Serum amyloid A in HFpEF and cardiometabolic diseases

Area of Science:

• Cardiology and Metabolic Disease Research
• Inflammation and Immunology

Background:

• Heart failure with preserved ejection fraction (HFpEF) is a prevalent condition, with cardiometabolic HFpEF being a major subtype driven by metabolic dysfunction.
• Systemic inflammation and metabolic disturbances are key contributors to HFpEF pathogenesis, yet upstream inflammatory drivers beyond IL-6 and TNF-α are not fully understood.
• Serum amyloid A (SAA) proteins are emerging as significant players due to their elevated levels in chronic metabolic diseases.

Purpose of the Study:

• To review the clinical associations between elevated SAA levels and cardiometabolic conditions such as obesity, diabetes, MASLD, and hypertension.
• To discuss the potential pathogenetic mechanisms of SAA in cardiometabolic HFpEF, including its role in systemic inflammation, endothelial dysfunction, and myocardial fibrosis.
• To highlight SAA as a potential therapeutic target for cardiometabolic HFpEF and related diseases.

Main Methods:

• Literature review summarizing clinical associations of SAA with cardiometabolic diseases.
• Discussion of preclinical findings on SAA's role in inflammation and metabolic dysfunction.
• Emphasis on the pathogenetic mechanisms linking SAA to HFpEF.

Main Results:

• Elevated SAA levels are clinically associated with obesity, diabetes, MASLD, and hypertension.
• Preclinical studies suggest SAA contributes to systemic inflammation, endothelial dysfunction, and myocardial fibrosis.
• SAA is implicated as a potential driver of cardiometabolic HFpEF.

Conclusions:

• SAA is a significant emerging factor in the pathogenesis of cardiometabolic diseases, including HFpEF.
• Further research into SAA's role can advance the diagnosis and treatment of HFpEF and associated metabolic conditions.
• Targeting SAA may offer novel therapeutic strategies for cardiometabolic HFpEF.