Takehito Hayakawa

Cigarette smoking as a risk factor for stroke death in Japan NIPPON DATA80

Background and Purpose— Some previous Japanese cohort studies failed to show an association between smoking and stroke risk. Because such an association has been noted in other populations, this issue should be re-examined in a recent representative Japanese cohort with a higher total cholesterol level. Methods— A total of 9638 men and women aged 30 years and older without a history of cardiovascular disease (CVD) at baseline in 1980 were followed-up for 14 years. Results— We observed 203 stroke deaths (107 cerebral infarctions, 45 cerebral hemorrhages, and 51 others), 191 heart disease deaths, and 413 CVD deaths. The average serum total cholesterol level was ≈4.91 mmol/L. Cox proportional hazard ratios were calculated adjusting for age, systolic blood pressure, and other conventional risk factors. The hazard ratios for men who smoked 1 to 20 cigarettes/day for all strokes, cerebral infarction, and cerebral hemorrhage were 1.60 (95% CI, 0.91 to 2.79), 2.97 (CI, 1.27 to 6.98), and 0.42 (CI, 0.16 to 1.09), respectively, and for those who smoked ≥21 cigarettes/day, they were 2.17 (CI, 1.09 to 4.30), 3.26 (CI, 1.11 to 9.56), and 0.68 (CI, 0.20 to 2.33), respectively. For women who smoked ≥21 cigarettes/day, the hazard ratio for all strokes was 3.91 (CI, 1.18 to 12.90). For CVD, all heart disease, and ischemic heart disease, the hazard risks of smoking were significant (1.49 to 4.25) for men but not significant for women. Conclusions— Smoking in a cohort with moderate serum total cholesterol level was a potent risk factor for stroke, especially cerebral infarction, for both men and women, and for CVD and ischemic heart disease for men.

Relationship Between Metabolic Risk Factor Clustering and Cardiovascular Mortality Stratified by High Blood Glucose and Obesity NIPPON DATA90, 1990–2000

OBJECTIVE—Metabolic syndrome is diagnosed according to several criteria. Of these, some require glucose intolerance and others require obesity for the diagnosis. We investigated the relationship between metabolic risk factor clustering and cardiovascular disease (CVD) mortality stratified by high blood glucose or obesity. RESEARCH DESIGN AND METHODS—We followed 7,219 Japanese men and women without a history of CVD for 9.6 years. We defined high blood pressure, high blood glucose, high triglycerides, low HDL cholesterol, and obesity as metabolic factors. The multivariate adjusted hazard ratio (HR) for CVD mortality according to the number of clustering metabolic factors was calculated using the Cox proportional hazards model. RESULTS—During follow-up, 173 participants died of CVD. The numbers of metabolic risk factors and CVD mortality were positively correlated (Ptrend = 0.07). The HR was obviously higher among participants with than among those without high blood glucose and clustering of ≥2 other metabolic risk factors (HR 3.67 [95% CI 1.49–9.03]). However, the risk increase was only modest in participants without high blood glucose even if they had ≥2 other metabolic risk factors (1.99 [0.93–4.28]). Conversely, metabolic risk factor clustering was related to CVD mortality irrespective of obesity. CONCLUSIONS—Our findings suggest that glucose tolerance plays an important role in CVD mortality. Because the prevalence of nonobese participants with several metabolic risk factors was quite high and their CVD risk was high, excluding them from the diagnosis of metabolic syndrome because of the absence of obesity might overlook their risk.

Relationship between metabolic risk factor clustering and cardiovascular mortality stratified by high blood glucose and obesity: NIPPON DATA90, 1990-99

OBJECTIVE—Metabolic syndrome is diagnosed according to several criteria. Of these, some require glucose intolerance and others require obesity for the diagnosis. We investigated the relationship between metabolic risk factor clustering and cardiovascular disease (CVD) mortality stratified by high blood glucose or obesity. RESEARCH DESIGN AND METHODS—We followed 7,219 Japanese men and women without a history of CVD for 9.6 years. We defined high blood pressure, high blood glucose, high triglycerides, low HDL cholesterol, and obesity as metabolic factors. The multivariate adjusted hazard ratio (HR) for CVD mortality according to the number of clustering metabolic factors was calculated using the Cox proportional hazards model. RESULTS—During follow-up, 173 participants died of CVD. The numbers of metabolic risk factors and CVD mortality were positively correlated (Ptrend = 0.07). The HR was obviously higher among participants with than among those without high blood glucose and clustering of ≥2 other metabolic risk factors (HR 3.67 [95% CI 1.49–9.03]). However, the risk increase was only modest in participants without high blood glucose even if they had ≥2 other metabolic risk factors (1.99 [0.93–4.28]). Conversely, metabolic risk factor clustering was related to CVD mortality irrespective of obesity. CONCLUSIONS—Our findings suggest that glucose tolerance plays an important role in CVD mortality. Because the prevalence of nonobese participants with several metabolic risk factors was quite high and their CVD risk was high, excluding them from the diagnosis of metabolic syndrome because of the absence of obesity might overlook their risk.

Age-specific effects of systolic and diastolic blood pressures on mortality due to cardiovascular diseases among Japanese men (NIPPON DATA80*)

Objective To clarify the relationship between mortality due to cardiovascular diseases (CVD) and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in young and elderly Japanese men in the absence of antihypertensive treatments. Design A 19-year cohort study using the 1980 National Survey of Cardiovascular Diseases and the identification of the underlying causes of death using national vital statistics data. Methods In 1999, a 19-year follow-up study was conducted among participants randomly selected from the Japanese population for the 1980 National Survey of Cardiovascular Diseases. Among the male participants that were not receiving antihypertensive treatment, information was obtained for about 91.3% of the subjects (n = 3779). Age-adjusted mortality rates using the person-year method were calculated to compare the relationships of SBP and DBP levels with CVD mortality for different age groups (aged 30–64, 65–74, and 75 years or more). Results The total number of observed person-years was 64 598 and the number of CVD-related deaths after 19 years was 253. Both SBP and DBP levels were significantly and linearly related to CVD mortality in the age groups 30–64 years (P < 0.001 and P = 0.01, respectively) and 65–74 years (P < 0.001 and P = 0.03, respectively). In the group of participants that were at least 75 years old, however, no significant increase in the relative risk of CVD was observed with increasing DBP levels (P = 0.156), whereas the relative risk of CVD increased significantly with increasing SBP levels (P = 0.038). Multivariate analysis adjusting for major risk factors confirmed these relationships. Standardized hazard ratios (95% confidence intervals) of SBP were 1.53 (1.19–1.96) for 30–64 year olds, 1.70 (1.31–2.20) for 64–74 year olds, and 1.23 (1.03–1.47) for participants 75 years old or more, whereas those of DBP were 1.52 (1.12–2.06), 1.60 (1.21–2.10), and 1.10 (0.94–1.28), respectively. Conclusions These data show that elevated SBP is an independent risk factor for CVD mortality for Japanese men of all ages, whereas elevated DBP is not an independent risk factor for CVD mortality for elderly men.

Body Mass Index and Risk of Stroke Mortality among a Random Sample of Japanese Adults: 19-Year Follow-Up of NIPPON DATA80

Background: The relationship between body mass index (BMI) and stroke mortality remains unclear. The aim of the present study was to elucidate the relationship between BMI and stroke death in a representative cohort of Japanese men and women. Methods: We analyzed a database of 9,526 men and women aged 30 years and older who were randomly selected throughout Japan in 1980. These individuals had no history of stroke and were followed for 19 years. Hazard ratios (HR) and their 95% confidence intervals (CI) of deaths due to total stroke, cerebral infarction, and intracerebral hemorrhage were examined using Cox’s proportional hazards regression models of BMI levels. Results: A U-shaped association between BMI and cerebral infarction mortality was observed. Participants with the highest BMI category (BMI ≧ 30.0) showed a significantly highest HR for cerebral infarction (HR 2.46, 95% CI 1.01–5.99). The excess risk at the lower extreme of the BMI was confined to men. These associations did not change after excluding deaths occurring in the first 2 years of follow-up. Conclusions: In the Japanese general population, a U-shaped association between BMI and cerebral infarction mortality was found and the excess risk at the lower extreme of the BMI was confined to men.

Life expectancy among Japanese of different smoking status in Japan: NIPPON DATA80.

BACKGROUND The life expectancy is an important measure for describing health status among population. Several studies from the United States and Europe showed the harm of smoking by describing the life expectancies with different smoking status. No such study is examined in Japan, the country with the world s highest life expectancy irrespective of high smoking rate among men. METHODS The abridged life table method was applied to calculate the life expectancies of men and women among different smoking status from age 40 until age 85. Age-specific mortality rates stratified by different smoking status were obtained from follow-up data from random sample in Japanese population (NIPPON DATA80). RESULTS Proportion of current smokers was 62.9% in men and 8.8% in women at the baseline survey in 1980. The life expectancies of 40-year-old never smokers, ex-smokers and current smokers were 42.1, 40.4, and 38.6 years in men and 45.6, 45.9, and 43.4 years in women. The life expectancy of 40-year-old men who smoked less than one pack per day was 39.0 and was longer than that of those who smoked one or two packs (38.8) and more than two packs (38.1). CONCLUSION Life expectancy decreased gradually as the grade of smoking increased in the Japanese population.

Electrocardiogram screening for left high R-wave predicts cardiovascular death in a Japanese community-based population : NIPPON DATA90

Little is known about the efficacy of left ventricular hypertrophy diagnosed by electrocardiography for predicting cardiovascular disease in a general Japanese population. In a large cohort of participants selected randomly from the overall Japanese population, we attempted to evaluate the usefulness of a high amplitude R-wave (left high R-wave) on the electrocardiogram for predicting cardiovascular death. A total of 6,688 Japanese (mean age, 50.7 years old; 57% women) free of previous cardiovascular disease and use of antihypertensive agents at baseline were followed for 10 years, from 1990 to 2000. Left high R-wave on the electrocardiogram (the Minnesota Code, 3-1 or 3-3) was found in 9.4% of the 6,688 participants, in 14.6% of the 2,413 hypertensives and in 4.1% of the 4,275 normotensives. During the follow-up period, 128 participants died due to cardiovascular disease. After adjustment for systolic blood pressure and other risk factors, left high R-wave conferred an increased risk of cardiovascular death; the hazard ratio among all the participants was 1.88 (95% confidence interval, 1.22–2.89; p<0.01), that among hypertensives was 1.97 (1.20–3.24; p=0.01), and that among normotensives was 1.66 (0.69–3.98; p=0.26). The population attributable risk percent of left high R-wave for cardiovascular death was 7.6% among all participants, 12.4% among hypertensives and 4.1% among normotensives. Left high R-wave on electrocardiogram, irrespective of the level of systolic blood pressure, was a predictive marker for cardiovascular death among community-dwelling Japanese.

The value of combining serum alanine aminotransferase levels and body mass index to predict mortality and medical costs: A 10-year follow-up study of National Health Insurance in Shiga, Japan

BACKGROUND Evidence suggests that the predictive value of serum alanine aminotransferase (ALT) levels for prognosis, measured by indices such as all-cause mortality and medical costs, may be modified by body mass index (BMI). However, the relationship between serum ALT and BMI has not been satisfactorily elucidated. METHODS Four thousand, five hundred and twenty-four community dwelling Japanese National Health Insurance beneficiaries, 40-69 years old, were classified into five categories according to their serum ALT levels (IU/L) (ALT<20, 20≤ALT<30, 30≤ALT<40, 40≤ALT<50 and 50≤ALT) and followed for 10 years. Hazard ratios for all-cause mortality, with reference to the lowest serum ALT category, and medical costs per person were evaluated for each serum ALT category after analyzing interactions between serum ALT levels and BMI for all-cause mortality and for medical costs. RESULTS A significant interaction between serum ALT levels and BMI was observed. In participants below the median BMI, positive, graded relationships were identified between serum ALT levels and all-cause mortality as well as between serum ALT levels and personal medical costs. The multivariate-adjusted hazard ratio in the “50≤ALT” category showed an approximately 8-fold increase. However, in the participants at or above the median BMI, no significant relationships between serum ALT levels and all-cause mortality or personal medical costs were identified. CONCLUSIONS In these Japanese participants, the predictive value of serum ALT levels for prognosis was more evident if BMI was taken into account. A combination of high serum ALT levels and below median BMI was associated with excess mortality and medical costs.

Different effects of blood pressure on mortality from stroke subtypes depending on BMI levels: A 19-year cohort study in the Japanese general population - NIPPON DATA80

To evaluate the relationship between blood pressure and cerebrovascular death depending on body mass index (BMI) levels, we analysed a database of 9338 subjects from the National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged, which was originally conducted a baseline survey in 1980 and followed up in 1999. Relative risk (RR) and a 95% confidence interval (CI) of death from total stroke, cerebral infarction, and intracerebral haemorrhage after adjusting for age, sex, serum cholesterol, albumin, glucose, the use of antihypertensive agents, a past history of diabetes, BMI, smoking, and drinking were estimated with the Cox-proportional hazard model in the BMI tertile groups of a representative Japanese population. Cutoff points of BMI tertiles are 21.2 and 23.8 kg/m2. The results indicated that a 10 mmHg systolic blood pressure (SBP) increase was associated with mortality from intracerebral haemorrhage at low and middle BMI groups (RR= 1.38 and 1.23; 95% CI=1.17–1.62 and 1.03–1.47, respectively). SBP was positively associated with mortality from cerebral infarction in middle and high BMI groups (RR=1.19 and 1.21; 95% CI=1.06–1.33 and 1.06–1.38, respectively). The effects of diastolic blood pressure on intracerebral haemorrhage and infarction had the same tendency as those of SBP. These results suggested that the causal effect of blood pressure on stroke subtypes might be modified by BMI.

Impact of Hypertension on Medical Economics: A 10-Year Follow-Up Study of National Health Insurance in Shiga, Japan

Hypertension and related cardiovascular diseases may lead to an increase in medical costs for patients. We attempted to clarify the relationship between hypertension and long-term medical costs by a cohort study utilizing existing data as well as baseline blood pressures and medical costs over a 10-year period. The participants included 4,191 Japanese National Health Insurance beneficiaries aged 40–69 years, living in one area, who were not taking anti-hypertensive medication and did not have a history of major cardiovascular disease. They were classified into four categories according to their blood pressure. We evaluated the mean medical costs per month, cumulative hospitalization, and all-cause mortality for each blood pressure category. Hypertension-related medical costs attributable to hypertensive individuals, as compared to normotensive individuals, were estimated. There was a positively graded correlation between blood pressure and personal total medical costs, especially for men. The odds ratio for cumulative hospitalization and hazard ratio for all-cause mortality in severe hypertensive men were also higher than those in normotensive men. However, the hypertension-related medical costs for mild to moderate hypertensives were higher than those for severe hypertensives. The hypertension-related medical costs for all hypertensives accounted for 23.7% of the total medical costs for the Japanese population. In conclusion, high blood pressure was a useful predictor for excess medical costs; moreover, concomitant hypertension, regardless of the grade, increased the medical costs of Japanese National Health Insurance beneficiaries.