Sex Differences and Caffeine Impact in Adenosine-Induced Hyperemia

Abstract

Caffeine consumption before adenosine stress myocardial perfusion imaging (MPI) is known to affect the hemodynamic response and, thus, reduce the stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) assessments. However, it is not clear if any sex-specific differences in the hemodynamic response after caffeine consumption exist. This study aimed to evaluate if such differences exist and, if so, their impact on MBF and MFR assessments. Methods: This study comprised 40 healthy volunteers (19 women). All volunteers underwent 4 serial rest/stress MPI sessions using ⁸²Rb; 2 sessions were acquired without controlled caffeine consumption, and 2 sessions after oral ingestion of either 100 and 300 mg of caffeine or 200 and 400 mg of caffeine. For the caffeine imaging sessions, caffeine was ingested orally 1 h before the MPI scan. Results: Increase in plasma caffeine concentration (PCC) (mg/L) after consumption of caffeine was larger in women (MPI session without caffeine vs. MPI session with caffeine: women = 0.3 ± 0.2 vs. 5.4 ± 5.1, men = 0.1 ± 0.2 vs. 2.7 ± 2.6, both P < 0.001). Caffeine consumption led to reduced stress MBF and MFR assessments for men whereas no changes were reported for women (women [PCC < 1 mg/L vs. PCC ≥ 1 mg/L]: stress MBF = 3.3 ± 0.6 vs. 3.0 ± 0.8 mL/g/min, P = 0.07; MFR = 3.7 ± 0.6 vs. 3.5 ± 1.0, P = 0.35; men [PCC < 1 mg/L vs. PCC ≥ 1 mg/L]: stress MBF = 2.7 ± 0.7 vs. 2.1 ± 1.0 mL/g/min, P = 0.005; MFR = 3.8 ± 1.0 vs. 3.1 ± 1.4, P = 0.018). Significant differences in the stress MBF were observed for the 2 sexes (both P ≤ 0.001), whereas similar MFR was reported (both P ≥ 0.12). Conclusion: Associations between increases in PCC and reductions in stress MBF and MFR were observed for men, whereas women did not have the same hemodynamic response. Stress MBF was affected at lower PCCs in men than women.

Keywords: PET; adenosine; caffeine; myocardial flow reserve; stress myocardial blood flow.

Graphical abstract

FIGURE 1.

Imaging protocol. (A) Acquisition protocol for each of the 4 PET/CT imaging sessions. Both rest and stress scans were acquired over 6 min. (B) Study protocol for the 40 healthy volunteers. CTAC = computed tomographic attenuation correction.

FIGURE 2.

Rest MBF obtained in the volunteers sorted by sex and plasma caffeine concentration with and without RPP correction. W = women; M = men; RPP = rate pressure product; N = number of MPI sessions fulfilling the criteria.

FIGURE 3.

Stress MBF obtained in the volunteers sorted by sex and plasma caffeine concentration, with and without RPP correction. W = women; M = men; RPP = rate pressure product; N = number of MPI sessions fulfilling the criteria.

FIGURE 4.

Relationship between ingested caffeine (mg) and the corresponding plasma caffeine concentrations (mg/L). The plasma caffeine concentrations obtained at 75 and 90 min are given as mean ± SEM in both men (closed blue triangles, n = 9–20) and women (closed red circles, n = 9–18).

FIGURE 5.

Relationship between average plasma concentration of caffeine [mg/L] (log) and stress MBF. Points represent mean values, and vertical lines indicate SEM. MBF values were normalized to the maximum stress MBF obtained for the individual volunteers (men, closed blue triangles, n = 9–20, and women, closed red circles, n = 9–18, respectively).

FIGURE 6.

MFR obtained in the volunteers sorted by sex and plasma caffeine levels. W = women; M = men; RPP = rate pressure product; N = number of MPI sessions fulfilling the criteria.