石川 鎮清

Background In recent years some studies have shown that metabolic syndrome (MS) is associated with inflammation, indicated by high-sensitivity C-reactive protein (hsCRP), but there have been few population-based studies, especially in Japan. Methods and Results The study subjects were 2,191 men and women examined between 1992 and 1995 with the necessary data to ascertain MS as part of the Jichi Medical School Cohort Study. CRP was measured by nephelometry. There were 109 subjects defined as having MS (5.0%), and the proportion of MS cases was higher in men (9.4%) than in women (1.8%). Geometric mean and median CRP in the NIS group was higher than that in the non-MS (geometric mean; p < 0.001, median: 0.312 mg/L in MS and 0.122 mg/L). Proportion of MS increased with CRP, after the subjects were divided by tertile of CRP (odds ratio, 95% confidence interval 1(st) tertile as a reference; 2(nd) tertile: 2.9, 1.5-5.9, 3(rd) tertile: 5.7, 3. 1-11.1). Conclusion Inflammation, measured by the concentration of hsCRP, was elevated in cases of MS in the general Japanese population. Longitudinal data should be examined in the future.

Background: Although adverse psychosocial job characteristics are suspected predictors of suicide death, prospective studies based on established stress instruments are limited. Methods: In a multicenter community-based Japanese cohort study, we prospectively investigated the association between psychosocial job characteristics and the risk of death from suicide among male workers. Baseline examination was conducted from 1992 to 1995 to determine the socioeconomic, behavioural and biological variables in addition to the psychosocial job characteristics of 3,125 male workers aged 65 and under and free from major illness. Low job control and high job demands were measured as adverse psychosocial job characteristics according to a job demand-control model questionnaire. Suicide deaths were identified using the Cause-of-Death Register. Results: During the 9-year follow-up, 14 suicides were identified. The suicide death rate was 48.1 per 100,000 person years. Multivariate analysis revealed a more than fourfold increase in the risk of suicide among men with low control at work ( relative risk: 4.10; 95% confidence interval: 1.31-12.83) compared with counterpart men after adjustment for age, marital status, educational attainment, occupation, smoking status, alcohol consumption, total cholesterol level, and study area. Job demands were not associated with risk of death from suicide. Conclusions: By using a job demand-control model questionnaire, low control at work was revealed as a predictor of suicide death among Japanese male workers. The finding implies that job redesign aimed at increased worker control could be a worthwhile strategy in preventing, or at least reducing, the risk of suicide death. Copyright (c) 2007 S. Karger AG, Basel.

We prospectively investigated the association between psychosocial job characteristics according to the job demand-control model and the risk of mortality in a Japanese community-based working population. A baseline examination conducted from 1992 to 1995 determined the socioeconomic, behavioural, and biological risks in addition to the psychosocial job characteristics of 3178 male and 3331 female workers aged 65 and under and free from cancer and cardiovascular diseases. During the 9-year follow-up study, 157 men and 64 women died. In the follow-up, the results of Cox proportional hazards regression analysis revealed that men with concurrent high job demands and high job control (an active job) had the lowest risk of mortality from all causes. Compared with the low demand and high control job category, the multivariate relative risk of an active job was 0.53 (95% confidence interval: 0.31, 0.89). This finding appeared largely attributable to a reduction in cancer mortality. Job characteristics were not associated with cardiovascular diseases or external causes of mortality. For women, no significant associations were observed. The findings suggest that an active job has a beneficial effect on the health of Japanese male workers. Investigating of the effect of psychosocial job characteristics on cancer might therefore provide valuable insights into the health of workers. (c) 2006 Elsevier Ltd. All rights reserved.

Morning blood pressure (BP) level may play an important role in the pathogenesis of cardiovascular events; however, morning BP detected by home BP monitoring may remain uncontrolled in medicated hypertensive patients even when clinic BP is well controlled (masked morning hypertension: MMHT). We studied the determinants of MMHT in stably medicated hypertensive outpatients. In the Jichi Morning Hypertension Research (J-MORE) study, 969 consecutive hypertensive outpatients were recruited by 43 doctors in 32 different institutes. They had been under stable antihypertensive medication status at least for 3 months. Clinic BP was measured on 2 different days and self-measured BP monitoring was conducted twice consecutively in the morning and evening for 3 days. Four-hundred and five patients had well-controlled clinic 1313 (systolic BP [SBP]<140 mmHg and diastolic BP [DBP]<90 mmHg). Among them., 246 patients (60.7%) had MMHT (morning SBP >= 135 mmHg and/or DBP >= 85 mmHg). Compared with the patients with normal clinic BP and morning BID, the patients with MMHT had a significantly higher prevalence of regular alcohol drinkers (35.0% vs. 23.3%, p=0.012), a significantly higher number of antihypertensive drug classes (1.83 +/- 0.82 vs. 1.66 +/- 0.84, p=0.04) and a significantly higher clinic BP level (SBP: 130.4 +/- 7.6 mmHg vs. 127.8 +/- 8.4 mmHg, p=0.001; DBP: 75.5 +/- 7.6 mmHg vs. 73.6 +/- 7.6 mmHg, p=0.013). In logistic regression analysis, independent determinants for MMHT were regular alcohol drinking (odds ratio [OR]: 1.76; 95% confidence interval [CI]: 0.99-3.12; p=0.05) and higher-normal clinic BP (130/85 mmHg<clinic SBP/DBP<140/90 mmHg) (OR: 1.60; 95% CI: 1.05-2.44; p=0.03) after adjustment for confounding factors. The patients who both drank alcohol regularly and had a higher-normal clinic BP had 2.71 times higher risk for MMHT than those who did not drink alcohol regularly and had a relatively lower-normal clinic BP (<130/85 mmHg) (p<0.01). In conclusion, regular alcohol drinking is an independent determinant for MMHT detected by home BP monitoring in medicated hypertensive patients with well-controlled clinic BP.

BACKGROUND: Although several studies have reported increased mortality risk with early menopause, there were no studies examining the relationship between age at menopause and mortality in Japan. The goal of this analysis is to investigate the relationship between age at menopause and all-cause mortality among the Japanese. METHODS: Study subjects were 4,683 postmenopausal females in the Jichi Medical School Cohort Study, a population-based prospective study. Baseline data were obtained by questionnaire and health checkups between April 1992 and July 1995 in 12 rural areas in Japan. Main outcome measures were all-cause mortality derived from death certificates up to December 31, 2002. Cox's proportional hazard models were used to analyze the association of age at menopause with mortality. RESULTS: A total of 215 deaths were observed during the average of 9.2 year follow-up period. After adjusting for age, systolic blood pressure, serum total cholesterol level, serum high density lipoprotein cholesterol level, history of diabetes mellitus, body mass index, smoking habits, alcohol drinking habits, marital status, study area, and types of menopause, the hazard ratios (95% confidence intervals) of all-cause mortality were 2.10 (1.07-4.11), 0.68 (0.36-1.26), 0.94 (0.68-1.30), and 1.17 (0.63-2.20) for females with a menopause at ages younger than 40 years, 40-44, 50-54, and 55 or older, respectively, relative to those with menopause at age 45-49 years. CONCLUSIONS: Our data suggest that menopause aged younger than 40 years increases the risk of death from all causes among the Japanese.

Morning blood pressure is reported to be more closely related to hypertensive organ damages such as left ventricular mass index, microalbuminuria and silent cerebral infarcts, than blood pressure at other times of the day. Morning blood pressure may play an important role in the pathogenesis of hypertensive target organ damage. Increased sympathetic nerve activity is reported to be one of the mechanisms of morning hypertension; however, there are no available data that show whether strict home blood pressure control, especially in the morning period, can reduce target organ damage. The Japan Morning Surge-1 (JMS-1) study includes hypertensive outpatients with elevated morning systolic blood pressure (2:135 mmHg) as assessed by self-measured blood pressure monitoring at home. All enrolled patients are under stable antihypertensive medication status. Exclusion criteria are arrhythmia, chronic inflammatory disease, and taking alpha-blockers or beta-blockers. The target number of patients to be enrolled in the JMS-1 study is 600, and the aim is to evaluate differences in the markers of hypertensive target organ damage, such as brain natriuretic peptide and the urinary albumin excretion/creatinine ratio. All of the patients are randomized to an experimental group or a control group, with randomization to be carried out by telephone interviews with the patients' physicians. In the experimental group, patients begin taking additional anti hypertensive medication just before going to bed. This consists of doxazosin 1 mg/day, which then is increased to 2 mg1day and 4 mg/day, with a beta-blocker added after a 1-month interval until the morning systolic blood pressure is controlled to less than 135 mmHg. Patients in the control group continue the treatment they are receiving at the enrollment for 6 months. Blood pressure levels, adverse effects, and hypertensive target organ damage before and after the study are evaluated. In the JMS-1 study, we will evaluate whether strict morning blood pressure control by sympathetic nervous system blockade using an alpha-blocker, doxazosin, and with the addition of a beta-blocker if needed, can reduce hypertensive target organ damage.

BACKGROUND: The job characteristics scale of job strain, which combines high job demands and low decision latitude based on Karasek's model, has been applied to studies on health care and cardiovascular disease. However, little is known about the long-term stability of this scale with exposure of workers to job. We investigated the 5-year intraindividual variation in job characteristics scores among healthy community workers. METHODS: Subjects of the study were 458 community dwelling persons forming part of the Jichi Medical School Cohort Study at Yamato (currently, Minami-Uonuma city), Niigata prefecture. The Japanese version of the World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (WHO-MONICA) Psychosocial Study Questionnaire was implemented twice (from 1992 through 1995, and in 1999) to measure job demands and decision latitude levels. Intraclass correlation coefficients were computed to evaluate stability of scores of the questionnaire. RESULTS: Intraclass correlation coefficient of the decision latitude scores was 0.629 (95% confidence interval: 0.564 - 0.686) and that of the job demands scores was 0.551 (0.476 - 0.617). Subgroup analyses by age, sex, education level, years since first employment, number of co-workers, and job category and status at baseline revealed similar results. In contrast, subjects who experienced position changes within the same enterprise or changed jobs showed lower correlation coefficients of both decision latitude and job demands scores compared to those who experienced no change in job contents. CONCLUSION: The Japanese version of the WHO-MONICA Psychosocial Study Questionnaire showed statistically significant long-term stability and could be to some extent responsive to change in job strain levels.

BACKGROUND: There have been comparatively few large-scale cohort studies analyzing all-cause mortality due to cigarette smoking. The goal of this analysis is to investigate the relationship between smoking status and all-cause mortality, and to evaluate the effect of smoking in the Japanese. METHODS: The baseline data were collected between 1992 and 1995. Ultimately, 10,873 Japanese (4,280 males and 6,593 females) aged 19 years or older from 12 rural communities located across Japan participated in the study. This analysis is based on the results, including the information on those who died and moved out of the communities, obtained by December 31, 2001. The Cox's proportional hazards model was used to calculate the hazard ratio (HR) of mortality for smoking with adjustment for age, systolic blood pressure, total cholesterol, body mass index, alcohol drinking habit and education. RESULTS: The mean follow-up period was 8.2 years, during which time, 284 males and 192 females died. The multivariate-adjusted HRs for total mortality among former and current smokers compared with never smokers were 1.09 (95% confidence interval [Cl]: 0.73-1.61) and 1.65 (95% Cl: 1.16-2.35) in males, and 0.98 (95% Cl: 0.40-2.42) and 0.91 (95% Cl: 0.42-1.95) in females, respectively. Those for the consumption of 1-14, 15-24, and 25+ cigarettes per day among male smokers were 1.62, 1.57, and 1.89, respectively. In females, there was no great difference in all-cause mortality between smokers and never smokers. CONCLUSIONS: The results of our study confirm an increased risk in males of premature death from all causes among Japanese with a smoking habit.

Background: Morning blood pressure (BP) surge in ambulatory BP monitoring was a risk factor for stroke in our previous study. We studied the determinants of the morning minus evening systolic BP difference (ME difference) in self-measured BP monitoring, as a possible risk factor for stroke in medicated hypertensive patients. Methods: Nine hundred sixty-nine hypertensive outpatients receiving stable antihypertensive drug treatment were studied using self-measured BP monitoring in the morning and evening. Results: The ME difference ranged from -37.3 to 53.3 mm Hg (mean 7.9 mm Hg). The highest quartile (Q4) of the ME difference group (> 15.0 mm Hg) had older age (68.0 +/- 9.8 years v 66.2 +/- 10.3 years, P =.01) and higher prevalence of men (48.3% v 39.9%, P =.02), regular alcohol drinkers (34.7% v 26.0%, P =.01) and beta-blocker use (26.9% v 19.9%, P =.03) than the other quartile groups (Q1 to Q3), whereas there was no significant difference in the average of morning and evening (ME average) BP. In logistic regression analysis controlling for ME average and other confounding factors, independent risks for Q4 of ME difference were older age (10 years older: odds ratio [OR] 1.21, P =.01, 95% confidence interval (CI) 1.04-1.42), regular alcohol drinker (OR 1.51, P =.04, 95% CI 1.01-2.26), and beta-blocker use (OR 1.50, P =.02, 95% CI 1.06-2.12). Conclusions: Older age, beta-blocker use, and regular alcohol drinking were significant determinants of the exaggerated ME difference in medicated hypertensive patients.

Diabetes and hypertension are potent risk factors for cerebrovascular disease. We studied the effects of an angiotensin II type 1 receptor blockade (ARB) on brain damage in hypertensives in relation to diabetes. We studied cerebral metabolism ( by proton magnetic resonance spectroscopy) and hemodynamics (by phase-contrast magnetic resonance angiography) before and 3 to 4 months after candesartan therapy in 20 diabetic hypertensives (DHTs) and 20 matched nondiabetic hypertensives (HTs). Silent multiple cerebral infarcts detected by brain MRI were more common in DHTs than in HTs (50% versus 25%). Cerebral N-acetyl aspartate (NAA; an indicator of functional neuronal mass) was lower in DHTs than in HTs (8.35 versus 9.58 mmol/kg; P=0.007). Baseline quantitative volume flow in the internal carotid arteries (ICAs) and the middle cerebral arteries (MCAs) was comparable between the 2 groups, whereas cerebrovascular reserve (CVR) assessed using acetazolamide ( a cerebral arteriolar dilator) in ICAs (25% versus 35%; P=0.03) and MCAs (20% versus 31%; P=0.01) was lower in DHTs than in HTs. These baseline CVR and NAA values of DHT group were lower than those of 12 matched normotensives (CVR: 44% for ICA; 41% for MCA; NAA: 10.5 mmol/kg; all P<0.005). After candesartan therapy, CVR in ICAs and MCAs was significantly increased (P=0.001) independently of the reduction of the 24-hour blood pressure level, whereas the cerebral NAA level did not change. In conclusion, brain damage is advanced in DHTs. ARB partly improved the impaired cerebral microvascular function in DHTs.

BACKGROUND: Although sleep is one of the most important health-related factors, relationship between sleep duration and mortality has not been fully discussed. METHODS: Study subjects were 11,325 participants (4,419 males and 6,906 females) in the Jichi Medical School Cohort Study, a population-based prospective study. Baseline data were obtained by questionnaire and health checkups between April 1992 and July 1995 in 12 rural areas in Japan. Main outcome measures were all-cause and cause-specific mortality derived from death certificates up to December 31, 2001. Cox's proportional hazard models were applied to analyze the association of sleep duration with mortality. RESULTS: A total of 495 deaths (289 males and 206 females) were observed during the average of 8.2-year follow-up period. After adjusting for age, systolic blood pressure, serum total cholesterol, body mass index, smoking habits, alcohol drinking habits, education, and marital status, the hazard ratios (95% confidence intervals) of all-cause mortality for individuals sleeping shorter than 6 hours and 9 hours or longer were 2.4 (1.3-4.2) and 1.1 (0.8-1.6) in males, and 0.7 (0.2-2.3) and 1.5 (1.0-2.4) in females, respectively, relative to those with 7-7.9 hours sleep. CONCLUSION: Our data suggest that males with short sleep and females with long sleep were at an elevated risk of death.

Background: It remains uncertain which is the stronger predictor for stroke in older hypertensives, ambulatory pulse pressure (PP) or mean blood pressure (MBP). Methods: We studied the prognosis for stroke in 811 older hypertensives in whom ambulatory BP monitoring was performed. We also assessed silent cerebral infarct (SCI) by brain magnetic resonance imaging. Results: Silent cerebral infarcts were found in 50% of 515 subjects (64% of the total population) in whom we assessed SCI using brain magnetic resonance imaging. During a mean of a 42-month follow-up period, stroke events occurred in 59 subjects. After adjustment for covariates, for each 10 mm Hg increase in sleep PP, there was an independent 43% (95% confidence interval [CI]: 16%-75%, P = .001) increase in the stroke risk, and sleep MBP was not a significant factor after controlling for sleep PP. On the other hand, for each 10 mm Hg increase in awake MBP, there was an independent 48% (95% CI: 21%-81%, P = .0002) increase in the stroke risk, and awake PP was not a significant factor after controlling for awake MBP. After adjusting for SCI (a strong predictor, P < .0001) at baseline, the effects of awake MBP (38% risk increase for each 10 mm Hg, P = .007) and sleep PP (32% risk increase for each 10 mm Hg, P = .016) remained significant. Conclusions: In older hypertensives, the impacts of PP and MBP on stroke risk are different during sleep and awake periods. Sleep PP and awake MBP are both predictors of stroke events independently of SCI.

Background: Cardiovascular events occur most frequently in the morning. We aimed to study the effects of monotherapy with the long-acting angiotensin 11 receptor blocker valsartan compared with the long-acting calcium antagonist amlodipine on ambulatory and morning blood pressure (BP). Methods: We performed ambulatory BP monitoring before and after once-daily dose of valsartan (valsartan group, n = 38) and amlodipine (amlodipine group, n = 38) therapy in 76 hypertensive patients. To achieve the target BP of less than or equal to 140/90 mm Hg, valsartan was titrated from 40 mg/day to 160 mg/day (mean dose 124 mg/day) and amlodipine was titrated from 2.5 mg/day to 10 mg/day (mean dose 6.4 mg/day). Results: Both drugs significantly reduced clinic and 24-h systolic BP (SBP) and diastolic BP (DBP) (P < .002). However, the anti hypertensive effect of amlodipine was superior to that of valsartan in clinical SBP (-26 mm Hg v - 13 mm Hg, P = .001) and 24-h SBP (- 14 mm Hg v -7 mm Hg, P = .008). In addition, morning SBP was significantly reduced by amlodipine from 156 to 142 mm Hg (P < .001) but not by valsartan. Both agents reduced lowest night SBP to a similar extent (amlodipine 121 to 112 mm Hg, P < .001; valsartan 123 to 114 mm Hg, P < .002). Reduction in morning SBP surge (morning SBP minus lowest night SBP) was significantly greater in patients treated with amlodipine compared with those treated with valsartan (-6.1 mm Hg v +4.5 mm Hg, P < .02). Conclusions: Amlodipine monotherapy was more effective than valsartan monotherapy in controlling 24-h ambulatory BP and morning BP in hypertensive patients. (C) 2004 American Journal of Hypertension, Ltd.

Objective We conducted a large-scale cross-sectional study to assess the prevalence of Chlamydia pneumoniae and clarify the association between seropositivity and risk factors, such as smoking status, physical activity and body mass index in Japanese rural districts. Methods A total of 1,063 men and 1,573 women aged 18-94 years participated in 1999. Serum index values (ID) of IgA and IgG antibodies to C. pneumoniae were measured by ELISA. Index values were categorized as "negative" (IDless than or equal to1.10), "positive" (ID greater than or equal to 1.10) and "high positive" (ID greater than or equal to 3.00). Logistic regression analysis was performed to estimate the crude and adjusted odds ratios for C. pneumoniae seropositivity. Results The overall prevalence of C. pneumoniae IgA seropositivity was 52.5%, and that of IgG was 55.2%. Each seropositivity significantly increased with age. The prevalence among men was significantly higher than in women in C. pneumoniae IgG "high positive" subjects. Compared with never-smokers, the adjusted odds ratio of current smokers was 2.00 (95%CI: 1.45-2.77) for C. pneumoniae IgA seropositivity. The adjusted odds ratio of the higher tertiles of physical activity for C. pneumoniae IgG seropositivity was 1.42 (1.12-1.80) compared with the lower tertiles. In "high positive" subjects, smoking was associated with both immune complexes. Conclusion We confirmed a high prevalence of C. pneumoniae seropositivity among healthy Japanese adults. The results indicated that smoking and high physical activity were associated with C. pneumoniae infection.

To observe the association between adverse psychosocial job characteristics, measured by the Karasek job demand-control questionnaire, and a lipid profile, cross-sectional analyses were performed for a Japanese rural working population. The study population comprised 3,333 male and 3,596 female actively employed workers, aged 65 years and under. Among men, higher psychological demands were associated with high total cholesterol levels, with an adjusted difference from the top to bottom tertiles of 3.3 mg/dl (F = 3.03; p = 0.048). High demands were also positively associated with the total/HDL cholesterol ratio (F = 3.94; p = 0.020). Neither job control nor job strain (the ratio of demands to control) was associated with any of the lipid levels in either gender. A psychologically demanding job may be associated with an unfavorable lipid profile, but the impact of job strain on atherogenic lipids is negligible.

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 all of 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.

We have been conducting a cohort study titled the Jichi Medical School Cohort Study (The JMS Cohort Study) since 1992, which is aiming to clarify the risk factors of cardiovascular and cerebrovascu-lar diseases in the Japanese. The baseline data were gathered from April 1992 through July 1995 in 12 rural districts using a legal mass screening system. The total samples were 12,490 males and females, and the overall response rate for the total population was 63%. The mean ages were 55.2 years for males and 55.3 years for females, respectively. Smoking rates were 50.5% and 5.5%, and drinking rates were 75.1% and 25.0% for males and females, respectively. We also examined the Standardized mortality ratios (SMRs) of the cohort subjects for 7.6 year follow-up period. The SMRs were 0.68 [95% confidence interval (CI): 0.59-0.78] for males and 0.73 (95% CI: 0.62-0.85) for females for the cohort subjects, whereas the SMRs were 1.00 (95% CI 0.97-1.04) for males and 1.06 (95% CI: 1.02-1.10) for females for all residents. In this article, we outlined the cohort study and showed general characteristics of the baseline data, and the SMRs of the subjects. We have been following the eligible subjects, and are preparing to show some prospective data regarding cardiovascular and cerebrovascular risks in the near future.

主に以下の3つの研究を行った。<BR>1.疫学研究におけるインフォームド・コンセント(以下IC)の実態調査<BR>日本における疫学研究のICの現状について明らかにした,初めての研究である。233名(70.6%)の研究者が何らかの説明を行っており,156名(47.3%)が研究参加の同意も確認したと回答した。<BR>2.一般住民に対する疫学研究の倫理的問題に関する意識調査<BR>本調査を通じて,どのような健康情報の提供を求められているかによって,対象者が研究に関する情報を必要とする程度が異っていることが明らかになった。<BR>3.諸外国における疫学研究の倫理的問題についての情報収集および整理<BR>イギリスとアメリカの医療記録に関するアクセスについての法的・倫理的な状況について検討した。さらに,ICを巡る法的側面についての課題についての検討を行った。<BR>疫学研究におけるICのための倫理的なガイドラインを策定するに向けて,より多くの議論の機会を持つことが重要である。

OBJECTIVE - To examine the relationship between serum insulin and lipoprotein(a) [Lp(a)] concentrations in both sexes in a large population. RESEARCH DESIGN AND METHODS - The authors conducted a cross-sectional investigation of fasting serum concentrations of insulin and Lp(a), other blood tests, blood pressures, anthropological measurements, physical activity index, smoking habit, alcohol consumption, and menopause. The subjects were 1,121 men and 1,480 women, ranging between 30 and 90 years of age, who were voluntary participants in the Jichi Medical Cohort Study and who resided in one of five rural communities in Japan. RESULTS - In men, insulin, age, BMI, LDL cholesterol, triglycerides, glucose, and fibrinogen were significantly correlated with Lp(a). In women, insulin, age, IDL cholesterol, fibrinogen, and activated coagulation factor VII were significantly correlated with Lp(a). However, all correlations were weak in either sex. Insulin was inversely correlated with Lp(a) in both sexes. However, the coefficients were weak (r = -0.16 in men and r = -0.06 in women). In the partial correlation analyses, Lp(a) was not significantly associated with insulin in either sex. The result was not influenced by selecting the subjects on the basis of detectable values of insulin and Lp(a) and stratifying them by serum glucose level. CONCLUSIONS - There was no significant relationship found between serum insulin and Lp(a) concentrations in either sex of the cohort, which indicates that Lp(a) does not play a role in the increased risk of cardiovascular disease in hyperinsulinemic subjects.

We investigated the relationships between hyperinsulinemia (a major indicator of the insulin resistance syndrome), blood pressure, dyslipidemia, and coagulation factors in 2606 community-dwelling Japanese individuals as part of the Jichi Medical School Cohort Study. An age-related decrease of the fasting insulin level was found in men but not in women. Body mass index, systolic and diastolic blood pressure, triglyceride and fasting glucose levels, and factor VII activity all increased in both sexes as the insulin level became higher, while the HDL cholesterol level decreased. In addition, total cholesterol and LDL cholesterol levels increased as the insulin level became higher and lipoprotein(a) levels decreased in the men. Fibrinogen levels were not related to the insulin level in either sex. Multiple logistic regression analysis revealed that fasting insulin levels were positively correlated with body mass index and fasting glucose and factor VII activity levels, whereas they were negatively correlated with HDL cholesterol in both sexes. In addition, fasting insulin levels were positively correlated with LDL cholesterol levels in men and with triglyceride levels in women. Our results indicate that hyperinsulinemia is associated with high factor VII activity in a general Japanese population as well as with high blood pressure and dyslipidemia. The accumulation of these cardiovascular risk factors in hyperinsulinemic subjects appears to contribute to cardiovascular events in the Japanese as well as in westerners.