Abstract
Introduction:Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are widely used in congestive heart failure and chronic kidney disease, but up to 40% of patients will experience aldosterone breakthrough, with aldosterone levels rising above pre-treatment levels after 6–12 months of renin-angiotensin-aldosterone system blockade. Aldosterone breakthrough has been associated with worsening congestive heart failure and chronic kidney disease, yet the pathophysiology remains unclear. Breakthrough has not been associated with elevated peripheral blood pressure, but no studies have assessed its effect on central blood pressure.Methods:Nineteen subjects with well-controlled peripheral blood pressure on stable doses of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker had aldosterone levels checked and central blood pressure parameters measured using the SphygmoCor system. The central blood pressure parameters of subjects with or without breakthrough, defined as serum aldosterone >15 ng/dl, were compared.Results:Of the 19 subjects, six had breakthrough with a mean aldosterone level of 33.8 ng/dl, and 13 were without breakthrough with a mean level of 7.1 ng/dl. There was no significant difference between the two groups in any central blood pressure parameter.Conclusions:We found no correlation between aldosterone breakthrough and central blood pressure. The clinical impact of aldosterone breakthrough likely depends on its non-genomic, pro-fibrotic, pro-inflammatory effects rather than its regulation of extracellular volume.
Highlights
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are widely used in congestive heart failure and chronic kidney disease, but up to 40% of patients will experience aldosterone breakthrough, with aldosterone levels rising above pre-treatment levels after 6–12 months of renin-angiotensin-aldosterone system blockade
Of the 19 subjects evaluated, six were found to have aldosterone levels >15 ng/dl, classifying them as having aldosterone breakthrough as per our pre-defined criteria. Between those with and without aldosterone breakthrough, there was no difference in serum potassium levels but a significant difference was found in terms of the severity of chronic kidney disease (CKD)
Of quartiles for serum aldosterone levels 0–6 ng/dl (n=5), 6–9 ng/dl (n=5), 9–20 ng/dl (n=5), and >20 ng/dl (n=4), created four groups each with statistically significant differences in mean serum aldosterone level (Table 3). This grouping by quartiles did not reveal any statistically significant differences between the first and fourth quartiles nor any statistically significant trends in the overall dataset. In this cross-sectional study of 19 patients with CKD on long-standing Angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) therapy with well-controlled peripheral blood pressure (PBP), we found no evidence that aldosterone breakthrough, manifest in one-third of the study population, was associated with elevations in any Central blood pressure (CBP) parameters
Summary
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are widely used in congestive heart failure and chronic kidney disease, but up to 40% of patients will experience aldosterone breakthrough, with aldosterone levels rising above pre-treatment levels after 6–12 months of renin-angiotensin-aldosterone system blockade. Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used in patients with congestive heart failure (CHF) and chronic kidney disease (CKD) due to their impact on long-term outcomes, including overall mortality,[1,2] but approximately 30–50% of patients on angiotensin-converting enzyme (ACE) inhibition experience aldosterone breakthrough,[3] a phenomenon where aldosterone levels increase up to or above pre-treatment levels after 6–12 months of ACE inhibition.[4] Aldosterone breakthrough is not merely a function of inadequate ACE inhibition,[5] but the details of its underlying mechanism remain unknown.
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