Combined Effects Of Family History Of Cardiovascular Disease And Other Risk Factors On Stroke

Background and objectives:Stroke is an important public health problem all around the world and have already generated heavy disease burden.Stroke is also a multi-genes complex disease and its risk factors include two main aspects: heredity and environments.The Inner Mongolians who lived in agricultural and pastoral areas of Inner Mongolia are high-risk population of stroke.However,there is no large-population prospective study aiming at the combined effects of family history of cardiovascular disease(FHCVD)and other cardiovascular risk factors(CVRFs)on stroke in Inner Mongolians.Our study will use a cohort which have been followed up for almost ten years to explore the combined effects of FHCVD and heart rate on stroke in Inner Mongolians.Meanwhile,we will evaluate the effect of clustering of CVRFs on stroke incidence and find some high predictive clusters among Inner Mongolians in China.Our study will be beneficial to comprehend the risk factors of stroke and provide new evidence about therapeutic and preventive methods on stroke and promote the national health.Our study will also be beneficial to increase the level of disease prevention and control in Inner Mongolia population.Subjects and methods:1.Baseline investigation: A cross-section survey was conducted from May 2002 to June 2003,during which 2589 participants aged 20 years and older were recruited from 32 villages in 2 adjacent townships in Tongliao,Inner Mongolia Province.All study participants received written informed consent,and they were administered interview using a standard questionnaire,and the related physical examination and blood samples collection were conducted by trained staffs.Data on demographic characteristics,medical history,FHCVD,lifestyle(smoking and drinking),Blood pressure,height,weight,waist circumference and hip circumference were measured in all participants according to standard methods.Fasting blood samples were taken in the morning and separated in the field,and then were sent to laboratory under low temperature and frozen at-80?.Fasting plasma glucose(FPG),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and C-reactive protein(CRP)were tested in all participants.2.Follow-up survey: From 2004 to 2012,our group surveyed the 2589 subjects recruited in the baseline study four times(on average,one survey every two years).The outcome was defined as the first occurrence of stroke,including ischemic stroke,during the time from the baseline to the last follow-up.We interviewed the monitoring data and hospital medical records for the subjects who experienced a stroke by household to confirm the stroke events using standard questionnaires.3.Statistical analysis:According to the different status of FHCVD and heart rate,participants were categorized into four groups(participants without FHCVD and heart rate < 80,participants with FHCVD and heart rate<80,participants without FHCVD and heart rate?80,participants with FHCVD and heart rate?80).Cox proportional hazards model was used to compute hazard ratio(HR)and 95% Confidence Interval(95%CI)of FHCVD and heart rate on stroke.We also use Kaplan–Meier curves and compared the statistical differences of different curves by log-rank test.According to the different number of CVRFs clustering,participants were categorized into four groups: the participants with 0,1,2 and ?3 CVRFs.Cox proportional hazards model was used to compute HR and 95%CI of stroke incidence among four groups.FHCVD was combined with one or two CVRFs(dyslipidemia,diabetes,hypertension,waistline,overweight or obesity,and tachycardia).Every clusters' AUC and 95%CI was calculated and compared.Epidata3.0 software was used to establish a database,and all data was checked after data entry for two times.All statistical analyses were conducted using SAS?SPSS and Medcalc statistical software.All p-values were based on a 2-sided test and a significance level of 0.05.Results:During the follow-up period,among 2589 participants that were followed,there were a total of 2578 participants that were finally included in the analysis due to 6 participants being lost to follow-up and 5 having missed important data.Among the 2578 participants,there were 1058(41.04%)males,1520(58.86%)females and 338(13.11%)participants with FHCVD.There were 1433(55.59%)participants without FHCVD and heart rate<80,201(7.8%)participants with FHCVD and heart rate<80,807(31.30%)participants without FHCVD and heart rate?80,137(5.3%)participants with FHCVD and heart rate?80.During the 9.2 years' follow-up,124 new stroke cases and 76 new ischemic stroke cases occurred.The cumulative incidence of stroke was 4.8% and incidence density was 529/100000 person-years.The cumulative incidence of ischemic stroke was 2.9% and incidence density was 319/100000 person-years.The Kaplan–Meier curves results showed that the cumulative incidence of stroke were 3.84%,9.45%,4.09% and 12.41% for participants without FHCVD and heart rate<80,participants with FHCVD and heart rate<80,participants without FHCVD and heart rate ? 80,participants with FHCVD and heart rate ? 80,respectively.The cumulative incidence among the four groups were different and the difference among the four groups was statistically significant(P<0.0001).The cumulative incidence of ischemic stroke were 2.23%,5.47%,2.48% and 9.49% for participants without FHCVD and heart rate<80,participants with FHCVD and heart rate<80,participants without FHCVD and heart rate ? 80,participants with FHCVD and heart rate ? 80,respectively.The cumulative incidence among the four groups were different and the difference among the four groups was statistically significant(P<0.0001).Cox regression analysis for risk of stroke showed that age-and gender-adjusted HR(95% CI)of stroke in the participants with FHCVD and heart rate<80,participants without FHCVD and heart rate?80,participants with FHCVD and heart rate?80 were 1.64(0.97-2.77),1.21(0.79-1.87),2.20(1.27,3.81),compared with those without FHCVD and heart rate < 80.The HR of participants with FHCVD and heart rate?80 had statistical significance;After multiple adjustment,the HR were 1.07(0.61-1.87),1.08(0.68-1.70),1.76(0.98-3.15),respectively.The HR of participants with FHCVD and heart rate?80 had marginally statistical significance.Cox regression analysis for risk of ischemic stroke showed that age-and gender-adjusted HR of ischemic stroke in the participants with FHCVD and heart rate<80,participants without FHCVD and heart rate?80,participants with FHCVD and heart rate?80 were 1.61(0.81-3.22),1.26(0.72-2.21),2.89(1.51,5.53),compared with those without FHCVD and heart rate < 80.The HR of participants with FHCVD and heart rate?80 had statistical significance on ischemic stroke;After multiple adjustment,the HR were 1.04(0.49-2.21),1.26(0.70-2.26),2.70(1.33-5.51),respectively.The HR of participants with FHCVD and heart rate ? 80 remained statistical significance on ischemic stroke.Cox regression analysis for the clustering of CVRFs showed that unadjusted HR of stroke in the participants with 1,2,? 3 CVRFs were 2.99(1.47-6.08)? 4.51(2.23-9.12)?5.23(2.65-10.34),compared with those without CVRF.After multiple adjustments,the HR of stroke in the participants with 1,2,?3 CVRFs were 2.12(1.03-4.34)?2.91(1.40-5.97)?3.39(1.68-6.84),compared with those without CVRF.No matter unadjusted or adjusted,the HR increased with the increasing number of CVRFs(P<0.0001).The analysis of two CVRFs clustering showed that area under curve(AUC)of clustering of FHCVD and hypertension was 0.704(0.686–0.721),which was significantly higher than any other clustering(P <0.0001).The analysis of three CVRFs clustering showed that,on the basis of FHCVD,clustering of hypertension with other CVRFs and clustering of diabetes with tachycardia had higher AUC than other clustering(P<0.05).Conclusions:The incidence of stroke and ischemic stroke were high in in the Inner Mongolians.With the increasing of follow-up time,the incidence of stroke rising.Stroke had become an important disease and public health issues threaten to the health of the Inner Mongolians who lived in agricultural and pastoral areas.FHCVD is an important risk factor of ischemic stroke in Inner Mongolians.Furthermore,Mongolians with both FHCVD and faster heart rate had higher risk of ischemic stroke.The clustering of CVRFs significantly increased the risk of stroke.Hypertension is an important CVRF and an important prognostic value of stroke.On the basis of FHCVD,the cluster of hypertension with other CVRFs and the cluster of diabetes with tachycardia had higher predictive value for stroke than other clusters.