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  • 1.
    Wiberg, Bernice
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Risk Factors for Stroke in Adult Men: A Population-based Study2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the last decades our knowledge concerning cardiovascular risk factors has grown rapidly through results from longitudinal studies. However, despite new treatment, in Western countries coronary heart disease remains the leading cause of death and stroke is still the leading cause of severe disability.

    The studies reported in these papers examine the relationships between stroke/transient ischaemic attack (TIA) and a number of different factors measured on two different occasions in men born in Uppsala 1920-1924 and are epidemiological in their character.

    The findings indicate that in addition to already established risk factors, indices of an unhealthy dietary fat intake and high serum lipoprotein(a) are independent predictors of stroke/TIA. Among different glucometabolic variables a low insulin sensitivity index derived from the euglycaemic insulin clamp and proinsulin carries a high predictive value for later stroke, independently of diabetes.

    Moreover, cognitive test performance measured with Trail Making Test B at age 70 is a strong and independent predictor of brain infarction, indicating that the risk is already increased in the subclinical phase of milder cognitive dysfunction. Performance at a pre-stroke Trail Making Test is also of predictive value for mortality after first-ever stroke/TIA, but none of the studied pre-stroke variables or cognitive tests was found to be related to dependency after an event.

    In summary these studies provide further knowledge about predictors of stroke and of mortality after first-ever stroke. They also indicate the possible importance of new markers of risk, such as the level of lipoprotein(a), profile of fatty acids in the diet, low insulin sensitivity derived from clamp investigations, level of proinsulin, and cognitive performance measured with Trail Making Tests.

     

    List of papers
    1. Metabolic risk factors for stroke and transient ischemic attacks in middle-aged men: a community-based study with long-term follow-up
    Open this publication in new window or tab >>Metabolic risk factors for stroke and transient ischemic attacks in middle-aged men: a community-based study with long-term follow-up
    Show others...
    2006 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 37, no 12, p. 2898-2903Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND AND PURPOSE: The impact of lipometabolic and glucometabolic disturbances on stroke incidence remains to be characterized in detail. We investigated relations of a comprehensive panel of baseline lipometabolic and glucometabolic variables to incident fatal and nonfatal stroke or transient ischemic attack (TIA), and stroke subtypes. METHODS: A community-based prospective study of 2313 middle-aged men invited to a health survey at age 50. RESULTS: During a follow-up of up to 32 years, 421 developed stroke or TIA. In Cox proportional hazards analyses adjusting for treatment with cardiovascular drugs at baseline, 1-standard deviation increases in body mass index, systolic and diastolic blood pressures, serum proinsulin, and lipoprotein(a) were associated with 11 to 35% increased risk for subsequent stroke/TIA. Electrocardiographic left ventricular hypertrophy and smoking were also associated with a higher risk for stroke/TIA. Essentially the same variables were related to brain infarction/TIA. Higher proportions of palmitic (16:0), palmitoleic (16:1), and oleic acid (18:1) in cholesterol esters were associated with an increased risk, whereas a higher proportion of linoleic acid (18:2 n-6) was protective against stroke/TIA. Further adjusting all models also for hypertension, diabetes, the metabolic syndrome, serum cholesterol, atrial fibrillation, cardiovascular disease, smoking, and physical activity, essentially the same pattern was observed. CONCLUSIONS: Indices of an unhealthy dietary fat intake and a high serum lipoprotein (a) level predicted fatal and nonfatal stroke/TIA independently of established risk factors in a community-based sample of middle-aged men followed for 32 years.

    Keywords
    fatty acids, lipoproteins, risk factors, stroke
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-18469 (URN)10.1161/01.STR.0000249056.24657.8b (DOI)000243411500018 ()17053177 (PubMedID)
    Available from: 2006-12-21 Created: 2006-12-21 Last updated: 2017-12-08Bibliographically approved
    2. Insulin sensitivity measured by the euglycaemic insulin clamp and proinsulin levels as predictors of stroke in elderly men
    Open this publication in new window or tab >>Insulin sensitivity measured by the euglycaemic insulin clamp and proinsulin levels as predictors of stroke in elderly men
    2009 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, no 1, p. 90-6Article in journal (Refereed) Published
    Abstract [en]

    AIMS/HYPOTHESIS: Our aim was to investigate the predictive power of a panel of variables in glucose and insulin metabolism for the incidence of stroke or transient ischaemic attacks (TIA). We hypothesised that proinsulin and insulin resistance contributes to an increase of risk for fatal and non-fatal stroke/TIA, independently of diabetes and established risk factors. METHODS: The study is based on the Uppsala Longitudinal Study of Adult Men cohort. The examinations were performed at age 70 years. RESULTS: In 1,151 men free from stroke at baseline, 150 developed stroke or TIA during a median follow-up of 8.8 years. In unadjusted Cox proportional hazards analyses, a 1 SD increase of a predictor variable was associated with an increased risk for stroke/TIA, e.g. plasma insulin (HR 1.19, 95% CI 1.01-1.40), fasting intact proinsulin (HR 1.28, 95% CI 1.09-1.49); whereas a 1 SD increase in insulin sensitivity measured by the euglycaemic insulin clamp method decreased the risk for stroke/TIA (HR 0.81, 95% CI 0.68-0.96). The predictive values of fasting intact proinsulin and insulin sensitivity endured but not that of plasma insulin when adjusting for diabetes. In models adjusting for diabetes, hypertension, atrial fibrillation, electrocardiographic left ventricular hypertrophy, serum cholesterol and smoking, proinsulin remained as a significant predictor of later stroke/TIA (HR 1.22, 95% CI 1.00-1.48) whereas clamp insulin sensitivity did not (HR 0.87, 95% CI 0.71-1.07). CONCLUSIONS/INTERPRETATION: Fasting intact proinsulin level and insulin sensitivity at clamp predicted subsequent fatal and non-fatal stroke/TIA, independently of diabetes in elderly men whereas fasting insulin did not.

    Keywords
    Clamp, Insulin resistance, Proinsulin, Risk factors, Stroke
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-103482 (URN)10.1007/s00125-008-1171-0 (DOI)000261375400014 ()18949454 (PubMedID)
    Available from: 2009-05-19 Created: 2009-05-19 Last updated: 2017-12-13Bibliographically approved
    3. Cognitive function and risk of stroke in elderly men
    Open this publication in new window or tab >>Cognitive function and risk of stroke in elderly men
    Show others...
    2010 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 74, no 5, p. 379-385Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: Vascular risk factors are associated with ischemic changes in the cerebral white matter. We studied the predictive value of cognitive test performance especially related to subcortico-frontal pathways, together with a cognitive screening test, for later incidence of fatal or nonfatal stroke or TIAs and stroke subtypes. METHODS: A sample of 930 70-year-old men without previous stroke/TIA from the community-based Uppsala Longitudinal Study of Adult Men was investigated at baseline using Trail Making Tests (TMT) A and B and the Mini-Mental State Examination (MMSE). RESULTS: During up to 13 years of follow-up, 166 men developed a stroke or TIA; 105 participants had a brain infarction. In Cox proportional hazards analyses adjusting for education, social group, and traditional cardiovascular risk factors, a 1-SD increase in TMT-B time was associated with a higher risk for brain infarction (hazard ratio 1.48, 95% confidence interval 1.11-1.97). The risk of brain infarction was more than threefold higher in the highest (TMT-B = 146-240 s) compared to the lowest (TMT-B = 43-84 s) TMT-B quartile. TMT-A and MMSE results were not consistently related to stroke outcomes. CONCLUSION: Impaired performance in elderly men measured by Trail Making Test B, a cognitive test especially reflecting subcortico-frontal activities, was an independent predictor of subsequent brain infarction in this community-based sample of elderly men. Our results extend previous findings of cognitive decline as an independent predictor of stroke and indicate that the risk of brain infarction is increased already in the subclinical phase of cognitive deficit.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-123000 (URN)10.1212/WNL.0b013e3181ccc516 (DOI)000274154000006 ()20124202 (PubMedID)
    Available from: 2010-04-22 Created: 2010-04-22 Last updated: 2017-12-12Bibliographically approved
    4. Cognitive Function Prior to Stroke is a Risk Factor for Post-Stroke Mortality but Not Dependency
    Open this publication in new window or tab >>Cognitive Function Prior to Stroke is a Risk Factor for Post-Stroke Mortality but Not Dependency
    Show others...
    (English)Article in journal (Other academic) Submitted
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:uu:diva-120536 (URN)
    Available from: 2010-03-12 Created: 2010-03-12 Last updated: 2018-08-24
  • 2.
    Wiberg, Bernice
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cognitive Function Prior to Stroke is a Risk Factor for Post-Stroke Mortality but Not DependencyArticle in journal (Other academic)
  • 3.
    Wiberg, Bernice
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    The relationship between executive dysfunction and post-stroke mortality: a population-based cohort study2012In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, no 3, p. e000458-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    To study the associations of pre-stroke cognitive performance with mortality after first-ever stroke or transient ischaemic attack (TIA).

    DESIGN:

    A prospective cohort study.

    SETTING AND PARTICIPANTS:

    In participants having first-ever stroke or TIA during up to 14 years of post-test follow-up (n=155), we investigated the associations of pre-stroke variables and cognitive test results with post-stroke survival. The study is based on those participants of the Uppsala Longitudinal Study of Adult Men who performed cognitive function tests at approximately age 70 (n=919).

    PRIMARY OUTCOME MEASURES:

    Mortality after first-ever stroke or TIA related to pre-stroke executive performance.

    RESULTS:

    Eighty-four (54%) of the first-ever stroke/TIA patients died under a median follow-up of 2.5 years after the event. In Cox proportional hazard analyses adjusting for age, education, social group and traditional stroke risk factors, poor performance in Trail Making Test (TMT)-A was related to mortality (HR 1.88 per SD, 95% CI 1.31 to 2.71, p=0.001). The risk of mortality was approximately threefold higher in the highest tertile compared with the lowest tertile (HR TMT-A= 2.90 per SD, 95% CI 1.24 to 6.77, p=0.014). A similar pattern was seen for TMT-B, but Mini-Mental State Examination results were not related to risk of post-stroke mortality.

    CONCLUSION:

    Executive performance measured by TMT-A and -B before stroke was independently associated with long-term risk of mortality, after first-ever stroke or TIA in a population-based study of older men.

  • 4.
    Wiberg, Bernice
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Serum levels of monobenzylphthalate (MBzP) is related to carotid atherosclerosis in the elderly2014In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 133, p. 348-352Article in journal (Refereed)
    Abstract [en]

    Background and objective: Background exposure to environmental contaminants has recently emerged as a new risk factor for cardiovascular disease in general and to atheroclerosis in particular. This cross-sectional study was performed to evaluate if serum concentrations of the phthalate metabolite monobenzylphthalate (MBzP) are related to atheroclerosis in the carotid arteries. Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1003 subjects all aged 70) the prevalence of overt plaques and echogenicity (gray-scale median, GSM) of carotid artery plaques were recorded by ultrasound in both of the carotid arteries. The intima-media thickness (IMT) and echogenicity (IM-GSM) of the intima-media complex were also measured. The phthalate metabolite MBzP was analyzed in serum by a liquid chromatograph/tandem mass spectrometer. Results: The circulating level of the phthalate MBzP was related to intima-media thickness (IMT) when adjusting for gender, blood pressure, body mass index (BMI), waist circumference, HDL- and LDL-cholesterol, serum triglycerides, blood glucose and smoking (p=0.034). High levels of MBzP were also strongly associated with an echogenic IM-GSM and plaque GSM (p=0.0001 for both outcomes after adjustment) but not to plaque prevalence (p=0.42). Conclusion: The phthalate metabolite MBzP was strongly related to the echogenicity of intima-media and plaques and also to IMT, independently of traditional CV risk factors. This suggests a role for the phthalate MBzP in the development of atherosclerosis.

  • 5.
    Wiberg, Bernice
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Metabolic risk factors for stroke and transient ischemic attacks in middle-aged men: a community-based study with long-term follow-up2006In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 37, no 12, p. 2898-2903Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The impact of lipometabolic and glucometabolic disturbances on stroke incidence remains to be characterized in detail. We investigated relations of a comprehensive panel of baseline lipometabolic and glucometabolic variables to incident fatal and nonfatal stroke or transient ischemic attack (TIA), and stroke subtypes. METHODS: A community-based prospective study of 2313 middle-aged men invited to a health survey at age 50. RESULTS: During a follow-up of up to 32 years, 421 developed stroke or TIA. In Cox proportional hazards analyses adjusting for treatment with cardiovascular drugs at baseline, 1-standard deviation increases in body mass index, systolic and diastolic blood pressures, serum proinsulin, and lipoprotein(a) were associated with 11 to 35% increased risk for subsequent stroke/TIA. Electrocardiographic left ventricular hypertrophy and smoking were also associated with a higher risk for stroke/TIA. Essentially the same variables were related to brain infarction/TIA. Higher proportions of palmitic (16:0), palmitoleic (16:1), and oleic acid (18:1) in cholesterol esters were associated with an increased risk, whereas a higher proportion of linoleic acid (18:2 n-6) was protective against stroke/TIA. Further adjusting all models also for hypertension, diabetes, the metabolic syndrome, serum cholesterol, atrial fibrillation, cardiovascular disease, smoking, and physical activity, essentially the same pattern was observed. CONCLUSIONS: Indices of an unhealthy dietary fat intake and a high serum lipoprotein (a) level predicted fatal and nonfatal stroke/TIA independently of established risk factors in a community-based sample of middle-aged men followed for 32 years.

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