家族性低脑脂蛋白血症中的冠状动脉疾病：病例报告
摘要
背景/简介 一位 37 岁的白种女性因血脂异常转诊至心脏科进行评估。她的既往病史包括二尖瓣脱垂、吉尔伯特综合征、高血压和主动脉粥样硬化。该患者体力充沛，无吸烟史、糖尿病史或其他心血管风险因素。家族史中，患者的父亲和姐姐的高密度脂蛋白胆固醇水平较低，但没有已知的过早患上心血管疾病。体格检查显示体重指数（BMI）为 21，血压控制良好，心血管检查正常。初始血脂检查显示总胆固醇（TC）为 47 毫克/分升，高密度脂蛋白胆固醇（HDL-C）为 5 毫克/分升，低密度脂蛋白胆固醇（LDL-C）为 24 毫克/分升，甘油三酯为 80 毫克/分升，低密度脂蛋白胆固醇（VLDL）为 18 毫克/分升。进一步的实验室检测显示，载脂蛋白 B 为 52 毫克/分升，脂蛋白（a）正常，高敏 CRP 正常。肝功能检测、全血细胞计数、甲状腺功能检测、血清总蛋白和基本代谢轮廓也都正常。基因检测显示，ABCA1 基因有两个意义未定的变异[ABCA1 c.2879T>C (p.Leu960Pro); ABCA1 c.3626C>T（p.Pro1209Leu）]。目标/目的N/方法N/结果冠状动脉计算机断层扫描（CTCA）显示，左前降支（LAD）动脉中远端存在边缘阻塞性偏心钙化斑块区域，管腔直径狭窄 40-50%、左侧冠状动脉（LCX）近端有非阻塞性偏心钙化斑块，管腔直径狭窄小于 40%，右侧冠状动脉（RCA）中段有阻塞性斑块，管腔直径狭窄大于 50%，全心阿加斯顿评分为 981 分。使用分数血流储备（FFR）进行的CT冠状动脉造影扫描显示，RCA中段有一个模型狭窄，FFR测量值为0.81，显示正常，但整个病变部位的相对骤变（0.18）显著。有创冠状动脉造影显示患者为非阻塞性冠状动脉疾病，RCA 中段狭窄 50%，LAD 中段狭窄 40%，LCX 骨端狭窄 30%。患者开始接受他汀类药物和阿司匹林治疗。结论考虑到 ABCA1 基因变异，且没有丹吉尔病的表型发现，该患者被推测为家族性低脂蛋白血症。低高密度脂蛋白胆固醇水平与心血管风险之间的反比关系已在基于人群的观察性研究中得到充分证实。然而，临床试验未能显示出以提高高密度脂蛋白胆固醇水平为目标的治疗有临床益处。这类人群可能在遗传上具有较高的早期冠状动脉疾病风险，因此还需要进一步研究，以确定旨在预防这类人群患上 CAD 的最佳医疗方法。Background/Synopsis
A 37-year-old Caucasian female was referred for cardiology evaluation of dyslipidemia. Her past medical history included mitral valve prolapse, Gilbert syndrome, hypertension, and aortic atherosclerosis. The patient was physically active with no history of smoking, diabetes, or other cardiovascular risk factors. Family history was notable for low HDL-C levels in the patient's father and sister, with no known premature CAD. Physical examination revealed BMI of 21, well controlled blood pressure, and normal cardiovascular exam.
Initial lipid panel revealed total cholesterol (TC) 47 mg/dL, HDL-C 5 mg/dL, LDL-C 24 mg/dL, triglycerides 80 mg/dL, and VLDL 18 mg/dL. Further laboratory testing showed apolipoprotein B of 52 mg/dL, normal lipoprotein (a), and normal high-sensitivity CRP. Liver function tests, complete blood count, thyroid function tests, total serum protein, and basic metabolic profile were also normal. Genetic testing showed 2 variants of undetermined significance to the ABCA1 gene [ABCA1 c.2879T>C (p.Leu960Pro); ABCA1 c.3626C>T (p.Pro1209Leu)].
Objective/Purpose
N/A
Methods
N/A
Results
A coronary artery computed tomography (CTCA) demonstrated borderline obstructive areas of eccentric calcified plaque in the mid to distal left anterior descending (LAD) artery with 40-50% luminal diameter narrowing, nonobstructive eccentric calcified plaque in the proximal left circumflex (LCX) artery with less than 40% luminal diameter narrowing, and obstructive plaque in the mid right coronary artery (RCA) with greater than 50% luminal diameter narrowing, with whole-heart Agatston score of 981. A CT coronary angiography scan with fractional flow reserve (FFR) revealed a modeled stenosis in the mid RCA that demonstrated normal FFR measurement of 0.81, although was significant for abrupt relative change (.18) across the lesion. Invasive coronary angiography revealed nonobstructive coronary artery disease, demonstrating mid RCA 50% stenosis, mid LAD 40% stenosis, and ostial LCX 30% stenosis. The patient was initiated on statin and aspirin therapy. A fasting lipid profile at 2-month interval showed TC 26 mg/dL, LDL-C 5 mg/dL, and HDL-C remaining at 5 mg/dL.
Conclusions
Given ABCA1 gene variants, with absence of phenotypic findings of Tangier disease, the patient was presumed to have familial hypoalphalipoproteinemia. The inverse relationship between low HDL-C levels and cardiovascular risk has been well documented in population based observational studies. However, clinical trials have failed to show clinical benefit of therapy targeting increasing HDL-C levels. Further studies are needed to determine optimal medical therapy aimed at prevention of CAD in this population which may be genetically predisposed to higher risk of early coronary disease.
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