Nocturnal intermittent hypoxia and C reactive protein among middle-aged community residents: a cross-sectional survey.

BACKGROUND: There are conflicting results for the association between obstructive sleep apnoea and raised C reactive protein (CRP) levels. A study was undertaken to investigate whether nocturnal intermittent hypoxia, a surrogate marker for obstructive sleep apnoea, was associated with CRP levels among a community-dwelling Japanese population. METHODS: Among participants in the Circulatory Risk in Communities Study (CIRCS), 1422 male and 2466 female community residents aged 40-69 years were tested during sleep. No nocturnal intermittent hypoxia, mild nocturnal intermittent hypoxia and moderate to severe nocturnal intermittent hypoxia were defined using 3% oxygen desaturation index cut-off points at 5 and 15 events/h, respectively. High-sensitivity CRP levels were measured using a latex particle-enhanced immunonephelometric assay. Multivariate analysis was adjusted for age, sex, body mass index, smoking status, current alcohol intake, hypertension, hypercholesterolaemia, diabetes mellitus and menopausal status for women. RESULTS: Multivariable-adjusted mean CRP levels among men were 0.70 mg/l (95% CI 0.65 to 0.75) for no nocturnal intermittent hypoxia, 0.82 mg/l (95% CI 0.74 to 0.89) for mild nocturnal intermittent hypoxia and 0.84 mg/l (95% CI 0.70 to 1.00) for moderate to severe nocturnal intermittent hypoxia (p for trend=0.03). The values for women were 0.59 mg/l (95% CI 0.57 to 0.62), 0.66 mg/l (95% CI 0.59 to 0.73) and 0.82 mg/l (95% CI 0.62 to 1.03), respectively (p for trend=0.008). Compared with no nocturnal intermittent hypoxia, the prevalence of a high CRP level (>or=1.0 mg/l) was 1.4-1.7-fold higher for mild to severe nocturnal intermittent hypoxia in both sexes. CONCLUSIONS: Nocturnal intermittent hypoxia is associated with raised serum CRP levels among middle-aged Japanese subjects.

Nocturnal intermittent hypoxia and metabolic syndrome; the effect of being overweight: the CIRCS study.

AIM: We investigated whether nocturnal intermittent hypoxia, a surrogate marker for obstructive sleep apnea, is associated with metabolic syndrome and its components among Japanese. METHODS: We examined 1,710 male and 2,896 female community-dwelling Japanese aged 40 to 69, who participated in annual cardiovascular examinations and investigations of sleep. Nocturnal intermittent hypoxia was estimated based on a 3% oxygen desaturation index measured with pulse-oximetry during sleep. No, mild and moderate-to-severe nocturnal intermittent hypoxia were defined by <5, 5 to <15 and >or=15 events/hour, respectively. Metabolic syndrome was defined by modified criteria of the Adult Treatment Panel III guidelines. RESULTS: Compared with no nocturnal intermittent hypoxia, the multivariable odds ratio of metabolic syndrome was 1.9 (95% confidence interval: 1.6-2.4) for mild and 3.2 (2.2-4.7) for moderate-to-severe nocturnal intermittent hypoxia among men; 2.6 (2.1-3.4) and 5.8 (3.4-9.8) among women, respectively. When stratified by overweight status (body mass index >or=25 kg/m(2)), the multivariable odds ratio of two or more metabolic risk factors (other than overweight) associated with moderate-to-severe nocturnal intermittent hypoxia was 1.9 (1.2-3.1) among non-overweight subjects and 1.4 (0.9-2.1) among overweight subjects (p for interaction=0.002). CONCLUSIONS: Nocturnal intermittent hypoxia was associated with the accumulation of metabolic risk factors, especially among non-overweight individuals.

Measurement performance of reagent manufacturers by Centers for Disease Control and Prevention/Cholesterol Reference Method Laboratory Network lipid standardization specified for metabolic syndrome-focused health checkups program in Japan.

AIM: This study was designed to clarify the current measurement performance of 7 reagent manufacturers for high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and triglycerides (TG) specified for the metabolic syndrome (MetS)-focused health checkups program in Japan. METHODS: Twenty HDLC, 21 LDLC and 9 TG analytical reagent/instrument/calibrator systems (system), and combinations of reagent lots, instrument models and calibrator lots, underwent Centers for Disease Control and Prevention (CDC)/Cholesterol Reference Method Laboratory Network (CRMLN) lipid standardization. Eighty and 100% systems were requested to achieve an accuracy of within +/-1% and +/-2% of the reference value, so that a clinical laboratory can meet the CDC criteria. RESULTS: The CDC performance criteria of HDLC, LDLC and TG require an accuracy of within +/-5%, +/-4% and +/-5%, respectively. For HDLC, all 20 systems met the criteria. Fourteen (70.0%) and 18 (90.0%) systems were within +/-1% and +/-2%, respectively. For LDLC, 14 (66.7%) of 21 systems met the criteria, but 7 (33.3%) failed. Five (23.8%) and 17 (81.0%) systems were within +/-1% and +/-2%, respectively. For TG, 8 of 9 systems met the criteria. Two (22.2%) and 4 (44.4%) systems were within +/-1% and +/-2%, respectively. The minimum and maximum differences of a specified sample among manufacturers were 1.6 and 11.0 mg/dL for HDLC, 7.8 and 33.0 mg/dL for LDLC, and 2.8 and 27.4 mg/dL for TG, respectively. CONCLUSION: Homogeneous HDLC methods are acceptable for MetS, but further accuracy improvement of homogeneous LDLC and TG methods will be needed because of their poor performance.

Relationship of urinary cGMP excretion with aging and menopausal status in a general population.

AIM: Aging and postmenopausal women are associated with increased risks of cardiovascular disease; however, epidemiological evidence concerning the relationship of aging and the menopause with vascular biological activity is limited. METHODS: We investigated the relationship of aging and the menopause with urinary excretion of cyclic guanosine 3',5' monophosphate (cGMP) in 1,541 Japanese men and women aged 40 to 79 years. The 24-hour urinary excretion of cGMP was measured with a (125)I-labeled cGMP radioimmunoassay and was adjusted for urinary creatinine excretion (nmol/mmol creatinine). RESULTS: Aging was positively associated with urinary excretion of cGMP for both sexes. Postmenopausal women excreted significantly less urinary cGMP than premenopausal women after adjustment for age and other cardiovascular risk factors: 48.3+/-0.04 nmol/mmol vs. 61.5+/-0.07 nmol/mmol, p=0.006. CONCLUSIONS: Our data suggest that cGMP-related vasodilatation is impaired in postmenopausal women.

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.

The impact of the metabolic syndrome and its components on the incidence of ischemic heart disease and stroke: the Japan public health center-based study.

In this study, we aimed to examine the impact of the metabolic syndrome and its components on the risk of cardiovascular disease among a relatively less-obese population. A total of 8249 men and 15 064 women, aged 40-69 years, with no history of ischemic heart disease, stroke and/or cancer completed a risk-factor survey between 1993 and 1995. The metabolic syndrome was defined based on modified criteria of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF). Systematic cardiovascular surveillance was carried out throughout 2003, and 693 events of ischemic heart disease and stroke were identified. We observed significant associations of the metabolic syndrome with the risk of ischemic heart disease and ischemic stroke, but not with hemorrhagic stroke. The multivariable hazard ratio (95% confidence interval) of ischemic heart disease among men for the metabolic syndrome based on the AHA/NHLBI criteria was 2.25 (1.44-3.51) and that of ischemic stroke was 1.88 (1.40-2.52). The respective hazard ratios for the metabolic syndrome based on the IDF criteria were 1.61 (0.99-2.64) for ischemic heart disease and 1.94 (1.41-2.68) for ischemic stroke. The population-attributable fraction (PAF) of the metabolic syndrome based on the AHA/NHLBI criteria was higher than that based on the IDF criteria: 19 vs. 12% (P for difference=0.003) for ischemic cardiovascular disease among men, because non-overweight men with >or=2 risk factors were also at high risk (20% of the PAF). Our data suggest that the metabolic syndrome based on the AHA/NHLBI criteria predicts ischemic cardiovascular disease better than the syndrome based on the IDF criteria, because of the exclusion of non-overweight high-risk individuals from the reference group.

Establishment of long-term monitoring system for blood chemistry data by the national health and nutrition survey in Japan.

AIM: We established a monitoring system for the annual follow-up of blood chemistry data obtained by the National Health and Nutrition Survey in Japan. METHODS: Blood chemistry testing has been entrusted to SRL Inc. We used two external quality control assurance programs established by the Japan Medical Association (JMA) and by CDC/CRMLN during the previous 8-year period. Ten analytes were measured: total cholesterol, HDL cholesterol, triglycerides, urea nitrogen, uric acid, creatinine, AST (GOT), ALT (GPT), gamma-GT (gamma-GTP), and glucose. Total error (TE) was calculated from accuracy by the JMA program and precision by internal quality control of SRL. The permissible range of TE values was determined to be 50% of the evaluation limit on one side in the evaluation criteria of the College of American Pathologists (CAP). When TE fell within the permissible range, the follow-up of annual changes was considered possible. RESULTS: Annual follow-up of blood chemistry data was considered possible for all the analytes except urea nitrogen. Based on this study, new permissible TE ranges are proposed. CONCLUSION: We confirmed the functioning of the monitoring system for the annual follow-up of blood chemistry data obtained by the National Health and Nutrition Survey in Japan.

Effects of obesity and smoking on mental stress-induced blood pressure and augmentation index responses in normotensive young males: the J-SHIPP study.

Exaggerated blood pressure (BP) response to mental stress has been known to be a prognostic factor for cardiovascular disease. It has been argued that such unusual vascular reactivity to mental stress may arise from insulin resistance. To examine the vascular responses to mental stress, we evaluated the stress-related changes in BP and the augmentation index (AI), an index of arterial stiffness, in normotensive young males. Changes in late systolic BP (SBP2) representing central aortic pressure were also examined. Subjects were 86 males (21+/-2 years), 13 of whom were classified as obese (>or=25 kg/m(2)). AI was obtained from the radial arterial waveform as a ratio of the height of the late systolic peak to that of the first peak. Blood pressure and AI measurements were taken before, during and after a simple mental arithmetic test (MAT) lasting 3 min. Systolic BP (baseline 125+/-13, during MAT 133+/-13, post-MAT 124+/-11 mmHg; p<0.001) and heart rate (74+/-12, 81+/-13, 74+/-11 beats/min; p<0.001) were significantly increased during the MAT, whereas AI showed a slight reduction. In a separate analysis, the opposite response was observed between obese subjects showing increased AI (54+/-11, 56+/-13, 52+/-11%) and non-obese subjects who showed reduced AI (54+/-12, 51+/-12, 53+/-12%; p=0.032). The responses in SBP and SBP2 (obese 103+/-14, 117+/-12, 104+/-12; non-obese 98+/-13, 104+/-12, 97+/-12 mmHg; p=0.007) were also larger in the obese subjects. Stress-related transient increases in arterial stiffness may be involved in the exaggerated responses in aortic pressure in obese subjects.

[The metabolic syndrome and risk of stroke in a rural community in Japan].

PURPOSE: To clarify the association between the metabolic syndrome (MS) and stroke incidence with a prospective cohort study in a rural community. METHODS: We selected 4,627 people aged > or =40 years without any past history of stroke from total 4,672 participants of health checkups during 1996 to 1998 in O City, Ehime prefecture. These were followed until Dec 31, 2002 and assessed for incident stroke based on the stroke registration system in the whole community. MS was defined using baseline data for waist circumference and three risk factors: elevated blood pressure, dyslipidemia, and glucose intolerance. Sex and age-adjusted relative risks (RR) for incident stroke were estimated using Cox's proportional hazard model, and population attributable risks (PAR) were also calculated. RESULTS: During the mean 5.7 year-follow-up, 88 incident strokes (50 in men and 38 in women) were recorded; 11.4% cerebral hemorrhage; 5.7% subarachnoid hemorrhage; and 83.0% cerebral infarction. Percentages of individuals with MS in the stroke and non-stroke groups were 6.8% and 6.4%, respectively, with no significant different between the two. The highest PAR was found among individuals with a normal waist and one risk factor (36.3%). The sex and age-adjusted RR for MS and incident stroke was not significantly elevated, using subjects with a normal waist circumference and 0 risk factors as a reference group (RR, 1.00); however, the RR of persons with a normal waist level plus one or more risks was 2.53 (95% CI, 1.14-5.58), and that for individuals with a high waist circumference and > or = 1 risk factors, including MS, was 2.66 (95% CI, 1.14-6.21). CONCLUSION: The risk of incident stroke is increased in people with risk factor aggregation, regardless of visceral fat conditions. Since the PAR was higher for people with a normal waist circumference than a high waist circumference in this population, the results suggest that a health policy focusing on MS for stroke prevention would not be effective in rural communities in Japan.

A low level of C-reactive protein in Japanese adults and its association with cardiovascular risk factors: the Japan NCVC-Collaborative Inflammation Cohort (JNIC) study.

High-sensitivity C-reactive protein (hs-CRP) levels vary remarkably by race and ethnic group. We examined hs-CRP levels and their association with cardiovascular risk factors in the Japanese general population. The Japan National Cardiovascular Center (NCVC)-collaborative Inflammation Cohort (JNIC) Study recruited 5213 men and 7071 women aged > or = 40 years from seven communities in Japan during 2002-2004. hs-CRP was measured using nephelometry calibrated with CRM 470, the international plasma protein reference material. Traditional cardiovascular risk factors and their aggregation were studied in multivariate logistic models, stratified by overweight status. Median hs-CRP levels in men and women were 0.60 and 0.45 mg/L, respectively. The percentage of subjects with hs-CRP levels < 1.0, 1.0-3.0, and > 3.0 mg/L was 67.4%, 22.0%, and 10.6% in men, respectively, and 76.3%, 16.7%, and 7.0% in women. hs-CRP levels showed significant linear associations with traditional risk factors. Overweight, hypertension, dyslipidemia (men only), smoking (men only), and diabetes (women only) contributed significantly to elevated hs-CRP levels. Overweight individuals with hypertension, dyslipidemia, and diabetes had a high prevalence of elevated hs-CRP levels in both sexes. Japanese adults have very low hs-CRP levels. An aggregation of metabolic risk factors is associated with elevated hs-CRP levels among overweight individuals, particularly in women.

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.

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.

[Trends for stroke incidence, severity, and prognosis in a rural community with a long-term stroke prevention program].

OBJECTIVE: To examine the benefit of a long-term community-based stroke prevention program, we explored 35 years of surveillance data of stroke incidence for residents in a rural area in Japan. METHOD: The surveyed community was Ikawa town (population in 2000 was 6,116) in Akita prefecture, where a community-based stroke prevention program has been conducted since 1963. Incidence rates and numbers of stroke episodes, proportions for loss of consciousness and motor paralysis at onset, proportions for each seriousness category (A: death within one day after onset, B: death during 2-7 days after onset, C: survival more than 8 days after onset with complete hemiparesis, D: survival more than 8 days after onset with incomplete or no hemiparesis), and one-year survival rates and activity of daily living were investigated for 1964-69, 1970-79, 1980-89 and 1990-98. RESULTS: Stroke incidence declined 66% and 64% among the 30-69 years age group and 70 years over age group, respectively between 1964-69 and 1990-98. Incident numbers of stroke episodes declined 41% among those aged 30-69 years and, while it increased 100% in the 70 years over age group, this was much less than the increase rate of 271% rated for the corresponding aged population growth over time. In the 30-69 years age group, the proportion of patients with no loss of consciousness at onset increased from 53-64% during the former three periods to 79% in 1990-98. The proportion of patients with no motor paralysis also increased progressively over the study periods and the proportions for A or B categories in the seriousness classification decreased between 1964-69 and 1990-98 while the proportion in the D category increased between 1980-89 and 1990-98. One-year survival rates increased from 71% and 36% in 1964 to 86% and 61% in 1990-98 among the 30-69 years age group and 70 years over age group, respectively. With both, the numbers of totally dependent patients at one-year after onset, did not change significantly over time, despite the marked increase in the population of risk. CONCLUSION: The present study showed that a long-term community-based stroke prevention program can not only decrease stroke incidence and number of episodes, but also reduce the likelihood of severe stroke attack and improve prognosis, thereby suppressing the increase of totally dependent patients expected from growth of the old population in the community.

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 > or =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, < or =2 drinks per day, does not raise the risk of total stroke.

Can Blood Pressure in the Elderly be Reduced? Findings From a Long-term Population Survey in Japan.

To examine whether blood pressure (BP), a major risk factor of cardiovascular disease, can be controlled in the elderly as well as in middle-aged persons, we analyzed the data of observational studies on trends for BP and cardiovascular disease incidence in a northeast rural community of Japan. This community was the subject of an ongoing hypertension control program that was initiated in 1963. A significant decline in BP levels was noted in each sex-age group between 1963 and 1966 and 1987 and 1991. The decline was greater in older persons compared with younger individuals. The BP decline was attributable to an increase in antihypertensive medication use, beginning in the 1970s. We compared BP levels of untreated offspring and parents when both were 40 to 49 years old. Blood pressure levels were significantly lower in the offspring than in parents. This result and the large downward shift of BP distribution in the second decade of follow-up suggested that the improvements in diets and other environmental factors contributed to the BP decline. Between 1964 and 1968 and 1989 and 1992, stroke incidence declined 70% to 79% for all sex and age groups (40-69 and greater than 70 years). The number of totally dependent stroke patients decreased in both the middle-aged and the elderly between 1976 and 1991. The decline in stroke mortality tended to be larger in the surveyed community than in adjacent communities. These results indicated that hypertension control is effective in preventing stroke in the elderly as well as in the middle-aged.