2018-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/645939摘要：家族性高膽固醇血症病人(Familial hypercholesterolemia, FH)，是一種體染色體顯性遺傳的疾病，大部分是在低密度脂蛋白膽固醇接受體基因發生突變所致，導致低密度膽固醇無法有效代謝而在血液中累積升高，常造成早發性冠心病。根據2002 全國三高的調查，台灣地區居民的表現型上高膽固醇血症(CHO 260 mg/dL and LDL-C 190 mg/dL)且有家族史者，竟高達0.62%是值得特別注意的病人，除了積極用藥外應積極找尋適當的治療方針：包括飲食生活習慣的介入方法。本研究第一年是希望研究200 位FH 病人，100 位接受積極的飲食生活習慣的介入指導三天，另100 位病人則接受一般照顧(沒有介入)。將FH 病人根據膽固醇值及用藥將病人分為四類: (1) Very highcholesterol levels (such as CHO > 350 mg/dL) and treatment with statins plus ezetimibe (2) High cholesterollevels (>300 mg/dL) with high potency statins, such as atorvastatin 20 mg or rosuvastatin 10 mg per day (3)High cholesterol levels (260-300 mg/dL) can be controlled by low dose high potency statins or moderatepotency statins (4) High cholesterol levels such as >240 and < 280 mg/dL without medication。除了基礎檢查，在介入指導後第一、三、六、九、十二個月，參加研究的FH 病人皆要接受Dynapulse 心臟血管功能及血脂檢查。經由生活飲食習慣介入指導後，我們將可以從後續追蹤血液生化值結果，比較四組不同膽固醇值及不同降膽固醇用藥的FH 病人，其積極生活飲食習慣介入的效果是否不同。另外的FH 對照組也將同步做比較。第二年，將研究完成100 位FH 病人家戶的居家24-hour 空氣品質監測，包括空氣微粒(PM1.0, 2.5,10,TSP), TVOC, CO, CO2,甲醛、溫度與濕度。分析24-hour 空氣品質監測值，與同步監測的24-hour心臟血管功能檢查之相關性。第三年除了追蹤病人心臟血管功能及血之外，將作整個計畫第一年及第二年的整合分析。總之，本研究總結全氟碳化合物、塑化劑(鄰苯二甲酸酯類)、及Acrylamides 三種內分泌干擾化學物質的環境污染物暴露的健康效應，著重在心臟血管及代謝疾病方面。生活飲食習慣介入指導，對參加研究的FH 病人其膽固醇降低及心臟血管功能的效果。除了基因扮演的角色及貢獻外，居家生活環境(尤其是空氣品質)及飲食生活習慣(包括運動、睡眠及工作)對FH 病人的健康影響，我們能回答在降膽固醇方面及心臟血管功能的健康效應。據此詳細的研究，為了降膽固醇與促進心臟血管健康，對FH 病人提出居家環境及生活飲食習慣的建議。<br> Abstract: Familial hypercholesterolemia (FH) is an autosomal dominant disease with defects in the gene for thelow-density lipoprotein (LDL) receptor that include impaired uptake of plasma LDL cholesterol, resulting inhigh blood cholesterol levels and increased risk of premature cardiovascular disease (CVD). According to the2002 The Taiwanese Survey on Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), the highprevalence (0.62%) of FH in Taiwan indicated the urgent need of public health concern and development ofstrategy in the prevention and management of atherosclerotic disorders and cardiovascular complicationsassociated with FH. The most well-known treatment in clinical practice for FH is statins or plus ezetimibe, oradd on anti-PCSK 9. However, the role of intensive lifestyle and dietary therapy is limited and oftenoverlooked.In the first year, we will recruit 100 FH patients to receive intensive lifestyle and dietarymodification, include a 3-day training course by coach-assisted teaching and practicing fom thehyperlipidemia clinic, NTUH. Meanwhile, we will recruit another 100 FH patients as control groups forusual care without intervention. These 200 FH patients will be stratified into 4 categories according to theirbaseline cholesterol levels and medication, 25 patients in each category in both intervention and controlgroups. They will be defined as (1) Very high cholesterol levels (such as CHO > 350 mg/dL) and treatmentwith statins plus ezetimibe (2) High cholesterol levels (>300 mg/dL) with high potency statins, such asatorvastatin 20 mg or rosuvastatin 10 mg per day (3) High cholesterol levels (260-300 mg/dL) can becontrolled by low dose high potency statins or moderate potency statins (4) High cholesterol levels such as>240 and < 280 mg/dL without medication. We will study the lipid-lowering and cardiovascular effects bycouch-assisted intensive lifestyle and dietary modification. In the second year, we will study thecardiovascular effects of indoor air pollution by rea-time 24-h in-house air quality and cardiovascularfunction monitoring in 100 FH patients. The results of 24-h hemodynamics monitoring can also provideanother important information of cardiovascular assessment may benefit for CVD prevention also. In thethird year, we will follow up every participants and combined the results of 1st and 2nd year study, thenpropose a complete study to explore the cardiovascular effects of living environments, lifestyle and dietaryhabits on FH patients.In conclusion, this novel study is the first to investigate where environmental and lifestyle factorsplay an important role in genetic-based FH patients. We plan to propose a complete cardiovascularprevention strategy for FH patients in addition to medication.家族性高膽固醇血症病人生活飲食習慣介入指導環境汙染心臟血管健康Familial hypercholesterolemialifestyle and dietary modificationenvironmental pollutioncardiovascular function