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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*
Fulltext Recurrent depression predicts high leptin concentrations in patients with coronary artery disease over an 18-months follow-up period: Findings from the prospective multicenter randomized controlled SPIRR-CAD Trial

Ladwig KH, Marten-Mittag B, Olliges E, Johar H, Atasoy S, Holdenrieder S, et al.

J Affect Disord, 2025 Jan 15;369:174-181.
PMID: 39321975 DOI: 10.1016/j.jad.2024.09.146

BACKGROUND: Leptin, an adipokine suspected to play a role in coronary artery disease (CAD), may also be associated with deteriorated mental health. We investigated the prospective impact of recurrent depressed mood (RDM) on heightened plasma leptin levels in CAD patients.
METHODS: Derived from the randomized SPIRR-CAD trial, plasma leptin were measured by the Human Leptin DuoSet ELISA at baseline in 539 patients (including 115 (21.3 %) women and 424 (78.7 %) men) and in 373 participants after 18-months follow up (T3). RDM was based on the clinical course from baseline to follow-up assessed by the Hamilton Depression Rating Scale (HAMD). Multivariate binary logistic regression models identified predictors for heightened leptin at T3.
RESULTS: At baseline, highest leptin level (3rd tertile) was associated with type 2 diabetes (p = 0.009), heart failure symptoms (NYHA III) (p

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