Katsutoshi Okada

Intake of Fish and n3 Fatty Acids and Risk of Coronary Heart Disease Among Japanese The Japan Public Health Center-Based (JPHC) Study Cohort I

Background— Once- or twice-weekly consumption of fish (or a small amount of fish intake) reduces the risk of coronary heart disease and sudden cardiac death in Western countries. It is uncertain whether a high frequency or large amount of fish intake, as is the case in Japan, further reduces the risk. Methods and Results— To examine an association between high intake of fish and n3 polyunsaturated fatty acids and the risk of coronary heart disease, a total of 41 578 Japanese men and women aged 40 to 59 years who were free of prior diagnosis of cardiovascular disease and cancer and who completed a food frequency questionnaire were followed up from 1990–1992 to 2001. After 477 325 person-years of follow-up, 258 incident cases of coronary heart disease (198 definite and 23 probable myocardial infarctions and 37 sudden cardiac deaths) were documented, comprising 196 nonfatal and 62 fatal coronary events. The multivariable hazard ratios (HRs) and 95% confidence intervals in the highest (8 times per week, or median intake=180 g/d) versus lowest (once a week, or median intake=23 g/d) quintiles of fish intake were 0.63 (0.38 to 1.04) for total coronary heart disease, 0.44 (0.24 to 0.81) for definite myocardial infarction, and 1.14 (0.36 to 3.63) for sudden cardiac death. The reduced risk was primarily observed for nonfatal coronary events (HR=0.43 [0.23 to 0.81]) but not for fatal coronary events (HR=1.08 [0.42 to 2.76]). Strong inverse associations existed between dietary intake of n3 fatty acids and risk of definite myocardial infarction (HR=0.35 [0.18 to 0.66]) and nonfatal coronary events (HR=0.33 [0.17 to 0.63]). Conclusions— Compared with a modest fish intake of once a week or ≈20 g/d, a higher intake was associated with substantially reduced risk of coronary heart disease, primarily nonfatal cardiac events, among middle-aged persons.

Association of dietary intake of soy, beans, and isoflavones with risk of cerebral and myocardial infarctions in Japanese populations: the Japan Public Health Center-based (JPHC) study cohort I.

Background— Soy and isoflavones have been proposed to reduce the risk of cardiovascular risk factors, but their potential as preventatives for cardiovascular disease remains uncertain. We investigated the association of soy and isoflavone intake with risk of cerebral and myocardial infarctions (CI and MI). Methods and Results— To examine the association of soy and isoflavone intake with the risk of CI and MI, we studied 40 462 Japanese (40 to 59 years old, without cardiovascular disease or cancer at baseline). They completed a food-frequency questionnaire (1990–1992) and received follow-up to 2002. After 503 998 person-years of follow-up, we documented incidence of CI (n=587) and MI (n=308) and of mortality for CI and MI combined (n=232). For women, the multivariable hazard ratios and 95% confidence limits for soy intake ≥5 times per week versus 0 to 2 times per week were 0.64 (0.43 to 0.95) for risk of CI, 0.55 (0.26 to 1.09) for risk of MI, and 0.31 (0.13 to 0.74) for cardiovascular disease mortality. Similar but weaker inverse associations were observed between intake of miso soup and beans and risk of cardiovascular disease mortality. The multivariable hazard ratios for the highest versus the lowest quintiles of isoflavones in women were 0.35 (0.21 to 0.59) for CI, 0.37 (0.14 to 0.98) for MI, and 0.87 (0.29 to 2.52) for cardiovascular disease mortality. An inverse association between isoflavone intake and risk of CI and MI was observed primarily among postmenopausal women. No significant association of dietary intake of soy, miso soup, and beans and isoflavones with CI or MI was present in men. Conclusions— High isoflavone intake was associated with reduced risk of CI and MI in Japanese women. The risk reduction was pronounced for postmenopausal women.

Alcohol Consumption and Risk of Stroke Among Middle-Aged Men: The JPHC Study Cohort I

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.

Cigarette Smoking and Risk of Stroke and its Subtypes Among Middle-Aged Japanese Men and Women: The JPHC Study Cohort I

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.

Egg consumption, serum total cholesterol concentrations and coronary heart disease incidence: Japan Public Health Center-based prospective study

Limited egg consumption is often recommended to reduce serum cholesterol concentration for the prevention of CHD. We examined the association of egg consumption and total cholesterol concentration with the risk of CHD. A total of 90 735 subjects (19 856 men and 21 408 women, aged 40-59 years in cohort I; 23 463 men and 26 008 women, aged 40-69 years in cohort II) were followed from 1990-4 to the end of 2001 under the Japan Public Health Center-based prospective study. Total cholesterol was obtained in 36 % of the subjects. Men and women were combined for the analyses. The subjects were categorised into four groups according to egg consumption. Subjects with total cholesterol >or=2200 mg/l were less frequent in frequent egg consumption groups in both cohorts (trend P<0.0001). Subjects with <1 d/week of egg consumption were more likely to avoid a cholesterol-rich diet. Egg consumption was not associated with the risk of CHD, although total cholesterol was significantly related to the risk of CHD. The multivariate hazard ratio of CHD in subjects with total cholesterol >or=2400 v. <1800 mg/l was 2.17 (95 % CI 1.22, 3.85; trend P=0.0018). In conclusion, eating eggs more frequently, up to almost daily, was not associated with an increase in CHD incidence for middle-aged Japanese men and women. Subjects with hypercholesterolaemia were less frequently in frequent egg consumption groups, probably because they avoided eating eggs.

Cigarette smoking and risk of coronary heart disease incidence among middle-aged Japanese men and women: the JPHC Study Cohort I.

Background Few data have been available on the sex-specific magnitude of the smoking effect on the risk of coronary heart disease (CHD) in Asia. Design and methods A population-based prospective cohort study of 19 782 men and 21 500 women aged 40–59 years between 1990–1992 and 2001 was conducted to examine the relationship between smoking status and the risk of CHD. Results A total of 260 incidences of CHD were confirmed among men, including 174 myocardial infarctions (MI). The numbers among women were 66 and 43, respectively. The multivariate relative risk [95% confidence interval (CI)] for current smokers versus never-smokers in men after adjustment for cardiovascular risk factors, several life style factors and public health centre was 2.85 (1.98, 4.12) for total CHD and 3.64 (2.27, 5.83) for MI. These respective risks in women were 3.07 (1.48, 6.40) and 2.90 (1.18, 7.18). Among men, a dose-dependent relationship was observed between the number of cigarettes and the risk of MI. The population-attributable risk per cent (95% CI) of CHD was 46% (34, 55) in men and 9% (0, 18) in women. Smoking cessation, however, led to a rapid decline in the CHD risk within 2 years. Conclusion Smoking raises the risk of CHD significantly in both sexes of middle-aged Japanese, with large public health significance especially in men. Smoking cessation would have an immediate effect on risk reduction.

Intake of Folate, Vitamin B6 and Vitamin B12 and the Risk of CHD: The Japan Public Health Center-Based Prospective Study Cohort I

Objective: To investigate the association of dietary folate, vitamin B6 (VB6) and vitamin B12 (VB12) with the risk of coronary heart disease among middle-aged persons. Methods: A total of 40,803 subjects aged 40–59 years living in the community who were free of prior diagnoses of cardiovascular disease and cancer and who completed a food frequency questionnaire were followed from 1990–1992 to the end of 2001 in the Japan Public Health Center-based Prospective Study. Results: After 468,472 person-years of follow-up, 251 coronary heart disease incidents were documented. Coronary heart disease and definite myocardial infarction were inversely associated with dietary intake of folate, VB6 and VB12 after adjustment for age and sex, but the associations were attenuated after further adjustment for smoking, dietary and other cardiovascular risk factors. However, among non-multivitamin supplement users, multivariable hazard ratios (95% confidence intervals) in the highest vs. lowest quintiles of VB6 intake were 0.60 (0.37–0.97) for total coronary heart disease and 0.52 (0.29–0.91) for definite myocardial infarction, and the inverse associations with VB12 were marginally significant. The combination of below-median intake of three vitamins or of only B6 conferred a twice excess risk of total coronary heart disease. Conclusions: Dietary intake of VB6 was associated with a reduced risk of coronary heart disease among middle-aged non-multivitamin supplement users. Dietary folate and VB12 were also suggested to be protective factors for coronary heart disease.

Prognostic value of plasma high-sensitivity C-reactive protein levels in Japanese patients with stable coronary artery disease: The Japan NCVC-Collaborative Inflammation Cohort (JNIC) Study

High-sensitivity C-reactive protein (hsCRP) levels can predict cardiovascular events among apparently healthy individuals and patients with coronary artery disease (CAD). However, hsCRP levels vary among ethnic populations. We previously reported hsCRP levels in Japanese to be much lower than in Western populations. We investigated the prognostic value of hsCRP levels in Japanese patients with stable CAD. The hsCRP levels were measured in 373 Japanese patients who underwent elective coronary angiography and thereafter decided to receive only medical treatment. Patients were followed up for 2.9+/-1.5 years for major cardiovascular events (death, myocardial infarction, unstable angina, stroke, aortic disease, peripheral arterial disease, or heart failure). The median hsCRP level was 0.70 mg/l. During the follow-up, cardiovascular events occurred in 53 (14%) of the 373 patients. Compared with 320 patients without events, 53 with events had higher hsCRP levels (median 1.06 vs. 0.67 mg/l, P<0.05). To clarify the association between hsCRP levels and cardiovascular events, the 373 study patients were divided into tertiles according to hsCRP levels: lower (<0.4 mg/l), middle (0.4-1.2mg/l), and higher (>1.2mg/l). The Kaplan-Meier analysis demonstrated a significant difference in the event-free survival rate between higher vs. middle or lower tertiles (P<0.05). In multivariate Cox regression analysis, the hsCRP level of >1.0mg/l was an independent predictor for cardiovascular events (hazard ratio, 2.0; 95%CI, 1.1-3.4; P<0.05). Thus, in Japanese patients with stable CAD who received only medical treatment, higher hsCRP levels, even >1.0mg/l, were found to be associated with a significantly increased risk for further cardiovascular events.

Caregiver Burden for Impaired Elderly Japanese with Prevalent Stroke and Dementia under Long-Term Care Insurance System

Background: Limited data are available on caregiver burden for stroke and dementia patients. We examined the associations of prevalent stroke and dementia with family caregiver burden in Japanese general populations. Methods: A total of 916 Japanese home caregivers, whose family members were covered by long-term care insurance, responded to the caregiver burden questionnaire. The questionnaire included the caregiver’s age, sex and employment status, the patient-caregiver relationship, the patient‘s history of stroke, symptoms of dementia, care levels under long-term care insurance and the Zarit Caregiver Burden Interview. Results: The mean total score from the Zarit Caregiver Burden Interview was 12% higher in patients with stroke than in those without (p = 0.02) and 40% higher in those with dementia than in those without (p < 0.001). Compared with nonstroke patients without dementia, the mean total score was 21% higher in stroke patients without dementia (p = 0.01), 49% higher in nonstroke patients with dementia (p < 0.001) and 55% higher in stroke patients with dementia (p < 0.001). After adjustment for the caregiver’s age, sex and employment status, the patient-caregiver relationship, and the patient’s care level and community, the higher scores remained statistically significant for nonstroke patients with dementia and for stroke patients with dementia but not for stroke patients without dementia. Conclusions: Prevalent stroke and, more strongly, dementia were associated with increased family caregiver burden. Among patients with dementia, the presence of stroke did not enhance caregiver burden further.

Pulse pressure is an independent risk factor for stroke among middle-aged Japanese with normal systolic blood pressure: the JPHC study

Objective Although pulse pressure has been recognized a risk factor for coronary heart disease in both middle-aged and elderly, and for stroke in the elderly, the contribution of pulse pressure to the risk of stroke among the middle-aged is uncertain. Methods A total of 33 372 participants (11 684 men and 21 688 women aged 40–69 years) living in communities, free of prior diagnosis of cardiovascular disease and cancer, completed health check-up examination. They were followed from 1990–1992 to the end of 2004 in the Japan public health center-based prospective study on cancer and cardiovascular disease. After 422 864 person-years of follow-up, 1081 incident strokes (559 men and 522 women) were documented. Results Pulse pressure was positively associated with risk of stroke as was systolic and diastolic blood pressures. The multivariable hazard ratio of total stroke associated with a 1-SD increment (13.2 mmHg) of pulse pressure was 1.14 (1.05–1.24). The excess risk was observed for the stratum of systolic blood pressure below 140 mmHg, but not of higher systolic blood pressure levels after adjustment for diastolic blood pressure and other potential confounding factors; the multivariable hazard ratio of stroke associated with a 1-SD increment of pulse pressure was 1.32 (1.07–1.64) among persons with normal systolic blood pressure levels. Conclusions Pulse pressure is a risk factor for stroke among normotensive individuals with systolic blood pressure below 140 mmHg, which suggests that pulse pressure may be useful to predict the risk of stroke among middle-aged nonsystolic hypertensive patients.