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- Odermarsky, Michal, et al.
(författare)
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HLA, infections and inflammation in early stages of atherosclerosis in children with type 1 diabetes
- 2018
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 1432-5233 .- 0940-5429. ; 55:1, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- Aims This prospective study focuses on risk factors for arterial damage in children with type 1 diabetes (T1D). Methods Eighty children and adolescents with T1D were investigated twice, approximately 2 years apart, for carotid artery intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)-8. All subjects were genotyped for HLA. The number of respiratory tract infections (RTI) during the past year was obtained by a questionnaire in 56 patients. Results cIMT progression, defined as percentage (%) change of cIMT from baseline, correlated inversely with the % changes of both CAC (p = 0.04, r = − 0.3; n = 62) and FMD (p = 0.03, r = − 0.3; n = 47). In multivariate analysis, RTI frequency correlated significantly with cIMT progression irrespective of age, diabetes duration, BMI, and HbA1c (p = 0.03, r = 0.3). When patients were divided in relation to RTI, the association of DQ2/8 with cIMT progression remained significant in patients with over three infections/year (p = 0.04, r = 0.3). During follow-up, the group of DQ2/8 patients with hsCRP > 1 mg/l showed significantly higher levels of plasma MMP-8 than the non-DQ2/8 group. Conclusions The diabetes-risk genotype DQ2/8 and systemic inflammation contribute to pro-atherosclerotic vascular changes in children and adolescents with T1D.
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| 2. |
- Odermarsky, M., et al.
(författare)
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Human Leucocyte Antigen, Infections and Systemic Inflammatory Biomarkers in Early Atherosclerosis in Children and Adolescents with Type 1 Diabetes
- 2015
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Ingår i: Cardiology in the Young. - 1467-1107. ; 25:Suppl. 1, s. 33-33
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Konferensbidrag (refereegranskat)abstract
- Background: This prospective study focuses on factors associated with arterial damage in children with type 1 diabetes (T1D). Materials and Methods: Eighty children and adolescents with T1D (mean age 15, range: 8-20 yrs; mean diabetes duration 7, range: 0.5 to 19 years) were investigated twice, approximately 2 years apart, for carotid artery intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)-8. HLA genotypes were determined in dried spots of peripheral blood by polymerase chain reaction followed by hybridization assay. The number of respiratory tract infections (RTI) during the past year was obtained by a questionnaire in 56 patients. Results: cIMT progression (% change of cIMT from baseline) correlated inversely with the % changes of both CAC (p = 0.04, r=−0.3, n=62) and FMD (p=0.03, r=−0.3, n=67). RTI frequency correlated significantly with cIMT progression irre- spective of age, diabetes duration, BMI, and HbA1c (p=0.03, r=0.3, in multivariate analysis). When patients were divided in relation to DQ2/8 genotype and RTI, the association of DQ2/8 with cIMT progression remained significant in patients with over three infections/year (p = 0.04, r = 0.3). During follow-up, the group of DQ2/8 patients with CRP > 1 mg/l showed significantly higher levels of plasma MMP-8 than the non-DQ2/8 group. Conclusions: Diabetes-risk genotype DQ2/8 and inflammation con- tribute to vascular changes in children and adolescents with T1D.
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| 3. |
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| 4. |
- Pesonen, Erkki, et al.
(författare)
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Infections as a stimulus for coronary occlusion, obstruction, or acute coronary syndromes.
- 2009
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Ingår i: Therapeutic Advances in Cardiovascular Disease. - : SAGE Publications. - 1753-9447 .- 1753-9455.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: : Atherosclerosis is considered to be an inflammatory disease. Infections are a significant cause of inflammation. Acute infections might precipitate acute coronary syndromes (ACS) whereas chronic infections might be stimuli for the development of atherosclerosis. METHODS: : Coronary angiograms were done on 211 of 335 patients with ACS and the percentage of coronary obstruction was determined. Serum antibody levels to Chlamydia pneumoniae, C. pneumoniae heat shock protein 60 (CpnHSP60), human heat shock protein 60 (hHSP60), enterovirus (EV), herpes simplex virus (HSV), cytomegalovirus (CMV), and two major periodontal pathogens, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, were measured in healthy controls (n = 355) and all patients. RESULTS: : Serum antibody levels to periodontal pathogens did not correlate with ACS. However, IgA-class antibody levels to Aggregatibacter actinomycetemcomitans (p = 0.021), CpnHSP60 (p = 0.048) an hHSP60 (p = 0.038) were higher in patients with coronary occlusion or obstruction compared to those without any obstruction. Odds ratios for coronary changes in the highest quartile as compared to the lower quartiles were for A. actinomycetemcomitans IgA 7.84 (95% CI 1.02-60.39, p = 0.048), for CpnHSP60 IgA 8.61 (1.12-65.89, p = 0.038), and for human HSP60 IgA 3.51 (0.79-15.69, p = 0.100). CONCLUSIONS: : We have previously reported that EV and HSV titres correlated significantly to acute coronary events. They do not correlate to the degree of coronary obstruction as shown here. However, infection by A. actinomycetemcomitans or C. pneumoniae or host response against them associated with coronary obstruction. Clinical coronary events may arise by the effect of acute infections and obstructing lesions by a chronic inflammatory stimulus.
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| 5. |
- Pussinen, Pirkko J., et al.
(författare)
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The balance of serum matrix metalloproteinase-8 and its tissue inhibitor in acute coronary syndrome and its recurrence
- 2013
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 167:2, s. 362-368
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Tidskriftsartikel (refereegranskat)abstract
- Background: Matrix metalloproteinase-8 (MMP-8) is involved in the breakdown of the extracellular matrix increasing the vulnerability of atherosclerotic lesions. We analysed the diagnostic value of serum MMP-8 and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations in acute coronary syndrome (ACS) and their prognostic value in ACS recurrence. Methods: The population comprised 343 patients with ACS [including 108 unstable angina pectoris and 235 acute myocardial infarctions (AMI)] and 326 healthy controls. Additionally, 157 (45.8%) patients were resampled during the recovery. The ACS patients were followed up for 6 years. Results: MMP-8, TIMP-1, and their molar ratio distinguished the cases from the controls; C-statistic of the multivariate model (95% CI, p-value) including the MMP-8/TIMP-1 ratio regarding its discriminating ability for AMI was 0.922 (0.893-0.950, p < 0.001). After the acute phase of ACS, median MMP-8 and TIMP-1 concentrations decreased (p < 0.001) by 34.5 and 28.7%, respectively, but ended up on a different level than those found in the controls. In the follow-up, acute phase and recovery period TIMP-1 concentrations associated with cardiovascular death with hazard ratios 4.31 (2.00-9.26, p < 0.001) and 4.69 (1.10-20.01, p = 0.037), respectively. Conclusions: The increase of serum MMP-8 and TIMP-1 concentrations may reflect plaque instability and tissue damage. TIMP-1 concentrations are associated with poor outcome in patients with ACS. The findings may have practical implications in both diagnostics and therapeutics. (c) 2011 Elsevier Ireland Ltd. All rights reserved.
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| 6. |
- Putaala, Jukka, et al.
(författare)
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Searching for Explanations for Cryptogenic Stroke in the Young : Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design
- 2017
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 2:2, s. 116-125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.
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