Treatment of homozygous patients with familial hypercholesterolemia by double-filtration plasmapheresis

Two homozygous patients with familial hypercholesterolemia were treated by double-filtration plasmapheresis. The plasma separated by the first filter was subsequently led to the second filter of ethylene vinylalcohol co-polymer hollow fibers, which trap very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) preferentially to other plasma constituents. Serum, VLDL, IDL, LDL cholesterol levels decreased by 55, 68, 59 and 55%, respectively. HDL cholesterol levels decreased by 39%. Immunoglobulins and fibrinogen levels decreased significantly. Cutaneous and tendinous xanthomas became smaller. off     

Characteristics of patients resistant to antihypertensive drug therapy

In order to determine the features that characterize refractory hypertension (RH), patients aged less than 65 years in a hypertension clinic were screened. Thirty-six patients on triple drug therapy with a supine diastolic blood pressure (DBP) of greater than or equal to 5 mmHg above an identified target pressure (90-100 mmHg), or a systolic blood pressure (SBP) greater than or equal to 170 mmHg for the last 6 months (greater than or equal to 3 measurements) underwent a thorough clinical investigation. The frequency of renal artery stenosis (RAS) in the RH patients was 30%. The non-RAS patients had a low occupational status, 76% being either manual workers or unskilled non-manual workers (reference group: 42%; P less than 0.01). They were more obese (body mass index (BMI) 28.8 vs. 25.8; P less than 0.01), and had a longer duration of hypertensive disease. RH patients had a higher prevalence of non-insulin-dependent diabetes mellitus (18 vs. 6%; P less than 0.05), and showed a higher prevalence of nervous complaints and mental distress (44% vs. 12%; P less than 0.001) and musculo-skeletal pain (39% vs. 7%: P less than 0.001). It is suggested that refractory hypertension should be investigated and treated bearing psychosocial factors in mind, concurrently with a screening for secondary hypertension.     

Methodology of plasmapheresis in the treatment of patients with hereditary hypercholesterolemia

The plasma replacement procedure using the blood cell separator IBM-2997 provides for safe replacement of 2000-3000 ml plasma and a 35 to 45% reduction of the lipid concentration. Plasma replacement with 5% albumin solution per 50 to 70% of total volume allows to maintain normal total plasma protein levels throughout treatment. It was demonstrated that plasmapheresis with plasma ultrafiltrate return makes the procedure more tolerable for the patients, while their own electrolytes, amino acids, vitamins and some enzymes are retained. The reported technique for the discontinuation of the procedure reduces the volume of residual blood in the separation channel, preventing anemia.     

Use of plasma sorption in the treatment of hypercholesterolemia in patients with stenocardia

Plasma sorption was performed in patients with Functional Classes III-IV angina pectoris by using the sorbent FAS. A positive clinical effect was achieved in 81%. There was a significant reduction in the levels of total cholesterol and low density lipoprotein cholesterol. The concentration of high density lipoprotein cholesterol remained unchanged.     

双重血浆置换联合他汀治疗肾病综合征严重高胆固醇血症的疗效

目的:观察双重血浆置换(DFPP)联合他汀类降脂药治疗肾病综合征(NS)严重高胆固醇血症的作用,并分别与单独使用DFPP与他汀类药物进行对比。方法:选取南京军区南京总医院全军肾脏病研究所门诊患者12例,住院患者10例,临床表现为肾病综合征合并严重高胆固醇血症[总胆固醇(TC)10mmol/L]。门诊患者入选后在原有治疗基础上服阿托代他汀20mg/d(他汀组);住院患者入选后在原有治疗基础上,2例接受单纯DFPP治疗一次(DFPP组);8例接受DFPP一次治疗,同时在DFPP前3～4d开始服阿托代他汀20mg/d(联合组)。所有患者随访观察4周。结果:三组患者尿蛋白定量、血脂、血清肌酐(SCr)基线值比较无差异。DFPP单次治疗对血清白蛋白及IgG无明显影响,而IgA,IgM及纤维蛋白原显著下降(P0.01)。各种脂蛋白TC,三酰甘油,低密度脂蛋白,高密度脂蛋白,载脂蛋白A1、B及E下降率分别为85.8%±7.2%,80.1%±6.2%,86.9%±11.4%,66.4%±9%,54.1%±6.3%,86.4%±9.4%,70.3%±6.9%(P0.01)。三组患者随访4周后尿蛋白定量、SCr、血清白蛋白水平与治疗前无明显变化。DFPP组随访1周时TC水平为基线值85.9%,两周时恢复至基线水平,4周时略高于基线值;联合组患者随访1、2周时TC水平低于基线50%以下(显著低于另两组水平,P0.05),4周时为基线值70.2%;他汀组患者随访两周及4周TC水平保持在基线81%左右。随访期间三组患者TG水平较基线值无明显差别。结论:单次DFPP联合他汀药物虽不能改善NS患者对原发病治疗的反应性,但较两种方法单用能更有效地降低其高胆固醇血症。     

Thrombocyte function during the performance of plasmapheresis and immunosorption in patients with familial hypercholesterolemia

The impact of plasmapheresis (PA) and immunosorption (IS) of low density lipoproteins (LDLP) on platelets was examined in patients with familial hypercholesterolemia. PA and IS sessions resulted in a decrease of platelet counts, aggregation activity in relation to TXA2 analogue, U46619, and capacity for adhesion and spreading over type-4 collagen-coated surface. All effects were of similar markedness in both procedures, i.e. they were unrelated to PA or IS specificity, but rather were due to platelet interaction with extracorporeal circulation circuit. Platelet changes seen immediately after the procedure were transitory. Platelet counts and capacity for aggregation and adhesion were recovered by the time of the next procedure (1 or 2 weeks later). Long-term (more than 6 months') use of PA or IS did not essentially affect platelet counts, aggregation and adhesion, but rather undermined platelet spreading capacity.     

The renin-angiotensin-aldosterone system and antidiuretic hormone secretion during plasmapheresis in patients with high arterial hypertension refractory to drug therapy

Plasmapheresis (PP) was used in 28 patients with medication-resistant high arterial hypertension (AH). PP-induced changes in plasma renin activity and blood aldosterone, angiotensin II and antidiuretic hormone levels of patients with high AH are shown to be a compensatory-adaptive response, maintaining homeostasis. PP sessions (27 ml/kg body weight at a rate of 0.22 ml/kg/min, at the maximum) do not produce renin-angiotensin-aldosterone activation. Long-term hypotensive effect of PP in cases of high AH might be related to a gradual decrease in blood angiotensin II and systemic aldosterone synthesis. It is suggested that the hypotensive effect of PP may be due to an intricate interaction of effects, with humoral, receptor and circulatory re-adjustments of arterial BP control being the most prominent among those.     

Long-term changes in cholesterol biosynthesis and the effect of plasmapheresis therapy in a hypercholesterolemia homozygote

Synthesis of cholesterol was measured in a familial hypercholesterolemia homozygote on four occasions from age 1.1 to 9.9 years by the sterol balance technique. Both the fecal neutral steroid and fecal bile acid components of sterol balance were elevated initially. Over the decade of study, neutral steroid excretion/kg declined 61% whereas bile acid excretion/kg was unchanged. Chronic plasmapheresis therapy every two weeks for 3.4 years reduced plasma low-density lipoprotein cholesterol 54% but had little effect on the rate of cholesterol biosynthesis.     

Three different schedules of low-density lipoprotein apheresis compared with plasmapheresis in patients with homozygous familial hypercholesterolemia

PURPOSE: To determine the biochemical and clinical response of two patients with homozygous familial hypercholesterolemia to three different schedules of low-density lipoprotein apheresis compared with plasmapheresis. PATIENTS AND METHODS: Two female patients aged 17 years, both affected by homozygous familial hypercholesterolemia, underwent low-density lipoprotein apheresis using a dextran-sulfate/cellulose affinity column on successive twice-weekly, weekly, and biweekly schedules. Plasmapheresis was carried out only at biweekly intervals. Plasma lipids and apolipoproteins A1 and B were assayed before and after each procedure. Cardiac status was assessed before and after the study. RESULTS: On schedule 1 of apheresis, the immediate post-procedure low-density lipoprotein cholesterol levels declined to 60 mg/100 dL plasma. Quasi-steady-state values of low-density lipoprotein cholesterol and apolipoprotein B were also markedly reduced, with levels approaching the upper limits of normal for age and sex. This response was attenuated as the intervals between procedures were prolonged. No advantage of low-density lipoprotein apheresis over plasmapheresis was observed during the biweekly protocol except that after plasmapheresis high-density lipoprotein cholesterol levels declined by 50% or more compared with less than 10% after apheresis. The latter procedure, especially on schedules 1 and 2, caused an increase in the quasi-steady-state concentrations of both high-density lipoprotein cholesterol and apolipoprotein A1. Thus, mean low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and apolipoprotein B/apo A1 ratios were reduced by more than three- to four-fold during twice-weekly apheresis. Other laboratory parameters remained stable throughout except for iron and hemoglobin levels, which were reduced with both plasmapheresis and apheresis. Xanthomas regressed significantly in the one patient who had not been treated prior to the current trial. Cardiac changes were minor in both patients. CONCLUSION: Low-density lipoprotein apheresis proved safe and effective on an accelerated protocol as well as during more conventional schedules. Owing to its simplicity, selectivity, and safety, apheresis using a dextran-sulfate/cellulose column is possibly the optimum means currently available for the extracorporeal removal of low-density lipoprotein cholesterol.     

Effect of isolated ultrafiltration on plasma hormone levels in patients with heart failure resistant to drug therapy

The positive action exerted by isolated ultrafiltration on 69 patients with refractory heart failure was shown to be due to the complex interaction of effects produced by ultrafiltrate removal. Among the effects, a leading role is played by therapy for hyperaldosteronism and reduction of antidiuretic hormone levels along with improvement of the functional status of the liver and heart.     

Experiences using long-term (4-12 months) plasmapheresis in patients with hereditary hypercholesterolemia

A total of 122 plasmapheresis procedures were given to 4 patients with inherited hypercholesterolemia for 4 to 12 months, with 7 to 14 days' intervals, using a cellular blood separator. The method has been shown to produce a 35 to 45% reduction in total cholesterol (CS), LDLPCS and VLDLPCS, and an 8 to 38% rise in HDLP CS, which improves general condition and working capacity of the patients, makes anginal attacks less frequent and severe and normalizes arterial BP in patients with arterial hypertension.     

他汀类药物对藏族高尿酸血症合并高胆固醇血症患者疗效的研究

目的：探讨藏族人群血尿酸与颈动脉内-中膜厚度（IMT）的关系以及他汀类药物对藏族高尿酸血症合并血脂异常患者的疗效。方法：所有患者每晚口服阿托伐他汀20mg，连续12周。在服药前及治疗后12周采血测定血尿酸（UA），总胆固醇（TC），甘油三酯（TG）．高密度脂蛋白胆固醇（HDL-C），低密度脂蛋白胆固醇（LDL-C）．血尿素氮（BUN），肌酐（Cr），转氨酶水平。B型超声测量IMT。结果：80名人选患者均有血TC及尿酸异常。多元回归分析表明．服药前TC．TG．LDL（β=0．145-0．189），HDL（β=-0．181）和UA（β=0．284）与IMT相关（P〈0．05～〈0．01）。阿托伐他汀降低TC水平33．8％，TG24．9％．LDL-C12．2％．而HDL-C虽有升高趋势，但不显著（P〉0．05）。血尿酸水平明显降低达12．6％。结论：高尿酸血症与颈动脉粥样硬化相关。阿托伐他汀降低血脂、血尿酸含量有效。     

Mipomersen: a safe and effective antisense therapy adjunct to statins in patients with hypercholesterolemia

Mipomersen is an antisense oligonucleotide inhibitor of apolipoprotein (apo) B-100 currently in phase 3 of development for the treatment of hyperlipidemia in patients with a high risk for cardiovascular disease. The drug acts by inhibiting the production of apoB-100, which is the structural core for all atherogenic lipids, including low-density lipoprotein cholesterol (LDL-C). The agent has been shown to produce significant reductions in LDL-C from baseline values compared with placebos. Clinical trials have demonstrated that mipomersen reduces LDL-C up to 44% in patients with familial hypercholesterolemia and patients with significantly elevated LDL despite taking maximum doses of statins. Unlike other medications that target apoB-100, such as microsomal triglyceride transfer proteins, mipomersen does not cause hepatic steatosis or intestinal steatosis and does not affect dietary fat absorption. Adverse side effects encountered with mipomersen include flu-like symptoms, injection site reactions, and elevated liver transaminases. If future studies continue to show such promising results, mipomersen would likely be a viable additional lipid-lowering therapy for patients who are at high cardiovascular risk, intolerant to statins, and/or not at target lipid levels despite maximum doses of statin therapy. Clinical outcome studies looking at cardiovascular disease end points still need to be done.     

Effectiveness of low-dose colestipol therapy in patients with moderate hypercholesterolemia.

Recommended doses of bile-acid binding resins have an established hypocholesterolemic effect, but data on responses to low doses, especially in women and subjects with moderate hypercholesterolemia, are sparse. A double-blind, placebo-controlled, randomized trial of 3 low doses of colestipol hydrochloride was conducted in women and men with moderate hypercholesterolemia. Men and women with plasma low-density lipoprotein (LDL) cholesterol concentrations greater than 4 mmol/liter (155 mg/dl) and triglyceride concentrations less than 2.82 mmol/liter (250 mg/dl) were recruited for the study. Eligible patients (54 women and 98 men) were placed on the American Heart Association step I diet 6 weeks before randomization. Participants were subsequently assigned to 1 of 4 drug treatment groups (placebo, and 5, 10 and 15 g/day of colestipol in 2 divided doses) for an additional 12 weeks. Of the 152 patients randomized, 141 completed all aspects of the study. For the treatment groups--placebo, and 5, 10 and 15 g of colestipol--LDL cholesterol reductions (mmol/liter) were observed respectively (n = 141): 0.10 +/- 0.49 (2.7%), 0.65 +/- 0.41 (16.3%), 0.98 +/- 0.36 (22.8%) and 1.17 +/- 0.47 (27.2%) (p less than 0.001). Similar changes were observed in total cholesterol and apolipoprotein B concentrations. The apolipoprotein B/LDL cholesterol ratio increased significantly with increasing colestipol dosage. Modest but insignificant changes in plasma triglyceride levels occurred, and high-density lipoprotein cholesterol levels remained unchanged. A dose of 5 g/day of colestipol achieved 51% of the LDL cholesterol reduction noted with 15 g/day. Low-dose colestipol therapy is effective in the treatment of patients with moderate hypercholesterolemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of plasma- and thrombocytapheresis in patients with stenocardia

Marked microcirculatory changes, hemorheologic and immunologic disorders were found in anginal patients. Plasmapheresis with repeated thrombocytopheresis sessions as part of combined treatment improves these parameters, the improvement correlating with a stable clinical remission.     

118例高胆固醇血症患者调脂治疗达标情况分析

目的 调查高胆固醇血症患药物治疗达标率。方法 对现行调脂治疗持续时间≥2个月的118例高胆固醇血症患进行血脂检查,并根据1997年我国制定的《血脂异常防治建议》确定血脂是否达标。结果 总胆固醇（TC）和低密度脂蛋白胆固醇（LDL－C）总达标率分别为23．7％、38．1％,他汀类药物LDL－C总达标率高于海鱼油和绞股兰每日20mg辛伐他汀LDL－C达标率高于每日20mg氟伐他汀。结论 现行调脂治疗达标率较低,可能与选择药物的种类和药物剂量有关。