Combined Effects Of Smoking And Blood Pressure Caused By Cardiovascular Disease

BACKGROUD AND OBJECTIVE:Increased blood pressure (BP) and smoking are the first and second most common risk factors of cardiovascular diseases (CVD) in the world, including Chinese population, which also can be modified at lower cost compared to the other intervention, for example, blood-cholesterol-lowering. If these 2 risk factors have a synergistic impact on cardiovascular events, lowering BP and quitting smoking will contribute more to reducing CVD than would be expected from ignoring their interaction. We aimed to identify the joint effects of cigarette smoking in combination with BP as well as the independent impact on the risk of CVD incidence in Chinese adults.DESIGN AND METHODS:SubjectsIn the 1991 China National Hypertension Survey, a multi-stage random cluster sampling design was used to select a nationally representative sample of Chinese adults aged 15 years or older from all 30 provinces of mainland China. Overall,83,533 men and 86,338 women aged 40 years or older at their baseline examination were eligible to participate in the follow-up study in 1999-2000. A total of 158,666 (93.4%) study participants (or their proxies) were identified and interviewed as part of the follow-up study. In this report, study participants missing information on BP (n=283), cigarette smoking (n=14,578) were excluded from all analyses, and those with prevalent CVD (n=4,195) were excluded from the analysis of CVD incidence either.Baseline ExaminationBaseline data were collected in 1991. Data on demographic characteristics, medical history, and lifestyle risk factors were obtained using a standard questionnaire administered by trained staff. Cigarette smoking was defined as having smoked at least 1 cigarette per day for 1 year or more. For participants who reported past or current cigarette smoking, information on the number of cigarettes smoked per day along with the duration of cigarette smoking was also collected. Work-related physical activity was assessed. Alcohol consumption was defined as drinking alcohol at least 12 times during the last year. Body weight and height were measured in light indoor clothing without shoes according to a standardized protocol. Body mass index (BMI) was calculated as weight in kilograms divided by height in square meters. Three BP measurements were taken after the study participant had been seated quietly for 5 minutes using a standard mercury sphygmomanometer according to a standard protocol. The means of 3 systolic BP (SBP) and diastolic BP (DBP) measures were used in all analyses.Follow-Up ProceduresThe follow-up investigation, which was conducted between 1999 and 2000, included tracking study participants or their proxies to a present address, performing interviews to ascertain disease status and vital information, and obtaining hospital records and death certificates. An end point assessment committee within each province reviewed all abstracted information to confirm or reject the occurrence of study outcomes using pre-established criteria. A study-wide end point assessment committee at the Chinese Academy of Medical Sciences in Beijing, China reviewed all hospital records and death certificates and determined the final diagnosis of event or the underlying cause of death. All members of the local and study-wide end point assessment committees were blinded to the study participant's baseline risk factor information.Causes of death were coded according to the International Classification of Diseases, Ninth Revision (ICD-9). For this analysis, CVD incidence was defined as a confirmed diagnosis of CVD during the follow-up period or CVD listed as an underlying cause of death (ICD-9390.0 to 398.9,401.0 to 429.9, and 430.0 to 438.9) among those without a history of CVD.Statistical MethodsBaseline characteristics were compared between 4 categories of SBP levels (normal<120 mmHg, prehypertension 120 to 139 mmHg, Stage 1 hypertension 140 to 159 mmHg, and Stage 2 hypertension>160 mmHg), uncontrolled and controlled hypertension using%1 tests for categorical variables and ANOVA for continuous variables. Person-years of follow-up were calculated from the date of baseline examination until the date of CVD, death, or follow-up interview for each participant.Cox proportional hazards models were used in all analyses. The associations between BP and CVD incidence across smoking history were explored by categorical analyses in which participants were classified into 4 categories according to levels of baseline SBP and DBP, uncontrolled and controlled hypertension, with SBP<120 or DBP<80 mmHg as the reference group, adjusted for baseline age, education, alcohol consumption (in men), geographic region (north versus south), urbanization (rural versus urban), and the new onset diabetes during follow-up, respectively. These cut points were chosen on the basis of BP classification according to JNC7. The associations between smoking history and CVD incidence were studied by stratified analyses in which participants were classified into nonsmoking (reference category), former smoking and current smoking among those with normal as well as high BP(SBP≥140 mmHg or DBP≥90 mmHg). Dose-response relationships for current smokers were investigated using nonsmokers as the reference category compared with different levels of daily cigarettes smoked (1 to 9, 10 to 19, and≥20 cigarettes per day in men, while 1 to 19, and≥20 cigarettes per day in women), as well as of the pack-years (1 to 10.9,11 to 25.9 and≥26 pack-years in men, while 1-19.9, and≥20 pack-years in women) in both high and normal SBP study participants.To evaluate biological interaction between high BP and smoking history on CVD incidence, we used the method of the additive interaction according to Rothman. We dichotomized SBP at 140 mmHg or DBP at 90 mmHg, and smoking history as nonsmoking and current smoking, and assessed relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). These measures are defined as followWhere RRA and RRB are the adjusted relative risk (RR or HR) associated with risk factors A and B alone, and RRAB is the RR for those exposed to both risk factors. No interaction means that RERI and AP are equal to 0 and SI is equal to 1. Both the point estimation and the 95%confidence interval of the RERI, AP, and SI were assessed using a method that accounting for the asymmetric distribution of confidence limits for risk ratio.Statistical analyses were conducted using SAS statistical software (version 9.0; SAS Institute Inc).RESULTSDuring an average of 8.3 years follow-up, we recorded a total of 11,785 CVD events, of which 7753 were fatal CVD. Among hypertensive patients, only 9.5%and 9.0%were taking antihypertensive medication, and 23.5%and 24.5%achieved blood pressure control (<140/90 mm Hg), respectively, in men and women at baseline.Compared with those with SBP<120 or DBP<80 mmHg, a linear relationship between SBP or DBP and CVD incidence among nonsmokers, former smokers, and current smokers (all P<0.05 for linear trend) was found, with higher slope of CVD risk against the increased BP among current smokers, compared with among nonsmokers and former smokers. For example, compared with SBP SBP<120 mmHg, the multivariate-adjusted RRs for prehypertension, S1-HT, S2-HT, uncontrolled and controlled hypertensive SBP were 1.31 (95%CI 1.16,1.48),1.86(95%CI 1.63,2.12),3.02 (95%CI 2.63,3.47), 3.62(95%CI 2.98,4.41), and 1.56(95%CI 1.02,2.38), respectively, among male nonsmokers, while the corresponding figures were 1.42 (95%CI 1.29,1.56),2.37(95% CI 2.13,2.63),3.73 (95%CI 3.32,4.18),5.34(95%CI 4.59,6.21), and 1.49(95%CI 1.04, 2.13), respectively, among male current smokers. Among women, the linear relationships between BP and CVD incidence were persisted in nonsmokers, former and current smokers.Both former and current smoking was associated with the increased risk of CVD among men and women. For men, compared with nonsmoking, the relative risks (RR) for former smoking and current smoking were 1.60 (95%CI 1.36,1.89) and 2.17(95%CI 1.43, 3.30),0.62(95%CI 0.17,2.28) and 1.22(95%CI 1.12,1.33), respectively, for those with SBP<140 and SBP>140 mmHg. While in women, former smoking was still at an increased risk for CVD incidence, no matter how was the level of SBP. The relationships persisted in stratified analysis according to diastolic BP at baseline.We found a statistically significant additive interaction of high SBP (>140 mmHg) and current smoking for the risk of CVD after adjusting for other risk factors among men and women. As for men, the multivariate-adjusted RRs of CVD were 3.53 (95%CI 2.55, 4.88),1.42 (95%CI 1.04,1.94) and 1.76 (95%CI,1.63,1.91) for current smokers with high SBP, current smokers with normal SBP and nonsmokers with high SBP, respectively, with the reference category was nonsmokers with SBP<140 mmHg. The RERI, AP, and SI were 1.03(95%CI 0.53,2.03),31%(95%CI 13%,38%), and 1.78(95%CI 1.44,2.21), respectively, which meant there was 1.03 relative excess risk due to the additive interaction,31%of CVD exposed to both risk factors was attributable to the additive interaction, and the risk of total CVD incidence in those who had SBP>140 mmHg and current smoked was 1.78 times as high as the sum of risks in the participants exposed to a single risk factor alone. The relationships persisted in relation to diastolic BP in combination with current smoking in men and women.CONCLUSIONSIn conclusion, the prospective risk of incident CVD increased with elevated BP levels of both SBP and DBP, and both uncontrolled and controlled hypertensive patients were at increased risk in spite of antihypertensive drugs treatment offered, with smoking history modified this risk. Furthermore, the remaining high risk in controlled hypertensive patients calls for a more focused action to influence the global risk factors. Both former and current smoking was associated with the increased risk of CVD among men and women, and the excess risk for current smoking, compared with nonsmoking, was more than that for former smoking. A statistically significant additive interaction between high SBP or DBP and current smoking on the risk of CVD were found, after adjusting for other risk factors.