Air temperature and inflammatory and coagulation responses in men with coronary or pulmonary disease during the winter season

Background and Objective Air temperature changes are associated with increased cardiovascular and respiratory risk, but the roles of inflammatory and coagulation markers are not well understood. We investigated the associations between temperature and several blood markers in patients with coronary heart disease (CHD) and pulmonary disease (PD). Methods Two studies were conducted in Erfurt, Germany, over two successive winters. 578 and 381 repeated blood measurements were collected from 57 CHD and 38 PD patients, respectively. Data on patient characteristics and disease history were gathered at baseline. Meteorological data were collected from existing networks. Associations were analysed using additive mixed models with random patient effects. Effect modification by diabetes status was investigated only in CHD patients, as only two PD patients had diabetes. Results Mean daily air temperature varied between -13 degrees C and 16 degrees C in both study periods. A 10 degrees C decrease in the 5-day temperature average before blood withdrawal led to an increase in platelet counts (% change from the mean: 3.0%, 95% CI 0.6% to 5.5%) and fibrinogen (5.5%, 1.3% to 9.7%), no change in C-reactive protein in PD patients, and a decrease in C-reactive protein in CHD patients. A 2-day delayed increase in factor VII associated with temperature decrease was seen in CHD patients (4.9%; 0.7% to 9.2%), while PD patients showed no effect. `Effects in CHD patients without diabetes' into `Effects on factor VII in CHD patients without diabetes'. Conclusions This study suggests that temperature decrease is associated with change in several blood parameters. The complex interplay of blood markers at low temperature may contribute to the observed association between cold and cardiovascular mortality and morbidity

Particulate Matter (PM) Research Centers (1999–2005) and the Role of Interdisciplinary Center-Based Research

Objective: The U.S. Environmental Protection Agency funded five academic centers in 1999 to address the uncertainties in exposure, toxicity, and health effects of airborne particulate matter (PM) identified in the “Research Priorities for Airborne Particulate Matter” of the National Research Council (NRC). The centers were structured to promote interdisciplinary approaches to address research priorities of the NRC. In this report, we present selected accomplishments from the first 6 years of the PM Centers, with a focus on the advantages afforded by the interdisciplinary, center-based research approach. The review highlights advances in the area of ultrafine particles and traffic-related health effects as well as cardiovascular and respiratory effects, mechanisms, susceptibility, and PM exposure and characterization issues. Data sources and synthesis: The collective publications of the centers served as the data source. To provide a concise synthesis of overall findings, authors representing each of the five centers identified a limited number of topic areas that serve to illustrate the key accomplishments of the PM Centers program, and a consensus statement was developed. Conclusions: The PM Centers program has effectively applied interdisciplinary research approaches to advance PM science

Ozone effects on blood biomarkers of systemic inflammation, oxidative stress, endothelial function, and thrombosis: The Multicenter Ozone Study in oldEr Subjects (MOSES).

The evidence that exposure to ozone air pollution causes acute cardiovascular effects is mixed. We postulated that exposure to ambient levels of ozone would increase blood markers of systemic inflammation, prothrombotic state, oxidative stress, and vascular dysfunction in healthy older subjects, and that absence of the glutathione S-transferase Mu 1 (GSTM1) gene would confer increased susceptibility. This double-blind, randomized, crossover study of 87 healthy volunteers 55-70 years of age was conducted at three sites using a common protocol. Subjects were exposed for 3 h in random order to 0 parts per billion (ppb) (filtered air), 70 ppb, and 120 ppb ozone, alternating 15 min of moderate exercise and rest. Blood was obtained the day before, approximately 4 h after, and approximately 22 h after each exposure. Linear mixed effect and logistic regression models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. The definition of statistical significance was p<0.01. There were no effects of ozone on the three primary markers of systemic inflammation and a prothrombotic state: C-reactive protein, monocyte-platelet conjugates, and microparticle-associated tissue factor activity. However, among the secondary endpoints, endothelin-1, a potent vasoconstrictor, increased from pre- to post-exposure with ozone concentration (120 vs 0 ppb: 0.07 pg/mL, 95% confidence interval [CI] 0.01, 0.14; 70 vs 0 ppb: -0.03 pg/mL, CI -0.09, 0.04; p = 0.008). Nitrotyrosine, a marker of oxidative and nitrosative stress, decreased with increasing ozone concentrations, with marginal significance (120 vs 0 ppb: -41.5, CI -70.1, -12.8; 70 vs 0 ppb: -14.2, CI -42.7, 14.2; p = 0.017). GSTM1 status did not modify the effect of ozone exposure on any of the outcomes. These findings from healthy older adults fail to identify any mechanistic basis for the epidemiologically described cardiovascular effects of exposure to ozone. The findings, however, may not be applicable to adults with cardiovascular disease

Inhalation of Ultrafine Particles Alters Blood Leukocyte Expression of Adhesion Molecules in Humans

Ultrafine particles (UFPs; aerodynamic diameter < 100 nm) may contribute to the respiratory and cardiovascular morbidity and mortality associated with particulate air pollution. We tested the hypothesis that inhalation of carbon UFPs has vascular effects in healthy and asthmatic subjects, detectable as alterations in blood leukocyte expression of adhesion molecules. Healthy subjects inhaled filtered air and freshly generated elemental carbon particles (count median diameter ~ 25 nm, geometric standard deviation ~ 1.6), for 2 hr, in three separate protocols: 10 μg/m(3) at rest, 10 and 25 μg/m(3) with exercise, and 50 μg/m(3) with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 μg/m(3) UFPs with exercise. Peripheral venous blood was obtained before and at intervals after exposure, and leukocyte expression of surface markers was quantitated using multiparameter flow cytometry. In healthy subjects, particle exposure with exercise reduced expression of adhesion molecules CD54 and CD18 on monocytes and CD18 and CD49d on granulocytes. There were also concentration-related reductions in blood monocytes, basophils, and eosinophils and increased lymphocyte expression of the activation marker CD25. In subjects with asthma, exposure with exercise to 10 μg/m(3) UFPs reduced expression of CD11b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD4(+) T cells, basophils, and eosinophils. Inhalation of elemental carbon UFPs alters peripheral blood leukocyte distribution and expression of adhesion molecules, in a pattern consistent with increased retention of leukocytes in the pulmonary vascular bed

Heart Fatty Acid Binding Protein and cardiac troponin: development of an optimal rule-out strategy for acute myocardial infarction

Background: Improved ability to rapidly rule-out Acute Myocardial Infarction (AMI) in patients presenting with chest pain will promote decongestion of the Emergency Department (ED) and reduce unnecessary hospital admissions. We assessed a new commercial Heart Fatty Acid Binding Protein (H-FABP) assay for additional diagnostic value when combined with cardiac troponin (using a high sensitivity assay). Methods: H-FABP and high-sensitivity troponins I (hs-cTnI) and T (hs-cTnT) were measured in samples taken on-presentation from patients, attending the ED, with symptoms triggering investigation for possible acute coronary syndrome. The optimal combination of H-FABP with each hs-cTn was defined as that which maximized the proportion of patients with a negative test (low-risk) whilst maintaining at least 99 % sensitivity for AMI. A negative test comprised both H-FABP and hs-cTn below the chosen threshold in the absence of ischemic changes on the ECG. Results: One thousand seventy-nine patients were recruited including 248 with AMI. H-FABP 99 % sensitivity for AMI whilst classifying 40.9 % of patients as low-risk. The combination of H-FABP < 3.9 ng/mL and hs-cTnT < 7.6 ng/L with a negative ECG maintained the same sensitivity whilst classifying 32.1 % of patients as low risk. Conclusions: In patients requiring rule-out of AMI, the addition of H-FABP to hs-cTn at presentation (in the absence of new ischaemic ECG findings) may accelerate clinical diagnostic decision making by identifying up to 40 % of such patients as low-risk for AMI on the basis of blood tests performed on presentation. If implemented this has the potential to significantly accelerate triaging of patients for early discharge from the ED

The utility of presentation and 4-hour high sensitivity troponin I to rule-out acute myocardial infarction in the emergency department

Objectives: International guidance recommends that early serial sampling of high sensitivity troponin be used to accurately identify acute myocardial infarction (AMI) in chest pain patients. The background evidence for this approach is limited. We evaluated whether on presentation and 4-hour high-sensitivity troponin I (hs-cTnI) could be used to accurately rule-out AMI. Design and methods: hs-cTnI was measured on presentation and at 4-hours in adult patients attending an emergency department with possible acute coronary syndrome. We determined the sensitivity for AMI for at least one hs-cTnI above the 99th percentile for a healthy population or alone or in combination with new ischemic ECG changes. Both overall and sex-specific 99th percentiles were assessed. Patients with negative tests were designated low-risk. Results: 63 (17.1%) of 368 patients had AMI. The median (interquartile range) time from symptom onset to first blood sampling was 4.8. h (2.8-8.6). The sensitivity of the presentation and 4. h hs-cTnI using the overall 99th percentile was 92.1% (95% CI 82.4% to 97.4%) and negative predictive value 95.4% (92.3% to 97.4%) with 78.3% low-risk. Applying the sex-specific 99th percentile did not change the sensitivity. The addition of ECG did not change the sensitivity. Conclusion: Hs-cTnI >. 99th percentile thresholds measured on presentation and at 4-hours was not a safe strategy to rule-out AMI in this clinical setting irrespective of whether sex-specific 99th percentiles were used, or whether hs-cTnI was combined with ECG results

Betaine and Secondary Events in an Acute Coronary Syndrome Cohort

BACKGROUND: Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency and secondary events in acute coronary syndrome patients. METHODS: Plasma (531) and urine (415) samples were collected four months after discharge following an acute coronary event. Death (34), secondary acute myocardial infarction (MI) (70) and hospital admission for heart failure (45) events were recorded over a median follow-up of 832 days. PRINCIPAL FINDINGS: The highest and lowest quintiles of urinary betaine excretion associated with risk of heart failure (p = 0.0046, p = 0.013 compared with middle 60%) but not with subsequent acute MI. The lowest quintile of plasma betaine was associated with subsequent acute MI (p = 0.014), and the top quintile plasma betaine with heart failure (p = 0.043), especially in patients with diabetes (p<0.001). Top quintile plasma concentrations of dimethylglycine (betaine metabolite) and top quintile plasma homocysteine both associated with all three outcomes, acute MI (p = 0.004, <0.001), heart failure (p = 0.027, p<0.001) and survival (p<0.001, p<0.001). High homocysteine was associated with high or low betaine excretion in >60% of these subjects (p = 0.017). Median NT-proBNP concentrations were lowest in the middle quintile of plasma betaine concentration (p = 0.002). CONCLUSIONS: Betaine insufficiency indicates increased risk of secondary heart failure and acute MI. Its association with elevated homocysteine may partly explain the disappointing results of folate supplementation. In some patients, especially with diabetes, elevated plasma betaine also indicates increased risk