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题名:
基于就医人群探讨严重高胆固醇血症的临床特征
作者: 宋婧
答辩日期: 2016-05-18
导师: 陈红
专业: 内科学
授予单位: 北京大学
授予地点: 北京大学第二临床医学院
学位: 博士
关键词: 严重高胆固醇血症 ; 患病率 ; 临床特征 ; 甲状腺功能减退症 ; 继发性 ; 家族性高胆固醇血症
其他题名: linical Features of Severe Hypercholesterolemia: A Study Based on Patients of a Medical Center
分类号: R541.4
摘要:

基于就医人群探讨严重高胆固醇血症的临床特征

第一部分:基于就医人群探讨严重高胆固醇血症的临床特征——回顾性研究

背景  严重高胆固醇血症是动脉粥样硬化性疾病的危险因素之一,随着血脂研究领域的重大进展及干预手段的增强,严重高胆固醇血症的特征、危害及治疗逐渐受到国际广泛关注。既往我国的流行病学研究中虽有对于严重高胆固醇血症患病率的报道,但这部分人群的临床特征尚不明确。

目的  以就医人群为切入点,探讨严重高胆固醇血症患者的临床特征。

方法  回顾性连续入选2014年10月1日~2015年9月30日于北京大学人民医院行血脂检测的门诊及住院患者。总胆固醇(total cholesterol, TC)、低密度脂蛋白胆固醇(low density lipoprotein-cholesterol, LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein-cholesterol, HDL-C)、甘油三酯(triglycerides, TG)均通过标准方法进行检测。收集患者的基本人口学信息、诊疗相关信息、社会相关信息及血液检查结果等资料。根据LDL-C水平分为严重高胆固醇血症组(LDL-C≥4.92mmol/L)和非严重高胆固醇血症组(LDL-C 4.14~4.91mmol/L),分析两组间一般情况、血脂特点及血液检查的差异。以甲状腺功能减退症为切入点,描述继发性严重高胆固醇血症的血脂特点及临床特征。

结果

本研究共入选133376名患者,其中男性56804人(42.6%),平均年龄52.5±18.4岁。

严重高胆固醇血症患病率为1.7%(2217/133376),平均TC水平为8.20±1.78mmol/L,LDL-C水平为5.66±1.20mmol/L,HDL-C水平为1.42±0.40mmol/L,TG水平为1.95 (1.45 , 2.72) mmol/L。

根据年龄段分层,严重高胆固醇血症患者TC、LDL-C水平峰值出现于<20岁人群中。

与非严重高胆固醇血症患者相比,严重高胆固醇血症患者女性比例更高(65.2% vs 62.2%,p=0.008);内科就诊比例更高(54.0% vs 47.8%, p=0.000);合并高甘油三酯血症比例更高(37.6% vs 23.7%, p=0.000);合并肝功能异常(丙氨酸氨基转移酶:13.7% vs 9.5%, p=0.000;天门冬氨酸氨基转移酶:12.5% vs 7.8%, p=0.000)、肾功能异常(9.9% vs 6.2%, p=0.000)、肌酸激酶异常(5.4% vs 3.6%, p=0.000)、高尿酸血症(28.2% vs 25.8%, p=0.028)、空腹血糖异常(18.2% vs 15.3%, p=0.001)、甲状腺功能减退症(17.3% vs 11.0%, p=0.000)比例更高,均存在显著统计学差异。

严重高胆固醇血症人群中,甲状腺功能减退症患者占17.3%。甲状腺功能减退患者中,3.3%的患者合并严重高胆固醇血症。

结论  本中心就医人群中,严重高胆固醇血症的异常率为1.7%。严重高胆固醇血症人群TC、LDL-C水平峰值出现于<20岁人群中。严重高胆固醇血症患者合并高甘油三酯血症比例高。甲状腺功能减退症是常见的严重高胆固醇血症继发因素。

 

第二部分:基于住院患者人群探讨严重高胆固醇血症的临床特征——前瞻性研究

背景  随着血脂研究领域的重大进展及干预手段的增强,严重高胆固醇血症的特征、危害及治疗逐渐受到国际广泛关注。我国严重高胆固醇血症人群的临床特征尚不明确。由于回顾性研究无法收集详实的病史及用药信息,难以进一步分析严重高胆固醇血症患者人群合并疾病、用药及危险因素,因此本研究设计了前瞻性研究。

目的  以住院患者人群为切入点,探讨严重高胆固醇血症患者的临床特征。

方法  前瞻性入选2015年11月13日~2016年3月12日于北京大学人民医院行血脂检测的住院患者。总胆固醇(total cholesterol, TC)、低密度脂蛋白胆固醇(low density lipoprotein-cholesterol, LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein-cholesterol, HDL-C)、甘油三酯(triglycerides, TG)均通过标准方法进行检测。通过病史访谈、体格检查及病历资料收集患者的基本人口学信息、诊疗相关信息、社会相关信息、血液检查结果、合并疾病、合并用药、个人史、家族史、体征等资料。根据LDL-C水平分为严重高胆固醇血症组(LDL-C≥4.92mmol/L)和非严重高胆固醇血症组(LDL-C 4.14~4.91mmol/L),分析两组间一般情况、血脂特点、血液检查指标、继发影响因素、合并疾病、家族史、调脂治疗的差异。根据The Dutch Lipid Clinic Network Criteria (DLCN)、The Simon Broome Register Group Criteria (SBRG)及日本诊断标准对高胆固醇血症患者进行评分,描述临床诊断家族性高胆固醇血症的比例。

结果

本研究共入选13459名患者,其中男性6513人(48.4%),平均年龄51.8±20.1岁。

严重高胆固醇血症患病率为2.5% (339/13459),严重高胆固醇血症患者平均TC水平为8.43±2.12mmol/L,LDL-C水平为5.94±1.70mmol/L,HDL-C水平为1.40±0.49mmol/L,TG水平为2.03 ( 1.49 , 2.88 )mmol/L。

根据年龄段分层,严重高胆固醇血症患者TC、LDL-C水平峰值出现于<30岁人群中。

与非严重高胆固醇血症患者相比,严重高胆固醇血症患者内科就诊比例更高(46.9% vs 34.2%,p=0.000);合并高甘油三酯血症更高(41.6% vs 22.7%,p=0.000);合并肝功能异常(丙氨酸氨基转移酶:14.8% vs 10.0%,p=0.021;天门冬氨酸氨基转移酶:14.5% vs 9.8%,p=0.022)、高尿酸血症(33.6% vs 23.4%,p=0.000)比例更高,存在显著统计学差异。

严重高胆固醇血症人群中44.5% (151/339)患者合并继发性疾病因素,其中合并甲状腺功能减退、肾病综合征、慢性肾脏病患者分别占28.6% (97/339)、18.0% (61/339)和16.2% (55/339);27.1% (92/339)患者合并药物继发性因素,其中糖皮质激素、免疫抑制剂应用比例分别为24.5% (83/339)和15.6% (53/339)。

本研究中,根据DLCN、SBRG和日本诊断标准,临床诊断家族性高胆固醇血症的患者占6.5%,推算占总研究人群的0.16%。

结论  本中心住院患者人群中,严重高胆固醇血症的患病率为2.5%。严重高胆固醇血症患者中,常见的疾病继发影响因素为甲状腺功能减退症、肾病综合征和慢性肾脏病;常见的药物继发影响因素为免疫抑制剂及糖皮质激素。严重高胆固醇血症患者治疗不足。临床诊断FH占严重高胆固醇血症患者的6.5%,推算占总研究人群的0.16%。

英文摘要:

Clinical Features of Severe Hypercholesterolemia: A Study Based on Patients of a Medical Center

Part 1: Clinical Features of Severe Hypercholesterolemia: A Retrospective Deive Study.

Background  Severe hypercholesterolemia is a major risk factor of arteriosclerotic cardiovascular disease. With prompt advances and improvements of interventions, the features, harms and treatment of severe hypercholesterolemia are widely concerned. Previous epidemiological studies have shown the prevalence of severe hypercholesterolemia in China, but the clinical features of severe hypercholesterolemia patients are still not clear.

Objective  To investigate the clinical features of severe hypercholesterolemia in outpatients and inpatients of a medical center.

Methods  In this retrospective study, outpatients and inpatients were enrolled who underwent serum lipid test at Peking University People’s Hospital between October 1st 2014 and September 30th 2015. Fasting serum total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and triglycerides (TG) were measured by standard methods. Demographics and relevant clinical infomation were collected. According to LDL-C level, patients were classified into two groups: severe hypercholesterolemia (LDL-C≥4.92mmol/L) and mild hypercholesterolemia (LDL-C: 4.14~4.91mmol/L). The demographics and clinical data were compared between two groups. The clinical features of patients with secondary severe hypercholesterolemia such as hypothyroidism were described.

Results

1. A total of 133376 patients were included in this retrospective study. The proportion of male was 48.4%(56804/133376) and the mean age was 52.47±18.36 years old.

2. The prevalence of severe hypercholesterolemia was 1.7% overall. The mean level of TC, LDL-C, HDL-C and TG of severe hypercholesterolemia patients were 8.20±1.78mmol/L, 5.66±1.20mmol/L, 1.42±0.40mmol/L and 1.95 (1.45 , 2.72) mmol/L respectively.

3. Serum level of TC and LDL-C were highest in <20 years old group.

4. Compared with mild hypercholesterolemia, severe hypercholesterolemia patients have a higher proportion of female (65.2% vs 62.2%, p=0.008) and a higher proportion of patients from internal medicine departments (54.0% vs 47.8% , p=0.000). There is a higher proportion of combined dyslipidaemia in severe hypercholesterolemia group (37.6% vs 23.7% , p=0.000). The proportion of abnormal liver function ( ALT: 13.7% vs 9.5% , p=0.000; AST: 12.5% vs 7.8% , p=0.000), renal function ( 9.9% vs 6.2% , p=0.000), creatine kinase ( 5.4% vs 3.6%, p=0.000), fasting plasma glucose ( 18.2% vs 15.3% , p=0.001), hyperuricemia ( 28.2% vs 25.8% , p=0.028) and hypothyroidism ( 17.3% vs 11.0% , p=0.000) were also higher in severe hypercholesterolemia group.

5. Among patients with severe hypercholesterolemia, patients with hypothyroidism account for 17.3%. Among patients with hypothyroidism, the proportion of severe hypercholesterolemia was 3.3%.

Conclusion  The prevalence of severe hypercholesterolemia was 1.7% overall. The mean serum level of TC and LDL-C was highest in <20 years old group among severe hypercholesterolemia patients. The proportion of combined dyslipidaemia was high among severe hypercholesterolemia patients. Hypothyroidism is one of the most common secondary cause of severe hypercholesterolemia.

 

Part 2: Clinical Features of Severe Hypercholesterolemia: A Prospective Study Based on Inpatients.

Background  With prompt advances and improvements of interventions, the features, harms and treatment of severe hypercholesterolemia are widely concerned. The clinical features of severe hypercholesterolemia patients are still not clear. With limited clinical information collected in previous retrospective study, it is difficult to analyze the specific clinical features of severe hypercholesterolemia concerning complicating diseases, medication and risk factors. Thus, the prospective study was designed.

Objective  To investigate the clinical features of severe hypercholesterolemia based on inpatients.

Methods  In this prospective study, inpatients who underwent serum lipid test at Peking University People’s Hospital between November 13th 2015 and March 12th 2016. Fasting serum total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and triglycerides (TG) were measured by standard methods. Demographics and relevant clinical infomation concerning risk factors, clinical history and medications were collected. According to LDL-C level, patients were classified into two groups: severe hypercholesterolemia (LDL-C≥4.92mmol/L) and mild hypercholesterolemia (LDL-C: 4.14~4.91mmol/L). The demographics and clinical features were compared between two groups. The clinical features were described in patients with secondary causes of severe hypercholesterolemia. Familial hypercholesterolemia were clinical diagnosed according to The Dutch Lipid Clinic Network Criteria (DLCN), The Simon Broome Register Group Criteria (SBRG) and Japanese Criteria.

Results

1. A total of 13459 patients were included in this prospective study. The proportion of male was 48.4% (6513/13459) and the mean age was 51.8±20.1 years old.

2. The prevalence of severe hypercholesterolemia was 2.5% overall. The mean level of TC, LDL-C, HDL-C and TG of severe hypercholesterolemia patients were 8.43±2.12mmol/L, 5.94±1.70mmol/L, 1.40±0.49mmol/L and2.03 (1.49,2.88)mmol/L respectively.

3. Serum level of TC and LDL-C peaked at <30 years old group.

4. Compared with mild hypercholesterolemia, severe hypercholesterolemia patients have a higher proportion of patients were from internal medicine departments (46.9% vs 34.2%, p=0.000). More patients with severe hypercholesterolemia were mixed dyslipidemia (41.6% vs 22.7%, p=0.000). The proportion of abnormal liver function ( ALT: 14.8% vs 10.0% , p=0.021; AST: 14.5% vs 9.8% , p=0.022) and hyperuricemia ( 33.6% vs 23.4% , p=0.000) were also higher in severe hypercholesterolemia group.

5. The proportion of patients with secondary disease factors was 44.5%, and hypothyroidism (28.6%), nephrotic syndrome (18.0%) and onic kidney disease (16.2%) counted the most. A proportion of 27.1% patients have secondary medication factors, and the use of glucocorticoid (24.5%) and immunosuppressive agent (15.6%) were most common.

6. A total of 22 severe hypercholesterolemia patients (6.5%) were clinical diagnosed with familial hypercholesterolemia according to The Dutch Lipid Clinic Network Criteria (DLCN), The Simon Broome Register Group Criteria (SBRG) or Japanese Criteria, counted for 0.16% of all inpatients.

Conclusion  The prevalence of severe hypercholesterolemia was 2.5% among inpatients. The most common secondary disease factors were hypothyroidism, nephrotic syndrome and onic kidney disease. The most common secondary medication factors were glucocorticoid and immunosuppressive agent. The treatment rate of severe hypercholesterolemia was low. A total of 6.5% of severe hypercholesterolemia patients were clinical diagnosed with familial hypercholesterolemia, counted for 0.16% of all inpatients.

语种: 中文
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内容类型: 学位论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/124605
Appears in Collections:北京大学第二临床医学院_学位论文

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作者单位: 北京大学第二临床医学院

Recommended Citation:
宋婧. 基于就医人群探讨严重高胆固醇血症的临床特征[D]. 北京大学第二临床医学院. 北京大学. 2016.
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