Effects of a year-long aerobic exercise intervention on neuroendocrine, autonomic, and neural correlates of stress, emotion, and cardiovascular disease risk in midlife adults

• What is already known on this topic? It has been hypothesized that aerobic exercise may reduce cardiovascular disease risk along with indicators of stress- and emotion-related neuroendocrine, autonomic, and neural activity; however, prior evidence on stress- and emotion-related outcomes is mixed and largely correlational or cross-sectional. • What this study adds? This is the first 12-month registered clinical trial on aerobic exercise and concurrent measures of cardiovascular risk and stress- and emotion-related neuroendocrine, autonomic, and neural outcomes in midlife adults. Novel findings showed that aerobic exercise improved cardiorespiratory fitness and lowered cortisol levels. But, the intervention did not influence other stress- and emotion-related peripheral and neural (brain-based) biomarkers. • How this study might affect research, practice, or policy? Findings extend prior work by examining long-term intervention-related effects of aerobic exercise on concurrently assessed and multidimensional biomarkers of cardiovascular health and stress and emotion. These intervention findings may offer limited support for hypotheses that aerobic exercise broadly downregulates stress- and emotion-related physiology across multiple organ systems beyond the hypothalamic-pituitary-adrenal axis. Test whether an aerobic exercise intervention that improves cardiorespiratory fitness reduces (a) biomarkers of cardiovascular disease (CVD) risk and (b) indicators of stress- and emotion-related neuroendocrine, autonomic, and neural activity. In a preregistered 12-month clinical trial, 130 healthy adults aged 26 to 58 years (mean age = 41.4 years; 67.7% female) were randomized to (a) a 150 min per week of moderate-to-vigorous aerobic exercise group or (b) health-information control group. Intervention effects were examined for: (a) cardiometabolic and vascular risk factors (triglycerides, total cholesterol, high-density lipoproteins, glycosylated hemoglobin, pulse-wave velocity); (b) indicators of neuroendocrine and autonomic activity (hair cortisol, heart rate variability); (c) biomarkers of systemic and vascular inflammation (interleukin-6, intercellular adhesion molecule-1); and (d) neural, cardiovascular, and subjective responses to functional magnetic resonance imaging stressor and emotion task paradigms. There were 41 and 40 participants in the exercise and control groups, respectively, who completed follow-up assessments. In planned intention-to-treat analyses using generalized linear mixed models, a group-by-time interaction indicated that the exercise group exhibited a decrease from baseline to follow-up relative to the control group in hair cortisol (Between-Group Difference = –0.62; 95% confidence interval (95%CI): –1.14 to –0.10, p (False Discovery Rate) = 0.039). This reduction was also observed in per protocol analyses. No other effects on remaining outcomes were consistently observed in planned and per protocol analyses. A 12-month moderate-to-vigorous aerobic exercise intervention that improved cardiorespiratory fitness also reduced the stress-related biomarker, hair cortisol, but not other indicators of psychological stress and negative emotion processes implicated in CVD risk.