Hypertension and Smoking Are Associated With Reduced Regional Left Ventricular Function in Asymptomatic Individuals The Multi-Ethnic Study of Atherosclerosis

ObjectivesThis study sought to test the hypothesis that reduced regional left ventricular (LV) function is associated with traditional risk factors including hypertension, hypercholesterolemia, and smoking in asymptomatic individuals.BackgroundCoronary artery disease is the main etiology of congestive heart failure in the U.S. and Europe. However, the relationship between risk factors for coronary artery disease and decreased myocardial function has not been studied systematically in asymptomatic individuals.MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) is a cohort study designed to investigate the nature of atherosclerosis in asymptomatic individuals. A total of 1,184 participants (45 to 84 years old) underwent tagged cardiac magnetic resonance imaging. Regional LV function was quantified by analyzing peak systolic circumferential strain (Ecc) in regions corresponding to the left anterior descending (LAD), circumflex (LCX), and right coronary (RCA) territories. The association between risk factors and strains was studied using multiple linear regression.ResultsHigher diastolic blood pressure (DBP) was associated with lower Ecc (p ≤ 0.002). The Ecc’s in the LAD territory of participants with DBP <80, 80 to 84, 85 to 89, and ≥90 mm Hg were −15.6%, −14.8%, −14.2%, and −13.7%, respectively (p < 0.001). Similar results were documented in other territories and after multivariable analysis. Smokers had lower Ecc in the LAD and RCA regions compared with nonsmokers. Furthermore, dose response relationship between cigarette consumption measured in pack-years and regional LV dysfunction by Ecc was noted (p ≤ 0.01 in LAD and RCA territories). Finally, combined diastolic hypertension and smoking was associated with a greater reduction of regional LV function.ConclusionsHigher diastolic blood pressure and smoking are associated with decreased regional LV function in asymptomatic individuals

A framework for developing an evidence-based, comprehensive tobacco control program

BACKGROUND: Tobacco control is an area where the translation of evidence into policy would seem to be straightforward, given the wealth of epidemiological, behavioural and other types of research available. Yet, even here challenges exist. These include information overload, concealment of key (industry-funded) evidence, contextualization, assessment of population impact, and the changing nature of the threat. METHODS: In the context of Israel's health targeting initiative, Healthy Israel 2020, we describe the steps taken to develop a comprehensive tobacco control strategy. We elaborate on the following: a) scientific issues influencing the choice of tobacco control strategies; b) organization of existing evidence of effectiveness of interventions into a manageable form, and c) consideration of relevant philosophical and political issues. We propose a framework for developing a plan and illustrate this process with a case study in Israel. RESULTS: Broad consensus exists regarding the effectiveness of most interventions, but current recommendations differ in the emphasis they place on different strategies. Scientific challenges include integration of complex and sometimes conflicting information from authoritative sources, and lack of estimates of population impact of interventions. Philosophical and political challenges include the use of evidence-based versus innovative policymaking, the importance of individual versus governmental responsibility, and whether and how interventions should be prioritized.The proposed framework includes: 1) compilation of a list of potential interventions 2) modification of that list based on local needs and political constraints; 3) streamlining the list by categorizing interventions into broad groupings of related interventions; together these groupings form the basis of a comprehensive plan; and 4) refinement of the plan by comparing it to existing comprehensive plans. CONCLUSIONS: Development of a comprehensive tobacco control plan is a complex endeavour, involving crucial decisions regarding intervention components. "Off the shelf" plans, which need to be adapted to local settings, are available from a variety of sources, and a multitude of individual recommendations are available. The proposed framework for adapting existing approaches to the local social and political climate may assist others planning for smoke-free societies. Additionally, this experience has implications for development of evidence-based health plans addressing other risk factors

Strong mucosal immune responses in SIV infected macaques contribute to viral control and preserved CD4+ T-cell levels in blood and mucosal tissues

<p>Abstract</p> <p>Background</p> <p>Since there is still no protective HIV vaccine available, better insights into immune mechanism of persons effectively controlling HIV replication in the absence of any therapy should contribute to improve further vaccine designs. However, little is known about the mucosal immune response of this small unique group of patients. Using the SIV-macaque-model for AIDS, we had the rare opportunity to analyze 14 SIV-infected rhesus macaques durably controlling viral replication (controllers). We investigated the virological and immunological profile of blood and three different mucosal tissues and compared their data to those of uninfected and animals progressing to AIDS-like disease (progressors).</p> <p>Results</p> <p>Lymphocytes from blood, bronchoalveolar lavage (BAL), and duodenal and colonic biopsies were phenotypically characterized by polychromatic flow cytometry. In controllers, we observed higher levels of CD4+, CD4+CCR5+ and Gag-specific CD8+ T-cells as well as lower immune activation in blood and all mucosal sites compared to progressors. However, we could also demonstrate that immunological changes are distinct between these three mucosal sites.</p> <p>Intracellular cytokine staining demonstrated a significantly higher systemic and mucosal CD8+ Gag-specific cellular immune response in controllers than in progressors. Most remarkable was the polyfunctional cytokine profile of CD8+ lymphocytes in BAL of controllers, which significantly dominated over their blood response. The overall suppression of viral replication in the controllers was confirmed by almost no detectable viral RNA in blood and all mucosal tissues investigated.</p> <p>Conclusion</p> <p>A strong and complex virus-specific CD8+ T-cell response in blood and especially in mucosal tissue of SIV-infected macaques was associated with low immune activation and an efficient suppression of viral replication. This likely afforded a repopulation of CD4+ T-cells in different mucosal compartments to almost normal levels. We conclude, that a robust SIV-specific mucosal immune response seems to be essential for establishing and maintaining the controller status and consequently for long-term survival.</p

Association of Pro-B-Type Natriuretic Peptide With Cardiac Magnetic Resonance-Measured Global and Regional Cardiac Function and Structure Over 10 Years: The MESA Study.

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) is widely used to diagnose and manage patients with heart failure. We aimed to investigate associations between NT-proBNP levels and development of global and regional myocardial impairment, dyssynchrony, and risk of developing myocardial scar over time. Methods and Results We included 2416 adults (45-84 years) without baseline clinical cardiovascular disease from MESA (Multi-Ethnic Study of Atherosclerosis). NT-proBNP was assessed at baseline (2000-2002). Cardiac magnetic resonance-measured left ventricular parameters were assessed at baseline and year 10 (2010-2012). Tagged cardiac magnetic resonance and myocardial dyssynchrony were assessed. We used linear and logistic regression models to study the relationships between quartiles of NT-proBNP levels and outcome variables. Left ventricular parameters decreased over time. After 10-year follow-up and adjusting for cardiovascular disease risk factors, people in the highest quartile had significantly greater decline in left ventricular ejection fraction (-1.60%; 95% CI, -2.26 to -0.94; P<0.01) and smaller decline in left ventricular end systolic volume index (-0.47 mL/m2; 95% CI, -1.18 to 0.23; P<0.01) compared with those in the lowest quartile. Individuals in the highest quartile had more severe risk factor adjusted global, mid, and apical regional dyssynchrony compared with those in the lowest, second, and third quartiles (all P-trend<0.05). Compared with the lowest-quartile group, the adjusted odds ratios for having myocardial scar was 1.3 (95% CI, 0.7-2.2) for quartile 2; 1.2 (95% CI, 0.6-2.3) for quartile 3; and 2.7 (95% CI, 1.4-5.5) for quartile 4 (P-trend=0.012) for the total sample. Conclusions Among participants without baseline clinical cardiovascular disease, higher baseline NT-proBNP concentration was significantly associated with subclinical changes in developing myocardial dysfunction, more severe cardiac dyssynchrony, and higher odds of having myocardial scar over a 10-year period independent of traditional cardiovascular disease risk factors