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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 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— 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.

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— Studies have suggested differences in the association between obesity and ischemic stroke in black versus white populations. In this study, we explored ischemic stroke risk in relation to a variety of obesity measures by sex and race. Methods— Using data from the Atherosclerosis Risk in Communities Study, we obtained information on body mass index, waist circumference, and waist-to-hip ratio from 13 549 black and white participants who were aged 45 to 65 years between 1987 and 1989. All were free of cardiovascular disease and cancer at baseline. Incident strokes over a median follow-up of 16.9 years were ascertained from hospital records. Results— Although crude incidence rates of ischemic stroke varied more than 3-fold by race and sex, the relationship between higher measures of obesity and ischemic stroke risk was positive and linear across all groups. The crude incidence of ischemic stroke was 1.2 per 1000 person-years for white women with the lowest body mass index, ranging up to 8.0 per 1000 person-years for black men with the highest body mass index. Hazard ratios for the highest versus lowest quintile of body mass index, waist circumference, and waist-to-hip ratio ranged from 1.43 to 3.19, indicating increased stroke risk associated with obesity, however it was measured, even after adjustment for potential confounders. Additional adjustment for factors that may mediate the relationship, such as diabetes and hypertension, significantly attenuated the associations, suggesting that these factors may explain much of the stroke risk associated with obesity. Conclusions— Degree of obesity, defined by body mass index, waist circumference, or waist-to-hip ratio, was a significant risk factor for ischemic stroke regardless of sex or race.

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— 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— 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.

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— 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— 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.