Why is the Inhibition of the Renin-Angiotensin System Effective for Preventing Cardiac Events in Patients with Coronary Risk Factors or Coronary Artery Disease?

Primary and secondary strategies for preventing cardiac events remain a major challenge in cardiovascular diseases. To date, there is robust evidence that inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists significantly improves the outcome and prevents cardiac events in patients with coronary risk factors. This beneficial effect may be explained both by the reduction of arterial pressure, and by arterial pressure non-dependent effects. This observation raises at least one question: why does inhibition of the reninangiotensin system improve cardiac outcome of patients with risk factors? One answer could be that the renin-angiotensin system is up-regulated in these patients. Then one may ask another question: why and how is the renin-angiotensin system stimulated by markedly different conditions such as hypertension, diabetes, dyslipidemia, cigarette smoking and obesity? In these conditions, is there a common pathway that leads to stimulation of the renin-angiotensin system and explains the beneficial effect of inhibiting this system? On the basis of previous experimental and clinical studies, this review proposes an integrative pathophysiological representation of the path leading from major coronary risk factors to renin-angiotensin system activation and cardiac events mainly due to complications of coronary artery disease. This allows us to understand how the renin-angiotensin system is involved in coronary artery disease, and why inhibition of this system has such beneficial effects in patients with cardiovascular risk factors.