家族性高胆固醇血症一家系调查

目的：了解家族性高胆固醇血症的临床及遗传特征。方法：对家族性高胆固醇血症一家系４５名家族直系成员进行了调查，检查了所有成员血清总胆固醇（ＴＣ）、低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）及甘油三酯（ＴＧ）。结果：发现其中有１２例患家族性高胆固醇血症，患病率为男３２％（８／２５），女２０％（４／２０），总患病率为２６．７％。遗传方式符合常染色体显性遗传。临床特征为：①血清ＴＣ、ＬＤＬ－Ｃ自儿童期即增高，且随年龄的增长有逐渐增高的趋势，ＴＧ正常或稍高；②自３５岁后逐渐出现黄色瘤、运动试验阳性，４０岁后出现脂性角膜弓及心绞痛且逐渐加剧，５０岁后可出现心肌梗死甚至猝死。结论：家族性高胆固醇血症是一种常染色体显性遗传性疾病，血清ＴＣ、ＬＤＬ－Ｃ升高及黄色瘤、脂性角膜弓、早发冠状动脉粥样硬化性心脏病（冠心病）是其临床特征     

青藏铁路职工血脂4项水平的统计分析

目的研究职工血脂4项水平。方法根据2006年体验职工2016例的血脂4项（胆固醇，甘油三酯，高密度脂蛋白，低密度脂蛋白）调查资料（男／女=1069／947，年龄40～75岁），按照我国“血脂异常防治建议”对血脂4项水平进行统计分析。结果本组人群中50岁以上者只有1／3总胆固醇（TC）及甘油三酯（TG）都在合适水平，高TC超过半数。高TC明显多于高TG。男性中约有20％，女性中只有5％高密度脂蛋白胆固醇（HDL-C）降低；女性中25％～38％，男性中仅有11％～16％高密度脂蛋白（HDL—C）明显增高；高HDL—C多见于高TC者，而低HDL—C多见于高TG者。结论本调查结果显示中老年人血脂异常者已达2／3，表明动脉样硬化性心血管病的风险明显增高，防治血脂异常应有利于冠心病的预防。     

家族性高胆固醇血症遗传筛查一家系

家族性高胆固醇血症（FH）是一种常见遗传病,以低密度脂蛋白胆固醇（LDL-C）水平升高为特征,伴早发动脉粥样硬化性心血管疾病。该文报道FH的一家系,先证者系12岁女性患者,血浆LDL-C异常升高、有黄色瘤且早发冠心病,符合纯合子FH（HoFH）或复合杂合子FH（CHeFH）的临床表现。采用下一代测序技术对该家系成员进行...     

家族性高胆固醇血症与早发冠心病研究进展

家族性高胆固醇血症（familial hypercholesterol-emia,FH）是一种以血浆总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）水平增高及早发冠心病（pre-mature coronary artery disease,pCAD）为特征的常染色体显性遗传性疾病。     

高血压家族遗传因素与心血管病危险因素聚集关系的研究

目的：探讨高血压遗传因素与心血管病危险因素聚集的关系。方法：采用家系调查方法，对比分析高血压家系和对照家系直系亲属的危险因素个体聚集性。共调查高血压家系２５个，含直系亲属１５８例，其中包括高血压患者５４例，血压正常者１０４例；对照家系１５个，含直系亲属６５人。结果：超重（体重指数＞２５ｋｇ／ｍ２），高甘油三酯（甘油三酯＞２．０ｍｍｏｌ／Ｌ），高尿酸血症（男：尿酸＞３７４．９ｍｍｏｌ／Ｌ；女：尿酸＞３１５．４ｍｍｏｌ／Ｌ），高胰岛素血症（胰岛素＞１２．２μｍｏｌ）及低高密度脂蛋白胆固醇（低高密度脂蛋白胆固醇＜０．９１ｍｍｏｌ／Ｌ）５个危险因素中，具有１个以上至５个以上上述危险者的年龄标化百分比在高血压家系明显高于对照家系，将高血压家系中高血压患者剔除后比较，这种规律依然存在。结论：高血压家族遗传因素可能对心血管病危险因素聚集起着重要的作用     

早期应用不同剂量阿托伐他汀治疗老年急性冠脉综合征的疗效

目的：观察老年急性冠状动脉综合征（ACS）发病早期应用不同剂量的阿托伐他汀的临床疗效及安全性。方法：选择临床确诊为ACS的老年患者117例，随机分为阿托伐他汀10rag组（58例）和20mg组（59例），均为每晚服药一次，患者分别于用药前，用药后1个月、3个月测定总胆固醇（TC）、低密度脂蛋白胆固醇（LDL—c）、高密度脂蛋白胆固醇（HDL-C）、甘油三酯（TG）及高敏c反应蛋白（hsCRP），随访3个月内所有不良反应，观察主要不良心血管事件（MACE）的发生率。结果：（1）与治疗前比较，两组服药后第1个月、3个月的TC、LDL-C、hsCRP水平均明显降低（P均〈0．05），且3个月后与10mg组比较，20mg组下降水平TC[（4．07±1．03）mmol／L比（5．02±1．08）mmol／L]、LDL—C[（2．24±0．77）mmol／L比（3，03±1．07）mmol／L]、hsCRP[（27．90±1．90）mg／L比（36．00±3．80）mg／L]更显著（P均〈O．05）；（2）20mg组累计MACE发生率较10mg组显著减少（5．1％比19．0％，P〈O．05）；（3）两组不良反应发生率无显著差异，均无严重不良反应。结论：在急性冠脉综合征早期应用阿托伐他汀20mg／d，能更有效地降脂，抑制炎症因子，减少心脏血管事件的发生率，而且安全。     

北京地区急性冠心病事件死亡率1984～1993年变化趋势及影响因素的探讨

在北京地区70万自然人群中，对急性冠心病事件的死亡率及有关的危险因素进行了十年（1984～1993）监测。其结果显示：35～74岁男性年平均冠心病死亡率，90．1／10万，女性死亡率为53．9／10万；1993年死亡率比1984年男性增高17％，女性增高56％。1993年比1984年男性发病率增高36％，女性增高66％。同时期三次（1984~1985，1988～1989，1993年）在监测人群中进行心血管危险因素抽样调查，结果显示：第三次与第一次相比男性吸烟率增长25％；男女两性平均收缩压均增长0．133kPa（1mmHg）（0．8％）；平均总胆固醇水平男性上升11．2mg％（7．0％），女性上升7mp％（4．4％）。本研究提示：北京地区急性冠心病死亡率呈持续上升趋势，这种趋势推测主要受发病率上升的影响，人群中冠心病危险因素水平的增加是影响发病率上升的重要原因。     

脂肪肝与血脂的相关性分析

目的探讨脂肪肝与高脂血症的发病率,以及二者之间的关系。方法2007年在我院健康体检的郑州市企事业单位1016例干部职工,经B超诊断脂肪肝,并做血清总胆固醇（TC）、甘油三酯（TG）检测,观察脂肪肝及高脂血症发病率,脂肪肝与年龄、性别、血脂的关系。结果脂肪肝患病率68．11％,高脂血症者患病率60．83％,明显高于正常者。中老年及男性脂肪肝的患病率明显增高。脂肪肝患者的血清胆固醇、甘油三酯均明显增高。结论脂肪肝的发生与年龄、性别、血脂有密切关系。     

老年人代谢综合征患病调查分析

目的调查武汉1550例老年人代谢综合征（MS）患病情况。方法选择1550例老年人健康体检资料进行MS患病情况及其组分分析。结果MS总患病率为29．4％，男性为27．3％，女性为32．9％，女性高于男性（P〈0．01）；知识分子、在岗老年人MS患病率显著高于非知识分子及离退休老年人（P〈0．01）；80岁前MS及代谢异常组分患病率随年龄增加而增高；各年龄组女性MS患病率显著高于男性。具有1种以上代谢异常者达89．9％。无论男女均〉40％患有高血压；老年人MS以超重／肥胖＋血脂异常＋高血压为最主要表现形式，占50．7％。结论MS是老年人严重的健康问题，早发现、早预防控制意义重大。     

辛伐他汀并非诺贝特治疗急性冠脉综合征的疗效

目的：探讨联合应用辛伐他汀和非诺贝特对急性冠脉综合征（ACS）患者血脂参数及炎症因子的影响。方法：共人选58例ACS患者．随机分为：辛伐他汀组（20mg／d，18例）；非诺贝特组（200mg／d，18例）；联合治疗组（辛伐他汀20rag／d＋非诺贝特200mg／d，22例），疗程均为6个月。观察治疗前、后血清总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL—C）、一氧化氮（NO）、内皮素（ET）和C反应蛋白（CRP）含量的变化，以及药物不良反应。结果：各组治疗后血清TC、LDL-C、TG水平显著降低（P均〈0.05），血清HDL—C水平有不同程度增高。其中以联合治疗组最为明显（P均〈0．05）。和辛伐他汀组相比，非诺贝特组TC和LDL-C水平无明显差异（P〉0．05），而TG水平显著降低，HDL—C水平明显增高（P〈0．05），与治疗前相比，各组治疗后血清NO水平增高，CRP和ET水平降低（P〈0．05），联合治疗组较辛伐他汀组、非诺贝特组更显著（P均〈0.05），三组均无不良反应。结论：联合辛伐他汀和非诺贝特治疗可以更全面地改善ACS患者的血脂异常，其改善内皮功能和降低炎症因子的作用较单药治疗更有效。     

A Pedigree Analysis of a Family With Familial Hypercholesterolemia

Objective The current study was designed to investigate the features of a family with familial hypercholesterolemia(FH). Methods Twenty members of three generations in a family with FH were enrolled in the study. The data collected were from clinical observation and subjected to pedigree analysis. Results The proband was a 41 years old male who suffered from angina pectoris with multi-vessel stenosis of coronary artery at the age of 40. Among 20 members, 8 individuals were demonstrated with hypercholes-terolemia in this family with the total incidence of 40% [54.5% (6/11) in male and 22. 2% (2/9) in female The serum total cholesterol level was elevated in childhood from 7. 1 to 10. 8 mmol/L and tended to be raised with increasing age. In addition, the level of total cholesterol was found to be elevated both in a monozy-gote twin brothers and their offspring in the family. Conclusion FH appears to be a hereditary disease of autosomal dominance inheritance and the outcome of FH patients with coronary hea     

A pedigree analysis of familial hypercholesterolemia in monozygote twin brothers

The current study was designed to investigate the features of a family with familial hypercholesterolemia (FH). Twenty members of 3 generations in a family with hypercholesterolemia were enrolled in the study. The data collected were from clinical observation and subjected to pedigree analysis. The proband was a 41-year-old male who suffered from angina pectoris with multi-vessel stenosis of coronary arteries at the age of 40. Among 20 members, 8 individuals had FH in this family with a total incidence of 40% (54.5% [6/11] in male and 22.2% [2/9] in female). The serum total cholesterol level was increased in childhood from 7.1 to 10.8 mmol/L and tended to increase with increasing age. In addition, the level of total cholesterol was increased in monozygote twin brothers and their offspring in the family. This pedigree analysis showed that FH appears to be a hereditary disease of autosomal dominance, and attention should be paid, especially in the only son or daughter society of China.     

Positive family history for coronary heart disease and 'midband lipoproteins' are potential risk factors of carotid atherosclerosis in familial hypercholesterolemia

Patients with heterozygous familial hypercholesterolemia (FH) were examined with B-mode ultrasound in order to determine intima-media thickness (IMT) in the common carotid artery, and to uncover potential risk factors responsible for the development of IMT. Ninety seven FH subjects and 132 non FH type IIa hyperlipidemic subjects were involved in the present study. Age was found to correlate positively with IMT in both FH and non FH groups. FH individuals showed a higher IMT, along with elevated low density lipoprotein (LDL) cholesterol levels, compared with age-matched non FH individuals. To clarify potential factors contributing to the formation and development of carotid atherosclerosis, we divided the FH subjects into two subgroups, namely FH with high IMT group (HIG), and those with low IMT group (LIG). We investigated those two subgroups on the presence of angiographically documented coronary heart disease (CHD), of family history of CHD and of ‘midband lipoproteins’ by polyacrylamide gel electrophoresis (PAGE) analysis, by matching for age and LDL-cholesterol (LDL-C) level. Fifty percent of FH men in HIG was found to have CHD, whereas only 14% of those in LIG had CHD (P<0.05). Thirty-three percent of FH women in HIG was found to have CHD, whereas only 12% of those in LIG had CHD (P<0.05). Fifty percent of FH men in HIG was found to have ‘midband lipoproteins’, whereas only 7% of those in LIG had ‘midband lipoproteins’ (P<0.01). Seventy-three percent of FH women in HIG had ‘midband lipoproteins’, whereas only 21% of those in LIG had ‘midband lipoproteins’ (P<0.0005). Fifty-five percent of FH men in HIG was had positive family history for CHD, whereas only 14% of those in LIG had positive family history for CHD (P<0.05). Sixty-three percent of FH women in HIG was found to have positive family history for CHD, whereas only 29% of those in LIG had positive family history for CHD (P<0.05). Based on these findings, we propose that, besides age and elevated levels of LDL-C, positive family history for CHD and ‘midband lipoproteins’ are important determinants for the development of carotid atherosclerosis in FH individuals in Japanese population.     

Past,Present, and Future of Familial Hypercholesterolemia Management

Familial hypercholesterolemia (FH) is a monogenic form of severe hypercholesterolemia that, if left untreated, is associated with early onset of atherosclerosis. FH derives from genetic variants that lead to inefficient hepatic clearance of low-density lipoprotein (LDL) particles from the circulation. The FH phenotype is encountered in approximately 1 of every 300 people. The risk of atherosclerotic cardiovascular disease (ASCVD) is higher in those with FH than in normolipidemic individuals and in those with polygenic hypercholesterolemia. FH is usually diagnosed by clinical scores that consider hypercholesterolemia, family history of early ASCVD and hypercholesterolemia, and cutaneous stigmata. Genetic diagnosis is important and should be offered to individuals suspected of FH. Family cascade screening is important to identify asymptomatic hypercholesterolemic individuals. Despite the high risk of ASCVD, this risk is heterogenous in heterozygous FH and depends not only on high LDL cholesterol (LDL-C) but also on other risk biomarkers. Risk can be evaluated by considering biomarkers such as male sex, late-onset therapy (> age 40), LDL-C > 310 mg/dL, low high-density lipoprotein cholesterol, elevated lipoprotein(a), obesity, diabetes, and hypertension by using specific risk equations and by detecting subclinical coronary atherosclerosis. Statins are the main therapy for FH and change the natural history of ASCVD; however, most individuals persist with elevated LDL-C. PCSK9 inhibitors provide robust and safe LDL-C lowering in FH, although elevated costs preclude their widespread use. Newer therapies such as ANGPTL3 inhibitors add intensive LDL-C lowering for refractory forms of FH. Finally, while it is possible to normalize LDL-C in people with FH, the disease unfortunately is still severely underdiagnosed and undertreated.     

Familial Hypercholesterolemia,Familial Combined Hyperlipidemia,and Elevated Lipoprotein(a) in Patients With Premature Coronary Artery Disease

BackgroundFamilial hypercholesterolemia (FH), familial combined hyperlipidemia (FCHL), and elevated lipoprotein (a) (Lp[a]) increase risk of premature coronary artery disease (CAD). The objective of this study was to assess the prevalence of FH, FCHL, elevated Lp(a) and their impact on management in patients with premature CAD.MethodsWe prospectively recruited men ≤ 50 years and women ≤ 55 with obstructive CAD. FH was defined as Dutch Lipid Clinic Network scores ≥ 6. FCHL was defined as apolipoprotein B > 1.2 g/L, triglyceride and total cholesterol > 90th population percentile, and family history of premature cardiovascular disease. Lp(a) ≥ 50 mg/dL was considered to be elevated.ResultsAmong 263 participants, 9.1% met criteria for FH, 12.5% for FCHL, and 19.4% had elevated Lp(a). Among patients with FH, 37.5% had FH-causing DNA variants. Patients with FH, but not other dyslipidemias, were more likely than nondyslipidemic patients to have received lipid-lowering therapy before presenting with CAD (33.3% vs 12.3%, P = 0.04) and combined lipid-lowering therapy after the presentation (41.7% vs 7.7%, P < 0.001). One year after presentation, 58.3%, 54.5%, and 58.8% of patients with FH, FCHL, and elevated Lp(a) had low-density lipoprotein cholesterol (LDL-C) < 1.8 mmol/L, respectively, compared with 68.0 % in reference group. Patients with FCHL were more likely to have non–high-density lipoprotein (HDL) and apolipoprotein B above recommended lipid goals (70.0% and 87.9%, respectively).ConclusionsFH, FCHL, and elevated Lp(a) are common in patients with premature CAD and have differing impact on treatment and achievement of lipid targets. Assessment for these conditions in patients with premature CAD provides valuable information for individualized management.     

Identification and treatment of heterozygous familial hypercholesterolemia in children and adolescents

Heterozygous familial hypercholesterolemia (FH) is completely expressed at birth and early in childhood by significant elevations in plasma total and tow density lipoprotein (LDL) cholesterol levels. High density lipoprotein cholesterol can be low in such FH children; the triglyceride levels are usually within the normal range. Screening of children for heterozygous FH using a LDL cholesterol level is reasonably efficient in families with known FH, but for general population screening, the LDL cholesterol level is often too nonspecific. Screening of offspring with a positive family history of premature coronary artery disease will provide a panoply of different lipoprotein phenotypes, reflecting the presence of other genetic conditions, including familial combined hyperlipidemia. Guidelines have been developed by the National Cholesterol Education Program (NCEP) Expert Panel on Blood Cholesterol levels in Children and Adolescents to assist in the evaluation and treatment of children with high LDL cholesterol levels. Although heterozygous FH probably counts for ≤5% of premature coronary artery disease, its identification and treatment are important, because FH often causes marked premature coronary artery disease early in adulthood, and can be successfully treated with a combined dietary and drug approach.     

The Trp-Stop and Trp-Gly mutations in the LDL receptor gene: common causes of familial hypercholesterolemia in Denmark

Mutations in the gene for the low density lipoprotein (LDL) receptor cause the autosomal dominant disease familial hypercholesterolemia (FH), the prevalence of which is about 0.2% in most populations. By PCR-SSCP analysis and direct sequencing, we identified the receptor-negative Trp²³-Stop LDL receptor mutation (FH Cincinnati-5) in 10 of 63 FH probands and the receptor-defective Trp⁶⁶-Gly LDL receptor mutation (FH French Canadian-4) in another 10 of the 63 FH probands. These two mutations thus account for 30% of diagnosed FH families in Denmark. Comparison of the mean lipid concentrations (unadjusted and adjusted for age), including serum total cholesterol and LDL-cholesterol, showed no significant differences between the two groups of FH heterozygote probands (cholesterol: 10.7 mmol/l vs. 10.7 mmol/l) and between the probands and 16 and 22 non-proband family members with the Trp²³-stop (cholesterol: 10.1 mmol/l) and Trp⁶⁶-Gly (cholesterol: 10.7 mmol/l) mutations, respectively.     

Diagnostic, clinical, and therapeutic aspects of familial hypercholesterolemia in children

The clinical diagnosis of familial hypercholesterolemia (FH) in children is based on family history and laboratory findings. The best available value of low-density lipoprotein cholesterol (LDL-C) for the diagnosis of FH in children is >3.50 mmol/L (>135 mg/dL) when FH runs in the family. Levels below this concentration were only found in 4.3% of children that had a mutation in the LDL-receptor gene. In contrast, children with LDL-C equal to or above 3.50 mmol/L had 0.98 posttest probability of FH. Untreated FH carries a substantial burden of morbidity and mortality if left untreated or if inadequately treated. The guidelines of the American National Cholesterol Education Program suggested that drug treatment should be considered from the age of 10 years if LDL-C levels are greater than or equal to 4.9 mmol/L (190 mg/dL) or greater than or equal to 4.1 mmol/L (158 mg/dL) in the presence of other cardiovascular risk factors, including a positive family history of premature cardiovascular disease. Impaired flow mediated dilatation was more pronounced in FH children with a positive family history of premature cardiovascular disease. The currently prescribed diet is sometimes considered to be monotonous and can lead to problems with compliance. A reduction of the total intake fat and saturated fatty acids is important. Plant sterolesters should be evaluated in young FH children and can supplement drug and diet therapy, with an additional reduction of 10 to 15% of LDL-C. The use of resins leads to poor compliance, and statins are recommended for FH children and adolescents when drug treatment is indicated. Pravastatin, simvastatin, and atorvastatin decrease LDL-C 30 to 40% without serious adverse events and have a high degree of compliance.     

Long-term outcome after living donor liver transplantation for two cases of homozygous familial hypercholesterolemia from a heterozygous donor

AIM: We experienced two pediatric siblings with homozygous familial hypercholesterolemia (FH) who received living donor liver transplantation (LDLT) from their parents who were heterozygous for FH. METHODS: The elder brother presented orange cutaneous xanthomas and was diagnosed as homozygous FH at the age of one. The plasma lipid profile showed that his total cholesterol level was 898 mg/dL (23.2 mmol/L), LDL cholesterol level was 756 mg/dL (19.6 mmol/L) and triglyceride level was 60 mg/dL (0.7 mmol/L). There were no living donors with a normal LDL receptor in their family, and it was difficult to find a deceased donor in Japan; thus he underwent LDLT with his father as the donor. His sister was born 2 years after his LDLT. She underwent ABO-incompatible LDLT at the age of 2 with her mother as the donor. RESULTS: The boy's liver function tests normalized immediately after transplantation, and his cholesterol has remained controlled at around 280 mg/dL (7.2 mmol/L), with HMG-CoA reductase inhibitor for 6 years after LDLT. The girl's cholesterol remained stable at around 280 mg/dL (7.2 mmol/L) under treatment with HMG-CoA reductase inhibitor two years after LDLT. At present, the four patients, including the two donors, are leading normal daily lives. CONCLUSION: Living-donor liver transplantation from a donor with heterozygous FH is a feasible indication for the treatment of homozygous FH.