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Updated: Jul 25, 2025
Evaluation of Left Ventricular Structure and Function using 3D Echocardiography
Published on: October 28, 2020
Plasma Proteomic Patterns Show Sex Differences in Early Concentric Left Ventricular Remodeling
Anne-Mar van Ommen1, Ernest Diez Benavente1, N Charlotte Onland-Moret2
1Laboratory of Experimental Cardiology (A.-M.v.O., E.D.B., G.B.V., H.M.d.R.), University Medical Center Utrecht, Utrecht University, the Netherlands.
Insights
Concentric remodeling (cRM) affects about 1 in 4 women and men, increasing heart failure with preserved ejection fraction (HFpEF) and mortality risk. Inflammatory pathways and IFNA5 are key in women, suggesting new therapeutic targets.
Area of Science:
- Cardiology
- Cardiovascular Research
- Proteomics
Background:
- Concentric remodeling (cRM) is a precursor to heart failure with preserved ejection fraction (HFpEF).
- HFpEF is notably prevalent in women.
- Understanding cRM's development and risk factors is crucial for cardiovascular health, especially in women.
Purpose of the Study:
- To investigate the prevalence of cRM in a large outpatient cardiology population.
- To determine the association of cRM with HFpEF development and mortality.
- To identify sex-specific risk factors and molecular pathways involved in cRM.
Main Methods:
- Analysis of 60,593 patients from outpatient cardiology clinics for cRM, HFpEF, and mortality.
- Sex-stratified analysis of risk factors for relative wall thickness.
- Proteomic profiling of 4,534 plasma proteins in a 557-patient substudy to identify pathways involved in cRM.
Main Results:
- cRM was found in 23.5% of women and 27.6% of men, linked to increased HFpEF risk (HR 2.15) and mortality (HR 1.09).
- Risk factors for relative wall thickness were stronger in women.
- Elevated IFNA5 levels and activated inflammatory pathways were observed in women with cRM.
Conclusions:
- cRM is a common condition associated with adverse cardiovascular outcomes in both sexes.
- Sex differences in risk factors and inflammatory pathway activation, particularly involving IFNA5 in women, may explain HFpEF's female predominance.
- These findings offer potential for novel therapeutic strategies targeting cRM and HFpEF prevention and treatment.
Background:
Concentric remodeling (cRM) can precede heart failure with preserved ejection fraction (HFpEF), a condition prevalent in women.
Methods:
Patients (n=60 593, 54.2% women) visiting outpatient clinics of Cardiology Centers of the Netherlands were analyzed for cRM, HFpEF development, and mortality risk. We studied risk factors for relative wall thickness both sex-stratified and in women and men combined. Biomarker profiling was performed (4534 plasma proteins) in a substudy involving 557 patients (65.4% women) to identify pathways involved in cRM.
Results:
cRM was present in 23.5% of women and 27.6% of men and associated with developing HFpEF (HR, 2.15 [95% CI, 1.51-2.99]) and mortality risk (HR, 1.09 [95% CI, 1.00-1.19]) in both sexes. Age, heart rate, and hypertension were statistically significantly stronger risk factors for relative wall thickness in women than men. Higher circulating levels of IFNA5 (interferon alpha-5) were associated with higher relative wall thickness in women only. Pathway analysis revealed differential pathway activation by sex and increased expression of inflammatory pathways in women.
Conclusions:
cRM is prevalent in approximately 1 in 4 women and men visiting outpatient cardiology clinics and associated with HFpEF development and mortality risk in both sexes. Known risk factors for cRM were more strongly associated in women than men. Proteomic analysis revealed inflammatory pathway activation in women, with a central role for IFNA5. Differential biologic pathway activation by sex in cRM may contribute to the female predominance of HFpEF and holds promise for identification of new therapeutic avenues for prevention and treatment of HFpEF.
Registration:
URL: https://www.
Clinicaltrials:
gov; Unique identifier: NCT001747.
