Apparent Coronary Artery Disease Research Articles

Metabolic Syndrome and Cardiovascular Disease

Insulin resistance is characterized by an impaired physiological response to insulin. The constellation of insulin resistance, and several other metabolic and vascular disorders, is known as the insulin resistance syndrome, or metabolic syndrome. The characteristic features of metabolic syndrome include；central obesity, hypertension, dyslipidemia and glucose intolerance, and abnormalities in both the endothelial cells and vascular function. Several studies have shown that insulin resistance is a predictor of coronary artery disease (CAD). Recent studies have described relationships between the entire constellation of components in metabolic syndrome and the risk of CAD. The increasing prevalence of the insulin resistance syndrome, and its strong association with risk of CAD, has highlighted the potential importance of its early diagnosis and aggressive treatment. The managements of metabolic syndrome include lifestyle interventions, aggressive treatment of the identified CAD risk factors, and the treatments of abnormal glucose tolerance and insulin resistance. The connection between insulin resistance, metabolic syndrome and coronary disease must be recognized, and it is important not only to manage the obviously apparent CAD risk factors, but also to identify and manage other sought factors. (Korean Circulation

Relationship between dobutamine-induced regional wall motion abnormalities and coronary flow reserve in heart transplant patients without angiographic coronary artery disease

Background: Regional wall motion abnormalities (RWMA) demonstrated by dobutamine stress echocardiography (DSE) are a sensitive predictor of coronary artery disease (CAD) in heart transplant recipients. However, RWMA have been shown to occur in patients with angiographically “normal” coronary arteries. The reasons for this are unknown. We sought to determine if abnormal responses to dobutamine in this setting can be explained by microvascular dysfunction in the coronary circulation as detected by decreased coronary flow reserve (CFR). Methods: Twenty-six consecutive heart transplant patients were evaluated prospectively. Five of 26 (19.2%) patients (seven coronary arteries) were excluded for poor acoustic windows on echocardiography. Another three patients were excluded for angiographically apparent CAD. CFR and wall motion score index (WMSI) derived from DSE were measured in the remaining 18 patients and formed the basis of this study. Patients were divided into two groups based on the absence (Group 1; n = 5) or presence (Group 2; n = 13) of RWMA on DSE. CFR was measured with the Doppler Flo-Wire in 34 coronary arteries (18 patients) and correlated with WMSI. Results: In Group 1 patients, CFR measured in eight coronary arteries was normal (2.6 ± 0.4). In Group 2 patients, CFR measured in 26 coronary arteries also was normal (2.2 ± 0.6; p = NS vs Group 1). In Group 2, CFR was measured in 20 of 24 vessels assigned to segments that developed RWMA. Only 6 of these 20 vessels (30%) had abnormal CFR. Overall, there was no correlation between decreased CFR and the presence of RWMA induced by dobutamine. Conclusions: These data suggest that, in cardiac transplant patients with angiographically “normal” coronary arteries, inducible wall motion abnormalities during DSE cannot be attributed to coronary microvascular dysfunction as manifested by decreased CFR.

Relevance of C-reactive protein levels in peritoneal dialysis patients

C-reactive protein (CRP) levels are increased in 30 to 50% of dialysis patients and predict cardiovascular morbidity and mortality. It is usually considered that raised CRP levels reflect underlying atherosclerosis. However, many patients may have clinically apparent cardiovascular disease without raised CRP levels. This study was designed to assess both the risk factors for high CRP levels and the usefulness of the test as a marker of clinically apparent coronary artery disease (CAD), peripheral vascular disease (PVD) and the presence of ongoing infections/inflammatory disorders (INF-INFL) in peritoneal dialysis patients. A chart review of 190 prevalent peritoneal dialysis patients was performed. CRP, albumin, ferritin, erythropoietin (EPO) dose and resistance, Kt/V, and residual renal function values were obtained and a history or presence of cardiovascular disease (CAD, PVD) and presence of INF-INFL recorded. Data were analyzed by Chi-square, Spearman correlation and logistic regression. A total of 31% of patients had a raised CRP. INF-INFL was highly predictive of raised CRP levels (OR 16.97; 95% CI 5.41 to 53.14, P=0.000), whereas CAD and PVD either singly or in combination had no such association. The sensitivity/specificity for CRP as a test for INF-INFL was 83/77%. For CAD and PVD, the sensitivities were less than 40% and specificities 70%. Increased CRP values were more common in females but not in diabetics. Weak linear correlations existed between CRP levels and albumin, ferritin and residual renal function (r=-0.212, 0.228 and -0.163 respectively, P < 0.02). By regression analysis, INF-INFL predicted high CRP levels, but CAD and PVD did not. The majority of patients (57%) with high CRP had no identifiable cause; 40% of these patients had subsequent or previous normal CRP values. High transport status predicted high CRP levels (OR 7.28; 95% CI 1.417 to 37.36, P=0.006). The majority of elevated CRP levels in peritoneal dialysis patients occur without an obvious cause. Clinically apparent cardiovascular disease does not predict high CRP levels. CRP levels vary over time in the same patient, from normal to high or vice versa, for no obvious reason. Sources of inflammation other than CAD, PVD and clinically obvious INF-INFL in peritoneal dialysis patients remain to be identified.

Cardiac Risk Assessment before Vascular Surgery: A Prospective Study Comparing Clinical Evaluation, Dobutamine Stress Echocardiography, and Dobutamine Tc-99m Sestamibi Tomoscintigraphy

Preoperative evaluation for cardiac risk assessment before peripheral vascular surgery remains controversial. Between January and June 1994, a prospective open study was carried out in 156 patients scheduled for elective vascular procedures (63 carotid endarterectomies, 34 abdominal aortic aneurysms, 29 aortoiliac and 30 infrainguinal reconstructions) to compare the ability of clinical data, dobutamine stress echocardiography, and dobutamine Tc-99m sestamibi tomoscintigraphy to predict postoperative cardiac events. Pharmacological stress testing consisted of incremental dobutamine infusion (±1 mg atropine to achieve 85% of age-predicted maximal heart rate, with continuous echocardiographic monitoring, and injection of Tc-99m sestamibi after dobutamine infusion). Dobutamine echocardiography was abnormal in 36 patients (worsening resting wall motion abnormality in 11; new induced wall motion abnormality in 25). Dobutamine Tc-99m sestamibi tomoscintigraphy revealed a reversible perfusion defect in 34 patients, indicating the presence of myocardial ischaemia. As a result, eight patients underwent myocardial revascularization ( n = 5) or the proposed operation was cancelled ( n = 3). In the remaining 142 vascular procedures, there were eight (5.6%) adverse cardiac events: three myocardial infarctions (two fatal), three prolonged myocardial ischaemia, one acute congestive heart failure and one sustained ventricular arrhythmia in the post operative period. Univariate analysis selected unstable angina (relative risk (RR) 11.6), previous congestive heart failure (RR 6.4), Detsky's score of ≥15 (RR 3.0), positive dobutamine stress echocardiography (RR 3.7), and positive dobutamine tomoscintigraphy (RR 7.4) as significant predictors of postoperative cardiac events. In patients without clinical markers of coronary artery disease ( n = 66), non-invasive cardiac testing did not predict cardiac complications ( n = 2; one prolonged myocardial ischaemia; one infarction). In the subset of 76 patients with definite clinical or electrocardiographic evidence of ischaemic heart disease, dobutamine stress testing provided additional information, and optimized risk stratification: five of six patients who suffered a cardiac complication had a pathologic dobutamine stress test. Furthermore, a negative dobutamine stress test was characterized by a high negative predictive value (0.96 for echocardiography; 0.97 for tomoscintigraphy). The study further demonstrated that the cardiac response (ischaemic versus non-ischaemic) to dobutamine stress was concordantly classified by echocardiographic and tomoscintigraphic techniques in 96% of cases. It is concluded that complementary non-invasive cardiac stress testing by dobutamine is indicated only in patients with clinically apparent coronary artery disease.

Cardiac risk assessment before vascular surgery: a prospective study comparing clinical evaluation, dobutamine stress echocardiography, and dobutamine Tc-99m sestamibi tomoscintigraphy

Preoperative evaluation for cardiac risk assessment before peripheral vascular surgery remains controversial. Between January and June 1994, a prospective open study was carried out in 156 patients scheduled for elective vascular procedures (63 carotid endarterectomies, 34 abdominal aortic aneurysms, 29 aortoiliac and 30 infrainguinal reconstructions) to compare the ability of clinical data, dobutamine stress echocardiography, and dobutamine Tc-99m sestamibi tomoscintigraphy to predict postoperative cardiac events. Pharmacological stress testing consisted of incremental dobutamine infusion (±1 mg atropine to achieve 85% of age-predicted maximal heart rate, with continuous echocardiographic monitoring, and injection of Tc-99m sestamibi after dobutamine infusion). Dobutamine echocardiography was abnormal in 36 patients (worsening resting wall motion abnormality in 11; new induced wall motion abnormality in 25). Dobutamine Tc-99m sestamibi tomoscintigraphy revealed a reversible perfusion defect in 34 patients, indicating the presence of myocardial ischaemia. As a result, eight patients underwent myocardial revascularization ( n = 5) or the proposed operation was cancelled ( n = 3). In the remaining 142 vascular procedures, there were eight (5.6%) adverse cardiac events: three myocardial infarctions (two fatal), three prolonged myocardial ischaemia, one acute congestive heart failure and one sustained ventricular arrhythmia in the post operative period. Univariate analysis selected unstable angina (relative risk (RR) 11.6), previous congestive heart failure (RR 6.4), Detsky's score of ≥ 15 (RR 3.0), positive dobutamine stress echocardiography (RR 3.7), and positive dobutamine tomoscintigraphy (RR 7.4) as significant predictors of postoperative cardiac events. In patients without clinical markers of coronary artery disease ( n = 66), non-invasive cardiac testing did not predict cardiac complications ( n = 2; one prolonged myocardial ischaemia; one infarction). In the subset of 76 patients with definite clinical or electrocardiographic evidence of ischaemic heart disease, dobutamine stress testing provided additional information, and optimized risk stratification: five of six patients who suffered a cardiac complication had a pathologic dobutamine stress test. Furthermore, a negative dobutamine stress test was characterized by a high negative predictive value (0.96 for echocardiography; 0.97 for tomoscintigraphy). The study further demonstrated that the cardiac response (ischaemic versus non-ischaemic) to dobutamine stress was concordantly classified by echocardiographic and tomoscintigraphic techniques in 96% of cases. It is concluded that complementary non-invasive cardiac stress testing by dobutamine is indicated only in patients with clinically apparent coronary artery disease. © 1997 The International Society for Cardiovascular Surgery.

784-3 Prognostic Significance of Intimal Thickening Detected by Intracoronary Ultrasound in Heart Transplant Recipients

Intracoronary ultrasound (ICUS) is a sensitive tool for the detection of intimal thickening in coronary arteries of heart transplants recipients. However, the prognostic significance of this intimal thickening has not been proven. During a one year period, 90 transplant recipients had ICUS examination at the time of their annual angiogram. For each ICUS study an intimal index (II), defined as the ratio of the plaque area to the area within the media, was measured for the most diseased segment imaged. The angiogram at the time of ICUS was reviewed for the presence of visually apparent coronary artery disease (V-CADI· Those patients (n = 19) with V-CAD present at the time of ICUS were excluded from the study. The time since transplantation for the 71 pts without V-CAD ranged from 1 to 15 yrs, with a mean of 4.2 yrs and median of 3.9 yrs. The subsequent annual follow-up angiograms of the 71 patients without V-CAD at the time of ICUS were reviewed for the development of V-CAD. Mean duration of angiographic follow-up was 2.0 yrs (range 1–3 yrs). V-CAD developed on follow-up angiograms in 13 of the 71 pts. Mean time to development of V-CAD was 1.5 yrs. Forty-six patients had II &lt; 0.3, 4 (9%) of whom subsequently developed V-CAD. Twenty-five patients had II ≥ 0.3, 9 (36%) of whom developed V-CAD. Odds ratio for future V-CAD between pts with II &lt; 0.3 and II 2: 0.3 was 5.9 (95% CI 1.8 to 19.0, difference significant at p &lt; 0.01 by Fisher's Exact test). In a subgroup of 22 patients more than 5 years post transplantation at the time of ICUS, 12 had II &lt; 0.3 and 10 had II 2 ≥ 0.3. In this subgroup none of the 12 pts with II &lt; 0.3 developed V-CAD and only 1 of the 10 with II &gt; 0.3 developed V-CAD (difference not significant). Conclusion — Among patients more than 1 year and less than 5 years post-transplantation without visually apparent angiographic coronary artery disease, the presence of moderate to severe intimal thickening by ICUS is predictive of the future development of angiographically apparent CAD. Intimal thickening as detected by ICUS is of prognostic significance in patients with angiographically silent transplant coronary artery disease.

Electrocardiogram R Wave Amplitude Changes during Exercise: Relation to Left Ventricular Volume Changes

Changes in electrocardiogram R wave amplitude often are noted during exercise in patients with coronary artery disease. The mechanism of this change in amplitude is unclear, though a relation to left ventricular volume changes has been suggested. To assess ischemia-independent relations between exercise R wave amplitude changes and volume we used radionuclide angiography and electrocardiogram at rest and exercise in 24 patients with chronic aortic regurgitation (without apparent coronary artery disease) as a sole cardiac abnormality. Of the 24 patients studied, the left ventricular end-diastolic volume increased in 14 (58%) and decreased in 10 (42%), and the left ventricular end-systolic volume increased in 13 (54%) and decreased in 11 (46%). The R wave amplitude increased in 4 (17%), decreased in 9 (37%), and was unchanged in 11 (46%). No significant differences existed among the frequency of directional change of left ventricular volume between the groups defined by direction of R wave amplitude change. No correlation existed between R wave amplitude changes (rest to exercise) and end-diastolic and end-systolic volume changes. We conclude that R wave amplitude changes during exercise are not explained by variations in the left ventricular volume.

Baseline rest electrocardiographic abnormalities, antihypertensive treatment, and mortality in the Multiple Risk Factor Intervention Trial

The overall results of the Multiple Risk Factor Intervention Trial (MRFIT) showed a nonsignificant 7% lower coronary artery disease (CAD) mortality rate in the special-intervention (SI) as compared to the usual-care (UC) group. The initial results also suggested that the SI program was more effective than UC in the community in reducing the CAD mortality rate in nonhypertensive persons than in hypertensive persons, and that the SI program used was more effective in reducing CAD deaths among men without than men with electrocardiographic (ECG) abnormalities at rest. Furthermore, an unfavorable mortality trend in hypertensive SI men with ECG abnormalities at rest compared with UC men was noted (adjusted relative risk of 1.67). Further analyses in baseline-defined subgroups indicated that (1) the most common ECG abnormalities at rest were high R waves and ST-T changes, (2) the CAD mortality differential (SI/UC) was similar in the subgroup with these abnormalities and in the subgroup with other abnormalities at rest, (3) the apparent excess CAD mortality among hypertensive SI men with ECG abnormalities at rest was manifested chiefly as sudden death within 1 hour, and (4) the association between ECG abnormalities at rest and the CAD mortality rate among hypertensive men was independent of the baseline level of blood pressure or of the findings on the exercise electrocardiogram. However, CAD mortality in those with abnormalities on the electrocardiogram both at rest and during exercise was lower in the SI than the UC group. A possible explanation for the difference in outcome in the baseline-defined subgroup was an unexpectedly low UC mortality rate. However, within-group analysis revealed an interaction between ECG abnormalities at rest and diuretic treatment in the SI group, with the risk of CAD death for men prescribed diuretic drugs relative to men not prescribed diuretic drugs estimated as 3.34 among men with baseline ECG abnormalities at rest and as 0.95 among men without such abnormalities. No such effect was found in the UC group, in which men generally were prescribed lower doses of hydrochlorothiazide and chlorthalidone than SI men. However, analyses do not suggest an effect of diuretic dose or of hypokalemia on the CAD mortality rate in treated SI participants. Although subgroup analyses must be interpreted with caution, particularly those that go beyond the randomized clinical trial design by the MRFIT, these findings pose hypotheses for investigation by other researchers in systemic hypertension and may have implications for therapy.