Research Article
Effects of chronic hepatitis C infection on arterial stiffness

https://doi.org/10.1016/j.jash.2017.08.007Get rights and content

Highlights

  • A relation between chronic hepatitis C and arterial stiffness in general population is proposed.

  • A peripheral arterial stiffness index, Compliance Index, was found to be independently associated with chronic hepatitis C infection.

  • Peripheral arterial stiffness in chronic hepatitis C virus infection was not associated with a marker of general inflammation (high-sensitivity C-reactive protein); however, a role for more specific markers of inflammation cannot be ruled out.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is associated with increased arterial stiffness. Although chronic hepatitis C virus (HCV) infection was shown to be associated with metabolic disorder and chronic inflammation, the effects of chronic HCV infection on arterial stiffness remain unclear. This study recruited 221 patients including 32 normal controls, 72 NAFLD patients, and 117 subjects with HCV infection. Arterial stiffness was assessed by peripheral arterial stiffness index, Compliance Index (CI), and central arterial stiffness index, Stiffness Index derived from digital volume pulse by photoplethysmography. Levels of oxidative stress marker and inflammatory markers were also measured. The HCV group had significantly lower CI (4.8 ± 3.1 units vs. 3.9 ± 2.1 units vs. 3.0 ± 1.7 units; P for trend <.001) and higher Stiffness Index (7.0 ± 1.6 m/s vs. 8.3 ± 2.3 m/s vs. 8.4 ± 2.3 m/s; P for trend = .001) compared with the normal controls and NAFLD groups. Multivariate linear regression analysis showed that CI was independently correlated with systolic blood pressure (beta = −0.202, P = .013) and HCV infection (beta = −0.216, P = .036). Chronic HCV infection was independently associated with peripheral arterial stiffness. Peripheral arterial stiffness in chronic HCV infection was not associated with a marker of general inflammation (high-sensitivity C-reactive protein); however, a role for more specific markers of inflammation cannot be ruled out.

Introduction

Hepatitis C virus (HCV) infection has been reported to be associated with cardiovascular diseases, including coronary atherosclerosis,1, 2 heart failure,3 and carotid atherosclerosis.4, 5 However, it is unclear if HCV infection has an effect on arterial stiffness in hemodialysis patients.6, 7 It is also not clear whether HCV antibody seropositivity alone—regardless of HCV-RNA positivity—is associated with arterial stiffness. Nonalcoholic fatty liver disease (NAFLD) is one of the most frequently diagnosed chronic liver diseases among adults worldwide.8, 9 NAFLD has been shown to be significantly associated with an increased risk of cardiovascular disease,10 and some studies have indicated that NAFLD may be not only a marker but also an early mediator of arterial stiffness.11, 12, 13

We previously developed a novel Compliance Index (CI), derived from a dual-channel photoplethysmography system, to measure the relationship between volume and pressure changes in the fingertips; our data suggested that CI may be clinically useful for evaluating peripheral arterial stiffness.14, 15, 16, 17 Brachial–ankle pulse wave velocity (PWV)18 and carotid-radial PWV19 have also been used as surrogates of peripheral arterial stiffness. Stiffness Index (SI), derived from the digital volume pulse (DVP) measured by photoplethysmography, is an index of wave reflections and an acceptable marker of central arterial stiffness.20 Although carotid-femoral PWV is considered to be the gold standard measurement for aortic stiffness,21 different measurement tools and stiffness indices may reflect different clinical conditions. Our previous study has shown that peripheral arterial stiffness index changed more prominently than central index in metabolic disorder.17 Different results of previous studies for association between arterial stiffness and HCV infection are possible due to different measurements of central or peripheral arterial stiffness. Nowadays, there is little studies discussing the effects of chronic HCV infection on different arterial stiffness indices, such as peripheral (CI) or central (SI) arterial stiffness index.

We hypothesized that both chronic HCV infection and NAFLD may be associated with increased arterial stiffness. Understanding the mechanisms underlying this association is clinically important in devising preventive and therapeutic strategies for cardiovascular diseases. Indeed, the impact of NAFLD and chronic viral hepatitis on risk of cardiovascular disease may have important implications for screening/surveillance strategies for this group of patients.

We previously demonstrated an association between decreased CI and increased SI in subjects with NAFLD.16 To our knowledge, there are no studies comparing peripheral arterial stiffness index, CI, or central arterial stiffness index, SI, two reliable indices of early atherosclerosis, in patients with NAFLD and chronic HCV infection. The principal aim of this cross-sectional study was to compare CI and SI in patients with NAFLD and chronic HCV infection. We also aimed to identify possible mechanism(s) underlying this association.

Section snippets

Study Population

This study enrolled 32 control subjects, 72 patients with NAFLD, and 117 patients with chronic HCV infection, who were evaluated by liver ultrasonography between February 2010 and February 2014. All patients underwent a routine check-up and health examination.

Patients were subjected to a thorough laboratory investigation for infection, autoimmune hepatitis, genetic disease, drugs, alcohol, and occupational exposure to exclude other causes of liver disease. Patients with clinical or biochemical

Clinical Characteristics of Each Patient Group

This study recruited a total of 221 patients including 32 patients without fatty liver or HCV infection (14 men, age 42 ± 12 years), 72 patients with NAFLD but no HCV infection (47 men, age 44 ± 11 years), and 117 patients with HCV infection (54 men, age 52 ± 8 years). Forty-four (37.6%) of enrolled 117 HCV patients also had NAFLD. Patients with NAFLD as well as those with HCV had significantly higher BMI, waist circumference, and mean blood pressure compared with the normal controls (NC) group

Major Findings

In the present study, we showed that patients in the HCV groups had significantly stiffer arteries (indicated by lower CI and higher SI) compared with the NC group. Chronic HCV infection was independently associated with arterial stiffness: only peripheral arterial stiffness index (CI) but not central arterial stiffness index (SI). Patients in the NAFLD and HCV groups also had more severe inflammation (indicated by significantly higher levels of log hsCRP) compared with the NC group. The

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    Conflict-of-interest: none.

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    These authors contributed to this article equally.

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