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J Am Heart Assoc. 2016 Apr 29;5(5). pii: e002683. doi: 10.1161/JAHA.115.002683.

HIV and Hepatitis C-Coinfected Patients Have Lower Low-Density Lipoprotein Cholesterol Despite Higher Proprotein Convertase Subtilisin Kexin 9 (PCSK9): An Apparent "PCSK9-Lipid Paradox".

Author information

1
Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA payal.kohli.md@gmail.com.
2
Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA.
3
Department of Medicine UCSF, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA.
4
The Positive Health Program, San Francisco General Hospital, San Francisco, CA.
5
Amgen Inc, Thousand Oaks, CA.

Abstract

BACKGROUND:

Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors reduce low-density lipoprotein cholesterol (LDL-C) and improve outcomes in the general population. HIV-infected individuals are at increased risk for cardiovascular events and have high rates of dyslipidemia and hepatitis C virus (HCV) coinfection, making PCSK9 inhibition a potentially attractive therapy.

METHODS AND RESULTS:

We studied 567 participants from a clinic-based cohort to compare PCSK9 levels in patients with HIV/HCV coinfection (n=110) with those with HIV infection alone (n=385) and with uninfected controls (n=72). The mean age was 49 years, and the median LDL-C level was 100 mg/dL (IQR 77-124 mg/dL); 21% were taking statins. The 3 groups had similar rates of traditional risk factors. Total cholesterol, LDL-C, and high-density lipoprotein cholesterol levels were lower in coinfected patients compared with controls (P<0.001). PCSK9 was 21% higher in HIV/HCV-coinfected patients versus controls (95% CI 9-34%, P<0.001) and 11% higher in coinfected individuals versus those with HIV infection alone (95% CI 3-20%, P=0.008). After adjustment for cardiovascular risk factors, HIV/HCV coinfection remained significantly associated with 20% higher PCSK9 levels versus controls (95% CI 8-33%, P=0.001). Interleukin-6 levels increased in a stepwise fashion from controls (lowest) to HIV-infected to HIV/HCV-coinfected individuals (highest) and correlated with PCSK9 (r=0.11, P=0.018).

CONCLUSIONS:

Despite having lower LDL-C, circulating PCSK9 levels were increased in patients coinfected with HIV and HCV in parallel with elevations in the inflammatory, proatherogenic cytokine interleukin-6. Clinical trials should be conducted to determine the efficacy of targeted PCSK9 inhibition in the setting of HIV/HCV coinfection.

KEYWORDS:

HIV; hepatitis C virus; low‐density lipoprotein cholesterol; proprotein convertase subtilisin kexin 9

PMID:
27130349
PMCID:
PMC4889164
DOI:
10.1161/JAHA.115.002683
[Indexed for MEDLINE]
Free PMC Article

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