Trends for stroke incidence, severity, and prognosis in a rural community with a long-term stroke prevention program

OBJECTIVE: To examine the benefit of a long-term community-based stroke prevention program, we explored 35 years of surveillance data of stroke incidence for residents in a rural area in Japan. METHOD: The surveyed community was Ikawa town (population in 2000 was 6,116) in Akita prefecture, where a community-based stroke prevention program has been conducted since 1963. Incidence rates and numbers of stroke episodes, proportions for loss of consciousness and motor paralysis at onset, proportions for each seriousness category (A: death within one day after onset, B: death during 2-7 days after onset, C: survival more than 8 days after onset with complete hemiparesis, D: survival more than 8 days after onset with incomplete or no hemiparesis), and one-year survival rates and activity of daily living were investigated for 1964-69, 1970-79, 1980-89 and 1990-98. RESULTS: Stroke incidence declined 66% and 64% among the 30-69 years age group and 70 years over age group, respectively between 1964-69 and 1990-98. Incident numbers of stroke episodes declined 41% among those aged 30-69 years and, while it increased 100% in the 70 years over age group, this was much less than the increase rate of 271% rated for the corresponding aged population growth over time. In the 30-69 years age group, the proportion of patients with no loss of consciousness at onset increased from 53-64% during the former three periods to 79% in 1990-98. The proportion of patients with no motor paralysis also increased progressively over the study periods and the proportions for A or B categories in the seriousness classification decreased between 1964-69 and 1990-98 while the proportion in the D category increased between 1980-89 and 1990-98. One-year survival rates increased from 71% and 36% in 1964 to 86% and 61% in 1990-98 among the 30-69 years age group and 70 years over age group, respectively. With both, the numbers of totally dependent patients at one-year after onset, did not change significantly over time, despite the marked increase in the population of risk. CONCLUSION: The present study showed that a long-term community-based stroke prevention program can not only decrease stroke incidence and number of episodes, but also reduce the likelihood of severe stroke attack and improve prognosis, thereby suppressing the increase of totally dependent patients expected from growth of the old population in the community.     

Smoking cessation and mortality from cardiovascular disease among Japanese men and women: the JACC Study

To examine the effect of smoking cessation on cardiovascular disease mortality in Asians, the authors conducted a 10-year prospective cohort study of 94,683 Japanese (41,782 men and 52,901 women) aged 40-79 years who were part of the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). During 941,043 person-years of follow-up between 1989-1990 and 1999, 698 deaths from stroke, 348 from coronary heart disease, and 1,555 from total cardiovascular disease occurred in men and 550, 199, and 1,155, respectively, in women. For men, the multivariate relative risks for current smokers compared with never smokers were 1.39 (95% confidence interval (CI): 1.13, 1.70) for stroke, 2.51 (95% CI: 1.79, 3.51) for coronary heart disease, and 1.60 (95% CI: 1.39, 1.84) for total cardiovascular disease. The respective relative risks for women were 1.65 (95% CI: 1.21, 2.25), 3.35 (95% CI: 2.23, 5.02), and 2.06 (95% CI: 1.69, 2.51), with larger excess risks for persons aged 40-64 years than for older persons. The risk decline after smoking cessation occurred for coronary heart disease and total cardiovascular disease within 2 years and for total stroke after 2-4 years. For each endpoint and in both age subgroups of 40-64 and 65-79 years, most of the benefit of cessation occurred after 10-14 years following cessation. Findings imply the importance of smoking cessation at any age to prevent cardiovascular disease in Japanese.     

2008—2010年乳山市居民脑卒中、冠心病疾病负担分析

目的应用疾病负担指标衡量乳山市脑卒中、冠心病的危害程度,定量估计疾病对健康状况的影响程度和经济损失。方法利用乳山市2008—2010年本地户籍的脑卒中、冠心病患者资料,计算脑卒中、冠心病的潜在寿命损失年(years of potential life lost,PYLL)、致残率、经济损失。结果乳山市脑卒中、冠心病的总体死亡率分别为167.71/10万、117.60/10万,平均每例因脑卒中、冠心病死亡的PYLL分别为10.34、10.02年,PYLL率(减寿率)为3.68‰、2.92‰。结论乳山市脑卒中、冠心病的死亡率随着年龄的增加而增加,男性高于女性;脑卒中的疾病负担和济负担均于冠心病;40岁以上的疾病负担总负担的90%以上。     

Relationships of age at menarche and menopause, and reproductive year with mortality from cardiovascular disease in Japanese postmenopausal women: the JACC study

BACKGROUND: Early menopause is associated with increased risk of coronary heart disease in Caucasian women. However, this association has not been examined in Asian women. METHODS: We conducted a 10-year cohort study of 37,965 Japanese post-menopausal women aged 40-79 years in the Japan Collaborative Cohort (JACC) Study. Causes of death were determined based on the International Classification of Disease. RESULTS: There were 487 mortality of stroke and 178 mortality of coronary heart disease. Late menarche or early menopause, or shorter duration of reproductive period was not associated with risk of mortality from coronary heart disease. However, compared with women with age at menarche < or =13 years, those with age at menarche > or =17 years tended to have increased risk of mortality from stroke: the multivariable hazard ratio was 1.32 (95% confidence interval [CI]: 0.93-1.87, p = 0.10). Compared with women with age at menopause of > or =49 years, those with age at menopause of <49 years tended to have increased risk of coronary heart disease among women aged 40-64 years; the multivariable hazard ratio was 1.85 (95% CI: 0.92-3.73, p = 0.08). CONCLUSIONS: The possible association between early menopause and coronary heart disease among middle-aged women was consistent with the result of observational studies for Caucasian women, and can be explained by a protective effect of endogenous estrogen on the development of atherosclerosis.     

A prospective study of social networks in relation to total mortality and cardiovascular disease in men in the USA.

STUDY OBJECTIVE: Previous studies have established a relationship between low levels of social networks and total mortality, but few have examined cause specific mortality or disease incidence. This study aimed to examine prospectively the relationships between social networks and total and cause specific mortality, as well as cardiovascular disease incidence. DESIGN: This was a four year follow up study in an ongoing cohort of men, for whom information on social networks was collected at baseline. The main outcome measures were total mortality, further categorised into deaths from cardiovascular disease (stroke and coronary heart disease), total cancer, accidents/suicides, and all other causes; as well as stroke and coronary heart disease incidence. PARTICIPANTS: Altogether 32,624 US male health professionals aged 42 to 77 years in 1988, who were free of coronary heart disease, stroke, and cancer at baseline. RESULTS: A total of 511 deaths occurred during 122,911 person years of follow up. Compared with men with the highest level of social networks, socially isolated men (not married, fewer than six friends or relatives, no membership in church or community groups) were at increased risk for cardiovascular disease mortality (age adjusted relative risk, 1.90; 95% CI 1.07, 3.37) and deaths from accidents and suicides (age adjusted relative risk 2.22; 95% CI 0.76, 6.47). No excess risks were found for other causes of death. Socially isolated men were also at increased risk of stroke incidence (relative risk, 2.21; 95% CI, 1.12, 4.35), but not incidence of non-fatal myocardial infarction. CONCLUSIONS: Social networks were associated with lower total mortality by reducing deaths from cardiovascular disease and accidents/suicides. Strong social networks were associated with reduced incidence of stroke, though not of coronary heart disease. However, social networks may assist in prolonging the survival of men with established coronary heart disease.     

Relations between dietary sodium and potassium intakes and mortality from cardiovascular disease: the Japan Collaborative Cohort Study for Evaluation of Cancer Risks

BACKGROUND: Limited evidence is available about the relations between sodium and potassium intakes and cardiovascular disease in the general population. OBJECTIVE: The objective was to investigate relations between sodium and potassium intakes and cardiovascular disease in Asian populations whose mean sodium intake is generally high. DESIGN: Between 1988 and 1990, a total of 58,730 Japanese subjects (n = 23,119 men and 35,611 women) aged 40-79 y with no history of stroke, coronary heart disease, or cancer completed a lifestyle questionnaire including food intake frequency under the Japan Collaborative Cohort Study for Evaluation of Cancer Risk sponsored by the Ministry of Education, Sports and Science. RESULTS: After 745,161 person-years of follow-up, we documented 986 deaths from stroke (153 subarachnoid hemorrhages, 227 intraparenchymal hemorrhages, and 510 ischemic strokes) and 424 deaths from coronary heart disease. Sodium intake was positively associated with mortality from total stroke, ischemic stroke, and total cardiovascular disease. The multivariable hazard ratio for the highest versus the lowest quintiles of sodium intake after adjustment for age, sex, and cardiovascular disease risk factors was 1.55 (95% CI: 1.21, 2.00; P for trend < 0.001) for total stroke, 2.04 (95% CI: 1.41, 2.94; P for trend < 0.001) for ischemic stroke, and 1.42 (95% CI: 1.20, 1.69; P for trend < 0.001) for total cardiovascular disease. Potassium intake was inversely associated with mortality from coronary heart disease and total cardiovascular disease. The multivariable hazard ratio for the highest versus the lowest quintiles of potassium intake was 0.65 (95% CI: 0.39, 1.06; P for trend = 0.083) for coronary heart disease and 0.73 (95% CI: 0.59, 0.92; P for trend = 0.018) for total cardiovascular disease, and these associations were more evident for women than for men. CONCLUSIONS: A high sodium intake and a low potassium intake may increase the risk of mortality from cardiovascular disease.     

Prospective study of job insecurity and coronary heart disease in US women

PURPOSE: To examine prospectively the relationship between job insecurity and incidence of coronary heart disease (CHD) among women. METHODS: We conducted the study in 36,910 women from the Nurses' Health Study, a prospective cohort of female registered nurses residing in 11 US states. These women were 46 to 71 years old, and did not have diagnosed CHD, stroke, or cancer at baseline (1992). We collected information on job insecurity in 1992 and coronary heart disease incidence between baseline (June 1, 1992) and return of the 1996 questionnaire. RESULTS: During 4 years of follow-up, we documented 154 incident cases of CHD (113 non-fatal cases of myocardial infarction (MI) and 41 CHD deaths). After adjustment for a wide array of potential confounders, the relative risk (RR) of total CHD over 2-year follow-up was 1.35 (95% CI, 0.78-2.34) and 1.04 (95% CI, 0.69-1.57) over 4-year follow-up. Job insecurity appeared to significantly increase the risk of non-fatal MI in the short term (2-year follow-up: RR=1.89, 95% CI, 1.03-3.50), though not over a longer follow-up period (RR=1.28, 95% CI, 0.82-2.00), nor fatal CHD in the short term (RR=0.49, 95% CI, 0.22-2.08). CONCLUSIONS: These data suggest that job insecurity may increase the short-term risk of non-fatal MI in women.     

Pravastatin use and the five-year incidence of cancer in coronary heart disease patients: from the prevention of coronary sclerosis study

BACKGROUND: Although the short-term safety of statins is well established, their potential carcinogenicity in the long term is still being debated. The aim of this study was to investigate the association between statin-therapy and the incidence of cancer in coronary heart disease patients. METHODS: The subjects were 263 patients with coronary heart disease who were from Osaka prefecture and who were admitted to the Osaka Medical Center for Cancer and Cardiovascular Diseases between September 28, 1991 and March 31, 1995. The five-year cancer incidence among the subjects was checked using the database of the institution-based cancer registry of the hospital as well as the population-based Osaka Cancer Registry. The Cox's proportional hazards ratios (HRs) of all cancer incidence and observed/expected (O/E) ratios by cancer site were calculated. RESULTS: Cancer incidence was observed in 17 patients during the follow-up period. Age (HR=1.16 per one year of age) and continuous smoking during the period (HR=5.82 compared to not smoking during the period) were significantly associated with cancer incidence using multivariable analysis. After being adjusted for sex, age, total serum cholesterol level and smoking habit, the HR of cancer incidence with pravastatin use was 0.78 (95% confidence interval: 0.18-3.46). In the O/E analysis, significantly elevated risks were found for bladder cancer in all the subjects (HR=8.93), as well as in the pravastatin use patients (HR=13.76). CONCLUSIONS: Pravastatin use for 5 years did not indicate an increase in over all cancer risk.     

Serum triglycerides and risk of coronary heart disease among Japanese men and women

To examine the relation of triglycerides with coronary heart disease among populations with low mean total cholesterol, the authors conducted a 15.5-year prospective study ending in 1997 of 11,068 Japanese aged 40-69 years (4,452 men and 6,616 women with mean total cholesterol = 4.73 mmol/liter and 5.03 mmol/liter, respectively), initially free of coronary heart disease or stroke. There were 236 coronary heart disease events comprising 133 myocardial infarctions, 68 angina pectoris events, and 44 sudden cardiac deaths. The coronary heart disease incidence was greater in a dose-response manner across increasing quartiles of nonfasting triglycerides for both sexes. The multivariate relative risk of coronary heart disease adjusting for coronary risk factors and time since last meal associated with a 1-mmol/liter increase in triglycerides was 1.29 (95% confidence interval (CI): 1.09, 1.53; p = 0.004) for men and 1.42 (95% CI: 1.15, 1.75; p = 0.001) for women. The trend was similar for myocardial infarction, angina pectoris, and sudden cardiac death. The relation of triglycerides with coronary heart disease was not influenced materially by total cholesterol levels or, in a subsample analysis (51% of total sample), by high density lipoprotein cholesterol levels. Nonfasting serum triglycerides predict the incidence of coronary heart disease among Japanese men and women who possess low mean values of total cholesterol. Further adjustment for high density lipoprotein cholesterol suggests an independent role of triglycerides on the coronary heart disease risk.     

Solar activity and mortality in the United States.

Mortality from all causes, from coronary heart disease, and from stroke in the US was studied in relation to solar activity as measured by the geomagnetic index, Ap, on a daily basis for the years 1964-66 and on a monthly basis for the years 1964-71. The data did not support previous assertions by Soviet researchers of an association between solar activity and cardiovascular mortality.     

社区居民肥胖、中心性肥胖与冠心病发病风险的前瞻性队列研究

目的 探索肥胖、中心性肥胖与冠心病发病风险的关系。方法 2013年在上海市浦东新区社区居民中采用多阶段分层随机抽样选取人群开展基线调查,收集6685名队列研究对象的人口学特征、暴露因素、身体测量指标等信息。随访观察中位时间3.00年,记录队列人群的冠心病发病情况。单因素分析采用t检验、Kruskal-Wallis检验和卡方检验,多因素分析采用COX比例风险模型。结果 队列总计观察人年数为19759.93人年,共有260人发生冠心病,男性101例,女性159例。队列人群总体发病率3.89%,发病密度13.16/千人年。冠心病发病率随BMI升高呈上升趋势（〖XC小五号.EPS;P〗趋势=6.761,P=0.009）。中心性肥胖人群发病风险是正常人群的1.39倍(P =0.019, 95%CI: 1.06-1.82),中心性肥胖合并高血压患者发生冠心病的风险是正常人群的1.77倍(P=0.001, 95%CI:1.26-2.49)。结论 中心性肥胖是冠心病发病的重要危险因素。     

海南省成年人吸烟与心血管疾病发病风险的前瞻性研究

目的 探讨海南省成年人吸烟与各类心血管疾病发病风险的关联。方法 利用中英合作项目“中国慢性病前瞻性研究”项目海南省人群数据,剔除基线调查时自报患有冠心病、脑卒中和恶性肿瘤的个体后,纳入基线年龄为30～79岁的研究对象共28 940人,利用Cox回归分析计算非吸烟者、戒烟者和当前吸烟者的心血管疾病发病风险HR值和95%CI。结果 研究人群平均随访6.2年,累积随访177 279人年。随访期间男性1 310人,女性2 200人发病。男性吸烟率（47.0%）远高于女性吸烟率（0.3%）。多因素调整后,与非吸烟者相比,吸烟人群心血管疾病的发病风险有所增加,HR值(95%CI)分别为急性冠心病1.63(1.12～2.38)和缺血性心脏病1.53(1.22～1.91)。在当前吸烟者中,每天吸烟量多于30支的人群急性冠心病、缺血性脑卒中和出血性脑卒中的发病风险最高。结论 吸烟能够增加心血管疾病的发病风险,应基于不同心血管疾病风险制定吸烟者戒烟目标和全人群控烟措施。     

绵竹市农村居民1989-1998年恶性肿瘤、脑卒中、冠心病流行趋势分析

目的 掌握农村居民慢性非传染病的流行趋势，为制定防治对策提供依据。方法 按四川省慢性病监测方案，绵竹市在1989-1998年期间对6镇农村10万人群进行连续10年的恶性肿瘤，脑卒中，冠心病的发病，死亡监测。结果 总计发病1645例。死亡1412例，年平均发病率为144.94/10万，死亡率124.34/10万；恶性肿瘤发病率78.68/10万，死亡率70.13/10万；脑卒中发病率60.73/10万，死亡率51.19/10万；冠心病发病率5.55/10万。死亡率3.08/10万，3种病死亡占全死因的22.77%，发病年龄主要集中在45-65岁之间，恶性肿瘤前5位依次是；胃癌，食道癌，肝癌，肠癌，肺癌，脑卒中发病在45岁以后随年龄增加而急剧上升。结论 绵竹市农村肿瘤，脑卒中，冠心病发病率逐年上升，已成为危害居民健康的主要疾病。     

上海市经皮穿刺冠状动脉腔内成形术现状调查

目的了解上海市经皮穿刺冠状动脉腔内成形术（ＰＴＣＡ）现状，探讨今后发展方向。方法翻阅１９９７年独立开展ＰＴＣＡ手术医院所有病人病史。访问各有关导管室主任或主要操作人员。结果医院数１４家，超过２００例／年的医院１家。总例数４４０例，资料完整的２６０例，其中５６％为心肌梗塞，４８％为多支血管病变。院内主要心脏事件发生率为２．６％。支架植入病例数占总数的５６．５％。ＰＴＣＡ或ＰＴＣＡ加支架大于２０例／年的医院比小于２０例／年的医院住院天数、总费用低。结论上海市年病例数不多。减少并发症、降低成本需提高每家医院的年例数。预测支架植入病人将会增加。     

上海市社区中老年居民慢性病患病调查

目的了解上海市长宁区社区中老年居民慢性病患病情况和分布特征。方法采用横断面现况调查,研究对象为上海市长宁区某街道40～74岁男性和40～70岁女性,分别于2003年和1998年完成了6 488名男性和8 511名女性的健康调查,根据上海市人口普查资料的年龄构成计算慢性病标化患病率,并采用χ2检验比较不同特征人群的慢性病患病率差异。结果男、女性慢性病中高血压患病率最高,标化患病率分别为28.0%、22.6%;分别有40.9%男性和36.5%女性患有高血压、冠心病、糖尿病、慢性阻塞性肺病和脑卒中5种主要慢性病中的一种;体质指数(BMI)≥24者,高血压和冠心病的患病率较高;经常吸烟、饮酒的男性,脑卒中、高血压和慢性阻塞性肺病的患病率较高,而吸烟、饮酒对女性慢性病的影响较小。结论不同特征人群慢性病患病率有一定差异,控制肥胖和戒烟是重要的干预措施。     

甘肃省15~69岁常住居民吸烟和戒烟现状及其烟草危害知晓情况

目的了解甘肃省15~69岁常住居民吸烟和戒烟现状及其对烟草危害的知晓情况,为进一步做好烟草防控和戒烟宣传工作提供参考依据。方法于2015年11月—2016年2月采用多阶段随机抽样方法在甘肃省抽取21320名15~69岁常住居民进行面访调查。结果经加权调整后,甘肃省15~69岁常住居民的吸烟率为30.7%(95%CI=29.3%~31.5%),现在吸烟率为27.5%(95%CI=26.6%~28.7%),现在每日吸烟率为21.6%(95%CI=20.8%~22.7%),戒烟率为12.1%(95%CI=10.8%~13.2%);现在吸烟者中考虑1年内戒烟的居民仅占16.2%;甘肃省15~69岁常住居民对吸烟会导致中风、心脏病发作和阳痿的知晓率分别为28.2%、34.0%和18.2%,对"二手烟"会导致成人心脏病、儿童肺部疾病和肺癌的知晓率分别为34.5%、52.8%和54.9%。结论甘肃省15~69岁常住居民现在吸烟率较高,戒烟率较低,对烟草危害认识不足,现在吸烟者戒烟意愿不强。     

2012年新泰市居民死因监测分析

目的了解新泰市居民死因分布特点,为综合防治提供依据。方法对2012年新泰市死因监测资料进行统计分析。结果2012年新泰市报告居民死亡人数9390例,报告居民死亡率为670．19／10万。居民死亡率（／10万）,男性为775．77,女性为559．74（PdO．01）;0岁为228．30,25～29岁为79．94,30～34岁为94．53,35~39岁为108．00,40～44岁为181．87,45～49岁为327．96,50～54岁为48：1．29,55～59岁为849．80,60～64岁为1153．80,65～69岁为1913．47,70～74岁为3082．83,75～79岁为5296．22,80～84岁为10136．24,85～岁为19904．25。前5位死因,全部居民是恶性肿瘤、脑血管病、心脏病、呼吸系统疾病、伤害,分别占所有死亡人数（9390人）的28．01％、24．58％、22．90％、9．45％、8．82％,男性为恶性肿瘤、脑血管病、心脏病、伤害、呼吸系统疾病,占男性死亡的93．85％,女性为心脏病、脑血管病、恶性肿瘤、呼吸系统疾病、伤害,占女性死亡的93．61％。结论恶性肿瘤脑血管病、心脏病、呼吸系统疾病、伤害是新泰市居民的主要死因。     

Plasma fibrinogen and coronary heart disease in urban Japanese

There is little information on the relation of plasma fibrinogen concentration to the risk of coronary heart disease in Asians, including Japanese, whose plasma fibrinogen concentration has been reported to be low by Western standards. The authors conducted a prospective study with 4.8 years of follow-up of 11,977 men and women aged 21-89 years (mean value of fibrinogen = 267 mg/dl) living or working in Osaka, Japan, in 1990-1996 to examine the relation of plasma fibrinogen with the incidence of coronary heart disease (myocardial infarction and angina pectoris). Mean fibrinogen concentration was 293.6 mg/dl for men who developed coronary heart disease (n = 35) compared with 261.6 mg/dl for men free of coronary heart disease (n = 8,094; difference, p < 0.01), and 355.2 mg/dl for women who developed coronary heart disease (n = 6) compared with 276.8 mg/dl for women free of coronary heart disease (n = 3,842; difference, p < 0.01). With a Cox proportional hazards model to adjust for cardiovascular risk factors, the relative risk for the highest fibrinogen quartile (> or =295 mg/dl) compared with the lowest (<228 mg/dl) was 4.8 (95% confidence interval: 1.4, 16.8, p = 0.01) for coronary heart disease, and 3.8 (95% confidence interval: 1.1, 13.4, p = 0.04) for myocardial infarction. Plasma fibrinogen is useful to predict the risk of coronary heart disease among urban Japanese, whose mean plasma fibrinogen is relatively low.     

White blood cell count and incidence of coronary heart disease and ischemic stroke and mortality from cardiovascular disease in African-American and White men and women: atherosclerosis risk in communities study

The authors examined the association between white blood cell (WBC) count and incidence of coronary heart disease and ischemic stroke and mortality from cardiovascular disease in 13,555 African-American and White men and women from the Atherosclerosis Risk in Communities (ARIC) Study. Blood was drawn at the ARIC baseline examination, beginning in 1987-1989. During an average of 8 years of follow-up (through December 1996), there were 488 incident coronary heart disease events, 220 incident strokes, and 258 deaths from cardiovascular disease. After adjustment for age, sex, ARIC field center, and multiple risk factors, there was a direct association between WBC count and incidence of coronary heart disease (p < 0.001 for trend) and stroke (p for trend < 0.001) and mortality from cardiovascular disease (p for trend < 0.001) in African Americans. The African Americans in the highest quartile of WBC count (> or =7,000 cells/mm(3)) had 1.9 times the risk of incident coronary heart disease (95% confidence interval (CI): 1.19, 3.09), 1.9 times the risk of incident ischemic stroke (95% CI: 1.03, 3.34), and 2.3 times the risk of cardiovascular disease mortality (95% CI: 1.38, 3.72) as their counterparts in the lowest quartile of WBC count (<4,800 cells/mm(3)). These associations were similar in Whites and in never smokers. An elevated WBC count is directly associated with increased incidence of coronary heart disease and ischemic stroke and mortality from cardiovascular disease in African-American and White men and women.     

Combined postmenopausal hormone therapy and cardiovascular disease: toward resolving the discrepancy between observational studies and the Women's Health Initiative clinical trial

Observational research on postmenopausal hormone therapy suggests a 40-50% reduction in coronary heart disease incidence among women using these preparations. In contrast, the Women's Health Initiative clinical trial of estrogen plus progestin found an elevated incidence over a 5.6-year intervention period through July 7, 2002. Toward explaining this discrepancy, the authors analyzed data from this trial, which included 16,608 postmenopausal women aged 50-79 years, and corresponding data from 53,054 women in the Women's Health Initiative observational study, 33% of whom were estrogen-plus-progestin users at baseline. Estrogen-plus-progestin hazard ratio estimates for coronary heart disease, stroke, and venous thromboembolism in the observational study were 39-48% lower than those in the clinical trial following age adjustment. However, hazard ratios tended to decrease with increasing time from initiation of estrogen-plus-progestin use, and observational study hazard ratio estimates are heavily weighted by longer-term use while clinical trial hazard ratio estimates reflect shorter-term use. Following control for time from estrogen-plus-progestin initiation and confounding, hazard ratio estimates were rather similar for the two cohorts, although there was evidence of some remaining difference for stroke. These analyses have implications for both the design and the analysis of observational studies.