Early increase in levels of soluble inter-cellular adhesion molecule-1 (sICAM-1); potential risk factor for the acute coronary syndromes.

BACKGROUND: Studies have shown disparate results in relation to the role of plasma concentrations of cell adhesion molecules in atherosclerosis. Moreover, the differentiation of primary vs secondary alterations of these markers, in response to myocardial injury, has not been clear. We measured specific soluble cell adhesion molecules and inflammatory markers in men admitted acutely with chest pain and compared them to healthy controls. METHODS AND RESULTS: We prospectively studied men (total n=241), admitted acutely with chest pain (7.4+/-9.4 h, 71% within 10 h), unstable angina (n=67), acute myocardial infarction (n=47) and chest pain without ischaemic heart disease (n=45) and compared them with a stratified sample of randomly selected healthy controls (n=82). Soluble intercellular adhesion molecule (sICAM-1), endothelial selectin, vascular cell adhesion molecule, interleukin-6 and C-reactive protein were measured by ELISA and P-selectin expression by flow cytometry. Multiple regression analysis was used to control for the impact of classical risk factors. At baseline ICAM-1, interleukin-6 and C-reactive protein were significantly elevated in patient groups whereas no difference in vascular cell adhesion molecule or endothelial selectin was found. At 3 month follow-up, ICAM-1 level was unchanged in ischaemic heart disease patients. In all groups C-reactive protein and interleukin-6 levels were lower at review. ICAM-1 levels at follow-up were higher in ischaemic heart disease groups (but not in chest pain without ischaemic heart disease) relative to controls and remained so only in the unstable angina group following regression. sICAM-1, interleukin-6 and C-reactive protein strongly correlated with smoking. In the acute phase, ICAM-1 was confounded by smoking following regression and C-reactive protein and interleukin-6 remained significant in both ischaemic heart disease groups after multiple regression. There was no relationship to events which occurred in 23% of ischaemic heart disease patients (further acute myocardial infarction 5.3%, sudden cardiac death 0.9% or recurrent angina 16.7%). CONCLUSION: We found an inflammatory response with higher sICAM-1, interleukin-6 and C-reactive protein in patients presenting soon after developing an acute coronary syndrome. As sICAM-1 was not affected by the acute event this plasma marker may be an important risk factor for the development of the acute coronary syndrome, particularly unstable angina.     

Comparison of serum levels of inflammatory markers and allelic variant of interleukin-6 in patients with acute coronary syndrome and stable angina pectoris

OBJECTIVES: Although the relationship between atherosclerosis and inflammatory cells has been recognized in recent years, the effect of interleukin-6 (IL-6) genetic variants associated with atherosclerosis is still controversial. Therefore, we investigated the association between IL-6 polymorphism and levels of IL-6 in patients with coronary artery disease (CAD). METHODS: We conducted a case-control study on 294 unrelated participants who were referred to the cardiology department of the university hospital for coronary angiography because of suspected ischemic heart disease. Group I comprised patients with clinically acute coronary syndrome, and group II comprised patients (individuals matched for age and sex) with clinically stable angina pectoris; both groups were categorized, based on their angiographic findings, as either having angiographically documented less extensive CAD (1 vessel narrowed) or extensive CAD (> or =2 vessels narrowed). They were studied to examine effect of the IL-6 gene variants in CAD. Genotyping was determined by polymerase chain reaction. RESULTS: The IL-6 G/C-174 polymorphism was found in 19 of 106 (18%) in group I and in four of 188 (2%) in group II (P<0.001). Median IL-6 levels were significantly higher in group I (6.7+/-13.6 pg/ml) than in group II (4.1+/-3.8 pg/ml) (P<0.05). In addition, high sensitivity C-reactive protein levels were significantly higher in group I (8.2+/-6.2 mg/dl) than in group II (4.6+/-3.4 mg/dl) (P<0.001). CONCLUSION: These results demonstrated that the presence of the IL-6 G/C-174 polymorphism and increased IL-6 and high sensitivity C-reactive protein levels are strongly associated with the inflammatory system and the course of clinical and hemodynamically significant CAD.     

Left atrioventricular plane displacement at rest is reduced in relation to severity of coronary artery disease irrespective of prior myocardial infarction.

OBJECTIVE: To examine whether left atrioventricular plane displacement (AVPD) at rest was related to severity of coronary atherosclerosis. DESIGN AND PATIENTS: Global and regional left AVPD was evaluated by echocardiography in 159 consecutive patients with significant stenoses at coronary angiography and in 15 age-matched healthy controls. The setting was the University hospital with a primary catchment area of 250,000 inhabitants. RESULTS: Mean AVPD in controls, patients with one-, two-, and three-vessel disease was 13.5+/-1.1, 12.4+/-1.5, 11.3+/-2.2 and 10.9+/-2.1 mm, respectively (P<0.0001). Similar significant differences were found both in those with (n=69) and without (n=90) a diagnosis of prior myocardial infarction. Regional AVPD did not correspond to the localization of infarction or coronary atherosclerosis. CONCLUSION: Irrespective of a diagnosis of prior myocardial infarction, left AVPD was related to the degree and extent of coronary artery disease. It was significantly decreased compared to controls in patients with one-vessel disease, and was further decreased with increasing extent of coronary atherosclerosis. Determination of regional left AVPD could not be used to identify regions perfused by stenotic coronary arteries or regions affected by prior myocardial infarction.     

Relationship of Chlamydia pneumoniae infection to severity of coronary atherosclerosis in patients with chronic coronary artery disease and with normal coronary arteries]

OBJECTIVES: Recent studies have demonstrated an association between infection with Chlamydia (C.) pneumoniae and coronary artery disease. However, the association is less clear in the Japanese population. The relationship of C. pneumoniae infection to severity of coronary atherosclerosis was investigated in patients with chronic coronary artery disease and with normal coronary arteries. METHODS: Serum levels of IgA and IgG antibodies to C. pneumoniae outer membrane complex were measured by enzyme-linked immunosorbent assay and C-reactive protein (CRP) analyses in 130 patients who underwent coronary angiography. Patients with unstable angina and recent myocardial infarction were excluded. Results were divided into three groups according to Gensini coronary score (GCS): normal (n = 19, GCS = 0); mild atherosclerosis (n = 56, GCS = 1-19); and severe atherosclerosis (n = 55, GCS > or = 20). RESULTS: Cut off indices of IgA and IgG in the atherosclerosis groups (severe: 1.53 +/- 0.72 and 1.67 +/- 0.97, mild: 1.58 +/- 0.92 and 1.42 +/- 0.86, respectively) were higher than in the normal group (1.22 +/- 0.59 and 1.28 +/- 0.82), but there were no significant differences. There were no correlations between indices of IgA and IgG, and GCS. The normal CRP group (n = 118, < 0.3 mg/dl) and the high CRP group (n = 12, > or = 0.3 mg/dl) showed no differences in IgA and IgG indices and GCS. CONCLUSIONS: Serum antibody indices against C. pneumoniae are not associated with the severity of coronary atherosclerosis in chronic stable coronary artery disease.     

Elevated C-reactive protein levels and coronary microvascular dysfunction in patients with coronary artery disease.

AIMS: It is still unknown whether elevated C-reactive protein levels are responsible for coronary microcirculatory dysfunction in patients with coronary artery disease (CAD). This study was aimed at evaluating the association between C-reactive protein levels and endothelium-dependent and endothelium-independent coronary blood flow (CBF) responses in non-culprit arteries of patients with CAD. METHODS AND RESULTS: We studied 28 patients (14 with normal and 14 with elevated C-reactive protein levels, >5 mg/L) with single-vessel disease and otherwise angiographically normal coronary arteries undergoing percutaneous transluminal coronary angioplasty (PTCA). CBF was measured in the non-PTCA vessel using an intracoronary Doppler guide wire and quantitative coronary angiography at baseline, after intracoronary infusion of substance P and of adenosine, and expressed as per cent change from baseline. The increases in CBF during infusion of substance P and of adenosine were lesser in patients with elevated than in those with normal C-reactive protein levels (34+/-22 vs. 61+/-34%, P=0.04 and 131+/-53 vs. 189+/-89%, P=0.03, respectively). Multivariable analysis identified elevated C-reactive protein level as the only independent predictor of reduced response to substance P (P=0.01) and adenosine (P=0.02). CONCLUSION: In patients with CAD, evidence of systemic inflammation is independently associated with endothelium-dependent and endothelium-independent coronary microvascular dysfunction, which, in turn, may be critical to precipitate myocardial ischaemia, in particular, in unstable patients.     

Admission C-reactive protein levels and 30-day mortality in patients with acute myocardial infarction

BACKGROUND: Elevated C-reactive protein levels are associated with an increased risk of subsequent cardiovascular events in patients with unstable angina. However, limited information is available concerning the value of C-reactive protein levels in patients with acute myocardial infarction. METHODS: We prospectively studied 448 consecutive patients (mean [+/- SD] age, 60 +/- 12 years) with acute myocardial infarction. Serum C-reactive protein levels were measured within 12 to 24 hours of symptom onset, and divided into tertiles. Infarct size was determined by echocardiographic examination that was performed on day 2 or 3. Patients were followed for 30 days for mortality and subsequent cardiac events. RESULTS: At 30 days, 4 deaths (3%) occurred in patients in the lowest C-reactive protein tertile, 15 (10%) in patients in the middle tertile (P = 0.02 vs. the lowest tertile), and 33 (22%) in patients in the highest tertile (P <0.001 vs. the lowest tertile). In a multivariate analysis, C-reactive protein in the upper tertile was associated with 30-day mortality (relative risk = 3.0; 95% confidence interval [CI]: 1.3 to 7.2; P = 0.01) and the development of heart failure (odds ratio = 2.6; 95% CI: 1.5 to 4.6; P = 0.0006). C-reactive protein levels were not associated with the development of postinfarction angina, recurrent myocardial infarction, or the need for revascularization. CONCLUSION: Plasma C-reactive protein level obtained within 12 to 24 hours of symptom onset is an independent marker of 30-day mortality and the development of heart failure in patients with acute myocardial infarction. These findings suggest that C-reactive protein levels may be related to inflammatory processes associated with infarct expansion and postinfarction ventricular remodeling.     

State of the distal bed of the cardiac coronary arteries in ischemic heart disease]

The condition of the distal bed of the cardiac coronary arteries was studied in 150 patients with ischemic heart disease. It proved to be affected with stenotic atherosclerosis in 20,6% of cases. The distal bed in patients with the chronic stage of ischemic heart disease hardly differed from that in patients with acute myocardial infarction. Total revascularization may be accomplished in 33% of cases with affection of three vessels of the cardiac coronary bed with stenotic atherosclerosis and in 96,5% of cases with affection of one vessel.     

Significance of exercise induced ST elevation in patient without a history of previous myocardial infarct

Between 1980 and 1995, we observed twenty-five patients (22 males, 3 females) at the mean age of 50.6 +/- 13 years, without previous myocardial infarction who presented exercise induced ST elevation on a bicycle stress test. METHODS: Significant ST elevation was defined as a > or = 1 mm change present in > or = 1 lead measured 0.08 sec after the J point and in 3 consecutive beats. All patients have undergone coronary angiography in the days following the exercise test. RESULTS: Most of patients (56%) presented a history of typical angina that was either purely exertional (8 pts) or also occurred at rest (6 pts). Others (36%) had non typical angina or no angina (8%); 78% of pts were smokers. Sixteen patients (group I) had ST elevation during exercise (exercise duration: 7.6 +/- 4 min; peak heart rate: 135.5 +/- 29 batt/min; ST = 3.5 +/- 1.5 mm) and nine (group II) during the recovery phase (exercise duration 16.3 +/- 1.6 min; p < 0.05; peak heart rate 168 +/- 22 batt/min; p < 0.05; ST: 5.8 +/- 3 mm; p < 0.05). In group I, 1 patient had no vessel disease, 12 had one vessel disease, 3 had multivessel disease with 6 cases of hypersevere coronary stenose (> 90%). In group II, 4 patients had normal coronary arteries, there was one vessel coronary artery disease in 4 patients and multivessel in one subject, without hypersevere coronary stenosis. Correlation between anatomic location of stenosis and electrocardiographic ST elevation was excellent, particularly in case of single vessel disease (100%). All patients underwent one or more new exercise tests after therapeutic intervention (surgery n = 3; angioplasty n = 7; medical treatment n = 15), only 2 patients had persistent exercise induced ST elevation. During follow-up (5 +/- 3 years), 3 patients died (2 cardiac deaths) and 3 had recurrent angina controlled by new treatment. CONCLUSION: Exercise-induced ST elevation is a rare phenomenon in patients without prior myocardial infarction. When occurring purely during exercise, coronary lesions are frequent and often servere, in the other hand ST elevation of the recovery phase is frequently associate with normal arteries or less severe lesions. In most cases, revascularisation or medical therapy can abolish clinical and electrocardiographic abnormalities.     

No long-lasting or intermittent mast cell activation in acute coronary syndromes

BACKGROUND: Unstable coronary syndromes, such as acute myocardial infarction and unstable angina pectoris are mostly due to rupture of an atherosclerotic plaque. Recently mast cells were found to participate actively in the inflammatory process of atherosclerosis by excreting proteolytic and pro-inflammatory substances with the ability to cause plaque instability and rupture. Mast cell activity can be determined by measuring serum levels of tryptase, as has been demonstrated in patients with anaphylaxis and mastcytosis. HYPOTHESIS: Acute coronary events (acute myocardial infarction and unstable angina pectoris) are associated with increased mast cell activity, reflected by elevated serum tryptase levels. METHODS: Serum levels of tryptase were determined in the following three groups of patients: 13 patients with acute myocardial infarction, 10 patients with unstable angina pectoris, and 14 patients without ischaemic cardiovascular disease who were used as controls. Patients with known IgE mediated allergic diseases and/or anti-histaminical drugs were excluded. RESULTS: The groups were comparable for sex, blood pressure, smoking and cholesterol levels. The controls tended to be younger (P=0.05). Levels of tryptase did not differ between patients with acute myocardial infarction (7.9+/-4.6 microg/l), unstable angina pectoris (6.0+/-2.1 microg/l) or controls (6.9+/-4.1 microg/l), nor could a relation with levels of C-reactive protein be demonstrated. CONCLUSION: Serum levels of tryptase are not elevated in patients with acute coronary syndromes. This implies that increased mast cell activity, if any, in unstable coronary syndromes is not reflected systemically. Other, more specific methods will be needed to determine the activity of the mast cell in vivo.     

High-sensitivity C-reactive protein and cardiovascular risk in patients with coronary heart disease

High-sensitivity C-reactive protein levels have received widespread attention because of a multitude of prospective studies that have shown that high levels of high-sensitivity C-reactive protein identify increased risk of initial cardiovascular events in coronary heart disease patients and increased risk of recurrent cardiac events in patients with stable and unstable angina, patients with acute myocardial infarction, and patients undergoing elective coronary revascularization procedures. In contrast to several other inflammatory markers, high-sensitivity C-reactive protein measurements are standardized and reproducible. The clinical significance of a reliable inflammatory marker includes identification of high-risk individuals, a gauge to monitor the activity of the disease, and a potential therapeutic target to alter the inflammatory component of the disease process. This review focuses on the importance of high-sensitivity C-reactive protein in cardiovascular risk stratification in coronary heart disease patients and discusses several preventive therapies that may reduce cardiovascular risk through reduction in high-sensitivity C-reactive protein.     

Normal coronary arteries are rare in young patients with acute myocardial infarction.

OBJECTIVE: To delineate the angiographic extent of coronary atherosclerosis in young patients (<45 years) with acute myocardial infarction (MI). BACKGROUND: Prior studies suggest 20% of young patients with acute MI have normal coronary arteries. However, most such studies defined "normal" as absence of stenoses >50% luminal diameter, ignoring the presence of nonflow limiting disease that may harbor culprit plaques. METHODS: We retrospectively analyzed 131 patients <45 years old with ST-segment elevation MI undergoing emergency catheterization. Angiograms were analyzed for the presence and extent of disease, including lesion "complexity" indicative of plaque instability. "Normal" vessels were defined as absence of any disease. RESULTS: Mean patient age was 40 +/- 7 years. The infarct related artery and an obvious complex culprit lesion was identified in all (100%) cases (left anterior descending 44%, right coronary 38%, and circumflex 18%). Single vessel disease involving the culprit vessel only was identified in 60% of cases, whereas additional disease was found in 40% of others (two-vessel in 29% and three-vessel disease in 11% of patients). CONCLUSION: These findings demonstrate that young patients with acute MI typically manifest an identifiable complex culprit atherosclerotic coronary lesion. Furthermore, they often have multivessel atherosclerosis.     

C-reactive protein and coronary events following percutaneous coronary angioplasty

PURPOSE: We investigated the associations between baseline C-reactive protein levels in patients undergoing percutaneous coronary angioplasty and death, nonfatal myocardial infarction, and repeat revascularization during 14 months of follow-up. METHODS: In a single-center, prospective, cohort study, plasma levels of C-reactive protein were measured in 1458 consecutive patients undergoing elective or urgent coronary angioplasty. Patients were followed at 12 to 14 months for the occurrence of death, nonfatal myocardial infarction, and repeat revascularization. RESULTS: The incidence of death or myocardial infarction was 6.1% (44/716) in patients with an increased C-reactive protein level (>3 mg/L) and 1.5% (11/742) in patients with a normal level (relative risk [RR] = 4.4; 95% confidence interval [CI]: 2.2 to 8.5; P <0.0001). In a multivariate logistic regression model, an increased C-reactive protein level was an independent predictor of death or nonfatal myocardial infarction (RR = 3.6; 95% CI: 1.8 to 7.2; P =0.0001). The incidence of repeat revascularization was similar in patients with or without an increased C-reactive protein level (23% [168/716] vs. 22% [163/742], P = 0.54). Statin therapy at the time of the procedure was associated with a lower mean (+/- SD) C-reactive protein level (5.8 +/- 9.7 mg/L vs. 7.2 +/- 12.1 mg/L, P =0.02), but was not associated with the risk of death, nonfatal myocardial infarction, and repeat revascularization during follow-up. CONCLUSION: An increased C-reactive protein level is an independent prognostic indicator for the occurrence of death or nonfatal myocardial infarction following coronary angioplasty, but is not associated with the need for repeat revascularization.     

Clinical diagnosis and pathogenesis of myocardial infarction complicated by hypertrophic cardiomyopathy: review of eight cases

Among 144 patients with hypertrophic cardiomyopathy, eight (58.3 +/- 7.0 years, M:F = 7:1) had complicating myocardial infarction, which was diagnosed clinically and by elevated cardiac enzymes or new Q-waves on electrocardiography. Coronary occlusion or stenosis evidenced by coronary angiography and nuclear cardiological findings were investigated. In six of the eight patients, coronary atherosclerosis caused infarction. These patients had many coronary risk factors compared to the other two patients. Sixteen of the 144 patients (11%) with hypertrophic cardiomyopathy had coronary atherosclerosis, the rate of which is reportedly 10 to 20%. Two of the eight patients had no coronary atherosclerosis. One patient had a diffusely spastic diathesis provoked by the intravenous administration of ergonovine maleate during coronary angiography, suggesting that coronary spasm caused myocardial infarction. The other patient had recurrent episodes of supraventricular tachyarrhythmia and no evidence of spasm during coronary angiography, suggesting coronary embolism as a cause of myocardial infarction. Myocardial infarction in patients with hypertrophic cardiomyopathy and normal coronary arteries as advocated by Maron et al. may have such pathogenesis. We conclude that coronary angiography may be mandatory in patients with hypertrophic cardiomyopathy, especially those who have many coronary risk factors and anginal symptoms. In these patients, ST-T changes and abnormal Q-waves on electrocardiography sometimes may be misleading when diagnosing the occurrence of acute myocardial infarction by electrocardiography alone. In such cases, infarct-avid scintigraphy with 99 m-Tc pyrophosphate is preferable.     

Role of interleukin-17 and interleukin-17-induced cytokines interleukin-6 and interleukin-8 in unstable coronary artery disease

BACKGROUND: Atherosclerosis is a chronic inflammatory disease and interleukins are considered to play a key role in the chronic vascular inflammatory response that is typical of atherosclerosis. The serum levels of several of these cytokines have been found to positively correlate with coronary arterial disease and its sequelae. AIM: The aim of our study was to evaluate the levels of a comparatively new cytokine IL-17, in patients with stable and unstable coronary artery disease in order to assess whether unstable coronary artery disease patients had higher IL-17 levels. MATERIALS AND METHODS: We analyzed the concentrations of IL-17, IL-6, IL-8 and IL-10 using enzyme-linked immunosorbent assay and heat-sensitive C-reactive protein using latex particle-enhanced immunoturbidimetry in 58 consecutive unselected patients divided into three groups: stable angina (n=14), unstable angina (n=24) and acute myocardial infarction (n=20). We further compared them with 20 healthy controls. These 58 patients were also angiographically studied and divided into two groups: simple lesion (n=22) and complex lesion (n=36), on the basis of the coronary plaque morphology. RESULTS: Our results show increased concentrations of the proinflammatory cytokines IL-17, IL-6, IL-8 and heat-sensitive C-reactive protein, and decreased concentration of IL-10 in plasma of unstable angina and acute myocardial infarction patients. Plasma concentration of IL-17 was also positively correlated with plasma concentrations of IL-6 and heat-sensitive C-reactive protein. Our findings further showed that IL-17 values were higher in patients having angiographically visible complex types of lesions but no difference was observed between complex and simple lesion morphology patients. CONCLUSION: In conclusion, these findings point towards a role of inflammation in the form of increased activity of IL-17, IL-6 and IL-8 in patients of unstable angina and acute myocardial infarction and thus suggest that IL-17-driven inflammation may play a role in the promotion of clinical instability in patients with coronary artery disease.     

Prognostic value of levels of brain natriuretic peptide and genetic factors in patients after acute coronary syndrome

Prognostication of the course of disease in patients with high risk of unfavorable outcome of ischemic heart disease (IHD) is of great importance for creation of individualized strategy of treatment. We have investigated contribution of levels of brain natriuretic peptide (BNP) and genetic factors in the risk of development of complications of atherosclerosis in patients who have had acute coronary syndrome. We started to follow 324 patients on day 10 of stable state after acute coronary syndrome (55.1% with Q-wave myocardial infarction, 18.5% with non-Q myocardial infarction, 25.5% with unstable angina, men BNP level 624.5+/-32.13 mol/ml [70.3 - 4276.6]). Duration of followup was 2 years. Baseline BNP level in patients with unfavorable outcome during followup (fatal and nonfatal myocardial infarction and stroke) was 872.47+/-91.42 compared with 592.45+/-35.97 mol/ml in patients without unfavorable outcome (p=0,001). Multifactorial Cox analysis showed that carriage of T allele of polymorphic marker (--1654) of protein C gene, elevated BNP level, symptomatic atherosclerosis of peripheral arteries, history of MI, and use of thiazide diuretics were independently associated with unfavorable outcomes (p=0.026, <0.0001, <0.0001, =0.001, =0.024, respectively). Thus genetic factors and study of BNP allow to improve prediction of unfavorable outcome after exacerbation of IHD.     

Amounts of coronary arterial narrowing by atherosclerotic plaque at necropsy in patients with lower extremity amputation.

In 26 patients (mean age at death 68 +/- 9 years) who had undergone amputation (at mean age 63 +/- 12 years) of 1 or both lower extremities due to severe peripheral arterial atherosclerosis, the amounts of narrowing at necropsy in the 4 major (left main, left anterior descending, left circumflex, and right) epicardial coronary arteries were determined. During life, 15 of the 26 patients (58%) had symptoms of myocardial ischemia: angina pectoris alone in 1, acute myocardial infarction alone in 5, and angina and/or infarction plus congestive heart failure or sudden coronary death in 9. Twelve of the 26 patients (42%) died from consequences of myocardial ischemia: acute myocardial infarction in 5, sudden coronary death in 3, chronic congestive heart failure in 3, and shortly after coronary bypass surgery in 1. Grossly visible left ventricular necrosis or fibrosis, or both, was present in 21 patients (81%). Of the 26 patients, 24 (92%) had narrowing 76 to 100% in cross-sectional area of 1 or more major coronary arteries by atherosclerotic plaque. The mean number of coronary arteries per patient severely (> 75%) narrowed was 2.3 +/- 1.0/4.0. Of the 104 major coronary arteries in the 26 patients, 60 (58%) were narrowed > 75% in cross-sectional area by plaque. The 4 major coronary arteries in the 26 patients were divided into 5-mm segments and a histologic section, stained by the Movat method, was prepared from each segment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of endothelial function and inflammation in patients with cardiovascular risk factors, with and without a history of myocardial infarction

BACKGROUND: Endothelial dysfunction and inflammation, in particular their lack of improvement after risk reduction, might better reflect advanced atherosclerosis than just the presence of risk factors. The aim of this study was to compare endothelial function and inflammatory parameters in high-risk patients who had no history of myocardial infarction and in patients in a stable phase after myocardial infarction. METHODS: We compared endothelial function of the brachial artery, measured using high-resolution ultrasound, in 45 patients with hyperlipidaemia (Group 1), and in 45 patients in a stable period after myocardial infarction (Group 2). Forty-five healthy individuals served as a control group (Group 3). RESULTS: Compared to patients with treated hyperlipidaemia, patients after myocardial infarction had lower values of total and LDL cholesterol (p = 0.015; 0.005) and homocysteine (p < 0.005), but marginally higher IL-6 levels (p = 0.1). Other measurements were comparable. However, flow-mediated dilation of the brachial artery was significantly diminished in patients after myocardial infarction (10.6 +/- 3.0; 5.9 +/- 4.0; 14.0 +/- 1.9% for Groups 1-3; ANOVA p = 0.0001; respectively). CONCLUSIONS: We found that patients with previous myocardial infarction have substantially lower endothelial function and increased some inflammatory parameters than patients with a similar level of atherosclerotic risk profile but without clinically evident coronary artery disease.     

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.     

Extracoronary atherosclerosis in patients with chronic ischemic heart disease: relationship with risk factors and the severity of coronary artery disease.

AIM: The aim of the present study was to investigate the prevalence of carotid and/or peripheral atherosclerotic lesions in patients with chronic ischemic heart disease (previous acute myocardial infarction [AMI] or stable angina). METHODS: We studied 248 patients (168 male and 80 female), mean age 63+/-10 years, which were investigated for traditional risk factors. Systolic blood pressure, body mass index, lipid profile, fasting glucose and plasma fibrinogen were also measured. We assessed the prevalence of atherosclerotic lesions in carotid and lower limb arteries, by ultrasound duplex scanning (UDS). RESULTS: Angina was present in 33% of the patients, a previous AMI in 67%, a previous transient ischemic attack in 4% and a previous ischemic stroke in 6% of patients. A total of 195 patients underwent coronary angiography: 1 vessel was involved in 48% of patients, 2 vessels in 33%, and 3 vessels in 19%. Detecting peripheral atherosclerotic lesions by UDS, increased intima-media thickness (IMT) or plaques in carotid arteries were found in 232 patients (94%) and carotid stenosis >70% in 13 patients (5%). In lower limb arteries, IMT or plaques were present in 202 patients (82%) and a stenosis >70% in 18 patients (7%). Severity of coronary artery disease (CAD) was correlated to extracoronary atherosclerosis: carotid and lower limb arterial atherosclerosis was detected in 73% of patients with 1 vessel, in 83% of patients with 2 vessel, in 87% of those with 3 vessel CAD. CONCLUSION: Our study suggests that in patients with CAD, it is useful to screen the peripheral circulation by non-invasive tests, such as UDS. Patients with the diagnosis of ischemic heart disease and combined extracoronary atherosclerosis need a careful follow-up and a more aggressive therapy for secondary prevention.     

Comparison of usefulness of inflammatory markers in patients with versus without peripheral arterial disease in predicting adverse cardiovascular outcomes (myocardial infarction, stroke, and death)

We tested the hypothesis that a combination of measurements of different aspects of atherosclerosis, including burden of atherosclerosis and levels of inflammation, would contain more predictive information than either alone in an outpatient population. We enrolled 110 patients (62 +/- 15 years of age) who were referred to the noninvasive vascular laboratory for sequential Doppler pressure measurements of the lower extremities. We measured ankle-brachial index (ABI) and serum markers of inflammation and followed subjects for a mean of 2.25 years. Fifty subjects did not have peripheral arterial disease (PAD; ABI > or =0.9), whereas 60 did (ABI <0.9). Markers of inflammation, including C-reactive protein (3.83 +/- 0.9 vs 2.11 +/- 1.1, p = 0.019), were higher in subjects who had PAD. During follow-up, 42% developed an event (myocardial infarction, stroke, unplanned coronary or lower extremity revascularization, or death). Decreasing ABI (chi-square 7.3, p = 0.026) and increasing C-reactive protein (chi-square 22.1, p <0.001) increased the risk of an event. Risk increased sixfold between the lowest and highest groups for all events and fourfold for hard events (myocardial infarction, stroke, and death) using both C-reactive protein and ABI. In conclusion, patients who have PAD and increased inflammation are at highest risk for adverse cardiovascular outcomes. Characterizing atherosclerosis on the basis of these parameters provides important prognostic information.