Background-B-type natriuretic peptide (BNP) is a predictor of short-and medium-term prognosis across the spectrum of acute coronary syndromes (ACS). The N-terminal fragment of the BNP prohormone, N-BNP, may be an even stronger prognostic marker. We assessed the relation between subacute plasma N-BNP levels and long-term, all-cause mortality in a large, contemporary cohort of patients with ACS. Methods and Results-Blood samples for N-BNP determination were obtained in the subacute phase in 204 patients with ST-elevation myocardial infarction (MI): 220 with non-ST segment elevation MI and 185 with unstable angina in the subacute phase. After a median follow-up of 51 months, 86 patients (14%) had died. Median N-BNP levels were significantly lower in long-term survivors than in patients dying (442 versus 1306 pmol/L; PϽ0.0001). The unadjusted risk ratio of patients with supramedian N-BNP levels was 3.9 (95% confidence interval, 2.4 to 6.5).In a multivariate Cox regression model, N-BNP (risk ratio 2.1 [95% confidence interval, 1.1 to 3.9]) added prognostic information above and beyond Killip class, patient age, and left ventricular ejection fraction. Adjustment for peak troponin T levels did not markedly alter the relation between N-BNP and mortality. In patients with no evidence of clinical heart failure, N-BNP remained a significant predictor of mortality after adjustment for age and ejection fraction (risk ratio, 2.4 [95% confidence interval, 1.1 to 5.4]). Conclusions-N-BNP is a powerful indicator of long-term mortality in patients with ACS and provides prognostic information above and beyond conventional risk markers.

Serum OPG is strongly predictive of long-term mortality and HF development in patients with ACS, independent of conventional risk markers.

Objective-To determine whether the level of lysophosphatidylcholine (lysoPC) generated by lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with severity of inflammation in human atherosclerotic plaques. Elevated plasma Lp-PLA2 is associated with increased cardiovascular risk. Lp-PLA2 inhibition reduces atherosclerosis. Lp-PLA2 hydrolyzes low-density lipoprotein-oxidized phospholipids generating lysoPCs. According to in vitro studies, lysoPCs are proinflammatory but the association between their generation and plaque inflammation remains unknown. Methods and Results-Inflammatory activity in carotid plaques (162 patients) was determined immunohistochemically and by analyzing cytokines in homogenates (multiplex immunoassay). LysoPCs were quantified using mass spectrometry and Lp-PLA2 and the lysoPC metabolite lysophosphatidic acid (LPA) by ELISA. There was a strong correlation among lysoPC 16:0, 18:0, 18:1, LPA, and Lp-PLA2 in plaques. LysoPC 16:0, 18:0, 18:1, LPA, and Lp-PLA2 correlated with interleukin-1, interleukin-6, monocyte chemoattractant protein-1, macrophage inflammatory protein-1, regulated on activation normal T-cell expressed and secreted, and tumor necrosis factor- in plaques. High lysoPC and Lp-PLA2 correlated with increased plaque macrophages and lipids and with low content of smooth muscle cells, whereas LPA only correlated with plaque macrophages. Lp-PLA2, lysoPC 16:0, 18:0, and 18:1, but not LPA were higher in symptomatic than in asymptomatic plaques. Conclusion-The

BackgroundRecent evidence suggests a link between autoimmunity and the intestinal microbial composition in several rheumatic diseases including systemic sclerosis (SSc). The objective of this study was to investigate the prevalence of intestinal dysbiosis in SSc and to characterise patients suffering from this potentially immunomodulatory deviation.MethodsThis study consisted of 98 consecutive patients subject to in-hospital care. Stool samples were analysed for intestinal microbiota composition using a validated genome-based microbiota test (GA-map™ Dysbiosis Test, Genetic Analysis, Oslo, Norway). Gut microbiota dysbiosis was found present as per this standardised test. Patients were examined regarding gastrointestinal and extraintestinal manifestations of SSc by clinical, laboratory, and radiological measures including esophageal cineradiography, the Malnutrition Universal Screening Tool (MUST), levels of plasma transthyretin (a marker of malnutrition) and faecal (F-) calprotectin (a marker of intestinal inflammation).ResultsA majority (75.5%) of the patients exhibited dysbiosis. Dysbiosis was more severe (rs = 0.31, p = 0.001) and more common (p = 0.013) in patients with esophageal dysmotility. Dysbiosis was also more pronounced in patients with abnormal plasma levels of transthyretin (p = 0.045) or micronutrient deficiency (p = 0.009). In 19 patients at risk for malnutrition according to the MUST, 18 exhibited dysbiosis. Conversely, of the 24 patients with a negative dysbiosis test, only one was at risk for malnutrition. The mean ± SEM levels of F-calprotectin were 112 ± 14 and 45 ± 8 μg/g in patients with a positive and negative dysbiosis test, respectively. Dysbiosis was more severe in patients with skin telangiectasias (p = 0.020), pitting scars (p = 0.023), pulmonary fibrosis (p = 0.009), and elevated serum markers of inflammation (p < 0.001). However, dysbiosis did not correlate with age, disease duration, disease subtype, or extent of skin fibrosis.ConclusionsIn this cross-sectional study, intestinal dysbiosis was common in patients with SSc and was associated with gastrointestinal dysfunction, malnutrition and with some inflammatory, fibrotic and vascular extraintestinal features of SSc. Further studies are needed to elucidate the potential causal relationship of intestinal microbe-host interaction in this autoimmune disease.

This study shows that suPAR in human carotid plaques and plasma is associated with the presence of symptoms and that plaque suPAR is associated with the vulnerable inflammatory plaque. These findings strengthen the hypothesis of suPAR as a future marker of vulnerable atherosclerotic plaques.

Based on detailed echocardiographic measures over a 2-year observation period, we found only minor differences between the two groups. However, the potential treatment effect on LVMI and the within-group differences in IVSd-mean suggest that longer follow-up may yield larger and clinically important differences.

Objective-The aim of this study was to assess the short-and long-term prognostic significance of levels in patients with acute coronary syndromes (ACS). Methods and Results-In patients hospitalized with ACS (median age, 66 years; 30% females), we evaluated associations of serum IL-18 levels from day 1 (nϭ1261) with the short-(Ͻ3 months) and long-term (median, 7.6 years) risk of death, development of congestive heart failure (CHF), and myocardial infarction (MI). IL-18 was not significantly associated with short-term mortality. In the long term, IL-18 levels were significantly related to all-cause mortality, even after adjustment for clinical confounders (hazard ratio [HR], 1.19; 95% confidence interval, 1.07 to 1.33; Pϭ0.002). Long-term, cardiovascular mortality was univariately related to IL-18, and the adjusted relation between noncardiovascular mortality and IL-18 was highly significant (HR, 1.36; 95% confidence interval, 1.11 to 1.67; Pϭ0.003). IL-18 independently predicted CHF, MI, and cardiovascular death/CHF/MI in both the short and long term. Measurements from day 1 of ACS and 3 months after ACS had a similar power to predict late outcome. Conclusion-The addition of the measurement of IL-18 to clinical variables improved the prediction of risk of all-cause and noncardiovascular mortality. The association between IL-18 and noncardiovascular mortality is intriguing and warrants further study.

. Objective.  We investigated whether levels of C‐reactive protein (CRP), interleukin‐6 (IL‐6), secretory phospholipase A2 group IIA (sPLA2‐IIA) and intercellular adhesion molecule‐1 (ICAM‐I) predict late outcomes in patients with acute coronary syndromes (ACS). Design.  Prospective longitudinal study. CRP (mg L−1), IL‐6 (pg mL−1), sPLA2‐IIA (ng mL−1) and ICAM‐1 (ng mL−1) were measured at days 1 (n = 757) and 4 (n = 533) after hospital admission for ACS. Their relations to mortality and rehospitalization for myocardial infarction (MI) and congestive heart failure (CHF) were determined. Setting.  Coronary Care Unit at Sahlgrenska University Hospital, Gothenburg, Sweden. Subjects.  Patients with ACS alive at day 30; median follow‐up 75 months. Results.  Survival was related to day 1 levels of all markers. After adjustment for confounders, CRP, IL‐6 and ICAM‐1, but not sPLA2‐IIA, independently predicted mortality and rehospitalization for CHF. For CRP, the hazard ratio (HR) was 1.3 for mortality (95% confidence interval (CI): 1.1–1.5, P = 0.003) and 1.4 for CHF (95% CI: 1.1–1.9, P = 0.006). For IL‐6, HR was 1.3 for mortality (95% CI: 1.1–1.6, P < 0.001) and 1.4 for CHF (95% CI: 1.1–1.8, P = 0.02). For ICAM‐1, HR was 1.2 for mortality (95% CI: 1.0–1.4, P = 0.04) and 1.3 for CHF (95% CI: 1.0–1.7, P = 0.03). No marker predicted MI. Marker levels on day 4 provided no additional predictive value. Conclusions.  In patients with ACS, CRP, IL‐6, sPLA2‐IIA and ICAM‐1 are associated with long‐term mortality and CHF, but not reinfarction. CRP, IL‐6 and ICAM‐1 provide prognostic information beyond that obtained by clinical variables.