冠心病患者可溶性细胞粘附分子的检测及其临床意义

目的 :检测冠心病 (CHD)患者可溶性细胞间粘附分子 1(sICAM 1)及P 选择素的变化 ,探讨其在CHD发病机制中的意义。方法 :用ELISA法和酶法分别检测 6 8例CHD患者和 5 5例对照者的血清sICAM 1、P 选择素、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和甘油三酯 (TG)、总胆固醇水平 ,Gensini积分法评价冠状动脉病变程度 ,进行统计学分析。结果 :CHD患者血清sICAM 1和P 选择素水平均较对照组高 ,且差异有非常显著性意义 (均P <0 .0 0 1) ;sICAM 1水平与冠状动脉病变程度显著相关 (r =0 .6 6 2 ,P <0 .0 0 1) ;TG与sICAM 1水平呈正相关 (r =0 .4 0 3,P <0 .0 1) ;P 选择素与冠状动脉病变程度无明显关系。结论 :sICAM 1及P 选择素可能参与了CHD的发病过程 ,血清sICAM 1的检测有助于临床病情分析 ,TG是影响sICAM 1水平的因素之一。     

血脂康对冠心病粘附分子表达的影响

目的 探讨动脉粥样硬化(AS)时血脂异常对单核细胞(MC)粘附分子表达及调脂干预对其产生的影响.方法 选择冠心病不稳定性心绞痛(UA)患者30例,并经血脂康调脂治疗3个月后随访,同时选取正常对照者30例,检测研究对象的TC、LDL-c、MC表面CD11a、CD11b和CD18阳性细胞百分率,观察其变化以及测定冠心病患者血脂康调脂治疗前后血清P-选择素、ICAM-1、Ox-LDL的水平,分析之间的相关性.结果 不稳定性心绞痛患者血清Ox-LDL水平明显增高,与血清P-选择素水平呈显著正相关关系;LDL与CD11a、CD18相关显著.经血脂康调脂治疗后,患者在血清TC、LDL-c水平下降的同时,血清P-选择素、ICAM-1、Ox-LDL水平也显著降低,提示通过血脂康调脂干预治疗,能够阻止不稳定性心绞痛患者冠状动脉粥样病变的炎症反应,改善血管内皮细胞功能,延缓冠状动脉粥样病变的进展.结论 血脂康抑制Ox-LDL诱导的粘附分子表达是其独立于调脂之外的另一抗AS作用.     

Circulating endothelial cell/leucocyte adhesion molecules in ischaemic heart disease

Increased levels of the endothelial markers soluble E-selectin ( P  = 0.011), soluble thrombomodulin ( P  = 0.0001) and von Willebrand factor (VWF, P  < 0.0001) were found in 116 patients with ischaemic heart disease compared to an equal number of age- and sex-matched asymptomatic controls. In a multivariate analysis of the markers versus the major risk factors for atherosclerosis, VWF correlated with total cholesterol ( P  = 0.002) and E-selectin with sex (lower in women, P  = 0.004) and triglycerides ( P  = 0.007). The data point to profound differences in the release mechanisms of these three endothelial cell products and suggests that further studies into the roles of these molecules in coronary artery disease are warranted.     

Prognostic markers in young patients with premature coronary heart disease

ObjectivesTo evaluate the survival and prognostic implications of cardiovascular, inflammatory and prothrombotic risk factors in young patients with premature coronary heart disease (CHD).MethodsFollow-up data were obtained from 353 young patients with a first cardiac event (men ≤45 years and women ≤55 years). Baseline characteristics on traditional risk factors were collected at the time of the first event, and plasma levels of C-reactive protein (CRP), von Willebrand Factor (VWF), and fibrinogen were measured one to three months after the first event to exclude an acute phase response. We performed age and sex adjusted Cox regression analyses to assess the relationship between these factors and recurrent events with three different endpoints: all cause mortality, recurrent cardiac event (myocardial infarction or revascularisation procedure), and any recurrent event (cardiac event, cerebrovascular event or all cause mortality).ResultsDuring a total follow-up time of 1483 person years (mean 4.2 years), 11 patients died (3%), 42 patients had a recurrent cardiac event (12%), and 53 patients had any recurrent event (15%). CRP was associated with an increased risk of any recurrent event (HR 1.28[95% CI = 1.02–1.59] per unit increase in lnCRP). Also, both CRP (5.00[1.04–24.04]) and fibrinogen (5.04[1.05–24.23]) were associated with all cause mortality when levels were above the 50th percentile.ConclusionsFifteen percent of young patients with a first cardiac event have a recurrent event or die within a median follow-up of 4.2 years. In these young patients we have shown that, independently of cardiovascular risk factors, high CRP levels contribute to the risk of recurrent events, including all cause mortality, and high fibrinogen levels are associated with all cause mortality.     

螺内酯对冠心病患者内皮细胞功能的影响

目的　本实验旨在探讨螺内酯对冠心病患者内皮细胞功能的影响。方法　选择 5 0例冠心病患者作为实验组 ,5 0例健康者作为对照组 ,给药前先测定实验组和对照组的内皮素 (ET)、血栓素 A2 (TXA2 )、一氧化氮 (NO)、前列环素 (PGI2 ) ,再予以实验组螺内酯 2 0 m g/ d,3个月后再测定实验组的 ET、TXA2 、NO、PGI2 并进行比较。结果　给药前实验组的 ET、TXA2 水平较对照组高 ,NO、PGI2 水平较对照组低 ;给药后 NO、PGI2 水平较给药前高 ,ET、TXA2 较给药前低。结论　螺内酯可以有效地改善血管内皮细胞功能 ,对逆转冠心病患者内皮细胞功能紊乱起着重要的作用。     

早发冠心病患者脂蛋白脂酶基因多态性与血脂关系研究

目的:探讨早发冠心病(CHD)患者脂蛋白脂酶(LPL)基因多态性特征及其与血脂关系。方法:收集106例早发CHD患者(早发CHD组)血脂参数等资料,应用聚合酶链反应-限制性片段长度多态性方法,分析LPL的P、H基因型及其等位基因频率分布(HindⅢ和PVUⅡ酶切),并与81例非CHD者(对照组)进行比较。结果:早发CHD组血清胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)水平较对照组明显升高(P<0.05),高密度脂蛋白胆固醇(HDL-C)水平较对照组降低(P<0.05)。早发CHD组P+,H+等位基因频率高于对照组(P<0.05)。H+H+基因型TC、TG明显高于H+H-基因型,HDL-D低于H+H-基因型;P+P+基因型TG明显高于P-P-基因型,HDL-C低于P-P-基因型(均P<0.05)。结论:早发CHD患者血清TC、TG和LDL-C高于对照组,HDL-C低于对照组;P+,H+等位基因频率高于对照组。H+H+和P+P+基因型影响血脂水平。     

Social burden and lifestyle in adults with congenital heart disease

We aimed to evaluate how the presence and severity of congenital heart disease (CHD) influence social life and lifestyle in adult patients. A random sample (n = 1,496) from the CONgenital CORvitia (n = 11,047), the Dutch national registry of adult patients with CHD, completed a questionnaire on educational attainment, employment and marital statuses, and lifestyle (response 76%). The Utrecht Health Project provided a large reference group (n = 6,810) of unaffected subjects. Logistic regression models were used for subgroup analyses and to adjust for age, gender, and socioeconomic status where appropriate. Of all patients 51.5% were men (median age 39 years, interquartile range 29 to 51) with mild (46%), moderate (44%), and severe (10%) CHD. Young (<40-year-old) patients with CHD were more likely to have achieved a lower education (adjusted odds ratios [ORs] 1.6 for men and 1.9 for women, p <0.05 for the 2 comparisons), significantly more often unemployed (adjusted ORs 5.9 and 2.0 for men and women, respectively), and less likely to be in a relationship compared to the reference group (adjusted ORs 8.5 for men and 4.5 for women). These poorer outcomes were seen in all severity groups. Overall, the CHD population smoked less (adjusted OR 0.5, p <0.05), had more sports participation (adjusted OR 1.2, p <0.05), and had less obesity (adjusted OR 0.7, p <0.05) than the reference group. In conclusion, there was a substantial social disadvantage in adult patients with CHD, which was seen in all severity groups and primarily in young men. In contrast, adults with CHD had healthier lifestyles compared to the reference group.     

Sedentary lifestyle and antecedents of cardiovascular disease in young adults

BACKGROUND: The aim of this study was to determine whether sedentary young individuals are characterized by reductions in determinants of vascular health and insulin sensitivity relative to their physically active, age-matched peers. METHODS: A total of 135 otherwise healthy young men (n = 68) and women (n = 67) <40 years of age (28 +/- 5 years) were studied in this investigation and stratified into three groups based on physical activity status: 1) sedentary (n = 73); 2) physically active (n = 24); and 3) endurance-trained (n = 38). Arterial compliance and flow-mediated dilation were determined by diastolic pulse contour wave analysis and echocardiographic imaging of the brachial artery respectively. Insulin sensitivity was estimated from the homeostasis model for insulin resistance and the 13C-glucose breath test. RESULTS: Both conduit (16.4 +/- 0.5 v 19.5 +/- 0.7 mL/mmHg x 10; P < .01) and resistant (8.5 +/- 0.3 v 10.7 +/- 0.5 mL/mmHg x 100; P < .01) artery compliance were significantly lower in sedentary subjects than in physically active or endurance-trained subjects, whereas flow-mediated dilation was not different between the groups. The HOMA(IR) was 2.5-fold higher in the sedentary group than in the endurance-trained group (P < .05). CONCLUSIONS: Sedentary individuals are characterized by reductions in both arterial compliance and insulin sensitivity relative to their endurance-trained peers, independent of changes in conventional risk factors for cardiovascular disease. These findings lend further support for the need for regular physical activity in the prevention of cardiovascular disease in individuals of all ages.     

Effect of posture on heart rate variability spectral measures in children and young adults with heart disease

BACKGROUND: Reduction of heart rate variability as a consequence of heart disease and postural change has been well documented. However, the data on the effect of postural change in pediatric patients are incomplete and the effect is not fully understood. The aim of the study was to investigate effect of postural change on heart rate variability in relation to the extent of severity of heart disease. METHODS: The dependence of heart rate variability on posture in 41 children and young adults (8-20 years) with heart disease has been investigated and compared with control. Short-term electrocardiograms (ECGs) were assessed in supine rest and active standing, and spectral measures of heart rate variability were determined. RESULTS: Two types of response to the change of supine to standing posture were determined in both healthy and diseased subjects. In majority of subjects, the increased heart rate induced by standing was accompanied by a decrease in high-frequency power. However, in about 30% of all subjects, increased heart rate during standing was accompanied by an increased high-frequency power. Independently of posture and disease, high-frequency and low-frequency power were positively correlated. In subjects characterized by a reduction of heart rate variability in standing, the high-frequency power in both postures is reduced in diseased subjects compared to control. CONCLUSIONS: These results demonstrate that in this age range, the response to posture is not unique because of the difference in high-frequency power, which implies a variety of vagal modulations of heart rate.     

Serum lipids and coronary heart disease in heterozygous familial hypercholesterolemia in the Hokuriku District of Japan

The serum cholesterol and triglyceride levels and the incidence of ischemic heart disease were studied in 122 (55 men and 67 women) consecutive heterozygous familial hypercholesterolemic patients in the Hokuriku district of Japan. (1) The mean +/-SD of serum cholesterol level was 354.0 +/- 71.0 mg/100 ml, which was lower than those of the Western countries by about 60--70 mg/100 ml. (2) The mean +/-SD of serum triglyceride level was 116.5 +/- 54.0 mg/100 ml. (3) The average serum cholesterol values in the 20--50-year-old group showed no differences from those of the Western countries. However, in the above 50 years of age group the serum cholesterol levels were much lower than those in the United States. (4) The occurrence of ischemic heart disease in 83 heterozygous familial hypercholesterolemic patients was 43.3%. The incidence of myocardial infarction was 20.5%. Thus, familial hypercholesterolemia is as highly atherogenic as that of the Western countries even in Japan where the low incidence of coronary heart disease in the general population has been attributed to the low level of serum cholesterol.     

Diet and lifestyle influences on risk of coronary heart disease

Coronary heart disease (CHD) stems from the interplay between genetic and environmental factors. However, modifiable environmental factors, especially diet and lifestyle, are largely responsible for increased risk of CHD at population levels. Although cigarette smoking, obesity, and physical inactivity are well-established causes of CHD, the role of specific dietary factors has not been clearly defined until more recently. Cumulative evidence indicates that types of fats and carbohydrates are more important than total amounts in determining risk of CHD. Epidemiologic and clinical trial data strongly support that dietary patterns rich in fruits, vegetables, whole grains, and nuts can reduce risk of CHD. Diet and lifestyle modification, combined with pharmacologic treatment of hypertension and high lipid levels (if necessary), could prevent the vast majority of CHD events.     

Markers of low-grade inflammation and soluble cell adhesion molecules in Chinese patients with coronary artery disease

BACKGROUND: Inflammation plays an important role in atherosclerosis. Markers of low-grade chronic inflammation, such as C-reactive protein (CRP) and soluble cell adhesion molecules (sCAMs), have been associated with coronary artery disease (CAD). OBJECTIVE: To evaluate the significance of inflammatory markers as novel risk factors for CAD in the Chinese population. METHODS: High-sensitivity CRP (hs-CRP); sCAMs, including vascular cell adhesion molecule-1 (sVCAM-1), intercellular cell adhesion molecule-1 (sICAM-1), P-selectin (sP-selectin) and E-selectin (sE-selectin); and white blood cell (WBC) count were measured in 170 angiographically defined CAD patients (70% or greater stenosis affecting at least one vessel) and 177 healthy control subjects in the Chinese population in Singapore. RESULTS: The levels of hs-CRP, sVCAM-1 and sP-selectin, and the WBC count were higher in CAD patients than in control subjects (P<0.001, P<0.05, P<0.05 and P<0.001, respectively). There were no significant differences in the levels of sICAM-1 and sE-selectin between the two groups. Patients with unstable angina or myocardial infarction had higher levels of hs-CRP, and higher WBC and monocyte counts than those with stable angina or atypical chest pain (all P<0.05). The level of sP-selectin in patients with multivessel disease was higher than in those with single-vessel disease (P<0.05). Overall, the levels of hs-CRP and sCAMs showed a significant correlation with the lipid profile and the WBC count. CONCLUSIONS: The present study suggests that inflammatory markers, including hs-CRP and WBC count, together with sP-selectin and sVCAM-1, could serve as markers of atherogenesis in Chinese patients with CAD, with potential diagnostic and therapeutic implications.     

Circulating adhesion molecules in patients with stable coronary artery disease

To evaluate platelet and endothelial function in patients with stable coronary artery disease (CAD), we investigated levels of the plasma-soluble (s) adhesion molecules E-selectin (sE-selectin), P-selectin (sP-selectin), and intercellular adhesion molecule-1 (sICAM-1) in 74 patients (mean age, 53 +/- 8 years) with angiographically documented coronary artery disease. Levels were compared to 27 matched healthy control subjects. Patients were excluded if they had recent cardiovascular events or any illness that might influence platelet and endothelial cell function. Concentrations of sP-selectin were significantly higher in patients with stable CAD (276 +/- 61 ng/mL) compared with control subjects (188 +/- 32 ng/mL) (P = .0001), whereas sE-selectin and sICAM-1 levels were similar between the 2 groups. Pooling both groups showed that sICAM-1 correlated weakly with triglycerides (r = 0.240, P = .01) and sP-selectin correlated weakly with low-density lipoprotein cholesterol (r = 0.204, P = .04). Although plasma sICAM-1 concentrations were significantly increased in hypercholesterolemic patients compared with those of normocholesterolemic patients (P = .04), sP-selectin and sE-selectin levels were similar between the 2 groups. In conclusion, significantly increased sP-selectin levels, indicating platelet activation, were found in patients with stable CAD. No other sign of endothelial cell activation in these patients could be detected. Moreover, sP-selectin levels seem to reflect the activation of platelets rather than of endothelial cells.     

Evaluation of serum levels of solubilized adhesion molecules and cytokine receptors in coronary heart disease

OBJECTIVES

The diagnostic importance of circulating solubilized tumor necrosis factor-alpha receptor II (sTNF-RII) and interleukin-2 receptor in coronary heart disease (CHD) was evaluated. In addition, these variables were correlated with solubilized adhesion molecule levels (i.e., intracellular adhesion molecule [ICAM], vascular cell adhesion molecule [VCAM], and E-selectin).

BACKGROUND

Atherosclerosis is considered to be a chronic inflammatory process. Because the immunologic network presents an abundance of positive and negative feedback mechanisms, information obtained from different immunologic variables might be highly redundant.

METHODS

In a cross-sectional study design, 60 patients with angiographically proven CHD were compared with 60 individuals who had undergone coronary angiography but in whom no evidence of stenosis could be found (control subjects). Angiography was performed at least one year before the study. Cytokine levels were determined by enzyme-linked immunosorbent assay technique and evaluated by univariate and multivariate statistical methods.

RESULTS

All immunologic variables except E-selectin (p = 0.08) significantly discriminated between patients and control subjects. Coronary artery bypass graft surgery after angiography did not lead to significant differences in the variables investigated in the patients with bypass surgery as compared with the subjects without bypass surgery. Receiver-operating characteristics analysis showed comparable test accuracy for solubilized adhesion molecules and cytokine receptors. Multivariate logistic regression analysis, including age, revealed that only ICAM and sTNF-RII were independently correlated with the presence of CHD. Patients belonging to the third tertile of at least one of these two variables demonstrated a 1.6- to 2-fold increased relative risk for the presence of CHD.

CONCLUSIONS

We concluded that both circulating ICAM and TNF-RII should be further evaluated as markers for atherosclerotic changes in the coronary system.     

Expression of endothelial cell adhesion molecules in neovascularized tissue

OBJECTIVE: Recent studies indicate that endothelial cells of newly formed blood vessels are activated and exhibit a distinct phenotype that may influence the responses of these microvessels to an inflammatory stimulus. The objective of this study was to compare the basal and cytokine-stimulated expression of endothelial cell adhesion molecules in neovascularized tissue to normal (nonproliferating) vascular beds. METHODS: The expression of P- and E-selectin. VCAM-1, ICAM-1, ICAM-2, and PECAM-1 was measured, using the dual radiolabeled mAb technique, in subcutaneously implanted (for 10-15 days) polyurethane sponges, skin, heart, lung, and intestine of male C57BL/6 mlice (background). RESULTS: Basal values of PECAM-1 and ICAM-2 revealed a low vascular density in the implanted sponge matrices that is comparable to skin. When normalized for vascular surface area (PECAM-1 or ICAM-1 expression), the basal level of E- and P-selectin expression was highest in neovascularized sponge and skin. TNF-alpha elicited an increased expression of all endothelial CAMs, except PECAM-1 and ICAM-2, but the responses were blunted in sponge and skin, relative to other vascular beds. CONCLUSIONS: These findings indicate that endothelial cells in newly formed blood vessels exhibit a pattern of basal and cytokine-induced expression of certain adhesion glycoproteins that is similar to nonproliferating cutaneous vessels.