Naoko Mukai

Secular Trends in Cardiovascular Disease and Its Risk Factors in Japanese Half-Century Data From the Hisayama Study (1961–2009)

Background— Changes in lifestyle and advances in medical technology during the past half century are likely to have affected the incidence and mortality of cardiovascular disease and the prevalence of its risk factors in Japan. Methods and Results— We established 5 cohorts consisting of residents aged ≥40 years in a Japanese community, in 1961 (n=1618), 1974 (n=2038), 1983 (n=2459), 1993 (n=1983), and 2002 (n=3108), and followed up each cohort for 7 years. The age-adjusted incidence of stroke decreased greatly, by 51% in men and by 43% in women, from the 1960s to the 1970s, but this decreasing trend slowed from the 1970s to the 2000s. Among the stroke subtypes, ischemic stroke in both sexes and intracerebral hemorrhage in men showed a similar pattern. Stroke mortality decreased as a result of the decline in incidence and a significant improvement in survival rate. Although the incidence of acute myocardial infarction did not change in either sex, disease mortality declined slightly in women. From the 1960s to the 2000s, blood pressure control among hypertensive individuals improved significantly and the smoking rate decreased, but the prevalence of glucose intolerance, hypercholesterolemia, and obesity increased steeply. Conclusions— Our findings suggest that in Japanese, the decreasing trends in the incidence of ischemic stroke have recently slowed down, and there has been no clear change in the incidence of acute myocardial infarction, probably because the benefits of hypertension control and smoking cessation have been negated by increasing metabolic risk factors. # Clinical Perspective {#article-title-30}Background— Changes in lifestyle and advances in medical technology during the past half century are likely to have affected the incidence and mortality of cardiovascular disease and the prevalence of its risk factors in Japan. Methods and Results— We established 5 cohorts consisting of residents aged ≥40 years in a Japanese community, in 1961 (n=1618), 1974 (n=2038), 1983 (n=2459), 1993 (n=1983), and 2002 (n=3108), and followed up each cohort for 7 years. The age-adjusted incidence of stroke decreased greatly, by 51% in men and by 43% in women, from the 1960s to the 1970s, but this decreasing trend slowed from the 1970s to the 2000s. Among the stroke subtypes, ischemic stroke in both sexes and intracerebral hemorrhage in men showed a similar pattern. Stroke mortality decreased as a result of the decline in incidence and a significant improvement in survival rate. Although the incidence of acute myocardial infarction did not change in either sex, disease mortality declined slightly in women. From the 1960s to the 2000s, blood pressure control among hypertensive individuals improved significantly and the smoking rate decreased, but the prevalence of glucose intolerance, hypercholesterolemia, and obesity increased steeply. Conclusions— Our findings suggest that in Japanese, the decreasing trends in the incidence of ischemic stroke have recently slowed down, and there has been no clear change in the incidence of acute myocardial infarction, probably because the benefits of hypertension control and smoking cessation have been negated by increasing metabolic risk factors.

Association between ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cardiovascular disease: The Hisayama Study

OBJECTIVE We examined the association between the ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) or the docosahexaenoic acid (DHA)/AA and the development of cardiovascular disease in a general Japanese population. METHODS A total of 3103 community-dwelling Japanese individuals aged ≥40 years were followed up for an average of 5.1 years. Serum EPA/AA ratios were categorized into quartiles. The risk estimates were computed using a Cox proportional hazards model. RESULTS During the follow-up period, 127 subjects experienced cardiovascular events. Age- and sex-adjusted incidence rates of cardiovascular disease increased with lower serum EPA/AA ratios in individuals with high-sensitivity C-reactive protein (HS-CRP) of ≥1.0 mg/L (p for trend = 0.006), whereas no clear association was observed in those with HS-CRP of <1.0 mg/L (p for trend = 0.27). The multivariable-adjusted risk of cardiovascular disease increased significantly, by 1.52 times (95% confidence interval 1.12-2.04) per 0.20 decrement in serum EPA/AA ratio in subjects with HS-CRP of ≥1.0 mg/L. A lower serum EPA/AA ratio was significantly associated with an increased risk of coronary heart disease, but there was no evidence of an association with stroke. The magnitude of the influence of the serum EPA/AA ratio on the cardiovascular risk increased significantly with elevating HS-CRP levels taken as a continuous variable (p for heterogeneity = 0.007). However, no such association was observed for DHA/AA ratio. CONCLUSION Our findings suggest that a lower serum EPA/AA ratio is associated with a greater risk of cardiovascular disease, especially coronary heart disease, among subjects with higher HS-CRP levels in the general Japanese population.

Angiopoietin-Like Protein 2 and Risk of Type 2 Diabetes in a General Japanese Population: The Hisayama Study

OBJECTIVE To examine, for the first time, the association between a novel inflammatory cytokine, angiopoietin-like protein (ANGPTL) 2, and the development of type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS A total of 2,164 community-dwelling Japanese individuals aged 40 to 79 years without diabetes were followed up for 7 years. Serum ANGPTL2 levels were divided into quartile categories at baseline: <2.15, 2.16–2.71, 2.72–3.40, and ≥3.41 ng/mL. During follow-up, 221 participants developed T2DM. RESULTS In multivariate analyses, after adjusting for comprehensive risk factors and high-sensitivity C-reactive protein (hs-CRP) levels, the risk of developing T2DM was significantly higher in the highest ANGPTL2 quartile than in the lowest quartile (hazard ratio, 1.80; 95% CI, 1.14–2.85; P = 0.01). CONCLUSIONS Elevated serum ANGPTL2 levels were positively associated with the development of T2DM in a general population, independent of other risk factors including hs-CRP levels.

White-Coat and Masked Hypertension Are Associated With Carotid Atherosclerosis in a General Population: The Hisayama Study

Background and Purpose— On the basis of combined measurements of clinic blood pressure (CBP) and home blood pressure (HBP), blood pressure status can be divided into normotension, white-coat hypertension (WCHT), masked hypertension (MHT), and sustained hypertension (SHT). Despite the clear impact of MHT and SHT on clinical and subclinical arterial disease, uncertainty about the influence of WCHT remains. The objective of this study was to investigate the associations of WCHT, MHT, and SHT with carotid atherosclerosis in a general population. Methods— This is a cross-sectional survey of 2915 community-dwelling Japanese aged ≥40 years. Normotension was defined as CBP<140/90 and HBP<135/85 mm Hg; WCHT, CBP≥140/90 and HBP<135/85 mm Hg; MHT, CBP<140/90 and HBP≥135/85 mm Hg; and SHT, CBP≥140/90 and HBP≥135/85 mm Hg. Mean intima-media thickness of carotid arteries was measured using a computer-automated system, and carotid stenosis was defined as diameter stenosis ≥30%. Results— There were 1374 subjects (47.1%) with normotension, 200 (6.9%) with WCHT, 639 (21.9%) with MHT, and 702 (24.1%) with SHT. The geometric average of mean intima-media thickness was significantly higher among subjects with WCHT (0.73 mm), MHT (0.77 mm), and SHT (0.77 mm) than those with normotension (0.67 mm; all P<0.001 versus normotension). Compared with normotension, all types of hypertension were also associated with increased likelihood of carotid stenosis (age- and sex-adjusted odds ratio, 2.36 [95% confidence interval, 1.27–4.37] for WCHT, 1.95 [1.25–3.03] for MHT, and 3.02 [2.01–4.54] for SHT). These associations remained significant even after adjustment for other cardiovascular risk factors. Conclusions— WCHT, as well as MHT, and SHT were associated with carotid atherosclerosis in a general Japanese population.

Magnesium intake decreases Type 2 diabetes risk through the improvement of insulin resistance and inflammation: the Hisayama Study

Early studies have shown that magnesium intake decreases the risk of Type 2 diabetes, but the results are still inconsistent. We prospectively examined the association between magnesium intake and incidence of Type 2 diabetes in a general Japanese population.

Combined effects of smoking and hypercholesterolemia on the risk of stroke and coronary heart disease in Japanese: the Hisayama study.

Background: Cigarette smoking is an established risk factor for stroke and coronary heart disease (CHD) in Western countries. However, it is uncertain whether or not smoking raises the risk of stroke in Japanese. We examined the influence of smoking on the development of stroke and CHD and the effects of interactions between smoking and hypercholesterolemia on these outcomes in a general Japanese population. Methods: A total of 2,421 community-dwelling Japanese individuals, aged 40–79 years, with no history of cardiovascular disease, were followed up for 14 years. Results: During the follow-up, 194 total stroke and 112 CHD events occurred. Compared with never smokers, the multivariate-adjusted hazard ratios for the occurrence of total stroke were 1.53 (95% confidence interval = 0.90–2.61) in former smokers, 1.90 (1.18–3.06) in current light smokers (<20 cigarettes/day) and 2.01 (1.11–3.65) in current heavy smokers (≧20 cigarettes/day). The multivariate-adjusted hazard ratios for the development of CHD were 1.10 (0.56–2.15), 1.88 (1.02–3.47) and 2.31 (1.17–4.57), respectively. In regard to stroke subtypes, current smoking was an independently significant risk factor for ischemic stroke and subarachnoid hemorrhage. Furthermore, the combination of smoking and hypercholesterolemia synergistically increased the risks of total stroke and CHD (all p for interaction <0.05). Conclusion: Our findings suggest that smoking raises the risks of ischemic stroke, subarachnoid hemorrhage and CHD occurrence in the Japanese population, and that this effect is strengthened by hypercholesterolemia.

Prevalence and Causes of Functional Disability in an Elderly General Population of Japanese : The Hisayama Study

Background There are limited data on the prevalence and causes of disability in the elderly general population in Japan. Methods In a population-based cross-sectional study of 1550 Japanese aged 65 years or older, we examined the prevalence of functional disability (defined as a Barthel Index score of ≤95) and its causes. Results A total of 311 of the participants had a disability (prevalence 20.1%). The prevalence of disability increased with age and doubled with every 5-year increment in age. Prevalence was higher in women than in men, especially among those aged 85 years or older. With respect to the cause of functional disability, dementia accounted for 23.5%, stroke for 24.7%, orthopedic disease for 12.9%, and other disease for 38.9% of cases in men; in women, the respective values were 35.8%, 9.3%, 31.0%, and 23.9%. Regarding age, dementia was the most frequent cause of disability in subjects aged 75 years or older, whereas stroke was most common in subjects aged 65 to 74 years. Approximately two-thirds of cases of total dependence were attributed to dementia in both sexes, whereas the main cause of slight or moderate/severe dependence was stroke in men and orthopedic disease in women. Among participants with total dependence, 94.8% resided in a hospital or health care facility. Conclusions Our findings indicate that functional disability is common among Japanese elderly adults and that its major cause is stroke in men and dementia in women.

Impact of Metabolic Syndrome Compared With Impaired Fasting Glucose on the Development of Type 2 Diabetes in a General Japanese Population: The Hisayama study

OBJECTIVE We examined whether metabolic syndrome predicts incident type 2 diabetes more effectively than impaired fasting glucose (IFG) in a general Japanese population. RESEARCH DESIGN AND METHODS A total of 1,935 nondiabetic subjects aged 40–79 years were followed-up prospectively for a mean of 11.8 years. RESULTS During the follow-up, 286 subjects developed type 2 diabetes. Compared with those without metabolic syndrome, the multivariate-adjusted hazard ratio (HR) for incident type 2 diabetes was significantly higher in subjects of both sexes with metabolic syndrome, even after adjustment for confounding factors, age, family history of diabetes, total cholesterol, alcohol intake, smoking habits, and regular exercise (men: HR 2.58 [95% CI 1.85–3.59]; women: 3.69 [2.58–5.27]). The multivariate-adjusted HR of metabolic syndrome for type 2 diabetes was slightly lower in men and similar in women compared with that of IFG. The multivariate-adjusted HR for type 2 diabetes rose progressively as the number of metabolic syndrome components increased in both subjects with and without IFG. In stratified analysis, the multivariate-adjusted risk of type 2 diabetes was significantly higher in subjects with metabolic syndrome alone (2.37 [1.45–3.88]) or IFG alone (3.49 [2.57–4.74]) and markedly increased in subjects with both metabolic syndrome and IFG (6.76 [4.75–9.61]) than in subjects with neither metabolic syndrome nor IFG. Furthermore, the multivariate-adjusted risk for type 2 diabetes was also significantly higher in subjects with both metabolic syndrome and IFG than in those with either one alone (both P < 0.001). CONCLUSIONS Our findings suggest that metabolic syndrome significantly increases the risk of incident type 2 diabetes, independent of IFG, and is therefore a valuable tool to identify individuals at high risk of type 2 diabetes.

Milk and Dairy Consumption and Risk of Dementia in an Elderly Japanese Population: The Hisayama Study

To determine the effect of milk and dairy intake on the development of all‐cause dementia and its subtypes in an elderly Japanese population.

Trends in the prevalence of type 2 diabetes and prediabetes in community-dwelling Japanese subjects: The Hisayama Study.

We examined secular trends in the prevalence of type 2 diabetes and prediabetes in community‐dwelling Japanese subjects.