Insertion/deletion polymorphism of angiotensin converting enzyme gene in Korean hypertensive adolescents

The essential role of the renin-angiotensin system (RAS) in controlling blood pressure has been well established. Genes encoding components of the RAS have been proposed as candidate genes that determine genetic predisposition to hypertension and the risk of developing cardiovascular complications. The purpose of this study was to analyze angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms in Korean hypertensive adolescents, and to determine the association between ACE genotype and cardiovascular risk. Forty hypertensive adolescents (16–17 years old, systolic blood pressure (BP) ≥140 mm Hg and/or diastolic BP ≥90 mm Hg) and a control group of twenty normotensive adolescents were included in the study. Obesity index (OI) and body mass index (BMI) were calculated. Skin fold thickness and arm circumference were also measured. Fat mass and fat distribution were analyzed by bioelectrical impedance. Blood pressure was measured at resting state by oscillometric methods. Serum aldosterone, renin, insulin, ACE, homocysteine, vitamin B12, and folate levels were evaluated after a fasting period of 12 h. The carotid intima-media thickness (IMT) and carotid artery diameter were measured by carotid ultrasound. Pulse wave velocity (PWV) and ankle-brachial index (ABI) were also measured. Polymerase chain reaction (PCR) was conducted to amplify DNA from blood samples of each individuals to analyze ACE I/D polymorphism. Genotype frequencies of I/I were 37.5%, I/D 45.0% and D/D 17.5%. Serum ACE levels were 33.5 ± 8.7 U/l in I/I genotype, 48.6 ± 19.8 U/l in I/D genotype and 61.4 ± 22.7 U/l in D/D genotype, which showed that ACE levels were significantly higher in those with D/D or I/D genotype than in I/I genotype. Carotid IMT was significantly greater in D/D group than in I/I group. In conclusion, the D allele is associated with the increased level of ACE in Korean hypertensive adolescents.     

血管紧张素转换酶基因多态性对高血压病患者左室肥厚与重构的影响

目的 :探讨血管紧张素转换酶 ( ACE)基因多态性对高血压病 ( EH)患者左室肥厚与重构的影响。方法 :对 68例 EH患者进行超声心动图检查 ,测定左室重量指数 ( L VMI)和室壁相对厚度( RWT) ,并从外周血白细胞中抽提人类基因组脱氧核糖核酸 ( DNA) ,应用 ACE基因第 16内含子多态区两侧序列作为引物 ,聚合酶链式反应测定 ACE基因型。结果 :经纠正其他因素影响后 ,DD型患者 L VMI和室壁相对厚度均高于 II型患者 ( P <0 .0 5 ) ,经多元线性逐步回归分析 ,收缩期血压、性别、ACE基因型均与 LVMI独立相关 (总 R2 =0 .36) ,而收缩期血压、体重指数、ACE基因型均与 RWT独立相关 (总 R2 =0 .49)。结论 :ACE基因型分别可解释 LVMI和 RWT总变异的 3.8%和 2 .0 % ,ACE基因 DD型可能是中国汉族 EH患者左室肥厚与重构的新的独立危险因素 ,应重视此类患者的防治。     

Angiotensin converting enzyme gene polymorphism in type 2 diabetes mellitus

The aim of this study is the assessment of the association of human angiotensin-converting enzyme gene I/D polymorphism with type 2 diabetes in 155 diabetic patients and 139 healthy individuals. These polymorphism were studied using polymerase chain reaction. Angiotensin converting enzyme gene DD genotype associated with type 2 diabetes in overweight and obese patients and patients with normal total plasma cholesterol. There is also association of DD genotype with arterial hypertension and with myocardial infarction in type 2 diabetic patients.     

血管紧张素转换酶2基因A9570G多态性与高血压合并左心室肥厚的相关性研究

目的探讨血管紧张素转换酶2基因(ACE2)A9570G多态性与高血压合并左心室肥厚的关系。方法选择高血压合并左心室肥厚(LVH)患者172例(LVH组)、高血压未合并LVH患者153例(NLVH组)以及对照组80例,应用聚合酶链反应(PCR)方法检测入选者ACE2基因A9570G多态性,按性别分别比较不同组别中基因型分布及等位基因频率的差异。结果在女性,3组间等位基因频率比较差异有统计学意义(P=0.007),基因型分布差异也有统计学意义(P=0.034),其中LVH组GG基因型及G等位基因频率分别为30.0%和61.0%,高于NLVH组(18.7%和44.8%)及对照组(15.0%和40.0%)。在男性,3组间等位基因/基因型频率比较差异有统计学意义(P=0.002),其中LVH组G基因型/等位基因频率为69.0%,高于NLVH组(47.6%)及对照组(40.0%)。结论 ACE2基因A9570G多态性与高血压患者左心室肥厚相关。     

维生素D受体基因多态性与糖尿病的相关性

目的研究维生素D受体（VDR）基因BsmⅠ酶切位点多态性是否与糖尿病（DM）的易感性相关。方法采用PCR-RFLP方法分型并用x^2检验比较各组间基因型及等位基因频率的分布。结果全部研究对象中共见BB、bb、Bb三种基因型。1型糖尿病（T1DM）BB基因型频率为2％，Bb基因型频率为47％，分别明显高于对照组的0．5％和9．2％，而2型糖尿病（T2DM）的BB基因型频率为0．6％，Bb基因型频率为10．8％，与对照组分别相似。结论VDR基因BsmⅠ位点多态性与T2DM的易感性可能无关（P〉0．05），但与T1DM的易感性密切相关（P〈0．05）。     

Deletion polymorphism of the angiotensin converting enzyme gene is associated with an increase in left ventricular mass in men with type 2 diabetes mellitus.

Previous studies evaluating the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism have revealed that expression of the DD genotype is associated with an increase in myocardial infarction, cardiomyopathy, and left ventricular (LV) mass in nondiabetic patients. In the present study, a cross-sectional analysis was performed to evaluate the potential relationship between the ACE I/D genotypes and the LV mass index in 289 non-insulin-dependent diabetes mellitus (NIDDM) subjects without known coronary artery disease. Two dimensional directed M-mode echocardiograms along with selected patient characteristics were obtained from the study population. The distribution of the I/D polymorphism was as follows: 63 were II (22%), 137 were ID (47%), and 89 were DD (31%). Univariately, the DD genotype was associated with an increase in LV mass in men but not in women. When subjected to a multiple regression model that included age, systolic blood pressure, duration of diabetes, duration of hypertension, presence of the black race, and the presence of the DD genotype, the DD genotype was independently associated with an increase in the LV mass index with a parameter estimate of 10.5 g/m2 (95% CI = 3.9, 17.0; P < .002) in the male subjects. Thus, in this NIDDM study population, male patients with the DD genotype are independently associated with an increased LV mass.     

Association of angiotensin converting enzyme gene polymorphisms with left ventricular hypertrophy.

The angiotensin converting enzyme gene (ACE) is of much interest as a candidate gene conferring an individual's genetic susceptibility to left ventricular hypertrophy (LVH). LVH has long been thought to be an end point of essential hypertension (EH), rather than a separate entity, though it is influenced by a unique set of hormonal, vascular and genetic factors. In this study, we attempted to determine whether two representative polymorphisms of the ACE gene, ACE I/D and 2350 G>A, known to be associated with EH and to have a highly significant influence on plasma ACE levels, could implicate ACE as a quantitative trait locus (QTL) for LVH. We carried out a retrospective, case-control study of the two ACE polymorphisms amongst 180 nationals (50 LVH patients and 130 controls) from the United Arab Emirates (Emirati)--an ethnic group characterized by an absence of alcohol intake and cigarette smoking--for putative correlations with LVH. Clinical diagnoses of LVH were based on echocardiographic and ECG criteria. ACE I/D and 2350 G>A genotypes were determined by polymerase chain reaction (PCR) and restriction digestion. Univariate and multivariate logistic regression analyses revealed an association between ACE polymorphisms and LVH. Haplotype analysis further supported this finding. The ACE I/D and ACE 2350 G>A polymorphisms were in strong linkage disequilibrium and were independently associated with LVH, suggesting that ACE is likely to be a QTL for LVH. In conclusion, This is the first association study of the ACE 2350 G>A polymorphism with LVH; the results showed that this polymorphism, along with ACE I/D, is associated with LVH.     

Neutral endopeptidase and angiotensin I converting enzyme insertion/deletion gene polymorphism in humans

Neutral endopeptidase (NEP) hydrolyses angiotensins (Ang) I and II and generates angiotensin-(1-7) [Ang-(1-7)]. In humans, the insertion/deletion (I/D) angiotensin-I converting enzyme (ACE) gene polymorphism determined plasma ACE levels by 40%. In rats, a similar polymorphism determines ACE levels which are inversely associated to NEP activity. The objective of this study is to evaluate the relationship between ACE expression and plasma NEP activity in normotensive subjects and in hypertensive patients. In total, 58 consecutive patients with hypertension, evaluated in our Hypertension Clinic, were compared according to their ACE I/D genotypes with 54 control subjects in terms of both plasma ACE activity and NEP activities. Plasma ACE activity was elevated 51 and 70% in both DD ACE groups (normotensives and hypertensives) compared with their respective ID and II ACE groups (P<0.001). A significant effect of the ACE polymorphism and of the hypertensive status on ACE activity was observed (P<0.001). In normotensive DD ACE subjects, NEP activity was 0.30+/-0.02 U/ml, whereas in the normotensive II ACE and in the normotensive ID ACE subjects NEP activity was increased 65 and 48%, respectively (P<0.001). In the hypertensive DD ACE patients, NEP activity was 0.47+/-0.03 U/mg. An effect of the I/D ACE genotypes on NEP activity (P<0.04) and an interaction effect between the I/D ACE genotype and the hypertensive status were also observed (P<0.001). These results are consistent with a normal and inverse relationship between the ACE polymorphism and NEP activity in normotensive humans (as is also observed in rats). This normal relationship is not observed in hypertensive patients.     

I/D gene polymorphism of the angiotensin-converting enzyme and left ventricular hypertrophy. Response to converting enzyme inhibitors

BACKGROUND: The present study was designed to assess whether the angiotensin-converting enzyme (ACE) gene I/D polymorphism influence the ACE inhibitors effect on the regression of left ventricular hypertrophy. METHODS: Sixty hypertensive subjects never treated by antihypertensive drugs, aged 46 +/- 11 years, were included in the study. Follow-up with ACE inhibitor treatment was 60 +/- 26 months. Genotypes for ACE I/D polymorphism (DD, ID or II) were determined by PCR. The left ventricular mass index (LVMI) was assessed by two-dimensional directed M-mode echocardiography. RESULTS: ACE genotype distribution was in agreement with the Hardy-Weinberg equilibrium: 21 patients had the DD genotype, 29 were ID, and 10 were II. At baseline, age, systolic arterial pressure and LVMI didn't differ on the basis of genotype. Body mass index was significantly higher in II than in ID and DD groups. Regression of LVMI with ACE inhibitor treatment was similar in the 3 genotypes (-8.9%, -0.6%, -12.1% in DD, ID and II groups respectively). In addition, decrease of systolic arterial pressure was identical in 3 groups. CONCLUSION: ACE gene I/D polymorphism seems not to influence regression of left ventricular hypertrophy by ACE inhibitors in essential hypertension.     

I/D polymorphism of angiotensin I converting enzyme gene and insulin resistance and some parameters of metabolic syndrome in patients with type 2 diabetes

Insulinresistance is a component of the metabolic syndrome and important pathogenetic factor of type 2 diabetes mellitus. There are evidences that activation of the renin-angiotensin system (RAS) can decrease insulin sensitivity of tissues. As I/D polymorphism of angiotensin converting enzyme (ACE) gene can influence the activity of RAS, it may also influence insulin resistance. Aim. To assess the relationship between the I/D polymorphism of ACE gene and degree of insulin resistance and intensity of metabolic syndrome in type 2 diabetic patients. Study group and methods. Examined group: 108 type 2 diabetic patients (38 women and 70 men), with mean duration of disease 9.07 +/- 6.68 years, mean age 59.98 +/- 9.10 years. Assessed parameters: body mass index (BMI), waist/hip ratio (WHR), arterial blood pressure. Laboratory tests: concentration of the glycosylated hemoglobin (HbA 1c), glucose, insulin, total cholesterol, HDL and LDL cholesterol, triglycerides, creatinine, uric acid. Insulin resistance was calculated by the HOMA rate. Criterion of insulin resistance was rate > or = 2.5. The diagnosis and assessment of intensity of metabolic syndrome was performed according to criteria of National Education Cholesterol Adult Treatment Program the Panel III. I/D ACE gene polymorphism was evaluated by polymerase chain reaction (PCR). Results. Groups with 11, ID and DD genotype were not different in age, BMI, WHR, duration of diabetes, the prevalence and duration of arterial hypertension, degree of metabolic control and insulinresistance assessed by HOMA rate and intensity of metabolic syndrome. DD genotype carriers had significant higher systolic and diastolic blood pressure (147.8 +/- 19.8 mmHg vs 138.2 +/- 16.5 mmHg, p = 0,02; 89.2 +/- 9.6 mmHg vs 81.7 +/- 8.6, p = 0,003, respectively) than II patients. Conclusion. In type 2 diabetic patients the I/D genotype of ACE gene is not associated with the increased insulin resistance assessed by HOMA rate and intensity of metabolic syndrome.     

Prevalence of the angiotensin I converting enzyme insertion/deletion polymorphism, plasma angiotensin converting enzyme activity, and left ventricular mass in a normotensive Chilean population.

The aim of this study was to estimate the prevalence of the different alleles of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and associated plasma ACE activity, as well as cardiac echocardiographic structure, in a healthy Chilean population. We selected 117 healthy normotensive subjects (aged 45 to 60 years, middle socioeconomic status, nonobese, and nondiabetic) from a population-based study concerning the prevalence of risk factors for chronic diseases (Conjunto de Acciones Para la Reducción Multifactorial de las Enfermedades no Transmisibles [CARMEN]). The frequencies of the I and D alleles were 0.57 and 0.43, respectively. Mean plasma ACE activity was 15.3 +/- 3.9 U/mL. Compared with subjects with the II genotype, plasma ACE activity was significantly higher in subjects with the ID and DD genotypes with no difference between them. No correlation was observed between blood pressure and plasma ACE activity. Among the three different genotypes there was no difference in left ventricular (LV) dimensions or in LV mass. No correlation between plasma ACE activity and LV mass was observed for either gender or different genotypes. Multivariate linear regression analysis using LV mass and LV mass index as dependent variables showed independent effects (P < .05) for gender (higher LV mass in men) and diastolic blood pressure, but not for the DD genotype. In conclusion, in this population, the presence of the D allele on the ACE gene determined higher circulating ACE activity. However, in this normotensive healthy population, male gender and diastolic blood pressure, but not the presence of the D allele, were associated with increased LV mass.     

Insertion/deletion angiotensin converting enzyme gene polymorphism affects the microvascular structure of the kidney in patients with nondiabetic renal disease

OBJECTIVE: It has been reported that the deletion allele of the insertion/deletion polymorphism of the angiotensin I converting enzyme gene is associated with increased cardiovascular risk and progressive renal disease, including immunoglobulin A nephropathy. We therefore investigated the relationship between angiotensin converting enzyme polymorphism and intrarenal microvascular structure in 56 patients with nondiabetic renal disease. METHODS AND RESULTS: We determined various cardiovascular hormones of the renin-angiotensin system and angiotensin converting enzyme gene polymorphism in 56 patients with nondiabetic renal diseases who underwent a renal biopsy. The patients were divided into three groups by angiotensin converting enzyme genotype (insertion/insertion, n = 21; insertion/deletion, n = 23; deletion/deletion, n = 12) using polymerase chain reaction methods. The angiotensin converting enzyme insertion/ deletion and deletion/deletion genotypes were associated with a significantly higher interlobular artery wall : lumen ratio than the insertion/insertion genotype (insertion/insertion 0.27 +/- 0.01, insertion/deletion 0.32 +/- 0.01, deletion/deletion 0.33 +/- 0.02; P < 0.05). Afferent arteriolar and tubulo-interstitial injury scores were similar among the three genotypes. Although serum angiotensin converting enzyme activity was higher in the deletion/deletion than in the other two genotypes (insertion/insertion 9.7 +/- 0.7, insertion/deletion 10.7 +/- 0.9, deletion/deletion 14.0 +/- 2.4 IU/I; P < 0.05), other factors of the renin-angiotensin system, including blood pressure and serum creatinine levels, were not different among the three groups. CONCLUSIONS: The angiotensin converting enzyme deletion/deletion genotype may be considered a risk factor for the development of microvascular wall thickening in nondiabetic renal diseases.     

Relationship between insertion/deletion polymorphism of angiotensin converting enzyme gene and type 2 diabetic kidney disease

<正>Objective To explore the interaction of angiotensin converting enzyme (ACE) insertion/deletion(I/D) polymorphism (rs1799752) with diabetic kidney disease(DKD) development as well as its interaction with smoking and obesity in Chinese type 2 diabetic mellitus     

ACE基因插入/缺失多态与国人肺血栓栓塞症的关联研究

目的探讨血管紧张素转换酶(ACE)基因插入/缺失(ID)多态是否与肺血栓栓塞症存在关联,D等位基因是否增加国人肺血栓栓塞的危险。方法放射性核素肺通气-灌注扫描和(或)超高速CT检查并结合临床资料确诊的肺血栓栓塞症患者72例及性别、年龄匹配的健康对照者72名。调查静脉血栓形成和肺栓塞相关危险因素。酚-氯仿法提取基因组DNA,聚合酶链反应(PCR)鉴定ACE基因I/D多态点基因型。结果(1)病例组外伤、手术史及下肢静脉炎、静脉曲张发生率显著高于对照组,肺血栓栓塞家族史、心血管疾病家族史、口服避孕药、吸烟及饮酒史两组间差异无显著性。(2)健康对照组I、D等位基因频率分别为66％和34％,基因型分布符合Hardy-Weinberg平衡。Ⅱ、ID和DD基因型及I、D等位基因频率在病例和对照组差异无显著性。(3)进一步分别按显性、隐性和加性作用方式探讨ACE基因I/D多态与肺血栓栓塞症的关系,发现DD基因型个体肺栓塞危险显著增加(OR=2.51,P＜0.05),提示D等位基因为隐性作用方式。(4)将肺血栓栓塞患者按有无明确静脉血栓形成及肺栓塞环境诱因分组,结果显示无明确环境诱因组DD基因型频率显著高于对照组(27.1％vs14.3％;OR=2.64,P＜0.05),而有明确环境诱因组与对照组相比DD基因型频率差异无显著性。将肺血栓栓塞患者按是否合并下肢静脉血栓形成分组,结果显示肺栓塞合并下肢静脉血栓形成组DD基因型频率显著高于健康对照组(32.4％vs14.3％;OR=3.36,P＜0.05),单纯肺栓塞组与健康对照组比较差异无显著性。结论ACE基因I/D多态与国人肺血栓栓塞有关,D等位基因为隐性作用方式。DD基因型显著增加无明确静脉血栓形成及肺栓塞环境诱因个体肺栓塞危险;有下肢静脉血栓形成病史的DD基因型个体肺栓塞危险亦显著增加。     

Influence of insertion-deletion polymorphism of the angiotensin converting enzyme gene on left ventricular hypertrophy in patients with aortic stenosis--differences in men and women

The role of different parameters (including genetic factors) on the timing and extend of left ventricle hypertrophy in patients with aortic stenosis is not defined. In our study we analyze the influence of clinical, echocardiographic parameters and I/D polymorphism of the angiotensin converting enzyme gene on the left ventricle hypertrophy (left ventricle mass index) in this group of patients. The study was done with the group of 302 pts with aortic stenosis--120 women and 182 men; mean age 58 +/- 11 yrs. Stepwise (backward) regression was used to assess the influence of the analyzed parameters (age, gender, history of hypertension, EF, MGA, presence of significant coronary artery disease and I/D ACE polymorphism) on the LVH in the all pts and in the women and the men separately. In the whole group the LVMI depends on EF (t = -6.5; p = 0.0001--higher LVMI in lower EF), MGA (t = 3.9; p = 0.0001--higher LVMI in higher MGA) and gender (t = 2.8; p = 0.005--higher LVMI in men). In women LVMI was related with EF (t = -3.6; p = 0.001--higher LVMI in lower EF), age (t = 2.9; p = 0.004--higher LVMI in older pts) and MGA (t = 2.5; p = 0.013--higher LVMI in higher MGA). In men the LVMI depends on EF (t = -4.8; p = 0.0001--higher LVMI in lower EF) and MGA (t = 1.98; p = 0.049--higher LVMI in higher MGA). Significant relationship between LVMI and results of I/D ACE polymorphism was observed both in women and men. I/D polymorphism relationship with LVMI was divergent in these 2 groups--association of higher LVMI with lack of DD type of polymorphism in women and presence of DD polymorphism in men. CONCLUSIONS: 1. Left ventricle hypertrophy in pts aortic stenosis is higher in men than in women. 2. In women left ventricle hypertrophy is related with ejection fraction, maximal aortic gradient, age and I/D ACE polymorphism; in men it is related to EF, MGA and I/D ACE polymorphism. 3. The influence of I/D ACE polymorphism on the left ventricle hypertrophy is divergent in women and men--in women related to the lack of DD polymorphism, in men related to the presence of DD polymorphism.     

2型糖尿病肾病与血管紧张素转换酶基因多态性的研究

目的 探讨２型糖尿病肾病与ＡＣＥ基因Ｉ／Ｄ多态性。方法 应用ＰＣＲ方法检测了３６例健康对照者、５８例糖尿病肾病和５０例有糖尿病肾病、病程大于５年的２型糖尿病病人的ＡＣＥ基因Ｉ／Ｄ基因型。结果 三组间ＡＣＥ基因ＩＩ、ＩＤ、ＤＤ三种基因型和Ｉ、Ｄ两种等位基因的频率分布无显著性差异;在三种基因型之间,尿白蛋白排泄率和血肌酐水平也无显著性差异。结论 ＡＣＥ基因Ｉ／Ｄ多态生与中国汉族２型糖尿病肾病无关联,Ａ     

血管紧张素转换酶基因多态性与2型糖尿病并发高血压的相关性研究

目的 :研究血管紧张素转换酶 (ACE)基因多态性与 2型糖尿病并发高血压的关系。方法 :应用 PCR方法分析 149例 2型糖尿病患者及正常对照者的 ACE基因型。结果 :1ACE基因型及等位基因构成比 ,正常对照组与 2型糖尿病组无显著性差异 ;2并发高血压组 DD型及 D等位基因频率显著高于无高血压组 (P <0 .0 5 )。结论 :ACE基因 I/ D多态性与 2型糖尿病并发高血压有关。     

血管紧张素转换酶基因多态性与非胰岛素依赖型糖尿病伴微血管病变相关性的研究

目的　探讨血管紧张素转换酶 (ACE)基因多态性与非胰岛素依赖型糖尿病 (NIDDM )伴微血管病变的关系。方法　应用多聚酶链反应 (PCR)技术 ,对 15 1名NIDDM患者及 10 0名正常对照者的ACE基因插入 /缺失 (I/D)型多态性进行检测。结果　NIDDM患者DD型的发生频率明显高于正常人 (P <0 0 1) ;NIDDM伴糖尿病肾病者DD型发生频率明显高于无糖尿病肾病者 (P <0 0 5 ) ;NIDDM伴糖尿病眼底病变者DD型发生频率明显高于无糖尿病眼底病变者 (P <0 0 5 )。     

血管紧张素Ⅱ1型受体基因多态性与高血压左室重构的相关性研究

目的 :探讨血管紧张素Ⅱ 1型受体 (AT1R)基因A116 6C多态性与原发性高血压 (EH)及其左室重构的关系。方法 :测定 10 4例EH患者和 15 4例健康对照者的血压 ,身高 ,体重 ,空腹血糖、总胆固醇、甘油三酯浓度 ;测定EH患者的左室重量指数 (LVMI)并记录病程 ;多聚酶链式反应 限制性酶切法 (PCR RFLP)鉴定AT1R基因 116 6位点基因型。结果 :EH组AT1R基因AC/CC基因型频率高于对照组 (0 .2 0 2∶0 .0 97,P <0 .0 5 ) ,116 6C等位基因频率高于对照组 (0 .115∶0 .0 5 2 ,P <0 .0 1) ;用协方差分析排除病程、收缩压、总胆固醇等混杂因素的作用后发现 ,EH组中AC/CC基因型患者LVMI高于AA基因型者 (12 7.37∶115 .98,P <0 .0 5 )。结论 :AT1R基因 116 6位点AC/CC基因型及C等位基因与EH及其左室重构有关。