| 1. |
- Ay, Hakan, et al.
(författare)
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Pathogenic Ischemic Stroke Phenotypes in the NINDS-Stroke Genetics Network
- 2014
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Ingår i: Stroke. - 0039-2499. ; 45:12, s. 3589-3596
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. METHODS: Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. RESULTS: The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70-0.75). CONCLUSIONS: This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.
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| 2. |
- Pesonen, Erkki, et al.
(författare)
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Dual role of infections as risk factors for coronary heart disease.
- 2007
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 192:2, s. 370-375
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of the study was to explore whether exposure to microbial agents determines the prevalence of acute coronary events. Methods and results: Patients with unstable angina pectoris and myocardial infarction (N = 335) and their paired controls were investigated. The subjects answered a questionnaire about their childhood contagious diseases: varicella, scarlet fever, measles, rubella, mononucleosis and mumps. Blood samples were taken for bacterial and viral serology. The odds ratio for CHD was highest in the upper quartile of the enterovirus (EV), herpes simplex virus (HSV) and Chlamydia pneumoniae HSP60 IgG antibody titers (1.86, p = 0.001, 1.57, p < 0.048 and 1.70, p = 0.016, respectively). The antibody titers increased cumulatively the risk for CHD (odds ratios 1.89, 2.24, 3.92 and p-values < 0.001, 0.001 and 0.047). Childhood contagious diseases (n = 6) had a protecting effect against CHD (odds ratio 0.86, p = 0.013). The risk for acute coronary events decreased significantly with increasing number of childhood contagious diseases (p = 0.007). Conclusions: Infections have a dual role in the genesis of CHD. EV, HSV and C. pneumoniae heat shock protein 60 IgG antibodies are associated with increased risk for CHID. Protection from infections usually suffered during the childhood before the era of MMR vaccination may predispose the individual to CHD.
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| 3. |
- Pesonen, Erkki, et al.
(författare)
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Elevated infection parameters and infection symptoms predict an acute coronary event.
- 2008
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Ingår i: Therapeutic Advances in Cardiovascular Disease. - : SAGE Publications. - 1753-9447 .- 1753-9455. ; 2:6, s. 419-424
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The etiology and significance of flu-like symptoms often appearing before myocardial infarction should be clarified. METHODS: In a case-control study of 323 matched controls and a random sample of 110 out of 351 cases the presence of infection symptoms during the preceding four weeks before admission were asked and blood samples taken. RESULTS: Enterovirus (EV), herpes simplex virus (HSV), and Chlamydia pneumoniae IgA titers were significantly higher in cases than in controls (p<0.001, 0.008 and 0.046, respectively). Flu-like symptoms appeared significantly more often in patients than in controls the most common one being fatigue (p<0.001). In controls with fatigue, EV and HSV titers showed a trend to be higher (1.50 vs 1.45 and 4.29 vs 3.73) than in controls without fatigue but only HSV titers were statistically significantly higher (3.47 vs 3.96, p = 0.02). Even CRP and amyloid A concentrations (3.49 vs 2.08, p<0.0001 and 5.70 vs 3.77 mg/l, p = 0.003, respectively) as well as C4 (0.40 vs 0.44, p = 0.02) were higher in controls with fatigue. CONCLUSIONS: Odds ratios for a coronary event in a logistic regression model were 4.79 for fatigue and 2.72 for EV antibody levels in their fourth quartile. A linear-by-linear association test showed increasing number of single symptoms with higher EV titer quartiles (p = 0.004).
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| 4. |
- Pesonen, Erkki, et al.
(författare)
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Mannose-binding lectin as a risk factor for acute coronary syndromes.
- 2009
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Ingår i: Annals of Medicine. - : Informa UK Limited. - 1365-2060 .- 0785-3890. ; 41, s. 591-598
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Tidskriftsartikel (refereegranskat)abstract
- Background. Mannose-binding lectin (MBL) is a multifunctional protein involved in innate immunity. We tested whether MBL and elevated viral and bacterial antibodies were risk factors for acute coronary events. Design. Controlled cohort study. Methods. A total of 354 patients with unstable angina pectoris (UA) or acute myocardial infarction (AMI) were compared with 334 paired controls. Results. Enterovirus titres were associated with increased risk of UA (odds ratio 10.04, P<0.001) and AMI (odds ratio 3.18, P=0.003), but titres did not correlate with either MBL concentration or genotype. Chlamydia pneumoniae heat shock protein 60 IgG concentrations were also associated with increased risk of UA (odds ratio 1.63, P=0.049). Compared to asymptomatic controls, patients had lower complement C3 serum concentrations (P<0.001), higher MBL serum concentration, and more frequently had MBL genotypes that determined high MBL levels (P<0.001). High MBL genotypes had odds ratios of 1.16 (P=0.010) for UA and 1.12 (P=0.007) for AMI. The elevation of MBL concentrations in the acute phase correlated with MBL concentrations after recovery (r=0.85, P<0.001). Conclusions. Elevated microbial titres, indicating an on-going inflammation, were associated with cardiovascular events. MBL might have a dual role both decreasing susceptibility to infections and increasing the risk of acute coronary syndromes.
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| 5. |
- Platonov, Pyotr, et al.
(författare)
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Permanent atrial fibrillation in patients without structural heart disease is not associated with signs of infection by Chlamydia pneumoniae and Helicobacter pylori.
- 2008
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Ingår i: Acta Cardiologica. - 0001-5385. ; 63:4, s. 479-484
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective of this study was to explore the role of Chlamydia pneumoniae and Helicobacter pylori infections in patients with idiopathic permanent atrial fibrillation. METHODS AND RESULTS: Sera from 72 patients with permanent atrial fibrillation without structural heart disease (mean age 69.6 years, 23 women) were analysed for IgG antibodies against Chlamydia pneumoniae and Helicobacter pylori and compared in a I:I age- and sex-matched case:control manner with those pooled from a healthy reference population of 72 individuals from the same geographical area. After excluding patients with other possible or definite factors known either to cause atrial fibrillation or to affect the prevalence of seropositivity to these agents, the frequency of seropositivity due to one or both of the infectious agents was compared. Serum C-reactive protein (CRP) level was assessed using immunoturbidimetry technique. Both agents were equally common in men and women. Neither seropositivity to Chlamydia pneumoniae (76% vs. 83%, patients vs. control subjests, ns) nor to Helicobacter pylori (57% contra 55%, patients vs. controls, ns) alone reached significance in the comparisons between patients with atrial fibrillation and control subjects. Serum CRP was higher in patients with AF (5.3 mg/L vs. 2.8 mg/L, P < 0.001). CONCLUSIONS: Though presence of permanent AF is associated with elevated CRP levels, this elevation is not the result of earlier infections with Chlamydia pneumoniae or Helicobacter pylori or their combination.
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