Long-term effects of benidipine hydrochloride on severe left ventricular hypertrophy and collagen metabolism in patients with essential hypertension

OBJECTIVES: The long-term effects of benidipine on left ventricular hypertrophy (LVH) and collagen metabolism were examined in patients with essential hypertension. METHODS: Forty patients with untreated essential hypertension were given benidipine at a dose of 6 mg a day. Routine echocardiographic parameters, serum concentrations of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed before and 12 months after treatment with benidipine. Patients were classified according to left ventricular mass index (LVMI) into three groups: severe LVH (LVMI > or = 159), mild LVH (159 > LVMI > or = 125) and no LVH (LVMI < 125). RESULTS: Serum levels of free TIMP-1 to MMP-1 ratio were significantly higher in patients with severe LVH than in the other two groups before treatment. There was a significant positive correlation between the free TIMP-1 to MMP-1 ratio and LVMI in all study subjects (r = 0.51, p < 0.01). Twelve months after treatment, percentage changes of the LVMI and free TIMP-1 to MMP-1 ratio were significantly larger in the patients with severe LVH (-27% and -54%) than with mild LVH (-12% and -23%) or no LVH (-4% and -11%), respectively. Changes in the systolic blood pressure but not changes in the free TIMP-1 to MMP-1 ratio correlated with changes in the LVMI in patients with mild LVH (r = 0.78, p < 0.01). Changes in the free TIMP-1 to MMP-1 ratio but not changes in the systolic blood pressure correlated with changes in the LVMI in patients with severe LVH (r = 0.69, p < 0.01). CONCLUSIONS: Long-term administration of benidipine reduced left ventricular mass and normalized systemic collagen type I degradation abnormalities in essential hypertensive patients with severe but not mild LVH.     

Metabolism of collagen is altered in hypertensives with increased intima media thickness

BACKGROUND: Increased intima media thickness (IMT) of common carotid arteries (CCAs) and left ventricular mass index (LVMI) are independent risk factors for vascular events and may be related to accumulation of extracellular proteins due to altered metabolism of collagen. METHODS: IMT and LVMI were measured ultrasonographically in 50 males with newly diagnosed, untreated, essential hypertension (HTN, 37.7 +/- 13.1 years), and 14 controls (C, 32.6 +/- 9.7 years). Serum levels of procollagen type I carboxy-terminal propeptide (PICP), procollagen type III amino-terminal propeptide (PIIINP), carboxy-terminal telopeptide (ICTP), matrix metalloproteinase (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were determined using immunoassays. RESULTS: IMT was significantly higher in HTN than in C (0.6 +/- 0.1 vs 0.4 +/- 0.1 mm, p < 0.001) as well as LVMI (119.5 +/- 39.9 vs 106.8+/-18.7 g/m2, p = 0.04) and serum TIMP-1 (in HNT 691.7 +/- 124.6 ng/ml; in C 577.5+/-70.8 ng/ml, p < 0.001). Other parameters did not differ between these groups. The sum of PICP and ICTP was higher in HTN (165.0 +/- 46.9 microg/l), than in C (147.1 +/- 26.0 microg/l, p = 0.03). TIMP-1 correlated with IMT (r = 0.33, p = 0.02) in hypertensives. CONCLUSIONS: We suggest that the collagenase-anticollagenase system is abnormal in essential hypertension and contributes to cardiovascular remodeling. Increased IMT may be related to the accumulation of extracellular proteins due to altered metabolism of collagen.     

Elevated serum markers for collagen synthesis in patients with hypertrophic cardiomyopathy and diastolic dysfunction

Summary Objectives The hypothesis of impaired collagenolysis in patients with hypertrophic cardiomyopathy (HCM) was tested by measuring serum markers of type-I collagen metabolism. These markers were correlated with echocardiographic parameters of diastolic function. Background HCM is a common disease in the adult population with a wide range of clinical manifestations. Left ventricular hypertrophy and increased intramyocardial collagen content are known to cause diastolic dysfunction in patients with HCM. Methods In 26 patients with HCM and 38 control subjects (aged: 57±3 and 54±2 years, p=n.s.) serum levels of collagenolytic matrixmetalloproteinase-1 (MMP-1) and its inhibitor TIMP-1, the markers for collagen type-I synthesis (PICP) and degradation (ICTP) were determined by ELISA and RIA. Diastolic function were determined by Doppler echocardiography. Results Free TIMP-1 was elevated in HCM compared to controls (216,78±9,89 vs 183.77±7.57 ng/ml ; p=0.006) as well as PICP (165.92±10.26 vs 114.57±6.38 g/l; p<0.001). Free MMP-1 was significantly lower in HCM (1.13±0.20 vs 2.33±0.34; p=0.01). ICTP did not differ. The MMP-1/TIMP-1 ratio was significantly lower in HCM (0.006±0.001 vs 0.012±0.001, p=0.003). PICP correlated positively with diastolic E/A ratio (r=0.389; p=0.05) and septal thickness (r=0.484; p=0.01). Conclusions Serum marker of collagen synthesis (PICP) is increased in patients with HCM. Increased marker for inhibition of collagenolysis (TIMP-1) and a disturbed balance of collagen synthesis and degradation (ratio) with a predominance of inhibition of collagenolysis indicates collagen accumulation (fibrosis), which explains passive diastolic dysfunction in patients with HCM.     

Treatment with spironolactone for 24 weeks decreases the level of matrix metalloproteinases and improves cardiac function in patients with chronic heart failure of ischemic etiology

BACKGROUND:

The myocardial extracellular matrix is believed to be central to the remodelling that takes place following myocardial infarction. The contribution of markers of collagen metabolism to this process remains less well understood. The present study examined the contribution of some of the markers of collagen metabolism in cardiac remodelling, as well as the effect of spironolactone on the remodelling process.

OBJECTIVES:

To investigate the pathological contribution of markers of collagen metabolism, including matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), type I collagen carboxyterminal telopeptide (ICTP) and procollagen type I carboxyterminal propeptide (PICP), in cardiac remodelling following ischemic cardiomyopathy, and to examine the pharmacoregulatory effects of spironolactone on collagen metabolism.

METHOD:

Eighty-six consecutive patients (62 men and 24 women) with chronic heart failure of ischemic etiology (patient group) and 25 age-matched controls were enrolled in the study. The subjects in the patient group were randomly assigned into a spironolactone or nonspironolactone group. Plasma levels of MMP-9, TIMP-1, ICTP and PICP were measured using ELISA and radioimmunoassay techniques. Furthermore, left ventricular diastolic diameter and ejection fraction were assessed using two-dimensional and Doppler echocardiography.

RESULTS:

The plasma concentrations of MMP-9, TIMP-1 and the MMP-9 to TIMP-1 ratio, as well as ICTP, were significantly increased in the patient group. The PICP to ICTP ratio in the patient group was significantly lower than that in the age-matched control subjects. After a follow-up period of 24 weeks, the PICP to ICTP ratio increased, and MMP-9, TIMP-1 and the MMP-9 to TIMP-1 ratio decreased in the spironolactone subgroup.

CONCLUSIONS:

Biomarkers of collagen degradation were elevated and correlated with depressed heart function; spironolactone may partially reverse the dysregulation in collagen metabolism.     

替米沙坦对压力超负荷左心室肥厚大鼠心肌Ⅰ型胶原代谢的影响

目的:探讨压力超负荷左心室肥厚大鼠Ⅰ型胶原代谢特点及替米沙坦的干预效果。方法:24只雄性SpargueDawley大鼠随机分为假手术组(n=8)、左心室肥厚组(n=8)和替米沙坦组(n=8)。行腹主动脉缩窄术建立高血压左心室肥厚大鼠模型。各组干预4周后处死大鼠,称其体质量及左心室质量,计算左心室质量指数(LVMI)。将左心室心肌行Masson染剂染色,观察并测量其胶原容积分数(CVF)。用ELISA法检测3组大鼠血清Ⅰ型前胶原羧基端肽(PICP)及Ⅰ型胶原羧基端交联肽(ICTP)的浓度,并计算PICP/ICTP的比值,直线相关分析PICP及PICP/ICTP比值与CVF的相关性。结果:与假手术组相比,左心室肥厚组左心室质量、LVMI、CVF、血清PICP及PICP/ICTP的比值均显著升高(均P0.05);与左心室肥厚组相比,替米沙坦组左心室质量、LVMI、CVF、血清PICP、PICP/ICTP的比值均显著降低(均P0.05)。3组间的ICTP相比较,差异无统计学意义;PICP及PICP/ICTP比值均与CVF呈正相关(r值分别为0.830、0.842,均P0.01)。结论:压力超负荷左心室肥厚大鼠Ⅰ型胶原合成增加、降解相对不足,合成与降解的不平衡是造成其左心室心肌间质纤维化的原因之一。替米沙坦可以抑制Ⅰ型胶原的合成,纠正其合成与降解不平衡,从而有效地抑制及逆转心肌间质纤维化。     

Elevated serum markers of collagen degradation in patients with mild to moderate dilated cardiomyopathy

BACKGROUND AND AIMS: Left ventricular (LV) dilation and myocardial remodelling are hallmarks of heart failure in idiopathic dilated cardiomyopathy (DCM). Interstitial collagen is essential for LV integrity and function while degradation of collagen by collagenases, especially matrix-metalloproteinases (MMPs), are suggested to contribute to ventricular dilation. In the present study, serological markers of collagen metabolism were investigated. METHODS AND RESULTS: Serum levels of MMP-1 and its inhibitor (TIMP-1), the markers for collagen degradation type I (collagen carboxyterminal telopeptide (ICTP)) and synthesis (carboxyterminal propeptide of type I procollagen (PICP)) were quantified by ELISA and RIA of 43 patients with DCM and 47 age-matched control subjects. Free MMP-1 serum concentration was significantly increased in the DCM group (5.29+/-0.83 vs. 2.22+/-0.29 ng/ml; P=0.01) as well as the free TIMP-1 concentration (206.54+/-12.65 vs. 181.44+/-8.55 ng/ml; P=0.05). The free MMP-1/TIMP-1-ratio was higher in DCM than in the control group (0.030+/-0.005 vs. 0.012+/-0.001; P=0.01). ICTP was significantly increased (7.60+/-1.21 vs. 3.44+/-0.19 microg/l; P<0.001). PICP was not significantly increased (125.29+/-8.93 microg/l vs. 113.11+/-5.47 microg/l; P=n.s.). Free MMP-1 and MMP-1/TIMP-1-ratio correlated with LV end diastolic diameter [cm/m(2) body surface area (BSA)] (r=0.28; P=0.03 and r=0.34; P=0.01, respectively) as well as with cardiac index (CI) (r=-0.32; P=0.04 and r=-0.33; P=0.04, respectively) in patients with DCM. CONCLUSION: Serum markers of collagen degradation are elevated and might be valuable markers for progression of LV dilation in patients with DCM.     

Associations of serum salusin-alpha levels with atherosclerosis and left ventricular diastolic dysfunction in essential hypertension

Serum salusin-alpha, is decreased in essential hypertension and acute coronary syndrome. The study is aimed to explore whether serum salusin-alpha is associated with atherosclerosis and left ventricular (LV) diastolic dysfunction in essential hypertension. Echocardiography, carotid ultrasonography, brachial-ankle pulse wave velocity (BaPWV) and serum salusin-alpha levels were determined in 60 hypertensive patients (29 with and 31 without carotid plaque) and 30 normotensive controls. Hypertensive patients with plaque, compared with those without plaque or the controls, had the lowest values of salusin-alpha. Then the hypertensive patients were divided into left ventricular hypertrophy (LVH) and non-LVH groups according to the echocardiography. Similarly, hypertensive patients with LVH showed the lowest serum salusin-alpha levels. In all subjects, serum salusin-alpha levels were negatively correlated with carotid mean-intima-media thickness (IMT), BaPWV, left ventricle mass index (LVMI) and E/E' (r=-0.488, P<0.001; r=-0.381, P<0.001; r=-0.294, P=0.006; r=-0.303, P=0.005; respectively). Serum salusin-alpha levels were independent predictors of BaPWV, carotid strain, carotid distensibility, mean-IMT, LVMI and E'/A' (β=-0.399, 0.283, 0.237, -0.346, -0.306, 0.469; P=0.002, 0.031, 0.016, 0.005, 0.012 and 0.001, respectively) in multiple linear regression models. These results suggest that serum salusin-alpha may be associated with atherosclerosis and LV diastolic dysfunction in essential hypertension.     

替米沙坦对压力超负荷左心室肥厚大鼠心肌I型胶原代谢的影响

目的：探讨压力超负荷左心室肥厚大鼠I型胶原代谢特点及替米沙坦的干预效果。方法：24只雄性Spargue—Dawley大鼠随机分为假手术组（n=8）、左心室肥厚组（n=8）和替米沙坦组（n=8）。行腹主动脉缩窄术建立高血压左心室肥厚大鼠模型。各组干预4周后处死大鼠,称其体质量及左心室质量,计算左心室质量指数（LVMI）。将左心室心肌行Masson染剂染色,观察并测量其胶原容积分数（CVr）。用ELISA法检测3组大鼠血清I型前胶原羧基端肽（PICP）及I型胶原羧基端交联肽（ICTP）的浓度,并计算PICP／ICTP的比值,直线相关分析PICP及PICP／IC—TP比值与CVF的相关性。结果：与假手术组相比,左心室肥厚组左心室质量、LVMI、CVF、血清PICP及PICP／ICTP的比值均显著升高（均P〈0．05）;与左心室肥厚组相比,替米沙坦组左心室质量、LVMI、CVF、血清PICP、PICP／ICTP的比值均显著降低（均P〈0．05）。3组问的ICTP相比较,差异无统计学意义;PICP及PICP／ICTP比值均与CVF呈正相关（r值分别为0．830、0．842,均P〈0．01）。结论：压力超负荷左心室肥厚大鼠I型胶原合成增加、降解相对不足,合成与降解的不平衡是造成其左心室心肌间质纤维化的原因之一。替米沙坦可以抑制I型胶原的合成,纠正其合成与降解不平衡,从而有效地抑制及逆转心肌间质纤维化。     

Relation between plasma brain natriuretic peptide, serum indexes of collagen type I turnover, and left ventricular remodeling after reperfused acute myocardial infarction

The aim of the study is to investigate the relation between plasma brain natriuretic peptide (BNP), collagen type I turnover, and left ventricular (LV) remodeling after primary angioplasty. Echo-Doppler, BNP, carboxy-terminal telopeptide of procollagen type I (ICTP), C-terminal propeptide of procollagen type I (PICP), and their ratio PICP/ICTP (as an index of coupling between the synthesis and degradation of collagen type I) were evaluated at days 1 and 3 and months 1 and 6 after primary angioplasty in 56 consecutive patients with a first large acute myocardial infarction (AMI). During the 6 months after AMI, a direct relation was shown between BNP and ICTP (day 1, r = 0.54, p = 0.000; day 3, r = 0.64, p = 0.000; month 1, r = 0.64, p = 0.000; month 6, r = 0.41, p = 0.005) and BNP and PICP/ICTP (day 1, r = -0.54, p = 0.003; day 3, r = -0.58, p = 0.000; month 1, r = -0.50, p = 0.000; month 6, r = -0.30, p = 0.043), but not between BNP and PICP. Using analysis of covariance, relations between BNP and ICTP and PICP/ICTP were independent from infarct size. Patients with LV remodeling had significantly higher plasma ICTP and BNP levels and lower PICP/ICTP than patients without LV remodeling. Day-1 ICTP independently predicted 6-month remodeling (exp beta = 2.14, 95% confidence interval 1,120 to 3,550, p = 0.01). In conclusion, a relation exists between plasma BNP collagen type I turnover and LV remodeling after reperfused AMI.     

高血压患者动态脉搏波速度与左室肥厚和左心功能的关系

目的 探讨高血压患者动态脉搏波速度（pulse wave velocity, PWV）与左心室重构和左室舒张功能的关系。方法 本研究回顾性收集在2011年5月-2013年1月期间,于卫生部北京医院门诊或住院的≥18岁的原发性高血压患者,采用Mobil-O-Graph PWA无创动态血压监测仪测量动态血压和动态PWV。同期进行超声心动图检查,评估左心室结构和功能。采用Pearson相关分析,比较动态PWV和左室结构功能参数之间的相关性。采用二元Logistics回归分析,分析动态PWV、年龄、性别、体重指数、糖尿病、吸烟、血脂异常和是否服用降压药物对左室肥厚（LVH）的影响。结果 总共有136患者纳入此研究。平均年龄55.4±14.1岁,72.1%为男性。动态PWV平均值为8.10±1.97ms-1,动态PWV与左心室质量指数（LVMI）（r=0.257,p=0.003）和左心房前后径（r=0.431,p<0.001）呈显著正相关,与E/A比值呈显著负相关（r=-0.337,p<0.001）。二元logistic回归分析显示,高血压患者动态PWV是LVH的独立危险因素。结论：高血压患者中,动态PWV与LVMI相关,可能是LVH的独立危险因素。     

基质金属蛋白酶与老年高血压患者左心室肥厚的相关性

目的通过测定老年高血压患者血清基质金属蛋白酶1(MMP-1)、MMP-9、基质金属蛋白酶抑制剂1(TIMP-1)水平与左心室后壁厚度(LVPWT)、左心室质量指数(LVMI),探讨基质金属蛋白酶在老年人高血压心室重构中的作用。方法 60岁以上老年高血压患者89例,根据有无左心室肥厚分为两组,高血压合并左心室肥厚32例,高血压无左心室肥厚57例,另52名健康老年人设为对照组超声心动图测LVPWT及LVMI。酶联免疫吸附法(ELISA)测定血清MMP-1、TIMP-1水平。结果健康对照组、高血压无左心室肥厚组、高血压合并左心室肥厚组LVPWT、LVMI、TIMP-1和MMP-9水平逐渐升高(均为P<0.05),而血清MMP-1水平逐渐降低(均为P<0.05)。LVMI、LVPWT与血清MMP-9、TIMP-1水平呈正相关(均为P<0.05),与MMP-1水平呈负相关(均为P<0.05)。结论 MMP-9水平与左心室质量、左心室壁厚度呈正相关,而MMP-1水平与之呈负相关。细胞外基质重构可能与老年高血压有关。     

Alterations in the pattern of collagen deposition may contribute to the deterioration of systolic function in hypertensive patients with heart failure.

OBJECTIVES: We sought to assess the distribution of collagen deposits and collagen degradation in hypertensive patients with either systolic heart failure (SHF) or diastolic heart failure (DHF). BACKGROUND: Increased collagen synthesis and deposition have been described in the myocardium of heart failure (HF) hypertensive patients. METHODS: We studied 39 HF hypertensive patients subdivided into two groups: 16 with SHF and 23 with DHF. Endomyocardial biopsies were performed to quantify mysial (i.e., perimysial plus endomysial) and perivascular and scar-related collagen volume fraction (CVF). Matrix metalloproteinase (MMP)-1 and its tissue inhibitor matrix metalloproteinase (TIMP)-1 were analyzed in cardiac samples by Western blot and immunohistochemistry, and in blood samples by enzyme-linked immunosorbent assay. RESULTS: Mysial CVF was lower in SHF hypertensive patients than in normotensive (p < 0.05) and DHF hypertensive patients (p < 0.01). Perivascular and scar-related CVF was higher (p < 0.05) in the two groups of hypertensive patients than in normotensive subjects, and in SHF hypertensive compared with DHF hypertensive patients. The MMP-1:TIMP-1 ratio was increased (p < 0.05) in tissue and serum samples from the SHF hypertensive group compared with the other two groups of subjects. The MMP-1 expression was increased (p < 0.01) in the interstitium and cardiomyocytes of SHF hypertensive patients compared with DHF hypertensive and normotensive subjects. The serum MMP-1:TIMP-1 ratio was inversely correlated with ejection fraction (r = -0.510, p < 0.001) and directly correlated with left ventricular end-diastolic diameter (r = 0.549, p < 0.001) in all subjects. CONCLUSIONS: These findings show that the pattern of collagen deposits and the balance of the MMP-1/TIMP-1 system are different in the myocardium of SHF and DHF hypertensive patients. It is proposed that excessive degradation of mysial collagen may be related to the compromise of systolic function in HF hypertensive patients.     

Enhanced radial late systolic pressure augmentation in hypertensive patients with left ventricular hypertrophy

BACKGROUND: Wave reflection augments central blood pressure (BP) in late systole, thus increasing cardiac afterload. We examined the relationship between late systolic pressure augmentation in the peripheral radial artery pulse wave and the existence of left ventricular hypertrophy (LVH) in hypertension. METHODS: Brachial BP, radial augmentation index (AI(r)), and carotid-femoral pulse wave velocity (PWV(cf)) were determined in 77 untreated hypertensive patients aged 56 +/- 10 years. Cardiac structure and function were assessed by ultrasound, and LVH was defined based on the LV mass index (LVMI). Using multivariate analysis, patient characteristics were compared between those with (+) and without (-) LVH. RESULTS: The LVMI was correlated independently and positively with AI(r) (beta = 0.33, P = .004) and the brachial mean arterial pressure (MAP; beta = 0.25, P = .03). The ratio of early to atrial peak velocities (E/A ratio) of the diastolic transmitral flow tended to be correlated negatively with the AI(r). The LVH (+) group had a significantly higher AI(r) than the LVH (-) group [LVH (+), 97% v LVH (-), 89%, P = .003]; this difference remained significant even after adjustment for age, gender, MAP, and heart rate. The adjusted relative risk of LVH was 1.99 for each 10% AI(r) increase (P = .005). In contrast, LVMI was not correlated with the PWV(cf), and the PWV(cf) was not different between the LVH (+) and LVH (-) groups. Moreover, there was no significant correlation between PWV(cf) and AI(r). CONCLUSIONS: These results suggest that the peripheral AI(r) measurement is clinically useful in predicting LVH. Enhanced wave reflection may be related to the development of LVH in hypertensive patients.     

TIMP-1: a marker of left ventricular diastolic dysfunction and fibrosis in hypertension

This study was designed to document noninvasively the pathological mechanisms responsible for myocardial fibrosis and to assess the clinical utility of plasma markers of collagen synthesis and degradation as screening tools for the assessment of fibrosis in hypertension. We studied 100 never-treated hypertensive patients and 50 normal subjects. Echocardiographic assessment was made of left ventricular (LV) mass and diastolic filling using measurement of E:A ratio, E wave deceleration time (E dec), and isovolumic relaxation time (IVRT). The presence of diastolic dysfunction was taken as a surrogate marker for the presence of myocardial fibrosis. Plasma carboxy-terminal propeptide of collagen type I (PICP), carboxy-terminal telopeptide of collagen type I (CITP), and tissue inhibitor of matrix metalloproteinases type I (TIMP-1) were measured as markers of collagen synthesis, degradation, and inhibition of degradation, respectively. Plasma TIMP-1 was significantly elevated in the hypertensive cohort (358 ng/mL versus 253 ng/mL, P<0.001) as were CITP (5.2 microg/L versus 2.9 microg/L, P<0.001), and PICP (200 microg/L versus 166 microg/L, P<0.05). TIMP-1 was significantly elevated in patients with diastolic dysfunction (421 ng/mL versus 283 ng/mL P<0.01) and correlated with markers of diastolic filling, namely E:A ratio (r=0.26, P<0.05) and E Dec (r=0.41, P<0.01). A plasma TIMP-1 level of >500 ng/mL had a specificity of 97% and a positive predictive value of 96% in predicting diastolic dysfunction. In patients with untreated hypertension, there is evidence of increased collagen synthesis, degradation, and inhibition of degradation resulting in fibrosis. Our results demonstrate that plasma TIMP-1 correlates with markers of LV diastolic filling, is predictive of LV dysfunction, and is a potential noninvasive marker of fibrosis.     

Impact of systolic time intervals on the relationship between arterial stiffness and left ventricular hypertrophy

ObjectivesArterial stiffness is correlated with left ventricular hypertrophy (LVH) and is susceptible to left ventricular performance. Therefore, if left ventricular systolic function is unknown, the relationship between arterial stiffness and LVH is controversial. This study was to assess the impact of the ratio of brachial pre-ejection period (bPEP) to brachial ejection time (bET), a marker of left ventricular systolic function, on the relationship between brachial-ankle pulse wave velocity (baPWV) and LVH.MethodsA total of 1146 patients were included in the study. The baPWV and bPEP/bET were measured using an ABI-form device. Patients were classified into four groups. Groups 1, 2, 3, and 4 were patients with bPEP/bET ≤ 0.38 and baPWV below the median, bPEP/bET > 0.38 but baPWV below the median, bPET/bET ≤ 0.38 but baPWV above the median, and bPET/bET > 0.38 and baPWV above the median, respectively.ResultsPatients in groups 3 and 4 (high baPWV) and patients in group 2 (low baPWV but high bPEP/bET) were associated with increased left ventricular mass index (LVMI) and LVH (all P < 0.001). In a multivariate model, baPWV was significantly associated with LVMI (P = 0.007) and LVH (P = 0.025). Further adjustment for bPEP/bET made the association between baPWV and LVMI (P = 0.150) and LVH (P = 0.173) disappear.ConclusionsThe bPEP/bET has an important impact on the relationship between baPWV and LVH. Therefore, the value of bPEP/bET obtained from the same examination should be considered while interpreting the relationship between baPWV and LVH.     

高血压左室肥厚及心功能与血浆脑钠肽浓度变化的关系探讨

目的 探讨高血压患者左室肥厚及左室舒张功能与血浆脑钠肽（BNP）浓度的关系.方法 高血压患者62例,其中伴左心室肥厚组患者32例,不伴左心室肥厚组患者30例;健康对照组30名.高血压患者给予厄贝沙坦片75～150 mg/d,治疗6个月.所有对象行超声心动图测定左心室重量指数（LVMI）、E/A（二尖瓣舒张期E峰/A峰）比值.采用美国博适Triage及其试剂盒快速测定血浆BNP水平,对BNP与LVMI、E/A比值作相关分析.结果 高血压左心室肥厚患者组的血浆BNP水平（ng/L）明显高于高血压不伴左心室肥厚患者组和健康对照组（54.8±16.9比36.7±15.4,P＜0.05;54.8±16.9比16.4±12.7,P＜0.05）.经厄贝沙坦治疗后,高血压左心室肥厚患者组血浆BNP水平（ng/L）明显下降（54.8±16.9比36.8±12.6,P＜0.05）,E/A比值明显上升（0.86±0.57比1.09±0.65,P＜0.05）,差异有统计学意义,且与LVMI呈显著正相关 （r＝0.57,P＝0.028）,与E/A比值呈显著负相关（r＝-0.68,P＝0.009）.结论 血浆BNP浓度能较好地反映高血压患者左心室肥厚及左室舒张功能状态.     

冠心病患者脉搏波传导速度与心功能的相关性

目的研究冠心病患者脉搏波传导速度(PWV)与心功能的相关性。方法选取经冠状动脉造影确诊为冠心病者366例,收集一般临床资料,测定肱踝PWV(baPWV),行超声心动图检查等,同时在入选患者中选取44例行多普勒组织成像。结果冠心病患者baPWV与室间隔厚度(r=0.306,P<0.001)、左心室后壁厚度(r=0.365,P<0.001)、左心室质量分数(r=0.293,P<0.001)和E/Ea(r=0.458,P<0.01)呈显著正相关,与射血分数(r=-0.210,P<0.001)、Ea(r=-0.428,P<0.01)、Ea/Aa(r=-0.331,P<0.05)呈显著负相关。在除外高血压等的影响后,偏相关分析显示,baPWV与室间隔厚度(r=0.231,P<0.001)、左心室后壁厚度(r=0.320,P<0.001)、左心室质量分数(r=0.233,P<0.001)、射血分数(r=-0.182,P<0.001)、Ea(r=-0.429,P<0.01)、Ea/Aa(r=-0.339,P<0.05)、E/Ea(r=0.437,P<0.01)仍显著相关。冠心病患者不同心功能分级组间的baPWV差异有统计学意义(P<0.05),baPWV随临床心功能恶化而升高。结论 baPWV与冠心病患者左心室肥厚、左心室收缩和舒张功能、临床心功能均具有相关性,baPWV可以作为评估冠心病患者心功能的一个指标。     

Plasma tissue inhibitor of metalloproteinases-1 and transforming growth factor beta 1--possible non-invasive biomarkers of hepatic fibrosis in patients with chronic B and C hepatitis

BACKGROUND/AIMS: The role of transforming growth factor-beta 1 (TGF-beta 1) in liver fibrosis is in part related to impairment of extracellular matrix breakdown by stimulation of tissue inhibitor of metalloproteinases-1 (TIMP-1) gene. The aim of the study was to evaluate association between TGF-beta 1 and TIMP-1 in relation to liver injury in chronic viral hepatitis B and C. METHODOLOGY: Association between plasma TGF-beta 1 and TIMP-1 was evaluated in 28 consecutive patients undergoing liver biopsy for chronic viral hepatitis B and C (CH-B, CH-C) and these tests were correlated with hepatic fibrosis, inflammation and liver function tests. Moreover carboxyterminal cross-linked telopeptide of type 1 procollagen (ICTP) and carboxyterminal propeptide of type 1 collagen (PICP) were also measured for assessment of extracellular matrix breakdown or synthesis, respectively. RESULTS: Chronic viral hepatitis B and C resulted in a significant increase in plasma TIMP-1 levels but not TGF-beta 1. Among biochemical markers of liver injury, significant correlation with TGF-beta 1 and TIMP-1 was demonstrated in respect to aminotransferase activities in both groups. TIMP-1 showed significant correlation with ICTP levels in both CH-B (r = 0.59) and CH-C (r = 0.62), whereas TGF-beta 1 was correlated with ICTP only in CH-C patients (r = 0.75). PICP did not demonstrate any correlation with either TGF-beta 1 or TIMP-1. Hepatic fibrosis, but not inflammation, correlated significantly with TGF-beta 1 (CH-B: r = 0.73; CH-C: r = 0.79) and TIMP-1 (CH-B: r = 0.66; CH-C: r = 0.71) in both groups and there was a significant correlation between TIMP-1 and TGF-beta 1 in the CH-B group (r = 0.83) and CH-C group (r = 79). CONCLUSIONS: These results support the role of TIMP-1 in a TGF-beta 1-dependent mechanism for liver fibrosis and suggest their plasma levels can be used as a possible early non-invasive marker of liver fibrosis useful for chronic hepatitis management.     

不同年龄段高血压病患者二尖瓣血流E/A比值与左心房及左心室重构的相关性

目的 分析不同年龄段高血压病患者二尖瓣血流E/A比值与左心房及左心室重构的相关性。方法 高血压病患者1 082（男549,女533）例,根据E/A>1和E/A<1分为两组,又将两组分别按年龄分为青年组、中年组、老年组,测量左心房内径指数（LADi）、左心室质量指数（LVMI）、收缩压（SBP）、舒张压（DBP）及脉压。结果 ①E/A>1组和E/A<1组 LADi随着年龄的增大而增大。E/A>1组LVMI随着年龄的增大而增大,E/A<1组LVMI随着年龄的增大而降低。②青年组中E/A比值与LVMI呈负相关（r=-0.377）,老年组中E/A比值与LADi呈正相关（r=0.243）。结论 伴随年龄的增大E/A比值的改变在青年组与心室重构密切相关,在老年组与心房重构密切相关。     

Collagen type-I degradation is related to arterial stiffness in hypertensive and normotensive subjects

Although arterial stiffness is an independent cardiovascular risk factor associated with both aging and hypertension, relatively little is known regarding the structural changes in the vessel wall that occur with vessel stiffening. We determined if collagen type-I metabolism is related to arterial stiffening in both hypertensive and normotensive subjects. Arterial stiffness was assessed by aortic pulse wave velocity (PWV) and augmentation index (AIx) in 46 subjects (48.7 +/- 2 years, 32 hypertensives) and related to circulating markers of collagen type-I turnover. Collagen synthesis was assessed by the measurement of carboxy-terminal peptide of procollagen type-I (PIP) and collagen degradation by the measurement of carboxy-terminal telopeptide of collagen type-I (ICTP), by quantitative immunoassay. Matrix metalloproteinase-1 (MMP-1) and the tissue inhibitor of metalloproteinase-1 (TIMP-1) were also quantified by immunoassay. The ratio of collagen type-I synthesis to degradation was negatively correlated with both PWV (P<0.05) and AIx (P<0.05), whereas plasma MMP-1 levels displayed a positive correlation with both PWV (P<0.01) and AIx (P<0.01), after adjustment for age and mean arterial pressure. The relationship between collagen type-I turnover and arterial stiffness was similar in both the normotensive and hypertensive subjects. Although circulating markers of collagen synthesis were increased in the hypertensive subjects, this was not related to arterial stiffness. Collagen type-I degradation is increased in relation to collagen type-I synthesis in subjects with stiffer arteries. Matrix metalloproteinase-1, the enzyme responsible for collagen type-I degradation, is positively related to both large elastic and muscular artery stiffness in normotensive and hypertensive subjects.