Sonographic fatty liver, overweight and ischemic heart disease

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1 PO Box 2345, Beijing , Chin World J Gstroenterol 2005;11(31): World Journl of Gstroenterology ISSN [email protected] ELSEVIER 2005 The WJG Press nd Elsevier Inc. All rights reserved. CLINICAL RESEARCH Sonogrphic ftty liver, overweight nd ischemic hert disese Yu-Cheng Lin, Huey-Ming Lo, Jong-Dr Chen Yu-Cheng Lin, Jong-Dr Chen, Deprtment of Fmily Medicine nd Center for Environmentl nd Occuptionl Medicine, Shin Kong Wu Ho-Su Memoril Hospitl, Tipei 111, Tiwn, Chin Huey-Ming Lo, Deprtment of Internl Medicine, Shin Kong Wu Ho-Su Memoril Hospitl; School of Medicine, Fu Jen Ctholic University, Tipei 111, Tiwn, Chin Correspondence to: Dr. Jong-Dr Chen, Deprtment of Fmily Medicine nd Center for Environmentl nd Occuptionl Medicine, Shin Kong Wu Ho-Su Memoril Hospitl, 95,Wen Chng Rod, Shih Lin, Tipei 111, Tiwn, Chin. [email protected] Telephone: Fx: Received: Accepted: Abstrct AIM: To demonstrte the prevlence of sonogrphic ftty liver, overweight nd ischemic hert disese (IHD) mong the mle workers in Tiwn, nd to investigte the possible ssocition of these three fctors. METHODS: From July to September 2003, totl of mle ircrft-mintennce workers ged from 22 to 65 yers (men 40.5) underwent n nnul helth exmintion, including nthropometricl evlution, blood pressure mesurement, personl medicl history ssessment, biochemicl blood nlysis, bdominl ultrsonogrphic exmintion nd digitl electrocrdiogrphy (ECG). The Student s t-test, χ 2 test nd multivrite logistic regression nlysis were utilized to evlute the reltionship between IHD nd slient risk fctors. RESULTS: The ll-over prevlence of overweight ws 41.4%, nd tht of ftty liver ws 29.5% (mild, moderte nd severe ftty liver being 14.5%, 11.3%, nd 3.7%, respectively); while the prevlence of ischemic chnges on ECG ws 17.1% in this study. The bnorml rtes for conventionl IHD risk fctors including hypertension, dyslipidemi, hyperglycemi nd overweight incresed in ccordnce with the severity of ftty liver. Overweight nd severity of ftty liver were independently ssocited with incresed risks for developing IHD. Overweight subjects hd 1.32-fold (95%CI: ) incresed IHD risk. Prticipnts with mild, moderte, nd severe ftty liver hd 1.88-fold (95%CI: ), 2.37-fold (95%CI: ) nd 2.76-fold (95%CI: ) incresed risk for developing IHD. The prevlence of ischemic ECG for the ftty liver-ffected subjects with or without overweight ws 30.1% nd 19.1%, while tht of overweight subjects free from ftty liver ws 14.4%. Compred to the subjects without ftty liver nor overweight, IHD risk for the three subgroups bove ws s follows: OR: 2.95 (95%CI: ), OR: 1.60 (95%CI: ) nd OR: 1.11 (95%CI: ), respectively. CONCLUSION: The presence of ftty liver nd its severity should be crefully considered s independent risk fctors for IHD. Results of the study suggest the synergistic effect between ftty liver nd overweight for developing IHD. Abdominl sonogrphic exmintion my provide vluble informtion for IHD risk ssessment in ddition to limited report bout liver sttus, especilly for overweight mles The WJG Press nd Elsevier Inc. All rights reserved. Key words: Ftty liver; Ischemic hert disese; Overweight; Mle; Middle-ged Lin YC, Lo HM, Chen JD. Sonogrphic ftty liver, overweight nd ischemic hert disese. World J Gstroenterol 2005; 11(31): INTRODUCTION Ftty chnge in the liver is closely ssocited with overweight sttus nd metbolic impirments such s hyperglycemi, nd dyslipidemi [1-3] which re lso regrded s fctors for therosclerosis [1,4,5] nd ischemic hert disese (IHD) [6-9]. However, the ssocition between ftty liver nd IHD is witing for epidemiologicl investigtion. Since resting electrocrdiogrm (ECG) nd bdominl sonogrphic exmintion re two routine, non-invsive helth exmintions used in medicl check-ups in Tiwn [10-15], we hd the opportunity to exmine the ssocition between ftty liver nd ischemic ECG chnges, the hllmrk of IHD nd strong predictor for crdic events [16-18]. The purpose of this study ws to evlute the reltionships between ftty liver nd IHD utilizing epidemic dt. Dt nlyses were controlled for conventionl risk fctors, especilly overweight. MATERIALS AND METHODS Subjects Records from totl of mle ircrft mintennce workers who underwent periodic helth exmintion from July to September Methods The helth exmintions included nthropometricl evlution, mesurement of weight nd height, systolic nd distolic blood pressure. Definition of overweight ws BMI 25 kg/m 2, bsed on WHO criteri [19]. A questionnire bout personl medicl history, including lcohol (usge more thn once week: yes vs no) nd tobcco (current usge: yes vs no) consumption ws filled by the exminees.

2 Lin YC et l. Ftty liver reltes to ischemic hert disese 4839 Biochemicl blood tests were conducted by Hitchi utonlyzer model 7150 (Hitchi Corp, Tokyo, Jpn), including fsting plsm glucose, levels of triglyceride, nd totl, low, nd high-density lipoprotein (LDL, HDL) cholesterol. The definition of hypertension ws systolic blood pressure 18.7 kp or distolic blood pressure 12 kp. The cut points of hyperglycemi, hypocholesterolemi, hypercholesterolemi, nd hypertriglyceridemi were fsting sugr 6.1 mmol/l, HDL <1.0 mmol/l, totl cholesterol 5.2 mmol/l nd triglyceride 17.0 mmol/l. Abdominl ultrsonogrphic exmintions were performed using convex-type rel-time electronic scnners (Toshib SSA-340 with 3.75 MHz convex-type trnsducer) by three gstrointestinl specilists who were blind to the medicl history nd blood test results of the exminees. The definition of ultrsonic ftty liver ws bsed on comprtive ssessment of imge brightness reltive to the kidneys, in line with previously reported dignostic criteri [10,20-23]. Severity of ftty liver ws clssified ccording to the following modified scoring system [10,13,15,22,23] : brightness compred to kidneys (0-3), blurring of gll bldder wll (0-3), blurring of heptic veins (0-3), blurring of portl vein (0-3), fr gin ttenution (0-3). Severity ws defined s mild (totl scores of 2-6), moderte (7-10), nd severe (11-15) ftty liver. A digitl electrocrdiogrph recorder (Kenz Crdico 1207; Suzuken Co., Ltd 8, Higshi Kth-mchi, Higshiku Ngoy , Jpn.) ws used for IHD ssessment. IHD ws defined bsed on evidence of resting ECG ischemic bnormlities, s expressed in computerized Minnesot code ( , , ) [12,16-18]. The Student s t nd χ 2 tests were used for nlyzing continuous vribles nd ctegoricl vribles, respectively. Multivrite logistic regression ws utilized to evlute the reltionship between IHD nd slient risk fctors. SAS softwre ws used for sttisticl nlysis (Version 8.0; SAS Institute, Cry, NC, USA). RESULTS After 63 cses whose dt were incomplete (e.g., biochemicl blood test, questionnire) were excluded, totl of subjects were enrolled in the finl nlysis. The excluded subjects hd similr distribution of nthropometric mesurement nd biochemicl dt s subjects in finl nlysis. As shown in Tble 1, the ge for this smple popultion rnged from 22 to 63 yers (men, 40.5), the men vlue of BMI ws 24.6 kg/m 2. The over-ll prevlence of overweight ws 41.4%, while tht of ftty liver ws 29.5%. The prevlence of ischemic chnges in the resting ECG ws 17.1%. The mens nd stndrd devitions for serum blood sugr nd therogenic lipid profile were 5.7±1.1 mmol/l of fsting sugr, 5.1±0.9 mmol/l of totl cholesterol, 1.3±0.3 mmol/l of HDL cholesterol, 3.3±0.8 mmol/l of LDL cholesterol, nd 17.1±13.9 mmol/l of triglyceride. Tble 1 Bseline chrcteristics of middle-ged mle workers in Tiwn from periodic helth exmintion (men±sd, n = 2 025) Risk fctor Vlue Rnge Age (yr) 40.5± Height (cm) 169.6± Body weight (kg) 70.9± BMI (body mss index) (kg/m 2 ) 24.6± Systolic blood pressure (kp) 17.1± Distolic blood pressure (kp) 10.6± Fsting sugr (mmol/l) 5.7± Cholesterol totl (mmol/l) 5.1± Cholesterol HDL (mmol/l) 1.3± Cholesterol LDL (mmol/l) 3.3± Triglyceride (mmol/l) 17.1± ECG with ischemic chnges (n, %) 347 (17.1) Ftty liver (n, %) 597 (29.5) Overweight (n, %) 839 (41.4) Smoking (n, %) 702 (34.7) Alcohol use (n, %) 444 (21.9) Risk-fctor distribution mong subgroups strtified ccording to the severity of ftty liver, is presented in Tble 2. The prevlence of mild, moderte nd severe ftty liver ws 14.5%, 11.3%, nd 3.7%, respectively. The bnorml rtes for conventionl IHD risk fctor including hypertension, dyslipidemi, hyperglycemi nd overweight incresed in ccordnce with the severity of ftty liver (Figure 1). Tble 2 Assessment of risk fctors strtified ccording to severity of ftty liver (FL) n = Risk fctors Non FL Mild FL Moderte FL Severe FL (70.5%) 294 (14.5%) 228 (11.3%) 75 (3.7%) Age (yr) 39.8± ± ±9.4 c 42.6±9.5 e BMI (body mss index) (kg/m 2 ) 23.9± ± ±2.7 c 29.0±3.1 e Systolic blood pressure (kp) 16.9± ± ±2.2 c 18.3±2.6 e Distolic blood pressure (kp) 10.5± ± ±1.5 c 11.4±1.7 e Fsting sugr (mmol/l) 5.6± ± ±1.5 c 6.1±1.6 e Cholesterol totl (mmol/l) 5.0± ± ±0.9 c 5.3±0.9 e Cholesterol HDL (mmol/l) 1.3± ± ±0.2 c 1.1±0.2 e Cholesterol LDL (mmol/l) 3.3± ± ±0.8 c 3.4±0.9 e Triglyceride (mmol/l) 15.0± ± ±20.9 c 27.3±22.3 e ECG with ischemic chnges (n, %) 191 (13.4) 67 (22.8) 64 (28.1) c 25 (33.3) e Overweight (n, %) 457 (32.0) 143 (48.6) 170 (74.6) c 69 (92.0) e Smoking (n, %) 491 (34.4) 106 (36.1) 84 (36.8) 21 (28.0) Alcohol use (n, %) 304 (21.3) 73 (24.8) 54 (23.7) 13 (17.3) P<0.05 vs non FL group; c P<0.05 vs non FL group; e P<0.05 vs non FL group.

3 4840 ISSN CN / R World J Gstroenterol August 21, 2005 Volume 11 Number 31 Abnorml rte (%) of risk fctors Systolic hypertension Non-ftty liver Mild ftty liver Moderte ftty liver Severe ftty liver Distolic hypertension Hyperglycemi Hypo-HDL cholesterolemi Hyper-LDL cholesterolemi Hypercholesterolemi Hypertriglyceridemi IHD risk fctors strtified by the severity of ftty liver Overweight Figure 1 Abnorml rtes of IHD risk fctors for middle-ged mle workers in Tiwn. Multivrible nlysis nd odds rtios for IHD re summrized in Tble 3. Results showed tht overweight, incresed systolic blood pressure nd ftty liver severity were independently ssocited with IHD risk. Overweight subjects hd 1.32-fold (95%CI: ) incresed IHD risk. Prticipnts with mild, moderte, nd severe ftty liver experienced 1.88-fold (95%CI: ), 2.37-fold (95%CI: ), nd 2.76-fold (95%CI: ) incresed risk for developing IHD. The prevlence of ischemic ECG nd odds rtios (OR) for IHD of the middle-ged mle workers in Tiwn, strtified ccording to overweight nd ftty liver sttus, re presented in Tble 4. The prevlence of ischemic ECG nd the risk for IHD of the ftty liver-ffected subjects with or without overweight nd the overweight subjects free from ftty liver ws 30.1%, OR: 2.95 (95% CI: ), 19.1%, OR:1.60 (95% CI: ) nd 14.4%, OR: 1.11 (95% CI: ), respectively, compred to the subjects without ftty liver nor overweight. Result of test for interction between ftty liver nd overweight ws significnt (P<0.05). DISCUSSION Stress test or even coronry ctheteriztion exmintion nturlly hs better specificitiy in IHD dignosis, nd biopsy of liver is the gold stndrd for heptostetosis. However, in the viewpoints of sfety, ethic nd screening purpose, resting ECG nd bdominl sonogrphic exmintion hve cceptble relibility nd re prcticl tools of epidemiologicl survey [10,16-18,21]. Our study indictes tht dult mle workers with ftty liver re more likely to develop IHD compred to subjects Tble 3 Multivrite logistic regression nlysis for the risk fctors for IHD Risk fctors Odds rtio 95% CI Age (yr) Systolic blood pressure Distolic blood pressure Fsting sugr Cholesterol totl Cholesterol HDL Cholesterol LDL Triglyceride Overweight Ftty liver b Mild ftty liver Moderte ftty liver Severe ftty liver 2.76 d Smoking Alcohol consumption P<0.05 vs Non FL group; b P<0.001 vs Non FL group; d P < vs Non FL group. without ftty liver. This finding is comptible to previous studies demonstrting tht ftty liver, s developer of oxidtive stress plys crdinl role in crdic dysfunction [24,25]. Of prticulr significnce is the fct tht non-overweight subjects with ftty liver experience significntly incresed IHD risk (OR: 1.6). As Prk et l. [26], concluded, for non-obese men with ftty liver, systemic inflmmtory response increses, nd systemic inflmmtory response is the integrl prt of the therosclerotic process [27,28]. IHD prevention for nonoverweight subjects hving ftty liver should be emphsized in clinicl prctice. Findings of this study show synergistic interction between ftty liver nd overweight, this combintion mkes middle-ged mles hve significntly highest IHD risk (OR: 2.95) in the four entities (Tble 4). Similr findings hve been shown in studies bout insulin resistnce [7,10,26,29-31], these studies mnifested tht both overweight nd ftty liver re closely correlted with insulin resistnce, which ggrvtes the therogenic metbolic process [32,33], ccelerting the development of therosclerosis [34] nd IHD [35]. For overweight middle-ged mle workers with ftty liver, comprehensive mngement for IHD risk reduction is needed. Serum sugr nd lipids hd insignificnt effects on developing IHD in this study, these findings re similr to our previous study bsed on Estern popultion [36]. Genetic differences [37] nd differences in diet components [38] my hve ffected these findings. Smoking nd drinking did not show significnt effects on developing IHD in this study, the prtil explntion Tble 4 Odds rtio for IHD strtified ccording to ftty liver (FL) nd overweight sttus Non-overweight (n = 1 186) Overweight (n = 839) Non-FL FL Non-FL FL (n = 970) (n = 216) (n = 458) (n = 381) Ischemic ECG (%) 125 (12.9) 41 (19.1) 66 (14.4) 115 (30.1) 1 OR (95%CI) 1.0 (-) 1.60 c ( ) 1.11 ( ) 2.95 b ( ) P<0.05 vs overweight nd ftty, djusted for ge, blood pressure, blood sugr nd lipid profile; b P<0.001 vs non-overweight nd non-fl group; c P<0.05 vs non-overweight nd non-fl group; 1 OR: djusted odds rtio; CI: confidence intervl.

4 Lin YC et l. Ftty liver reltes to ischemic hert disese 4841 might be tht binry questionnire could provide only limited informtion bout the dose-effect, which is importnt in the development of IHD, nd then leds to the unstedy results [36,39]. The findings of this study demonstrte tht ftty liver is n independent risk fctor for IHD. Abdominl sonogrphic exmintion my not only provide limited report bout the liver sttus, but lso cn provide vluble informtion for IHD risk ssessment, especilly for those who re overweight. ACKNOWLEDGMENTS The uthors would like to cknowledge the personnel of the Deprtment of Fmily Medicine nd Internl Medicine, Shin Kong Wu Ho-Su Memoril Hospitl for their full support nd generous ssistnce. REFERENCES 1 Akhoshi M, Amski Y, Sod M, Toming T, Ichimru S, Nkshim E, Seto S, Yno K. Correltion between ftty liver nd coronry risk fctors: popultion study of elderly men nd women in Ngski, Jpn. 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