Plasma Amyloid-β in Relation to Cardiac Function and Risk of Heart Failure in General Population

Zhu, Fei; Wolters, Frank J.; Yaqub, Amber; Leening, Maarten J.G.; Ghanbari, Mohsen; Boersma, Eric; Ikram, M. Arfan; Kavousi, Maryam

doi:10.1016/j.jchf.2022.09.006

Cited by 14 publications

(12 citation statements)

References 39 publications

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“…Factors such as increased adiposity, myocardial lipid accumulation and cardiomyocyte mitochondrial dysfunction have all been implicated in the development of diastolic dysfunction in obesity. Data generated in the present study indicates that Aβ 42 is a unifying link between all of these factors and is supported by a recent study, published while the current manuscript was in preparation, proving the association between circulating Aβ and heart failure in the general population 54 . Our data advances our understanding of the impact of obesity on the heart and identify an actionable target for therapeutic intervention in obesity-induced heart failure.…”

Section: Discussionsupporting

confidence: 88%

“…While preparing this manuscript, it was reported that plasma concentrations of both Aβ 42 and Aβ 40 are associated with heart failure in the general population, particularly in males 54 . While the association was stronger for Aβ 40 , this could be due to the greater propensity for Aβ 42 to leave the circulation and accumulate in vascular beds and in tissues 62 .…”

Section: Discussionmentioning

confidence: 99%

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Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in male mice with obesity

Hall,

Czeczor,

Connor

et al. 2024

Nat Commun

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There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer’s disease. The role of amyloid beta 42 (Aβ42) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aβ42, which is increased from adipose tissue of male mice with obesity and is associated with higher plasma Aβ42. Increasing circulating Aβ42 levels in male mice without obesity has no effect on systemic glucose homeostasis but has obesity-like effects on the heart, including reduced cardiac glucose clearance and impaired cardiac function. The closely related Aβ40 isoform does not have these same effects on the heart. Administration of an Aβ-neutralising antibody prevents obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Aβ-neutralising antibody administration in established obesity prevents further deterioration of cardiac function. Multi-contrast transcriptomic analyses reveal that Aβ42 impacts pathways of mitochondrial metabolism and exposure of cardiomyocytes to Aβ42 inhibits mitochondrial complex I. These data reveal a role for systemic Aβ42 in the development of cardiac disease in obesity and suggest that therapeutics designed for Alzheimer’s disease could be effective in combating obesity-induced heart failure.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in male mice with obesity

Hall,

Czeczor,

Connor

et al. 2024

Nat Commun

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“…In patients with AD, Aβ40 and Aβ42 could be identified within cardiomyocytes and the cardiac interstitium 18 . In the general population circulating Aβ40 has been associated with elevated levels of NT-proBNP and Troponin-T as well as worse cardiac function and higher risk of new-onset HF 46, 47 . In HF, Aβ40 was not associated with cognitive decline but with increased mortality 48 .…”

Section: Discussionmentioning

confidence: 99%

Neurodegeneration is strongly linked to heart failure severity and outcomes: framing the cardiocerebral syndrome

Wurm,

Prausmüller,

Ponleitner

et al. 2023

Preprint

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Background and Objectives: Cognitive impairment is prevalent in patients with heart failure with reduced ejection fraction (HFrEF), affecting self-care and outcomes. Novel blood-based biomarkers have emerged as potential diagnostic tools for neurodegeneration. This study aimed to assess neurodegeneration in HFrEF by measuring neurofilament light chain (NfL), total tau (t-tau), amyloid-beta 42 (Aβ42), and 40 (Aβ40) in a large, well-characterised cohort. Methods: The study included 470 HFrEF patients from a biobank-linked prospective registry at the Medical University of Vienna. High-sensitivity single-molecule assays were used for measurement. Unplanned hospitalisations and all-cause death were recorded as outcome parameters. Results: All markers, but not the Aβ42/Aβ40 ratio, correlated with heart failure (HF) severity, i.e. NTproBNP and NYHA class, comorbidity burden and were significantly associated with all-cause death and HF-hospitalisations [crude HR for 1-log unit increase (95%CI): 4.44 (3.02-6.53), 5.04 (2.97-8-58), 3.90 (2.27-6.72) and 5.14 (2.84-9.32) for all-cause death and 2.48 (1.60-3.85), 3.44 (1.95-6.04), 3.13 (1.84-5.34) and 3.48 (1.93-6.27) for HHF, p<0.001 for all]. These markers remained significant after adjustment in multivariate models including NT-proBNP. NfL and t-tau showed the highest prognostic ability in the receiver operating characteristic analysis [AUC: 0.72, 0.68, 0.66, 0.67 for NfL, t-tau, Aβ40 and Aβ42, respectively]. The performance of NfL was comparable to that of NT-proBNP [C-index: 0.70 vs 0.72, p=0.225]. Conclusions: Neurodegeneration is directly interwoven with the progression of HF. Biomarkers, particularly NfL, may help identify patients profiting from detailed neurological workups. Further research is necessary to test if early diagnosis or optimised HFrEF treatment can preserve cognitive function.

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“…Early menarche, occurring before the age of 12, is linked to an elevated risk of CVD, metabolic syndrome, and diabetes, whereas a delay in onset translates to a substantial reduction in mortality and lower rates of ischemic heart disease and stroke. 13,14 Similarly, early menopause, especially before the age of 45, stands as a notable risk factor independently associated with a higher incidence of coronary heart disease, stroke, and heart failure. 13,14 The mechanism driving this association Figure 1 Key female-specific risk factors for cardiovascular disease across a woman's reproductive lifespan.…”

Section: Female-specific Risk Factorsmentioning

confidence: 99%

Sex Disparities in Cardiovascular Disease

Mahowald,

Esmail,

Ezzeddine

et al. 2024

Methodist DeBakey Cardiovascular Journal

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Cardiovascular disease is the leading cause of death in women. It remains underdiagnosed, undertreated, and portends worse outcomes in women than men. Disparities exist in every stage of science, from bench research to the editorial board of major journals and in every cardiovascular subspecialty. This review summarizes differences in cardiovascular risk factors and disparities in management and outcomes of ischemic heart disease, heart failure, aortic stenosis, and atrial fibrillation. It also provides an overview of female representation as participants and leaders of clinical trials, editorial boards, and academic institutions. Strategies to overcome these disparities are proposed with examples of successful programs.

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Plasma Amyloid-β in Relation to Cardiac Function and Risk of Heart Failure in General Population

Cited by 14 publications

References 39 publications

Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in male mice with obesity

Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in male mice with obesity

Neurodegeneration is strongly linked to heart failure severity and outcomes: framing the cardiocerebral syndrome

Sex Disparities in Cardiovascular Disease

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