Search

Introduction: Procollagen type 1 N-terminal Propeptide (P1NP) is a precursor protein of collagen type 1, a major component of cardiac extracellular matrix. The association of P1NP to clinical outcome in patients with suspected acute coronary syndrome (ACS) has so far not been investigated. The objective of the present study was to assess the predictive value of P1NP concerning adverse clinical outcome in patients admitted for suspected ACS. Methods: Plasma P1NP was measured with an enzyme immune assay in samples taken upon admission from patients enrolled in the Risk markers in Acute Coronary Syndrome (RACS) study (NCT00521976), a Norwegian single center study including patients with suspected ACS from November 2002 to September 2003. The primary endpoint was a composite of all-cause mortality, myocardial infarction (MI), or stroke within 1 year. Additional analyzes included the composite and its individual components at 1, 2, and 7 years, and cardiac death at 1 and 2 years. Associations between quartiles of P1NP and the endpoints were assessed in both univariate analyzes and in stepwise multivariable Cox regression analyzes fitted with significant clinical variables, past medical history, medication, TnT, BNP, and eGFR before P1NP was introduced. Results: Samples were available from 813 patients (Mean age 69.6 years, 61.4 % males, 52.9% elevated TnT). Mean P1NP levels was 46.2 ng/mL (CI 44.8-47.6). In multivariable Cox analyzes, P1NP was found to be significantly associated with the composite of all-cause mortality, MI, or stroke at 1 year (HR [Q4vsQ1] 1.82, CI 1.12-2.98; p=0.017). This association did not remain significant beyond 1 year. No association was seen for any of the individual components, or cardiac death, at any timepoint, or in patients with elevated TNT (p>0.05 for all). Conclusions: This first study on P1NP in suspected ACS revealed a significant association with adverse clinical outcome (all-cause death, MI, or stroke) at 1 year. However, no predictive value was found concerning outcome for the individual components of the primary endpoint, or cardiac death, at any timepoint, or in patients with elevated TNT.

Background: Several studies have demonstrated a correlation between low vitamin D levels and cardiovascular risk. Vitamin D is a fat soluble vitamin that can either be ingested (mainly from fatty fish), or created in the skin on exposure to sun. Objectives: To assess the collected prognostic utility of vitamin D measured as 25-hydroxyvitamin D [25(OH)D] in 1852 patients hospitalized with chest pain and suspected acute coronary syndrome (ACS) recruited from two continents located at opposite sides of the Equator; coastal-Norway and inland Northern-Argentina, where the vitamin D source is either a combination of diet and sun exposure or mainly sun exposure, respectively. Data from both areas were collected in a similar registry and pooled in the present analysis. Methods: 2-year follow-up data including all-cause mortality, cardiac death and sudden cardiac death (SCD) in the total- as well as in the troponin T (TnT) positive (TnT > 0.01 ng/mL) patient population were analyzed in quartiles of 25(OH)D, applying univariate and multivariable analysis. Variables included in the Cox regression model were country, TnT, hs-CRP, BNP, creatinine, age, gender, BMI, recruitment seasons and 14 other conventional risk factors for coronary heart disease. Results: At follow-up, 292 patients had died. 859 patients were TnT positive and of these 186 died. In multivariable Cox regression models for all-cause mortality, cardiac death and SCD in the total patient population, the adjusted hazard ratios (HR) for 25(OH)D in the highest quartile (Q4) as compared to the lowest quartile (Q1) were 0.52 (95% confidence interval (CI), 0.34-0.80), p=0.003, 0.54 (95% CI, 0.31-0.96), p=0.037 and 0.42 (95% CI, 0.18-0.98), p=0.045, respectively. In the TnT positive patient population the respective HRs were 0.43 (95% CI, 0.26-0.72), p=0.001, 0.47 (95% CI, 0.25-0.90), p=0.023 and 0.32 (95% CI, 0.12-0.87), p=0.025. Conclusion: Vitamin D status may serve as a prognostic indicator in chest pain patients with suspected ACS.

Dopaminergic (DA) agonist-induced yawning in rats seems to be mediated by DA D3 receptors, and low doses of several DA agonists decrease locomotor activity, an effect attributed to presynaptic D2 receptors. Effects of several DA agonists on yawning and locomotor activity were examined in rats and mice. Yawning was reliably produced in rats, and by the cholinergic agonist, physostigmine, in both the species. However, DA agonists were ineffective in producing yawning in Swiss-Webster or DA D2R and DA D3R knockout or wild-type mice. The drugs significantly decreased locomotor activity in rats at one or two low doses, with activity returning to control levels at higher doses. In mice, the drugs decreased locomotion across a 1000-10 000-fold range of doses, with activity at control levels (U-91356A) or above control levels [(+/-)-7-hydroxy-2-dipropylaminotetralin HBr, quinpirole] at the highest doses. Low doses of agonists decreased locomotion in all mice except the DA D2R knockout mice, but were not antagonized by DA D2R or D3R antagonists (L-741 626, BP 897, or PG01037). Yawning does not provide a selective in-vivo indicator of DA D3R agonist activity in mice. Decreases in mouse locomotor activity by the DA agonists seem to be mediated by D2 DA receptors.

D-dimer and fibrin monomer both reflect a prothrombotic potential. There are limited data available comparing these two markers of activated coagulation in a prospective manner in an unselected patient population presenting to the emergency department with chest pain. In addition, their role in risk stratification in patients with acute coronary syndrome is still under evaluation. Therefore, we wanted to assess the prognostic value of these markers with respect to long-term all-cause mortality in 871 patients admitted to the emergency department. Blood samples were obtained immediately following admission. After a follow-up period of 24 months, 123 patients had died. In the univariate analysis, both D-dimer and fibrin monomer predicted all-cause mortality within 2 years with an odds ratio of 7.78 (95% confidence interval, 3.95-15.33) and 4.19 (95% confidence interval, 2.42-7.28), respectively, in the highest quartile (Q4) compared with the lowest quartile (Q1). However, in the multivariable logistic regression model for death within 2 years, the odds ratio of D-dimer and fibrin monomer was 1.80 (95% confidence interval, 0.81 to 3.97) and 1.04 (95% confidence interval, 0.53 to 2.04) in Q4 compared with Q1, respectively, and added no prognostic information above and beyond age, known coronary heart disease, B-type natriuretic peptide and the index diagnoses of ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction and unstable angina pectoris. In an unselected patient population hospitalized with chest pain and potential acute coronary syndrome, neither D-dimer nor fibrin monomer provided complementary prognostic information to established risk determinants during long-term follow-up.

Background: Several studies have demonstrated an inverse relationship between cardiovascular risk and levels of vitamin D and omega-3. Objectives: To assess the impact of high-dose treatment of concentrated omega-3 (ethylester form) on serum vitamin D measured as 25-hydroxyvitamin D [25(OH)D] in 288 patients hospitalized with a myocardial infarction who were randomly assigned into a daily dose of either 4 g highly concentrated omega-3 fatty acids (114 patients) or corn oil (114 patients), administered in a double-blind manner over 12 months. Four mg of alfa-tocopherol was added to each capsule to protect against fatty acid oxidation. Supplementation with other fish-oil products was discontinued. 25(OH)D was measured at baseline, at 6 weeks and 12 months follow-up. Changes in 25(OH)D were compared statistically. Results: Median 25(OH)D levels in the two groups are shown in Table 1. The increase in 25(OH)D was statistically significant in both treatment groups at 12 months; p < 0.001 for n-3 polyunsaturated fatty acids (PUFAs) and p = 0.011 for corn oil. A statistical significant rise in 25(OH)D was already apparent in the n-3 PUFA patients at 6 weeks follow-up (p < 0.001). There was no significant difference between intergroup changes after 6 weeks intervention (p = 0.867) or after 12 months intervention (p = 0.267) (Mann-Whitney Rank Sum Test). Conclusion: A statistical significant early rise in vitamin D at 6 weeks follow-up was noted in the omega-3 group of patients, persisting at 12 months, but these changes were not reflected as compared to corn oil, probably due to the fact that both compounds are biologically active.

Background: The purpose of this study was to assess the distribution of serum lipids including total cholesterol, HDL cholesterol and triglycerides across quartiles of vitamin D in blood samples collected from 982 chest-pain patients with a suspected acute coronary syndrome (ACS) from Salta, Northern-Argentina. Methods: Vitamin D status was obtained by determination of 25-hydroxy-vitamin D (25(OH)D) in serum. Blood samples for measurement of 25(OH)D and circulating lipid fractions in serum were obtained immediately following admission. Results: In the total population the concentration of total cholesterol, HDL cholesterol and triglycerides was found to differ significantly across quartiles of 25(OH)D, p = 0.016, p = 0.01 and p = 0.000, respectively. See Figure 1, 2 and 3, respectively. In the Troponin T (TnT) positive population (TnT > 0.01 ng/mL), only total cholesterol and triglycerides differed significantly across the 25(OH)D quartiles, p = 0.000 and p = 0.003, respectively, whereas HDL cholesterol alone differed in the TnT negative group, p = 0.025. Conclusion: Concentrations of the main lipid fractions are related to the vitamin D status in patients admitted with chest pain and suspected ACS.

Background: Several studies have shown a correlation between low vitamin D levels and cardiovascular risk. Serum concentration of 25-hydroxy-vitamin D (25(OH)D) is an established marker of vitamin D status. The purpose of this study was to assess the prognostic utility of 25(OH)D status in 871 chest-pain patients with suspected acute coronary syndrome (ACS) from Western-Norway. Methods: Serum samples for determination of 25(OH)D were obtained at admission. Baseline data consisted of serum levels of Troponin T (TnT), high sensitive C-reactive protein, creatinine, glucose, lipids and B-type natriuretic peptide measured in EDTA plasma, as well as clinical parameters, including age, gender, previous MI, angina pectoris, previous revascularizations (percutaneous coronary intervention or coronary artery bypass graft), congestive heart failure, diabetes mellitus, smoking status, hypercholesterolemia (total cholesterol > 250 mg/dl or statin treated hypercholesterolemia), beta-blocker prior to enrolment, hypertension, body mass index and seasons (defined as November through April and May through October). The main endpoint was total mortality in the total population and in the TnT positive group (TnT > 0.01 ng/mL). Multivariate analysis was performed in 794 patients with a complete set of baseline variables. Results: The mean age was 69.6 and 39% were females. After 24 months follow-up, 136 patients had died. The mean vitamin D value was 53.8 nM (95% CI, 52.2 nM - 55.4 nM) between November 2002 and April 2003, and 50.2 nM (95%CI, 48.1 nM - 52.3 nM) between May 2003 and October 2003; p = 0.008. In the univariate analysis of all cause mortality in the total population, the hazard ratio (HR) for 25(OH)D in the highest quartile as compared to the lowest quartile was 0.63 (95% confidence interval (CI), 0.38 - 1.03), p = 0.065, and in the TnT positive patients the HR was 0.58 (95% CI, 0.33 - 1.03), p = 0.062. No difference in mortality was found between the vitamin D quartiles in the TnT negative population. The results remained statistically non-significant in the multivariate analysis. Conclusion: In an univariate analysis there was a trend towards higher mortality in the lowest quartile of vitamin D as compared to the highest quartile in our chest pain population with suspected ACS. Furthermore, there was a statistically significant seasonal difference in vitamin D levels.

Elevated plasma levels of long pentraxin 3 (PTX3), high-sensitive C-reactive protein (hsCRP) and B-type natriuretic peptide (BNP) are found in acute coronary syndromes (ACS). The aim of this study was to assess the prognostic value of PTX3 as compared to BNP and hsCRP, and their combination, as a prognostic marker of mortality in acute chest pain patients. PTX3 was measured in EDTA plasma with a new, high-sensitive ELISA method (PPMX, Tokyo, Japan). BNP was analysed in EDTA plasma using the Microparticle Enzyme Immunoassay (MEIA) Abbott AxSYM®. HsCRP was measured with the use of an immunoturbidimetric assay (Tinaquant® C-reactive protein (latex) high sensitive assay, Roche Diagnostics). The blood samples were taken on admission in 795 patients. The patients were followed for 24 months concerning mortality. For statistical analysis, the study cohort was divided into quartiles (Q1–4) according to PTX3 levels. A multiple logistic regression was fitted which included standard risk measures. At 24 months follow-up, 121 of the 784 patients included in the model had died. The odds ratio for comparing Q4 versus Q1 for PTX3, BNP and hsCRP were 4.34, 3.35 and 0.52 (p=0.001, p=0.024 and p=0.096), respectively, and the combination of PTX3 and BNP showed an incremental prognostic value (figure ). PTX3 is a new independent marker that strongly predicts long-term all-cause mortality in patients with acute chest pain and the combination of this marker with BNP adds substantially to the prognostic value as compared to either marker alone. Figure The number of biomakers greater than the median for % death in 24 months (p

Long Pentraxin 3 (PTX3) is a newly identified member of the Pentraxin protein family that includes C-reactive protein (CRP). Unlike CRP, PTX3 is produced by the major cell types involved in atherosclerotic lesions in response to inflammatory stimuli. Increased PTX3 levels are found in acute coronary syndromes (ACS). Its role in long-term prediction of clinical outcome is, however, unknown. The aim of the current study was to assess the predictive value of PTX3 concerning all-cause mortality in patients hospitalized for acute chest pain. Plasma PTX3 was measured with a new, high-sensitive ELISA method (PPMX, Tokyo, Japan) in blood samples taken on admission in 784 patients admitted for acute chest pain suggestive of ACS. The patients were followed for 24 months concerning clinical outcome. For statistical analysis, the study cohort was divided into quartiles according to PTX3 levels. A multiple logistic regression model was fitted to include standard risk measures. At 24 months follow-up 121 patients had died. By logistic regression, the odds Odds Ratio for death among patients with highest PTX3 levels was 3.13 as compared to those with lowest levels (p=0.007) (table). Long Pentraxin 3 is a new, independent marker that strongly predicts long-term all-cause mortality in patients with acute chest pain.