Low Levels of Selenoprotein P Are Associated With Cognitive Impairment in Patients Hospitalized for Heart Failure.

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: The 187 participants had a mean age of 73 (± 11.9) years; 31% were female and had a mean body mass index of 28.1 (± 5.6) kg/m2. 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.

Association between low selenoprotein P concentrations and anaemia in hospitalized heart failure patients.

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.

Galectin-4 is associated with diabetes and obesity in a heart failure population.

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.

The impact of myocardial fibrosis biomarkers in a heart failure population with atrial fibrillation-The HARVEST-Malmö study.

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.

Physical Inactivity Is Associated With Post-discharge Mortality and Re-hospitalization Risk Among Swedish Heart Failure Patients-The HARVEST-Malmö Study.

Background: Several studies have examined the role of physical activity as a predictor of heart failure (HF) mortality and morbidity. Here, we aimed to evaluate the role of self-reported physical activity as an independent risk factor of post-discharge mortality and re-hospitalization in patients hospitalized for HF, as well as study the association between physical activity and 92 plasma proteins associated with cardiovascular disease (CVD). Methods: Four-hundred-and-thirty-four patients hospitalized for HF (mean age 75 years; 32% women) were screened for physical activity derived from questionnaires in the Swedish national public health survey. The median follow-up time to death and re-hospitalization was 835 (interquartile range, 390-1,432) and 157 (43-583) days, respectively. Associations between baseline reported physical activity, mortality and re-hospitalization risk were analyzed using multivariable Cox regression analysis. Plasma samples from 295 study participants were analyzed with a proximity extension assay consisting of 92 proteins. Associations between proteins and physical activity were explored using a false discovery rate of <5%, and significant associations were taken forward to multivariate analyses. Results: In the multivariate Cox regression model, physical inactivity, defined as physical activity time <1 h throughout the week was associated with increased risk of all-cause mortality (HR 1.71; CI95% 1.26-2.31; p = 5.9 × 10-4) as well as all-cause re-hospitalization (HR 1.27; CI95% 1.01-1.60; p = 0.038). Further, physical inactivity was associated with elevated plasma levels of Metalloproteinase inhibitor 4, Soluble interleukin 1 receptor-like 1, Elafin and Transferrin receptor protein 1, which are implicated in myocardial fibrosis, migration and apoptosis. Conclusions: Self-reported low weekly physical activity is associated with increased risk of mortality and re-hospitalization in patients hospitalized for HF independent of traditional risk factors. Furthermore, physical inactivity was associated with elevated levels of 4 proteins linked to cardiovascular disease.

Exploring biomarkers associated with deteriorating vascular health using a targeted proteomics chip: The SABPA study.

ABSTRACT: In this observational study, by the use of a multiplex proteomic platform, we aimed to explore associations between 92 targeted proteins involved in cardiovascular disease and/or inflammation, and phenotypes of deteriorating vascular health, with regards to ethnicity.Proteomic profiling (92 proteins) was carried out in 362 participants from the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study of black and white African school teachers (mean age 44.7 ±â€Š9.9 years, 51.9% women, 44.5% Black Africans, 9.9% with known cardiovascular disease). Three proteins with <15% of samples below detectable limits were excluded from analyses. Associations between multiple proteins and prevalence of hypertension as well as vascular health [Carotid intima-media thickness (cIMT) and pulse wave velocity (PWV)] measures were explored using Bonferroni-corrected regression models.Bonferroni-corrected significant associations between 89 proteins and vascular health markers were further adjusted for clinically relevant co-variates. Hypertension was associated with growth differentiation factor 15 (GDF-15) and C-X-C motif chemokine 16 (CXCL16). cIMT was associated with carboxypeptidase A1 (CPA1), C-C motif chemokine 15 (CCL15), chitinase-3-like protein 1 (CHI3L1), scavenger receptor cysteine-rich type 1 protein M130 (CD163) and osteoprotegerin, whereas PWV was associated with GDF15, E-selectin, CPA1, fatty acid-binding protein 4 (FABP4), CXCL16, carboxypeptidase B (CPB1), and tissue-type plasminogen activator. Upon entering ethnicity into the models, the associations between PWV and CPA1, CPB1, GDF-15, FABP4, CXCL16, and between cIMT and CCL-15, remained significant.Using a multiplex proteomic approach, we linked phenotypes of vascular health with several proteins. Novel associations were found between hypertension, PWV or cIMT and proteins linked to inflammatory response, chemotaxis, coagulation or proteolysis. Further, we could reveal whether the associations were ethnicity-dependent or not.

Glucose-Dependent Insulinotropic Peptide in the High-Normal Range Is Associated With Increased Carotid Intima-Media Thickness.

OBJECTIVE: While existing evidence supports beneficial cardiovascular effects of glucagon-like peptide 1 (GLP-1), emerging studies suggest that glucose-dependent insulinotropic peptide (GIP) and/or signaling via the GIP receptor may have untoward cardiovascular effects. Indeed, recent studies show that fasting physiological GIP levels are associated with total mortality and cardiovascular mortality, and it was suggested that GIP plays a role in pathogenesis of coronary artery disease. We investigated the associations between fasting and postchallenge GIP and GLP-1 concentrations and subclinical atherosclerosis as measured by mean intima-media thickness in the common carotid artery (IMTmeanCCA) and maximal intima-media thickness in the carotid bifurcation (IMTmaxBulb). RESEARCH DESIGN AND METHODS: Participants at reexamination within the Malmö Diet and Cancer-Cardiovascular Cohort study (n = 3,734, mean age 72.5 years, 59.3% women, 10.8% subjects with diabetes, fasting GIP available for 3,342 subjects, fasting GLP-1 available for 3,299 subjects) underwent oral glucose tolerance testing and carotid ultrasound. RESULTS: In linear regression analyses, each 1-SD increment of fasting GIP was associated with increased (per mm) IMTmeanCCA (ß = 0.010, P = 0.010) and IMTmaxBulb (ß = 0.014; P = 0.040) in models adjusted for known risk factors and glucose metabolism. In contrast, each 1-SD increment of fasting GLP-1 was associated with decreased IMTmaxBulb (per mm, ß = -0.016, P = 0.014). These associations remained significant when subjects with diabetes were excluded from analyses. CONCLUSIONS: In a Swedish elderly population, physiologically elevated levels of fasting GIP are associated with increased IMTmeanCCA, while GLP-1 is associated with decreased IMTmaxBulb, further emphasizing diverging cardiovascular effects of these two incretin hormones.

Learning echocardiography- what are the challenges and what may favour learning? A qualitative study.

BACKGROUND: Echocardiography is a frequently used imaging modality requiring extensive training to master. In order to develop curriculums and teaching material fully favouring students learning within echocardiography, this study aims to investigate students' experiences of learning echocardiography, focusing on that which is perceived as the main challenges as well as what might aid learning within the area. The findings could serve as a foundation in the development of new teaching material or curriculums. METHODS: A qualitative study was performed with data gathered through two audio-recorded focus group interviews with four third year students from the biomedical laboratory programme at Malmö University in each group. Data was analysed by manifest content analysis. RESULTS: Findings were clustered into two categories reflecting the main findings in the text - practical skills and bridging the theory-practice-gap. Students expressed that main challenges when initially learning echocardiography were the projections and handling the probe as well as connecting ultrasound physics and measurements to practical application. Things that aided their learning were immediate feedback, "playing" with the ultrasound machine, video lectures, the possibility to swiftly alternate between practice and theory as well as the learning by their mistakes in a risk-free environment. CONCLUSIONS: This study shows the main challenges when initially learning echocardiography and what might be helpful during the learning process. These findings may be useful when developing curriculums or new teaching material within echocardiography. One suggestion might be to develop digital resources such as virtual laboratories (vLABs).

Effect of food intake on myocardial performance index.

BACKGROUND: Myocardial performance index (MPI) has been investigated in a variety of populations, but the effect of food intake has not been evaluated. We assessed whether myocardial performance index is affected by food intake in healthy subjects. METHODS: Twenty-three healthy subjects aged 25.6 ± 4.5 years were investigated. MPI was measured before, 30 min after, and 110 min after a standardized meal. RESULTS: MPI decreased significantly (P < 0.05) from fasting values 30 min after the meal, and had almost returned to baseline after 110 min. MPI decreased from 0.28 ± 0.06 (fasting) to 0.20 ± 0.07 30 min after eating. At 110 min after eating the index value was almost back to the baseline value 0.26 ± 0.06. (P = 0.15). CONCLUSIONS: This study shows that myocardial performance index is affected by food intake in healthy subjects.

Effect of food intake on left and right ventricular systolic tissue Doppler measurements.

Systolic tissue Doppler measurements (s') have been used to measure the velocity in myocardial motion and are a valuable tool for evaluating the systolic function of the left and right ventricles. Digestion of food is known to significantly alter hemodynamics and may therefore affect s'. The effect of food intake on s' parameters has not yet been studied. We assessed whether s' is affected by food intake. Nineteen healthy subjects aged 26·2 ± 4·2 years were investigated. s' was measured with pulsed tissue Doppler imaging in the right and left ventricles before the subjects ate a standardized meal and also 30 and 110 min after the meal. Three measurements were taken in each projection, and a mean value was calculated for each. s' increased significantly (P<0·05) from fasting to 30 min after food intake in every measured site except in the left inferolateral wall (P = 0·15, NS). Several, but not all, variables returned to base value 110 min after food intake. This study shows that food intake affects the tissue Doppler variables used to evaluate systolic heart function. Further studies are needed in older healthy subjects and older subjects with various cardiovascular diseases.