早发急性冠状动脉综合征患者家族性高胆固醇血症院内诊疗现状调查

目的 探讨早发急性冠状动脉综合征(ACS)患者家族性高胆固醇血症(FH)的患病率及诊疗现状. 方法 回顾性收集2016年1月至2017年12月收治于第906医院的早发ACS患者275例,收集患者的人口学资料、既往病史、血脂水平、冠状动脉造影检查结果及药物治疗情况等,采用荷兰脂质监测指南标准进行评分并分为可能FH组(评分...     

Prevalence and pharmacologic management of familial hypercholesterolemia in an unselected contemporary cohort of patients with stable coronary artery disease

Introduction

Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated plasma levels of low‐density lipoprotein cholesterol (LDL‐C) associated with premature cardiovascular disease.

Methods

Using the data from the START (STable Coronary Artery Diseases RegisTry) study, a nationwide, prospective survey on patients with stable coronary artery disease (CAD), we described prevalence and lipid lowering strategies commonly employed in these patients. The study population was divided into “definite/probable FH,” defined as a Dutch Lipid Clinic Network (DLCN) score ≥6, “possible FH” with DLCN 3‐5, and “unlikely FH” in presence of a DLCN <3.

Results

Among the 4030 patients with the DLCN score available, 132 (3.3%) were classified as FH (2.3% with definite/probable and 1.0% with possible FH) and 3898 (96.7%) had unlikely FH. Patients with both definite/probable and possible FH were younger compared to patients not presenting FH. Mean on‐treatment LDL‐C levels were 107.8 ± 41.5, 84.4 ± 40.9, and 85.8 ± 32.3 (P < 0.0001) and a target of ≤70 mg/dL was reached in 10.9%, 30.0%, and 22.0% (P < 0.0001) of patents with definite/probable, possible FH, and unlikely FH, respectively. Statin therapy was prescribed in 85 (92.4%) patients with definite/probable FH, in 38 (95.0%) with possible FH, and in 3621 (92.9%) with unlikely FH (P = 0.86). The association of statin and ezetimibe, in absence of other lipid‐lowering therapy, was more frequently used in patients with definite/probable FH compared to patients without FH (31.5% vs 17.5% vs 9.5%; P < 0.0001).

Conclusions

In this large cohort of consecutive patients with stable CAD, FH was highly prevalent and generally undertreated with lipid lowering therapies.     

早发冠心病患者外周血白细胞端粒长度的变化

目的探讨早发冠状动脉粥样硬化性心脏病(冠心病)患者外周血白细胞端粒长度变化。方法选取2010年1月至2011年11月在青岛市立医院心内科住院的冠心病患者80例,男性43例,女性37例,所有患者为病例组。病例组按照Gensini积分分为4组,A组、B组、C组、D组。病例组按照病变范围分为单支组,双支组和多支组。选取同期经冠状动脉造影或冠状动脉CTA检查排除冠心病的76例查体者为对照组。检测两组生化指标、血压以及端粒相对长度(T/S)。结果病例组外周血白细胞端粒长度T/S比值为0.87±0.31,对照组端粒长度T/S比值为1.12±0.25,病例组外周血白细胞端粒相对长度较对照组明显缩短,差异具有统计学意义(P0.05)。A组、B组、C组和D组患者外周血白细胞端粒长度T/S比值分别为:0.89±0.41,0.91±0.32,0.87±0.29,0.84±0.34,4组比较差异无统计学意义(P均0.05)。单支组、双支组、多支组3组患者外周血白细胞端粒长度T/S比值分别为:0.88±0.35,0.85±0.47,0.89±0.26,3组比较差异无统计学意义(P均0.05)。结论早发冠心病患者外周血白细胞端粒相对长度缩短。早发冠心病外周血白细胞端粒相对长度与冠状动脉的狭窄程度及病变范围无明显相关。     

Konno Ross procedure,coronary artery bypass graft and mitral valve replacement in a 12-year-old girl with homozygous familial hypercholesterolemia

BackgroundFamilial hypercholesterolemia (FH) is a genetic disorder caused by a mutation of the gene for the low density lipoprotein receptor. This mutation can lead to elevated plasma cholesterol levels and subsequently to premature coronary artery disease. Management of patients with FH is complicated and surgery is accompanied by high risk, even in skillful hands.Case presentationA 12-year-old female patient was referred to our department in January 2013 with chest pain and dyspnea. Her history showed that he had documented evidence of homozygous HF (HFH) since 2 years of age and that she underwent a Ross–Konno procedure for valvular aortic stenosis, 3 years ago. Electrocardiography showed ST depression in the inferolateral derivations and ST elevation in aVr. The echocardiography showed LV systolic dysfunction and important mitral regurgitation. Coronary angiography demonstrated stenosis in the distal part of the left main and severe three vessel coronary artery disease. The patient presented critical acute myocardial ischemia immediately after coronary angiography. She was referred for surgery. The left anterior descending artery was bypassed using saphenous vein and both right coronary artery and marginal artery using sequential saphenous vein. The mitral valve was replaced with mechanic prosthesis. The postoperative course was uneventful. She was prescribed atorvastatin accompanied by cholestyramine and diet modulation.ConclusionHFH patients are at increased risk of developing coronary artery disease and also sudden death unless the condition is recognized and treated promptly. Surgery remains the most effective means of prolonging the life of these patients.     

左卡尼汀对冠心病高胆固醇血症的疗效观察

目的观察左卡尼汀在冠心病高胆固醇血症患者中的临床疗效及其安全性。方法选择冠心病伴高胆固醇的患者40例,予左卡尼汀3.0 g/d,连续15 d静脉滴注,以后改用左卡尼汀口服液1.0 g,3次/d,连续15 d。治疗前后比较每周心绞痛发作次数以及硝酸甘油片用量,心电图、超声心动图、血脂、肝肾功能生化指标变化。结果左卡尼汀治疗24周后患者心绞痛发生次数及硝酸甘油片用量显著减少,ST段缺血型下移之和∑ST减小,心脏指数和左室射血分数显著改善;左卡尼汀治疗后2周总胆固醇和甘油三脂降低,高密度脂蛋白胆固醇升高。结论左卡尼汀可以缓解冠心病患者的临床症状,减轻心肌缺血,改善心功能,并且可以调节血脂水平,不良反应少。     

Aortic stiffness is increased in patients with premature coronary artery disease: A tissue Doppler imaging study

BackgroundAtherosclerosis and arterial stiffening may coexist and the correlation of these parameters in patients with premature coronary artery disease (CAD) has not been well elucidated. Tissue Doppler imaging of the ascending aorta may be used in the assessment of elastic properties of the great arteries.ObjectiveTo investigate the correlation between aortic stiffness and premature CAD using parameters derived from two-dimensional and tissue Doppler imaging (TDI) echocardiography of the ascending aorta.MethodsFifty consecutive subjects younger than 40 years old who were hospitalized with diagnosis of acute coronary syndrome and had undergone coronary angiography were recruited. The control group included 70 age–sex matched individuals without a diagnosis of CAD. Aortic stiffness index (SI), aortic distensibility (D), and pressure-strain elastic modulus (E_p) were calculated from the aortic diameters measured by two-dimensional M-mode echocardiography and blood pressure obtained by sphygmomanometry. Aortic systolic velocity (S_Ao), and early (E_Ao) and late (A_Ao) diastolic velocities were determined by pulse-wave TDI from the anterior wall of ascending aorta 3 cm above the aortic cusps in parasternal long-axis view.ResultsStiffness index was higher [median 5.40, interquartile range (IQR) 5.98 vs. median 4.14 IQR 2.43; p = 0.03] and distensibility was lower (median 2.86 × 10⁻⁶ cm²/dyn, IQR 2.51 × 10⁻⁶ cm²/dyn vs. median 3.46 × 10⁻⁶ cm²/dyn, IQR 2.38 × 10⁻⁶ cm²/dyn; p = 0.04) in patients with CAD compared to the control group. E_Ao was significantly lower in the CAD group (7.2 ± 1.8 cm/s vs. 9.2 ± 2.4 cm/s, p < 0.01). The difference in E_Ao remained significant when CAD patients with a left ventricular ejection fraction >55% was compared to the control group. S_Ao and A_Ao velocities of ascending aorta were similar in control and CAD groups. There was a significant correlation between E_Ao velocity and aortic stiffness index (r = −0.28, p = 0.01), distensibility (r = 0.19, p = 0.04) and elastic modulus (r = −0.24, p = 0.01). In multivariate regression analysis, decreased levels of high-density lipoprotein cholesterol [odds ratio (OR): 1.12 95% CI 1.06–1.19; p = 0.01] and E_Ao (OR: 1.41 95% CI 1.12–1.79; p = 0.01) measurements remained as the variables independently correlated with premature CAD in the study group.ConclusionArterial stiffness is increased in patients with premature CAD. E_Ao of the anterior wall of ascending aorta measured with pulse-wave TDI echocardiography is correlated with arterial stiffening and is decreased in patients with premature CAD.     

Serum gamma glutamyl transferase: a novel biomarker for screening of premature coronary artery disease

Background

We aimed to elucidate the association between gamma glutamyl transferase (GGT) activity with prevalence of premature coronary artery disease (CAD) in young Pakistani patients undergoing diagnostic coronary angiography.

Methods

A total of 218 young adults (age≤45 years) underwent diagnostic angiography. Serum samples were taken from all the patients and analyzed for serum GGT activity, cholesterol and triglycerides.

Results

Coronary artery disease patients had significantly increased GGT activity (P=.001) and exhibited a significant positive correlation with blood pressure, cholesterol, blood glucose, and smoking and negative correlation with total antioxidant status (P<.01).

Conclusion

The study revealed good diagnostic accuracy at cutoff of 35 U/L with a sensitivity of 92%, specificity of 81%, and diagnostic odds ratio of 48 in estimation of premature CAD in young Pakistanis.     

青年冠心病患者冠状动脉病变特点及相关危险因素分析

目的探讨冠状动脉粥样硬化性心脏病(冠心病)的临床特点在青年与老年患者间的差异。方法回顾性分析48例青年冠心病患者与156例老年冠心病患者的临床资料,着重分析比较两组的危险因素及冠状动脉造影结果。结果青年组冠心病患者女性比例占6.25%(3/48),明显低于老年组的33.33%(52/156),差异有统计学意义(P0.01)。青年组体质量指数明显高于老年组,差异有统计学意义[(27.03±2.73)kg/m2vs.(25.16±3.05)kg/m2,P0.01]。青年组大量吸烟的比例也远高于老年组,差异有统计学意义[75.00%(36/48)vs.36.54%(57/156),P0.01]。老年组合并原发性高血压、糖尿病的发生率高于青年组,差异有统计学意义[51.28%(80/156)vs.16.67%(8/48),P0.01;30.77%(48/156)vs.6.25%(3/48),P0.01]。青年组血浆总胆固醇,低密度脂蛋白胆固醇及三酰甘油浓度与老年组比较,差异无统计学意义(P0.05)。青年组高密度脂蛋白胆固醇浓度低于老年组,差异有统计学意义[(0.85±1.80)mmol/Lvs.(1.08±0.23)mmol/L,P0.01]。青年组血浆尿酸浓度高于老年组,差异有统计学意义[(349.10±67.02)mmol/lvs.(323.77±73.82)mmol/L,P0.01]。青年组冠状动脉病变以单支病变为主,且左前降支病变发生率最高。结论男性、肥胖、大量吸烟为青年冠心病主要发病危险因素,低高密度脂蛋白胆固醇浓度和高尿酸浓度也可能为青年冠心病的危险因素;青年冠状动脉病变轻,以单支病变为主。     

中性粒细胞和淋巴细胞的比值及单核细胞和淋巴细胞的比值与早发冠心病的相关性分析

目的 探讨中性粒细胞和淋巴细胞的比值(NLR)及单核细胞和淋巴细胞的比值(MLR)在早发冠心病人群中的分布特征及是否与早发冠心病患者的冠状动脉病变严重程度相关。方法 收集2020年8月至2021年2月因胸痛疑诊冠心病,就诊于陕西省人民医院男性＜55岁,女性＜65岁的患者247例,均行冠脉造影,其中早发冠心病组143例,其中SCAD组47例, NSTE-ACS组49例,STEMI组47例,除外早发冠心病的104例为对照组。比较NLR、MLR在两组患者中的分布特征,分析NLR、MLR与早发冠心病Gensini积分的相关性及早发冠心病的独立危险因素。结果 与对照组相比,早发冠心病组的NLR及MLR的水平明显高（3.79 比 2.08,Z=-7.01, P＜0.001, 0.34比 0.24,Z=-5.65, P＜0.001）。NLR水平在STEMI组＞NSTE-ACS组及SCAD组（P＜0.05）,NSTE-ACS组＞SCAD组（P＜0.05）;MLR水平在STEMI组＞NSTE-ACS组及SCAD组（P＜0.05）,但NSTE-ACS组和SCAD组的MLR水平差异无统计学意义（P＞0.05）。NLR、MLR水平与Gensini评分之间存在正相关（r=0.383, P＜0.05; r=0.285, P＜0.05）。多因素logistic回归分析,NLR(OR=1.288, 95%CI 1.067～1.547,P=0.01）和MLR(OR=3.270, 95%CI 2.414～8.585, P=0.03）是早发冠心病的独立危险因素。NLR诊断早发冠心病的界值点为2.28,（敏感度74.1 %,特异度63.5 %）,MLR诊断早发冠心病的界值点为0.248,（敏感度72 %,特异度 56.7 %）。结论 NLR和MLR水平与早发冠心病患者的冠脉严重程度相关,是早发冠心病的独立危险因素。     

Long-term effect of low-density lipoprotein apheresis in patients with heterozygous familial hypercholesterolemia

Clinical efficacy and safety of the therapeutic tool which directly removes LDL particles from circulation (LDL apheresis) have already been established in the treatment for refractory hypercholesterolemia in patients with familial hypercholesterolemia (FH). Two clinical studies with event-based assessment have demonstrated remarkably beneficial outcomes of long-term LDL apheresis using dextran sulfate cellulose columns plus adjunctive cholesterol-lowering drug therapy in the prevention of cardiovascular events in heterozygous FH with coronary artery disease. The results of several studies with angiographic and ultrasound-based assessment indicate a possible role for LDL apheresis in restructuring and stabilization of atherosclerotic lesions. These clinical improvements caused by LDL apheresis in heterozygous FH support the efficacy and importance of aggressive cholesterol-lowering therapy for secondary prevention of atherosclerotic cardiovascular disease in hypercholesterolemic patients.     

Search for familial hypercholesterolemia patients in an Italian community: A real-life retrospective study

Background and aimsFamilial hypercholesterolemia (FH) is a common inherited disorder of low-density lipoprotein (LDL) catabolism that causes elevated LDL-cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease (ASCVD). Despite the availability of effective treatments, FH remains underdiagnosed and undertreated. The aims of the study were to identify putative FH subjects using data from laboratory and cardiology databases, genetically characterize suspected FH patients referred to the Lipid Clinic and monitor attainment of treatment goals in identified patients.Methods and resultsWe retrieved the electronic health records of 221,644 individuals referred to laboratory for routine assessment and of 583 ASCVD patients (age ≤65) who underwent percutaneous transluminal coronary angioplasty (PTCA). We monitored the lipid profiles of subjects with LDL-C ≥ 250 mg/dl identified by laboratory survey (LS-P), PTCA patients and patients from the Lipid Clinic (LC-P). The laboratory survey identified 1.46% of subjects with LDL-C ≥ 190 mg/dl and 0.08% with LDL-C ≥ 250 mg/dl. Probable/definite FH was suspected in 3% of PTCA patients. Molecularly-confirmed FH was found in 44% of LC-P subjects. Five new LDLR mutations were identified. The 50% LDL-C reduction target was achieved by 70.6% of LC-P patients. Only 18.5% of PTCA patients reached the LDL-C < 55 mg/dl target.ConclusionBy using a combined approach based on laboratory lipid profiles, documented ASCVD and Lipid Clinic data, we were able to identify subjects with a high probability of being FH. Attainment of LDL-C goals was largely suboptimal. Efforts are needed to improve FH detection and achievement of lipid targets.     

Conventional risk factors of coronary artery disease in a tertiary care hospital of Chandigarh in Northern part of India

There are conflicting reports about the role of conventional risk factors in coronary artery disease from some of the studies in India. The present study tried to determine the association of conventional risk factors in patients with coronary artery disease (CAD) and correlate with findings on coronary angiography.

Material and methods

Study was conducted at the PGIMER in 1003 consecutive patients with angiographic proven coronary artery disease. They were assessed for cardiovascular risk factors like age, sex, history of smoking, diabetes, hypertension (physician diagnosed) and family history of CAD. Anthropometric data for height, weight, body mass index (BMI), waist circumference and waist hip ratio were recorded using standard methods. Lipid profile and blood sugar estimation was done.

Results

The mean age was 56 ± 10.8 years with 82.8% were males. Hypertension, diabetes mellitus, history of smoking, family history and dyslipidemia were present in 59.6%, 25.8%, 32%, 6.8%, and 56% respectively. Central obesity was seen in 75.6% of male (WHR > 0.90) and 88.3% of female (WHR > 0.80) patients. Single, double and triple vessel disease was present in 50.4%, 28.2% and 16% cases respectively. Types A, B and C lesions were seen in 32.7%, 41.3%, and 37.6% cases respectively. About two fifth (39.8%) cases presented with acute myocardial infarction, 22.4% with unstable angina/NSTEMI and 37.8% with chronic stable angina. Logistic regression analysis showed that diabetes, waist hip ratio and raised triglycerides were significantly associated with increasing severity of lesion. Further diabetes also showed significant association with increased vessel wall involvement. Health promotion programmes focusing on conventional risk factors and secondary prevention focusing on early diagnosis, management and lifestyle modifications may be the key interventions for prevention and control of CAD.     

The extended abnormalities in lipoprotein metabolism in familial hypercholesterolemia: Developing a new framework for future therapies

Familial hypercholesterolemia (FH) is a dominantly inherited disorder characterized by marked elevation of plasma low-density lipoprotein (LDL) cholesterol concentrations and premature coronary artery disease (CHD). In addition to impaired LDL receptor-mediated clearance of LDL particles, in vitro and in vivo studies suggest that hepatic oversecretion of apolipoprotein (apo) B may contribute to the hypercholesterolemia in FH. This may be due to an effect of the expanded hepatic pool of cholesterol (a consequence of increased receptor-independent uptake of LDL) and/or a direct effect of the LDL receptor on apoB secretion. Hepatic oversecretion of apoB may depend on the type and severity of the genetic mutation causing FH. FH can also increase plasma Lp(a) concentration by an undefined mechanism that may not directly involve the LDL receptor pathway. Decreased catabolism of triglyceride-rich lipoproteins could also be due to deficient LDL receptor function, accounting for postprandial dyslipidemia in FH. The metabolism of high-density lipoprotein (HDL) in FH is poorly understood, but preliminary data suggest abnormal HDL composition and functionality, as well as altered transport of apoA-I. Beyond effects related to specific genetic defects in the LDL pathway, co-existing secondary causes, particularly obesity and insulin resistance, and other genetic variants may also perturb lipoprotein metabolism in individuals with FH. Furthermore, residual risk remains high in statin-treated FH. Knowledge of an extended metabolic framework will, therefore, provide the basis for judiciously selecting new pharmacotherapies to treat FH, including apoB antisense oligonucleotides, microsomal transfer protein (MTP) inhibitors and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.     

Long-term effect of low-density lipoprotein apheresis in patients with homozygous familial hypercholesterolemia

Patients that are homozygous for familial hypercholesterolemia (FH) exhibit severe hypercholesterolemia, cutaneous and tendon xanthomas and premature atherosclerosis beginning in childhood. They are resistant to drug therapy and low-density lipoprotein (LDL) apheresis is the practical treatment. Here we review the technique of LDL apheresis treatment, the long-term effects of LDL apheresis, the effect of apheresis on pregnancy, and the drugs that have proven beneficial in patients with homozygous FH. We also record our experiences of treating eight homozygous FH patients using the LDL apheresis treatment. Among the eight patients, one has been free from cardiovascular disease and two patients have each regressed once. In two patients, aortic valve stenosis developed and the other two patients died for acute myocardial infarction. Furthermore, two patients delivered healthy babies in spite of coronary artery disease. Thus, LDL apheresis therapy has the possibility of preventing the progression of atherosclerosis, but the prognosis assessed by long-term observation is still not satisfactory. A recent clinical trial showed some efficacy of the combination therapy of LDL apheresis and atorvastatin for reducing serum cholesterol levels in homozygous FH, suggesting that this combination therapy may be useful for prevention of atherosclerosis in patients homozygous for FH.