Harry Staines

Low Levels of the Omega-3 Index are Associated with Sudden Cardiac Arrest and Remain Stable in Survivors in the Subacute Phase

In previous studies, low blood levels of n-3 fatty acids (FA) have been associated with increased risk of cardiac death, and the omega-3 index (red blood cell (RBC) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) expressed as weight percentage of total FA) has recently been proposed as a new risk factor for death from coronary artery disease, especially following sudden cardiac arrest (SCA). As blood samples often haven been harvested after the event, the aim of our study was to evaluate the stability of RBC fatty acids following SCA. The total FA profile, including the omega-3 index, was measured three times during the first 48xa0h in 25 survivors of out-of-hospital cardiac arrest (OHCA), in 15 patients with a myocardial infarction (MI) without SCA and in 5 healthy subjects. We could not demonstrate significant changes in the FA measurements in any of the groups, this also applied to the omega-6/omega-3 ratio and the arachidonic acid (AA)/EPA ratio. Furthermore, we compared the omega-3 index in 14 OHCA-patients suffering their first MI with that of 185 first-time MI-patients without SCA; mean values being 4.59% and 6.48%, respectively (pxa0=xa00.002). In a multivariate logistic regression analysis, a 1% increase of the omega-3 index was associated with a 58% (95% CI: 0.25–0.76%) reduction in risk of ventricular fibrillation (VF). In conclusion, the omega-3 index remained stable after an event of SCA and predicted the risk of VF.

(n-3) Fatty Acid Content of Red Blood Cells Does Not Predict Risk of Future Cardiovascular Events following an Acute Coronary Syndrome

A reduced risk of fatal coronary artery disease has been associated with a high intake of (n-3) fatty acids (FA) and a direct cardioprotective effect by their incorporation into myocardial cells has been suggested. Based on these observations, the omega-3 index (eicosapentaenoic acid + docosahexaenoic acid in cell membranes of RBC expressed as percent of total FA) has been suggested as a new risk marker for cardiac death. In this study, our aim was to evaluate the omega-3 index as a prognostic risk marker following hospitalization with an acute coronary syndrome (ACS). The omega-3 index was measured at admission in 460 patients with an ACS as defined by Troponin-T (TnT) > or = 0.02 microg/L. During a 2-y follow-up, recurrent myocardial infarctions (MI) (defined as TnT > 0.05 microg/L with a typical MI presentation) and cardiac and all-cause mortality were registered. Cox regression analyses were used to relate the risk of new events to the quartiles of the omega-3 index at inclusion. After correction for age, sex, previous heart disease, hypertension, diabetes, smoking, high-sensitivity C-reactive protein, brain natriuretic peptide, creatinine, total cholesterol, HDL-cholesterol, triacylglycerol, homocysteine, BMI, and medication, there was no significant reduction in risk for all-cause mortality, cardiac death, or MI with increasing values of the index. In conclusion, we could not confirm the omega-3 index as a useful prognostic risk marker following an ACS.

The long-term prognostic value of multiple biomarkers following a myocardial infarction

INTRODUCTIONnWe assessed the long-term prognostic value of multiple cardiac biomarkers after an acute myocardial infarction (MI) in order to evaluate a multimarker approach to risk stratification.nnnMATERIAL AND METHODSnBlood samples from 298 patients hospitalized with a myocardial infarction were subsequently tested for NT-proBNP, hsCRP, MMP-9, PAPP-A, MPO, sCD40L and FM.nnnRESULTSnDuring the median follow-up period of 45 months, 83 patients suffered at least one TnT- positive event. In the unadjusted analysis NT-proBNP predicted future ACS or cardiac death with a hazard ratio (HR) of 1.83 (95% confidence interval (CI), 1.17-2.87, p=0.009) in Q4 as compared to the three lower quartiles (Q1-3). However, NT-proBNP was dependent on chronic heart failure and HDL-cholesterol in the stepwise multivariable model, with a hazard ratio (HR) in Q4 of 1.38 (95% CI, 0.82-2.33, p=0.229). The other biomarkers were not found to be related to the primary event following the index MI.nnnCONCLUSIONnIn a patient population consisting of 298 subjects hospitalized with a MI, a multimarker approach with NT-proBNP, hsCRP, MMP-9, PAPP-A, MPO, sCD40L and FM rendered no additional prognostic information beyond conventionally used stratification tools in the acute phase. However, this does not preclude clinical valuable prognostic information by a biomarker such as NT-proBNP.

The long pentraxin 3 (PTX3): a novel prognostic inflammatory marker for mortality in acute chest pain

The long pentraxin 3 (PTX3) is a recently identified member of the pentraxin protein family that includes C-reactive protein. PTX3 is produced by the major cell types involved in atherosclerotic lesions in response to inflammatory stimuli, and elevated plasma levels are found in several conditions including acute coronary syndromes (ACS). The aim of this study was to assess the value of PTX3 as a prognostic marker of mortality and recurrent ischaemic events in a consecutive series of patients admitted with acute chest pain and potential ACS. The patients received follow-up for 24 months. Blood samples were taken on admission for measurement of PTX3, high sensitive C-reactive protein (hsCRP), B-type natriuretic peptide (BNP), and troponin T. All-cause mortality at 24 months in the study cohort was 15.2%. Patients in the upper PTX3 quartiles had a significantly higher death risk than those in the lowest quartile (Q3: hazard ratio [HR] 2.36; 95% CI 1.12-4.99; p = 0.024, and Q4: HR 3.60; 95% CI 1.68-7.72; p = 0.001). Elevated BNP levels were also significantly associated with a fatal outcome (Q3: HR 3.05; 95% CI 1.16-7.99; p = 0.024; and Q4: HR 3.90; 95% CI 1.48-10.26; p = 0.006). Elevation in hsCRP was not associated with increased death risk. As PTX3 predicted mortality independently of BNP, the combination of these two biomarkers showed an incremental prognostic value. PTX3 is a new biomarker related to inflammation that, independently of BNP, strongly predicts long-term all-cause mortality in patients with acute chest pain. The combination of these two biomarkers enhances the prognostic value over either marker alone.

Activated factor XII type A predicts long-term mortality in patients admitted with chest pain.

Summary.u2002 Background: We assessed the relation between admission levels of activated factor XII type A (XIIaA), and long‐term all‐cause and cardiac mortality and recurrent troponin T (TnT) positive cardiovascular events in a consecutive cohort of 870 patients admitted with a clinically strongly suspected acute coronary syndrome (ACS). Methods and results: After a 24‐month follow‐up period, 138 patients (15.8%) had died and 155 (17.8%) had suffered from a recurrent TnT positive (TnTu2003>u20030.05u2003ngu2003mL−1) event. XIIaA levels were significantly lower in long‐term survivors than in patients who died (22.9 (17.7–32.1) vs. 27.2 (20.0–39.7)u2003pmolu2003L−1 [median, 25 and 75% percentiles], Pu2003<u20030.001). The unadjusted hazard ratio for death within 2u2003years in patients with XIIaA in the highest quartile was 2.49 (95% confidence interval (CI), 1.52–4.06) as compared with patients with XIIaA in the lowest quartile. In a stepwise Cox regression model for death within 2u2003years, XIIaA added prognostic information for all‐cause mortality (HR 2.05; 95% CI, 1.21–3.47) above and beyond age, a history of heart failure, ST‐segment elevation, TnT and B‐type natriuretic peptide (BNP). In the subgroup of patients with an admission TnTu2003≤u20030.05u2003ngu2003mL−1, XIIaA provided independent prognostic information for all‐cause mortality (HR 3.88; 95% CI, 1.66–9.08) and for the combined endpoint of death or recurrent TnT positive event (HR 2.46; 95% CI, 1.34–4.50). Conclusion: XIIaA, a recently identified in vivo form of activated factor XII is an independent indicator of long‐term all‐cause mortality in patients admitted with chest pain, providing prognostic information above and beyond conventional risk factors.

Serum 25(OH)D Is a 2-Year Predictor of All-Cause Mortality, Cardiac Death and Sudden Cardiac Death in Chest Pain Patients from Northern Argentina

Background Several studies have shown an association between vitamin D deficiency and cardiovascular risk. Vitamin D status is assessed by determination of 25-hydroxyvitamin D [25(OH)D] in serum. Methods We assessed the prognostic utility of 25(OH)D in 982 chest-pain patients with suspected acute coronary syndrome (ACS) from Salta, Northern Argentina. 2-year follow-up data including all-cause mortality, cardiac death and sudden cardiac death were analyzed in quartiles of 25(OH)D, applying univariate and multivariate analysis. Results There were statistically significant changes in seasonal 25(OH)D levels. At follow-up, 119 patients had died. The mean 25(OH)D levels were significantly lower among patients dying than in long-term survivors, both in the total population and in patients with a troponin T (TnT) release (nu200a=u200a388). When comparing 25(OH)D in the highest quartile to the lowest quartile in a multivariable Cox regression model for all-cause mortality, the hazard ratio (HR) for cardiac death and sudden cardiac death in the total population was 0.37 (95% CI, 0.19–0.73), pu200a=u200a0.004, 0.23 (95% CI, 0.08–0.67), pu200a=u200a0.007, and 0.32 (95% CI, 0.11–0.94), pu200a=u200a0.038, respectively. In patients with TnT release, the respective HR was 0.24 (95% CI, 0.10–0.54), pu200a=u200a0.001, 0.18 (95% CI, 0.05–0.60), pu200a=u200a0.006 and 0.25 (95% CI, 0.07–0.89), pu200a=u200a0.033. 25(OH)D had no prognostic value in patients with no TnT release. Conclusion Vitamin D was shown to be a useful biomarker for prediction of mortality when obtained at admission in chest pain patients with suspected ACS. Trial registration ClinicalTrials.gov NCT01377402

B-type natriuretic peptide is a long-term predictor of all-cause mortality, whereas high-sensitive C-reactive protein predicts recurrent short-term troponin T positive cardiac events in chest pain patients: a prognostic study

BackgroundFew studies have addressed whether the combined use of B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) improves risk stratification for mortality and cardiovascular events in a population with chest pain and suspected acute coronary syndromes (ACS). Therefore, we wanted to assess the incremental prognostic value of these biomarkers with respect to long-term all-cause mortality and recurrent troponin T (TnT) positive cardiac events in 871 patients admitted to the emergency department.MethodsBlood samples were obtained immediately following admission.ResultsAfter a follow-up period of 24 months, 129 patients had died. The BNP levels were significantly higher among patients dying than in long-term survivors (401 (145–736) versus 75 (29–235) pq/mL [median, 25 and 75% percentiles], p = 0.000). In a multivariable Cox regression model for death within 2 years, the hazard ratio (HR) for BNP in the highest quartile (Q4) was 5.13 (95% confidence interval (CI), 1.97–13.38) compared to the lowest quartile (Q1) and was associated with all-cause mortality above and beyond age, congestive heart failure and the index diagnosis ST-segment elevation myocardial infarction. HsCRP rendered no prognostic information for all-cause mortality. However, within 30 days, the adjusted HR for patients with recurrent TnT cardiac positive events hsCRP in Q4 was 14.79 (95% CI, 1.89–115.63) compared with Q1 and was associated with recurrent ischemic events above and beyond age, hypercholesterolemia and TnT values at admission.ConclusionBNP may act as a clinically useful biomarker when obtained at admission in an unselected patient population following hospitalization with chest pain and potential ACS, and may provide complementary prognostic information to established risk determinants at long-term follow-up. Our data do not support the hypothesis that the additional assessment of hsCRP will lead to better risk stratification for survival than BNP alone.Trial registrationNCT00521976

Long-term prognostic utility of pentraxin 3 and D-dimer as compared to high-sensitivity C-reactive protein and B-type natriuretic peptide in suspected acute coronary syndrome.

Background Vascular inflammation plays a key role in the development of atherosclerosis and acute coronary syndrome (ACS), and pentraxin 3 (PTX3) is one of several novel, promising markers of inflammation. In addition, D-dimer might serve as a marker of thrombogenesis and a hypercoagulable state following plaque rupture. The present study assesses the prognostic utility of these two biomarkers as compared to high-sensitivity C-reactive protein (hsCRP) and B-type natriuretic peptide (BNP), in addition to conventional clinical risk factors for coronary heart disease in patients with suspected ACS. Methods Chest pain patients with suspected ACS (nu2009=u2009871) were consecutively included in a prospective, observational study with a follow-up time of 84 months. Results At 7-year follow-up, 332 patients had died and 203 had suffered an adverse troponin T-positive, non-fatal cardiac event. In the multivariate analysis, levels of PTX3 above 5.88u2009ng/mL (median) and D-dimer above 436u2009µg/L (lower limit upper quartile) independently predicted mortality (HR 1.60 [95% CI 1.10–2.33]; pu2009=u20090.014 and HR 1.83 [95% CI 1.20–2.78]; pu2009=u20090.005, respectively). Also, BNP levels above 310.75u2009pg/mL (lower limit upper quartile) (HR 2.16 [95% CI 1.37–3.42]; pu2009=u20090.001), but not hsCRP, independently predicted mortality. Only hsCRP and BNP also predicted future myocardial infarction (HR 1.59 [95% CI 1.05–2.40]; pu2009=u20090.029 and HR 1.91 [95% CI 1.10–3.31]; pu2009=u20090.021, respectively). Conclusion High levels of PTX3, D-dimer and BNP were found to be independent, long-term predictors of all-cause mortality in chest pain patients with a suspected ACS. hsCRP and BNP also predicted future myocardial infarction.

The prognostic utility of D-dimer and fibrin monomer at long-term follow-up after hospitalization with coronary chest pain.

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.

B-type natriuretic peptide and high sensitive C-reactive protein predict 2-year all cause mortality in chest pain patients: a prospective observational study from Salta, Argentina

BackgroundSeveral mechanisms are involved in the pathophysiology of the Acute Coronary Syndrome (ACS). We have addressed whether B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) in admission samples may improve risk stratification in chest pain patients with suspected ACS.MethodsWe included 982 patients consecutively admitted with chest pain and suspected ACS at nine hospitals in Salta, Northern Argentina. Total and cardiac mortality were recorded during a 2-year follow up period. Patients were divided into quartiles according to BNP and hsCRP levels, respectively, and inter quartile differences in mortality were statistically evaluated applying univariate and multivariate analyses.Results119 patients died, and the BNP and hsCRP levels were significantly higher among these patients than in survivors. In a multivariable Cox regression model for total death and cardiac death in all patients, the hazard ratio (HR) in the highest quartile (Q4) as compared to the lowest quartile (Q1) of BNP was 2.32 (95% confidence interval (CI), 1.24-4.35), p = 0.009 and 3.34 (95% CI, 1.26-8.85), p = 0.015, respectively. In the TnT positive patients (TnT > 0.01 ng/mL), the HR for total death and cardiac death in Q4 as compared to Q1 was 2.12 (95% CI, 1.07-4.18), p = 0.031 and 3.42 (95% CI, 1.13-10.32), p = 0.029, respectively.The HR for total death for hsCRP in Q4 as compared to Q1 was 1.97 (95% CI, 1.17-3.32), p = 0.011, but this biomarker did not predict cardiac death (p = 0.21). No prognostic impact of these two biomarkers was found in the TnT negative patients.ConclusionBNP and hsCRP may act as clinically useful biomarkers when obtained at admission in a population with suspected ACS.Trial RegistrationClinicalTrials.gov Identifier: NCT01377402.