Publications by authors named "Dennis W T Nilsen"

55 Publications

Changes in eicosapentaenoic acid and docosahexaenoic acid and risk of cardiovascular events and atrial fibrillation: A secondary analysis of the OMEMI trial.

J Intern Med 2022 Jan 4. Epub 2022 Jan 4.

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

Background: The cardiovascular benefit from n-3 polyunsaturated fatty acids (PUFAs) after acute myocardial infarction (AMI) is controversial, and the importance of serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations for clinical events is unclear.

Objectives: To assess changes in EPA and DHA serum concentrations during n-3 PUFA supplementation and their association with incident cardiovascular events.

Methods: In the OMEMI trial, elderly patients with a recent AMI were randomized to 1.8 g/day of EPA/DHA or control (corn oil) for 2 years. The primary outcome was a composite of AMI, coronary revascularization, stroke, heart failure hospitalization, or all-cause death (major adverse cardiovascular event [MACE]) and the secondary outcome was new-onset atrial fibrillation (AF).

Results: EPA and DHA measurements were available in 881 (92% of survivors) participants at randomization and study completion. EPA and DHA increased in the active treatment arm (n = 438) by a median of 87% and 16%, respectively. Greater on-treatment increases in EPA and DHA were associated with decreasing triglycerides, increasing high-density lipoprotein cholesterol, and lower baseline EPA and DHA concentrations. Greater on-treatment increases in EPA were associated with lower risk of MACE (adjusted hazard ratio 0.86 [95% confidence interval, CI, 0.75-0.99], p = 0.034), and higher risk of AF (adjusted hazard ratio (HR) 1.36 [95% CI 1.07-1.72], p = 0.011). Although there were similar tendencies for DHA changes and outcomes, these associations were not statistically significant (HR 0.84 [0.66-1.06] for MACE and 1.39 [0.90-2.13] for AF).

Conclusion: Greater on-treatment increases in EPA were associated with lower risk of MACE and higher risk of new-onset AF. These data suggest that the cardiovascular effects of increasing n-3 PUFA levels through supplements are complex, involving both potential benefits and harm.
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http://dx.doi.org/10.1111/joim.13442DOI Listing
January 2022

Complement component 7 is associated with total- and cardiac death in chest-pain patients with suspected acute coronary syndrome.

BMC Cardiovasc Disord 2021 10 14;21(1):496. Epub 2021 Oct 14.

Department of Clinical Science, University of Bergen, Bergen, Norway.

Background: Complement activation has been associated with atherosclerosis, atherosclerotic plaque destabilization and increased risk of cardiovascular events. Complement component 7 (CC7) binds to the C5bC6 complex which is part of the terminal complement complex (TCC/C5b-9). High-sensitivity C-reactive protein (hsCRP) is a sensitive marker of systemic inflammation and may reflect the increased inflammatory state associated with cardiovascular disease.

Aim: To evaluate the associations between CC7 and total- and cardiac mortality in patients hospitalized with chest-pain of suspected coronary origin, and whether combining CC7 with hsCRP adds prognostic information.

Methods: Baseline levels of CC7 were related to 60-months survival in a prospective, observational study of 982 patients hospitalized with a suspected acute coronary syndrome (ACS) at 9 hospitals in Salta, Argentina. A cox regression model, adjusting for conventional cardiovascular risk factors, was fitted with all-cause mortality, cardiac death and sudden cardiac death (SCD) as the dependent variables. A similar Norwegian population of 871 patients was applied to test the reproducibility of results in relation to total death.

Results: At follow-up, 173 patients (17.7%) in the Argentinean cohort had died, of these 92 (9.4%) were classified as cardiac death and 59 (6.0%) as SCD. In the Norwegian population, a total of 254 patients (30%) died. In multivariable analysis, CC7 was significantly associated with 60-months all-cause mortality [hazard ratio (HR) 1.26 (95% confidence interval (CI), 1.07-1.47) and cardiac death [HR 1.28 (95% CI 1.02-1.60)], but not with SCD. CC7 was only weakly correlated with hsCRP (r = 0.10, p = 0.002), and there was no statistically significant interaction between the two biomarkers in relation to outcome. The significant association of CC7 with total death was reproduced in the Norwegian population.

Conclusions: CC7 was significantly associated with all-cause mortality and cardiac death at 60-months follow-up in chest-pain patients with suspected ACS.

Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01377402, NCT00521976.
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http://dx.doi.org/10.1186/s12872-021-02306-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515738PMC
October 2021

Angiopoietin-2 and angiopoietin-like 4 protein provide prognostic information in patients with suspected acute coronary syndrome.

J Intern Med 2021 10 8;290(4):894-909. Epub 2021 Jul 8.

Department of Cardiology, Stavanger University Hospital, Stavanger, Norway.

Background: Plasma levels of angiopoietin-2 (ANGPT2) and angiopoietin-like 4 protein (ANGPTL4) reflect different pathophysiological aspects of cardiovascular disease. We evaluated their association with outcome in a hospitalized Norwegian patient cohort (n = 871) with suspected acute coronary syndrome (ACS) and validated our results in a similar Argentinean cohort (n = 982).

Methods: A cox regression model, adjusting for traditional cardiovascular risk factors, was fitted for ANGPT2 and ANGPTL4, respectively, with all-cause mortality and cardiac death within 24 months and all-cause mortality within 60 months as the dependent variables.

Results: At 24 months follow-up, 138 (15.8%) of the Norwegian and 119 (12.1%) of the Argentinian cohort had died, of which 86 and 66 deaths, respectively, were classified as cardiac. At 60 months, a total of 259 (29.7%) and 173 (17.6%) patients, respectively, had died. ANGPT2 was independently associated with all-cause mortality in both cohorts at 24 months [hazard ratio (HR) 1.27 (95% confidence interval (CI), 1.08-1.50) for Norway, and HR 1.57 (95% CI, 1.27-1.95) for Argentina], with similar results at 60 months [HR 1.19 (95% CI, 1.05-1.35) (Norway), and HR 1.56 (95% CI, 1.30-1.88) (Argentina)], and was also significantly associated with cardiac death [HR 1.51 (95% CI, 1.14-2.00)], in the Argentinean population. ANGPTL4 was significantly associated with all-cause mortality in the Argentinean cohort at 24 months [HR 1.39 (95% CI, 1.15-1.68)] and at 60 months [HR 1.43 (95% CI, 1.23-1.67)], enforcing trends in the Norwegian population.

Conclusions: ANGPT2 and ANGPTL4 were significantly associated with outcome in similar ACS patient cohorts recruited on two continents.

Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT00521976. ClinicalTrials.gov Identifier: NCT01377402.
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http://dx.doi.org/10.1111/joim.13339DOI Listing
October 2021

Activated factor XI-antithrombin complex presenting as an independent predictor of 30-days mortality in out-of-hospital cardiac arrest patients.

Thromb Res 2021 08 29;204:1-8. Epub 2021 May 29.

Stavanger University Hospital, Department of Cardiology, Stavanger, Norway; University of Bergen, Department of Clinical Science, Bergen, Norway.

Background: Cardiac arrest and cardiopulmonary resuscitation (CPR) are associated with activated coagulation and microvascular fibrin deposition with subsequent multiorgan failure and adverse outcome.

Objectives: Activated Factor XI-antithrombin (FXIa-AT) complex, activated Factor IX-antithrombin (FIXa-AT) complex and thrombin-antithrombin (TAT) complex were measured as markers of coagulation activation, and evaluated as independent prognostic indicators in out-of-hospital cardiac arrest (OHCA) patients.

Methods: From February 2007 until December 2010 blood samples were collected in close approximation to CPR from patients with OHCA of assumed cardiac origin. Follow-up samples in survivors were drawn 8-12 h and 24-48 h after hospital admission. All measurements were determined by ELISA.

Results: Thirty-seven patients presented with asystole and 77 with ventricular fibrillation as first recorded heart rhythm. At 30-days follow-up, 70 patients (61.4%) had died. All patients had elevated levels of FXIa-AT complex, FIXa-AT complex and TAT. Initial levels were significantly higher in non-survivors compared to 30-days survivors. A significant increase in risk of 30-days all-cause mortality was observed through increasing quartiles of all three biomarkers in univariate Cox regression analysis. Compared to the lowest quartile (Q1), only FXIa-AT complex levels in Q3 (HR 3.17, p = 0.011) and Q2 (HR 3.02, p = 0.016) were independently associated with all-cause mortality in the multivariable analysis. FIXa-AT complex and TAT-complex did not behave as independent predictors.

Conclusions: Complexes of FXIa-AT were independently associated with 30-days survival in OHCA-patients.

Clinical Trial Registration: ClinicalTrials. gov, NCT02886273.
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http://dx.doi.org/10.1016/j.thromres.2021.05.014DOI Listing
August 2021

Incidence and risk factors for major bleeding among patients undergoing percutaneous coronary intervention: Findings from the Norwegian Coronary Stent Trial (NORSTENT).

PLoS One 2021 4;16(3):e0247358. Epub 2021 Mar 4.

Clinic for Heart Disease, St. Olav's University Hospital, Trondheim, Norway.

Introduction: Bleeding is a concern after percutaneous coronary intervention (PCI) and subsequent dual antiplatelet therapy (DAPT). We herein report the incidence and risk factors for major bleeding in the Norwegian Coronary Stent Trial (NORSTENT).

Materials And Methods: NORSTENT was a randomized, double blind, pragmatic trial among patients with acute coronary syndrome or stable coronary disease undergoing PCI during 2008-11. The patients (N = 9,013) were randomized to receive either a drug-eluting stent or a bare-metal stent, and were treated with at least nine months of DAPT. The patients were followed for a median of five years, with Bleeding Academic Research Consortium (BARC) 3-5 major bleeding as one of the safety endpoints. We estimated cumulative incidence of major bleeding by a competing risks model and risk factors through cause-specific Cox models.

Results: The 12-month cumulative incidence of major bleeding was 2.3%. Independent risk factors for major bleeding were chronic kidney disease, low bodyweight (< 60 kilograms), diabetes mellitus, and advanced age (> 80 years). A myocardial infarction (MI) or PCI during follow-up increased the risk of major bleeding (HR = 1.67, 95% CI 1-29-2.15).

Conclusions: The 12-month cumulative incidence of major bleeding in NORSTENT was higher than reported in previous, explanatory trials. This analysis strengthens the role of chronic kidney disease, advanced age, and low bodyweight as risk factors for major bleeding among patients receiving DAPT after PCI. The presence of diabetes mellitus or recurrent MI among patients is furthermore a signal of increased bleeding risk.

Clinical Trial Registration: Unique identifier NCT00811772; http://www.clinicaltrial.gov.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247358PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932162PMC
August 2021

N-terminal pro-B-type natriuretic peptide as a prognostic indicator for 30-day mortality following out-of-hospital cardiac arrest: a prospective observational study.

BMC Cardiovasc Disord 2020 08 24;20(1):382. Epub 2020 Aug 24.

Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway.

Background: Early risk stratification applying cardiac biomarkers may prove useful in sudden cardiac arrest patients. We investigated the prognostic utility of early-on levels of high sensitivity cardiac troponin-T (hs-cTnT), copeptin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with out-of-hospital cardiac arrest (OHCA).

Methods: We conducted a prospective observational unicenter study, including patients with OHCA of assumed cardiac origin from the southwestern part of Norway from 2007 until 2010. Blood samples for later measurements were drawn during cardiopulmonary resuscitation or at hospital admission.

Results: A total of 114 patients were included, 37 patients with asystole and 77 patients with VF as first recorded heart rhythm. Forty-four patients (38.6%) survived 30-day follow-up. Neither hs-cTnT (p = 0.49), nor copeptin (p = 0.39) differed between non-survivors and survivors, whereas NT-proBNP was higher in non-survivors (p <  0.001) and significantly associated with 30-days all-cause mortality in univariate analysis, with a hazard ratio (HR) for patients in the highest compared to the lowest quartile of 4.6 (95% confidence interval (CI), 2.1-10.1), p <  0.001. This association was no longer significant in multivariable analysis applying continuous values, [HR 0.96, (95% CI, 0.64-1.43), p = 0.84]. Similar results were obtained by dividing the population by survival at hospital admission, excluding non-return of spontaneous circulation (ROSC) patients on scene [HR 0.93 (95% CI, 0.50-1.73), P = 0.83]. We also noted that NT-proBNP was significantly higher in asystole- as compared to VF-patients, p <  0.001.

Conclusions: Early-on levels of hs-cTnT, copeptin and NT-proBNP did not provide independent prognostic information following OHCA. Prediction was unaffected by excluding on-scene non-ROSC patients in the multivariable analysis.

Trial Registration: ClinicalTrials. gov, NCT02886273 .
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http://dx.doi.org/10.1186/s12872-020-01630-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445901PMC
August 2020

Initial Phase NT-proBNP, but Not Copeptin and High-Sensitivity Cardiac Troponin-T Yielded Diagnostic and Prognostic Information in Addition to Clinical Assessment of Out-of-Hospital Cardiac Arrest Patients With Documented Ventricular Fibrillation.

Front Cardiovasc Med 2018 7;5:44. Epub 2018 Jun 7.

Division of Cardiology, Stavanger University Hospital, Stavanger, Norway.

Aim: Sudden cardiac arrest (SCA) secondary to ventricular fibrillation (VF) may be due to different cardiac conditions. We investigated whether copeptin, hs-cTnT and NT-proBNP in addition to clinical assessment may help to identify the etiology of SCA and yield prognostic information.

Methods And Results: EDTA-blood was collected prior to or at hospital admission from patients with SCA of assumed cardiac origin. Clinical data were obtained from hospital records. VF was the primary heart rhythm in 77 patients who initially were divided into 2 groups based on whether they had an ischemic or non-ischemic mechanism as the most likely cause of SCA. They were further divided into 4 groups according to whether or not they had a history of previous heart disease. The patients were categorized by baseline clinical information, ECG, echocardiography and coronary angiography; Group 1 (n = 43): SCA with first AMI, Group 2 (n = 10): SCA with AMI and previous MI, Group 3 (n = 3): SCA without AMI and without former heart disease, Group 4 (n = 18): SCA without AMI and with known heart disease. Copeptin and hs-cTNT did not differ between patient groups, whereas NT-proBNP was significantly higher in patients with established heart disease without AMI and differed between non-AMI and AMI. Furthermore, NT-proBNP was significantly elevated in non-survivors as compared to survivors.

Conclusion: NT-proBNP provided both diagnostic and prognostic information in blood samples collected close to out-of-hospital resuscitation of VF patients, whereas copeptin and hs-cTnT failed to do so.

Clinical Trial Registration: ClinicalTrials.gov, NCT02886273.
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http://dx.doi.org/10.3389/fcvm.2018.00044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001003PMC
June 2018

Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles.

J Am Heart Assoc 2018 04 12;7(8). Epub 2018 Apr 12.

Department of Clinical Science, University of Bergen, Norway.

Background: Although choline metabolism has been associated with atherosclerotic heart disease, less research attention has been paid to the associations of choline and its oxidative metabolite betaine with cardiac arrhythmias.

Methods And Results: We evaluated associations of plasma concentrations and dietary intakes of choline and betaine with long-term atrial fibrillation (AF) risk in a community-based cohort, HUSK ([the Hordaland Health Study] n=6949), and validated the findings in 2 patient cohorts: the Western Norway Coronary Angiography Cohort (n=4164) and the NORVIT (Norwegian B-Vitamin) Trial (n=3733). Information on AF was obtained from the CVDNOR (Cardiovascular Disease in Norway) project. In HUSK, WECAC (Western Norway Coronary Angiography Cohort), and NORVIT, 552, 411, and 663 AF cases were identified during a median follow-up time of 10.9, 7.3, and, 8.7 years, respectively. Plasma concentrations of choline and betaine were significantly positively associated with later AF risk after multivariable adjustments in HUSK. Such associations were independently replicated in the 2 external prospective patient cohorts. The pooled hazard ratio was 1.13 (95% confidence interval 1.08-1.19, <0.001) and 1.16 (95% confidence interval 1.10-1.22, <0.001) per SD increment for log-transformed choline and betaine, respectively. Moreover, dietary intake of choline was marginally associated with AF risk (pooled hazard ratio 1.29, 95% confidence interval 1.01-1.66, fifth versus first quintile), whereas no significant association was observed between dietary betaine and AF risk.

Conclusions: Our findings indicate that plasma concentrations as well as dietary intake of choline, but not betaine, are associated with subsequent risk of AF, suggesting a potential role of choline metabolism in the pathogenesis of AF.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov.Unique identifier: NCT00671346.
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http://dx.doi.org/10.1161/JAHA.117.008190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015426PMC
April 2018

Fibrinogen and Neopterin Is Associated with Future Myocardial Infarction and Total Mortality in Patients with Stable Coronary Artery Disease.

Thromb Haemost 2018 04 19;118(4):778-790. Epub 2018 Feb 19.

Department of Clinical Science, University of Bergen, Bergen, Norway.

Systemic fibrinogen and neopterin are related to inflammation. We investigated the prognostic utility and possible interactions of these biomarkers in stable coronary artery disease (SCAD) patients undergoing coronary angiography. We included 3,545 patients with suspected stable angina with a median follow-up of 7.3 and 10.2 years for incident acute myocardial infarction (AMI) and all-cause mortality, respectively. Prospective associations were explored by Cox regression. Potential effect modifications were investigated according to strata of fibrinogen, neopterin or high-sensitivity troponin T (hsTnT) below and above the median, as well as gender and smoking habits. During follow-up, 543 patients experienced an AMI and 769 patients died. In a multivariable model, the hazard ratios (HRs; 95% confidence interval [CI]) per 1 SD increase for fibrinogen in relation to these endpoints were 1.30 (1.20, 1.42;  < 0.001) and 1.22 (1.13, 1.31;  < 0.001), respectively. For neopterin, the HRs (95% CI) were 1.31 (1.23, 1.40;  < 0.001) and 1.24 (1.15, 1.34;  < 0.001), respectively. No significant interaction between fibrinogen and neopterin was observed. The prognostic utility of neopterin for incident AMI was improved in patients with an hsTnT above the median, for total mortality in non-smokers, and for both total mortality and AMI in females. In conclusion, both fibrinogen and neopterin were associated with future AMI and total mortality, but had low discriminatory impact. No interaction was observed between these two biomarkers. The prognostic utility of neopterin was improved in patients with hsTnT levels above the median, and in females and non-smokers.
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http://dx.doi.org/10.1055/s-0038-1629912DOI Listing
April 2018

The prognostic utility of dihomo-gamma-linolenic acid (DGLA) in patients with acute coronary heart disease.

Int J Cardiol 2017 Dec 29;249:12-17. Epub 2017 Sep 29.

Department of Medicine, Stavanger University Hospital, 4068 Stavanger, Norway; Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.

Background: We previously investigated the prognostic utility of red blood cell (RBC) n-3 fatty acids (FAs) in survivors of an acute myocardial syndrome (ACS) but found no relationship with all-cause mortality and cardiac death or MI after two years. Here we extend our follow-up to 7years, focusing on the potential predictive power of RBC n-6 FAs.

Methods: We included 398 ACS patients presenting with increased troponin-T (TnT) levels for whom baseline RBC FA data were available. Cox regression analysis was used to relate the risk of future events to RBC n-6 FA levels, both continuously and by quartile.

Results: At 7-year follow-up, 183 (46.0%) had died, 128 (32.2%) had experienced another MI and 24 (6.0%) had had a stroke. Death or MI occurred in 227 patients (57.0%); and death, MI or stroke in 235 patients (59.0%). In a multivariable Cox regression model for total death, the hazard ratio (HR) in the highest as compared to the lowest quartile of dihomo-γ-linolenic acid (DGLA) was 0.55 [95% confidence interval (CI), 0.35-0.88, p=0.012, for death or MI [HR 0.62 (95% CI, 0.41-0.94), p=0.025], and for the fully combined endpoint [HR 0.57 (95% CI, 0.38-0.86), p=0.006]. Similar results were found in the per 1-SD analysis. No other RBC n-6 FAs significantly predicted these outcomes in multivariable models.

Conclusion: RBC DGLA levels had significant independent prognostic value in post-ACS patients. These findings need confirmation, and the possible biochemical pathways by which higher DGLA membrane levels may be cardioprotective should be explored.
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http://dx.doi.org/10.1016/j.ijcard.2017.09.202DOI Listing
December 2017

Vitamin D Uptake in Patients Treated with a High-Dosed Purified Omega-3 Compound in a Randomized Clinical Trial Following an Acute Myocardial Infarction.

Front Cardiovasc Med 2017 24;4:41. Epub 2017 Jul 24.

Department of Cardiology, Stavanger University Hospital, Stavanger, Norway.

Background: Fish is the natural dietary source of vitamin D. Reports on the influence of purified omega-3 fatty acids on its uptake are scarce.

Objectives: We investigated the impact of a purified high-dose omega-3 compound compared to corn oil on 25-hydroxyvitamin D [25(OH)D] levels following an acute myocardial infarction.

Methods: 228 patients were randomized 1:1 to receive a daily dose of either 4 g omega-3 (OMACOR) or an equal dose of corn oil, administered double-blindly for 12 months. Total omega-3 and omega-6 measurements were available in 40 randomly picked patients.

Results: There was no significant intergroup difference in 25(OH)D changes at 12 months follow-up ( = 0.12), but there was a minor statistical significant intragroup increase in 25(OH)D in both intervention arms ( < 0.001 for n-3 polyunsaturated fatty acids and  = 0.013 for corn oil, respectively). A positive correlation was noted between 25(OH)D and omega-3 prior to inclusion;  = 0.418,  = 0.007, attenuated at 12 months by purified omega-3 intervention;  = 0.021,  = 0.93. No positive correlation was observed between omega-6 and 25(OH)D.

Conclusion: Long-term treatment with a high dose of purified omega-3 as compared to corn oil did not improve serum concentrations of vitamin D.

Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT01422317.
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http://dx.doi.org/10.3389/fcvm.2017.00041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522877PMC
July 2017

Suggested Cut-Off Values for Vitamin D as a Risk Marker for Total and Cardiac Death in Patients with Suspected Acute Coronary Syndrome.

Front Cardiovasc Med 2016 26;3. Epub 2016 Feb 26.

Department of Cardiology, Stavanger University Hospital, Stavanger, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.

Background: Several studies have demonstrated an association between low vitamin D levels and cardiovascular risk. Vitamin D cut-off levels are still under debate.

Objectives: To assess two cut-off levels, 40 and 70 nmol/L, respectively, for vitamin D measured as 25-hydroxyvitamin D in chest pain patients with suspected acute coronary syndrome.

Methods: We investigated 1853 patients from coastal-Norway and inland Northern-Argentina. A similar database was used for pooling of data. Two-year follow-up data including all-cause mortality, cardiac death, and sudden cardiac death in the total patient population were analyzed, applying univariate and multivariable analysis.

Results: Two hundred fifty-five patients with known vitamin D concentrations died. In the multivariable analysis, there was a decrease in total mortality above a cut-off level of 40 nmol/L and a decrease in cardiac death above a cut-off level of 70 nmol/L [HRs of 0.66 (95% CI, 0.50-0.88), p = 0.004 and 0.46 (95% CI, 0.22-0.94), p = 0.034, respectively].

Conclusion: Vitamin D cut-off levels of 40 and 70 nmol/L were related to total mortality and cardiac death, respectively.
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http://dx.doi.org/10.3389/fcvm.2016.00004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767896PMC
March 2016

Borderline Values of Troponin-T and High Sensitivity C-Reactive Protein Did Not Predict 2-Year Mortality in TnT Positive Chest-Pain Patients, Whereas Brain Natriuretic Peptide Did.

Front Cardiovasc Med 2015 8;2:16. Epub 2015 Apr 8.

Department of Research, Stavanger University Hospital , Stavanger , Norway ; Department of Clinical Medicine, University of Bergen , Bergen , Norway.

Background: Troponin-T (TnT), high-sensitive C-reactive protein (hsCRP), and Brain Natriuretic Peptide (BNP) have been shown to be independent prognostic indicators of total and cardiac death during short- and long-term follow-up.

Methods: We investigated prospectively the prognostic value of admission samples of TnT, hsCRP, and BNP in 871 chest-pain patients from South-Western Norway and 982 patients from Northern Argentina, based on a similar protocol and database setup. Follow-up was 2 years for the pooled population. The prognostic value of the selected biomarkers was investigated in quartiles of 239 patients with TnT values greater than 0.01 and up to and including 0.1 ng/mL, with continuous TnT as a potential confounder.

Results: After 24 months, 69 patients had died, of whom 38 died from cardiac causes. In the selected range of TnT, this biomarker was not significantly different between patients who died and survived (mean 0.0452 and 0.0457, p = 0.887). The BNP levels were significantly higher among patients dying than in long-term survivors [340 (142-656) versus 157 (58-367) pg/mL (median, 25 and 75% percentiles), p < 0.001]. In a multivariable Cox regression model for death within 2 years, the hazard ratio (HR) for BNP in the highest quartile (Q4) as compared to the lowest (Q1) was significantly related to total mortality [HR 2.84 (95% confidence interval (CI), 1.13-7.17)], p = 0.027, in addition to age (p ≤ 0.001) and hypercholesterolemia (p = 0.043). For cardiac death, the HR for BNP was 5.18 (95% CI, 1.06-25.3), p = 0.042. Several other variables (age, congestive heart failure, ST elevation myocardial infarction, and study country) were also significantly related to cardiac death. In a multivariable Cox regression model, hsCRP rendered no significant prognostic information for all-cause mortality (p = 0.089) or for cardiac mortality (p = 0.524).

Conclusion: In patients with borderline TnT values (greater than 0.01 and up to and including 0.1 ng/mL), this biomarker as well as hsCRP did not render prognostic information, whereas BNP was found to be a strong prognostic indicator of 2-year total and cardiac mortality.
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http://dx.doi.org/10.3389/fcvm.2015.00016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671363PMC
December 2015

Use of Loop Diuretics is Associated with Increased Mortality in Patients with Suspected Coronary Artery Disease, but without Systolic Heart Failure or Renal Impairment: An Observational Study Using Propensity Score Matching.

PLoS One 2015 1;10(6):e0124611. Epub 2015 Jun 1.

Department of Heart Disease, Haukeland University Hospital, Bergen, Norway; Section for Cardiology, Department of Clinical Science, University of Bergen, Bergen, Norway.

Background: Loop diuretics are widely used in patients with heart and renal failure, as well as to treat hypertension and peripheral edema. However, there are no randomized, controlled trials (RCT) evaluating their long term safety, and several observational reports have indicated adverse effects. We sought to evaluate the impact of loop diuretics on long term survival in patients with suspected coronary artery disease, but without clinical heart failure, reduced left ventricular ejection fraction or impaired renal function.

Method And Findings: From 3101 patients undergoing coronary angiography for suspected stable angina pectoris, subjects taking loop diuretics (n=109) were matched with controls (n=198) in an attempted 1:2 ratio, using propensity scores based on 59 baseline variables. During median follow-up of 10.1 years, 37.6% in the loop diuretics group and 23.7% in the control group died (log-rank p-value 0.005). Treatment with loop diuretics was associated with a hazard ratio (95% confidence interval) of 1.82 (1.20, 2.76), and the number needed to harm was 7.2 (4.1, 30.3). Inclusion of all 3101 patients using propensity score weighting and adjustment for numerous covariates provided similar estimates. The main limitation is the potential of confounding from unmeasured patient characteristics.

Conclusions: The use of loop diuretics in patients with suspected coronary artery disease, but without systolic heart failure or renal impairment, is associated with increased risk of all-cause mortality. Considering the lack of randomized controlled trials to evaluate long term safety of loop diuretics, our data suggest caution when prescribing these drugs to patients without a clear indication.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124611PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452510PMC
March 2016

Glycated hemoglobin and long-term prognosis in patients with suspected stable angina pectoris without diabetes mellitus: a prospective cohort study.

Atherosclerosis 2015 May 28;240(1):115-20. Epub 2015 Feb 28.

Department of Heart Disease, Haukeland University Hospital, 5021 Bergen, Norway; Department of Clinical Science, University of Bergen, Mailbox 7804, 5021 Bergen, Norway; K. G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Mailbox 7804, 5021 Bergen, Norway. Electronic address:

Objective: Associations of glycated hemoglobin A1c (HbA1c) levels to incident coronary and cardiovascular events among non-diabetic patients with coronary artery disease are unclear. We investigated relations of HbA1c to long-term prognosis in such patients.

Methods: A prospective cohort of 2519 patients undergoing elective coronary angiography for suspected stable angina pectoris (SAP) was divided into pre-defined categories according to HbA1c (%) levels (<5.0, 5.0-5.6 (reference), 5.7-6.4), and followed for median 4.9 years. The primary end-point was major coronary events (including non-fatal and fatal acute myocardial infarctions, and sudden cardiac death). Secondary end-points were death from cardiovascular disease (CVD) and all-cause mortality. Hazard ratios (HRs) (95% confidence intervals [CIs]) were obtained by Cox regression.

Results: Median age at inclusion was 62 years, 73% were males, median HbA1c was 5.6% and random plasma-glucose 5.4 mmol/L. After multivariate adjustment, HbA1c levels within the pre-diabetic range were not associated with risk of major coronary events, HR (95% CI): 1.13 (0.79-1.62); P=0.49, death from CVD or all-cause mortality HR (95% CI): 0.95 (0.55-1.66) and 1.04 (0.70-1.53), respectively; P≥0.85. Similarly, there was no significant association between HbA1c values within the lowest category and risk of study outcomes, (P≥0.18).

Conclusion: In non-diabetic patients with suspected SAP, there was no overall association between HbA1c levels and prognosis, questioning an independent role of glycemia in the pathogenesis of atherosclerotic complications in these patients.
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http://dx.doi.org/10.1016/j.atherosclerosis.2015.02.053DOI Listing
May 2015

Prognostic utility of vitamin D in acute coronary syndrome patients in coastal Norway.

Dis Markers 2015 5;2015:283178. Epub 2015 Feb 5.

Department of Cardiology, Stavanger University Hospital, Stavanger, Norway ; Department of Clinical Science, University of Bergen, Bergen, Norway.

Background: An inverse relationship between cardiovascular risk and levels of vitamin D and omega-3 index may exist.

Objectives: To evaluate the prognostic utility of serum 25-hydroxyvitamin D [25(OH)D] in 871 patients with suspected acute coronary syndrome (ACS) and to assess the seasonal correlation between 25(OH)D and the omega-3 index in 456 ACS patients from southwestern Norway.

Results: In the univariate analysis the hazard ratio (HR) at 2-year follow-up for all-cause mortality in the highest as compared to the lowest quartile of 25(OH)D in the total population was 0.61 (95% confidence interval (CI), 0.37-1.00), P = 0.050. At 7-year follow-up, the corresponding HR for all-cause mortality was 0.66 (95% CI, 0.49-0.90), P = 0.008, and for females alone 0.51 (95% CI, 0.32-0.83), P = 0.006. Quartile survival did not differ in the multivariable analysis, whereas 25(OH)D < 40 nM (<16 ng/mL) was found to be independently related to mortality. Seasonal differences in 25(OH)D, but not for the omega-3 index, were noted, and the two biomarkers were positively correlated, especially during winter-spring; Pearson's correlation coefficient was 0.358, P < 0.001.

Conclusion: Vitamin D levels are related to survival, especially in females, and correlate with the omega-3 index.
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http://dx.doi.org/10.1155/2015/283178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334438PMC
October 2015

Elevated plasma dimethylglycine is a risk marker of mortality in patients with coronary heart disease.

Eur J Prev Cardiol 2015 Jun 26;22(6):743-52. Epub 2014 Mar 26.

Department of Clinical Science, University of Bergen, Norway Department of Heart Disease, Haukeland University Hospital, Bergen, Norway KG Jebsen Centre for Diabetes Research, Bergen, Norway.

Aim: To investigate whether plasma dimethylglycine was associated with and improved risk prediction of mortality among patients with coronary heart disease (CHD).

Methods: By Cox modelling, we explored the association between plasma dimethylglycine and mortality in two independent cohorts of patients with suspected stable angina pectoris (SAP) (n = 4156) and acute myocardial infarction (AMI) (n = 3733). We also assessed any improvement in risk prediction by adding plasma dimethylglycine to established CHD risk factors.

Results: Median follow-up time was 4.7 and 7.0 years among patients with SAP and AMI, respectively. Across both cohorts, elevated plasma dimethylglycine levels were linearly associated with increased risk of all-cause mortality (age and gender adjusted hazard ratios (95% confidence interval, CI) were 1.72 (1.21-2.46) and 1.76 (1.42-2.18) when comparing the fourth versus the first plasma dimethylglycine quartile in patients with SAP and AMI, respectively). There was a particularly strong risk association between plasma dimethylglycine and cardiovascular, as compared with non-cardiovascular, mortality (age and gender adjusted hazard ratios (95% CI) 1.94 (1.21-3.11) and 1.43 (0.83-2.47) among patients with SAP and 1.97 (1.50-2.59) and 1.44 (1.02-2.04) among patients with AMI, respectively). The relationship between dimethylglycine and all-cause and cardiovascular mortality was only slightly attenuated in analyses adjusted for established CHD risk factors. Plasma dimethylglycine also improved risk prediction for all-cause and cardiovascular mortality, and especially among patients with AMI.

Conclusions: Elevated plasma dimethylglycine was associated with and improved risk prediction of mortality in patients with suspected or verified CHD. This relationship was stronger for death from cardiovascular, as compared with non-cardiovascular, causes.
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http://dx.doi.org/10.1177/2047487314529351DOI Listing
June 2015

Comparison of outcomes in patients with ST-segment elevation myocardial infarction discharged on versus not on statin therapy (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trial).

Am J Cardiol 2014 Apr 31;113(8):1273-9. Epub 2014 Jan 31.

Cardiovascular Research Foundation, New York, New York; Division of Cardiology, Columbia University Medical Center, New York, New York.

Statin therapy is indicated after ST-segment elevation myocardial infarction (STEMI) to reduce recurrent ischemic events, but approximately 6% of patients with STEMI do not receive a statin prescription at discharge. This substudy aimed to define the clinical outcomes and patient characteristics associated with statin nonprescription after STEMI. We compared clinical, angiographic, and procedural characteristics and in-hospital, 30-day, 1-year, 2-year, and 3-year outcomes in 3,512 patients discharged after STEMI with and without (6%) statin prescriptions in the harmonizing outcomes with revascularization and stents in acute myocardial infarction trial (www.clinicaltrials.gov, NCT00433966). Statin nonprescription was associated with female sex, nonwhite race, previous bypass surgery, heart failure, renal impairment, anemia, thrombocytopenia, care in the United States, lower prescription rates of antiplatelets and neurohormonal antagonists, less percutaneous coronary intervention and stents, and, in 26% of cases, angiographically normal or nonobstructed coronary arteries. At every time point of follow-up after discharge, patients with no discharge statin prescription had significantly higher rates of net adverse clinical events, major adverse cardiac events, major bleeding unrelated to bypass surgery, and death. After multivariable adjustment, absence of a discharge statin prescription independently predicted 3-year major adverse cardiac event (hazard ratio 1.54, 95% confidence interval 1.15 to 2.07, p=0.0037) and death (hazard ratio 2.30, 95% confidence interval 1.41 to 3.77, p=0.0009). In conclusion, within the framework of this randomized trial of patients presenting with STEMI, approximately 6% of patients were discharged without statin therapy. Absence of a discharge statin prescription after STEMI was an independent predictor of ischemic events including death.
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http://dx.doi.org/10.1016/j.amjcard.2014.01.401DOI Listing
April 2014

Vitamin d predicts all-cause and cardiac mortality in females with suspected acute coronary syndrome: a comparison with brain natriuretic Peptide and high-sensitivity C-reactive protein.

Cardiol Res Pract 2013 17;2013:398034. Epub 2013 Nov 17.

Department of Cardiology, Stavanger University Hospital, 4068 Stavanger, Norway ; Cardiology Research Institute, Catholic University of Salta, A4400ANG Salta, Argentina.

Vitamin D may not only reflect disease but may also serve as a prognostic indicator. Our aim was to assess the gender-specific utility of vitamin D measured as 25-hydroxy-vitamin D [25(OH)D] to predict all-cause and cardiac death in patients with suspected acute coronary syndrome (ACS) and to compare its prognostic utility to brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hsCRP). Blood samples were harvested on admission in 982 patients. Forty percent were women (65.9 ± 12.6 years). Mortality was evaluated in quartiles of 25(OH)D, BNP, and hsCRP, respectively, during a 5-year follow-up, applying univariate and multivariate analyses. One hundred and seventy-three patients died; 78 were women. In 92 patients (37 women), death was defined as cardiac. In women, the univariate hazard ratio (HR) for total death of 25(OH)D in Quartile (Q) 2 versus Q1, Q3 versus Q1, and Q4 versus Q1 was 0.55 (95% CI 0.33-0.93), 0.29 (95% CI 0.15-0.55), and 0.13 (95% CI 0.06-0.32), respectively. In females, it was an independent predictor of total and cardiac death, whereas BNP and hsCRP were less gender-specific. No gender differences in 25(OH)D were noted in a reference material. Accordingly, vitamin D independently predicts mortality in females with suspected ACS.
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http://dx.doi.org/10.1155/2013/398034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855936PMC
December 2013

Dietary intake of n-3 long-chain polyunsaturated fatty acids and risk of myocardial infarction in coronary artery disease patients with or without diabetes mellitus: a prospective cohort study.

BMC Med 2013 Oct 8;11:216. Epub 2013 Oct 8.

Department of Clinical Science, University of Bergen, 5021 Bergen, Norway.

Background: A beneficial effect of a high n-3 long-chain polyunsaturated fatty acid (LCPUFA) intake has been observed in heart failure patients, who are frequently insulin resistant. We investigated the potential influence of impaired glucose metabolism on the relation between dietary intake of n-3 LCPUFAs and risk of acute myocardial infarction (AMI) in patients with coronary artery disease.

Methods: This prospective cohort study was based on the Western Norway B-Vitamin Intervention Trial and included 2,378 patients with coronary artery disease with available baseline glycosylated hemoglobin (HbA1c) and dietary data. Patients were sub-grouped as having no diabetes (HbA1c <5.7%), pre-diabetes (HbA1c ≥5.7%), or diabetes (previous diabetes, fasting baseline serum glucose ≥7.0, or non-fasting glucose ≥11.1 mmol/L). AMI risk was evaluated by Cox regression (age and sex adjusted), comparing the upper versus lower tertile of daily dietary n-3 LCPUFA intake.

Results: The participants (80% males) had a mean age of 62 and follow-up of 4.8 years. A high n-3 LCPUFA intake was associated with reduced risk of AMI (hazard ratio 0.38, 95%CI 0.18, 0.80) in diabetes patients (median HbA1c = 7.2%), whereas no association was observed in pre-diabetes patients. In patients without diabetes a high intake tended to be associated with an increased risk (hazard ratio1.45, 95%CI 0.84, 2.53), which was significant for fatal AMI (hazard ratio 4.79, 95%CI 1.05, 21.90) and associated with lower HbA1c (mean ± standard deviation 4.55 ±0.68 versus 4.92 ±0.60, P = 0.02). No such differences in HbA1c were observed in those with pre-diabetes or diabetes.

Conclusions: A high intake of n-3 LCPUFAs was associated with a reduced risk of AMI, independent of HbA1c, in diabetic patients, but with an increased risk of fatal AMI and lower HbA1c among patients without impaired glucose metabolism. Further studies should investigate whether patients with diabetes may benefit from having a high intake of n-3 LCPUFAs and whether patients with normal glucose tolerance should be careful with a very high intake of these fatty acids.

Trial Registration: This trial is registered at clinicaltrials.gov as NCT00354081.
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http://dx.doi.org/10.1186/1741-7015-11-216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853070PMC
October 2013

Socioeconomic assessment and impact of social security on outcome in patients admitted with suspected coronary chest pain in the city of salta, Argentina.

Cardiol Res Pract 2013 29;2013:807249. Epub 2013 May 29.

Department of Cardiology, Stavanger University Hospital, Postboks 8100, 4068 Stavanger, Norway ; Institute of Medicine, University of Bergen, Postboks 7804, 5020 Bergen, Norway ; Cardiology Research Institute, Catholic University of Salta, España 311, A4400ANG Salta, Argentina.

Low socioeconomic status is associated with increased mortality from coronary heart disease. We assessed total mortality, cardiac death, and sudden cardiac death (SCD) in relation to socioeconomic class and social security in 982 patients consecutively admitted with suspected coronary chest pain, living in the city of Salta, northern Argentina. Patients were divided into three socioeconomic classes based on monthly income, residential area, and insurance coverage. Five-year follow-up data were analyzed accordingly, applying univariate and multivariate analyses. At follow-up, 173 patients (17.6%) had died. In 92 patients (9.4%) death was defined as cardiac, of whom 59 patients (6.0%) were characterized as SCD. In the multivariate analysis, the hazard ratios (HRs) for all-cause and cardiac mortality in the highest as compared to the lowest socioeconomic class were 0.42 (95% confidence interval (CI), 0.22-0.80), P = 0.008, and 0.39 (95% CI, 0.15-0.99), P = 0.047, respectively. Comparing patients in the upper socioeconomic class to patients without healthcare coverage, HRs were 0.46 (95% CI, 0.23-0.94), P = 0.032, and 0.37 (95% CI, 0.14-1.01), P = 0.054, respectively. In conclusion, survival was mainly tied to socioeconomic inequalities in this population, and the impact of a social security program needs further attention.
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http://dx.doi.org/10.1155/2013/807249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681265PMC
July 2013

Potential benefits of ticagrelor beyond platelet inhibition.

Cardiology 2013 20;125(1):31-3. Epub 2013 Apr 20.

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http://dx.doi.org/10.1159/000350358DOI Listing
October 2013

Long-term prognostic utility of PAPP-A and calprotectin in suspected acute coronary syndrome.

Scand Cardiovasc J 2013 Apr 13;47(2):88-97. Epub 2013 Feb 13.

Department of Medicine, Stavanger University Hospital, Stavanger, Norway.

Background: Vascular inflammation plays a key role in the development of acute coronary syndrome (ACS). Pregnancy-associated plasma protein A (PAPP-A) and calprotectin are two of several novel promising markers of inflammation. The present study evaluates the prognostic utility of these two biomarkers in patients with suspected ACS.

Methods: Chest pain patients with suspected ACS (N = 871) were consecutively included in a prospective, observational study with a mean follow-up time of 84 months. Blood samples were drawn at admission, prior to treatment with heparin.

Results: Total mortality was 38.9%. In univariate analyses, high PAPP-A levels were associated with significant increased mortality. The hazard ratio [HR] in quartile (Q) 3 and Q4 were 1.57 (95% confidence interval (CI), 1.14-2.18), p = 0.006, and 1.41 [95% CI 1.02-1.97], p = 0.040, respectively, as compared to Q1. Calprotectin in the upper quartile (Q4) was associated with total mortality [HR1.94 (95% CI 1.42-2.66)], p = < 0.001, the combined endpoint of death or recurrent myocardial infarction (MI) [HR 1.68 (95% CI 1.26-2.24), p = < 0.001], and recurrent MI [HR 1.60 (95% CI 1.06-2.41); p = 0.024]. However, neither PAPP-A nor calprotectin was found to be an independent predictor of future adverse events.

Conclusion: In this study, high levels of PAPP-A and calprotectin were associated with adverse clinical outcome in chest pain patients with clinically suspected ACS. However, neither of the two biomarkers was an independent predictor of long-term prognosis.
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http://dx.doi.org/10.3109/14017431.2013.764571DOI Listing
April 2013

Omega-3 Status and the Relationship between Plasma Asymmetric Dimethylarginine and Risk of Myocardial Infarction in Patients with Suspected Coronary Artery Disease.

Cardiol Res Pract 2012 31;2012:201742. Epub 2012 Dec 31.

Institute of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.

Background. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. A previous rat study revealed an ADMA lowering effect following treatment with omega-3 polyunsaturated fatty acids (n-3 PUFAs). We sought to examine if an association between plasma ADMA and risk of acute myocardial infarction (AMI) was modified by serum n-3 PUFA status. Methods. The cohort included 1364 patients who underwent coronary angiography for suspected coronary artery disease in 2000-2001. Fatal and nonfatal AMI events were registered until December 31, 2006. Risk associations with AMI were estimated across ADMA quartiles (linear trend) and the upper decile. Results. No association between concentration of any n-3 PUFA and ADMA was observed. Only ADMA levels in upper decile were significantly associated with AMI with a multivariate adjusted hazard ratio (HR) (95% confidence interval) versus the rest of the population of 2.11 (1.34, 3.32). The association was strengthened among patients with below median levels of α-linolenic acid (ALA) (HR 3.12 (1.64, 5.93)), but was only influenced by longer chain n-3 PUFA after additional adjustments for HbA1c, estimated glomerular filtration rate, and hypercholesterolemia. Conclusions. The association of ADMA with risk of AMI is influenced by serum n-3 PUFA and particularly ALA.
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http://dx.doi.org/10.1155/2012/201742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549394PMC
January 2013

Cardiac resynchronization therapy improves minute ventilation/carbon dioxide production slope and skeletal muscle capillary density without reversal of skeletal muscle pathology or inflammation.

Europace 2013 Jun 15;15(6):857-64. Epub 2013 Jan 15.

Department of Cardiology, Stavanger University Hospital, N-4001 Stavanger, Norway.

Aims: We evaluated the effects of cardiac resynchronization therapy (CRT) on skeletal muscle pathology and inflammation in patients with heart failure.

Methods And Results: Stable patients (n = 21, 14 males, mean age 70 ± 7 years) with symptomatic heart failure (mean left ventricular ejection fraction 24 ± 6%) and an indication for CRT were included. Ergospirometry, skeletal muscle open biopsy, and blood sampling were performed prior to implantation and after 6 months of CRT. After CRT there was a reduction in both left ventricular end-diastolic diameter (LVEDD; 6.8 ± 0.8 vs. 6.3 ± 0.7 cm, P < 0.001) and native QRS duration (D) minus biventricular paced QRSD (172.9 ± 23 vs. 136.3 ± 23 ms, P ≤ 0.001). These changes were associated with an increase in peak slope oxygen uptake (consumption) (VO₂) (13.3 ± 2.2 vs. 14.5 ± 2.6 mL/kg/min, P = 0.07) and an improvement in the minute ventilation/carbon dioxide production slope (VE/VCO₂) slope (41.6 ± 7.4 vs. 39.1 ± 5.6, P = 0.012). There were no statistically significant changes in levels of pro-inflammatory cytokines, in mediators of mitochondrial biosynthesis or skeletal muscle pathology, except for an increase in skeletal muscle capillary density (4.5 ± 2.4 vs. 7.7 ± 3.3%, P = 0.002). Both the reduction of QRS duration and the increase in peak VO₂ correlated significantly with the change in mitochondrial density (r = 0.57, P = 0.008 and r = 0.54, P = 0.027, respectively).

Conclusion: Cardiac resynchronization therapy, with improved functional status and reduced LVEDD resulted in increased peak VO₂, improvement in VE/VCO₂ slope and capillary density in skeletal muscle, with no reduction in systemic pro-inflammatory cytokines, increase in intramuscular levels of mediators of mitochondrial biosynthesis or improvement in skeletal muscle ultrastructure per se. ClinicalTrials.gov Identifier: NCT01019915.
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http://dx.doi.org/10.1093/europace/eus428DOI Listing
June 2013

The role of long-chained marine N-3 polyunsaturated Fatty acids in cardiovascular disease.

Cardiol Res Pract 2012 13;2012:303456. Epub 2012 Dec 13.

Department of Medicine, Stavanger University Hospital, 4011 Stavanger, Norway.

This paper reviews the current evidence regarding long-chained marine omega-3 polyunsaturated fatty acids (PUFAs) and cardiovascular disease (CVD), their possible mechanisms of action, and results of clinical trials. Also, primary and secondary prevention trials as studies on antiarrhythmic effects and meta-analyses are summarized. However, the individual bioavailability of n-3 PUFAs along with the highly different study designs and estimations of FAs intake or supplementation dosages in patient populations with different background intake of n-3 PUFAs might be some of the reasons for the inconsistent findings of the studies evaluating the impact of n-3 PUFAs on CVD. The question of an optimum dose of n-3 PUFAs or whether there exists a dose-response relation for n-3 PUFA supplementation is widely discussed. Moreover, the difficulties in interpreting meta-analyses are clearly demonstrated by two recently published meta-analyses (Rizos et al. and Delgado Lista et al.), evaluating the efficacy of n-3 PUFAs on CVD, including 12 common studies, but drawing opposite conclusions. We definitely need more large-scale, randomized clinical trials of long duration, also reporting harmful effects of n-3 PUFAs.
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http://dx.doi.org/10.1155/2012/303456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532917PMC
January 2013

Long-term prognosis of patients presenting with ST-segment elevation myocardial infarction with no significant coronary artery disease (from the HORIZONS-AMI trial).

Am J Cardiol 2013 Mar 19;111(5):643-8. Epub 2012 Dec 19.

Department of Cardiology, Stavanger University Hospital, Stavanger, Norway.

The clinical features and prognosis of patients with ST-segment elevation myocardial infarction (STEMI) and no significant coronary artery disease (CAD) have not been well studied. We examined the outcomes of patients with STEMI in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial according to the presence or absence of significant CAD. "No-CAD" was defined by the absence of any lesion with a diameter stenosis of ≥30% on quantitative coronary angiography of the baseline coronary angiogram. Of 3,602 patients, 127 (3.5%) had no-CAD. Of these, 86 (67.7%) had angiographically normal coronary arteries, and 41 (32.3%) had mild disease (diameter stenosis <30%). Eight patients had previously been treated with coronary artery bypass grafting. Compared to patients with CAD, patients with no-CAD were younger, had a lower body mass index, were more frequently black, had a lower prevalence of smoking and previous angina, and had a greater left ventricular ejection fraction. Cardiac enzymes were elevated in fewer patients with no-CAD than in those with CAD (63.2% vs 98.7%, p <0.001). At 3 years of follow-up, the patients with no-CAD versus CAD had lower rates of major adverse cardiovascular events (7.7% vs 22.2%, p = 0.002), net adverse clinical events (major adverse cardiovascular events or major bleeding not related to coronary artery bypass grafting, 12.5% vs 26.9%, p = 0.005), and postprocedure coronary revascularization (0% vs 19.5%, p <0.001). The differences in the rates of death or reinfarction, stroke, and major bleeding were not statistically significant. In conclusion, 3.5% of patients with STEMI had no significant CAD. The 3-year prognosis for these patients was favorable compared to that of patients with STEMI and with obstructive CAD.
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http://dx.doi.org/10.1016/j.amjcard.2012.11.011DOI Listing
March 2013

Omega-3 index and prognosis in acute coronary chest pain patients with a low dietary intake of omega-3.

Scand Cardiovasc J 2013 Apr 12;47(2):69-79. Epub 2012 Dec 12.

Cardiology Research Institute, Catholic University of Salta, Salta, Argentina.

Background: The omega-3 index (eicosapentaenoic acid + docosahexaenoic acid) content in red blood cell membranes has been suggested as a novel risk marker for cardiac death. Objective. To assess the ability of the omega-3 index to predict all-cause mortality, cardiac death and sudden cardiac death following hospitalization with an acute coronary syndrome (ACS), and to include arachidonic acid (AA) in risk assessment.

Material And Methods: The omega-3 index was measured in 572 consecutive patients (median 63 years and 59% males) admitted with chest pain and suspected ACS in an inland Northern Argentinean city with a dietary habit that was essentially based on red meat and a low intake of fish. Clinical endpoints were collected during a 5-year follow-up period, median 3.6 years, range 1 day to 5.5 years. Stepwise Cox regression analysis was employed to compare the rate of new events in the quartiles of the omega-3 index measured at inclusion. Multivariable analysis was performed.

Results: No statistical significant differences in baseline characteristics were noted between quartiles of the omega-3 index. The median of the adjusted omega-3 index was 3.6%. During the follow-up period, 100 (17.5%) patients died. Event rates were similar in all quartiles of the omega-3 index, with no statistical significant differences. AA added no prognostic information.

Conclusion: In a population with a low intake of fish and fish oils, the adjusted omega-3 index did not predict fatal events following hospitalization in patients with acute chest pain and suspected ACS.
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http://dx.doi.org/10.3109/14017431.2012.747220DOI Listing
April 2013

Coronary reperfusion and clinical outcomes after thrombus aspiration during primary percutaneous coronary intervention: findings from the HORIZONS-AMI trial.

Catheter Cardiovasc Interv 2013 Oct 26;82(4):594-601. Epub 2013 Jun 26.

Department of Cardiology, Stavanger University Hospital, Stavanger, Norway; Institute of Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.

Objectives: To assess the quality of coronary reperfusion and long-term clinical outcomes of patients enrolled in the HORIZONS-AMI trial according to the use of thrombus aspiration (TA).

Background: The impact of manual TA on microvascular perfusion and clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) is unsettled.

Methods: In this retrospective, nonrandomized, subgroup analysis, the authors evaluated thrombolysis in myocardial infarction (TIMI) flow, tissue myocardial perfusion grade (TMPG), ST-segment resolution (STR), net adverse clinical events (NACE), and major adverse cardiac events (MACE) in patients undergoing pPCI with or without manual TA.

Results: A total of 318 patients had pPCI with upfront TA, and 2,917 patients had pPCI without TA. Patients who had TA were more likely to have TIMI 0/1 flow at baseline (75.1% vs. 63.7%, P < 0.0001). There was no difference in the rates of final TIMI 3 flow (90.2% vs. 92.3%, P = 0.19) or dynamic TMPG 2-3 (77.4% vs. 76.4%, P = 0.68). STR ≥70% was similar in both groups at 60 minutes but higher in the TA group at discharge (71.8% vs. 64.6%, P = 0.02). After multivariable adjustment, TA did not predict MACE at 30 days (HR 0.96 [0.51-1.80], P = 0.90), 1 year (HR 1.03 [0.68-1.55], P = 0.89), or 3 years (HR 1.13 [0.86-1.48], P = 0.39). Stent thrombosis did not differ at 1 year or 3 years.

Conclusions: In STEMI patients undergoing pPCI, the use of manual TA was associated with improved STR at discharge, but not with any difference in final TIMI flow, TMPG, or MACE.
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http://dx.doi.org/10.1002/ccd.24705DOI Listing
October 2013
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