The association of calcium supplementation and incident cardiovascular events in the Multi-ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Many US adults use calcium supplements to address inadequate dietary intake and improve bone health. However, recent reports have suggested that use of calcium supplements may elevate cardiovascular disease (CVD) risk. In this study, we examined associations between baseline calcium supplement use and incident myocardial infarction (MI) (n = 208 events) and CVD events (n = 641 events) over 10.3 years in men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 6236), with dietary calcium intake at baseline also examined as a supplementary objective. METHODS AND RESULTS: Using Cox proportional hazards models, no compelling associations between calcium intake from supplements or diet and incident CVD events were observed upon multivariate adjustment for potential confounders. An association with lower MI risk was observed comparing those with low levels of calcium supplement use (1-499 mg) to those using no calcium supplements (hazard ratio 0.69, 95% CI 0.48, 0.98, p = 0.039). Relationships were homogeneous by gender, race/ethnicity, or chronic kidney disease. Results were also similar when the analysis was limited to postmenopausal women only. CONCLUSION: Analysis of incident MI and CVD events in the MESA cohort does not support a substantial association of calcium supplement use with negative cardiovascular outcomes.

Effects of hormone therapy on blood pressure and the renin-angiotensin system in postmenopausal women.

Observational studies have documented an association between lower rates of cardiovascular disease and hormone therapy (HT). Meanwhile, randomized clinical trials have documented increased rates of myocardial infarction and stroke in women receiving hormone therapy. These seemingly discordant findings have stimulated new research to examine estrogen's effects on the cardiovascular system, including its effects on blood pressure, regulation of the renin-angiotensin system (RAS), and the clinical consequences of hypertension. In the last 6 years several studies have better defined the mechanisms by which HT affect the RAS, blood pressure, and the clinical effects of hypertension. Recent studies documented increases in angiotensinogen synthesis and the suppression of active renin with estrogen replacement. Genotype may be a factor in determining the degree of suppression of angiotensin converting enzyme levels that occurs with estrogen therapy. Estrogen supplementation in postmenopausal women increases systemic angiotensin II, a potent vasoconstrictor. This vasopressor effect is attenuated by an estrogen-induced reduction of angiotensin II type 1 receptor expression. Renal blood flow reduction, in the absence of blood pressure changes, have been reported after estrogen replacement, and an increased risk of total stroke has been demonstrated in hypertensive women on HT compared to normotensive women on this therapy. Estrogen replacement affects many components of the RAS, but its effect on this system has little effect on blood pressure. Further studies are needed to describe the effects of estrogen replacement on abnormal vasculature and how these effects relate to myocardial infarction and stroke.

Utility of fast cine magnetic resonance imaging and display for the detection of myocardial ischemia in patients not well suited for second harmonic stress echocardiography.

BACKGROUND: Some patients referred for pharmacological stress testing with transthoracic echocardiography (TTE) are unable to undergo testing owing to poor acoustic windows. Fast cine MRI can be used to assess left ventricular contraction, but its utility for detection of myocardial ischemia in patients poorly suited for echocardiography is unknown. METHODS AND RESULTS: One hundred fifty-three patients (86 men and 67 women aged 30 to 88 years) with poor acoustic windows that prevented adequate second harmonic TTE imaging were consecutively referred for MRI to diagnose inducible myocardial ischemia during intravenous dobutamine and atropine. Diagnostic studies were completed in an average of 53 minutes. No patients experienced myocardial infarction, ventricular fibrillation, exacerbation of congestive heart failure, or death. In patients who underwent computer-assisted quantitative coronary angiography, the sensitivity and specificity for detecting a >50% luminal diameter narrowing were 83% and 83%, respectively. In the 103 patients with a negative MRI examination, the cardiovascular occurrence-free survival rate was 97%. CONCLUSIONS: Fast cine cardiac MRI provides a mechanism to assess left ventricular contraction and diagnose inducible myocardial ischemia in patients not well suited for stress echocardiography.

Assessment of coronary arterial restenosis with phase-contrast magnetic resonance imaging measurements of coronary flow reserve.

BACKGROUND: After successful percutaneous coronary arterial revascularization, 25% to 60% of subjects have restenosis, a recurrent coronary arterial narrowing at the site of the intervention. At present, restenosis is usually detected invasively with contrast coronary angiography. This study was performed to determine if phase-contrast MRI (PC-MRI) could be used to detect restenosis noninvasively in patients with recurrent chest pain after percutaneous revascularization. METHODS AND RESULTS: Seventeen patients (15 men, 2 women, age 36 to 77 years) with recurrent chest pain >3 months after successful percutaneous intervention underwent PC-MRI measurements of coronary artery flow reserve followed by assessments of stenosis severity with computer-assisted quantitative coronary angiography. The intervention was performed in the left anterior descending coronary artery in 15 patients, one of its diagonal branches in 2 patients, and the right coronary artery in 1 patient. A PC-MRI coronary flow reserve value /=70% and >/=50%, respectively. CONCLUSIONS: Assessments of coronary flow reserve with PC-MRI can be used to identify flow-limiting stenoses (luminal diameter narrowings >70%) in patients with recurrent chest pain in the months after a successful percutaneous intervention.

Visualization and functional assessment of proximal and middle left anterior descending coronary stenoses in humans with magnetic resonance imaging.

BACKGROUND: Coronary artery bypass grafting improves survival in patients with >70% luminal diameter narrowing of the 3 major epicardial coronary arteries, particularly if there is involvement of the proximal portion of the left anterior descending (LAD) coronary artery. Measurement of coronary flow reserve can be used to identify functionally important luminal narrowing of the LAD artery. Although magnetic resonance imaging (MRI) has been used to visualize coronary arteries and to measure flow reserve noninvasively, the utility of MRI for detecting significant LAD stenoses is unknown. METHODS AND RESULTS: Thirty subjects (23 men, 7 women, age 36 to 77 years) underwent MRI visualization of the left main and LAD coronary arteries as well as measurement of flow in the proximal, middle, or distal LAD both at rest and after intravenous adenosine (140 microgram/kg per minute). Immediately thereafter, contrast coronary angiography and when feasible, intracoronary Doppler assessments of coronary flow reserve, were performed. There was a statistically significant correlation between MRI assessments of coronary flow reserve and (a) assessments of coronary arterial stenosis severity by quantitative coronary angiography and (b) invasive measurements of coronary flow reserve (P<0.0001 for both). In comparison to computer-assisted quantitative coronary angiography, the sensitivity and specificity of MRI for identifying a stenosis >70% in the distal left main or proximal/middle LAD arteries was 100% and 83%, respectively. CONCLUSIONS: Noninvasive MRI measures of coronary flow reserve correlated well with similar measures obtained with the use of intracoronary Doppler flow wires and predicted significant coronary stenoses (>70%) with a high degree of sensitivity and specificity. MRI-based measurement of coronary flow reserve may prove useful for identification of patients likely to obtain a survival benefit from coronary artery bypass grafting.

Short-term administration of estrogen and vascular responses of atherosclerotic coronary arteries.

OBJECTIVES: This experiment sought to determine the effect of short-term administration of estrogen on endothelium-dependent dilation in the coronary arteries of 13 surgically postmenopausal female cynomolgus monkeys. BACKGROUND: Long-term estrogen replacement therapy prevents impaired endothelium-dependent dilation of atherosclerotic coronary arteries in postmenopausal female monkeys. However, it remains unclear whether this action of estrogen is due to long-term effects on plasma lipids and atherogenesis or to direct short-term effects on the endothelium. METHODS: The monkeys consumed an atherogenic diet for 18 months after bilateral ovariectomy. Vascular responses were measured just before euthanasia and necropsy. Dextrose in water (control), acetylcholine, 10(-6)M, and nitroglycerin were infused for 2.5 min each both before and 20 min after intravenous injection of 54 ng ethinyl estradiol. RESULTS: Quantitative coronary angiography revealed that the arteries constricted (-17 +/- 3%) in response to intracoronary infusion of acetylcholine before estrogen treatment but dilated (+5 +/- 3%) 20 min after intravenous injection of ethinyl estradiol (p less than 0.05). Coronary arteries dilated in response to nitroglycerin both before and after administration of estrogen (p greater than 0.05). Vascular responses of coronary arteries, both before and after administration of estrogen, were not associated with variation in plasma lipid concentrations, blood pressure, heart rate or plaque size. CONCLUSIONS: Estrogen affects endothelium-dependent coronary dilation within 20 min of administration and may have rapid direct effects on the vascular endothelium.

Pravastatin has cholesterol-lowering independent effects on the artery wall of atherosclerotic monkeys.

OBJECTIVES: This study examined the direct effects of pravastatin on the artery wall of atherosclerotic monkeys after dietary lipid lowering. BACKGROUND: Clinical trials suggest that hepatic hydroxymethylglutaryl coenzyme A reductase inhibitors may reduce the risk of coronary heart disease out of proportion to their effect on angiographically assessed lumen stenosis. METHODS: Thirty-two cynomolgus monkeys were fed an atherogenic diet for 2 years (progression phase) and then fed a lipid-lowering diet either containing (n = 14) or not containing (n = 18) pravastatin in the diet for an additional 2 years (treatment phase). As designed, total plasma cholesterol and high density lipoprotein concentrations did not differ between groups at the beginning of or during the treatment phase of the experiment (p > 0.05). RESULTS: Quantitative angiography revealed that coronary arteries of the pravastatin-treated monkeys dilated 10 +/- 3%, whereas those from untreated control monkeys constricted -2 +/- 2% in response to acetylcholine (p < 0.05). There were no treatment effects on plaque size of coronary arteries measured at the end of the treatment phase of the study (0.110 +/- 0.048 mm2 [untreated] vs. 0.125 +/- 0.051 mm2 [pravastatin]; p > 0.05) or on the amount of reduction in plaque size in common iliac arteries during the treatment phase of the study (48 +/- 5% [untreated] vs. 45 +/- 6% [pravastatin]; p > 0.05). However, histochemical analysis of the atherosclerotic lesions indicated that the arteries from pravastatin-treated monkeys had significantly fewer macrophages in the intima and media, less calcification and less neovascularization in the intima (p < 0.05). CONCLUSIONS: We conclude that compared with control monkeys, the arteries of pravastatin-treated monkeys had better dilator function and plaque characteristics more consistent with plaque stability than those of monkeys not receiving pravastatin. These beneficial arterial effects of pravastatin occurred independently of plasma lipoprotein concentrations and despite similar changes in plaque size between the groups.

Qualitative and quantitative contrasts in the mechanisms of lumen enlargement by coronary balloon angioplasty and directional coronary atherectomy.

OBJECTIVES: This study was designed to define and contrast the mechanisms of lumen enlargement from coronary balloon angioplasty and directional coronary atherectomy using intracoronary ultrasound imaging in vivo. BACKGROUND: The mechanisms of lumen enlargement produced by percutaneous transluminal coronary balloon angioplasty and directional coronary atherectomy are not known because the coronary artery wall has not previously been studied both before and after dilation. METHODS: We used intracoronary ultrasound to quantitate coronary lumen, vessel and plaque area both before and immediately after successful coronary angioplasty (n = 30) and directional coronary atherectomy (n = 25) at the site of most severe stenosis. RESULTS: Angioplasty increased lumen area by 2.80 +/- 0.25 mm2 (mean +/- SE, p < 0.0001). Eighty-one percent of this lumen gain resulted from an increase in vessel area and the remaining 19% from a reduction in plaque area. Lumen gain of individual lesions was separated into three groups: 67% had an increase in vessel area (vessel expansion), 13% had a decrease in plaque area and 20% had a combination of both. In contrast, vessel expansion contributed only 22% of the lumen gain with directional coronary atherectomy, with the majority (78%) of increase in lumen size coming from a reduction in plaque area. Directional coronary atherectomy increased lumen area from 2.36 +/- 0.05 to 7.00 +/- 0.28 mm2 (p < 0.0001). Plaque reduction was the sole mechanism in 60% of lesions, vessel expansion was the sole mechanism in 12% and a combination of both mechanisms occurred in 28%. Lumen enlargement of eccentric lesions treated with directional coronary atherectomy was more commonly associated with plaque reduction (p < 0.02), whereas eccentricity did not affect the mechanism of lumen enlargement with coronary angioplasty. CONCLUSIONS: This is the first study to systematically examine the coronary artery wall in vivo at the site of a severe stenosis both before and after catheter-based interventions in humans. Lumen enlargement from coronary angioplasty occurs predominantly from vessel expansion or stretching, although a reduction in plaque area contributes to the lumen gain in many patients and is the sole mechanism in a few. Lumen gain from directional coronary atherectomy is predominantly from reduction in plaque area (probably owing to tissue removal), although vessel stretching (balloon effect) occurs and is the sole mechanism in a small minority of vessels. Plaque reduction is more common in directional coronary atherectomy of eccentric lesions.

Individual and combined effects of estrogen/progestin therapy and lovastatin on lipids and flow-mediated vasodilation in postmenopausal women with coronary artery disease.

OBJECTIVES: We sought to examine the individual and combined effects of estrogen/progestin therapy versus lovastatin on lipids and flow-mediated vasodilation in postmenopausal women with heart disease. BACKGROUND: Little information is available regarding the relative benefits of estrogen replacement therapy versus reductase inhibitors and the potential utility of their combination as lipid-lowering therapy for postmenopausal women. METHODS: We conducted a randomized, double-blind, crossover trial in 24 postmenopausal women, each of whom received the following drug regimens during three consecutive six-week treatment periods: 1) hormone replacement (oral dose of 0.625 mg/day conjugated equine estrogens and 2.5 mg/day medroxyprogesterone acetate); 2) 20 mg lovastatin/day and 3) hormone replacement plus lovastatin. RESULTS: Total and low density lipoprotein (LDL) cholesterol were significantly lowered and high density lipoprotein (HDL) cholesterol was significantly increased by all three regimens compared with baseline (p < 0.05). Lovastatin was more effective than estrogen/progestin in reducing LDL (p < 0.001), but estrogen/progestin was slightly more effective in increasing HDL. The hormone replacement and lovastatin regimen blocked the estrogen-associated increase in triglycerides. Hormone replacement (alone and with lovastatin) resulted in increases in brachial artery flow-mediated vasodilator capacity (p = 0.01 for both regimens) and the area under the curve (p = 0.016 and p = 0.005, respectively) compared with baseline. Percent dilation was greatest after the hormone replacement regimen, whereas the area under the curve was greatest after hormone replacement plus lovastatin (69% improvement vs. baseline). CONCLUSIONS: In postmenopausal women with coronary disease and hyperlipidemia, conjugated equine estrogen produced significant improvements in lipids and vasodilator responses despite the concurrent administration of low dose medroxyprogesterone acetate. Low dose lovastatin produced greater reductions in LDL, but less dramatic improvements in vasodilator responses. Estrogen/progestin plus lovastatin may provide additional benefits via a greater reduction in the LDL/HDL ratio and attenuation of estrogen-associated hypertriglyceridemia. More information is needed about the safety and efficacy of such combinations of hormone replacement and reductase inhibitor therapy.

Variability in measures of coronary lumen dimensions using quantitative coronary angiography.

OBJECTIVES: The purpose of this study was to determine the true total variability of quantitative coronary angiographic measures and their components in the clinical setting. BACKGROUND: Many studies describe quantitative coronary angiographic variability on the basis of repeated quantitative coronary angiographic measures from the same cineangiogram. Although these studies characterize well the performance of quantitative coronary angiographic analysis methods, they do not include other potentially important sources of variability in results of this procedure, such as day to day variations in patients and equipment or variability in selection of frames for analysis. METHODS: Coronary angiograms from 20 patients who underwent diagnostic angiography followed by percutaneous transluminal coronary angioplasty an average of 2.9 days later were reviewed. A total of 30 lesions well visualized in both films were analyzed multiple times using an automated first-derivative edge-detection quantitative coronary angiographic technique. RESULTS: The coefficient of variation for quantitative coronary angiographic measures of the same lesions from separate angiograms ranged from 8.11% to 14.01%. Average diameter was the least variable and percent diameter stenosis the most variable. Day to day variations in the patient, procedure and equipment accounted for an average of 30% of the total variability. Of the remaining variability, only 13.26% was due to variability in frame selection. CONCLUSIONS: These results provide useful information for planning clinical studies using quantitative coronary angiography, identify areas where additional improvements in this technology are needed and define more clearly the applicability of quantitative coronary angiography in the setting of routine clinical practice.

Plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate in patients undergoing diagnostic coronary angiography.

Serum levels of DHEA sulfate are inversely associated with cardiovascular death in men, and urinary dehydroepiandrosterone (DHEA) levels are inversely associated with clinical manifestations of coronary artery disease. These observations may be related to the antiproliferative effects of DHEA, resulting in inhibition of atherosclerotic intimal hyperplasia. To examine the relation between these steroids and a direct measure of coronary atherosclerosis, plasma DHEA and DHEA sulfate levels were determined in 206 middle-aged patients (103 men, 103 women) undergoing elective coronary angiography. Plasma DHEA sulfate levels were lower in men with at least one stenosis greater than or equal to 50% compared with those without any stenosis greater than or equal to 50% (4.9 +/- 2.7 versus 6.1 +/- 3.5 nmol/ml, p = 0.05). Levels of DHEA sulfate were also inversely related to the number of diseased coronary vessels (r = -0.20, p = 0.05) and a continuous measure of the extent of coronary atherosclerosis (r = -0.25, p = 0.01) in men. The association between DHEA sulfate levels and extent of coronary artery disease was independent of age and other conventional risk factors for coronary disease. In women, there was no association between plasma DHEA or DHEA sulfate levels and coronary disease. These data demonstrate a consistent, independent, inverse, dose-response relation between plasma DHEA sulfate levels and angiographically defined coronary atherosclerosis in men. Plasma DHEA sulfate may be another important and potentially modifiable risk factor for the development and progression of coronary atherosclerosis.

Cardiac cycle-dependent changes in aortic area and distensibility are reduced in older patients with isolated diastolic heart failure and correlate with exercise intolerance.

OBJECTIVES: The goal of this study was to determine if cardiac cycle-dependent changes in proximal thoracic aortic area and distensibility are associated with exercise intolerance in elderly patients with diastolic heart failure (DHF). BACKGROUND: Aortic compliance declines substantially with age. We hypothesized that a reduction in cardiac cycle-dependent changes in thoracic aortic area and distensibility (above that which occurs with aging) could be associated with the exercise intolerance that is prominent in elderly diastolic heart failure patients. METHODS: Thirty subjects (20 healthy individuals [10 < 30 years of age and 10 > 60 years of age] and 10 individuals > the age of 60 years with DHF) underwent a magnetic resonance imaging (MRI) study of the heart and proximal thoracic aorta followed within 48 h by maximal exercise ergometry with expired gas analysis. RESULTS: The patients with DHF had higher resting brachial pulse and systolic blood pressure, left ventricular mass, aortic wall thickness and mean aortic flow velocity, and, compared with healthy older subjects, they had a significant reduction in MRI-assessed cardiac cycle-dependent change in aortic area and distensibility (p < 0.0001) that correlated with diminished peak exercise oxygen consumption (r = 0.79). After controlling for age and gender in a multivariate analysis, thoracic aortic distensibility was a significant predictor of peak exercise oxygen consumption (p < 0.04). CONCLUSIONS: Older patients with isolated DHF have reduced cardiac cycle-dependent changes in proximal thoracic aortic area and distensibility (beyond that which occurs with normal aging), and this correlates with and may contribute to their severe exercise intolerance.

Estrogen replacement and brachial artery flow-mediated vasodilation in older women.

It remains unclear whether estrogen therapy (with or without progestin) improves endothelial function in older postmenopausal women with or at risk for coronary heart disease. To address this issue, we analyzed brachial artery flow-mediated vasodilation in the Cardiovascular Health Study, a longitudinal study of cardiovascular risk factors in subjects over 65 years of age. At the tenth annual Cardiovascular Health Study examination, 1662 women returned for follow-up. Eighteen percent (n=291) were current users of estrogen replacement, most of whom (75.9%, n=221) took unopposed estrogen. Brachial artery ultrasound examinations measuring vasodilation in response to a flow stimulus (hyperemia) were performed on 1636 women. There were no statistical differences in brachial flow-mediated vasodilator responses between users and nonusers, even after adjustment for potential confounders. Absence of an effect was most notable in women over 80 years old and in those with established cardiovascular disease. However, among women without clinical or subclinical cardiovascular disease or its risk factors, there was a significant association between hormone replacement therapy use and flow-mediated vasodilator responses (P=0.01). Among older postmenopausal women, favorable vascular effects of estrogen may be limited to those who have not yet developed atherosclerotic vascular disease. These data emphasize the importance of ongoing efforts to determine the role of hormone replacement therapy for primary prevention of cardiovascular disease.

Should patients with heart disease exercise in the morning or afternoon?

OBJECTIVE: To compare the cardiovascular risk of exercise in the morning and afternoon in patients with established heart disease. DESIGN: Retrospective cohort study. PATIENTS: Patients with established heart disease referred for participation in a comprehensive cardiac rehabilitation program. INTERVENTION: Supervised, submaximal exercise (1 hour three times per week) performed either in the morning (7:30 AM) or the afternoon (3 PM). MAIN OUTCOME: Documented cardiac events that occurred while patients were exercising in the rehabilitation programs. RESULTS: There were five cardiac events in 168,111 patient-hours of exercise in the morning, with an incidence of 3.0 +/- 1.3 events per 100,000 patient-hours. There were two events during the 84,491 patient-hours of exercise in the afternoon, for an incidence of 2.4 +/- 1.5 events per 100,000 patient-hours (not significant). The risk ratio of cardiac events during exercise in the morning compared with the afternoon was 1.27 (95% confidence interval, 0.25 to 6.55). CONCLUSION: In patients with coronary artery disease, the incidence of cardiac events is low during regular, submaximal exercise whether performed in the morning or the afternoon.

Association of hormone replacement therapy and carotid wall thickness in women with and without diabetes.

OBJECTIVE: Atherosclerosis is the major underlying cause of death for women with type 2 diabetes. We examined the relationship between use of postmenopausal hormone replacement therapy(HRT) and subclinical atherosclerosis among women with type 2 diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance. RESEARCH DESIGN AND METHODS: A cross-sectional analysis was conducted among 623 postmenopausal women in the Insulin Resistance Atherosclerosis Study (IRAS). Current users of HRT, n = 200, were compared with 104 former users and 319 never users. Intimal-medial wall thicknesses (IMTs) of the common carotid (CCA) and internal carotid (ICA) arteries were used as measures of atherosclerosis. RESULTS: Significant differences between HRT user groups were noted for certain demographic, socioeconomic, and lifestyle factors. After adjustment for these and other coronary heart disease risk factors, current users had a 69 microm thinner ICA IMT than never users (P = 0.06). Former users had a 96 pm thinner ICA IMT than never users (P = 0.03). No significant difference was observed for the CCA. Although women with type 2 diabetes had thicker carotid IMT than women without diabetes, the association between HRT use and thinner IMT was similar in both groups. The difference between current and never users was attenuated by adjustment for HDL and LDL cholesterol. Neither duration of HRT use nor HRT regimen was associated with IMT in either artery. CONCLUSIONS: This analysis suggests that current and former use of HRT is associated with reduced atherosclerosis and that women with type 2 diabetes may receive the same benefit from HRI as women without diabetes.

Differential effects of E and droloxifene on C-reactive protein and other markers of inflammation in healthy postmenopausal women.

Although increased levels of C-reactive protein have been linked to E therapy, the significance of this finding and whether it occurs with the selective ER modulators are unknown. Thirty-five healthy postmenopausal women were enrolled in a placebo-controlled, two-period cross-over design trial to evaluate the effects of 0.625 mg oral conjugated E and 60 mg droloxifene, a structural analog of tamoxifen, on serum levels of C-reactive protein, IL-6, and endothelial cell adhesion molecules. E treatment resulted in 65.8% higher levels of C-reactive protein (P = 0.0002) and 48.1% higher levels of IL-6 (P < 0.001), but also resulted in a 10.9% reduction in soluble E-selectin (P = 0.002) and borderline reductions in vascular cell adhesion molecule-1. In contrast, droloxifene had no effect on C-reactive protein and IL-6, but did produce a significant 11% reduction in E-selectin (P < 0.00001). However, droloxifene also resulted in an 11.6% increase in vascular cell adhesion molecule-1 (P < 0.007). These data provide additional evidence of a proinflammatory effect of E that may have adverse cardiovascular consequences. However, these changes were also accompanied by a reduction in E-selectin, suggesting an antiinflammatory effect at the level of the endothelium. The net clinical impact of these changes is not yet well established. In contrast, droloxifene had little or no proinflammatory effects on C-reactive protein and IL-6 and had mixed effects on endothelial adhesion molecules. This observation provides additional rationale for continuing to evaluate the potential cardiovascular benefits of selective ER modulators.

Nifedipine overdose.

A 59-year-old man ingested 900 mg of nifedipine. Profound hypotension, sinus and atrioventricular node dysfunction, and hyperglycemia resulted. The patient's condition responded favorably to aggressive treatment with intravenous fluids, calcium, and dopamine. Similar effects and response to therapy have been reported in 17 cases of verapamil overdose and are briefly summarized. The effects of nifedipine overdose are discussed, and preliminary recommendations about its management are offered. With increasing use of nifedipine and other calcium channel blockers, more incidents of overdose can be expected.

Comparison of standard- and extended-length participation in cardiac rehabilitation on body composition, functional capacity, and blood lipids.

Participation in a standard-length outpatient cardiac rehabilitation program (CRP) for 3 months is known to result in positive changes in body composition, functional capacity, and blood lipids in patients with coronary artery disease. However, there has been little attempt to compare patients who remain active in a formal CRP for an extended length of >1 year with patients who exit after a standard length of 3 months. Consequently, 50 patients underwent a series of tests including a maximal graded exercise treadmill test, assessment of body composition, and fasting blood lipid analysis, at entry to CRP and after a follow-up period that ranged from 1 to 5 years. All patients participated in a standard multidisciplinary cardiac rehabilitation program for 3 months. Twenty-five patients discontinued participation after 3 months and received no other contact from the program staff until follow-up, whereas 25 patients remained active in the program until follow-up. After statistically adjusting for baseline differences between the groups, significant differences were observed between the extended- and standard-length groups at follow-up for body weight (177 vs 183 lbs), percent fat (22% vs 24%), METS (10.5 vs 8.4), high-density lipoprotein level cholesterol (44 vs 39 mg/dl), total cholesterol/high-density lipoprotein ratio (5.2 vs 6.1), and triglycerides (134 vs 204 mg/dl), respectively. No significant differences in the adjusted means were observed between the groups at follow-up for total cholesterol (209 vs 219 mg/dl) and low-density lipoprotein cholesterol (136 vs 138 mg/dl). Data from this study demonstrate the efficacy of extended participation in CRP on body composition, functional capacity, and blood lipids. Greater efforts need to be directed at retaining patients in low-cost, center-based maintenance programs and at extending monitoring of patients exiting standard length CRPs.

Interactive effects of soy protein and estradiol on coronary artery reactivity in atherosclerotic, ovariectomized monkeys.

OBJECTIVE: Results of recent clinical trials indicate that mammalian estrogens may be less effective in reducing coronary heart disease risk than once thought. This study was designed to determine whether mammalian estrogen's coronary artery dilator benefits could be enhanced by adding soy with phytoestrogens. DESIGN: Forty-five atherosclerotic, ovariectomized monkeys were fed one of four diets: (1) atherogenic diet with casein/lactalbumin as source of protein (Casein, n = 12); (2) casein diet with micronized estradiol equivalent to a woman's dose of 1 mg/day (Casein + E2, n = 12); (3) atherogenic diet with soy protein with phytoestrogens (129 mg woman/day equivalent) (Soy, n = 11); and (4) the soy diet plus estradiol (Soy + E2, n = 10). METHODS: Quantitative angiography and intravascular Doppler were done after 6 months of experimental diet to measure changes in diameter and coronary flow reserve in the circumflex coronary artery in response to intracoronary acetylcholine and nitroglycerin. RESULTS: Arteries from the E2 and Soy + E2 groups dilated in response to acetylcholine 5 +/- 3% and 12 +/- 5%, respectively (p < 0.05 vs. Casein). There was an interactive effect of soy and E2 on dilator response to acetylcholine (p < 0.05). Flow reserve was greatest in animals fed casein + E2 and soy + E2 (2.3 +/- 0.3 and 2.6 +/- 0.5, respectively; p < 0.05 vs. Casein). Soy protein alone had no effect on coronary artery reactivity (p > 0.05). CONCLUSION: Soy protein itself does not affect coronary artery dilator responses but interacts with estradiol to promote dilator responses to acetylcholine.

Dehydroepiandrosterone and cardiac allograft vasculopathy.

BACKGROUND: Tissue culture, animal model, and epidemiologic studies suggest that dehydroepiandrosterone may inhibit atherosclerosis through its potent antiproliferative effects. Because cardiac allograft vasculopathy is predominantly a proliferative abnormality of intimal and medial smooth muscle cells, plasma levels of dehydroepiandrosterone may play an important role in the development of this disease. METHODS: Sixty-one cardiac allograft recipients who survived for 1 year or more and had at least one annual follow-up cardiac catheterization were included in the study. Plasma levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, and free dehydroepiandrosterone (dehydroepiandrosterone not bound to sex hormone-binding globulin) were measured in all 61 subjects and compared with the presence or absence of cardiac allograft vasculopathy as defined by angiography. RESULTS: Plasma levels of total and free dehydroepiandrosterone were lower in subjects in whom cardiac allograft vasculopathy developed (p = 0.005 and 0.003, respectively). Furthermore, the time to development of cardiac allograft vasculopathy was shorter in subjects with low levels of total and free dehydroepiandrosterone (p = 0.062 and 0.046, respectively). This relationship was maintained after adjusting for age, gender, cholesterol, prednisone use, and blood pressure. CONCLUSIONS: Low plasma levels of dehydroepiandrosterone may facilitate and high levels may retard the development of cardiac allograft vasculopathy.