| Objective:More than 140 million people live in the three plateau areas with an altitude of more than 2500 m.Most highlanders can be successfully adapted to the high-altitude environment.However,about 5%～10% of highlanders suffer from chronic highaltitude diseases.High-altitude pulmonary hypertension(HAPH)is one of them.However,there have been no large epidemiological studies done in the native Tibetans in China to determine the prevalence,risk factors and cardiac structure and function using an echo Doppler-based screening method.At the same time,the association between EPAS1 gene polymorphisms and HAPH in the Tibetan population remains unclear.To study the prevalence and related risk determinants of HAPH in native Tibetans.To evaluate cardiac structure and function of highlanders exposed to chronic highaltitude environment.To explore the association between EPAS1 gene polymorphism and HAPH in native Tibetans.Methods:A total of 1886 residents over 18 years old(female: 57.6%,average age: 48 ±15years old)were enrolled by the multi-stage,stratified and random sampling method in Luhuo County,Ganzi Prefecture,Sichuan Province.The survey included questionnaire,physical examination.finger pulse oxygen test,and echocardiography.Cardiac structure and function of HAPH patients,borderline pulmonary hypertension person and healthy highlanders matched for age,gender and BMI were compared.The genotypes of EPAS1 rs13419896,rs12619696,rs1868092,rs4953388,rs495334,rs1562453,rs4953354,rs186778 and rs6735530 and its relationship with HAPH were evaluated.Results:1.The prevalence of HAPH among native Tibetans in Luhuo county of Sichuan province was 7.4%.2.In binary logistic regression analysis,the risk factors of HAPH in native Tibetans include aging,male,overweight and obesity,male waist circumference ≥90cm,female waist circumference ≥ 80 cm,blood pressure ≥ 135 mm Hg,male HDL-C < 1.03mmol/L,female HDL-C < 1.29mmol/L,HGB,HCT and RBC increased,Sp O2 and e GFR decreased.3.Multi-variate logistic analysis showed that advanced age(OR=1.051,95%CI:1.033-1.069),low pulse oxygen saturation(OR=1.096,95%CI:1.047-1.148)and waist circumference ≥ 90 cm in men or waist circumference ≥ 80 cm in women(OR=1.845,95%CI:1.088-3.130)were independent risk factors for HAPH in native Tibetans.4.There was no significant difference in cardiac structure between the Tibetan population living in high altitude areas and the Han population in the plain after adjusting for body surface area(p > 0.05).5.Compared with people with mPAP < 20 mm Hg,tricuspid annular plane systolic excursion(TAPSE),right ventricular fractional area change(RV FAC)and RV TEI index in HAPH patients decreased(1.99 ±0.28 vs.2.22 ±0.27,0.36 ±0.06 vs.0.46±0.09,0.51 ±0.16 vs.0.42 ±0.11,p < 0.05).The free wall and global strain rate of right ventricle decreased(-20.7 ±3.5 vs.-25.4 ±3.5,-18.7 ±3.1 vs.-22.7 ±3.4,p < 0.05).6.Compared with subjects with mPAP<20mm Hg,TAPSE,RV FAC,and the RV global strain rate did not change in participants with PAP between 20 and 30 mm Hg,but RV TEI index(0.47 ±0.15 vs.0.42 ±0.11,p < 0.05)and the right ventricular free wall strain rate(RV FLS)decreased(-23.9±3.8vs.-25.4 ±3.5,p < 0.05).7.With the increase of mPAP,the left ventricular end-diastolic diameter,left ventricular end-diastolic volume,left ventricular end-systolic volume,left ventricular mass index and stroke volume decreased(46.5±4.2vs.45.2±3.2vs.44.1±3.2,104.5±22.4vs.96.8±17.4vs.93.4±18.6,34.3±11.3vs.30.4±8.9vs.28.9±8.9,79.2±21.1vs.75.4 ±17.8vs.71.3 ±18.6,70.7±14.7vs.66.4±13.0vs.64.7±12.9).The MV Em decreased(8.3±1.6vs.8.0±1.9vs.6.6±1.2)and MV E/Em increased(9.0±2.3vs.9.2±4.0vs.10.8±3.7,p=0.002).The multiple linear regression analysis showed that MV Em and MVE / Em were negatively correlated with mPAP(p= 0.000 and 0.012,respectively)after adjusting confounding factors.8.MV Em was significantly lower in normal pulmonary pressure group compared with those without metabolic syndrome(Met S)(7.8±1.2 vs.8.5±1.7,p=0.028);In the 20≤ mean pulmonary artery pressure ≤30mm Hg group,the m V Em and m V E/A of patients with Mets were decreased(7.2±1.9 vs.8.2±1.9,p=0.046;0.9±0.4 vs.1.3±0.7,p=0.027,respectively);In HAPH group,MV E/Em was increased in patients with Mets(12.6±4.6vs.10.0±3.0,p=0.005)9.After adjusting for age,sex,BMI,blood lipids,hemoglobin,Sp O2 and other confounding factors,it was found that rs1867785 locus,GG or GA type of EPAS1 gene increased the risk of HAPH in Tibetans(GG+GA/AA: OR=2.192,95%CI:1.029-4.670,p < 0.05).10.After adjusting for age,sex,BMI,blood lipids,hemoglobin,Sp O2 and other confounding factors,it was found that rs6735530 locus,GG or GA type of EPAS1 gene decreased the risk of HAPH in Tibetans(GG/GA+AA: OR=0.338,95%CI:0.168-0.682,P < 0.01).Conclusion:1.HAPH as measured by echocardiography affected 7.4% of native Tibetans residing at an average altitude of 3500 m in western Sichuan Province,China.Age,low pulse oxygen saturation and abdominal obesity are independent risk factors of HAPH.Weight control may potentially protect subjects from HAPH.2.RV systolic function decreased in native Tibetans with PAP between 20 and30 mm Hg,which provides a theoretical basis for early detecting subjects with highrisk to develop to HAPH.3.After chronic high-altitude exposure,the left ventricular diastolic function(LVDD)changes in native Tibetans,which is closely related to pulmonary artery pressure.In addition,metabolic syndrome further aggravates LVDD.4.The rs1867785 and rs6735530 polymorphisms of EPAS1 gene are associated with the prevalence of HAPH in native Tibetan population. |
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