Impact of use of antihypertensive drugs on resting energy expenditure and body composition: A matched-pair analysis of users and non-users.

BACKGROUND AND AIMS: The effects of antihypertensive medications - particularly beta blockers and renin-angiotensin system (RAS) blockers - on resting energy expenditure (REE) remain controversial. Clarifying these effects is clinically relevant for nutritional counseling in patients with hypertension. This study examined whether long-term use of these agents is associated with alterations in REE. METHODS: In this strictly matched-pair, controlled, cross-sectional study, 46 hypertensive but otherwise healthy men receiving beta blockers and/or RAS blockers for ≥ 6 months (long-term users, LU) were enrolled (age: 64.0 ± 7.9 years; BMI: 28.3 ± 4.1 kg/m2; fat-free mass (FFM): 61.9 ± 6.9 kg; treatment duration 11.0 ± 7.5 years). Participants were classified as beta blocker users (LU-B; partially with RAS blockers) or users of RAS blockers alone (LU-A). Each LU was pair-matched with a healthy male non-user (NU; n = 46; age: 62.3 ± 7.9 years; BMI: 26.9 ± 4.1 kg/m2; FFM: 62.0 ± 6.2 kg) based on FFM (±5%), skeletal muscle mass (±5%), and age (±5 years). REE was measured under standardized conditions by indirect calorimetry using a flow-based dilution canopy hood system. Body composition was assessed by bioelectrical impedance analysis. Physical activity and adverse effects at therapy initiation were systematically recorded. RESULTS: Long-term antihypertensive therapy was not associated with differences in REE compared with matched NU in the total group (LU: 1668 ± 176 vs. NU: 1642 ± 145 kcal/day; p = 0.406), nor across subgroups, irrespective of normalization to body weight or FFM. Sensitivity analyses showed similar deviations (±15%) from predicted REE using the Harris-Benedict equation in all LU subgroups compared with matched NU. Linear mixed-effects models showed no independent effects of medication, identifying FFM and pulse as the only significant predictors of REE. In contrast to the findings for REE, participants receiving RAS blocker therapy with or without beta blockers (n = 38) exhibited significantly higher fat mass (FM; +3.7 kg; p = 0.029) and VCO2 production (+9 ml/min; p = 0.008) compared with NU, whereas no differences were observed with beta blocker monotherapy (n = 8, FM: +0.9 kg; p = 0.817; VCO2: -1 ml/min; p = 0.889). The positive correlation between FM and VCO2 (r = 0.363; p < 0.001) was exclusively present in LU and not observed in NU. Self-reported weight gain at therapy initiation was more frequent among LU-B versus LU-A (6/19 vs. 1/27; p = 0.015), whereas physical activity levels and adverse effects did not differ between treatment groups. CONCLUSION: Long-term antihypertensive therapy in older men was not associated with clinically substantial deviations from expected REE. Although minor effects cannot be entirely ruled out, the results suggest that standard equations for estimating REE remain a reasonable guide for this population. However, additional verification is recommended. Despite similar physical activity and FFM, participants on RAS blocker therapy showed higher FM and VCO2 production. This may potentially reflect underlying differences in adiposity, clinical phenotype, or residual indication bias. While the cross-sectional nature of this study precludes causal inferences, these exploratory findings underscore the importance of monitoring body composition and lifestyle during antihypertensive treatment. STUDY ID NUMBER: NCT02682537 (clinical trials.gov).