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Objectives: To evaluate associations between psychosocial factors and sleep characteristics commonly linked to cardiovascular disease risk among racially/ethnically diverse women., Methods: Women from the AHA Go Red for Women cohort (N = 506, 61% racial/ethnic minority, 37 ± 16years) were assessed using self-reported questionnaires. Logistic regression models were adjusted for age, race, ethnicity, education, and insurance., Results: Women with depression had ∼3-fold higher odds of short sleep (95%CI=1.69-4.61), 2-fold higher odds of poor sleep quality and obstructive sleep apnea risk (95%CI=1.42-3.70 and 1.34-4.24), 4-fold higher odds of insomnia (95%CI=2.42-6.59), and greater likelihood of having an evening chronotype (OR:2.62, 95%CI=1.41-4.89). Low social support was associated with insomnia (OR:1.79, 95%CI=1.18-2.71) and evening chronotype (OR:2.38, 95%CI=1.35-4.19). Caregiving was associated with short sleep (OR:1.73, 95%CI=1.08-2.77) and obstructive sleep apnea risk (OR:2.46, 95%CI=1.43-4.22)., Conclusions: Depression, caregiver strain, and low social support are significantly associated with poor sleep and evening chronotype, highlighting a potential mechanism linking these psychosocial factors to cardiovascular disease risk., Competing Interests: Declaration of conflicts of interest None., (Copyright © 2023 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Depression leads to poor health outcomes in patients with coronary heart disease (CHD). Despite guidelines recommending screening and treatment of depressed patients with CHD, few patients receive optimal care. We applied behavioral and implementation science methods to (1) identify generalizable, multilevel barriers to depression screening and treatment in patients with CHD and (2) develop a theory-informed, multilevel implementation strategy for promoting guideline adoption., Methods: We conducted a narrative review of barriers to depression screening and treatment in patients with CHD (ie, medications, exercise, cardiac rehabilitation, or therapy) comprising data from 748 study participants. Informed by the behavior change wheel framework and Expert Recommendations for Implementing Change, we defined multilevel target behaviors, characterized determinants (capability, opportunity, motivation), and mapped barriers to feasible, acceptable, and equitable intervention functions and behavior change techniques to develop a multilevel implementation strategy, targeting health care systems/providers and patients., Results: We identified implementation barriers at the system/provider level (eg, Capability: knowledge; Opportunity: workflow integration; Motivation: ownership) and patient level (eg, Capability: knowledge; Opportunity: mobility; Motivation: symptom denial). Acceptable, feasible, and equitable intervention functions included education, persuasion, environmental restructuring, and enablement. Expert Recommendations for Implementing Change strategies included learning collaborative, audit, feedback, and educational materials. The final multicomponent strategy (iHeart DepCare) for promoting depression screening/treatment included problem-solving meetings with clinic staff (system); educational/motivational videos, electronic health record reminders/decisional support (provider); and a shared decision-making (electronic shared decision-making) tool with several functions for patients, for example, patient activation, patient treatment selection support., Conclusions: We applied implementation and behavioral science methods to identify implementation barriers and to develop a multilevel implementation strategy for increasing uptake of depression screening and treatment in patients with CHD as a use case. The multilevel implementation strategy will be evaluated in a future hybrid II effectiveness-implementation trial.

Background: Perception of body size is a key factor driving health behavior. Mothers directly influence children's nutritional and exercise behaviors. Mothers of ethnic minority groups and lower socioeconomic status are less likely to correctly identify young children as overweight or obese. Little evaluation has been done of the inverse--the child's perception of the mother's weight., Objective: To determine awareness of weight status among mother-child dyads (n = 506)., Design: Cross-sectional study conducted in an outpatient pediatric dental clinic of Columbia University Medical Center, New York, NY., Participants: Primarily Hispanic (82.2 %) mothers (n = 253), 38.8 ± 7.5 years of age, and children (n = 253), 10.5 ± 1.4 years of age, responding to a questionnaire adapted from the validated Behavioral Risk Factor Surveillance System., Main Measures: Anthropometric measures-including height, weight, and waist circumference-and awareness of self-size and size of other generation were obtained., Key Results: 71.4 % of obese adults and 35.1 % of overweight adults underestimated size, vs. 8.6 % of normal-weight (NW) adults (both p < 0.001). Among overweight and obese children, 86.3 % and 62.3 % underestimated their size, vs. 14.9 % NW children (both p < 0.001). Among mothers with overweight children, 80.0 % underestimated their child's weight, vs. 7.1 % of mothers with NW children (p < 0.001); 23.1 % of mothers with obese children also underestimated their child's weight (p < 0.01). Among children with obese mothers, only 13.0 % correctly classified the adult's size, vs. 76.5 % with NW mothers (p < 0.001). Among obese mothers, 20.8 % classified overweight body size as ideal, vs. 1.2 % among NW mothers (p < 0.001)., Conclusion: Overweight/obese adults and children frequently underestimate their size. Adults misjudge overweight/obese children as being of normal weight, and children of obese mothers often underestimate the adult's size. Failure to recognize overweight/obesity status among adults and children can lead to prolonged exposure to obesity-related comorbidities.

Background: While knowledge of cardiovascular disease (CVD) has improved, it remains low among minority women, thereby contributing to disparities and posing health challenges. Moreover, substantial numbers of women do not recognize that excess weight imposes CVD risk and increases morbidity and decreases survival. In order to test the hypothesis that CVD knowledge is reduced among overweight and obese women, CVD knowledge and weight perception was compared among Hispanic and non-Hispanic white (NHW) women., Methods: Data from 382 Hispanic and 301 NHW women, participants in the Heart Health in Action database (n=829), were analyzed from a structured behavioral risk factor surveillance system (BRFSS) questionnaire to assess demographics, risk factors, and CVD knowledge. Multivariable logistic regression analysis was utilized to test for differences between Hispanic and NHW women regarding knowledge with covariates of age, education, and body mass index (BMI)., Results: Hispanics (27%) were less likely than NHW (88%) to correctly identify the leading cause of death among women, (p<0.0001). Years living in the United States did not relate to the percentage of respondents who correctly identified the leading cause of death among women or knew the symptoms of a heart attack. Differences between Hispanic and NHW remained significant after adjustment for age, education, and BMI (p<0.0001). Hispanics (69.4%) were less likely than NHW (82.9 %) to correctly estimate weight (p<0.0001). Underestimation of weight was greater among Hispanics (24.8%) than NHW (5.0%); 48.5% of overweight Hispanic participants versus 12.7% of overweight NHW participants underestimated weight (p<0.0001) and 17.2% of obese Hispanic versus 0% of NHW obese participants (p=0.001) underestimated weight. The percentage underestimating the silhouette corresponding to their weight was related to years in the United States: 29.3% for<10 years, 38.3% with 10-19 years, and 49.3% with ≥20 years (p=0.01 for trend)., Conclusions: Effective prevention strategies for at-risk populations need to target CVD knowledge and awareness among overweight and obese Hispanic women.

To assess weight loss attempt among a Latino immigrant population from the Dominican Republic we analyzed data on 585 overweight and obese Dominicans from a cross-sectional survey using Chi-square statistics, Student's t-tests, and logistic regression models. We found 58% of the overweight and obese tried to lose weight. Female gender (OR 2.28, CI 1.53-3.39), overweight perception (OR 2.37, CI 1.57-3.60) and weight loss advice from health professionals (OR 1.90, CI 1.24-2.91) were strongly associated with weight loss attempt. Individuals with diabetes were more likely to receive advice to lose weight (OR 2.58, CI 1.18-5.63; yet, they were more satisfied with their weight (40.5 vs. 27.8%, p < 0.021), and no difference in their weight loss attempt (p = 0.849) was detected compared to individuals without diabetes. We conclude a significant proportion of overweight and obese Dominican immigrants do not attempt to lose weight. Overweight perception and, except among individuals with diabetes, weight loss advice were strong inducements to weight loss attempt.

Background: It is not known whether cardiovascular disease (CVD) risk level is related to knowledge of the leading cause of death of women or heart attack symptoms., Hypothesis: Women with higher CVD risk estimated by Framingham Risk Score (FRS) or metabolic syndrome (MS) have lower CVD knowledge., Methods: Women visiting primary care clinics completed a standardized behavioral risk questionnaire. Blood pressure, weight, height, waist size, fasting glucose, and lipid profile were assessed. Women were queried regarding CVD knowledge., Results: Participants (N = 823) were Hispanic women (46%), non-Hispanic white (37%), and non-Hispanic black (8%). FRS was determined in 278: low (63%), moderate (29%), and high (8%); 24% had ≥3 components of MS. The leading cause of death was answered correctly by 54%, heart attack symptoms by 67%. Knowledge was lowest among racial/ethnic minorities and those with less education (both P< 0.001). Increasing FRS was inversely associated with knowing the leading cause of death (low 72%, moderate 68%, high 45%, P = 0.045). After multivariable adjustment, moderate/high FRS was inversely associated with knowing symptoms (moderate odds ratio [OR] 0.52, 95% confidence interval [CI]: 0.28-0.98; high OR 0.29, 95% CI: 0.11-0.81), but not the leading cause of death. MS was inversely associated with knowing the leading cause of death (P< 0.001) or heart attack symptoms (P = 0.018), but not after multivariable adjustment., Conclusions: Women with higher FRS were less likely to know heart attack symptoms. Efforts to target those at higher CVD risk must persist, or the most vulnerable may suffer disproportionately, not only because of risk factors but also inadequate knowledge., (© 2013 Wiley Periodicals, Inc.)

Background: Inadequate cardiovascular disease (CVD) knowledge has been cited to account for the imperfect decline in CVD among women over the last 2 decades., Hypothesis: Due to concerns that at-risk women might not know the leading cause of death or symptoms of a heart attack, our goal was to assess the relationship between CVD knowledge race/ethnicity, education, and body mass index (BMI)., Methods: Using a structured questionnaire, CVD knowledge, socio-demographics, risk factors, and BMI were evaluated in 681 women., Results: Participants included Hispanic, 42.1% (n = 287); non-Hispanic white (NHW), 40.2% (n = 274); non-Hispanic black (NHB), 7.3% (n = 50); and Asian/Pacific Islander (A/PI), 8.7% (n = 59). Average BMI was 26.3 ± 6.1 kg/m(2) . Hypertension was more frequent among overweight (45%) and obese (62%) than normal weight (24%) (P < 0.0001), elevated total cholesterol was more frequent among overweight (41%) and obese (44%) than normal weight (30%) (P < 0.05 and P < 0.01, respectively), and diabetes was more frequent among obese (25%) than normal weight (5%) (P < 0.0001). Knowledge of the leading cause of death and symptoms of a heart attack varied by race/ethnicity and education (P < 0.001) but not BMI. Concerning the leading cause of death among women in the United States, 87.6% (240/274) NHW answered correctly compared to 64% (32/50) NHB (P < 0.05), 28.3% (80/283) Hispanic (P < 0.0001), and 55.9% (33/59) A/PI (P < 0.001). Among participants with ≤12 years of education, 21.2% knew the leading cause of death and 49.3% knew heart attack symptoms vs 75.7% and 75.5%, respectively, for >12 years (both P < 0.0001)., Conclusions: Effective prevention strategies for at-risk populations need to escalate CVD knowledge and awareness among the undereducated and minority women., (© 2011 Wiley Periodicals, Inc.)

Unlabelled: Abstract Background: The diversity of the U.S. population and disparities in the burden of cardiovascular disease (CVD) require that public health education strategies must target women and racial/ethnic minority groups to reduce their CVD risk factors, particularly in high-risk communities, such as women with the metabolic syndrome (MS)., Methods: The data reported here were based on a cross-sectional face-to-face survey of women recruited from four participating sites as part of the national intervention program, Improving, Enhancing and Evaluating Outcomes of Comprehensive Heart Care in High-Risk Women. Measures included baseline characteristics, sociodemographics, CVD related-knowledge and awareness, and Framingham risk score (FRS)., Results: There were 443 of 698 women (63.5%) with one or more risk factors for the MS: non-Hispanic white (NHW), 51.5%; non-Hispanic black (NHB), 21.0%; Hispanic, 22.6%. Greater frequencies of MS occurred among Hispanic women (p<0.0001), those with less than a high school education (70.0%) (p<0.0001), Medicaid recipients (57.8%) (p<0.0001), and urbanites (43.3%) (p<0.001). Fewer participants with MS (62.6%) knew the leading cause of death compared to those without MS (72.1%) (p<0.0001). MS was associated with a lack of knowledge of the composite of knowing the symptoms of a heart attack plus the need to call 911 (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.17-0.97, p=0.04)., Conclusions: Current strategies to decrease CVD risk are built on educating the public about traditional factors, including hypertension, smoking, and elevated low-density lipoprotein cholesterol (LDL-C). An opportunity to broaden the scope for risk reduction among women with cardiometabolic risk derives from the observation that women with the MS have lower knowledge about CVD as the leading cause of death, the symptoms of a heart attack, and the ideal option for managing a CVD emergency.

Objective: The purpose of this study was to improve the fund of knowledge, reduce cardiovascular disease (CVD) risk, and attain Healthy People 2010 objectives among women in model women's heart programs., Methods: A 6-month pre/post-longitudinal educational intervention of high-risk women (n = 1310) patients at six U.S. women's heart programs consisted of comprehensive heart health counseling and use of American Heart Association/American College of Cardiology (AHA/ACC) Evidence-Based Guidelines as enhancement to usual care delivered via five integrated components: education/awareness, screening/risk assessment, diagnostic testing/treatment, lifestyle modification/rehabilitation, and tracking/evaluation. Demographics, before and after knowledge surveys, clinical diagnoses, laboratory parameters, and Framingham risk scores were also determined. Changes in fund of knowledge, awareness, and risk reduction outcomes and Healthy People 2010 objectives were determined., Results: At 6 months, there were statistically significant improvements in fund of knowledge, risk awareness, and clinical outcomes. Participants attained or exceeded >90% of the Healthy People 2010 objectives. Proportions of participants showing increased knowledge and awareness of CVD as the leading killer of women, of all signs and symptoms of a heart attack, and calling 911 increased significantly (11.1%, 25.4%, and 34.6%, respectively). Health behavior counseling for physical activity, diet, and diabetes as CVD risk factors increased significantly (28.3%, 28.2%, and 12.5%, respectively). There was a statistical 4.1% increase in participants with systolic blood pressure (SBP) <140/90 mm Hg, a 4.7% decrease in participants with total cholesterol (TC) >240 mg/dL, a 4.5% decrease in participants with TC >200 mg/dL, a 5.9% decrease in participants with high-density lipoprotein cholesterol (HDL-C) <50 mg/dL, a 4.4% decrease in participants with HDL-C <40 mg/dL, and an 8.8% increase in diabetics with low-density lipoprotein cholesterol (LDL-C) <100 mg/dL., Conclusions: CVD prevention built around a comprehensive heart care model program and AHA/ACC Evidence-Based Guidelines can be successful in improving knowledge and awareness, CVD risk factor reduction, and attainment of Healthy People 2010 objectives in high-risk women. Thus, these programs could have a dramatic and lasting impact on the health of women.

Aims: Improving, Enhancing and Evaluating Outcomes of Comprehensive Heart Health Care Programs for High Risk Women has funded six diverse centers to provide chronic disease risk factor screening and lifestyle interventions for women and focuses specifically on low-income, minority women., Results: This article describes the rationale for these diverse programs across the country, all focusing on improving outcomes for women with or at risk for cardiovascular disease (CVD). The six programs include College of Physicians and Surgeons at Columbia University, Christ Community Health Services in Memphis, Women's Heart Center of Fox Valley Cardiovascular Consultants, University of Minnesota, University of California Davis Women's Cardiovascular Medicine Program, and Yale-New Haven Hospital's Women's Heart Advantage., Conclusions: We present six differing approaches to women's heart programs. Based on this experience, promoting CVD prevention in women is a feasible healthcare delivery strategy for health promotion and for delivering preventive strategies for high-risk women. It is possible to deliver heart-healthy programs through existing healthcare infrastructures. These programs provide important models for public health, voluntary, and other health organizations to develop networks for population-based, targeted, relatively low cost programs that support Healthy People 2010 objectives for lifestyle changes and cardiovascular health. Ongoing longitudinal analysis of the programs will provide information about clinical outcomes and sustainability of such programs beyond the funding period.

Background: Metabolic syndrome has the highest prevalence among Mexican-American women. Little information is available for Caribbean Hispanics, the largest and fastest growing ethnic minority in the United States. We sought to evaluate the frequency of metabolic syndrome and its relationship with race/ethnicity, socioeconomic position, and education in women of largely Caribbean Hispanic origin., Methods: There were 204 women enrolled in a cross-sectional study who had demographics, fasting glucose, lipid profile, waist circumference, and blood pressure determined. Metabolic syndrome (defined by the National Cholesterol Education Program/Adult Treatment Panel III [NCEP/ATP III]) was analyzed using univariate and multivariate logistic regression to test age, race/ethnicity, education, health insurance, and residence on the risk of metabolic syndrome. A P value <0.05 was considered significant., Results: Mean age was 58 +/- 11 years, Hispanic 44.1% (93% Caribbean), non-Hispanic white (NHW) 38.7%, and non-Hispanic black 9.8%. Education was some high school (

Background: Inadequate participation in physical activity is a serious public health issue in the United States, with significant disparities among population groups. In particular, there is a scarcity of information about physical activity among Caribbean Hispanics, a group on the rise., Methods: Our goal was to accumulate data on physical activity among Caribbean Hispanic women living in New York and determine the relation between physical activity and age, marital status, education, income, primary language, and children in the household. To this end, a survey adapted from the National Health Interview Survey of the National Center for Health Statistics assessing type, frequency, and duration of physical activity was administered., Results: There were 318 self-identified Hispanic women who participated. Total activity time, mean 385 +/- 26 minutes, and education (r = 0.14, p < 0.01) were significantly related. Women who had attended some college had greater total activity time than those with some high school education (p = 0.046) or < 8th grade education (p = 0.022). Walking as a form of transportation was the most frequent pursuit, 285 +/- 21 minutes. Age (r = -0.34, p < 0.001) and education (r = 0.25, p < 0.001) correlated with nonwalking activity time (leisure time). Nonwalking activity times were greater in younger, that is, 18-29 years (p < 0.001) and college-educated women (p < 0.001). Physical activity recommendations were met by 11%; and 17% reported no physical activity., Conclusions: Among Caribbean Hispanic women living in New York City, the current recommendations for physical activity are met by 11%, and physical activity and education are significantly related. Our observation that education is a critical factor related to physical activity suggests that programs to address the promotion of a physically active lifestyle are needed.

Health-care providers are in a unique position to encourage people to make healthy lifestyle choices. However, lifestyle modification counseling is a complex task, made even more so by the cultural and socioeconomic diversity of patient populations. The objective of this study is to evaluate the prevalence and predictors of attending and physician-in-training weight control counseling in an urban academic internal medicine clinic serving a unique low-income multiethnic high-risk population. In 2006, patients (n = 256) from the Associates in Internal Medicine clinic (Division of General Medicine at the New York Presbyterian Hospital, Columbia University Medical Center, New York, NY) were recruited and completed a questionnaire, which assessed demographic variables, health conditions, access to health-care services, physician weight control counseling, and weight loss attempts. Seventy-nine percent of subjects were either overweight or obese. Only 65% of obese subjects were advised to lose weight. Attending physicians were more likely than physicians-in-training to counsel subjects on weight control (P < 0.01). Factors that were significantly (P < 0.05) associated with different types of weight control counseling included obesity, cardiovascular disease (CVD) risk factors, female gender, nonblack race, college education, married status, and attending physician. Subjects advised to lose weight were more likely to report an attempt to lose weight (P < 0.01). Rates of weight control counseling among physicians are suboptimal, particularly among physicians-in-training. Training programs need to promote effective clinical obesity prevention and treatment strategies that address socioeconomic, linguistic, and cultural factors.

Background: Although non-Hispanic white women have an increased risk of developing breast cancer, the disease-specific survival is lower for African American and Hispanic women. Little is known about disparities in follow-up after an abnormal mammogram. The goal of this study was to investigate potential disparities in follow-up after an abnormal mammogram., Methods: A retrospective cohort study of 6722 women with an abnormal mammogram and documented follow-up from January 2000 through December 2002 was performed at an academic medical center in New York City. The outcome was the number of days between the abnormal mammogram and follow-up imaging or biopsy. Cox proportional hazards models were used to assess the effect of race/ethnicity and other potential covariates., Results: The median number of days to diagnostic follow-up after an abnormal mammogram was greater for African American (20 days) and Hispanic (21 days) women compared with non-Hispanic white (14 days) women (p < 0.001). Racial/ethnic disparities remained significant in a multivariable model controlling for age, Breast Imaging Reporting and Data System (BIRADS) category, insurance status, provider practice location, and median household income., Conclusions: After an abnormal mammogram, African American and Hispanic women had longer times to diagnostic follow-up compared with non-Hispanic white women. Future efforts will focus on identifying the barriers to follow-up so that effective interventions may be implemented.

Background: Physical inactivity is a growing problem facing American women. As little as 150 minutes of moderate physical activity (PA) weekly can reduce the risk of chronic diseases, such as heart disease and stroke. We developed a survey to determine levels and predictors of PA in a diverse population of urban women with access to healthcare., Methods: From February to September 2004, women visiting an academic health center completed a self-administered PA survey. Total activity time (TAT) was calculated as the sum of all activity (walking, jogging or running, dancing, calisthenics, bicycling, aerobics, swimming) recorded over the preceding 2 weeks. Analysis of variance (ANOVA) models were used to assess the effect of different variables on TAT., Results: The survey was completed by 242 women, mean age of 43.4 years. Ninety percent were insured; 66% were non-Hispanic white, 16% were Hispanic, and 10% were African American. Seventy-six percent of women were college graduates. Only 58% of participants recorded >or=150 minutes of PA/week. TAT was related to education, with a significant difference between high school and college graduates (290 +/- 80 vs. 502 +/- 40 min [SEM], p < 0.05)., Conclusions: Education was strongly associated with TAT among these insured, diverse, and well-educated women. Only 58% exercised >or=150 minutes/week, underscoring the need to target exercise programs for all women and to close the gap between women of lower and higher educational attainment.

On the 10th anniversary of the establishment of a Center for Women's Health (CWH) program, the opportunity to share the successes and limitations in developing a centralized approach to women's healthcare is provided. The development of the CWH at the Columbia University Medical Center, New York-Presbyterian Hospital was prompted by concerns that the health status for women is worse than for men in terms of disability, morbidity, and chronic illness. Moreover, women move through cycles of health and illness differently from men, and gender inequalities in research design and implementation and underrepresentation of women in clinical studies contributed to knowledge gaps concerning women's health, possibly leading to suboptimal care. The goal in developing a program was (1) to provide outstanding medical care to women based on prevention and treatment of unique aspects of women's health, (2) to develop professional training and multidisciplinary educational programs promoting knowledge, understanding, and credible scientific efforts, and (3) to foster collaborative research and communication among researchers, practitioners, policymakers, and organizations. In this paper, the clinical and educational programmatic activities and lessons learned are described.

This prospective study was designed to characterize the time course and variability of hemostatic and fibrinolytic risk factors over the course of a menstrual cycle in normal premenopausal women. Plasminogen activator inhibitor (PAI-1), tissue plasminogen activator, von Willebrand factor, fibrinogen, and fibrin D-dimer predict risk of coronary heart disease. Yet there is limited information describing the status of endogenous hormone concentrations and hemostatic and coagulation factors in premenopausal women. Twenty premenopausal women, mean age 34 +/- 7 yr, underwent testing over a cycle to measure endogenous hormones and hemostatic factors: estradiol and progesterone, FSH, LH; PAI-1, tissue plasminogen activator, von Willebrand factor, fibrin D-dimer, and fibrinogen as well as lipids: total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides. There was cyclical variability in estradiol (P < 0.01) and progesterone (P < 0.001) during the follicular and luteal phases. Moreover, there was intra- and interindividual cyclical variation in hemostatic risk factors. Measures of PAI-1 (P < 0.01) and D-dimer (P < 0.05) differed during the follicular and luteal phases. As estradiol concentration increased, PAI-I decreased. There was a significant correlation between total cholesterol and PAI-1 (r = 0.56, P < 0.05), low-density lipoprotein-cholesterol and PAI-1 (r = 0.50, P < 0.05) as well as between total cholesterol and fibrinogen (r = 0.61, P < 0.05). There is significant cyclical variability in estradiol, FSH, and progesterone as well as the hemostatic factors, PAI-1 and fibrin D-dimer. Characterization of emerging hemostatic risk factors enhances understanding of normal physiology, provides insight into the relation between estrogen and hemostatic factors, and raises the potential for predicting coronary heart disease even in relatively young women.

Cardiovascular disease (CVD) is the primary cause of death in women, and women with type 2 diabetes mellitus are at greater risk of CVD compared with nondiabetic women. The increment in risk attributable to diabetes is greater in women than in men. The extent to which hyperglycemia contributes to heart disease risk has been examined in observational studies and clinical trials, although most included only men or did not analyze sex differences. The probable adverse influence of hyperglycemia is potentially mediated by impaired endothelial function, and/or by other mechanisms. Beyond high blood glucose level, a number of other common risk factors for CVD, including hypertension, dyslipidemia, and cigarette smoking, are seen in women with diabetes and require special attention. Presentation and diagnosis of CVD may differ between women and men, regardless of the presence of diabetes. Recognizing the potential for atypical presentation of CVD in women and the limitations of common diagnostic tools are important in preventing unnecessary delay in initiating proper treatment. Based on what we know today, treatment of CVD should be at least as aggressive in women-and especially in those with diabetes-as it is in men. Future trials should generate specific data on CVD in women, either by design of female-only studies or by subgroup analysis by sex.

Objectives: We sought to test whether one month of daily oral conjugated equine estrogen (CEE) or transdermal estradiol alters hemostatic factors in postmenopausal subjects., Background: Estrogen replacement therapy and hormonal replacement therapy (HRT) effect an early increase in cardiovascular events in postmenopausal women. Circulating plasma von Willebrand factor (vWF) antigen is a marker of generalized endothelial dysfunction and atherothrombosis., Methods: Thirty-eight healthy postmenopausal women (average 59 +/- 7 years) were randomized to receive daily oral CEE, 0.625 mg (n = 21); transdermal estradiol, 0.1 mg/day (n = 7); or oral placebo (n = 10) for one month. Blood samples were collected at baseline and after two weeks and four weeks of therapy for measurement of circulating plasma hormones, lipid concentrations, and hemostatic factors., Results: Oral CEE decreased total cholesterol (p < 0.01) and low-density lipoprotein cholesterol (p < 0.01), although it increased both triglycerides (p < 0.05) and high-density lipoprotein cholesterol (p < 0.01). Transdermal estradiol had no significant effect on lipids. Plasminogen activator inhibitor-1 antigen declined in both oral CEE and transdermal estradiol users, but did not achieve statistical significance. Fibrin D-dimer antigen did not vary significantly in any group. However, oral CEE users had a significant increase in vWF from baseline to four weeks (p < 0.03) and a decrease in tissue-type plasminogen activator antigen from baseline to four weeks (p < 0.004), which was significantly different from the change observed in the transdermal estradiol group (p < 0.05)., Conclusions: These data suggest that the oral CEE-mediated increase in plasma vWF may have clinical relevance given the early atherothrombotic effects of HRT in postmenopausal women.

Because the use of herbal therapies in the U.S. is escalating, it is essential to be aware of clinical and adverse effects, doses and potential drug-herb interactions. A consumer poll in 1998 indicated that one-third of respondents use botanical remedies, and nearly one in five taking prescription medications also used herbs, high-dose dietary supplements or both. An estimated 15 million adults are at risk for potential adverse interactions involving prescription medications and herbs or vitamin supplements, yet most practicing physicians have little knowledge of herbal remedies or their effects. Herbal products are marketed without the proof of efficacy and safety that the Food and Drug Administration (FDA) requires of drugs. The Dietary Supplement and Health Education Act of 1994 allocates responsibility to manufacturers for ensuring safety and efficacy with no specific requirements to submit documentation. Manufacturers may state a product's physiologic effects but may not make claims for the treatment or cure of specific diseases. Consumers and practitioners have little information about product safety, contraindications, interactions or effectiveness and are reliant on manufacturers to provide accurate labeling. Recently, the growing number of foods with herbs has raised concerns at the FDA, which requires evidence that food additives are safe. Considering that the growing appeal of herbal remedies is likely to continue, physicians, particularly cardiologists, must become familiar with the available cardiovascular information on herbs. This review highlights the existing data on the efficacy, adverse effects and interactions for herbal therapies that impact on the cardiovascular system.

In every year since 1984, cardiovascular disease has claimed the lives of more females than males. More than 450,000 women succumb to heart disease annually, and 250,000 die of coronary artery disease. Despite the proportions, most women believe they will die of breast cancer. The perception that heart disease is a man's disease and that women are more likely to die of breast cancer is alarming. Although women develop heart disease about 10 years later than men, they are likely to fare worse after a heart attack. The poorer outcomes are due, in part, to the failure to identify heart attack symptoms. Approximately 35% of heart attacks in women are believed to go unnoticed or unreported. However, because of increased age, women are more likely to have co-morbid diseases such as diabetes and hypertension. In women, not only is "tightness" or discomfort in the chest a warning sign, but in addition, nausea and dizziness are common indicators of myocardial ischemia. Other symptoms include breathlessness, perspiration, a sensation of fluttering in the heart, and fullness in the chest. In comparison to men, women are less likely to undergo tertiary care interventions such as cardiac catheterization, angioplasty, thrombolytic therapy, and bypass surgery; to participate in cardiac rehabilitation; and to return to work full-time after myocardial infarction. In the past, most research about treatments for heart disease focused on men, and gender differences have been ignored. Recent studies are enrolling enough women to test if there are differences between men and women in outcomes. One of the major areas of research relates to estrogen and hormonal replacement therapy to reduce the relative risk of heart attack and stroke. The Women's Health Initiative is a major NIH-sponsored trial that addresses the issue of primary prevention of cardiac disease by hormonal replacement therapy. The results will be available in 2004. The Heart Estrogen/Progestin Replacement Study (HERS), disappointingly, did not show a significant reduction of coronary events in women taking hormonal replacement therapy, nor did the Estrogen Replacement and Atherosclerosis (ERA) trial of 309 postmenopausal women who underwent coronary angiography. New insight into the role of vitamins, phytoestrogens and other natural sources, and selective estrogen receptor modulators may provide other options for management. Until then, modification of risk factors and healthy life style choices are recommended for reducing the risk of cardiac disease. In fact, the key to a healthy heart in the year 2000 appears closely tied to life style choices. Prevention of disease is the key, and current recommendations are simply to stop smoking, or do not start; treat and control blood pressure >140/90 mm Hg; manage elevated lipids by diet, exercise, and cholesterol-lowering medications (if necessary); treat diabetes; lose weight so that BMI is <25; walk for 20-30 minutes at least three times a week; and take an aspirin tablet daily.

Postmenopausal estrogen replacement therapy (ERT) has been associated with a reduced risk of coronary artery disease (CAD). Whether this apparent cardioprotective effect is mediated by a cardiovascular benefit during exercise, however, has not been clearly defined. To evaluate rest and exercise variables with and without ERT, a randomized crossover trial was conducted in 23 postmenopausal women, ranging in age from 44 to 75 years, mean age 57+/-8 years. The rest and exercise variables were compared on ERT and during a drug-free period. The baseline measure was compared to the effects after 4 weeks of ERT and after 4 drug-free weeks. Echocardiographic treadmill exercise variables of heart rate (HR), blood pressure, rate-pressure product (RPP), and cardiac dimensions were determined at baseline and at the end of each treatment period. In response to ERT, there was a decrease in low-density lipoprotein (LDL) cholesterol (drug-free: 142+/-40 mg/dl, ERT: 124+/-34 mg/dl) and an increase in high-density lipoprotein (HDL) cholesterol (drug-free: 52+/-14 mg/dl, ERT: 62+/-15 mg/dl, both p<0.01). At rest, the study population had no overall significant change in HR, blood pressure, RPP, or left ventricular end-systolic and end-diastolic diameters when ERT was compared to the drug-free period. However, subjects with the fastest baseline resting HR had the greatest decrease in HR with ERT relative to the drug-free period (p<0.05). During exercise, ERT effected no change in peak HR, blood pressure, or RPP, although end-systolic diameter decreased slightly (p<0.05). With ERT, subject age correlated negatively with systolic blood pressure (p<0.05) and RPP (p<0.01); both blood pressure and RPP decreased in older subjects. In conclusion, ERT has differential effects dependent on baseline HR and age.

Objective: To examine the impact of age on the effects of desipramine (DMI) on autonomic input to the heart., Method: Twenty-four-hour electrocardiograms were obtained from 42 subjects, aged 7 to 66 years, while off and on DMI. To obtain measures of autonomic input to the heart, heart rate variability was assessed via spectral analysis of RR interval variability., Results: DMI treatment was associated with a significant increase in 24-hour mean heart rate and significant decreases in RR interval variability in all spectral bands, including in the high-frequency band, which provides a measure of parasympathetic input to the heart. RR interval variability was greater in younger individuals both off and on DMI., Conclusions: DMI treatment was associated with a marked decline in RR interval variability, indicating that DMI affects autonomic input to the heart. Specifically, DMI reduced parasympathetic input, which, in theory, may increase vulnerability to arrhythmias. However, the magnitude of DMI's impact on RR interval variability did not vary with age.

Objective: In light of recent reports of sudden death in children being treated with desipramine (DMI), 3 of which were associated with physical exercise, the authors examined the effects of DMI on exercise in children and adults before and during DMI treatment., Method: Before treatment, 22 subjects (9 children, 13 adults) participated in a graded treadmill exercise test. Outcome measures included exercise tolerance, cardiovascular, and electrocardiographic parameters at progressive intensity levels and serum norepinephrine (NE) levels before and after exercise testing. Subjects were then treated with DMI, titrated to an average DMI dosage of 3 mg/kg, and underwent repeated exercise testing., Results: DMI treatment was associated with a significant elevation of circulating NE levels in the pre-exercise assessment. Exercise tolerance was not affected by DMI, and blood pressure and heart rate effects were modest. The cardiovascular impact of DMI treatment was similar in children and adults. One 31-year-old subject exhibited a brief episode of ventricular tachycardia associated with exercise during DMI treatment., Conclusions: DMI has only minor effects on the cardiovascular response to exercise, and these effects do not appear age-related. However, DMI may increase the risk of exercise-associated arrhythmias in rare individuals.

The development of a centralized program in women's health is a challenge in a decentralized academic medical center and in the environment of healthcare transformation. The Center for Women's Health at the Columbia-Presbyterian Medical Center has allowed the clinical and educational abilities of an academic faculty interested in gender-specific health to operate in the delivery of coordinated care. Within the structure of an academic environment come advantages and unique opportunities for solving deficiencies in healthcare but also the need to overcome obstacles inherent in a large system. Flexibility and creative problem solving are key to meeting the challenges of the changing environment of healthcare. Here we describe ventures to develop a model program of clinical care and education in the gender science of women's health.

The pathogenesis of blood pressure (BP) rise in aging women remains unexplained, and one of the many incriminating factors may include abnormalities in arteriolar resistance vessels. The aim of this study was to determine the effects of unopposed estrogen on arteriolar distensibility, baroreceptor sensitivity (BRS), BP changes, and rate-pressure product (RPP). We tested the hypotheses that estrogen replacement therapy (ERT) enhances arteriolar distensibility and ameliorates BRS, which leads to decreases in BP and RPP. Postmenopausal women participated in a single-blind crossover study; the participants of this study, after baseline measurements, were randomly assigned to receive estrogen (ERT) or a drug-free treatment with a 6-wk washout period between treatments. The single-blind design was instituted because subjects become unblinded due to physiological changes (i.e., fluid shifts, weight gain, and secretory changes) associated with estrogen intake. However, investigators and technicians involved in data collection and analyses remained blind. After each treatment, subjects performed identical autonomic tests, during which electrocardiograms, beat-by-beat BPs, and respiration were recorded. The area under the dicrotic notch of the BP wave was used as an index of arteriolar distensibility. The magnitude of the reflex bradycardia after a precipitous rise in BP was used to determine BRS. Power spectral analysis of heart rate variability was used to assess autonomic activity. BPs were recorded from resistance vessels in the finger using a beat-by-beat photoplethysmographic device. RPP, a noninvasive marker of myocardial oxygen consumption, was calculated. Repeated-measures analyses of variance revealed a significantly enhanced arteriolar distensibility and BRS after ERT (P < 0.05). A trend of a lower sympathovagal balance at rest was observed after ERT, however, this trend did not reach statistical significance (P = 0.061) compared with the other treatments. The above autonomic changes produced significantly lower systolic and diastolic BP changes and RPPs (P < 0.05) at rest and during isometric exercise. We conclude that short-term unopposed ERT favorably enhances arteriolar distensibility, BRS, and hemodynamic parameters in postmenopausal women. These findings have clinical implications in the goals for treating cardiovascular risk factors in aging women.

Objective: The purpose of this study was to determine the cardiovascular effects of fluoxetine in depressed patients with cardiac disease., Method: Twenty-seven depressed patients (26% of whom were female and whose average age was 73 years) who had congestive heart failure, conduction disease, and/or ventricular arrhythmia were studied in an open medication trial of fluoxetine, up to 60 mg/day, for 7 weeks. The main outcome measures were heart rate and rhythm measured by 24-hour ECG recordings, ejection fraction determined by radionuclide angiography, cardiac conduction intervals, and blood pressure. Baseline values were compared with those at weeks 2 and 7 of fluoxetine treatment. In 60 comparable patients, values of these same cardiovascular measures at baseline and after 3 weeks of treatment with a tricyclic antidepressant, nortriptyline, were also examined., Results: Fluoxetine induced a statistically significant 6% decrease in heart rate, a 2% increase in supine systolic pressure, and a 7% increase in ejection fraction. There was no effect on cardiac conduction, ventricular arrhythmia, or orthostatic blood pressure. Overall, 4% of the fluoxetine patients had an adverse cardiovascular effect. In contrast, nortriptyline treatment caused a significant increase in heart rate and orthostatic hypotension, and 20% of the nortriptyline-treated patients had an adverse cardiovascular effect., Conclusions: In depressed patients with heart disease, fluoxetine treatment was not associated with the cardiovascular effects documented for the tricyclic antidepressants or with significant adverse cardiac events. However, limited conclusions about fluoxetine's cardiovascular effects and safety can be drawn from this study of only 27 patients monitored for 7 weeks.

One third of women between the ages of 50 and 75 have cardiovascular disease, which accounts for more than 50% of all deaths among women annually. Cardiovascular disease not only is the leading cause of death among women; it is more lethal and less aggressively treated in women than in men. Twice as many women--505,440--die from heart disease as from all forms of cancer combined. Despite the compelling statistics, only 8% of women consider cardiovascular disease a personal health threat. The scenario is troubling because women appear to understand so little or to deny their cardiac risks and so not recognize their ability to control them. Clearly, there is an urgent and compelling need for physicians to take an active role in identifying health behaviors that may affect the risk of cardiovascular disease in their female patients. Dialogue between the physician and patient should begin early to foster preventive steps, and the communication and education must continue throughout the patient's life span. Cardiovascular risk factors, including cigarette smoking, physical inactivity, hypertension, elevated cholesterol, overweight, diabetes, and menopause, should be identified and addressed for all women.

To assess the peripheral vascular effects of estrogen in women without coronary disease, normal postmenopausal women (mean age 56 +/- 8 years) participated in a randomized, crossover trial using treadmill exercise echocardiography, and received oral conjugated estrogen, 0.625 mg/day or underwent a drug-free period. There was no significant effect on heart rate, blood pressure, double product, left ventricular end-systolic and end-diastolic diameters, or electrocardiographic measures after estrogen. In contrast to the profound effects reported in patients with cardiac disease, oral estrogen in normal women does not bestow significant benefit on treadmill exercise echocardiographic variables at rest or during modest levels of exercise.

Atrial fibrillation is the most common sustained arrhythmia reported in the United States; an estimated 1-2 million Americans have chronic nonvalvular atrial fibrillation. This disorder is associated with a substantial risk of stroke. Several recent studies provide evidence that anticoagulation therapy is indicated for stroke prevention in patients with nonvalvular atrial fibrillation after recovery from a minor stroke. Clinical and echocardiographic criteria help to identify those patients who are at especially high risk for thromboembolic stroke and are candidates for carefully controlled anticoagulation. In an effort to reduce the possibility of thromboembolic events following either chemical or electrical cardioversion, the American College of Chest Physicians has recently prepared guidelines for the use of anticoagulation in the conversion of atrial fibrillation. The efficacy of antiarrhythmic drug therapy for cardioversion is often difficult to assess. Furthermore, it is associated with major risks, including heart failure and exacerbation of arrhythmia, and minor risks, including systemic intolerance. A new National Institutes of Health trial, Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), will clarify the true risks and benefits of antiarrhythmic therapy for conversion of atrial fibrillation to sinus rhythm. Patients who cannot tolerate drug therapy may benefit from interruption of conduction in the bundle of His, followed by implantation of a permanent pacemaker, the use of radiofrequency energy ablation, or the implantation of an atrial defibrillator. Some patients may benefit from surgical procedures, such as left atrial isolation, the corridor operation, and the maze operation.

Background: To evaluate factors that explain sex differences affecting mortality after cardiac transplantation, a retrospective analysis of adult patients undergoing orthotopic cardiac transplantation was undertaken at the Columbia-Presbyterian Medical Center., Methods and Results: The study population consisted of 379 patients (75 women, 304 men) > or = 18 years of age who survived for > or = 48 hours after undergoing orthotopic cardiac transplantation between March 1985 and March 1992. The following were analyzed: incidence of death and treated rejection episodes, donor and recipient cytomegalovirus (CMV) matches, use of OKT3 induction therapy, and donor and recipient HLA mismatches. Women 49 +/- 12 years old and men 47 +/- 12 years old were characterized by differences in race and diagnosis. Women were more likely to be nonwhite (P < .01) and have idiopathic cardiomyopathy than were men (P < .01). A trend toward an increase in first-year rejection frequency was seen in women compared with men (P = .08). Overall actuarial survival was significantly reduced in women after transplantation (P < .05). At 36 months, female actuarial survival was 64 +/- 7% versus 76 +/- 3% for men (P < .05). The majority of patients in this study did not receive CMV prophylaxis. Univariate analysis revealed that only CMV(+) donor status and the use of OKT3 induction therapy affected survival in women. Multivariate analysis revealed a marked reduction in survival in female recipients of CMV(+) donors given OKT3 induction therapy. At 36 months, only 25% of women were still alive compared with 86% of women with neither risk factor (P < .001). Even without OKT3 induction there was markedly reduced survival in women with mismatched CMV status, ie, CMV(-) recipients of CMV(+) donors; 17% survival after 36 months versus 86% in women who were CMV(+) recipients (P < .05). Although at this institution during the study time period, CMV prophylaxis was not routinely employed and OKT3 induction was selectively used in higher-risk patients, conclusions regarding differences in outcome that are sex dependent are valid., Conclusions: (1) Women are at risk for reduced actuarial survival up to 3 years after cardiac transplantation. (2) Univariate analysis shows that women are selectively at risk for death when receiving hearts from CMV(+) donors and after receiving OKT3 induction therapy. (3) Multivariate analysis reveals that women are at even greater risk for death when receiving hearts from CMV(+) donors in conjunction with OKT3 induction therapy. (4) In the absence of OKT3 use, the greatest risk of death occurs in CMV(-) women transplanted with CMV(+) donor hearts. (5) When female to male survival curves are compared, factors that influenced survival in women did not appear to be problematic in men.

To test the relationship between plasma moricizine concentration and the electrocardiogram (ECG) and arrhythmia suppression, 17 symptomatic cardiac patients with 30 or more ventricular premature complexes per hour were studied. Seven patients were mature adults, less than 60 years of age; and ten were elderly adults, more than 60 years of age. During steady-state moricizine therapy, patients had plasma moricizine concentration determined over a dosing interval, and had standard 12-lead ECG and a 24-hour ambulatory ECG recorded. The mean moricizine dose was 215 +/- 29 mg every 8 hours; mean maximal moricizine concentration was 1.4 +/- 0.84 micrograms/ml; and mean t1/2 beta was 1.5 +/- 0.7 hours. Baseline age-related differences were found, including prolonged electrocardiographic intervals (PR and QRS) (P < .05), increased ventricular arrhythmias (P < .05), and reduction in creatinine clearance (P < .05) in the elderly. Compared with pretreatment values, PR (P < .05) and QRS (P < .05) prolongation was observed, and was more marked in elderly patients. Over a dosing interval, there were dynamic changes on the ECG that paralleled plasma moricizine concentration; that is, peak and nadir intact moricizine concentration occurred simultaneously with ECG changes: QRS and JTc prolonged (P < .05), and PR prolongation approached significance (P = 0.09). Suppression of ventricular premature complexes of 80% or more occurred in 15 patients, and ventricular tachycardia was abolished in 10 of 12 patients. Probit analysis revealed that the therapeutic antiarrhythmic concentration ranged from 0.20 to 3.6 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To assess the effects of desipramine (DMI) on autonomic control of the heart., Methods: Blood pressure, RR interval (the time between successive heart beats), and RR interval variability, a noninvasive measure of autonomic control of the heart, were assessed in 13 subjects younger than 30 years old., Results: DMI treatment was associated with an increase in blood pressure, a decrease in RR interval, and a decline in low and high frequency RR interval variability., Conclusions: These preliminary data suggest that, in young people, DMI treatment produces a substantial decrease in parasympathetic input to the heart and an increase in the ratio of sympathetic to parasympathetic input, changes that in certain circumstances have been associated with an increased risk of arrhythmia. In exploring the cardiac effects of the tricyclic antidepressants (TCAs) in young people, the impact of TCAs on autonomic input to the heart should be examined.

Background: Many clinicians believe that doxepin is the safest tricyclic with respect to cardiovascular effects. This belief has persisted for two decades despite the absence of rigorous prospective evaluation., Method: To address this issue, the authors studied the cardiovascular effects of doxepin in 32 depressed patients with preexisting left ventricular impairment, ventricular arrhythmias, and/or conduction disease., Results: Doxepin (1) did not have a robust effect on heart rate, (2) did not adversely affect left ventricular function, (3) did have a significant antiarrhythmic effect, (4) slowed cardiac conduction, and (5) caused a significant increase in orthostatic hypotension. Five (16%) of the 32 patients dropped out due to cardiovascular side effects. The overall dropout rate was 41%., Conclusions: The cardiovascular effects of doxepin in depressed patients with heart disease are comparable to those documented for imipramine and nortriptyline. Doxepin afforded no greater margin of cardiovascular safety; in fact, the drug was poorly tolerated by this patient population.

The mechanism of action of moricizine, a new antiarrhythmic agent used in the Cardiac Arrhythmia Suppression Trial, is incompletely characterized. In addition, because moricizine is extensively metabolized, plasma moricizine concentration has an unknown relation to myocardial drug effect. Signal-averaged and standard electrocardiograms (ECGs) were used to monitor moricizine's myocardial effects in 16 patients with frequent ventricular premature complexes taking 600 to 900 mg daily. Three signal-averaged ECG variables were measured: total filtered QRS duration (fQRS), root-mean-square voltage in the terminal 40 ms of the QRS complex (V40) and the terminal low amplitude duration less than 40 microV (LAS). At steady state, plasma samples were collected and serial recordings of signal-averaged and standard ECGs were taken at 0, 1, 2, 4, 6 and 8 h after moricizine administration. A 24 h ambulatory ECG was recorded throughout the test period. Moricizine prolonged the fQRS (p less than 0.05) and decreased the V40 (p less than 0.05) of the signal-averaged ECG and prolonged the QRS (p less than 0.05) and corrected JT (JTc) intervals (p less than 0.05) of the standard ECG. The time course of the signal-averaged and standard ECG variables paralleled plasma moricizine concentration; that is, the maximal changes occurred at 1 to 2 h and declined to time 0 values at 8 h. The maximal changes were: fQRS (+8%), V40 (-33%), QRS (+8%) and JTc (+4%). Thus, dynamic changes were observed for intraventricular conduction (fQRS, QRS) and ventricular repolarization (JTc) over the dosing interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: The cardiovascular effects of therapeutic plasma levels of tricyclic antidepressants in depressed patients with and without preexisting cardiac disease have been well characterized and include orthostatic hypotension and conduction delay. Bupropion, structurally unrelated to tricyclic antidepressants, is relatively free of cardiac side effects in depressed patients without cardiac disease. However, it is unknown whether bupropion is safe for depressed patients with preexisting heart disease, so the authors studied the cardiovascular effects of bupropion in such patients., Method: The subjects were 36 inpatients with DSM-III major depression and preexisting left ventricular impairment (N = 15), ventricular arrhythmias (N = 15), and/or conduction disease (N = 21). The patients continued their cardiac drug regimens and received bupropion for 3 weeks (mean +/- SD dose = 442 +/- 47 mg/day). Cardiovascular functioning was measured by pulse, blood pressure, high-speed ECG, 24-hour portable ECG, and radionuclide angiography., Results: Although bupropion caused a rise in supine blood pressure, it did not cause significant conduction complications, did not exacerbate ventricular arrhythmias, had a low rate of orthostatic hypotension, and had no effect on pulse rate. However, bupropion treatment was discontinued for 14% of the patients because of adverse effects, including exacerbation of baseline hypertension in two patients., Conclusions: The cardiovascular profile of bupropion may make this drug a useful agent in the treatment of the depressed patient with preexisting cardiovascular disease. Further studies, with longer durations of bupropion treatment and more subjects, are needed to confirm these findings.

Myocardial amiodarone and desethylamiodarone concentrations were measured at multiple sites in the explanted heart in four patients who underwent cardiac transplantation. Patients were taking amiodarone, 200 to 400 mg/day (mean 300 +/- 115), for 88 to 428 days (mean 229 +/- 148). The mean cumulative dose was 58 +/- 21.3 g. Plasma amiodarone concentration in three subjects was 204, 312 and 419 ng/ml and desethylamiodarone concentration was 268, 513 and 880 ng/ml, respectively. Significant interindividual variability in myocardial concentrations of amiodarone and desethylamiodarone was observed (p less than 0.05). Mean myocardial amiodarone concentration ranged from 4 +/- 1.0 to 29 +/- 17.2 micrograms/g (p less than 0.05); mean desethylamiodarone concentration ranged from 22 +/- 8.8 to 141 +/- 102.5 micrograms/g (p less than 0.05). At each site, save for fat, myocardial desethylamiodarone concentration was higher than amiodarone concentration. Greater intraindividual variability was observed in myocardial desethylamiodarone compared with amiodarone concentration particularly in septal and scar tissue (p = NS). No significant relation was found between myocardial concentration and duration of treatment. In patients with significant ventricular disease, usefulness of plasma amiodarone and desethylamiodarone concentration to estimate myocardial concentration is limited by intra- and interindividual variability.

Low dose quinidine-mexiletine combination therapy was compared with quinidine monotherapy in 15 patients with frequent ventricular premature complexes and nonsustained ventricular tachycardia in a dose escalation cross-over study. Oral combination therapy was initiated with quinidine gluconate (165 mg) plus mexiletine (150 mg) every 8 h. If ventricular premature complexes were not suppressed greater than or equal to 80% and nonsustained ventricular tachycardia greater than or equal to 90%, the dose was increased to a maximum of 330 mg of quinidine plus 200 mg of mexiletine. Quinidine monotherapy was initiated with 330 mg and escalated to a maximum of 660 mg every 8 h if criteria for effectiveness were not met. Combination quinidine-mexiletine therapy suppressed 80% of ventricular premature complexes in 13 of 14 patients and suppressed 100% of episodes of ventricular tachycardia in 6 of 8 patients (mean quinidine dose 200 +/- 70 mg; mean mexiletine dose 146 +/- 24 mg every 8 h). The mean effective trough quinidine and mexiletine concentration was 1.0 +/- 0.7 and 0.9 +/- 0.4 microgram/ml, respectively. Monotherapy was less effective; that is, greater than or equal to 80% suppression of ventricular premature complexes was observed in 5 of 15 patients and 100% suppression of ventricular tachycardia in 2 of 9 patients. The mean quinidine monotherapy dose was 462 +/- 155 mg every 8 h; the mean quinidine concentration was 1.8 +/- 0.8 microgram/ml. Adverse systemic effects occurred in 3 patients on quinidine-mexiletine therapy and in 11 on quinidine monotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

A group of 45 depressed patients treated with imipramine hydrochloride were examined in an attempt to identify factors that might influence the risk of developing orthostatic hypotension. Although the literature suggests that age and/or heart disease influences the occurrence of orthostatic hypotension, these conclusions are controversial. To pursue this issue, a sample of older depressed patients, many with severe cardiovascular disease, was chosen. The incidence of orthostatic hypotension rose dramatically among those with severe heart disease. There was a significant association between symptomatic orthostatic hypotension and cardiac medication (p less than .01), and trends between orthostatic hypotension and both ejection fraction (p = .11) and baseline forearm resistance (p = .16). The sample is too small to permit determination of the relative independent importance of these variables or the contribution of specific cardiovascular drugs among these sicker cardiac patients.

Indecainide, a new type Ic antiarrhythmic agent, and quinidine sulfate were compared in a randomized double-blind parallel study. Cardiac patients with greater than or equal to 30 ventricular premature complexes per hour hour received indecainide, 50 mg, or quinidine, 200 mg every 6 hours, and the doses were increased until more than 80% suppression was noted, adverse effects occurred or a maximal dose of 100 mg of indecainide or 400 mg of quinidine given every 6 hours. Efficacy was achieved in 8 of 10 taking indecainide (p less than 0.05) and 7 of 9 taking quinidine (p less than 0.05). At least 90% of episodes of ventricular tachycardia were suppressed in 4 of 7 patients taking indecainide and 1 of 4 taking quinidine. No adverse effects were observed in the 7 patients who responded to indecainide and the 4 who responded quinidine, resulting in short-term efficacy without adverse effects in 7 patients (70%) taking indecainide and 4 (44%) taking quinidine. The effective or maximal mean daily indecainide and quinidine doses were 190 +/- 32 mg and 1,022 +/- 291 mg, respectively; mean trough indecainide and quinidine concentrations were 617 +/- 247 ng/ml and 3.3 +/- 1.4 micrograms/ml, respectively. Indecainide prolonged mean PR and QRS intervals (p less than 0.05), but not QT and QTc intervals. Quinidine did not change PR or QRS intervals but prolonged QTc interval (p less than 0.05). During dosing, 1 patient discontinued indecainide treatment because of nausea; 3 discontinued quinidine because of gastrointestinal complaints.(ABSTRACT TRUNCATED AT 250 WORDS)

Imipramine is an effective antiarrhythmic agent against ventricular arrhythmias and complex features of ventricular premature depolarizations at plasma concentrations ranging from 100 to 400 ng per ml. Imipramine's effects on the electrocardiogram are similar to procaine amide and quinidine producing a slight prolongation of PR and QRS intervals. A relatively long half-life of elimination, mean = 9 + 3.7 hours, and no significant adverse effect on left ventricular function suggest imipramine will be useful even for patients with depressed cardiac function.

Sixteen severely depressed patients participated in a double-blind randomized, crossover study to compare the effects of desmethylimipramine and imipramine on left ventricular function and the electrocardiogram. Following a drug-free week, patients had 3 weeks of therapy each with desmethylimipramine and imipramine. During each treatment period systolic time intervals, echocardiograms and high-fidelity electrocardiograms were recorded. There was no difference between desmethylimipramine and imipramine on (1) systolic time intervals, (2) shortening fraction or mean velocity of circumferential shortening, or (3) the electrocardiogram. There was a difference between the drug-free period and desmethylimipramine or imipramine on the PEPc (P less than 0.05) and the PEP/LVET ratio (P less than 0.05); on the R-R (P less than 0.05), PR (P less than 0.05), QRS (P less than 0.05), and QTc (P less than 0.05) intervals; but no difference on the LVETc or shortening fraction or the mean velocity of circumferential shortening. Drugs such as desmethylimipramine and imipramine which prolong intraventricular conduction can probably be expected to prolong the PEP and PEP/LVET. For this reason systolic time intervals have limitations in assessing myocardial function and the echocardiogram more reliably estimates myocardial performance in patients receiving tricyclic antidepressants.

The electrocardiographic effects of imipramine hydrochloride at therapeutic plasma concentrations were determined in 44 depressed patients during a 6-week clinical outcome study of depression. During each week of the protocol, i.e., 2 weeks of control and 4 weeks of drug treatment, a standard 12-lead ECG, high-speed, high-fidelity ECG tracings, and a 24-hour continuous ECG recording were obtained. PR, QRS, and QTc intervals, T-wave amplitude, heart rate and frequency of ventricular premature depolarizations (VPDs) were measured. The plasma concentration of imipramine and desmethylimipramine was measured three times a week. Imipramine prolonged the PR (p less than 0.001), QRS (p less than 0.001) and QTc (p less than 0.001) intervals, increased the heart rate (p less than 0.001) and lowered T-wave amplitude (p less than 0.05) during the 4 weeks of treatment. No patient developed high-grade atrioventricular block or severe intraventricular conduction abnormalities. In addition, imipramine had a potent antiarrhythmic action in patients who were recovering from depression. Ten of 11 patients who had more than 10 VPDs/hour had 90% or greater arrhythmia suppression during antidepressant treatment with imipramine at plasma concentrations ranging from 100--302 ng/ml.

Procainamide (PA) has been a mainstay of treatment against acute and chronic supraventricular and ventricular arrhythmias for more than 30 years. PA's clinical pharmacology has been studied extensively and its bioavailability (75-95%); volume of distribution (1.5-2.5 liters per kg), plasma protein-binding (15-25%), half-time for elimination (3-7 hours), and metabolism are known. PA's efficacy against acute ventricular arrhythmias and chronic stable VPDs is associated with plasma drug concentrations of 4 to 10 micrograms per ml; but much higher plasma concentrations may be required against sustained ventricular arrhythmias. From 30 to 60% of a PA dose is excreted as the metabolite, N-acetylprocainamide (NAPA), and PA's metabolism is determined genetically (fast or slow acetylation phenotype). Studies in patients with VPDs indicate that NAPA is also antiarrhythmic, although the contribution of NAPA to the antiarrhythmic effect after PA is not known. Studies in patients with the systemic lupus-like syndrome from PA show that NAPA is not associated with this. Investigations comparing efficacy and adverse effects of PA with those of new antiarrhythmic agents available for clinical trials are indicated in the future.