In a trial involving patients with heart failure and a mildly reduced or preserved ejection fraction, dapagliflozin reduced the risk of worsening heart failure or cardiovascular death.
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.
Selenium is a nutrient with antioxidant effects and thus is protective against cardiovascular disease (1), as demonstrated by a meta-analysis revealing a significant inverse correlation between ...selenium levels and the incidence of atherosclerotic coronary heart disease (CHD) (2). ...the effect of selenium supplementation on CHD risk is still controversial, and a recent meta-analysis of 16 randomized controlled trials (RCTs) showed that selenium supplementation was not sufficient to reduce mortality despite favorable effects on inflammatory biomarkers (3). Cross-sectional analyses of quality of life, according to a Kansas City Cardiomyopathy Questionnaire overall score, revealed that each 1 SD increase of SePP was associated with a decreased risk of low health-related quality of life (n = 47), defined as a summary score <50 in the fully adjusted model (body mass index, systolic blood pressure, smoking, prevalent atrial fibrillation, prevalent diabetes, prior HF, and log-transformed N-terminal pro–B-type natriuretic peptide) (odds ratio: 0.68; 95% confidence interval CI: 0.47 to 0.97; p = 0.035).
The "Shrunken pore syndrome" (SPS) is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFR
/eGFR
-ratio. Studies have demonstrated a high risk ...for cardiovascular morbidity and mortality for patients with SPS. In this discovery study, we explored associations between SPS and proteins implicated in cardiovascular disease and inflammation in patients with heart failure.
Plasma samples from 300 individuals in HARVEST-Malmö trial hospitalized for the diagnosis of heart failure (mean age 74.9 ± 11.5 years; 30.0% female), were analyzed with a proximity extension assay consisting of 92 proteins. A Bonferroni-corrected p-value of 0.05/92 = 5.4 × 10
was considered significant in the initial age and sex-adjusted analyses. Presence of SPS was defined as eGFR
≤ 60% of eGFR
.
SPS presented with significant associations (p < 5.4 × 10
) in age and sex-adjusted logistic regressions with elevated levels of six proteins; scavenger receptor cysteine rich type 1 protein M130, tumor necrosis factor receptor 1, tumor necrosis factor receptor 2, osteoprotegerin, interleukin-2 receptor subunit alpha, and tyrosine-protein kinase receptor UFO. All proteins remained associated (p < 0.05) with SPS after multivariate adjustments.
In heart failure patients, SPS was associated with proteins linked to atherosclerosis and cell proliferation.
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.
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 Malmö 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.
ObjectivesIn an acute heart failure (AHF) setting, proenkephalin A 119–159 (penKid) has emerged as a promising prognostic marker for predicting worsening renal function (WRF), while bioactive ...adrenomedullin (bio-ADM) has been proposed as a potential marker for congestion. We examined the diagnostic value of bio-ADM in congestion and penKid in WRF and investigated the prognostic value of bio-ADM and penKid regarding mortality, rehospitalisation and length of hospital stay in two separate European AHF cohorts.MethodsBio-ADM and penKid were measured in 530 subjects hospitalised for AHF in two cohorts: Swedish HeArt and bRain failure inVESTigation trial (HARVEST-Malmö) (n=322, 30.1% female; mean age 75.1+11.1 years; 12 months follow-up) and Italian GREAT Network Rome study (n=208, 54.8% female; mean age 78.5+9.9 years; no follow-up available).ResultsPenKid was associated with WRF (area under the curve (AUC) 0.65, p<0.001). In multivariable logistic regression analysis of the pooled cohort, penKid showed an independent association with WRF (adjusted OR (aOR) 1.74, p=0.004). Bio-ADM was associated with peripheral oedema (AUC 0.71, p<0.001), which proved to be independent after adjustment (aOR 2.30, p<0.001). PenKid was predictive of in-hospital mortality (OR 2.24, p<0.001). In HARVEST-Malmö, both penKid and bio-ADM were predictive of 1-year mortality (aOR 1.34, p=0.038 and aOR 1.39, p=0.030). Furthermore, bio-ADM was associated with rehospitalisation (aOR 1.25, p=0.007) and length of hospital stay (β=0.702, p=0.005).ConclusionIn two different European AHF cohorts, bio-ADM and penKid perform as suitable biomarkers for early detection of congestion severity and WRF occurrence, respectively, and are associated with pertinent clinical outcomes.
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.
Aim
The aim of this study was to assess the predictive role of biomarkers, associated with cardiovascular stress and its neuroendocrine response as well as renal function, in relation to mortality ...and risk of re‐hospitalization among consecutive patients admitted because of heart failure (HF).
Methods and results
A total of 286 patients (mean age, 75 years; 29% women) hospitalized for newly diagnosed or exacerbated HF were analysed. Associations between circulating levels of mid‐regional pro‐adrenomedullin (MR‐proADM), copeptin, C‐terminal pro‐endothelin‐1, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), cystatin C, and all‐cause mortality as well as risk of re‐hospitalization due to cardiac causes were assessed using multivariable Cox regression models. A two‐sided Bonferroni‐corrected P‐value of 0.05/5 = 0.010 was considered statistically significant. All biomarkers were related to echocardiographic measurements of cardiac dimensions and function. A total of 57 patients died (median follow‐up time, 17 months). In the multivariable‐adjusted Cox regression analyses, all biomarkers, except C‐terminal pro‐endothelin‐1, were significantly associated with increased mortality: NT‐proBNP hazard ratio (HR) 1.85, 95% confidence interval (CI) 1.17–2.17; P = 4.0 × 10−4, MR‐proADM (HR 1.94, 95% CI 1.36–2.75; P = 2.2 × 10−4), copeptin (HR 1.70, 95% CI 1.22–2.36; P = 0.002), and cystatin C (HR 2.11, 95% CI 1.56–2.86; P = 1.0 × 10−6). A total of 90 patients were re‐hospitalized (median time to re‐hospitalization, 5 months). In multivariable Cox regression analyses, NT‐proBNP was the only biomarker that showed significant association with risk of re‐hospitalization due to cardiac causes (HR 1.43, 95% CI 1.10–1.87; P = 0.009).
Conclusions
Among patients hospitalized for HF, elevated plasma levels of NT‐proBNP, MR‐proADM, copeptin, and cystatin C are associated with higher mortality after discharge, whereas NT‐proBNP is the only biomarker that predicts the risk of re‐hospitalization due to cardiac causes.
Aims
This study aimed to investigate the association between the ‘Shrunken pore syndrome’ (SPS) and risk of death, 30 day rehospitalization, and health‐related quality of life (QoL) in heart failure ...(HF) patients. SPS is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFRcystatin C/eGFRcreatinine ratio.
Methods and results
A total of 373 patients hospitalized for HF mean age 74.8 (±12.1) years; 118 (31.6%) women were retrieved from the HeARt and brain failure inVESTigation trial (HARVEST‐Malmö). Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) formulas were used for estimation of glomerular filtration rate (eGFR). Presence of SPS was defined as eGFRcystatin C ≤ 60% of eGFRcreatinine. In Cox regression multivariate models, associations between SPS, risk of death (median follow‐up time 1.8 years), and risk of 30 day rehospitalization were studied. Associations between SPS and impaired QoL were studied using multivariate logistic regressions. In multivariate models, SPS was associated with all‐cause mortality 124 events; hazard ratio (HR) 1.99; 95% confidence interval (95% CI) 1.23–3.21; P = 0.005 and with 30 day rehospitalization (70 events; HR 1.82; CI 95% 1.04–3.18; P = 0.036). Analyses of QoL, based on a Kansas City Cardiomyopathy Questionnaire overall score < 50, revealed that SPS was associated with higher risk of low health‐related QoL (odds ratios 2.15; CI 95% 1.03–4.49; P = 0.042).
Conclusions
The results of this observational study show for the first time an association between SPS and poor prognosis in HF. Further studies are needed to confirm the results in HF cohorts and experimental settings to identify pathophysiological mechanisms.
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