Heterogeneity of microvascular dysfunction in women with chest pain not attributable to coronary artery disease: implications for clinical practice

Background Women with chest pain in the absence of obstructive coronary artery disease (CAD) frequently have coronary microvascular dysfunction and inducible myocardial ischemia. Microvascular dysfunction is commonly diagnosed by demonstrating abnormal flow reserve in a single coronary artery during angiography. Therefore, diagnostic accuracy is dependent on homogeneity of microvascular dysfunction in the myocardium. Methods In the Women's Ischemia Syndrome Evaluation (WISE), 34 women with chest pain and no significant CAD and 9 female control subjects underwent ¹³N-NH₃ positron emission tomography to measure adenosine-induced changes in myocardial perfusion (ie, coronary flow reserve [CFR]). Flow reserve was correlated among the left anterior descending (LAD), circumflex (LCx), and right (RCA) coronary artery distributions. Results The mean CFR in the LAD, LCx, and RCA was 2.85 ± 1.35, 2.58 ± 0.94, and 3.24 ± 1.42, respectively. Concordance in the classification of microvascular function as normal (CFR ≥2.5) versus abnormal was present in the LAD and RCA, LAD and LCx, and RCA and LCx distributions in only 71.8%, 66.7%, and 61.6% of patients, respectively. There was a modest degree of correlation of CFR between the LAD and RCA (r = 0.79, P < .001), LAD and LCx (r = 0.61, P < .001), and LCx and RCA (r = 0.57, P < .001). Comparison of CFR in the 3 coronary arteries simultaneously in all patients demonstrated that the LCx had values that were significantly lower than the RCA and LAD distributions. Conclusion Substantial discordance of classification of microvascular function among coronary artery distributions in women with chest pain and no CAD suggests that microvascular dysfunction is distributed heterogeneously in the myocardium. Assessment of CFR in a single coronary artery during cardiac catheterization may not provide an accurate assessment of the coronary microcirculation in women with chest pain not attributable to CAD. (Am Heart J 2003;145:628-35.)     

Peripheral vascular endothelial function testing for the diagnosis of coronary artery disease

Background

Abnormalities in endothelium-dependent vasodilation may be detected in arteries before the development of overt atherosclerosis, and their presence may predict stress-induced ischemia as assessed by ST-segment depression and/or perfusion defects. Brachial artery ultrasound during reactive hyperemia is a noninvasive method of assessing peripheral vasomotion, measured by flow-mediated vasodilation (FMD). The purpose of the current study was to assess whether endothelium-dependent FMD of the brachial artery, by ultrasound imaging, predicts the presence of angiographically assessed coronary artery disease (CAD).

Methods

One hundred ninety-eight in-hospital patients (age, 59 ± 9 years; 78 women) with chest pain syndrome and without previous myocardial infarction or revascularization procedures were enrolled in the present study. All of the patients, at testing time, were not receiving nitrate therapy and underwent, on different days, coronary angiography and endothelium-dependent FMD testing of the brachial artery by high-resolution ultrasound. The result of the flow-mediated dilation (%FMD) is defined as the percent change in the internal diameter of the brachial artery during reactive hyperemia related to baseline. A coronary vessel was considered to have a significant obstruction if its diameter was narrowed by 50% or more on quantitative computer-assisted analysis. A prognostically validated angiographic Duke score (from 0 = normal to 100 = severe left main disease) was calculated.

Results

The %FMD was lower in patients with (n = 69) compared with those without (n = 129) CAD (4.64% ± 4.36% vs 7.39% ± 5.68%; P = .01). By multivariate analysis, the %FMD (P = .01; odds ratio [OR], 1.13; 95% confidence interval [CI], 1.05 to 1.23), male sex (P = .01; OR, 3.47; 95% CI, 1.64 to 7.36), and cigarette smoking habit (P < .01; OR, 4.00; 95% CI, 2.50 to 6.35) were independent predictors of CAD. %FMD was poorly albeit significantly correlated with the severity of CAD (%FMD Duke score, P < .01, r = −0.25). The receiver operator characteristic curve showed the %FMD optimal cutoff value as ≤8.84, with sensitivity of 90%, specificity of 37%, negative predictive value of 90%, and positive predictive value of 43%.

Conclusions

In patients with chest pain, a depressed FMD of the brachial artery was a sensitive indicator of CAD, but it showed poor specificity, and it appeared to be unable to predict both the extent and the severity of angiographically assessed CAD.     

Effect of intravenous testosterone on myocardial ischemia in men with coronary artery disease

Background Studies on the effect of estrogen on atherosclerotic coronary artery disease (CAD) risk in women have produced conflicting results. Similar confusion, but fewer data, exists on the effect of testosterone on CAD risk in men. Methods We used ^99mTc sestamibi single-photon emission computed tomography (SPECT) myocardial perfusion imaging to examine the acute effect of intravenous testosterone in 32 men (mean age, 69.1 ± 6.4 years) with provocable myocardial ischemia on standard medical therapy. Patients performed 3 exercise (n = 18) or adenosine (n = 16) stress tests during the infusion of placebo or 2 doses of testosterone designed to increase testosterone 2 or 6 times baseline. Results Serum testosterone increased 137 ± 58% and 488 ± 113%, and estradiol levels increased 27 ± 46% and 76 ± 57%, (P < .001 for all) during the 2 testosterone infusions. There were no differences among the placebo or testosterone groups in peak heart rate, systolic blood pressure, maximal rate pressure product, perfusion imaging scores, or the onset of ST-segment depression. Conclusions Acute testosterone infusion has neither a beneficial nor a deleterious effect on the onset and magnitude of stress-induced myocardial ischemia in men with stable CAD. (Am Heart J 2002;143:249-56.)     

Mild renal insufficiency is associated with angiographic coronary artery disease in women

BACKGROUND: Mild renal insufficiency is associated with an increased risk for cardiovascular events in women with coronary artery disease (CAD). However, the relationship between mild renal insufficiency and atherosclerotic CAD in women is not known. Methods and Results- Women with chest pain who were referred for coronary angiography in the NHLBI Women's Ischemia Syndrome Evaluation (WISE) study underwent quantitative coronary angiography, blood measurements of creatinine, lipids, and homocysteine, and assessment of CAD risk factors. Fifty-six women had mild renal insufficiency (serum creatinine 1.2 to 1.9 mg/dL), and 728 had normal renal function (creatinine <1.2 mg/dL). Creatinine correlated with angiographic CAD severity score (r=0.11, P<0.004) and maximum coronary artery stenosis (r=0.11, P<0.003). Compared with women with normal renal function, those with mild renal insufficiency were more likely to have significant angiographic CAD (>/=50% diameter stenosis in >/=1 coronary artery) (61% versus 37%; P<0.001) and CAD in multiple vessels (P<0.001 for association) and had greater maximum percent diameter coronary stenosis (59+/-35% versus 38+/-36%; P<0.001). Mild renal insufficiency was associated with significant angiographic CAD independent of age and risk factors (OR=1.9, 95%CI=1.1 to 3.5). After controlling for homocysteine in 509 women, mild renal insufficiency remained predictive of CAD (OR=3.2, 95%CI=1.4 to 7.2). CONCLUSIONS: In women with chest pain, mild renal insufficiency is an independent predictor of significant angiographic CAD. Mildly increased serum creatinine is probably a marker for unmeasured proatherogenic factors.     

Effect of cigar smoking on endothelium-dependent brachial artery dilation in healthy young adults

Background Cigar smoking has become a quickly growing trend among teenagers, women, and young adults. The objective was to explore whether cigar smoking affects flow-mediated vasodilation in healthy, non-smoking young adults. Methods This was a prospective randomized trial with open design. It was performed in a cardiology teaching program in a private community hospital that serves as a major referral center within the greater Miami area. Apparently healthy, non-smoking young adult cardiology trainees and staff between the ages of 20 and 45 years were randomly assigned to a cigar smoking group (n = 15) or a control group (n = 14). The main outcome measures were the difference in percent diameter increase in the brachial artery after reactive hyperemia and sublingual nitroglycerin between members of the cigar smoking and control groups at baseline, measured after cigar smoking, and at 5 hours. Results Twenty-nine participants were randomized. Percent diameter increase in the brachial artery was measured with the use of high-resolution ultrasonography. Baseline percent diameter increase after reactive hyperemia and sublingual nitroglycerin was similar in both groups (6.2% vs 6.7%, P = .4 and 22% vs 23%, P = .5, respectively). We observed a 2.5% increase in brachial artery diameter with hyperemia after cigar smoking compared with a 9.4% increase in the control group, P = .045. Values after nitroglycerin were similar between groups, P = .2. Between-group analysis showed no significant difference in percent dilation after reactive hyperemia at 5 hours, P = .4, but a significant difference was seen after sublingual nitroglycerin, P = .02. Conclusions These data are compatible with the possibility that cigar smoking may have an acute effect on endothelium-dependent, flow-mediated brachial artery dilation and do not support the possibility of an immediate effect on endothelium-independent vasodilation. Taken together, these results suggest that cigars are not an innocuous alternative to cigarette smoking. (Am Heart J 2002;143:83-6.)     

Impact of geographic miss on adjacent coronary artery segments in diffuse in-stent restenosis with beta-radiation therapy: angiographic and intravascular ultrasound analysis

Background The impacts of geographic miss on edge restenosis have not been sufficiently evaluated. Methods β-Radiation therapy with rhenium 188-filled balloon after rotational atherectomy for diffuse in-stent restenosis was performed in 50 patients. We evaluated the impacts of geographic miss on adjacent coronary artery segments beyond the stent by angiographic (QCA) and intravascular ultrasound (IVUS) analysis in 50 irradiated lesions and 100 edges. Serial IVUS and QCA comparisons between postradiation and 6 months' follow-up were available in 44 and 47 of 50 patients, respectively. QCA measurements of minimal lumen diameter (MLD) and IVUS analysis were performed in the reference and radiation segments. Edges that were touched by the angioplasty balloon but were not adequately covered by radiation constituted the geographic miss edges. Results Geographic miss was observed in 55.6% and 52.6% in QCA and IVUS analysis, respectively. Edge restenosis after radiation therapy in 3 patients was associated with geographic miss. In contrast to uninjured edges (postradiation 2.9 ± 0.6 mm to follow-up 2.8 ± 0.6 mm, P = .292), MLD in the radiation segment by QCA analysis significantly decreased from 2.7 ± 0.4 mm to 2.4 ± 0.6 mm in geographic miss edges (P = .002). IVUS analysis showed that significant positive remodeling in the radiation segment occurred in uninjured edges (vessel area from 15.4 ± 4.4 mm² to 15.8 ± 4.4 mm², P = .001) but not in geographic miss edges (vessel area from 12.8 ± 3.6 mm² to 13.0 ± 3.6 mm², P = .119). Conclusion The geographic miss might be one of the predictors, which resulted in decreased MLD at follow-up in β-radiation therapy. Sufficient lesion coverage with radiation might be associated with positive remodeling in the radiation segment. (Am Heart J 2002;143:327-33.)     

Coronary artery calcification,atherogenic lipid changes,and increased erythrocyte volume in black injection drug users infected with human immunodeficiency virus-1 treated with protease inhibitors

Background Protease inhibitors (PIs) may be associated with accelerated atherosclerosis in individuals infected with human immunodeficiency virus (HIV). We assessed the effects of HIV PIs on subclinical atherosclerosis. Methods The lipid profiles, C-reactive protein (CRP) levels, coronary artery calcification (CAC) scores, and blood cell morphologic changes were quantified in 98 black adult participants, aged 25 to 45 years, with HIV-1 infection in Baltimore, Md. Fifty-five participants (56.1%) were taking PIs; 43 participants (43.9%) were not. The Student t and χ² tests were used as a means of detecting the between-group differences. Results Participants in both the PI and non-PI groups were similar in age, sex, body mass index, blood pressure, heart rate, and red and white blood cell counts. Compared with the non-PI group, the PI group had significantly higher serum total cholesterol (4.8 ± 1.0 vs 3.8 ± 0.7 mmol/L, P < .001) and LDL cholesterol (2.9 ± 0.8 vs 2.1 ± 0.7 mmol/L, P < .001) levels and red blood cell mean corpuscular volume (92.2 ± 9.3 vs 86.8 ± 7.2 μm³, P = .048). The CAC scores in the PI group were also higher than those in the non-PI group (11.0 ± 28.6 [n = 43] vs 1.7 ± 5.8, P = .043). CAC scores were marginally associated with log-transformed duration of the PI therapy (P = .055). Serum CRP levels remained unchanged (5.5 ± 13.6 mg/L [n = 45] vs 3.9 ± 5.5 mg/L, P = .467). Serum total cholesterol level, LDL cholesterol level, red blood cell mean corpuscular volume, and CAC scores were indicated by means of regression analyses to be associated with log-transformed duration of the PI therapy. Conclusions The use of PIs is associated with coronary artery calcification, atherogenic lipid changes, and increased erythrocyte volume in individuals infected with HIV-1. (Am Heart J 2002;144:642-8.)     

Prognostic significance of coronary artery calcium in asymptomatic subjects with usual cardiovascular risk

Background Coronary calcium detected noninvasively is an attractive way to diagnose atherosclerosis before the development of symptoms. This study examines the prognostic value of coronary calcium in asymptomatic subjects with usual cardiovascular risk. Methods and Results In 425 asymptomatic subjects, 229 men (aged 45.1 ± 14 years) and 196 women (aged 42.7 ± 13 years), coronary calcium presence was studied by digital cinefluoroscopy. The majority (76%) had no or at most one risk factor. Subjects were followed up for 58.4 ± 12.7 months for cardiac events. Coronary calcium was present in 76 of 425 (17.9%) subjects. Cardiac events were observed in 21 subjects: 2 cardiac deaths, 7 acute myocardial infarctions, 3 coronary artery bypass grafts, 3 coronary angioplasty procedures, 3 events of unstable angina, and 10 events of stable angina pectoris. Survival curve analysis showed significant differences in all the studied end points between subjects with and those without calcium. Coronary calcium was an independent predictor of all events (3.6-fold increase, P < .008), cardiac death/myocardial infarction/revascularization (13.9-fold increase, P < .02), and stable angina (7.4-fold increase, P < .007). However, calcium did not independently predict cardiac death/myocardial infarction or acute coronary syndromes. Conclusions Coronary calcium in asymptomatic subjects with usual cardiovascular risk adds significant incremental information to risk factors information for the development of symptomatic coronary artery disease. (Am Heart J 2003;145:542-8.)     

Altered coronary flow properties in diffuse coronary artery ectasia

Objectives The purpose of this study was to investigate coronary blood flow properties in patients with diffuse coronary artery ectasia (CAE) associated with exercise-induced myocardial ischemia.Methods Seventeen patients with diffuse CAE and without coexisting coronary artery stenosis were enrolled in the study (CAE group). CAE was defined as luminal dilatation 1.5 to 2 times that of the adjacent normal coronary artery segment or the diameter of the corresponding coronary artery of the control group when there was no normal segment. The age- and sex-matched control group (n = 20) comprised patients with normal epicardial coronary arteries. Coronary blood flow velocities were obtained invasively by use of Doppler scanning flow wire. Coronary flow reserve (CFR) was measured by administration of intracoronary papaverine as the hyperemic stimulus. Volumetric coronary blood flow was estimated by multiplying the velocity time integral of coronary blood flow with the cross-sectional area of the coronary artery and the heart rate.Results Fifteen patients with CAE, but none of the patients in the control group, had electrocardiographic signs of myocardial ischemia at peak exercise on ergometry. Baseline average peak velocities (APVs) of coronary blood flow were similar in the 2 groups. Peak hyperemic APVs of coronary blood flow were lower in the CAE group than in the control group (17.5 ± 7.4 cm/s vs 41.5 ± 12.6 cm/s, respectively, P < .001). Volumetric coronary blood flow was significantly higher in the CAE group than in the control group, both at rest and at hyperemia (146.3 ± 71.2 cm³/min vs 45.1 ± 16.1 cm³/min, respectively, P < .001, and 202 ± 87.3 cm³/min vs 104.1 ± 37.6 cm³/min, respectively, P < .003). The mean CFR of the CAE group was significantly reduced compared with that of the control group (1.51 ± 0.31 vs 2.67 ± 0.52, respectively, P < .001).Conclusions The CFR is significantly reduced in patients with diffuse CAE compared to a matched control group. Although volumetric coronary blood flow is significantly higher in CAE, microcirculatory dysfunction that is reflected as depressed CFR may be the underlying cause of exercise-induced myocardial ischemia. (Am Heart J 2003;145:66-72.)     

Effects of isolated coronary artery ectasia on electrocardiographic parameters reflecting ventricular heterogeneity

Isolated coronary ectatic but otherwise normal epicardial coronary arteries are an infrequent angiographic finding. We sought to determine whether coronary artery ectasia (CAE) may alter QT-interval duration and dispersion. The study population consisted of 24 patients with isolated CAE and otherwise normal epicardial coronary arteries (group 1) and sex- and age-matched subjects with atypical chest pain and otherwise normal coronary flow (group 2). Both groups underwent a routine standard 12-lead surface electrocardiogram recorded at 50 mm/s during rest. QT dispersion (QTd), corrected QT (QTc), and corrected QT dispersion (QTcd) were calculated. Distribution of sex, age, body mass index, and cardiac risk factors were similar in the 2 groups. Mean heart rate was similar in the 2 groups (74 ± 10 vs 70 ± 7, P > .05). In group 1, QTd, QTcd, and QTc were significantly higher than those of group 2 (QTd, 40 ± 17 vs 29 ± 10 milliseconds [P < .05]; QTcd, 43 ± 19 vs 30 ± 10 milliseconds [P < .05]; QTc, 410 ± 21 vs 397 ± 19 milliseconds [P < .05]). In conclusion, CAE was found to be associated with prolonged QT interval and increased QTd. Microvascular dysfunction and/or ischemia may be responsible mechanisms.     

Small high-density lipoprotein is associated with monocyte subsets in stable coronary artery disease

Objective: High-density lipoprotein (HDL) particles are heterogeneous in structure and function and the role of HDL subfractions in atherogenesis is not well understood. It has been suggested that small HDL may be dysfunctional in patients with coronary artery disease (CAD). Monocytes are considered to play a key role in atherosclerotic diseases. Circulating monocytes can be divided into three subtypes according to their surface expression of CD14 and CD16. Our aim was to examine whether monocyte subsets are associated with HDL subfractions in patients with atherosclerosis. Methods: We included 90 patients with angiographically stable CAD. Monocyte subsets were defined as classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14+CD16++; NCM). HDL subfractions were measured by electrophoresis on polyacrylamide gel. Results: Serum levels of small HDL correlated with circulating pro-inflammatory NCM and showed an inverse relationship to circulating CM independently from other lipid parameters, risk factors, inflammatory parameters or statin treatment regime, respectively. IM were not associated with small HDL. In particular, patients with small HDL levels in the highest tertile showed dramatically increased levels of NCM (14.7 ± 7% vs. 10.7 ± 5% and 10.8 ± 5%; p = 0.006) and a decreased proportion of CM (79.3 ± 7% vs. 83.7 ± 6% and 83.9 ± 6%; p = 0.004) compared to patients in the two lower tertiles. In contrast, intermediate HDL, large HDL and total HDL were not associated with monocyte subset distribution. Conclusion: Small HDL levels are associated with pro-inflammatory NCM and inversely correlated with CM. This may suggest that small HDL could have dysfunctional anti-inflammatory properties in patients with established CAD.     

Coronary CT angiography versus standard of care strategies to evaluate patients with potential coronary artery disease; effect on long term clinical outcomes

Background: Previous studies have shown that computed tomography coronary angiography (CTA) in patients with suspected coronary artery disease (CAD) predicts short term adverse events. However, there is no current data on whether identifying atherosclerosis on CTA impacts outcomes. We performed a case–control study to assess whether information from CTA can improve outcomes. Methods: 4244 symptomatic patients (mean age 58 ± 9, 62.5% male) without known CAD who underwent CTA (n = 2538) to rule out CAD were matched to 1706 patients who underwent standard of care in an academic cardiology clinic. Patients were propensity-matched by gender, age, ethnicity, CAD risk factors and follow-up duration. The primary outcome measure was all-cause mortality. Multivariable Cox proportional hazards models incorporated age, gender and traditional risk factors for coronary disease as well as pre-test probability of CAD. Results: There were no significant differences in age, gender, conventional risk factors between groups (p > 0.05). During a mean follow up of 80 ± 11 months, the overall death rate was 6.3% (270 deaths). Death rate was significantly lower in CTA group (n = 106, 4.2%) as compared to the control group (n = 184, 10.8%, p = 0.001). Event free survival was 95.8% and 89.2% in CTA and standard of care groups, respectively. Risk-adjusted hazard ratio of death were 2.5 (95%CI: 1.6–6.7, p = 0.003) in standard of care cohort as compared to CTA group. Multivariate analysis demonstrated that undergoing coronary CTA resulted in a risk reduction of 32%, p = 0·0001. Conclusions: Improved knowledge of atherosclerosis or increased anti-atherosclerotic therapies among those undergoing CTA may have contributed to improved survival. Our results provide evidence of potential benefit from scanning for atherosclerosis with CTA in symptomatic patients. Large randomized trials are warranted.     

Determinants of tissue Doppler measures of regional diastolic function during dobutamine stress echocardiography

Background Diastolic dysfunction induced by ischemia may alter transmitral blood flow, but this reflects global ventricular function, and pseudonormalization may occur with increased preload. Tissue Doppler may assess regional diastolic function and is relatively load-independent, but limited data exist regarding its application to stress testing. We sought to examine the stress response of regional diastolic parameters to dobutamine echocardiography (DbE). Methods Sixty-three patients underwent study with DbE: 20 with low probability of coronary artery disease (CAD) and 43 with CAD who underwent angiography. A standard DbE protocol was used, and segments were categorized as ischemic, scar, or normal. Color tissue Doppler was acquired at baseline and peak stress, and waveforms in the basal and mid segments were used to measure early filling (Em), late filling (Am), and E deceleration time. Significant CAD was defined by stenoses >50% vessel diameter. Results Diastolic parameters had limited feasibility because of merging of Em and Am waves at high heart rates and limited reproducibility. Nonetheless, compared with normal segments, segments subtended with significant stenoses showed a lower Em velocity at rest (6.2 ± 2.6 cm/s vs 4.8 ± 2.2 cm/s, P < .0001) and peak (7.5 ± 4.2 cm/s vs 5.1 ± 3.6 cm/s, P < .0001). Abnormal segments also showed a shorter E deceleration time (51 ± 27 ms vs 41 ± 27 ms, P = .0001) at base and peak. No changes were documented in Am. The same pattern was seen with segments identified as ischemic with wall motion score. However, in the absence of ischemia, segments of patients with left ventricular hypertrophy showed a lower Em velocity, with blunted Em responses to stress. Conclusion Regional diastolic function is sensitive to ischemia. However, a number of practical limitations limit the applicability of diastolic parameters for the quantification of stress echocardiography. (Am Heart J 2002;144:516-23.)     

High-molecular weight adiponectin is associated with coronary artery angiographic findings in Asian Indians

Asian Indians (AIs) have a higher prevalence and a more aggressive form of coronary artery disease (CAD), and it has been suggested that hypoadiponectinemia may have a role in this accelerated CAD. The present study was undertaken to determine the extent and severity of angiographic findings in 2 groups of CAD patients matched for age and sex, AIs (n = 29) vs whites (n = 30), and to elucidate the potential relationship between adiponectin (total and high-molecular weight [HMW] form) and the severity and extent of coronary angiographic findings in both groups. Angiographic findings were assessed using the modified Gensini index; and 2 scores, scores 1 and 2, were used to assess the severity and extent. Both Gensini index scores 1 and 2 were higher in the AI group compared with the white group (144.4 ± 87.1 vs 93.5 ± 56.3 and 127.2 ± 86.5 vs 80.1 ± 39.3, respectively; P < .05). Adiponectin levels were similar in both groups. Total adiponectin and HMW adiponectin were positively associated with Gensini index score 1 (r = 0.62, P = .004 and r = 0.64, P = .003) and score 2 (r = 0.51, P = .021 and r = 0.54, P = .013), respectively, in AI men, whereas there was no significant association in white men. Thus, AIs had more severe CAD compared with whites; and in AI men with CAD, total adiponectin and HMW adiponectin were associated with the severity of angiographic scores.     

Electrocardiogram abnormalities predict angiographic coronary artery disease in women with chest pain: results from the NHLBI WISE Study

BACKGROUND AND HYPOTHESIS: Noninvasive risk stratification for coronary artery disease (CAD) isless accurate in women than in men. Based on recent reports that gender-specific exercise electrocardiogram (ECG) parameters predict CAD, we evaluated the independent predictive value of the resting ECG for angiographic CAD in women with chest pain. METHODS: Women (n = 850, mean age 58 years) with chest pain in the NHLBI Women's Ischemia Syndrome Evaluation (WISE) underwent 12-lead ECG testing and quantitative coronary angiography. RESULTS: Significant angiographic CAD (> or = 50% stenosis in > or = 1 coronary) was present in 39% of women. Q waves in < or = 2 contiguous ECG leads were present in 107 women (13%), including 49 of 657 (7%) without history of infarction. Among 585 women without prior infarction orrevascularization, 48% of those with Q waves in contiguous leads versus 26% of others, had significant CAD (p = 0.003; odds ratio [OR] = 2.5, 95% confidence interval [CI] = 1.3-4.8). Women with Q waves in < or = 2 inferior ECG leads were particularly likely to have CAD (63 vs. 26% of others, p < 0.001; OR = 4.6,95% CI = 2.0-10.8). Other ECG findings predictive of CAD were any ST-T abnormality (OR = 1.9,95% CI = 1.3-2.8) and T-wave inversion (OR = 2.4, 95% CI = 1.3-4.2). In risk-adjusted analysis, inferior Q waves and T-wave inversion independently predicted significant CAD. When considered together with radionuclide perfusion test results, T-wave inversion on resting ECG added significant independent predictive value (OR = 2.8, 95% CI = 1.1-7.2, p = 0.03). CONCLUSIONS: Selected resting ECG parameters independently predict angiographic CAD in women with chest pain, including women who have also undergone radionuclide stress testing. Prospective studies should consider resting ECG parameters in diagnostic algorithms for CAD in women.     

Centered versus noncentered source for intracoronary artery radiation therapy: a model based on the Scripps Trial

Background The Scripps Trial was a randomized study of intracoronary artery radiation therapy with iridium 192 used to treat restenotic vessels. We used the intravascular ultrasound data from the Scripps Trial to investigate whether a lumen-centered gamma or beta radiation source would reduce radiation dose heterogeneity compared with the noncentered source position used. Methods Analysis included 28 patients with stent placement in 20 native vessels and 8 saphenous vein grafts enrolled in this trial. Radiation dosimetry for gamma radiation was calculated to deliver 800 cGy to the far field target, provided the maximum dose to the near field target did not exceed 3000 cGy. Prescribed dosimetry for beta radiation by use of yttrium 90 was 1600 cGy at 2 mm distance from the source. Results The calculated average minimum source to target distance by use of a lumen-centered source increased by 0.18 mm from 1.70 ± 0.25 to 1.88 ± 0.36 mm, whereas the maximum distance decreased by 0.17 mm from 3.64 ± 0.60 to 3.47 ± 0.43 mm (P < .05). On the basis of these distances, the maximum radiation dose, as well as radiation dose heterogeneity (ratio of maximum to minimum), would have been reduced in 22 of 28 patients by use of a lumen-centered gamma or beta source (P < .005). The reduction in dose heterogeneity was substantially greater with a beta source compared with a gamma source (48% vs 16% reduction). Conclusions Centering of the intracoronary artery radiation therapy delivery catheter within the vessel lumen can significantly reduce radiation dose heterogeneity when compared with a noncentered source position. This dose reduction is substantially greater for a beta compared with a gamma source. (Am Heart J 2002;143:342-8.)     

Fibrinogen: associations with cardiovascular events in an outpatient clinic

Background Fibrinogen, known to influence the coagulation process, is an independent risk factor for coronary artery disease (CAD). However, its association with myocardial infarction (MI) and its predictive potential for short-term mortality, in an ongoing clinical practice, has not been characterized. Objectives In a high-risk outpatient practice we sought to demonstrate whether baseline fibrinogen levels related to MI rather than CAD alone, and whether baseline serum fibrinogen levels predicted mortality over a short-term follow-up. Methods and Results From a total of 2126 patients with baseline fibrinogen measurements (mean age, 56 ± 12 years, 35% female), 1187 patients with CAD (n = 606 with MI) and 939 patients without CAD were evaluated in an active preventive cardiology unit of a large city hospital. Logistic regression models were used to determine the association of fibrinogen with differing CAD presentations. Fibrinogen quartile showed a significant correlation with CAD both univariately and after adjustment for Framingham risk score (odds ratio [OR] = 1.22, P < .001). Fibrinogen levels were significantly associated with the presence of CAD and history of MI (adjusted OR = 1.25, P = .001). Fibrinogen did not show a significant association to CAD when MI was not considered in the analysis (OR = 1.01, P = .82). In this same clinical cohort, after a mean follow-up of 24 ± 13 months, 41 patients had died. Consistent with the observed association with MI, fibrinogen quartile showed a graded independent relation to mortality in a cohort of both men and women (hazard ratio = 1.81, P < .001). Conclusions In the clinical setting of an outpatient clinic, fibrinogen was directly associated with the presence of MI and was revealed to be an independent short-term predictor of mortality. (Am Heart J 2002;143:277-82.)     

Metabolic disorders induced by highly active antiretroviral therapy and their relationship with vascular remodeling of the brachial artery in a population of HIV-infected patients

Antiretroviral therapy has positively modified the natural history of HIV infection; but this treatment can induce metabolic abnormalities, including dyslipidemia, fat redistribution, high blood pressure, and insulin resistance. The metabolic syndrome, a clustering of the metabolic disorders, is frequently detected among HIV patients, especially those on antiretroviral treatment. All the arteries can modify their diameter in response to a chronic injury. This process, defined vascular remodeling, was demonstrated for the brachial artery. It is well known that the diameter of the brachial artery was correlated with the number of the elements of the metabolic syndrome and was associated with the severity of coronary artery disease. On this basis, we postulate that brachial arterial enlargement may be a process potentially correlated with the metabolic disorders induced by antiretroviral therapy. We tested this hypothesis in a large population of HIV-infected patients in which we measured brachial artery diameter, as an indicator of artery remodeling, by noninvasive, ultrasonographic technique. Our population consisted of 570 patients, with a mean age of 46.3 ± 7.1 years. All the patients were chronically treated with highly active antiretroviral therapy. Brachial artery diameter was correlated with insulin resistance, evaluated by the homeostasis model assessment of insulin resistance index (r = 0.18, P < .0001). There was a significant linear increase in brachial artery diameter as the number of components of the metabolic syndrome increased: brachial artery diameter for those with 0, 1, 2, 3, or + characteristics was 39.3 ± 7.2, 41.0 ± 6.8, 42.0 ± 7.3, and 43.8 ± 7.9 mm, respectively (P < .001 for trend). In multivariable logistic regression analysis, brachial artery diameter was independently correlated with the presence of metabolic syndrome. Our results are in line with the hypothesis that, among HIV-infected patients chronically treated with antiretroviral therapy, those with a larger brachial artery diameter are at high risk for metabolic disorders, including a more severe insulin resistance and the presence of metabolic syndrome.     

Angiographic changes in saphenous vein grafts are predictors of clinical outcomes

Background Previous studies have suggested that angiographic evidence of disease progression in coronary arteries increases the risk of subsequent coronary clinical events. This study ascertained whether patients enrolled in the Post Coronary Artery Bypass Graft Clinical Trial (POST CABG) who had substantial progression of atherosclerosis in ≥1 saphenous vein grafts (on the basis of assessment of baseline and follow-up angiograms obtained 4-5 years after study entry), but who had not reported clinical symptoms before follow-up angiography, were at a higher risk of subsequent events than patients who did not have substantial progression of atherosclerosis (decrease ≥0.6 mm in lumen diameter at site of greatest change from baseline). Methods All 1351 patients enrolled in the trial underwent baseline angiography; only the 961 patients who had follow-up angiography and no coronary events before the follow-up study were included in this analysis. The clinical center staff contacted patients to ascertain the events that had occurred after follow-up angiography (approximately 3.4 years later). Results Sixty-nine patients had died; 870 patients or relatives were interviewed, and 22 patients could not be contacted. Univariable estimates of relative risk associated with substantial progression ranged from 2.2 (P < .001) for cardiovascular death or nonfatal myocardial infarction to 3.3 (P < .001) for revascularization. Multivariable and univariable estimates of risk were similar. Conclusions The findings provide evidence that patients who had substantial progression of atherosclerosis in vein grafts are at an increased risk for subsequent coronary events and suggest that angiographic changes in vein grafts are appropriate surrogate measures for clinical outcomes. (Am Heart J 2003;145:262-9.)     

Postexercise hypotension differs between white and black women

Background Because data are lacking, we examined the acute effect of exercise on ambulatory blood pressure (BP) in premenopausal white women (n = 18) and black women (n = 15) with normal (n = 21) and high (n = 12) BP. Methods Women performed 40 minutes of control and moderate-intensity exercise. BP and hormones were measured before, during, and after the control and exercise periods. By means of RMANCOVA (repeated measures analysis of covarience), we tested whether BP and hormones differed with time and between ethnic, BP, and experimental groups. Multiple regression analysis was used to examine hormonal mediators of the postexercise BP response. Results Among white women with hypertension, average daytime systolic (S) and diastolic (D) BP decreased 11.0 ± 3.3 mm Hg (−2.9, −19.1; P = .017) and 8.2 ± 2.8 mm Hg (−1.2, −13.9; P = .000), from 142.6 ± 5.8 mm Hg and 96.1 ± 2.8 mm Hg, respectively, after exercise. Among black women with high BP, mean daytime SBP rose 12.5 ± 5.2 mm Hg (−2.0, 27.1; P = .000) after exercise, from 121.8 ± 6.1 mm Hg, whereas DBP was similar before and after exercise (81.4 ± 4.3 mm Hg and 82.8 ± 4.7 mm Hg, respectively). In white women without hypertension, daytime SBP and DBP were similar before and after exercise. In black women without hypertension, mean daytime SBP increased 6.3 ± 2.6 mm Hg (0.4, 12.1; P = .000) after exercise from 103.6 ± 1.4 mm Hg, and DBP did not change. In black women, hypertension (P = 0.000) and exercise-mediated insulin decreases (P = .005) explained 85.6% of the postexercise SBP response (P = .000). In white women, hypertension (P = .003) and baseline plasma renin (P = .049) accounted for 53.3% of the postexercise SBP response (P = .001). Exercise acutely reduced daytime BP in white women, but not in black women with high BP. Conclusion Endurance exercise may adversely affect the BP of black women. (Am Heart J 2003;145:364-70.)