| 1. |
- Al-Majdoub, Mahmoud, et al.
(författare)
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Population-level analysis to determine parameters that drive variation in the plasma metabolite profiles
- 2018
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- The plasma metabolome is associated with multiple phenotypes and diseases. However, a systematic study investigating clinical determinants that control the metabolome has not yet been conducted. In the present study, therefore, we aimed to identify the major determinants of the plasma metabolite profile. We used ultra-high performance liquid chromatography (UHPLC) coupled to quadrupole time of flight mass spectrometry (QTOF-MS) to determine 106 metabolites in plasma samples from 2503 subjects in a cross-sectional study. We investigated the correlation structure of the metabolite profiles and generated uncorrelated metabolite factors using principal component analysis (PCA) and varimax rotation. Finally, we investigated associations between these factors and 34 clinical covariates. Our results suggest that liver function, followed by kidney function and insulin resistance show the strongest associations with the plasma metabolite profile. The association of specific phenotypes with several components may suggest multiple independent metabolic mechanisms, which is further supported by the composition of the associated factors. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
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| 2. |
- Daka, Bledar, et al.
(författare)
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Circulating concentrations of endothelin-1 predict coronary heart disease in women but not in men: A longitudinal observational study in the Vara-Skövde Cohort
- 2015
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2015 Daka et al.Background: The vasoconstricting peptide endothelin-1 has been proposed to be a marker of cardiovascular disease. Our aim was to investigate whether circulating endothelin-1 levels predict coronary heart disease (CHD) in Sweden. Methods: In 2002-2005, 2816 adult participants (30-74 years) were randomly selected from two municipalities in south-western Sweden. Cardiovascular risk factors and endothelin-1 levels were assessed at baseline, and incident CHD was followed-up in all participants through 2011. After exclusion of 50 participants due to known CHD at baseline and 21 participants because of unsuccessful analysis of endothelin-1, 2745 participants were included in the study. In total, 72 CHD events (52 in men and 20 in women) were registered during the follow-up time. Results: We showed that baseline circulating endothelin-1 levels were higher in women with incident CHD than in women without CHD (3.2 pg/ml, SE: 0.36 vs 2.4 pg/ml, SE: 0.03, p = 0.003) whereas this difference was not observed in men (2.3 pg/ml, SE: 0.16 vs 2.3 pg/ml, SE: 0.04, p = 0.828). An age-adjusted Cox proportional regression analysis showed an enhanced risk of CHD with increasing baseline endothelin-1 levels in women (hazard ratio (HR) = 1.51, 95 % CI = 1.1-2.1, p = 0.015) but not in men (HR = 0.98, 95 % CI = 0.8-1.2, p = 0.854). Furthermore, the predictive value of endothelin-1 for incident CHD in women was still significant after adjustments for age, HOMA-IR, apolipoprotein (apo)B/apoA1 and smoking (HR = 1.53, CI = 1.1-1.2, p = 0.024). Conclusion: Circulating endothelin-1 levels may predict CHD in women.
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| 3. |
- Daka, Bledar, et al.
(författare)
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Low concentrations of serum testosterone predict acute myocardial infarction in men with type 2 diabetes mellitus
- 2015
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Ingår i: Bmc Endocrine Disorders. - : Springer Science and Business Media LLC. - 1472-6823. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the present study was to investigate the associations between endogenous testosterone concentrations and the incidence of acute myocardial infarction (AMI) in men and women with and without type 2 diabetes. Methods: The study comprised 1109 subjects >= 40 years of age (mean age 62 +/- 12 years) participating in a baseline survey in Sweden in 1993-94. Information about smoking habits and physical activity was obtained using validated questionnaires. Serum concentrations of testosterone and sex hormone-binding globulin (SHBG) were obtained using radioimmunoassay. Diagnosis of type 2 diabetes was based on WHO's 1985 criteria. Individual patient information on incident AMI was ascertained by record linkage with national inpatient and mortality registers from baseline through 2011. Results: The prevalence of type 2 diabetes at baseline was 10.0 % in men and 7.5 % in women. During a mean follow-up of 14.1 years (+/- 5.3), there were 74 events of AMI in men and 58 in women. In age-adjusted Cox models, a significant inverse association between concentrations of testosterone and AMI-morbidity was found in men with type 2 diabetes (HR = 0.86 CI (0.75-0.98)). In a final model also including waist-to-hip ratio, systolic blood pressure, total cholesterol and active smoking, the association still remained statistically significant (HR = 0.754 CI (0.61-0.92)). Conclusion: Low concentrations of testosterone predicted AMI in men with type 2 diabetes independent of other risk factors. Trials with testosterone investigating the effect regarding cardiovascular outcome are still lacking. Future trials in this field should take into account a modification effect of diabetes.
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| 4. |
- Frostegård, Johan, et al.
(författare)
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Antibodies against Phosphorylcholine among New Guineans Compared to Swedes: An Aspect of the Hygiene/Missing Old Friends Hypothesis.
- 2017
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Ingår i: Immunological investigations. - : Informa UK Limited. - 1532-4311 .- 0882-0139. ; 46:1, s. 59-69
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Tidskriftsartikel (refereegranskat)abstract
- We here study antibodies against phosphorylcholine (anti-PC) which we reported to be inversely associated with atherosclerosis, cardiovascular disease (CVD), and autoimmune conditions. In previous studies, we determined that this inverse association is more pronounced at low levels with high risk and at high levels, with decreased risk. We compare individuals from Kitava, New Guinea (with low risk of these conditions), with Swedish controls.We studied a group of 178 individuals from Kitava (age 20-86), and compared those above age 40 (n = 108) with a group of age- and sex-matched individuals from a population based cohort in Sweden (n = 108). Traditional risk factors for CVD and fatty acids were determined. IgM, IgG, and IgA anti-PC were tested by enzyme-linked immunosorbent assay (ELISA).All anti-PC measures were significantly lower among Swedish controls as compared to Kitavans (p < 0.001), independent of traditional risk factors. Having low levels of anti-PC, defined as below 25th percentile of values among Swedish controls, was associated with this cohort after adjustment for other risk factors (OR 5.7, 95% CI 2.2-14.7 for IgM; OR 31.7, 95% CI 3.9-252 for IgA; and OR 11.1, 95% CI 2.4-51 for IgG).PC is highly exposed on microorganisms and helminths (common on Kitava) exposing much PC which humans and hominids may have been exposed to for millions of years. We propose that low anti-PC levels in the developed world could be a new aspect of the hygiene hypothesis, generating a pro-inflammatory and pro-atherosclerotic state.
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| 5. |
- Kaszuba, Elzbieta, et al.
(författare)
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Heart failure and levels of other comorbidities in patients with chronic obstructive pulmonary disease in a Swedish population : A register-based study
- 2016
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite the fact that heart failure and chronic obstructive pulmonary disease (COPD) often exist together and have serious clinical and economic implications, they have mostly been studied separately. Our aim was to study prevalence of coexisting heart failure and COPD in a Swedish population. A further goal was to describe levels of other comorbidity and investigate where the patients received care: primary, secondary care or both. Methods: We conducted a register-based, cross-sectional study. The population included all people older than 19 years, living in Östergötland County in Sweden. The data were obtained from the Care Data Warehouse register from the year 2006. The diagnosis-based Adjusted Clinical Groups Case-Mix System 7.1 was used to describe the comorbidity level. Results: The prevalence of the diagnosis of heart failure in patients with COPD was 18.8 % while it was 1.6 % in patients without COPD. Age standardized prevalence was 9.9 and 1.5 %, respectively. Standardized relative risk for the diagnosis of heart failure in patients with COPD was 6.6. The levels of other comorbidity were significantly higher in patients with coexisting heart failure and COPD compared to patients with either heart failure or COPD alone. Primary care was the only care provider for 36.2 % of patients with the diagnosis of heart failure and 20.7 % of patients with coexisting diagnoses of heart failure and COPD. Primary care participated furthermore in shared care of 21.5 % of patients with the diagnosis of heart failure and 21.7 % of patients with coexisting diagnoses of heart failure and COPD. The share of care between primary and secondary care varied depending on levels of comorbidity both in patients with coexisting heart failure and COPD and patients with heart failure alone. Conclusion: Patients with coexisting diagnoses of heart failure and COPD are common in the Swedish population. Patients with coexisting heart failure and COPD have higher levels of other comorbidity than patients with heart failure or COPD alone. Primary care in Sweden participates to a great extent in care of patients with diagnoses of heart failure alone and coexisting heart failure and COPD.
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| 6. |
- Kaszuba, Elzbieta, et al.
(författare)
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Impact of heart failure and other comorbidities on mortality in patients with chronic obstructive pulmonary disease : A register-based, prospective cohort study
- 2018
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Ingår i: BMC Family Practice. - : Springer Science and Business Media LLC. - 1471-2296. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multimorbidity has already become common in primary care and will be a challenge in the future. Primary care in Sweden participates to a great extent in the care of patients with two severe, chronic conditions: chronic obstructive pulmonary disease (COPD) and heart failure. Both conditions are characterized by high mortality and often coexist. Age, sex, heart failure and other comorbidities are considered to be the major predictors of mortality in patients with COPD. We aimed to study the impact of heart failure, other comorbidities, age and sex on mortality in patients with COPD. Methods: A register-based, prospective cohort study conducted in Blekinge County in Sweden with about 150,000 inhabitants. The study population was comprised of people aged ≥35 years. The data about diagnoses of COPD and heart failure came from the 2007 health care register, in which we found 984 individuals with a diagnosis of COPD. Date of death was collected from January 1st, 2008 -August 31st, 2015. The diagnosis-based Adjusted Clinical Groups (ACG) Case-Mix System 7.1 was used to describe comorbidity. Each individual was assigned one of six comorbidity levels called resource utilization bands (RUB) graded from 0 to 5. Results: Estimated eight year mortality in patients with COPD and coexisting heart failure was seven times higher than in patients with COPD alone - odds ratio 7.06 (95% CI 3.88-12.84). Adjusting for age and male sex resulted in odds ratio 3.75 (95% CI 1.97-7.15). Further adjusting for other comorbidities resulted in odds ratio 3.26 (95% CI 1.70-6.25). The mortality was strongly associated with the highest comorbidity level - RUB 5 where the odds ratio was 5.19 (95% CI 2.59-10.38). Conclusion: Heart failure has an important impact on mortality in patients with COPD. The mortality in patients with COPD and coexisting heart failure was strongly associated with age, male sex and other comorbidities. Of those three predictors, only other comorbidities can be influenced. Heart failure and other comorbidities should be recognized early and properly treated in order to improve survival in patients with coexisting COPD and heart failure.
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| 7. |
- Molvin, John, et al.
(författare)
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Using a Targeted Proteomics Chip to Explore Pathophysiological Pathways for Incident Diabetes-The Malmo Preventive Project
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Multiplex proteomic platforms provide excellent tools for investigating associations between multiple proteins and disease (e.g., diabetes) with possible prognostic, diagnostic, and therapeutic implications. In this study our aim was to explore novel pathophysiological pathways by examining 92 proteins and their association with incident diabetes in a population-based cohort (146 cases of diabetes versus 880 controls) followed over 8 years. After adjusting for traditional risk factors, we identified seven proteins associated with incident diabetes. Four proteins (Scavenger receptor cysteine rich type 1 protein M130, Fatty acid binding protein 4, Plasminogen activator inhibitor 1 and Insulin-like growth factor-binding protein 2) with a previously established association with incident diabetes and 3 proteins (Cathepsin D, Galectin-4, Paraoxonase type 3) with a novel association with incident diabetes. Galectin-4, with an increased risk of diabetes, and Paraoxonase type 3, with a decreased risk of diabetes, remained significantly associated with incident diabetes after adjusting for plasma glucose, implying a glucose independent association with diabetes.
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| 8. |
- Odeberg, Jacob, et al.
(författare)
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Influence of pre-existing inflammation on the outcome of acute coronary syndrome: a cross-sectional study
- 2016
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Inflammation is a well-established risk factor for the development of coronary artery disease (CAD) and acute coronary syndrome (ACS). However, less is known about its influence on the outcome of ACS. The aim of this study was to determine if blood biomarkers of inflammation were associated specifically with acute myocardial infarction (MI) or unstable angina (UA) in patients with ACS. Setting: Patients admitted to the coronary care unit, via the emergency room, at a central county hospital over a 4-year period (1992-1996). Participants: In a substudy of Carlscrona Heart Attack Prognosis Study (CHAPS) of 5292 patients admitted to the coronary care unit, we identified 908 patients aged 30-74 years, who at discharge had received the diagnosis of either MI (527) or UA (381). Main outcome measures: MI or UA, based on the diagnosis set at discharge from hospital. Results: When adjusted for smoking, age, sex and duration of chest pain, concentrations of plasma biomarkers of inflammation (high-sensitivity C reactive protein >2 mg/L (OR=1.40 (1.00 to 1.96) and fibrinogen (p for trend=0.035)) analysed at admission were found to be associated with MI over UA, in an event of ACS. A strong significant association with MI over UA was found for blood cell markers of inflammation, that is, counts of neutrophils (p for trend <0.001), monocytes (p for trend <0.001) and thrombocytes (p for trend=0.021), while lymphocyte count showed no association. Interestingly, eosinophil count (p for trend=0.003) was found to be significantly lower in patients with MI compared to those with UA. Conclusions: Our results show that, in patients with ACS, the blood cell profile and degree of inflammation at admission was associated with the outcome. Furthermore, our data suggest that a pre-existing low-grade inflammation may dispose towards MI over UA.
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| 9. |
- Privšek, Ernest, et al.
(författare)
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Epidemiological and clinical implications of blood pressure measured in seated versus supine position
- 2018
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Ingår i: Medicine. - 1536-5964. ; 97:31, s. 11603-11603
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Tidskriftsartikel (refereegranskat)abstract
- The evidence concerning how posture influences blood pressure is not consistent. The aim of this cross-sectional study was to consider the clinical and epidemiological implications of blood pressure measured in seated versus supine position, and to investigate the impact of age, sex, body mass index (BMI), and diabetes on these differences.This study included 1298 individuals (mean age 58.6 ± 11.8 years) from the Vara-Skövde cohort at the 10 years' follow-up visit in 2014. Physical examination included blood pressure measurements in seated and supine position. Self-reported information on diabetes status, hypertension, ongoing medication, leisure time physical activity, and smoking habits were obtained. Linear regression models accounted for differences in age, sex, BMI, and known diabetes.Both systolic and diastolic blood pressure were significantly higher in the seated position [1.2 mm Hg, P < .001, 95% confidence interval (95% CI) 0.79-1.54 and 4.2 mm Hg, P < .001, 95% CI 4.08-4.71, respectively]. The prevalence of high blood pressure in seated position was higher (19.9%) than in supine position (13.5%). Linear regression analysis showed that age (β = -0.215, P < .001) and diabetes (β = -0.072, P = .012) were associated with smaller differences in postural diastolic blood pressure and BMI (β = 0.124, P < .001) with greater difference.This study showed substantial postural differences in blood pressures measured in office. Measuring blood pressure in the supine position shows lower blood pressure readings when compared with the seated position. Clinicians should be aware of how age, BMI, and diabetes influence these differences.
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