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Circulating branched-chain amino acids and incident heart failure in type 2 diabetes: The Hong Kong Diabetes Register

Lim LL, Lau ESH, Fung E, Lee HM, Ma RCW, Tam CHT, et al.

Diabetes Metab Res Rev, 2020 03;36(3):e3253.
PMID: 31957226 DOI: 10.1002/dmrr.3253

AIM: Levels of branched-chain amino acids (BCAAs, namely, isoleucine, leucine, and valine) are modulated by dietary intake and metabolic/genetic factors. BCAAs are associated with insulin resistance and increased risk of type 2 diabetes (T2D). Although insulin resistance predicts heart failure (HF), the relationship between BCAAs and HF in T2D remains unknown.
METHODS: In this prospective observational study, we measured BCAAs in fasting serum samples collected at inception from 2139 T2D patients free of cardiovascular-renal diseases. The study outcome was the first hospitalization for HF.
RESULTS: During 29 103 person-years of follow-up, 115 primary events occurred (age: 54.8 ± 11.2 years, 48.2% men, median [interquartile range] diabetes duration: 5 years [1-10]). Patients with incident HF had 5.6% higher serum BCAAs than those without HF (median 639.3 [561.3-756.3] vs 605.2 [524.8-708.7] μmol/L; P = .01). Serum BCAAs had a positive linear association with incident HF (per-SD increase in logarithmically transformed BCAAs: hazard ratio [HR] 1.22 [95% CI 1.07-1.39]), adjusting for age, sex, and diabetes duration. The HR remained significant after sequential adjustment of risk factors including incident coronary heart disease (1.24, 1.09-1.41); blood pressure, low-density lipoprotein cholesterol, and baseline use of related medications (1.31, 1.14-1.50); HbA1c , waist circumference, triglyceride, and baseline use of related medications (1.28, 1.11-1.48); albuminuria and estimated glomerular filtration rate (1.28, 1.11-1.48). The competing risk of death analyses showed similar results.
CONCLUSIONS: Circulating levels of BCAAs are independently associated with incident HF in patients with T2D. Prospective cohort analysis and randomized trials are needed to evaluate the long-term safety and efficacy of using different interventions to optimize BCAAs levels in these patients.

Matched MeSH terms: Heart Failure/blood
Galectin-3 is associated with severe heart failure and death: A hospital-based study in Chinese patients

Wang N, Dang M, Zhang W, Lei Y, Liu Z

Scand J Immunol, 2020 May;91(5):e12826.
PMID: 31514240 DOI: 10.1111/sji.12826

Heart failure (HF) is a serious disease syndrome characterized by elevated pro-inflammatory cytokines and inflammatory mediators presume to have significant contribution on disease progression. Galectins are carbohydrate-binding proteins responsible of various physiological functions. Role of galectins in heart failure has been ill-defined. In the present case-controls study, 136 patients clinically diagnosed with heart failure and 125 healthy Chinese controls were recruited. Levels of galectins (Gal-1, 3 and 9) and cytokines (IFN-γ, IL-17A, IL-4 and TGF-β) were quantified by ELISA. Increased levels of galectin-1 and 3 was observed in HF patients and associated with clinical severity. In addition, pro-inflammatory cytokines such as IFN-γ and IL-17A were increased in patients whereas, anti-inflammatory TGFβ was decreased. Galectin-3 was positively correlated with IFN-γ, IL-17A and inversely with TGF-β. Furthermore, ROC curve analysis suggested galectin-3 as a promising biomarker for diagnosis and HF and clinical severity. Interestingly, a two-year follow-up indicated significant association of elevated galectin-3 with mortality due to HF. In conclusion, galectin-3 associated with HF and clinical manifestations possibly by inducing pro-inflammatory cytokines and could be a possible biomarker of HF and severe clinical conditions.

Matched MeSH terms: Heart Failure/blood*
Fulltext Interleukin 6 and Development of Heart Failure With Preserved Ejection Fraction in the General Population

Chia YC, Kieneker LM, van Hassel G, Binnenmars SH, Nolte IM, van Zanden JJ, et al.

J Am Heart Assoc, 2021 06;10(11):e018549.
PMID: 33998283 DOI: 10.1161/JAHA.120.018549

Background The cause of heart failure with preserved ejection fraction (HFpEF) is poorly understood, and specific therapies are lacking. Previous studies suggested that inflammation plays a role in the development of HFpEF. Herein, we aimed to investigate in community-dwelling individuals whether a higher plasma interleukin 6 (IL-6) level is associated with an increased risk of developing new-onset heart failure (HF) over time, and specifically HFpEF. Methods and Results We performed a case-cohort study based on the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study, a prospective general population-based cohort study. We included 961 participants, comprising 200 participants who developed HF and a random group of 761 controls. HF with reduced ejection fraction or HFpEF was defined on the basis of the left ventricular ejection fraction of ≤40% or >40%, respectively. In Cox proportional hazard regression analyses, IL-6 levels were statistically significantly associated with the development of HF (hazard ratio [HR], 1.28; 95% CI, 1.02-1.61; P=0.03) after adjustment for key risk factors. Specifically, IL-6 levels were significantly associated with the development of HFpEF (HR, 1.59; 95% CI, 1.16-2.19; P=0.004), whereas the association with HF with reduced ejection fraction was nonsignificant (HR, 1.05; 95% CI, 0.75-1.47; P=0.77). In sensitivity analyses, defining HFpEF as left ventricular ejection fraction ≥50%, IL-6 levels were also significantly associated with the development of HFpEF (HR, 1.47; 95% CI, 1.04-2.06; P=0.03) after adjustment for key risk factors. Conclusions IL-6 is associated with new-onset HFpEF in community-dwelling individuals, independent of potential confounders. Our findings warrant further research to investigate whether IL-6 might be a novel treatment target to prevent HFpEF.

Matched MeSH terms: Heart Failure/blood*
Effects of Statin Treatment on Inflammation and Cardiac Function in Heart Failure: An Adjusted Indirect Comparison Meta-Analysis of Randomized Trials

Bonsu KO, Reidpath DD, Kadirvelu A

Cardiovasc Ther, 2015 Dec;33(6):338-46.
PMID: 26280110 DOI: 10.1111/1755-5922.12150

Statins are known to prevent heart failure (HF). However, it is unclear whether statins as class or type (lipophilic or hydrophilic) improve outcomes of established HF.

Matched MeSH terms: Heart Failure/blood
Fulltext Cognitive impairment in Asian patients with heart failure: prevalence, biomarkers, clinical correlates, and outcomes

Dong Y, Teo SY, Kang K, Tan M, Ling LH, Yeo PSD, et al.

Eur J Heart Fail, 2019 05;21(5):688-690.
PMID: 30938010 DOI: 10.1002/ejhf.1442
Matched MeSH terms: Heart Failure/blood