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Aim: Frailty is a multidimensional geriatric syndrome that indicates increasing vulnerability and decreasing resistance to stressors. Social support (SS) is linked both to cardiovascular disease and to frailty. However, few cohort studies evaluated SS as a potential predictor of frailty, and none involved coronary disease populations. The aim of this study was to evaluate the role of perceived SS (PSS) - a specific component of SS - in the prediction of frailty development in myocardial infarction (MI) survivors, controlling for other psychosocial risk factors., Method: A cohort of 558 patients aged ≤65 years, admitted for first-ever MI to hospitals in central Israel, was studied. PSS and other clinical and sociodemographic variables were assessed at baseline. Frailty was assessed via a frailty index of deficit accumulation 10-13 years later. Logistic regression models were constructed to assess the odds ratios (OR) for frailty associated with PSS as well as other covariates., Results: At last follow-up, 154 (28%) met the criteria for frailty. In the logistic regression models, higher PSS level was associated with lower frailty risk (unadjusted OR = 0.63, 95%CI 0.53-0.76; multivariable-adjusted OR = 0.80, 95%CI 0.64-0.98). Below average family income, poor self-rated health and higher depression scores were all associated with the development of frailty, in both the unadjusted and adjusted models., Conclusions: PSS predicts frailty development post-MI, which has important implications for prognosis and healthcare use., (© The European Society of Cardiology 2014.)

Background: Frailty describes the heterogeneity of vulnerability in older people and has been shown to predict mortality, disability, and institutionalization. Little is known about the clinical relevance of frailty post myocardial infarction (MI)., Design: The Rockwood frailty index, based on accumulation of deficits, was adapted in a cohort of MI survivors followed up for 20 years, in order to assess trajectory and predictive value for clinical outcomes., Methods: Participants were 1521 patients aged ≤65 years admitted to one of eight Israeli hospitals with first acute MI between 1992 and 1993. A frailty index (on a 0-1 continuous scale) was developed comprising 32 variables, including self-rated health, functional limitations, comorbidity, weight loss, and physical activity. Frailty was assessed at baseline and 10-13 years after MI., Results: Median frailty score increased from 0.08 to 0.19 during follow up. Participants in the frailest group (≥0.25) at baseline had twice the multivariable-adjusted mortality risk of those in the least frail group (<0.10) (hazard ratio, HR, 2.02, 95% CI 1.46-2.79). Frailty index modelled as a time-dependent variable showed a substantially stronger association (HR 3.61, 95% CI 2.82-4.63) and provided incremental value in risk discrimination beyond clinical and socio-demographic variables (p < 0.001 for improvement in c-statistic). The frailest patients were more than twice as likely to be hospitalized during follow up compared to the least frail (adjusted rate ratio 2.14, 95% CI 1.63-2.81)., Conclusions: Frailty, calculated via an index of deficits, was associated with mortality and hospitalizations following MI. Beyond predictive value, accurate identification of frailty may indicate which individuals will benefit most from preventive interventions., (© The European Society of Cardiology 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: Frailty predicts mortality and hospitalizations in post-myocardial infarction (MI) patients. Socioeconomic status (SES) demonstrates a clear relationship with post-MI outcomes and is also associated with community frailty; however this relationship has yet to be evaluated in post-MI patients. We investigated the predictive value of socioeconomic factors in the development of post-MI frailty., Methods: A cohort of 1151 post-MI patients was followed up from initial hospitalization in 1992-1993 for 10-13 years. Individual and neighborhood SES measures were assessed at baseline and frailty was assessed during follow-up via an index of deficit accumulation. Logistic regression models and discrimination indices enabled determination of the predictive value of socioeconomic factors over basic clinical variables in classifying frailty risk., Results: During follow-up, 399 patients (35%) developed frailty. Individual and neighborhood SES were significantly and independently associated with the risk of developing frailty. Low income patients had more than twice the risk of becoming frail compared with those with high income [odds ratio (OR), 2.29, 95% CI 1.41-3.73]; while being in the lower vs. upper neighborhood SES tertile was associated with a 60% increased odds (OR, 1.60, 95% CI 1.03-2.49). Inclusion of multilevel SES yielded substantial gains in c-statistic (0.70 to 0.76), net reclassification improvement (21.4%) and integrated discrimination improvement (6.4%) over basic clinical factors (all p<0.001), indicating increased predictive value and gains in sensitivity and specificity., Conclusions: Individual and neighborhood socioeconomic factors influence the development of frailty post-MI, and contribute to risk discrimination in this population., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Chronic environmental exposure to particulate matter <2.5μm in diameter (PM2.5) has been associated with cardiovascular disease; however, the effect of air pollution on myocardial infarction (MI) survivors is not clear. We studied the association of chronic exposure to PM2.5 with death and recurrent cardiovascular events in MI survivors., Methods: Consecutive patients aged ≤65years admitted to all medical centers in central Israel after first-MI in 1992-1993 were followed through 2005 for cardiovascular events and 2011 for survival. Data on sociodemographic and prognostic factors were collected at baseline and during follow-up. Residential exposure to PM2.5 was estimated for each patient based on data recorded at air quality monitoring stations. Cox and Andersen-Gill proportional hazards models were used to study the pollution-outcome association., Results: Among the 1120 patients, 469 (41.9%) died and 541 (48.3%) experienced one or more recurrent cardiovascular event. The adjusted hazard ratios associated with a 10μg/m(3) increase in PM2.5 exposure were 1.3 (95% CI 0.8-2.1) for death and 1.5 (95% CI 1.1-1.9) for multiple recurrences of cardiovascular events (MI, heart failure and stroke)., Conclusion: When adjustment for socio-demographic factors is performed, cumulative chronic exposure to PM2.5 is positively associated with recurrence of cardiovascular events in patients after a first MI., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Frailty, a multidimensional syndrome of increased vulnerability, is prevalent post-myocardial infarction (MI) and predicts mortality and recurrent events. We investigated whether chronic exposure to particulate matter ≤2.5 μm in diameter (PM2.5) is associated with the development of post-MI frailty., Methods: Participants (n = 1120) were aged 65 or less and admitted to hospital in central Israel with first MI in 1992 and 1993. Daily measures of PM2.5 recorded at air quality monitoring stations were summarized and chronic exposure was estimated individually using the geo-coded residential location. Frailty assessment was conducted via an index based on deficit accumulation, and those defined as frail (applying a threshold of ≥0.25) at baseline were excluded. Remaining participants who survived to follow-up 10 to 13 years post-MI (n = 848) were reassessed for frailty. Logistic regression models were constructed to evaluate the role of PM2.5 exposure in frailty risk prediction., Results: Mean exposure to PM2.5 was 24.2 μg/m(3) (range, 16.9-28.6). A total of 301 participants (35.5%) developed frailty during follow-up. Adjusting for sociodemographic and clinical variables, PM2.5 exposure was associated with increased odds of developing frailty (odds ratio, 1.53; 95% confidence interval, 1.22-1.91, comparing the 75th vs. 25th percentiles). Addition of PM2.5 exposure to the multivariable model resulted in an integrated discrimination improvement of 1.60% (P = .005) and a net reclassification index of 6.51% (P = .02)., Conclusions: An association was observed between exposure to PM2.5 and incidence of frailty, providing a potential intermediary between air pollution and post-MI outcomes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: Depression is prevalent in the aftermath of myocardial infarction (MI), and has been linked with mortality however few studies have investigated hospital admissions in MI survivors. Using a prospective cohort design, we examined the long-term relationship between depressive symptoms, post-MI hospital admissions and secondary prevention measures, in order to assess the burden of post-MI depression on patients and the healthcare system., Methods: A cohort of 632 patients aged ≤65 years, admitted for first-ever MI to 1 of the 8 hospitals in central Israel, was followed up for 10-13 years. Depressive symptoms were assessed at initial hospitalization using the Beck Depression Inventory. Rehospitalization and adoption of secondary prevention measures were recorded throughout follow-up., Results: Depressive symptoms were significantly associated with days of hospitalization during follow-up (RR, 1.37, CI, 1.26-1.49), an association which remained significant after risk adjustment (RR, 1.14, CI, 1.04-1.26). The association appeared stronger for cardiac-related admissions than for other, non-cardiac admissions. Depressed patients were less likely to stop smoking (OR, 0.75, CI, 0.60-0.94), be physically active (OR, 0.80, CI, 0.69-0.94) and participate in cardiac rehabilitation (OR, 0.74, CI, 0.59-0.92)., Conclusion: Post-MI depressive symptoms were shown to be associated with increased hospital admissions, particularly cardiac admissions, and with reduced adoption of secondary prevention behaviors. These findings have implications for patients' prognosis and quality of life and for healthcare costs. Depressive symptoms, even at the sub-clinical level, should be monitored in post-MI patients in order to identify those at greater risk of rehospitalization., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Akt2 protein kinase has been shown to promote cell migration and actin polymerization in several cell types, including macrophages. Because migrating macrophages constitute an important inflammatory response after myocardial ischemia, we determined cardiac macrophage expression after ischemia-reperfusion (I/R) injury and cryo-injury in mice lacking Akt2 (Akt2-KO). At 7 days post-I/R, Akt2-KO cardiac tissues showed an increase in immunohistochemical staining for macrophage markers (Galectin 3 and F4/80) compared with wild-type (WT) mice, indicating macrophage density was increased in the injured Akt2-KO myocardium. This change was time dependent because macrophage density was similar between WT and Akt2-KO myocardium at 3 days post-I/R, but by 7 and 14 days post-I/R, macrophage density was significantly increased in Akt2-KO myocardium. Concomitantly, infarct size was larger and cardiac function was reduced in Akt2-KO mice subjected to I/R. However, when cryo-infarction produced similar infarct sizes in the anterior wall in both WT and Akt2-KO mice, macrophage density remained higher in Akt2-KO mouse myocardium, suggesting Akt2 regulates myocardial macrophage density independent of infarct size. Consistently, bone marrow from Akt2-KO mice enhanced myocardial macrophage density in both C57/B6 WT and Akt2-KO recipient mice. Finally, reciprocal ex-vivo coculturing of macrophages and cardiac myocytes showed that activated Akt2-KO peritoneal macrophages had reduced mobility and adhesion when compared with WT littermate controls. Thus, although Akt-2 KO mice did not affect the initial inflammation response after injury and Akt2 deficiency has been shown to impair cell migration or motility in macrophages, our data suggested a novel mechanism in which increasing retention of Akt2-KO macrophages resulted in increasing cardiac Akt2-KO macrophage density in the myocardial space.

Background: Physical activity confers a survival advantage after myocardial infarction (MI), yet the majority of post-MI patients are not regularly active. Since sense of coherence (SOC) has been associated with health outcomes and some health behaviours, we investigated whether it plays a role in post-MI physical activity. We examined the predictive role of SOC in the long-term trajectory of leisure time physical activity (LTPA) after MI using a prospective cohort design., Methods: A cohort of 643 patients aged ≤ 65 years admitted to hospital in central Israel with incident MI between February 1992 and February 1993 were followed up for 13 years. Socioeconomic, clinical and psychological factors, including SOC, were assessed at baseline, and LTPA was self-reported on 5 separate occasions during follow-up. The predictive role of SOC in long-term trajectory of LTPA was assessed using generalized estimating equations., Results: SOC was consistently associated with engagement in LTPA throughout follow-up. Patients in the lowest SOC tertile had almost twice the odds (odds ratio,1.99; 95% confidence interval,1.52-2.60) of decreasing their engagement in LTPA as those in the highest tertile. A strong association remained after controlling for disease severity, depression, sociodemographic and clinical factors., Conclusion: Our evidence suggests that SOC predicts LTPA trajectory post-MI. Assessment of SOC can help identify high-risk MI survivors, who may require additional help in following secondary prevention recommendations which can dramatically improve prognosis.

Background: Area-level SES is independently associated with myocardial infarction (MI) prognosis, yet the mechanisms for this association remain speculative., Purpose: Using a population-based cohort of MI patients, this study examined whether neighborhood SES predicts long-term trajectory of leisure-time physical activity (LTPA), an established prognostic factor., Methods: Patients aged ≤65 years (n=1410) admitted to hospital in central Israel with first MI in 1992-1993, were followed up through 2005. LTPA was reported on five successive occasions: at baseline, 3-6 months, 1-2 years, 5 years, and 10-13 years post-MI. Generalized estimating equations (GEEs) with ordinal outcome variable (LTPA classified as regular, irregular, or none) were used to determine the independent predictive role of neighborhood SES in LTPA trajectory post-MI. Analyses were conducted in 2010-2011., Results: Engagement in LTPA was poor, with point prevalence rates ranging from 33% to 37% for inactivity and from 19% to 27% for irregular activity throughout follow-up. The GEE-derived ORs (95% CIs) for decreased LTPA level in the lower and middle vs upper neighborhood SES tertiles were 2.49 (2.05, 3.02) and 1.60 (1.33, 1.92) after age and gender adjustment, and 1.55 (1.26, 1.90) and 1.23 (1.02, 1.49) after multivariable adjustment for individual SES measures, cardiovascular risk factors, MI characteristics, and disease-severity indices, respectively (p for trend <0.001)., Conclusions: Low neighborhood SES is a powerful predictor of poor LTPA uptake in MI survivors, even after extensive adjustment for individual SES and baseline clinical profile. LTPA may thus represent an intermediate mechanism between neighborhood SES and post-MI outcome, which provides prevention opportunities., (Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The relationship of risk factors to outcomes has traditionally been assessed by measures of association such as odds ratio or hazard ratio and their statistical significance from an adjusted model. However, a strong, highly significant association does not guarantee a gain in stratification capacity. Using recently developed model performance indices, we evaluated the incremental discriminatory power of individual and neighborhood socioeconomic status (SES) measures after myocardial infarction (MI)., Methods: Consecutive patients aged ≤65 years (N=1178) discharged from 8 hospitals in central Israel after incident MI in 1992 to 1993 were followed-up through 2005. A basic model (demographic variables, traditional cardiovascular risk factors, and disease severity indicators) was compared with an extended model including SES measures (education, income, employment, living with a steady partner, and neighborhood SES) in terms of Harrell c statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)., Results: During the 13-year follow-up, 326 (28%) patients died. Cox proportional hazards models showed that all SES measures were significantly and independently associated with mortality. Furthermore, compared with the basic model, the extended model yielded substantial gains (all P<0.001) in c statistic (0.723 to 0.757), NRI (15.2%), IDI (5.9%), and relative IDI (32%). Improvement was observed both for sensitivity (classification of events) and specificity (classification of nonevents)., Conclusions: This study illustrates the additional insights that can be gained from considering the IDI and NRI measures of model performance and suggests that, among community patients with incident MI, incorporating SES measures into a clinical-based model substantially improves long-term mortality risk prediction.

Background: Smoking has been causally linked to cardiovascular disease, and smoking cessation after myocardial infarction (MI) has been associated with a 50% reduction in mortality. Post-MI smokers are a vulnerable population for which efforts to encourage cessation should be maximized. We examined the determinants of smoking cessation after MI., Methods: A population-based cohort of 768 Israeli smokers was followed-up longitudinally after first MI. Data were collected at study entry on demographic, socioeconomic, smoking behaviour, and clinical variables. Psychosocial measures were obtained in a subsample (n = 330). Self-reported smoking status was assessed at 3-6 months, 1-2 years, 5 years, and 10-13 years after MI. Generalized estimating equation analyses determined which factors were significant predictors of smoking status., Results: Point abstinence rates throughout follow-up ranged from 55% to 70%, while continuous abstinence rates were 59% after 1-2 years, 44% after 5 years, and 35% after 10-13 years, among survivors. Variables most strongly associated with persistent smoking were young age, long duration and high intensity of pre-MI smoking, low education, poor family income, lack of a steady partner, non-diabetic status, and short hospital stay at the index MI. Significant psychosocial predictors were low sense of coherence and high depression., Conclusions: Determinants of smoking cessation after MI are multifactorial and include demographic, socioeconomic, smoking behaviour, clinical and psychosocial measures. Post-MI hospitalization is a window of opportunity for smoking cessation interventions. Patients should be assessed for psychosocial characteristics and those with low sense of coherence and high depression should be provided with targeted help to quit.

Background: Data linking neighborhood socioeconomic status (SES) to stroke risk are scarce. We examined long-term stroke incidence according to neighborhood SES in a population-based cohort of patients hospitalized with first myocardial infarction (MI)., Methods: Consecutive patients aged 65 years or less, discharged from 8 hospitals in central Israel after incident MI in 1992-1993, were followed for stroke through 2005. Individual demographic, socioeconomic, and clinical data were obtained at study entry. We estimated neighborhood SES through a composite census-derived index developed by the Israel Central Bureau of Statistics., Results: During a median follow-up of 13 years, 196 incident ischemic strokes occurred in 1410 patients. Accounting for death as a competing risk, patients residing in disadvantaged neighborhoods had higher rates of ischemic stroke (cumulative survival estimates: 81%, 88%, and 89% in increasing tertiles of neighborhood SES). Upon multivariable adjustment for individual SES measures (including income, education, and employment), cardiovascular risk factors, MI characteristics and severity indices, and acute management, the overall hazard ratio for stroke in the lower versus upper tertile of neighborhood SES was 1.5 (95% confidence interval [CI] = 1.0-2.3); after 13 years, the adjusted absolute risk difference was 7.9 incident stroke cases per 100 participants with MI (95% CI = 1.7-14.1)., Conclusions: Poor neighborhood SES is associated with increased risk of ischemic stroke post-MI. The association is only partly attributable to individual SES and other baseline characteristics. The potential mechanisms for this association require further study.

The benefits of leisure time physical activity (LTPA) in cardiovascular prevention are well established. While cardiac rehabilitation programmes have been demonstrated as improving myocardial infarction (MI) prognosis, the strength of the association between LTPA and post-MI survival has yet to be quantified. We evaluated long-term survival after MI of inactive, irregularly active, and regularly active patients and examined trajectories of LTPA and their relationship to mortality risk. Consecutive patients aged ≤65 years (n = 1,521), discharged from 8 hospitals in central Israel after first MI in 1992-1993, were followed through 2005. Extensive clinical and sociodemographic data, including self-reported LTPA habits, were obtained at baseline and at 4 subsequent interviews. Pre-MI inactive patients (54%) had lower socioeconomic status, higher prevalence of risk factors and comorbidities and more severe MI. The point prevalence rate of regular LTPA at all follow-up interviews was approximately 40% and 18% were regularly active throughout the entire follow-up. Over a median follow-up of 13.2 years, 427 deaths occurred. After multivariable adjustment, no association was observed between pre-MI LTPA and death. However, with LTPA categories modelled as time-dependent variables, providing an estimation of cumulative assessment and accounting for changes in LTPA post-MI, a strong inverse graded association was revealed (multivariable-adjusted hazard ratios, 0.56 [95% CI: 0.42-0.74] for regular and 0.71 [95% CI: 0.54-0.95] for irregular activity vs. none). Similar estimates were obtained among pre-MI sedentary patients. In summary, after MI, regularly active patients had about half the risk of dying compared with inactive patients, irrespective of pre-MI habits.

Background: Cardiovascular disease is a leading cause of morbidity and mortality worldwide and epidemiological studies have consistently shown an increased risk for cardiovascular events in relation to exposure to air pollution. The Israel Study of First Acute Myocardial Infarction was designed to longitudinally assess clinical outcomes, psychosocial adjustment and quality of life in patients hospitalized with myocardial infarction. The current study, by introducing retrospective air pollution data, will examine the association between exposure to air pollution and outcome in myocardial infarction survivors. This report will describe the methods implemented and measures employed. The study specifically aims to examine the relationship between residential exposure to air pollution and long-term risk of recurrent coronary event, heart failure, stroke, cardiac and all-cause death in a geographically defined cohort of patients with myocardial infarction., Methods/design: All 1521 patients aged < or =65 years, admitted with first myocardial infarction between February 1992 and February 1993 to the 8 hospitals serving the population of central Israel, were followed for a median of 13 years. Data were collected on sociodemographic, clinical and environmental factors. Data from air quality monitoring stations will be incorporated retrospectively. Daily measures of air pollution will be summarised, allowing detailed maps to be developed in order to reflect chronic exposure for each participant., Discussion: This study addresses some of the gaps in understanding of the prognostic importance of air pollution exposure after myocardial infarction, by allowing a sufficient follow-up period, using a well-defined community cohort, adequately controlling for multiple and multilevel confounding factors and providing extensive data on various outcomes.

Abstract Background Physical activity confers a survival advantage after myocardial infarction (MI), yet the majority of post-MI patients are not regularly active. Since sense of coherence (SOC) has been associated with health outcomes and some health behaviours, we investigated whether it plays a role in post-MI physical activity. We examined the predictive role of SOC in the long-term trajectory of leisure time physical activity (LTPA) after MI using a prospective cohort design. Methods A cohort of 643 patients aged ≤ 65 years admitted to hospital in central Israel with incident MI between February 1992 and February 1993 were followed up for 13 years. Socioeconomic, clinical and psychological factors, including SOC, were assessed at baseline, and LTPA was self-reported on 5 separate occasions during follow-up. The predictive role of SOC in long-term trajectory of LTPA was assessed using generalized estimating equations. Results SOC was consistently associated with engagement in LTPA throughout follow-up. Patients in the lowest SOC tertile had almost twice the odds (odds ratio,1.99; 95% confidence interval,1.52-2.60) of decreasing their engagement in LTPA as those in the highest tertile. A strong association remained after controlling for disease severity, depression, sociodemographic and clinical factors. Conclusion Our evidence suggests that SOC predicts LTPA trajectory post-MI. Assessment of SOC can help identify high-risk MI survivors, who may require additional help in following secondary prevention recommendations which can dramatically improve prognosis.