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Related Concept Videos

Pathophysiology of Heart Failure01:17

Pathophysiology of Heart Failure

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Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
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Heart Failure I: Introduction01:27

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Heart failure refers to a clinical syndrome caused by structural or functional cardiac disorders that prevent the heart from pumping an adequate amount of blood to meet the body's metabolic needs. This condition often arises from myocardial infarction or ischemia, leading to decreased cardiac output, reduced tissue perfusion, impaired gas exchange, fluid volume imbalance, and decreased functional ability.Heart failure can result from disruptions in the mechanisms that regulate cardiac output...
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Heart Failure II: Pathophysiology01:29

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Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
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Epigenetic Regulation01:37

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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Cutoff Value of Phase Angle by Bioelectrical Impedance Analysis at Admission as a Prognostic Factor in Patients with Acute Heart Failure
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Causality between heart failure and epigenetic age: a bidirectional Mendelian randomization study.

Fengjun Zhang1, Shanshan Deng2,3, Jing Zhang4

  • 1College of Acupuncture and Massage, Shandong University of Traditional Chinese Medicine, Jinan, China.

ESC Heart Failure
|July 15, 2023
PubMed
Summary

Epigenetic age, a marker of biological aging, causally increases heart failure (HF) risk. This Mendelian randomization study in European populations suggests that advanced epigenetic age predicts higher HF incidence, highlighting aging as a key factor in heart disease.

Keywords:
Bidirectional Mendelian randomization (MR) studyCausalityEpigenetic ageGenome-wide association study (GWAS)Heart failure (HF)

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Area of Science:

  • Cardiovascular Disease Epidemiology
  • Genetics and Aging Research
  • Biomarkers of Aging

Background:

  • Heart failure (HF) is a common cardiovascular disease in older adults with a poor prognosis.
  • Understanding the causal relationship between aging and HF is crucial for developing effective interventions.
  • Epigenetic age serves as a biological marker of aging, distinct from chronological age.

Purpose of the Study:

  • To investigate the causal relationship between epigenetic age and heart failure (HF) using a bidirectional Mendelian randomization (MR) approach.
  • To assess whether genetically predicted epigenetic age influences the risk of developing HF.
  • To determine if HF genetically influences epigenetic age.

Main Methods:

  • A bidirectional Mendelian randomization (MR) analysis was performed using genome-wide association study data for epigenetic age clocks (GrimAge, HorvathAge, HannumAge, PhenoAge) and HF.
  • The inverse-variance weighted (IVW) method was the primary analytical approach.
  • Sensitivity analyses, including MR-Egger, weighted median, heterogeneity, leave-one-out, and pleiotropy analyses, were conducted to ensure robustness.

Main Results:

  • The epigenetic PhenoAge clock showed a statistically significant causal effect, increasing the risk of heart failure (HF).
  • The IVW analysis indicated an odds ratio (OR) of 1.015 (95% CI 1.002-1.028, P=0.028) for PhenoAge predicting HF.
  • Other epigenetic age measures and the reverse causal analysis (HF on epigenetic age) did not yield statistically significant results.

Conclusions:

  • This bidirectional MR study provides evidence for a causal link between genetically predicted epigenetic age and heart failure (HF) in individuals of European descent.
  • The findings suggest that biological aging, as reflected by epigenetic age, is a contributing factor to HF development.
  • Further investigation into epigenetic age across diverse populations and with additional HF genetic data is recommended.