Combined Effects Of CVD Family History And C-reactive Protein And Smoking And Hypertension On Stroke

ObjectiveWe aimed to evaluate the independent and combined effects of cardiovascular disease(CVD)family history and high serum C-reactive protein(CRP)level,to investigate the independent and combined effects of smoking and hypertension on the stroke incidence based on a 9.2-year prospective study among Inner Mongolians in China.Study participants and methodStudy participantsMongolians aged 20 years and older were recruited between 2002-2003 from 32 villages in the counties of Kezuohou Banner and Naiman Banner in Inner Mongolia,an autonomous region in north China.Among them,886 persons were excluded from the study for the reasons of refusing to participate in the study or already having CVDs or endocrine diseases which may affect the outcome of this study.Thus,2589 individuals were finally included in the study.Baseline surveyThe information on demographic features,personal medical history,family history of CVD and lifestyle risk factors were collected for all participants face to face by trained staff with a standard questionnaire designed by ourselves.Body weight,height and waist circumference were measured using standard methods.Blood pressure measurements were taken 3 times and the mean value of the 3 records was used in analysis.Overnight fasting blood samples were obtained to measure total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,triglycerides,fasting plasma glucose,CRP etc.Follow-up researchOur study followed all participants for 4 times in total from 2004 to 2012,and the relevant data of occurrence of stroke or death during the follow-up period was collected.Statistical analysisWe categorized all participants into four groups: no CVD family history /low CRP level,no CVD family history /high CRP level,CVD family history /low CRP level,and CVD family history /high CRP level.The cumulative stroke incidence rates among the four groups were estimated using the Kaplan-Meier curves and compared by log-rank test.We used Cox proportional hazards models to compute the hazard ratios(HRs)of total stroke,ischemic stroke and hemorrhagic stroke among the four groups by adjusting for important confounding factors.We set a multiplicative interaction term of CVD family history and CRP in the Cox proportional hazards model and tested its effect on the total stroke,ischemic stroke and hemorrhagic stroke incidences.According to the status of smoking and hypertension,the participants were categorized into 4 subgroups: non-smokers without hypertension,smokers without hypertension,non-smokers with hypertension,and smokers with hypertension.The cumulative incidence rates of stroke among the 4 subgroups were estimated using Kaplan–Meier curves and compared by log-rank test.The HRs of total stroke,ischemic stroke and hemorrhagic stroke across the 4 subgroups were computed in the Cox proportional hazards models in the same way.All statistical analyses were conducted using SAS 9.4 statistical software.Two-tailed P<0.05 was considered statistically significant.ResultsBy the end of July 31,2012,we have followed 2589 participants for an average of 9.2 years.A total of 124 stroke events occurred during the follow-up period,the cumulative incidence of stroke was 4.79%,and the incidence density was 519 per 100,000 person-years.Among all stroke events,there were 76 cases(61.29%)of ischemic stroke,46 cases(37.10%)of hemorrhagic stroke,and 2(1.61%)cases of unknown type stroke.Among all participants,there were 953 patients with hypertension(37.39%),1131 smokers(44.37%),and 330 individuals having the CVD family history(12.75%).After adjusting for important confounding factors,there was no association between CVD family history,CRP and the risk of total stroke,ischemic stroke and hemorrhagic stroke.The cumulative stroke incidence rates in the no CVD family history /low CRP level,no CVD family history /high CRP level,CVD family history /low CRP level,and CVD family history /high CRP level groups were 3.44%,4.36%,7.34% and 12.67%,respectively.The log-rank test showed significant differences in the incidence rates of stroke among the four subgroups.Compared with no CVD family history /low CRP level group,CVD family history /high CRP level group was associated with an increased risk of total stroke(HR: 1.73;95%CI: 1.01-2.96;P=0.045)and ischemic stroke(HR: 2.04;95%CI: 1.05-3.98;P=0.036),but there was no significant change in the risk of hemorrhagic stroke.The combination of family history of CVD and high CRP level increased the risk of stroke,but there was no interaction between them on the risk of stroke.After adjusting for important confounding factors,hypertension increased the risk of total stroke(HR: 2.71;95%CI: 1.71-4.29;P=0.001),ischemic stroke(HR: 1.84;95%CI: 1.05-3.23 P=0.032)and hemorrhagic stroke(HR: 5.94;95%CI: 2.51-14.04;P<0.001).Smoking increased the risk of ischemic stroke(HR: 1.89;95%CI: 1.11-3.22;P=0.018),but it was not significantly associated with the risk of stroke or hemorrhagic stroke.During the follow-up period,the cumulative incidence rates of stroke in non-smokers without hypertension,smokers without hypertension,non-smokers with hypertension,and smokers with hypertension group were 1.17%,2.78%,7.78% and 11.78%,respectively.The log-rank test showed that the incidence rates of stroke were significantly different among four subgroups.In the Cox proportional hazards model,compared with the non-smokers without hypertension group,non-smokers with hypertension(HR: 2.81;95%CI: 1.39-5.69;P=0.004)and smokers with hypertension(HR: 3.17;95%CI: 1.56-6.41;P=0.001)had increased risk of stroke.The combination of smoking and hypertension increased the risk of stroke,ischemic stroke and hemorrhagic stroke,and there was interaction between them on the risk of stroke,ischemic stroke rather than hemorrhagic stroke.ConclusionAmong Mongolian population,the effect of CVD family history or high CRP level on stroke incidence alone may be relatively small,whereas there is combined effect between these two factors on stroke risk.Coexistence of the two factors may increase the risk of stroke,especially for ischemic stroke.These results indicate that it is necessary to lower CRP levels in the population with CVD family history to prevent stroke.Among Mongolian population,hypertension is an independent risk factor for stroke,both for ischemic stroke and hemorrhagic stroke.Smoking is an independent risk factor for stroke,particularly for ischemic stroke.There was a significant interaction between smoking and hypertension on the risk of ischemic stroke.These findings suggest that it is of great importance for hypertensive to quit smoking and for smokers to undergo antihypertensive therapy in order for better prevention of stroke.