Akira Okayama

Serum C-reactive protein levels can be used to predict future ischemic stroke and mortality in Japanese men from the general population

BACKGROUNDnHigh C-reactive protein (CRP) levels have been reported to be associated with an increased risk of atherosclerotic cardiovascular events. The relationship of CRP levels to the risk of cerebrovascular events in the Japanese population, which has a lower prevalence of coronary artery disease and a lower CRP level than Western populations, has not been fully clarified. The present study examined the predictive value of serum high sensitivity CRP (hs-CRP) levels for future cerebrovascular events and mortality in the general Japanese population.nnnMETHODSnThe subjects for this community-based, prospective cohort study were recruited from the general population (n=7901, male only, mean age=64.0 years). Serum hs-CRP levels and cardiovascular risk factors were determined at baseline. The mean follow-up period was 2.7 years. After excluding subjects with a cardiovascular history, the relationships between hs-CRP levels and cerebrovascular events and mortality were assessed.nnnRESULTSnDuring follow-up, 130 participants had a first stroke (95 ischemic strokes), and 161 participants died. The hs-CRP tertile level was a significant predictor for a first ischemic stroke (3rd tertile, HR=1.77: 95% Cl, 1.04-3.03, compared with the 1st tertile), after adjustment for age and classical cardiovascular risk factors. Similar trends were observed for the prediction of all-cause mortality (3rd tertile, HR=2.26: 95% Cl, 1.49-3.42, compared with the 1st tertile).nnnCONCLUSIONnCRP levels can be used to predict future ischemic stroke and mortality in Japanese men from the general population, independently from traditional cardiovascular risk factors.

Predictive value of plasma B-type natriuretic peptide for ischemic stroke: a community-based longitudinal study.

OBJECTIVEnStructural heart diseases including atrial fibrillation are precursors for ischemic stroke. Plasma B-type natriuretic peptide (BNP) has been reported to be increased in patients with several types of structural heart diseases. However, the predictive value of plasma BNP for ischemic stroke remains unknown. We have studied the predictive ability of plasma BNP for future development of stroke in community dwelling adults.nnnMETHODSnSubjects of this community-based study were recruited from the general population (n=13,466). Plasma BNP levels and cardiovascular risk factors were determined at baseline. The incidence of ischemic stroke in the cohort was identified from regional stroke registry data. A multivariate Cox regression analysis was performed to analyze the relationship between plasma BNP levels and the risk of stroke.nnnRESULTSnDuring a mean follow-up period of 2.8 years, 102 participants (65 males, 37 females) experienced a first ischemic stroke. In men, after adjustment for classical cardiovascular risk factors and atrial fibrillation, the hazard ratio (HR) for ischemic stroke was significantly elevated in the highest plasma BNP quartile (HR=2.38; 95% CI=1.07-5.29). In women, the relationship between plasma BNP levels and risk of ischemic stroke was of marginal significance after adjusting for the presence or absence of atrial fibrillation (HR=3.03; 95% CI=0.84-10.92, P=0.09).nnnCONCLUSIONnElevated plasma BNP levels predict the risk of ischemic stroke within men from the general population.

Cardiovascular risk factors in the Japanese northeastern rural population

BACKGROUNDnPeople living in the northeastern part of Japan have high prevalences of hypertension and stroke. The current status of cardiovascular risk factors in them should be elucidated.nnnMETHODSnThe survey was carried out from 2002 to 2004 in the northeastern part of the main island of Japan. A total of 26,472 Japanese men and women were enrolled (acceptance rate: 84.5%). Sex- and age-specific prevalences of cardiovascular risk factors were determined. Mean values of predictive markers (high-sensitivity C reactive protein (hsCRP), brain natriuretic peptide (BNP) and microalbuminuria) were also determined in each group. Risk factor-related variables in non-hypertensive subjects and hypertensive subjects were compared.nnnRESULTSnProportions of subjects with hypertension, diabetes and dyslipidemia were 46.0%, 7.6%, and 30.3%, respectively, in males and 38.6%, 4.0%, and 38.5%, respectively, in females. Mean values of hsCRP and BNP were 1.41 mg/L and 26.5 pg/mL, respectively, in males and 1.01 mg/L and 23.7 pg/mL, respectively, in females. Proportions of male and female subjects with microalbuminuria were 22.0% and 23.4%, respectively. These markers become higher with advance of age. Prevalence of atrial fibrillation was 1.56%, and it increased with advance of age in both men and women. High prevalences of cardiovascular risk factors in this area were found. Hypertensive subjects who did not take anti-hypertension medication accounted for about 20% of total subjects and their blood pressure remained poorly controlled.nnnCONCLUSIONnAttention should be given to cardiovascular risk factors in the Japanese northeastern rural population.

Comparison of low-density lipoprotein cholesterol concentrations measured by a direct homogeneous assay and by the Friedewald formula in a large community population

BACKGROUNDnWe compare the direct homogeneous low-density lipoprotein cholesterol (LDL-C) assay with the Friedewald formula (FF) for determination of LDL-C in a large community-dwelling population.nnnMETHODSnA total of 21,194 apparently healthy subjects aged 40 to 79 years with triglyceride (TG) concentrations <4.52 mmol/l were enrolled. LDL-C were directly measured by the enzymatic homogeneous assay (LDL-C (D)) and also estimated by the FF (LDL-C (F)). Paired t-test, Pearsons correlation coefficient and linear regression analysis were performed and the concordances of the National Cholesterol Education Program (NCEP) risk category were estimated.nnnRESULTSnBoth in fasting (n=3270) and nonfasting samples (n=17,924), LDL-C (D) highly correlated with LDL-C (F): r=0.971 and 0.955, respectively. Concordant results for NCEP categories were 84.8% for fasting samples and 80.1% for nonfasting samples. However, the bias between the 2 measurements increased in samples with TG concentrations >1.69 mmol/l, especially in nonfasting samples.nnnCONCLUSIONSnThe results showing less variability of the direct LDL-C assay than that of the FF in nonfasting samples suggest that epidemiological studies can use LDL-C measured by the direct assay both in fasting and nonfasting samples.

Relation of adult height with stroke mortality in Japan: NIPPON DATA80.

Background and Purpose— The age-adjusted stroke mortality rate in Japan was the highest in the world from 1950 to the 1970s, but it started to dramatically decrease after 1965. In addition to improved management of high blood pressure, the increase in average height might also contribute to this reduction. The present study investigates whether height is an independent risk for stroke mortality in Japan. Methods— Among participants of the National Survey on Cardiovascular Diseases in 1980 who were randomly selected from the Japanese population, we followed up 3969 and 4955 Japanese men and women without prior cardiovascular disease for a maximum of 19 years and observed 158 and 132 stroke deaths. Results— Height was inversely correlated with age and with crude stroke mortality. The relationship was attenuated in men when we adjusted for age or other possible confounders (multivariate adjusted relative hazards of a 5-cm increase of height for stroke mortality: 0.92, 95% CI: 0.79 to 1.08). For women, the inverse relationship (relative hazard: 0.77: 95% CI: 0.64 to 0.91) remained after multivariate adjustment. These relationships persisted when we stratified participants by age. Conclusions— Height is inversely related to stroke mortality and the relationship is statistically significant among Japanese women.

A cross-sectional study on the brainstem auditory evoked potential among workers exposed to carbon disulfide.

SummaryIn order to clarify the chronic effect of carbon disulfide (CS2) on the central nervous system (CNS), the brainstem auditory evoked potential (BAEP) was measured in spinning workers exposed to CS2 in a viscose rayon manufacturing factory and unexposed workers in Japan. Workers exposed to CS2 were divided into three groups according to length of exposure: current spinning workers with an exposure duration of more than 240 months (L group, n = 34), current spinning workers with an exposure duration of 24–84 months (S group, n = 25), and former spinning workers with an exposure duration of more than 120 months (R group, n = 16). Unexposed controls were selected from workers in a nylon filament factory using the same criteria (N group; n = 40). BAEP records were analyzed based on the latencies of three main components (I, III, V) and interpeak latencies (I–III IPL, III–V IPL, I–V IPL). Latencies of component V, III–V IPL, and I–V IPL in the L group were significantly greater (P < 0.01, P < 0.05, P < 0.05, respectively). The significantly, higher III–V IPL in the L group suggested that in humans, chronic exposure to CS2 involves the auditory ascending tract in the brainstem. Recovery from this neurotoxic effect is apparently possible, as the BAEP parameters in the R group were not significantly higher than those of the N group despite the long previous CS2 exposure of the R group.

Dietary intake of n-3 polyunsaturated fatty acids is inversely associated with CRP levels, especially among male smokers

OBJECTIVEnTo examine whether dietary intake of n-3 polyunsaturated fatty acid (n-3PUFA) is associated with serum C-reactive protein (CRP) levels with regard to smoking status in the Japanese general population in a cross-sectional study.nnnMETHODS AND RESULTSnA total of 14,191 participants aged 40-69 years were enrolled and divided into quartile groups according to their intake of n-3PUFA. Multivariate-adjusted logarithm-transformed CRP levels were compared between the quartile groups with regard to smoking status after adjusting for traditional risk factors and intake of saturated fatty acids. Adjusted CRP levels were inversely associated with dietary intake of n-3PUFA for both the male subjects and female subjects (p<0.05 for trend). A linear trend was not seen between intake of n-3PUFA and adjusted CRP levels in male nonsmokers. Adjusted CRP level in the lowest quartile group of n-3PUFA was significantly higher than the levels in other groups in male smokers.nnnCONCLUSIONnSufficient dietary intake of n-3PUFA may attenuate inflammatory reaction and this effect is more evident among high-risk populations such as male smokers although the small numbers of female ex-smokers and nonsmokers limited statistical power to draw strong conclusions about these groups.

Prognostic Values of Clockwise and Counterclockwise Rotation for Cardiovascular Mortality in Japanese Subjects A 24-Year Follow-Up of the National Integrated Project for Prospective Observation of Noncommunicable Disease and Its Trends in the Aged, 1980–2004 (NIPPON DATA80)

Cardiovascular Epidemiology, Kyoto Women’s University, Kyoto; Dept of Health Science, Shiga University of Medical Science, Otsu; Dept of Preventive Medicine & Public Health, Keio University, Tokyo; Dept of Environmental Medicine, Hyogo Medical School, Nishinomiya; Dept of Preventive Cardiology, National Cardiovascular Center, Suita; Radiation Effects Association, Tokyo; Radiation Effects Research Foundation, Hiroshima; First Institute for Health Promotion and Health Care, Tokyo, JapanBackground— Although clockwise rotation and counterclockwise rotation are distinct findings of the ECG, their prognostic significance is rarely studied. Methods and Results— We studied prognostic values of clockwise and counterclockwise rotation on total, cardiovascular disease (CVD), and subtype mortality using the National Integrated Project for Prospective Observation of Noncommunicable Disease and Its Trends in the Aged, 1980–2004 (NIPPON DATA80) database with a 24-year follow-up. At baseline in 1980, data were collected on study participants aged ≥30 years from randomly selected areas in Japan. We followed 9067 participants (44% men; mean age, 51 years). During the 24-year follow-up, mortality was as follows: 2581 total, 887 CVD, 179 coronary heart disease, 173 heart failure, and 411 stroke. The multivariate-adjusted hazard ratio (HR) with the use of the Cox model including biochemical and other ECG variables revealed that clockwise rotation was significantly positively associated with heart failure in men and women combined (HR=1.79; 95% confidence interval [CI], 1.13–2.83; P=0.013), CVD in men and in men and women combined (HR=1.49; 95% CI, 1.12–1.98; P=0.007 in men; HR=1.28; 95% CI, 1.02–1.59; P=0.030 in combined), and total mortality in men and in men and women combined (HR=1.19; 95% CI, 1.00–1.49; P=0.0496 in men; HR=1.15; 95% CI, 1.00–1.32; P=0.045 in combined). Counterclockwise rotation was significantly inversely associated stroke in men and women combined (HR=0.77; 95% CI, 0.62–0.96; P=0.017), CVD in men and in men and women combined (HR=0.74; 95% CI, 0.59–0.94; P=0.011 in men; HR=0.81; 95% CI, 0.70–0.94; P=0.006 in combined), and total mortality in women (HR=0.87; 95% CI, 0.77–0.98; P=0.023). Conclusions— We found a significant positive association of clockwise rotation and a significant inverse association of counterclockwise rotation with CVD mortality in men and in men and women combined, independent of confounding factors including other ECG changes.

Prehypertension Subtype With Elevated C-Reactive Protein: Risk of Ischemic Stroke in a General Japanese Population

BACKGROUNDnPrehypertension (PreHT) and low-grade inflammation are both known to be related to the incidence of cardiovascular events. This cohort study investigated whether the high-risk group for future ischemic stroke among PreHT subjects can be predicted by stratification of high-sensitivity C-reactive protein (hsCRP).nnnMETHODSnA total of 22,676 subjects aged 40-80 years from the general population who had no cardiovascular history underwent baseline measurement of serum hsCRP, and were followed for the incidence of ischemic stroke.nnnRESULTSnDuring the mean follow-up period of 2.7 years, 143 subjects had a first ischemic stroke. In a Cox multivariable model after adjustment for cardiovascular risk factors, there was no significant difference in hazard ratio (HR) for incidence of ischemic stroke between the normotension (NT) and PreHT subjects (HR = 1.72, 95% confidence interval (CI): 0.93-3.18, vs. NT subjects). In contrast, the HR for incidence of ischemic stroke in PreHT subjects with higher hsCRP levels (≥0.5 mg/l in men, ≥0.4 mg/l in women, more than median levels according to sex) was increased compared to NT subjects with lower hsCRP levels (HR = 2.63, 95% CI: 1.11-6.24). Moreover, the HR for incidence of ischemic stroke in PreHT subjects with lower CRP levels (HR = 0.91, 95% CI: 0.31-2.73) did not differ from that in NT subjects with lower hsCRP levels.nnnCONCLUSIONSnThis study showed that, in a Japanese general population, hsCRP was a marker for relatively short-term risk of ischemic stroke in PreHT subjects.

Serum Selenium Levels in Hemodialysis Patients Are Significantly Lower than Those in Healthy Controls

Serum selenium levels have been thought to be decreased in hemodialysis patients; however, results of previous studies have been inconsistent. Population-based hemodialysis patients (n = 1,041) and randomly recruited healthy controls (n = 384) were enrolled. Serum selenium levels were determined by inductively coupled plasma mass spectrometry and compared in hemodialysis patients and controls using analysis of covariance after adjustment for confounding factors with p < 0.1 as the result of the multiple regression analysis. Age, serum albumin levels, hsCRP levels, LDLC levels, HDLC levels, regular drinking habit and hemodialysis treatment were significantly associated with serum selenium levels in multiple regression analysis. Multivariate-adjusted means (95% CIs) of serum selenium levels were 103 µg/l (101–105) in hemodialysis patients and 117 µg/l (114–121) in controls. Selenium levels in hemodialysis patients were decreased. Whether decreased serum selenium levels contribute to increased risks for morbidity and mortality in hemodialysis patients should be examined.