PMID- 35892670 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230308 IS - 2227-9059 (Print) IS - 2227-9059 (Electronic) IS - 2227-9059 (Linking) VI - 10 IP - 8 DP - 2022 Jul 22 TI - Fatty Liver as Potential Biomarker of Atherosclerotic Damage in Familial Combined Hyperlipidemia. LID - 10.3390/biomedicines10081770 [doi] LID - 1770 AB - 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. FAU - Mandraffino, Giuseppe AU - Mandraffino G AUID- ORCID: 0000-0003-0272-2237 AD - Lipid Center, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. AD - Internal Medicine Unit, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. FAU - Morace, Carmela AU - Morace C AD - Lipid Center, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. AD - Internal Medicine Unit, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. FAU - Franze, Maria Stella AU - Franze MS AUID- ORCID: 0000-0002-9815-5275 AD - Medicine and Hepatology Unit, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. FAU - Nassisi, Veronica AU - Nassisi V AUID- ORCID: 0000-0003-1003-8179 AD - Internal Medicine Unit, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. FAU - Sinicropi, Davide AU - Sinicropi D AD - Internal Medicine Unit, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. FAU - Cinquegrani, Maria AU - Cinquegrani M AUID- ORCID: 0000-0002-7694-1259 AD - Internal Medicine Unit, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. FAU - Saitta, Carlo AU - Saitta C AD - Medicine and Hepatology Unit, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. FAU - Scoglio, Riccardo AU - Scoglio R AD - Italian College of General Practitioners and Primary Care Professionals (SIMG), Section Messina, 98122 Messina, Italy. FAU - Marino, Sebastiano AU - Marino S AD - Italian College of General Practitioners and Primary Care Professionals (SIMG), Section Messina, 98122 Messina, Italy. FAU - Belvedere, Alessandra AU - Belvedere A AD - Italian College of General Practitioners and Primary Care Professionals (SIMG), Section Messina, 98122 Messina, Italy. FAU - Cairo, Valentina AU - Cairo V AD - Internal Medicine Unit, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. AD - Medicine and Hepatology Unit, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. FAU - Lo Gullo, Alberto AU - Lo Gullo A AUID- ORCID: 0000-0003-4383-0314 AD - Unit of Rheumatology, Department of Medicine, ARNAS Garibaldi Hospital, 95100 Catania, Italy. FAU - Scuruchi, Michele AU - Scuruchi M AD - Lipid Center, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. FAU - Raimondo, Giovanni AU - Raimondo G AD - Medicine and Hepatology Unit, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. FAU - Squadrito, Giovanni AU - Squadrito G AUID- ORCID: 0000-0003-0508-4816 AD - Internal Medicine Unit, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy. LA - eng PT - Journal Article DEP - 20220722 PL - Switzerland TA - Biomedicines JT - Biomedicines JID - 101691304 PMC - PMC9332610 OTO - NOTNLM OT - FCH OT - HOMA-IR OT - NAFLD OT - carotid atherosclerosis OT - liver fibrosis OT - liver ultrasound OT - noninvasive diagnosis COIS- The authors declare no conflict of interest. EDAT- 2022/07/28 06:00 MHDA- 2022/07/28 06:01 PMCR- 2022/07/22 CRDT- 2022/07/27 04:55 PHST- 2022/06/17 00:00 [received] PHST- 2022/07/20 00:00 [revised] PHST- 2022/07/20 00:00 [accepted] PHST- 2022/07/27 04:55 [entrez] PHST- 2022/07/28 06:00 [pubmed] PHST- 2022/07/28 06:01 [medline] PHST- 2022/07/22 00:00 [pmc-release] AID - biomedicines10081770 [pii] AID - biomedicines-10-01770 [pii] AID - 10.3390/biomedicines10081770 [doi] PST - epublish SO - Biomedicines. 2022 Jul 22;10(8):1770. doi: 10.3390/biomedicines10081770.