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.     

Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease

OBJECTIVES: The purpose of this study was to determine whether lowering homocysteine levels with folic acid, with or without antioxidants, will improve endothelial dysfunction in patients with coronary artery disease (CAD). BACKGROUND: Elevated plasma homocysteine levels are a risk factor for atherosclerosis. Homocysteine may promote atherogenesis through endothelial dysfunction and oxidative stress. METHODS: In a double-blind, placebo-controlled, randomized trial, we used vascular ultrasound to assess the effect of folic acid alone or with antioxidants on brachial artery endothelium-dependent flow-mediated dilation (FMD). Seventy-five patients with CAD (screening homocysteine level > or =9 micromol/liter) were randomized equally to one of three groups: placebo, folic acid alone or folic acid plus antioxidant vitamins C and E. Patients were treated for four months. Plasma folate, homocysteine, FMD and nitroglycerin-mediated dilation were measured before and after four months of treatment. RESULTS: Plasma folate, homocysteine and FMD were unchanged in the placebo group. Compared with placebo, folic acid alone increased plasma folate by 475% (p < 0.001), reduced plasma homocysteine by 11% (p = 0.23) and significantly improved FMD from 3.2 +/- 3.6% to 5.2 +/- 3.9% (p = 0.04). The improvement in FMD correlated with the reduction in homocysteine (r = 0.5, p = 0.01). Folic acid plus antioxidants increased plasma folate by 438% (p < 0.001), reduced plasma homocysteine by 9% (p = 0.56) and insignificantly improved FMD from 2.6 +/- 2.4% to 4.0 +/- 3.7% (p = 0.45), as compared with placebo. Nitroglycerin-mediated dilation did not change significantly in any group. CONCLUSIONS: Folic acid supplementation significantly improved endothelial dysfunction in patients with coronary atherosclerosis. Further clinical trials are required to determine whether folic acid supplementation may reduce cardiovascular events.     

Prognostic value of brachial artery endothelial function and wall thickness.

OBJECTIVES: We sought to examine the prognostic value of brachial artery (BA) flow-mediated vasodilation (FMD) and intima-media thickness (IMT) in patients admitted for invasive evaluation of chest pain. BACKGROUND: Both FMD and IMT of the BA have been associated with coronary risk factors and the presence of coronary artery disease (CAD). Recent studies on the prognostic value of FMD have been conflicting. METHODS: In 398 consecutive patients (age 54 +/- 9 years) undergoing coronary angiography, FMD and IMT of the BA were measured using high-resolution ultrasound (13 MHz). Patients were divided into two groups according to the FMD median (7.6%). After a mean follow-up of 39 +/- 12 months, cardiovascular events were documented. RESULTS: No difference was found in the number of cardiovascular events between groups. On multivariate Cox regression analysis, including age, number of risk factors, BA diameter, presence of CAD, FMD, and IMT, only the presence of CAD and IMT remained significantly associated with cardiovascular events. CONCLUSIONS: Intima-media thickness predicted late (up to 4 years) cardiovascular events in a large population admitted for evaluation of chest pain. In contrast, the long-term prognostic value of a single baseline measure of BA-FMD seems to be limited.     

Brachial reactivity and extent of coronary artery disease in patients with first ST-elevation acute myocardial infarction

We examined peripheral endothelial function, as measured by brachial artery reactivity, in 49 stable patients with a first episode of acute ST-segment elevation myocardial infarction to examine the relation between extent of coronary disease and peripheral vascular reactivity. Brachial artery reactivity was assessed by ultrasound and flow-mediated dilation (FMD) was calculated as the change in brachial artery diameter after release of suprasystolic blood pressure cuff inflation. FMD was classified as abnormal in (< or =6%) 19 patients (group 1) and as normal in 30 patients (group 2). Average FMDs were 2 +/- 2% in group 1 and 11 +/- 4% in group 2. Patients in group 1 were older (62 +/- 5 vs 54 +/- 11 years, p = 0.02) and more often had a history of hypertension (n = 10, 52%, vs 6, 20%, p = 0.017). Patients with abnormal endothelial function (group 1) had a larger number of coronary obstructive (>or =50%) lesions (3.6 +/- 2.4 vs 2.0 +/- 1.7, p = 0.01) and more extensive coronary disease (1.9 +/- 0.8 vs 1.4 +/- 0.8 vessel disease, p = 0.05). In patients with 3-vessel disease, FMD was lower (4.0 +/- 1.8% vs 8.2 +/- 0.8%, p = 0.04) than in those with lesser coronary involvement. In conclusion, in patients with a first episode of ST-segment elevation myocardial infarction, there was a strong correlation between extent of coronary artery disease and brachial artery reactivity. Patients with localized coronary disease had relatively normal brachial reactivity, whereas those with diffuse coronary disease had more severe abnormal brachial artery reactivity.     

Long-term prognostic role of flow-mediated dilatation of the brachial artery after acute coronary syndromes without ST elevation

Coronary endothelial vasodilator dysfunction is associated with increased cardiac events; the close relation between coronary vasomotor dysfunction and brachial artery vasoreactivity has been previously described. This study assessed the prognostic value of noninvasively assessed brachial artery vasoreactivity in survivors of acute coronary syndromes without ST-segment elevation. We examined 98 men (63.1 +/- 10.8 years) who were referred to our hospital for acute coronary syndromes without ST-segment elevation. Brachial artery endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent nitrate-mediated dilation were examined in all patients using high-resolution echocardiographic Doppler ultrasound within 24 hours of admission. Plasma malondialdehyde, a marker of oxidative stress, and left ventricular ejection fraction were also assessed. Twenty-seven patients underwent coronary revascularization. Patients were followed for 24.8 +/- 5.9 months. Cardiovascular death, myocardial infarction, stroke, and unstable angina were designated as cardiovascular events (CEs). Twenty CEs were recorded. Kaplan-Meyer analysis showed that patients with FMD <1.9% (tertile 1 of FMD values) were more likely to have CEs than those with FMD >1.9% (log rank 5.29, p = 0.021). Multivariate Cox regression analysis showed that FMD <1.9% predicted CEs with an adjusted hazard ratio of 3.035 (95% confidence interval 1.148 to 8.023, p = 0.025) after adjustment for age, risk factors, troponin T, ejection fraction, revascularization procedures, number of diseased vessels, and medication. In conclusion, endothelium-dependent dilation of the brachial artery is a strong independent predictor of adverse outcome in survivors of acute coronary syndromes without ST-segment elevation.     

Endothelial function in patients with vasculogenic erectile dysfunction

OBJECTIVES: Erectile dysfunction (ED) commonly coexists with coronary artery disease (CAD) and/or risk factors for atherosclerosis. Because the silent or documented atherosclerosis or vascular risk factors are very frequent, the possibility of endothelial dysfunction in ED patients is expected to be increased. Our aim was to evaluate the endothelial functions in patients with vasculogenic ED with vascular risk factors and compare them with age-matched non-ED patients or healthy controls. DESIGN: We studied 36 patients with presumed vasculogenic ED, 39 age-matched patients with similar risk factors without ED and 25 age-matched healthy controls without ED, known cardiovascular disease or risk factors. Erectile function was evaluated by the International Index of Erectile Dysfunction (IIEF) scores. Brachial artery flow-mediated dilatation (FMD) and nitroglycerine-mediated dilatation (NMD) were measured. RESULTS: Baseline demographics were similar except the IIEF score and duration of diabetes in patients with ED. Brachial artery FMD and NMD were significantly reduced in patients with ED (3.2+/-3. vs. 6+/-4, p<0.0001 for FMD, 12.2+/-6 vs. 15.4+/-6 p=0.032 for NMD). In patients with similar risk factors but without ED, FMD was significantly lower but NMD were not different compared with healthy controls (6+/-4 vs. 10.2+/-3, p<0.0001 for FMD and 15.4+/-8 vs. 16.4+/-6, p=0.81). IIEF scores were weakly correlated with FMD (r=0.25, p=0.028) in patients with ED. There were significant correlations between FMD and NMD in patients with ED (r=0.46, p=0.05) and with risk factors (r=0.72, p<0.0001) but not in healthy controls (r=0.54, p=0.792). Vasculogenic ED patients have more markedly impaired endothelial and smooth muscle functions compared with patients with similar risk factors but no ED.     

Aortic valve sclerosis is associated with systemic endothelial dysfunction

OBJECTIVES: We sought to examine the association between aortic valve sclerosis (AVS) and systemic endothelial manifestations of the atherosclerotic process. BACKGROUND: Clinical and experimental studies suggest that AVS is a manifestation of the atherosclerotic process. Systemic endothelial dysfunction is an early sign of the atherosclerotic process and can be assessed by ultrasonography of the brachial artery. METHODS: A total of 102 in-hospital patients (76 men; mean age 63.5 +/- 9.7 years) referred to the stress echocardiography laboratory underwent: 1) transthoracic echocardiography, with specific assessment of AVS (thickened valve leaflets with a transaortic flow velocity <2.5 m/s); 2) stress echocardiography; 3) coronary angiography, with evaluation of the Duke score (from 0 [normal] to 100 [most severe disease]); and 4) an endothelial function study, with assessment of endothelium-dependent, post-ischemic, flow-mediated dilation (FMD). RESULTS: Aortic valve sclerosis was present in 35 patients (group I) and absent in 67 (group II). Groups I and II were similar in terms of the frequency of stress-induced wall motion abnormalities (35.3% vs. 19.4%, p = NS) and the angiographic Duke score (33.8 +/- 28.6 vs. 35.2 +/- 29.1, p = NS). Patients with AVS showed a markedly lower FMD than those without AVS (2.2 +/- 3.5% vs. 5.3 +/- 5.3%, p < 0.01). On multivariate analysis, only FMD was highly predictive of AVS, with an odds ratio of 1.18 for each percent decrease in FMD (95% confidence interval 1.05 to 1.32; p = 0.01). CONCLUSIONS: Aortic valve stenosis is associated with systemic endothelial dysfunction. This observation may provide a mechanistic insight into the emerging association between AVS and cardiovascular events.     

External counterpulsation therapy improves endothelial function in patients with refractory angina pectoris

OBJECTIVES: The goal of this study was to investigate the influence of short-term external counterpulsation (ECP) therapy on flow-mediated dilation (FMD) in patients with coronary artery disease (CAD). BACKGROUND: In patients with CAD, the vascular endothelium is usually impaired and modification or reversal of endothelial dysfunction may significantly enhance treatment. Although ECP therapy reduces angina and improves exercise tolerance in patients with CAD, its short-term effects on FMD in patients with refractory angina pectoris have not yet been described. METHODS: We prospectively assessed endothelial function in 20 consecutive CAD patients (15 males), mean age 68 +/- 11 years, with refractory angina pectoris (Canadian Cardiovascular Society [CCS] angina class III to IV), unsuitable for coronary revascularization, before and after ECP, and compared them with 20 age- and gender-matched controls. Endothelium-dependent brachial artery FMD and endothelium-independent nitroglycerin (NTG)-mediated vasodilation were assessed before and after ECP therapy, using high-resolution ultrasound. RESULTS: External counterpulsation therapy resulted in significant improvement in post-intervention FMD (8.2 +/- 2.1%, p = 0.01), compared with controls (3.1 +/- 2.2%, p = 0.78). There was no significant effect of treatment on NTG-induced vasodilation between ECP and controls (10.7 +/- 2.8% vs. 10.2 +/- 2.4%, p = 0.85). External counterpulsation significantly improved anginal symptoms assessed by reduction in mean sublingual daily nitrate consumption, compared with controls (4.2 +/- 2.7 nitrate tablets vs. 0.4 +/- 0.5 nitrate tablets, p <0.001 and 4.5 +/- 2.3 nitrate tablets vs. 4.4 +/- 2.6 nitrate tablets, p = 0.87, respectively) and in mean CCS angina class compared with controls (3.5 +/- 0.5 vs. 1.9 +/- 0.3, p <0.0001 and 3.3 +/- 0.6 vs. 3.5 +/- 0.5, p = 0.89, respectively). CONCLUSIONS: External counterpulsation significantly improved vascular endothelial function in CAD patients with refractory angina pectoris, thereby suggesting that improved anginal symptoms may be the result of such a mechanism.     

Impaired endothelial function in coronary heart disease patients with depressive symptomatology

OBJECTIVES: The purpose of this study was to assess whether depressive symptomatology was associated with vascular endothelial dysfunction in patients with coronary heart disease (CHD). BACKGROUND: In patients with CHD, the presence of depression is associated with a two to four times increased risk of mortality, but the disease pathways involved are uncertain. Endothelial dysfunction is an established risk factor for cardiovascular events in patients with CHD. METHODS: Flow-mediated dilation (FMD) of the brachial artery, a measure of endothelial function, was assessed in 143 patients (99 men, 44 women), ages 40 to 84 years (mean age, 63 +/- 10 years), with documented CHD. RESULTS: Patients with significant depressive symptomatology, as indicated by a Beck Depression Inventory (BDI) score > or = 10 (n = 47) showed attenuated FMD (p = 0.001) compared with patients that were not depressed (BDI < 10; n = 96). The use of antidepressant medication was associated with improved FMD (p < 0.05). CONCLUSIONS: The increased risk of cardiovascular events in CHD patients with elevated symptoms of depression may be mediated, in part, by endothelial dysfunction.     

Short- and long-term changes of flow-mediated vasodilation in patients under statin therapy

BACKGROUND: Flow-mediated vasodilation (FMD) of the brachial artery (BA) has been shown to improve in response to lipid-lowering therapy and other therapeutic interventions, usually within 1 to 2 months. Whether FMD remains improved under therapy in the longer term is unknown. HYPOTHESIS: The aim of this study was to examine the short- and long-term changes of FMD under statin therapy. METHODS: Flow-mediated vasodilation and nitroglycerin-mediated vasodilation (NMD) of the BA were measured with high-resolution ultrasound (13 MHz) at baseline and at 4 and 10 months in 18 consecutively recruited patients with coronary artery disease (CAD), in whom statin therapy was newly established. RESULTS: The decrease of total plasma cholesterol levels after 4 and 10 months of statin therapy (243 +/- 31 vs. 186 +/- 30 vs. 191 +/- 40 mg/dl; p < 0.001) was accompanied by an increase in FMD from 4.4 +/- 3.8% at baseline to 9.6 +/- 2.7% at 4 months and to 9.5 +/- 2.6% at 10 months (p < 0.001). Nitroglycerin-mediated vasodilation showed a trend toward improvement after 4 months (14.6 +/- 7.5 vs. 19.1 +/- 3.6 vs. 19.4 +/- 5.6%; NS). The FMD/NMD ratio also rose significantly after 4 months and remained improved after 10 months of statin therapy (0.31 +/- 0.25 vs. 0.52 +/- 0.16 vs. 0.50 +/- 0.14; p < 0.01). CONCLUSION: Statin therapy is associated with sustained improvement of endothelial function up to 10 months. These data support the utility of FMD for the assessment of vascular function in response to lipid-lowering therapy or other therapeutic interventions in long-term studies.     

Are coronary artery anomalies an accelerating factor for coronary atherosclerosis development?

The relevance of benign congenital coronary anomalies (CAAs) in the atherosclerotic process is still confused despite the number of single reports of coronary artery disease in CAAs. The present study is aimed at assessing the role of CAAs on the progression of coronary artery disease (CAD). A review of the last 15,000 coronary angiographies was performed to select patients with CAAs, and they were divided into 2 groups on the basis of the presence (group I) or the absence (group II) of CAD. Clinical and instrumental records of the selected patients were reviewed and the numbers of cardiovascular events for each group (acute myocardial infarct, unstable angina, silent ischemia, bypass or percutaneous transluminal coronary angioplasty (PTCA) interventions, and cardiovascular death) were recorded from the date of diagnosis to July 2002. Group I (22 patients, mean age 64.1 +/- 9.1 years, F/M = 10/12) and group II (17 patients, mean age 66.5 +/- 10.6 years, F/M = 7/10) were similar for age and ejection fraction values. The presence of risk factors was statistically higher in group I. The number of patients with cardiovascular events was significantly higher in group I: 50% (11 patients) in group I vs 12% (2 patients) in group II, p<0.05). Repeated coronary angiography in 8/11 patients of group I and in the 2 patients of group II confirmed that the causes of the events were precedent atherosclerotic lesions in 7 patients and newly developed lesions in 3. At a mean follow-up of 60.4 +/- 12.3 months, mean actuarial survival was lower in group I than in group II (74.8% vs 100%, p=0.045), whereas mean event-free survival was 41.7% in group I and 88.7% in group II (p=0.02). Benign CAAs do not seem per se to be an accelerating factor for coronary atherosclerosis development in patients with no or few classical risk factors.     

Combined use of endothelial function assessed by brachial ultrasound and high-sensitive C-reactive protein in predicting cardiovascular events

BACKGROUND: Endothelial function plays a key role in determining the clinical manifestations of atherosclerotic lesions. Elevated high-sensitive C-reactive protein (hsCRP) relates to long-term prognosis of cardiovascular disease. HYPOTHESIS: We test the hypothesis that combined use of endothelial function and hsCRP could increase predictive value of future cardiovascular events. METHODS AND RESULTS: 205 patients were followed up for a median period of 24 months. Endothelial function was assessed using brachial ultrasound to measure endothelium-dependent flow-mediated vasodilation (FMD). Cox regression analyses were conducted for the 205 subjects, with cardiovascular events being defined as myocardial infarction, hospitalization due to congestive heart failure, percutaneous coronary intervention, coronary artery bypass grafting, and ischemic stroke. Twenty nine (14%) developed cardiovascular events. Both FMD and hsCRP were significantly predictive of cardiovascular events (relative risk for patients with FMD<3% as compared to those with FMD>6%, 4.65, 95% confidence interval (CI): 1.30-16.66, p=0.018; relative risk for the highest as compared with the lowest tertile of hsCRP level, 3.59, 95% CI: 1.32-9.74, p=0.012, respectively). Further risk analysis was performed among four groups classified by FMD (FMD >or= 6% or<6%) and half percentile of hsCRP (hsCRP >or= 1 or<1 mg/dL). Relative risks for the FMD<6%/hsCRP >or= 1 mg/dL group compared to FMD >or= 6%/hsCRP<1 mg/dL group increased markedly to 12.598 (95% CI: 1.69 to 94.14, p=0.014) for cardiovascular events. CONCLUSIONS: Patients with suspected coronary artery disease may benefit from risk stratification based on both endothelium-dependent FMD and hsCRP, since combined these two factors contribute significantly toward the incidence of cardiovascular events.     

Analysis of differences in flow-mediated dilation in relation to the treatment of coronary patients

INTRODUCTION: Flow-mediated dilation (FMD) is thought to be related to the development of coronary disease. We were interested in knowing the degree of FMD in a large sample of coronary patients in relation to the therapy they were given in clinical practice. PATIENTS AND METHOD: We studied 1,081 coronary patients (age 68 +/- 12 years, 73% male) in which FMD was evaluated in the brachial artery. The patients were classified into 5 treatment groups (416 who receive 2 or more treatments were excluded): group A: 81 controls treated with aspirin, group B: 198 treated with ACE inhibitors, group C: 106 with calcium antagonists, group D: 145 with beta-blockers, and group E: 135 with lipid lowering medication (93% statins). RESULTS: ANOVA was used to analyze the differences between groups. With regard to the number of risk factors present in each group, the patients treated with ACE inhibitors (2.44 +/- 0.79 vs 2.14 +/- 0.89; p < 0.05) and statins (3.45 +/- 0.70 vs 2.14 +/- 0.89; p < 0.05) had more risk factors than GrA and higher levels of LDL-cholesterol (ACE inhibitors 145.0 +/- 33.5 vs 128.5 +/- 32.2 and statins 157.8 +/- 45.3 vs 128.5 +/- 32.2; p < 0.05). GrB had a higher glycemia than controls (123.4 +/- 32.2 vs 114.7 +/- 33.7; p < 0.05). The control group was younger than the therapeutic groups (p < 0.05). Compared with the control group, FMD was significantly higher only in the group treated with ACE inhibitors (3.42 +/- 6.01 vs 0.82 +/- 6.04; p < 0.05). Multivariate logistical regression showed that treatment with ACE inhibitors and statins (p < 0.05) were independent predictors of FMD > 4%. CONCLUSION: Treatment with ACE inhibitors or statins was predictive of the normalization of FMD in coronary patients in clinical practice.     

Epicardial coronary artery constriction to cold pressor test is predictive of cardiovascular events in hypertensive patients with angiographically normal coronary arteries and without other major coronary risk factor

Epicardial coronary endothelial dysfunction independently predicts cardiovascular events in patients with coronary risk factors. This study was designed to evaluate outcome of hypertensive patients on the basis of their epicardial coronary function assessed by cold pressor test (CPT). Control subjects (n = 68, 48.8 +/- 7.6 years) and hypertensive patients (n = 83, 51.3 +/- 7.9 years) with angiographically normal coronary arteries and without other major coronary risk factor underwent epicardial coronary reactivity assessment to CPT using quantitative angiography. Cardiovascular events were recorded with a mean follow-up of 115 months (range 84-132). In control subjects, dilation occurred in 88.2%, no change in 11.8% (mean diameter change: +14.6 +/- 9.3%). In hypertensive patients, dilation occurred in 13.3%, no change in 25.3% (mean diameter change for both: +10.9 +/- 11.2%), and constriction in 61.4% (mean diameter change: -12.7 +/- 3.4%). Endothelium-independent dilation was normal in control subjects and hypertensive patients. In control subjects, there were three cardiovascular events in two subjects (2.9%). In hypertensive patients, there were 17 cardiovascular events in 12 patients (14.5%, P < 0.01 versus control subjects), with 15 cardiovascular events in the 10/51 patients (19.6%) with coronary artery constriction, and two cardiovascular events in the 2/32 patients (6.3%) with no change or dilation (P < 0.05). In conclusion, in hypertensive patients with angiographically normal coronary arteries and without other major coronary risk factors, epicardial coronary artery dysfunction assessed by the cold pressor test is predictive of long-term cardiovascular events.     

Usefulness of flow-mediated dilation of the brachial artery and/or the intima-media thickness of the carotid artery in predicting coronary narrowing in patients suspected of having coronary artery disease.

It has been reported that flow-mediated dilation (FMD) of the brachial artery and the carotid intima-media thickness (IMT), markers of atherosclerosis, are altered in patients with coronary artery disease (CAD), but it is still not known if the presence of CAD can be detected using these markers. We examined whether the presence of CAD can be detected by FMD of the brachial artery and/or IMT. Eighty-one patients who underwent coronary angiography for the first time were enrolled. In each patient, brachial artery diameter responses to FMD and the administration of nitroglycerin spray, and carotid IMT were measured using high-resolution ultrasound (10 MHz) before coronary angiography. CAD was defined as >50% stenosis of a major coronary artery. Fifty-six patients had CAD. FMD was lower and IMT was greater in patients with CAD (FMD, 2.9 +/- 0.2% vs 9.4 +/- 0.5%; IMT, 1.09 +/- 0.05 vs 0.79 +/- 0.04 mm, both p <0.0001). Nitroglycerin-induced dilation did not differ in the 2 groups. Multivariate analysis showed that FMD was the only predictor of the presence of CAD (p = 0.0026). Receiver-operating characteristic analysis demonstrated that a cutoff value for FMD for detecting the presence of CAD was 6%, with a sensitivity of 0.93 (52 of 56) and a specificity of 0.88 (22 of 25). These findings suggest that FMD but not IMT may be used to detect the presence of CAD in patients with suspected CAD.     

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.     

The impact of coronary revascularization on long-term outcomes after surgical repair of abdominal aortic aneurysm]

BACKGROUND: Complications due to undetectable coronary artery disease are the major causes of morbidity and mortality in the surgical treatment of abdominal aortic aneurysm (AAA). The aim of our study was to evaluate the importance of significant coronary artery disease identification and the impact of coronary revascularization on early and late outcomes after surgical repair of AAA. METHODS: Between January 1994 and July 2004, 210 patients (204 males and 6 females, mean age 68 +/- 12 years) were candidates to elective surgical repair of AAA. Coronary angiography was performed in 122 patients (58%) in presence of angina symptoms, previous myocardial infarction, echocardiographic or scinti-scan evidence of myocardial ischemia. Coronary revascularization was performed in 83 patients (39.5%). The population was divided into two groups: coronary artery bypass graft/coronary angioplasty (CABG/PTCA) + AAA group (83 patients submitted to CABG surgery [n = 61], or PTCA [n = 22], for significant coronary artery disease before surgical repair of AAA), AAA group (127 patients without significant coronary artery disease, operated for AAA). Follow-up (90% complete) had a mean duration of 42 +/- 23 months. RESULTS: CABG/PTCA + AAA group compared to AAA group presented major symptoms of angina (p = 0.001), higher incidence of previous myocardial infarction (67 vs 10%, p < 0.0001), lower mean value of left ventricular ejection fraction (50 vs 54%, p = 0.01). Operative mortality was 0.95%, and was not related to any cardiac morbidity: operative mortality was observed in the AAA group (2 patients died of anossic cerebral damage and respiratory failure) and was absent in the CABG/PTCA + AAA group (p = 0.8). The overall 8-year survival in the AAA group and in the CABG/PTCA + AAA group was 80 +/- 11 vs 95 +/- 2.8%, respectively (p = 0.7). Freedom from cardiac late death and freedom from cardiac events (recurrence of angina, myocardial infarction, congestive heart failure) were high in both groups (93 +/- 6.4 vs 97 +/- 2.3%, p = 0.6; and 91 +/- 6.6 vs 89 +/- 6.7%, p = 0.5, respectively). In the CABG/PTCA + AAA group symptoms for angina (p = 0.0002) and dyspnea (p < 0.0001) significantly improved during the follow-up. CONCLUSIONS: Significant coronary artery disease was not negligible (39.5%) in patients candidates to surgical repair of AAA. Identification and correction of coronary artery disease prior to AAA surgery is the most important strategy to reduce the risk of vascular procedure. The beneficial impact of coronary revascularization on early and late outcomes is evident, in terms of satisfactory survival and freedom from cardiac adverse events. Therefore, coronary angiography is strongly suggested to optimize early and long-term results.     

Enhanced coronary calcification determined by electron beam CT is strongly related to endothelial dysfunction in patients with suspected coronary artery disease

BACKGROUND: Coronary artery calcification determined by electron beam CT (EBCT) is strongly associated with total plaque burden but is not related to systemic vascular inflammation.Aims: We sought to test the hypothesis that enhanced coronary artery calcification, a marker of atherosclerosis and plaque burden, was related to endothelial dysfunction in patients with suspected coronary artery disease (CAD). METHODS AND RESULTS: One hundred twenty-four subjects with suspected CAD were enrolled. Coronary artery calcification was detected by EBCT. A noninvasive method of brachial ultrasound was used to measure endothelium-dependent flow-mediated vasodilation (FMD) and endothelium-independent nitroglycerin-mediated vasodilation (NMD). Serum high-sensitivity C-reactive protein (hsCRP) and monocyte chemoattractant protein-1 (MCP-1) levels were also determined. Of the 124 patients, the calcium scores ranged from 0 to 4,394. All subjects were classified into three groups according to coronary calcium scores: group 1, score 0 (n = 26); group 2, scores 1 to 199 (n = 50); group 3, scores > or = 200 (n = 48). There was an inverse association between the degree of coronary artery calcification and the endothelium-dependent FMD in the three groups (6.9 +/- 0.6% vs 5.3 +/- 0.3% vs 3.7 +/- 0.3%, respectively; p < 0.001) but not the endothelium-independent NMD. Besides, no significant difference in serum levels of hsCRP and MCP-1 were found among the three groups. However, both the serum levels of hsCRP and MCP-1 were correlated significantly with endothelium-dependent FMD (r = - 0.211, p = 0.019; and r = - 0.188, p = 0.037, respectively). By multivariate analysis, enhanced coronary calcification was a strong independent predictor of endothelial dysfunction (p < 0.001). CONCLUSION: Enhanced coronary artery calcification strongly predicted endothelial dysfunction in patients with suspected CAD. Also, serum levels of hsCRP and MCP-1 were significantly correlated with endothelial function. These findings suggested that both calcium deposition and inflammation were involved in endothelial dysfunction.     

Morphologic rather than functional or mechanical sonographic parameters of the brachial artery are related to angiographically evident coronary atherosclerosis

OBJECTIVES: The purpose of this study was to determine the relationship among coronary atherosclerosis and functional, morphologic, and mechanical parameters assessed noninvasively within the brachial artery (BA). BACKGROUND: Flow-mediated vasodilation (FMD) of the BA, intima-media thickness (IMT) of the carotid artery, and distensibility of the aorta have been correlated with the presence of coronary artery disease (CAD). METHODS: The BA was examined with high-resolution ultrasound (13 MHz) in 117 male patients, in whom coronary angiography was performed. Coronary artery disease (> or =30% diameter stenosis in > or =1 major branch) was found in 84 patients, and 33 patients had smooth coronary arteries (non-CAD). Wall cross-sectional area (WCSA) was calculated from resting diameter and IMT. RESULTS: The BA-WCSA (5.3 +/- 1.5 mm(2) vs. 4.4 +/- 1.4 mm(2), p = 0.002) and IMT (0.37 +/- 0.07 mm vs. 0.31 +/- 0.07 mm, p < 0.001) were significantly greater in patients with CAD compared with non-CAD patients. Flow-mediated vasodilation and distensibility were similar among groups. Using logistic regression analyses adjusting for age, positive family history, hypertension, hypercholesterolemia, smoking, FMD, and distensibility, only WCSA (p < 0.01) and IMT (p < 0.001) correlated independently with the presence of CAD. CONCLUSIONS: Morphologic but not functional and mechanical parameters of the BA are associated with the presence of CAD. Among BA sonographic parameters, IMT and WCSA seem to be the most accurate ones for the estimation of coronary atherosclerotic risk.     

First time myocardial revascularization in patients younger than 70 years. Single versus double internal mammary artery.

BACKGROUND: We evaluated the early and late outcomes of bilateral internal mammary artery (BIMA) grafting, with or without saphenous vein grafts (SVGs), compared to single internal mammary artery and SVGs in patients < 70 years undergoing first myocardial revascularization. METHODS: From September 1986 to December 1999, 1389 patients underwent first myocardial revascularization using the left internal mammary artery (LIMA) to the left anterior descending artery and SVGs (n = 480) or BIMA (one internal mammary artery on the left anterior descending artery) with or without SVGs (n = 909). Propensity score analysis was used to select 952 (476 of each group) patients with the same preoperative and operative characteristics. Thirty-day outcome and 10-year freedom from all-cause death, cardiac death, acute myocardial infarction (AMI), AMI in a grafted area, redo/percutaneous transluminal coronary angioplasty (PTCA), redo/PTCA in a grafted artery, cardiac events and any events, were evaluated. Follow-up ranged from 3.5 to 16.8 years (mean 8.8+/-4.0 years). RESULTS: Thirty-day mortality was 2.9% in the LIMA group and 1.9% in the BIMA group, p = NS; the BIMA group showed a better 10-year freedom from all-cause death (92.4+/-2.1 vs 87.5+/-3.5%, p = 0.0216), cardiac death (97.4+/-0.9 vs 91.9+/-1.4%, p = 0.0042), AMI (98.7+/-0.5 vs 94.2+/-1.2%, p = 0.0034), AMI in a grafted area (98.9+/-0.5 vs 94.7+/-1.3%, p = 0.0017), cardiac events (95.4+/-1.2 vs 86.8+/-1.8%, p = 0.0026) and any events (88.8+/-2.2 vs 80.7+/-2.1%, p = 0.0124). Cox analysis confirmed that LIMA + SVGs was a risk factor independent of lower freedom from all the above-mentioned events. CONCLUSIONS: Double mammary artery in patients < 70 years who had a first time myocardial revascularization gives a better clinical outcome even 10 years after the operation.