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Advances in the novel approach to control ischemic heart disease and heart failure using stem cells or progenitor cells from bone marrow, mesenchyme, or myocardial tissue itself have demonstrated efficacy for increasing left ventricular function, decreasing infarct scar tissue, improving exercise tolerance and heart failure symptoms, and, in some studies, decreasing mortality and reducing rehospitalization for intractable angina or subsequent myocardial infarction. The most common techniques utilize injections of cells into the coronary vasculature or directly into specific areas of vulnerable myocardium. Although few adverse effects have been noted in clinical trials of these procedures, further clinical trials over the next decade should provide further advances in interventional techniques, ancillary supporting technologies to enhance cell regeneration, and applications in ischemic heart disease, cardiomyopathies, and cardiac genetic disorders.

OBJECTIVE The presence of subclinical disease measures has been directly associated with the development of cardiovascular disease (CVD) in whites. African Americans (AAs) in the U.S. are at higher risk of CVD compared with non-Hispanic whites; however, data on the prevalence of subclinical disease measures in AAs and their association to CVD remain unclear and may explain the higher CVD risk in this group. RESEARCH DESIGN AND METHODS We evaluated 4,416 participants attending the first examination of the Jackson Heart Study (mean age 54 years; 64% women) with available subclinical disease measures. RESULTS There were 1,155 participants (26%) with subclinical disease, defined as the presence of one or more of the following: peripheral arterial disease, left ventricular hypertrophy, microalbuminuria, high coronary artery calcium (CAC) score, and low left ventricular ejection fraction. In cross-sectional analyses using multivariable-adjusted logistic regression, participants with metabolic syndrome (MetS) or diabetes (DM) had higher odds of subclinical disease compared with those without MetS and DM (odds ratios 1.55 [95% CI 1.30–1.85] and 2.86 [95% CI 2.32–3.53], respectively). Furthermore, the presence of a high CAC score and left ventricular hypertrophy were directly associated with the incidence of CVD (265 events) in multivariable-adjusted Cox proportional hazards regression models (P < 0.05). In prospective analyses, having MetS or DM significantly increased the hazard of incident CVD, independent of the presence of subclinical disease (P < 0.001). CONCLUSIONS In our community-based sample of AAs, we observed a moderately high prevalence of subclinical disease, which in turn translated into a greater risk of CVD, especially in people with MetS and DM.

Preamble 2356 1. Introduction 2357 2. Overview of Acs 2358 3. Initial Evaluation and Management: Recommendations 2358 4. Early Hospital Care: Recommendations 2363 5. Myocardial Revascularization: Recommendations 2369 6. Late Hospital Care, Hospital Discharge, and Posthospital Discharge Care: Recommendations 2371

Jeffrey L. Anderson, MD, FACC, FAHA, Chair Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect Nancy M. Albert, PhD, RN, FAHA Biykem Bozkurt, MD, PhD, FACC, FAHA Ralph G. Brindis, MD, MPH, MACC Lesley H. Curtis, PhD, FAHA David DeMets, PhD[††][1] Lee A. Fleisher, MD, FACC, FAHA Samuel

Objectives The objective of this study is to investigate the distribution and determinants of diastolic function in a middle-aged cohort of African Americans (AA). Background The distribution and determinants of left ventricular (LV) diastolic function in AA are not well-described despite high rates of AA with diastolic heart failure and a five-fold higher risk of death in those with diastolic dysfunction (DD) compared to normal diastolic function. Methods Four categories of diastolic function were defined in JHS participants undergoing echocardiograms at the first examination (2001-2004) using mitral and pulmonary vein velocities. Investigators used logistic regression to assess the independent relation of DD to traditional risk factors and LV systolic dysfunction. Results Of the 3,571 study participants (mean age, 56 ± 12 years; 63.9% female), 70.4% had normal diastolic function, and 18.0%, 10.6%, and 0.9% had mild, moderate, and severe DD, respectively. In the multivariable analysis, DD was significantly related to age (OR 1.2, 95% CI 1.1-1.4), male sex (OR 1.3 CI 1.0-1.5), LV systolic dysfunction (OR 1.5, CI 1.2-2.0), body mass index (OR 0.8, CI 0.8-0.9), and heart rate (OR 1.2; CI 1.1-1.2). The severity of DD was significantly related with age (OR 0.3; CI 0.3, 0.4), male sex (OR 1.6; CI 1.2-2.2), hypertension (OR 0.6, CI 0.4-0.8), and heart rate (OR 0.7; CI 0.6-0.8). Conclusion This is the largest community-based analysis of LV diastolic function in middle-aged AA. DD was present in 29.5% and independently related to several traditional risk factors and LV systolic dysfunction.

Background Though left ventricular mass ( LVM ) predicts cardiovascular events ( CVD ) and mortality in African Americans, limited data exists on factors contributing to change in LVM and its prognostic significance. We hypothesized that baseline blood pressure ( BP ) and body mass index ( BMI ) and change in these variables over time are associated with longitudinal increases in LVM and that such increase is associated with greater incidence of CVD . Methods and Results We investigated the clinical correlates of change in standardized logarithmically transformed‐ LVM indexed to height2.7 (log‐ LVMI ) and its association with incident CVD in 606 African Americans (mean age 58±6 years, 66% women) who attended serial examinations 8 years apart. Log‐ LVMI and clinical covariates were standardized within sex to obtain z scores for both visits. Standardized log‐ LVMI was modeled using linear regression (correlates of change in standardized log‐ LVMI ) and Cox proportional hazards regression (incidence of CVD [defined as coronary heart disease, stroke, heart failure and intermittent claudication]). Baseline clinical correlates (standardized log‐ LVM , BMI , systolic BP ) and change in systolic BP over time were significantly associated with 8‐year change in standardized log‐ LVMI . In prospective analysis, change in standardized LVM was significantly (P=0.0011) associated with incident CVD (hazards ratio per unit standard deviation change log‐ LVMI 1.51, 95% CI 1.18 to 1.93). Conclusions In our community‐based sample of African Americans, baseline BMI and BP , and change in BP on follow‐up were key determinants of increase in standardized log‐ LVMI , which in turn carried an adverse prognosis, underscoring the need for greater control of BP and weight in this group.

Atherosclerosis complicated by plaque rupture or disruption and thrombosis is primarily responsible for the development of acute coronary syndromes. Plaques with a large extracellular lipid-rich core, thin fibrous cap due to reduced collagen content and smooth muscle density, and increased numbers of activated macrophages and mast cells, appear to be vulnerable to rupture. Plaque disruption tends to occur at points at which the plaque surface is weakest and most vulnerable, which coincide with points at which stresses, resulting from biomechanical and hemodynamic forces acting on plaques, are concentrated. Reduced matrix synthesis as well as increased matrix degradation predisposes vulnerable plaques to rupture in response to extrinsic mechanical or hemodynamic stresses. Modification of endothelial dysfunction and reduction of vulnerability to plaque rupture and thrombosis may lead to plaque stabilization. The broad concept of plaque stabilization, although attractive, has not yet been rigorously validated in humans. This article reviews the mechanism of atherosclerosis development and the pathophysiology of acute coronary syndromes in order to provide a molecular and cellular basis for understanding how plaque passivation might be accomplished in clinical medicine.

Background and Purpose— Previous studies have demonstrated that echocardiographic left ventricular mass (LVM) is an independent risk factor for stroke in whites. Despite the greater burden of stroke, the echocardiographic predictors of stroke in African Americans remain poorly understood. Methods— This investigation is a retrospective analysis of prospectively collected data from the Jackson, Miss (all African American), cohort of the Atherosclerotic Risk in the Communities study. Between 1993 and 1995, 2445 participants received an echocardiogram, and a random subset (n=778) received cerebral MRI evaluating presence of infarcts or white matter disease (WMD; >3 on a scale of 0 to 9). Compared with the entire Jackson cohort, the random subset was older, had a lower body mass index (BMI), and a higher systolic blood pressure (SBP). Logistic regression models examined the relations of LVM indexed by height (LVM/height) to MRI findings adjusted for age, gender, BMI, SBP, hypertensive medications, diabetes, total/high-density lipoprotein cholesterol, smoking status, and history of myocardial infarction. Results— The 667 participants (63% women; 62±4 years of age) had a high prevalence of hypertension (68%), obesity (46%), echocardiographic left ventricular hypertrophy (49%), MRI stroke (n=133), and WMD (n=92). Adjusted LVM/height was significantly associated with prevalent MRI stroke (odds ratio [OR], 1.3; 95% CI, 1.1 to 1.7; P =0.02) and WMD (OR, 1.5; 95% CI, 1.1 to 1.9; P =0.006; OR expressed per 1 SD LVM/height, 45 g/m). Conclusion— In this randomized subset of a population-based cohort of African American adults, LVM/height was related to MRI evidence of prevalent cerebrovascular disease. The current study supports the hypothesis that LVM/height is an important risk factor for stroke in multiple ethnicities.

The distribution of echocardiographic left ventricular (LV) mass differs among ethnicities. Because ethnic-specific echocardiographic criteria for LV hypertrophy (LVH) are not established, we determined whether threshold values derived from overwhelmingly white populations are appropriate for blacks, a subgroup having more LVH. Between 1992 and 1994, LV mass was measured echocardiographically in the Jackson, Mississippi, black cohort of the Atherosclerosis Risk in Communities study. Participants free of prevalent cardiovascular disease (CVD) (n=1616; mean±SD, age 59±5.7; 65% women and 57% with hypertension) were included. The optimal LVH threshold value was selected from the continuum of LV mass index (LVMI=LV mass/height 2.7 ) using 3 methods: (1) the best operating point from the area under the resulting receiver-operating characteristic (ROC) curve predicting incident CVD; (2) the value with the smallest probability value associated with incident CVD; and (3) visual inspection of functions of LVMI and CVD in the general additive model (GAM) plot. At a median follow-up of 6.8 years, there were 192 events (coronary heart disease=87, stroke=62, and congestive heart failure=43; incidence=17.6/1000 person-years). The best operating point from the resulting ROC analysis was 51.2 g/m 2.7 for sensitivity (53.4%) and specificity (61.5%). The Cox and GAM models adjusted for age, gender, systolic blood pressure, hypertension, diabetes, smoking, total cholesterol-to-high-density lipoprotein ratio, LVH by ECG criterion, and socioeconomic status found 50 to 51 g/m 2.7 as the optimal threshold for LVH in middle-aged blacks, corresponding to a minimum probability value and to a log-hazard ratio of zero, respectively. Because these values are close to the 51 g/m 2.7 established from predominantly white populations, this cutpoint is appropriate for both groups.

Coronary heart disease is the leading cause of morbidity and mortality in women older than the age of 50 in the United States today. Traditional cardiovascular risk factors (hyperlipidemia, glucose intolerance, and hypertension) are more clearly associated with significant cardiovascular risk after menopause. The increased incidence of cardiovascular events in postmenopausal women and the evidence that cardiovascular disease on average manifests a decade later in women compared with men suggests that estrogen deficiency may predispose women to a higher cardiovascular risk. Numerous biologic mechanisms have been proposed that relate use of hormone therapy (HT) to improved lipid profiles, insulin sensitivity, and vascular reactivity. Early observational trials in the last 2 decades showed a significant decrease in cardiovascular events. Recently published randomized clinical trial results, however, have led to uncertainty about the earlier established cardiovascular benefits of HT. To complicate issues further, alternative estrogenlike compounds, selective estrogen receptor modulators, are being introduced that appear to convey similar cardiovascular benefit and notably less cancer risk than HT. The newly released randomized trials on hormone and nonhormonal agents are reviewed.

Diabetes mellitus and the metabolic syndrome (MS) are reaching epidemic proportions in the United States, and cardiovascular disease continues to be the leading cause of death among patients with diabetes. A range of noninvasive screening tools may help reduce the morbidity and mortality of patients with diabetes because of early detection of subclinical cardiovascular disease and active monitoring of the effectiveness of therapy. Surrogate markers of subclinical disease include conventional and contrast-enhanced ultrasound imaging of carotid artery intima-media thickness (c-IMT), 2-dimensional echocardiography, coronary artery calcium imaging, cardiac magnetic resonance imaging, ankle-brachial indices, and brachial artery reactivity testing. Because these noninvasive imaging tools are relatively comfortable and entail relatively low risk to the patient, they are ideal for initial screening and for the repeated imaging that is required for monitoring the effectiveness of therapy. Moreover, when used in large numbers of patients with diabetes, prediabetes, and the MS, these imaging tools may be useful in developing and validating thresholds for the use of lipid-lowering therapy as well as clear therapeutic goals for this population. In addition, contrast-enhanced c-IMT scans now produce real-time images of the vasa vasorum and neovascularization of atherosclerotic plaque, potentially causing a paradigm shift in our view of the genesis of atherosclerosis and affecting treatment options for all populations. Thus, surrogate markers may not only help improve individual patient outcomes, they also may help direct scarce medical resources to maximize medical benefits, improve overall medical care, and minimize costs and untoward side effects.

In the United States, cardiovascular disease remains the leading cause of death in postmenopausal women. Despite these alarming trends in the prevalence, the magnitude of the problem is still underappreciated. Women traditionally have been underrepresented in clinical trials with poor enrollment, and information for prevention and treatment of coronary heart disease (CHD) is extrapolated from populations of men. In addition to biologic risk factors for CHD, psychosocial risk factors have also been studied more in men than women. Both traditional coronary and psychosocial risk factors are reviewed as to how they uniquely affect women. A comprehensive approach, encompassing life-style changes, coping strategies and pharmacologic interventions for both prevention and treatment of CHD in women is emphasized.

Because of the proliferation of clinical trials relevant to preventive cardiology, this new section of the journal is being initiated to review recently published findings from randomized clinical studies with the potential to significantly alter medical practice. Each issue of Preventive Cardiology will address one or more of these trials with commentary by Philip R. Liebson, MD, editor of the section. Dr. Liebson is Professor of Medicine and Preventive Medicine and Associate Director, Section of Cardiology, Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL. He is a member of our founding Editorial Board with extensive experience and investigative activity in clinical cardiology and preventive cardiology. It is hoped that this series will promote discussion and comment by our readers on recent publications concerning the prevention of cardiovascular disease and we welcome letters to the editor.

The primary management strategy for the post-myocardial infarction patient continues to be controversial despite published guidelines. In part, this is the consequence of study designs that are not directly applicable to individual patients, but also to the rapidly changing pharmacological and mechanical device armamentarium that rapidly renders clinical trial results obsolete within a few years. This review attempts to highlight those areas where there is consensus as well as to explicate those situations where common clinical practice appears to be in conflict with accepted guidelines.

Left ventricular hypertrophy (LVH) is a strong risk factor for cardiovascular events. It is present in a substantial percentage of persons with hypertension and accounts for an increased risk for sudden cardiac death, coronary heart disease and heart failure. LVH remodeling patterns are associated with characteristic hemodynamic effects and variable prognosis. Although early studies of LVH relied on electrocardiography, echocardiography is now the clinical and research standard in virtually all studies of left ventricular (LV) structure and function in hypertension and effects of therapeutic intervention. LV mass itself is indexed by some measure of body size to standardize measurement results. Clinical trials evaluating regression of LV mass following treatment of hypertension depend upon accurate test-retest reliability of sonography and reader interpretation. The design of such studies should take into account the diversity of participant demographics, have treatment groups of an adequate size, encompass a study period of at least 1 year to interpret results adequately and have a randomized double-blind design of comparison groups. Regression of LV mass as a surrogate end point for an adverse outcome event in prognostic studies requires evidence of a strong incremental association between LVH and the outcome.

OBJECTIVE We assessed the relation of diabetes and insulin resistance (IR) on left ventricular (LV) structure and function in African Americans. RESEARCH DESIGN AND METHODS Among those receiving echocardiograms in cycle 1 of the Jackson Heart Study, we assessed the sex-specific relation of fasting blood glucose (FBG), diabetes, and IR to LV structure and function, adjusting for age, systolic blood pressure, antihypertensive medications, and BMI. RESULTS Among 2,399 participants, LV mass index (Pwomen = 0.0002 and Pmen = 0.02), posterior wall thickness (Pwomen = 0.01 and Pmen = 0.05), and interventricular septal wall thickness (Pwomen = 0.01) were related to FBG categories. Among those with normal FBG and no diabetes, concentric remodeling and low ejection fraction in women and LV mass index and posterior wall thickness in men were related to IR. CONCLUSIONS In the largest study of its kind in a community-based cohort of African Americans, we found a relation of FBG category and IR to LV structure and function.

Preamble e346 1. Introduction e347 2. Overview of Acs e349 3. Initial Evaluation and Management e350 4. Early Hospital Care e359

Background The diagnosis of diastolic heart failure is generally made in patients who have the signs and symptoms of heart failure and a normal left ventricular (LV) ejection fraction. Whether the diagnosis also requires an objective measurement of parameters that reflect the diastolic properties of the ventricle has not been established. Methods and Results We hypothesized that the vast majority of patients with heart failure and a normal ejection fraction exhibit abnormal LV diastolic function. We tested this hypothesis by prospectively identifying 63 patients with a history of heart failure and an echocardiogram suggesting LV hypertrophy and a normal ejection fraction; we then assessed LV diastolic function during cardiac catheterization. All 63 patients had standard hemodynamic measurements; 47 underwent detailed micromanometer and echocardiographic-Doppler studies. The LV end-diastolic pressure was >16 mm Hg in 58 of the 63 patients; thus, 92% had elevated end-diastolic pressure (average, 24±8 mm Hg). The time constant of LV relaxation (average, 51±15 ms) was abnormal in 79% of the patients. The E/A ratio was abnormal in 48% of the patients. The E-wave deceleration time (average, 349±140 ms) was abnormal in 64% of the patients. One or more of the indexes of diastolic function were abnormal in every patient. Conclusions Objective measurement of LV diastolic function serves to confirm rather than establish the diagnosis of diastolic heart failure. The diagnosis of diastolic heart failure can be made without the measurement of parameters that reflect LV diastolic function.

Left ventricular hypertrophy (LVH) is considered an adaptation to a pressure load on the left ventricle and is common in hypertensive patients. The condition is a profound risk factor for cardiovascular events, greater than and independent of blood pressure. It is now recognized in hypertension management guidelines as an indication for more stringent blood pressure control. All of the first-line antihypertensive agents have been shown to variably regress LVH, but no definitive evidence yet shows that one agent is superior to others in decreasing risk independent of blood pressure control. Although some evidence suggests that reduction of LVH is associated with improved prognosis independent of blood pressure control, relative efficacy of drug classes in this regard has yet to be demonstrated. At present, recommendations for optimal therapy in hypertensive patients with LVH must rest on the presence of underlying cardiac and noncardiac conditions, with the understanding that the major classes of antihypertensive agents will probably decrease LVH.

The prevention of CHD should be a major priority among primary care physicians and subspecialists who have any dealing with the cardiovascular system. There is ample evidence from epidemiologic studies for the impact of specific risk factors on CHD events. There is also ample evidence from observational studies and clinical trials that interventions of lifestyle and pharmacologic therapy can decrease morbidity and mortality from CHD before or after the first event. It behooves the physician who wishes to practice good medicine to understand the pathophysiologic roles of the risk factors and the evidence from epidemiologic studies and clinical trials for their association with cardiovascular disease. It is important to determine the efficacy of interventions, both lifestyle and pharmacologic, in modifying CHD risk. To be effective in doing so, the practicing physician has to have the motivation to determine target goals for risk factor modification in each patient, to understand the patient's own motivations in modifying risk factors, and to define clearly with the patient the expectations of such interventions. Although there are guidelines for risk factor modification in modification of cholesterol and in hypertension, the periodic renewal of these guidelines reflects the changing concepts of risk and its modification. A cardiovascular risk factor intervention categorization is presented in Table 12. The physician must be convinced that such intervention is beneficial to the patient, cost-effective, and thus fulfills the expectations of medical practice. The practice of medicine in the evaluation and treatment of coronary heart disease has always been challenging and stimulating. The prevention of CAD disease should ultimately provide the greatest accomplishment.

Abstract —Left ventricular (LV) hypertrophy and concentric remodeling have been defined by using a variety of indexation methods and partition values (PVs) for LV mass and relative wall thickness (RWT). The effects of these methods on the distribution of LV geometric patterns in hypertensive subjects remain unclear. Echocardiograms were obtained in 941 patients with stage I to III hypertension and LV hypertrophy by ECG. LV mass was calculated by using different methods of indexation for body size and different PVs to identify hypertrophy: LV mass/body surface area (g/m 2 ) PV for men/women 116/104, 125/110, or 125/125; LV mass/height (g/m) PV 143/102 or 126/105; and LV mass/height 2.7 (g/m 2.7 ) PV 51/51 or 49.2/46.7. RWT was calculated by either 2×end-diastolic posterior wall thickness (PWT)/end-diastolic LV internal dimension (LVID) or end-diastolic interventricular septum dimension+end-diastolic PWT/end-diastolic LVID. LV hypertrophy or remodeling was present in 63% to 86% of subjects, and LV hypertrophy was present in 42% to 77%. By any index, eccentric hypertrophy was the common LV geometric pattern. Use of interventricular septum dimension+PWT/LVID to calculate RWT slightly increased the prevalence of normal geometry and eccentric hypertrophy compared with the use of 2×PWT/LVID. Subjects with LV hypertrophy identified by only LV mass/height 2.7 PV 49.2/46.7 were more obese, whereas those identified by only LV mass/body surface area PV 116/104 were taller and thinner than those in the 2 concordant groups with or without LV hypertrophy by both criteria. By either criterion, there were no significant differences between different LV geometric patterns in clinical cardiovascular disease. Hypertensive patients with LV hypertrophy by ECG have a high prevalence of geometric abnormalities, especially eccentric hypertrophy, irrespective of method of indexation or PV. LV mass indexation by body surface area or height 2.7 identifies lean and obese subjects, respectively. We found no difference in prevalent cardiovascular disease in subjects identified by either criterion, suggesting a similar high risk.

The presence of left ventricular hypertrophy (LVH) as a treatable entity is of particular importance in patients with primary hypertension. Because LVH is associated with a strong risk of adverse clinical events (eg, heart failure, ischemic events, and cardiovascular death) and because evidence from retrospective studies suggests that regression of LVH, along with a decrease in blood pressure, may help modify these outcomes, the use of antihypertensive agents that have been shown to promote regression of LVH has been recommended. These include diuretics, betablockers (except those with intrinsic sympathomimetic activity [ISA]), angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, peripheral alpha1-blockers, and central alpha2-stimulators. Agents to be avoided include direct arterial vasodilators (eg, hydralazine and minoxidil), which have strong sympathetic stimulating properties and tend to maintain LVH despite lowering blood pressure. The use of ACE inhibitors is increasing. Unfortunately, the cost of these agents is higher than that of some other classes of agents, such as diuretics, which show excellent evidence of regression of hypertrophy. African-American and elderly persons, in particular, may benefit from diuretics for treatment of hypertension as well as reduction of left ventricular (LV) mass. Beta-blockers should be considered in the elderly, especially those with greatly thickened LV walls and small chamber sizes, factors associated with hyperdynamic systolic performance, systolic midcavity obliteration, and diastolic relaxation abnormalities on echocardiography. Calcium channel blockers may also be useful in patients with LVH who have normal systolic performance and diastolic compliance abnormalities. The purpose of serial echocardiographic studies in patients already being treated for hypertension is to ensure that LV geometry has not worsened and that function is unchanged or improved (especially with respect to previously noted diastolic Doppler inflow abnormalities). Considerable changes in estimated LV mass (>60 g on serial intrapatient evaluation) are needed before the clinician can conclude with confidence that LV mass has decreased. More specific definitive recommendations based on the outcomes of current large-scale clinical trials are awaited.

Objectives. The goal of this review is to reevaluate the unstable coronary syndromes in the setting of new therapies and biochemical markers. Background. Patients with acute coronary syndromes comprise a large subset of many cardiology practices. Patients with unstable angina (UA) and non-Q wave myocardial infarction (NQMI) may sustain a small amount of myocardial loss but have significant amounts of viable, yet ischemic, myocardium, placing them at high risk for future cardiac events. In the past, enzyme differentiation of NQMI from UA was considered important to assess prognosis and direct therapy. Methods. Manuscripts published in peer-reviewed journals over the past three decades were reviewed and selected for this review. Recent abstracts were also considered and cited where appropriate. Results. In the late 1990’s, although UA and NQMI remain parts of a spectrum, it is apparent that the distinction between these two entities is no longer sufficient to identify high risk patients; rather, specific electrocardiographic changes, aspects of the clinical history, newer biochemical markers, and angiographic findings help to better distinguish higher risk individuals from a large patient population with unstable coronary syndromes and these factors usually determine therapy. Conclusions. Based on these results, it is likely that newer therapies such as glycoprotein IIb/IIIa receptor antagonists, low molecular weight heparins, and coronary stents will be directed toward these high risk patients.

The relation between the circadian occurrence of ventricular premature depolarizations (VPD) and sudden arrhythmic death was examined in a subset of patients entered into the Cardiac Arrhythmia Suppression Trial (CAST). Ambulatory electrocardiographic recordings with hourly measurement of VPD frequency were available in 357 patients. Forty percent of the patients (142 of 357) demonstrated circadian variation in VPD frequency between 6:00 a.m. and 9:59 a.m. that was significantly higher (p (Am J Cardiol 1996;78:881–885)

This trial involved 107 patients in a two-group, parallel, double-blind, randomized study comparing the diuretic, hydrochlorothiazide (HCTZ) (dose 25 to 50 mg) and the α 1 antagonists, doxazosin (dose 2 to 16 mg). All randomized participants were followed for at least 1 year. Participants were recruited from the community. The study was carried out in four phases: Phase I—Baseline; Phase II—Monotherapy Titration; Phase III—Combination Therapy Titration; and Phase IV—Maintenance. The following measures were carried out: blood pressure, biochemistries, lipids/lipoproteins, quality of life, ambulatory electrocardiograms, echocardiograms, adverse experiences, and drug adherence. Both drugs were well tolerated, with only 4% taken off doxazosin and 7% off HCTZ. Adverse experiences were uncommon and mostly mild. Both drugs were effective in managing hypertension over 1 year of therapy. There was no difference noted in terms of efficacy of blood pressure lowering between the two study drugs, nor was there any evidence of tolerance developing or of any serious adverse effects. Average final doses for drugs were 7.8 mg for doxazosin and 36 mg for HCTZ. The results show that, over the course of 1 year, both drugs significantly lowered systolic and diastolic pressures compared to baseline; doxazosin (−19 and −16 mm Hg); HCTZ (−22 and 15 mm Hg). Blood pressure lowering was not significantly different between drugs. Sitting heart rate was not affected by drugs. Changes in quality of life measures were similar between groups. Echocardiographic measures at 1 year showed significant between-drug differences in change in left internal end systolic and diastolic dimensions and end systolic stress. Both doxazosin and HCTZ were effective drugs over 1 year for treating hypertension.

The echocardiogram (Echo) is the validity standard for left ventricular mass (LVM) and LV hypertrophy (LVH). Numerous studies have confirmed modest correlations between the electrocardiogram (ECG) and Echo for LVM and low ECG sensitivity for Echo-LVH. In spite of this, investigators continue modeling ECG parameters to optimize their relation with the Echo. The authors studied the association between eight ECG criteria and Echo-LVM estimates in a biracial population of men and women with mild hypertension. The Echo-LVM was determined by the Penn convention and expressed in grams, g/m, g/m 2 , and g/m 2.7 . The ECGs and Echos were recorded at baseline, 3 months, and annually for 4 years. The ECGs were computer processed to define the following criteria: (1) Casale/Devereux, (2) Cornell product, (3) Cornell voltage, (4) 12-lead voltage product, (5) sum of the 12-lead, (6) Rautaharju, (7) Sokolow-Lyon, and (8) Romhilt-Estes point score. The major findings were: (1) correlations between the ECG and Echo were modest for level and minimal for change, (2) Echo indexing did not alter correlations with ECG criteria, (3) white men and women show higher correlations for level and change than blacks, (4) repeatability of the Echo-LVM index was 0.7, making it a “moving” validity standard for the ECG, (5) further ECG modeling to predict Echo-LVH, especially in whites, is not a productive approach, and (6) ECG measurements should be combined with other non-ECG characteristics when detecting LVH, and future ECG-LVM studies should investigate the prognostic value of ECG characteristics and use disease outcome as the validity standard.

Objectives.This study was performed to assess the effect of cigarette smoking cessation on overall mortality and the incidence of arrhythmic death in the population of the Cardiac Arrhythmia Suppression Trial (CAST).Background.Cigarette smoking is a known risk factor for sudden cardiac death. Some of the adverse effects of smoking have been shown to dissipate with smoking cessation, but the time frame over which these changes occur and the population that stands to benefit have not been well delineated. CAST was a multicenter double-blind placebo-controlled study to determine whether suppression of ventricular ectopic activity by means of antiarrhythmic drugs in patients with left ventricular dysfunction after acute myocardial infarction would reduce the incidence of arrhythmic death.Methods.Of 2,752 patients randomized to blinded therapy, 1,026 were smoking at the time of their baseline examination and completed a 4-month follow-up visit. Of these, 517 stopped smoking by the time of this visit (“quitters”) and 509 continued to smoke (“smokers”).Results.Over a mean follow-up period of slightly

Rationale and Objectives. Cine magnetic resonance (MR) imaging is a relatively new technique that can be used to study cardiac function with high spatial and temporal resolution. However, detailed functional analysis of the entire cardiac cycle with cine MR imaging is time consuming and labor intensive. We analyzed diastolic function using a semiautomatic routine that reduces the time necessary for analysis. Methods. Twenty subjects (10 normal control subjects and 10 patients with isolated diastolic dysfunction) were examined. Short-axis cine MR images were obtained at 32 phases of the cardiac cycle. A semiautomatic boundary-finding routine was used to determine left ventricular (LV) volumes at each phase. Volume-versus-time and first-derivative curves were created from these data. Several parameters derived from the MR imaging curves were used to characterize diastole. Results. Two parameters—the ratio of early peak filling rate to late peak filling rate and the percentage of filling during early diastole—perfectly distinguished subjects with LV diastolic dysfunction from the normal control subjects. The semiautomatic analysis method substantially reduced the time necessary for analyzing the MR imaging data, compared with manual analysis. Conclusion. Cine MR imaging, especially with time-saving techniques such as our service automatic analysis method, has promise as a research and clinical tool in evaluating LV diastolic function.

Renal effects of mild hypertension and therapy have not been established. Since urinary albumin and N-acetyl-beta-D-glucosaminidase excretions reflect renal effects of hypertension, they were related to blood pressure, other cardiovascular risk factors, cardiac target organ effects, and response to therapy in mild hypertension (diastolic blood pressure 85-99 mm Hg). Participants were from two clinics of the Treatment of Mild Hypertension Study (TOMHS), a multicenter randomized, double-blind, controlled trial. Participants received nutritional-hygienic therapy and one of five active drugs or placebo. Urinary albumin and N-acetyl-beta-D-glucosaminidase excretions were assessed prospectively using office "spot" collections from one clinic (n = 213) and retrospectively using overnight collections from the other clinic (n = 210). Relationships were determined between protein excretions and blood pressure, age, gender, race, blood glucose, cholesterol concentrations, and indices of body mass and left ventricular mass and function at baseline. Treatment effects were assessed after 3 to 12 months. Spot and overnight albumin excretions related positively to baseline systolic blood pressure by univariate analyses. Spot albumin excretion related positively to systolic blood pressure, age, creatinine clearance, and left ventricular function while overnight albumin excretion related positively to left ventricular mass and female gender by multiple regression analyses. Spot, but not overnight, albumin excretion declined significantly with active drug therapy. N-acetyl-beta-D-glucosaminidase excretion did not relate to blood pressure or decline with therapy. The combined results suggest albumin excretion correlates with blood pressure, decreases with antihypertensive drug therapy, and is associated with greater left ventricular function and mass, as well as glomerular filtration rate, even at mild levels of hypertension.

Objective . The purpose of this study was to assess the relation between the time of awakening and the time of onset of acute myocardial infarction. Background . Previous investigation has shown the onset of symptoms of acute myocardial infraction to have a primary peak 1 to 2 h after awakening. In studies not corrected for time of awakening, there appears to be a late afternoon/early evening peak, but data correlating the onset of symptoms with awakening have been limited by small numbers of patients, perhaps precluding identification of a secondary peak. Methods . In the Cardiac Arrhythmia Suppression Trial (CAST), 3,549 patients had a documented myocardial infarction and entered antiarrhythmic drug titration. Of these, 3,309 had data on the onset of symptoms relative to the time of awakening and form the basis of this report. Results . A total of 870 patients (26.3%) were awakened by symptoms. Of the remaining 2,439 patients who were not awakened by symptoms, 798 (32.7%) experienced the onset of symptoms in the 1st 4 h after awakening (with the highest number in the 1st h), after which the incidence of symptom onset decreased in a linear fashion, with a secondary peak 11 to 12 h after awakening. Both peaks are statistically significant. A similar pattern was seen in most of the subgroups examined (based on age, gender and various other demographic characteristics). Conclusions . Analysis of the very large CAST data base confirms the relation between awakening and onset of symptoms of myocardial infarction, suggesting involvement of the morning catecholamine surge. A secondary peak in symptom onset, occurring 11 to 12 h after awakening, is a new observation and may relate to ingestion of the evening meal or other trigger factors concentrated in those hours.

Intravascular ultrasound evaluation of the coronary arteries by means of a selective coronary catheter attached to an ultrasound unit has afforded precise depiction of coronary lumen diameter and area at the level of the catheter tip. The arterial wall at this level can be evaluated for lipid, fibrous tissue, calcification, wall dissections, and intraluminal thrombi. The technique has the advantage over coronary angioscopy and angiography in that it does not require infusions or injections to allow visualization, and it has the ability to depict the inside of the arterial wall. The current disadvantages include the inability to visualize the vessel segments distal to the catheter tip. Three-dimensional reconstruction techniques allow depiction of the segment of the artery traversed by the catheter tip. The use of Doppler ultrasound imaging provides information on coronary flow velocities through coronary obstructions. Intravascular ultrasound images may provide information that complements the coronary arteriogram and may have an impact on patient care and clinical investigation strategies.

The recently published Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) in patients with vascular disease or high-risk diabetes, as the largest published comparative trial of these agent classes, provides further evidence concerning the comparison between the angiotensin-receptor blockers (ARBs) and the angiotensin-converting enzyme inhibitors (ACEIs). In this trial, telmisartan (an ARB) was non-inferior to ramipril (an ACEI) in reducing fatal and nonfatal cardiovascular events. Moreover, ONTARGET is an example of a high-quality noninferiority trial. However, the combination of the 2 agents was associated with more adverse effects without an increase in benefit. The study differed from several other comparative studies in which the dose and choice of ACEI was left to individual physicians. Further, in ONTARGET, the ACEI was not titrated to the maximum dose and patients with heart failure were excluded.

Background Cardiovascular risk associated with diabetes may be partially attributed to left ventricular structural abnormalities. However, the relations between left ventricular structure and diabetes have not been extensively studied in African-Americans. Methods We studied 514 male and 965 female African-Americans 51 to 70 years old, in whom echocardiographic left ventricular mass measurements were collected for the ARIC Study. In these, we investigated the independent association of diabetes with left ventricular structural abnormalities. Results Diabetes, hypertension and obesity prevalences were 22%, 57% and 45%, respectively. Unindexed left ventricular mass was higher with diabetes in both men (238.3 ± 79.4 g vs. 213.7 ± 58.6 g; p < 0.001) and women (206.4 ± 61.5 g vs. 176.9 ± 50.1 g; p < 0.001), respectively. Prevalence of height-indexed left ventricular hypertrophy was higher in women while increased relative wall thickness was similar in men and women. Those with diabetes had higher prevalences of height-indexed left ventricular hypertrophy (52% vs. 32%; p < 0.001), and of increased relative wall thickness (73% vs. 64%; p = 0.002). Gender-adjusted associations of diabetes with left ventricular hypertrophy (OR = 2.29 95%CI:1.79–2.94) were attenuated after multiple adjustments in logistic regression (OR = 1.50 95%CI:1.12–2.00). Diabetes was associated with higher left ventricle diameter (OR = 2.13 95%CI:1.28–3.53) only in men and with higher wall thickness (OR = 1.89 95%CI:1.34–2.66) only in women. Attenuations in diabetes associations were frequently seen after adjustment for obesity indices. Conclusion In African-Americans, diabetes is associated with left ventricular hypertrophy and, with different patterns of left ventricular structural abnormalities between genders. Attenuation seen in adjusted associations suggests that the higher frequency of structural abnormalities seen in diabetes may be due to factors other than hyperglycemia.

Cine magnetic resonance (MR) imaging of the heart detected evidence of left ventricular (LV) diastolic filling abnormality in patients with LV wall thickening but normal systolic function and normal diastolic function by routine Doppler echocardiography. Cine MR imaging may be more sensitive than routine echocardiography in detecting abnormalities of LV diastolic function.

Echocardiographically determined left ventricular (LV) hypertrophy may be a stronger risk factor of cardiovascular disease (CVD) for women than for men, although it is unclear whether reported gender differences are real or attributable to confounding. We evaluated echocardiographic LV hypertrophy (defined as LV mass/height(2.7) >/=51 g/m(2.7)) collected from the African-American population of the Atherosclerosis Risk in Communities Study. Incident CVD events (57 in men, 62 in women) were determined during a median follow-up of 4.9 years (interquartile range 4.3 to 5.6) and included nonfatal myocardial infarction, cardiac death, coronary revascularization, and stroke. We conducted 2 analyses. First, we created matched samples of 340 men and 812 women who had LV hypertrophy based on propensity score and estimated the gender-specific incidence rate ratios and population-attributable risks. Second, we evaluated the complete cohort (604 men and 1,113 women) with Poisson's regression after adjusting for age, body mass index, hypertension, diabetes mellitus, ratio of total cholesterol to high-density lipoprotein cholesterol, current smoking, and education level. LV hypertrophy was significantly predictive of incident CVD, and the association shown by analyses of matched propensity scores was similar in men and women (incidence rate ratio 1.88 vs 1.92, p = 0.97 for men, population-attributable risk 0.22 vs 0.26, p

A substantial number of older hypertensive patients have stage 1 isolated systolic hypertension (systolic blood pressure between 140 and 159 mm Hg and diastolic blood pressure P P P