Inhaled combusted cannabis use is associated with proatherogenic changes in young people: A cross-sectional study

BackgroundInhaled combusted cannabis and co-use of combusted cannabis and nicotine electronic cigarettes (nECIGs) are on the rise, yet their long-term cardiovascular risk is unclear due to the high prevalence of confounders in observational human studies. Using primary plasma and monocytes and a novel ex vivo mechanistic model of two early steps in atherogenesis, this study examined whether chronic combusted cannabis use is associated with atherogenic changes, as estimated by 1) monocyte transendothelial migration (MTEM), and 2) monocyte-derived foam cell formation (MDFCF), and whether nECIG co-use further amplifies this risk. MethodsA cross-sectional parallel group comparison study was conducted in healthy adults (21-30 years) who chronically 1) used combusted cannabis, 2) co-used both combusted cannabis and nECIGs, and 3) were non-using controls. Using our ex vivo atherogenesis assay, primary outcomes of MTEM, MDFCF, and median fluorescence intensity (MFI) of the lipid-staining fluorochrome BODIPY were determined using primary plasma and autologous primary monocytes from participants. Using flow cytometry and the fluorochrome CELLROX, cellular oxidative stress (COS) in monocytes was determined. ResultsOf the 134 participants, 59 used cannabis, 26 co-used cannabis/nECIG, and 49 were non-using controls. The groups had similar age, sex, and race. Median MTEM was 1.13 fold greater in people who used cannabis compared to non-users 27.8% (IQR 26.1:29.2%) vs 24.5%, (IQR 22.9:27.4%), p<0.0001, and tended to be greater in people who co-used cannabis/nECIG by 1.22-fold 34.1%, (IQR 29.9:38.3%, p=0.17). Median MDFCF and MFI were also increased in people who used cannabis compared to non-users (MDFCF 36.3%, IQR 31.8:35.8%, vs 26.6%, IQR 23.8:25.8%, 1.36-fold and MFI 1163.8, IQR 1042.8:1155.0, vs 940.2 IQR 849.9:1101.4, 1.24-fold) and were further increased in people who co-used cannabis/nECIG (MDFCF 48.7%, IQR 37.3:52.4%, 1.34-fold, MFI 1433.7, IQR 1263.8:1686.4, 1.23-fold; all comparisons p<0.008). Foam cell formation, but not transendothelial migration, was strongly positively correlated with COS. All primary outcomes increased with greater frequency of cannabis and/or nECIG use. ConclusionsIn healthy young adults, exclusive cannabis use is associated with increased atherogenic properties of monocytes and plasma, and this atherogenic effect is further amplified by co-use of nECIGs.