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”
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-05-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.115.002683 |
| _version_ | 1818393475461152768 |
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| author | Payal Kohli Peter Ganz Yifei Ma Rebecca Scherzer Sophia Hur Bernard Weigel Carl Grunfeld Steven Deeks Scott Wasserman Rob Scott Priscilla Y. Hsue |
| author_facet | Payal Kohli Peter Ganz Yifei Ma Rebecca Scherzer Sophia Hur Bernard Weigel Carl Grunfeld Steven Deeks Scott Wasserman Rob Scott Priscilla Y. Hsue |
| author_sort | Payal Kohli |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T05:45:54Z |
| format | Article |
| id | doaj.art-8ea2c13a98a340928d034938fc83eaf0 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-14T05:45:54Z |
| publishDate | 2016-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-8ea2c13a98a340928d034938fc83eaf02022-12-21T23:14:53ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802016-05-015510.1161/JAHA.115.002683HIV and Hepatitis C–Coinfected Patients Have Lower Low‐Density Lipoprotein Cholesterol Despite Higher Proprotein Convertase Subtilisin Kexin 9 (PCSK9): An Apparent “PCSK9–Lipid Paradox”Payal Kohli0Peter Ganz1Yifei Ma2Rebecca Scherzer3Sophia Hur4Bernard Weigel5Carl Grunfeld6Steven Deeks7Scott Wasserman8Rob Scott9Priscilla Y. Hsue10Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CADivision of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CADepartment of Medicine UCSF, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CADepartment of Medicine UCSF, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CADivision of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CADivision of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CADepartment of Medicine UCSF, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CAThe Positive Health Program, San Francisco General Hospital, San Francisco, CAAmgen Inc, Thousand Oaks, CAAmgen Inc, Thousand Oaks, CADivision of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CABackgroundProprotein 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.https://www.ahajournals.org/doi/10.1161/JAHA.115.002683hepatitis C virusHIVlow‐density lipoprotein cholesterolproprotein convertase subtilisin kexin 9 |
| spellingShingle | Payal Kohli Peter Ganz Yifei Ma Rebecca Scherzer Sophia Hur Bernard Weigel Carl Grunfeld Steven Deeks Scott Wasserman Rob Scott Priscilla Y. Hsue 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” Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease hepatitis C virus HIV low‐density lipoprotein cholesterol proprotein convertase subtilisin kexin 9 |
| 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” |
| title_full | 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” |
| title_fullStr | 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” |
| title_full_unstemmed | 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” |
| title_short | 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” |
| title_sort | 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 |
| topic | hepatitis C virus HIV low‐density lipoprotein cholesterol proprotein convertase subtilisin kexin 9 |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.115.002683 |
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