Editorials
Renin Activity as a Key Predictor of Major Adverse Cardiac Events
2019 Volume 83 Issue 6 Pages 1204-1205
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2019 Volume 83 Issue 6 Pages 1204-1205
In recent decades there has been substantial improvement in the prognosis of acute myocardial infarction (AMI), mainly because of advances in the rapid restoration of coronary blood flow by percutaneous coronary intervention, as well as in secondary prevention therapies.1 However, patients with clinical complications such as cardiogenic shock, heart failure, and chronic kidney disease at the onset of AMI still have a poor prognosis.
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The renin-angiotensin system (RAS) is a complex system that regulates systemic functions through body salt and blood volume control.2 The RAS also exerts proliferative action at the vascular level, leading to angiogenesis and the progression of atherosclerosis3,4 thereby contributing to the development of ischemic heart disease.5 Furthermore, RAS activation is a key mechanism in cardiac remodeling in patients with AMI and of disease progression in those with ischemic and non-ischemic heart failure;5 chronic overactivation of the RAS is associated with cardiovascular adverse events.6 The occurrence of these processes in AMI is further supported by the fact that angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers have beneficial effects in patients with hypertension, myocardial infarction, and heart failure.7–9
In the acute phase of hospital admission for AMI, activation of both the sympathetic nervous system and the RAS system has been observed; these activations subside within the first 72 h in patients without left ventricular dysfunction and overt heart failure.10 In contrast, persistent RAS activation at the time of hospital discharge is an independent predictor of cardiovascular disease death in postinfarction patients.11 However, the meaning of an elevation in plasma renin activity (PRA) on admission remains unascertained in the setting of AMI.
In this issue of the Journal, Kamon et al12 report that elevated PRA on admission was independently associated with major adverse cardiac events (MACE, defined here as cardiovascular death and hospitalization for heart failure) in 878 AMI patients who underwent emergency coronary angiography. These findings were consistent, regardless of previous medication with RAS inhibitors or β-blockers before the onset of AMI. The results were also consistent when the analysis included patients who were treated with diuretics in the acute phase.
How do we interpret these findings of Kamon et al? Did PRA increase as a result of acute reduction of renal blood flow caused by AMI and the subsequent decrease in cardiac output? Did the high PRA reflect the activation of neurohormonal factors and increased sympathetic tone after AMI? Did the high PRA merely reflect decreased fluid volume because of fasting? Or did the high PRA reflect the presence of comorbidity such as heart failure or kidney dysfunction in AMI patients? (Figure) As PRA is reportedly not correlated with plasma norepinephrine level or with atrial natriuretic peptide or B-type natriuretic peptide (BNP) level in patients with AMI and heart failure,13,14 PRA is unlikely to be a mere reflection of blood volume changes or sympathetic activity. With our current level of knowledge, we can say only that PRA is a neurohormonal biomarker for cardiovascular disease, but its role as a biomarker differs from that of BNP or N-terminal proBNP in the acute phase of AMI.
Possible mechanisms of elevation in plasma renin activity in patients with acute myocardial infarction. High plasma renin activity on admission was an independent predictor for poor prognosis. ACE, angiotensin-converting enzyme, ARB, angiotensin receptor blocker.
Kamon et al previously demonstrated that high PRA is a strong and independent prognostic indicator in patients with acute decompensated heart failure treated with RAS inhibitors.15 In the present study, they have extended this statement to include patients in the acute phase of AMI. In accordance with their findings, measuring PRA could constitute a new application of a classical method of risk stratification in the acute phase of AMI. The report by Kamon et al is of interest for the following reasons. First, high PRA at admission after AMI was associated with a poor prognosis independent of BNP level or ejection fraction. Therefore, measuring PRA on admission should facilitate improved selection of high-risk patients in combination with measurement of BNP or ejection fraction in AMI patients. Second, the findings will be useful from a clinical perspective, because PRA is a consistent prognostic indicator regardless of treatment with RAS inhibitors, β-blockers, or diuretics – a common scenario in patients with hypertension.
When interpreting the results, we need to keep several limitations in mind. Most importantly, this was a retrospective, single-center study, so generalization to other populations needs to be validated. Second, whether high PRA in AMI really reflects activation of the RAS remains unknown. Measuring angiotensin II and aldosterone together with PRA would provide deeper insights. Third, whether high PRA on admission is associated with chronic RAS activation must still be determined.
In summary, the study by Kamon and colleagues leads us to rediscover the importance of measuring PRA in the acute phase of AMI. High PRA on admission may help us to select a subset of patients at increased risk of cardiovascular death or hospitalization for heart failure in the future.
T. Kondo and Y. Nakano belong to a department endowed by Actelion Pharmaceuticals Japan, Ltd.
