Higher proprotein convertase subtilisin/kexin 9 (PCSK9) levels are associated with marijuana consumption and low CD4 values in people living with HIV (PLWHIV) who have never received treatment with statins, according study results published in Atherosclerosis.
Over the last decade, PCSK9 has emerged as a potential target for treatment modalities in patients with hypercholesterolemia. PCSK9-inhibitors have demonstrated a 50% reduction in low-density lipoprotein (LDL) cholesterol in patients with hypercholesterolemia. Further, PCSK9-inhibitors have also shown the ability to stabilize atherosclerosis and reduce major adverse cardiovascular events in high-risk patients. PLWHIV are a subgroup of this high-risk population, and are particularly vulnerable to higher cardiovascular risk as a result of the use of antiretroviral medications. However, much is unknown about the PCSK9 levels in PLWHIV. Therefore, to appropriately tailor lipid-lowering strategies in patients with HIV, the PCSK9 profile needs to be better characterized. This cross-sectional study assessed exploratory factors associated with high PCSK9 levels.
In total, 239 PLWHIV were included from the Swiss HIV cohort study. Patients were aged ≥40 years and were naïve to statin therapy. Patients were screened for PCSK9 levels via blood sample collection. Clinical, behavioral, and biomarker categories were investigated with regard to their effect on PCSK9 levels. The clinical category included age, sex, ethnicity, cardiovascular risk factors, body mass index, CD4 levels (low level defined as ≤200 cells/µL), blood cell levels, and antiretroviral therapy. The behavioral category included tobacco and marijuana smoking, alcohol consumption, and physical activity. The biomarker category included C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-8, IL-10, and monocyte chemoattractant protein (MCP)-1. Of the patients included in the study, 14.6% reported marijuana consumption: 57.1% of these reported daily use and 6.3% reported occasional use.
Results were consistent in individuals without HIV in that PCSK9 levels were correlated with low LDL cholesterol. Further, in patients with HIV higher PCSK9 levels were associated with marijuana consumption and low CD4 values (P =.023 and P = .020, respectively). Marijuana consumption also seemed to have a dose-response effect on PCSK9 levels (P <.001) and this association persisted after adjustment for the calculated Framingham risk score (P =.003) and additional clinical variables (P =.027). Borderline significance was observed for IL-8, gender, and ethnicity (all P values ≤.10). In the multivariate models containing potential predictors of PCSK9 levels, researchers identified 2 predictors that reached statistical significance: daily marijuana consumption (P =.027) and low CD4 levels (P =.031).
Overall, the study authors concluded that, “In HIV-infected individuals naïve of statin treatment, marijuana consumption and low CD4 values are associated with higher PCSK9 levels independently of clinically relevant confounding factors.”
Gencer B, Pagano S, Vuilleumier N, et al. Clinical behavioral and biomarker predictors of PCSK9 levels in HIV-infected patients naïve of statin therapy: a cross-sectional analysis from the Swiss HIV cohort [published online February 20, 2019]. Atherosclerosis. doi:10.1016/j.atherosclerosis.2019.02.015