高血压患者吸烟与心血管疾病死亡和全因死亡风险关系的前瞻性队列研究
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摘要
背景与目的
高血压和吸烟均能增加心血管疾病(cardiovascular disease, CVD)死亡和全因死亡风险,是全球死亡的第一和第二位危险因素。在我国,高血压患病率和吸烟比例均较高,已成为严重的公共卫生问题。2008-2010年对全球13个中低收入国家≥15岁人群烟草调查结果显示,全球吸烟率为30%。目前全球每年至少有540万人死于吸烟,预计2030年该数字将超过800万。
目前国内已开展的定量分析吸烟对CVD死亡和全因死亡风险影响的研究大多针对一般人群,仅有一项前瞻性队列研究专门针对高血压患者,但局限于老年单纯收缩期高血压患者,样本量较小,随访时间较短。由于高血压和吸烟在人群中共存比例较高,在高血压患者中暴露于吸烟危险因素可能会使这些患者CVD死亡和全因死亡风险进一步升高。在高血压患者中,吸烟量和血压水平同时升高对CVD死亡和全因死亡风险的影响未见报道。因此,本研究旨在探讨吸烟对高血压患者CVD死亡和全因死亡风险的影响,同时分析吸烟量和血压同时升高对高血压患者CVD死亡和全因死亡风险是否存在协同作用。
材料与方法
本研究36943名高血压患者均来自1991-2000年全国高血压调查流行病学随访研究。1991年采用标准化方案进行基线调查,收集人口统计学信息、吸烟信息和个人疾病史等。1999-2000年开展随访研究。吸烟的定义为：每日吸烟至少1支以上且连续吸烟1年以上。将吸烟叶按照1.0g烟叶等于1支香烟转换为吸香烟支数。采用Cox比例风险回归模型分析多种吸烟指标(累计吸烟量、每日吸烟量、吸烟年限和开始吸烟年龄)与高血压患者CVD死亡和全因死亡风险的关系,并获得高血压患者CVD死亡和全因死亡相对风险(relative risk, RR)及其95%置信区间(95%confidence interval,95%CI),并计算相应的人群归因危险度。
结果
本研究平均随访8.3年。36943名高血压患者中,7194人(男性3765人,女性3429人)在随访期间死亡,其中3785人(男性1978人,女性1807人)死于CVD。CVD和全因总死亡率分别为1368.1/10万人年和2600.1/10万人年。
总体上,在调整基线年龄、性别、受教育文化程度、饮酒、体力活动、体重指数、城乡(城市／农村)和地域(南方／北方)后,与不吸烟者相比,吸烟能够增加高血压患者CVD死亡和全因死亡风险,RR(95%CI)分别为1.28(1.19,1.38)和1.31(1.24,1.38),相应人群归因危险度分别为9.08%和9.96%。
在多因素调整后,吸烟量与高血压患者CVD死亡和全因死亡风险之间均呈剂量反应关系。以不吸烟者为参照组,累计吸烟量0.1-19包年和≥120包年组的CVD死亡RR(95%CI)分别为1.19(1.07,1.32)和1.34(1.23,1.46),总死亡RR(95%CI)分别为1.23(1.14,1.32)和1.36(1.28,1.45)；每日吸烟量1-10支和>10支组CVD死亡RR(95%CI)分别为1.30(1.19,1.42)和1.25(1.14,1.37),总死亡RR(95%CI)分别为1.23(1.14,1.32)和1.36(1.28,1.45)(线性趋势检验P均<0.001)。同样,吸烟年限与高血压患者CVD死亡和总死亡风险也存在剂量反应关系(线性趋势检验P<0.001),当吸烟年限>35年时,CVD死亡和全因死亡风险增加均超过30%,RR(95%CI)分别为1.31(1.21,1.42)和1.34(1.27,1.43)。此外,无论何时开始吸烟,吸烟均能增加高血压患者CVD死亡和全因死亡风险,开始吸烟年龄≤20岁和>20岁CVD死亡风险分别增加36%和19%,全因死亡分别增加42%和19%,且均具有统计学意义。血压分层分析结果显示,相同血压水平时(除收缩压<140mmHg和脉压<50mmHg),吸烟量与高血压患者CVD死亡和全因死亡风险仍呈剂量反应关系(线性趋势检验P均<0.05)。
另外,吸烟量和血压水平同时升高会进一步增加高血压患者CVD死亡和全因死亡风险。与相应血压水平最低(SBP<140mmHg, DBP<0mmHg,脉压<50mmHg或1级高血压)且不吸烟组相比,血压水平最高(SBP≥160mmHg, DBP≥100mmHg,脉压≥70mmHg或2级及以上高血压)且累计吸烟量≥20包年组CVD死亡相对风险分别升高至2.34,2.77,2.22和2.31,全因死亡相对风险分别升高至3.03,2.30,1.83和1.97,且均具有统计学意义。
排除基线调查后1年内死亡者,基线调查时戒烟者或基线调查时2周内服用降血压药物治疗者,吸烟量与高血压患者CVD死亡和全因死亡风险之间的剂量反应关系仍然具有统计学意义。
结论
吸烟能够增加高血压患者CVD死亡和全因死亡风险,血压和吸烟量的同时升高能进一步增加高血压患者CVD死亡和全因死亡的风险。鉴于我国是世界上最大的烟草生产国和消费国,人群中高血压患病率和吸烟率均较高,而吸烟和血压升高并存时能进一步增加高血压患者CVD死亡和全因死亡风险,因此有必要对高血压病人同时开展降血压和戒烟指导,从而减少我国高血压患者的心血管疾病死亡和总死亡。
Background and objectives
Hypertension and tobacco smoking have been identified as the first and second leading cause of death worldwide, respectively. In China, both hypertension and smoking are major public health challenges because of their high prevalence and concomitant risks of cardiovascular disease (CVD) and all-cause mortality. According to the Global Adult Tobacco Survey conducted during2008-2010in13low-and-middle income countries, the prevalence of current smoking is estimated at about30%. A total of5.4million deaths each year worldwide are attributed to currently tobacco use, and the number is projected to strikingly increase to more than8million by2030.
Several studies, attempting to quantify the risk of mortality from CVD and all-cause attributable to smoking, have been conducted in general population in China. To date, only one study was specially conducted in older isolated systolic hypertensive patients. In which, risk estimates were based on a small sample size patients with a short period of follow-up.
Hypertension and smoking co-exist more often than expected, which further amplifies risk of CVD and all-cause mortality. The combined effect of blood pressure and smoking on risk of CVD and all-cause mortality has not been well investigated in hypertensive patients. In this report, we examined the effect of tobacco smoking on deaths from CVD and all-causes, as well as to answer the question:whether cigarette smoking exacerbates the effect of blood pressure on the risk of CVD and all-cause mortality among hypertensive patients?
Materials and methods
36943participants (aged≥40years) were hypertensive patients who took part in the China National Hypertension Survey Epidemiology Follow-up Study. Data on smoking and other variables were obtained in1991and follow-up evaluation was conducted in1999-2000. Smoking was defined as having smoked at least one cigarette per day for at least1year, and1g of tobacco was considered to be equivalent to1cigarette. Cox proportional hazards models were applied to estimate relative risks (RRs) and95% confidence intervals (CIs) for CVD and all-cause mortality in relation to smoking.
Results
During a mean follow-up of8.3years,7194deaths (3765men and3429women) were documented in this cohort study. Of these deaths,3785(1978men and1807women) were attributable to CVD. The crude mortality rate was1368.1per100000person-years for CVD and2600.1per100000person-years for all-cause events, respectively. After adjustment for age, sex, education level, body mass index, physical activity, alcohol consumption, urbanization, and geographic region, compared with patients never smoked, the respective RRs (95%CIs) for CVD and all-cause mortality were1.28(1.19,1.38) and1.31(1.24,1.38) for patients who were smokers. The corresponding population attributable risks were9.08%and9.96%, respectively.
There was a significant dose response association between smoking and risk of CVD and all-cause mortality in hypertensive patients. In terms of pack-years of smoking, compared with never smokers, the RR (95%CI) of CVD mortality was1.19(1.07,1.32) for light smokers (0.1-19pack years of smoking) and1.34(1.23,1.46) for heavy smokers (≥20pack years of smoking); the corresponding RRs of all cause mortality were1.23(1.14,1.32) and1.36(1.28,1.45)(P for linear trends≤0.001). As for cigarettes smoked per day, the respective RR (95%CI) of CVD mortality was1.30(1.19,1.42) and1.25(1.14,1.37) for those who smoked1-10and>10cigarettes per day; the corresponding RRs of all cause mortality were1.23(1.14,1.32) and1.36(1.28,1.45)(P for linear trends≤0.001). In addition, a significant upward trend was also observed with the total number of years of smoking for risk of CVD and all-cause mortality (P for linear trends≤0.001). A higher risk was observed in hypertensive patients who started smoking in their early life. In stratified analysis according to blood pressure level, the positive dose-response relationship between smoking and risk of CVD and all-cause mortality remained in systolic blood pressure (SBP) groups (140-159and≥160mmHg), diastolic blood pressure (DBP) groups (<90,90-99and≥100mmHg), pulse pressure (PP) groups (50-69, and≥70mmHg) and all stages of hypertension (all P for linear trends≤0.05).
In general, a synergistic effect on the risk of CVD and all-cause mortality existed between cigarette smoking and blood pressure category in hypertensive patients. Compared with never smokers with SBP<140mmHg, the RRs (95%CIs) for heavy smokers with SBP≥160mmHg were substantially increased to2.34and3.03for CVD and all-cause mortality, separately. Heavy smokers with DBP≥100mmHg respectively experienced177%and130%excess risk for CVD and all-cause mortality compared to never smokers with DBP<90mmHg. In addition, compared to never smokers with PP <50mmHg, heavy smokers with PP>70mmHg were significantly associated with a122%and183%greater risk of CVD and all-cause mortality, respectively. The respective RRs (95%CIs) for CVD and all-cause mortality were2.31(2.07,2.59) and2.30(1.99,2.65) in heavy smokers with stage2and3hypertension compared with never smokers with stage1hypertension.
The dose response relationship existed even after excluding hypertensive patients who were former smokers, taking anti-hypertensive medications within two weeks before baseline, or who died during the first1year of follow-up.
Conclusions
Smoking not only significantly increased the risk of CVD and all-cause mortality among hypertensive groups, but the combined effect on the risk of CVD and all-cause mortality existed between cigarette smoking and blood pressure category. Cigarette smoking does exacerbate the effect of blood pressure on the risk of cardiovascular and all-cause mortality in hypertensive patients. Given high prevalences of both smoking and hypertension in China, besides hypertension management, smoking cessation should be an essential component for preventing deaths related to smoking for hypertensive patients.
高血压和吸烟均能增加心血管疾病(cardiovascular disease, CVD)死亡和全因死亡风险,是全球死亡的第一和第二位危险因素。在我国,高血压患病率和吸烟比例均较高,已成为严重的公共卫生问题。2008-2010年对全球13个中低收入国家≥15岁人群烟草调查结果显示,全球吸烟率为30%。目前全球每年至少有540万人死于吸烟,预计2030年该数字将超过800万。
目前国内已开展的定量分析吸烟对CVD死亡和全因死亡风险影响的研究大多针对一般人群,仅有一项前瞻性队列研究专门针对高血压患者,但局限于老年单纯收缩期高血压患者,样本量较小,随访时间较短。由于高血压和吸烟在人群中共存比例较高,在高血压患者中暴露于吸烟危险因素可能会使这些患者CVD死亡和全因死亡风险进一步升高。在高血压患者中,吸烟量和血压水平同时升高对CVD死亡和全因死亡风险的影响未见报道。因此,本研究旨在探讨吸烟对高血压患者CVD死亡和全因死亡风险的影响,同时分析吸烟量和血压同时升高对高血压患者CVD死亡和全因死亡风险是否存在协同作用。
材料与方法
本研究36943名高血压患者均来自1991-2000年全国高血压调查流行病学随访研究。1991年采用标准化方案进行基线调查,收集人口统计学信息、吸烟信息和个人疾病史等。1999-2000年开展随访研究。吸烟的定义为：每日吸烟至少1支以上且连续吸烟1年以上。将吸烟叶按照1.0g烟叶等于1支香烟转换为吸香烟支数。采用Cox比例风险回归模型分析多种吸烟指标(累计吸烟量、每日吸烟量、吸烟年限和开始吸烟年龄)与高血压患者CVD死亡和全因死亡风险的关系,并获得高血压患者CVD死亡和全因死亡相对风险(relative risk, RR)及其95%置信区间(95%confidence interval,95%CI),并计算相应的人群归因危险度。
结果
本研究平均随访8.3年。36943名高血压患者中,7194人(男性3765人,女性3429人)在随访期间死亡,其中3785人(男性1978人,女性1807人)死于CVD。CVD和全因总死亡率分别为1368.1/10万人年和2600.1/10万人年。
总体上,在调整基线年龄、性别、受教育文化程度、饮酒、体力活动、体重指数、城乡(城市／农村)和地域(南方／北方)后,与不吸烟者相比,吸烟能够增加高血压患者CVD死亡和全因死亡风险,RR(95%CI)分别为1.28(1.19,1.38)和1.31(1.24,1.38),相应人群归因危险度分别为9.08%和9.96%。
在多因素调整后,吸烟量与高血压患者CVD死亡和全因死亡风险之间均呈剂量反应关系。以不吸烟者为参照组,累计吸烟量0.1-19包年和≥120包年组的CVD死亡RR(95%CI)分别为1.19(1.07,1.32)和1.34(1.23,1.46),总死亡RR(95%CI)分别为1.23(1.14,1.32)和1.36(1.28,1.45)；每日吸烟量1-10支和>10支组CVD死亡RR(95%CI)分别为1.30(1.19,1.42)和1.25(1.14,1.37),总死亡RR(95%CI)分别为1.23(1.14,1.32)和1.36(1.28,1.45)(线性趋势检验P均<0.001)。同样,吸烟年限与高血压患者CVD死亡和总死亡风险也存在剂量反应关系(线性趋势检验P<0.001),当吸烟年限>35年时,CVD死亡和全因死亡风险增加均超过30%,RR(95%CI)分别为1.31(1.21,1.42)和1.34(1.27,1.43)。此外,无论何时开始吸烟,吸烟均能增加高血压患者CVD死亡和全因死亡风险,开始吸烟年龄≤20岁和>20岁CVD死亡风险分别增加36%和19%,全因死亡分别增加42%和19%,且均具有统计学意义。血压分层分析结果显示,相同血压水平时(除收缩压<140mmHg和脉压<50mmHg),吸烟量与高血压患者CVD死亡和全因死亡风险仍呈剂量反应关系(线性趋势检验P均<0.05)。
另外,吸烟量和血压水平同时升高会进一步增加高血压患者CVD死亡和全因死亡风险。与相应血压水平最低(SBP<140mmHg, DBP<0mmHg,脉压<50mmHg或1级高血压)且不吸烟组相比,血压水平最高(SBP≥160mmHg, DBP≥100mmHg,脉压≥70mmHg或2级及以上高血压)且累计吸烟量≥20包年组CVD死亡相对风险分别升高至2.34,2.77,2.22和2.31,全因死亡相对风险分别升高至3.03,2.30,1.83和1.97,且均具有统计学意义。
排除基线调查后1年内死亡者,基线调查时戒烟者或基线调查时2周内服用降血压药物治疗者,吸烟量与高血压患者CVD死亡和全因死亡风险之间的剂量反应关系仍然具有统计学意义。
结论
吸烟能够增加高血压患者CVD死亡和全因死亡风险,血压和吸烟量的同时升高能进一步增加高血压患者CVD死亡和全因死亡的风险。鉴于我国是世界上最大的烟草生产国和消费国,人群中高血压患病率和吸烟率均较高,而吸烟和血压升高并存时能进一步增加高血压患者CVD死亡和全因死亡风险,因此有必要对高血压病人同时开展降血压和戒烟指导,从而减少我国高血压患者的心血管疾病死亡和总死亡。
Background and objectives
Hypertension and tobacco smoking have been identified as the first and second leading cause of death worldwide, respectively. In China, both hypertension and smoking are major public health challenges because of their high prevalence and concomitant risks of cardiovascular disease (CVD) and all-cause mortality. According to the Global Adult Tobacco Survey conducted during2008-2010in13low-and-middle income countries, the prevalence of current smoking is estimated at about30%. A total of5.4million deaths each year worldwide are attributed to currently tobacco use, and the number is projected to strikingly increase to more than8million by2030.
Several studies, attempting to quantify the risk of mortality from CVD and all-cause attributable to smoking, have been conducted in general population in China. To date, only one study was specially conducted in older isolated systolic hypertensive patients. In which, risk estimates were based on a small sample size patients with a short period of follow-up.
Hypertension and smoking co-exist more often than expected, which further amplifies risk of CVD and all-cause mortality. The combined effect of blood pressure and smoking on risk of CVD and all-cause mortality has not been well investigated in hypertensive patients. In this report, we examined the effect of tobacco smoking on deaths from CVD and all-causes, as well as to answer the question:whether cigarette smoking exacerbates the effect of blood pressure on the risk of CVD and all-cause mortality among hypertensive patients?
Materials and methods
36943participants (aged≥40years) were hypertensive patients who took part in the China National Hypertension Survey Epidemiology Follow-up Study. Data on smoking and other variables were obtained in1991and follow-up evaluation was conducted in1999-2000. Smoking was defined as having smoked at least one cigarette per day for at least1year, and1g of tobacco was considered to be equivalent to1cigarette. Cox proportional hazards models were applied to estimate relative risks (RRs) and95% confidence intervals (CIs) for CVD and all-cause mortality in relation to smoking.
Results
During a mean follow-up of8.3years,7194deaths (3765men and3429women) were documented in this cohort study. Of these deaths,3785(1978men and1807women) were attributable to CVD. The crude mortality rate was1368.1per100000person-years for CVD and2600.1per100000person-years for all-cause events, respectively. After adjustment for age, sex, education level, body mass index, physical activity, alcohol consumption, urbanization, and geographic region, compared with patients never smoked, the respective RRs (95%CIs) for CVD and all-cause mortality were1.28(1.19,1.38) and1.31(1.24,1.38) for patients who were smokers. The corresponding population attributable risks were9.08%and9.96%, respectively.
There was a significant dose response association between smoking and risk of CVD and all-cause mortality in hypertensive patients. In terms of pack-years of smoking, compared with never smokers, the RR (95%CI) of CVD mortality was1.19(1.07,1.32) for light smokers (0.1-19pack years of smoking) and1.34(1.23,1.46) for heavy smokers (≥20pack years of smoking); the corresponding RRs of all cause mortality were1.23(1.14,1.32) and1.36(1.28,1.45)(P for linear trends≤0.001). As for cigarettes smoked per day, the respective RR (95%CI) of CVD mortality was1.30(1.19,1.42) and1.25(1.14,1.37) for those who smoked1-10and>10cigarettes per day; the corresponding RRs of all cause mortality were1.23(1.14,1.32) and1.36(1.28,1.45)(P for linear trends≤0.001). In addition, a significant upward trend was also observed with the total number of years of smoking for risk of CVD and all-cause mortality (P for linear trends≤0.001). A higher risk was observed in hypertensive patients who started smoking in their early life. In stratified analysis according to blood pressure level, the positive dose-response relationship between smoking and risk of CVD and all-cause mortality remained in systolic blood pressure (SBP) groups (140-159and≥160mmHg), diastolic blood pressure (DBP) groups (<90,90-99and≥100mmHg), pulse pressure (PP) groups (50-69, and≥70mmHg) and all stages of hypertension (all P for linear trends≤0.05).
In general, a synergistic effect on the risk of CVD and all-cause mortality existed between cigarette smoking and blood pressure category in hypertensive patients. Compared with never smokers with SBP<140mmHg, the RRs (95%CIs) for heavy smokers with SBP≥160mmHg were substantially increased to2.34and3.03for CVD and all-cause mortality, separately. Heavy smokers with DBP≥100mmHg respectively experienced177%and130%excess risk for CVD and all-cause mortality compared to never smokers with DBP<90mmHg. In addition, compared to never smokers with PP <50mmHg, heavy smokers with PP>70mmHg were significantly associated with a122%and183%greater risk of CVD and all-cause mortality, respectively. The respective RRs (95%CIs) for CVD and all-cause mortality were2.31(2.07,2.59) and2.30(1.99,2.65) in heavy smokers with stage2and3hypertension compared with never smokers with stage1hypertension.
The dose response relationship existed even after excluding hypertensive patients who were former smokers, taking anti-hypertensive medications within two weeks before baseline, or who died during the first1year of follow-up.
Conclusions
Smoking not only significantly increased the risk of CVD and all-cause mortality among hypertensive groups, but the combined effect on the risk of CVD and all-cause mortality existed between cigarette smoking and blood pressure category. Cigarette smoking does exacerbate the effect of blood pressure on the risk of cardiovascular and all-cause mortality in hypertensive patients. Given high prevalences of both smoking and hypertension in China, besides hypertension management, smoking cessation should be an essential component for preventing deaths related to smoking for hypertensive patients.
引文
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[1]Yang G, Kong L. Emergence of chronic non-communicable diseases in China[J]. Lancet,2008,372(9650):1697-705.
[2]Kearney PM, Whelton M. Global burden of hypertension:analysis of worldwide data[J]. Lancet,2005,365(9455):217-23.
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[4]Testa MA, Simonson DC. Assesment of quality-of-life outcomes [J]. N Engl J Med,1996,334(13):835-40.
[5]Bardage C, I sac son DG. Hypertension and health-related quality of life. an epidemiological study in Sweden[J]. J Clin Epidemiol,2001, 54(2):172-81.
[6]Michaud CM, Murray CJ. Burden of disease--implications for future research[J]. JAMA,2001,285(5):535-9.
[7]Marseille E, Hofmann PB. HIV prevention before HAART in sub-Saharan Africa[J]. Lancet,2002,359(9320):1851-6.
[8]Perkovic V, Huxley R. The burden of blood pressure-related disease: a neglected priority for global health[J]. Hypertension,2007, 50(6):991-7.
[9]李立明,饶克勤.中国居民2002年营养与健康状况调查[J].中华流行病学杂志,2005,26(7)：478-84.
[10]Gu D, Reynolds K. Prevalence, awareness, treatment, and control of hypertension in china[J]. Hypertension,2002,40(6):920-7.
[11]Elmer PJ, Grimm R, Jr.. Lifestyle intervention:results of the Treatment of Mild Hypertension Study (TOMHS)[J]. Prev Med,1995, 24(4):378-88.
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