvastatin 40 mg/d; ENHANCE Study, ezetimibe 10 mg/d plus simvastatin 20 mg/d) and CA atherosclerosis (REVERSAL Study, atorvastatin 80 mg/d), as well as atherosclerosis regression (ASTEROID Study, rosuvastatin 40 mg/d), was demonstrated. Aggressive lipid-lowering effect (-40-50%), observed for high statin doses in modern regression clinical trials, was well-tolerated, with no severe adverse events. The results and principles of regression studies could be widely used in clinical practice, to optimise the treatment of severe DLP and atherosclerosis

Atorvastatin: evidence base 15 years later

HMG-CoA inhibitors have been widely used in primary and secondary prevention of atherosclerosis for more than 30 years. The evidence base for statins includes dozens of randomized clinical trials (RCT), involving hundreds of thousands patients. According to the results of the latest meta-analyses, reducing low-density lipoprotein cholesterol (LDL-CH) level by 1 mmol/l in statin-treated patients could decrease cardiovascular risk by 0,8 %. Atorvastatin (Liprimar®) is a modern synthetic statin, which has been thoroughly studied in several RCTs over the last 15 years. These trials demonstrated its effectiveness and tolerability in patients with chronic coronary heart disease, acute coronary syndrome (ACS), Type 2 diabetes mellitus, and arterial hypertension. In the studies comparing atorvastatin (10-80 mg/d) to other statins, baseline LDL-CH levels were reduced by 53 % in atorvastatintreated patients. Atorvastatin therapy was also well tolerated. Compared to placebo, atorvastatin therapy in the dose of 10 and 80 mg/d was associated with the incidence of hepatic transaminase elevation of 0,1 % and 0,6 %, respectively. This evidence base (in particular, the results of the trials on 80 mg/d atorvastatin therapy in ACS patients) has been a cornerstone of modern clinical guidelines, recommending target LDL-CH levels of 2 mmol/l. Currently, atorvastatin is the most widely prescribed statin in the majority of both developed and developing countries. Increasing initial dose and prescribing high-dose atorvastatin therapy (40-80 mg/d) could facilitate an improvement in treatment quality and a reduction in high levels of cardiovascular mortality inRussia