SEX DIFFERENCES IN THE ADMINISTRATION-TIME-DEPENDENT EFFECTS OF LOW-DOSE ASPIRIN ON AMBULATORY BLOOD PRESSURE IN HYPERTENSIVE SUBJECTS

Abstract

Previous studies have revealed sex differences in blood pressure (BP) regulation, pathophysiology of hypertension, and treatment responses to medication. On the other hand, low-dose aspirin has been shown to reduce BP when administered at bedtime, as opposed to upon awakening, in hypertensive subjects and pregnant women at risk for preeclampsia. The purpose of this research was to investigate the potential sex differences in the administration-time-dependent influence of aspirin on BP. We studied 130 men and 186 women with untreated mild hypertension, 44.1 ± 13.2 yrs of age, randomized to receive aspirin (100 mg/day) either on awakening or at bedtime daily for three months. BP was measured for 48 h before and after treatment. With ASA on awakening, ambulatory BP was unchanged in men and slightly but significantly elevated in women (1.7/1.4 mmHg in the 48 h SBP/DBP means, respectively; p < 0.023). BP was significantly reduced after aspirin at bedtime and to a larger extent in women (−8.0/−5.6 mmHg in SBP/DBP) than men (5.5/3.4 mmHg, respectively; p < 0.009 between men and women). Factors influencing a stronger response of BP to aspirin at bedtime included female sex, elevated fasting glucose, and high glomerular filtration rate. This study corroborates the significant administration-time-dependent effect of low-dose aspirin on ambulatory BP in subjects with untreated mild hypertension, while documenting significant sex differences in the BP response to aspirin. Accordingly, results indicate that bedtime is the optimal time for aspirin ingestion in both men and women. This timed administration of low-dose aspirin could provide a cost-effective valuable approach for BP control and potential added cardiovascular protection, especially in hypertensive women. (Author correspondence: [email protected])

Keywords:

• Aspirin
• Hypertension
• Sex differences
• Ambulatory blood pressure monitoring
• Chronotherapy
• Circadian

ACKNOWLEDGMENTS

This work is dedicated to the loving memory of Dr. Manuel Iglesias and Dr. Eugene Kanabrocki. Their frienship and research collaboration have been a constant light guiding our lives.

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.