| 21. |
- Strand, Magnus, et al.
(författare)
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Estrogen Receptor Alpha Gene Polymorphisms and First-Ever Intracerebral Hemorrhage.
- 2007
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Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 24:6, s. 500-508
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Signaling through estrogen receptor alpha (ER alpha) regulates vasodilatation and atherogenesis. Since hypertension and atherosclerosis are major mechanisms in stroke development, we hypothesized that genetic variants of the ER alpha gene (ESR1) are determinants of future ischemic stroke or intracerebral hemorrhage (ICH). METHODS: In a population-based prospective nested case-control study, the relationships between ESR1 polymorphisms (c.454-397T>C and c.454-351A>G) and ischemic stroke and ICH were examined in univariate and multivariate models using conditional logistic regression, which included established risk factors.Definitive first-ever stroke events (n = 388), including ischemic stroke (n = 320), ICH (n = 61), and unspecified stroke (n = 7) cases, and controls without cardiovascular disease (n = 773), matched for age, sex, and geographical region were included. RESULTS: Carriers of the c.454-397T/T genotype had a significantly (p = 0.017) increased risk of ICH (OR 2.31, 95% CI 1.16-4.60) in a univariate analysis. This association persisted (OR 3.94, 95% CI 1.54-10.03), after adjustment for stroke risk determinants. Carriers of c.454-397T/T or c.454-397T/C genotypes had significantly (p = 0.002 and p = 0.004, respectively) higher mean systolic blood pressure (SBP), than carriers of c.454-397C/C, and a similar relationship was observed for diastolic blood pressure (DBP). The combinations of c.454-397T/T genotype and hypertension (OR 21.46, 95% CI 5.20-88.51), or high SBP (OR 18.17, 95% CI 4.91-67.31) or DBP (OR 11.94, 95% CI 3.75-38.03), were strongly associated with increased risk of ICH. CONCLUSIONS: In this population,the c.454-397T/T genotype associates with first-ever ICH, particularly in combination with hypertension. This implies that alterations in ER alpha-mediated signaling may be involved in the pathophysiology of this disease, with a putative impact on primary prevention.
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| 22. |
- Strand, Magnus, et al.
(författare)
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Polymorphisms at the osteoprotegerin and interleukin-6 genes in relation to first-ever stroke.
- 2007
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Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 24:5, s. 418-425
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Arterial calcification and osteoporosis often coexist, especially in postmenopausal women. Osteoporosis associates with a substantially increased risk of stroke in elderly women, suggesting that impaired estrogen signaling may link stroke and osteoporosis. Osteoprotegerin (OPG, TNFRSF11B) and interleukin-6 (IL-6, IL6) are putative target genes for estrogen signaling and have been implicated in both cardiovascular diseases and osteoporosis. We hypothesized that specific polymorphisms in these genes may be associated with increased risk of ischemic stroke or intracerebral hemorrhage (ICH). METHODS: We performed a population-based prospective nested case-control study, in which the relationships between polymorphisms (OPG-1181G/C, OPG-950T/C and IL6-174G/C) and ischemic stroke and ICH were examined. Definitive first-ever stroke events (n = 388), i.e. ischemic stroke (n = 320), ICH (n = 61) and unspecified stroke (n = 7) cases, and controls without cardiovascular disease (n = 773), matched for age, sex and geographical region were studied. Univariate and multivariate models using conditional logistic regression, which included traditional risk factors, were used to test for association. RESULTS: Carriers of the OPG-1181C/C genotype had a significantly (p = 0.018) increased risk of ICH (OR, 2.69; 95% CI, 1.19-6.12) in the univariate analysis. After adjustments (hypertension, diabetes, BMI and triglycerides), this genotype remained significantly (p = 0.005) associated with ICH (OR, 6.04; 95% CI, 1.71-21.29). By contrast, no correlations were found between this genotype and ischemic stroke, nor between the OPG-950T/C or IL6-174G/C polymorphisms and stroke subtypes. CONCLUSIONS: In this population, the OPG-1181C/C genotype associates with first-ever ICH, implying that alterations in OPG-mediated signaling in the vasculature may be involved in the pathophysiology of this disease.
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| 23. |
- Söderström, Elisabet, et al.
(författare)
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Plasma folate, but not homocysteine, is associated with Apolipoprotein A1 levels in a non-fortified population
- 2013
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Ingår i: Lipids in Health and Disease. - : Springer Nature. - 1476-511X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elevated total plasma homocysteine (tHcy) in humans is associated with cardiovascular disease but prevention trials have failed to confirm causality. Reported reasons for this association have been that homocysteine and its major genetic determinant methylenetetrahydrofolate reductase (MTHFR) may have an effect on HDL and Apolipoprotein (Apo) A1 levels. We wanted to study if tHcy and its major determinants were correlated with Apo A1 levels in a large population without folate fortification.Methods: This study was a prospective incident nested case-referent study within the Northern Sweden Health and Disease Study Cohort (NSHDSC), including 545 cases with first myocardial infarction and 1054 matched referents, median age at inclusion was 59 years. Univariate and multiple regression analyzes was used to study the associations between apolipoproteins Apo A1 and B, tHcy, folate and vitamin B12 in plasma as well as MTHFR polymorphisms 677C>T and 1298A>C.Results: Apo A1 and Apo B were strongly associated with the risk of a first myocardial infarction. tHcy was not associated with Apo A1 levels. Instead, folate had an independent positive association with Apo A1 levels in univariate and multiple regression models. The associations were seen in all men and women, among referents but not among cases. MTHFR polymorphisms had no clear effect on Apo A1 levels.Conclusions: Analyzing over 1500 subjects we found an independent positive association between plasma folate (major dietary determinant of tHcy) and Apo A1 levels among those who later did not develop a first myocardial infarction. No association was seen between tHcy and Apo A1.
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| 24. |
- Thøgersen, Anna M., et al.
(författare)
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Changes in plasma C-reactive protein and hemostatic factors prior to and after a first myocardial infarction with a median follow-up time of 8 years
- 2009
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Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 20:5, s. 340-346
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to determine whether a first myocardial infarction leads to increased plasma levels of hemostatic factors and high sensitive C-reactive protein (hs-CRP) and whether the association between theses biomarkers and myocardial infarction was greater at follow-up compared with baseline. Of more than 36,000 persons screened in northern Sweden, 78 developed a first myocardial infarction (on average 18 months after sampling) in a population-based, prospective, nested patient-referent study. Fifty of these had participated in a follow-up health survey (on average 8 and a half years between surveys) and were sex-matched and age-matched with 56 referents. The mean increases in hs-CRP, tissue plasminogen activator (tPA) mass, plasminogen activator inhibitor-1 mass, and tPA/plasminogen activator inhibitor-1 complex concentration and von Willebrand factor among patients and referents were comparable during follow-up. Conditional logistic regression indicated that hs-CRP was not significantly associated with first myocardial infarction in a univariate analysis, whereas high plasma levels of tPA and creatinine were significantly associated with outcome at baseline and follow-up. tPA/plasminogen activator inhibitor-1 complex was not superior to tPA as a risk marker in this study. A first myocardial infarction did not in this study induce significantly different changes in plasma levels of hs-CRP and hemostatic factors among patients compared with referents during follow-up.
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| 25. |
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| 26. |
- Van Guelpen, Bethany, et al.
(författare)
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Folate, vitamin B12, and risk of ischemic and hemorrhagic stroke: a prospective, nested case-referent study of plasma concentrations and dietary intake.
- 2005
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Ingår i: Stroke; a journal of cerebral circulation. - 1524-4628 .- 0039-2499. ; 36:7, s. 1426-31
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Folate metabolism has been implicated in stroke. However, the possibility of a role for folate and vitamin B12, independent of their effects on homocysteine status, remains to be explored. The aim of this prospective, nested case-referent study was to relate plasma and dietary intake levels of folate and vitamin B12 to risk of stroke, taking into consideration plasma homocysteine concentrations and methylenetetrahydrofolate reductase polymorphisms. METHODS: Subjects were 334 ischemic and 62 hemorrhagic stroke cases and matched double referents from the population-based Northern Sweden Health and Disease Cohort. RESULTS: Plasma folate was statistically significantly associated with risk of hemorrhagic stroke in an inverse linear manner, both in univariate analysis and after adjustment for conventional risk factors including hypertension (odds ratio [OR] for highest versus lowest quartile 0.21 (95% confidence interval [CI], 0.06 to 0.71; P for trend=0.008)). Risk estimates were attenuated by inclusion of homocysteine in the model (OR, 0.34; 95% CI, 0.08 to 1.40; P for trend=0.088). A similar pattern was observed for increasing folate intake (multivariate OR, 0.07; 95% CI, 0.01 to 0.55; P for trend=0.031 without homocysteine, and OR, 0.16, 95% CI, 0.02 to 1.23; P for trend=0.118 with homocysteine in the analysis). We found little evidence of an association between plasma or dietary folate and risk of ischemic stroke. Neither plasma nor dietary vitamin B12 was associated with risk of either stroke subtype. CONCLUSIONS: The results of this study suggest a protective role for folate, possibly in addition to its effects on homocysteine status, in hemorrhagic but not ischemic stroke.
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| 27. |
- Van Guelpen, Bethany, et al.
(författare)
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Plasma folate and total homocysteine levels are associated with the risk of myocardial infarction, independently of each other and of renal function.
- 2009
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Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 266:2, s. 182-95
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate the relationship between plasma folate, vitamin B12 and total homocysteine concentrations, dietary intake of folate and vitamins B12, B6 and B2, and the risk of first acute myocardial infarction (MI). DESIGN: Nested case-referent study with up to 13 years of follow-up. SETTING: The population-based Northern Sweden Health and Disease Study, with 73 879 participants at the time of case ascertainment. SUBJECTS: A total of 571 MI cases (406 men) and 1569 matched referents. Of the cases, 530 had plasma samples available, and 247 had dietary B-vitamin intake data. RESULTS: Plasma concentrations of folate were inversely associated, and total homocysteine positively associated, with the risk of MI, independently of each other and of a number of established and novel cardiovascular risk factors, including renal function [multivariate odds ratio for highest vs. lowest quintile of folate 0.52 (95% CI 0.31-0.84), P for trend = 0.036, and homocysteine 1.92 (95% CI 1.20-3.09), P for trend = 0.006]. For plasma vitamin B12 concentrations, and vitamin B12, B6 and B2 intake, no clear risk relationship was apparent. Though not statistically significant, the results for folate intake were consistent with those for plasma concentrations. CONCLUSIONS: In this large prospective study of a population without mandatory folic acid fortification, both folate and homocysteine were strongly associated with the risk of myocardial infarction, independently of each other and of renal function. Although randomized trials of folic acid supplementation are needed to determine causality, our findings highlight the potential importance of folate, or sources of folate, in incident cardiovascular disease.
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| 28. |
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| 29. |
- Warensjö, Eva, et al.
(författare)
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Stroke and plasma markers of milk fat intake : a prospective nested case-control study
- 2009
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Ingår i: Nutrition Journal. - : Springer Science and Business Media LLC. - 1475-2891 .- 1475-2891. ; 8, s. 21-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dairy products are high in saturated fat and are traditionally a risk factor for vascular diseases. The fatty acids 15:0 and 17:0 of plasma lipids are biomarkers of milk fat intake. The aim of the present study was to evaluate the risk of a first-ever stroke in relation to the plasma milk fat biomarkers. METHODS: A prospective case-control study was nested within two population based health surveys in Northern Sweden. Among 129 stroke cases and 257 matched controls, plasma samples for fatty acid analyses were available in 108 cases and 216 control subjects. Proportions of 15:0 and 17:0 of plasma lipids, weight, height, blood lipids, blood pressures, and lifestyle data were employed in conditional logistic regression modelling. RESULTS: The proportions of fatty acids 17:0 and 15:0+17:0 of total plasma phospholipids were significantly higher in female controls than cases, but not in men. 17:0 and 15:0+17:0 were significantly and inversely related to stroke in the whole study sample as well as in women. The standardised odds ratio (95% CI) in women to have a stroke was 0.41 (0.24-0.69) for 17:0 in plasma phospholipids. Adjustment for traditional cardiovascular risk factors, physical activity and diet had marginal effects on the odds ratios. A similar, but non-significant, trend was seen in men. CONCLUSION: It is hypothesised that dairy or milk fat intake may be inversely related to the risk of a first event of stroke. The intriguing results of this study should be interpreted with caution. Follow up studies with greater power, and where intakes are monitored both by dietary recordings and fatty acid markers are needed.
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| 30. |
- Weinehall, Lars, 1948-, et al.
(författare)
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High remaining risk in poorly treated hypertension : the "rule of halves" still exists
- 2002
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 20:10, s. 2081-2088
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Tidskriftsartikel (refereegranskat)abstract
- To estimate risk factors for stroke, to examine how different categories of patients with increased blood pressure are associated with risk for first-ever stroke event, and to estimate the proportions of these categories in a geographically defined population in northern Sweden. Setting : The study was nested within the Vasterbotten Intervention Program and the Northern Sweden MONICA cohorts. Design and participants : A population-based cross-sectional study and an incident case-control study were carried out. The incident case-control study comprised 129 cases of first-ever stroke diagnosed during 1985-96, with two randomly selected controls per case, chosen from the same geographically defined population. The cross-sectional study was based on 59 735 participants. Blood pressure status was categorized as: normotensive [systolic blood pressure (SBP) <140 mmHg and diastolic blood pressure (DBP) <90 mmHg]; treated and adequately controlled hypertension (SBP <140 mmHg and DBP <90 mmHg); treated but poorly controlled hypertension (SBP >=140 mmHg or DBP >=90 mmHg, or both); untreated hypertension (SBP >=140 mmHg or DBP >=90 mmHg, or both); newly detected increased blood pressure (SBP >=140 mmHg or DBP >=90 mmHg, or both). Main outcome measure: Risk for first-ever stroke. Results: In the cross-sectional study, 68% of individuals were normotensive, 3% had treated and adequately controlled hypertension, 6% had treated but poorly controlled hypertension, 7% had untreated hypertension, and 16% had newly detected increased blood pressure. In univariate analysis of the case-control study, history of diabetes, daily smoking, obesity, increased blood pressure and the hypertension categories 'treated but poorly controlled' and 'untreated' were associated with an increased stroke risk. In multivariate logistic regression analysis, only diabetes and the hypertension categories treated but poorly controlled and untreated remained significant, with odds ratios 6.1 (95% confidence interval 2.4 to 15.3) and 4.3 (95% confidence interval 1.7 to 10.5), respectively. Only one of the 129 individuals who suffered stroke had treated and adequately controlled hypertension. Conclusions : The study illustrates the importance of adequate blood pressure control and, at the same time, that the vast majority in the population with increased blood pressure did not receive optimal care. Thus the 'rule of halves' still exists, and the high remaining risk in poorly treated hypertensive individuals in Sweden is remarkable and requires attention from the medical profession.
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