Abstract 17751: PCSK9 is Elevated in HIV+ Patients

Abstract

Purpose: Proprotein convertase subtilisin kexin 9 (PCSK9) is induced by inflammation and inhibits LDL receptor expression. Increased PCSK9 might explain the dyslipidemia observed in HIV patients, which has been previously attributed to HIV medication, HIV disease, and/or chronic inflammation. We aimed to compare PCSK9 levels in HIV patients and uninfected controls and identify predictors of elevated PCSK9 in HIV. Methods: We measured PCSK9 levels in 567 participants (495 HIV, 72 controls) from an outpatient cohort in San Francisco using a high affinity ELISA assay. Poisson regression models were used to determine factors associated with PCSK9. Results: The median age of all participants was 50 years (IQR 43-55) and 89% were male; 34% were smokers, 25% had hypertension, the median LDL was 103 mg/dL (IQR 80-127), and 21% were on statins. HIV patients and controls had similar rates of traditional risk factors except prior CAD was more common in HIV patients. Half of the HIV patients were treated and suppressed on HIV medication. Unadjusted PCSK9 levels were 11% higher in HIV patients vs. controls [mean 430 ng/ml (SD 166) vs. 386 ng/ml (SD134), p=0.015] with some HIV patients having extremely elevated levels >1000 ng/ml. After adjustment for demographics and statin use, HIV remained independently associated with 10% higher PCSK9 levels (p=0.03). In addition, older age, other race, statin use, Hepatitis C (HCV), higher triglycerides, current smoking and Lp(a)>90 nmol/L were all independently associated with higher PCSK9 levels in adjusted analysis. In contrast, neither inflammatory markers (IL-6, hs-CRP) nor CD4+ count or HIV viral load were associated with higher PCSK9. Conclusion: PCSK9 is increased in HIV-infected individuals. Traditional risk factors, HCV, and Lp(a)>90 nmol/L were also independently associated with PCSK9. Future studies should explore whether PCSK9 inhibition may be used to treat dyslipidemia and statin resistance in HIV+ patients.