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Article

A Comparative Study on the Presence and Reversibility of Subclinical Arterial Damage in HCV-Infected Individuals and Matched Controls

by
Theodoros Androutsakos
1,*,
Dimitrios Mouziouras
2,3,
Stamatia Katelani
1,
Mina Psichogiou
4,
Petros P. Sfikakis
5,
Athanase D. Protogerou
1,3 and
Antonios A. Argyris
3
1
Clinic/Laboratory of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece
2
Department of Gastroenterology, Laiko General Hospital, School of Medicine, National and Kapodistrian University Athens, 11527 Athens, Greece
3
Cardiovascular Prevention and Research Unit, Clinic/Laboratory of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece
4
First Department of Internal Medicine, Laiko General Hospital, School of Medicine, National and Kapodistrian University Athens, 11527 Athens, Greece
5
First Department of Propaedeutic Medicine, Laiko General Hospital, School of Medicine, National and Kapodistrian University Athens, 11527 Athens, Greece
*
Author to whom correspondence should be addressed.
Viruses 2023, 15(6), 1374; https://doi.org/10.3390/v15061374
Submission received: 14 April 2023 / Revised: 12 June 2023 / Accepted: 14 June 2023 / Published: 15 June 2023
(This article belongs to the Section Human Virology and Viral Diseases)
Review Reports Versions Notes

Abstract

:
Background: The arterial pathology and mechanisms of increased cardiovascular disease (CVD) risk in HCV-infected individuals are not yet clear. The aim of this study was to identify types of arterial pathology in treatment-naive chronic HCV patients and to test their reversibility after successful treatment. Methods: Consecutive, never-treated, HCV-infected patients were compared with age and CVD-related risk factors, matched controls, healthy individuals (HI), patients with rheumatoid arthritis (RA) and people living with HIV (PLWH), in terms of arterial stiffening by pulse wave velocity, arterial atheromatosis/hypertrophy by carotid plaques/intima-media thickness and impaired pressure wave reflections by augmentation index. After three months of sustained virological response (SVR) administered using direct-acting antivirals, vascular examination was repeated in HCV-infected patients to test drug and viral-elimination effect in subclinical CVD. Results: Thirty HCV patients were examined at baseline; fourteen of them were re-examined post-SVR. Compared with HI, HCV patients had significantly more plaques, which is similar to that of RA patients and the PLWH group. No other differences were found in all other vascular biomarkers, and regression among HCV patients also revealed no differences 3 months post-SVR. Conclusions: Accelerated atheromatosis, rather than arterial stiffening, arterial remodeling and peripheral impaired hemodynamics is the underlying pathology leading to increased CVD risk in HCV patients.

1. Introduction

Chronic hepatitis C virus (HCV) infection constitutes a major global health issue. It is estimated that more than 70 million individuals are infected with HCV worldwide, with at least 400,000 deaths occurring each year [1,2]. However, the landscape of chronic HCV infection treatment has changed substantially in the last decade with the emergence of direct-acting antiviral drugs (DAAs) as a first-line treatment against HCV infection, leading to more than 95% sustained virological response (SVR) in all patients, irrespective of the presence of cirrhosis, comorbidities or genotype [3,4,5].
Chronic HCV infection is characterized by a variety of extrahepatic manifestations (EHMs); among them, cardiovascular disease (CVD) is the most important as patients with chronic HCV exhibit increased cardiovascular mortality [6,7]. Interestingly, the arterial pathology and mechanisms linked to increased cardiovascular events are not yet clear [7]. The use of DAAs and the subsequent eradication of HCV seem to lead to a decrease in CVD-related events [8,9], however, studies focusing on the early steps of CVD by measuring subclinical arterial damage show contradictory results [10,11,12].
The aim of the present study was to identify evidence of accelerated subclinical arterial damage in treatment-naive patients with chronic HCV, without established CVD. To this end, we investigated three different types of arterial damage: (i) arterial stiffening by carotid to femoral pulse wave velocity (cfPWV), (ii) arterial atheromatosis/hypertrophy by common carotid plaques/intima-media thickness (IMT) and (iii) impaired pressure wave reflections by augmentation index (AIx75). In order to test the hypothesis of accelerated subclinical arterial disease in HCV-infected individuals, we used the following comparators: (i) a matched group of apparently healthy individuals (HI) and (ii) two other matched groups, consisting of patients with rheumatoid arthritis (RA) and people living with HIV (PLWH); both these groups have been extensively investigated in the literature due to the presence of accelerated subclinical arterial damage. Finally, in order to investigate the possibility of arterial damage reversibility in HCV patients after successful eradication of HCV, the above-mentioned vascular examination was repeated 3 months post-SVR.

2. Materials and Methods

2.1. Study Population—Chronic HCV Patients

Study population consisted of consecutive patients with treatment-naive, chronic HCV infection, referred for evaluation and treatment to the outpatient hepatology clinic of the Pathophysiology department of the “Laiko” General Hospital from October 2018 to November 2019. Inclusion criteria were the presence of HCV infection (defined as detectable HCV RNA in peripheral blood) and age > 18 years; exclusion criteria were the inability to receive treatment (due to poor compliance, concurrent alcoholism or intravenous drug use), concurrent viral hepatitis other than HCV infection and the presence of autoimmune liver disease or cancer. The study was approved by the Ethical/Scientific Committee of the “Laiko” Hospital and all participants provided informed consent according to the declaration of Helsinki.
Medical history was obtained through patients’ interviews and their medical charts. Duration of HCV infection was defined as the duration between patients’ HCV diagnosis (via PCR assessment of HCV viral load) and enrollment day. All patients underwent transient elastography before DAA initiation; liver stiffness was graded between 1 (normal liver) and 4 (cirrhotic liver) according to EASL guidelines for non-invasive assessment of HCV infection [13]. On the inclusion date, blood was drawn and thorough laboratory testing (including serum transaminases, serum total, high and low-density cholesterol and serum triglycerides levels, glycosylated hemoglobin and serum glucose levels) were performed. Type 2 diabetes mellitus (T2DM) was defined as concurrent antidiabetic treatment or levels of blood sugar ≥ 126 mg/dL or ≥ 200 mg/dL for fasting and non-fasting patients, respectively, or glycosylated hemoglobin of (HbA1c) ≥ 6.5%. Dyslipidemia was defined as concurrent lipid modifying treatment or LDL ≥ 130 mg/dL in double check at least 3 months apart according to guidelines [14,15]. Arterial hypertension was defined as systolic/diastolic blood pressure (SBP)/(DBP) ≥ 130 and/or ≥80 mmHg using 24 h ambulatory blood pressure monitoring (ABPM) or through the concurrent use of anti-hypertensive treatment [16].
Regimens used for HCV treatment followed the national and international guidelines at the time each patient was treated, after completing baseline vascular examinations [17]. SVR was defined as the absence of HCV RNA in a patient’s blood 3 months after DAA treatment, according to guidelines [17].

2.2. Study Matched-Control Groups

Three separate groups were used as comparators: (i) a group with HI, (ii) a group of patients with RA and (iii) a group with PLWH. The selection of RA and PLWH as non-healthy matched control groups was based on the fact that these populations have been extensively investigated in the past regarding the presence of accelerated subclinical arterial damage by our group [18,19,20,21,22,23,24], as well as by others [25,26,27,28]. All 3 control groups were CVD-free and were recruited from the outpatient CVD prevention clinic of our hospital.
For each separate control group, HCV patients were matched 1:1 for possible confounders, including age, smoking habits, history of hypertension, dyslipidemia, T2DM, body mass index (BMI), SBP during the examination.

2.3. Assessment of Subclinical Arterial Damage

All participants underwent vascular examination, which was performed by the same experienced physician. All participants were on steady medication for at least one month and were asked to abstain from any vasoactive medication in the morning of the vascular assessment. Blood pressure measurements were conducted in the morning (8:30–12:30 a.m.) in the supine position, after at least 10 min of rest, in a controlled room temperature (22–25 °C). A validated, automated device (Microlife Watch BP Office, Microlife AG, Widnau, Switzerland) was used; 3 branchial blood pressure measurements (with 1 min interval between each measurement) were recorded. The average of all 3 measurements, as well as the calculated mean arterial pressure (MAP) was used in the statistical analysis. cfPWV and AIx75 were assessed according to the methodology described elsewhere, using the SphygmoCor apparatus (AtCor Medical, Sydney, Australia) [29,30]. Briefly, cf-PWV was calculated by the ratio of the estimated pulse transit time and the distance travelled by the pressure wave between the two recording sites. Pressure waves were first recorded at the carotid artery and then at the femoral artery. The time delay between the two waves (transit time) was determined using registration with a simultaneously recorded ECG. Two sequential measurements of cfPWV were performed and their average value was used in the analysis. AIx was also assessed as an index of pressure wave reflections and corrected to a heart rate of 75 beats/min. Using radial applanation tonometry and a generalized transfer function applied to the non-invasively acquired peripheral signal, an aortic waveform was calculated. AIx was then generated as the augmentation pressure (systolic pressure minus the inflection pressure) divided by the pulse pressure (systolic minus diastolic pressure), expressed as a percentage [31]. Left and right IMT at the common carotid artery and atheromatic plaques at the carotid and femoral beds were assessed using B mode vascular ultrasonography (Logiq V5 Expert, GE Healthcare, Fairfield, CT, USA). IMT was measured adjacent to any plaque (if present) at the far wall of the common carotid artery in the end-diastole of the cardiac cycle, via a semi-automatic software. Atheromatic plaque was defined as local increase in the IMT by ≥50% compared to the adjacent vessel wall or a bulging to the lumen IMT ≥ 1.5 mm [30]. For all vascular biomarkers, 2 consecutive measurements were obtained and the mean value was used in the analysis.
In order to test the hypothesis of arterial damage reversibility after HCV eradication, a scheduled follow-up vascular examination was performed 3 months post-SVR in patients with HCV infection.
A validated brachial-cuff ABPM device was used for the evaluation of blood pressure in HCV patients (Mobil-O-Graph; IEM, Stolberg, Germany); out of office blood pressure measurements were also used in all other groups.

2.4. Statistics

All statistical analyses were performed using the STATA 13 software package [32]. Statistical significance was defined as a p-value of <0.05. For description purposes, frequencies distributions and medians (interquartile range) or mean plus standard deviations were used for age, MAP, heart rate, BMI and duration of HCV infection. Wilcoxon sign-rank test was performed between all comparison groups. All comparisons on the presence of atheromatic plaques were performed through McNemar chi-squared test. In multivariable linear regression, further adjustment for MAP was carried out, heart rate during the vascular examination was measured to compare left IMT, right IMT and PWV between HCV patients and their respective matched controls, and AIx5 was adjusted only for MAP. For the presence of atheromatic plaques univariable conditional logistic regression was performed, since all patients were matched. In order to further investigate the differences in vascular biomarkers among HCV patients, multivariable linear regression, as well as univariable logistic was performed. The covariates used were the ones listed above, in addition to duration of HCV infection, stage of liver fibrosis and age.

3. Results

3.1. HCV Baseline Measurement

Overall, 29 treatment-naive patients (23 men and 6 women, mean age: 46.6 ± 10.7 years) with chronic HCV infection were included in the study; one was excluded due to concurrent arterial hypertension. Twenty-eight patients were treated with glecaprevir/pibrentasvir (GP), while one was treated with grazoprevir/elbasvir. The baseline characteristics of HCV-infected individuals are presented in Table 1. Table 2 summarizes the measured vascular biomarkers of the comparison groups.

3.2. HCV Patients’ Comparisons with the Matched Control Group

Effective 1:1 matching was achieved for HI, RA patients and PLWH in 29, 19 and 20 untreated patients with HCV, respectively (Table 1).
Concerning arterial stiffness, cfPWV was consistently lower in HCV patients, as compared to PLWH in unadjusted models, but not HI; however, after adjustment for possible confounders, no differences were observed between HCV and any of the three control groups (Table 2 and Table 3).
Regarding atheromatosis, plaque occurrence was almost double in HCV patients compared to the HI control group, reaching statistical significance (Table 3); on the contrary, no differences were observed between HCV patients and RA or PLWH. HCV patients had significantly lower left IMT compared to matched RA patients in unadjusted models, with this difference being attenuated in adjusted models. In addition, no differences between HCV and any of the other control groups regarding left or right IMT were observed (Table 2 and Table 3).
Finally, Aix75 was found to be statistically lower in HCV patients compared to RA patients, however, after adjustment for MAP during the vascular examination, this difference was eliminated (Table 2 and Table 3). No other differences between HCV patients and HI, as well as PLHW were observed (Table 2 and Table 3).

3.3. HCV Patients Follow-Up Visit 3 Months Post-SVR

All treated patients achieved SVR; however only 14 of them (all having received GP treatment) presented for the vascular follow-up re-examination 3 months post-SVR (Table 4). No differences were observed in any of the vascular indices among these 14 patients at the follow-up visit. In unadjusted models, PWV was significantly lower at 3 months; nevertheless, after adjustment for MAP differences between visits, no treatment effect was observed (Table 5).

3.4. HCV Patients’ In-Group Analysis

Data on duration of HCV infection and stage of liver fibrosis were available for 22 out of the 30 HCV patients enlisted (Table 1). The duration of HCV infection without treatment was found to have a positive association with all the vascular biomarkers under investigation, apart from PWV; however, statistical significance was not reached for any of them (Table 6). As far as liver fibrosis is concerned, it seemed that advanced fibrosis was associated with the elevation in all vascular biomarkers, except PWV, even though statistical significance was not reached in any of them; the only exception was the higher values of left IMT in patients with liver cirrhosis (grade 4 fibrosis) (Table 6).

4. Discussion

The CVD complications of chronic HCV infection have gained much attention in recent years, since a variety of studies and meta-analyses suggest that a significant—and probably causative—correlation between the two aforementioned diseases exists, with HCV-infected individuals showing a higher probability for coronary artery disease (CAD), stroke, acute myocardial injury and CVD-related death [33,34,35,36]. In one of the largest meta-analysis, Petta S. et al. showed that HCV-infected individuals showed an odds ratio of 1.65 for overall CVD deaths and a 2-fold higher risk for the presence of carotid plaques [33]. However, the exact pathogenesis of these phenomena still remains elusive.
This single-center prospective study in patients with treatment-naive, CVD-free, chronic HCV infection, aimed at (i) identifying the presence of early steps in different types of arterial damage (atheromatosis, arterial hypertrophy, arterial stiffening and impaired pressure wave reflections) using control groups at low or high CVD risk, as well as aimed at (ii) assessing the hypothesis of arterial damage reversibility in HCV patients after SVR. Clear evidence of accelerated subclinical atheromatosis, with higher prevalence of atheromatic plaques in HCV-infected individuals—but not of other types of arterial damage—was observed.
The present results suggest that accelerated subclinical atheromatosis might represent the very early step in the sequel of CVD development in treatment-naive HCV-infected patients, and this finding that is in line with existing evidence. On the contrary, all other types of arterial damage, as evaluated by the gold standard biomarkers applied herein, seem to be preserved, at least in the early stages of CVD development. It is plausible to suggest that HCV virus directly affects the endothelial layer by promoting atherogenesis, without affecting the elastic compartment of the medial layer, thus sparing arterial hypertrophy (no increase in IMT in plaque—free arterial segments) and arterial stiffening (no increase in PWV). The underlying mechanism for this predilection might be related to the hepatic and systemic inflammation induced by HCV, resulting in increased levels of proatherogenic cytokines and chemokines, mainly interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-a) and fibrinogen and an imbalance between pro- and anti-inflammatory cytokines, leading to chronic inflammation and oxidative stress and subsequent endothelial damage of blood vessels [37,38].
On the other hand, our analysis among HCV patients provides evidence that HCV infection has most probably some effect in arterial hypertrophy as well, since IMT shows a statistically significant elevation for every year of chronic HCV infection in both carotids, while excessive liver fibrosis caused by the virus also seems to affect arterial thickening.
Our findings are partly in concordance with the first pivotal Japanese study which revealed the possible link between hepatitis C virus and subclinical vascular damage [39,40]. In these studies, HCV-infected patients were found to have increased atheromatic burden, translated in statistically significant differences in both the prevalence of atheromatic plaques and IMT, compared to controls. It is important to mention that measurement methods used can influence the IMT values, and this can describe the discrepancies observed between studies. More specifically, many researchers prefer to use the mean value of multiple mean or maximum IMT measurements, while there is also deviation in the carotid segment where IMT is evaluated (carotid bulb vs. common carotid artery vs. internal carotid artery). Furthermore, some prefer to include atheromatic plaques in the IMT measurements leading to greater values reported [41].
In the present study, plaque burden in HCV-infected individuals was twice as much when compared with HI and equal to that observed in RA patients and PLWH. It has been previously described [18,19,20,21,22,23,24,25,26,27,28] that both these conditions (RA and PLWH) have almost double—than their control groups—the burden of subclinical atheromatosis. RA patients have higher incidence of CVD and almost 40% of all deaths are attributed to CVD complications [42]. Moreover, CVD risk in RA is underestimated by the currently available international CVD risk score [43] and testing for subclinical carotid plaque presence has been proposed in order to optimize risk reclassification in RA patients [44]. Likewise, PLWH seem to have increased CVD risk which is underestimated by the available CVD risk scores [45], however, international recommendations regarding CVD risk reclassification have not yet incorporated arterial indices/risk modifiers.
No evidence of early arterial stiffening or arterial remodeling (hypertrophy and impaired peripheral pressure wave reflections) in patients with HCV infection was found in this study. Any changes in arterial properties during the follow-up period in HCV-infected patients was most probably related to MAP changes rather than arterial wall modifications. We have previously described that the abovementioned arterial properties, although reported in the literature to be impaired in populations with chronic inflammation (e.g., RA), are most probably only transiently impaired and reversible upon effective treatment and regression of inflammation [45,46,47]. Of note, plaque regression was not examined in the present study since 6 months is per se not an adequate time to study such an effect.
Our findings suggest that HCV virus per se rarely causes vascular damage, but most probably enhances the effect of well-known risk factors, such as age. Moreover, a larger duration of infection and hepatic cirrhosis seems to be accompanied with increased atherogenesis, but decreased arterial stiffness, expressed through PWV, though in our cohort, statistical significance was not reached. The decreased arterial stiffness could be explained by the splanchnic and peripheral arterial vasodilation found in patients with cirrhosis, leading to significant alterations in vascular properties [48].
The first novelty and strength of the present study lies on the simultaneous and comprehensive evaluation of multiple types of subclinical arterial damage (i.e. arterial stiffness, arterial remodeling, atheromatosis and impaired pressure wave reflections) at multiple arterial sites, with the use state-of-the art vascular biomarkers, that are well accepted as CVD risk modifiers [49,50,51,52,53,54,55,56]. The second novelty of the study lies in the use of multiple control groups, including—for the first time—two well-studied, high CVD risk populations (i.e., RA and PLWH). The main limitations of the present study are the relatively small sample size, the absence of long follow-up, as well as the big percentage of dropout during the follow-up period at three months post-SVR, making it mandatory to validate our findings in large, well designed, long-term studies in the future.

5. Conclusions

The present findings suggest that atheromatosis, rather than arterial stiffening, arterial remodeling and peripheral impaired hemodynamics, is the underlying pathophysiological mechanism leading to increased CVD risk in HCV patients. Future large cohort studies should be undertaken in order to confirm our findings and optimize CVD prevention strategies.

Author Contributions

Conceptualization, T.A., A.D.P. and A.A.A.; Formal analysis, D.M.; Investigation, S.K., M.P., P.P.S. and A.A.A.; Methodology, T.A., A.D.P. and A.A.A.; Writing—original draft, T.A., D.M., S.K., M.P., P.P.S., A.D.P. and A.A.A.; Writing—review and editing, T.A., D.M., S.K., M.P., P.P.S., A.D.P. and A.A.A. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study complied with the principles of the 1975 Declaration of Helsinki (6th revision, 2008) and the general data protection rules (GDPR) of the European Union and was approved by the Ethics Committee of the “Laiko” University Hospital of Athens, Greece.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

All data regarding this article are available upon reasonable request.

Acknowledgments

The authors would like to thank all the patients who participated in this study.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Jefferies, M.; Rauff, B.; Rashid, H.; Lam, T.; Rafiq, S. Update on global epidemiology of viral hepatitis and preventive strategies. World J. Clin. Cases 2018, 6, 589–599. [Google Scholar] [CrossRef] [PubMed]
  2. WHO. Global Hepatitis Programme. Global Hepatitis Report 2017. Available online: https://www.who.int/publications/i/item/9789241565455 (accessed on 28 February 2023).
  3. Falade-Nwulia, O.; Suarez-Cuervo, C.; Nelson, D.R.; Fried, M.W.; Segalm, J.B.; Sulkowski, M.S. Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection: A Systematic Review. Ann. Intern. Med. 2017, 166, 637–648. [Google Scholar] [CrossRef] [Green Version]
  4. Manns, M.P.; Buti, M.; Gane, E.; Pawlotsky, J.M.; Razavi, H.; Terrault, N.; Younossi, Z. Hepatitis C virus infection. Nat. Rev. Dis. Prim. 2017, 3, 17006. [Google Scholar] [CrossRef]
  5. De Pace, V.; Morelli, M.C.; Ravaioli, M.; Maggi, F.; Galli, S.; Vero, V.; Re, M.C.; Cescon, M.; Pistello, M. Efficacy, Safety, and Predictors of Direct-acting antivirals in Hepatitis C Virus Patients with Heterogeneous Liver Diseases. New Microbiol. 2019, 42, 189–196. [Google Scholar]
  6. Bailey, A.L.; Al-Adwan, S.; Sneij, E.; Campbell, N.; Wiisanen, M.E. Atherosclerotic Cardiovascular Disease in Individuals with Hepatitis C Viral Infection. Curr. Cardiol. Rep. 2021, 23, 52. [Google Scholar] [CrossRef] [PubMed]
  7. Babiker, A.; Jeudy, J.; Kligerman, S.; Khambaty, M.; Shah, A.; Bagchi, S. Risk of Cardiovascular Disease Due to Chronic Hepatitis C Infection: A Review. J. Clin. Transl. Hepatol. 2017, 5, 343–362. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  8. Petta, S.; Adinolfi, L.E.; Fracanzani, A.L.; Rini, F.; Caldarella, R.; Calvaruso, V.; Cammà, C.; Ciaccio, M.; Di Marco, V.; Grimaudo, S.; et al. Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with severe liver fibrosis. J. Hepatol. 2018, 69, 18–24. [Google Scholar] [CrossRef]
  9. Di Minno, M.N.D.; Ambrosino, P.; Buonomo, A.R.; Pinchera, B.; Calcaterra, I.; Crispo, M.; Scotto, R.; Borgia, F.; Mattia, C.; Gentile, I. Direct-acting antivirals improve endothelial function in patients with chronic hepatitis: A prospective cohort study. Intern. Emerg. Med. 2020, 15, 263–271. [Google Scholar] [CrossRef]
  10. Chen, J.Y.; Cheng, P.N.; Chiu, Y.C.; Chiu, H.C.; Tsai, W.C.; Tsai, L.M. Persistent augmentation of central arterial stiffness following viral clearance by direct-acting antivirals in chronic hepatitis C. J. Viral. Hepat. 2021, 28, 159–167. [Google Scholar] [CrossRef]
  11. Ichikawa, T.; Miyaaki, H.; Miuma, S.; Motoyoshi, Y.; Narita, S.; Toda, S.; Takahashi, Y.; Honda, T.; Yajima, H.; Uehara, R.; et al. Carotid Intima-media Thickness and Small Dense Low-density Lipoprotein Cholesterol Increase after One Year of Treatment with Direct-acting Antivirals in Patients with Hepatitis C Virus Infection. Intern. Med. 2019, 58, 1209–1215. [Google Scholar] [CrossRef] [Green Version]
  12. Schmidt, F.P.; Zimmermann, T.; Wenz, T.; Schnorbus, B.; Ostad, M.A.; Feist, C.; Grambihler, A.; Schattenberg, J.M.; Sprinzl, M.F.; Münzel, T.; et al. Interferon- and ribavirin-free therapy with new direct acting antivirals (DAA) for chronic hepatitis C improves vascular endothelial function. Int. J. Cardiol. 2018, 271, 296–300. [Google Scholar] [CrossRef] [PubMed]
  13. European Association for Study of Liver; Asociacion Latinoamericana para el Estudio del Higado. EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J. Hepatol. 2015, 63, 237–264. [Google Scholar] [CrossRef] [Green Version]
  14. Stone, N.J.; Robinson, J.G.; Lichtenstein, A.H.; BaireyMerz, C.N.; Blum, C.B.; Eckel, R.H.; Goldberg, A.C.; Gordon, D.; Levy, D.; Lloyd-Jones, D.M.; et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014, 129 (Suppl. S2), S1–S45, published correction appears in Circulation 2014, 129 (Suppl. S2), S46–S48; published correction appears in Circulation 2015, 132, e396. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  15. Alberti, K.G.; Zimmet, P.Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet. Med. 1998, 15, 539–553. [Google Scholar] [CrossRef]
  16. Williams, B.; Mancia, G.; Spiering, W.; AgabitiRosei, E.; Azizi, M.; Burnier, M.; Clement, D.; Coca, A.; De Simone, G.; Dominiczak, A.; et al. 2018 Practice Guidelines for the management of arterial hypertension of the European Society of Hypertension and the European Society of Cardiology: ESH/ESC Task Force for the Management of Arterial Hypertension. J. Hypertens. 2018, 36, 2284–2309, published correction appears in J. Hypertens. 2019, 37, 456. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  17. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C: Final update of the series☆. J. Hepatol. 2020, 73, 1170–1218, published correction appears in J. Hepatol. 2023, 78, 452. [Google Scholar] [CrossRef]
  18. Psichogiou, M.; Kapelios, C.J.; Konstantonis, G.; Argyris, A.; Nasothimiou, E.; Papadopoulou, M.; Kitas, G.; Papaioannou, T.G.; Daikos, G.L.; Sfikakis, P.P.; et al. Prevalence, Incidence, and Contributors of Subclinical Atheromatosis, Arteriosclerosis, and Arterial Hypertrophy in HIV-Infected Individuals: A Single-Center, 3-Year Prospective Study. Angiology 2019, 70, 448–457. [Google Scholar] [CrossRef]
  19. Protogerou, A.D.; Fransen, J.; Zampeli, E.; Argyris, A.A.; Aissopou, E.; Arida, A.; Konstantonis, G.D.; Tentolouris, N.; Makrilakis, K.; Psichogiou, M.; et al. The Additive Value of Femoral Ultrasound for Subclinical Atherosclerosis Assessment in a Single Center Cohort of 962 Adults, Including High Risk Patients with Rheumatoid Arthritis, Human Immunodeficiency Virus Infection and Type 2 Diabetes Mellitus. PLoS ONE 2015, 10, e0132307. [Google Scholar] [CrossRef] [Green Version]
  20. Kapelios, C.J.; Argyris, A.A.; Protogerou, A.D.; Katsarolis, I.; Arida, A.; Papadopoulou, M.; Ntaroutsou, E.; Kitas, G.; Sfikakis, P.P.; Psichogiou, M. Progression of Subclinical Vascular Damage in People Living With HIV Is Not Predicted by Current Cardiovascular Risk Scores: A Prospective 3-Year Study. J. Acquir. Immune DeficSyndr. 2020, 83, 504–512. [Google Scholar] [CrossRef]
  21. Kapelios, C.J.; Masouris, G.; Argyris, A.; Konstantinidis, I.; Gamaletsou, M.N.; Kontos, A.; Zormpala, A.; Spiliopoulos, S.; Sipsas, N.V.; Protogerou, A.D. Detection of Subclinical Coronary Artery Lesions by Framingham Risk Score, Peripheral Artery Atheromatosis and Coronary Artery Calcium Score: A Pilot Study in Asymptomatic Individuals Living with HIV. AIDS Res. Hum. Retrovir. 2021, 37, 343–349. [Google Scholar] [CrossRef]
  22. Zampeli, E.; Protogerou, A.; Stamatelopoulos, K.; Fragiadaki, K.; Katsiari, C.G.; Kyrkou, K.; Papamichael, C.M.; Mavrikakis, M.; Nightingale, P.; Kitas, G.D.; et al. Predictors of new atherosclerotic carotid plaque development in patients with rheumatoid arthritis: A longitudinal study. Arthritis Res. Ther. 2012, 14, R44. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  23. Protogerou, A.; Zampeli, E.; Tentolouris, N.; Makrilakis, K.; Kitas, G.; Sfikakis, P.P. Subclinical femoral atheromatosis in rheumatoid arthritis: Comparable prevalence to diabetes mellitus in a case-control study. Ann. Rheum. Dis. 2012, 71, 1534–1536. [Google Scholar] [CrossRef]
  24. Bonou, M.; Kapelios, C.J.; Protogerou, A.D.; Mavrogeni, S.; Aggeli, C.; Markousis-Mavrogenis, G.; Psichogiou, M.; Barbetseas, J. Cardiac adiposity as a modulator of cardiovascular disease in HIV. HIV Med. 2021, 22, 879–891. [Google Scholar] [CrossRef] [PubMed]
  25. Mangili, A.; Polak, J.F.; Quach, L.A.; Gerrior, J.; Wanke, C.A. Markers of atherosclerosis and inflammation and mortality in patients with HIV infection. Atherosclerosis 2011, 214, 468–473. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  26. Mangili, A.; Polak, J.F.; Skinner, S.C.; Gerrior, J.; Sheehan, H.; Harrington, A.; Wanke, C.A. HIV infection and progression of carotid and coronary atherosclerosis: The CARE study. J. Acquir. Immune DeficSyndr. 2011, 58, 148–153. [Google Scholar] [CrossRef]
  27. Choy, E.; Ganeshalingam, K.; Semb, A.G.; Szekanecz, Z.; Nurmohamed, M. Cardiovascular risk in rheumatoid arthritis: Recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment. Rheumatology 2014, 53, 2143–2154. [Google Scholar] [CrossRef] [Green Version]
  28. Arida, A.; Protogerou, A.D.; Kitas, G.D.; Sfikakis, P.P. Systemic Inflammatory Response and Atherosclerosis: The Paradigm of Chronic Inflammatory Rheumatic Diseases. Int. J. Mol. Sci. 2018, 19, 1890. [Google Scholar] [CrossRef] [Green Version]
  29. Laurent, S.; Cockcroft, J.; Van Bortel, L.; Boutouyrie, P.; Giannattasio, C.; Hayoz, D.; Pannier, B.; Vlachopoulos, C.; Wilkinson, I.; Struijker-Boudier, H.; et al. Expert consensus document on arterial stiffness: Methodological issues and clinical applications. Eur. Heart J. 2006, 27, 2588–2605. [Google Scholar] [CrossRef] [Green Version]
  30. Vlachopoulos, C.; Xaplanteris, P.; Aboyans, V.; Brodmann, M.; Cífková, R.; Cosentino, F.; De Carlo, M.; Gallino, A.; Landmesser, U.; Laurent, S.; et al. The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society. Atherosclerosis 2015, 241, 507–532. [Google Scholar] [CrossRef] [Green Version]
  31. Karamanoglu, M.M.A.R.; O'ROURKE, M.F.; Avolio, A.P.; Kelly, R.P. An analysis of the relationship between central aortic and peripheral upper limb pressure waves in man. Eur. Heart J. 1993, 14, 160–167. [Google Scholar] [CrossRef]
  32. StataCorp. Stata User’s Guide, in Version 13.0; Stata Press: College Station, TX, USA, 2021. [Google Scholar]
  33. Petta, S.; Maida, M.; Macaluso, F.S.; Barbara, M.; Licata, A.; Craxì, A.; Cammà, C. Hepatitis C Virus Infection Is Associated With Increased Cardiovascular Mortality: A Meta-Analysis of Observational Studies. Gastroenterology 2016, 150, 145–155.e4; quiz e15–e16. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Adinolfi, L.E.; Restivo, L.; Guerrera, B.; Sellitto, A.; Ciervo, A.; Iuliano, N.; Rinaldi, L.; Santoro, A.; Li Vigni, G.; Marrone, A. Chronic HCV infection is a risk factor of ischemic stroke. Atherosclerosis 2013, 231, 22–26. [Google Scholar] [CrossRef] [PubMed]
  35. Butt, A.A.; Xiaoqiang, W.; Budoff, M.; Leaf, D.; Kuller, L.H.; Justice, A.C. Hepatitis C virus infection and the risk of coronary disease. Clin. Infect. Dis. 2009, 49, 225–232. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Pothineni, N.V.; Delongchamp, R.; Vallurupalli, S.; Ding, Z.; Dai, Y.; Hagedorn, C.H.; Mehta, J.L. Impact of hepatitis C seropositivity on the risk of coronary heart disease events. Am. J. Cardiol. 2014, 114, 1841–1845. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  37. Zampino, R.; Marrone, A.; Restivo, L.; Guerrera, B.; Sellitto, A.; Rinaldi, L.; Romano, C.; Adinolfi, L.E. Chronic HCV infection and inflammation: Clinical impact on hepatic and extra-hepatic manifestations. World J. Hepatol. 2013, 5, 528–540. [Google Scholar] [CrossRef]
  38. Okuda, M.; Li, K.; Beard, M.R.; Showalter, L.A.; Scholle, F.; Lemon, S.M.; Weinman, S.A. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 2002, 122, 366–375. [Google Scholar] [CrossRef] [Green Version]
  39. Ishizaka, N.; Ishizaka, Y.; Takahashi, E.; Tooda, E.; Hashimoto, H.; Nagai, R.; Yamakado, M. Association between hepatitis C virus seropositivity, carotid-artery plaque, and intima-media thickening. Lancet 2002, 359, 133–135. [Google Scholar] [CrossRef]
  40. Ishizaka, Y.; Ishizaka, N.; Takahashi, E.; Unuma, T.; Tooda, E.; Hashimoto, H.; Nagai, R.; Yamakado, M. Association between hepatitis C virus core protein and carotid atherosclerosis. Circ. J. 2003, 67, 26–30. [Google Scholar] [CrossRef] [Green Version]
  41. Naqvi, T.Z.; Lee, M.S. Carotid intima-media thickness and plaque in cardiovascular risk assessment. JACC Cardiovasc. Imaging 2014, 7, 1025–1038. [Google Scholar] [CrossRef] [Green Version]
  42. England, B.R.; Thiele, G.M.; Anderson, D.R.; Mikuls, T.R. Increased cardiovascular risk in rheumatoid arthritis: Mechanisms and implications. BMJ 2018, 361, k1036. [Google Scholar] [CrossRef]
  43. Agca, R.; Heslinga, S.C.; Rollefstad, S.; Heslinga, M.; McInnes, I.B.; Peters, M.J.; Kvien, T.K.; Dougados, M.; Radner, H.; Atzeni, F.; et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann. Rheum. Dis. 2017, 76, 17–28. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  44. So-Armah, K.; Benjamin, L.A.; Bloomfield, G.S.; Feinstein, M.J.; Hsue, P.; Njuguna, B.; Freiberg, M.S. HIV and cardiovascular disease. Lancet HIV 2020, 7, e279–e293. [Google Scholar] [CrossRef] [PubMed]
  45. Greenberg, J.D.; Furer, V.; Farkouh, M.E. Cardiovascular safety of biologic therapies for the treatment of RA. Nat. Rev. Rheumatol. 2011, 8, 13–21. [Google Scholar] [CrossRef]
  46. Ridker, P.M. Moving beyond JUPITER: Will inhibiting inflammation reduce vascular event rates? Curr. Atheroscler. Rep. 2013, 15, 295. [Google Scholar] [CrossRef] [Green Version]
  47. Balogh, E.; Pusztai, A.; Hamar, A.; Végh, E.; Szamosi, S.; Kerekes, G.; McCormick, J.; Biniecka, M.; Szántó, S.; Szűcs, G.; et al. Autoimmune and angiogenic biomarkers in autoimmune atherosclerosis. Clin. Immunol. 2019, 199, 47–51. [Google Scholar] [CrossRef] [PubMed]
  48. Møller, S.; Bendtsen, F. The pathophysiology of arterial vasodilatation and hyperdynamic circulation in cirrhosis. Liver Int. 2018, 38, 570–580. [Google Scholar] [CrossRef] [Green Version]
  49. Blacher, J.; Asmar, R.; Djane, S.; London, G.M.; Safar, M.E. Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension 1999, 33, 1111–1117. [Google Scholar] [CrossRef] [Green Version]
  50. Boutouyrie, P.; Tropeano, A.I.; Asmar, R.; Gautier, I.; Benetos, A.; Lacolley, P.; Laurent, S. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: A longitudinal study. Hypertension 2002, 39, 10–15. [Google Scholar] [CrossRef] [Green Version]
  51. Laurent, S.; Boutouyrie, P.; Asmar, R.; Gautier, I.; Laloux, B.; Guize, L.; Ducimetiere, P.; Benetos, A. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001, 37, 1236–1241. [Google Scholar] [CrossRef] [Green Version]
  52. Sutton-Tyrrell, K.; Najjar, S.S.; Boudreau, R.M.; Venkitachalam, L.; Kupelian, V.; Simonsick, E.M.; Havlik, R.; Lakatta, E.G.; Spurgeon, H.; Kritchevsky, S.; et al. Elevated aortic pulse wave velocity, a marker of arterial stiffness, predicts cardiovascular events in well-functioning older adults. Circulation 2005, 111, 3384–3390. [Google Scholar] [CrossRef]
  53. Reference Values for Arterial Stiffness’ Collaboration. Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: ‘establishing normal and reference values’. Eur. Heart J. 2010, 31, 2338–2350. [Google Scholar] [CrossRef]
  54. Touboul, P.J.; Hennerici, M.G.; Meairs, S.; Adams, H.; Amarenco, P.; Bornstein, N.; Csiba, L.; Desvarieux, M.; Ebrahim, S.; Hernandez Hernandez, R.; et al. Mannheim carotid intima-media thickness and plaque consensus (2004–2006–2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany. Cerebrovasc. Dis. 2012, 34, 290–296. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  55. Den Ruijter, H.M.; Peters, S.A.; Anderson, T.J.; Britton, A.R.; Dekker, J.M.; Eijkemans, M.J.; Engström, G.; Evans, G.W.; de Graaf, J.; Grobbee, D.E.; et al. Common carotid intima-media thickness measurements in cardiovascular risk prediction: A meta-analysis. JAMA 2012, 308, 796–803, published correction appears in JAMA 2013, 310, 1739. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  56. Engelen, L.; Ferreira, I.; Stehouwer, C.D.; Boutouyrie, P.; Laurent, S.; Reference Values for Arterial Measurements Collaboration. Reference intervals for common carotid intima-media thickness measured with echotracking: Relation with risk factors. Eur. Heart J. 2013, 34, 2368–2380. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Table
Table 1. Baseline characteristics of the treatment-naive HCV patients and of the matched HI, RA and PLWH groups.
Table 1. Baseline characteristics of the treatment-naive HCV patients and of the matched HI, RA and PLWH groups.
HCV
n = 29		Controls
n = 29		RA
n = 19		PLWH
n = 20
Age (years)46.3 ± 10.746.6 ± 10.550.1 ± 91046.1 ± 11.3
Male sex [n (%)]23 (79.3)23 (79.3)14 (774)18 (90)
Hypertension [n (%)]0 (0)0 (0)0 (0)0 (0)
Diabetes mellitus [n (%)]0 (0)0 (0)0 (0)0 (0)
Dyslipidemia [n (%)]3 (10.3)3 (10.3)1 (5.2)1 (5)
Cardiovascular disease [n (%)]1 (3.4)1 (3.4)2 (10.4)0 (0)
Smokers [n (%)]18 (62.1)18 (62.1)10 52.6)14 (70)
Ex-smokers [n (%)]5 (17.2)5 (17.2)4 (21)3 (15)
Duration of HCV infection (years)12.4 ± 9.3
Liver fibrosis grading
Grade 113 (43)
Grade 25 (17)
Grade 32 (7)
Grade 42 (7)
BMI (kg/m2)25.± 4.224.5 ± 2.826.1 ± 4.425.5 ± 4.5
Heart rate (beats/min)65 ± 765 ± 1165 ± 866 ± 8
Mean arterial pressure (mmHg)87 ± 8.189.5 ± 8.287.5 ± 8.887 ± 8.3
Dyslipidemia medication [n (%)]0 (0)3 (10)1 (5)0 (0)
p: non-significant for all comparisons of matched HI, RA and PLWH groups with HCV group. Abbreviations: BMI: Body mass index; HCV: Hepatitis C virus; HI: Healthy individuals; RA: Rheumatoid Arthritis; PLWH: People living with HIV.
Table
Table 2. Unadjusted comparison of vascular biomarkers between treatment-naive HCV patients and control groups.
Table 2. Unadjusted comparison of vascular biomarkers between treatment-naive HCV patients and control groups.
Vascular BiomarkersHCV
(n = 29)		HI
(n = 29)		HCV
(n = 19)		RA
(n = 19)		HCV
(n = 20)		PLWH
(n = 20)
PWV (m/s)6.9 ± 1.07.4 ± 1.56.9 ± 0.937.8± 1.96.8 ± 0.97.2 ± 0.8 *
Right IMT (mm)0.59 ± 0.130.59 ± 0.110.63 ± 0.140.75 ± 0.140.62 ± 0.150.65 ± 0.13
Left IMT (mm)0.63 ± 0.150.66 ± 0.110.65 ± 0.150.75 ± 0.14 *0.59 ± 0.140.59 ± 0.06
AIx75 (%)20.3 ± 11.021.1 ± 1223 ± 9.228.9 ± 10.218.1 ± 11.417.5 ± 13.9
Plaques [n (%)]17 (58.6)10 (34.5)8 (42)11 (58)11 (55)10 (50)
Wilcoxon sign-rank test or Mc Neymar chi-squared test were performed as appropriate. * p < 0.05 for comparisons with HCV group. Abbreviations: HI: Healthy individuals; AIx75: Augmentation index adjusted for 75 bpm; HCV: Hepatitis C virus; IMT: Intima media thickness; PLWH: People Living With HIV; PWV: Pulse wave velocity; RA: Rheumatoid arthritis.
Table
Table 3. Adjusted comparison of vascular biomarkers between treatment-naive HCV patients and matched groups.
Table 3. Adjusted comparison of vascular biomarkers between treatment-naive HCV patients and matched groups.
Vascular BiomarkersbOdds Ratiop
PWV (m/s)
HCV vs. HI−0.4-0.21
HCV vs. RA−0.97-0.07
HCV vs. PLWH−0.39-0.13
Left IMT (mm)
HCV vs. HI0.01-0.87
HCV vs. RA−0.07-0.13
HCV vs. PLWH−0.01-0.73
Right IMT (mm)
HCV vs. HI0.02-0.55
HCV vs. RA−0.07-0.17
HCV vs. PLWH−0.01-0.98
AIx75 (%)
HCV vs. HI1.3-0.66
HCV vs. RA−5.2-0.14
HCV vs. PLWH0.1-0.98
Atheromatic plaques
HCV vs. HI1.12.90.04
HCV vs. RA0.211.240.74
HCV vs. PLWH0.6920.42
Linear regression models adjusted for blood pressure and heart rate, except for Aix75, which is adjusted only for blood pressure. Logistic regression model was unadjusted for any covariate. Abbreviations: HI: healthy individuals; AIx75: augmentation index adjusted for 75 bpm; HCV: hepatitis C virus; IMT: intimal-medial thickness; PWV: pulse wave velocity; RA: rheumatoid arthritis; PLWH: people living with HIV.
Table
Table 4. Comparison of characteristics among HCV patients at baseline and 3 months post-SVR.
Table 4. Comparison of characteristics among HCV patients at baseline and 3 months post-SVR.
HCV Baseline
n = 14		HCV 3 Months after SVR
n = 14
Age (years)45.5 ± 10.445.5 ± 10.4
Male sex [n (%)]12 (86)12 (86)
Hypertension [n (%)]0 (0)0 (0)
Diabetes mellitus [n (%)]0 (0)0 (0)
Dyslipidemia [n (%)]1 (7)1 (7)
Cardiovascular disease [n (%)]1 (7)1 (7)
Smokers [n (%)]7 (50)7 (50)
Ex-smokers [n (%)]3 (21)3 (21)
BMI (kg/m2)25.2 ± 3.528.8 ± 3.5
Heart rate (beats/min)66 ± 764 ± 8
Mean arterial pressure (mmHg)82 ± 10.183.6 ± 13.7
Antihypertensive medication [n (%)]0 (0)0 (0)
Dyslipidemia medication [n (%)]0 (0)0 (0)
Diabetes mellitus medication [n (%)]0 (0)0 (0)
Abbreviations: BMI: Body mass index; HCV: Hepatitis C virus, SVR: Sustained virological response.
Table
Table 5. Comparison of vascular biomarkers in HCV patients at baseline (before treatment initiation) and follow-up (3 months after sustained virological response).
Table 5. Comparison of vascular biomarkers in HCV patients at baseline (before treatment initiation) and follow-up (3 months after sustained virological response).
Vascular BiomarkersBaselineFollow-Upp *p **
PWV (m/s)6.74 ± 0.836.38 ± 1.040.020.08
Left IMT (mm)0.62 ± 0.140.59 ± 0.110.780.34
Right IMT (mm)0.57 ± 0.090.58 ± 0.10.570.89
AIx75 (%)19.4 ± 10.722.4 ± 12.30.610.57
*: Wilcoxon sign-rank test. **: multivariate linear regression model. Abbreviations: AIx75: augmentation index adjusted for 75 bpm; HCV: hepatitis C virus; IMT: intimal-medial thickness; PWV: pulse wave velocity.
Table
Table 6. Comparison of vascular biomarkers among HCV patients: regression models.
Table 6. Comparison of vascular biomarkers among HCV patients: regression models.
CovariatesPWV (m/s)Right IMT (mm)Left IMT (mm)AIx75 (%)Plaques
HCV Duration (years)−0.030.0040.0050.020.97
Liver fibrosis grading
Grade 1 (reference)
Grade 20.0030.0060.032.90.2
Grade 3−1.4−0.010.00012.30.28
Grade 4−0.790.010.219.41.001
p: non-significant for all comparisons. Abbreviations: AIx75: augmentation index adjusted for 75 bpm; HCV: hepatitis C virus; IMT: intimal-medial thickness; PWV: pulse wave velocity.
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Androutsakos, T.; Mouziouras, D.; Katelani, S.; Psichogiou, M.; Sfikakis, P.P.; Protogerou, A.D.; Argyris, A.A. A Comparative Study on the Presence and Reversibility of Subclinical Arterial Damage in HCV-Infected Individuals and Matched Controls. Viruses 2023, 15, 1374. https://doi.org/10.3390/v15061374

AMA Style

Androutsakos T, Mouziouras D, Katelani S, Psichogiou M, Sfikakis PP, Protogerou AD, Argyris AA. A Comparative Study on the Presence and Reversibility of Subclinical Arterial Damage in HCV-Infected Individuals and Matched Controls. Viruses. 2023; 15(6):1374. https://doi.org/10.3390/v15061374

Chicago/Turabian Style

Androutsakos, Theodoros, Dimitrios Mouziouras, Stamatia Katelani, Mina Psichogiou, Petros P. Sfikakis, Athanase D. Protogerou, and Antonios A. Argyris. 2023. "A Comparative Study on the Presence and Reversibility of Subclinical Arterial Damage in HCV-Infected Individuals and Matched Controls" Viruses 15, no. 6: 1374. https://doi.org/10.3390/v15061374

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