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  • 1.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Tomas L
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Gustafsson, Kerstin M
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Logander, Elisabeth
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    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).2015In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, no 2, p. 335-340Article in journal (Refereed)
    Abstract [en]

    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.

  • 2.
    Berglund, Ulf
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Abciximab bolus with optional infusion in intervention for ST-elevation myocardial infarction2013In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 47, no 4, p. 230-235Article in journal (Refereed)
    Abstract [en]

    Objectives. The standard abciximab regimen is a bolus dose followed by a 12-h infusion. Whether the bolus dose alone is sufficient for ST-elevation myocardial infarction patients receiving a high loading dose of clopidogrel is unknown. Design. In an observational study, 693 consecutive patients were treated with abciximab during percutaneous coronary intervention for ST-elevation myocardial infarction. Totally 354 patients received standard strategy of abciximab bolus and infusion followed by 339 patients that recieved abciximab bolus only (271 patients) or bolus and infusion if suboptimal result (68 patients) in combination with a higher loading dose of clopidogrel (600 mg) the modified strategy. Results. The two groups were similar regarding baseline characteristics and in hospital bleeding events. At 30 days, the composite of death, re-infarction or target vessel revascularization was 9.1% in the standard and 7.5% in the modified strategy (p = 0.45). The rate of stent thrombosis was lower in the modified strategy group with 0% and 2.3% in the standard group (pandlt;0.001) and the mean total medical cost was lower in the modified strategy group with 8032 and 8665 in the standard group (pandlt;0.001). Conclusions. In primary percutaneous coronary intervention with a loading dose of 600 mg clopidogrel, it seems safe and cost-saving to give abciximab bolus with optional infusion.

  • 3.
    Garvin, Peter
    et al.
    Linköping University, Department of Medicine and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Carstensen, John
    Linköping University, Department of Medicine and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Jonasson, Lena
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences.
    Kristenson, Margareta
    Linköping University, Department of Medicine and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Association between ambulatory saliva cortisol levels and plasma levels of matrix metalloproteinase-9 in a normal populationManuscript (Other academic)
    Abstract [en]

    Background: Psychosocial strain has been demonstrated to be a risk factor for coronary artery disease (CAD) and also to be associated with a dysfunctional HPA-axis. Based on a proposal on cortisol resistance in maladaptive monocytes as a potential mechanism linking psychosocial strain with CAD, this study aimed at testing the association between levels of salivary cortisol and matrix metalloproteinase-9 (MMP-9) in a normal population.

    Methods: 359 participants (50 % women) aged 45-69 were enrolled to this study, randomly drawn from a normal population in Sweden. Saliva samples were collected thrice per day (at awakening, 30 minutes after awakening, and just before going to bed) during three consecutive days. Cortisol levels at awakening and 30 minutes after awakening were used to estimate the diurnal peak. Cortisol was analyzed using a radioimmunoassay method. MMP-9 was measured in plasma using an ELISA-method.

    Results: After adjustment for age and sex, significant trends regarding MMP-9 were found both for cortisol peak quintiles (beta +1.9 ng/mL per quintile, p=0.029) and cortisol evening values (beta +2.1 ng/ml per quintile, p=0.017). These findings were consistent in regressions either excluding participants with known diagnoses of myocardial infarction, angina pectoris, rheumatoid arthritis, diabetes, cancer with ongoing treatment, chronic obstructive lung disease, osteoporosis and hypothyroidism, or adjusting for these diseases, also after adjustment for cardiovascular risk factors.

    Conclusions: The associations found between cortisol levels and MMP-9 in a normal population hint at a potential pathway linking prolonged psychosocial strain with cardiovascular events.

  • 4.
    Garvin, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science.
    Jonasson, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Carstensen, John
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Department of Health and Society, Tema Health and Society.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Kristenson, Margareta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science. Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences.
    Levels of circulating matrix metallo proteinase-9 is associated to psychosocial factors and lifestyle2006In: XIV International Symposium on Atherosclerosis,2006, 2006Conference paper (Other academic)
  • 5.
    Garvin, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science.
    Jonasson, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Kristenson, Margareta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science. Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences.
    Nijm, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Psychosocial factors in atherosclerosis2006In: XIV International Symposium on Atherosclerosis,2006, 2006Conference paper (Other academic)
  • 6.
    Garvin, Peter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Plasma Matrix Metalloproteinase-9 Levels Predict First-Time Coronary Heart Disease: An 8-Year Follow-Up of a Community-Based Middle Aged Population2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, p. e0138290-Article in journal (Refereed)
    Abstract [en]

    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.

  • 7.
    Garvin, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Social Medicine and Public Health Science.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Arts and Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Circulating Matrix Metalloproteinase-9 Is Associated with Cardiovascular Risk Factors in a Middle-Aged Normal Population2008In: PLoS ONE, ISSN 1932-6203, Vol. 3, no 3, p. e1774-Article in journal (Refereed)
    Abstract [en]

    Background: Elevated levels of circulating matrix metalloproteinase-9 (MMP-9) have been demonstrated in patients with established coronary artery disease (CAD). The aim of this study was to analyse levels of MMP-9 in a population free from symptomatic CAD and investigate their associations with cardiovascular (CV) risk factors, including C-reactive protein (CRP).

     

    Methods: A cross-sectional study was performed in a population based random sample aged 45–69 (n = 345, 50% women). MMP-9 levels were measured in EDTA-plasma using an ELISA-method. CV risk factors were measured using questionnaires and standard laboratory methods.

    Results: Plasma MMP-9 was detectable in all participants, mean 38.9 ng/mL (SD 22.1 ng/mL). Among individuals without reported symptomatic CAD a positive association (p<0.001) was seen, for both men and women, of MMP-9 levels regarding total risk load of eight CV risk factors i.e. blood pressure, dyslipidemia, diabetes, obesity, smoking, alcohol intake, physical activity and fruit and vegetable intake. The association was significant also after adjustment for CRP, and was not driven by a single risk factor alone. In regression models adjusted for age, sex, smoking, alcohol intake and CRP, elevated MMP-9 levels were independently positively associated with systolic blood pressure (p = 0.037), smoking (p<0.001), alcohol intake (p = 0.003) and CRP (p<0.001). The correlation coefficient between MMP-9 and CRP was r = 0.24 (p<0.001).

     

    Conclusions: In a population without reported symptomatic CAD, MMP-9 levels were associated with total CV risk load as well as with single risk factors. This was found also after adjustment for CRP

     

  • 8.
    Garvin, Peter
    et al.
    Linköping University, Department of Medicine and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Carstensen, John
    Linköping University, Department of Medicine and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Jonasson, Lena
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Kristenson, Margareta
    Linköping University, Department of Medicine and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Plasma Levels of Matrix Metalloproteinase-9 are Independently Associated With Psychosocial Factors in a Middle-Aged Normal Population2009In: PSYCHOSOMATIC MEDICINE, ISSN 0033-3174, Vol. 71, no 3, p. 292-300Article in journal (Refereed)
    Abstract [en]

    Objective: To test the association between psychosocial factors and circulating levels of matrix metalloproteinase-9 (MMP-9) in a normal population sample. Psychosocial factors have been associated with inflammatory markers and are of prognostic significance for coronary artery disease (CAD). The degrading enzyme MMP-9 is upregulated in inflammatory processes and hypothesized to play a role in the rupture of atherosclerotic plaques. Methods: A total of 402 participants (50% women), aged 45 to 69 years, were drawn randomly from a normal population. Psychosocial instruments covered depression (Center for Epidemiological Studies Depression Questionnaire, CES-D), vital exhaustion, hostile affect, cynicism, mastery, self-esteem, sense of coherence (SOC), emotional support, and social integration. Plasma MMP-9 was measured by an enzyme-linked immunosorbent assay method. Linear regression models were adjusted for age, sex, known CAD, rheumatoid arthritis, cancer, cardiovascular risk factors including C-reactive protein and ongoing medication. Results: After full adjustment, there were independent associations of elevated MMP-9 levels with CES-D (+2.9 ng/ml per SD, p=.02), hostile affect (+3.0 ng/ml per SD, p=.02), cynicism (+3.5 ng/ml per SD, p=.006), and SOC (-2.5 ng/ml per SD, p=.046). A principal component analysis extracted three components. The first was mainly extracted from CES-D, vital exhaustion, self-esteem, mastery, and SOC; the second was mainly extracted from hostile affect and cynicism. Both were independently associated with MMP-9 (p=.02, p=.04) when run in the same model. Conclusions: MMP-9 levels were associated with psychosocial factors in a middle-aged normal population sample, independently of traditional risk factors. The findings may constitute a possible link between psychosocial factors and cardiovascular risk.

  • 9.
    Li, Wei
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Lidebjer, Caroline
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Yuan, Ximing
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology.
    Szymanowski, Aleksander
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Backteman, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Leanderson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology.
    Swahn, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Jonasson, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    NK cell apoptosis in coronary artery disease. Relation to oxidative stress2008In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 199, no 1, p. 65-72Article in journal (Refereed)
    Abstract [en]

    Objective: Natural killer (NK) cells, key elements in initiation and modulation of immune responses, were recently found to be reduced in coronary artery disease (CAD). To clarify mechanisms behind this reduction, we here investigated NK cell apoptosis in CAD patients. Since oxidative stress has been linked to NK cell apoptosis, we related the findings to oxidative stress in vivo and evaluated the ex vivo susceptibility of NK cells to oxidized lipids. Methods and results: The number of apoptotic NK cells in peripheral blood was significantly increased in CAD patients compared to controls. Purified NK cells from CAD patients also showed a higher rate of spontaneous apoptosis ex vivo. Dose- and time-dependent effects of oxidized LDL and 7β-hydroxycholesterol (7βOH) on apoptosis and ROS production were determined in NK cells from blood donors. Thereafter, purified NK cells from CAD patients and healthy controls were exposed to the oxidized lipids in a paired design. NK cells from patients were more susceptible to apoptosis induced by oxidized LDL, in particular 7βOH, compared to cells from controls. Plasma measurements of LDL protein oxidation and lipid peroxidation did not show any differences between patients and controls. On the other hand, plasma carotenoids were significantly decreased in patients and inversely correlated to NK cell apoptosis rate. Conclusion: The rate of spontaneous NK cell apoptosis was increased in CAD patients. Although NK cells in CAD patients were more sensitive to oxidized lipids ex vivo, indicating a mechanism contributing to the reduced NK cell activity in CAD, the data could not verify an obvious link between NK cell apoptosis and increased oxidative stress in vivo. © 2007 Elsevier Ireland Ltd. All rights reserved.

  • 10.
    Nijm, Johnny
    et al.
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Östergötlands Läns Landsting, Heart Centre, Department of Cardiology. Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences.
    Jonasson, Lena
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    High serum matrix metalloproteinase-9 level is associated with diurnal salivary cortisol in patients with acute myocardial infarction - a 3-months follow-upManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are closely associated with inflammation and an increasing body of evidence suggests a role in coronary plaque rupture. We have recently shown that an impaired cortisol secretion is related to the enhanced inflammatory activity in patients with coronary disease. In the present paper, we studied the MMP profile in myocardial infarction (MI), its change over time and relation to diurnal salivary cortisol.

    Methods: Thirty patients with a first-time MI were assessed at day 1-3, 2 weeks and 3 months. Serum samples were assayed for C-reactive protein (CRP), interleukin-6 (IL-6), MMP-9, MMP-2, MMP-3 and TIMP-1. Free cortisol was measured in a 24-h urine sample and in repeated saliva samples 30 minutes after awakening and in the evening.

    Results: At 1-3 days, the patients showed increased levels of MMP-9, TIMP-1, IL-6 and CRP and decreased levels of MMP-2 compared to healthy controls. At 2 weeks and 3 months, the MMP-2, IL-6 and CRP levels in patients were similar to controls while the MMP-3 levels increased during follow-up. On the other hand, the levels of MMP-9 and TIMP-1 as well as the MMP-9/TIMP- ratio remained significantly increased in patients from the acute event to 3 months. At all time points, the MI patients showed a flat diurnal cortisol rhythm, as manifested by increased evening cortisol levels. At 2 weeks and 3 months, the evening salivary cortisol was an independent predictor of serum MMP-9 and TIMP-1, but not of MMP-2 or MMP-3.

    Conclusion: In a 3-months follow-up of patients with acute MI, the serum MMP-9, TIMP-1 and MMP-9/TIMP- 1 ratio remined significantly elevated despite rapid normalizations of MMP-2, IL-6 and CRP. Moreover, MMP-9 and TIMP-1 showed a close association with a flat diurnal cortisol rhythm. The data indicate a link between imbalanced MMP pattern and dysfunctional cortisol response in coronary disease with potential implications for plaque progression.

  • 11.
    Nilsson, Lena
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Respiratory monitoring using reflection mode photoplethysmography: clinical and physiological aspects2007In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 51, no 1, p. 130-Article, review/survey (Refereed)
    Abstract [en]

    No abstract available.

  • 12.
    Nilsson, Lennart
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Appel, Carl-Fredrik
    Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Hultkvist, Henrik
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Faculty of Medicine and Health Sciences.
    Vánky, Farkas
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Faculty of Medicine and Health Sciences.
    Evaluation of the Valve Academic Research Consortium-2 Criteria for Myocardial Infarction in Transcatheter Aortic Valve Implantation: A Prospective Observational Study2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, p. e0130423-Article in journal (Refereed)
    Abstract [en]

    Objective To evaluate the relevance of the individual components of the Valve Academic Research Consortium (VARC)-2 criteria for periprocedural myocardial infarction (MI) in transcatheter aortic valve implantation (TAVI). The association between biomarkers and adverse procedural outcome has been established. However, the additive prognostic importance of signs and symptoms are more uncertain. Methods A total of 125 consecutive TAVI patients were prospectively included in this study. Biomarkers for MI were analyzed and signs and symptoms according to VARC-2 criteria were collected from clinical records. Results The criteria of elevated biomarkers and of signs or symptoms were found in 27 (22%) and 32 (26%) of the patients, respectively. According to VARC-2 definition, 12 (10%) had MI. VARC-2 definition of MI, Troponin T (TnT) greater than 600 ng/L, and presence of signs or symptoms correlated with 6 months mortality, prolonged ICU stay, elevation of N-terminal prohormone brain natriuretic peptide, and renal impairment. No signs or symptoms were found in 7 (44%) of the patients who fulfilled the criterion of elevated TnT greater than 600 ng/L. In the group with positive TnT criterion, there were no significant differences between those with and without signs or symptoms in respect to levels of TnT (1014 [585-1720] ng/L versus 704 [515-905] ng/L, p = 0.17) or creatine kinase-MB (36 [25-52] mu g/L versus 29 [25-39] mu g/L, p = 0.32). In the multivariate Cox regression analysis, TnT greater than 600 ng/L was the only significant independent variable associated with 6-months postprocedural mortality. Conclusions Myocardial injury in TAVI, measured with biomarkers, correlates well with adverse procedural outcome. In this study it is also the strongest predictor for early postprocedural mortality. The additional requirement of signs or symptoms for the diagnosis of MI results in omission of a considerable number of clinically significant MI.

  • 13.
    Nilsson, Lennart
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Cherfan, P
    Höglund Hospital.
    Jonasson, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Simvastatin treatment reduces C-reactive protein but not pro-inflammatory cytokines2006In: VIII Svenska Kardiovaskulära Vårmötet,2006, 2006Conference paper (Other academic)
    Abstract [en]

      

  • 14.
    Nilsson, Lennart
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Norrköping.
    Eriksson, Per
    Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm.
    Cherfan, Pierre
    Department of Medicine, Högland Hospital, Eksjö.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Effects of simvastatin on proinflammatory cytokines and matrix metalloproteinases in hypercholesterolemic individuals.2011In: Inflammation, ISSN 0360-3997, E-ISSN 1573-2576, Vol. 34, no 4, p. 225-230Article in journal (Refereed)
    Abstract [en]

    Statins are potent lipid-lowering drugs but anti-inflammatory effects have also been suggested. Our aim was to investigate the effects of simvastatin on proinflammatory cytokines and matrix metalloproteinases (MMPs). Eighty hypercholesterolemic men were randomized to simvastatin 40 mg or placebo for 6 weeks. Simvastatin treatment significantly reduced C-reactive protein (CRP) levels while interleukin (IL)-6 levels remained unchanged. The ex vivo release of IL-1beta and IL-6 was not altered by simvastatin, whereas the release of TNF-alpha and IL-8 increased after 6 weeks of simvastatin treatment. Similarly, the circulating levels of MMP-3 and TIMP-1 remained unaffected by simvastatin while MMP-9 increased. However, none of the effects except for the CRP reduction within the simvastatin group reached statistical significance when compared to the placebo group. Our findings are in contrast to previous in vitro and animal data and question the in vivo relevance of some of the pleiotropic effects of simvastatin.

  • 15.
    Nilsson, Lennart
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Hallen, Jonas
    Oslo University Hospital Ulleval.
    Atar, Dan
    Oslo University Hospital Ulleval.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Early measurements of plasma matrix metalloproteinase-2 predict infarct size and ventricular dysfunction in ST-elevation myocardial infarction2012In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 98, no 1, p. 31-36Article in journal (Refereed)
    Abstract [en]

    Background Immediate reopening of the acutely occluded infarct-related artery via primary PCI is the preferred treatment in ST-elevation myocardial infarction (STEMI). However, the sudden reinitiation of blood flow can lead to a local acute inflammatory response with further endothelial and myocardial damage, so-called reperfusion injury. The activation of matrix metalloproteinases (MMPs) is suggested to be a key event in this process. Objectives To investigate circulating MMPs, tissue inhibitors of metalloproteinases (TIMPs) and myeloperoxidase (MPO) in relation to infarct size, left ventricular dysfunction and remodelling in a STEMI population undergoing PCI. Methods 58 Patients with STEMI undergoing primary PCI were included. Blood samples were collected at baseline before PCI and at 12, 24 and 48 h for later analysis of MMPs, TIMPs and MPO by ELISA. Infarct size, left ventricular (LV) dysfunction and remodelling were assessed by cardiac MRI at 5 days and 4 month after STEMI. Results Plasma MMP-2 at 0 and 12 h showed a consistent and significant correlation with infarct size and LV dysfunction measured both at 5 days and at 4 months and correlated well with troponin I measurements. For TIMP-1 and TIMP-2 some support was found for associations with infarct size and LV dysfunction, but these were not as consistent as for MMP-2. MMP-8, MMP-9 and MPO did not overall correlate with measures of infarct size, LV dysfunction or remodelling. Conclusions In patients with STEMI, circulating levels of MMP-2, measured early and even before reperfusion therapy, are strongly associated with infarct size and LV dysfunction. This provides further evidence for the role of MMP-2 in ischaemia-reperfusion injury.

  • 16.
    Nilsson, Lennart
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Szymanowski, Aleksander
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Soluble TNF Receptors Are Associated with Infarct Size and Ventricular Dysfunction in ST-Elevation Myocardial Infarction2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 2Article in journal (Refereed)
    Abstract [en]

    Objectives

    The aim of the study was to investigate circulating markers of apoptosis in relation to infarct size, left ventricular dysfunction and remodeling in an ST-elevation myocardial infarction (STEMI) population undergoing primary percutaneous coronary intervention (PCI).

    Background

    Immediate re-opening of the acutely occluded infarct-related artery via primary PCI is the treatment of choice in STEMI to limit ischemia injury. However, the sudden re-initiation of blood flow can lead to a local acute inflammatory response with further endothelial and myocardial damage, so-called reperfusion injury. Apoptosis is suggested to be a key event in ischemia-reperfusion injury, resulting in LV-dysfunction, remodeling and heart failure.

    Methods

    The present study is a prespecified substudy of the F.I.R.E. trial. We included 48 patients with STEMI undergoing primary PCI. Blood samples were collected prior to PCI and after 24 hours. Plasma was separated for later analysis of soluble tumor necrosis factor receptor (sTNFR) 1, sTNFR2, sFas and sFas ligand (sFasL) by ELISA. Infarct size, left ventricular (LV) dysfunction and remodeling were assessed by cardiac magnetic resonance imaging at five days and four months after STEMI.

    Results

    The levels of sTNFR1 at 24 h as well as the relative increases in sTNFR1 and sTNFR2 over 24 h showed consistent and significant correlations with infarct size and LV-dysfunction at four months. Moreover, both sTNFRs correlated strongly with Troponin I and matrix metalloproteinase (MMP)-2 measurements. Soluble Fas and sFasL did not overall correlate with measures of infarct size or LV-dysfunction. None of the apoptosis markers correlated significantly with measures of remodeling.

    Conclusions

    In STEMI patients, circulating levels of sTNFR1 and sTNFR2 are associated with infarct size and LV dysfunction. This provides further evidence for the role of apoptosis in ischemia-reperfusion injury.

  • 17.
    Nilsson, Lennart
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Wieringa, Wouter G.
    University of Groningen, Netherlands.
    Pundziute, Gabija
    University of Groningen, Netherlands.
    Gjerde, Marcus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Neutrophil/Lymphocyte Ratio Is Associated with Non-Calcified Plaque Burden in Patients with Coronary Artery Disease2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, p. e108183-Article in journal (Refereed)
    Abstract [en]

    Background: Elevations in soluble markers of inflammation and changes in leukocyte subset distribution are frequently reported in patients with coronary artery disease (CAD). Lately, the neutrophil/lymphocyte ratio has emerged as a potenti al marker of both CAD severity and cardiovascular prognosis. Objectives: The aim of the study was to investigate whether neutrophil/lymphocyte ratio and other immune-inflammatory markers were related to plaque burden, as assessed by coronary computed tomography angiography (CCTA), in patients with CAD. Methods: Twenty patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and 30 patients with stable angina (SA) underwent CCTA at two occasions, immediately prior to coronary angiography and after three months. Atherosclerotic plaques were classified as calcified, mixed and non-calcified. Blood samples were drawn at both occasions. Leukocyte subsets were analyzed by white blood cell differential counts and flow cytometry. Levels of C-reactive protein (CRP) and interleukin(IL)-6 were measured in plasma. Blood analyses were also performed in 37 healthy controls. Results: Plaque variables did not change over 3 months, total plaque burden being similar in NSTE-ACS and SA. However, non-calcified/total plaque ratio was higher in NSTE-ACS, 0.25(0.09-0.44) vs 0.11(0.00-0.25), pless than0.05. At admission, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios, CD4+ T cells, CRP and IL-6 were significantly elevated, while levels of NK cells were reduced, in both patient groups as compared to controls. After 3 months, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios and CD4+ T cells remained elevated in patients. Neutrophil/lymphocyte ratios and neutrophil counts correlated significantly with numbers of non-calcified plaques and also with non-calcified/total plaque ratio (r = 0.403, p = 0.010 and r = 0.382, p = 0.024, respectively), but not with total plaque burden. Conclusions: Among immune-inflammatory markers in NSTE-ACS and SA patients, neutrophil counts and neutrophil/lymphocyte ratios were significantly correlated with non-calcified plaques. Data suggest that these easily measured biomarkers reflect the burden of vulnerable plaques in CAD.

  • 18.
    Nord, Anette
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Svensson, Leif
    Karolinska Institute, Sweden.
    Hult, Hakan
    Karolinska Institute, Sweden.
    Kreitz-Sandberg, Susanne
    Linköping University, Department of Behavioural Sciences and Learning, Education, Teaching and Learning. Linköping University, Faculty of Educational Sciences.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Effect of mobile application-based versus DVD-based CPR training on students practical CPR skills and willingness to act: a cluster randomised study2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 4, p. e010717-Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim was to compare students practical cardiopulmonary resuscitation (CPR) skills and willingness to perform bystander CPR, after a 30 min mobile application (app)-based versus a 50 min DVD-based training. Settings: Seventh grade students in two Swedish municipalities. Design: A cluster randomised trial. The classes were randomised to receive app-based or DVD-based training. Willingness to act and practical CPR skills were assessed, directly after training and at 6 months, by using a questionnaire and a PC Skill Reporting System. Data on CPR skills were registered in a modified version of the Cardiff test, where scores were given in 12 different categories, adding up to a total score of 12-48 points. Training and measurements were performed from December 2013 to October 2014. Participants: 63 classes or 1232 seventh grade students (13-year-old) were included in the study. Primary and secondary outcome measures: Primary end point was the total score of the modified Cardiff test. The individual variables of the test and self-reported willingness to make a life-saving intervention were secondary end points. Results: The DVD-based group was superior to the app-based group in CPR skills; a total score of 36 (3338) vs 33 (30-36) directly after training (pamp;lt;0.001) and 33 (30-36) and 31 (28-34) at 6 months (pamp;lt;0.001), respectively. At 6 months, the DVD group performed significantly better in 8 out of 12 CPR skill components. Both groups improved compression depth from baseline to follow-up. If a friend suffered cardiac arrest, 78% (DVD) versus 75% (app) would do compressions and ventilations, whereas only 31% (DVD) versus 32% (app) would perform standard CPR if the victim was a stranger. Conclusions: At 6 months follow-up, the 50 min DVD-based group showed superior CPR skills compared with the 30 min app-based group. The groups did not differ in regard to willingness to make a life-saving effort.

  • 19.
    Nord, Anette
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Svensson, Leif
    Department of Medicine, Center for Resuscitation Science, Karolinska Institute, Solna, Sweden.
    Karlsson, Thomas
    Health Metrics Unit, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg University, Gothenburg, Sweden.
    Claesson, Andreas
    Department of Medicine, Center for Resuscitation Science, Karolinska Institute, Solna, Sweden.
    Herlitz, Johan
    Prehospen-Center for Prehospital Research, Faculty of Caring Science, Work Life and Social Welfare, University of Borås, Borås, Sweden.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Increased survival from out-of-hospital cardiac arrest when off duty medically educated personnel perform CPR compared with laymen.2017In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 120, p. 88-94Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bystander cardiopulmonary resuscitation (CPR) has been proved to save lives; however, whether survival is affected by the training level of the bystander is not fully described.

    AIM: To describe if the training level of laymen and medically educated bystanders affect 30-day survival in out-of-hospital cardiac arrests (OHCA).

    METHODS: This observational study included all witnessed and treated cases of bystander CPR reported to the Swedish Registry of Cardiopulmonary Resuscitation between 2010 and 2014. Bystander CPR was divided into two categories: (a) lay-byCPR (non-medically educated) and (b) med-byCPR (off duty medically educated personnel).

    RESULTS: During 2010-2014, 24,643 patients were reported to the OHCA registry, of which 6850 received lay-byCPR and 1444 med-byCPR; 16,349 crew-witnessed and non-witnessed cases and those with missing information were excluded from the analysis. The median interval from collapse to call for emergency medical services was 2min in both groups (p=0.97) and 2min from collapse to start of CPR for lay-byCPR versus 1min for med-byCPR (p<0.0001). There were no significant differences in CPR methods used; 64.3% (lay-byCPR) and 65.7% (med-byCPR) applied compressions and ventilation, respectively (p=0.33). The 30-day survival was 14.7% for lay-byCPR and 17.2% for the med-byCPR group (p=0.02). The odds ratio adjusted for potential confounders regarding survival (med-byCPR versus lay-byCPR) was 1.34 (95% confidence interval, 1.11-1.62; p=0.002).

    CONCLUSIONS: In cases of OHCA, medically educated bystanders initiated CPR earlier and an increased 30-day survival was found compared with laymen bystanders. These results support the need to improve the education programme for laypeople.

  • 20. Sheikine, Y
    et al.
    Bang, CS
    Nilsson, Lennart
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Samnegård, A
    Hamsten, A
    Jonasson, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Eriksson, P
    Sirsjö, A
    Decreased plasma CXCL16/SR-PSOX concentration is associated with coronary artery disease2006In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 188, no 2, p. 462-466Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate for the first time whether the plasma CXCL16 concentration is altered in coronary artery disease (CAD) patients. Background: Accumulating evidence suggests that the novel chemokine/scavenger receptor CXCL16/SR-PSOX is involved in the development of atherosclerosis and CAD. Methods: Using ELISA we assessed the plasma CXCL16 concentration in 40 stable angina pectoris (SAP) patients, 17 unstable angina pectoris/non-ST-elevation myocardial infarction (UAP/non-STEMI) patients, 387 survivors of a first myocardial infarction (MI) and healthy control subjects (44 controls for SAP and UAP/non-STEMI patient groups and 387 controls for post-MI patients). Results: SAP patients exhibited significantly lower median CXCL16 levels (2111 pg/ml) than the corresponding control subjects (2678 pg/ml) (P = 0.0012). UAP/non-STEMI patients also appeared to have lower CXCL16 levels (2192 pg/ml) compared with controls (NS). Patients investigated 3 months after MI tended (P = 0.07) to have lower CXCL16 levels (2529 pg/ml) than the corresponding controls (2638 pg/ml). There were no significant correlations between CXCL16 levels and different measures of CAD severity determined by quantitative coronary angiography in post-MI patients. Neither patients nor controls exhibited significant correlations between CXCL16 levels and plasma lipoprotein fractions, inflammatory cytokines, C-reactive protein or numbers of inflammatory cells in peripheral blood. Conclusions: The finding that lower plasma CXCL16 concentration is associated with CAD might indicate a potential atheroprotective function of CXCL16. © 2005 Elsevier Ireland Ltd. All rights reserved.

  • 21.
    Szymanowski, Aleksander
    et al.
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Alfredsson, Joakimjoaal38
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Tomas L.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Swahn, Eva
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jonasson, Lena
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Soluble markers of apoptosis in myocardial infarction patients during acute phase and 6-month follow up2015Manuscript (preprint) (Other academic)
    Abstract [en]

    Objectives

    The aim of the study was to investigate circulating markers of apoptosis in the acute phase and at follow8up in patients with ST8elevation myocardial infarction (STEMI) or non8ST8elevation myocardial infarction (NSTEMI).

    Background

    Myocardial cell death during acute MI results from necrosis, apoptosis and autophagy. An elevated rate of apoptosis can continue for several days after the acute event, contributing to an increased final infarct size. Moreover, a lower but still increased apoptosis can continue for months resulting in left ventricular (LV) dysfunction and heart failure. Few studies have analysed markers of apoptosis longitudinally in MI patients.  Also, it is not known whether STEMI and NSTEMI patients differ in regard to these markers. 

    Methods

    This study is a prespecified substudy of the APACHE trial. We included 61 STEMI and 40 NSTEMI patients. Blood samples for analysis of soluble tumor necrosis factor receptor (sTNFR) 1, sTNFR2, sFas, sFas ligand (sFasL) and IL86 were collected at baseline prior to PCI, at 3 days and at 6 months. High sensitivity troponin T (hsTnT) was measured at 688 hours and echocardiography was performed at 283 days after admission to hospital.

    Results

    STEMI compared to NSTEMI patients showed very similar temporal patterns for each of the markers of apoptosis analyzed. Levels of sTNFRs increased from baseline to day 3 and the absolute increase as well as day 3 levels correlated significantly with TnT. At 6 months, sTNFR1 had returned to baseline whereas levels of sTNFR2 were still elevated. Soluble Fas and sFasL did not change from baseline to day 3, and both markers were significantly lower in the acute phase compared to 6 months. Indeed, sFas at day 3 correlated negatively with TnT. At all time points, plasma sTNFRs were significantly higher in patients with reduced LV function, whereas no such associations with sFas or sFasL was observed. 

    Conclusions

    The TNF and Fas/FasL pathways of apoptosis, as reflected by soluble markers, show markedly different temporal changes after an acute MI, indicating diverse roles of these two systems. STEMI compared to NSTEMI patients showed very similar temporal patterns for all the analyzed markers, suggesting apoptosis to be equally involved in myocardial damage of either infarct type.

  • 22.
    Szymanowski, Aleksander
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Li, Wei
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Lundberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Evaldsson, Chamilly
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Backteman, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Soluble Fas ligand is associated with natural killer cell dynamics in coronary artery disease2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 233, no 2, p. 616-622Article in journal (Refereed)
    Abstract [en]

    Objective: Apoptosis of natural killer (NK) cells is increased in patients with coronary artery disease (CAD) and may explain why NK cell levels are altered in these patients. Soluble forms of Fas and Fas ligand (L) are considered as markers of apoptosis. Here, we investigated whether plasma levels of Fas and FasL were associated with NK cell apoptosis and NK cell levels in CAD patients. Methods: Fas and FasL in plasma were determined by ELISA in 2 cohorts of CAD patients; one longitudinal study measuring circulating NK cells and apoptotic NK cells by flow cytometry 1 day, 3 months and 12 months after a coronary event and one cross-sectional study measuring NK cell apoptosis ex vivo. Both studies included matched healthy controls. Fas and FasL were also determined in supernatants from NK cells undergoing cytokine-induced apoptosis in cell culture. Results: In the 12-month longitudinal study, plasma FasL increased by 15% (p less than 0.001) and NK cell levels by 31% (p less than 0.05) while plasma Fas did not change. Plasma FasL and NK cell levels were significantly related at 3 months and 12 months, r = 0.40, p less than 0.01. Furthermore, plasma FasL, but not plasma Fas, correlated with NK cell apoptosis ex vivo in CAD patients, r = 0.54, p less than 0.05. In vitro, cytokine-induced apoptosis of NK cells resulted in abundant release of FasL. Conclusion: In CAD patients, FasL in plasma is associated with both apoptotic susceptibility of NK cells and dynamic changes in circulating NK cells. NK cells are also themselves a potential source of soluble FasL. Our findings link NK cell status to a soluble marker with possible atheroprotective effects thereby supporting a beneficial role of NK cells in CAD.

  • 23.
    Vallejo-Vaz, Antonio J.
    et al.
    University of London Imperial Coll Science Technology and Med, England.
    Rao Kondapally Seshasai, Sreenivasa
    St Georges University of London, England.
    Kees Della Cole; Hovingh, G.
    Not Found:[Vallejo-Vaz, Antonio J.; Ray, Kausik K.] Univ London Imperial Coll Sci Technol and Med, Sch Publ Hlth, London, England; [Seshasai, Sreenivasa Rao Kondapally; Della Cole] St Georges Univ London, Cardiovasc and Cell Sci Res Inst, London, England; [Hovingh, G. Kees; Kastelein, John J. P.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands; [Mata, Pedro] Fdn Hipercolesterolemia Familiar, Madrid, Spain; [Raal, Frederick J.] Univ Witwatersrand, Fac Hlth Sci, Johannesburg, South Africa; [Santos, Raul D.] Univ Sao Paulo, Med Sch Hosp, Heart Inst InCor, Sao Paulo, Brazil; [Soran, Handrean] Univ Manchester, Fac Med and Hlth Sci, Manchester, Lancs, England; [Watts, Gerald F.] Univ Western Australia, Royal Perth Hosp, Cardiovasc Med, Perth, WA 6009, Australia; [Abifadel, Marianne] St Joseph Univ, Fac Pharm, Lab Biochem and Mol Therapeut, Beirut, Lebanon; [Aguilar-Salinas, Carlos A.] Inst Nacl Ciencias Med and Nutr Salvador Zubiran, Mexico City, DF, Mexico; [Akram, Asif; Car, Josip] Univ London Imperial Coll Sci Technol and Med, Sch Publ Hlth, Global eHlth Unit, London, England; [Alnouri, Fahad] Prince Sultan Cardiac Ctr Riyadh, Cardiovasc Prevent and Rehabil Unit, Riyadh, Saudi Arabia; [Alonso, Rodrigo] Lipid Clin, Dept Nutr, Clin Condes, Santiago, Chile; [Al-Rasadi, Khalid] Sultan Qaboos Univ Hosp, Muscat, Oman; [Banach, Maciej] Med Univ Lodz, Dept Hypertens, Lodz, Poland; [Bogsrud, Martin P.] Natl Advisory Unit Familial Hypercholesterolemia, Oslo, Norway; [Bourbon, Mafalda] Univ Lisbon, Inst Nacl Saude Doutor Ricardo Jorge and BioISI, Biosyst and Integrat Sci Inst, P-1699 Lisbon, Portugal; [Bruckert, Eric] Hop La Pitie Salpetriere, Endocrinol Metab and Prevent Cardiovasc, Inst and IHU Cardiometab ICAN E3M, Paris, France; [Car, Josip] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 639798, Singapore; [Corral, Pablo] FASTA Univ, Sch Med, Mar Del Plata, Buenos Aires, Argentina; [Descamps, Olivier] Hop Jolimont, Haine St Paul, Belgium; [Dieplinger, Hans] Med Univ Innsbruck, Austrian Atherosclerosis Soc, A-6020 Innsbruck, Austria; [Durst, Ronen] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel; [Freiberger, Tomas] Masaryk Univ, Ctr Cardiovasc Surg and Transplantat Brno and Ceitec, Brno, Czech Republic; [Gaspar, Isabel M.] Univ Lisbon, Lisbon Med Sch, Ctr Hosp Lisboa Ocidental and Genet Lab, Dept Med Genet, P-1699 Lisbon, Portugal; [Genest, Jaques] McGill Univ, Montreal, PQ, Canada; [Harada-Shiba, Mariko] Natl Cerebral and Cardiovasc Ctr Res Inst, Osaka, Japan; [Jiang, Lixin] Natl Ctr Cardiovasc Dis, Beijing, Peoples R China; [Kayikcioglu, Meral] Ege Univ, Sch Med, Dept Cardiol, Izmir, Turkey; [Lam, Carolyn S. P.] Natl Heart Ctr Singapore, Singapore, Singapore; [Lam, Carolyn S. P.] Duke Natl Univ Singapore, Singapore, Singapore; [Latkovskis, Gustavs] Univ Latvia, Latvian Res Inst Cardiol, Paul Stradins Clin Univ Hosp, Riga, Latvia; [Laufs, Ulrich] Univ Saarland, Homburg, Germany; [Liberopoulos, Evangelos] Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece; [Nilsson, Lennart] Linkoping Univ, Dept Med and Hlth Sci, Linkoping, Sweden; [Nordestgaard, Borge G.] Univ Copenhagen, Copenhagen Univ Hosp, Herlev and Gentofte Hosp, Copenhagen, Denmark.
    Kastelein, John J. P.
    University of Amsterdam, Netherlands.
    Mata, Pedro
    Fdn Hipercolesterolemia Familiar, Spain.
    Raal, Frederick J.
    University of Witwatersrand, South Africa.
    Santos, Raul D.
    University of Sao Paulo, Brazil.
    Soran, Handrean
    University of Manchester, England.
    Watts, Gerald F.
    University of Western Australia, Australia.
    Abifadel, Marianne
    St Joseph University, Lebanon.
    Aguilar-Salinas, Carlos A.
    Institute Nacl Ciencias Medical and Nutr Salvador Zubiran, Mexico.
    Akram, Asif
    University of London Imperial Coll Science Technology and Med, England.
    Alnouri, Fahad
    Prince Sultan Cardiac Centre Riyadh, Saudi Arabia.
    Alonso, Rodrigo
    Lipid Clin, Chile.
    Al-Rasadi, Khalid
    Sultan Qaboos University Hospital, Oman.
    Banach, Maciej
    Medical University of Lodz, Poland.
    Bogsrud, Martin P.
    National Advisory Unit Familial Hypercholesterolemia, Norway.
    Bourbon, Mafalda
    University of Lisbon, Portugal.
    Bruckert, Eric
    Hop La Pitie Salpetriere, France.
    Car, Josip
    University of London Imperial Coll Science Technology and Med, England; Nanyang Technology University, Singapore.
    Corral, Pablo
    FASTA University, Argentina.
    Descamps, Olivier
    Hop Jolimont, Belgium.
    Dieplinger, Hans
    Medical University of Innsbruck, Austria.
    Durst, Ronen
    Hadassah Hebrew University, Israel.
    Freiberger, Tomas
    Masaryk University, Czech Republic.
    Gaspar, Isabel M.
    University of Lisbon, Portugal.
    Genest, Jaques
    McGill University, Canada.
    Harada-Shiba, Mariko
    National Cerebral and Cardiovasc Centre Research Institute, Japan.
    Jiang, Lixin
    National Centre Cardiovasc Disease, Peoples R China.
    Kayikcioglu, Meral
    Ege University, Turkey.
    Lam, Carolyn S. P.
    National Heart Centre Singapore, Singapore; Duke National University of Singapore, Singapore.
    Latkovskis, Gustavs
    University of Latvia, Latvia.
    Laufs, Ulrich
    University of Saarland, Germany.
    Liberopoulos, Evangelos
    University of Ioannina, Greece.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Nordestgaard, Borge G.
    University of Copenhagen, Denmark.
    ODonoghue, John M.
    Global eHealth Unit, School of Public Health, Imperial College London, London, UK.
    Sahebkar, Amirhossein
    Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
    Schunkert, Heribert
    Deutsches Herzzentrum Munchen, Klinikan der TU Munchen, Munich Heart Alliance, Germany.
    Shehab, Abdulla
    CMHS, UAE University, AlAin, United Arab Emirates.
    Stoll, Mario
    Cardiovascular Genetic Laboratory, Cardiovascular Health Commission, Montevideo, Uruguay.
    Su, Ta-Chen
    Department of Internal Medicine and Cardiovascular Centre, National Taiwan University Hospital, Taipei, Taiwan.
    Susekov, Andrey
    Laboratory of Clinical Lipidology, Cardiology Research Complex, Moscow, Russia.
    Widen, Elisabeth
    Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
    Catapano, Alberico L.
    University of Milan and Multimedica IRCCS Milan, Italy.
    Ray, Kausik K.
    University of London Imperial Coll Science Technology and Med, England.
    Familial hypercholesterolaemia: A global call to arms2015In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 243, no 1, p. 257-259Article in journal (Refereed)
    Abstract [en]

    n/a

  • 24.
    Vánky, Farkas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Hultkvist, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Svedjeholm, Rolf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Is the present definition of mycardial infarction in transcatheter aortic valve implantation relevant for the postprocedulal outcome?2015Conference paper (Other academic)
    Abstract [en]

    Background: The association between biomarkers and adverse procedural outcome has been established. However, the additive prognostic importance of signs and symptoms according to the Valve Academic Research Consortium (VARC)-2 criteria for periprocedural myocardial infarction (MI) are more uncertain.

    Aim: To evaluate the relevance of the individual components of the VARC-2 criteria for periprocedural myocardial infarction (MI) in transcatheter aortic valve implantation (TAVI).Methods: A total of 125 consecutive TAVI patients were prospectively included in this study. Biomarkers for MI were analyzed and signs and symptoms according to VARC-2 criteria were collected from clinical records.

    Results: The criteria of elevated biomarkers and of signs or symptoms were found in 27 ( 22%) and 32 ( 26%) of the patients, respectively. According to VARC-2 definition, 12 (10%) had MI. VARC-2 definition of MI, Troponin T (TnT) >600 ng/L, and presence of signs or symptoms correlated with 6 month mortality, prolonged ICU stay, elevation of N-terminal prohormone brain natriuretic peptide, and renal impairment. No signs or symptoms were found in 7 (4 4%) of the patients who fulfilled the criterion of elevated TnT>600 ng/L. In the group with positive TnT criterion, there were no significant differences between those with and without signs or symptoms in respect to levels of TnT (1014 [585-1720] ng/L versus 704 [515-905] ng/L, p=0.17) or creatine kinase-MB ( 36 [25-52] μg/L versus 29 [25-39] μg/L, p=0.32). In the multiple logistic regression model, TnT>600 ng/L turned out as the only independent variable associated with 6-month mortality, OR 7.89 (95% CI 2.21-28.1, p = 0.001).

    Conclusion: Myocardial injury in TAVI, measured with TnT, correlates well with adverse procedural outcome. The additional requirement of signs or symptoms for the diagnosis of MI results in omission of a considerable number of clinically significant MI.

  • 25.
    Wetterö, Jonas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Jonasson, Lena
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Reduced serum levels of autoantibodies against monomeric C-reactive protein (CRP) in patients with acute coronary syndrome2009In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 400, no 1-2, p. 128-131Article in journal (Refereed)
    Abstract [en]

    Introduction: Inflammation is pivotal in atherosclerosis. Minor C-reactive protein (CRP) response reflects low-grade vascular inflammation and the high-sensitivity CRP test with levels >= 3.0 mg/l predicts coronary vascular events and survival in angina pectoris as well as in healthy subjects. We and others recently reported autoantibodies against monomeric CRP (anti-CRP) in rheumatic conditions, e.g. systemic lupus erythematosus (SLE), and a connection between anti-CRP and cardiovascular disease in SLE has been suggested.

    Patients and methods: Anti-CRP serum levels were determined with ELISA in 140 individuals; 50 healthy controls and 90 patients with angiographically verified coronary artery disease of which 40 presented with acute coronary syndrome (ACS) and 50 with stable angina pectoris (SA).

    Results: Significantly lower anti-CRP levels were observed in ACS compared to SA and controls (p=0.019). ACS patients, who had not been prescribed statins before their respective cardiovascular event, had lower anti-CRP (p = 0.049). BMI correlated directly to anti-CRP levels in cross section analysis (p = 0.043), but there was no association between anti-CRP and smoking or cholesterol.

    Discussion: In ACS, it is plausible that ruptured plaques and inflamed tissue may be more prone to opsonization by monomeric CRP leading to consumption of anti-CRP, Hypothetically, surface-bound anti-CRP could thereby enhance the local inflammation in plaques.

  • 26.
    Wiklund, P.-G.
    et al.
    Department of Public Health and Clinical Medicine, Umeå University Hospital, Sweden, Department of Medicine, University Hospital, SE-901 85 Umeå, Sweden.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Ardnor, S.N.
    Department of Medical Clinical Genetics, Umeå University, Sweden.
    Eriksson, P.
    Atherosclerosis Research Unit, King Gustav V Research Institute, Karolinska Hospital, Stockholm, Sweden.
    Johansson, L.
    Department of Public Health and Clinical Medicine, Umeå University Hospital, Sweden.
    Stegmayr, B.
    Department of Public Health and Clinical Medicine, Umeå University Hospital, Sweden.
    Hamsten, A.
    Atherosclerosis Research Unit, King Gustav V Research Institute, Karolinska Hospital, Stockholm, Sweden.
    Holmberg, D.
    Department of Medical Clinical Genetics, Umeå University, Sweden.
    Asplund, K.
    Department of Public Health and Clinical Medicine, Umeå University Hospital, Sweden.
    Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke: Replicated findings in two nested case-control studies based on independent cohorts2005In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 36, no 8, p. 1661-1665Article in journal (Refereed)
    Abstract [en]

    Background and Purpose - Impaired fibrinolytic function secondary to elevated plasminogen activator inhibitor-1 (PAI-1) levels has been implicated in ischemic stroke. PAI-1 levels are determined by genetic factors and environmental factors, triglyceride levels in particular. The aim of this study was to investigate the common functional 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene and the risk of stroke. Methods - A nested case-control study design was applied, using baseline data for 2 independent cohorts obtained at population-based surveys in northern Sweden. In study A, there were 113, and in study B, there were 275 individuals without major concomitant disease at baseline who later experienced a first-ever stroke. Blood samples obtained at baseline were analyzed for potential risk factors, including the 4G/5G polymorphism of the PAI-1 gene. Results - The 4G allele of the PAI-1 polymorphism was associated with an increased risk of future ischemic stroke in both studies (odds ratio [OR] of 4G homozygosity, 1.87, 95% CI, 1.12 to 3.15 in study A, OR of 4G homozygosity, 1.56, 95% CI, 1.12 to 2.16 in study B). Individuals with the combination of hypertriglyceridemia and 4G homozygosity were at the greatest risk of developing stroke. Multiple logistic regression analysis identified 4G homozygosity, systolic blood pressure, and diabetes as independent predictors of ischemic stroke. Conclusions - Identical findings in 2 independent studies strongly suggest a true and clinically important association between PAI-1 4G/5G genotype and risk of future ischemic stroke. The observed modification of the genotype effect by triglycerides may be interpreted as a gene-environment interaction. © 2005 American Heart Association. Inc.

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