Gender-Related Differences in Heart Failure Biomarkers

Important differences in comorbidities and clinical characteristics exist between women and men with heart failure (HF). In particular, differences in the kinetics of biological circulating biomarkers—a critical component of cardiovascular care—are highly relevant. Most circulating HF biomarkers are assessed daily by clinicians without taking sex into account, despite the multiple gender-related differences observed in plasma concentrations. Even in health, compared to men, women tend to exhibit higher levels of natriuretic peptides and galectin-3 and lower levels of cardiac troponins and the cardiac stress marker, soluble ST2. Many biological factors can provide a reliable explanation for these differences, like body composition, fat distribution, or menopausal status. Notwithstanding, these sex-specific differences in biomarker levels do not reflect different pathobiological mechanisms in HF between women and men, and they do not necessarily imply a need to use different diagnostic cut-off levels in clinical practice. To date, the sex-specific prognostic value of HF biomarkers for risk stratification is an unresolved issue that future research must elucidate. This review outlines current evidence regarding gender-related differences in circulating biomarkers widely used in HF, the pathophysiological mechanisms underlying these differences, and their clinical relevance.

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Biomarkers for the diagnosis and management of heart failure

Heart Failure Reviews ◽

10.1007/s10741-021-10105-w ◽

2021 ◽

Author(s):

Vincenzo Castiglione ◽

Alberto Aimo ◽

Giuseppe Vergaro ◽

Luigi Saccaro ◽

Claudio Passino ◽

...

Keyword(s):

Heart Failure ◽

Risk Stratification ◽

Adverse Outcome ◽

Volume Overload ◽

High Sensitivity ◽

Circulating Biomarkers ◽

Diagnosis And Management ◽

Conflicting Evidence ◽

Galectin 3

AbstractHeart failure (HF) is a significant cause of morbidity and mortality worldwide. Circulating biomarkers reflecting pathophysiological pathways involved in HF development and progression may assist clinicians in early diagnosis and management of HF patients. Natriuretic peptides (NPs) are cardioprotective hormones released by cardiomyocytes in response to pressure or volume overload. The roles of B-type NP (BNP) and N-terminal pro-B-type NP (NT-proBNP) for diagnosis and risk stratification in HF have been extensively demonstrated, and these biomarkers are emerging tools for population screening and as guides to the start of treatment in subclinical HF. On the contrary, conflicting evidence exists on the role of NPs as a guide to HF therapy. Among the other biomarkers, high-sensitivity troponins and soluble suppression of tumorigenesis-2 are the most promising biomarkers for risk stratification, with independent value to NPs. Other biomarkers evaluated as predictors of adverse outcome are galectin-3, growth differentiation factor 15, mid-regional pro-adrenomedullin, and makers of renal dysfunction. Multi-marker scores and genomic, transcriptomic, proteomic, and metabolomic analyses could further refine HF management.

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Mind–Body Interventions in Patients With Heart Failure: State of the Science

Journal of Applied Gerontology ◽

10.1177/07334648211053000 ◽

2021 ◽

pp. 073346482110530

Author(s):

Wanich Suksatan ◽

Thitipong Tankumpuan

Keyword(s):

Heart Failure ◽

Tai Chi ◽

Psychological Symptoms ◽

Behavioral Outcomes ◽

Current Evidence ◽

Future Research ◽

Failure State ◽

Patients With Heart Failure ◽

Mental Wellness ◽

State Of The Science

Complementary and alternative medicine are broadly considered mind–body interventions (MBIs) that support physical and mental wellness in patients with heart failure (HF). The aims of this review were to integrate and summarize current evidence from MBIs in patients with HF and to identify gaps for future research. We used PRISMA guideline and conducted a literature search through six databases. Fifteen publications met the criteria, published between 2013 and 2021. This review stipulated that MBIs included yoga, Tai Chi, meditation, reflexology, massage, relaxation, and breathing interventions. The findings emphasized that MBIs could reduce physical and psychological symptoms and improve health outcomes in patients with HF. MBIs had encouraging results for patients with HF on selected physiological and behavioral outcomes. Despite the early state of the evidence in this field, it seems that MBIs will play an essential role in the future for alleviating the symptoms of patients with HF.

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Biomarkers in patients with myocardial fibrosis

Open Life Sciences ◽

10.1515/biol-2017-0039 ◽

2017 ◽

Vol 12 (1) ◽

pp. 337-344 ◽

Cited By ~ 4

Author(s):

Zhe An ◽

Guang Yang ◽

Haikuo Zheng ◽

Wei Nie ◽

Guohui Liu

Keyword(s):

Heart Failure ◽

Cardiovascular Diseases ◽

Early Detection ◽

Myocardial Fibrosis ◽

Gold Standard ◽

Cardiac Fibrosis ◽

Collagen Deposition ◽

Circulating Biomarkers ◽

Galectin 3 ◽

Noninvasive Assessment

AbstractMyocardial fibrosis is observed in many cardiovascular diseases including hypertension, heart failure and cardiomyopathy. Myocardial fibrosis has been proved to be reversible and treatable only under timely intervention, which makes early detection and assessment of fibrosis crucial. Aside from tissue biopsy as the gold standard for the diagnosis of myocardial fibrosis, circulating biomarkers have been adopted as noninvasive assessment of this lesion. Dysregulated collagen deposition is thought to be the major cause of myocardial fibrosis. Collagens, procollagens, TGF-β, TIMP, galectin-3, and microRNAs are thought to be indicators of myocardial fibrosis. In this review, we summarize the molecules that are frequently used as biomarkers in diagnosis of cardiac fibrosis. Mechanisms of fibrosis that they take part in are also introduced.

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Interaction of Galectin-3 Concentrations with the Treatment Effects of β-Blockers and RAS Blockade in Patients with Systolic Heart Failure: A Derivation-Validation Study from TIME-CHF and GISSI-HF

Clinical Chemistry ◽

10.1373/clinchem.2015.246850 ◽

2016 ◽

Vol 62 (4) ◽

pp. 605-616 ◽

Cited By ~ 6

Author(s):

Sandra Sanders-van Wijk ◽

Serge Masson ◽

Valentina Milani ◽

Peter Rickenbacher ◽

Marco Gorini ◽

...

Keyword(s):

Heart Failure ◽

Failure Time ◽

Plasma Concentrations ◽

Systolic Heart Failure ◽

Renin Angiotensin System ◽

End Points ◽

Reduced Ejection Fraction ◽

Standard Medical Therapy ◽

Galectin 3 ◽

Β Blockers

Abstract BACKGROUND Galectin-3 predicts prognosis in heart failure (HF) and may help to select HF patients in need of intensified therapy. METHODS This retrospective post hoc analysis included 219 patients from the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure (TIME-HF) and 631 patients from Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) with HF who had reduced ejection fraction and available galectin-3 plasma concentrations. The interaction between galectin-3, β-blockers, renin-angiotensin system (RAS) blockade, and spironolactone on outcome was evaluated in TIME-CHF and validated in GISSI-HF. End points were all-cause mortality and the composite of mortality with HF hospitalization or any hospitalization. RESULTS High galectin-3 concentrations were associated with adverse outcome in both cohorts and remained significantly associated with death after multivariate adjustment [hazard ratio 2.42 (95% CI 1.17–5.01), P = 0.02, in TIME-CHF; 1.47 (1.02–2.10), P = 0.04, in GISSI-HF). In TIME-CHF, patients with low galectin-3 plasma concentrations had a better prognosis when β-blockers were up-titrated, whereas patients with high galectin-3 plasma concentrations did not (interaction P < 0.05 for mortality and death with or without hospitalization). Opposite trends were seen for RAS blockade but were not statistically significant. Patients with high galectin-3 plasma concentrations had neutral prognosis when receiving spironolactone, whereas patients with low galectin-3 plasma concentrations had worse prognosis when receiving spironolactone (interaction P < 0.10 for death with or without hospitalization). In the GISSI-HF validation cohort, these interactions were confirmed for β-blockers (P < 0.05 for all end points) and consistent for RAS blockade (P < 0.10 for death with or without hospitalization), but inconsistent for spironolactone. CONCLUSIONS Galectin-3 is a mediocre prognostic marker, and galectin-3 concentrations interact with the treatment effect of β-blockers and possibly RAS blockade in patients with systolic HF.

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Correlation between microRNA expression levels and plasma concentrations of biomarkers of post-transplant complications in heart transplant recipients

Russian Journal of Transplantology and Artificial Organs ◽

10.15825/1995-1191-2020-3-69-78 ◽

2020 ◽

Vol 22 (3) ◽

pp. 69-78

Author(s):

D. A. Velikiy ◽

O. E. Gichkun ◽

A. A. Ulybysheva ◽

S. O. Sharapchenko ◽

A. V. Marchenko ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Plasma Concentrations ◽

Serum Levels ◽

Expression Level ◽

Healthy Individuals ◽

Expression Levels ◽

Post Transplant ◽

Galectin 3 ◽

Transplant Complications

Objective: to analyze the correlation between the expression levels of microRNA-101, microRNA-142, microRNA-27, microRNA-339, and microRNA-424 and the plasma concentrations of biomarkers that are potentially significant for the diagnosis of post-transplant complications in heart recipients. Materials and methods. The study enrolled 72 heart recipients, among whom were 56 men (77.8%). The average age of recipients was 48.6 ± 10.9 (16 to 70) years. There were 38 patients with severe chronic heart failure, among whom were 29 men (76.3%). Patients’ mean age was 48.8 ± 9.9 (26 to 70) years. The control group consisted of 12 healthy individuals who did not differ significantly by sex and age. microRNA expression levels in blood plasma were measured via quantitative polymerase chain reaction. Plasma concentrations of VEGF-A, PLGF, MCP-1, and sCD40L were determined using a multiplex method. ST2 and Galectin-3 concentrations were measured via enzyme-linked immunosorbent assay. Results. Patients with end-stage chronic heart failure were found to have significantly higher expression levels of microRNA-27, microRNA-339 and microRNA-424 in blood plasma compared with the healthy individuals. In potential heart recipients, the expression le vels of microRNA-339 and microRNA-424 correlated with serum galectin-3 concentrations, microRNA-101 expression levels correlated with PLGF-1 concentrations, while microRNA-27 expression levels correlated with plasma MCP-1 concentrations. In the early post-transplant period, the expression levels of microRNA-101, microRNA-339, and microRNA-424 in heart recipients were significantly lower than in patients with severe chronic heart failure. In the early post-transplant period (one year or more after transplantation), microRNA-101 and microRNA-27 expression levels were significantly higher than in heart recipients. A year or more after transplantation, the following correlations were found in heart recipients: microRNA-142 expression level correlated with serum levels of galectin-3 (p = 0.05), microRNA-27 and microRNA-424 expression levels correlated with ST2 concentrations (p = 0.02), microRNA-27 expression level correlated with PLGF-1 concentrations (p = 0.02), while microRNA-101 expression level correlated with serum levels of PAPP-A (p = 0.05). Conclusion. In heart recipients, the expression levels of microRNA-142, microRNA-27, microRNA-424, and microRNA-101 correlate with the concentration levels of biomarkers of fibrosis (Galectin-3), rejection (ST2), neoangiogenesis (PLGF), and tissue destruction (PAPP-A). A comprehensive analysis of pre- and post-translational markers may open up new perspectives in diagnosis, assessment of the risks of post-transplant complications, and in understanding the processes leading to their development.

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Atrial fibrillation in acute heart failure: A position statement from the Acute Cardiovascular Care Association and European Heart Rhythm Association of the European Society of Cardiology

European Heart Journal Acute Cardiovascular Care ◽

10.1177/2048872619894255 ◽

2020 ◽

Vol 9 (4) ◽

pp. 348-357 ◽

Cited By ~ 3

Author(s):

Bulent Gorenek (Chair) ◽

Sigrun Halvorsen ◽

Gulmira Kudaiberdieva ◽

Hector Bueno ◽

Isabelle C Van Gelder ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Acute Heart Failure ◽

Heart Rhythm ◽

Underlying Disease ◽

Position Statement ◽

Current Evidence ◽

Team Approach ◽

European Society Of Cardiology ◽

Cardiovascular Care

Atrial fibrillation and acute heart failure frequently co-exist and can exacerbate each other. Their combination leads to increased morbidity and mortality. However, the prevalence and significance, as well as the treatment, of atrial fibrillation in acute heart failure are not well studied. Management of atrial fibrillation in acute heart failure requires a multidisciplinary team approach. Treatment of underlying disease(s), identification and treatment of potentially correctable causes and precipitating factors and anticoagulation are crucial. In this article, current evidence on atrial fibrillation in the setting of acute heart failure is summarised. The recommendations on management of atrial fibrillation in the prehospital stage, the treatment of reversible causes, when and how to use rate or rhythm control, maintenance of sinus rhythm, catheter ablation and pacing, anticoagulation, as well as measures on prevention of atrial fibrillation are provided.

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Atrial Fibrillation and the Prognostic Performance of Biomarkers in Heart Failure

Clinical Chemistry ◽

10.1093/clinchem/hvaa287 ◽

2020 ◽

Author(s):

Eugene S J Tan ◽

Siew-Pang Chan ◽

Oi-Wah Liew ◽

Jenny P C Chong ◽

Gerard K T Leong ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Risk Stratification ◽

Natriuretic Peptide ◽

Primary Outcome ◽

High Sensitivity ◽

Circulating Biomarkers ◽

Prognostic Performance ◽

All Cause Mortality ◽

Galectin 3

Abstract Background Consideration of circulating biomarkers for risk stratification in heart failure (HF) is recommended, but the influence of atrial fibrillation (AF) on prognostic performance of many markers is unclear. We investigated the influence of AF on the prognostic performance of circulating biomarkers in HF. Methods N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-atrial natriuretic peptide, C-type natriuretic peptide (CNP), NT-proCNP, high-sensitivity troponin-T, high-sensitivity troponin-I, mid-regional-propeptide adrenomedullin, co-peptin, growth differentiation factor-15, soluble Suppressor of Tumorigenicitiy (sST2), galectin-3, and procalcitonin plasma concentrations were measured in a prospective, multicenter study of adults with HF. AF was defined as a previous history of AF, and/or presence of AF/flutter on baseline 12-lead electrocardiogram. The primary outcome was the composite of HF-hospitalization or all-cause mortality at 2 years. Results Among 1099 patients (age 62 ± 12years, 28% female), 261(24%) patients had AF. Above-median concentrations of all biomarkers were independently associated with increased risk of the primary outcome. Significant interactions with AF were detected for galectin-3 and sST2. In considering NT-proBNP for additive risk stratification, sST2 (adjusted hazard ratio [AHR]1.85, 95%confidence interval [C.I.] 1.17-2.91) and galectin-3 (AHR1.85, 95%C.I. 1.09-2.45) were independently associated with increased primary outcome only in the presence of AF. The prognostic performance of sST2 was also stronger in AF for all-cause mortality (AF: AHR2.82, 95%C.I. 1.26-6.21; non-AF: AHR1.78, 95% C.I. 1.14-2.76 without AF), while galectin-3 predicted HF-hospitalization only in AF (AHR1.64, 95%C.I. 1.03-2.62). Conclusions AF modified the prognostic utility of selected guideline-endorsed HF-biomarkers. Application of markers for prognostic purposes in HF requires consideration of the presence or absence of AF. Clinical trial registration ACTRN12610000374066

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Protective role of peroxiredoxin-4 in heart failure

Clinical Science ◽

10.1042/cs20191072 ◽

2020 ◽

Vol 134 (1) ◽

pp. 71-72

Author(s):

Naseer Ahmed ◽

Masooma Naseem ◽

Javeria Farooq

Keyword(s):

Heart Failure ◽

Cardiac Fibroblasts ◽

Protective Role ◽

Oxidative Stress Markers ◽

Stress Markers ◽

Total Antioxidant ◽

Galectin 3 ◽

Consequent Increase ◽

And Oxidative Stress

Abstract Recently, we have read with great interest the article published by Ibarrola et al. (Clin. Sci. (Lond.) (2018) 132, 1471–1485), which used proteomics and immunodetection methods to show that Galectin-3 (Gal-3) down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. Authors concluded that ‘antioxidant activity of Prx-4 had been identified as a protein down-regulated by Gal-3. Moreover, Gal-3 induced a decrease in total antioxidant capacity which resulted in a consequent increase in peroxide levels and oxidative stress markers in cardiac fibroblasts.’ We would like to point out some results stated in the article that need further investigation and more detailed discussion to clarify certain factors involved in the protective role of Prx-4 in heart failure.

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