| 1. |
- Ali, Amna, et al.
(author)
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Autonomic dysfunction is associated with cardiac remodelling in heart failure patients
- 2018
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In: Heart Failure Clinics. - : Wiley. - 1551-7136 .- 2055-5822. ; 5:1, s. 46-52
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Journal article (peer-reviewed)abstract
- AIMS: Orthostatic hypotension (OH) is a cardinal sign of autonomic dysfunction and a common co-morbidity in heart failure (HF). The role of autonomic dysfunction in the development of structural cardiac anomalies in HF patients has not been sufficiently explored. We aimed to assess relations between orthostatic blood pressure (BP) responses during active standing and echocardiographic changes in a series of patients admitted for HF.METHODS AND RESULTS: One hundred and forty-nine patients hospitalized for HF [mean age: 74 years; 30% women; ejection fraction (LVEF) 40 ± 16%] were examined with conventional echocardiograms and active-standing test. Associations of cardiac remodelling parameters with the difference between supine and standing (after 3 min) systolic/diastolic BP were examined. Systolic BP decreased (-1.1 ± 15 mmHg), whereas diastolic BP increased (+1.0 ± 9.5 mmHg) after 3 min of active standing. A total of 34 patients (23%) met conventional OH criteria; i.e. systolic/diastolic BP decreases by ≥20/10 mmHg. In the multivariable linear regression analysis, adjusted for traditional cardiovascular risk factors and LVEF, a decrease in systolic BP upon standing was associated with greater left atrial volume [β per -10 mmHg: 2.37, standard error (SE) = 1.16, P = 0.043], and greater left ventricular mass (β per -10 mmHg: 5.67, SE = 2.24, P = 0.012), but not with other echocardiographic parameters. No significant associations were observed between signs of cardiac remodelling and decrease in diastolic BP.CONCLUSIONS: Orthostatic decrease in systolic BP among older HF patients is associated with structural cardiac changes such as increased left atrial volume and left ventricular mass, independently of traditional risk factors and left ventricular dysfunction.
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| 2. |
- Christensson, Anders, et al.
(author)
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The shrunken pore syndrome is associated with declined right ventricular systolic function in a heart failure population – the HARVEST study
- 2016
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 76:7, s. 568-574
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Journal article (peer-reviewed)abstract
- The close relationship between heart and kidney diseases was studied with respect to the ‘Shrunken pore syndrome’ that is characterized by a difference in renal filtration between cystatin C and creatinine. Patients were retrieved from the HeARt and brain failure inVESTigation trail (HARVEST) which is an ongoing study undertaken in individuals hospitalized for the diagnosis of heart failure. Ninety-five of 116 patients who underwent transthoracic echocardiograms (TTE) were eligible for this study. We used four different formulas for estimated glomerular filtration rate (eGFR); CKD-EPIcreatinine, CKD-EPIcystatin C, LMrev and CAPA. Presence of the syndrome was defined as eGFR cystatin C ≤ 60% of eGFR creatinine and absence of the syndrome as eGFR cystatin C >90% and <110% of eGFR creatinine. In a linear regression model, adjusted for age and sex, and the ‘Shrunken pore syndrome’ defined by the equation pair CAPA and LMrev and the equation pair CKD-EPIcystatin C and CKD-EPIcreatinine, echocardiographic parameters were studied. The ‘Shrunken pore syndrome’ showed statistically significant associations with measurements of right ventricular (RV) systolic function; (TAPSE and RV S’) (according to the equation pair CKD-EPIcystatin C and CKD-EPIcreatinine). In conclusion, heart failure patients with the ‘Shrunken pore syndrome’ are at increased risk of having RV systolic dysfunction whilst heart failure patients without ‘Shrunken pore syndrome’ seem protected. These findings may indicate common pathophysiological events in the kidneys and the heart explaining the observed increased risk of mortality in subjects with the ‘Shrunken pore syndrome’.
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| 3. |
- Dieden, Anna, et al.
(author)
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Galectin-4 is associated with diabetes and obesity in a heart failure population
- 2023
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13, s. 1-10
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Journal article (peer-reviewed)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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| 4. |
- Holm, Hannes, et al.
(author)
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Cognitive test results are associated with mortality and rehospitalization in heart failure: Swedish prospective cohort study
- 2020
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In: ESC Heart Failure. - : WILEY PERIODICALS, INC. - 2055-5822. ; 7:5, s. 2948-2955
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Journal article (peer-reviewed)abstract
- Aims We aimed to search for associations between cognitive test results with mortality and rehospitalization in a Swedish prospective heart failure (HF) patient cohort. Methods and results Two hundred and eighty-one patients hospitalized for HF (mean age, 74 years; 32% women) were assessed using cognitive tests: Montreal Cognitive Assessment (MoCA), A Quick Test of Cognitive speed, Trail Making Test A, and Symbol Digit Modalities Test. The mean follow-up time censored at rehospitalization or death was 13 months (interquartile range, 14) and 28 months (interquartile range, 29), respectively. Relations between cognitive test results, mortality, and rehospitalization risk were analysed using multivariable Cox regression model adjusted for age, sex, body mass index, systolic blood pressure, atrial fibrillation, diabetes, smoking, educational level, New York Heart Association class, and prior cardiovascular disease. A total of 80 patients (29%) had signs of cognitive impairment (MoCA score < 23 points). In the fully adjusted Cox regression model using standardized values per 1 SD change of each cognitive test, lower score on MoCA [hazard ratio (HR), 0.75; confidence interval (CI), 0.60-0.95;P = 0.016] and Symbol Digit Modalities Test (HR, 0.66; CI, 0.48-0.90;P = 0.008) yielded significant associations with increased mortality. Rehospitalization risk (n = 173; 62%) was significantly associated with lower MoCA score (HR, 0.84; CI, 0.71-0.99;P = 0.033). Conclusions Two included cognitive tests were associated with mortality in hospitalized HF patients, independently of traditional risk factors. In addition, worse cognitive test scores on MoCA heralded increased risk of rehospitalization.
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| 5. |
- Jujić, Amra, et al.
(author)
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Association between low selenoprotein P concentrations and anaemia in hospitalized heart failure patients
- 2024
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In: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 11:2, s. 877-882
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Journal article (peer-reviewed)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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| 6. |
- Jujic, Amra, et al.
(author)
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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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In: Journal of Cardiac Failure. - : Elsevier. - 1071-9164 .- 1532-8414.
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Journal article (peer-reviewed)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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| 7. |
- Jujic, Amra, et al.
(author)
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Selenoprotein P deficiency is associated with higher risk of incident heart failure
- 2023
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In: Free Radical Biology & Medicine. - 0891-5849. ; 207, s. 11-16
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Journal article (peer-reviewed)abstract
- AbstractIntroductionSelenium deficiency has been associated with mortality, cardiovascular disease and worsened prognosis in heart failure (HF). In a recent population-based study, high selenium levels were shown to be associated with reduced mortality and reduced incidence of HF, but only in non-smokers. Here, we aimed to examine if selenoprotein P (SELENOP), a main selenium carrier protein, is associated with incident HF.Materials and methodsSELENOP concentrations were measured in plasma of 5060 randomly selected subjects from the population-based prospective cohort “Malmö Preventive Project” (n = 18240) using an ELISA approach. Exclusion of subjects with prevalent HF (n = 230) and subjects with missing data on co-variates included in the regression analysis (n = 27) resulted in complete data for 4803 subjects (29.1% women, mean age 69.6 ± 6.2 years, 19.7% smokers). Cox regression models adjusted for traditional risk factors were used to analyse SELENOP's association with incident HF. Further, subjects within the quintile with the lowest SELENOP concentrations were compared to subjects in the remaining quintiles.ResultsEach 1 standard deviation increment in SELENOP levels was associated with lower risk of incident HF (n = 436) during a median follow-up period of 14.7 years (hazard ratio (HR) 0.90; CI95% 0.82–0.99; p = 0.043). Further analyses showed that subjects in the lowest SELENOP quintile were at the highest risk of incident HF when compared to quintiles 2–5 (HR 1.52; CI95% 1.21–1.89; p = 2.5 × 10−4).ConclusionLow selenoprotein P levels are associated with a higher risk of incident HF in a general population. Further studies are warranted.
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| 8. |
- Kharraziha, Isabella, et al.
(author)
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Impaired cerebral oxygenation in heart failure patients at rest and during head-up tilt testing
- 2021
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In: ESC Heart Failure. - : Wiley. - 2055-5822. ; 8:1, s. 586-594
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Journal article (peer-reviewed)abstract
- AIMS: Heart failure (HF) confers potentially negative effects on the brain and autonomic nervous system. The measurement cerebral tissue oxygen saturation (SctO2 ) may aid in understanding such effects. We aimed to investigate if compensated HF affects SctO2 at rest and during orthostatic challenge.METHODS AND RESULTS: Non-invasive haemodynamic monitoring and near-infrared spectroscopy were applied during head-up tilt (HUT) in 61 HF patients [mean (SD) 71 (11) years, 82% male, New York Heart Association (NYHA) class I-III] and 60 controls [60 (12) years, 42% male). Group differences in continuous variables were compared using Student's t-test. Associations between HF and SctO2 were studied using multivariable linear regression models adjusted for age, sex, diabetes, smoking, systolic blood pressure (SBP), and heart rate in supine position and after 10 min of HUT. Mean SctO2 was lower in HF patients compared with controls both in the supine position (67 vs. 71%; P < 0.001) and after 10 min of HUT (64 vs. 69%; P < 0.001). The HUT-induced SctO2 decrease was greater in HF patients compared with controls (P = 0.026). SBP did not change in neither HF patients nor controls during HUT, whereas diastolic blood pressure and heart rate increased in both groups. HF was associated with lower SctO2 in supine (B = -2.5%, P = 0.023) and after 10 min of HUT (B = -2.6%, P = 0.007) after multivariable adjustments.CONCLUSIONS: Cerebral tissue oxygenation is lower in HF patients both at rest and during orthostasis compared with subjects without HF. Future studies should test if the lower cerebral oxygenation associates with negative prognosis and with impaired cognitive function.
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| 9. |
- Korduner, Johan, et al.
(author)
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Galectin-4 levels in hospitalized versus non-hospitalized subjects with obesity: the Malmo Preventive Project
- 2022
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In: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 21:1
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Journal article (peer-reviewed)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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| 10. |
- Magnusson, Martin, et al.
(author)
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Cystatin C and risk of diabetes and the metabolic syndrome - Biomarker and genotype association analyses
- 2016
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Journal article (peer-reviewed)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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