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.     

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.     

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.     

Coronary atherosclerosis is associated with left ventricular dysfunction and dilatation in aortic stenosis

Patients with aortic stenosis develop widely variable patterns of left ventricular hypertrophy and dysfunction. We postulated that coronary atherosclerosis (CAD) may be associated with impaired left ventricular function and chamber dilatation in patients with aortic stenosis. Left ventricular mass and volumes were quantified from two-dimensional echocardiography and correlated with coronary angiography in 78 patients with severe aortic stenosis and no previous myocardial infarction or regional wall motion abnormalities. Eighteen patients (group 1) had smooth coronary arteries, 25 patients had irregular coronary arteries with 50% or less stenosis (group 2), and 35 patients had obstructive CAD (group 3). Even though the calculated valve area was similar in all three study groups, group 1 patients had higher values for ejection fraction (65 +/- 9%, 51 +/- 17%, and 48 +/- 13%; p = 0.0002), systolic mass-to-volume ratio (9.2 +/- 3.9, 5.6 +/- 2.8, and 5.2 +/- 2.2; p = 0.0001), and cardiac index (2.9 +/- 0.7, 2.5 +/- 0.7, and 2.3 +/- 0.6 l/min.min2; p = 0.015) than patients in groups 2 and 3, respectively (mean +/- SD). Mean circumferential wall stress was inversely related to severity of CAD. Multivariate analysis showed that CAD is an independent predictor of ejection fraction and mass-to-volume ratio in this group of patients. Thus, in an elderly population with severe aortic stenosis, patients with both obstructive and nonobstructive CAD have an increased incidence of left ventricular enlargement and systolic dysfunction.     

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.     

Detection of subclinical coronary atherosclerosis using two-dimensional, high-resolution transthoracic echocardiography

OBJECTIVES: We evaluated whether two-dimensional high-resolution transthoracic echocardiography (HR-2DTTE) can detect changes in arterial wall thickness and size associated with subclinical coronary artery disease (CAD). BACKGROUND: Arterial wall thickening, compensatory arterial enlargement and a preserved arterial lumen characterize subclinical atherosclerosis. Detection of these changes during the asymptomatic stage of CAD may allow early treatment and prevention of acute coronary events. METHODS: Twenty-six patients with angiographically proven CAD and 29 normal volunteers underwent HR-2DTTE evaluation of the left anterior descending coronary artery (LAD) using an ATL 5000 echograph (Advanced Technology Laboratories, Bothell, Washington) with a 4 to 7 MHz transducer. Significant (>70%) LAD stenosis was present in 15 patients (mean 82%); 11 patients did not have significant LAD stenosis (mean 26%) and represented a surrogate for subclinical LAD disease. Wall thickness, maximal luminal diameter and external diameter of the LAD were measured. RESULTS: Left anterior descending coronary artery wall thickness was larger in patients (1.9 +/- 0.4 mm) than it was in volunteers (0.9 +/- 0.1 mm, p < 0.001). The external diameter of the LAD was (6.0 +/- 1.1 mm) in patients and (3.9 +/- 0.7 mm) in volunteers (p < 0.001). Luminal diameter was 2.2 +/- 0.5 mm in patients and 2.1 +/- 0.6 mm in volunteers (p = NS). There was no difference in wall thickness (1.9 +/- 0.4 mm vs. 2.0 +/- 0.4 mm), luminal diameter (2.2 +/- 0.5 mm vs. 2.2 +/- 0.4 mm) and external diameter (5.9 +/- 1.0 mm vs. 6.2 +/- 1.2 mm) between the patients with <70% and >70% LAD stenosis. CONCLUSIONS: Left anterior descending coronary artery wall thickness and external diameter are significantly increased in patients with CAD as compared with normal subjects, and HR-2DTTE is sensitive enough to detect these differences. Wall thickness and external diameter are increased to the same extent in patients with obstructive and subclinical LAD disease.     

Usefulness of brachial artery reactivity to isometric handgrip exercise in identifying patients at risk and with coronary artery disease

The change in brachial artery (BA) diameter after release of an occluding cuff has been used as a measure of endothelial function, to characterize atherosclerotic risk factors, and as a surrogate marker for coronary artery disease (CAD). We compared the change in BA diameter to isometric handgrip (IHG) with the occlusion release method to determine if a physiologic stress could be used to distinguish patients at risk and with CAD. BA diameter was measured by ultrasound during and after IHG, and after occlusion release in 93 subjects. At 120 seconds after release of IHG, BA diameter increased by 9.99 +/- 8.3% (p <0.001) in 26 average-risk patients, increased 1.84 +/- 5.7% in 37 high-risk patients, and decreased 3.9 +/- 5.6% in 30 patients with CAD (p = 0.0001 for trend and p < 0.01 between groups). There was a good correlation between change in BA diameter to IHG and occlusion release (r = 0.763 and p = 0.0001). The capacity for IHG and BA occlusion to characterize subjects by group was comparable with the exception of high-risk patients versus patients with CAD (80.5% for IHG vs 71.6% for occlusion and release, p = 0.086). BA response to IHG may be useful for identifying risk factors, patients at risk and with preclinical CAD, and the assessment of treatment strategies.     

Evidence of endothelial dysfunction in angiographically normal coronary arteries of patients with coronary artery disease

Acetylcholine causes endothelium-dependent dilation of normal arteries in most animal species. The effect of acetylcholine on normal human coronary arteries is controversial. Pathologic studies and epicardial echocardiography have shown that diffuse atherosclerosis is often present despite angiographic evidence of discrete coronary artery disease (CAD). Therefore, we postulated that acetylcholine would cause vasoconstriction of coronary arteries that are angiographically normal in patients with CAD. Coronary artery diameter, measured by automated quantification of digitized cineangiograms, was determined before and after the intracoronary infusion of 0.2 mM acetylcholine at 0.8-1.6 ml/min. The diameter of stenotic or irregular segments of six atherosclerotic coronary arteries decreased from 1.80 +/- 0.42 mm before acetylcholine to 1.26 +/- 0.46 mm after acetylcholine (p = 0.0025). Acetylcholine had a significantly different effect on the diameter of two groups of coronary arteries that are angiographically normal. Acetylcholine caused a 0.16 +/- 0.09-mm increase in the diameter of 14 normal coronary arteries in patients without CAD, whereas it caused a 0.26 +/- 0.12-mm decrease in the diameter of 14 normal coronary arteries in patients with CAD (p less than 0.01). Thus, the normal response to intracoronary acetylcholine is vasodilation, suggesting that endothelium-derived relaxing factor is released from normal human coronary endothelium. The vasoconstrictive effect of acetylcholine in the angiographically normal coronary arteries of patients with CAD suggests the presence of a diffuse abnormality of endothelial function.     

Changes in left anterior descending coronary artery wall thickness detected by high resolution transthoracic echocardiography

Recently, it has been demonstrated that high-resolution transthoracic echocardiography (HRTTE) is able to detect differences in the wall thickness of the left anterior descending coronary artery (LAD) between patients with coronary artery disease (CAD) and normal volunteers. The aim of this study was to further validate this technique. One hundred ten volunteers, 58 patients with angiographically proved CAD and 52 control subjects, underwent assessments of their LADs using HRTTE. Anterior and posterior wall thicknesses differed between subjects in the CAD group and controls (1.9 +/- 0.6 vs 1.2 +/- 0.3 mm, p <0.001, and 1.8 +/- 0.5 vs 1.2 +/- 0.3 mm, p <0.001, respectively). External LAD diameter was also greater in subjects in the CAD group compared with controls (5.2 +/- 1.9 vs 4.4 +/- 0.9 mm, respectively, p = 0.01). However, there was no difference in luminal diameter between subjects in the CAD group and the controls (1.9 +/- 0.9 vs 2.1 +/- 0.8 mm, respectively, p = 0.3). In conclusion, HRTTE demonstrated that LAD wall thicknesses and external diameters in patients with CAD were significantly larger than in normal volunteers. Luminal diameter, however, was maintained in the 2 groups, indicating that subjects in the CAD group had undergone positive remodeling at the site measured. This objectively visualized evidence of coronary atherosclerosis with HRTTE would likely be undetected during coronary angiography.     

Flow-dependent vasomotor dysfunction of the popliteal artery related to common carotid artery intima-media thickness

This study was designed to assess a possible correlation between flow-mediated endothelium-dependent vasodilation in the popliteal artery and the intima-media thickness of the common carotid artery. Impaired vasodilation is one of early markers of atherosclerosis that has not been studied on the popliteal artery. An increase in intima-media thickness of the common carotid artery is also considered to be an indication of early stages of atherosclerosis. With use of ultrasound, the diameter of the popliteal artery was measured at rest and during reactive hyperemia after 5-minute arterial occlusion. Subsequently, the intima-media thickness was measured in left common carotid arteries in 27 patients with hyperlipidemia, in 10 patients with confirmed coronary artery disease, and in 20 healthy individuals. In healthy individuals, popliteal artery diameter increased by mean of 6.6 +/- 3.5% (p < 0.01) in relation to hyperemia. In patients with hyperlipidemia before therapy and in patients with coronary disease, no increase in diameter occurred (mean, 0.44% and -1.6%, respectively). The difference between healthy individuals and patients was statistically significant at p < 0.001. The popliteal artery seems to respond similarly to the brachial artery. When comparing the change in popliteal artery diameter and intima-media thickness of common carotid arteries, a strong negative correlation (r = -0.5713, p < 0.001) was observed in all subjects.     

Decreased insulin sensitivity is associated with the extent of coronary artery disease in patients with angina

BACKGROUND: Insulin resistance has been proposed as an important risk factor in the development of atherosclerosis. AIM: To evaluate the association of insulin resistance and coronary atherosclerosis, we investigated the correlation between insulin sensitivity and the degree of coronary stenosis in patients with angina pectoris. METHODS: The study population consisted of 74 subjects with angina (54 men and 20 women) aged from 31 to 73 years. Coronary angiograms were evaluated by three semiquantitative scoring systems (vessel score, stenosis score and extent score) to estimate the extent of focal and diffuse coronary artery disease (CAD). Insulin sensitivity (K(ITT)) was determined by the insulin tolerance test. RESULTS: There were significant correlations existed between K(ITT) and all three coronary scores. Multivariate analysis revealed significant and independent correlations of all three coronary scores with K(ITT) (vessel score: beta = -0.349, p = 0.004; stenosis score: beta = -0.487, p < 0.001; extent score: beta = -0.481, p < 0.001), even in patients without diabetes mellitus (vessel score: beta = -0.387, p = 0.008; stenosis score: beta = -0.469, p < 0.001; extent score: beta = -0.559, p < 0.001). K(ITT) was significantly lower in patient with diffuse CAD than without diffuse CAD (2.13 +/- 0.66 vs. 2.57 +/- 0.79%/min, p < 0.05). However, K(ITT) was not different between patients with and without focal CAD. CONCLUSIONS: Insulin sensitivity has statistically significant and independent associations with the extent of coronary stenosis. These results suggest that insulin resistance may play a major role in the development of diffuse coronary artery stenosis.     

Interrelation between the extent of atherosclerosis in the thoracic aorta, carotid intima-media thickness and the extent of coronary artery disease

Intima-media thickness (IMT) of the common carotid artery and atherosclerosis of the thoracic aorta have been shown to correlate with coronary artery disease (CAD). This study compares the relation between wall changes in the thoracic aorta and the carotid arteries and the angiographic severity and extent of atherosclerotic lesions in the coronary arteries in patients with verified CAD. Atherosclerotic wall changes in the carotid arteries and the thoracic aorta were measured by B-mode ultrasonography and transesophageal echocardiography (TEE), respectively, in 37 subjects aged 65+/-10 years with angiographically verified CAD. The mean value of the common carotid IMT of the right and left sides was 0.87+/-0.21 mm. All subjects had carotid plaques. TEE detected grades II-IV atherosclerotic plaques in the thoracic aorta in 32 of the 37 (86%) patients. A significant correlation was seen between the extent of coronary artery stenosis and aortic plaques score (r=0.46, p=0.008). Mean carotid IMT was also significantly correlated with coronary artery stenosis extent score (r=0.44, p=0.007). Moreover, a significant correlation was seen between the aortic plaque score and the mean carotid IMT (r=0.39, p=0.02). In conclusion, we found a clear and significant relationship between wall changes in the thoracic aorta, common carotid IMT and the angiographic extent of coronary artery stenosis in patients with severe CAD. These findings indicate a potential of B-mode ultrasonography of the carotid arteries and transesophageal echocardiographic aortic examination in the diagnostic and prognostic evaluation of patients with suspected CAD.     

Abnormal flow-mediated epicardial vasomotion in human coronary arteries is improved by angiotensin-converting enzyme inhibition: a potential role of bradykinin

OBJECTIVES: This study was performed to determine whether angiotensin converting enzyme (ACE) inhibition improves endothelium-dependent flow-mediated vasodilation in patients with atherosclerosis or its risk factors and whether this is mediated by enhanced bradykinin activity. BACKGROUND: Abnormal coronary vasomotion due to endothelial dysfunction contributes to myocardial ischemia in patients with atherosclerosis, and its reversal may have an antiischemic action. Previous studies have shown that ACE inhibition improves coronary endothelial responses to acetylcholine, but whether this is accompanied by improved responses to shear stress remains unknown. METHODS: In 19 patients with mild atherosclerosis, metabolic vasodilation was assessed during cardiac pacing. Pacing was repeated during separate intracoronary infusions of low-dose bradykinin (BK) and enalaprilat. Endothelium-dependent and -independent vasodilation was estimated with intracoronary BK and sodium nitroprusside respectively. RESULTS: Enalaprilat did not alter either resting coronary vascular tone or dilation with sodium nitroprusside, but potentiated BK-mediated dilation. Epicardial segments that constricted abnormally with pacing (-5+/-1%) dilated (3+/-2%) with pacing in the presence of enalaprilat (p = 0.002). Similarly, BK at a concentration (62.5 ng/min) that did not alter resting diameter in the constricting segments also improved the abnormal response to a 6+/-1% dilation (p < 0.001). Cardiac pacing-induced reduction in coronary vascular resistance of 27+/-4% (p < 0.001) remained unchanged after enalaprilat. CONCLUSIONS: Thus ACE inhibition: A) selectively improved endothelium-dependent but not-independent dilation, and B) abolished abnormal flow-mediated epicardial vasomotion in patients with endothelial dysfunction, in part, by increasing endogenous BK activity.     

Relationship of metabolic syndrome with quantum of coronary artery disease in Indian patients with chronic stable angina

Background: The current study was aimed to ascertain presence and severity of coronary artery lesions in patients of Type 2 diabetic mellitus (DM) with coronary artery disease (CAD), in our population, by using scoring system analysis of the coronary angiography. Methods: 147 consecutive patients with Type 2 DM of chronic stable angina (CSA) were enrolled in the study with 147 age- and sex-matched patients of CSA who did not have diabetes to serve as control. All of them underwent coronary angiography and were evaluated by using four scores to quantify the coronary artery lesions. The scores analyzed were coronary score, extent score, severity score, and atherosclerosis score. Other major risk factors such as smoking and hypertension lipid profile were also evaluated. Results: Type 2 diabetics with CAD had higher coronary score (0.91 +/- 0.63 in diabetics vs. 0.43 +/- 0.39, p < 0.001), extent score (4.91 +/- 3.1 vs. 2.3 +/- 1.8, p < 0.001), severity score (1.85 +/- 0.41 vs. 1.2 +/- 0.32, p < 0.001), and atherosclerosis score (0.52 +/- 0.31 vs. 0.21 +/- 0.26, p < 0.001) as compared to non-diabetics with CAD. Left main stem involvement, 2-vessel disease, and 3-vessel disease were also more frequent in the diabetics. These diabetes also had higher incidence of obesity, hypertension, and dyslipidemia. Conclusions: In our population, diabetics suffer from higher prevalence of diffuse and extensive coronary atherosclerosis. The grades of stenosis in coronary arteries are also higher in diabetic patients when compared with non-diabetics with CAD, as was the prevalence of other components of the metabolic syndrome.     

Common carotid intima-media thickness is correlated with myocardial flow reserve in patients with coronary artery disease: a useful non-invasive indicator of coronary atherosclerosis

BACKGROUND: The common carotid intima-media thickness (IMT) is correlated with the angiographically determined coronary artery stenosis. However, their correlation is weak, which limits the clinical application of the IMT as a predictor of coronary artery stenosis. The IMT reflects diffuse early-phase atherosclerosis, whereas the angiographically determined coronary artery stenosis is a late-phase phenomenon. The latter is localized and rapidly progressive with plaque rupture and acute thrombosis. Instead of the angiographically determined coronary artery stenosis, we employed myocardial flow reserve (MFR) that reflects diffuse early-phase coronary atherosclerosis and impaired coronary vasodilatation function. We evaluated the relationship between the IMT and the MFR. METHODS: Twenty-three patients with angiographically diagnosed coronary artery disease (CAD) underwent B-mode ultrasound examination to measure their common carotid IMT and positron emission tomography (PET) with dipyridamole intervention to obtain their MFR. We also performed B-mode ultrasound examination in 21 patients with hypertension without CAD and in 15 control subjects. RESULTS: The common carotid IMT in patients with CAD was thickened (0.92+/-0.15 vs. 0.81+/-0.14 mm in patients with hypertension (P<0.05) and 0.69+/-0.13 mm in control subjects (P<0.01)). The IMT was inversely correlated with the MFR (r=0.51, P<0.01). The correlations between the MFR and most of the coronary risk factors (age, blood pressure, serum cholesterol level and triglyceride level, HbA1c level, smoking index) did not reach statistical significance. CONCLUSIONS: Thickened common carotid IMT is also an indicator of reduced MFR or early-phase coronary atherosclerosis.     

Relationship between plasma oxidized low-density lipoprotein and the coronary vasomotor response to acetylcholine in patients with coronary artery disease

The present study examined the relation of plasma oxidized low-density lipoprotein (LDL) levels to plasma LDL cholesterol levels and the impairment of endothelium-dependent coronary vasorelaxation in patients with coronary artery disease (CAD). In the first study, the relationship between plasma levels of oxidized LDL and LDL cholesterol were investigated in 88 patients with CAD. In the second study, the changes in the diameter of the left anterior descending (LAD) and the left circumflex (LCX) coronary arteries were measured after intracoronary administration of acetylcholine (15 microg) and isosorbide dinitrate (2.5 mg) in 15 patients with CAD. Plasma oxidized LDL levels were determined with a sandwich enzyme-linked immunosorbent assay. Plasma oxidized LDL levels did not correlate with plasma LDL cholesterol levels (r=-0.03, p=NS). The % diameter changes (mean+/-SEM) in the LAD and LCX after intracoronary acetylcholine were -8.3+/-3.5% and -10+/-4.2%, respectively. The % diameter changes in the LAD and LCX after intracoronary isosorbide dinitrate were 23+/-4.8% and 23+/-5.1%, respectively. The % diameter changes in the LAD and LCX inversely correlated with plasma oxidized LDL levels after intracoronary acetylcholine (LAD: r=-0.55, p=0.03; LCX: r=-0.59, p=0.02), but were not after intracoronary isosorbide dinitrate. Plasma LDL cholesterol, triglyceride, and high-density lipoprotein cholesterol levels did not correlate with the coronary vasoreaction to acetylcholine. In conclusion, plasma oxidized LDL levels do not correlate with plasma LDL-cholesterol levels and are related to impairment of endothelium-dependent coronary vasodilation in patients with CAD.     

Asymmetrical dimethylarginine: a novel risk factor for coronary artery disease

BACKGROUND: Asymmetrical dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase and has been associated with systemic atherosclerosis; however, the role of ADMA in patients with coronary artery disease (CAD) has not been investigated. HYPOTHESIS: The present study was designed to determine whether the plasma ADMA level predicts the presence of CAD independently, and whether the plasma ADMA level correlates with the extent and severity of coronary atherosclerosis. METHODS: In all, 97 consecutive patients with angina and positive exercise stress test were enrolled prospectively for coronary angiography. According to the result of angiography, the subjects were divided into two groups: Group I (n = 46): patients with normal coronary artery or mild CAD (< 50% stenosis of major coronary arteries); Group 2 (n = 51): patients with significant CAD (> or = 50% stenosis of majorcoronary arteries). Plasma levels of ADMA and L-arginine were determined by high-performance liquid chromatography. In addition, we used coronary atherosclerotic score to assess the extent and severity of CAD. RESULTS: The plasma levels of ADMA in Group 2 patients were significantly higher than those in Group 1 patients (0.66 +/- 0.17 microM vs. 0.44 +/- 0.09 microM, p < 0.001); these were accompanied by significantly lower plasma L-arginine/ADMA ratio in patients with significant CAD (Group 1 vs. 2: 194.0 +/- 55.3 vs. 136.7 +/- 50.3, p < 0.001). In a multivariate stepwise logistic regression analysis, both plasma ADMA level and plasma L-arginine/ADMA ratio were identified as independent predictors for CAD. Moreover, there were significant positive and negative correlations between coronary atherosclerotic score and plasma ADMA level as well as plasma L-arginine/ADMA ratio, respectively (plasma ADMA level: r = 0.518, p < 0.001; L-arginine/ADMA ratio: r = -0.430, p < 0.001). CONCLUSIONS: Both plasma ADMA level and plasma L-arginine/ADMA ratio were useful in predicting the presence of significant CAD and correlated significantly with the extent and severity of coronary atherosclerosis. Our findings suggest that plasma ADMA level may be a novel marker of CAD.     

Atherosclerotic burden in coronary and peripheral arteries in patients with first clinical manifestation of coronary artery disease

The aim of our study was to assess the atherosclerotic burden in patients with the first symptoms of coronary artery disease (CAD). The study population consisted of 100 consecutive patients (new-onset severe angina or myocardial infarction) and 70 age- and sex-matched volunteers without symptoms of CAD. Functional and morphologic atherosclerotic markers were sought in carotid, brachial, and femoral arteries of all subjects by means of high-resolution ultrasonography while coronary arteriography was performed in the CAD patients only. A total of 347 coronary lesions, 230 (66%) of them obstructive, were discovered in the CAD patients as well as 105 peripheral plaques, of which 26 (25%) were obstructive. The mean percent diameter stenosis of the culprit coronary lesion was 83.8% ± 15.8%, the mean vessel score 1.7 ± 0.8 (range 0–3), the mean stenosis score 19.8 (range 1.5–89.0), and the mean extent score 49.1% (range 10%–65%). Endothelium-dependent vasodilation, as assessed by the brachial flow-mediated response (FMR), was reduced by 50% in the CAD patients (P < 0.001 vs controls); it was also observed in carotid and femoral arteries by the cold pressor test. Furthermore, endothelium-independent vasodilation was significantly impaired in all investigated peripheral arteries of the CAD patients (P < 0.05–0.001 vs controls). Intima-media thickness (IMT) was increased in the carotid arteries of the CAD patients by 43%, in brachial arteries by 20%, and in femoral arteries by 57% (P < 0.01–0.001 vs controls). Decreased FMR or increased carotid IMT were found to be independent risk factors for the CAD, and they correlated with the coronary vessel and extent scores. Peripheral atherosclerosis was more developed in older patients but was similar in patients with different clinical presentation. Hyperlipidemia, a positive family history, and smoking were associated with premature CAD. In conclusion, the atherosclerotic process was quite advanced in coronary as well as peripheral arteries of our patients with the first clinical presentation of CAD. Received: February 1, 2002 / Accepted: May 24, 2002 Correspondence to A. Cerne     

Short-term sibutramine therapy is associated with weight loss and improved endothelial function in obese patients with coronary artery disease

In obese patients with coronary artery disease (CAD), the vascular endothelium is usually impaired, and the modification or reversal of endothelial dysfunction may significantly enhance treatment. Sibutramine, a serotonin and norepinephrine transporter blocker, is widely used as an adjunctive obesity treatment, but its impact on endothelial function in obese patients with CAD has not yet been investigated. Eighty consecutive obese, nonhypertensive, stable patients with CAD (65 men; mean age 65 +/- 11 years, mean body mass index 32 +/- 3 kg/m2) were randomly assigned to either sibutramine 10 mg/day (n = 40) or routine treatment (n = 40; controls) for 4 months. The percentage improvement in endothelium-dependent brachial artery flow-mediated dilation (%FMD) and endothelium-independent nitroglycerin-mediated vasodilation were assessed at baseline and after 4 months using high-resolution ultrasound. At baseline, all patients had %FMD of 5.4 +/- 3.1% and percentage improvement in endothelium-independent nitroglycerin-mediated vasodilation of 9.2 +/- 2.9%, showing no significant differences. After 4 months, however, initial body weight was reduced by 11.4 +/- 1.2% in the sibutramine group compared with only 2.2 +/- 1.3% in controls (p <0.001), demonstrating a significant improvement in postintervention %FMD (8.9 +/- 2.4%, p = 0.01, compared with baseline) in the sibutramine group compared with controls (5.2 +/- 3.6%, p = 0.68, compared with baseline). No significant therapeutic effect on the percentage improvement in endothelium-independent nitroglycerin-mediated vasodilation was seen in either group (9.2 +/- 2.5% vs 9.1 +/- 3.0%, respectively, p = 0.792). In addition, sibutramine therapy was associated with significant C-reactive protein reduction compared with routine treatment (44% vs 9%, p = 0.035). Thus, short-term therapy with sibutramine, together with diet and lifestyle intervention, is associated with improved endothelial function assessed by brachial artery %FMD in nonhypertensive, stable patients with CAD.     

Angiographic coronary artery disease is associated with progressively higher levels of fasting plasma glucose

This study evaluated the association between progressively higher levels of fasting glycemia (G) and insulin resistance parameters with coronary artery disease (CAD) in patients referred for coronary angiography. All 145 patients (age 58.4+/-0.9 years, 51.7% men) underwent clinical and laboratory evaluation before coronary angiography and subjects were divided into four groups: normal (N, <88 mg/dl), high-normal (H-N, 89-99 mg/dl), impaired fasting glucose (IFG, 100-125 mg/dl) and diabetes (DM, >126 mg/dl or known diabetics). Arteriographic evidence of CAD was determined by two criteria: (1) a 30% or greater diameter stenosis in at least one major coronary artery; (2) a 70% or greater diameter stenosis in at least one major coronary artery. HOMA-IR increased progressively according to each group: N=1.74+/-0.2, H-N=3.14+/-0.3, IFG=4.67+/-0.6 and DM=8.00+/-2.9; p=0.001. The proportion of patients with CAD according to both criteria increased with each G level: CAD criteria 1: N=39.4%, H-N=50%, IFG=60% and DM=69.6%, p=0.006; CAD criteria 2: N=27.3%, H-N=30%, IFG=36% and DM=50%, p=0.03. We demonstrated a significant association between subtle disturbances of the glucose metabolism, assessed by subnormal levels of fasting glucose and insulin resistance parameters, and angiographically documented coronary artery disease.