Plasma nitric oxide level and its role in slow coronary flow phenomenon

Previous studies have suggested that microvascular abnormalities and endothelial dysfunction cause slow coronary flow (SCF). The objective of this study was to assess the plasma nitric oxide (NO) level and determine its role in the pathogenesis of SCF phenomenon. Thirty-six patients with SCF (group 1) and otherwise patent coronary arteries and 34 subjects with normal coronary flow (group 2) were included in the study. Coronary flow was quantified according to the TIMI Frame Count (TFC) method. Brachial artery endothelium-dependent flow-mediated dilatation (FMD) and nitroglycerin (NTG)-induced endothelium-independent dilatation were studied in both groups. In addition, plasma NO levels were measured and their contribution to FMD was determined. The sex, age, body mass index, arterial blood pressure, and heart rate distributions were similar in both groups. TFC was significantly higher in group 1 compared to group 2 for each artery. The plasma NO level was lower in patients with SCF than in control subjects (18.4 +/- 4.4 versus 25.2 +/- 6.3 micromol/L P = 0.001). FMD was significantly smaller in group 1 than in group 2 (4.0 +/- 3.2% versus 10.6 +/- 5.8%, P = 0.0001). The percent NTG-induced dilatation was similar in the two groups (16.8 +/- 1.1% versus 17.1 +/- 1.1%, P = 0.42). In group 1, the plasma NO level was correlated with percent of FMD. Also, the plasma NO level was inversely correlated with TFC for each artery. Reduced NO bioactivity as well as impaired FMD support the presence of endothelial damage in the pathogenesis of SCF phenomenon.     

老年阻塞性睡眠呼吸暂停低通气综合征患者血管内皮舒张功能的变化

目的 评价老年阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者血管内皮舒张功能的变化.方法 老年中重度OSAHS患者30例及对照组28例,分别测定血浆一氧化氮(NO)含量;用高分辨率超声检测基础状态、反应性充血时(内皮依赖性血管扩张)及含服硝酸甘油后(非内皮依赖性血管扩张)的肱动脉内径,计算不同状态下肱动脉的扩张率以评估血管内皮功能.老年中重度OSAHS患者经过4周经鼻持续气道内正压通气(nCPAP)治疗后重复多导睡眠监测、血浆NO含量和血管内皮功能测定.结果 老年中重度OSAHS组的血浆NO含量[(50.35±8.65)gmol/Li较对照组[(57.31±9.31)μmol/Li降低(t=2.95,P=0.005),接受4周的nCPAP治疗后血浆NO含量[(55.77±8.87)μmol/Li有明显升高(t=2.40,P=0.02).老年中重度OSAHS组反应性充血时肱动脉内径扩张率[(9.78±4.82)%较对照组[(13.21±5.81)%]明显减低(t=2.45,P=0.017);而对照组和老年中重度OSAHS组由硝酸甘油介导的血管扩张率分别为(16.87±6.15)%和(14.74±5.82)%(t=1.36,P=0.18).老年中重度OSAHS组接受4周nCPAP治疗后反应性充血时肱动脉内径扩张率为(14.33±6.13)%,较治疗前明显改善(t=3.20,P=0.002),而硝酸甘油介导的血管扩张率为(15.15±4.21)%,较治疗前无明显变化(t=0.31,P=0.76).结论 老年中重度OSAHS组患者存在血管内皮功能异常,nCPAP治疗能有效修复这些损害,其机制可能与纠正间断缺氧有关.     

Impaired endothelial function in hypertensive elderly patients evaluated by high resolution ultrasonography.

BACKGROUND: Multiple investigations both in experimental models and in middle-aged patients with essential hypertension have demonstrated impaired endothelium-dependent vasodilation. OBJECTIVE: To determine whether hypertension exerts an additional negative effect on endothelial function of large arteries in hypertensive elderly patients who may already be affected by endothelial dysfunction due to aging. PATIENTS AND METHODS: Thirteen elderly patients with hypertension (69 9 years of age [mean SD]) were compared with 13 matched healthy elderly subjects (72 6 years of age). High resolution vascular ultrasound was used to measure brachial artery responses to reactive hyperemia (with increased flow causing endothelium-dependent dilation) and to sublingual nitroglycerine (causing endothelium-independent dilation). RESULTS: Flow-mediated diameter (FMD) was significantly impaired in the hypertensive elderly group (6.7 3.3% versus 13.3 3.8% in the control group, P<0.05). No significant difference could be found in nitroglycerine-induced dilation between the elderly control group (12.1 4.9%) and the hypertensive elderly (10.2 6.8%). On simple linear analysis, FMD was inversely correlated with age (r=-0.60, P=0. 03) in the healthy elderly group. FMD in the hypertensive elderly was inversely related to age (r=-0.41, P=0.04) and mean blood pressure (r=-0.67, P=0.01). CONCLUSIONS: This study showed decreased FMD with aging even in the healthy elderly, with a further decline in hypertensive elderly compared with healthy elderly subjects. This impairment of FMD in the hypertensive elderly group was related to age and mean blood pressure, indicating that aging and hypertension may impair endothelial function in the brachial artery of elderly patients with hypertension.     

Arterial elasticity identified by pulse wave analysis and its relation to endothelial function in patients with coronary artery disease

Patients with coronary artery disease (CAD) have impaired endothelial function. Arterial elasticity is modulated by endothelial function. The association between arterial elasticity and endothelial function has not been reported in patients with CAD. The present study was designed to investigate whether endothelial dysfunction contributes to impaired arterial elasticity. Thirty patients with CAD and 30 control subjects were recruited. Large and small artery elasticity indices were non-invasively assessed using pulse wave analysis. Brachial artery endothelium-dependent and -independent function were assessed by vascular response to flow-mediated vasodilation (FMD) and sublingual nitroglyceride (NTG), respectively. C1 large artery elasticity index was not different in the CAD group compared with the control group. However, C2 small artery elasticity index was significantly reduced in the CAD group compared with the control group. Flow-mediated vasodilation (FMD) was also impaired in the CAD group compared with the control group. Flow-mediated vasodilation (FMD) in the brachial artery correlated with C2 small arterial elasticity index. But NTG-mediated brachial artery vasodilation was similar between the two groups. The present findings suggest that the patients with CAD have reduced C2 small arterial elasticity index and impaired FMD. Endothelial dysfunction is involved in diminished arterial elasticity, suggesting that C2 small arterial elasticity index is a novel surrogate measure for the clinical evaluation of endothelial function.     

Vascular reactivity is impaired in genetic females taking high-dose androgens

Objective. To assess the vascular effects of high-dose androgen treatment in genetic females.Background. Male gender is an independent risk factor for coronary artery disease, suggesting either a protective effect of estrogens and/or a deleterious effect of androgens. We have recently demonstrated that androgen deprivation is associated with enhanced vascular reactivity in adult men, however, the effects of androgen excess on vascular function in humans has not been reported previously.Methods. We studied vascular reactivity in two groups of genetic females: 12 female-to-male transsexuals receiving long-term high-dose androgens, and 12 healthy female control subjects, matched for age and smoking history. Using external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (leading to flow-mediated dilatation [FMD], which depends on normal endothelial function) and after sublingual nitroglycerin (NTG), an endothelium-independent dilator.Results. Testosterone levels were higher (15.2 ± 8.7 vs. 1.9 ± 1.3 mmol/L, p < 0.001) and high-density lipoprotein cholesterol levels were lower (1.2 ± 0.2 vs. 1.6 ± 0.4 mmol/L, p = 0.02) in the transsexuals compared with the control subjects. In each group, nine of 12 subjects were current or ex-smokers, leading to impaired FMD in both groups (5.1 ± 3.7% in the transsexuals vs. 6.9 ± 4.1% in controls, p = 0.28). The NTG response was significantly decreased in the transsexuals (15.9 ± 4.9% vs. 22 ± 5.8% in controls, p = 0.01), independent of the effects of age, cholesterol or vessel size.Conclusions. Long-term treatment with high-dose androgens is associated with impaired vascular reactivity in genetic females, consistent with a deleterious effect of androgen excess on arterial physiology.     

Flow mediated dilatation and carotid intimal media thickness in South Indian type 2 diabetic subjects

OBJECTIVE: The aims of this study were to determine: (1). endothelial function in type 2 diabetic subjects with and without diabetic microvascular complications using flow mediated dilatation method (FMD); (2). influence of other variables on FMD; and (3). the correlation between FMD and carotid intimal media thickness (IMT). RESEARCH, DESIGN AND METHODS: In this cross-sectional study, flow mediated dilatation (FMD) and intimal media thickness (IMT) were determined using high resolution ultrasonography in 20 non-diabetic subjects, in 23 type 2 diabetic subjects without any complications and in 23 type 2 diabetic patients with nephropathy and retinopathy. RESULTS: Age-adjusted mean (S.D.) FMD value in diabetic subjects (8.9 +/- 5%) was lower (P < 0.0001) when compared with the group of control subjects (18.8 +/- 7.5 %. However, there was no difference in the age-adjusted FMD values between diabetic subjects with and without complications (7.3 +/- 3.3 % versus 10.5 +/- 5.9 %). FMD levels did not vary significantly between sexes in both non-diabetic and diabetic groups. FMD correlated negatively with carotid IMT (r = -0.23, P < 0.05). In multiple linear regression analysis, age adjusted FMD was associated only with type 2 diabetes with complications (P = 0.012). The variance explained was 21.9%. CONCLUSION: Abnormal FMD and increased carotid IMT were present in type 2 diabetes. Both these parameters negatively correlated with each other supporting an association between impaired FMD and atherogenesis. As these abnormalities existed even in diabetic subjects with no microvascular complications, it is likely that they preceded the development of these complications.     

Impaired endothelium-dependent forearm vasodilation in idiopathic dilated cardiomyopathy is related to severe left ventricular dysfunction and elevated serum tumor necrosis factor levels

INTRODUCTION AND OBJECTIVES: Endothelial dysfunction has been found in patients with idiopathic dilated cardiomyopathy (IDC), but its mechanism remains unknown. Our aim was to investigate whether forearm endothelium-dependent vasoreactivity correlates with cardiac disease severity or neurohormonal activation. PATIENTS AND METHOD: We studied 23 patients with IDC and 10 healthy sex- and age-matched controls using brachial artery ultrasound to assess flow-mediated dilation (FMD) and nitroglycerin-induced vasodilation (NIV). In the IDC group, we determined plasma neurohormone and cytokine levels at the same time. RESULTS: FMD was significantly less in the IDC group compared with the control group [--0.06 (2.8)% vs 4.4 (4.6)%, respectively; P<.01], whereas NIV was similar in both groups [15.0 (6.4)% vs 14.0 (7.4)%, respectively; P=NS]. FMD was significantly less in patients with poorer left ventricular (LV) function and more severe LV dilatation, and in those with a higher tumor necrosis factor-alpha (TNF-alpha) level. NIV was similar in all patient subgroups. There was a significant inverse correlation between the TNF-alpha plasma level and FMD (r=-0.75; P<.01). No correlation was found between the plasma levels of other neurohormones and FMD. CONCLUSIONS: FMD, but not NIV, was impaired in patients with IDC compared with control subjects. In patients, there were significant associations between FMD impairment and the severity of LV dilatation, the severity of LV systolic dysfunction, and the plasma TNF-alpha level. The strongest correlation was observed between TNF-alpha plasma level and FMD. These data suggest that TNF-alpha may be implicated in endothelial dysfunction in patients with IDC.     

Circulating adhesion molecules and carotid artery structural changes in patients with noninsulin-dependent diabetes mellitus

Hypertension and non insulin-dependent diabetes mellitus (NIDDM) are well-known risk factors for atherosclerotic disease. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) may exert a relevant role in the pathogenesis of atherosclerosis; their prognostic relevance has been recently demonstrated. The aim of the study was to investigate possible inter-relation between circulating adhesion molecule levels, carotid artery structure and endothelial function in 15 patients with NIDDM, as well as in 15 patients with both NIDDM and essential hypertension (NIDDM+EH) compared with 15 normal subjects (NS) and 15 euglycaemic patients with EH, matched for age, sex and body weight. All subjects were submitted to a biopsy of the gluteal subcutaneous fat. Small arteries were dissected and mounted on a micromyograph, and the media-to-lumen (M/L) ratio was then calculated. Carotid artery structure was investigated by Doppler ultrasound. Endothelial function was evaluated by investigation of the flow-mediated dilatation (FMD) of the brachial artery. ICAM-1 and VCAM-1 plasma levels were measured by ELISA. ICAM-1 and VCAM-1 plasma levels were significantly greater and FMD smaller in EH, NIDDM and NIDDM+EH than in NS, but no difference was observed among the three pathological groups. Carotid artery structural changes were more pronounced in NIDDM+EH. No significant difference was observed among NIDDM, EH and NS. The M/L ratio of subcutaneous small resistance arteries was significantly greater in NIDDM+EH than in NIDDM or EH. NS had a smaller M/L ratio than the other groups. Significant correlations were observed between ICAM-1 plasma levels and indices of carotid artery structure in diabetic patients. However, the relations were close only in NIDDM+EH. In conclusion, our data suggest that NIDDM+EH may present more pronounced vascular structural alterations than NIDDM, and that adhesion molecules plasma levels are closely inter-related with carotid artery structural alterations, at least in NIDDM+EH, but not with M/L ratio of small resistance arteries.     

Effects of cyclooxygenase inhibition on endothelial function in hypertensive patients treated with angiotensin-converting enzyme inhibitors

BACKGROUND: Cyclooxygenase inhibition restores endothelium-dependent vasodilatation in hypertension, but it is unknown whether it restores endothelial function in hypertensive patients treated with angiotensin-converting enzyme (ACE) inhibitors. HYPOTHESIS: The purpose of the present study was to evaluate the effects of cyclooxygenase inhibition on endothelial function in hypertensive patients treated with ACE inhibitors. METHODS: Endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent glyceryl trinitrate-induced dilatation were investigated in 10 patients treated with enalapril (ACE group), 11 patients treated with manidipine and metoprolol (non-ACE group), and 12 normotensive control subjects. After administration of 1000 mg of aspirin, FMD was investigated once again. Plasma cyclic guanosine monophosphate (cGMP) and eicosanoids were also measured during reactive hyperemia before and after aspirin administration. RESULTS: Flow-mediated dilatation was more impaired in the non-ACE group than in the ACE group (8.3 +/- 3.8%, 5.7 +/- 1.7%, respectively, p<0.04). Glyceryl trinitrate-induced dilatation was similar in the ACE group, the non-ACE group, and in the control subjects. In the ACE group, FMD was reduced after administration of aspirin (5.3 +/- 4.2%, p<0.05). The percent change in FMD after administration of aspirin correlated significantly with percent change in cGMP (r=0.77, p<0.03; y-intercept, -62.1%, p<0.01). After aspirin administration, levels of thromboxane B2 and 6-keto-prostaglandin(1alpha) were significantly decreased compared with those before aspirin administration in all groups. CONCLUSIONS: Cyclooxygenase inhibition may reduce the beneficial effect on endothelium-dependent vasodilatation induced by ACE inhibitors. The results suggested that prostacyclin in addition to nitric oxide plays a significant role in the restoration of endothelial function in hypertensive patients treated with ACE inhibitors.     

Vitamin C preserves endothelial function in patients with coronary heart disease after a high-fat meal

BACKGROUND: It has been suggested that an oxidative mechanism is involved with the impaired endothelium-dependent vasodilatation that occurs after a high-fat meal. Hypothesis: The study was undertaken to evaluate the effect of a single oral dose of vitamin C (2 g) on postprandially impaired endothelium-dependent vasodilatation in patients with coronary heart disease (CHD). METHODS: This study included 74 patients with CHD and 50 subjects without CHD with risk factors. The two groups were divided into two subgroups that did or did not receive 2 g of vitamin C (CHD/VitC and CHD/control, n = 37; non-CHD/VitC and non-CHD/control, n = 25) after a high-fat meal (800 calories, 50 g fat). Serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in the fasting state and at 2, 4, 5, and 7 h after the high-fat meal were measured. Endothelial function was assessed in the brachial artery by high-resolution ultrasound at baseline and at 4 h postprandially. RESULTS: The postprandial serum triglyceride concentration increased significantly at 2-5 h after the high-fat meal in all groups. The fasting flow-mediated dilatation (FMD) (p < 0.02) and nitroglycerin-induced dilatation (NID) (p < 0.05) of patients with CHD were impaired compared with those of non-CHD subjects. Postprandial FMD was significantly aggravated in the non-CHD/control group (p < 0.01) and the CHD/control group (p < 0.001), but the postprandial FMD in patients and subjects taking vitamin C showed no significant change, although the CHD/VitC group had a mild tendency toward improvement (p = 0.064) and non-CHD/VitC group had a mild tendency toward aggravation (p = 0.852). The change of NID after a high-fat meal did not reach statistical significance in the four groups. The decrement of postprandial FMD correlated positively with the increment of 2-h serum triglyceride concentration in the patients without vitamin C (n = 62, r = 0.545, p < 0.001). CONCLUSIONS: The postprandial state after a high-fat meal is critical in atherogenesis, as it induces endothelial dysfunction through an oxidative stress mechanism. Vitamin C treatment has a promising benefit for patients with CHD.     

Impact of acute caffeine ingestion on endothelial function in subjects with and without coronary artery disease

Although coffee is a widely used, pharmacologically active beverage, its impact on the cardiovascular system is controversial. To explore the effect of acute caffeine ingestion on brachial artery flow-mediated dilation (FMD) in subjects without coronary artery disease (CAD; controls) and patients with CAD, we prospectively assessed brachial artery FMD in 40 controls and 40 age- and gender-matched patients with documented stable CAD on 2 separate mornings 1 week to 2 weeks apart. After overnight fasting, discontinuation of all medications for ≥12 hours, and absence of caffeine for >48 hours, participants received capsules with caffeine 200 mg or placebo. One hour after drug ingestion, participants underwent brachial artery FMD and nitroglycerin-mediated dilation (NTG) using high-resolution ultrasound. As expected, patients with CAD were more often diabetic, hypertensive, obese, dyslipidemic, and smoked more than controls (p <0.01 for all comparisons). Aspirin, Clopidogrel, angiotensin-converting enzyme inhibitors, β blockers, and statins were significantly more common in patients with CAD than in controls (p <0.01 for all comparisons). At baseline, FMD, but not NTG, was significantly lower in patients with CAD compared to controls. Acute caffeine ingestion significantly increased FMD (patients with CAD 5.6 ± 5.0% vs 14.6 ± 5.0%, controls 8.4 ± 2.9% vs 18.6 ± 6.8%, p <0.001 for all comparisons) but not NTG (patients with CAD 13.0 ± 5.2% vs 13.8 ± 6.1%, controls 12.9 ± 3.9% vs 13.9 ± 5.8%, p = NS for all comparisons) and significantly decreased high-sensitivity C-reactive protein (patients with CAD 2.6 ± 1.4 vs 1.4 ± 1.2 mg/L, controls 3.4 ± 3.0 vs 1.2 ± 1.0 mg/L, p <0.001 for all comparisons) in the 2 groups compared to placebo. In conclusion, acute caffeine ingestion significantly improved endothelial function assessed by brachial artery FMD in subjects with and without CAD and was associated with lower plasma markers of inflammation.     

Contribution of plasma lipid disturbances to vascular endothelial function in patients with slow coronary flow

Previous studies have suggested that microcirculatory abnormalities cause slow coronary flow (SCF). However, the underlying mechanism of this phenomenon has not yet been well documented. Therefore, the aim of this study was to determine the role of plasma lipid disturbances in pathogenesis of slow coronary flow (SCF). Forty patients with SCF (group I) and 37 subjects with normal coronary arteries (group II) were included in the study. In each subject plasma lipid concentrations (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglyceride [TG]) and brachial artery flow-mediated dilatation (FMD) and nitroglycerin (NTG)-induced dilatation were measured. Total cholesterol level was found to be similar in the 2 groups. In group I, HDL-C level was lower than in group II (34 +/-3 vs 40 +/-4 mg/dL, p=0.0001). In group I, TG level was higher than in group II (213 +/-29 vs 198 +/-24 mg/dL p=0.002). In group I, FMD was smaller than that of group II (3.48 +/-3.1% vs 10.4 +/-5.6%, p=0.0001). The percent NTG-induced dilatation was not different between the groups (15.5 +/-5.3% vs 17.3 +/-6.9%, p=0.27). On regression analysis; there was a significant relationship between percent of FMD and HDL-C (r =0.65, p=0.0001). When the 2 groups were analyzed separately, HDL-C was still related to percent of FMD in both groups (r =0.47 p=0.002 and r =0.45 p=0.005, respectively). Multivariate regression analysis showed that only plasma HDL-C was independently related to FMD (F=7.5 p=0.0001). In patients with SCF, reduced flow-mediated dilatation was detected and was found to be associated with plasma lipid disturbances, principally low HDL and high TG levels.     

Impaired vascular reactivity in African-American patients with type 2 diabetes mellitus and microalbuminuria or proteinuria despite angiotensin-converting enzyme inhibitor therapy

BACKGROUND: Microalbuminuria, an early indicator of diabetic nephropathy that reflects other vascular abnormalities, usually improves or resolves with angiotensin-converting enzyme inhibitor (ACEI) therapy. Persistent microalbuminuria despite ACEI therapy may be associated with poor prognosis for cardiovascular disease and mortality. African-Americans are reported to respond less well to ACEI and are at increased risk of disease progression. METHODS AND RESULTS: We compared flow-mediated dilatation (FMD) and nitroglycerine-dependent dilatation (NDD) in African-American diabetic subjects with persistent microalbuminuria (n = 35) despite ACEI therapy and those in whom microalbuminuria had resolved (n = 15). The two groups were not statistically different in terms of blood pressure, age, sex, lipids, and hemoglobin A1c. FMD was reduced in the microalbuminuria group, compared with subjects without microalbuminuria (4.2 vs. 11.4%; P < 0.0001). Similarly, NDD was reduced in the microalbuminuria group, compared with subjects without microalbuminuria (10.8 vs.16.6%; P = 0.011). The FMD in African-American patients with persistent microalbuminuria was also significantly lower than in clinically similar Caucasian patients whose microalbuminuria had persisted despite ACEI therapy (4.2 vs. 7.5%; P = 0.03). On multiple regression analysis, persistent microalbuminuria is the only predictor of abnormal endothelial function in these patients. CONCLUSIONS: Our study clearly demonstrates that African-American type 2 diabetic subjects with persistent microalbuminuria have severely impaired FMD and NDD, compared with matched patients who had microalbuminuria that was eliminated by ACEI. This may explain the poor prognosis for cardiovascular disease in patients who have persistent microalbuminuria. Alternative strategies for reducing microalbuminuria in high-risk patients who do not respond adequately to ACEI therapy such as African-Americans are needed.     

Endothelial dysfunction predictor of structural changes of arterial wall in type I diabetes.

AIM: We examined whether alteration in vascular endothelial function exists in non-insulin dependent diabetes mellitus (NIDDM) and whether impaired endothelium-dependent responses in those patients are associated with increased intima-media thickness (IMT), the time sequence of their appearance and the role of individual risk factors in development of structural deterioration of arterial wall. METHODS: Ultrasound technique was used to measure brachial artery flow mediated dilation (FMD) response and carotid IMT in 38 young adults with type I diabetes aged 22-34 years and 35 healthy controls aged 22-36 years. RESULTS: Patients had significantly lower FMD than controls (4.15/2.8/ vs 11.3/3.6/, P<0.0001) and was in all diabetic patients below the mean value of controls. Further, carotid intima-media was in insulin dependent diabetes mellitus (IDDM) patients significantly thicker than in healthy subjects (0.65/0.04 vs 0.56/0.04, P=0.0001) and was related to body mass and body mass index, to the age of patients, the duration of diabetes and several risk variables. In a multivariate model FMD was most significantly and independently associated to IMT. However, significant thickening of intima-media was observed only in patients with progressed deterioration of FMD and it appeared in those subjects with long-lasting disease. IMT was also influenced by urinary albumin excretion and low-density lipoprotein (LDL) cholesterol concentration. CONCLUSIONS: Endothelium dependent FMD response is impaired in IDDM and is associated with increased carotid artery IMT. Significant thickening of intima-media appears in patients with advanced deterioration of FMD that is related to the duration of the disease. These data suggest that advanced endothelial dysfunction in IDDM may predispose to development of morphologic atherosclerotic lesions of arterial wall.     

老年糖代谢紊乱患者血管内皮功能与血小板膜糖蛋白的研究

目的检测2型糖尿病(T2DM)、糖耐量异常(IGT)、空腹血糖受损(IFG)患者肱动脉内皮功能的变化与血小板活化程度的关系。方法分别选取老年T2DM(T2DM组)、IGT(IGT组)、IFG(IFG组)患者和健康体检者(对照组)各20例,空腹静脉血测定空腹血糖(FPG)、TG、TC、HDL-C、LDL-C、糖化血红蛋白(HbA1c)、血小板膜糖蛋白CD61和CD62P。采用高分辨率血管外彩色超声测定肱动脉血流介导的血管扩张功能(FMD)和含服硝酸甘油后肱动脉内径变化(NTG)。结果 T2DM组、IGT组、IFG组FMD较对照组明显下降,而T2DM组NTG较IGT组、IFG组、对照组明显下降(P0.05)。多因素线性相关分析,FMD与FPG、TG、TC、LDL-C呈负相关。T2DM组、IGT组、IFG组CD61和CD62P较对照组明显升高(P0.05)。CD61与FPG、TC、HbA1c、LDL-C呈正相关,与HDL-C呈负相关;CD62P与FPG、TG、TC、HbA1c、LDL-C呈正相关,与HDL-C呈负相关。FMD与CD61、CD62P呈负相关。结论内皮功能损害和血小板活化在T2DM前期就已经存在,两者互相促进。     

Lipoprotein analyses in varying degrees of glucose tolerance. Comparison between non-insulin-dependent diabetic, impaired glucose tolerant, and control populations

Atherosclerosis is the major cause of death in diabetic patients. Lipoproteins and lipids are frequently altered in non-insulin-dependent diabetes. These lipoprotein alterations are of interest because of their possible role in the origin of the accelerated atherosclerosis found in diabetes. Because of the link between lipoproteins and diabetes, serum lipids and lipoproteins were measured in 215 middle-aged patients (107 female, 108 male) with varying degrees of glucose tolerance: control subjects, subjects with impaired glucose tolerance (IGT), and patients with non-insulin-dependent diabetes mellitus (NIDDM). In male subjects, levels of fasting total triglycerides were significantly greater in those with NIDDM compared with control subjects. In female subjects, fasting total cholesterol levels were significantly greater in NIDDM compared with IGT. Both high-density lipoprotein (HDL) cholesterol and HDL2 cholesterol values were significantly lower in both sexes with NIDDM compared with control subjects. Low-density lipoprotein (LDL) cholesterol levels were elevated in the male subjects with IGT. No differences in HDL cholesterol or its subfractions were seen in both sexes with IGT compared with control subjects. Bivariate analyses showed that the reduced HDL cholesterol and HDL subfraction levels were most closely associated with both total triglycerides and weight. This study shows that reduced HDL cholesterol and HDL2 cholesterol levels occur in NIDDM, whereas persons with "impaired glucose tolerance" do not have the dramatic alterations in HDL levels.     

Carvedilol improves endothelium-dependent dilatation in patients with coronary artery disease

OBJECTIVE: Flow-mediated, endothelium-dependent dilatation (FMD) of the coronary and peripheral circulation is impaired by increased oxidative stress in patients with coronary artery disease (CAD). Carvedilol is a novel beta-blocker that also shows an antioxidant effect in vitro. However, the effect of carvedilol on endothelial dysfunction associated with established coronary atherosclerosis has not been examined in the clinical setting. METHODS: We studied 29 patients with CAD, including 17 with recent myocardial infarction and 12 with stable effort angina pectoris. Nineteen patients received carvedilol (10 with infarction and 9 with angina), and 10 were treated with placebo (7 with infarction and 3 with angina). We also studied 13 age- and sex-matched control subjects. Brachial FMD during reactive hyperemia and nitroglycerin-induced, endothelium-independent dilatation were assessed by high-resolution ultrasound. RESULTS: FMD was smaller in patients with CAD compared with controls, although nitroglycerin-induced dilatation was similar. Carvedilol significantly improved FMD after long-term treatment (5. 1% +/- 0.4% at baseline to 7.8% +/- 0.3% after 4 months; P <.01) but not after short-term treatment (5.1% +/- 0.4% at baseline to 5.0% +/- 0.7% after 2 hours). Placebo therapy had no effect on endothelial dysfunction. Neither carvedilol nor placebo had an effect on nitroglycerin-induced dilatation after short- and long-term treatment. Long-term carvedilol therapy also significantly decreased the plasma level of thiobarbituric acid-reactive substances compared with placebo (carvedilol, 5.8 +/- 0.4 nmol/mL to 4.6 +/- 0.3 nmol/mL, P <.01; placebo, 5.9 +/- 0.4 nmol/mL to 5.8 +/- 0.4 nmol/mL, P = not significant). CONCLUSION: These findings suggest that the improvement of endothelial function by carvedilol may be caused by its antioxidant activity.     

Vascular endothelial function in patients with slow coronary flow

BACKGROUND: Slow coronary flow (SCF) in a normal coronary angiogram is a well-recognized clinical entity, but its etiopathogenesis remains unclear. DESIGN: The aim of the study was to determine endothelial function in patients with SCF using a flow-mediated dilatation (FMD) technique in the brachial artery. METHODS: Coronary flow was quantified using the corrected thrombosis in myocardial infarction (TIMI) frame count (CTFC) method. Endothelial function was studied in 27 patients with SCF (23 men, four women, mean age 47.6+/-8.7 years) and in 30 people with normal coronary flow (NCF) (22 men and eight women, mean age 47.5+/-7.4 years). RESULTS: The flow-mediated diameter increase in the SCF group was significantly smaller than that in the NCF group (3.48+/-0.10% compared with 9.11+/-0.10%, P < 0.001). The percentage of nitroglycerine (NTG)-induced dilatation was not significantly different between patients with SCF and people with NCF (16.8+/-1.1% compared with 17.1+/-1.1%, P = 0.87). Simple regression analysis showed that mean CTFC (CTFC(m)) was strongly and inversely related to the percentage of FMD (r = -0.29, P < 0.01) in all participants. When the patients with SCF were excluded, CTFC(m) was still inversely related to the percentage of FMD (r = -0.36, P < 0.05). CTFC(m) was also inversely related to NTG-induced dilatation in the 57 participants (r = -0.23, P < 0.05). Multiple regression analysis showed that CTFC(m) was inversely related to the percentage of FMD only (r = -0.37, P < 0.05). CONCLUSIONS: These findings suggest that endothelial function is impaired in people with SCF and that CTFC correlates well with endothelial dysfunction.     

C-反应蛋白、内皮功能变化与急性冠状动脉综合征相关性研究

目的　探讨 C-反应蛋白及肱动脉流量介导的血管舒张在急性冠状动脉综合征中的变化及其相关性。方法　急性冠状动脉综合征 (ACS)组 5 1例 ,其中急性心肌梗死 (AMI) 15例 ,不稳定性心绞痛 (U AP) 36例 ;选择 2 2例冠状动脉造影除外冠心病的患者为对照组。用速率散射比浊法测血清 C-反应蛋白 (CRP) ,用高分辨率超声测肱动脉反应性充血引起的流量介导血管扩张 (FMD)与硝酸甘油介导的血管扩张 (NTG)。结果　 ACS组 CRP高于对照组(0 .94± 1.45 mg/ dl vs0 .2 7± 0 .2 1mg/ dl,P<0 .0 5 ) ,AMI亚组 CRP明显高于 UAP亚组与对照组 (1.6 4± 1.82mg/ dl vs0 .6 5± 1.17m g/ dl、 0 .2 7± 0 .2 1m g/ dl,P<0 .0 5 ) ,UAP亚组高于对照组 (0 .6 5± 1.82 m g/ dl vs0 .2 7±0 .2 1m g/ dl,P>0 .0 5 )。ACS组的 FMD明显低于对照组 (4 .6 1± 2 .2 1mm vs9.2 3± 3.45 mm,P<0 .0 5 ) ,而 NTG与对照组比较则无差别。经 logisitic回归分析 ,CRP的风险比值 (OR)值大于 1,是 ACS的危险因素 ,FMD的 OR值小于 1,是 ACS的保护因素。经前进法观察 CRP与 FMD在急性冠脉综合征中的作用是相互独立的。结论　急性冠状动脉综合征患者 C-反应蛋白升高 ,内皮功能受损 ,二者是 ACS发生的独立危险因素     

Endothelial Function and Arterial Compliance are not Impaired in Subjects With Heart Failure of Non-Ischemic Origin

BackgroundPatients with heart failure and underlying ischemic heart disease (IHD) exhibit both endothelial dysfunction and increased arterial stiffness. We investigated whether this is also the case in heart failure of nonischemic etiology.Methods and ResultsEleven patients with heart failure and IHD, 12 patients with heart failure from angiographically verified idiopathic nonischemic dilated cardiomyopathy (DCM), and 16 healthy subjects of similar age and sex were compared. Endothelium-dependent and independent function were evaluated by ultrasonic measurement of flow-mediated dilatation (FMD) and glyceryl trinitrate (GTN)-induced dilatation of the brachial artery respectively. Vascular compliance was assessed by carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx). Heart failure severity was similar in IHD and DCM patients. FMD was impaired in the subjects with IHD as compared with control subjects (4.8 ± 0.3 vs. 8.0 ± 3.6 %, P < .01), but not in those with DCM. GTN-induced vasodilatation was not different in patients and controls. PWV was also increased in IHD patients compared with controls (12.1 ± 3.6 vs. 8.0 ± 1.6 m/s, P < .01), but not in DCM patients. AIx was similar in patients and controls.ConclusionHeart failure of nonischemic etiology is not associated with abnormalities of endothelium-mediated dilatation or of arterial compliance. The findings of our study now need to be confirmed in larger studies.