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Sökning: WFRF:(Leander Karin) > Doktorsavhandling

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1.
  • Leander, Karin (författare)
  • Family history in relation to myocardial infarction, and analyses of gene-environment interactions involving factors of haemostasis
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Family history of coronary heart disease (CHD) has frequently been shown to increase the risk of MI. However, the mechanisms are not well understood. Probably, both genetic- and environmental effects contribute. It is possible that family history in combination with other cardiovascular risk factors is of particular importance in the aetiology of myocardial infarction (MI). Haemostatic factors seem to contribute in the causation of MI, although this is not established. Plasma fibrinogen and plasminogen activator inhibitor-1 (PAI-1) are two potentially important risk factors, with their genetic variants possibly influencing effects. The potential involvements of these factors in interactions with other cardiovascular risk factors are poorly understood. The aims of the present thesis were to assess the influence of family history of CHD on risk of first non-fatal MI in men and women, respectively, and to explore its potential role as a biologically interacting factor. The thesis also aimed to study the importance of fibrinogen and the G-455 A polymorphism, and PAI-1 and the 4G/5G polymorphism, in relation to risk of MI. Here a particular aim was also to explore potential synergistic effects for exposure combinations involving these factors regarding risk of MI. A final aim was to explore which cardiovascular risk factors may be most important for the long-term prognosis after a non-fatal MI. Data are derived from the Stockholm Heart Epidemiology Program (SHEEP), a populationbased case-control study of MI performed between 1992 and 1994 at the ten emergency hospitals within the county of Stockholm. The present analyses were restricted to 1643 men and women who had suffered a first-time non-fatal MI, and 2339 controls. Data on exposures were available from questionnaires, anthropometric measurements, blood samples, and medical records. A family history of CHD (defined as >=1 first-degree relative affected before the age of 65) was observed to be associated with risk of MI in both men and women. Synergistic effects were observed in women exposed to family history of CHD in combination with current smoking and with a high LDL/HDL quotient, respectively. In men, family history of CHD and diabetes mellitus seemed to act in synergy. High level of plasma fibrinogen was associated with increased risk of MI in both men and women, although the OR decreased after adjusting for other cardiovascular risk factors. Presence of the A-455 allele was associated with increased fibrinogen level but not with increased risk of MI. No clear synergistic effects were observed. High plasma PAI-1 activity was associated with increased risk of MI, and in men it also interacted with smoking in increasing the risk synergistically. In women, presence of the 4G allele was associated although weakly with increased risk of MI. Diabetes mellitus, job strain and abdominal adiposure had an impact on prognosis after MI in men. In women, prognostic importance was particularly noted for diabetes mellitus and for low level of Apolipoprotein AI. In both men and women the size of the initial infarction also had a prognostic value. In male survivors of MI, family history of CHD increased the risk of death from CHD during follow-up. In conclusion, this thesis suggests the occurrence of several biological interactions between risk factors for MI. The involvement of family history in such interactions indicates that gene-environment interaction may be in operation. After MI, several primary and secondary exposures have an influence on the prognosis.
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2.
  • Nilsson, Sigrid, 1997- (författare)
  • Vasomotor Symptoms, Cardiovascular Risk and the Role of Physical Activity in Midlife Women
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: The menopausal transition is, for most women, accompanied by hot flushes and night sweats (i.e., vasomotor symptoms, VMS). VMS has been associated with a worsened cardiovascular risk profile, but whether VMS constitutes an independent risk marker for developing subclinical atherosclerotic cardiovascular disease (ASCVD) is still uncertain. Visceral adipose tissue (VAT) contributes more to systemic low-grade inflammation than abdominal subcutaneous adipose tissue (ASAT), enhancing atherosclerosis development. Physical activity is an effective behavioral strategy to maintain and improve cardiovascular health. Whether a resistance training intervention (RTI) could reduce low-grade inflammation and VAT volume in postmenopausal women with VMS remains unclear, and whether the RTI-associated effects could be maintained over time requires further investigation.Material and Methods: This thesis is based on three studies. Study 1 was conducted on a subset of participants from the cross-sectional population-based Swedish CArdioPulmonary BioImage Study (SCAPIS), including women 50-64 years of age. The women underwent comprehensive cardiovascular assessments and completed an extensive female-specific questionnaire. VMS was assessed on a 4-point scale. Subclinical ASCVD was detected via coronary computed tomography angiography (CCTA), computed tomography (CT), and carotid ultrasound. Study 2 is a sub-study of 65 postmenopausal women with VMS and low physical activity, randomized to either three days/week of an RTI or unchanged physical activity for 15 weeks. Women underwent anthropometric measurements, magnetic resonance imaging (MRI), and blood sampling at baseline and after 15 weeks. During the last followup contact in Study 2 after two years, 35 women agreed to attend an additional clinic visit to reevaluate cardiovascular risk markers, marking the inception of Study 3.Results: Of 2995 women included in Study 1, 14.2% reported severe VMS (n = 425), 18.1% moderate VMS (n = 543), and 67.7% no or mild VMS (n = 2027). Current or previous severe VMS, but not moderate VMS, was significantly associated with CCTA-detected coronary atherosclerosis, with odds ratio (OR) before and after multivariable adjustment 1.36, 95% confidence interval (CI) 1.08 – 1.72 and 1.33, 95% CI 1.02 – 1.72, respectively. This association was only present for >5 years durations of severe VMS or when the onset of severe VMS occurred before menopause. Adjustment for menopausal hormone therapy strengthened the association for women with severe VMS >5 years (OR 1.67, 95% CI 1.16 – 2.40). Women compliant with an RTI had compared to a control group (CG), decreased adiponectin (p < 0.01), ASAT (p < 0.01), VAT (p < 0.01), total abdominal adipose tissue (TAAT) (p < 0.01) and fat ratio (p <0.001). Furthermore, an RTI reduced moderate to severe VMS frequency to six months post-intervention compared to a CG, but did neither contribute to preserved cardiovascular health markers nor improved health-related quality of life (HRQoL) after two years compared to a CG.Conclusions: There is a need for extra vigilance regarding cardiovascular risk factors in the group of women suffering from severe VMS. Implementing a 15-week RTI in these women could counteract the VAT redistribution and alter the frequency of moderate to severe VMS with maintained effects up to six months.
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