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Introduction: Previous studies have suggested an association between insulin resistance (IR) trajectories and adverse changes in cardiac structure and function in nondiabetic populations. We studied the associations between IR trajectories and incident heart failure (HF) and all-cause death in nondiabetic participants of the Atherosclerosis Risk in Communities (ARIC) study. We hypothesized that long-term moderate and high IR levels would increase the risk of incident HF and all-cause death. Methods: We included 7,835 participants (3,505 men and 4,330 women) aged 45-64 from the ARIC study without diabetes mellitus at any visit, and no history of prevalent HF, myocardial infarction, stroke, arterial or coronary surgery, or cancer at baseline. We estimated IR using Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), triglyceride glucose (TyG) index and metabolic score for IR (METS-IR). Serum insulin was not available at visits 2 and 3, so HOMA-IR was calculated for visits 1, 4, and 5. Latent class analysis identified two HOMA-IR trajectories, low-increasing and high-increasing, and three trajectories for TG/HDL-C, TyG index, and METS-IR: low-increasing, moderate-stable, and high-decreasing. We employed Cox proportional-hazards models to examine the associations of IR trajectories with incident HF and all-cause death adjusting for potential confounders. Results: Compared to participants in the low-increasing group, those in the high-increasing group of HOMA-IR were more likely to have incident HF and all-cause death (Table 1). For TG/HDL-C, TyG index and METS-IR, we found an increased risk of incident HF in the moderate-stable and high-decreasing groups relative to the low-increasing group. For all-cause death, consistent associations were found only in women (Table 1). Conclusions: Reduction of insulin resistance in nondiabetic individuals may be a suitable target for prevention strategies to reduce cardiovascular disease.

Objectives To investigate glucose levels as a risk factor for unrecognized myocardial infarctions (UMIs). Design Cohort Setting Cardiovascular Health Study. Participants Individuals aged 65 and older with fasting glucose measurements (N=4,355; normal fasting glucose (NFG), n = 2,041; impaired fasting glucose (IFG), n = 1,706; DM: n = 608; 40% male, 84% white, mean age 72.4 ± 5.6). Measurements The relationship between glucose levels and UMI was examined. Participants with prior coronary heart disease (CHD) or UMI on initial electrocardiography were excluded. Using Minnesota codes, UMI was identified according to the presence of pathological Q‐waves or minor Q‐waves with ST‐T abnormalities. Crude and adjusted hazard ratios (HRs) were calculated. Analyses were adjusted for age, sex, body mass index (BMI), hypertension, antihypertensive and lipid‐lowering medication use, total cholesterol, high‐density lipoprotein cholesterol, and smoking status. Results Over a mean follow‐up of 6 years, there were 459 incident UMIs (NFG, n=202; IFG, n=183; DM, n=74). Participants with IFG were slightly more likely than those with NFG to experience a UMI (hazard ratio (HR)=1.11, 95% confidence interval (CI)=0.91–1.36, p = .30), and those with DM were more likely than those with NFG to experience a UMI (HR=1.65, 95% CI=1.25–2.13, p

Approximately 45% of first of myocardial infarctions (MI) are silent. People with diabetes are more likely to have MIs than those without diabetes. Little is known, however, about silent MIs (SMIs) among those with prediabetes. The prognosis of SMIs is similar to clinical MIs making timely detection imperative. We aimed to assess the association between prediabetes and incident SMI in four long duration cohort studies. We pooled data from the following studies: Cardiovascular Health, Atherosclerotic Risk in Communities, Health Aging and Body Composition, and Multi-Ethnic Study of Atherosclerosis (n=30,898). Population characteristics were: mean age 61.3 years, 45% male, 66.4% white, 40.0% had hypertension and 35.3% had hyperlipidemia. Diabetes status was based on fasting glucose (100-125mg/dL=prediabetes and >=126mg/dL=diabetes). Participants were also defined as having diabetes if they were taking medications for diabetes or reported a previous diagnosis. At baseline, 36% did not have diabetes, 50% had prediabetes and 14% had diabetes. Among participants with prediabetes, 3% experienced SMI over a mean follow-up of 9.6 years compared with 2% among those without diabetes. In Cox Proportional Hazards Models, we found an increased risk of incident SMI among those with prediabetes compared to those without diabetes (Hazard Ratio=1.25; 95% CI: 1.04-1.5, p=0.02), adjusting for age, sex, race, smoking status, hypertension, and high cholesterol. Significant baseline predictors of SMI in addition to having prediabetes included being male, older age, current smoking, and hypertension. People with prediabetes, comprising 50% of these cohort study populations, may be at increased risk for SMI, and could benefit from increased focus on prevention and treatment of cardiovascular risk factors. Disclosure J.C. Zgibor: None. M. Malmi: None. W. Wang: None. K.E. Kip: None. D.D. Schocken: None. A.C. Alman: None. R.B. Stacey: None.

Cardiovascular disease (CVD) remains the number one cause of mortality in the Western world. This study aims to determine which lifestyle factors are associated with mean carotid intima media thickness (IMT), a safe and reliable predictor of future CVD risk.A prospective cross-sectional analysis of 592 subjects. Measures were made of body composition, anthropometric measures, fitness, diet (measured with a 3-day food diary), laboratory results, and mean carotid IMT. Multivariate analyses show that higher mean IMT values are associated with increasing age (p0.0001), male gender (p = 0.0002), higher systolic blood pressure (BP; p = 0.0008), higher body mass index (BMI; p = 0.0005), and lower intake of zinc (p = 0.0001). Bivariate analyses controlling for age and gender, with and without statin use, showed that higher mean IMT scores were statistically associated with higher diastolic BP (p = 0.007), higher total cholesterol/high-density lipoprotein (HDL) ratio (p0.0001), higher triglyceride/HDL ratio (p = 0.0001), lower aerobic capacity measures (p = 0.0007), higher body fat percentage and waist circumference (p0.0001), higher fasting glucose level (p = 0.028), and lower intake of magnesium (p = 0.019), fish (p = 0.007), and fiber (p = 0.02). Other factors that were not associated with mean IMT include total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP); intake of saturated fat, potassium, calcium, sodium, or vitamin K; percentage of calories from protein, fat, or carbohydrate; measures of strength (assessed with push-up and sit-up testing); and reported exercise.Aerobic fitness and dietary intake of fiber, fish, magnesium, and zinc are inversely associated with carotid IMT scores. Of the traditional CVD risk factors, only systolic BP, fasting glucose, body composition, and total cholesterol/HDL ratio have a direct relationship with mean carotid IMT.

Electrocardiographic left ventricular hypertrophy (LVH) has many faces with countless features. Beyond the classic measures of LVH, including QRS voltage and duration, the left ventricular (LV) strain pattern is an element whereby characteristic R-ST depression is followed by a concave ST segment that ends in an asymmetrically inverted T wave. The LV strain pattern generally appears in states of increased systemic blood pressure and must be differentiated from similar but not identical ST-T waves indicating ischemia. The LV strain pattern has been found in population studies to be associated with poor prognosis and increased risk of adverse cardiovascular outcomes. Regression of LV strain pattern parallels decline in systemic BP during clinical trials of anti-hypertensive therapies but does not indicate or serve as a surrogate for decrease in LV mass. Newer techniques in data collection and processing may allow the process of strain to be studied in more detail to determine the ways in which electrical remodeling of the left ventricle as characterized by LVH with 'repolarization abnormalities' indicates how CV risk might be managed by using LV strain pattern as an electrocardiographic biomarker.

The traditional approach to the ECG diagnosis of left ventricular hypertrophy (LVH) is focused on the best estimation of left ventricular mass (LVM) i.e. finding ECG criteria that agree with LVM as detected by imaging. However, it has been consistently reported that the magnitude of agreement is rather low as reflected in the low sensitivity of ECG criteria. As a result, the majority of cases with true anatomical LVH could be misclassified by using ECG criteria of LVH. Despite this limitation, it has been reported that the ECG criteria for LVH provide independent information on the cardiovascular risk even after adjusting for LVM. Understanding possible reasons for the frequent discrepancy between common ECG LVH criteria and LVH by echo or MRI would help understanding the genesis of ECG changes that occur as a consequence of increased LV mass.

Objectives This study was designed to test the hypothesis of whether amlodipine reduces the risk for death in patients with heart failure due to a nonischemic cardiomyopathy. Background A pre-specified subgroup analysis in an earlier, large-scale, placebo-controlled study suggested that amlodipine might reduce the risk for death in patients with heart failure due to a nonischemic cardiomyopathy. Methods To evaluate this hypothesis, 1654 patients with severe heart failure due to a nonischemic cardiomyopathy (ejection fraction Results There were 278 deaths in the amlodipine group and 262 deaths in the placebo group (hazard ratio: 1.09; 95% confidence interval [CI]: 0.92 to 1.29; p = 0.33). The differences between the 2 groups in the risks for cardiovascular death and hospitalization were also not significant. When the results from patients with a nonischemic cardiomyopathy in both the earlier trial and in the current study were combined, there was no evidence of a favorable or unfavorable effect of amlodipine on mortality (hazard ratio: 0.97; 95% CI: 0.83 to 1.13; p = 0.66). Both trials, however, observed higher frequencies of peripheral edema and pulmonary edema and lower frequencies of uncontrolled hypertension and chest pain in patients treated with amlodipine. Conclusions These results of the current trial, viewed together with the results from the earlier study, indicate that amlodipine does not exert favorable effects on the clinical course of patients with heart failure, regardless of the presence or absence of underlying coronary artery disease. These findings indicate the need for great caution when striking benefits are observed in subgroups of patients or in trials not primarily designed to assess such effects.

The 4th Report provides a brief review of publications focused on the electrocardiographic diagnosis of left ventricular hypertrophy published during the period of 2010 to 2016 by the members of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy. The Working Group recommended that ECG research and clinical attention be redirected from the estimation of LVM to the identification of electrical remodeling, to better understanding the sequence of events connecting electrical remodeling to outcomes. The need for a re-definition of terms and for a new paradigm is also stressed.

Objectives The aim of this study was to assess the efficacy of exercise and antidepressant medication in reducing depressive symptoms and improving cardiovascular biomarkers in depressed patients with coronary heart disease. Background Although there is good evidence that clinical depression is associated with poor prognosis, optimal therapeutic strategies are currently not well defined. Methods One hundred one outpatients with coronary heart disease and elevated depressive symptoms underwent assessment of depression, including a psychiatric interview and the Hamilton Rating Scale for Depression. Participants were randomized to 4 months of aerobic exercise (3 times/week), sertraline (50–200 mg/day), or placebo. Additional assessments of cardiovascular biomarkers included measures of heart rate variability, endothelial function, baroreflex sensitivity, inflammation, and platelet function. Results After 16 weeks, all groups showed improvement on Hamilton Rating Scale for Depression scores. Participants in both the aerobic exercise (mean −7.5; 95% confidence interval: −9.8 to −5.0) and sertraline (mean −6.1; 95% confidence interval: −8.4 to −3.9) groups achieved larger reductions in depressive symptoms compared with those receiving placebo (mean −4.5; 95% confidence interval: −7.6 to −1.5; p = 0.034); exercise and sertraline were equally effective at reducing depressive symptoms (p = 0.607). Exercise and medication tended to result in greater improvements in heart rate variability compared with placebo (p = 0.052); exercise tended to result in greater improvements in heart rate variability compared with sertraline (p = 0.093). Conclusions Both exercise and sertraline resulted in greater reductions in depressive symptoms compared to placebo in patients with coronary heart disease. Evidence that active treatments may also improve cardiovascular biomarkers suggests that they may have a beneficial effect on clinical outcomes as well as on quality of life. (Exercise to Treat Depression in Individuals With Coronary Heart Disease; NCT00302068 )

This document has been developed as an expert consensus document by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA), in collaboration with the American Academy of Neurology (AAN), the American College of Physicians (ACP), the American Geriatrics Society (AGS), the American Society of Hypertension (ASH), the American Society of Nephrology (ASN), the American Society for Preventive Cardiology (ASPC), the Association of Black Cardiologists (ABC), and the European Society of Hypertension (ESH). Expert consensus documents are intended to inform practitioners, payers, and other interested parties of the opinion of ACCF and document cosponsors concerning evolving areas of clinical practice and/or technologies that are widely available or new to the practice community. Topics chosen for coverage by expert consensus documents are so designed because the evidence base, the experience with technology, and/or clinical practice are not considered sufficiently well developed to be evaluated by the formal ACCF/AHA practice guidelines process. Often the topic is the subject of considerable ongoing investigation. Thus, the reader should view the expert consensus document as the best attempt of the ACCF and document cosponsors to inform and guide clinical practice in areas where rigorous evidence may not yet be available or evidence to date is not widely applied to clinical practice. When feasible, expert consensus documents include indications or contraindications. Typically, formal recommendations are not provided in expert consensus documents as these documents do not formally grade the quality of evidence, and the provision of “Recommendations” is felt to be more appropriately within the purview of the ACCF/AHA practice guidelines. However, recommendations from ACCF/AHA practice guidelines and ACCF appropriate use criteria are presented where pertinent to the discussion. The writing committee is in agreement with these recommendations. Finally, some topics covered by expert consensus documents will be addressed subsequently by the ACCF/AHA …

The increase in heart failure (HF) rates throughout the developed and developing regions of the world poses enormous challenges for caregivers, researchers, and policymakers. Therefore, prevention of this global scourge deserves high priority. Identifying and preventing the well-recognized illnesses that lead to HF, including hypertension and coronary heart disease, should be paramount among the approaches to prevent HF. Aggressive implementation of evidence-based management of risk factors for coronary heart disease should be at the core of HF prevention strategies. Questions currently in need of attention include how to identify and treat patients with asymptomatic left ventricular systolic dysfunction (Stage B HF) and how to prevent its development. The relationship of chronic kidney disease to HF and control of chronic kidney disease in prevention of HF need further investigation. Currently, we have limited understanding of the pathophysiological basis of HF in patients with preserved left ventricular systolic function and management techniques to prevent it. New developments in the field of biomarker identification have opened possibilities for the early detection of individuals at risk for developing HF (Stage A HF). Patient groups meriting special interest include the elderly, women, and ethnic/racial minorities.Future research ought to focus on obtaining a much better knowledge of genetics and HF, especially both genetic risk factors for development of HF and genetic markers as tools to guide prevention. Lastly, a national awareness campaign should be created and implemented to increase public awareness of HF and the importance of its prevention. Heightened public awareness will provide a platform for advocacy to create national research programs and healthcare policies dedicated to the prevention of HF.

PURPOSE Coronary heart disease (CHD) remains the leading cause of death in women. Despite positive outcomes associated with cardiac rehabilitation (CR), investigations of women are sparse. This article presents the baseline physiological and psychosocial profiles of 182 women in the Women's-Only Cardiac Rehabilitation study. METHOD Women were randomized to a women's-only motivational interviewing or traditional CR group. Physiological measures included lipid profiles, body mass index, functional capacity, and anthropomorphic measures. Psychosocial measures included optimism, hope, social support, anxiety, depression, quality of life, and health perceptions. The median age was used to split the sample to examine data on 92 younger ( 64 years) women. RESULTS With a mean age of 63 years, 66.5% were white, 47% were retired, and 54% were married. Most women were physically inactive (83%), hypertensive (76%), and overweight (56%). Most women (71.4%) met the criteria for metabolic syndrome. Younger women demonstrated significantly worse psychosocial profiles than older women. More of the younger women (64%) had depressive symptoms than older women (37%). Younger women demonstrated a mean Center for Epidemiological Studies Depression Scale score of 20.8 +/- 12.4, whereas older women had a substantially lower mean score of 14.9 +/- 9.5 (P < .001). Younger participants also reported significantly more anxiety than older participants (38.8 +/- 13.4 vs 32.8 +/- 10.6, P < .001). CONCLUSION Younger women enrolled in a CR clinical trial had adverse baseline risk factor profiles placing them at high risk for disease progression.

Background: Almost 25% of initial myocardial infarctions (MI) are unrecognized or clinically-silent (UMI). The prognostic implications of a UMI parallel those of symptomatic MIs. With diabetes mellitus (DM) being a known risk factor for UMI, further investigation is warranted regarding impaired fasting glucose (IFG) as a risk factor for UMI. Up to one-third of Americans have IFG . Therefore the relationship between UMI and IFG may have significant public health and clinical ramifications. Methods: The relationship between IFG and UMI was examined in the Cardiovascular Health Study: a cohort of individuals aged ≥ 65 years old. At year 2, there were 5,018 participants who had an initial 12-lead electrocardiogram (ECG). Of these participants, those with prior coronary heart disease (CHD), incident CHD, or a UMI on initial ECG were excluded. Our study population consisted of 1,714 participants without exclusions with measured fasting glucose (normal fasting glucose, NFG; n = 844), IFG (n=679), and DM (n=191) who underwent a baseline 12-lead electrocardiogram (ECG). Using Minnesota code, an UMI was identified by the presence of pathological Q waves or minor Q waves with ST-T abnormalities. Crude and adjusted hazard ratios (HRs) were calculated. Cox proportional hazard models were used to adjust for age, gender, body mass index, hypertension, anti-hypertensive medication use, total cholesterol, HDL cholesterol, lipid-lowering medication use, and cigarette use. Results: The sample was 36% male, 95% white, and had a mean age of 72.4 ± 5.6 years. Over a mean follow-up of 8.1 years, there were 94 UMIs identified among NFG subjects, 110 among IFG subjects, and 35 among DM subjects. Relative to NFG, the crude risk ratio estimates for UMI with IFG and DM were 1.53 (95% CI: 1.16-2.01) and 1.85 (1.24-2.70), respectively. With adjustment, the HR for UMI in IFG compared with NFG was 1.37 (95% CI: 1.03-1.83; p=0.032), and the HR for UMI in DM compared with NFG was 1.59 (95% CI: 1.24-2.70; p=0.035). Conclusion: Impaired fasting glucose increased the risk for a subsequent unrecognized myocardial infarction. Considering the enormous number of individuals at risk, these findings suggest the need for more aggressive CVD prevention activities.

Introduction: CVD remains the number one cause of mortality in the western world. Carotid intima-media thickness (IMT) is a safe & reliable predictor of future CVD risk. This study assesses which lifestyle factors best predict a change in IMT over time. Hypothesis: We assessed the null hypothesis that all lifestyle changes are effective. Methods: A prospective cross-sectional analysis of 289 men & women undergoing health & cardiovascular risk screening every 1-2 years at an outpatient wellness center in Florida. This study reflects the first visit at the clinic, & a second visit that occurred on average 2.8 years later. These subjects ranged in age from 23-65 (mean = 48.2). In addition to testing, subjects received nutrition, fitness, & health coaching. Measurements were made of fitness using VO2max stress testing, diet intake using a 3-day dietary intake survey. Laboratory & anthropometric measures were obtained fasting. Mean IMT scores used high resolution B-mode ultrasonography of the common carotid arteries. Each subject had ≥10 images collected from the far wall of both distal 1 cm of the common carotid arteries at end diastole. The carotid intimal thickness was measured as a continuous variable, using both multivariate & bivariate linear regression, adjusting for age & gender; as our site IMT precision was = 3%, we selected a 4% change as significant. Results: The average decrease in IMT score in this cohort was -0.018 mm over 2.8 years, a 2.04% reduction. The bivariate analyses showing a significant association with a ≥4% reduction in IMT in 62 of 288 subjects; they were a decrease in: Body mass index (BMI) (p=0.047), body fat (p=0.025), total cholesterol (TC) (p=0.031), LDL cholesterol (p=0.028), TC/HDL (0.002), or an increase in dietary intake of: magnesium (p=0.0001), fiber (p=0.017), vitamin D (p=0.016), vitamin K (p=0.001), potassium (p=0.001), & calcium (p=0.024). In a multivariate analysis, starting a statin medication (p=0.0007), a decrease in BMI (p=0.042), baseline IMT, male gender, diastolic BP decrease, & years of follow up were predictive of 4% IMT decline. Prior use of a statin medication was not significant. Conclusions: In conclusion, this study shows that a reduction in IMT score over 2.8 years is associated with a decrease in: BMI, body fat, TC, LDL, TC/HDL ratio, & diastolic BP; or, an increase in intake of: magnesium, fiber, vitamins K & D, potassium, & calcium; or, starting a statin medication.

Numerous clinical studies have established that angiotensin II receptor blockers are effective as antihypertensive therapy and are well tolerated. Studies demonstrate that adding an angiotensin II receptor blocker to existing antihypertensive regimens reduces cardiovascular and renal risk, which may, in part, be a result of blocking the effects of angiotensin II. Though the antihypertensive dose response of these agents is well documented, the dose response for optimal target organ protection has not yet been clarified. A review of recent studies of angiotensin II receptor blockers in hypertension, acute myocardial infarction, heart failure, and nephropathy provide some data on specific drugs, doses, and risk reduction. Taken as a whole, these studies suggest the highest doses tested, which are at the upper limit of the antihypertensive range, provide greater risk reduction than lower doses. What is unknown is whether even higher doses or full-dose angiotensin II receptor blockers plus full-dose angiotensin-converting enzyme inhibitors might provide even greater risk reduction. Data from ongoing trials will provide additional insight.

Background: It has been estimated that approximately 25% of initial myocardial infarctions (MI) are unrecognized (UMI). The prognostic implications of UMI’s have been shown to be as severe as those of symptomatic MI’s. Risk factors for UMI’s are not well understood. Because diabetes mellitus is known to be a risk factor for UMI, it is reasonable to investigate impaired fasting glucose (IFG) as a candidate risk factor. Additionally, it has recently been estimated that up to one-third of all adult Americans have IFG. Methods: The relationship between IFG and UMI was examined in the Multi-Ethnic Study of Atherosclerosis (MESA): a cohort of individuals aged 45 to 84 years without clinical cardiovascular disease. At baseline, participants with normal fasting glucose (NFG; n = 4955) and IFG (n=930) underwent a baseline 12-lead electrocardiogram (ECG). Using Minnesota code, an UMI was identified by the presence of pathological Q waves or minor Q waves with ST-T abnormalities. Crude and adjusted odds ratios (ORs) were calculated. Logistic regression was used to adjust for covariates in 2 models. Model 1 adjusted for age, race, gender, and body mass index. Model 2 adjusted for model 1 + systolic blood pressure, diastolic blood pressure, anti-hypertensive medication use, total cholesterol, HDL cholesterol, lipid-lowering medication use, and cigarette use. Results: The sample was 46% male, 41% white, 26% black, 20% Hispanic, and 12% Asian. There were 72 UMIs identified in the normal fasting glucose (NFG) subjects and 30 UMIs among the IFG subjects. The two corresponding prevalences (1.4% vs. 3.2%) resulted in a crude OR for UMI of 2.26 (95% Confidence Interval (CI): 1.47-3.48; p Conclusion: Unrecognized myocardial infarctions by electrocardiogram are associated with impaired fasting glucose in a population without overt cardiovascular disease. Because of the high prevalence of impaired fasting glucose, the implications of this finding may have ramifications for a large proportion of the adult population.

Introduction: Cardiovascular disease (CVD) remains the number one cause of mortality in the western world. Carotid intimal media thickness (carotid IMT) is a safe and reliable predictor of future CVD risk. Hypothesis: The study aims to assess the hypothesis that lifestyle factors impact carotid IMT, and determine which nutrition and fitness risk factors best predict mean carotid IMT scores. Methods: A prospective cross-sectional analysis of 592 men and women undergoing health and cardiovascular risk screening. This study reflects the first visit of these subjects, age 23 to 65 (mean = 48.2), who are followed longitudinally and who were participants at a “wellness” oriented program for patients who are generally well-educated and mostly in good health. Measurements were made of fitness using VO2max stress testing and push-up and sit-up scores following the American College of Sports Medicine testing protocols, diet intake using a 3-day dietary intake survey and computerized analyses. Mean carotid IMT scores were obtained using high resolution B-mode ultrasonography of the common carotid arteries. Each subject had ≥10 images collected from the far wall of the right and left distal 1 cm of the common carotid arteries at end diastole. The carotid intimal thickness was measured as a continuous variable, using both multivariate linear and bivariate linear regression. Multivariate analyses adjusted for potential confounders using multiple linear regression and included measures of body composition, blood pressure, fasting lipid and glucose levels, and statin use. Results: Multivariate analyses show that higher mean carotid IMT values are associated with increasing age (p Conclusions: In this database, aerobic fitness and dietary intake of fiber, fish, magnesium, and zinc are associated with lower carotid IMT scores. Further studies are warranted to explore the impact of emerging lifestyle factors on cardiovascular risk and clinical outcomes.

The present investigation was designed to determine whether atrial natriuretic peptides (ANPs) consisting of amino acids 1–30[ i.e. long-acting natriuretic hormone (LANH)], 31–67 (vessel dilator), 79–98 (kaliuretic hormone), and 99–126 (atrial natriuretic hormone [ANH]) of the 126-amino acid ANH prohormone decrease the circulating concentrations of total and free T4 and/or free T3 in healthy humans (n = 30). Vessel dilator, kaliuretic hormone, LANH, and ANH decreased the circulating concentrations of total T4 by 61%, 58%, 47%, and 55% and of free T4 by 60%, 67%, 79%, and 79%, whereas free T3 decreased 72%, 67%, 71%, and 67% (P < 0.05 for each), respectively, when infused at 100 ng/kg BW·min for 60 min. Vessel dilator, kaliuretic hormone, LANH, and ANH simultaneously increased circulating TSH concentrations 4- to 12.5-fold (P < 0.004). The decreases in T4 and T3 with reciprocal increases in TSH lasted 2–3 h after cessation of the respective ANP infusions. The reciprocal increase in TSH with the decreases in T4 and T3 suggests that their modulation of T4 and T3 concentrations occurs in the thyroid rather than in the pituitary or hypothalamus, because TSH would be decreased in the circulation if their inhibitory effects were in either the hypothalamus or pituitary.

The atrial natriuretic peptide (ANP) gene synthesizes a 126-amino acid (aa) prohormone from which four peptide hormones are derived. These 4 peptide hormones consisting of aa 1 to 30 (ie, long-acting natriuretic peptide [LANP]), aa 31 to 67 (vessel dilator), aa 79 to 98 (kaliuretic peptide), and aa 99 to 126 (ie, ANP) have diuretic, natriuretic, and/or kaliuretic properties. ANP has been reported to have its natriuretic and protein-excreting effects via both the proximal and distal tubules, but where in the kidney the other three peptide hormones have their natriuretic and/or diuretic effects is unknown. Further, it has never been investigated as to whether these three other peptide hormones enhance protein excretion. The present investigation was designed to determine (1) if these atrial peptides enhance protein excretion and (2) if their effects involve the proximal tubules of healthy humans by examining the excretion rate of beta2-microglobulin, a marker of proximal tubule function. Twenty-four healthy human subjects were studied following the infusion of 100 ng/kg body weight/min for 60 minutes of each of the respective peptides. LANP enhanced the excretion rate of beta2-microglobulin 2-fold within 20 minutes of beginning its infusion (P < .05) and was 2.5-fold higher than the preinfusion excretion rate at the end of the infusion. The excretion rate of beta2-microglobulin continued to be significantly (P < .01) increased for 3 hours after cessation of the LANP infusion, with the maximal excretion rate (ie, 3.8-fold increase) at 2.5 hours after stopping the infusion. Vessel dilator showed a more marked enhancement of beta2-microglobulin during its infusion, with the excretion rate increasing 2.5-fold at 20 minutes, and was increased 4-fold (P < .01) at the end of the infusion. With cessation of the vessel dilator infusion, the excretion rate of beta2-microglobulin decreased but was still elevated 2-fold (P < .05) 3 hours after stopping the infusion. Kaliuretic peptide enhanced the beta2-microglobulin excretion rate a maximal 3-fold, which occurred at the end of its infusion. The beta2-microglobulin excretion secondary to kaliuretic peptide remained 2-fold (P < .05) above baseline during the 3-hour postinfusion period. These peptide hormones similarly enhanced the albumin and total protein excretion rates 2- to 4-fold. These results indicate that LANP, vessel dilator, and kaliuretic peptide each (1) enhance protein excretion in healthy humans and (2) inhibit proximal tubular protein reabsorption.

Prostaglandin E2 (PGE2) increases in the circulation of persons with congestive heart failure (CHF), but the cause of this increase is unknown. Prostaglandins are not stored, therefore, they cannot be released in response to congestive heart failure itself but rather need to have their synthesis stimulated by a hormone or some other substance. Prostaglandin E2's biologic properties are nearly identical to four peptide hormones originating from amino acids 1–30 [long acting natriuretic peptide], 31–67 [vessel dilator], 79–98 [kaliuretic peptide] and 99–126 [atrial natriuretic peptide, ANP] of the 126 amino acid ANP prohormone. ANP previously has been found to have no effect on circulating PGE2 concentrations in persons with CHF. The present investigation was designed to determine if one or more of the other three atrial natriuretic peptides might increase PGE2 when infused at their respective 100 ngkg body weight/minute concentrations for 60 minutes in persons with congestive heart failure. Vessel dilator increased PGE2 8-fold (P < 0.001) in the first 20 minutes of its infusion with PGE2 remaining 2–3 fold increased (P < 0.05) for 60 minutes after stopping its infusion. Long acting natriuretic peptide did not increase PGE2 until 40 minutes of its infusion but it caused the maximal increase (27-fold; P < 0.001) of PGE2 of the three peptide hormones tested. Kaliuretic peptide's stimulated increase of PGE2 also began in a delayed fashion but its effects lasted the longest, with PGE2being increased (P < 0.05) for two hours after the cessation of kaliuretic peptide's infusion. This investigation demonstrates that 1) three endogenous peptide hormones increase PGE2 in the circulation and 2) suggests that the known increase in PGE2 in CHF may be in part secondary to these peptides.

This study was designed to study the pathogenesis of cardiomyopathy in animals with longstanding (6 months) diabetes mellitus. Male Wistar rats were made diabetic by the injection of streptozotocin (35 mg/kg) intraperitoneal at 6 months of age. Myocardial contractility was evaluated at 1 year of age by an echocardiogram. Blood was collected at that time to measure blood glucose and hemoglobin A1c as an indicator of metabolic control. Serum carnitine was also measured on the same sample to evaluate the availability of this substance so essential for fatty acid metabolism in the myocardium. Myocardial anatomy was evaluated by both light and electron microscopy after the animals had diabetes for 6 months. It was found that the left ventricular volume was greater at the end of systole and diastole. There was the suggestion of left ventricular fractional shortening and calculated reduced ejection fraction indicating decreased contractility consistent with cardiomyopathy. The hearts had no evidence of coronary vascular occlusion, and the serum cholesterol was normal. Myocardial ultrastructure revealed abnormal-appearing mitochondria consistent with carnitine deficiency. Serum and myocardial carnitine levels in the animals with diabetes and reduced myocardial function were low. Carnitine levels and metabolism could be important in the pathogenesis of diabetic cardiomyopathy.

PURPOSE: To investigate whether subjective sleep complaints are an independent predictor of myocardial infarction (MI) in a community of older adults and to gain clues as to why the association between sleep complaints and incident MI exists. METHODS: Using longitudinal data from the Piedmont study on 2960 adults aged 65 or older who were free of symptomatic heart disease at baseline, we screened 19 potential confounders to determine if any, alone or in combination, could explain the observed relationship between incident MI and sleep complaints. RESULTS: During the three-year follow-up period, there were 152 incident MIs. Restless sleep (incidence density ratio (IDR) = 1.58, 95% confidence interval (CI) = 1.11, 2.24) and trouble falling asleep (IDR = 1.68, 95% CI = 1.09, 2.60) predicted incident MI after adjusting for age, gender, and race. IDRs were not substantially impacted by controlling for smoking, blood pressure, diabetes or obesity. After adjustment for education, number of prescription medicines, self-rated health, and depression score, all IDRs were nullified. In particular, self-rated health and depression were strong independent risk factors for MI. CONCLUSIONS: A subjective sleep complaint increases the likelihood of a first MI in older adults without overt coronary heart disease (CHD) independently of classic coronary risk factors and appears to be a marker for a syndrome of depression and malaise that may have a causal relationship to MI.

Background —Vessel dilator, a 37–amino acid peptide hormone synthesized in the heart, enhances urine flow 4- to 12-fold and sodium excretion 3- to 6-fold in healthy humans. The present investigation was designed to determine whether vessel dilator might have similar beneficial effects in persons with congestive heart failure (CHF). Methods and Results —Vessel dilator (100 ng/kg body weight per minute) given intravenously for 60 minutes to NYHA class III CHF subjects increased urine flow 2- to 13-fold, which was still increased ( P P P Conclusions —These results indicate that vessel dilator has significant beneficial diuretic, natriuretic, and hemodynamic properties in humans with congestive heart failure.

Psychological and physiological similarities have been proposed between habitual runners and anorexia nervosa patients. Method: Twenty male runners, 20 female runners, and 17 anorexia nervosa patients were evaluated using several psychological measures (Minnesota Multiphasic Personality Inventory, Leyton Obsessional Inventory, and three measures of body image) and physiological measures (physical examination, anthropometric assessment, and exercise treadmill tests). Results: Anorexia nervosa patients had significantly more evidence of psychopathology on all the psychological measures than either group of runners. There were suggestive similarities between female runners and anorexics on some of the body image tests. Fat content was in the normal range for both groups of runners and low in the anorexia nervosa group. Abnormalities were seen on the treadmill tests in all three groups, but there were no statistically significant differences. Conclusion: Despite hypothetical similarities, this study found that anorexia nervosa patients and habitual runners have few similar psychological or physiological features. © 1998 by John Wiley & Sons, Inc. Int J Eat Disord 23:133–143, 1998.

Background: Urodilatin is a 32-amino-acid (AA) peptide formed in the kidney. Methods: High-performance gel permeation chromatography and high-pressure liquid chromatography evaluation of plasma followed by sensitive urodilatin and atrial natriuretic peptide (ANP) assays revealed that urodilatin does circulate distinctly from ANP. Results: Urodilatin circulates at very low levels (i.e 9–12 pg/ml). Infusion of ANP increased the circulating concentration of urodilatin 135-fold (p < 0.001), suggesting that some of the effects of ANP may be mediated by urodilatin while long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide did not affect urodilatin in healthy humans (n = 30). Only ANP decreased the renal clearance of urodilatin (60–75%, p < 0.01). Urodilatin was metabolized into peptides smaller than 5 AAs as well as excreted intact into urine. Conclusion: Urodilatin circulates and is increased by ANP in humans.

Objectives: The present investigation was designed to determine the best endogenous plasma marker of early congestive heart failure (CHF). Methods: Forty volunteers with mild CHF (New York Heart Association Class I, n = 12), moderate (Class II, n = 8), or severe (Class III and Class IV, each= n of 5) and 10 age-matched healthy individuals had the simultaneous evaluation of their respective plasma samples by the following radioimmunoassays: atrial natriuretic peptide, ANP; three N-terminal ANP prohormone assays, i.e., proANPs 1–30, 31–67, and 79–98 with the numbers referring to their amino acid (a.a.) sequences in their 126 a.a. prohormone; brain (BNP) and C-natriuretic peptides; N-terminal BNP prohormone; adrenomedullin; neuropeptide Y and endothelin. Results: ProANPs 31–67, 1–30 and 79–98 had 100% ( P = 0.01), 83% ( P = 0.09) and 50% ( P = 0.74) sensitivity in differentiating Class I CHF subjects from healthy subjects. The ANP, BNP, NT-proBNP, CNP, adrenomedullin, neuropeptide Y, and endothelin assays could not differentiate mild CHF subjects from healthy individuals. Logistic regression analysis revealed that only proANP 31–67 significantly ( P = 0.0001) discriminated between early CHF (5226±377 pg/ml) and healthy individuals (1595±157 pg/ml). The positive and negative predictive values of proANP 31–67 were excellent (100% for each). The peptides measured in these assays were found to be independent markers of CHF with respect to left ventricular ejection fraction. Conclusions: ProANPs 31–67 is the most sensitive marker in discriminating NYHA Class I CHF subjects from healthy individuals. The ANP, BNP, NT-proBNP, CNP, adrenomedullin, neuropeptide Y and endothelin radioimmunoassays cannot discern mild CHF. These peptides are independent of left ventricular ejection fraction.

Long-acting natriuretic peptide (LANP), vessel dilator, and atrial natriuretic factor (ANF) (each infused at 100 ng/kg body weight [BW].min for 60 minutes) increased the circulating concentration of calcitonin gene-related peptide (CGRP) threefold to fourfold in 30 healthy humans. Within 30 minutes of stopping ANF infusion, the CGRP circulating concentration had returned to preinfusion levels, whereas its increase secondary to the other atrial peptides was still significant 2 to 3 hours after cessation of their infusions. There was a 50% decreased excretion (P.001) of CGRP into the urine secondary to LANP and vessel dilator, which correlated with the increase of CGRP in the circulation. The ANF-induced 50% decreased CGRP excretion occurred after the circulating concentration of CGRP had returned to preinfusion levels. Kaliuretic peptide did not affect CGRP circulating concentration or excretion into urine. These data suggest that LANP and vessel dilator inhibit the metabolic breakdown of CGRP as part of their mechanism of increasing CGRP in plasma, whereas the ANF effect of increasing CGRP in plasma appears to be secondary to stimulating the release of CGRP.

Objectives. We sought to determine whether the beneficial effects of amlodipine in heart failure may be mediated by a reduction in tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels. We postulated that TNF-alpha and IL-6 levels may also have predictive value in patients with congestive heart failure (CHF). Background. The molecular mechanism for progression of CHF may involve cytokine overexpression. The effect of amlodipine on cytokine levels in patients with CHF is unknown. Methods. In the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) trial, we used enzyme-linked immunosorbent assay to measure plasma levels of TNF-alpha in 92 patients and IL-6 in 62 patients in New York Heart Association functional classes III and IV randomized to receive amlodipine (10 mg/day) or placebo. Blood samples were obtained for cytokine measurement at baseline and at 8 and 26 weeks after enrollment. Results. The baseline amlodipine and placebo groups did not differ in demographics and cytokine levels. Mean (±SD) plasma levels of TNF-alpha were 5.69 ± 0.32 pg/ml, and those of IL-6 were 9.23 ± 1.26 pg/ml at baseline. These levels were elevated 6 and 10 times, respectively, compared with those of normal subjects (p < 0.001). Levels of TNF-alpha did not change significantly over the 26-week period (p = 0.69). However, IL-6 levels were significantly lower at 26 weeks in patients treated with amlodipine versus placebo (p = 0.007 by the Wilcoxon signed-rank test). An adverse event—CHF or death—occurred more commonly in patients with higher IL-6 levels. Conclusions. Amlodipine lowers plasma IL-6 levels in patients with CHF. The beneficial effect of amlodipine in CHF may be due to a reduction of cytokines such as IL-6. (J Am Coll Cardiol 1997;30:35–41)

Background: Little is known about the composition and source of weight loss after bariatric surgery for morbid obesity. Purpose: This study was undertaken to determine changes in weight, body mass index (BMI), lean body weight (LBW), fat weight (FW) and left ventricular cardiac mass (LVM) following vertical banded gastroplasty (VBG). Methods: After VBG for morbid obesity, 26 women and four men (mean age = 39.1 years) were weighed and had body composition analysis undertaken at intervals. Thirteen patients underwent echocardiography preoperatively and 1 year postoperatively to determine change in LVM and LVM index. Results: Over 12 months there was significant weight loss for all weight parameters examined (p < 0.05). Fat weight loss was most significant; total weight loss and reduction of BMI were significant but less so than fat loss (Wilcoxon's signed ranks test). LBW loss had the smallest contribution to weight loss (p < 0.0001). There was a significant loss of LVM and posterior cardiac wall thickness (p < 0.05). Conclusions: VBG can lead to loss of lean body weight and left ventricular mass, and more dramatically, fat weight, body weight, and BMI. Cardiac mass and lean body mass are preferentially conserved relative to body fat with weight loss after VBG.

Adrenomedullin (ADM) is a new 52 amino acid peptide originally isolated from extracts of human pheochromocytoma. ADM's biologic properties are nearly identical to those of atrial natriuretic peptides. Thus, the 4 peptide hormones originating from amino acids 1-30 [long acting natriuretic peptide], 31-67 [vessel dilator], 79-98 [kaliuretic peptide] and 99-126 [atrial natriuretic factor; ANF] of the 126 amino acid ANF prohormone as well as ADM have blood pressure lowering and diuretic properties. The present investigation was designed to determine if one or more of these 4 atrial natriuretic peptides increase adrenomedullin within the circulation of healthy humans. Infusion of 100 ng/kg body weight/minute for 60 minutes of the respective atrial peptides resulted in a 4-fold (P < 0.001) increase in the circulating concentration of adrenomedullin secondary to the ANF infusion but no increase in adrenomedullin with the long acting natriuretic peptide, vessel dilator, or kaliuretic peptide infusions. The four-fold increase of adrenomedullin in the circulation persisted throughout the infusion of ANF, but returned to pre-infusion levels within 30 minutes of stopping the ANF infusion. Infusion of 10 pg/kg body weight/minute for 60 minutes of ANF resulted in a 2 1/2-fold increase (P < 0.05) in the circulating concentration of adrenomedullin. There was a significant (P < 0.01) diuresis and blood pressure lowering effect with each of the atrial natriuretic peptides in the present investigation. This investigation suggests that 1) atrial natriuretic factor increases the release of adrenomedullin and 2) that the diuretic and blood pressure lowering effects previously attributed to atrial natriuretic factor may be partially due to adrenomedullin since both increased during the ANF infusion and both have similar biologic effects. As opposed to atrial natriuretic factor, adrenomedullin was not increased by long acting natriuretic peptide, vessel dilator, or kaliuretic peptide suggesting that their biologic effects do not involve adrenomedullin.

The present investigation was designed to examine the effect of four atrial peptide hormones with vasodilatory properties on the circulating immunoreactive (ir) levels of the vasoconstrictive peptide endothelin (ET) in 36 healthy human subjects. Circulating levels of human ET and cyclic guanosine monophosphate ([cGMP], a potential mediator of the effects of atrial peptides), were measured every 30 minutes during 1-hour preinfusion, 1-hour infusion, and 3-hour postinfusion periods. Atrial natriuretic factor ([ANF] amino acid (aa) 99 to 126 of the 126-aa ANF prohormone) and kaliuretic peptide (aa 79 to 98 of this same prohormone) significantly (P

Atrial natriuretic factor (ANF), consisting of amino acids 99-126 of the 126 amino acid ANF prohormone, increases cyclic guanosine monophosphate (GMP) (thought to be the mediator of its physiologic effects) in plasma and urine of human subjects. Long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide, consisting of amino acid 1-30, 31-67, and 79-98, respectively, of this same prohormone have natriuretic, diuretic, kaliuretic, and blood pressure lowering properties in humans. These three new peptide hormones increase cyclic GMP in vitro but were never investigated to determine whether they also cause extrusion of cyclic GMP from cells, resulting in an increase of cyclic GMP in plasma and/or urine. Infusion of each of these peptide hormones at their 100 ng/kg body weight/min concentrations for 60 minutes into healthy humans resulted in a sevenfold increase in cyclic GMP in plasma and urine secondary to ANF, but no significant increase secondary to the other atrial peptide hormones. Based on the current data, ANF has a unique effect on the metabolism of cyclic GMP, causing it to be extruded from the cell, whereas the other three atrial peptides represent the more classical metabolism of cyclic GMP via cyclic GMP phophodiesterases.

BACKGROUND Three peptides consisting of amino acids 1-30, 31-67, and 79-98 of the 126-amino acid atrial natriuretic factor prohormone (proANF), which have blood pressure-lowering, diuretic, natriuretic, and/or kaliuretic properties in animals, were investigated to determine if they have similar properties in humans. METHODS AND RESULTS Thirty-six healthy, normotensive human volunteers (18 men and 18 women, ages 20 to 58 years) were divided into six similar groups based on age, sex, weight, blood pressure, and heart rate. After a 60-minute baseline period, 100 ng of proANFs 1-30, 31-67, 79-98, or ANF/kg body wt per minute was given intravenously for 60 minutes followed by a 3-hour postinfusion data collection period. Each of the atrial natriuretic peptides decreased systolic and diastolic blood pressures (P < .05), with proANF 31-67 causing the largest decrease. Urine flow increased 4- to 12-fold and was still significantly increased (P < .01) for 2 to 3 hours after stopping the respective infusions of proANFs 1-30, 31-67, and 79-98. Atrial natriuretic factor (ANF) increased urine flow 4- to 11-fold but by 2 hours after infusion was significantly increased in only 1 of 6 subjects. Sodium excretion increased 3- to 8-fold, 3- to 6-fold, 0- to 2-fold (NS), and 3- to 11-fold, respectively, with proANFs 1-30, 31-67, 79-98, and ANF. Natriuretic effects of proANFs 1-30 and 31-67 were significantly prolonged (P < .001) compared with ANF. ProANFs 1-30, 31-67, 79-98, and ANF increased potassium excretion 2- to 3-fold, 0-fold, 3- to 4-fold, and 2-fold, respectively. High-performance gel permeation chromatography followed by the respective radioimmunoassays revealed that proANFs 1-30, 31-67, 79-98, and 68-98, as well as ANF circulate as distinct peptides. CONCLUSIONS ProANFs 1-30, 31-67, and 79-98, as well as ANF have significant blood pressure-lowering and diuretic properties. ProANFs 1-30 and 31-67 also have natriuretic properties in humans that are significantly (P < .001) prolonged compared with ANF. ProANF 79-98, although not possessing any natriuretic property, is the strongest stimulator of potassium excretion of the four atrial natriuretic peptides.

The aim of this study was to assess the efficacy of exercise and antidepressant medication in reducing depressive symptoms and improving cardiovascular biomarkers in depressed patients with coronary heart disease.Although there is good evidence that clinical depression is associated with poor prognosis, optimal therapeutic strategies are currently not well defined.One hundred one outpatients with coronary heart disease and elevated depressive symptoms underwent assessment of depression, including a psychiatric interview and the Hamilton Rating Scale for Depression. Participants were randomized to 4 months of aerobic exercise (3 times/week), sertraline (50-200 mg/day), or placebo. Additional assessments of cardiovascular biomarkers included measures of heart rate variability, endothelial function, baroreflex sensitivity, inflammation, and platelet function.After 16 weeks, all groups showed improvement on Hamilton Rating Scale for Depression scores. Participants in both the aerobic exercise (mean -7.5; 95% confidence interval: -9.8 to -5.0) and sertraline (mean -6.1; 95% confidence interval: -8.4 to -3.9) groups achieved larger reductions in depressive symptoms compared with those receiving placebo (mean -4.5; 95% confidence interval: -7.6 to -1.5; p = 0.034); exercise and sertraline were equally effective at reducing depressive symptoms (p = 0.607). Exercise and medication tended to result in greater improvements in heart rate variability compared with placebo (p = 0.052); exercise tended to result in greater improvements in heart rate variability compared with sertraline (p = 0.093).Both exercise and sertraline resulted in greater reductions in depressive symptoms compared to placebo in patients with coronary heart disease. Evidence that active treatments may also improve cardiovascular biomarkers suggests that they may have a beneficial effect on clinical outcomes as well as on quality of life. (Exercise to Treat Depression in Individuals With Coronary Heart Disease; NCT00302068).

Depression is known to co-occur with coronary heart disease (CHD). Depression may also inhibit the effectiveness of cardiac rehabilitation (CR) programs by decreasing adherence. Higher prevalence of depression in women may place them at increased risk for non-adherence.To assess the impact of a modified, stage-of-change-matched, gender-tailored CR program for reducing depressive symptoms among women with CHD.A two-group randomized clinical trial compared depressive symptoms of women in a traditional 12-week CR program to those completing a tailored program that included motivational interviewing guided by the Transtheoretical Model of behavior change. Women in the experimental group also participated in a gender-tailored exercise protocol that excluded men. The Center for Epidemiological Studies Depression (CES-D) Scale was administered to 225 women at baseline, post-intervention, and at 6-month follow-up. Analysis of Variance was used to compare changes in depression scores over time.Baseline CES-D scores were 17.3 and 16.5 for the tailored and traditional groups, respectively. Post-intervention mean scores were 11.0 and 14.3; 6-month follow-up scores were 13.0 and 15.2, respectively. A significant group by time interaction was found for CES-D scores (F(2, 446)=4.42, p=.013). Follow-up tests revealed that the CES-D scores for the traditional group did not differ over time (F(2, 446)=2.00, p=.137). By contrast, the tailored group showed significantly decreased CES-D scores from baseline to post-test (F(1, 223)=50.34, p.001); despite the slight rise from post-test to 6-month follow-up, CES-D scores remained lower than baseline (F(1, 223)=19.25, p.001).This study demonstrated that a modified, gender-tailored CR program reduced depressive symptoms in women when compared to a traditional program. To the extent that depression hinders CR adherence, such tailored programs have potential to improve outcomes for women by maximizing adherence. Future studies should explore the mechanism by which such programs produce benefits.

BACKGROUND Chronic ischemic heart disease may lead to ventricular dilation and congestive heart failure (ischemic cardiomyopathy [ICM]). The changes in cardiac myocyte shape associated with this dilation, however, are not known. METHODS AND RESULTS Left ventricular myocyte dimensions were assessed in cells isolated from explanted human hearts obtained from patients with ICM (n = 6) who were undergoing heart transplantation. Cells were also examined from three nonfailing donor hearts with normal coronary arteries (NCA). Compared with cells from patients with NCA, myocyte length was 40% longer in hearts from patients with ICM (197 +/- 8 versus 141 +/- 9 microns, p less than 0.01), cell width was not significantly different, and cell length/width ratio was 49% greater (11.2 +/- 0.9 versus 7.5 +/- 0.6, p less than 0.01). Sarcomere length was the same in myocytes from both groups. The extent of myocyte lengthening is comparable to the increase in end-diastolic diameter commonly reported in patients with ICM. CONCLUSIONS These data suggest that increased myocyte length (an intracellular event), instead of myocyte slippage (an extracellular event), is largely responsible for the chamber dilation in ICM. Furthermore, maladaptive remodeling of myocyte shape (e.g., increased myocyte length/width ratio) may contribute to the elevated wall stress (e.g., increased chamber radius/wall thickness) in ICM.

Self-care is advocated as a method of improving outcomes from heart failure (HF), the final common pathway for several prevalent illnesses, including hypertension and coronary artery disease. HF is widespread in aging populations across the world.1 The burden of HF is manifested in poor quality of life (QOL)2,3 and early mortality.4 In addition, there are >3 million ambulatory care and emergency department visits5 and well over 1 million hospitalizations for HF in the United States annually,6 which contributes to the exorbitant costs associated with HF. Much of this healthcare utilization is thought to be preventable if patients engage in consistent self-care.7,8 This scientific statement seeks to highlight concepts and evidence important to the understanding and promotion of self-care in persons with HF. Specifically, the document describes what is known about (1) the self-care behaviors required of HF patients, (2) factors that make self-care challenging for patients, (3) interventions that promote self-care, and (4) the effect of self-care on HF outcomes. The review ends with evidence-based recommendations for clinicians and direction for future research. Self-care is defined as a naturalistic decision-making process that patients use in the choice of behaviors that maintain physiological stability (symptom monitoring and treatment adherence) and the response to symptoms when they occur.9 The term naturalistic decision making is used to describe how people make decisions in real-world settings. Naturalistic decision makers focus on process rather than outcomes, make decisions based on the situation, let the context influence their decision-making processes, and base practical decisions on the information available at the moment.10 In HF, self-care maintenance requires following the advice of providers to take medications, eat a low-sodium diet, exercise, engage in preventive behaviors, and actively monitor themselves for signs and symptoms. Self-care management refers to decision making in …