Published papers

Few studies have focused on the effect of organ damage on achievement of long-term home blood pressure (BP) control. Based on the nationwide home BP-based trial data, we aimed to investigate the factors associated with home BP control, in particular, left ventricular hypertrophy (LVH) using the electrocardiogram in patients who started antihypertensive drug treatment. According to the trial protocol, we defined BP as controlled when systolic home BP reached specified targets (125-134 mm Hg in usual control (UC), n=1261; <125 mm Hg in tight control (TC), n=1288). At baseline, before drug treatment started, the mean Sokolow-Lyon voltage was 2.57±0.87 mV, and the mean Cornell product was 1573±705 mm·ms. The numbers of patients who achieved the target BP level in the UC and TC groups were 892 (70.7%) and 576 (44.7%), respectively. In both the UC and TC groups, systolic home BP at baseline was significantly lower in patients who achieved target levels than in those who did not achieve target levels (P<0.0001). Sokolow-Lyon voltage was significantly lower in patients who achieved target levels than in those who did not (P≤0.0055). The Cornell product levels in each group were similar (P≥0.12), although significantly different between patients who did or did not achieve the target level when the UC and TC groups were combined for analysis (P=0.031). Sokolow-Lyon voltage was significantly associated with achievement of home BP control in the multivariable-adjusted model (odds ratio, 1.13; 95% confidence intervals, 1.02-1.26; P=0.015), but Cornell product was not (P=0.13). These results indicate the difficulty of sufficient antihypertensive treatment when untreated patients had target organ damage, that is, LVH diagnosed by Sokolow-Lyon voltage.

The lifetime risk estimate conveys the probability of disease in the remaining lifetime for an index age. These estimates may be useful for general audience-targeted knowledge translation activities against hypertension. There are only a few reports on the impact of hypertension on the lifetime risk of cardiovascular events. The Suita Study, a cohort study of urban residents, was established in 1989. We included all participants who were coronary heart disease (CHD) free at baseline. Age (in years) was used as the timescale. Age-specific incidence rates were calculated with the person-year method within 5-year bands. We estimated the sex- and index-age-specific lifetime risk of first-ever CHD, taking the competing risk of death into account. We followed 5834 participants from 1989 to 2007 for a total of 75 387.5 person-years. At age 45 years, the competing risk of death-adjusted lifetime risk for all CHD for men was 14.12% for normotensive men and 26.95% for hypertensive men. The competing risk of death-adjusted lifetime risk for all CHD at 45 years of age for women was 6.21% for normotensive women and 14.85% for hypertensive women. This increased lifetime risk of CHD for hypertensive patients was observed among both men and women across all index ages. Although the overall lifetime risk of CHD was lower than in the Western population, hypertension showed a significant effect on the residual lifetime risk of CHD among Japanese middle-aged men and women. This easy-to-understand knowledge may be used as an important index to assist public health education and planning.

© 2019 The Author(s). Background: Care coordination between general practitioners (GPs) and cardiovascular specialists is expected to play a key role in establishing appropriate oral anticoagulant (OAC) treatment in atrial fibrillation (AF) patients. The aim of this study was to assess the impact of care coordination on oral anticoagulant therapy in the management of AF in Japan. Methods: This study was a multi-center, single-arm, prospective cohort study with retrospective chart and claims data review for historical controls. The study included three study periods: a 12-month pre-campaign period; a 12-month campaign period for AF screening and care coordination; and a 3-month post-campaign period for follow-up of care coordination. During the campaign period, patients aged ≥65 years who attended participating GP clinics underwent opportunistic AF screening by GPs under the campaign. At the discretion of the GP, newly diagnosed AF patients after the screening were referred to a cardiovascular specialist for care coordination. To assess the impact of care coordination and evaluate the effects of the campaign, implementation of care coordination, antithrombotic therapies, and patient-reported outcomes were compared between patients with and without care coordination, and between patients during the pre-campaign and campaign periods. Results: There were 86 newly diagnosed AF patients during the pre-campaign period and 90 during the campaign period. The percentage of patients with care coordination increased from 3.5% (3/86) in the pre-campaign period to 14.4% (n = 13/90) during the campaign period. The percentage of patients who received OAC therapies, according to the definition from the Japanese AF medication guideline, increased from 55.8% (48/86) to 71.1% (64/90) during the campaign period regardless of care coordination. Younger patients were referred to cardiovascular specialists for care coordination. Implementation of OAC therapy did not differ between patients with and without care coordination. Adherence to OAC therapy was low regardless of care coordination. Conclusions: This GP-targeted campaign was effective at raising awareness regarding the implementation of care coordination and appropriate OAC therapy at local clinical practices in Japan. Improvement of adherence to OAC therapy in elderly patients is a critical issue, and measures such as education programs targeted to patients and healthcare professionals should be undertaken.

© 2020, The Japanese Society of Hypertension. Lifetime risk is an informative estimate to motivate people to change lifestyle behaviors, especially from a younger age, in public health education. The impact of the combination of hypertension and diabetes on the lifetime risk of cardiovascular mortality has not been investigated in Asian populations. A pooled analysis of individual data from nine cohorts was performed. A total of 57,339 Japanese men and women were eligible for the analysis. We used the modified Kaplan–Meier approach and estimated the remaining lifetime risk of cardiovascular mortality starting from the index age of 35 years. Participants were classified into four categories defined by hypertension and diabetes. The lifetime risk was increased in the order of those without either risk, those without hypertension but with diabetes, those with hypertension but without diabetes, and those with both risks. The lifetime risk of cardiovascular mortality at the 35-year index age was as follows: 7.8% in men and 6.2% in women for those without either hypertension or diabetes, 13.2% in men and 9.5% in women for those without hypertension but with diabetes, 17.2% in men and 11.7% in women for those with hypertension but without diabetes, and 19.4% in men and 15% in women for those with both risks. These findings reinforce the need for a life-course perspective in the management of hypertension and diabetes from a younger age.

Background The reason why coexistence of preserved estimated glomerular filtration rate (eGFR) and albuminuria contributes to a high risk of death and which cause of death increases all-cause mortality have not been elucidated. Methods A total of 16,759 participants aged 40 to 69 years with normal or mildly reduced eGFR (45-119 ml/min/1.73 m2) were enrolled and divided into six groups (group 1, eGFR: 90-119 without albuminuria; group 2, eGFR: 90-119 with albuminuria; group 3, eGFR: 60-89 without albuminuria (reference); group 4, eGFR: 60-89 with albuminuria; group 5, eGFR: 45-59 without albuminuria; group 6, eGFR: 45-59 with albuminuria) based on GFR estimated by using the CKD-EPI study equation modified by a Japanese coefficient and albuminuria (urine albumin-creatinine ratio ≥ 30 mg/g). Outcomes included all-cause death (ACD), cardiovascular death (CVD) and neoplasm-related death (NPD). Multivariable-adjusted mortality rate ratios (RR) and their 95% confidence intervals (CIs) in the groups were estimated by Poisson's regression analysis. Results The highest risk of ACD (RR (95% CIs): 3.95 (2.08-7.52)), CVD (7.15 (2.25-22.7)) and NPB (3.25 (1.26-8.38)) was observed in group 2. Subjects in group 2 were relatively young and had the highest levels of body mass index, blood pressure and HbA1c and the highest prevalence of diabetes and metabolic syndrome. Conclusion Coexistence of preserved eGFR and albuminuria increases risks for ACD, CVD and NPD. Relatively young metabolic persons having both preserved eGFR and albuminuria should be considered as a very high-risk population. © 2013 Elsevier Ireland Ltd.

Objective - Associations between HbA1c and cardiovascular diseases (CVD) have been reported mainly in Western countries. It is not clear whether HbA1c measurements are useful for assessing CVD mortality risk in East Asian populations. Research Design and Methods - The risk for cardiovascular death was evaluated in a large cohort of participants selected randomly from the overall Japanese population. A total of 7,120 participants (2,962men and 4,158 women; mean age 52.3 years) free of previous CVD were followed for 15 years. Adjusted hazard ratios (HRs) and 95% CIs among categories of HbA1c (<5.0%, 5.0-5.4%, 5.5-5.9%, 6.0-6.4%, and ≥6.5%) for participants without treatment for diabetes and HRs for participants with diabetes were calculated using a Cox proportional hazards model. Results - During the study, there were 1,104 deaths, including 304 from CVD, 61 from coronary heart disease, and 127 from stroke (78 from cerebral infarction, 25 from cerebral hemorrhage, and 24 from unclassified stroke). Relations to HbA1c with all-cause mortality and CVD death were graded and continuous, and multivariate-adjusted HRs for CVD death in participants with HbA1c 6.0-6.4% and ≥6.5%were 2.18 (95% CI 1.22-3.87) and 2.75 (1.43-5.28), respectively, compared with participants with HbA1c <5.0%. Similar associations were observed between HbA1c and death from coronary heart disease and death from cerebral infarction. Conclusions - High HbA1c levels were associated with increased risk for all-cause mortality and death from CVD, coronary heart disease, and cerebral infarction in general East Asian populations, as in Western populations. © 2013 by the American Diabetes Association.

Familial hypercholesterolemia (FH) is a highly prevalent autosomal dominant hereditary disease, generally characterized by three major signs, hyper-low-density-lipoprotein (LDL) cholesterolemia, tendon/skin xanthomas and premature coronary artery disease (CAD). Because the risk of CAD is very high in these patients, they should be identified at an early stage of their lives and started on intensive treatment to control LDL-cholesterol. We here introduce a new guideline for the management of FH patients in Japan intending to achieve better control to prevent CAD. Diagnostic criteria for heterozygous FH are 2 or more of 1) LDL-cholesterol ≥180 mg/dL, 2) tendon/skin xanthoma(s), and 3) family history of FH or premature CAD within second degree relatives, for adults; and to have both 1) LDL-cholesterol ≥140 mg/dL and 2) family history of FH or premature CAD within second degree relatives, for children. For the treatment of adult heterozygous FH, intensive lipid control with statins and other drugs is necessary. Other risks of CAD, such as smoking, diabetes mellitus, hypertension etc., should also be controlled strictly. Atherosclerosis in coronary, carotid, or peripheral arteries, the aorta and aortic valve should be screened periodically. FH in children, pregnant women, and women who wish to bear a child should be referred to specialists. For homozygotes and severe heterozygotes resistant to drug therapies, LDL apheresis should be performed. The treatment cost of homozygous FH is authorized to be covered under the program of Research on Measures against Intractable Diseases by the Japanese Ministry of Health, Labour, and Welfare.

Life expectancy (LE) is a measure that describes the health status of a population. The few published studies that have examined the impact of hypertension on LE were predominantly performed in Western populations. The effect of hypertension on LE has not been reported in an Asian population. Thus, we examined the impact of hypertension on LE in the Japanese population, which has the highest LE worldwide. The abridged life table method was applied to calculate the LEs of both normotensive and hypertensive men and women aged 40-85 years. Hypertensive participants were categorized as having either stage 1 or stage 2 hypertension. Age-specific mortality rates across different groups were estimated using the person-year method based on the follow-up data from a representative Japanese population in a national survey (NIPPON DATA80). The proportion of hypertensive patients in the baseline survey was 50.5% for men and 41.4% for women. The LE of 40-year-old men and women was 41.7 years and 48.7 years, respectively, in normotensive participants and 39.5 and 45.8 years, respectively, in hypertensive participants. The LE difference between normotensive and hypertensive participants was 2.2 years for men and 2.9 years for women. LE decreased with increasing stages of hypertension. Similar patterns of LE, with respect to blood pressure (BP) status, were observed in all index ages and for both genders. At the population level, hypertension leads to decreased LE and affects both genders similarly. Our findings highlight the importance of preventing high BP and the consequences of hypertension in Japanese population. © 2012 The Japanese Society of Hypertension All rights reserved.

Background and Purpose-: An educational campaign by mass media has been associated with great increases in the knowledge about early symptoms of stroke. However, few studies were conducted with a controlled community intervention study. Methods-: To clarify the effects of a 1-year television campaign for the whole population on improvement of knowledge about stroke symptoms in 2 cities, a campaign area and a control area in Japan were selected. Before and after the campaign, 1960 randomly selected residents aged 40 to 74 years answered a telephone survey regarding knowledge of early stroke symptoms. We calculated the percentage and 95% CIs of participants who correctly chose all 5 early symptoms of stroke in each area and in each year. Results-: Before the campaign, 53% of participants (95% CI, 50%-55%) in the campaign area and 46% (95% CI, 44%-49%) in the control area correctly chose 5 early symptoms. After the 1-year television campaign, knowledge was significantly improved only in the campaign area (campaign area, 63%; 95% CI, 60%-66%; control area, 51%; 95% CI, 48%-54%). After sex stratification, only women showed improved knowledge of early symptoms. The audience rate for the campaign television programs was found to be higher in women than in men. Conclusions-: A 1-year stroke educational television campaign effectively improved knowledge about early stroke symptoms among Japanese women aged 40 to 74 years. No impact was found among men in this age group. Future studies should examine the impact of this approach on stroke knowledge among younger individuals and whether there are any behavioral changes that contribute to earlier presentation for treatment. © 2011 American Heart Association, Inc.

The World Health Organization (WHO) includes insulin resistance among its criteria for diagnosing metabolic syndrome (MetS); however, previous epidemiologic studies have limited their research to settled populations only. This study aims to clarify the relationship between plasma insulin and metabolic factors on a broader scale by studying data obtained from nomadic and settled Mongolian populations. A cross-sectional epidemiologic study of 200 nomads and 256 farmers was performed in Inner Mongolia, Republic of China. Plasma insulin levels and other metabolic factors, such as blood pressure, serum lipids and obesity, were measured. Participants were classified into 3 categories according to their plasma insulin levels. Cut-off values grouped into tertiles of fasting insulin for all participants were 6.73 nmol/L and 10.33 nmol/L. The mean number of metabolic risk factors, waist circumference, fasting plasma glucose and triglyceride were higher, and the mean HDL cholesterol was lower in the higher fasting insulin tertile among farmers after adjusting for age, gender, smoking, alcohol drinking and total cholesterol. However, no MetS factors were statistically related with fasting insulin tertile levels among nomads. In nomads, hyperinsulinemia may not be an indicator of MetS due to their specific life-style.

Background: The National Nutritional Survey in Japan (NNSJ) was initiated in 1946. Using the majority of the participants for NNSJ, the National Survey on Circulatory Disorders (NSCD) has been conducted every 10 year since 1960. We compared fatty acids intakes obtained from NNSJ and serum lipid profiles from NSCD conducted in 1990. Methods: A total of 8344 community residents (4856 women and 3488 men, age ≥ 30) from 300 randomly selected districts participated in the both surveys in 1990. At baseline, history, physical, and blood biochemical measurement and a nutritional survey were performed. We estimated nutrient intakes of each household member by dividing household intake data proportionally using average intakes by sex and age groups calculated for NNSJ95. Results: Total fat, saturated fatty acids (SFA), poly-unsaturated fatty acids (PUFA), dietary cholesterol, and Keys dietary lipid factor (KEYS) were inversely associated with age in both men and women (all Ps < 0.001). In women, age and body mass index (BMI) adjusted serum total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), and low-density lipoprotein cholesterol (LDLc) were positively associated with SFA, total fat intakes (%kcal), and with KEYS (P < 0.001). In men, age-BMI adjusted HDLc was not associated with SFA, total fat intakes, and with KEYS factors unlike in women. Other associations were similar to those in women. Conclusions: The total fatty acids, SFA intakes, and KEYS lipid factor obtained from NNSJ were significantly associated with serum total and LDL cholesterol from the National Survey on Circulatory Disorders conducted in 1990. © 2010 by the Japan Epidemiological Association.

OBJECTIVE - In white adipose tissue, adipocytes and adipocyte precursor cells are enmeshed in a dense network of type I collagen fibrils. The fate of this pericellular collagenous web in diet-induced obesity, however, is unknown. This study seeks to identify the genetic underpinnings of proteolytic collagen turnover and their association with obesity progression in mice and humans. RESEARCH DESIGN AND METHODS - The hydrolysis and degradation of type I collagen at early stages of high-fat diet feeding was assessed in wild-type or MMP14 (MT1-MMP)-haploinsufficient mice using immunofluorescent staining and scanning electron microscopy. The impact of MMP14-dependent collagenolysis on adipose tissue function was interrogated by transcriptome profiling with cDNA microarrays. Genetic associations between MMP14 gene common variants and obesity or diabetes traits were examined in a Japanese cohort (n = 3,653). RESULTS - In adult mice, type I collagen fibers were cleaved rapidly in situ during a high-fat diet challenge. By contrast, in MMP14 haploinsufficient mice, animals placed on a high-fat diet were unable to remodel fat pad collagen architecture and display blunted weight gain. Moreover, transcriptional programs linking type I collagen turnover with adipogenesis or lipogenesis were disrupted by the associated decrease in collagen turnover. Consistent with a key role played by MMP14 in regulating high-fat diet-induced metabolic programs, human MMP14 gene polymorphisms located in proximity to the enzyme's catalytic domain were closely associated with human obesity and diabetes traits. CONCLUSIONS - Together, these findings demonstrate that the MMP14 gene, encoding the dominant pericellular collagenase operative in vivo, directs obesogenic collagen turnover and is linked to human obesity traits. © 2010 by the American Diabetes Association.

Background: Several studies have reported that insulin resistance was a major risk factor for the onset of type 2 diabetes mellitus in individuals without diabetes or obesity. We aimed to clarify the association between insulin resistance and glycemic control in Japanese subjects without diabetes or obesity. Methods: We conducted a community-based cross-sectional study including 1083 healthy subjects (323 men and 760 women) in an urban area. We performed multivariate regression analyses to estimate the association between the homeostasis model assessment of insulin resistance (HOMA-IR) values and markers of glycemic control, including glycated haemoglobin (HbA1c), 1,5-anhydroglucitol (1,5-AG), and fasting plasma glucose (FPG) levels, after adjustment for potential confounders. Results: Compared with the lowest tertile of HOMA-IR values, the highest tertile was significantly associated with HbA1c and FPG levels after adjustment for potential confounders, both in men (HbA1c: β = 1.83, P = 0.001; FPG: β = 0.49, P < 0.001) and women (HbA1c: β = 0.82, P = 0.008; FPG: β = 0.39, P < 0.001). The highest tertile of HOMA-IR values was inversely associated with 1,5-AG levels compared with the lowest tertile (β = -18.42, P = 0.009) only in men. Conclusions: HOMA-IR values were associated with markers of glycemic control in Japanese subjects without diabetes or obesity. Insulin resistance may influence glycemic control even in a lean, non-diabetic Asian population.

© 2020 Lippincott Williams and Wilkins. All rights reserved. Background and Purpose-In previous studies, isolated nonspecific ST-segment and T-wave abnormalities (NSSTTAs), a common finding on ECGs, were associated with greater risk for incident coronary artery disease. Their association with incident stroke remains unclear. Methods-The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a population-based, longitudinal study of 30 239 white and black adults enrolled from 2003 to 2007 in the United States. NSSTTAs were defined from baseline ECG using the standards of Minnesota ECG Classification (Minnesota codes 4-3, 4-4, 5-3, or 5-4). Participants with prior stroke, coronary heart disease, and major and minor ECG abnormalities other than NSSTTAs were excluded from analysis. Multivariable Cox proportional hazards regression was used to examine calculate hazard ratios of incident ischemic stroke by presence of baseline NSSTTAs. Results-Among 14 077 participants, 3111 (22.1%) had NSSTTAs at baseline. With a median of 9.6 years follow-up, 106 (3.4%) with NSSTTAs had ischemic stroke compared with 258 (2.4%) without NSSTTAs. The age-adjusted incidence rates (per 1000 person-years) of stroke were 2.93 in those with NSSTTAs and 2.19 in those without them. Adjusting for baseline age, sex, race, geographic location, and education level, isolated NSSTTAs were associated with a 32% higher risk of ischemic stroke (hazard ratio, 1.32 [95% CI, 1.05-1.67]). With additional adjustment for stroke risk factors, the risk of stroke was increased 27% (hazard ratio, 1.27 [95% CI, 1.00-1.62]) and did not differ by age, race, or sex. Conclusions-Presence of NSSTTAs in persons with an otherwise normal ECG was associated with a 27% increased risk of future ischemic stroke.