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Factors affecting circadian variability
1LSUMC School of Medicine, New Orleans, Louisiana, USA. tgiles@lsumc.edu
Insights
Cardiovascular events like heart attack and stroke often occur in the morning. Long-acting angiotensin II receptor antagonists may offer sustained 24-hour cardiovascular protection by inhibiting the renin-angiotensin system.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Chronobiology
Background:
- Cardiovascular events, including myocardial infarction, ischemia, sudden cardiac death, and stroke, exhibit a diurnal pattern, with increased frequency in the morning.
- Physiological functions such as blood pressure, heart rate, sympathetic activity, vascular tone, platelet aggregation, and coagulation show daily variations, contributing to morning cardiovascular risk.
- The renin-angiotensin system (RAS), mediated by angiotensin II (Ang II), plays a crucial role in blood pressure regulation, fluid balance, and target-organ damage.
Purpose of the Study:
- To investigate the role of the renin-angiotensin system (RAS) in the diurnal variation of cardiovascular events.
- To evaluate the potential cardiovascular benefits of inhibiting the RAS, particularly with Ang II receptor antagonists.
- To assess the efficacy of long-acting Ang II receptor antagonists in providing sustained 24-hour cardiovascular protection.
Main Methods:
- Review of existing literature on diurnal patterns of cardiovascular events and physiological parameters.
- Analysis of the mechanism of action of angiotensin II (Ang II) and the renin-angiotensin system (RAS).
- Examination of studies on Ang II receptor antagonists, focusing on their selectivity, duration of action, and impact on blood pressure and cardiovascular outcomes.
Main Results:
- Cardiovascular events demonstrate a significant morning peak, linked to diurnal variations in hemodynamic and hemostatic factors.
- Inhibition of the RAS via Ang II receptor antagonists offers a therapeutic strategy for hypertension and target-organ damage.
- Long-acting Ang II receptor antagonists provide smooth, sustained antihypertensive effects, suggesting consistent 24-hour cardiovascular risk reduction.
Conclusions:
- The diurnal variation in cardiovascular events is influenced by physiological changes throughout the day.
- Angiotensin II receptor antagonists represent a key therapeutic approach for managing hypertension and associated cardiovascular risks.
- Sustained inhibition of the RAS with long-acting agents may be crucial for achieving comprehensive 24-hour cardiovascular protection.
Abstract:
Several unfavorable cardiovascular events show a well-defined pattern in their occurrence throughout the day. Myocardial infarction and ischemia, sudden cardiac death and stroke occur with greater frequency in the morning hours after awakening. Multiple biologic functions such as blood pressure, heart rate, sympathetic neurotransmission, vascular tone, platelet aggregability, and coagulation parameters also show a diurnal variation and appear to contribute to adverse cardiac outcomes. Recent studies have emphasized the importance of 24 h control in decreasing cardiovascular risk. The renin-angiotensin system (RAS), through the important effector peptide, angiotensin II (Ang II), has potent effects on blood pressure, salt and water homeostasis, and target-organ damage. Inhibiting the RAS consequently becomes an important therapeutic avenue for treating hypertension and target-organ damage. Ang II receptor antagonists selectively compete with the binding of Ang II to the Ang II type 1 receptor and, by inhibiting the multiple activities mediated by Ang II at this receptor, may confer cardiovascular benefits additional to that of blood pressure control. Ang II receptor antagonists with an intrinsically long duration of action that produce smooth, sustained antihypertensive activity over the dosing period provide a similar 24 h benefit of Ang II inhibition.