Effects of oral soy protein on markers of inflammation in postmenopausal women with mild hypercholesterolemia

Background Nitric oxide (NO) may protect arteries against atherosclerosis, as suggested by experimental studies. Estrogen therapy enhances the bioactivity of NO in the vasculature of healthy postmenopausal women, but is not acceptable for long-term use by many women. Observational studies have demonstrated beneficial cardiovascular effects of soy protein in premenopausal and postmenopausal women. We examined whether the consumption of isolated soy protein may improve markers of vascular inflammation in postmenopausal women with hypercholesterolemia. Methods and Results In a randomized, double-blind, placebo-controlled, crossover study, 24 postmenopausal women with hypercholesterolemia received 25 g of soy protein or a placebo daily for 6 weeks, with treatment periods separated by 1 month. Markers of vascular inflammation were measured by enzyme-linked immunosorbent assay methods, including: soluble interleukin-2 receptor (sIL-2r), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). There was no effect of soy protein in comparison with placebo on the inflammatory markers: the sIL-2r level was 942.2 ± 335.3 pg/mL with soy protein and 868.5 ± 226.9 pg/mL with placebo (P = .311); E-selectin was 39.6 ± 16.5 ng/mL with soy protein and 42.1 ± 17.6 ng/mL with placebo (P = .323); P-selectin was 157.9 ± 67.9 ng/mL with soy protein and 157.5 ± 47.6 ng/mL with placebo, (P = .977); ICAM-1 was 266.0 ± 81.3 ng/mL with soy protein and 252.5 ± 82.7 ng/mL with placebo (P = .435); VCAM-1 was 402.7 ± 102.1 ng/mL with soy protein and 416.4 ± 114.8 ng/mL with placebo (P = .53). Conclusions Consumption of 25 g of isolated soy protein daily for 6 weeks does not substantially affect markers of vascular inflammation in postmenopausal women with hypercholesterolemia. (Am Heart J 2003;145:e7.)     

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.)     

Large brachial artery diameter is associated with angiographic coronary artery disease in women

Background Noninvasive methods are needed for the identification of women at highest risk for coronary artery disease (CAD) who might benefit most from aggressive preventive therapy. Identification of brachial artery atherosclerosis, which correlates with coronary artery atherosclerosis, may be useful to estimate or stratify CAD risk. Because atherosclerosis disrupts the arterial architecture that regulates vessel size, we hypothesized that noninvasively measured large brachial artery diameter is a manifestation of atherosclerosis that is associated with angiographic CAD in women with chest pain. Methods We examined 376 women (mean age, 57.1 years) with chest pain in the National Heart, Lung, and Blood Institute's Women's Ischemia Syndrome Evaluation study who underwent B-mode ultrasound scan measurement of brachial artery diameter at rest and during hyperemic stress (to quantify flow-mediated dilation), quantitative coronary angiography, and risk factor assessment. Results Large resting brachial artery diameter was associated with significant angiographic CAD (3.90 ± 0.79 mm vs 3.52 ± 0.59 mm in women with CAD vs no CAD; P < .001). Impaired flow-mediated dilation, which correlated with resting diameter (r = −0.17; P = .001), was weakly associated with significant CAD (2.74% ± 7.11% vs 4.48% ± 9.52% in CAD vs no CAD; P = .046). After adjustment for age, body size, and CAD risk factors, women with large resting brachial artery diameters (>4.1 mm) had 3.6-fold increased odds (95% confidence interval, 1.8 to 7.1; P < .001) of significant angiographic CAD compared with those with small brachial arteries (≤3.6 mm). Conclusion Large resting brachial artery diameter is an independent predictor of significant CAD in women with chest pain. Therefore, a simple ultrasonographic technique may be useful in the identification of women with chest pain who are at increased risk for CAD. (Am Heart J 2002;143:802-7.)     

Electron beam tomography and angiography: sex differences

Background We sought to study a large cohort of symptomatic women to determine the clinical use of electron beam tomography (EBT), with evaluation of the sensitivity and specificity of obstructive coronary disease and the differences between premenopausal and postmenopausal cohorts. Methods Patients who underwent angiography for evaluation of coronary artery disease (CAD) and EBT within 3 months were enrolled. Receiver operating characteristic curves were used to establish relationships between EBT calcium scores and angiographic disease. Results We studied 1120 symptomatic patients, 387 women and 733 men. We found no significant differences with respect to sensitivity for obstructive disease (96% in men and women). However, women had a significantly higher specificity (46% in men versus 57% in women; P = .01). The area under the curves for coronary calcium score predicting angiographic disease was 0.85 for all patients and 0.84 in women. Evaluation of scores on the basis of age revealed a 14.4-year lag between men and women. One hundred thirty-five women had negative EBT study results (score, zero; no calcium present), with 6 with single-vessel disease and 129 with normal coronaries or nonobstructive disease only (negative predictive value, 96%). Conclusion EBT may have a great value in evaluation of women with possible CAD. The high sensitivity and high negative predictive value may serve as the basis for a new diagnostic approach to filter symptomatic women with suspected CAD before coronary angiography. (Am Heart J 2002;143:877-82.)     

Coronary artery calcification in black women and white women

Background Coronary calcification is a potent independent predictor of coronary risk. Sex-specific risk categories based on calcium scores have been established, but ethnic differences in coronary calcification have been little studied. This prospective cohort study compares coronary calcification, assessed by computed tomography, in postmenopausal black women and white women. Methods and Results Computed tomographic scans were performed on 128 black women and 733 white women without known coronary artery disease (mean age 63 ± 8 years). Although coronary risk factors were more prevalent among black women (P < .0001), total calcium scores were similar to those in white women. By use of the Framingham algorithm, higher calcium scores were associated with higher 10-year risk of myocardial infarction or coronary death. In multiple regression analysis, age was independently associated with higher calcium scores in both ethnic groups (P = .002 for black women, P < .0001 for white women). Diabetes mellitus and not exercising at least 3 times per week were independently associated with higher calcium scores in white women but not black women. Educational level, body mass index, current hormone replacement therapy, hysterectomy, dietary fat consumption, family history of premature coronary disease, hypertension, self-reported high cholesterol, and current smoking were not independently associated with coronary calcium score in black women, white women, or the combined cohort; neither was ethnicity an independent predictor of coronary calcification. Conclusions Despite higher dietary fat consumption, higher body mass index, and greater prevalence of hypertension, diabetes, and smoking, black women had coronary calcium scores similar to those of white women. Ethnicity was not an independent predictor of coronary calcification. (Am Heart J 2003;145:724-9.)     

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.)     

Predictors and implications of residual plaque burden after coronary stenting: an intravascular ultrasound study

Background Residual plaque burden after coronary stenting may be visualized by use of intravascular ultrasound. Determinants and implications of residual atherosclerotic plaque burden after coronary stenting are not well established. In particular, the implications of residual plaque burden, after adjusting for confounding factors, are still unknown. Methods Sixty-two consecutive patients (age 56 ± 9 years) undergoing coronary stenting under intravascular ultrasound imaging guidance were prospectively studied. A total of 616 slices were analyzed (every 2 mm of stent length) from motorized pull-back recordings. Residual plaque burden was calculated as residual plaque/vessel area × 100. Results In 565 slices (89%), both residual plaque area and stent area could be measured. Mean residual plaque burden was 46.5% ± 6%. By use of multiple regression analysis, lesion plaque area and reference segment plaque burden were identified as independent predictors of residual plaque burden after stenting. In addition, a significant correlation was found between residual plaque burden and most relevant angiographic parameters at follow-up (including minimal lumen diameter, percent diameter stenosis, and loss index), which persisted after adjustment. Furthermore, stents with a residual plaque burden ≥46% had higher a restenosis rate (relative risk [RR] 4.4, 95% CI 1.09-18.2, P = .03). On logistic regression analysis, residual plaque burden (RR 4.8, 95% CI 4.1-5.6, P = .01) and diabetes (RR 4.3, 95% CI 3.6-5.1, P = .03) emerged as the only independent predictors of restenosis. Conclusions The amount of residual plaque burden after coronary stenting plays an independent role on the late angiographic outcome of these patients. (Am Heart J 2003;145:254-61.)     

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.)     

Randomized comparison of cilostazol versus ticlopidine hydrochloride for antiplatelet therapy after coronary stent implantation for prevention of late restenosis

Background Cilostazol is a newly developed antiplatelet drug that has been widely applied for clinical use. Its antiplatelet action appears to be mainly related to inhibition of intracellular phosphodiesterase activity. Recently, cilostazol has been used for antiplatelet therapy after coronary stent implantation. However, its evaluation has not been established yet. Methods This prospective randomized trial was designed to investigate the efficacy of cilostazol for the prevention of late restenosis and acute or subacute stent thrombosis in comparison with ticlopidine hydrochloride. One hundred thirty consecutive patients, scheduled for elective coronary stenting, were randomly assigned to receive oral aspirin (81 mg/day) plus ticlopidine hydrochloride therapy (200 mg/day; group I) or aspirin plus cilostazol therapy (200 mg/day; group II). These medications were started at least 2 days before coronary intervention and continued until follow-up coronary angiography was performed 6 months later. Results Subacute stent thrombosis was observed in 2 patients of group I but in no patients of group II. Major cardiac events were similarly present in both groups. Elevated transaminase levels were observed more frequently in group I than in group II (P < .05). Each of the quantitative coronary angiography variables before and immediately after coronary stenting were similar in both groups. At follow-up angiography, however, late lumen loss (0.69 ± 0.79 mm vs 0.28 ± 0.40 mm; P < .01) and loss index (0.42 ± 0.56 vs 0.16 ± 0.27; P < .01) were smaller in group II than in group I. Restenosis rate (13% vs 31%; P < .05) and target lesion revascularization rate (7% vs 21%; P < .05) were both lower in group II than in group I. Conclusion Aspirin plus cilostazol therapy may be an effective regimen for prevention of not only stent thrombosis but also restenosis. (Am Heart J 2002;144:303-8.)     

Effect of cardiac rehabilitation on functional outcomes after coronary revascularization

Background Current guidelines recommending cardiac rehabilitation (CR) after coronary revascularization are largely based on early studies that evaluated only a subset of the population and failed to assess the impact of CR on a patient's perception of their functional status. The main objective of this study was to evaluate the impact of CR in a diverse contemporary population on patient functional outcomes. Methods We studied the effect of CR on 6-month SF-36 Physical Functioning (PF) in 700 patients (mean age 67 ± 11 years, 37% women) who underwent coronary bypass grafting or percutaneous intervention from August 1998 to July 2000. Results Overall CR participation was 24%. At baseline, CR participants had higher PF (mean 62.5 vs 52.5, P < .001). After adjusting for baseline clinical variables and PF score, CR was associated with significant improvement in 6-month PF (+5.0, 95% CI 1.0-9.0). This improvement was observed in all patient subgroups, but tended to be greater in magnitude in men versus women, patients aged <70 years versus ≥70 years, and patients with coronary bypass grafting versus patients with percutaneous intervention. CR participants also tended to be more likely to engage in regular exercise (63% vs 55%, P = .06) and modify their diet (82% vs 73%, P = .07). Rates of rehospitalization and repeat revascularization were similar among CR participants and nonparticipants. Conclusions CR after coronary revascularization is associated with improved functional outcomes and adoption of secondary preventive measures. Innovative strategies to facilitate CR enrollment and tailoring programs to better address the needs of all patient subgroups would extend these benefits to more eligible patients. (Am Heart J 2003;145:445-51.)     

Home-based versus hospital-based exercise programs in patients with coronary artery disease: effects on coronary vasomotion

Background In a randomized study, we recently documented that a vigorous, hospital-based exercise training (ET) program improves coronary endothelial function in coronary artery disease. The aim of this consecutive study was to assess whether a home-based exercise program with reduced average training duration can sustain previously achieved effects on coronary endothelial function.Methods Nineteen patients with coronary endothelial dysfunction documented by acetylcholine-induced vasoconstriction were randomly assigned to a training group (n = 10) or a control group (n = 9). After 4 weeks of inhospital training (60 min of bicycle ergometry per day), all training patients were enrolled in a 5-month home-based program of 20 minutes' ergometry training per day and 1 group training session per week. At baseline, after 4 weeks and 6 months, endothelium-mediated vasodilation was assessed by quantitative coronary angiography after intracoronary infusions of acetylcholine. Average peak velocity (APV) was measured with a Doppler wire. Coronary blood flow (CBF) was calculated by multiplying vascular cross-sectional area and APV.Results CBF increased in response to 7.2 μg/min acetylcholine, from 27% ± 11% at the beginning of the study to 110% ± 24% after 4 weeks (P < .01 vs control group). After 6 months, the increase in CBF was lower versus inhospital training (67% ± 18%, P < .05 vs 4 weeks). Changes in APV between 1 and 6 months correlated with daily training durations (r = 0.65, P = .03).Conclusions Home-based ET sustained part of the effects of hospital-based ET on endothelium-dependent vasodilation in coronary artery disease. However, acetylcholine-induced increases in CBF were lower after home-based ET, suggesting a relation between daily training duration and improvement of coronary vasomotion. (Am Heart J 2003;145:e3.)     

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.)     

A new thrombolytic agent,monteplase, is independent of the plasminogen activator inhibitor in patients with acute myocardial infarction: initial results of the COmbining Monteplase with Angioplasty (COMA) trial

Background Both thrombolytic therapy and coronary angioplasty have been inconsistent together for primary acute myocardial infarction (AMI) therapy, because conventional thrombolytic agents accelerate plasminogen activator inhibitor-1 (PAI-1) activity. However, combining newly developed mutant tissue-type plasminogen activators with coronary angioplasty should be reconsidered. Methods This study was designed to investigate clinical usefulness of such an agent, monteplase, for treatment of AMI in light of PAI-1 kinetics. One hundred fifty-four consecutive patients with AMI were randomly assigned to receive direct coronary angioplasty (Group I) or coronary angioplasty after pretreatment with intravenous monteplase (Group II). In 90 of these patients, total PAI-1 antigen levels were serially measured. Results Baseline PAI-1 levels at admission were higher in patients with occluded infarct-related arteries than in patients with patent arteries in Group I (39 ± 4 vs 20 ± 2 ng/mL, P < .01) and in Group II (36 ± 3 vs 27 ± 2 ng/mL, P < .05). In the high PAI-1 level subgroup (≥27 ng/mL, n = 53), Group II showed a higher patency rate than Group I (56 vs 18%, P < .01). Multiple logistic regression analysis indicated that patency could be predicted by the PAI-1 level in Group I (Wald χ²= 3.94, P = .02, odds ratio 0.924, 95% CI 0.855-0.999), but not in Group II. Serial change patterns in the PAI-1 level were identical in Group I and Group II. Conclusion Because monteplase can be used independently of PAI-1 kinetics, a combination of monteplase administration at a community hospital with prompt transfer to a tertiary center for coronary intervention may be a powerful strategy for AMI. (Am Heart J 2002;144:e5.)     

Usefulness of an echo-contrast agent for assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery with transthoracic doppler scan echocardiography

Background This study assessed the feasibility of transthoracic Doppler scan echocardiography (TTDE) combined with echo-contrast agent in measuring coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) in the left anterior descending artery. Methods In 68 consecutive patients who underwent cardiac angiography, TTDE was recorded before and after induction of a hyperemic condition with intravenous administration of adenosine triphosphate (0.14 mg/kg/min). After CFV values returned to baseline, the same measurements were repeated while an echo-contrast agent was continuously infused. CFVR was assessed as the ratio of hyperemic to basal CFV. The pulsed wave Doppler scan quality was graded from 1 to 3 (TTDE score: 1, no signal detection; 2, poor definition of outline; 3, optimal outline definition). Results Before enhancement, CFVR could not be measured in 20 patients. Prevalence of delayed stenosis (Thrombolysis In Myocardial Infarction [TIMI] II grade flow) in these patients (30%) was significantly greater than in those whose CFVRs could be measured without enhancement (2%; P <.01). TTDE scores both at baseline and after hyperemia were significantly improved with contrast enhancement (before, 2.8 ± 0.6; after, 3.0 ± 0.3; P <.01; before, 2.6 ± 0.7; after, 3.0 ± 0.3; P <.01; respectively). Overall contrast enhancement increased the rate of successful CFVR measurement from 70% to 97% (P <.01). Sensitivity and specificity of significant left anterior descending artery stenosis detection with CFVR of <2.0 were 94.4% and 87.8%, respectively. Conclusion These data suggest that administration of echo-contrast agent improves pulse wave Doppler scan quality and thus the feasibility of measuring CFVR. (Am Heart J 2002;143:668-75.)     

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.)     

Improvements in blood rheology after cardiac rehabilitation and exercise training in patients with coronary heart disease

Objectives Our purpose was to examine the effect of cardiac rehabilitation and exercise training on blood rheology in patients with coronary heart disease (CHD). Although increased blood and plasma viscosity have been associated with an increased risk of CHD, the effects of cardiac rehabilitation and exercise training on blood rheology in patients with CHD are uncertain. Methods We assessed whole blood effective viscosity (μ), hematocrit standardized blood viscosity (μ₄₅), red blood cell transport efficiency (τ_rbc), and plasma viscosity (PV) in 23 nonsmoking patients with CHD before and after a phase II cardiac rehabilitation and exercise training program. In addition, we compared the group data with the data of a healthy reference group of 10 subjects. Results Patients with CHD had significantly elevated μ (3.35 ± 0.35 cp vs 3.06 ± 0.19 cp, P < .05) and μ₄₅ (3.51 ± 0.29 cp vs 3.12 ± 0.06 cp, P < .001) and reduced τ_rbc (12.7% ± 1.0% · cp^-1 vs 14.2% ± 0.7% · cp^-1, P < .001) compared with healthy subjects. After rehabilitation, patients with CHD had reductions in PV (1.85 ± 0.18 cp vs 1.77 ± 0.11 cp, P < .01) and μ₄₅ (3.58 ± 0.22 cp vs 3.39 ± 0.22 cp, P < .0001) and an increase in τ_rbc (12.4% ± 0.8% · cp^-1 vs 13.2% ± 0.9% · cp^-1, P < .0001). Conclusions Cardiac rehabilitation improves blood rheology in patients with CHD by reducing μ₄₅ and PV and elevating τ_rbc. These improvements may contribute to the increased functional capacity and reduced morbidity and mortality that is associated with participation in cardiac rehabilitation and exercise programs. (Am Heart J 2002;143:349-55.)     

A randomized trial assessing the effect of coumarins started before coronary angioplasty on restenosis: results of the 6-month angiographic substudy of the Balloon Angioplasty and Anticoagulation Study (BAAS)

Background Thrombus formation during coronary angioplasty may play a role in the restenosis process.Methods The effect of pretreatment with coumarins on 6-month angiographic outcome was studied. In addition, the effect of “optimal” anticoagulation, defined as an international normalized ratio >70% of the follow-up time in the target range, was studied. A total of 261 patients were assigned to aspirin alone (ASA group) and 270 patients to aspirin plus coumarins started 1 week before the procedure (coumarin group).Results The mean international normalized ratio was 2.7 ± 1.2 at the start of the procedure and 3.1 ± 0.5 during follow up. Quantitative coronary analysis was performed on 301 lesions in the ASA group and of 297 lesions in the coumarin group. At 6 months, the minimal luminal diameter was similar in the ASA and coumarin groups. Optimal anticoagulation, however, was an independent predictor of a larger minimal luminal diameter at follow up (P = .01).Conclusion Overall, coumarins do not improve angiographic outcome 6 months after coronary angioplasty. (Am Heart J 2003;145:58-65.)     

Treatment of acromegaly improves myocardial abnormalities

Background Treatment for acromegaly decreases left ventricular (LV) mass, but it is not clear whether diastolic dysfunction is also reversible. With Doppler echocardiography, before and after effective therapy, we assessed the LV morphology and function of patients with acromegaly who were free of complications. Methods In 15 patients with active acromegaly (age range, 33.4 ± 9.3 years), we compared LV Doppler echocardiographic indices, before and after transsphenoidal surgery or radiotherapy or before and after both procedures, noting a significant drop in plasma levels of growth hormone (<2.0 ng/mL after oral glucose tolerance testing). Patients did not have arterial hypertension, diabetes mellitus, thyroid dysfunction, or coronary artery disease. Occasionally, in this series, patients had no symptoms of heart failure, and patients who underwent treatment with somatostatin analog drugs were not included because they did not have a significant hormonal drop. The follow-up period after hormonal control was 2.7 ± 1.7 years. We also studied 15 healthy control subjects matched for age, sex, and body surface area. Results Patients with acromegaly compared with healthy control subjects had increased LV mass index, relative wall thickness, and deteriorated diastolic function. After therapy, most of the abnormalities improved: LV mass index (104 ± 21 g/m² × 87 ± 21 g/m²; P <.01), LV relative wall thickness (0.40 ± 0.06 × 0.35 ± 0.04; P <.01), proto/telediastolic transmitral peak flow velocity ratio (1.17 ± 0.33 × 1.49 ± 0.34; P <.001), and isovolumetric relaxation period (126 ± 18 ms × 113 ± 13 ms; P <.05). Conclusion Treatment of acromegaly in patients without clinical heart failure improves both LV morphology and diastolic function. Avoidance of progression to more advanced forms of acromegalic cardiomyopathy should be possible. (Am Heart J 2002;143:873-6).     

Implantation of CD133 Stem Cells in Patients Undergoing Coronary Bypass Surgery: IMPACT-CABG Pilot Trial

Background

The Implantation of Autologous CD133⁺ Stem Cells in Patients Undergoing CABG (IMPACT-CABG) trial is investigating the feasibility, safety, and efficacy of intramyocardial injections of autologous CD133⁺ stem cells during coronary artery bypass grafting (CABG) in patients with chronic ischemic cardiomyopathy. We are reporting the results of the first 5 open-label patients.

Methods

Bone marrow was harvested from iliac crests and stem cells were isolated using the CliniMACS CD133⁺ Reagent System (Miltenyi Biotec, GmbH, Bergisch Gladbach, Germany). Patients received CABG, followed by CD133⁺ cellular injection in the revascularized hypokinetic myocardium.

Results

Five males New York Heart Association (NYHA) class III patients aged 64 ± 10 years were treated. Immunomagnetic cell processing allowed an average of 100 ± 48-fold enrichment in CD133⁺ cells, with 92 ± 11% recovery after selection. Mean number of CD133⁺ cells injected was 8.4 ± 1.2 million. There were no protocol-related complications during the 18-month follow-up and all patients improved to NYHA class I. Six-month echocardiography showed no significant improvement in left ventricular ejection fraction (34 ± 2% at baseline vs 38 ± 12%: P = 0.50). However, cardiac magnetic resonance showed that systolic wall thickening increased from 15.0 ± 10.5% to 29.0 ± 22.1% (P = 0.01). In addition, mean segmental wall thickness also improved in comparison with baseline (10.7 ± 2.7% to 12.1 ± 4.8%; P < 0.01).

Conclusions

This work represents the first Canadian experience with CD133⁺ stem cells for the treatment of chronic ischemic cardiomyopathy. These results demonstrate the initial safety and feasibility of the IMPACT-CABG pilot trial. Subsequent patients are now being randomized to receive either CD133⁺ stem cell or placebo.     

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.)