Sex differences in estimates of cardiac autonomic function using time domain based method of heart rate variability: effects of oral capsaicin

Heart rate variability (HRV) estimates autonomic nervous system (ANS) influence on the heart and is sex-specific. Sensory afferents exhibit sex-specificity; although, there is a paucity of data on the potential effects of Capsaicin, an agonist for transient receptor potential vanilloid channel-1 (TRPV1 ), on cardiac ANS activity and if the effect is sex-dependent. Given the predictive nature of HRV on risk of developing hypertension, understanding the sex differences in factors governing HRV is paramount. Purpose: Therefore, this study sought to determine the sex-specificity in the effect of capsaicin on cardiac autonomic function estimated through HRV. It was hypothesized that females would have lower HRV than the age-matched males and that capsaicin could attenuate these sex differences. Methods: HRV was measured in 38 young males (M: n=25) and females (F: n=13), in a blinded crossover design, after acute ingestion of placebo or capsaicin capsules. Resting measurements of HR, RR interval, root mean square of successive differences (RMSSD), natural log-transformed RMSSD (LnRMSSD), standard deviation of n-n intervals (SDNN), number of pairs of successive n-n intervals that differ by more than 50 msec (NN50), and percent NN50 to total n-n intervals (PNN50) were obtained using standard techniques. Results: Under placebo, males had significantly lower minimum HR (M: 49±9.7 vs. F: 58±16 beats/min, p=0.038, d=-0.738) and significantly higher NN50 (M: 141±118 vs. F: 33±23, p=0.003, d=-0.129) than females. There was a main effect of sex on HR (M: 59±9.3 vs. F: 65±12 beats/min, p=0.036, η2 =0.098), minimum HR (M: 47±8.3 vs. F: 56±12 beats/min, p=0.014, η2 =0.124), and NN50 (M: 177±143 vs. F: 29±17, p<0.001, η2 =0.249). There was a significant interaction of sex and treatment (p=0.02, η2 =0.027) for RMSSD, where males increased (Placebo: 78±55 vs. Capsaicin: 91±64 ms), and females decreased (Placebo: 105±83 vs. Capsaicin 76±43 ms). Conclusion: This study recapitulates previously documented sex differences in HR and HRV. Acute ingestion of capsaicin increased RMSSD in men, but decreased RMSSD in women, suggesting a sexual dimorphism in parasympathetic response, perhaps due to differences in TRPV1-sensitive afferents or sensitivity. The physiological ramifications of these findings, specifically in the regulation of blood pressure and ultimately cardiovascular disease risk remain to be explored, especially in the transition to menopause in women.