Aya Higashiyama

Serum 1,5-anhydro-d-glucitol levels predict first-ever cardiovascular disease: An 11-year population-based Cohort study in Japan, the Suita study

OBJECTIVEnSerum 1,5-anhydro-D-glucitol (1,5-AG) is well-known to be a useful clinical marker of both short-term glycemic status and postprandial hyperglycemia. In addition, previous epidemiological studies have shown that an increased postload glucose level in an oral glucose tolerance test is a risk factor for cardiovascular diseases (CVD). However, no previous prospective study has reported the association between serum 1,5-AG levels and the risk of CVD. In this study, we examined whether serum 1,5-AG levels can predict the incidence of first-ever CVD.nnnMETHODSnOur study was a population-based cohort study in an urban area of Japan. Study subjects comprised 2095 initially healthy Japanese (991 men and 1104 women, mean age: 58.5 years) with no history of coronary heart disease (CHD) or stroke. They were followed up for an average of 11.1 years, and 147 CVD events (64 CHD and 83 strokes) were observed.nnnRESULTSnThe adjusted hazard ratios (HRs) of all CVD in men increased linearly (p=0.004). The HR in the category with serum 1,5-AG levels of 14.0 μg/mL or less was 2.22 (95% confidence interval; 1.24-3.98) compared to the reference category (24.5 μg/mL or greater). Similar results were also shown with a sensitivity analysis in non-diabetic men. Conversely, no significant relationship between serum 1,5-AG levels and CVD risks was observed in women.nnnCONCLUSIONSnOur results suggest that measurement of serum 1,5-AG levels is useful to detect individuals, especially men, at higher risk for CVD, regardless of the presence or absence of diabetes.

Alcohol consumption and cardiovascular disease incidence in men with and without hypertension: the Suita study

The relationship between alcohol consumption and the risk for cardiovascular disease (CVD) is U-shaped, whereas alcohol drinking is linearly associated with blood pressure, and the CVD risk also increases linearly according to blood pressure level. Accordingly, we investigated the net effect of alcohol consumption and hypertension on CVD and its subtypes in this study. A 13-year prospective study of 2336 Japanese men who were free from CVD was performed; ex-drinkers were excluded. The participants were divided into eight groups classified by the combination of the presence of hypertension (systolic/diastolic blood pressure ⩾140/90u2009mmu2009Hg) and alcohol consumption (never-, current- (light, moderate and heavy) drinkers). Multivariate-adjusted hazard ratios (HRs) for the incidence of CVD, coronary artery disease (CAD) and stroke due to the combination of hypertension and alcohol consumption were calculated and compared with non-hypertensive never-drinkers. The HRs for CVD and its subtypes were higher in hypertensives than those in non-hypertensives; in hypertensives without medication for hypertension, the relationship between alcohol consumption and the risks for CVD and CAD was U-shaped, with the highest and most significant increase in never-drinkers. The risk for total stroke was the highest in heavy-drinkers, which was significant. In non-hypertensives, there was no evident increase or decrease in the HRs for CVD and its subtypes in drinkers. Accordingly, controlling blood pressure is important to prevent CVD. In hypertensives, heavy drinking should be avoided to prevent CVD, although light-to-moderate drinking could be protective for CAD. Furthermore, in non-hypertensives, drinkers may need to continuously monitor their blood pressure.

A revised definition of the metabolic syndrome predicts coronary artery disease and ischemic stroke after adjusting for low density lipoprotein cholesterol in a 13-year cohort study of Japanese: The Suita Study

OBJECTIVEnRecently, several major organizations have proposed a unified definition for the metabolic syndrome (MetS), which should be evaluated in multiethnic groups. The effect of Mets on the incidence of cardiovascular disease needs to be assessed after adjusting for serum low density lipoprotein cholesterol (LDLC), a major risk factor for atherosclerotic diseases. This is especially needed to be evaluated in Asian populations with low incidence of coronary artery disease (CAD).nnnMETHODSnWe conducted a 13-year prospective study of 4939 Japanese living in an urban area. The MetS was defined using a unified classification that included cut-off points for waist circumference in Asians. The multivariable adjusted hazard ratios (HRs) of MetS for CAD and stroke were calculated using a Cox proportional model adjusted for other potential confounding factors with LDLC.nnnRESULTS AND CONCLUSIONnDuring the follow-up period, there were 155 cases of CAD and 204 of stroke including 118 cerebral infarctions. In participants under 65 years old, the multivariable HRs of MetS for CAD were 1.21 (95% C.I., 0.64-2.28) in men and 4.44 (95% C.I., 1.73-11.4) in women; the HRs for ischemic stroke were 3.24 (95% C.I., 1.55-6.77) in men and 3.99 (95% C.I., 1.34-11.8) in women. In participants aged 65 years old and over, MetS only showed a significant association with CAD in men (HR 1.89, 95% C.I., 1.11-3.21). Serum LDLC was associated with increased risk of CAD in men irrespective of age group; however, it was not associated with CAD in women. There was no association between serum LDLC and ischemic stroke in any group stratified by sex and the age of 65. These results indicate that the new uniform MetS definition is useful for detecting high risk individuals, especially for middle-aged population. However, continuous screening for hypercholesterolemia is necessary to prevent CAD, especially in men, even in Asian countries such as Japan.

Long-Term Outcome of Healthy Participants with Atrial Premature Complex: A 15-Year Follow-Up of the NIPPON DATA 90 Cohort

Background Atrial premature complexes (APC) are among the most frequently encountered electrocardiographic abnormalities. However, their prognostic value among healthy individuals is unclear. This study aimed to clarify the role of APC in predicting cardiovascular events in a large Japanese community cohort using long-term follow-up data. Methods National Integrated Project for Prospective Observation of Non-communicable Disease And its Trends in the Aged, 1990-2005, (NIPPON DATA 90) was a large cohort study of cardiovascular disease (CVD) in Japan. A total of 7692 otherwise healthy participants with no history of myocardial infarction, stroke, atrial fibrillation, or atrial flutter were enrolled (men, 41.5%; mean age, 52.5 ± 13.7 years). Results A total of 64 (0.8%) participants had at least one beat of APC on screening 12-lead electrocardiogram. During the follow-up of 14.0 ± 2.9 years (total, 107,474 patient-years), 338 deaths occurred due to CVD. The association between APC and CVD outcome was assessed using Cox proportional hazard models. Cox regression analysis revealed that the presence of APC was an independent predictor for CVD deaths (HR: 2.03, 95% CI: 1.12–3.66, P = 0.019). The association of APC on CVD death was more evident in participants with hypertension (P-value for interaction, 0.03). Conclusions APC recorded during the screening electrocardiogram are significantly associated with an increased risk of CVD deaths in a Japanese community-dwelling population and are a strong prognostic factor for hypertensive participants.

Association With Serum Gamma-Glutamyltransferase Levels and Alcohol Consumption on Stroke and Coronary Artery Disease The Suita Study

Background and Purpose— Light-to-moderate alcohol consumption is associated with reduced risk for cardiovascular disease, whereas high serum &ggr;-glutamyltransferase (GGT) level is associated with cardiovascular disease. However, whether light-to-moderate alcohol drinking is still related to reduced risk of cardiovascular disease irrespective of GGT level is uncertain. Methods— We performed a 12.5-year cohort study of 2336 men (excluding exdrinkers) who were free from cardiovascular disease. They were classified into 4 groups according to alcohol consumption: never, and current light, moderate, or heavy drinker. The multivariate-adjusted hazard ratios of alcohol consumption for incidence of coronary artery disease, total stroke, and ischemic stroke compared with those of never drinkers were assessed with stratification by GGT median (32 IU/L). Results— In participants with GGT >32 IU/L, the hazard ratios of all current drinkers for total and ischemic stroke were higher than those of never drinkers. However, in all current drinkers with GGT ⩽32 IU/L, the multivariate-adjusted hazard ratios for total and ischemic stroke were lower than in never drinkers. Conclusions— In men with above GGT median, alcohol drinking even with light-to-moderate consumption could be a risk factor for ischemic stroke.

Blood Pressure, Low-Density Lipoprotein Cholesterol, and Incidences of Coronary Artery Disease and Ischemic Stroke in Japanese: The Suita Study

BACKGROUNDnBlood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) are risk factors for coronary artery disease (CAD) and ischemic stroke. However, the hazards of their coexistence are not fully understood in Asian populations. We investigated whether the relationship between BP and cardiovascular disease (CVD) outcomes are modified by LDL-C level in a Japanese population.nnnMETHODSnIndividuals aged 30-79 years (n = 5,151) were classified into 6 groups according to LDL-C levels (<140 and ≥140mg/dL or lipid medication) and BP levels (optimal BP, prehypertension, and hypertension; reference: low LDL-C and optimal BP). Hazard ratios (HRs) were calculated after adjusting for age, high-density lipoprotein cholesterol, diabetes, smoking status, and alcohol consumption. The effect modification of LDL-C on BP-CVD association was assessed using likelihood ratio tests.nnnRESULTSnThere were 264 CAD and 215 ischemic stroke events during 13 years of follow-up. With low LDL-C, the HRs of prehypertension and hypertension for CAD were 2.01 and 4.71, respectively. Similar trends of HRs were observed with high LDL-C (optimal BP = 2.09, prehypertension = 3.45, hypertension = 5.94). However, the HRs for ischemic stroke did not differ between normal and high LDL-C levels at the same BP level. The apparent effect modification of LDL-C was not observed in the BP-CVD association in either CAD (P = 0.48) or ischemic stroke (P = 0.39).nnnCONCLUSIONSnThe HRs for CAD in prehypertensive and hypertensive groups were higher than those in the optimal BP group at the same LDL-C levels in a Japanese population; however, there was no statistical effect modification of LDL-C on the BP-CAD association.

Effect of Age on the Association Between Waist-to-Height Ratio and Incidence of Cardiovascular Disease : The Suita Study

Background Waist-to-height ratio (WHtR) has been shown to be a useful screening tool for metabolic syndrome and cardiovascular disease (CVD). We investigated the association of WHtR with CVD incidence by age group. Methods We conducted a 13.0-year cohort study of Japanese adults (2600 men and 2888 women) with no history of CVD. WHtR was calculated as waist circumference (cm) (WC) divided by height (cm). We stratified participants by sex and age group (30–49, 50–69, ≥70 years). Using the Cox proportional hazards model, we calculated hazard ratios (HRs) and 95% CIs for CVD in relation to WHtR quartile for participants aged 50 to 69 years and 70 years or older. Results Men aged 50 to 69 years in the highest quartile had significantly increased risks of CVD and coronary heart disease as compared with the lowest quartile; the HRs (95% CI) were 1.82 (1.13–2.92) and 2.42 (1.15–5.12), respectively. Women aged 50 to 69 years in the highest quartile had a significantly increased risk of stroke (HR, 2.43; 95% CI, 1.01–5.85). No significant results were observed in men or women aged 70 years or older. The likelihood ratio test showed that the predictive value of WHtR was greater than that of WC among men aged 50 to 69 years. Conclusions The association between WHtR and CVD risk differed among age groups. WHtR was useful in identifying middle-aged Japanese at higher risk of CVD and was a better predictor than WC of CVD, especially in men.

LOX-1 ligands containing apolipoprotein B and carotid intima-media thickness in middle-aged community-dwelling US Caucasian and Japanese men

OBJECTIVEnThe serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than LDL cholesterol (LDLC), total LDL particles and usual measurement of oxidized LDL. The association between LAB and intima-media thickness (IMT) of carotid artery was investigated by ultrasound in US and Japan men.nnnMETHODSnParticipants were 297 US Caucasian and 310 Japanese men, aged 40-49 years without past history of cardiovascular disease. Serum LAB levels were measured by ELISAs with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody.nnnRESULTSnSerum LAB levels [median (interquartile range), μg/L] were 1321 (936, 1730) in US Caucasians and 940 (688, 1259) in Japanese. For Caucasian men, average IMT was higher in higher LAB quartile, which was 0.653, 0.667, 0.688, and 0.702 mm, respectively (p for trend = 0.02). Linear regression analysis showed serum LAB was significantly associated with IMT after adjustment for LDLC or total LDL particles in addition to other traditional or novel risk factors for atherosclerosis such as C-reactive protein. However, there was no significant relationship between LAB and IMT in Japanese men.nnnCONCLUSIONnSerum LAB, a new candidate biomarker for residual risk, was associated with an increased carotid IMT in US Caucasian men independently of various risk factors; however, ethnic difference should be clarified in the future.

Serum polyunsaturated fatty acid composition and serum high-sensitivity C-reactive protein levels in healthy Japanese residents: The KOBE study

Background/ObjectivesSerum polyunsaturated fatty acid (PUFA) composition reflects dietary intake and is related to risks for cardiovascular diseases. We hypothesized that serum n-3 PUFA composition, especially including long-chain n-3 PUFA such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is associated with inflammatory status, which is related to increased risk for cardiovascular diseases.Subjects/MethodsWe investigated the relationship between serum PUFA composition and high-sensitivity C-reactive protein (hs-CRP) levels in a cross-sectional study among 1,102 healthy men and women aged 40–74 years who reside in Kobe City. Multiple linear regression models that predict hs-CRP level were prepared to confirm the contribution of serum total n-3 PUFA, long-chain n-3 PUFA, EPA and DHA compositions after adjusting for other PUFAs and atherosclerotic risk factors.ResultsThe serum n-3 PUFA, particularly long-chain n-3 PUFA, compositions were inversely associated with the hs-CRP levels. The standardized regression coefficient was −0.089 (p < 0.01) for total n-3 PUFA, −0.091 (p < 0.01) for long-chain n-3 PUFA, −0.071 (p = 0.03) for EPA, and −0.068 (p = 0.04) for DHA. The n-6 PUFA compositions were also inversely associated with the hs-CRP levels (−0.169 [p < 0.01] for total n-6 PUFA and −0.159 [p < 0.01] for linoleic acid).ConclusionsThe serum n-3 PUFA compositions were inversely related with the hs-CRP levels, similar associations were also observed in n-6 PUFA compositions. Our results suggest that dietary PUFA intake was inversely associated with attenuated inflammation in healthy Japanese population.

Cumulative impact of axial, structural, and repolarization ECG findings on long-term cardiovascular mortality among healthy individuals in Japan: National Integrated Project for Prospective Observation of Non-Communicable Disease and its Trends in the Aged, 1980 and 1990:

Aims Various cohort studies have shown a close association between long-term cardiovascular disease (CVD) outcomes and individual electrocardiographic (ECG) abnormalities such as axial, structural, and repolarization changes. The combined effect of these ECG abnormalities, each assumed to be benign, has not been thoroughly investigated. Methods and Results Community-dwelling Japanese residents from the National Integrated Project for Perspective Observation of Non-Communicable Disease and its Trends in the Aged, 1980–2004 and 1990–2005 (NIPPON DATA80 and 90), were included in this study. Baseline ECG findings were classified using the Minnesota Code and categorized into axial (left axis deviation, clockwise rotation), structural (left ventricular hypertrophy, atrial enlargement), and repolarization (minor and major ST–T changes) abnormalities. The hazard ratios of the cumulative impacts of ECG findings on long-term CVD death were estimated by stratified Cox proportional hazard models, including adjustments for cohort strata. In all, 16,816 participants were evaluated. The average age was 51.2u2009±u200913.5 years; 42.7% participants were male. The duration of follow up was 300,924 person-years (mean 17.9u2009±u20095.8 years); there were 1218 CVD deaths during that time. Overall, 4203 participants (25.0%) had one or more categorical ECG abnormalities: 3648 (21.7%) had a single abnormality, and 555 (3.3%) had two or more. The risk of CVD mortality increased as the number of abnormalities accumulated (single abnormality HR 1.29, 95% CI 1.13–1.48; ≥2 abnormalities HR 2.10, 95% CI 1.73–2.53). Conclusions Individual ECG abnormalities had an additive effect in predicting CVD outcome risk in our large-scale cohort study.