Impact of left ventricular ejection fraction on endothelial function in patients with coronary artery disease

BACKGROUND: Endothelial dysfunction is present in patients with coronary artery disease (CAD) or with congestive heart failure. HYPOTHESIS: This study was performed to evaluate the impact of systolic heart function on endothelial function in patients with CAD. METHODS: The study population consisted of 283 consecutive patients (mean age 59 years, 176 men) undergoing coronary angiography. Endothelial function was assessed by measuring flow-mediated vasodilation (FMD) of the brachial artery. RESULTS: Patients (n = 236) with an ejection fraction (EF) > or = 55% on routine echocardiogram were younger (mean age 58 vs. 62 years), showed a lower prevalence of diabetes (15 vs. 38%) and myocardial infarction (13 vs. 66%), and showed a higher FMD (4.8 +/- 2.4 vs. 4.0 +/- 2.0%, p < 0.05) than patients (n = 47) with an EF < 55%. The correlation coefficient between FMD/endothelial function and EF/systolic heart function was 0.149 (p < 0.02) in the overall study population. Multivariate analysis showed that of age, gender, frequency of diabetes mellitus, myocardial infarction, and CAD extent, EF was the only significant independent parameter correlating with FMD in patients with CAD. CONCLUSIONS: Compared with the other tested risk factors, EF surprisingly was the only significant independent parameter correlating with endothelial function in patients with CAD. Our results support the view that endothelial function is an independent prognostic factor in patients with CAD.     

Correlation of epicardial and systemic flow-mediated vasodilation in patients with atypical angina but no evidence of atherosclerotic disease

BACKGROUND: Atypical angina represents a diagnostic challenge and can be observed in the absence of significant coronary atherosclerosis. Endothelial dysfunction is a relevant marker of prognosis, considering cardiovascular events. The aim of the present study was to compare flow-mediated vasodilation (FMD) in systemic peripheral and epicardial coronary arteries. If noninvasive measurements of FMD in systemic arteries correlated with invasive measurements of coronary FMD, this may facilitate diagnostic approaches and determination of prognosis in patients with atypical angina in the future. Patients with atherosclerosis were excluded, because structural changes of coronary vessels may impair adequate comparison. METHODS: Endothelial function (ENF) of epicardial and systemic arteries was examined in 61 consecutive patients with atypical angina in whom significant atherosclerosis was excluded by coronary angiography. ENF of the epicardial arteries was examined during heart catheterization, measuring diameter changes of the proximal left anterior descending coronary artery (LAD) in response to reactive hyperemia, induced by locally administered adenosine via infusion catheter to the mid-segment of the LAD (coronary FMD [FMDc]). ENF of the radial artery was examined with high-resolution ultrasound, measuring peripheral FMD (FMDp) in response to reactive hyperemia induced by distal cuff occlusion. Endothelium-independent vasoreactivity to glycerol trinitrate was assessed. RESULTS: In patients with atypical angina in the absence of atherosclerosis, there was a significant correlation in ENF between coronary and systemic arteries (r=0.437; P=0.001). The underlying disease was myocardial inflammation (Inf) in 48 patients, in whom the mean (+/- SD) ENF of epicardial (FMDc-Inf 3.40+/-5.55%) and systemic (FMDp-Inf 3.69+/-2.93%) arteries was significantly impaired (P<0.001), compared with 13 control (Co) patients who had normal myocardial biopsies (FMDc-Co 14.51+/-8.62%; FMDp-Co 7.69+/-3.42%). FMD of coronary (r=-0.353; P=0.005) and systemic (r=-0.542; P<0.001) arteries correlated significantly with myocardial inflammation and endothelial activation. CONCLUSIONS: There was a significant correlation in FMD between coronary and systemic arteries in patients with atypical angina but without significant atherosclerosis. Inflammatory processes are associated with endothelial dysfunction of both vascular regions.     

Endothelial dysfunction in young patients with acute ST-elevation myocardial infarction

Endothelial dysfunction may be particularly important in the pathogenesis of young patients with acute myocardial infarction (AMI), because they have different clinical characteristics compared with older patients. We investigated endothelial function in relation to AMI in this young age group. From January 2005 to March 2008, 29 of 31 consecutive patients with acute ST-elevation myocardial infarction (STEMI) who were <40 years old and received direct percutaneous coronary intervention (PCI) were enrolled in the study. We compared the coronary risk factors and flow-mediated vasodilation (FMD) in the brachial artery between the acute STEMI patients and 29 age- and gender-matched controls that did not have AMI. Baseline brachial artery diameter and responses to glyceryl trinitrate were similar between the two groups. In contrast, FMD was significantly lower in the young acute STEMI group than in the control (3.47 ± 4.08 vs. 7.45 ± 4.67%, p = 0.001) and correlated with the Thrombolysis in Myocardial Infarction (TIMI) risk score. The impaired FMD in the acute STEMI group was independent of smoking, hyperlipidemia, hypertension, nitrate use, or body mass index. In multiple logistic regression analysis, only FMD and age, not traditional cardiovascular risk factors, were found to be significantly associated with acute STEMI (odds ratio = 0.75, 95% CI 0.63-0.90, p < 0.01). In conclusion, independent of conventional risk factors, severe endothelial dysfunction occurs in young acute STEMI patients and correlates with TIMI score. In addition to age, impaired FMD is the only significant factor associated with acute STEMI in this young population.     

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.     

Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events and restenosis in patients undergoing coronary stent implantation: a prospective study

BACKGROUND: Endothelial dysfunction plays a key role in atherosclerosis and predicts future cardiovascular events in individuals with or without coronary artery disease and improves with risk reduction therapy. We sought to determine the predictive value of endothelial dysfunction for long-term cardiovascular events and in-stent restenosis in patients undergoing percutaneous coronary intervention (PCI). METHODS: Using high-resolution ultrasound, we assessed endothelial function by using the brachial artery flow-mediated dilation (FMD) method in 135 patients with coronary artery disease before elective coronary stenting. Patients were prospectively followed up for an average of 12 months after PCI. RESULTS: Thirty patients had an event during follow-up including cardiac death (four patients), myocardial infarction (nine patients), unstable angina/non-ST elevation myocardial infarction (15 patients), and stroke (two patients) and in-stent restenosis was determined in 16 of these patients. Endothelium-dependent FMD was significantly lower in patients who had an event compared with those without an event (4.7+/-1.9 vs. 6.0+/-2.0%, P=0.007), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. FMD was the only predictor of cardiovascular events (P=0.03). Impaired endothelial function was associated with a significantly higher incidence of cardiovascular events and in-stent restenosis by Kaplan-Meier analysis. When a cutoff point of 7.5% was used, flow-mediated dilation had a sensitivity of 93%, specificity of 37%, and negative predictive value of 95% for cardiovascular events. CONCLUSION: Impaired brachial artery FMD is associated with long-term cardiovascular events and in-stent restenosis in patients undergoing PCI. Noninvasive assessment of endothelial function may serve as a surrogate marker for the estimation of future cardiovascular event risk and long-term follow-up in these patients.     

Advanced endothelial dysfunction in diabetic patients with multiple risk factors; importance of insulin resistance

AIM: Endothelial dysfunction is considered an early event in the development of atherosclerosis. The present study was undertaken to determine whether the accumulation of cardiovascular risk factors and insulin resistance are associated with endothelial function in diabetic patients.METHODS: 101 patients with type 2 diabetes without macroangiopathy stratified by the number of cardiovascular risk factors (dyslipidemia, hypertension, obesity) and 9 normal control subjects were studied for vascular endothelial functions by measuring flow-mediated vasodilation (FMD) using a high-resolution ultrasound method, brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness (IMT), and the ankle-brachial index (ABI).RESULTS: FMD negatively correlated with baPWV and carotid IMT, and positively correlated with ABI. FMD was significantly lower in diabetic patients associated with 3 other risk factors than in those with diabetes alone. In subjects with fasting plasma glucose < or = 140mg/dL, FMD showed significant negative correlations with fasting insulin levels and homeostasis model assessment (HOMA)-R. Multivariate analysis revealed that insulin resistance as represented by HOMA-R and systolic blood pressure showed a significant association with impaired FMD.CONCLUSION: The present results suggest that the accumulation of cardiovascular risk factors is associated with endothelial dysfunction in diabetic patients, and that insulin resistance as well as high blood pressure could play a pathogenic role in the development of endothelial dysfunction.     

Close association of endothelial dysfunction with insulin resistance and carotid wall thickening in hypertension

BACKGROUND: Endothelial dysfunction has been regarded as an early stage in the atherosclerotic process. Endothelial dysfunction and insulin resistance were observed in hypertensive subjects and were associated with carotid wall thickening. METHODS: We examined the determinants of endothelial dysfunction including insulin sensitivity and carotid wall thickening. A total of 41 subjects with nondiabetic essential hypertension were studied. Endothelial function of brachial artery and carotid wall thickening were assessed noninvasively using ultrasound technique. In brachial artery, we measured flow-mediated endothelium-dependent vasodilation (FMD) and glyceryl trinitrate-induced endothelium-independent vasodilation (GTN). We estimated intima-media thickness of the common carotid artery (IMT). Insulin sensitivity was measured according to the steady-state plasma glucose (SSPG) method. High SSPG levels indicated insulin resistance. RESULTS: On univariate analysis, there were significant negative correlations between FMD and SSPG (r = -0.695, P <.0001) or IMT (r = -0.449, P <.004). The FMD was negatively correlated significantly with age and with systolic and diastolic blood pressures (BP). A significant negative correlation was observed between GTN and SSPG. There was a significant positive relation between SSPG and IMT. On multiple regression analysis including systolic BP, SSPG, and age as independent variables and FMD as a dependent variable, FMD was independently related to SSPG (P <.03) and systolic BP (P <.02). If the presence of SSPG, diastolic BP, and age were entered as independent variables against FMD, FMD was independently related to SSPG (P <.002). CONCLUSIONS: One of the major determinants of endothelial function was insulin resistance. Our findings suggest that endothelial dysfunction and early structural vascular changes were related to insulin resistance.     

Vascular endothelial dysfunction is associated with reversible myocardial perfusion defects in the absence of obstructive coronary artery disease.

BACKGROUND: The purpose of this study was to investigate whether endothelial dysfunction contributes to abnormal myocardial perfusion imaging (MPI) observed in patients without obstructive coronary artery disease (CAD). It is unclear whether reversible MPI defects detected in the absence of obstructive CAD represent underlying vascular pathology or are false-positive MPI results. Recent evidence suggests that coronary endothelial dysfunction might play a role in the pathogenesis of these defects. METHODS AND RESULTS: We prospectively recruited 36 patients with chest discomfort, reversible abnormalities on MPI, and nonobstructive or absent CAD (stenosis <50% on coronary angiography). The control group (n = 55) consisted of patients with chest discomfort and similar cardiac risk factors but with normal MPI findings. Vascular endothelial function was assessed in the brachial artery by ultrasound as the response to hyperemia and reported as percent flow-mediated dilation (FMD). Response to sublingual nitroglycerin was used as an indicator of endothelium-independent vasodilation. The patients with abnormal MPI findings and nonobstructive CAD had a significantly lower FMD (9.0% +/- 7.2%), indicating endothelial dysfunction, compared with those with similar risk factors and normal MPI findings (12% +/- 5.2%) (P = .03). Baseline brachial artery size and endothelium-independent dilation were similar between groups. On multivariate analysis, only endothelial dysfunction was predictive of reversible MPI defects. CONCLUSIONS: Patients with chest pain and reversible MPI defects but without obstructive CAD have lower FMD indicative of endothelial dysfunction, as compared with similar patients with normal MPI findings. The possibility of a causal link between reversible MPI defects and endothelial dysfunction needs further exploration.     

Impaired endothelial function in patients with myocardial bridge

OBJECTIVE: The relationship between myocardial bridging (MB) and ischemic heart disease is still controversial. In this study, we aimed to evaluate the existing atherosclerosis and noninvasive endothelial function of brachial artery in patients with MB. METHODS: The present study included 50 patients (group I) who had MB in left anterior descending (LAD) on coronary angiography. All of the coronary artery segments were evaluated by intravascular ultrasound (IVUS). Endothelial function was assessed with measurement of flow-mediated dilatation (FMD) and nitrate-dependent dilatation in the brachial artery. The study also included 30 healthy control subjects (group II). Patients in the group I were further subdivided into two subgroups based on the findings on IVUS: group IA included 20 patients without atherosclerotic lesions and group IB included 30 patients with atherosclerotic coronary artery disease in addition to MB. RESULTS: FMD values were found to be significantly lower in the patients with MB (group I) than in the control (6.4 +/- 3% vs 11 +/- 4%, P <0.001). In regard to FMD values in subgroups, FMD was 7 +/- 2% in the group IA and 5.8 +/- 1% in the group IB (P = 0.023). On IVUS, atherosclerotic plaque was found proximal to the bridge in the same coronary artery segment in addition to MB in 75% of the patients in group I (group IB). No atherosclerotic plaque was found in within or distal segments of MB. CONCLUSION: Endothelial function is impaired in patients with MB and there is an increased tendency for atherosclerosis proximal to the bridge in the patients with MB. Endothelial dysfunction is more severe in the patients with atherosclerosis proximal to the bridge.     

Effects of prostaglandin E1alpha cyclodextrin [corrected] treatment on endothelial dysfunction in patients with systemic sclerosis

OBJECTIVE: Systemic sclerosis (SSc) is characterized by an altered nitric oxide (NO): endothelin I ratio and by endothelial dysfunction. AIMS: To verify the effects of prostaglandin E1 (PGE1) alpha-cyclodestrin treatment on endothelial function, quantified as flow-mediated dilation (FMD) of the radial artery. METHODS: In 16 women with SSc (age 57 +/- 2.7 years, means +/- SE) in whom a diagnosis of SSc had been made several years earlier (7.1 +/- 1.2 years), FMD was evaluated by an echotracking technique on the radial artery, using trinitroglycerin vasodilation as a non-endothelial measure of the vessel's ability to increase its diameter maximally. FMD was evaluated after 4 months washout period and after 4 months cyclic infusion of PGE1 alpha-cyclodestrin. Expired NO was measured at the same time. RESULTS: PGE1 alpha-cyclodestrin cyclic infusions did not modify systolic and diastolic blood pressure, heart rate or trinitroglycerin radial artery vasodilation. On the other hand, it induced a marked and significant increase in FMD of the radial artery, which was also accompanied by an increase in blood flow and expired NO. CONCLUSIONS: Endothelial dysfunction and reduced FMD associated with SSc are improved by cyclic treatment with PGE1 alpha-cyclodestrin. This effect occurs together with a concomitant increase in expired NO, suggesting its direct positive influence on endothelial function. It may also partly explain the clinical beneficial effect of the drug in SSc.     

Impaired endothelium-dependent vasodilation in the brachial artery in variant angina pectoris and the effect of intravenous administration of vitamin C

Endothelial dysfunction in the coronary artery contributes to the pathogenesis of variant angina, and endothelial dysfunction in variant angina may be associated with increased oxidant stress in the systemic arteries. We investigated whether endothelial dysfunction exists in the peripheral artery in patients with variant angina, and also examined the effect of vitamin C, an antioxidant, on endothelium-dependent vasodilation. Using high-resolution ultrasound, both the flow-mediated vasodilation (FMD, endothelium-dependent vasodilation) and sublingual nitroglycerin-induced vasodilation (NTG-D, endothelium-independent vasodilation) in the brachial artery were measured in 28 patients with variant angina and 24 control subjects who had normal coronary arteries. FMD was significantly impaired in patients with variant angina compared with control subjects (1.8 +/- 2.2% vs 6.4 +/- 4.9%, p <0.001). FMD and NTG-D before and after intravenous administration of either vitamin C or placebo were measured in 17 patients with variant angina. FMD significantly improved after the administration of vitamin C (from 2.2 +/- 2.4% to 4.5 +/- 1.6%, p <0.01), but not after administration of the placebo (from 2.0 +/- 2.6% to 1.7 +/- 1.9%). The improved FMD due to vitamin C in patients with variant angina, however, was not significantly different from that in the control subjects. NTG-D was not significantly different between patients with variant angina and control subjects (14.0 +/- 7.8% vs 13.6 +/- 5.0%) and it was also not affected by vitamin C. In conclusion: (1) FMD in the brachial artery is impaired in patients with variant angina, and (2) the acute administration of the antioxidant, vitamin C, was observed to reverse this endothelial dysfunction. These findings support the theory that the systemic inactivation of nitric oxide due to oxidative stress might exist in patients with variant angina.     

Effect of tirofiban on percutaneous coronary intervention-induced endothelial dysfunction in patients with stable coronary artery disease

Recent studies demonstrated that glycoprotein (GP) IIb/IIIa receptor antagonists improve endothelial dysfunction of forearm resistance vessels in patients with stable coronary artery disease. However, it remains unclear whether these findings can be extended to the conductance vessel level. In this study, we aimed to evaluate the acute effect of tirofiban on endothelial function of arterial conductance vessels in patients undergoing percutaneous coronary intervention (PCI). Endothelial function was examined by ultrasonographic measurement of flow-mediated vasodilation (FMD) of the brachial artery. Endothelium-independent vasodilation was determined in response to nitroglycerin. Sixty-six patients who underwent PCI were included in the study. Thirty-three patients received a bolus of 10 microg/kg body weight of tirofiban, whereas 33 patients who did not receive tirofiban served as the control group. FMD was measured in all patients before and 30 minutes after PCI. Tirofiban significantly improved FMD (6.0 +/- 0.4% before vs 7.8 +/- 0.5% after PCI, p <0.0001), whereas FMD deteriorated in patients in the control group (6.1 +/- 0.6% before vs 4.7 +/- 0.7% after PCI, p = 0.006). Nitroglycerin-induced dilation remained unaltered in response to PCI. In another group of 11 patients with coronary artery disease, FMD did not change after coronary angiography without coronary intervention. In conclusion, PCI induces endothelial dysfunction in forearm conductance vessels that can be reversed with tirofiban.     

Patients with systemic lupus erythematosus show increased platelet activation and endothelial dysfunction induced by acute hyperhomocysteinemia

OBJECTIVE: Hyperhomocysteinemia adversely affects the endothelium, although the exact mechanism is unclear. Systemic lupus erythematosus (SLE) is an inflammatory disease with a high atherothrombotic tendency. We examined whether acute hyperhomocysteinemia exacerbates endothelial and platelet dysfunction in patients with SLE. METHODS: Twelve SLE patients and 15 controls were recruited. Oral methionine was used to achieve acute hyperhomocysteinemia. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery; also assessed were the levels of von Willebrand factor (vWF) and plasminogen activator inhibitor type 1 (PAI-1). Platelet activation was assessed by the levels of beta-thromboglobulin (beta-TG), fibrinogen binding, and P-selectin expression using flow cytometry. RESULTS: After oral methionine loading, vWF levels increased significantly, whereas FMD remained unchanged in both groups. PAI-1 increased significantly only in controls. Fibrinogen binding to platelets increased significantly only in SLE patients. Beta-TG remained unchanged in SLE patients but increased significantly in controls. Platelet P-selectin expression did not change in either group. CONCLUSION: These results suggest that the prothrombotic tendency after acute hyperhomocysteinemia is mediated by endothelial dysfunction and platelet activation in patients with SLE and healthy controls.     

Combined hormone replacement therapy improves endothelial function in healthy postmenopausal women

OBJECTIVES: Large scale epidemiological studies suggest that hormone replacement therapy (HRT) reduces cardiovascular events in postmenopausal women. Improvement in endothelial function may contribute to this protective effect. DESIGN: In a prospective, double blind study, 61 healthy postmenopausal women were randomized to receive either oral continuous combined HRT [oestradiol 2 mg and norethisterone acetate (NETA) 1 mg per day] or placebo. Endothelial function, assessed by flow-mediated vasodilation (FMD) of the brachial artery and expression of soluble endothelial cell adhesion molecules (CAM) were determined before, after 3 and 6 months of therapy. RESULTS: The FMD was significantly improved in women on combined HRT (from 5.97% to 10.94% after 3 months and to 10.58% after 6 months; both P < 0.01 versus baseline values) and did not change in the placebo group (6.92% at baseline, 5.86% after 3 and 6.26% after 6 months). After 3 months of combined HRT, significant decreases of 24.6% for E-selectin and 13.9% for intercellular adhesion molecule-1 (ICAM-1) were observed (both P < 0.01 versus baseline values) and were sustained after 6 months of therapy, whilst no differences emerged in the placebo group. CONCLUSIONS: Oestradiol and norethisterone acetate improve endothelial function by both enhancing FMD and reducing the levels of soluble E-selectin and ICAM-1 in healthy postmenopausal women.     

Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women

OBJECTIVES:; The aim of the present study was to assess whether optimized antihypertensive treatment is effective in modifying endothelial function and whether an improvement in flow-mediated vasodilation (FMD) in response to treatment, as an expression of reversible endothelial dysfunction, could predict a more favorable prognosis in a population of postmenopausal women. BACKGROUND: Hypertensive postmenopausal women have been shown to have abnormal endothelium-dependent vascular function. However, FMD may change over time, according to antihypertensive treatment; the prognostic value of these changes has not been investigated. METHODS: A total of 400 consecutive postmenopausal women with mild-to-moderate hypertension and impaired FMD underwent ultrasonography of the brachial artery at baseline and after six months, while optimal control of blood pressure was achieved using antihypertensive therapy. They were then followed up for a mean period of 67 months (range 57 to 78). Endothelial function was measured as FMD of the brachial artery, using high-resolution ultrasound. RESULTS: After six months of treatment, FMD had not changed (< or = 10% relative to baseline) in 150 (37.5%) of 400 women (group 1), whereas it had significantly improved (>10% relative to baseline) in the remaining 250 women (62.5%) (group 2). During follow-up, we noticed 32 events (3.50 per 100 person-years) in group 1 and 15 events (0.51 per 100 person-years) in group 2 (p < 0.0001). CONCLUSIONS: This study demonstrates that a significant improvement in endothelial function may be obtained after six months of antihypertensive therapy and clearly identifies patients who possibly have a more favorable prognosis.     

Association between insulin resistance and endothelial dysfunction in type 2 diabetes and the effects of pioglitazone

Endothelial dysfunction is regarded as an early stage of atherosclerosis, and plays a role in the development of atherosclerotic diseases. Insulin resistance is related to the atherosclerotic process. In this study, we examined the association between endothelial function and insulin resistance in 48 subjects with type 2 diabetes. In addition, the effects of pioglitazone treatment on endothelial function and insulin resistance were investigated in a subgroup of subjects. Endothelial function of the brachial artery was non-invasively assessed using ultrasound technique. We measured flow-mediated endothelium-dependent vasodilation (FMD) and glyceryl trinitrate-induced endothelium-independent vasodilation (GTN). Insulin sensitivity was measured by the steady-state plasma glucose (SSPG) method. High SSPG levels indicate insulin resistance. There was a significant inverse correlation (r=-0.462, p<0.001) between SSPG and FMD. Systolic blood pressure was inversely correlated with FMD (r=-0.360, p<0.013). By multiple regression analysis, insulin resistance was the sole predictor of FMD. The effects of chronic treatment with pioglitazone were assessed in 10 subjects with type 2 diabetes. The increase in FMD significantly correlated with the decrease in SSPG. There is a significant association between vascular endothelial dysfunction and insulin resistance in type 2 diabetes. This result was supported by the effects of the insulin sensitizer, pioglitazone.     

Additive effect of homocysteine- and cholesterol-lowering therapy on endothelium-dependent vasodilation in patients with cardiovascular disease

Aim : Endothelial dysfunction is a marker for development and progression of atherosclerosis. Statin therapy improves endothelial function in cardiovascular patients by reducing LDL‐cholesterol and by pleiotropic effects. B‐group vitamin supplementation restores endothelial function mainly by reducing homocysteine‐induced oxidative stress. Thus, we evaluated the effect of rosuvastatin, B‐group vitamins and their combination on endothelial function in high‐risk cardiovascular patients. Methods : Thirty‐six patients with cardiovascular disease were randomly, double‐blinded assigned to either rosuvastatin 10 mg (group R, n = 18) or vitamin supplementation consisting of folic acid 1 mg, vitamin B12 0.4 mg, and B6 10 mg (group V, n = 18) for 6 weeks. After 6 weeks all patients received rosuvastatin and vitamin supplementation in combination for additional 6 weeks. Endothelial function was assessed by flow‐mediated vasodilation (FMD) at baseline and after 6‐ and 12‐week treatment. Results : At baseline, FMD, plasma lipids, vitamins, and homocysteine were comparable between both groups. After 6 weeks, FMD improved in both groups (from 4.4 ± 1.6 to 6.9 ± 1.4% group R, P= 0.0004 and from 4.9 ± 1.8 to 6.4 ± 1.8% group V, P= 0.0002). This improvement in FMD was mainly associated with a decrease of plasma lipids in group R and a decrease of homocysteine in group V. After 12 weeks, the combined therapy with rosuvastatin and vitamins further improved FMD to the normal range in 26/33 patients compared to 5/36 at baseline (P < 0.0001). Conclusions : In conclusion, both treatments, rosuvastatin and B‐group vitamin supplementation, improved endothelial function in high‐risk cardiovascular patients. The combination of both therapies had an additive effect on endothelial function suggesting different mechanisms of action.     

Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease

OBJECTIVES: The goal of this study was to prospectively examine the long-term predictive value of brachial-artery endothelial dysfunction for future cardiovascular events. BACKGROUND: Brachial-artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors. The prospective relation between endothelial function determined by brachial-artery ultrasound and long-term cardiovascular risk is unknown. METHODS: We examined brachial-artery endothelial function using ultrasound in 199 patients with peripheral arterial disease before elective vascular surgery. Patients were prospectively followed with an average follow-up of 1.2 years after surgery. RESULTS: Thirty-five patients had an event during follow-up, including cardiac death (5 patients), myocardial infarction (17 patients), unstable angina (10 patients), or stroke (3 patients). Preoperative endothelium-dependent flow-mediated dilation (FMD) was significantly lower in patients with an event (4.4 +/- 2.8%) compared with those without an event (7.0 +/- 4.9%, p < 0.001), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. In a Cox proportional-hazards model, independent predictors of events included age (p = 0.003), more invasive surgery (surgery other than carotid endarterectomy, p = 0.02), and impaired brachial-artery endothelial function (p = 0.002). Risk was approximately nine-fold higher in patients with FMD <8.1% (lower two tertiles) compared with those in the upper tertile (odds ratio 9.5; 95% confidence interval 2.3 to 40). CONCLUSIONS: Impaired brachial-artery endothelial function independently predicts long-term cardiovascular events in patients with peripheral arterial disease. The findings suggest that noninvasive assessment of endothelial function using brachial-artery FMD may serve as a surrogate end point for cardiovascular risk.     

Peripheral vascular endothelial function correlates with exercise capacity in women

BACKGROUND: Vascular endothelial function has been observed to correlate with exercise capacity in predominantly male populations. Gender-based differences exist in the clinical course of coronary artery disease, and previous studies indicate that estrogen may influence endothelial function. These observations raise the possibility that the relationship between endothelial function and exercise capacity in women may differ from that in men. HYPOTHESIS: This study aimed to determine whether peripheral vascular endothelial function correlates with exercise capacity in women. METHODS: Women who were referred for clinically indicated exercise testing with technetium-99 myocardial perfusion imaging were consecutively recruited. To ensure a population free of exercise limitation due to ischemic heart disease, women without myocardial perfusion defects were included for analysis in this study (n = 105). Endothelial function was assessed by brachial artery ultrasound flow-mediated vasodilation (FMD). Exercise capacity was defined as the duration of exercise on a symptom-limited Bruce protocol. RESULTS: Mean FMD was 11.8 +/- 0.6%, and median FMD was 12%. Subjects with an FMD less than the median of 12% had a significantly shorter exercise time than those with FMD > or = 12% (411 +/- 17 vs. 482 +/- 24 s, p = 0.014). There was a significant correlation between FMD and exercise time (r = 0.34, p < 0.001). Age and body mass index were additional predictors of exercise time; however, the relationship between FMD and exercise time was independent of these variables. CONCLUSION: Brachial artery FMD correlates with exercise capacity in women, even in the absence of ischemic heart disease.     

Association of obstructive sleep apnea with endothelial function and heart remodeling in hypertension: A cross-sectional study

BackgroundThis study aims to analyze the association of obstructive sleep apnea (OSA) with endothelial function and heart structure in patients with hypertension and lay a clinical foundation for preventing and treating endothelial dysfunction and heart remodeling in patients with hypertension.MethodsA cross-sectional study design was adopted in this study. From April 2020 to April 2021, 143 patients with hypertension were included and classified into two groups according to the severity of OSA: 81 patients with hypertension without OSA [apnea-hypopnea index (AHI) < 5 events/hour] serving as the control group; 62 patients with hypertension with moderate-severe OSA (AHI ≥ 15 events/hour) serving as the OSA group. The endothelial function and heart structure were assessed by flow‐mediated vasodilation (FMD) and transthoracic echocardiography. Logistic regression analyses were conducted to identify factors associated with endothelial dysfunction and heart remodeling.ResultsCompared with the control group, patients with OSA had significantly greater interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) (P < 0.05), and FMD exhibited a significant decrease (P < 0.05). Logistic regression analyses demonstrated that gender and AHI were associated with FMD (P < 0.05), and FMD was associated with LVMI (P < 0.05).ConclusionsOSA was associated with endothelial dysfunction and heart remodeling in patients with hypertension. Endothelial dysfunction may be crucial for the development of heart remodeling in patients with hypertension with OSA.