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".
| dc.contributor.author | Kohli, Payal | |
| dc.contributor.author | Ganz, Peter | |
| dc.contributor.author | Ma, Yifei | |
| dc.contributor.author | Scherzer, Rebecca | |
| dc.contributor.author | Hur, Sophia | |
| dc.contributor.author | Weigel, Bernard | |
| dc.contributor.author | Grunfeld, Carl | |
| dc.contributor.author | Deeks, Steven | |
| dc.contributor.author | Wasserman, Scott | |
| dc.contributor.author | Scott, Rob | |
| dc.contributor.author | Hsue, Priscilla Y | |
| dc.date.accessioned | 2024-04-01T15:17:14Z | |
| dc.date.available | 2024-04-01T15:17:14Z | |
| dc.date.issued | 2016-04 | |
| dc.description.abstract | BackgroundProprotein 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 resultsWe 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).ConclusionsDespite 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. | |
| dc.identifier | JAHA.115.002683 | |
| dc.identifier.issn | 2047-9980 | |
| dc.identifier.issn | 2047-9980 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Ovid Technologies (Wolters Kluwer Health) | |
| dc.relation.ispartof | Journal of the American Heart Association | |
| dc.relation.isversionof | 10.1161/jaha.115.002683 | |
| dc.rights.uri | ||
| dc.subject | Humans | |
| dc.subject | Hepatitis C, Chronic | |
| dc.subject | HIV Infections | |
| dc.subject | Cholesterol | |
| dc.subject | Interleukin-6 | |
| dc.subject | Hydroxymethylglutaryl-CoA Reductase Inhibitors | |
| dc.subject | Case-Control Studies | |
| dc.subject | Adult | |
| dc.subject | Middle Aged | |
| dc.subject | Female | |
| dc.subject | Male | |
| dc.subject | Dyslipidemias | |
| dc.subject | Cholesterol, LDL | |
| dc.subject | Cholesterol, HDL | |
| dc.subject | Coinfection | |
| dc.subject | Proprotein Convertase 9 | |
| dc.title | 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". | |
| dc.type | Journal article | |
| pubs.begin-page | e002683 | |
| pubs.issue | 5 | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Medicine | |
| pubs.organisational-group | Medicine, Cardiology | |
| pubs.publication-status | Published | |
| pubs.volume | 5 |
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