| 1. |
- Alves Dias, Joana, et al.
(författare)
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Low-grade inflammation, oxidative stress and risk of invasive post-menopausal breast cancer - A nested case-control study from the Malmö diet and cancer cohort
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Although cancer promotes inflammation, the role of inflammation in tumor-genesis is less well established. The aim was to examine if low-grade inflammation is related to post-menopausal breast cancer risk, and if obesity modifies this association. Methods; In the Malmo Diet and Cancer cohort, a nested case-control study was defined among 8,513 women free of cancer and aged 55.73 years at baseline (1991.96); 459 were diagnosed with invasive breast cancer during follow-up (until December 31st, 2010). In laboratory analyses of blood from 446 cases, and 885 controls (matched on age and date of blood sampling) we examined systemic inflammation markers: oxidized (ox)-LDL, interleukin (IL)- 1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, white blood cells, lymphocytes and neutrophils. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer risk was calculated using multivariable conditional logistic regression. Results: Inverse associations with breast cancer were seen in fully-adjusted models, for 2nd and 3rd tertiles of ox-LDL, OR (95% CI): 0.65 (0.47.0.90), 0.63 (0.45.0.89) respectively, p-trend = 0.01; and for the 3rd tertile of TNF-α, 0.65 (0.43.0.99), p-trend = 0.04. In contrast, those in the highest IL-1β category had higher risk, 1.71 (1.05.2.79), p-trend = 0.01. Obesity did not modify associations between inflammation biomarkers and breast cancer. Conclusion; Our study does not suggest that low-grade inflammation increase the risk of post-menopausal breast cancer.
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| 2. |
- Borné, Yan, et al.
(författare)
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Total and Differential Leukocyte Counts in Relation to Incidence of Diabetes Mellitus: A Prospective Population-Based Cohort Study.
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: High concentrations of leukocytes in blood have been associated with diabetes mellitus. This prospective study aimed to explore whether total and differential leukocyte counts are associated with incidence of diabetes. A missense variant R262W in the SH2B3 (SH2B adaptor protein 3) gene, coding for a protein that negatively regulates hematopoietic cell proliferation, was also studied in relation to incidence of diabetes. METHODS AND RESULTS: Leukocyte count and its subtypes (neutrophils, lymphocytes and mixed cells) were analyzed in 26,667 men and women, 45-73 years old, from the population-based Malmö Diet and Cancer study. Information about the R262W polymorphism (rs3184504) in SH2B3 was genotyped in 24,489 subjects. Incidence of diabetes was studied during a mean follow-up of 14 years. Cox proportional hazards regression was used to examine incidence of diabetes by total and differential leukocyte counts. Mendelian randomization analysis using R262W as an instrumental variable was performed with two-stage least squares regression. A total of 2,946 subjects developed diabetes during the follow-up period. After taking several possible confounders into account, concentrations of total leukocyte count, neutrophils and lymphocytes were all significantly associated with incidence of diabetes. The adjusted hazard ratios (95% confidence interval; quartile 4 vs quartile 1) were 1.37 (1.22-1.53) for total leukocytes, 1.33 (1.19-1.49) for neutrophils and 1.29 (1.15-1.44) for lymphocytes. The R262W polymorphism was strongly associated with leukocytes (0.11x109 cells/l per T allele, p = 1.14 x10-12), lymphocytes (p = 4.3 x10-16), neutrophils (p = 8.0 x10-6) and mixed cells (p = 3.0 x10-6). However, there was no significant association between R262W and fasting glucose, HbA1c or incidence of diabetes. CONCLUSIONS: Concentrations of total leukocytes, neutrophils and lymphocytes are associated with incidence of diabetes. However, the lack of association with the R262W polymorphism suggests that the associations may not be causal, although limitations in statistical power and balancing pleiotropic effects cannot be excluded.
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| 3. |
- Gijsberts, Crystel M, et al.
(författare)
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Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events.
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| 4. |
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| 5. |
- Lorenz, M. W., et al.
(författare)
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Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration
- 2018
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Aims Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
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| 6. |
- Magnusson, Martin, et al.
(författare)
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Cystatin C and risk of diabetes and the metabolic syndrome - Biomarker and genotype association analyses
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Background We recently reported a relationship between plasma levels of cystatin C and incidence of the metabolic syndrome (MetS) among the first 2,369 subjects who participated in the reexamination study of the population-based Malmö and Diet Cancer Cardiovascular cohort (MDC-CC-re-exam). In this study we aimed to replicate these results and also investigate if cystatin C was causally associated with MetS and diabetes. Methods We estimated the effect size of the strongest GWAS derived cystatin C SNP (major allele of rs13038305) on plasma cystatin C in the now completed MDC-CC-re-exam (n = 3,734) and thereafter examined the association between plasma cystatin C (403 cases of diabetes and2665 controls) as well as rs13038305 (235 cases and 2425 controls) with incident diabetes. The association of rs13038305 and incident MetS (511 cases of MetS and 1980 controls) was similarly investigated in the whole MDC-CC-re-exam. We also attempted to replicate our previously shown association of cystatin C with incident MetS in subjects from the MDC-CC-re-exam (147 cases and 711 controls) that were not included in our previous report. Results In the entire MDC-CC-re-exam, each copy of the major allele of rs13038305 was associated with approximately 0.30 standard deviation (SD) higher plasma concentration of cystatin C (β = 0.33, p = 4.2E-28 ) in age and sex adjusted analysis. Cystatin C in plasma was not associated with incident diabetes after adjustment for known diabetes risk factors (OR per 1 SD increment 0.99 (0.86-1.13), p = 0.842). In the replication cohort of MDC-CC-re-exam, the OR (95% CI) for incident MetS in subjects belonging to quartiles 1, 2, 3 and 4 of plasma cystatin C levels was 1.00 (reference), 1.21 (0.70-2.07), 1.62 (0.95-2.78) and 1.72 (1.01-2.93) (ptrend = 0.026) in age and sex adjusted analysis. In the entire MDC-CC-re-exam the odds ratio for incident MetS and diabetes per copy of the major rs13038305 allele was 1.13, (0.95-1.34), p = 0.160 and 1.07, 95% CI 0.89-1.30, p = 0.478, respectively. Conclusion We were able to replicate our previously shown association between high levels of cystatin C and increased risk of future development of MetS. However, a causal involvement of cystatin C in the etiology of MetS or diabetes seems unlikely since genetic elevation of plasma cystatin C was not significantly related to incidence of these diseases.
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| 7. |
- Muhammad, Iram Faqir, et al.
(författare)
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Acute phase proteins as prospective risk markers for arterial stiffness : The Malmö Diet and Cancer cohort
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: Arterial stiffness plays a significant role in the development and progression of adverse cardiovascular events and all-cause mortality. This observational study aims to explore the relationship between six acute phase proteins namely, ceruloplasmin, alpha-1-antitrypsin, orosomucoid, haptoglobin, complement C3 and C-reactive protein (CRP), and carotid-femoral pulse wave velocity (c-f PWV) in a population-based cohort, and to also explore the effect of low-grade inflammation on the relationship between diabetes and c-f PWV. Method: The study consisted of participants from the Malmö Diet and Cancer study with data from baseline examinations (1991–1994) and follow-up examinations (2007–2012). Arterial stiffness was measured at follow-up by determining c-f PWV. After excluding participants with missing data, the total study population included 2338 subjects. General linear models were used to assess the relationship between baseline acute phase proteins and c-f PWV. Results: After adjusting for traditional risk factors the participants in the 4th quartile vs 1st quartile of alpha-1-antitrypsin (geometric mean: 10.32 m/s vs 10.04 m/s) (<0.05), C3 (10.35 m/s vs 10.06 m/s) (p<0.05) and CRP (10.37 m/s vs 9.96 m/s) (<0.001) showed significant association with c-f PWV. Diabetes at follow-up was also associated with high c-f PWV, however, this relationship was independent of low grade inflammation. Conclusion: Alpha-1-antitrypsin, C3 and CRP are associated with arterial stiffness. The results indicate that low grade inflammation is associated with arterial stiffness in addition to established cardiovascular risk factors.
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| 8. |
- Norby, Faye L, et al.
(författare)
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Association of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation : The AFGen Consortium
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts.METHODS: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score.RESULTS: During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98-1.03); 0.98 (0.96-1.01); 0.98 (0.95-1.02); 0.99 (0.97-1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97-1.03); 1.01 (0.99-1.04).CONCLUSIONS: In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.
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| 9. |
- Sandberg, Jacob, et al.
(författare)
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Breathlessness and incidence of COPD, cardiac events and all-cause mortality : A 44-year follow-up from middle age throughout life
- 2019
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Breathlessness is prevalent in the general population and may be associated with adverse health outcomes. This study aimed to evaluate the association of breathlessness with Chronic Obstructive Pulmonary Disease (COPD) events, cardiac events and all-cause mortality from middle-age throughout life. Methods Breathlessness was measured in 699, 55-year old men residing in Malmö, Sweden using modified Medical Research Council (mMRC). COPD events (hospitalisation, death or diagnosis) cardiac events and all-cause mortality was assessed using The Swedish Causes of Death Register and Hospital Discharge Register. Data was analyzed using Cox- and competing risks (Fine-Gray) regression analysis. Results 695 (99%) of 699 participants died and four emigrated during follow up. Eighty-seven (12%) had mMRC = 1 and 19 (3%) had mMRC2. Breathlessness was associated with COPD events; adjusted Sub-Hazard Ratio 2.1 (95% CI, 1.2–3.6) for mMRC = 1 and 7.5 (2.6–21.7) for mMRC 2 but not associated with cardiac events when adjusting for competing events and confounding. Breathlessness was associated increased all- cause mortality (Hazard Ratios of 1.4 (1.1–1.7) (mMRC = 1) and 3.4 (2.1–5.6) (mMRC 2)). Conclusion Breathlessness is associated with increased risk of COPD events and increase in all-cause mortality from age 55 until death.
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| 10. |
- Svensson, Patrik, et al.
(författare)
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Cystatin C Is Not Causally Related to Coronary Artery Disease.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Strong and independent associations between plasma concentration of cystatin C and risk of cardiovascular disease (CVD) suggests causal involvement of cystatin C.
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