Acute mental stress-induced adrenergic reactivity profiles predict distinct cardiometabolic risk trajectories over three years: the SABPA study

OBJECTIVES: We previously characterised acute mental stress-induced alpha (α)- and beta (β)-adrenergic-haemodynamic reactivity profiles cross-sectionally and related them to unique cardiometabolic risk outcomes. Whether these profiles predict future cardiometabolic risk remains unclear. We compared three-year cardiometabolic risk outcomes between predominant α- and β-responders and evaluated the prognostic value of each profile for predicting cardiometabolic risk. METHODS: Participants (aged 20-65 years) were stratified at baseline as predominant α- (n = 43) or β-responders (n = 59) defined by lowest and highest population quartiles, respectively, of reactivity in both cardiac output and Windkessel arterial compliance. Remaining participants were classified as mixed-α/β-responders (n = 227). Hypertension and central obesity at baseline and follow-up were defined using international guidelines. Other outcomes included cardiac stress (cardiac troponin-T ≥4.2 pg/ml), abnormal-glucose-tolerance (Abnl-GT; HbA1c ≥5.7% and/or fasting glucose ≥5.6 mmol/l and/or using antidiabetic medication), 10-year atherosclerotic cardiovascular disease (ASCVD)-risk (UCLA composite score), 24-h ischaemic events (Holter-electrocardiography) and an adverse lipid profile (high total cholesterol, low high-density-lipoprotein (HDL)-cholesterol and high triglycerides) defined by South African Heart Association/Lipid and Atherosclerosis Society of Southern Africa guidelines. Three-year risk for each outcome by adrenergic profile were estimated using covariate-adjusted Cox-proportional hazard models. RESULTS: At three-year follow-up, α-responders had higher prevalence of hypertension, Abnl-GT, low HDL-cholesterol, and 10-year ASCVD-risk than β-responders (all P ≤ 0.025). Both α- and β-adrenergic reactivity profiles were associated with increased three-year risk of 10-year ASCVD, cardiac stress, central obesity, and Abnl-GT (all P ≤ 0.047). The α-adrenergic reactivity profile uniquely predicted elevated risk of hypertension, high total cholesterol, and low HDL-cholesterol (all P ≤ 0.009), whereas the β-adrenergic reactivity profile was associated with lower risk of hypertension and high total cholesterol but higher risk of 24-h ischaemic events (all P ≤ 0.016). CONCLUSION: Acute mental stress-induced α- and β-adrenergic reactivity profiles independently predicted distinct cardiometabolic outcomes over three-years, delineating differential pathways of cardiometabolic risk. These findings support the potential utility of adrenergic reactivity phenotypes to refine individual, psychophysiological-linked cardiometabolic risk stratification.