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.     

Increase of inflammatory state in overweight adults with combined hyperlipidemia

BACKGROUND AND AIM: Elevated levels of acute phase reactants are found in patients with cardiovascular disease. It is suggested that adipose tissue is a determinant of a low level of inflammatory state in overweight persons. The aim of the study was to determine, whether combined hyperlipidemia, which is an important factor of atherosclerosis, has influence on the inflammatory response in overweight adults. METHODS AND RESULTS: Levels of soluble cell adhesion molecules sICAM-1, sE-selectin and sP-selectin, PAI-1 Ag (by Elisa test), orosomucoid (ORM) and transferrin (TRF) (by microturbidimetry) and fibrinogen (FBG) according to Clauss were examined in peripheral blood of overweight adults (n 33, body mass index 27.1 +/- 1.8 kg/m2) with combined hyperlipidemia and in equal numbers of age, sex and BMI matched non-hyperlipidemic group. Overweight adults with combined hyperlipidemia had significantly higher plasma levels of sICAM-1 (376.5 +/- 107.4 ng/mL vs 239.3 +/- 60.4 ng/mL; p < 0.001), sE-selectin (70.4 +/- 20.2 ng/mL vs 48.5 +/- 25.6 ng/mL; p = 0.005), sP-selectin (228.2 +/- 88.6 ng/mL vs 123.1 +/- 45.3 ng/mL; p < 0.001) and positive acute phase proteins ORM (0.82 +/- 0.16 g/L vs 0.64 +/- 0.20 g/L; p = 0.005), FBG (3.42 +/- 0.54 g/L vs 2.74 +/- 0.57 g/L; p = 0.037) and PAI-1 Ag (97.9 +/- 40.6 ng/mL vs 56.4 +/- 25.6 ng/mL; p < 0.05), and a decrease of negative acute phase protein TRF (2.14 +/- 0.40 g/L vs 2.77 +/- 0.45 g/L; p < 0.001) compared to the results in overweight non-hyperlipidemic controls. CONCLUSIONS: It is suggested that overweight adults have an increase of inflammatory response dependent on hyperlipidemia. It was apparent from the elevation of sE--selectin, sP--selectin and sICAM-1 and from an increase of systemic inflammatory response according to the increase of "positive" acute phase proteins (APRs) and the decrease of "negative" APR protein levels in these patients.     

微粒化力平脂治疗原发性高脂血症疗效的初步观察

22例原发性高脂血症患者服用微粒化力平脂200mg，每晚一次，共8周，并随机设立空白对照11例。结果显示：治疗8周后，患者血清甘油三酯明显降低（P＜0．001），显效率为86．4％，高密度脂蛋白胆固醇明显升高（P＜0．01），纤维蛋白原明显降低（P＜0．01），而血清总胆固醇降低未达到统计学意义。结论：微粒化力平脂特别适用于IV型高脂血症患者并对纤维蛋白原升高者有益。     

Effect of simvastatin on high density lipoprotein subfractions and apolipoproteins in Type IIa hypercholesterolemia

Summary Changes in plasma concentrations of high density lipoproteins (HDL) and triglycerides may partly explain the ability of cholesterol-lowering drugs to decrease the incidence of coronary heart disease. We measured the response of fasting plasma lipids, lipoproteins, and apolipoproteins in 46 subjects with Type IIa hypercholesterolemia treated with simvastatin for 3 months. The initial dose of simvastatin (10 mg/day) was subsequently increased up to 40 mg/day if the plasma cholesterol concentration had not fallen below 5.2 mmol/l. Plasma concentrations of HDL cholesterol and of the apolipoproteins AI and AII were increased by simvastatin. The increase in HDL cholesterol (9%) was due to increases in both subfractions (HDL₂ 17%; HDL₃ 7%), changes that would be consistent with a beneficial effect on cardiovascular risk. Simvastatin decreased plasma triglyceride concentrations by 25%. Plasma total cholesterol concentrations fell by 35% after 3 months of treatment; this fall was proportional to the initial concentration and was due almost entirely to a 45% fall in low density lipoprotein cholesterol. In contrast, plasma concentrations of lipoprotein Lp(a) were not affected by simvastatin.     

SERUM LIPID AND APOLIPOPROTEIN A AND B LEVELS IN FAMILIAL HYPERCHOLESTEROLEMIA

Serum lipid and apolipoprotein A (apo A) and B (apo B) levels were studied in a family with familial hypercholesterolemia (FH), which comprised two heterozygous parents, five heterozygous children, one homozygote and one normal child. Lipid levels were compared with those of age- and sex-matched normal controls. All subjects with FH had total serum cholesterol and low density lipoprotein-cholesterol (LDL-C) levels greater than the 90th percentile value for the reference range. High density lipoprotein-cholesterol (HDL-C) levels were less than the corresponding 13th percentile in heterozygous subjects. The homozygous child had grossly elevated levels of LDL-C and apo B, and very low levels of HDL-C and apo A. The most powerful discriminating variable between normal, heterozygous and homozygous family members was the LDL-C/HDL-C ratio.     

Detecting familial hypercholesterolemia by serum lipid profile screening in a hospital setting: Clinical,genetic and atherosclerotic burden profile

Background and aims

Familial hypercholesterolemia (FH) is underdiagnosed and public cholesterol screening may be useful to find new subjects. In this study, we aim to investigate the prevalence of FH patients in a hospital screening program and evaluate their atherosclerotic burden using intima-media thickness (IMT).

降脂通脉胶囊联合藻酸双酯钠治疗高脂血症的临床研究

目的探讨降脂通脉胶囊联合藻酸双酯钠片治疗高脂血症的临床疗效。方法选择2018年3月-2019年3月在陕西省荣誉军人康复医院治疗的高脂血症患者86例,根据用药的差别分为对照组(43例)和治疗组(43例)。对照组口服藻酸双酯钠片,50mg/次,3次/d;治疗组在对照组基础上口服降脂通脉胶囊,2.0g/次,3次/d。两组患者经4周治疗。观察两组患者临床疗效,同时比较治疗前后两组患者高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)、胆固醇(TC)、嗜酸性粒细胞阳离子蛋白(ECP)、摄食抑制因子-1(NSF-1)、硫氧还蛋白相互作用蛋白(TXNIP)、肿瘤坏死因子-α(TFN-α)、白细胞介素-1β(IL-1β)、脂联素(ADP)、超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)水平。结果治疗后,对照组临床有效率为81.40%,显著低于治疗组的97.67%,两组比较差异有统计学意义(P<0.05)。治疗后,两组患者TC、TG、LDL-C、ECP、IL-1β、TFN-α、TXNIP、NSF-1和MDA水平均显著降低(P<0.05),而HDL-C、ADP、SOD和GSH-Px水平均显著升高(P<0.05),且治疗组患者这些指标明显好于对照组(P<0.05)。结论降脂通脉胶囊联合藻酸双酯钠片治疗高脂血症可有效降低血脂指标,促进机体细胞因子和氧化应激指标的改善,具有一定的临床推广应用价值。     

Long-term follow-up and successful treatment of pulmonary alveolar proteinosis without hypercholesterolemia with statin therapy: a case report

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the accumulation of excessive surfactant lipids and proteins in alveolar macrophages and alveoli. Oral statin therapy is a novel treatment for PAP with hypercholesterolemia. However, this treatment has never been described in a patient without hypercholesterolemia. Here, we present a case of successful treatment with atorvastatin for a patient with possibly unclassified PAP without hypercholesterolemia who responded poorly to whole lung lavage therapy and inhaled granulocyte-macrophage colony-stimulating factor. After 18 months of atorvastatin treatment, the patient experienced improvements in dyspnea, radiographic abnormalities and pulmonary function. The present case study supports the feasibility of statin therapy for PAP regardless of the level of cholesterol.     

Phenotypic characterization and predictive analysis of p.Asp47Asn LDL receptor mutation associated with Familial Hypercholesterolemia in a Chilean population

BackgroundFamilial hypercholesterolemia (FH) is an inherited disorder mainly caused by mutations in the LDL receptor (LDL-R) and characterized by elevation of low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease.ObjectiveIn this study, we evaluated the clinical phenotype of the p.Asp47Asn, described as an uncertain pathogenic variant, and its effect on the structure of LDL-R and ligand interactions with apolipoproteins.Methods27 children and adolescents with suspected FH diagnosis were recruited from a pediatric endocrinology outpatient clinic. Blood samples were collected after 12 h fasting for lipid profile analysis. DNA sequencing was performed for six FH-related genes by Ion Torrent PGM platform and copy number variation by MLPA. For index cases, a familial cascade screening was done restricted to the same mutation found in the index case. In silico analysis were developed to evaluate the binding capacity of LDL-R to apolipoproteins B100 and E.ResultsLipid profile in children and adolescents demonstrated higher LDL-C levels in p.Asp47Asn carriers compared to the wild type genotype. In silico analysis predicted a reduction in the binding capacity of the ligand-binding modules LA1-2 of p.Asp47Asn LDL-R for ApoB100 and ApoE, which was not produced by local structural changes or folding defects but as a consequence of a decreased apparent affinity for both apolipoproteins.ConclusionThe clinical phenotype and the structural effects of p.Asp47Asn LDL-R mutation suggest that this variant associates to FH.     

Prognostic impact of cascade screening for familial hypercholesterolemia on cardiovascular events

BackgroundFamilial hypercholesterolemia (FH) is an autosomal dominant disorder mainly caused by mutations in the low-density lipoprotein (LDL) receptor or associated genes, resulting in elevated serum cholesterol levels and an increased risk of premature atherosclerotic cardiovascular disease (ASCVD).ObjectiveWe aimed to evaluate the prognostic impact of cascade screening for FH.MethodsWe retrospectively investigated the health records of 1050 patients with clinically diagnosed FH, including probands and their relatives who were cascade-screened, who were referred to our institute. We used Cox models that were adjusted for established ASCVD risk factors to assess the association between cascade screening and major adverse cardiac events (MACE). The median period of follow-up evaluating MACE was 12.3 years (interquartile ranges [IQR] = 9.1–17.5 years), and MACE included death associated with ASCVD, or acute coronary syndrome.ResultsDuring the observation period, 113 participants experienced MACE. The mean age of patients identified through cascade screening was 18-years younger than that of the probands (38.7 yr vs. 57.0 yr, P < 0.0001), with a lower proportion of ASCVD risk factors. Interestingly, patients identified through cascade screening under milder lipid-lowering therapies were at reduced risk for MACE (hazard ratio [HR] = 0.67; 95%CI = 0.44 to 0.90; P = 0.0044) when compared with the probands, even after adjusting for those known risk factors, including age, and prior ASCVD.ConclusionsThe identification of patients with FH via cascade screening appeared to result in better prognosis.