| 1. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Weight gain and blood pressure
- 2020
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 38:3, s. 387-394
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Andersson, Jonas, et al.
(författare)
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GDF-15 is associated with sudden cardiac death due to incident myocardial infarction
- 2020
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Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 152, s. 165-169
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Preventing sudden cardiac death (SCD) due to acute myocardial infarction (MI) in previously healthy patients is challenging. Proteomic analysis may lead to an understanding of biological mechanisms and provide predictive biomarkers.Methods: In this prospective, nested case-control study from northern Sweden, 87 candidate cardiovascular protein biomarkers were studied in 244 individuals who later died within 24 h from an incident MI and 244 referents without MI and individually matched for age, sex and date of health examination and alive at the date of event in the index person. Association analysis was conducted using conditional logistic regression. Bonferroni correction was applied to avoid false positive findings.Results: Ten proteins were associated with future SCD due to acute MI in the non-adjusted analysis. The strongest association were found for growth differentiation factor 15 (GDF-15) with an odds ratio (OR) of 1.79 (95% confidence interval [CI] 1.41, 2.25) per standard deviation increase in protein, and urokinase-type plasminogen activator receptor with an OR of 1.66 (95% CI 1.34, 2.06). In models adjusted for lipid levels, body mass index, education, smoking, hypertension and C-reactive protein, only association with GDF-15 remained (OR 1.47 (95% 1.11, 1.95)).Conclusion: Elevated levels of GDF-15 are associated with increased risk of SCD within 24 h of incident MI. Further research may enable the use of GDF-15 together with other clinical and biological markers to guide primary preventive interventions for individuals at high risk for SCD.
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| 3. |
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| 4. |
- Byhamre, Marja Lisa, et al.
(författare)
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Swedish snus use is associated with mortality : a pooled analysis of eight prospective studies
- 2020
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 49:6, s. 2041-2050
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The health consequences of the use of Swedish snus, including its relationship with mortality, have not been fully established. We investigated the relationship between snus use and all-cause and cause-specific mortality (death due to cardiovascular diseases, cancer diseases and all other reasons, respectively) in a nationwide collaborative pooling project.METHODS: We followed 169 103 never-smoking men from eight Swedish cohort studies, recruited in 1978-2010. Shared frailty models with random effects at the study level were used in order to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of mortality associated with snus use.RESULTS: Exclusive current snus users had an increased risk of all-cause mortality (aHR 1.28, 95% CI 1.20-1.35), cardiovascular mortality (aHR 1.27, 95% CI 1.15-1.41) and other cause mortality (aHR 1.37, 95% CI 1.24-1.52) compared with never-users of tobacco. The risk of cancer mortality was also increased (aHR 1.12, 95% CI 1.00-1.26). These mortality risks increased with duration of snus use, but not with weekly amount.CONCLUSIONS: Snus use among men is associated with increased all-cause mortality, cardiovascular mortality, with death from other causes and possibly with increased cancer mortality.
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| 5. |
- Chorell, Elin, 1981-, et al.
(författare)
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Lysophospholipids as Predictive Markers of ST-Elevation Myocardial Infarction (STEMI) and Non-ST-Elevation Myocardial Infarction (NSTEMI)
- 2021
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Ingår i: Metabolites. - : MDPI. - 2218-1989 .- 2218-1989. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The present study explored patterns of circulating metabolites and proteins that can predict future risk for ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). We conducted a prospective nested case-control study in northern Sweden in individuals who developed STEMI (N = 50) and NSTEMI (N = 50) within 5 years and individually matched controls (N = 100). Fasted plasma samples were subjected to multiplatform mass spectrometry-based metabolomics and multiplex protein analyses. Multivariate analyses were used to elucidate infarction-specific metabolite and protein risk profiles associated with future incident STEMI and NSTEMI. We found that altered lysophosphatidylcholine (LPC) to lysophosphatidylethanolamine (LPE) ratio predicted STEMI and NSTEMI events in different ways. In STEMI, lysophospholipids (mainly LPEs) were lower, whereas in NSTEMI, lysophospholipids (mainly LPEs) were higher. We found a similar response for all detected lysophospholipids but significant alterations only for those containing linoleic acid (C18:2, p < 0.05). Patients with STEMI had higher secretoglobin family 3A member 2 and tartrate-resistant acid phosphate type 5 and lower platelet-derived growth factor subunit A, which are proteins associated with atherosclerosis severity and plaque development mediated via altered phospholipid metabolism. In contrast, patients with NSTEMI had higher levels of proteins associated with inflammation and macrophage activation, including interleukin 6, C-reactive protein, chemerin, and cathepsin X and D. The STEMI risk marker profile includes factors closely related to the development of unstable plaque, including a higher LPC:LPE ratio, whereas NSTEMI is characterized by a lower LPC:LPE ratio and increased inflammation.
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| 6. |
- Eriksson, Maria A., 1965-, et al.
(författare)
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Leptin levels are not affected by enalapril treatment after an uncomplicated myocardial infarction, but associate strongly with changes in fibrinolytic variables in men
- 2020
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 80:4, s. 303-308
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Tidskriftsartikel (refereegranskat)abstract
- Leptin, an adipocyte-derived hormone, is involved in the regulation of body weight and is associated with obesity-related complications, notably cardiovascular disease (CVD). A putative link between obesity and CVD could be induction of plasminogen activator inhibitor-1 (PAI-1) synthesis by leptin. In this study, we hypothesized that the beneficial effect of the angiotensin-converting enzyme inhibitor (ACE(i)) enalapril on PAI-1 levels is mediated by effects on leptin levels. The association between leptin and components of the fibrinolytic system was evaluated in a non-prespecified post hoc analysis of a placebo-controlled randomized, double-blind trial where the effect of the ACE(i) enalapril on fibrinolysis was tested. A total of 46 men and 37 women were randomized to treatment with enalapril or placebo after (median 12 months) an uncomplicated myocardial infarction. At baseline, the participants were stable and had no signs of congestive heart failure. Leptin and fibrinolytic variables (mass concentrations of PAI-1, tissue plasminogen activator (tPA) and tPA-PAI complex) were measured at baseline, and after 10 days, 6 months and 12 months. Enalapril treatment did not change leptin levels, which increased significantly during 1 year of follow-up (p = .007). Changes in leptin levels were strongly associated with changes of tPA mass (p = .001), tPA-PAI complex (p = .003) and of PAI-1 (p = .006) in men, but not in women. Leptin levels are not influenced by treatment with an ACE(i). In contrast, leptin associates strongly with changes in fibrinolytic variables notably with a sex difference, which could be of importance for obesity-related CVD.
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| 7. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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| 8. |
- Johansson, Kristina, 1986-
(författare)
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Biomarkers and risk of intracerebral hemorrhage : population-based studies in northern Sweden
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundIntracerebral hemorrhage (ICH) is a disease associated with a high morbidity and mortality and treatment options for the condition are limited. Even though an ICH event usually comes as a surprise to the affected individual, pathogenetic processes often have occurred before the sudden ICH event and may have preceded disease onset by years. It is possible that individuals at increased risk of ICH could be identified using biomarkers, for example markers of hemostasis and fibrinolysis. Even if these biomarkers are not part of the causal chain, they could be used as risk indicators to better define high-risk groups. Another approach could be to measure already established risk markers for ICH, such as self-reported alcohol consumption, using a blood biomarker. That could increase measurement reliability and consequently the accuracy of the estimates of ICH risk.AimsThe aim of this thesis was to investigate potential biomarkers and risk of ICH. Specific aims were to evaluate the associations between factor XII, D-dimer, von Willebrand factor (VWF), ABO blood groups with focus on blood group O, phosphatidylethanol (PEth), and risk of ICH.MethodsIn our first study, aiming to investigate the association between factor XII and risk of hemorrhagic stroke, we followed participants of the health examination northern Sweden MONItoring trends and determinants in CArdiovascular disease (MONICA) performed in 1994 as a cohort until 2011. Factor XII concentrations were measured in blood samples drawn at the baseline health examination where the participants also answered a questionnaire regarding lifestyle factors and medical history. Diagnosis codes from the National Patient Register and the Swedish Cause of Death Register were used to find cases of hemorrhagic stroke, defined as ICH or subarachnoid hemorrhage. In the subsequent studies, the associations between biomarkers (factor XII, D-dimer, VWF, ABO blood groups, and PEth) and risk of ICH were investigated using a matched, nested case-referent design including individuals that had participated in the Västerbotten Intervention Programme, the MONICA and the Mammography Screening Project in 1985–2007. The participants donated blood samples at baseline for future research which were stored at -80 degrees C until biomarker analyses. The majority of the participants also underwent a baseline health examination including a questionnaire. First-ever ICH diagnoses during the study period 1985–2007 were validated using medical records and autopsy reports. To each case, two referents were matched for age, sex, geographical region, health examination date and health examination setting. ResultsIn the cohort study of the association between factor XII concentrations and risk of hemorrhagic stroke, 1,852 participants were included among which 30 experienced a hemorrhagic stroke event. There was an association between high factor XII and risk of hemorrhagic stroke in a multivariable model (hazard ratio 1.51; 95% confidence interval [CI] 1.03–2.21 per standard deviation [SD] of factor XII). In the case-referent study of the association between factor XII and risk of ICH, 70 cases with ICH and 137 matched referents were included. We found no association between factor XII and risk of ICH in a multivariable model (odds ratio [OR] 1.06; 95% CI 0.57–1.97 per SD of factor XII). The study of the association between D-dimer and risk of ICH included 141 cases and 255 matched referents. We found an association between D-dimer and risk of ICH in a multivariable model (OR 1.36; 95% CI 1.05–1.77 per SD of D-dimer). When stratifying the analysis for time between blood sampling and ICH event in tertiles, the association remained significant in the cases with the shortest time between blood sampling and ICH event in a multivariable model (OR 1.78; 95% CI 1.05–3.05 per SD of D-dimer). The study investigating the association between VWF and risk of ICH included 139 cases and 276 referents. We found no association between VWF and risk of ICH in a multivariable model (OR 0.85; 95% CI 0.54–1.34 per SD of VWF). In the analysis investigating the associations between ABO blood groups and risk of ICH, 162 cases and 317 referents were included. We found no association between blood group O compared to non-O blood groups and risk of ICH (OR 0.96; 95% CI 0.65–1.42). In the study of the association between PEth concentrations and risk of ICH, 97 cases and 180 referents were included. There was an association between PEth concentrations > 0.30 µmol/L compared to < 0.01 µmol/L and risk of ICH in a multivariable model (OR 4.64; 95% CI 1.49–14.40).ConclusionsHigh concentrations of D-dimer and PEth are associated with an increased risk of ICH. Our conclusion of the two studies investigating the association between factor XII and risk of hemorrhagic stroke and ICH respectively is that there is no association between factor XII and risk of ICH. We found no association between VWF or blood group O and risk of ICH.
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| 9. |
- Johansson, Kristina, et al.
(författare)
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Phosphatidylethanol Levels, As a Marker of Alcohol Consumption, Are Associated With Risk of Intracerebral Hemorrhage
- 2020
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Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 51:7, s. 2148-2152
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Previous observational studies have shown a moderately increased risk of intracerebral hemorrhage (ICH) with high self-reported alcohol consumption. However, self-reported data tend to underestimate alcohol consumption. Phosphatidylethanol is a specific biomarker reflecting alcohol intake during the last month and correlates with the amount of alcohol consumed. The present study aimed to investigate the association between phosphatidylethanol levels and the risk of future ICH.Methods: This population-based nested case-referent study was conducted within the Northern Sweden Health and Disease Cohort. At baseline, all participants underwent a health examination, including a questionnaire with questions about alcohol consumption. A blood sample was collected and stored at −80°C, and phosphatidylethanol 16:0/18:1 levels were measured in packed erythrocytes. Cases (n=97) were diagnosed with a first-ever ICH between 1985 and 2007. Two referents (n=180) were matched to each case.Results: The mean age at baseline was 55 years, 39% of participants were women, and the mean time from blood sampling to ICH was 7.3 years. Only phosphatidylethanol and hypertension remained independently associated with ICH in a multivariable model. Participants with phosphatidylethanol >0.30 μmol/L had an increased risk of ICH compared with those with phosphatidylethanol <0.01 μmol/L (odds ratio, 4.64 [95% CI, 1.49–14.40]).Conclusions: High blood concentrations of phosphatidylethanol were associated with an increased risk of future ICH. This association was independent of hypertension and other risk factors for ICH. Our findings suggest that phosphatidylethanol, as a marker of alcohol consumption, may be used as a risk marker of future ICH.
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| 10. |
- Johansson, Kristina, et al.
(författare)
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Von Willebrand factor, ABO blood group, and risk of first-ever intracerebral hemorrhage : A prospective nested case-control study
- 2020
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Ingår i: Thrombosis Research. - : Elsevier. - 0049-3848 .- 1879-2472. ; 195, s. 77-80
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Low levels of von Willebrand factor (VWF) were associated with intracerebral hemorrhage (ICH) in a previous study. Persons with blood group O have lower VWF levels than other ABO blood groups. This study aimed to investigate the association between VWF and the risk of ICH in adults, as well as the association between ABO blood group and risk of ICH.Methods: This population-based, nested case-control study was conducted using data and blood samples from health examinations between 1985 and 2007. All participants were followed, and cases with first-ever ICH were identified and validated. One or two controls were matched to each case.Results: During a median follow-up time from blood sampling to ICH of 5.6 years, 176 cases with ICH were identified. The mean age at health examination was 57 years; 50% of participants were women. There was an association between hypertension and risk of ICH, but there was no association between VWF level and risk of ICH. There was no association between blood group O and risk of ICH.Conclusions: To our knowledge this is the largest prospective study investigating the association between VWF, ABO blood group and ICH. We found no association between VWF or blood group O and risk of future ICH.
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