Shizukiyo Ishikawa

Ambulatory blood pressure is a better marker than clinic blood pressure in predicting cardiovascular events in patients with/without type 2 diabetes.

BACKGROUND The prognostic significance of ambulatory blood pressure (ABP) has not been established in patients with type 2 diabetes (T2DM). METHODS In order to clarify the impact of ABP on cardiovascular prognosis in patients with or without T2DM, we performed ABP monitoring (ABPM) in 1,268 subjects recruited from nine sites in Japan, who were being evaluated for hypertension. The mean age of the patients was 70.4 +/- 9.9 years, and 301 of them had diabetes. The patients were followed up for 50 +/- 23 months. We investigated the relation between incidence of cardiovascular diseases (CVDs) and different measures of ABP, including three categories of awake systolic blood pressure (SBP <135, 135-150, and >150 mm Hg), sleep SBP (<120, 120-135, and >135 mm Hg), and dipping trends in nocturnal blood pressure (BP) (dippers, nondippers, and risers). Cox regression models were used in order to control for classic risk factors. RESULTS Higher awake and sleep SBPs predicted higher incidence of CVD in patients with and without diabetes. In multivariable analyses, elevated SBPs while awake and asleep predicted increased risk of CVD more accurately than clinic BP did, in both groups of patients. The relationships between ABP level and CVD were similar in both groups. In Kaplan-Meier analyses, the incidence of CVD in nondippers was similar to that in dippers, but risers experienced the highest risk of CVD in both groups (P < 0.01). The riser pattern was associated with a approximately 150% increase in risk of CVD, in both groups. CONCLUSIONS These findings suggest that ABPM is a better predictor of cardiovascular risk than clinic BP, and that this holds true for patients with or without T2DM.

Short Sleep Duration as an Independent Predictor of Cardiovascular Events in Japanese Patients With Hypertension

BACKGROUND It is not known whether short duration of sleep is a predictor of future cardiovascular events in patients with hypertension. METHODS To test the hypothesis that short duration of sleep is independently associated with incident cardiovascular diseases (CVD), we performed ambulatory blood pressure (BP) monitoring in 1255 subjects with hypertension (mean [SD] age, 70.4 [9.9] years) and followed them for a mean period of 50 (23) months. Short sleep duration was defined as less than 7.5 hours (20th percentile). Multivariable Cox hazard models predicting CVD events were used to estimate the adjusted hazard ratio and 95% confidence interval (CI) for short sleep duration. A riser pattern was defined when mean nighttime systolic BP exceeded daytime systolic BP. The end point was a cardiovascular event: stroke, fatal or nonfatal myocardial infarction (MI), and sudden cardiac death. RESULTS In multivariable analyses, short duration of sleep (<7.5 hours) was associated with incident CVD (hazard ratio [HR], 1.68; 95% CI, 1.06-2.66; P = .03). A synergistic interaction was observed between short sleep duration and the riser pattern (P = .09). When subjects were classified according to their sleep time and a riser vs nonriser pattern, the group with shorter sleep duration plus the riser pattern had a substantially and significantly higher incidence of CVD than the group with predominant normal sleep duration plus the nonriser pattern (HR, 4.43; 95% CI, 2.09-9.39; P < .001), independent of covariates. CONCLUSIONS Short duration of sleep is associated with incident CVD risk and the combination of the riser pattern and short duration of sleep that is most strongly predictive of future CVD, independent of ambulatory BP levels. Physicians should inquire about sleep duration in the risk assessment of patients with hypertension.

Dietary patterns and levels of blood pressure and serum lipids in a Japanese population.

Background Associations between dietary patterns and cardiovascular disease risk factors remain unclear. The objective of this study was to evaluate the association between dietary patterns derived from factor analysis and the levels of blood pressure and serum lipids in a Japanese population. Methods We conducted a cross-sectional analysis among 6886 (in the analysis on blood pressure) and 7641 (in the analysis on serum lipids) Japanese subjects aged 40-69 years. Dietary patterns were identified from a food frequency questionnaire by factor analysis. Associations between dietary patterns and blood pressure and serum lipids were examined after taking potential confounders into account. Results Three dietary patterns were identified: vegetable, meat, and Western. In men, the meat pattern was associated with higher total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol. The Western pattern was associated with higher total and LDL cholesterol. In women, the vegetable pattern was associated with lower systolic and diastolic blood pressure and pulse pressure, and higher HDL cholesterol. The meat pattern was associated with higher total and HDL cholesterol. The Western pattern was associated with higher total, HDL, and LDL cholesterol, and the least intake pattern of Western diet was associated with higher systolic and diastolic blood pressures. Conclusions Dietary patterns of a Japanese population were related to cardiovascular disease risk factors, especially in women.

Prospective Study on Occupational Stress and Risk of Stroke

BACKGROUND No prospective studies have examined the association between occupational stress according to the job demand-control model and the risk of stroke in Asian populations. METHODS We conducted a multicenter community-based prospective study of 6553 Japanese male and female workers. Occupational stress was evaluated using a Japanese version of the job demand-control model questionnaire. We used the Cox proportional hazards model to evaluate the association between occupational stress and stroke. RESULTS During a mean follow-up of 11 years, we identified 147 incident strokes. Multivariable analysis revealed a more than 2-fold increase in the risk of total stroke among men with job strain (combination of high job demand and low job control) (hazard ratio, 2.73; 95% confidence interval, 1.17-6.38) compared with counterpart men with low strain (combination of low job demand and high job control) after adjustment for age, educational attainment, occupation, smoking status, alcohol consumption, physical activity, and study area. Additional adjustments for biologic risk factors attenuated the hazard ratio, but there continued to be statistical significance (hazard ratio, 2.53; 95% confidence interval, 1.08-5.94). In women, no statistically significant differences were found for any stroke incidence among the job characteristic categories. CONCLUSION Occupational stress related to job strain was associated with incident strokes among Japanese men.

Effect of dosing time of angiotensin II receptor blockade titrated by self-measured blood pressure recordings on cardiorenal protection in hypertensives: the Japan Morning Surge-Target Organ Protection (J-TOP) study

Objectives To study the impact of the dosing time of an angiotensin II receptor blocker (ARB) titrated by self-measured home blood pressure (HBP) on cardiorenal damage in hypertensives. Methods We conducted an open-label multicenter trial, the J-TOP study, that enrolled 450 hypertensives with self-measured systolic HBP more than 135 mmHg. The study patients were stratified into three groups according to the difference between their morning and evening SBPs difference: a morning hypertension group (morning and evening difference at least 15 mmHg; n = 170), a morning and evening hypertension group (0 mmHg ≤ morning and evening difference <15 mmHg; n = 198), and an evening hypertension group (morning and evening difference <0 mmHg; n = 82). Individuals were then randomly allocated to receive bedtime dosing or awakening dosing of candesartan (± diuretic as needed) titrated to achieve a target systolic HBP less than 135 mmHg. The 6-month change in the urinary albumin/creatinine ratio (UACR) was assessed. Results In total patients, the UACR was more markedly reduced in the bedtime-dosing group than in the awakening-dosing group (−45.7 vs. −34.5%, P = 0.02), whereas there were no differences in the reduction of any of the HBPs including the sleep blood pressures (BPs) between the two groups. Among the three subgroups stratified by the morning and evening difference, the difference in the UACR reduction between the bedtime-dosing and awakening-dosing groups was only significant in the morning hypertension group (−50.6 vs. −31.3%, P = 0.02). Conclusion In HBP-guided antihypertensive treatment in hypertensives, bedtime dosing of an ARB may be superior to awakening dosing for reducing microalbuminuria.

Sleep Duration and Incidence of Cardiovascular Events in a Japanese Population: The Jichi Medical School Cohort Study

Background Although sleep is one of the most important health-related factors, the relationship between sleep duration and the incidence of cardiovascular events has not been fully described. Methods The present study comprised the 11 367 study subjects (4413 men and 6954 women) of the Jichi Medical School Cohort Study, a population-based prospective study. Baseline data were obtained by questionnaire and health examinations between April 1992 and July 1995 in 12 rural areas in Japan, and the main outcome measures were the incidence of cardiovascular diseases (stroke and myocardial infarction [MI]). Cox proportional hazards models were used to analyze the association between sleep duration and the incidence of cardiovascular events. Results A total of 481carciovascular events (255 men and 226 women) were observed during an average follow-up period of 10.7 years. After adjusting for age, systolic blood pressure, serum total cholesterol, body mass index, smoking habits, and alcohol drinking habits, the hazard ratios (95% confidence intervals) for the incidence of cardiovascular diseases for individuals sleeping less than 6 hours and 9 hours or longer were 2.14 (1.11–4.13) and 1.33 (0.93–1.92) in men, and 1.46 (0.70–3.04) and 1.28 (0.88–1.87) in women, respectively, relative to those who reported sleeping 7 to 7.9 hours per day. Conclusions Our data indicate that men who sleep less than 6 hours a day have a higher risk of cardiovascular events than those sleeping 7 to 7.9 hours.

Association between job characteristics and health behaviors in Japanese rural workers

Associations between job characteristics defined by the Karasek’s job demand-control model and health behaviors were investigated in a cross-sectional analysis of 6,759 Japanese rural workers. High psychological demands were associated with heavy smoking, exaggerated prevalence of alcohol drinking, and high work-related physical activity. Low job control was associated with lower consumption of vegetables, a smaller quantity number of cigarettes smoked, and a low level of work-related physical activity. Job strain, a combined measure obtained from the ratio of demands to control, was associated with lower vegetable consumption, low prevalence of smoking, and high prevalence of current alcohol drinking. Stratified analyses by occupations and gender provided some but not allof the explanations for the unexpected findings. The results indicate a possible association between psychosocial job characteristics and health behaviors. A few unexpected findings prevent complete support to one of the hypothetical pathways that the job characteristics lead to cardiovascular disease through behaviors.

Association of Adiponectin With Cerebrovascular Disease A Nested Case–Control Study

Background and Purpose— Even though adiponectin is associated with many traditional cardiovascular risk factors, studies assessing the association between adiponectin and cerebrovascular disease (CVD) are scarce. We assessed the odds of CVD at different plasma levels of adiponectin. Methods— A nested case–control study was conducted involving 5243 subjects, drawn from 12 490 subjects of the Jichi Medical School Cohort Study, whose blood samples had been drawn between 1992 and 1995. Over an average of 9.7 years of follow-up, through 2005, 179 patients with cerebrovascular events were identified, in addition to 630 controls matched for age, sex, and community (total n=809). Odds ratios were estimated relative to the highest quartile of adiponectin level. Results— There was neither a significant difference in the odds of stroke between the lowest and highest adiponectin quartiles, nor a significant linear trend toward a reduced risk of stroke at higher adiponectin levels. These results did not change after excluding participants with diabetes, impaired glucose metabolism, or metabolic syndrome. The odds of ischemic stroke in the lowest quartile were significantly higher than in the highest quartile, when adjusted for age and sex (OR 2.04 [95% CI, 1.09 to 3.80]). However, the odds failed to achieve statistical significance when adjusted further for other cardiovascular risk factors. Again exclusion of subjects with diabetes, impaired glucose metabolism, or metabolic syndrome did not alter results. Conclusions— Adiponectin levels are not independently associated with stroke or brain infarction. The use of adiponectin as a cerebrovascular disease predictor may be premature.

Frequency of Citrus Fruit Intake Is Associated With the Incidence of Cardiovascular Disease: The Jichi Medical School Cohort Study

Background It has been reported that fruit intake protects against cardiovascular disease (CVD). However, most of the relevant studies were conducted in Western countries, and only a few investigated Japanese populations. The present cohort study assessed the effect of citrus fruit intake on the incidence of CVD and its subtypes in a Japanese population. Methods A baseline examination consisting of physical and blood examinations and a self-administered questionnaire was conducted during the period from April 1992 through July 1995. Dietary habits were assessed using a food frequency questionnaire that was divided into 5 categories. Citrus fruit was examined separately due to its frequent consumption by the general Japanese population. Using the Cox proportional hazards model, data from 10 623 participants (4147 men, 6476 women) who had no history of CVD or carcinoma were analyzed to assess the association between frequency of citrus fruit intake and CVD incidence. Results Frequent intake of citrus fruit was associated with a lower incidence of CVD: the hazard ratio for almost daily intake versus infrequent intake of citrus fruit was 0.57 (95% confidence interval: 0.33–1.01, P for trend = 0.04) in men and 0.51 (0.29–0.88, P for trend = 0.02) in women. Frequent intake of citrus fruit was also associated with lower incidences of both all stroke and cerebral infarction, but not hemorrhagic stroke or myocardial infarction. Conclusions Frequent intake of citrus fruit may reduce the incidence of CVD, especially cerebral infarction, in men and women.

Low-grade inflammation is a risk factor for clinical stroke events in addition to silent cerebral infarcts in Japanese older hypertensives : the Jichi Medical School ABPM Study, wave 1

Background and Purpose— High-sensitivity C-reactive protein (hsCRP), a marker of inflammation, is associated with atherosclerosis, hypertensive target organ damage, and cardiovascular events. In the general Japanese population, the level of hsCRP is reported to be lower than that in Western countries, and the relationships among hsCRP, silent cerebral infarcts (SCIs), and clinical stroke events in older Japanese hypertensives remain unclear. Methods— We conducted brain MRI and measured hsCRP at baseline in 514 older Japanese hypertensives (clinic blood pressure ≥140/90 mm Hg, age ≥50 years old) who were enrolled in the Jichi Medical School ABPM Study, wave 1. They were followed up for an average of 41 months (range: 1 to 68 months, 1751 person-years) and the incidence of subsequent clinical stroke events was evaluated. Results— The subjects with SCIs at baseline (n=257) had a higher hsCRP level than those without SCIs (geometric mean hsCRP [SD range]; 0.19 [0.18 to 0.21] versus 0.14 [0.13 to 0.16] mg/L, P=0.007) after adjustment for confounding factors, and the OR for the presence of SCIs was increased with the quartile of hsCRP levels. In Cox regression analysis, the patients with above median hsCRP level (≥0.21 mg/L) (hazard ratio [HR]: 2.50, 95% CI: 1.24 to 5.00, P=0.01) and those with SCIs (HR: 4.60, 95% CI: 1.91 to 11.03, P=0.001) at baseline had independently higher risks for clinical stroke events after adjustment for age, smoking status, antihypertensive medication use, and 24-hour systolic blood pressure level. Compared with the patients with below median hsCRP level without SCIs, those with above median hsCRP level and SCIs at baseline had a higher risk for clinical stroke events (HR: 7.32, 95% CI: 2.17 to 24.76, P=0.001), although those with below median hsCRP level and SCIs (HR: 2.46, 95% CI: 0.64 to 9.47, P=0.19) and those with above median hsCRP level without SCIs (HR: 1.11, 95% CI: 0.22 to 5.55, P=0.90) did not have significant risks. Conclusion— High-sensitivity C-reactive protein is a risk factor for clinical stroke events in addition to silent cerebral infarcts in Japanese older hypertensives, indicating that the risk for clinical stroke events increases with preexisting hypertensive target organ damage in the brain and additionally with ongoing low-grade inflammation.