LDL Cholesterol Reduction Variability with Different Types and Doses of Statins in Monotherapy or Combined with Ezetimibe. Results from the Spanish Arteriosclerosis Society Dyslipidaemia Registry.

PURPOSE: Low-density lipoprotein (LDL) cholesterol reduction by statin therapy is dose-dependent, varies among different statins, and has wide inter-individual variability. The present study aimed to compare mean LDL cholesterol reduction and its variability achieved with different doses of the three statins most frequently used in monotherapy or combined with ezetimibe in a real clinical setting. METHODS: Of 5620 cases with primary hypercholesterolemia on the Spanish Arteriosclerosis Society Registry, 1004 with non-familial hypercholesterolemia and complete information on drug therapy and lipid profile were included. RESULTS: The lowest mean percentage LDL cholesterol reduction was observed with simvastatin 10 mg (32.5 ± 18.5%), while the highest mean percentage LDL reduction was obtained with rosuvastatin 40 mg (58.7 ± 18.8%). As to combined treatment, the lowest and highest mean percentage LDL cholesterol reductions were obtained with simvastatin 10 mg combined with ezetimibe (50.6 ± 24.6%) and rosuvastatin 40 mg combined with ezetimibe (71.6 ± 11.1%), respectively. Factors associated with a suboptimal response were male sex, lower age, body mass index, and baseline LDL cholesterol levels. Combined treatment was associated with less variability in LDL cholesterol reduction (OR 0.603, p < 0.001). CONCLUSION: In a real clinical setting, rosuvastatin was superior to the other statins in lowering LDL cholesterol, both as monotherapy or combined with ezetimibe. Factors associated with a suboptimal response in LDL cholesterol decline were male sex, age, body mass index, and baseline LDL cholesterol levels. Combined treatment was associated with less variability in LDL cholesterol improvement.

Impact of statin therapy on LDL and non-HDL cholesterol levels in subjects with heterozygous familial hypercholesterolaemia.

BACKGROUND AND AIMS: Cardiovascular risk in heterozygous familial hypercholesterolaemia (HeFH) is driven by LDL cholesterol levels. Since lipid response to statin therapy presents individual variation, this study aimed to compare mean LDL and non-HDL cholesterol reductions and their variability achieved with different types and doses of the most frequently prescribed statins. METHODS AND RESULTS: Among primary hypercholesterolaemia cases on the Spanish Arteriosclerosis Society registry, 2894 with probable/definite HeFH and complete information on drug therapy and lipid profile were included. LDL cholesterol reduction ranged from 30.2 ± 17.0% with simvastatin 10 mg to 48.2 ± 14.7% with rosuvastatin 40 mg. After the addition of ezetimibe, an additional 26, 24, 21 and 24% reduction in LDL cholesterol levels was obtained for rosuvastatin, 5, 10, 20 and 40 mg, respectively. Subjects with definite HeFH and a confirmed genetic mutation had a more discrete LDL cholesterol reduction compared to definite HeFH subjects with no genetic mutation. A suboptimal response (<15% or <30% reduction in LDL cholesterol levels, respectively with low-/moderate-intensity and high-intensity statin therapy) was observed in 13.5% and, respectively, 20.3% of the subjects. CONCLUSION: According to the LDL cholesterol reduction in HeFH patients, the ranking for more to less potent statins was rosuvastatin, atorvastatin and simvastatin; however, at maximum dosage, atorvastatin and rosuvastatin were nearly equivalent. HeFH subjects with positive genetic diagnosis had a lower lipid-lowering response. Approximately 1 in 5 patients on high-intensity statin therapy presented a suboptimal response.

Evaluation of bendopnea in severe obstructive sleep apnea syndrome.

BACKGROUND: Bendopnea is a symptom described in heart failure (HF) that is related to short-term prognosis; however, its frequency and characteristics in respiratory diseases such as OSAS is still unknown. This study was carried out to evaluate the prevalence of bendopnea in patients with severe obstructive sleep apnea syndrome (OSAS) METHODS: We conducted a study of 95 patients attending a sleep disorders unit with severe OSAS. Bendopnea was considered when shortness of breath occurred within 30s of bending forward. RESULTS: Bendopnea was present in 33/95 of the patients included (34.7%). The median age was 62 years (52-71), 65 were men (68.4%), with a median weight of 92 (81-107) and BMI of 34kg/m2 (±7.1). The median duration of shortness of breath was 5s (2-10). The presence of bendopnea was related to age (p<.0001), obesity (p .004), respiratory diseases (p .01) and HF (p .03). Admission rate was higher in those with bendopnea without reaching statistical significance. CONCLUSION: One-third of patients with severe OSAS present bendopnea. This symptom is related to a higher prevalence of comorbidities (HF, obesity and other respiratory diseases). It is also related to a higher CT90.

iPCSK9 treatment of Familial Hypercholesterolemia in a patient diagnosed as Congenital Muscular Dystrophy with contraindication for statin use. / Tratamiento de la hipercolesterolemia familiar con iPCSK9 en un paciente diagnosticado de distrofia muscular congénita con contraindicación para la toma de estatinas.

Statins are contraindicated in patients with myopathies. Until a few years ago, in those patients with Familial Hypercholesterolemia who also presented muscular dystrophies and didnt reach adequate cholesterol plasmatic levels, the next therapeutic ladder was lipoapheresis. When iPCSK9 first appeared, lipoapheresis could be suspended in some of these patients, sustaining nevertheless proper levels of cholesterol. We present the case of a 27 year-old male, diagnosed with Congenital Muscular Dystrophy in the early childhood. He was referred to the Unit of Lipidology presenting hypercholesterolemia which, after genetic test, was assessed as Heterozygous Familial Hypercholesterolemia. Despite of treatment with diet and ezetimibe, cLDL blood levels abide high, being consequently included in lipoapheresis programme, therewith obtained levels of cLDL of 70mg/dl. In providing iPCSK9, lipoapheresis was withdrawn and treatment with alirocumab 150mg fortnightly introduced, unveiling a positive response, and sustaining cLDL levels around 75mg/dl.

[The role of atherogenic dyslipidaemia in clinical practice guidelines]. / El papel de la dislipemia aterogénica en las guías de práctica clínica.

BACKGROUND AND OBJECTIVE: Atherogenic dyslipidaemia is underdiagnosed, undertreated, and under-controlled. The aim of the present study was to assess the positioning of clinical guidelines as regards atherogenic dyslipidaemia. MATERIAL AND METHOD: The major clinical guidelines of scientific societies or official agencies issued between January 1, 2012 and March 31, 2015 were collected from the MEDLINE database. High-density lipoprotein (HDL) cholesterol, triglycerides, atherogenic dyslipidaemia, non-HDL cholesterol, and apolipoprotein (apo) B were gathered from the 10 selected guidelines, and it was assessed whether these parameters were considered a cardiovascular risk factor, a therapeutic target, or proposed a pharmacological strategy. RESULTS: American guidelines, except the National Lipid Association (NLA), do not consider HDL cholesterol and triglycerides in cardiovascular prevention. The NLA emphasises the relevance of atherogenic dyslipidaemia. The Canadian guidelines introduced non-HDL cholesterol and ApoB as alternative targets, and proposes non-statin treatment in the presence of low HDL cholesterol and hypertriglyceridaemia. The International Atherosclerosis Society (IAS) and National Institute for Health and Care Excellence (NICE) guidelines promote the importance of non-HDL cholesterol. European, Brazilian and Japanese guidelines highlight HDL cholesterol and triglycerides, but with the limitation that the main evidence comes from sub-analysis of clinical studies. CONCLUSIONS: The clinical guidelines analysed do not consider, or unconvincingly address, the importance of atherogenic dyslipidaemia.

[Therapeutic targets in the treatment of dyslipidemia: HDL and non-HDL cholesterol]. / Dianas terapéuticas en el tratamiento de las dislipemias: colesterol no unido a lipoproteínas de alta densidad y colesterol unido a lipoproteínas de alta densidad.

Atherogenic dyslipidemia (AD) consists of the combination of an increase in very low density lipoproteins (VLDL), which results in increased plasma triglyceride (TG) levels, with a reduction of levels of high-density lipoprotein bound cholesterol (HDL-C), also accompanied by a high proportion of small and dense LDL particles. AD is considered the main cause of the residual risk of experiencing cardiovascular disease (CVD), which is still presented by any patient on treatment with statins despite maintaining low-density lipoprotein bound cholesterol (LDL-C) levels below the values considered to be the objective. Non-HDL cholesterol (non-HDL-c) reflects the number of atherogenic particles present in the plasma. This includes VLDL, intermediate density lipoproteins (IDL) and LDL. Non-HDL-c provides a better estimate of cardiovascular risk than LDL-c, especially in the presence of hypertriglyceridemia or AD. The European guidelines for managing dyslipidemia recommend that non-HDL-c values be less than 100 and 130 mg/dL for individuals with very high and high cardiovascular risk, respectively. However, these guidelines state that there is insufficient evidence to suggest that raising HDL-c levels incontrovertibly results in a reduction in CVD. Therefore, the guidelines do not set recommended HDL-c levels as a therapeutic objective. The guidelines, however, state that individuals with AD on treatment with statins could benefit from an additional reduction in their risk by using fibrates.

Use of expert consensus to improve atherogenic dyslipidemia management.

INTRODUCTION AND OBJECTIVES: Although atherogenic dyslipidemia is a recognized cardiovascular risk factor, it is often underassessed and thus undertreated and poorly controlled in clinical practice. The objective of this study was to reach a multidisciplinary consensus for the establishment of a set of clinical recommendations on atherogenic dyslipidemia to optimize its prevention, early detection, diagnostic evaluation, therapeutic approach, and follow-up. METHODS: After a review of the scientific evidence, a scientific committee formulated 87 recommendations related to atherogenic dyslipidemia, which were grouped into 5 subject areas: general concepts (10 items), impact and epidemiology (4 items), cardiovascular risk (32 items), detection and diagnosis (19 items), and treatment (22 items). A 2-round modified Delphi method was conducted to compare the opinions of a panel of 65 specialists in cardiology (23%), endocrinology (24.6%), family medicine (27.7%), and internal medicine (24.6%) on these issues. RESULTS: After the first round, the panel reached consensus on 65 of the 87 items discussed, and agreed on 76 items by the end of the second round. Insufficient consensus was reached on 3 items related to the detection and diagnosis of atherogenic dyslipidemia and 3 items related to the therapeutic goals to be achieved in these patients. CONCLUSIONS: The external assessment conducted by experts on atherogenic dyslipidemia showed a high level of professional agreement with the proposed clinical recommendations. These recommendations represent a useful tool for improving the clinical management of patients with atherogenic dyslipidemia. A detailed analysis of the current scientific evidence is required for those statements that eluded consensus.