| BACKGROUND AND OBJECTIONNonalcoholic fatty liver disease(NAFLD),a hepatic manifestation of metabolic syndrome,has been considered as a risk factor of adverse cardiovascular prognosis and was associated with chronic kidney disease(CKD).Elevated brachial-ankle pulse wave velocity(ba-PWV)and carotid intima-media thickness(CIMT)have been adopted as indicators of subclinical atherosclerosis.Low-grade albuminuria,as an early marker of endothelial dysfunction and kidney damage,has been associated with metabolic disorders and cardiovascular diseases.However,epidemiological studies manifesting the associations of subclinical atherosclerosis and low-grade albuminuria with NAFLD and hepatic fibrosis remain controversy.Therefore,we aimed to investigate the impact of vascular indicators,including ba-PWV,CIMT and low-grade albuminuria on incident NAFLD and liver fibrosis based on a community population aged 40 years or older through a non-invasive method.SUBJECTS AND METHODSA prospective observational cohort study was conducted in Jiading District,Shanghai of China,from March 2010 to May 2014.A total of 10375 subjects aged ≥ 40 years were interviewed at baseline.A standard questionnaire was inquired by trained staff through face-to-face interviews to collect sociodemographic information,including age,sex,educational levels,smoking and drinking status,medical and family history,as well as lifestyle factors.All participants underwent physical examinations and biochemical detection.Ba-PWV and CIMT were measured at baseline.The upper quartiles of two indicators were assessed as subclinical atherosclerosis status.Baseline urinary albumin excretion was obtained by a first-voided early morning spot urine sample.Low-grade albuminuria was defined as the upper quartile of urinary albumin-to-creatine ratio(ACR).At follow-up visit,NAFLD was diagnosed by hepatic ultrasonography and liver fibrosis was assessed by non-invasive markers,including NAFLD fibrosis score(NFS)≥-1.455,fibrosis-4 score(FIB-4)≥ 1.3 and aspartate aminotransferase to platelet ratio index(APRI)≥ 0.5.RESULTS1.Association of subclinical atherosclerosis with incident NAFLD and fibrosis assessed by non-invasive markers:We included 3433 subjects who were aged ≥ 40 years and free of NAFLD at baseline.A total of 654(19.1%)subjects developed NAFLD during the follow-up of 4.3(4.2-4.5)years.In addition,412(12.0%),468(14.4%)and 97(3.4%)patients with NAFLD progressed to NFS ≥-1.455,FIB-4 ≥ 1.3 and APRI ≥ 0.5,respectively.After adjusting for potential confounders,each standard deviation(SD)increment of ba-PWV was associated with 20.0%(OR 1.20;95% confidence interval [CI] 1.07-1.33),22.0%(OR 1.22;95% CI1.08-1.39),17.0%(OR 1.17;95% CI 1.04-1.32)and 37.0%(OR 1.37;95% CI 1.07-1.75)higher risk of incident NAFLD,higher NFS,FIB-4 and APRI,respectively.Compared with the lowest quartile of ba-PWV,the highest quartile of ba-PWV had 63.0%(OR 1.63;95% CI 1.20-2.22),112.0%(OR 2.12;95% CI 1.42-3.17),86.0%(OR 1.86;95% CI1.28-2.69;P = 0.0011)and 201.0%(OR 3.01;95% CI 1.29-7.04)higher risk of incident NAFLD,higher NFS,FIB-4 and APRI,respectively.Besides,per SD increase of CIMT was associated with a 12.0%(OR 1.12;95% CI 1.01-1.24)higher risk of incident NAFLD.After stratified by glycemic status,the association of ba-PWV with incident NAFLD and higher probability of fibrosis remained significant whereas CIMT was only associated with NAFLD occurrence in non-diabetic population.2.Association of low-grade albuminuria with incident NAFLD and fibrosis assessedby non-invasive markers:We enrolled 3308 participants without NAFLD at recruitment.After 4.3(4.2-4.5)years of follow-up,622(18.8%)were detected as incident NAFLD.Additionally,389(11.8%),448(14.3%)and 91(3.3%)of the patients with NAFLD were assessed to progress to NFS≥-1.455,FIB-4 ≥ 1.3 and APRI ≥ 0.5,respectively.After adjusting for potential confounders,each SD increment of ACR was associated with a significant higher risk of incident NAFLD(OR 1.13;95% CI 1.02-1.25)and higher values of NFS(OR 1.17;95%CI 1.04-1.32),FIB-4(OR 1.12;95% CI 1.02-1.24)and APRI(OR 1.24;95% CI1.02-1.51),respectively.Besides,patients with low-grade albuminuria imposed 53.0%(OR1.53;95% CI 1.12-2.09),91.9%(OR 1.92;95% CI 1.30-2.84),82.3%(OR 1.82;95%CI 1.27-2.62)and 147.0%(OR 2.47;95% CI 1.20-5.09)greater risk on incident NAFLD and higher values of NFS,FIB-4 and APRI,respectively.This significance was persisted in the subgroup of non-diabetic population.CONCLUSIONS:Our study demonstrated that elevated ba-PWV and low-grade albuminuria were independently associated with incident NAFLD and higher probability of hepatic fibrosis,whereas CIMT was associated with incident NAFLD but not with hepatic fibrosis.The association was remained significant in non-diabetic patients but not in diabetic patients.Future prospective studies are warranted to validate our findings. |
