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Supplemental Digital Content is available in the text., Background and Purpose: The effect of green tea and coffee consumption on mortality among cardiovascular diseases survivors is unknown. We examined the association between green tea and coffee consumption and mortality among persons with and without stroke or myocardial infarction (MI). Methods: In the Japan Collaborative Cohort Study, 46 213 participants (478 stroke survivors, 1214 MI survivors, and 44 521 persons without a history of stroke or MI), aged 40 to 79 years at baseline (1988–1990), completed a lifestyle, diet, and medical history questionnaire and were followed up regarding mortality until 2009. The Cox proportional hazard model was used to calculate the multivariable hazard ratios with 95% CIs of all-cause mortality after adjusting for potential confounding factors. Results: During the 18.5-year median follow-up period, 9253 cases were documented. Green tea consumption was inversely associated with all-cause mortality among stroke or MI survivors; the multivariable hazard ratios (95% CIs) for stroke survivors were 0.73 (0.42–1.27) for 1 to 6 cups/wk, 0.65 (0.36–1.15) for 1 to 2 cups/d, 0.56 (0.34–0.92) for 3 to 4 cups/d, 0.52 (0.31–0.86) for 5 to 6 cups/d, and 0.38 (0.20–0.71) for ≥7 cups/d, compared with nondrinkers. A similar inverse association was observed for MI survivors, but not evident for those without a history of stroke or MI. Coffee consumption was inversely associated with all-cause mortality in persons without a history of stroke or MI; the multivariable hazard ratios (95% CIs) were 0.86 (0.82–0.91) for 1 to 6 cups/wk, 0.86 (0.80–0.92) for 1 cup/d, and 0.82 (0.77–0.89) for ≥2 cups/d, compared with nondrinkers. The corresponding hazard ratios (95% CIs) for MI survivors were 0.69 (0.53–0.91), 0.78 (0.55–1.10), and 0.61 (0.41–0.90). No such association was observed for stroke survivors. Conclusions: Green tea consumption can be beneficial in improving the prognosis for stroke or MI survivors, whereas coffee consumption can also be so for persons without a history of stroke or MI as well as MI survivors.

Background: Both green tea and coffee consumption have been associated with lower risks of mortality from cardiovascular disease (CVD) and all causes in general population, but little is known about those impact on persons with history of CVD. We examined the association of those consumption with these mortalities among persons with and without history of stroke or myocardial infarction in general population. Methods: The study subjects were 60,664 participants (896 stroke and 1751 myocardial infarction survivors and 58,017 persons with no history of stroke or myocardial infarction), aged 40-79 years at the baseline (1988-1990), who completed a lifestyle and medical history questionnaire including self-administered food frequency under the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). Results: During the median follow-up of 18.5 years, a total of 12,745 (7,458 men and 5,287 women) deaths including 3,737 CVD deaths were documented. Green tea and coffee consumption were inversely associated with CVD and all-cause mortality among myocardial infarction survivors as well as persons without history of stroke or myocardial infarction. After adjustment for known cardiovascular risk factors, the lower risks of mortality from CVD and all-causes associated with frequent green tea consumption (5-6 and ≥7 cups/day) or coffee consumption (≥2 cups/day) remained statistical. Conclusions: Both green tea and coffee consumption were inversely associated with risks of CVD and all-cause mortality among myocardial infarction survivors and persons without history of stroke or myocardial infarction.

Background and Purpose— There is growing evidence about the importance of vitamin D for cardiovascular health. Therefore, we examined the relationship between dietary vitamin D intake and risk of mortality from stroke and coronary heart disease in Japanese population. Methods— A prospective study encompassing 58 646 healthy Japanese adults (23 099 men and 35 547 women) aged of 40 to 79 years in whom dietary vitamin D intake was determined via a self-administered food frequency questionnaire. The median follow-up period was 19.3 years (1989–2009). The hazard ratios and 95% confidence intervals of mortality were calculated using categories of vitamin D intake. Results— During 965 970 person-years of follow-up, 1514 stroke and 702 coronary heart disease deaths were documented. Vitamin D intake was inversely associated with risk of mortality from total stroke especially intraparenchymal hemorrhage but not from coronary heart disease; the multivariable hazard ratios (95% confidence intervals) for the highest (≥440 IU/d) versus lowest (P for trend=0.04) for total stroke and 0.66 (0.46–0.96; P for trend=0.04) for intraparenchymal hemorrhage. Conclusions— Dietary vitamin D intake seems to be inversely associated with mortality from stroke.

Background and Purpose— There have been consistent findings reported that marital transition (ie, change in marital status during a given time period) is associated with risk of cardiovascular disease; however, few studies have been conducted on stroke risk, particularly stroke subtypes. Moreover, no studies have examined the moderating effect of living arrangement and employment status on the association between marital transition and stroke risk. Methods— We examined sex-specific associations between marital transition and stroke risk using data from Japan Public Health Center–based Prospective Study. We included 24 162 men and 25 626 women who were married at prebaseline (5 years before baseline). Marital transition was determined by marital status at baseline. Weighted hazard ratios of stroke risk were estimated by Cox proportional regression analysis with inverse probability of weighting using a propensity score. Results— An increased risk of stroke, particularly hemorrhagic stroke, was observed among men and women with marital transition (ie, married to unmarried); weighted hazard ratios (95% confidence interval [CI]) for men and women were 1.26 (1.13–1.41) and 1.26 (1.09–1.45), respectively. Participants with marital transition and lived with children had increased stroke risk. Living with parents buffered the increased stroke risk owing to marital transition among men; however, no such effect was identified among women. Elevated stroke risk owing to marital transition was magnified among women if they were unemployed; weighted hazard ratio=2.98 (95% CI, 1.66–5.33). Conclusions— Living arrangement and employment status modified the positive associations between marital transition and stroke risk, which differed by sex.

Background and Purpose— There is limited evidence on the association between total physical activity and stroke in Asian populations experiencing a greater burden of hemorrhagic stroke than Western populations. We aimed to understand their optimal level of physical activity for stroke prevention. Methods— A total of 74 913 Japanese people 50 to 79 years of age without histories of cardiovascular disease or cancer were followed from 2000 to 2012. Results— During the 698 946 person-years of follow-up, we documented a total of 2738 incident cases of stroke, including 1007 hemorrhagic strokes (747 intraparenchymal and 260 subarachnoid hemorrhages) and 1721 ischemic strokes (1206 nonembolic and 515 embolic infarctions). Individuals in the second or third metabolic equivalents of task–hours per day quartile had the lowest risks of total stroke (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.75–0.93), intraparenchymal hemorrhage (HR, 0.79; 95% CI, 0.64–0.97), subarachnoid hemorrhage (HR, 0.78; CI, 0.55–1.11), and nonembolic infarction (HR, 0.78; CI, 0.67–0.92), whereas those in the fourth quartile had the lowest risk of embolic infarction (HR, 0.76; CI, 0.59–0.97). Cubic spline graphs revealed a steep decrease in stroke risk (30% risk reduction) from the lowest level to a plateau at 5 to 10 metabolic equivalents of task–hours per day (50th percentile). The associations of total physical activity level with hemorrhage stroke showed U or J shape, which were because of vigorous-intensity activities, whereas the association with ischemic stroke showed L shape. Conclusions— For Japanese people, moderate levels of total physical activity, particularly achieved by moderate-intensity activities, may be optimal for stroke prevention because excessive vigorous-intensity activities might not be beneficial or even disadvantageous for prevention of hemorrhagic stroke.

Background and Purpose—Little research has been conducted to examine the effect of inconsistencies in socioeconomic status on cardiovascular health. In particular, no studies have been reported in Asian countries, including Japan, which is thought to have high socioeconomic status inconsistency among women.Methods—We examined the effect of status inconsistency between education level and occupation on stroke risk in a prospective 20-year study of 14 742 middle-aged Japanese women included in the prospective Japan Public Health Center-based (JPHC) Study Cohort I in 1990. Status inconsistency between education level and occupation was determined (qualified, overqualified, and underqualified), and the association with risk of stroke was examined. Cox proportional regression analysis was used to determine hazard ratios, which were adjusted for age, marital status, and geographical area.Results—Adjusted hazard ratio for stroke in overqualified compared with qualified women was 2.06 (95% confidence interval, 1.13–3.78). Adjusted hazard ratios for stroke among highly educated manual workers and workers in service industry were 3.47 (95% confidence interval, 1.54–7.84) and 3.21 (95% confidence interval, 1.49–6.90), respectively, when compared with highly educated professionals/managers.Conclusions—High academic qualifications without an appropriate job could be a risk factor for stroke among Japanese women. Our result suggests that status inconsistency could be a potential explanation for the increased stroke risk among highly educated women.

Background and Purpose— Few prospective studies have examined the impact of both green tea and coffee consumption on strokes. We investigated the association of the combination of those consumption with stroke incidence in a general population. Methods— We studied 82 369 Japanese (aged 45–74 years; without cardiovascular disease [CVD] or cancer in 1995 and 1998 for Cohort I and II, respectively) who received 13 years of mean follow-up through the end of 2007. Green tea and coffee consumption was assessed by self-administered food frequency questionnaire at baseline. Results— In the 1 066 718 person-years of follow-up, we documented the incidence of strokes (n=3425) and coronary heart disease (n=910). Compared with seldom drinking green tea, the multivariable-adjusted hazard ratios (95% confidence intervals) of all strokes were 0.86 (0.78–0.95) and 0.80 (0.73–0.89) in green tea 2 to 3 and ≥4 cups/d, respectively. Higher green tea consumption was associated with inverse risks of CVD and strokes subtypes. Compared with seldom drinking coffee, the multivariable-adjusted hazard ratios (95% confidence intervals) of all strokes were 0.89 (0.80–0.99), 0.80 (0.72–0.90), and 0.81 (0.72–0.91) for coffee 3 to 6 times/week and 1 and ≥2 times/day, respectively. Coffee consumption was associated with an inverse risk of CVD and cerebral infarction. Higher green tea or coffee consumption reduced the risks of CVD and stroke subtypes (especially in intracerebral hemorrhage, P for interaction between green tea and coffee=0.04). None of the significant association was observed in coronary heart disease. Conclusions— Higher green tea and coffee consumption were inversely associated with risk of CVD and stroke in general population.

Background and Purpose— An individualized risk score for the development of stroke may be a useful tool to motivate patients to modify their risk behaviors. We developed and validated a point-based prediction model (risk score) for stroke incidence using a Japanese cohort of general men and women. Methods— The Japan Public Health Center-based prospective study cohort II (age range, 40–69 years at baseline in 1993–1994; n=15 672) was used to derive the point-based model according to Cox regression results. The model was externally validated using the Japan Public Health Center study cohort I and also by bootstrap methods within cohort II. The model discrimination was evaluated by the area under the receiver operating characteristic curve, model calibration, by the Grønnesby–Borgan χ 2 statistic. Vascular age was also calculated. Results— During 14 years of follow-up, 790 incident stroke cases occurred. Variables selected for the model were age, sex, current smoking, body mass index, blood pressure, antihypertensive medication use, and diabetes mellitus. Interactions of sex with current smoking and of antihypertensive medication use with systolic blood pressure were statistically significant. The point-based model discriminated reasonably well (area under the receiver operating characteristic curve, 0.73). The area under the receiver operating characteristic curve of the point-based model applied externally to cohort I was reasonably good: 0.69. A 50-year-old man with diabetes mellitus and hypertension has an estimated vascular age of 69 years. High normal blood pressure and grade 1 hypertension accounted for one third of the stroke incidence. Conclusions— We developed score to predict 10-year stroke risk using variables that are easily available in the community setting.

Background and Purpose— High-density lipoprotein (HDL) cholesterol is an established protective factor for ischemic stroke. However, the contribution of HDL subclasses to stroke risk and its subtypes is uncertain. Methods— A prospective nested case–control study of 40- to 85-year-old Japanese was undertaken using frozen serum samples collected from 5280 men and 7524 women. They participated in cardiovascular risk surveys from 1985 to 1999 (1 community) and 1989 to 1998 (2 communities) under Circulatory Risk in Communities Study. HDL cholesterol subclasses were classified by high-performance liquid chromatography into 3 subgroups: S-HDL (very small or small HDL), M-HDL (medium HDL), and L-HDL (large or very large HDL) cholesterol. One control subject per case was matched by sex, age, community, serum storage year, and fasting status. Results— In 2005, we identified 241 strokes (155 ischemic and 86 hemorrhagic). S-HDL and M-HDL cholesterol levels were inversely associated with total stroke risk, ischemic stroke, specifically lacunar infarction, and hemorrhagic stroke. After adjustment for cardiovascular risk factors, these associations remained statistically significant. Multivariable conditional odds ratios (95% confidence interval) for 1 SD (0.12 mmol/L) increment of S-HDL cholesterol levels were 0.34 (0.23–0.52) for total stroke, 0.38 (0.23–0.63) for ischemic stroke, 0.33 (0.18–0.61) for lacunar infarction, 0.30 (0.14–0.65) for hemorrhagic stroke, and 0.30 (0.12–0.77) for intraparenchymal hemorrhage. The respective multivariable odds ratios for 1SD (0.10 mmol/L) increment of M-HDL cholesterol levels were 0.56 (0.41–0.75), 0.63 (0.45–0.88), 0.59 (0.40–0.87), 0.41 (0.21–0.80), and 0.38 (0.16–0.90). No associations were found between L-HDL cholesterol levels and risk of total stroke and its subtypes. Conclusions— Small- to medium-sized HDL, not large HDL, cholesterol levels were inversely associated with total stroke risk.

Background and Purpose— Because of limited evidence, we investigated a long-term impact of changes in employment status on risk of stroke. Methods— This was a prospective study of 21 902 Japanese men and 19 826 women aged 40 to 59 years from 9 public health centers across Japan. Participants were followed up from 1990 to 1993 to the end of 2009 to 2014. Cox proportional hazard ratio of stroke (incidence and mortality) and its types (hemorrhagic and ischemic) was calculated according to changes in the employment status within 5 years interval between 1990 to 1993 and 1995 to 1998 (continuously employed, job loss, reemployed, and continuously unemployed). Results— During the follow-up period, 973 incident cases and 275 deaths from stroke in men and 460 cases and 131 deaths in women were documented. Experiencing 1 spell of unemployment was associated with higher risks of morbidity and mortality from total, hemorrhagic, and ischemic stroke in both men and women, even after propensity score matching. Compared with continuously employed subjects, the multivariable hazard ratio (95% confidence interval) for total stroke incidence in job lost men was 1.58 (1.18–2.13) and in job lost women was 1.51 (1.08–2.29), and those for total stroke mortality were 2.22 (1.34–3.68) in men and 2.48 (1.26–4.77) in women. The respective hazard ratio (95% confidence interval) in reemployed men was 2.96 (1.89–4.62) for total stroke incidence and 4.21 (1.97–8.97) for mortality, whereas those in reemployed women were 1.30 (0.98–1.69) for incidence and 1.28 (0.76–2.17) for mortality. Conclusions— Job lost men and women and reemployed men had increased risks for both hemorrhagic and ischemic stroke incidence and mortality.

Supplemental Digital Content is available in the text., Background and Purpose— The prediction of genetic predispositions to ischemic stroke (IS) may allow the identification of individuals at elevated risk and thereby prevent IS in clinical practice. Previously developed weighted multilocus genetic risk scores showed limited predictive ability for IS. Here, we investigated the predictive ability of a newer method, polygenic risk score (polyGRS), based on the idea that a few strong signals, as well as several weaker signals, can be collectively informative to determine IS risk. Methods— We genotyped 13 214 Japanese individuals with IS and 26 470 controls (derivation samples) and generated both multilocus genetic risk scores and polyGRS, using the same derivation data set. The predictive abilities of each scoring system were then assessed using 2 independent sets of Japanese samples (KyushuU and JPJM data sets). Results— In both validation data sets, polyGRS was shown to be significantly associated with IS, but weighted multilocus genetic risk scores was not. Comparing the highest with the lowest polyGRS quintile, the odds ratios for IS were 1.75 (95% confidence interval, 1.33–2.31) and 1.99 (95% confidence interval, 1.19–3.33) in the KyushuU and JPJM samples, respectively. Using the KyushuU samples, the addition of polyGRS to a nongenetic risk model resulted in a significant improvement of the predictive ability (net reclassification improvement=0.151; P

Background and Purpose— Understanding associations of carotid atherosclerosis with stroke subtypes may contribute to more effective prevention of stroke. Methods— Between 1987 and 1989, 13 560 men and women aged 45 to 64 years and free of clinical stroke took part in the first examination of the Atherosclerosis Risk in Communities (ARIC) study. Incident strokes were ascertained by hospital surveillance. Results— During an average follow-up of 15.7 years, 82 incident hemorrhagic and 621 incident ischemic strokes (131 lacunar, 358 nonlacunar, and 132 cardioembolic strokes) occurred. The incidence rates of hemorrhagic and ischemic strokes were greater across higher carotid intima-media thickness levels. Although this positive association was observed for all stroke subtypes, the age-, gender-, and race-adjusted risk ratios were higher for cardioembolic and nonlacunar strokes than for hemorrhagic and lacunar strokes. Compared with participants in the lowest quintile (P for trend P for interaction=0.07). Conclusions— Carotid atherosclerosis was associated with increased risk of all stroke subtypes, but the association of carotid atherosclerosis with stroke may vary by subtypes.

Background and Purpose— Hypertension is a major risk factor for stroke. However, a substantial decrease in blood pressure levels in Japanese during the past 3 decades may have reduced contributions of hypertension to risk of stroke. The population attributable fraction, the percentage of outcomes attributable to exposure, of blood pressure for the incidence of stroke was investigated during 3 survey periods between 1963 and 1994 by means of a population-based cohort study. Methods— We explored 3 cohort data of residents aged 40 to 69 years in 4 Japanese communities in 1963 to 1971 (n=5439), 1975 to 1984 (n=9945), and 1985 to 1994 (n=11 788) baseline surveys. Mean follow-up period for each cohort was 10 years. Results— Higher blood pressure levels were associated with higher risk of stroke. Positive associations were also observed even within nonhypertension levels. From the first to the third cohorts, the blood pressure category with a majority of stroke incidence shifted from severe or moderate hypertension to mild hypertension. The population attributable fraction of the severe hypertension category in the first, second, and third cohorts were 20%, 14%, and 9%, respectively, and those of the moderate hypertension category were 19%, 24%, and 11%, respectively, whereas those of the mild hypertension category were 17%, 26%, and 23%, respectively. The results were similar when participants on antihypertensive medication were excluded. Conclusions— The higher risk of stroke incidence with higher blood pressure levels even in nonhypertension categories and the shift of stroke burden from severe/moderate hypertension to mild hypertension support the early management of hypertension and primary prevention of high blood pressures for the prevention of stroke.

Background and Purpose— Previous studies have demonstrated the association between alcohol consumption and cardiovascular mortality. However, the sex-specific association between alcohol consumption and mortality from stroke and coronary heart disease remains unclear. Methods— Between 1988 and 1990, 34 776 men and 48 906 women aged 40 to 79 years completed a self-administered questionnaire including information about alcohol consumption. They were followed-up for a median duration of 14.2 years. Results— Of the 83 682 respondents, 1628 died from stroke and 736 died from coronary heart disease. For men, heavy drinking (≥46.0 g ethanol/day) was associated with increased mortality from total, hemorrhagic, and ischemic strokes, whereas light-to-moderate drinking was associated with reduced mortality from total cardiovascular disease, compared with not drinking. The respective multivariable hazard ratios (95% CI) were 1.48 (1.22 to 1.80) for total stoke, 1.67 (1.17 to 2.38) for hemorrhagic stroke, 1.35 (1.04 to 1.75) for ischemic stroke, and 0.88 (0.78 to 1.00) for total cardiovascular disease. Women who were heavy drinkers (≥46.0 g ethanol/day) showed increased mortality from coronary heart disease, and there was reduced mortality from total cardiovascular disease for drinkers of 0.1 to 22.9 g ethanol per day compared with mortality for nondrinkers. The respective multivariable hazard ratios (95% CI) for the 2 categories of drinkers were 4.10 (1.63 to 10.3) and 0.75 (0.62 to 0.91). Conclusions— Heavy alcohol consumption is associated with increased mortality from total stroke, particularly hemorrhagic stroke, and total cardiovascular disease for men, and from coronary heart disease for women, whereas light-to-moderate drinking may be associated with reduced mortality from cardiovascular disease for both sexes.

Background and Purpose— Little research has been conducted into variations in women’s health in relation to educational level and social roles in Japan. We sought to examine the effect of educational level on risk of cardiovascular disease and its modification by social roles at work and at home under the Japan Public Health Center-based Prospective Study (JPHC Study) Cohort I. Methods— We calculated the adjusted hazard ratios of educational level for cardiovascular disease incidence within a 12-year study of 20 543 Japanese women aged 40 to 59 without history of stroke or heart disease. Results— The respective age and area-adjusted hazard ratios for junior high school education and college or higher education compared to high school education were 1.63 (95% CI: 1.29, 2.06) and 1.41(95% CI: 0.96, 2.05) for total stroke, 2.20 (95% CI: 1.34, 3.60) and 2.20 (95% CI: 1.08, 4.48) for subarachnoid hemorrhage, and 1.90 (95% CI: 1.30, 2.76) and 1.60 (95% CI: 0.87, 2.93) for ischemic stroke. The U-shaped association with risk of total stroke was primarily observed for working women with single social roles at home. No association was found between educational level and risk of coronary heart disease or intraparenchymal hemorrhage. Conclusions— A potential benefit of multiple social roles was suggested for stroke risk reduction among highly educated working women.

Background and Purpose— Although it has been hypothesized that a high intake of dietary calcium may reduce the risk of cardiovascular disease (CVD), no prospective studies have been conducted to examine the specific association between calcium intake and incidence of stroke or coronary heart disease among Japanese with a low average calcium intake. Methods— To investigate the association between calcium intake and risk of CVD, a total of 41 526 Japanese men and women age 40 to 59 years without a history of CVD or cancer and who had completed a food consumption frequency questionnaire were enrolled in this study. The subjects were followed up from 1990 to 1992 to 2003, and after 533 692 person-years of follow-up, 1321 incident cases of stroke (664 ischemic, 425 intraparenchymal hemorrhage, and 217 subarachnoid hemorrhage) and 322 of coronary heart disease were documented. Results— Total calcium intake showed an inverse association with the risk of total stroke; the multivariable hazard ratio and 95% CIs for the highest versus the lowest quintile were 0.70 (95% CI, 0.56 to 0.88; P for trend=0.02). Dairy calcium intake was inversely associated with risks of total and ischemic stroke with respective multivariable hazard ratios (95% CIs) of 0.69 (0.56 to 0.85; P for trend=0.007) and 0.69 (0.52 to 0.93; P for trend=0.05). Dietary calcium intake was not significantly associated with risk of coronary heart disease. Conclusions— Dietary calcium intake, especially calcium from dairy products, was found to be associated with a reduced incidence of stroke among middle-aged Japanese.

Background and Purpose— Studies conducted in Western countries have found a robust association between social support and cardiovascular outcomes (eg, prognosis after myocardial infarction and functional recovery after stroke). However, less is known about the influence of social support on the same outcomes among Asian populations. In this prospective cohort study, we sought to examine the impact of social support on the incidence and mortality of coronary heart disease and stroke among the Japanese. Methods— We examined prospectively the association between social support and risk of coronary heart disease and stroke incidence and mortality within a cohort of 44 152 Japanese men and women aged 40 to 69 years, free of previous diagnosis of cancer and cardiovascular disease. A total of 301 cases of newly diagnosed coronary heart disease, 1057 strokes, 191 coronary heart disease deaths, and 327 stroke deaths occurred between the baseline questionnaire (1993–1994) and the end of follow-up in January 2004. Results— The multivariate hazard ratios and 95% CI for stroke mortality in the highest social support versus lowest social support group was 1.45 (1.00 to 2.10) overall, 1.59 (1.01 to 2.51) for men, and 1.25 (0.63 to 2.46) for women. Social support was not associated with stroke incidence or coronary heart disease incidence and mortality. Conclusions— Low social support was associated with higher risk of stroke mortality in men. However, social support was not associated with stroke incidence, suggesting social support may be more important in stroke prognosis than preventing incidence.

Background and Purpose— The association between breakfast intake and the risk of cardiovascular disease, including stroke, among Asian people remains unknown. We sought to prospectively investigate whether the omission of breakfast is related to increased risks of stroke and coronary heart disease in general Japanese populations. Methods— A total of 82 772 participants (38 676 men and 44 096 women) aged 45 to 74 years without histories of cardiovascular disease or cancer were followed up from 1995 to 2010. Participants were classified as having breakfast 0 to 2, 3 to 4, 5 to 6, or 7 times/wk. The hazard ratios of cardiovascular disease were estimated using Cox proportional hazards models. Results— During the 1 050 030 person-years of follow-up, we documented a total of 4642 incident cases, 3772 strokes (1051 cerebral hemorrhages, 417 subarachnoid hemorrhages, and 2286 cerebral infarctions), and 870 coronary heart disease. Multivariable analysis showed that those consuming no breakfast per week compared with those consuming breakfast everyday had hazard ratios (95% confidence interval; P for trend) of 1.14 (1.01–1.27; 0.013) for total cardiovascular disease, 1.18 (1.04–1.34; 0.007) for total stroke, and 1.36 (1.10–1.70; 0.004) for cerebral hemorrhage. Similar results were observed even after exclusion of early cardiovascular events. No significant association between the frequency of breakfast intake and the risk of coronary heart disease was observed. Conclusions— The frequency of breakfast intake was inversely associated with the risk of stroke, especially cerebral hemorrhage in Japanese, suggesting that eating breakfast everyday may be beneficial for the prevention of stroke.

Background and Purpose— We aimed to examine the impact of fibrinogen concentrations on the incidence of stroke. Methods— We examined the association between fibrinogen and risk of total stroke and stroke subtypes in an 11-year prospective study of 4608 men and 7589 women aged 40 to 79 years with no history of stroke and/or coronary heart disease. The analysis was repeated, stratified by smoking status, to examine whether the association between fibrinogen and stroke was modified by smoking. Results— There were 317 incident total strokes comprising 103 hemorrhagic strokes (70 intraparenchymal hemorrhages [22.1% of strokes], 33 subarachnoid hemorrhages [10.4%]), 206 ischemic strokes (65.0%), and 8 strokes of undetermined type (2.5%). The multivariable hazard ratio (95% CI) for the highest versus lowest fibrinogen quartiles after adjustment for age, sex, area, and known cardiovascular risk factors was 2.5 (1.3 to 5.0), P P P =0.01, for hemorrhagic stroke and 4.4 (1.3 to 15.2), P =0.02, for intraparenchymal hemorrhage. Conclusions— High plasma fibrinogen concentration can be a predictor for risk of intraparenchymal hemorrhage.

We thank Drs Liao et al1 for their interest in our article.2 The authors are concerned that our results may be misleading because we combine all types of stroke for determining outcome. In response to the concerns by Dr Liao et al, we conducted our analysis by subtype of stroke. We performed a similar analysis to that in Table 4 in our previous article2 and estimated adjusted hazard ratios (HRs) for subarachnoid hemorrhage, intraparenchymal hemorrhage, and ischemic stroke …

Background and Purpose— Although overweight is an important risk factor for cardiovascular disease in Western countries, the impact of overweight has not been well elucidated in Japan, where its prevalence is low. Methods— A total of 104 928 Japanese (43 889 men and 61 039 women) aged 40 to 79 years, free of stroke, coronary heart disease, and cancer at entry participated in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by Monbusho (JACC Study) between 1988 and 1990. Systematic surveillance was completed until the end of 1999, with 1 042 835 person years of follow-up, and the underlying causes of death were determined based on the International Classification of Diseases. Results— There were 765 total strokes (191 intraparenchymal hemorrhages), 379 coronary heart diseases, and 1707 total cardiovascular diseases for men; and for women, there were 685 (145), 256, and 1432, respectively. Compared with persons with body mass index (BMI) 23.0 to 24.9, those with BMI ≥27.0 kg/m 2 had a higher risk of coronary heart disease; for men and women, the respective multivariate relative risk (95% CI) was 2.05 (1.35 to 3.13) and 1.58 (0.95 to 2.62). Persons with BMI 2 had higher risk of total stroke and intraparenchymal hemorrhage, for men and women, the respective multivariate relative risk was 1.29 (1.01 to 1.49) and 1.92 (1.49 to 2.47) for total stroke and 1.96 (1.16 to 3.31) and 2.32 (1.36 to 3.97) for intraparenchymal hemorrhage. These excess risks did not alter materially when deaths within 5 years were excluded or when smoking status was taken into account. Conclusions— For Japanese men and women, high BMI was associated with increased risk of coronary heart disease, whereas low BMI was associated with intraparenchymal hemorrhage.

Background and Purpose— We examined sex-specific relationships of smoking with risk of total stroke and stroke subtypes in Asian populations because of the limited data available. Methods— A total of 19 782 men and 21 500 women aged 40 to 59 years who were free of prior diagnosis of stroke, coronary heart disease, or cancer and reported their smoking status were followed in the Japan Public Health Center–based Prospective Study on Cancer and Cardiovascular Disease (JPHC Study) from 1990 to 1992 to the end of 2001. Results— During a 461 761 person-year follow-up, 702 total strokes were documented among men, of which 619 were confirmed by imaging studies, including 219 intraparenchymal hemorrhages, 73 subarachnoid hemorrhages, and 327 ischemic strokes. The respective numbers of cases among women were 447, 411, 129, 106, and 176. Multivariate relative risks (95% CIs) for current smokers compared with never-smokers after adjustment for cardiovascular risk factors and public health center were 1.27 (1.05 to 1.54) for total stroke, 0.72 (0.49 to 1.07) for intraparenchymal hemorrhage, 3.60 (1.62 to 8.01) for subarachnoid hemorrhage, and 1.66 (1.25 to 2.20) for ischemic stroke. The respective multivariate relative risks among women were 1.98 (1.42 to 2.77), 1.53 (0.86 to 4.25), 2.70 (1.45 to 5.02), and 1.57 (0.86 to 2.87). There was a dose-response relation between the number of cigarettes smoked and risks of ischemic stroke for men. A similar positive association was observed between smoking and risks of lacunar infarction and large-artery occlusive infarction, but not embolic infarction. Conclusions— Smoking raises risks of total stroke and subarachnoid hemorrhage for both men and women and risk of ischemic stroke, either lacunar or large-artery occlusive infarction, for men.

Background and Purpose— The impact of light-to-moderate alcohol consumption on risk of stroke has not been well examined in a single study, although the effect is hypothesized to differ among stroke subtypes from meta-analyses. Methods— A total of 19 544 men aged 40 to 59 years living in communities were followed-up from 1990 to 1992 to the end of 2001 in the Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Disease (JPHC Study). Results— After 214 504 person-years of follow-up, 694 incident strokes were documented, of which 611 were confirmed by imaging studies or autopsy, including 219 intraparenchymal hemorrhages, 73 subarachnoid hemorrhages, and 319 ischemic strokes. Alcohol consumption was positively associated with age-adjusted risk of total stroke with a 68% excess risk among drinkers of ≥450 g ethanol per week compared with occasional drinkers. This excess risk was confined primarily to hemorrhagic stroke, which remained statistically significant even after controlling for hypertension and other cardiovascular risk factors (RR: 2.15; 95% CI: 1.22 to 3.79). There was a lower risk of ischemic stroke, more specifically lacunar infarction, a higher risk of hemorrhagic stroke, and no excess risk of total stroke among drinkers of 1 to 149 g ethanol per week compared with occasional drinkers; the respective multivariate RR (95% CI) was 0.59 (0.37 to 0.93), 0.43 (0.22 to 0.87), 1.73 (0.98 to 3.07), and 0.98 (0.71 to 1.36). Conclusions— We found differential effects of light-to-moderate alcohol consumption on risks of hemorrhagic and ischemic strokes among middle-aged men. Light-to-moderate alcohol consumption, ie, ≤2 drinks per day, does not raise the risk of total stroke.

Background and Purpose— The present study aimed to identify risk factors for mortality due to subarachnoid hemorrhage (SAH) using a comprehensive questionnaire from the Japan Collaborative Cohort (JACC) Study, a Japan-wide population-based prospective study. Methods— A total of 109 293 individuals (45 551 men and 63 742 women, aged 40 to 79 years) free of stroke at entry participated in the JACC Study between 1988 and 1990. Participants were followed up annually until they died or moved away from the surveyed community, or until the end of 1999. A diagnosis of death from SAH was based on the International Classification of Diseases , 10th revision (ICD-10). The age-adjusted univariate and multivariate hazard ratios (HR) and 95% confidence intervals (CI) of various factors were calculated in sex-stratified and sex-specific analyses using the Cox proportional hazards regression model. Results— A total of 244 individuals (88 men and 156 women) died from SAH during the follow-up of 1 086 963 person-years. Our univariate analyses confirmed that preference for salty foods and history of blood transfusion, as well as hypertension, family history of stroke, cigarette smoking, heavy alcohol consumption, and low BMI, had statistically significant associations with mortality due to SAH. Multivariable analyses revealed that history of blood transfusion was an independent significant risk factor (HR=4.2 [95%CI, 2.1 to 8.5]) for men, while preference for salty foods or heavy drinking were not. Conclusions— History of blood transfusion was found to be an independent risk. The association between SAH and blood transfusion warranted further study.

Background and Purpose— An effect of multivitamin supplement on stroke risk is uncertain. We aimed to examine the association between multivitamin use and risk of death from stroke and its subtypes. Methods— A total of 72 180 Japanese men and women free from cardiovascular diseases and cancers at baseline in 1988 to 1990 were followed up until December 31, 2009. Lifestyles including multivitamin use were collected using self-administered questionnaires. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of total stroke and its subtypes in relation to multivitamin use. Results— During a median follow-up of 19.1 years, we identified 2087 deaths from stroke, including 1148 ischemic strokes and 877 hemorrhagic strokes. After adjustment for potential confounders, multivitamin use was associated with lower but borderline significant risk of death from total stroke (HR, 0.87; 95% confidence interval, 0.76–1.01), primarily ischemic stroke (HR, 0.80; 95% confidence interval, 0.63–1.01), but not hemorrhagic stroke (HR, 0.96; 95% confidence interval, 0.78–1.18). In a subgroup analysis, there was a significant association between multivitamin use and lower risk of mortality from total stroke among people with fruit and vegetable intake Conclusions— Multivitamin use, particularly frequent use, was associated with reduced risk of total and ischemic stroke mortality among Japanese people with lower intake of fruits and vegetables.

Background and Purpose —We sought to examine the relationship between depressive symptoms and the incidence of stroke among Japanese men and women. Methods —A 10.3-year prospective study on the relationship between depressive symptoms and the incidence of stroke was conducted with 901 men and women aged 40 to 78 years in a rural Japanese community. Depressive symptoms were measured at baseline with the use of the Zung Self-Rating Depression Scale (SDS). The incidence of stroke was ascertained under systematic surveillance. Results —During the 10-year follow-up, 69 strokes (39 ischemic strokes, 10 intracerebral hemorrhages, 10 subarachnoid hemorrhages, and 10 unclassified strokes) occurred. Age- and sex-adjusted prevalence of mild depression (SDS scores ≥40) at baseline was 25% among subjects with incident stroke and 12% among subjects without stroke ( P Conclusions —Depressive symptoms predict the risk of stroke, specifically ischemic stroke among Japanese.

Response: We thank Dr Chen for his interest in our article and his valuable suggestions on this topic. As you know, in our study, we found that higher green tea drinking (≥2 cups/d) or coffee consumption (≥1 cup/d) was inversely associated with the risk of cardiovascular disease and stroke, especially of intracerebral hemorrhage.1 In a further analysis, we found significant decreases in the incidence of stroke among participants who drank green tea (multivariable-adjusted hazard ratio [HR], 0.88; 95% confidence intervals [CIs], 0.81–0.95) or coffee (HR, 0.88; 95% CIs, 0.82–0.94) as a whole (≥1 cup/wk) compared with nondrinkers. In addition, the participants who drank green tea ≥4 cups/d (HR, 0.86; 95% …

Background and Purpose Understanding the effects of alcohol intake on stroke and other cardiovascular diseases is an important issue for public health. Methods A 10.5-year prospective study of the relationship between alcohol intake and cardiovascular disease incidence was conducted in 2890 men, aged 40 to 69 years and free of a history of stroke and coronary heart disease, in three rural communities of Japan. Results One hundred seventy-eight strokes (40 intracerebral hemorrhages, 18 subarachnoid hemorrhages, 104 nonhemorrhagic strokes, and 16 unclassified strokes), 34 coronary heart disease events, and 19 sudden unclassified deaths occurred. Drinkers of ≥70 g/d ethanol had an approximately 2.5 times higher age-adjusted risk of all stroke than never-drinkers; the excess risk was more evident for hemorrhagic stroke than nonhemorrhagic stroke. When hypertension category, serum total cholesterol level, cigarette smoking, and diabetes mellitus were taken into account, these excess risks were reduced but remained significant for all stroke (2.0; 95% confidence interval, 1.3 to 3.1) and hemorrhagic stroke (3.4; 95% confidence interval, 1.2 to 9.2). A J-shaped relationship was suggested between alcohol intake and risk of nonhemorrhagic stroke; drinkers of Conclusions Heavy drinking appeared to increase the risk of hemorrhagic stroke, in part due to hypertension, and to increase the risk of sudden death, which was probably due to drinking per se. Light or moderate alcohol consumption seemed to protect against nonhemorrhagic stroke and coronary heart disease.

This report examines the hypothesis that the higher risk of stroke among Japanese men in Japan compared with those in Hawaii is related to pathology in small intracerebral arteries by comparing the prevalence of such lesions in autopsied participants from two cohorts of Japanese men in Japan and Hawaii. Existing histological sections from the left basal ganglia from 232 men from Japan and 175 men of Japanese ancestry in Hawaii were examined for selected abnormalities in arteries between 100 and 300 microns in diameter by three pathologists. The presence of lacunar infarcts was also noted, and information about cerebral infarcts, cerebral hemorrhages, and atherosclerosis in the circle of Willis was available for the Hawaii group. Lacunar infarcts and all small intracerebral artery lesions except medial fibrosis were more common at every age in Japan than in Hawaii. By cause of death, all lesions were three or more times more prevalent among men who died of stroke than of noncardiovascular causes in both areas. In the Hawaii group, the small intracerebral artery lesions were significantly associated with autopsy evidence of cerebral and lacunar infarcts, and with atherosclerosis in the large arteries of the circle of Willis. Among a large number of risk factors measured at the baseline examination in Hawaii, only high blood pressure and reported usual Asian diet were significantly associated with one or more measures of small intracerebral artery lesions. An overview of the accumulated data indicated that small intracerebral artery pathology plays an important role in the high risk of stroke in Japanese men in Japan compared with those in Hawaii. These studies support the idea that hypertension is a necessary factor in the causal pathway, but also indicate that some other factors are involved. Some aspect of an Asian diet continues to be of importance for future research.

Background and Purpose— Although diabetes mellitus has been recognized as a risk factor for ischemic stroke, evidence is limited for ischemic stroke subtypes among Asians. Methods— A survey was conducted of a total of 13 129 men and 22 528 women aged 40 to 69 years at baseline. During the median 12.0-year follow-up, there were 526 incidences of ischemic strokes (259 lacunar infarctions, 91 large-artery occlusive, and 140 embolic infarctions). Results— The risk of ischemic stroke for both sexes was approximately 2 to 4 times higher for diabetic subjects than for those with normal glucose levels. Significant excess risks of lacunar and embolic infarction for both sexes and of large-artery occlusive infarctions for women were also observed in diabetic subjects. Diabetes mellitus was not associated with risk of intraparenchymal or subarachnoid hemorrhage for either sex. Conclusions— Diabetes mellitus is a significant risk factor for ischemic stroke and all subtypes of ischemic stroke for middle-aged Japanese.

Background and Purpose— Only a few reports have dealt with the association of antioxidant vitamin intakes with mortality or morbidity from cardiovascular disease in Asia. We investigated the relation of dietary vitamins A, E, and C intake with mortality from cardiovascular disease for Japanese men and women. Methods— The subjects were 23 119 men and 35 611 women aged 40 to 79 years without a history of cardiovascular disease or cancer who responded to the food frequency questionnaire as part of the Japan Collaborative Cohort Study for Cancer Risk (JACC) Study. They were followed up for a median period of 16.5 years. Hazard ratios were calculated per quintile of dietary vitamins A, E, and C intake by using Cox proportional hazard model. Results— During the 859 962 person-year follow-up, there were 2690 deaths (1343 men and 1347 women) from cardiovascular disease, comprising 1227 (607 men and 620 women) from stroke and 557 (311 men and 246 women) from coronary heart disease. The multivariable hazard ratios (95% CI) associated with the highest versus lowest quintiles of vitamin C intake were 0.70 (0.54 to 0.92) for total stroke, 0.63 (0.41 to 0.97) for coronary heart disease, and 0.79 (0.66 to 0.94) for total cardiovascular disease for women, but the inverse associations observed were weak and did not reach statistical significance for men. No significant association was observed between vitamins A or E intake and risk of mortality for either men or women. Conclusions— Vitamin C intake is inversely associated with mortality from cardiovascular disease for Japanese women.

The relation between serum total cholesterol levels and stroke is controversial. The Akita Pathology Study provides data on the association of serum total cholesterol, different types of stroke, and distribution of stenosis in cerebral arteries. The data are based on 750 autopsied men aged 30 years and older who were admitted to a local hospital in northeast Japan between 1966 and 1984. The overall autopsy rate was 88%. The grade of stenosis in the cerebral arteries was determined blindly by one pathologist using Baker's method for basal cerebral arteries (atherosclerosis scores) and using microscopic examination of a single basal ganglion slide for the intracerebral penetrating arteries (arteriolosclerosis scores). The age-adjusted mean value of serum total cholesterol concentration was 164 mg/dL for cerebral hemorrhage, 177 mg/dL for infarction in penetrating artery regions, and 200 mg/dL for infarction in cortical artery regions. Mean serum cholesterol was lower in deaths caused by cerebral hemorrhage than in those caused by myocardial infarction and other cardiovascular disease. Mean atherosclerosis score of basal cerebral arteries was low for cerebral hemorrhage, intermediate for penetrating artery infarction, and high for cortical artery infarction. Stenosis of both basal and penetrating arteries was minimum or absent in cases of cerebral hemorrhage. Only the basal arteries were stenotic in cases of cortical artery infarction, whereas both basal and penetrating arteries were stenosed in cases of penetrating artery infarction. There were positive associations of serum cholesterol with stenosis of basal and penetrating arteries. Among cases of cerebral hemorrhage, serum total cholesterol levels were even lower in men with no significant stenosis in either basal or penetrating arteries than in men with stenosis in either type of artery. The association of serum cholesterol with pathogenesis varies among stroke types. Elevated serum cholesterol levels were associated with the presence of cortical artery infarction, while low serum cholesterol levels were associated with cerebral hemorrhage.

Background and Purpose— The association of dietary folate and B vitamin intakes with risk of cardiovascular disease is controversial, and the evidence in Asian populations is limited. Methods— A total of 23 119 men and 35 611 women, age 40 to 79 years, completed a food frequency questionnaire in the Japan Collaborative Cohort Study. During the median 14-year follow-up, there were 986 deaths from stroke, 424 from coronary heart disease, and 2087 from cardiovascular disease. Results— Dietary folate and vitamin B 6 intakes were inversely associated with mortality from heart failure for men and with mortality from stroke, coronary heart disease, and total cardiovascular disease for women. These inverse associations did not change materially after adjustment for cardiovascular risk factors. No association was found between vitamin B 12 intake and mortality risk. Conclusions— High dietary intakes of folate and vitamin B 6 were associated with reduced risk of mortality from stroke, coronary heart disease, and heart failure among Japanese.

Background and Purpose— Although serum γ-glutamyltranspeptidase (GGT) levels have been associated with cardiovascular disease incidence, few studies have taken into account the effect of alcohol intake on GGT levels. In this study, we examined the relationship between GGT and stroke incidence according to drinking status. Methods— We conducted a prospective cohort study of Japanese women (N=6281) and men (N=3471) aged 40 to 69 years living in communities under systematic surveillance for stroke incidence. Results— During the 18-year follow-up, 202 (3.2%) women and 230 (6.6%) men had strokes. Serum GGT levels were positively associated with risk of total stroke for women but not men. The multivariable hazard ratios of total stroke for the highest quartile of GGT compared with the lowest quartile were 1.56 (95% CI, 1.01 to 2.39) for women and 1.37 (95% CI, 0.89 to 2.11) for men. Moreover, GGT was associated with total and ischemic stroke risks for never-drinking women. Conclusions— Serum GGT is associated with risk of total and ischemic strokes for Japanese women, especially never-drinkers.

Background and Purpose— Limited evidence was available on the metabolic syndrome and risk of cardiovascular disease in Asia. The purpose of this study is to examine the association of the metabolic syndrome and risk of ischemic cardiovascular disease in Japanese men and women. Methods— We conducted an 18-year prospective study of 9087 Japanese people aged 40 to 69 years (3595 men and 5492 women), initially free of ischemic heart disease or stroke. During follow-up, there were 116 (74 men and 42 women) cases of ischemic heart disease and 256 (144 men and 112 women) ischemic strokes. Metabolic syndrome was defined by the modified criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII), with the presence of ≥3 of the following factors: (1) serum triglycerides ≥1.69 mmol/L (150 mg/dL); (2) HDL-cholesterol 2 . Results— For both sexes, high blood pressure, high triglycerides and low HDL cholesterol were associated with increased risks of ischemic heart disease or stroke after adjustment for cardiovascular risk factors. A dose-response relationship was found between the number of metabolic risk factors and incidence of these cardiovascular end points. The multivariable hazard ratio (95% CI) associated with metabolic syndrome was 2.4 (1.4 to 4.0) in men and 2.3 (1.2 to 4.3) in women for ischemic heart disease, and 2.0 (1.3 to 3.1) and 1.5 (1.0 to 2.3), respectively, for ischemic stroke. The contribution of metabolic syndrome to the risks was independent of serum total cholesterol levels but stronger among smokers. Conclusions— The metabolic syndrome is a major determinant of ischemic cardiovascular disease among middle-aged Japanese men and women, in particular among smokers.

Background and Purpose— Higher proportions of hemorrhagic stroke and lacunar infarction were reported in rural Japan compared with those in Western countries. We examined the relative proportions of stroke subtypes in an urban Japanese city where westernized lifestyles are more common than in rural areas. Methods— Stroke registration was performed in 1992, 1997, and 2002 for residents ≥40 years of age who were admitted with acute strokes to all of the 10 hospitals with ≥90 beds in Yao City, Osaka, Japan. Strokes were classified as intraparenchymal hemorrhage, subarachnoid hemorrhage, or ischemic strokes (embolic infarction, large-artery occlusive infarction, lacunar infarction, and unclassified thrombotic infarction) by criteria using computed tomography or MRI. Results— A total of 650 first-ever strokes were registered. The age-adjusted proportion of each stroke subtype was not significantly different among the 3 study periods in both men and women. Throughout the 3 periods, intraparenchymal hemorrhage, subarachnoid hemorrhage, and ischemic stroke accounted for 26%, 7%, and 65% in men, respectively. In women, the respective proportions were 29%, 21%, and 44%. The proportion of each subtype for total ischemic strokes was as follows: 51% to 61% lacunar infarction, 25% to 26% large-artery occlusive infarction, and 11% to 17% embolic infarction. Conclusions— Our study showed that hemorrhagic stroke represented a large proportion of all strokes, especially among women, and lacunar infarction was the most common subtype of ischemic stroke among both men and women in Yao City, which differed from findings in Western countries.

Background and Purpose— No prospective studies have examined the association between calcium intake and the risk of cardiovascular disease in Japanese populations with a low mean calcium intake. Methods— Between 1988 and 1990, 110 792 Japanese subjects (46 465 men and 64 327 women) 40 to 79 years of age without a history of stroke, coronary heart disease, or cancer, completed a lifestyle questionnaire including food intake frequency under the Japan Collaborative Cohort (JACC) Study for Evaluation of Cancer Risk Sponsored by Monbusho. By the end of 1999, after 515 029 person years of follow-up, 566 deaths from stroke (101 subarachnoid hemorrhages, 140 intraparenchymal hemorrhages, and 273 ischemic strokes) and 234 deaths from coronary heart disease had been documented. Results— The intake of total calcium tended to be inversely associated with mortality from total stroke but not from coronary heart disease or total cardiovascular disease for men and women. The inverse association with dairy calcium intake was apparent for total stroke, both hemorrhagic and ischemic. The multivariate relative risk for men with highest versus lowest quintiles of dairy calcium intake was 0.53 (95% CI, 0.34 to 0.81) for total stroke, 0.46 (0.23 to 0.91) for hemorrhagic stroke, and 0.53 (0.29 to 0.99) for ischemic stroke; corresponding relative risks for women were 0.57 (0.38 to 0.86), 0.51 (0.28 to 0.94), and 0.50 (0.27 to 0.95). Conclusions— Dietary calcium intake from dairy products was associated with reduced mortality from stroke for Japanese men and women.

Background and Purpose— The association between minor ST-T abnormalities and stroke incidence has not been well elucidated. We sought to examine the relationship between nonspecific minor or major ST-T abnormalities and the incidence of stroke among Japanese men and women. Methods— A 15.4-year prospective study was conducted with 10 741 men and women aged 40 to 69 years in 4 Japanese communities. Electrocardiograms were taken at baseline and were read according to the Minnesota Code. The incidence of stroke was ascertained using systematic surveillance. Results— During the 15.4-year follow-up, 602 strokes (339 ischemic strokes, 129 intracerebral hemorrhages, 80 subarachnoid hemorrhages, and 54 unclassified strokes) occurred. Both men and women with major ST-T abnormalities had approximately 3-fold higher age-adjusted relative risk and 2-fold higher multivariate-adjusted relative risk of total stroke than did those without such abnormalities. Men with minor ST-T abnormalities had a 2.3-fold higher age-adjusted relative risk of total stroke, both ischemic and hemorrhagic, than did those without such abnormalities. After we adjusted further for hypertension category, the relative risk for minor ST-T abnormalities was reduced substantially but remained statistically significant: 1.8 (95% CI, 1.3 to 2.4) for total stroke, 1.9 (95%CI, 1.3 to 2.8) for ischemic stroke, and 1.7 (95% CI, 1.0 to 3.0) for hemorrhagic stroke. For women, however, there was no relation between minor ST-T abnormalities and stroke incidence. Conclusions— Minor ST-T abnormalities have predictive value for the risk of total stroke, both ischemic and hemorrhagic, among middle-aged Japanese men, as do major ST-T abnormalities for both sexes.

Background and Purpose — The role of serum fatty acids as a risk factor for stroke and stroke subtypes is largely unknown. Methods — A prospective nested case-control study of Japanese 40 to 85 years of age was conducted through the use of frozen serum samples from 7450 participants in cardiovascular risk surveys collected from 1984 to 1989 for 1 community and 1989 to 1992 for the other 2 communities. By the end of 1998, we identified 197 incident strokes whose subtypes were confirmed by imaging studies. Three controls per case were selected by matching for sex, age, community, year of serum storage, and fasting status. Results — Compared with controls, total (n=197), hemorrhagic (n=75), and ischemic (n=122) strokes had similar proportions of n3 polyunsaturated fatty acids, lower proportions of linoleic and arachidonic acids, and higher proportions of saturated and monosaturated acids, determined by gas chromatography. The multivariate odds ratios associated with a 1-SD increase in linoleic acid (5%) after adjustment for hypertension, diabetes, serum total cholesterol, and other cardiovascular risk factors were 0.72 [95% confidence interval (CI), 0.59 to 0.89] for total stroke, 0.66 (95% CI, 0.49 to 0.88) for ischemic stroke, 0.63 (95% CI, 0.46 to 0.88) for lacunar infarction, and 0.81 (95% CI, 0.59 to 1.12) for hemorrhagic stroke. The respective odds ratios for saturated fatty acids (4%) were 1.13 (95% CI, 1.05 to 1.65), 1.35 (95% CI, 1.01 to 1.79), 1.44 (95% CI, 1.03 to 2.01), and 1.21 (95% CI, 0.82 to 1.80). Further adjustment for other fatty acids attenuated these relations, but the relation between linoleic acid and risk of ischemic stroke remained statistically significant. Conclusions — A higher intake of linoleic acid may protect against ischemic stroke, possibly through potential mechanisms of decreased blood pressure, reduced platelet aggregation, and enhanced deformability of erythrocyte cells.

Background and Purpose —In secondary prevention, aspirin reduces risk of ischemic stroke. In primary prevention of stroke, however, the role of aspirin is uncertain, especially in women. Methods —In 1980, 79 319 women in the Nurses’ Health Study cohort, 34 to 59 years of age and free of diagnosed cardiovascular disease, cancer, and rheumatoid arthritis, completed questionnaires that included information on aspirin use. Data on aspirin use were updated in 1982, 1984, and 1988. By 1994, after 994 231 person-years of follow-up, 503 incident strokes (295 ischemic strokes, 100 subarachnoid hemorrhages, 52 intraparenchymal hemorrhages, and 56 strokes of undetermined type) were documented. Results —There was no clear relationship between aspirin use and risk of total stroke; risk was slightly reduced among women who took 1 to 6 aspirin per week and slightly increased among women who took 7 or more aspirin per week. Women who took 1 to 6 aspirin per week had a lower risk of large-artery occlusive infarction compared with women who reported no aspirin use; after simultaneous adjustment for other cardiovascular risk factors and selected nutrients, the multivariate relative risk was 0.50 (95% CI 0.29 to 0.85, P =0.01). Women who took 15 or more aspirin per week had an excess risk of subarachnoid hemorrhage; the multivariate relative risk was 2.02 (95% CI 1.04 to 3.91, P for trend=0.02). The reduction in large-artery occlusive infarction with aspirin was of greater magnitude for older, hypertensive, or smoking women than for younger, nonhypertensive, or nonsmoking women; the elevation in subarachnoid hemorrhage with aspirin was also more apparent for older or hypertensive women than for younger or nonhypertensive women. Aspirin use was not associated with risk of other subtypes of stroke. Conclusions —These prospective data indicate that women who take 1 to 6 aspirin per week have a reduced risk of large-artery occlusive infarction, but those who use 15 or more aspirin per week have an increased risk of subarachnoid hemorrhage. This observational study suggests benefits of aspirin for ischemic stroke with low frequency of use and hazards for hemorrhagic stroke with high frequency of use, particularly among older or hypertensive women. Thus, the effect on total stroke will depend on the dose of aspirin and the distribution of stroke subtypes and risk factors in the population.

Background and Purpose —High intakes of calcium, potassium, and magnesium have been hypothesized to reduce risks of cardiovascular disease, but only a few prospective studies have examined intakes of these cations in relation to risk of stroke. Methods —In 1980, 85 764 women in the Nurses’ Health Study cohort, aged 34 to 59 years and free of diagnosed cardiovascular disease and cancer, completed dietary questionnaires from which we calculated intakes of calcium, potassium, and magnesium. By 1994, after 1.16 million person-years of follow-up, 690 incident strokes (129 subarachnoid hemorrhages, 74 intraparenchymal hemorrhages, 386 ischemic strokes, and 101 strokes of undetermined type) had been documented. Results —Intakes of calcium, potassium, and magnesium were each inversely associated with age- and smoking-adjusted relative risks of ischemic stroke, excluding embolic infarction of nonatherogenic origin (n=347). Adjustment for other cardiovascular risk factors, including history of hypertension, attenuated these associations, particularly for magnesium intake. In a multivariate analysis, women in the highest quintile of calcium intake had an adjusted relative risk of ischemic stroke of 0.69 (95% CI, 0.50 to 0.95; P for trend=0.03) compared with those in the lowest quintile; for potassium intake the corresponding relative risk was 0.72 (95% CI, 0.51 to 1.01; P for trend=0.10). Further simultaneous adjustment for calcium and potassium intake suggested an independent association for calcium intake. The association of risk with calcium intake did not appear to be log linear; the increase in risk was limited to the lowest quintile of intake, and intakes >≈600 mg/d did not appear to reduce risk of stroke further. The inverse association with calcium intake was stronger for dairy than for nondairy calcium intake. Intakes of calcium, potassium, and magnesium were not related to risk of other stroke subtypes. Conclusions —Low calcium intake, and perhaps low potassium intake, may contribute to increased risk of ischemic stroke in middle-aged American women. It remains possible that women in the lowest quintile of calcium intake had unknown characteristics that made them susceptible to ischemic stroke.

Background and Purpose —Although randomized clinical trials have demonstrated the benefit of antihypertensive treatment in preventing stroke, the effectiveness of community-based programs is largely unknown. We investigated long-term community-based prevention activities. Methods —In rural northeastern Japan, people aged ≥30 years numbered 3219 in the full intervention community and 1468 in the minimal intervention community in 1965. Systematic blood pressure screening and health education began in 1963. Stroke was registered through 1987. Results —More than 80% of people aged 40 to 69 years were screened in both communities in the 1960s. One community charged for screening services after 1968, whereas the other community intensified intervention; subsequently, screening rates and the follow-up of hypertensive individuals declined in the minimal intervention community, especially in men. In men, stroke incidence declined more ( P Conclusions —Delivery of hypertension control services through intensive, free, community-wide screening and health education was effective in prevention of stroke for men in a community.