Association Of Different Obesity And Metabolically Risk Factors And The Risk Of Incident Hypertension:A Prospective Cohort Study

Obese people are often accompanied by excessive accumulation of fat with abnormal characteristics of insulin resistance,dyslipidemia and other metabolic abnormalities,which are known as metabolically unhealthy obesity.However,a meta-analysis suggested that about 35%of obese adults aged 20 years and over exhibit good metabolic status(called "metabolically healthy obesity" phenotype).The association between metabolically healthy obesity and human health is still not completely clear,and the findings on the risk of cardiovascular disease are still inconsistent.Therefore,it is urgent to explore the potential relationship between obesity and human health from the perspective of metabolism.Hypertension is one of the most common chronic non-communicable diseases worldwide,and also a major risk factor of cardiovascular disease.Understanding the association of metabolically healthy obesity and hypertension might be helpful to explain the underlying mechanism linking metabolically healthy obesity and cardiovascular disease risk.There are few epidemiological studies focusing on the association between different metabolically healthy obesity and the incidence of hypertension.The results are inconsistent and the following problems exist:1)studies used different metabolically healthy definitions when estimating the associated hypertension risk,so comparing existing data is difficult;2)most studies were mainly focused on overweight/general obesity(OWGO),but overlooked abdominal obesity(AO),which is closely related to metabolism;3)obesity and metabolically status may change with age and lifestyle,but the associations of dynamic changes of obesity or metabolic measurements and hypertension were not clear.Limited evidence was available on the dynamic change of obesity and metabolic status and its association with hypertension risk.Therefore,this study will explore the association between different obesity and metabolically risk factors and hypertension risk to provide prospective evidence for the prevention of hypertension.Objectives1.To explore the relationship between different metabolically healthy and obesity phenotypes and risk of hypertension.2.To examine the relationship between dynamic changes of obesity measurements in terms of body mass index(BMI),waist circumference(WC)and waist-to-height ratio(WHtR)and risk of hypertension.3.To examine the relationship between dynamic changes of metabolic components based on metabolically unhealthy status in terms of fasting plasma glucose(FPG),triglyceride(TG)and high-density lipoprotein cholesterol(HDL-C)and risk of hypertension.4.To analyze the change of metabolically healthy obesity phenotypes and compare their relationship to hypertension risk.MethodsA prospective cohort study was designed to conduct baseline examination in a rural area in Henan province during 2007 to 2008.A total of 20194 rural adults aged? 18 years were recruited by cluster random sampling.Information on demographic,behavioral risk factors,disease history,anthropometric and laboratory measurements were collected by questionnaire interview,physical examination and blood sample collection.These participants were then followed up with the same procedures as the baseline examination during 2013 to 2014.We excluded participants with baseline hypertension,or had missing data on anthropometric and laboratory measurements at baseline,or died during follow-up,or were lost to follow-up.A total of 10293 eligible study participants were included in the final analysis.Modified Poisson Regression models were used to estimate the relative risks(RRs)and 95%confidence intervals(CIs)for incident hypertension associated with different metabolically healthy and obesity phenotypes.To examine the potential modification effects by known associated factors,we performed a series of subgroup analyses stratified by sex,age,smoking,alcohol drinking,physical activity,and family history of hypertension.Interactions were assessed by multiplicative interactions terms in the adjusted models.Sensitivity analyses were finally conducted to test the robustness of our findings.Based on 10293 study participants:1)we excluded participants who had missing data on obesity measurements at follow-up and got 10210 people to assess the association of obesity measurements change and hypertension;2)we excluded participants who had missing data on laboratory measurements at follow-up and got 8999 people to assess the association of laboratory measurements change and hypertension;3)we excluded participants who had missing data on obesity and laboratory measurements at follow-up and got 8990 people to assess the association of metabolically healthy obesity phenotypes change and hypertension.Dynamic changes of obesity measurements(BMI,WC and WHtR)were calculated as measurements at follow-up minus that at baseline.We classified participants based on their metabolic components(FPG,TG and HDL-C)healthy status at baseline and follow-up.Modified Poisson Regression models were used to explore the association between dynamic changes of above measurements and hypertension risk.The component ratio of different metabolically healthy obesity phenotypes at follow-up were calculated for each phenotype at baseline,respectively.RRs and 95%CIs of hypertension associated with dynamic change of metabolically healthy obesity phenotypes were calculated as compared with the stable groups accordingly.Results1.During a median follow-up of 6.0 years,we identified 2071 new hypertension cases among 10293 study participants.The cumulative incidence of hypertension was 20.1%.The RRs and 95%CIs of hypertension for metabolically healthy/OWGO,metabolically unhealthy/non-OWGO and metabolically unhealthy/OWGO were 1.59(1.23-2.06),1.62(1.37-1.92)and 2.51(2.13-2.96),respectively,as compared with metabolically healthy/non-OWGO.The RRs and 95%CIs of hypertension for metabolically healthy/AO,metabolically unhealthy/non-AO and metabolically unhealthy/AO were 1.54(1.16-2.05),1.62(1.38-1.90)and 2.53(2.15-2.97),respectively,as compared with metabolically healthy/non-AO.Age may influence the association between metabolically healthy obesity phenotypes and risk of hypertension(Pinteraction<0.05).2.With the increase of the relative dynamic change of BMI,WC and WHtR,the risks of hypertension were significantly increased(Ptrend<0.001).Age and baseline BMI may affect the relationship between dynamic change of BMI and the risk of hypertension(Pinteraction<0.05).The relationship between change of AO(based on WC or WHtR)and hypertension risk might be different depending on sex(Pinteraction<0.05).3.When the group with normal FPG level at baseline and follow-up was used as the reference,the RRs and 95%CIs of hypertension increased by 22%(RR:1.22,95%CI:1.06-1.41),15%(RR:1.15,95%CI:1.02-1.31)and 19%(RR:1.19,95%CI:1.05-1.34)for participants with abnormal FPG status at only baseline,follow-up,or both survey times,respectively.When the group with normal TG level at baseline and follow-up was used as the reference,the risk of hypertension for the normal TG at baseline but abnormal at follow-up group significantly increased(RR:1.14,95%CI:1.01-1.28).Age may modify the association between dynamic changes of FPG and TG and risk of hypertension(Pinteraction<0.05).However,we did not find significant association between change in HDL-C and risk of hypertension.4.For people with metabolically healthy/non-obesity phenotype at baseline,about 40%and 10%developed metabolically unhealthy/non-obesity and metabolically unhealthy/obesity phenotypes at follow-up,respectively.Of those with metabolically healthy/obesity phenotype at baseline,approximately 60%developed metabolically unhealthy/obesity at follow-up.For participants with metabolically healthy/non-OWGO,metabolically healthy/OWGO or metabolically unhealthy/non-OWGO(based on BMI criteria)at baseline,people who developed metabolically unhealthy/OWGO at follow-up were at higher risk of hypertension,as compared with those had stable status.The RRs and 95%CIs were:2.48(1.76-3.49),1.58(1.04-2.41)and 1.44(1.20-1.73),respectively.For participants with metabolically healthy/non-AO,metabolically healthy/AO or metabolically unhealthy/non-AO(based on WC criteria)at baseline,people who developed metabolically unhealthy/AO at follow-up had increased risk of hypertension,as compared with those had stable status.The RRs and 95%CIs were:2.02(1.43-2.84),1.64(1.02-2.61)and 1.35(1.13-1.60),respectively.Conclusions1.Metabolically healthy obesity was associated with increased risk of hypertension.We found a large proportion of metabolically unhealthy phenotype among non-obese people,which was also associated with greater risk of hypertension.This result indicates that screening for metabolically risk factors also should be implemented among non-obese people who may be potentially at high risk of hypertension but easily ignored.2.Relative or absolute dynamic changes in obesity measurements(BMI,WC and WHtR)were significantly associated with risk of hypertension.The risk of hypertension was significantly increased in those who were non-obese at baseline but obese at follow-up and in those who were obese at both baseline and follow-up,as compared with those who were not obese at baseline or follow-up.Thus,long-term obesity control programs should be implemented to prevent hypertension.3.Compared with the stable status of normal level of FPG and TG,people who had normal FPG or TG at baseline but developed abnormal status at follow-up were at greater risk of hypertension.The association between changes of FPG and TG and hypertension might be modified by age.4.For people with baseline metabolically healthy obesity status,about 60%of people developed different degrees of metabolically unhealthy obesity phenotype at follow-up.The risk of hypertension was significantly increased,suggesting that the metabolically healthy obesity phenotype was not a benign metabolic state of obesity,but an intermediate transitional state of metabolically unhealthy obesity.