Protein synthesis of the pro-inflammatory S100A8/A9 complex in plasmacytoid dendritic cells and cell surface S100A8/A9 on leukocyte subpopulations in systemic lupus erythematosus

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease with chronic or episodic inflammation in many different organ systems, activation of leukocytes and production of pro-inflammatory cytokines. The heterodimer of the cytosolic calcium-binding proteins S100A8 and S100A9 (S100A8/A9) is secreted by activated polymorphonuclear neutrophils (PMNs) and monocytes and serves as a serum marker for several inflammatory diseases. Furthermore, S100A8 and S100A9 have many pro-inflammatory properties such as binding to Toll-like receptor 4 (TLR4). In this study we investigated if aberrant cell surface S100A8/A9 could be seen in SLE and if plasmacytoid dendritic cells (pDCs) could synthesize S100A8/A9. Methods: Flow cytometry, confocal microscopy and real-time PCR of flow cytometry-sorted cells were used to measure cell surface S100A8/A9, intracellular S100A8/A9 and mRNA levels of S100A8 and S100A9, respectively. Results: Cell surface S100A8/A9 was detected on all leukocyte subpopulations investigated except for T cells. By confocal microscopy, real-time PCR and stimulation assays, we could demonstrate that pDCs, monocytes and PMNs could synthesize S100A8/A9. Furthermore, pDC cell surface S100A8/A9 was higher in patients with active disease as compared to patients with inactive disease. Upon immune complex stimulation, pDCs up-regulated the cell surface S100A8/A9. SLE patients had also increased serum levels of S100A8/A9. Conclusions: Patients with SLE had increased cell surface S100A8/A9, which could be important in amplification and persistence of inflammation. Importantly, pDCs were able to synthesize S100A8/A9 proteins and up-regulate the cell surface expression upon immune complex-stimulation. Thus, S100A8/A9 may be a potent target for treatment of inflammatory diseases such as SLE

Behavior in a stressful situation, personality factors, and disease severity in patients with acute myocardial infarction: baseline findings from the prospective cohort study SECAMI (The Secondary Prevention and Compliance following Acute Myocardial Infarction-study)

<p>Abstract</p> <p>Background</p> <p>Psychosocial stress has been identified as a risk factor in association with cardiovascular disease but less attention has been paid to heterogeneity in vulnerability to stress. The serial Color Word Test (CWT) measures adaptation to a stressful situation and it can be used to identify individuals that are vulnerable to stress. Prospective studies have shown that individuals with a maladaptive behavior in this test are exposed to an increased risk of future cardiovascular events. The aim of the present study was to investigate whether maladaptive behavior in the serial CWT alone or in combination with any specific personality dimension was associated with severity of myocardial infarction (MI).</p> <p>Methods</p> <p>MI-patients (n = 147) completed the test and filled in a personality questionnaire in close proximity to the acute event. The results were analyzed in association with four indicators of severity: maximum levels above median of the cardiac biomarkers troponin I and creatine kinase-MB (CKMB), Q-wave infarctions, and a left ventricular ejection fraction (LVEF) ≤ 50%.</p> <p>Results</p> <p>Maladaptive behavior in the serial CWT together with low scores on extraversion were associated with maximum levels above median of cardiac troponin I (OR 2.97, CI 1.08-8.20, p = 0.04) and CKMB (OR 3.33, CI 1.12-9.93, p = 0.03). No associations were found between the combination maladaptive behavior and low scores on extraversion and Q-wave infarctions or a decreased LVEF.</p> <p>Conclusions</p> <p>Maladaptive behavior in combination with low scores on extraversion is associated with higher cardiac biomarker levels following an MI. The serial CWT and personality questionnaires could be used to identify individuals vulnerable to the hazardous effects of stress and thereby are exposed to an increased risk of a more severe infarction.</p

Marital status and occupation in relation to short-term case fatality after a first coronary event - a population based cohort

<p>Abstract</p> <p>Background</p> <p>Although marital status and low occupation level has been associated with mortality, the relationship with case fatality rates (CFR) after a coronary event (CE) is unclear. This study explored whether incidence of CE and short-term CFR differ between groups defined in terms of marital status and occupation, and if this could be explained by biological and life-style risk factors.</p> <p>Methods</p> <p>Population-based cohort study of 33,224 subjects (67% men), aged 27 to 61 years, without history of myocardial infarction, who were enrolled between 1974 and 1992. Incidence of CE, and CFR (death during the first day or within 28 days after CE, including out-of-hospital deaths) was examined over a mean follow-up of 21 years.</p> <p>Results</p> <p>A total of 3,035 men (6.0 per 1000 person-years) and 507 women (2.4 per 1000) suffered a first CE during follow-up. CFR (during the 1^stday) was 29% in men and 23% in women. After risk factor adjustments, unmarried status in men, but not in women, was significantly associated with increased risk of suffering a CE [hazard ratios (HR) 1.10, 95% CI: 0.97-1.24; 1.42: 1.27-1.58 and 1.77: 1.31-2.40 for never married, divorced and widowed, respectively, compared to married]. Unmarried status, in both gender, was also related with an increased CFR (1^stday), taking potential confounders into account (odds ratio (OR) 2.14, 95% CI: 1.63-2.81; 1.91: 1.50-2.43 and 1.49: 0.77-2.89 for never married, divorced and widowed, respectively, compared to married men. Corresponding figures for women was 2.32: 0.93-5.81; 1.87: 1.04-3.36 and 2.74: 1.03-7.28. No differences in CFR (1^stday) were observed between occupational groups in neither gender.</p> <p>Conclusions</p> <p>In this population-based Swedish cohort, short-term CFR was significantly related to unmarried status in men and women. This relationship was not explained by biological-, life-style factors or occupational level.</p

The impact of personality factors on delay in seeking treatment of acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Early hospital arrival and rapid intervention for acute myocardial infarction is essential for a successful outcome. Several studies have been unable to identify explanatory factors that slowed decision time. The present study examines whether personality, psychosocial factors, and coping strategies might explain differences in time delay from onset of symptoms of acute myocardial infarction to arrival at a hospital emergency room.</p> <p>Methods</p> <p>Questionnaires on coping strategies, personality dimensions, and depression were completed by 323 patients ages 26 to 70 who had suffered an acute myocardial infarction. Tests measuring stress adaptation were completed by 180 of them. The patients were then categorised into three groups, based on time from onset of symptoms until arrival at hospital, and compared using logistic regression analysis and general linear models.</p> <p>Results</p> <p>No correlation could be established between personality factors (i.e., extraversion, neuroticism, openness, agreeableness, conscientiousness) or depressive symptoms and time between onset of symptoms and arrival at hospital. Nor was there any significant relationship between self-reported patient coping strategies and time delay.</p> <p>Conclusions</p> <p>We found no significant relationship between personality factors, coping strategies, or depression and time delays in seeking hospital after an acute myocardial infraction.</p

Inflammation-sensitive plasma proteins are associated with increased incidence of heart failure: A population-based cohort study.

BACKGROUND: Although inflammation has been associated with different cardiovascular diseases, the relationships with future heart failure (HF) are unclear. This population-based study explored whether elevated plasma levels of inflammatory proteins are associated with incidence of HF. METHODS: Five inflammation-sensitive plasma proteins (ISPs, fibrinogen, ceruloplasmin, haptoglobin, orosomucoid, and alpha1-antitrypsin) was measured in 6071 men (mean age 46 years) without history of myocardial infarction (MI) or stroke. Incidence of hospitalizations due to HF (primary diagnosis) was monitored over 22 years of follow-up, in relation to the number of elevated ISPs (i.e., in the 4th quartile). Subjects with myocardial infarction during follow-up were censored. RESULTS: During the follow-up, 159 men were hospitalized due to HF. Baseline levels of all ISPs, except for haptoglobin, were significantly higher in men who developed HF. After adjustments for confounding factors, the hazard ratios (HR) of HF were 1.00 (reference), 1.7 (95% CI: 1.1-2.7), 2.0 (CI: 1.2-3.3) and 2.6 (CI: 1.6-4.1), respectively, in men with none, one, two and three or more ISPs in the 4th quartile (trend: p<0.001). Of the individual ISPs, fibrinogen, ceruloplasmin and alpha1-antitrypsin showed significant relationships with incidence of HF after adjustment for risk factors. CONCLUSION: Plasma levels of inflammatory markers are associated with long-term incidence of hospitalizations due to HF in middle-aged men

Survival rate 28 days after hospital admission with first myocardial infarction. Inverse relationship with socio-economic circumstances.

Objective. To study to what extent geographical differences of the mortality from ischaemic heart disease (IHD) can be accounted for by the 28-day case fatality rate (CFR) following first hospital admittance for acute myocardial infarction (MI) and whether the geographical pattern of survival has any relationship with socio-economic circumstances. Design. Register-based surveillance study. Setting. Seventeen residential areas in Malmo, Sweden. Subjects. All 5533 patients were admitted during 1986-1995 for a first acute MI at Malmo University Hospital. Main outcome measures. CFR is based on record linkage with national registers. Area-specific cardiovascular and socio-economic scores (SES) are based on previous cross-sectional studies. Results. In patients below 75 years of age, differences of the 28-day CFR accounted for 20-30% of the geographical variance in mortality from IHD. No corresponding association was found in older age groups. Patients from areas with low SES had the highest CFR, 23.8%. The odds ratios of fatal outcome for patients from areas with median and low SES (versus high SES) were 1.23 (95% CI: 1.01-1.50) and 1.25 (95% CI: 1.03-1.52), respectively (P for trend: 0.060). The strongest correlation was observed in men below 75 years of age (P for trend: 0.007). During the study period there was an improvement of the survival rate for patients from high and medium SES areas but no corresponding change for patients coming from areas having a low SES. Conclusions. In patients below 75 years, geographical differences of the mortality from IHD were related to differences of the 28-day CFR following hospital admittance for a first MI. Rates of survival were inversely related to socio-economic circumstances in the patient's residential area