HEART RATE VARIABILITY AND BAROREFLEX SENSITIVITY AS PREDICTORS OF ANTIHYPERTENSIVE DRUG RESPONSES

Objective: Treatment goals in hypertension are not often met, while essential hypertension remains the leading risk factor of global disease burden. We studied whether blood pressure (BP) responses to four antihypertensive monotherapies are associated with baseline heart rate variability (HRV) and baroreflex sensitivity (BRS). Design and method: The GENetics of drug RESponsiveness in essential hypertension (the GENRES Study) is a randomized, double-blinded, placebo-controlled, and rotational study with four antihypertensive drug monotherapies (amlodipine, bisoprolol, hydrochlorothiazide, and losartan). From the GENRES Study, we included 223 moderately hypertensive middle-aged males (age 50.8 ± 6.3 years, baseline office systolic/diastolic BP 152 ± 13 / 100 ± 7 mmHg). Continuous five-minute ECG and BP recordings were performed in a standardized environment after the first placebo treatment period of the study. The measurements were converted to time and frequency (0.025-0.40 Hz) domain heart rate variability and baroreflex sensitivity data using power spectral density methods. We analyzed heart rate adjusted and unadjusted HRV and BRS associations with 24-hour ambulatory (ABP) responses to each antihypertensive drug monotherapy. Since smoking is associated with heart rate variability, we also studied smokers (n = 35) and non-smokers (n = 188) separately. Results: Among all studied individuals, the strongest observed association was between weaker baseline high-frequency (0.15-0.40 Hz) HRV and lower 24-hour diastolic ABP response to bisoprolol (r = -0.13, P = .06). This association was stronger in smokers (r = -0.42, P = .02) than in non-smokers (r = -0.07, P = .33). The results remained consistent regardless of heart rate adjustments. Conclusions: There were only modest associations between baseline HRV and BRS and antihypertensive drug BP responses in the whole study population. However, in smokers, lower high-frequency HRV, apparently reflecting lower parasympathetic component of heart rate modulation, was associated with lower BP response to bisoprolol.