| 1. |
- Dieden, Anna, et al.
(författare)
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Galectin-4 is associated with diabetes and obesity in a heart failure population
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- An association between high Galectin-4 (Gal-4) and prevalence of diabetes in subjects with heart failure (HF) has previously been reported. The purpose of this study was to confirm these findings, as well as to further investigate this association, in a Swedish HF population. In addition, a second aim was to explore Gal-4’s association with obesity and biomarkers of metabolism and heart failure. Gal-4 was measured using a proximity extension array technique in 324 hospitalized HF patients within the Swedish HeArt and bRain failure investigation trial cohort. Obesity was defined as BMI ≥ 30. Multivariable logistic regression models were used to explore associations between Gal-4 and diabetes/obesity, and linear regression models were used to explore the associations between Gal-4 and biomarkers. A total of 309 participants (29.1% female; mean age 74.8 years) provided complete data for the analysis of associations between Gal-4 and diabetes. Additionally, for the analysis of heart failure phenotype, complete data was available for 230 subjects. Gal-4 was positively associated with prevalent diabetes (OR 2.60; CI 95% 1.56–4.32). In multivariable models, Gal-4 levels were significantly associated with obesity, but only for subjects with diabetes (OR 2.48; 1.09–5.62). Additionally, Gal-4 demonstrated a significant association with the incretin Glucose-dependent insulinotropic polypeptide (GIP), as well as with biomarkers of HF. In the stratified analyses, the association between Gal-4 and diabetes was prominent in patients with reduced ejection fraction (n = 160, OR 3.26; 95%CI 1.88–5.66), while it was not observed in those without (n = 70, 1.96 (0.75–5.10)). In this cross-sectional, observational study, higher Gal-4 levels in HF patients were associated with higher GIP levels. Further, increased levels of Gal-4 were associated with increased likelihood of diabetes, and obesity. This association was particularly pronounced in individuals with HF characterized by reduced ejection fraction. Additionally, Gal-4 levels were significantly elevated in heart failure patients with diabetes and obesity.
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| 2. |
- Jujic, Amra, et al.
(författare)
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Antibodies against phosphorylcholine in hospitalized versus non‑hospitalized obese subjects
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Obesity associates with reduced life expectancy, type 2 diabetes, hypertension and cardiovascular disease, and is characterized by chronic inflammation. Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein, dead cells and some microorganisms. Antibodies against PC (anti-PC) have anti-inflammatory properties. Here, we explored the role of anti-PC in hospitalized versus non-hospitalized obese. One-hundred-and-twenty-eight obese (BMI ≥ 30 kg/m2) individuals (59.8 (± 5.5) years, 53.9% women) from the Malmö Diet and Cancer Cardiovascular Cohort were examined and IgM, IgG1 and IgG2 anti-PC were analyzed by ELISA. Individuals with at least one recorded history of hospitalization prior to study baseline were considered hospitalized obese (HO). Associations between IgM, IgG1 and IgG2 anti-PC and HO (n = 32)/non-hospitalized obese (NHO) (n = 96), but also with metabolic syndrome and diabetes were analysed using logistic regressions. Both IgM and IgG1 anti-PC were inversely associated with HO, also after controlling for age and sex. When further adjusted for waist circumference, systolic blood pressure, glucose levels and smoking status, only IgG1 anti-PC remained significantly associated with HO. In multivariate models, each 1 standard deviation of increment in anti-PC IgG1 levels was inversely associated with prevalence of HO (odds ratio 0.57; CI 95% 0.33–0.98; p = 0.044). IgG2 anti-PC did not show any associations with HO. Low levels of IgM and IgG1 anti-PC are associated with higher risk of being a HO individual independent of sex and age, IgG1 anti-PC also independently of diabetes and metabolic syndrome. The anti-inflammatory properties of these antibodies may be related to inflammation in obesity and its complications.
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| 3. |
- Jujić, Amra, et al.
(författare)
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Association between low selenoprotein P concentrations and anaemia in hospitalized heart failure patients
- 2024
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Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 11:2, s. 877-882
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Tidskriftsartikel (refereegranskat)abstract
- Aims Heart failure (HF) patients with anaemia tend to have a worse outcome, with increased hospitalization rates, decreased exercise tolerance, and higher mortality compared to those without anaemia. Limited research exists on the association between selenium deficiency and anaemia specifically in HF patients, despite previous findings of a correlation in different populations. The BIOSTAT-CHF study demonstrated that higher selenium levels in HF patients were associated to a lower risk of anaemia and iron deficiency. This study investigates the relationship between selenoprotein P (SELENOP) concentrations, a major contributor and functional biomarker of selenium transport, and anaemia, Hb levels, and iron status in hospitalized HF patients.Methods and results SELENOP was analysed in 320 hospitalized HF subjects, with complete data available for 310 subjects. The relationships between continuous SELENOP concentrations and 1) Hb concentrations, 2) anaemia (Hb < 115 g/L (women), <130 g/L (men)), and 3) iron status (as measured by transferrin receptor 1 (TfR1) which increases in iron deficiency) were evaluated using multivariable logistic and linear regression models. Additionally, SELENOP concentrations in the lowest quartile were related to anaemia, haemoglobin, and iron state in multivariable logistic and linear models. The mean age of the study population was 75.0 +/- 11.6 years, and 30% were women. Anaemia was present in 133 subjects (42.9%). SELENOP concentrations were positively correlated with haemoglobin concentrations (0.238; P < 0.001) and negatively with TfR1 concentrations (-0.238, P < 0.001). In multivariable regression models, higher SELENOP concentrations were associated with higher Hb concentrations (B = 3.23; P = 0.002) and lower TfR1 concentrations (B = -0.20; P < 0.001). Furthermore, SELENOP deficiency was associated with lower Hb concentrations (B = -7.64: P = 0.001), higher TfR1 concentrations (B = 0.31; P = 0.003), and higher odds of anaemia in HF patients (odds ratio 2.17; 95% confidence interval 1.23-3.82; P = 0.008).Conclusions In hospitalized heart failure patients, lower concentrations of SELENOP were associated with higher prevalence of anaemia.
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| 4. |
- Jujic, Amra, et al.
(författare)
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Low Levels of Selenoprotein P Are Associated With Cognitive Impairment in Patients Hospitalized for Heart Failure
- 2024
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Ingår i: Journal of Cardiac Failure. - : Elsevier. - 1071-9164 .- 1532-8414.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Selenoprotein P (SELENOP) is a transporter for selenium and has been shown to protect selenium-status maintenance in the brain against deficiency and to support neuronal development, neurogenesis and neurocognitive function. Selenium deficiency has previously been associated with cognitive impairment in various populations, but no studies have been carried out in subjects with heart failure (HF).PURPOSE: To explore whether SELENOP deficiency in subjects with acute HF is associated with cognitive impairment.METHODS: Plasma SELENOP, as measured by an immunoassay analysis, is a well-validated marker of plasma selenium status and has the benefit of providing information on the bioavailable fraction of selenium to preferentially supplied cells equipped with receptors for SELENOP uptake. SELENOP was measured in 320 subjects hospitalized for HF. Of the subjects, 187 also underwent 4 cognitive tests assessing global cognitive function: Montreal Cognitive Assessment (MoCA); information processing (Symbol Digit Modalities Test [SDMT]); visual attention and task switching (Trailmaking Test A [TMT-A]); and executive speed (A Quick Test of Cognitive Speed [AQT] form and color). Appropriate cutoffs were used for each cognitive test to define cognitive impairment. Cross-sectional associations between SELENOP concentrations and cognitive impairment, as defined by each cognitive test, were explored using multivariable logistic models. Further, multivariable logistic models exploring associations between selenium deficiency, defined as the lowest quartile of SELENOP levels, and cognitive impairment, defined by each cognitive test, were carried out.RESULTS: . Each 1 standard deviation increment in SELENOP concentrations was associated with lower odds of cognitive impairment, defined as a MoCA cut-off score < 23 (odds ratio [OR] 0.60; 95% CI 0.40-0.91; P = 0.017). Further, SELENOP concentrations in the lowest quartile (≤ 2.3 mg/L) were associated with cognitive impairment as measured by MoCA (OR 3.10; 95% CI 1.38-6.97; P = 0.006), SDMT (OR 2.26; 95% CI 1.10-4.67; P = 0.027) and TMT-A (OR 3.40; 95% CI 1.47-7.88; P = 0.004) but not by AQT form and color.CONCLUSIONS: In subjects admitted for HF, higher SELENOP concentrations were associated with better performance on the MoCA test, reflecting global cognition, and SELENOP deficiency was associated with cognitive impairment as defined by 3 cognitive tests.
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| 5. |
- Korduner, Johan, et al.
(författare)
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Galectin-4 levels in hospitalized versus non-hospitalized subjects with obesity: the Malmo Preventive Project
- 2022
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Obesity is strongly associated with the development of cardiovascular disease (CVD). However, the heterogenous nature of obesity in CVD-risk is still poorly understood. We aimed to explore novel CVD biomarkers and their possible association with presumed unhealthy obesity, defined as hospitalized subjects with obesity (HO). Methods Ninety-two proteins associated with CVD were analyzed in 517 (mean age 67 +/- 6 years; 33.7% women) individuals with obesity (BMI >= 30 kg/m(2)) from the Malmo Preventive Project cohort, using a proximity extension array technique from the Olink CVD III panel. Individuals with at least one recorded hospitalization for somatic disease prior to study baseline were defined as HO phenotypes. Associations between proteins and HO (n = 407) versus non-hospitalized subjects with obesity (NHO, n = 110), were analyzed using multivariable binary logistic regression, adjusted for traditional risk factors. Results Of 92 analyzed unadjusted associations between biomarkers and HO, increased levels of two proteins were significant at a false discovery rate < 0.05: Galectin-4 (Gal-4) and insulin-like growth factor-binding protein 1 (IGFBP-1). When these two proteins were included in logistic regression analyses adjusted for age and sex, Gal-4 remained significant. Gal-4 was independently associated with the HO phenotype in multivariable logistic regression analysis (OR 1.72; CI95% 1.16-2.54). Post-hoc analysis revealed that this association was only present in the subpopulation with diabetes (OR 2.26; CI95% 1.25-4.07). However, an interaction analysis was performed, showing no significant interaction between Gal-4 and prevalent diabetes (p = 0.16). Conclusions In middle-aged and older individuals with obesity, increased Gal-4 levels were associated with a higher probability of HO. This association was only significant in subjects with diabetes only, further implying a role for Gal-4 in diabetes and its complications.
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| 6. |
- Korduner, Johan, et al.
(författare)
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Metabolically healthy obesity (MHO) in the Malmö diet cancer study - Epidemiology and prospective risks
- 2019
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Ingår i: Obesity Research and Clinical Practice. - : Elsevier BV. - 1871-403X. ; 13:6, s. 548-554
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Metabolically healthy obesity (MHO) remains controversial, since the underlying mechanisms behind this phenotype remain unclear. We aimed to investigate the characteristics of MHO, as well as prospective risks.METHOD: A cross-sectional analysis was carried out in a subsample of 3812 obese subjects selected from the Malmo diet cancer study (n=28,403). Subjects with MHO (n=1182) were defined by having no records of hospitalization for somatic disorders prior to baseline examination. MHO subjects were further compared to subjects with metabolically unhealthy obesity, MUO (obese individuals with at least one recorded hospitalization: n=2630), and all non-obese cohort controls (NOC; n=24,591). Moreover, prospective risk analyses for incident cardiovascular (CV) morbidity and mortality were carried out.RESULTS: Compared to MUO individuals, MHO individuals reported a significantly lower proportion of sedentary life style (p=0.009), but also significantly lower HbA1c (p=0.012), fasting glucose (p=0.001) and triglyceride levels (p=0.011) than MUO. Cox-regression analysis (follow-up 20±6 years) showed both a significantly lower all-cause mortality risk for MHO individuals as compared to MUO (p=0.001), as well as lower incident CV morbidity risk (p=0.001). When comparing MHO individuals to NOC, there were no significant differences in neither mortality risk nor incident CV morbidity risk.CONCLUSION: Compared to MUO individuals, MHO individuals presented with a higher level of physical activity, a more favorable lipid- and glucose profile and a lower prospective risk of total mortality and CV morbidity during 20-years follow-up. Notably, no significant differences could be seen in mortality and CV morbidity risks when comparing MHO subjects to non-obese controls.
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| 7. |
- Korduner, Johan, et al.
(författare)
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Proteomic and Metabolomic Characterization of Metabolically Healthy Obesity: : A Descriptive Study from a Swedish Cohort
- 2021
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Ingår i: Journal of Obesity. - : Hindawi Limited. - 2090-0708 .- 2090-0716. ; 2021
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims. Obesity is a well-established risk factor for the development of numerous chronic diseases. However, there is a small proportion of obese individuals that seem to escape these aforementioned conditions—Metabolically Healthy Obesity (MHO). Our aim was to do a metabolic and biomarker profiling of MHO individuals. Method. Associations between different biomarkers (proteomics, lipidomics, and metabolomics) coupled to either MHO or metabolically unhealthy obese (MUO) individuals were analyzed through principal component analysis (PCA). Subjects were identified from a subsample of 416 obese individuals, selected from the Malmö Diet and Cancer study—Cardiovascular arm (MDCS-CV, n = 3,443). They were further divided into MHO (n = 143) and MUO (n = 273) defined by a history of hospitalization, or not, at baseline inclusion, and nonobese subjects (NOC, n = 3,027). Two distinctive principle components (PL2, PP5) were discovered with a significant difference and thus further investigated through their main loadings. Results. MHO individuals had a more metabolically favorable lipid and glucose profile than MUO subjects, that is, lower levels of traditional blood glucose and triglycerides, as well as a trend of lower metabolically unfavorable lipid biomarkers. PL2 (lipidomics, ) showed stronger associations of triacylglycerides with MUO, whereas phospholipids correlated with MHO. PP5 (proteomics, ) included interleukin-1 receptor antagonist (IL-1ra) and leptin with positive relations to MUO and galanin that correlated positively to MHO. The group differences in metabolite profiles were to a large extent explained by factors included in the metabolic syndrome. Conclusion. Compared to MUO individuals, corresponding MHO individuals present with a more favorable lipid metabolic profile, accompanied by a downregulation of potentially harmful proteomic biomarkers. This unique and extensive biomarker profiling presents novel data on potentially differentiating traits between these two obese phenotypes.
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| 8. |
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| 9. |
- Nezami, Zainu, et al.
(författare)
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The impact of myocardial fibrosis biomarkers in a heart failure population with atrial fibrillation-The HARVEST-Malmö study.
- 2022
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Ingår i: Frontiers in cardiovascular medicine. - : Frontiers Media S.A.. - 2297-055X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies suggest that circulating biomarkers of myocardial fibrosis are associated with worse prognosis in subjects with atrial fibrillation (AF). Here, we aimed to explore associations between fibrosis biomarkers, prevalent AF, and left atrial volume (LAV) enlargement in subjects with heart failure (HF). Additionally, we evaluated the prognostic impact of fibrotic biomarkers in HF with co-existing AF.Materials and methods: Patients hospitalized for HF (n = 316, mean age 75 years; 30% women) were screened for AF. Seven proteins previously associated with myocardial fibrosis [metalloproteinase inhibitor 4 (TIMP-4), suppression of tumorigenicity 2 (ST-2), galectin-3 (GAL-3), growth/differentiation factor-15 (GDF-15), and matrix metalloproteinase 2, 3, and 9 (MMP-3, MMP-3, and MMP-9, respectively)] were analyzed using a proximity extension assay. Proteins with significant Bonferroni-corrected associations with mortality and re-hospitalization risk were taken forward to multivariable Cox regression analyses. Further, Bonferroni-corrected multivariable logistic regression models were used to study associations between protein plasma levels, prevalent AF, and severely enlarged left atrial volume index (LAVI ≥ 48 ml/m2).Results: Prevalent AF was observed in 194 patients at the hospitalization of whom 178 (92%) were re-hospitalized and 111 (57%) died during the follow-up period. In multivariable logistic regression models, increased plasma levels of TIMP-4, GDF-15, and ST-2 were associated with the prevalence of AF, whereas none of the seven proteins showed any significant association with severely enlarged LAVI. Increased plasma levels of five proteins yielded significant associations with all-cause mortality in patients with co-existing AF; TIMP-4 (HR 1.33; CI95% 1.07-1.66; p = 0.010), GDF-15 (HR 1.30; CI95% 1.05-1.62; p = 0.017), GAL-3 (HR 1.29; CI95% 1.03-1.61; p = 0.029), ST-2 (HR 1.48; CI95% 1.18-1.85; p < 0.001), and MMP-3 (HR 1.33; CI95% 1.09-1.63; p = 0.006). None of the proteins showed any significant association with re-hospitalization risk.Conclusion: In this study, we were able to demonstrate that elevated levels of three plasma proteins previously linked to myocardial fibrosis are associated with prevalent AF in a HF population. Additionally, higher levels of five plasma proteins yielded an increased risk of mortality in the HF population with or without co-existing AF.
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| 10. |
- Nilsson, Peter M, et al.
(författare)
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Metabolically Healthy Obesity (MHO)-New Research Directions for Personalised Medicine in Cardiovascular Prevention
- 2020
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Ingår i: Current Hypertension Reports. - : Springer Science and Business Media LLC. - 1534-3111 .- 1522-6417. ; 22:2, s. 1-5
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE OF REVIEW: To discuss new findings on the heterogeneity of obesity and associated risks.RECENT FINDINGS: Obesity is a public health problem of immense importance on a global scale. However, epidemiological findings and clinical studies have revealed that obesity is a heterogeneous phenotype and that not all obese subjects run the same risk for complications. Current research has tried to describe so-called metabolically healthy obesity (MHO), defined by lack of risk factors included in the metabolic syndrome. These subjects will not escape long-term complications, but mortality risk is not increased. However, a new definition of MHO has recently been proposed, based on the lack of hospitalisation for somatic disease for decades in middle life. MHO subjects defined in this way are characterised by being "fat and fit" and also run a lower risk of long-term complications. If MHO could be better understood, this could contribute to a more diverse clinical approach to obesity based on personalised medicine.
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