Norepinephrine stress reactivity links to a lipid-rich coronary fat phenotype in humans: a cross-sectional study

Pericoronary adipose tissue (PCAT) attenuation from coronary computed tomography angiography (CCTA) is an imaging biomarker of coronary inflammation. Experimental evidence suggests that sympathetic activation and norepinephrine (NE) can alter perivascular adipose tissue (PVAT) composition. Whether NE stress reactivity relates to PVAT phenotype, as reflected by PCAT attenuation, or varies by chronic stress exposure is unclear. We studied 60 male physicians (30 with clinical burnout, 30 controls) without known cardiovascular disease. Participants underwent CCTA for PCAT assessment and Trier Social Stress Test to induce psychosocial stress. Plasma NE was measured at baseline, immediately, +15, +45, and +90 min poststress. Relative NE increase (immediately post stress minus baseline) was the primary NE index; absolute NE increase, NE area under the curve with respect to increase (AUC-I) and ground (AUC-G; total output) were secondary indices. Multivariable regression adjusted for burnout, age, waist circumference, low-density lipoprotein cholesterol, and segment stenosis score. Greater relative NE stress increase was independently associated with lower total PCAT attenuation (average across three coronary arteries; partial r² = 0.12, P = 0.010). Each 10% relative NE increase corresponded to ∼1 HU lower attenuation. Similarly, an absolute NE increase of 50 pg/mL (partial r² = 0.08, P = 0.036) and a 5,000-unit increase in NE AUC-I (partial r² = 0.07, P = 0.049) corresponded to ∼1 HU lower attenuation, whereas NE AUC-G showed no association (P = 0.35). Acute sympathetic stress reactivity, reflected by NE increase, is associated with a lipid-rich PVAT phenotype, as indicated by lower PCAT attenuation, supporting PVAT responsiveness to adrenergic stimulation. Excess NE reactivity may represent a biomarker of early coronary vulnerability.NEW & NOTEWORTHY This study highlights the association between acute norepinephrine (NE) stress reactivity and pericoronary adipose tissue (PCAT) attenuation, a marker of coronary inflammation. In male physicians, greater NE increase after acute psychosocial stress was linked to lower PCAT attenuation, reflecting a more lipid-rich perivascular adipose tissue phenotype. This suggests that heightened NE reactivity may indicate early coronary vulnerability. Burnout did not modify this relationship, pointing to NE reactivity as a distinct physiological pathway in cardiovascular risk.