| 1. |
- Alfredsson, Joakim, et al.
(författare)
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Individual long-term variation of platelet reactivity in patients with dual antiplatelet therapy after myocardial infarction.
- 2019
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Ingår i: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 30:5, s. 572-578
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Tidskriftsartikel (refereegranskat)abstract
- There is a large inter-individual variation in response to clopidogrel treatment, and previous studies have indicated higher risk of thrombotic events in those with high residual platelet reactivity (HPR). Less is known about individual variation over time. The aim of this prospective cohort study was to investigate intra-individual variation in platelet reactivity. Platelet aggregation in whole blood was assessed in 77 patients, at 3 days, 8 days and 6 months after admission for acute myocardial infarction and loading dose of clopidogrel. All patients were treated with aspirin and clopidogrel through 6-month follow-up. We found a significant increase in median ADP-stimulated aggregation from third to eighth day (195 vs. 250 AU*min, p-value = 0.001) but not from day 8 to 6 months (250 vs. 223 AU*min, p-value = 0.666). There was no significant change in the overall rate of HPR (15.6% vs 20.8%, p-value 0.503) or low platelet reactivity (LPR) (37.7% vs 33.8%, p-value = 0.609) from day 8 to 6-month follow-up. In contrast, more than one in four changed HPR status, 15.6% from non-HPR to HPR and 10.4% HPR to non-HPR. A shift in LPR status appeared even more frequent, occurring in about one of three patients. In spite of similar median aggregation and rate of HPR during 6-month follow-up, about one in four of the patients changed HPR status and one in three changed LPR status. This may be important information for a concept of risk stratification based on a single aggregation value early after an acute coronary syndromes.
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| 2. |
- Alfredsson, Joakim, et al.
(författare)
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Large early variation of residual platelet reactivity in Acute Coronary Syndrome patients treated with clopidogrel : Results from Assessing Platelet Activity in Coronary Heart Disease (APACHE).
- 2015
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Ingår i: Thrombosis Research. - : Pergamon Press. - 0049-3848 .- 1879-2472. ; 136:2, s. 335-340
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: There is a large inter-individual variation in response to clopidogrel treatment and previous studies have indicated higher risk of thrombotic events in patients with high residual platelet reactivity (HRPR), but the optimal time-point for testing is not established. The aim of this study was to investigate the optimal time-point for aggregometry testing and the risk of major adverse cardiac events associated with HRPR.METHOD AND RESULTS: We included 125 patients with ACS (73 with STEMI, and 71 received abciximab). The prevalence of HRPR varied substantially over time. The rate of HRPR in patients treated and not treated with abciximab were 43% vs 67% (p=0.01) before, 2% vs 23% (p=0.001) 6-8h after, 8% vs 9% (p=0.749) 3days after, and 23% vs 12% (p=0.138) 7-9 days after loading dose of clopidogrel. We found HRPR in 18% of the patients but only four ischemic events during 6months follow-up, with no significant difference between HRPR patients compared to the rest of the population. There were 3 TIMI major bleedings, all of which occurred in the low residual platelet reactivity (LRPR) group.CONCLUSION: There is a large variation in platelet reactivity over time, also depending on adjunctive therapy, which has a large impact on optimal time-point for assessment. We found HRPR in almost 1 in 5 patients, but very few MACE, and not significantly higher in HRPR patients. In a contemporary ACS population, with low risk for stent thrombosis, the predictive value of HRPR for ischemic events will probably be low.
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| 3. |
- Becriovic-Agic, Mediha
(författare)
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Susceptibility to Acute Decompensated Heart Failure in Two Common Mouse Strains
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Heart failure is a clinical syndrome characterized by an inability of the heart to meet oxygen demands of the body. During the initial stage of heart failure development compensatory mechanisms are activated to help the heart sustain proper function. Over time these compensatory mechanisms become inadequate resulting in decompensation. Acute decompensated heart failure is characterized by rapidly escalating heart failure symptoms, such as dyspnea and congestion, which require urgent treatment. The pathophysiology of decompensation and role of genetic background on this process is not completely understood. The aim of this thesis was to investigate the role of genetic background on susceptibility to develop acute decompensated heart failure.Balb/CJ and C57BL/6J mice are two common mouse strains that we found have different susceptibility to angiotensin II and high-salt diet (AngII+Salt) induced decompensation. Balb/CJ treated with AngII+Salt develop massive edema associated with anuria and high mortality within 4-6 days of treatment, while C57BL/6J mice do not. Due to the clinical symptoms of heart failure we hypothesized that Balb/CJ develop acute decompensated heart failure, and that the genetic background of this strain is responsible for the increased susceptibility to heart failure. AngII+Salt increased pulmonary and systemic vascular resistance, reduced left ventricle filling, and increased sodium and water retention in Balb/CJ mice. Increased pulmonary vascular resistance correlated with a higher angiotensin II response in isolated pulmonary arteries from Balb/CJ compared to C57BL/6J. Cardiac output was lower in Balb/CJ than C57BL/6J during AngII+Salt treatment even though they retained more sodium and water. This indicated that AngII+Salt impairs cardiac function in Balb/CJ mice. Oxidative stress was shown to play a role in AngII+Salt induced acute decompensation since treatment with an antioxidant reduced oxidative stress but impaired cardiac function and increased mortality in both strains. A linkage study was performed to reveal genes that are with high probability related to AngII+Salt induced decompensation in Balb/CJ mice. Quantative trait loci (QTLs) on chromosome 3 and 12 were linked to cardiac dysfunction and QTLs on chromosome 2 and 3 were linked to sodium and fluid balance. Foxo1 was found to be one of candidate genes for further study.Taken together, the data in this thesis shows that genetic background does play a large role in the development of acute decompensated heart failure. It reveals several candidate genes that could be studied in the setting of acute decompensated heart failure. Finally, it describes a new mouse model that could potentially be used for studying the pathophysiology of decompensation and identifying new drug targets.
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| 4. |
- Bergström, Ida, et al.
(författare)
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Annexin A1 in blood mononuclear cells from patients with coronary artery disease : Its association with inflammatory status and glucocorticoid sensitivity
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of glucocorticoid actions. In atherosclerotic tissue, increased expression of AnxA1 has been associated with protective plaque-stabilizing effects. Here, we investigated the expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Blood was collected from 57 patients with stable CAD (SCAD) and 41 healthy controls. We also included a minor group (n = 10) with acute coronary syndrome (ACS). AnxA1 mRNA was measured in PBMCs. Expression of AnxA1 protein (total and surface-bound) and glucocorticoid receptors (GR) were detected in PBMC subsets by flow cytometry. Also, salivary cortisol, interleukin(IL)-6 and IL-10 in plasma, and LPS-induced cytokine secretion from PBMCs, with or without dexamethasone, were assessed. AnxA1 mRNA was found to be slightly increased in PBMCs from SCAD patients compared with controls. However, protein expression of AnxA1 or GRs in PBMC subsets did not differ between SCAD patients and controls, despite SCAD patients showing a more proinflammatory cytokine profile ex vivo. Only surface expression of AnxA1 on monocytes correlated with dexamethasone-mediated suppression of cytokines. In ACS patients, a marked activation of AnxA1 was seen involving both gene expression and translocation of protein to cell surface probably reflecting a rapid glucocorticoid action modulating the acute inflammatory response in ACS. To conclude, surface expression of AnxA1 on monocytes may reflect the degree of glucocorticoid sensitivity. Speculatively, "normal" surface expression of AnxA1 indicates that anti-inflammatory capacity is impaired in SCAD patients.
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| 5. |
- Bergström, Ida
(författare)
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Pro- and anti-inflammatory actions in coronary artery disease : with focus on CD56+ T cells and Annexin A1
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- ¨The atherosclerotic process is considered to be driven by an imbalance between proand anti-inflammatory actions. Still, the inflammatory state in patients with coronary artery disease (CAD) remains to be clarified. Annexin A1 (AnxA1) is a glucocorticoidinduced protein which may have a key role in the anti-inflammatory response as a mediator of glucocorticoid effects.The general aim of this thesis was to deepen the knowledge of pro- and antiinflammatory mechanisms in CAD via phenotypic assessments of immune cell subsets, in particular CD56+ T cells, and exploration of AnxA1. The long-term goal is to reveal basic mechanisms that will lead to the development of biomarkers, which may be used for individualized treatment and monitoring.The AnxA1 protein was constitutively expressed in both neutrophils and peripheral blood mononuclear cells (PBMCs). However, it varied considerably across PBMC subsets, being most abundantly expressed in monocytes. The AnxA1 expression was also higher in CD56+ T cells than in CD56- T cells.The expression of total AnxA1 protein in neutrophils was higher in patients with stable angina (SA) compared with controls. However, this was not accompanied by altered neutrophil activation status. Instead, the neutrophils from patients exhibited an enhanced anti-inflammatory response to exogenous AnxA1, emphasizing the potential of AnxA1 as an inhibitor of neutrophil activity. Only patients with acute coronary syndrome (ACS) showed an increase in cell surface-associated AnxA1.CAD patients, independent of clinical presentation, had increased proportions of CD56+ T cells compared with controls, a phenomenon likely to represent immunological aging. The CD56+ T cells were found to exhibit a distinct proinflammatory phenotype compared with CD56- T cells. In all T cell subsets, the expression of cell surface-associated AnxA1 was significantly increased in ACS patients, while it tended to be increased in post-ACS patients. In addition, dexamethasone clearly inhibited activation of CD56+ T cells in in vitro assays, whereas AnxA1 did not. The findings highlight the need to clarify whether the role of AnxA1 is different in T cells than in innate immune cells.In PBMCs, the mRNA levels of AnxA1 were increased in CAD patients, particularly in ACS patients. Correspondingly, the monocytes in ACS patients exhibited increased AnxA1 protein levels, both totally and on the cell surface. However, only cell surface-associated AnxA1 in monocytes correlated with the glucocorticoid sensitivity of PBMCs ex vivo. We propose the expression of cell surfaceassociated AnxA1 to be a promising candidate marker of glucocorticoid sensitivity, which needs further investigations in larger cohorts and intervention trials. Furthermore, the fact that PBMCs in post-ACS patients exhibited pro-inflammatory activity but no increase in cell surface-associated AnxA1 allow us to speculate that the glucocorticoid action and/or availability might be insufficient in these patients.
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| 6. |
- Chung, Rosanna, et al.
(författare)
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Liberation of lutein from spinach : Effects of heating time, microwavereheating and liquefaction
- 2019
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Ingår i: Food Chemistry. - : Elsevier. - 0308-8146 .- 1873-7072. ; 277, s. 573-578
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Tidskriftsartikel (refereegranskat)abstract
- Lutein, abundant in dark leafy vegetables, has been associated with several health promoting effects. Still, to what extent different preparation conditions and practices affect the liberation of lutein from food is not fully understood. Here, we compared a range of domestic methods under realistic conditions to prepare spinach, the most common lutein-rich vegetable. After preparations, samples were processed by in vitro digestion and lutein was quantified by HPLC. Data indicate that short-term and medium-term heating of spinach, independent of heating method, substantially reduced liberated lutein and reduction was most pronounced after long boiling times. Interestingly, the loss of lutein in heated samples was partly compensated when samples were reheated in the microwave. However, the highest yield of liberated lutein was obtained from liquefied spinach. Additional dairy enhanced the liquefaction effect. Thus, for optimal liberation of lutein, liquefaction of raw spinach appears to be the method of choice.
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| 7. |
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| 8. |
- Chung, Rosanna W S, et al.
(författare)
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Lutein exerts anti-inflammatory effects in patients with coronary artery disease.
- 2017
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 262, s. 87-93
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Many coronary artery disease (CAD) patients exhibit chronic low-grade inflammation. Carotenoids are anti-oxidants with potential anti-inflammatory properties. Here, we first assessed relationships between interleukin (IL)-6 and individual carotenoids in plasma from CAD patients. Based on the results, we proceeded to assess anti-inflammatory effects of one carotenoid, lutein, in peripheral blood mononuclear cells (PBMCs) from CAD patients.METHODS: Lutein + zeaxanthin (isomers with lutein being dominant), β-cryptoxanthin, lycopene, α- and β-carotene and IL-6 were measured in plasma from 134 patients with stable angina (SA) and 59 patients with acute coronary syndrome. In 42 patients, plasma measurements were also performed 3 months after coronary intervention. PBMCs from SA patients were pre-treated with lutein (1, 5 and 25 μM) for 24 h followed by 24 h incubation ± lipopolysaccharide (LPS). Cell pellets were collected for IL-6, IL-1β and TNF mRNA and intracellular lutein. Cytokine secretion was measured in cell media.RESULTS: Only lutein + zeaxanthin were inversely correlated with IL-6 in SA patients at baseline (r = -0.366, p < 0.001) and follow-up (r = -0.546, p < 0.001). Ex vivo, lutein was taken up by PBMCs from SA patients in a dose- and time-dependent manner. Pre-treatment with lutein dose-dependently lowered LPS-induced secretion of IL-6, IL-1β (p < 0.01) and TNF (p < 0.05), and also reduced IL-6, IL-1β and TNF mRNA expression (p < 0.05).CONCLUSIONS: Clinical findings highlighted the inverse association between lutein and IL-6 in CAD patients. Anti-inflammatory effects of lutein in PBMCs from CAD patients were consolidated in ex vivo experiments. Taken together, these results show that lutein has the potential to play a role in resolution of chronic inflammation in CAD patients.
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| 9. |
- Fröbert, Ole, 1964-, et al.
(författare)
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Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial
- 2017
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Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 189, s. 94-102
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Tidskriftsartikel (refereegranskat)abstract
- Background: Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI.Methods/design: The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all cause death, a new AMI, or stent thrombosis at 1 year.Implications: The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI.
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| 10. |
- Garvin, Peter, et al.
(författare)
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Plasma Matrix Metalloproteinase-9 Levels Predict First-Time Coronary Heart Disease: An 8-Year Follow-Up of a Community-Based Middle Aged Population
- 2015
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 10:9, s. e0138290-
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Tidskriftsartikel (refereegranskat)abstract
- Background The enzyme in matrix metalloproteinase (MMP)-9 has been suggested to be an important determinant of plaque degradation. While several studies have shown elevated levels in patients with coronary heart disease, results in prospective population based studies evaluating MMP-9 in relation to first time coronary events have been inconclusive. As of today, there are four published studies which have measured MMP-9 in serum and none using plasma. Measures of MMP-9 in serum have been suggested to have more flaws than measures in plasma. Aim To investigate the independent association between plasma levels of MMP-9 and first-time incidence of coronary events in an 8-year follow-up. Material and Methods 428 men and 438 women, aged 45-69 years, free of previous coronary events and stroke at baseline, were followed-up. Adjustments were made for sex, age, socioeconomic position, behavioral and cardiovascular risk factors, chronic disease at baseline, depressive symptoms, interleukin-6 and C-reactive protein. Results 53 events were identified during a risk-time of 6 607 person years. Hazard ratio (HR) for MMP-9 after adjustment for all covariates were HR = 1.44 (1.03 to 2.02, p = 0.033). Overall, the effect of adjustments for other cardiovascular risk factors was low. Conclusion Levels of plasma MMP-9 are independently associated with risk of first-time CHD events, regardless of adjustments. These results are in contrast to previous prospective population-based studies based on MMP-9 in serum. It is essential that more studies look at MMP-9 levels in plasma to further evaluate the association with first coronary events.
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