Lower serum chloride in dogs with heart disease was associated with higher RAAS metabolites, with each 5 mmol/L decrease yielding 32–45% increases in angiotensin metabolites (P≤0.02).
Observational (n=147)
Does lower serum chloride concentration increase systemic RAAS activity in dogs with congestive heart failure?
Lower serum chloride concentrations are independently associated with enhanced systemic RAAS activation in dogs with naturally occurring heart disease.
Effect estimate: 32-45% increase in angiotensin metabolites and 39% increase in aldosterone per 5 mmol/L decrease
p-value: p=≤0.02
Chloride is a key determinant of macula densa signaling and renin release, but its relationship with systemic renin–angiotensin–aldosterone system (RAAS) activity in naturally occurring heart failure is incompletely defined. We evaluated associations between serum chloride concentration and circulating RAAS metabolites in 147 dogs (20 healthy, 39 preclinical heart disease, 88 congestive heart failure CHF). Circulating angiotensin metabolites, aldosterone, and ACE and ACE2 activity were quantified by liquid chromatography–mass spectrometry. Associations between serum chloride and RAAS components were assessed using HC3 robust multivariable linear regression adjusted for sex, ACE inhibitor use, and serum bicarbonate. Dogs with CHF had higher circulating RAAS metabolites than healthy and preclinical dogs. Serum chloride was inversely correlated with multiple RAAS metabolites, including Ang I (rₛ = −0.515) and Ang 1–7 (rₛ = −0.546; both P < 0.0001). Lower serum chloride was independently associated with higher concentrations of angiotensin peptides (Ang I, II, III, IV, and Ang 1–7) and aldosterone, with each 5 mmol/L decrease corresponding to 32–45% increases in angiotensin metabolites and a 39% increase in aldosterone (all adjusted P ≤ 0.02). Hypochloremia (<100 mEq/L) identified a distinct RAAS phenotype characterized by higher downstream angiotensin metabolites, including Ang II, III, and IV (all adjusted P ≤ 0.03). Chloride was not associated with ACE or ACE2 activity. Serum chloride is independently associated with systemic RAAS activation in dogs with heart disease, supporting an association between lower serum chloride concentrations and enhanced upstream of RAAS pathway flux.
Adin et al. (Sun,) conducted a observational in Congestive heart failure (n=147). Lower serum chloride concentration vs. Higher serum chloride concentration was evaluated on Circulating RAAS metabolites (angiotensin peptides and aldosterone) (32-45% increase in angiotensin metabolites and 39% increase in aldosterone per 5 mmol/L decrease, p=≤0.02). Lower serum chloride in dogs with heart disease was associated with higher RAAS metabolites, with each 5 mmol/L decrease yielding 32–45% increases in angiotensin metabolites (P≤0.02).