246 research outputs found
Pharmacogenomic insights into treatment and management of statin-induced myopathy
Although statins are generally well tolerated, the most common adverse drug reaction from statin therapy is myopathy. This article reviews the current pharmacogenomic knowledge of statin-induced myopathy. Furthermore, we will discuss the importance of recent pharmacogenetic advances for the treatment and management of statin-induced myopathy. Variation in the SLCO1B1 gene is associated with increased incidence of statin-induced myopathy, particularly with simvastatin and less so with other statins. If different pharmacokinetic enzymes and transporters are responsible for susceptibility to myopathy, this may explain differences in the occurrence of statin-induced myopathy in individual patients. Genotyping in patients suffering from statin-induced myopathy may help to personalize the choice of statin for the lowest chance of developing myopathy
Adiposity and the development of dyslipidemia in APOE epsilon 2 homozygous subjects:A longitudinal analysis in two population-based cohorts
Background and aims: Familial dysbetalipoproteinemia (FD), characterized by remnant lipoprotein accumulation and premature cardiovascular disease, occurs in homozygous carriers of the APOE epsilon 2 allele, but genetic predisposition alone does not suffice for the clinical phenotype. Cross-sectional studies suggest that a second metabolic hit-notably adiposity or insulin resistance-is required, but the association between these risk factors and development of FD has not been studied prospectively. Methods: For this study, we evaluated 18,987 subjects from two large prospective Dutch population-based cohorts (PREVEND and Rotterdam Study) of whom 118 were homozygous APOE epsilon 2 carriers. Of these, 69 subjects were available for prospective analyses. Dyslipidemia-likely to be FD-was defined as fasting triglyceride (TG) levels >3 mmol/L in untreated subjects or use of lipid lowering medication. The effect of weight, body mass index (BMI), waist circumference, type 2 diabetes mellitus and non-TG metabolic syndrome on development of dyslipidemia was investigated. Results: Eleven of the 69 epsilon 2 epsilon 2 subjects (16%) developed dyslipidemia-likely FD-during follow-up. Age-, sexand cohort-adjusted risk factors for the development of FD were BMI (OR 1.19; 95%CI 1.04-1.39), waist circumference (OR 1.26 95%CI 1.01-1.61) and presence of non-TG metabolic syndrome (OR 4.39; 95%CI 1.04-18.4) at baseline. Change in adiposity during follow-up was not associated with development of dyslipidemia. Conclusions: Adiposity increases the risk of developing an FD-like lipid phenotype in homozygous APOE epsilon 2 subjects. These results stress the importance of healthy body weight in subjects at risk of developing FD
Теоретичні та практичні аспекти приватизації в Україні
Цели статьи заключаются в изучении спроса покупателей на объекты приватизации и анализе финансового состояния предприятий к принятию решения
об их приватизации (на основе данных за I квартал 2006 года), раскрытии основных критериев целесообразности принятия решения о приватизации объектов ведения хозяйства.Цілі статті полягають у вивченні попиту покупців на об'єкти приватизації та
аналізі фінансового стану підприємств до прийняття рішення про їх приватизацію (на основі даних за I квартал 2006 року), розкритті основних критеріїв
доцільності прийняття рішення про приватизацію об'єктів господарювання
Ювілей Михайла Миколайовича Тарана
18 жовтня 2008 р. виповнилося 60 років відомому українському вченому-мінералогу, знаному в світі фахівцю в галузі фізики мінералів, доктору геолого-мінералогічних наук Михайлові Миколайовичу Тарану
Правила оформлення статей
Background For parents at high risk for cardiovascular events, presence of cardiovascular disease or risk factors in their offspring may be an indicator of their genetic load or exposure to (unknown) risk factors and might be related to the development of new or recurrent vascular events. Methods In 4,267 patients with vascular disease, hypertension, diabetes, or hypercholesterolemia enrolled in the SMART cohort, the presence of cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia, smoking, or overweight) and cardiovascular disease (coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysm) was assessed in their 10,564 children. The relation between presence of cardiovascular disease or cardiovascular risk factors in their offspring and new or recurrent vascular events was determined by Cox proportional hazard analyses. Results Of the patients, 506 (12%) had offspring with cardiovascular disease, hypertension, hypercholesterolemia, or diabetes. Smoking in offspring was present in 1,972 patients (46%), and overweight in 845 patients (20%). During a median follow-up of 7.0 years (interquartile range 3.7-10.4), the composite outcome of myocardial infarction (MI), stroke, or vascular mortality occurred in 251 patients. Patients with offspring with cardiovascular disease, hypertension, hypercholesterolemia, or diabetes had an increased risk of vascular mortality (hazard ratio [HR] 2.9, 95% CI 1.2-7.1), MI (HR 1.6, 95% CI 1.1-2.5), and the composite outcome (HR 1.5, 95% CI 1.1-2.2). Diabetes in offspring was related to an increased risk of the composite outcome (HR 2.7, 95% CI 1.5-5.0), MI (HR 3.3, 95% CI 1.7-6.6), and vascular mortality (HR 3.4, 95% CI 0.8-14.8). Smoking and overweight in offspring were not related to increased vascular risk in parents. Conclusions Presence of cardiovascular disease, hypertension, hypercholesterolemia, and diabetes in offspring, with diabetes mellitus being the most contributing cardiovascular risk factor, is related to an increased risk of developing new or subsequent vascular events in patients already at high vascular risk
Excess Early Postnatal Weight Gain Leads to Increased Abdominal Fat in Young Children
Background. Increased childhood weight gain has been associated with later adiposity. Whether excess early postnatal weight gain plays a role in childhood abdominal fat is unknown. Design. In the ongoing Wheezing Illnesses Study Leidsche Rijn (WHISTLER), birth cohort weight and length from birth to age 3 months were obtained. In the first 316 five-year-olds, intra-abdominal and subcutaneous fat were measured ultrasonographically. Individual weight and length gain rates were assessed in each child. Internal Z-scores of weight for length gain (WLG) were calculated. Multiple imputation was used to deal with missing covariates. Results. Per-1-unit increase in Z-score WLG from birth to 3 months, BMI, waist circumference, and subcutaneous fat were significantly higher; 0.51 kg/m2, 0.84 cm, and 0.50 mm, respectively. After multiple imputation, a trend towards significance was observed for intra-abdominal fat as well (0.51 mm/SD). In the associations with 5-year adiposity, no interaction between postnatal Z-score WLG and birth size was found. Conclusion. Excess early postnatal weight gain is associated with increased general and central adiposity, characterized by more subcutaneous and likely more intra-abdominal fat at 5 years of age
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Rs964184 (APOA5-A4-C3-A1) Is Related to Elevated Plasma Triglyceride Levels, but Not to an Increased Risk for Vascular Events in Patients with Clinically Manifest Vascular Disease
Background: Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients. Methods: Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events. Results: The minor allele of rs964184 was strongly associated with log plasma triglycerides (β 0.12; 95%CI 0.10-0.15, p = 1.1*10−19), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01–0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09–0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides 27 kg/m2, p for interaction = 0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p = 0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86–1.13). Conclusion: The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified by body mass index. There is no relation between rs964184 and recurrent vascular events in these patients
В портфеле редакции
OBJECTIVE Our aim is to compare the effect of type 2 diabetes on recurrent major cardiovascular events (MCVE) for patients with symptomatic vascular disease at different locations. RESEARCH DESIGN AND METHODS A total of 6,841 patients from the single-center, prospective Second Manifestations of ARTerial disease (SMART) cohort study from Utrecht, the Netherlands, with clinically manifest vascular disease with (n = 1,155) and without (n = 5,686) type 2 diabetes were monitored between 1996 and 2013. The effect of type 2 diabetes on recurrent MCVE was analyzed with Cox proportional hazards models, stratified for disease location (cerebrovascular disease, peripheral artery disease, abdominal aortic aneurysm, coronary artery disease, or polyvascular disease, defined as >= 2 vascular locations). RESULTS Five-year risks for recurrent MCVE were 9% in cerebrovascular disease, 9% in peripheral artery disease, 20% in those with an abdominal aortic aneurysm, 7% in coronary artery disease, and 21% in polyvascular disease. Type 2 diabetes increased the risk of recurrent MCVE in coronary artery disease (hazard ratio [HR] 1.67; 95% CI 1.25-2.21) and seemed to increase the risk in cerebrovascular disease (HR 1.36; 95% CI 0.90-2.07), while being no risk factor in polyvascular disease (HR 1.12; 95% CI 0.83-1.50). Results for patients with peripheral artery disease (HR 1.42; 95% CI 0.79-2.56) or an abdominal aortic aneurysm (HR 0.93; 95% CI 0.23-3.68) were inconclusive. CONCLUSIONS Type 2 diabetes increased the risk of recurrent MCVE in patients with coronary artery disease, but there is no convincing evidence that it is a major risk factor for subsequent MCVE in all patients with symptomatic vascular disease
Low-Density Lipoprotein Cholesterol, Non–High-Density Lipoprotein Cholesterol, Triglycerides, and Apolipoprotein B and Cardiovascular Risk in Patients With Manifest Arterial Disease
Low-density lipoprotein cholesterol (LDL-C) only partly represents the atherogenic lipid burden, and a growing body of evidence suggests that non–high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and apolipoprotein B (apoB) are more accurate in estimating lipid-related cardiovascular disease risk. Our objective was to compare the relation among LDL-C, non-HDL-C, triglycerides, and apoB and the occurrence of future vascular events and mortality in patients with manifest arterial disease. This is a prospective cohort study of 7,216 patients with clinically manifest arterial disease in the Secondary Manifestations of Arterial Disease Study. Cox proportional hazard models were used to quantify the risk of major cardiovascular events (MACE; i.e., stroke, myocardial infarction, and vascular mortality) and all-cause mortality. Interaction was tested for type of vascular disease at inclusion. MACE occurred in 1,185 subjects during a median follow-up of 6.5 years (interquartile range 3.4 to 9.9 years). Adjusted hazard ratios (HRs) of MACE per 1 SD higher were for LDL-C (HR 1.15, 95% confidence interval [CI] 1.09 to 1.22), for non-HDL-C (HR 1.17, 95% CI 1.11 to 1.23), for log(triglycerides) (HR 1.12, 95% CI 1.06 to 1.19), and for apoB HR (1.12, 95% CI 0.99 to 1.28). The relation among LDL-C, non-HDL-C, and cardiovascular events was comparable in patients with cerebrovascular disease, coronary artery disease, or polyvascular disease and absent in those with aneurysm of abdominal aorta or peripheral artery disease. In conclusion, in patients with a history of cerebrovascular, coronary artery, or polyvascular disease, but not aneurysm of abdominal aorta or peripheral artery disease, higher levels of LDL-C and non-HDL-C are related to increased risk of future MACE and of comparable magnitude
The relationship between walking speed and changes in cardiovascular risk factors during a 12-day walking tour to Santiago de Compostela: a cohort study
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