Soy protein diet significantly improves endothelial function and lipid parameters.

BACKGROUND: Replacement of animal protein with soy protein in the diet is associated with decreased cholesterol levels. However, the effects of soy protein diet on endothelial function are not well known. HYPOTHESIS: The aim of the study was to investigate the effects of soy protein diet on plasma lipids and endothelial function parameters assessed by two different methods. METHODS: Twenty hypercholesterolemic, nonsmoker male patients (age 50.1+/-11.8 years), with a normal body mass index, were included. After calculating their daily requirements, a diet with 25-30% of energy from fats. 10-12% from proteins, and the rest from carbohydrates was instituted. Sixty percent of the animal source proteins of the diet were substituted by soy. The anthropometric measures, lipid parameters, and endothelial functions of the subjects were assessed at baseline and 6 weeks after soy protein diet. Flow-mediated endothelium-dependent dilatation (EDD) and plasma thrombomodulin (TM) levels were evaluated as endothelial function parameters. RESULTS: After diet, plasma total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and triglyceride levels decreased significantly (p <0.001, p < 0.001, p = 0.039, and p = 0.001, respectively). The mean plasma TM levels were also significantly reduced with diet (p = 0.004). Studies of the brachial artery indicated a borderline dilatation in baseline brachial artery diameter (p = 0.05), however the diameter at reactive hyperemia was significantly larger after diet (p<0.001), resulting in a significant improvement of EDD (p = 0.002). CONCLUSION: Soy protein diet significantly improves plasma lipid profile in patients with hypercholesterolemia. Furthermore, the endothelial function, as judged by two different methods (EDD and plasma TM levels), also improves with soy protein diet.     

Precision Medicine Approaches to Vascular Disease: JACC Focus Seminar 2/5

In this second of a 5-part Focus Seminar series, we focus on precision medicine in the context of vascular disease. The most common vascular disease worldwide is atherosclerosis, which is the primary cause of coronary artery disease, peripheral vascular disease, and a large proportion of strokes and other disorders. Atherosclerosis is a complex genetic disease that likely involves many hundreds to thousands of single nucleotide polymorphisms, each with a relatively modest effect for causing disease. Conversely, although less prevalent, there are many vascular disorders that typically involve only a single genetic change, but these changes can often have a profound effect that is sufficient to cause disease. These are termed “Mendelian vascular diseases,” which include Marfan and Loeys-Dietz syndromes. Given the very different genetic basis of atherosclerosis versus Mendelian vascular diseases, this article was divided into 2 parts to cover the most promising precision medicine approaches for these disease types.     

Liver transplantation as a definitive treatment for familial hypercholesterolemia: A series of 36 cases

FH is a genetic disorder characterized by an increase in serum LDL and total cholesterol values. The afflicted patients are at increased risk of premature atherosclerosis and myocardial infarction. Different treatment modalities are present, including pharmacological agents and surgical procedures. The most effective method of therapy in refractive cases is liver transplantation. Herein, we report our experience on 36 cases of patients with FH undergoing liver transplantation in our center, the main referral center of liver transplantation in Iran. The clinical findings, hospital courses, post‐operative complications, and patient follow‐up are also described.     

The Return of Actionable Variants Empirical (RAVE) Study,a Mayo Clinic Genomic Medicine Implementation Study: Design and Initial Results

Objectives

To identify clinically actionable genetic variants from targeted sequencing of 68 disease-related genes, estimate their penetrance, and assess the impact of disclosing results to participants and providers.

肝脏调节胆固醇代谢稳态的研究进展

胆固醇代谢稳态是机体发挥生理功能的重要保障。胆固醇代谢紊乱引起的体内胆固醇异常积聚可导致肝脏脂肪病变以及高胆固醇血症,与动脉粥样硬化等心血管疾病的发生发展密切相关。肝脏在维持机体胆固醇代谢稳态过程中发挥着关键性作用,其胆固醇代谢涉及摄取、合成、生物转化以及外排等多个环节。文章就肝脏调节胆固醇代谢稳态的最新进展作一综述。     

Nonprogression of coronary artery atherosclerosis in homozygous familial hypercholesterolemia after 31 months of repetitive plasma exchange

The effects of plasma exchange performed every two weeks for 31 months in combination with diet and drug therapy were studied in a patient with receptor-defective homozygous familial hypercholesterolemia. Coronary angiography performed three years prior to commencing plasma exchange was compared to angiography 31 months after starting the program. Comparison of the angiograms taken six years apart showed no progression of coronary atheroma in the main left coronary artery in which a 30% narrowing was originally seen. An internal mammary artery-coronary artery bypass remained widely patent and showed no development of atherosclerosis. Plasma cholesterol levels were reduced 46% by plasma exchange, diet and drug compared to diet and drug alone. Achilles tendon xanthoma diminished significantly. It appears that plasma exchange combined with diet and drug therapy, while not producing regression of existing atheromatous lesions, does retard or prevent further progression.     

The implications of the ezetimibe and simvastatin in hypercholesterolemia enhances atherosclerosis regression trial: a return to first principles

To outward appearances, the publication of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial has led to a monolithic backlash against the use of ezetimibe by cardiologists for the treatment of hyperlipidemia. Rather than be swayed by popular opinion, we should each put the results of ENHANCE into context and ask the questions: should I put my trust in an imaging surrogate or in low‐density lipoprotein (LDL) cholesterol (LDL‐C), and how do the safety and efficacy of ezetimibe compare with other nonstatin lipid‐lowering agents? Copyright © 2008 Wiley Periodicals, Inc.     

Low-density lipoprotein apheresis in children with familial hypercholesterolemia: follow-up to 21 years

Twenty-seven patients (14 girls, 13 boys) affected by familial hypercholesterolemia who had begun low-density lipoprotein (LDL) apheresis treatment before the age of 15 were studied. The median age at diagnosis was 4 years and the blood LDL cholesterol level was 704 +/- 163 mg/dL. Screening was performed for homozygous or double heterozygous mutations of the LDL cholesterol receptor gene and mutations were found in 24 of the patients. The mean age at the beginning of treatment was 8.5 years and the mean length of follow up was 12.6 years. The two main procedures used were direct adsorption of lipoproteins and dextran sulfate cellulose adsorption. Nine patients experienced anaphylactic reactions due to bradykinin and six had to have their treatment changed. The LDL cholesterol level before the session was lowered by 45 +/- 11% of the value at diagnosis. The LDL cholesterol reduction in a session was 72 +/- 10%. Tendinous xanthomas disappeared or diminished dramatically in 62% of the children. In 22 patients no cardiovascular event occurred during LDL apheresis treatment. Three had angina pectoris; two others had surgical management of aortic stenosis, but no clinical manifestations. Seven children had normal cardiovascular pictures while on treatment. Eleven had abnormalities of the aortic root or coronary arteries, which in six cases had appeared before treatment; the other five children did not undergo prior cardiac evaluation. In five children the abnormalities appeared during treatment. Based on these data, LDL-apheresis can be recommended for the treatment of homozygous familial hypercholesterolemia, even in young children, with good efficiency on biological parameters, cutaneous lesions and cardiovascular events.     

Long-term effect of low-density lipoprotein apheresis in patients with heterozygous familial hypercholesterolemia

Clinical efficacy and safety of the therapeutic tool which directly removes LDL particles from circulation (LDL apheresis) have already been established in the treatment for refractory hypercholesterolemia in patients with familial hypercholesterolemia (FH). Two clinical studies with event-based assessment have demonstrated remarkably beneficial outcomes of long-term LDL apheresis using dextran sulfate cellulose columns plus adjunctive cholesterol-lowering drug therapy in the prevention of cardiovascular events in heterozygous FH with coronary artery disease. The results of several studies with angiographic and ultrasound-based assessment indicate a possible role for LDL apheresis in restructuring and stabilization of atherosclerotic lesions. These clinical improvements caused by LDL apheresis in heterozygous FH support the efficacy and importance of aggressive cholesterol-lowering therapy for secondary prevention of atherosclerotic cardiovascular disease in hypercholesterolemic patients.     

Diferencias clínicas y genéticas de los pacientes con hipercolesterolemia familiar heterocigota con y sin diabetes mellitus tipo 2

Introduction and objectivesThe lower prevalence of type 2 diabetes mellitus (T2DM) in patients with heterozygous familial hypercholesterolemia (HeFH) could explain why T2DM has not always been identified as an independent predictor of cardiovascular disease (CVD) in different familial hypercholesterolemia cohort studies. The aim of the present study was to evaluate clinical and genetic aspects of HeFH patients with T2DM in the dyslipidemia registry of the Spanish Arteriosclerosis Society.MethodsHeFH patients were classified according to the presence or absence of T2DM. The clinical, biochemical and genetic characteristics of the 2 groups were compared.ResultsOf the 2301 patients with primary hypercholesterolemia included in the registry, 1724 with a probable or definite diagnosis according to the Dutch Lipid Clinic Network score were finally included. HeFH patients with T2DM had a higher rate of CVD and a less favorable lipid profile, with higher total cholesterol (366.9 ± 86.7 mg/dL vs 342.0 ± 74.7 mg/dL; mean difference 24.894; 95%CI, 5.840-43.949) and non–high-density lipoprotein cholesterol (316.9 ± 87.8 mg/dL vs 286.4 ± 75.4 mg/dL; mean difference 30.500; 95%CI, 11.211-49.790) levels. No significant differences were found between the groups concerning the specific type of HeFH-causing mutation (P = .720). After adjustment for major risk factors, logistic regression analysis confirmed a relationship between T2DM and the presence of CVD (OR, 2.01; 95%CI, 1.18-3.43; P = .010).ConclusionsHeFH patients with T2DM have a higher rate of CVD and a less favorable lipid profile, regardless of genetic mutation type. In these patients, T2DM is associated with the presence of CVD.