| 1. |
- Andersson, Elisabeth, et al.
(author)
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Surveillance of indeterminate pulmonary nodules detected with CT in a Swedish population-based study (SCAPIS) : Psychosocial consequences and impact on health-related quality of life - A multicentre prospective cross-sectional study
- 2021
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:9
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Journal article (peer-reviewed)abstract
- Objectives: To investigate whether surveillance of pulmonary nodules detected with low-dose CT (LDCT) impacted health-related quality of life and psychosocial consequences in the Swedish population-based study, Swedish CArdioPulmonary bioImage Study (SCAPIS).Design: A prospective cross-sectional study.Settings and participants: This multicentre (five sites) observational study, which included a cohort from SCAPIS, consisted of 632 participants with indeterminate pulmonary nodules detected with LDCT. These participants continued surveillance for up to 36 months, during which lung cancer was not detected (surveillance group). Additionally, 972 participants with a negative pulmonary LDCT scan were included as a control group. Matching criteria were LDCT date (±2 weeks), gender and site.Outcome measures: All participants completed a health-related quality of life questionnaire (RAND-36) and the Consequences of Screening (COS) questionnaire, an average of 3 years after LDCT was conducted at entry into SCAPIS.Results: Participants were 51-70 years old at study commencement. Overall, the two groups did not differ in demographic or psychosocial variables, smoking habits or pulmonary medical history. Individuals from countries other than Sweden and those with low socioeconomic status were less likely to participate (p<0.001). No effects on health-related quality of life were observed via RAND-36. In COS, the surveillance group demonstrated a higher OR for anxiety about lung cancer (OR 3.96, 95% CI 2.35 to 6.66, p<0.001), experiencing a sense of dejection (OR 1.35, 95% CI 1.06 to 1.72, p=0.015) and thoughts about existential values (OR 1.30, 95% CI 1.04 to 1.60, p=0.018).Conclusions: Lung surveillance with LDCT contributed to significant experiences of sense of dejection, anxiety about lung cancer and development of thoughts about existential values among participants in the surveillance group compared with the controls. The risk of side effects should be communicated for informed decision-making about (non-)attendance in lung cancer screening.
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| 2. |
- Engström, Gunnar, et al.
(author)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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In: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Journal article (peer-reviewed)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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| 3. |
- Malinovschi, Andrei, 1978-, et al.
(author)
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Assessment of Global Lung Function Initiative (GLI) reference equations for diffusing capacity in relation to respiratory burden in the Swedish CArdioPulmonary bioImage Study (SCAPIS)
- 2020
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In: European Respiratory Journal. - Lausanne, Switzerland : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 56:2
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Journal article (peer-reviewed)abstract
- The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (DLCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired DLCO. We examined if the GLI LLN for DLCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden.Spirometry, DLCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15 040 participants, aged 50–64 years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women).Both the median and LLN for DLCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of DLCO DLCO >GLI LLN but DLCO >GLI LLN but versus 4.5%, p<0.001), chronic airflow limitation (8.5% versus 3.9%, p<0.001) and chronic bronchitis (8.3% versus 4.4%, p<0.01) than subjects (n=13 600) with normal DLCO (>GLI LLN and >SCAPIS LLN). No differences were found with regard to physician-diagnosed asthma.The GLI LLN for DLCO is lower than the estimated LLN in healthy, never-smoking, middle-aged Swedish adults. Individuals with DLCO above the GLI LLN but below the SCAPIS LLN had, to a larger extent, an increased respiratory burden. This suggests clinical implications for choosing an adequate LLN for studied populations.
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| 4. |
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| 5. |
- Bennermo, Marie, et al.
(author)
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Genetic and environmental influences on the plasma interleukin-6 concentration in patients with a recent myocardial infarction : a case-control study
- 2011
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In: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1079-9907 .- 1557-7465. ; 31:2, s. 259-264
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Journal article (peer-reviewed)abstract
- The aim was to study the stimuli responsible for triggering and sustaining the plasma concentration of the inflammatory marker interleukin-6 (IL-6) in patients with a first myocardial infarction before the age of 60 and healthy control subjects matched for age and sex. The plasma IL-6 concentration, antibodies against Chlamydia pneumoniae, cytomegalovirus, Epstein-Barr virus, Helicobacter pylori, herpes simplex type 1 and 2, and genotype for the IL6-174 G>C single-nucleotide polymorphism were determined 3 months after the acute event. The results showed that patients had higher IL-6 levels than control subjects, whereas there were no differences regarding individual or total number (pathogen burden) of positive antibody tests against the different pathogens or IL6 genotype distribution. The plasma IL-6 concentration was associated with the number of positive antibody tests in patients and control subjects, whereas patients irrespective of IL6 genotype had increased IL-6. Multivariate analysis, including traditional coronary heart disease risk factors, antibodies against pathogens, and IL6 genotype, explained 17% of the variation of the plasma IL-6 concentration. Neither pathogen burden nor IL6 genotype did contribute to the variation of plasma IL-6 levels, whereas smoking, body-mass index, hypertension, case-control status, and age were determinants of the plasma IL-6 concentration.
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| 6. |
- Bergström, Göran, 1964, et al.
(author)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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In: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Journal article (peer-reviewed)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 7. |
- Bergström, Göran, et al.
(author)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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In: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Journal article (peer-reviewed)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 8. |
- Ekblom Bak, Elin, 1981-, et al.
(author)
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Accelerometer derived physical activity and subclinical coronary and carotid atherosclerosis : cross-sectional analyses in 22 703 middle-aged men and women in the SCAPIS study
- 2023
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:11
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The aim included investigation of the associations between sedentary (SED), low-intensity physical activity (LIPA), moderate-to-vigorous intensity PA (MVPA) and the prevalence of subclinical atherosclerosis in both coronaries and carotids and the estimated difference in prevalence by theoretical reallocation of time in different PA behaviours.DESIGN: Cross-sectional.SETTING: Multisite study at university hospitals.PARTICIPANTS: A total of 22 670 participants without cardiovascular disease (51% women, 57.4 years, SD 4.3) from the population-based Swedish CArdioPulmonary bioImage study were included. SED, LIPA and MVPA were assessed by hip-worn accelerometer.PRIMARY AND SECONDARY OUTCOMES: Any and significant subclinical coronary atherosclerosis (CA), Coronary Artery Calcium Score (CACS) and carotid atherosclerosis (CarA) were derived from imaging data from coronary CT angiography and carotid ultrasound.RESULTS: High daily SED (>70% ≈10.5 hours/day) associated with a higher OR 1.44 (95% CI 1.09 to 1.91), for significant CA, and with lower OR 0.77 (95% CI 0.63 to 0.95), for significant CarA. High LIPA (>55% ≈8 hours/day) associated with lower OR for significant CA 0.70 (95% CI 0.51 to 0.96), and CACS, 0.71 (95% CI 0.51 to 0.97), but with higher OR for CarA 1.41 (95% CI 1.12 to 1.76). MVPA above reference level, >2% ≈20 min/day, associated with lower OR for significant CA (OR range 0.61-0.67), CACS (OR range 0.71-0.75) and CarA (OR range 0.72-0.79). Theoretical replacement of 30 min of SED into an equal amount of MVPA associated with lower OR for significant CA, especially in participants with high SED 0.84 (95% CI 0.76 to 0.96) or low MVPA 0.51 (0.36 to 0.73).CONCLUSIONS: MVPA was associated with a lower risk for significant atherosclerosis in both coronaries and carotids, while the association varied in strength and direction for SED and LIPA, respectively. If causal, clinical implications include avoiding high levels of daily SED and low levels of MVPA to reduce the risk of developing significant subclinical atherosclerosis.
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| 9. |
- Ekblom Bak, Elin, 1981-, et al.
(author)
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Accelerometer derived physical activity patterns in 27.890 middle‐aged adults : The SCAPIS cohort study
- 2022
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In: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 32:5, s. 866-880
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Journal article (peer-reviewed)abstract
- The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an “at-risk” behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.
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| 10. |
- Nastase Mannila, Maria
(author)
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Fibrinogen and susceptibility to myocardial infarction : role of gene-gene and gene-environment interactions
- 2006
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Doctoral thesis (other academic/artistic)abstract
- Fibrinogen, the precursor of fibrin, is a glycoprotein synthesized in the liver and maintained in plasma at concentrations normally ranging between 2-4 g/L. The fibrinogen molecule consists of two sets of three non-identical polypeptide chains, which are encoded by the fibrinogen gamma (FGG), fibrinogen alpha (FGA) and fibrinogen beta (FGB) genes clustered on chromosome 4. Elevated plasma fibrinogen concentration is considered an independent predictor of myocardial infarction (MI), while the role of the less abundant fibrinogen gamma chain variant has not as yet been explored in this context. The aim of the present thesis was to study the impact of genetic and environmental factors on total plasma fibrinogen and fibrinogen gamma concentrations, fibrin gel structure and the risk of MI, using well defined clinical cohorts and biochemical, molecular biological and molecular genetic techniques. The results presented in this thesis are based on findings from three case-control studies comprising survivors of a first MI and population-based controls. The Hypercoagulability and Impaired Fibrinolytic function MECHanisms (HIFMECH) study was designed to identify genetic and environmental factors underlying differences in risk of MI between high-risk (Stockholm and London) and low-risk (Marseille and San Giovanni Rotondo) centres in the North and in the South of Europe. The Stockholm Coronary Atherosclerosis Risk Factor (SCARF) and the Stockholm Heart Epidemiology Program (SHEEP) studies are two independent case-control studies undertaken to investigate genetic, biochemical and environmental factors predisposing to precocious MI. Both elevated total plasma fibrinogen and fibrinogen gamma concentrations related to MI. However, the former entity appeared to contribute differently to MI in the European centres participating in the HIFMECH study, and was an independent discriminator between cases and controls only in London. In general, IL6, smoking and BMI seem to contribute to the variation in total plasma fibrinogen concentration, while fibrinogen and the FGG 9340T>C and FGA 2224G>A haplotype tag single nucleotide polymorphisms (htSNPs) contribute to the plasma fibrinogen gamma concentration. Several SNPs were detected in candidate regions in the fibrinogen genes, presumed to play a role in the regulation of the plasma fibrinogen concentration and the fibrin clot structure and therefore to influence the risk of MI. Neither individual fibrinogen SNPs nor FGB haplotypes appeared to influence the risk of MI. On the other hand, fibrinogen haplotypes inferred using genotype data from the FGG 9340T>C and FGA 2224G>A htSNPs seemed to contribute to the risk of MI, independently of the plasma fibrinogen concentration. Effects on fibrin clot porosity appeared to partly explain the lowered risk of MI conferred by the haplotype consisting of the minor FGG 9340C and FGA 2224A alleles. Furthermore, the fibrinogen haplotypes seem to exert pleiotropic effects on the serum IL6 concentration that are consistent with their impact on the risk of MI, i.e. the haplotype that conferred an increased risk (containing the major FGG 9340T and F GA 2224G alleles) was associated with significantly higher IL6 concentrations than the seemingly protective haplotype (containing the minor FGG 9340C and FGA 2224A alleles). In addition, gene-gene and gene-enviromnent interaction analyses were performed. Risk factors such as dyslipidemia and high waist-to-hip ratio were stronger predictors of MI than the SNPs included in these analyses. However, a high-order interaction between the total plasma fibrinogen and fibrinogen gamma concentrations and the FGG 9340T>C and FGA 2224G>A htSNPs was noted, yielding a ~3 fold increase in the risk of MI. In conclusion, total plasma fibrinogen and fibrinogen gamma concentrations are related to MI. Also, genetic variation in the fibrinogen genes contribute to the risk of MI, and this relationship seems to be mediated via effects on plasma V' fibrinogen concentration and fibrin clot structure, and pleiotropic effects on serum IL6 concentration.
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| 11. |
- Nastase Mannila, Maria, et al.
(author)
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Identification of a Functional Apolipoprotein E Promoter Polymorphism Regulating Plasma Apolipoprotein E Concentration
- 2013
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In: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 33:5, s. 1063-1069
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Journal article (peer-reviewed)abstract
- OBJECTIVE:There is compelling evidence that the plasma apolipoprotein E (APOE) concentration, in addition to the APOE ε2/ε3/ε4 genotype, influences plasma lipoprotein levels, but the functional genetic variants influencing the plasma APOE concentration have not been identified.APPROACH AND RESULTSGenome-wide association studies in 2 cohorts of healthy, middle-aged subjects identified the APOE locus as the only genetic locus showing robust associations with the plasma APOE concentration. Fine-mapping of the APOE locus confirmed that the rs7412 ε2-allele is the primary genetic variant responsible for the relationship with plasma APOE concentration. Further mapping of the APOE locus uncovered that rs769446 (-427T/C) in the APOE promoter is independently associated with the plasma APOE concentration. Expression studies in 199 human liver samples demonstrated that the rs769446 C-allele is associated with increased APOE mRNA levels (P=0.015). Transient transfection studies and electrophoretic mobility shift assays in human hepatoma HepG2 cells corroborated the role of rs769446 in transcriptional regulation of APOE. However, no relationships were found between rs769446 genotype and plasma lipoprotein levels in 2 cohorts (n=1648 and n=1039) of healthy middle-aged carriers of the APOE ε3/ε3 genotype.CONCLUSIONS:rs769446 is a functional polymorphism involved in the regulation of the plasma APOE concentration.
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| 12. |
- Sundström, Johan, Professor, 1971-, et al.
(author)
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Weight gain and blood pressure
- 2020
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In: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 38:3, s. 387-394
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Although the causality of the obesity—hypertension association is established, the potential for prevention is not. We hypothesized that weight gain between early adulthood and mid-life is associated with higher mid-life blood pressure.METHODS: We investigated the hypothesis using a large contemporaneous population-based mid-life cohort of men and women aged 50-64 years. Recalled body weight at age 20 years was self-reported, and mid-life body weight and office blood pressures were measured in accordance with a detailed protocol.RESULTS: On average, men had gained 14.9 (95% CI 14.6-15.2) kg of weight, and women 14.6 (95% CI 14.4-14.9) kg, between age 20 years and the mid-life examination, corresponding to 0.40 (95% CI 0.39-0.41) kg/year for men and women. Both weight at age 20 years and weight at the mid-life examination were associated with mid-life blood pressures. On average, a 10 kg weight increase between age 20 years and mid-life was associated with 2.2 (95% CI 0.9-3.5) mmHg higher systolic and 1.7 (95% CI 0.9-2.5) mmHg higher diastolic mid-life blood pressure in men, and 3.2 (2.5-4.0) mmHg higher systolic and 2.4 (1.9-2.9) mmHg higher diastolic mid-life blood pressure in women. Mid-life weight was more closely associated than weight at age 20 years with mid-life blood pressure. For a given mid-life weight, blood pressure was higher in persons with higher weight gain from age 20 years.CONCLUSION: In sum, weight gain between early adulthood and mid-life was associated with higher mid-life blood pressure. The magnitude of the association indicates a potentially great public health impact of strategies to prevent weight gain throughout adulthood.
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