| 1. |
- Jaffe, Allan S., et al.
(författare)
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Single Troponin Measurement to Rule Out Myocardial Infarction: JACC Review Topic of the Week
- 2023
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Ingår i: Journal of the American College of Cardiology. - 0735-1097 .- 1558-3597. ; 82:1, s. 60-69
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Forskningsöversikt (refereegranskat)abstract
- The term “single-sample rule-out” refers to the ability of very low concentrations of high-sensitivity cardiac troponin (hs-cTn) on presentation to exclude acute myocardial infarction with high clinical sensitivity and negative predictive value. Observational and randomized studies have confirmed this ability. Some guidelines endorse use of a concentration of hs-cTn at the assay's limit of detection, while other studies have validated the use of higher concentrations, allowing this approach to identify a greater proportion of patients at low risk. In most studies, at least 30% of patients can be triaged with this approach. The concentration of hs-cTn varies according to the assay used and sometimes how regulations permit reporting. It is clear that patients need to be at least 2 hours from the onset of symptoms being evaluated. Caution is warranted, particularly with older patients, women, and patients with underlying cardiac comorbidities.
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| 2. |
- Jansson, Anna M, et al.
(författare)
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Prognostic value of circulating chromogranin A levels in acute coronary syndromes.
- 2009
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 30:1, s. 25-32
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Tidskriftsartikel (refereegranskat)abstract
- To determine whether circulating levels of chromogranin A (CgA) provide prognostic information independently of conventional risk markers in acute coronary syndromes (ACSs).
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| 3. |
- Katus, Hugo, et al.
(författare)
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Early diagnosis of acute coronary syndrome
- 2017
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:41, s. 3049-3055
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Forskningsöversikt (refereegranskat)abstract
- The diagnostic evaluation of acute chest pain has been augmented in recent years by advances in the sensitivity and precision of cardiac troponin assays, new biomarkers, improvements in imaging modalities, and release of new clinical decision algorithms. This progress has enabled physicians to diagnose or rule-out acute myocardial infarction earlier after the initial patient presentation, usually in emergency department settings, which may facilitate prompt initiation of evidence-based treatments, investigation of alternative diagnoses for chest pain, or discharge, and permit better utilization of healthcare resources. A non-trivial proportion of patients fall in an indeterminate category according to rule-out algorithms, and minimal evidence-based guidance exists for the optimal evaluation, monitoring, and treatment of these patients. The Cardiovascular Round Table of the ESC proposes approaches for the optimal application of early strategies in clinical practice to improve patient care following the review of recent advances in the early diagnosis of acute coronary syndrome. The following specific 'indeterminate' patient categories were considered: (i) patients with symptoms and high-sensitivity cardiac troponin <99th percentile; (ii) patients with symptoms and high-sensitivity troponin <99th percentile but above the limit of detection; (iii) patients with symptoms and high-sensitivity troponin >99th percentile but without dynamic change; and (iv) patients with symptoms and high-sensitivity troponin >99th percentile and dynamic change but without coronary plaque rupture/erosion/dissection. Definitive evidence is currently lacking to manage these patients whose early diagnosis is 'indeterminate' and these areas of uncertainty should be assigned a high priority for research.
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| 4. |
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| 5. |
- Martikainen, Teemu, et al.
(författare)
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Effects of curtailed sleep on cardiac stress biomarkers following high-intensity exercise.
- 2022
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Ingår i: Molecular metabolism. - : Elsevier. - 2212-8778. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Physical exercise - especially at high intensity - is known to impose cardiac stress, as mirrored by, e.g., increased blood levels of cardiac stress biomarkers, such as cardiac Troponin T (cTnT) and NT-proBNP. Here, we examined in healthy young participants whether a few nights of short sleep duration alters the effects of acute exercise on these blood biomarkers.METHODS: Sixteen men participated in a randomized order in a crossover design, comprising three consecutive nights of a) normal sleep duration (NS, 8.5 hours of sleep/night) and b) sleep restriction (SR, 4.25 hours of sleep/night). Blood was repeatedly sampled for determination of NT-proBNP and cTnT serum levels before and after a high-intensity exercise protocol (i.e., 75% VO2maxReserve cycling on an ergometer).RESULTS: Under pre-exercise sedentary conditions, blood levels of cTnT and NT-proBNP did not significantly differ between the sleep conditions (P>0.10). However, in response to exercise, the surge of circulating cTnT was significantly greater following SR than NS (+37-38% at 120-240 min post-exercise, P≤0.05). While blood levels of NT-proBNP rose significantly in response to exercise, they did not differ between the sleep conditions.CONCLUSION: Recurrent sleep restriction may increase the cardiac stress response to acute high-intensity exercise in healthy young individuals. However, our findings must be confirmed in for example older subjects or in patients with a history of heart disease.
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| 6. |
- Myhre, Peder Langeland, et al.
(författare)
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Circulating chromogranin B levels in patients with acute respiratory failure : data from the FINNALI Study
- 2017
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Ingår i: Biomarkers. - 1354-750X .- 1366-5804. ; 22:8, s. 775-781
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Circulating chromogranin B (CgB) levels are increased in situations characterized by systemic and myocardial stress, but whether CgB provides prognostic information in patients with acute respiratory failure (ARF) is unknown.METHODS: We included 584 patients with ARF, defined as ventilatory support >6 h, and with blood samples available on Intensive Care Unit (ICU) admission and day 3 (n = 479). CgB levels were measured by radioimmunoassay and follow-up was 90 days.RESULTS: One-hundred-sixty-nine patients (29%) died during follow-up. Admission CgB levels separated non-survivors from survivors: median 1234 (Q1-3 989-1742) vs. 917 (753-1224) pmol/L, respectively, p < 0.001. CgB levels on ICU admission (logarithmically transformed) were associated with time to death after adjustment for established risk indices available on ICU admission, including N-terminal pro-B-type natriuretic levels: HR 2.62 (95%C.I. 1.82-3.77), p < 0.001. Admission CgB levels also improved prognostication on top of SOFA and SAPS II scores as assessed by Cox regression analyses and the category-free net reclassification index. The area under the curve (AUC) for admission CgB levels to separate survivors and non-survivors was 0.72 (95%CI 0.67-0.76), while the AUC on day 3 was 0.60 (0.54-0.66).CONCLUSIONS: CgB levels measured on ICU admission provided additional prognostic information to established risk indices in ARF patients.
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| 7. |
- Myhre, Peder L, et al.
(författare)
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Performance of a Novel Research-Use-Only Secretoneurin ELISA in Patients with Suspected Acute Coronary Syndrome : Comparison with an Established Secretoneurin Radioimmunoassay
- 2021
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Ingår i: Cardiology. - : S. Karger. - 0008-6312 .- 1421-9751. ; 146:5, s. 566-574
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating secretoneurin (SN) concentrations, as measured by established radioimmunoassay (RIA), risk stratify patients with cardiovascular disease. We now report data for a recently developed research-use-only SN enzyme-linked immunosorbent assay (ELISA) in patients with suspected acute coronary syndrome (ACS).Methods: SN ELISA was developed according to industry standards and tested in 401 unselected chest pain patients. Blood samples were drawn <24 h from admission, and we adjudicated all hospitalizations as ACS or non-ACS. The mean follow-up was 6.2 years.Results: SN ELISA with 2 monoclonal sheep anti-SN antibodies has a measuring range of 10–250 pmol/L and demonstrates excellent analytical precision and accuracy across the range of SN concentrations. SN measured by ELISA and RIA correlated in the chest pain patients: rho = 0.39, p < 0.001. SN concentrations were higher in ACS patients (n = 161 [40%]) than in non-ACS patients (n = 240) for both assays, with an area under the curve (AUC) of 0.66 (95% CI: 0.61–0.71) for ELISA and 0.59 (0.54–0.65) for RIA. SN concentrations were also higher in nonsurvivors (n = 65 [16%]) than survivors, with an AUC of 0.72 (0.65–0.79) for ELISA versus 0.64 (0.56–0.72) for RIA, p = 0.007, for difference between assays. Adjusting for age, sex, blood pressure, previous myocardial infarction, atrial fibrillation, and heart failure in multivariable analysis, SN concentrations as measured by ELISA, but not RIA, remained associated with mortality, with a hazard ratio of 1.71 (1.03–2.84), p = 0.038.Conclusions: The novel SN ELISA has excellent performance, higher AUC for diagnosis, and superior prognostic accuracy compared to the established RIA in chest pain patients.
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| 8. |
- Myhre, Peder L., et al.
(författare)
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Prognostic Value of Secretoneurin in Patients with Acute Respiratory Failure : Data from the FINNALI Study
- 2016
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 62:10, s. 1380-1389
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We examined whether secretoneurin (SN), a biomarker associated with cardiomyocyte Ca2+ handling, provides prognostic information in patients with acute respiratory failure (ARF).METHODS: We included 490 patients with ARF, defined as ventilatory support >6 h, with blood samples available on admission to the intensive care unit (ICU). SN concentrations were measured by RIA.RESULTS: A total of 209 patients (43%) were hospitalized with cardiovascular (CV)-related ARF, and 90-day mortality rates were comparable between CV- and non CV-related ARF (n = 281): 31% vs 24%, P = 0.11. Admission SN concentrations were higher in nonsurvivors than in survivors in both CV -related (median 148 [quartile 1-3, 117-203] vs 108 [87-143] pmol/L, P < 0.001) and non CV-related ARF (139 [115-184] vs 113 [91-139] pmol/L, P < 0.001). In patients with CV -related ARF, SN concentrations on ICU admission were associated with 90-day mortality [odds ratio (OR) 1.97 (95% CI, 1.04-3.73, P = 0.04)] after adjusting for established risk indices, including N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentrations. SN also improved patient classification in CV -related ARF as assessed by the net reclassification index: 0.32 (95% CI, 0.04-0.59), P = 0.03. The area under the curve (AUC) of SN to predict mortality in patients with CV -related ARF was 0.72 (95% CI, 0.65-0.79), and the AUC of NT-proBNP was 0.64 (0.56-0.73). In contrast, SN concentrations on ICU admission did not provide incremental prognostic value to established risk indices in patients with non CV-related ARF, and the AUC was 0.67 (0.60-0.75).CONCLUSIONS: SN concentrations measured on ICU admission provided incremental prognostic information to established risk indices in patients with CV -related ARF, but not in patients with non CV-related ARF.
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| 9. |
- Nordenskjöld, Anna, 1977-
(författare)
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Unrecognized myocardial infarction and cardiac biochemical markers in patients with stable coronary artery disease
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: The overarching aim of the thesis was to explore the occurrence and clinical importance of two manifestations of myocardial injury; unrecognized myocardial injury (UMI) and altered levels of cardiac biochemical markers in patients with stable coronary artery disease (CAD).Methods: A prospective multicenter cohort study investigated the prevalence, localization, size, and prognostic implication of UMI in 235 patients with stable CAD. Late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging and coronary angiography were used. The relationship between UMI and severe CAD and cardiac biochemical markers was explored. In a substudy the short- and longterm individual variation in cardiac troponins I and T (cTnI, cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were investigated.Results: The prevalence of UMI was 25%. Subjects with severe CAD were significantly more likely to exhibit UMI than subjects without CAD. There was a strong association between stenosis ≥70% and presence of UMI in the myocardial segments downstream. The presence of UMI was associated with a significant threefold risk of adverse events during follow up. After adjustments UMI was associated with a nonsignificant numerically doubled risk. The levels of cTnI, NT-proBNP, and Galacin-3 were associated with the presence of UMI in univariate analyses. The association between levels of cTnI and presence of UMI remained significant after adjustment. The individual variation in cTnI, cTnT, and NT-proBNP in subjects with stable CAD appeared similar to the biological variation in healthy individuals.Conclusions: UMI is common and is associated with significant CAD, levels of biochemical markers, and an increased risk for adverse events. A change of >50% is required for a reliable short-term change in cardiac troponins, and a rise of >76% or a fall of >43% is required to detect a long-term reliable change in NT-proBNP.
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| 10. |
- Omland, Torbjörn, et al.
(författare)
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Circulating osteoprotegerin levels and long-term prognosis in patients with acute coronary syndromes.
- 2008
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 1558-3597 .- 0735-1097. ; 51:6, s. 627-33
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study was designed to assess the association between osteoprotegerin (OPG) levels on admission and long-term prognosis in patients with acute coronary syndromes (ACS). BACKGROUND: Osteoprotegerin, a member of the tumor necrosis factor receptor superfamily, has pleiotropic effects on bone metabolism, endocrine function, and the immune system. METHODS: Serum samples for OPG analysis were obtained within 24 h of admission in 897 ACS patients (median age 66 years, 71% men) and related to the incidence of death, heart failure (HF) hospitalizations, myocardial infarction (MI), and stroke. RESULTS: A total of 261 patients died during a median follow-up of 89 months. The baseline OPG concentration was strongly associated with increased long-term mortality (hazard ratio [HR] for HR per 1 SD increase in logarithmically transformed OPG level 1.7 [range 1.5 to 1.9] p < 0.0001) and HF hospitalizations (HR 2.0 [range 1.6 to 2.5]; p < 0.0001) but weaker with recurrent MI (HR 1.3 [range 1.0 to 1.5]; p = 0.02) and not with stroke (HR 1.2 [range 0.9 to 1.6]; p = 0.35). After adjustment for conventional risk markers, including troponin I, C-reactive protein (CRP), B-type natriuretic peptide (BNP), and ejection fraction, the association remained significant for mortality (HR 1.4 [range 1.2 to 1.7]; p < 0.0001) and HF hospitalization (HR 1.6 [range 1.2 to 2.1]; p = 0.0002), but not recurrent MI. By comparison of the area under the receiver-operating characteristics curves, OPG performed similarly to BNP and ejection fraction and significantly better than CRP and troponin I as a predictor of death. CONCLUSIONS: Serum OPG is strongly predictive of long-term mortality and HF development in patients with ACS, independent of conventional risk markers.
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| 11. |
- Omland, Torbjørn, et al.
(författare)
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N-terminal pro-B-type natriuretic peptide and long-term mortality in acute coronary syndromes.
- 2002
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Ingår i: Circulation. - 1524-4539. ; 106:23, s. 2913-8
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Tidskriftsartikel (refereegranskat)abstract
- B-type natriuretic peptide (BNP) is a predictor of short- and medium-term prognosis across the spectrum of acute coronary syndromes (ACS). The N-terminal fragment of the BNP prohormone, N-BNP, may be an even stronger prognostic marker. We assessed the relation between subacute plasma N-BNP levels and long-term, all-cause mortality in a large, contemporary cohort of patients with ACS.
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| 12. |
- Ottesen, Anett Hellebø, et al.
(författare)
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Glycosylated Chromogranin A in Heart Failure : Implications for Processing and Cardiomyocyte Calcium Homeostasis
- 2017
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Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chromogranin A (CgA) levels have previously been found to predict mortality in heart failure (HF), but currently no information is available regarding CgA processing in HF and whether the CgA fragment catestatin (CST) may directly influence cardiomyocyte function.METHODS AND RESULTS: CgA processing was characterized in postinfarction HF mice and in patients with acute HF, and the functional role of CST was explored in experimental models. Myocardial biopsies from HF, but not sham-operated mice, demonstrated high molecular weight CgA bands. Deglycosylation treatment attenuated high molecular weight bands, induced a mobility shift, and increased shorter CgA fragments. Adjusting for established risk indices and biomarkers, circulating CgA levels were found to be associated with mortality in patients with acute HF, but not in patients with acute exacerbation of chronic obstructive pulmonary disease. Low CgA-to-CST conversion was also associated with increased mortality in acute HF, thus, supporting functional relevance of impaired CgA processing in cardiovascular disease. CST was identified as a direct inhibitor of CaMKIIδ (Ca(2+)/calmodulin-dependent protein kinase IIδ) activity, and CST reduced CaMKIIδ-dependent phosphorylation of phospholamban and the ryanodine receptor 2. In line with CaMKIIδ inhibition, CST reduced Ca(2+) spark and wave frequency, reduced Ca(2+) spark dimensions, increased sarcoplasmic reticulum Ca(2+) content, and augmented the magnitude and kinetics of cardiomyocyte Ca(2+) transients and contractions.CONCLUSIONS: CgA-to-CST conversion in HF is impaired because of hyperglycosylation, which is associated with clinical outcomes in acute HF. The mechanism for increased mortality may be dysregulated cardiomyocyte Ca(2+) handling because of reduced CaMKIIδ inhibition.
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| 13. |
- Ottesen, Anett Hellebø, et al.
(författare)
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Secretoneurin is a novel prognostic cardiovascular biomarker associated with cardiomyocyte calcium handling.
- 2015
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 65:4, s. 339-51
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Secretoneurin (SN) levels are increased in patients with heart failure (HF), but whether SN provides prognostic information and influences cardiomyocyte function is unknown.OBJECTIVES: This study sought to evaluate the merit of SN as a cardiovascular biomarker and assess effects of SN on cardiomyocyte Ca(2+) handling.METHODS: We assessed the association between circulating SN levels and mortality in 2 patient cohorts and the functional properties of SN in experimental models.RESULTS: In 143 patients hospitalized for acute HF, SN levels were closely associated with mortality (n = 66) during follow-up (median 776 days; hazard ratio [lnSN]: 4.63; 95% confidence interval: 1.93 to 11.11; p = 0.001 in multivariate analysis). SN reclassified patients to their correct risk strata on top of other predictors of mortality. In 155 patients with ventricular arrhythmia-induced cardiac arrest, SN levels were also associated with short-term mortality (n = 51; hazard ratio [lnSN]: 3.33; 95% confidence interval: 1.83 to 6.05; p < 0.001 in multivariate analysis). Perfusing hearts with SN yielded markedly increased myocardial levels and SN internalized into cardiomyocytes by endocytosis. Intracellularly, SN reduced Ca(2+)/calmodulin (CaM)-dependent protein kinase II δ (CaMKIIδ) activity via direct SN-CaM and SN-CaMKII binding and attenuated CaMKIIδ-dependent phosphorylation of the ryanodine receptor. SN also reduced sarcoplasmic reticulum Ca(2+) leak, augmented sarcoplasmic reticulum Ca(2+) content, increased the magnitude and kinetics of cardiomyocyte Ca(2+) transients and contractions, and attenuated Ca(2+) sparks and waves in HF cardiomyocytes.CONCLUSIONS: SN provided incremental prognostic information to established risk indices in acute HF and ventricular arrhythmia-induced cardiac arrest.
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| 14. |
- Persson, Anita, 1971, et al.
(författare)
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Long-term prognostic value of mitral regurgitation in acute coronary syndromes.
- 2010
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Ingår i: Heart (British Cardiac Society). - : BMJ. - 1468-201X .- 1355-6037. ; 96:22, s. 1803-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To determine the additional prognostic value of mitral regurgitation (MR) over B-type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF) and clinical characteristics in patients with acute coronary syndromes (ACS). DESIGN: Long-term follow-up in a prospective ACS cohort with Doppler-assessed MR, echocardiographically-determined LVEF and plasma BNP levels by ELISA. SETTING: Single-centre university hospital. PATIENTS: 725 patients with ACS. MAIN OUTCOME MEASURES: Death and readmission for congestive heart failure. RESULTS: During a median follow-up of 98 months, 235 patients (32%) died. Significant MR (grade >1 of 4) was found in 90 patients (12%). In a multivariate model including MR grade >1, LVEF <0.40 and BNP >373 pg/ml (75th percentile), MR was significantly associated with long-term mortality (HR 2.28, 95% CI 1.67 to 3.12; p<0.0001). When also adjusting for conventional risk factors, MR remained significantly associated with mortality (HR 1.53, 95% CI 1.06 to 2.19; p=0.02), as well as with congestive heart failure (HR 2.08, 95% CI 1.29 to 3.35; p=0.003). CONCLUSIONS: MR is common in patients with ACS, provides independent risk information and should be taken into account in the evaluation of the long-term prognosis.
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| 15. |
- Røsjø, Helge, et al.
(författare)
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Chromogranin B in Heart Failure : a Putative Cardiac Biomarker Expressed in the Failing Myocardium
- 2010
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Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 3:4, s. 503-511
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChromogranin B (CgB) is a member of the granin protein family. Because CgB is often colocalized with chromogranin A (CgA), a recently discovered cardiac biomarker, we hypothesized that CgB is regulated during heart failure (HF) development.Methods and ResultsCgB regulation was investigated in patients with chronic HF and in a post–myocardial infarction HF mouse model. Animals were phenotypically characterized by echocardiography and euthanized 1 week after myocardial infarction. CgB mRNA levels were 5.2-fold increased in the noninfarcted part of the left ventricle of HF animals compared with sham-operated animals (P<0.001). CgB mRNA level in HF animals correlated closely with animal lung weight (r=0.74, P=0.04) but not with CgA mRNA levels (r=0.20, P=0.61). CgB protein levels were markedly increased in both the noninfarcted (110%) and the infarcted part of the left ventricle (70%) but unaltered in other tissues investigated. Myocardial CgB immunoreactivity was confined to cardiomyocytes. Norepinephrine, angiotensin II, and transforming growth factor-β increased CgB gene expression in cardiomyocytes. Circulating CgB levels were increased in HF animals (median levels in HF animals versus sham, 1.23 [interquartile range, 1.03 to 1.93] versus 0.98 [0.90 to 1.04] nmol/L; P=0.003) and in HF patients (HF patients versus control, 1.66 [1.48 to 1.85] versus 1.47 [1.39 to 1.58] nmol/L; P=0.007), with levels increasing in proportion to New York Heart Association functional class (P=0.03 for trend). Circulating CgB levels were only modestly correlated with CgA (r=0.31, P=0.009) and B-type natriuretic peptide levels (r=0.27, P=0.014).ConclusionsCgB production is increased and regulated in proportion to disease severity in the left ventricle and circulation during HF development.
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| 16. |
- Røsjø, Helge, et al.
(författare)
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Secretogranin II; a Protein Increased in the Myocardium and Circulation in Heart Failure with Cardioprotective Properties
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5, s. e37401-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several beneficial effects have been demonstrated for secretogranin II (SgII) in non-cardiac tissue. As cardiac production of chromogranin A and B, two related proteins, is increased in heart failure (HF), we hypothesized that SgII could play a role in cardiovascular pathophysiology. Methodology/Principal Findings: SgII production was characterized in a post-myocardial infarction heart failure (HF) mouse model, functional properties explored in experimental models, and circulating levels measured in mice and patients with stable HF of moderate severity. SgII mRNA levels were 10.5 fold upregulated in the left ventricle (LV) of animals with myocardial infarction and HF (p<0.001 vs. sham-operated animals). SgII protein levels were also increased in the LV, but not in other organs investigated. SgII was produced in several cell types in the myocardium and cardiomyocyte synthesis of SgII was potently induced by transforming growth factor-beta and norepinephrine stimulation in vitro. Processing of SgII to shorter peptides was enhanced in the failing myocardium due to increased levels of the proteases PC1/3 and PC2 and circulating SgII levels were increased in mice with HF. Examining a pathophysiological role of SgII in the initial phase of post-infarction HF, the SgII fragment secretoneurin reduced myocardial ischemia-reperfusion injury and cardiomyocyte apoptosis by 30% and rapidly increased cardiomyocyte Erk1/2 and Stat3 phosphorylation. SgII levels were also higher in patients with stable, chronic HF compared to age-and gender-matched control subjects: median 0.16 (Q1-3 0.14-0.18) vs. 0.12 (0.10-0.14) nmol/L, p<0.001. Conclusions: We demonstrate increased myocardial SgII production and processing in the LV in animals with myocardial infarction and HF, which could be beneficial as the SgII fragment secretoneurin protects from ischemia-reperfusion injury and cardiomyocyte apoptosis. Circulating SgII levels are also increased in patients with chronic, stable HF and may represent a new cardiac biomarker.
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| 17. |
- Åkerblom, Axel, 1977-
(författare)
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Biomarkers of Renal Function in Acute Coronary Syndromes
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis aimed to investigate cystatin C and creatinine-based estimates of glomerular filtration rate (eGFR), both at admission and during follow-up, on the combined endpoint of cardiovascular death and myocardial infarction in patients with acute coronary syndrome (ACS). We also evaluated two cystatin C assays and assessed genetic determinants of cystatin C concentrations.We used the PLATelet inhibition and Patient Outcomes study, where all types of ACS patients (n=18624) were randomized to ticagrelor or clopidogrel treatment. Multivariable Cox regression models, including clinical variables and biomarkers (troponin and NT-proBNP), and c-statistics were calculated.Cystatin C and the creatinine-based CKD-EPI equation exhibited similar significant prognostic impact on the combined endpoint, with Area Under Curves (AUC) 0.6923 and 0.6941, respectively. Follow-up samples of renal biomarkers did not improve risk prediction.Patients randomized to ticagrelor treatment were associated with a non-sustained larger increase in renal markers at discharge, but neither the change nor the difference between the randomized groups affected cardiovascular risk.Two different cystatin C assays exhibited good correlation 0.86 (95% confidence interval 0.85-0.86), however moderate level of agreement. Risk prediction with a combination of creatinine and cystatin C did not outperform the creatinine-based CKD-EPI equation, AUC: 0.6913 and 0.6924, respectively (n=13050).The genetic polymorphism rs6048952 independently affected the cystatin C concentration with mean levels of 0.85mg/L, 0.80mg/L and 0.73mg/L for the A/A, A/G, and G/G genotypes, respectively.The genetic polymorphism did not affect outcome overall, however in the non-ST-elevation ACS subgroup a signal that genetic polymorphism may be associated with cardiovascular death was observed (p=0.002).In conclusion: cystatin C or eGFR, irrespective of equation or assay, are important cardiovascular risk factors in ACS patients. Nonetheless, the incremental value of adding any renal variable, to a multivariable risk model, is small. Further research on the impact of cystatin C genetic polymorphism is warranted.
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