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Fatty Liver as Potential Biomarker of Atherosclerotic Damage in Familial Combined Hyperlipidemia

Familial combined hyperlipidemia (FCH) is a very common inherited lipid disorder, characterized by a high risk of developing cardiovascular (CV) disease and metabolic complications, including insulin resistance (IR) and type 2 diabetes mellitus (T2DM). The prevalence of non-alcoholic fatty liver dis...

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Autores principales: Mandraffino, Giuseppe, Morace, Carmela, Franzè, Maria Stella, Nassisi, Veronica, Sinicropi, Davide, Cinquegrani, Maria, Saitta, Carlo, Scoglio, Riccardo, Marino, Sebastiano, Belvedere, Alessandra, Cairo, Valentina, Lo Gullo, Alberto, Scuruchi, Michele, Raimondo, Giovanni, Squadrito, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332610/
https://www.ncbi.nlm.nih.gov/pubmed/35892670
http://dx.doi.org/10.3390/biomedicines10081770
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author Mandraffino, Giuseppe
Morace, Carmela
Franzè, Maria Stella
Nassisi, Veronica
Sinicropi, Davide
Cinquegrani, Maria
Saitta, Carlo
Scoglio, Riccardo
Marino, Sebastiano
Belvedere, Alessandra
Cairo, Valentina
Lo Gullo, Alberto
Scuruchi, Michele
Raimondo, Giovanni
Squadrito, Giovanni
author_facet Mandraffino, Giuseppe
Morace, Carmela
Franzè, Maria Stella
Nassisi, Veronica
Sinicropi, Davide
Cinquegrani, Maria
Saitta, Carlo
Scoglio, Riccardo
Marino, Sebastiano
Belvedere, Alessandra
Cairo, Valentina
Lo Gullo, Alberto
Scuruchi, Michele
Raimondo, Giovanni
Squadrito, Giovanni
author_sort Mandraffino, Giuseppe
collection PubMed
description Familial combined hyperlipidemia (FCH) is a very common inherited lipid disorder, characterized by a high risk of developing cardiovascular (CV) disease and metabolic complications, including insulin resistance (IR) and type 2 diabetes mellitus (T2DM). The prevalence of non-alcoholic fatty liver disease (NAFLD) is increased in FCH patients, especially in those with IR or T2DM. However, it is unknown how precociously metabolic and cardiovascular complications appear in FCH patients. We aimed to evaluate the prevalence of NAFLD and to assess CV risk in newly diagnosed insulin-sensitive FCH patients. From a database including 16,504 patients, 110 insulin-sensitive FCH patients were selected by general practitioners and referred to the Lipid Center. Lipid profile, fasting plasma glucose and insulin were determined by standard methods. Based on the results of the hospital screening, 96 patients were finally included (mean age 52.2 ± 9.8 years; 44 males, 52 females). All participants underwent carotid ultrasound to assess carotid intima media thickness (cIMT), presence or absence of plaque, and pulse wave velocity (PWV). Liver steatosis was assessed by both hepatic steatosis index (HSI) and abdomen ultrasound (US). Liver fibrosis was non-invasively assessed by transient elastography (TE) and by fibrosis 4 score (FIB-4) index. Carotid plaque was found in 44 out of 96 (45.8%) patients, liver steatosis was found in 68 out of 96 (70.8%) and in 41 out of 96 (42.7%) patients by US examination and HSI, respectively. Overall, 72 subjects (75%) were diagnosed with steatosis by either ultrasound or HSI, while 24 (25%) had steatosis excluded (steatosis excluded by both US and HSI). Patients with liver steatosis had a significantly higher body mass index (BMI) compared to those without (p < 0.05). Steatosis correlated with fasting insulin (p < 0.05), liver stiffness (p < 0.05), BMI (p < 0.001), and inversely with high-density lipoprotein cholesterol (p < 0.05). Fibrosis assessed by TE was significantly associated with BMI (p < 0.001) and cIMT (p < 0.05); fibrosis assessed by FIB-4 was significantly associated with sex (p < 0.05), cIMT (p < 0.05), and atherosclerotic plaque (p < 0.05). The presence of any grade of liver fibrosis was significantly associated with atherosclerotic plaque in the multivariable model, independent of alcohol habit, sex, HSI score, and liver stiffness by TE (OR 6.863, p < 0.001). In our cohort of newly diagnosed, untreated, insulin-sensitive FCH patients we found a high prevalence of liver steatosis. Indeed, the risk of atherosclerotic plaque was significantly increased in patients with liver fibrosis, suggesting a possible connection between liver disease and CV damage in dyslipidemic patients beyond the insulin resistance hypothesis.
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spelling pubmed-93326102022-07-29 Fatty Liver as Potential Biomarker of Atherosclerotic Damage in Familial Combined Hyperlipidemia Mandraffino, Giuseppe Morace, Carmela Franzè, Maria Stella Nassisi, Veronica Sinicropi, Davide Cinquegrani, Maria Saitta, Carlo Scoglio, Riccardo Marino, Sebastiano Belvedere, Alessandra Cairo, Valentina Lo Gullo, Alberto Scuruchi, Michele Raimondo, Giovanni Squadrito, Giovanni Biomedicines Article Familial combined hyperlipidemia (FCH) is a very common inherited lipid disorder, characterized by a high risk of developing cardiovascular (CV) disease and metabolic complications, including insulin resistance (IR) and type 2 diabetes mellitus (T2DM). The prevalence of non-alcoholic fatty liver disease (NAFLD) is increased in FCH patients, especially in those with IR or T2DM. However, it is unknown how precociously metabolic and cardiovascular complications appear in FCH patients. We aimed to evaluate the prevalence of NAFLD and to assess CV risk in newly diagnosed insulin-sensitive FCH patients. From a database including 16,504 patients, 110 insulin-sensitive FCH patients were selected by general practitioners and referred to the Lipid Center. Lipid profile, fasting plasma glucose and insulin were determined by standard methods. Based on the results of the hospital screening, 96 patients were finally included (mean age 52.2 ± 9.8 years; 44 males, 52 females). All participants underwent carotid ultrasound to assess carotid intima media thickness (cIMT), presence or absence of plaque, and pulse wave velocity (PWV). Liver steatosis was assessed by both hepatic steatosis index (HSI) and abdomen ultrasound (US). Liver fibrosis was non-invasively assessed by transient elastography (TE) and by fibrosis 4 score (FIB-4) index. Carotid plaque was found in 44 out of 96 (45.8%) patients, liver steatosis was found in 68 out of 96 (70.8%) and in 41 out of 96 (42.7%) patients by US examination and HSI, respectively. Overall, 72 subjects (75%) were diagnosed with steatosis by either ultrasound or HSI, while 24 (25%) had steatosis excluded (steatosis excluded by both US and HSI). Patients with liver steatosis had a significantly higher body mass index (BMI) compared to those without (p < 0.05). Steatosis correlated with fasting insulin (p < 0.05), liver stiffness (p < 0.05), BMI (p < 0.001), and inversely with high-density lipoprotein cholesterol (p < 0.05). Fibrosis assessed by TE was significantly associated with BMI (p < 0.001) and cIMT (p < 0.05); fibrosis assessed by FIB-4 was significantly associated with sex (p < 0.05), cIMT (p < 0.05), and atherosclerotic plaque (p < 0.05). The presence of any grade of liver fibrosis was significantly associated with atherosclerotic plaque in the multivariable model, independent of alcohol habit, sex, HSI score, and liver stiffness by TE (OR 6.863, p < 0.001). In our cohort of newly diagnosed, untreated, insulin-sensitive FCH patients we found a high prevalence of liver steatosis. Indeed, the risk of atherosclerotic plaque was significantly increased in patients with liver fibrosis, suggesting a possible connection between liver disease and CV damage in dyslipidemic patients beyond the insulin resistance hypothesis. MDPI 2022-07-22 /pmc/articles/PMC9332610/ /pubmed/35892670 http://dx.doi.org/10.3390/biomedicines10081770 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mandraffino, Giuseppe
Morace, Carmela
Franzè, Maria Stella
Nassisi, Veronica
Sinicropi, Davide
Cinquegrani, Maria
Saitta, Carlo
Scoglio, Riccardo
Marino, Sebastiano
Belvedere, Alessandra
Cairo, Valentina
Lo Gullo, Alberto
Scuruchi, Michele
Raimondo, Giovanni
Squadrito, Giovanni
Fatty Liver as Potential Biomarker of Atherosclerotic Damage in Familial Combined Hyperlipidemia
title Fatty Liver as Potential Biomarker of Atherosclerotic Damage in Familial Combined Hyperlipidemia
title_full Fatty Liver as Potential Biomarker of Atherosclerotic Damage in Familial Combined Hyperlipidemia
title_fullStr Fatty Liver as Potential Biomarker of Atherosclerotic Damage in Familial Combined Hyperlipidemia
title_full_unstemmed Fatty Liver as Potential Biomarker of Atherosclerotic Damage in Familial Combined Hyperlipidemia
title_short Fatty Liver as Potential Biomarker of Atherosclerotic Damage in Familial Combined Hyperlipidemia
title_sort fatty liver as potential biomarker of atherosclerotic damage in familial combined hyperlipidemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332610/
https://www.ncbi.nlm.nih.gov/pubmed/35892670
http://dx.doi.org/10.3390/biomedicines10081770
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