Abstract Body: Introduction: Aldosterone has been primarily recognized for its role in sodium retention and blood pressure regulation. Even so, there is now evidence that aldosterone influences the heart and many metabolic functions. This leads to inflammation of the blood vessels, scarring of the heart muscle, and brain involvement in controlling blood pressure. To better understand aldosterone signaling, we did a systematic review investigating its effects beyond the kidney, filling a major gap in our understanding.
Hypothesis: High aldosterone levels found in patients with heart failure with preserved ejection fraction (HFpEF) will independently connect to worse cardiovascular outcomes (heart failure hospitalization, cardiovascular death and stroke) beyond known risk factors such as hypertension.
Methods: All potential studies were identified and screened using the PRISMA method. All 18 studies, including 5 RCTs and 13 observational studies, were included. Outcomes related to the heart, nervous system, and metabolism, among other things, were reviewed. In RCTs, we evaluated study quality using the Cochrane Risk of Bias tool, and the Newcastle-Ottawa Scale was used for observational studies.
Results: Many studies in this area reveal that aldosterone seems to promote disease and dysfunction in the heart, arteries, and brain, aside from what it does in the kidneys. These RCTs found that using mineralocorticoid receptor antagonists reduced heart fibrosis and improved blood vessel functioning, despite only small reductions in blood pressure. Observational studies suggested that higher aldosterone levels in older people may raise the risk of left ventricular hypertrophy, stiffened arteries, and brain decline. Most RCTs were of low bias, and while some diversity was seen among observational studies, the findings consistently demonstrated an association.
Conclusions: The review, which is the first to thoroughly study aldosterone outside the kidney, proves that aldosterone contributes to damage in other organs. Our analysis shows that therapies that influence aldosterone's whole-body effects could be useful. Besides lowering blood pressure, discouraging aldosterone activity may also help protect the heart, motivating the search for new drugs that can protect against the effects of aldosterone other than on the kidneys.