Effect of Sex on Coronary Endothelial Dysfunction in People Living With HIV

BACKGROUND: Impaired coronary endothelial function (CEF) predicts cardiovascular events and occurs in people living with HIV (PLWH). Women compared with men living with HIV have worse cardiovascular outcomes, but prior CEF studies included few women. The authors aimed to compare CEF in women with HIV versus without HIV, investigate sex differences in CEF and PCSK9 (proprotein convertase subtilisin/kexin type 9) (a proinflammatory biomarker), and evaluate whether increased serum levels of PCSK9 are associated with CEF in PLWH. METHODS AND RESULTS: Magnetic resonance imaging was performed to measure CEF (as percent change in coronary cross-sectional area and coronary blood flow during isometric handgrip exercise, an endothelial-dependent stressor) and serum PCSK9 levels were measured in 106 PLWH and 76 people without HIV. CEF was significantly reduced in women with versus without HIV (cross-sectional area change −0.5%±9.7 versus 9.5%±3.2, respectively). After adjustment for age, body mass index, and menopausal status, women with HIV still had reduced CEF (percentage of cross-sectional area: ß −8.3 [−13 to −3.6], P=0.001) compared with women without HIV. PCSK9 was elevated in women living with HIV versus without (306 ng/ mL [200– 412 ng/mL] versus 180 ng/mL [154– 223 ng/mL], P<0.001), and no sex differences in either CEF or PCSK9 were detected in PLWH. Elevated PCSK9 was associated with impaired CEF in PLWH; however, no significant sex differences in the association were detected. CONCLUSIONS: Among PLWH, coronary endothelial dysfunction is present in women and comparable to men. PCSK9 is higher in women with versus without HIV and a significant inverse relationship between PCSK9 and CEF was shown. Future studies should determine whether PLWH would benefit from interventions to improve endothelial function.