Comparison of Publications on Heated Tobacco Products With Conventional Cigarettes and Implied Desirability of the Products According to Tobacco Industry Affiliation: A Systematic Review.

INTRODUCTION: Heated tobacco products (HTPs) have been advertised as "reduced-harm" tobacco products compared to conventional cigarettes (CC); however, no direct evidence supporting HTPs being desirable for human health exists. A previous systematic review reported that evidence on HTPs published in 2017 or earlier was primarily drawn from industry-related papers. We aimed to investigate whether tobacco industry-affiliated studies are more likely to conclude that HTPs are more desirable than CC. METHODS: PubMed and Ichushi-Web were searched up to March 15, 2022, for studies on HTPs published in 2017 or after. We selected studies that assessed any measures of HTPs and CC, including secondary analyses using gray literature in English or Japanese. We excluded review articles except for a meta-analysis that met the aforementioned criteria. Data on the authors' affiliations, grant, conflict of interest, category of research subjects, and interpretation were extracted. Research members in two groups independently assessed the papers; discrepancies were solved by discussion between the groups. RESULTS: Overall, 134 studies met the criteria. Eighty-seven (64.9%) of them were affiliated with the tobacco industry. Of the 134 studies, 56.3% (49/87) of the industry-affiliated studies versus 19.1% (9/47) of nonindustry-affiliated studies concluded that HTPs were more desirable than CC (p < .01). No study investigated clinically relevant outcomes, such as disease occurrence. CONCLUSIONS: Publications on HTPs in the biomedical literature from January 2017 to March 2022 were dominated by tobacco industry-affiliated studies. More than half of them concluded that HTPs were more desirable than CC compared to independent studies. IMPLICATIONS: Tobacco industry advertises HTPs as "reduced-harm" tobacco products compared to CC. HTP users tend to consider HTPs as alternative tobacco products less harmful than CC (ie, products for "harm reduction"). Our results demonstrated that papers written by tobacco industry-affiliated authors concluded that HTPs were more desirable than CC compared to papers by independent authors. However, all their judgments were based on surrogate outcomes. Surrogate outcomes are not necessarily linked to clinically relevant outcomes such as disease occurrence. Further studies on HTPs using clinically relevant outcomes are warranted by independent authors from tobacco industry.

[Determinants of salt taste threshold among urban residents: the KOBE study].

Objectives　Though having a high salt taste threshold has been associated with hypertension, its exact determinants remains unclear. This study aimed to identify the determinants of salt taste threshold in a community-based population and to determine the relationship between salt taste thresholds and the simultaneous presence of multiple determinants.Methods　Of the 1,117 participants of the baseline survey of the Kobe study, a cohort study of healthy urban residents, aged 40-74 years, with no history of cancer or cardiovascular diseases, nor undergoing treatment for hypertension, diabetes, or dyslipidemia, was conducted. Among them, 1,116 underwent the salt taste threshold test, and urine samples were collected to determine their estimated salt intake. The salt taste threshold test was carried out using SALSAVE®, with a salt taste threshold of 0.6% defined as normal, and that of 0.8% or more defined as high. A binomial logistic regression model was used, with high salt taste threshold as the objective variable, and life and family status, education, smoking and alcohol drinking status, intake status of salt dried fish, stress indicators, and daily salt intake (estimated from the urine sample) as the explanatory variables. A binomial logistic regression analysis was conducted, through multivariate analysis using the forced entry method, with factors influencing salt taste threshold as explanatory variables, and salt taste threshold (normal/high) as the objective variable. This analysis was performed excluding the urinary sodium-to-potassium ratio to account for multicollinearity with the estimated daily salt intake.Results　The mean age was 60.9±9.0 years for men, and 58.0±8.7 years for women. The salt taste threshold was normal in 80.9% (n=903) of the participants (73.6% [n=251] men and 84.1% [n=652] women), and high in 19.1% (n=213) of the participants (26.3% [n=90] men and 15.9% [n=123] women). Multivariate analysis revealed that smoking habits were significantly associated with a higher salt taste threshold, with an odds ratio (95% confidence interval) of 2.51 (1.33-4.74) for all participants. The odds ratio for a high salt taste threshold was 1.45 (1.03-2.03) for the top 25% estimated daily salt intake group, showing a significant association with a high salt taste threshold. In the analysis by sex, smoking habits were associated with higher salt taste thresholds, while an association with estimated daily salt intake was observed only in men.Conclusion　Smoking status and estimated daily salt intake were associated with higher salt taste thresholds in healthy urban residents.

Association between visceral fat accumulation and decline in the estimated glomerular filtration rate based on cystatin C in the Japanese urban population: the KOBE study.

Although metabolic syndrome, including visceral fat accumulation, causes kidney and cardiovascular diseases, the impact of visceral fat accumulation on mild decreased renal function remains unclear. This study examines the association between visceral fat area (VFA) measured by bioimpedance methods and the estimated glomerular filtration rate based on serum cystatin C (eGFRcys) in the Japanese urban population. This community-based cross-sectional study enrolled 952 individuals (287 men, 665 women) who participated in the second follow-up survey of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study. We compared the multivariate-adjusted means of eGFRcys among VFA quartile groups by gender using the analysis of covariance. Models were adjusted for age, high blood pressure, hypercholesterolemia, glucose intolerance, smoking, and alcohol use, and further adjusted for body mass index (BMI). The highest VFA quartile group had lower eGFRcys than the lowest VFA quartile group after adjusted for cardiometabolic risk factors, except for BMI (93.1 [95% confidence interval (CI), 90.1-96.2] vs. 82.1 [95% CI, 79.1-85.0] in men and 95.8 [95% CI, 94.1-97.5] vs. 89.4 [95% CI, 87.8-90.9] in women). Moreover, further adjustment for BMI revealed a similar result in men (93.5 [95% CI, 89.8-97.2] vs. 81.6 [95% CI, 77.9-85.3]), while no significant association was found in women. This study suggests a significant association between increased VFA levels and lower eGFRcys levels independent of cardiometabolic risk factors, such as glucose intolerance and hypercholesterolemia in men and women, as well as independent of BMI in men.

Effect of Chronic Kidney Disease or Anemia or Both on Cardiovascular Mortality in a 25-Year Follow-Up Study of Japanese General Population (From NIPPON DATA90).

The relation between chronic kidney disease (CKD) and cardiovascular disease (CVD) in the general population is well elucidated. In patients with CKD, anemia is associated with adverse outcomes. However, the effects of CKD and anemia on CVD in the general population remains poorly explored, especially in Asian populations. This study aimed to investigate the effect of CKD and/or anemia on CVD mortality in a long-term cohort study involving Japanese community dwellers. We assessed 7,339 participants (aged ≥30 years) with no CVD history. These participants were divided into 4 categories according to their CKD (estimated glomerular filtration rate <60 or urine protein >1+ by dipstick qualitative test) and/or anemia (hemoglobin: <13 g/100 ml [men], <12 g/100 ml [women]) statuses. For each category, we calculated the hazard ratios (HRs) of CVD mortality by using the Cox proportional hazards model after adjusting for age, body mass index, hypertension, diabetes, dyslipidemia, smoking, and alcohol drinking. Within 25 years of follow-up, 637 participants died because of CVD. The HRs of CVD in patients with CKD only, anemia only, and both were 1.27, 1.59, and 2.60 (95% confidence intervals [CI] 1.06 to 1.53, 1.34 to 1.90, and 1.80 to 3.76) in men and 1.42, 1.08, and 2.00 (95% CI 1.19 to 1.69, 0.99 to 1.18, and 1.54 to 2.60) in women, respectively. In conclusion, CKD with anemia is associated with an increased risk for CVD mortality in a general population in Japan.

Physique at Birth and Cardiovascular Disease Risk Factors in Japanese Urban Residents: the KOBE Study.

AIM: This study investigated the relationship between birth physique and cardiovascular risk factors in Japanese urban residents aged 40 years and more. METHODS: A self-administered questionnaire on birth physique was performed among 624 individuals (165 men and 459 women) who participated in the KOBE study. We examined whether self-reported birth physique and available recorded birth weights matched for 72 participants. Then the association between birth physique and risk factors for all participants was examined by gender. Body size at birth in the questionnaire (large, medium, small) was set as an exposure and laboratory values from the baseline survey (2010-2011) were used as outcomes. RESULTS: Mean (standard deviation) recorded birth weight of 72 participants was 3665 (318), 3051 (300), and 2653 (199) g, in the large, medium, and small group, respectively. In the analysis for all participants, odds ratio for having both hypertension and impaired glucose tolerance were significantly higher in the small versus large birth weight group, which was 7.42 (95% CI 1.75-31.50) for men and 4.44 (95% CI 1.14-17.30) for women after adjusting for age, body mass index, smoking/alcohol/exercise habits, and menstrual status in women. Similar results were observed in participants with recorded birth weight. CONCLUSIONS: The present study indicates that individuals with small physique at birth might be at higher risk for hypertension and impaired glucose tolerance in middle age compared to those with large birth weight.

Association between declines in objective masticatory performance and salivary stress markers: The Suita study.

Dentists often encounter patients suffering from psychological and social stress due to declines in masticatory performance, making this a critical issue to manage. We aimed to clarify the relationships between salivary stress markers as objective indices of chronic stress and objective masticatory performance in a general urban Japanese population. Data from 880 participants (mean age, 65.8 years) in the Suita study were used. Salivary interleukin (IL)-6 and cortisol concentrations were measured by enzyme-linked immunosorbent assay. Objective masticatory performance was determined by measuring the increase in surface area test gummy jelly after 30 times chewing. Participants were divided into two groups based on masticatory performance: a decreased group (lowest quartile) and a non-decreased group (second to fourth quartiles). Odds ratios (ORs) of higher salivary levels of stress markers (highest quartile) according to masticatory performance were estimated using logistic regression analysis adjusting for age, sex, periodontal status, salivary flow rate and smoking habit. Salivary IL-6 level was significantly higher in the decreased group than in the non-decreased group. Logistic regression analysis showed the adjusted OR for higher salivary IL-6 was significantly higher in the decreased group than in the non-decreased group (OR = 1.92; 95% confidence interval = 1.33-2.76; P < .001). No significant associations were found between salivary cortisol and decreased masticatory performance in any analyses. Declines in objective masticatory performance may correlate with higher salivary IL-6 level as an objective index of chronic stress.

Decrease in posterior occlusal support area can accelerate tooth loss: The Suita study.

Purpose A decrease in posterior occlusal support is considered to increase the load on remaining teeth and thus accelerate tooth loss. Therefore, a follow-up study was carried out to perform a longitudinal analysis of the association between the posterior occlusal support region and tooth loss.Methods The participants of the study were 806 Suita Study participants who underwent physical health checkups both at baseline and at follow-up. The participants were classified into three groups by posterior occlusal support area (POSA) using the Eichner Index at baseline: Perfect POSA group, Eichner A; Decreased POSA group, Eichner B1-3; and Lost POSA group, Eichner B4 and Eichner C1-2. Participants were also classified into two groups according to whether they had tooth loss during the follow-up period. Tooth loss risk factors were investigated through the construction of logistic regression models with tooth loss as the dependent variable and posterior occlusal support, sex, age, periodontal disease, stimulated salivary flow rate, smoking habit, drinking habit, denture wearing, utilization of dental services, brushing habits, diabetes mellitus, osteoporosis and number of years of follow-up as independent variables.Results In the results of the logistic regression model, the adjusted odds ratio (95%CI) for tooth loss with the Perfect POSA group as the reference was 3.19 (1.98-5.14) for the Decreased POSA group and 4.57 (1.97-10.62) for the Lost POSA group.Conclusions This study showed that decreased POSA accelerated tooth loss in the general urban population.

[The search for a predictor of deterioration of the nonspecific stress index K6 among urban residents: The KOBE study].

Objective　To explore health-related and socioeconomic factors that can predict future deterioration in Psychological Distress Scale (K6) scores.Method　We conducted a baseline (2010, 2011) self-administered questionnaire survey of the Kobe Orthopedic and Biomedical Epidemiological study (KOBE study) involving 1,117 participants who had no previous history of cancer or cardiovascular diseases and were not under treatment for hypertension, diabetes, or dyslipidemia. We used the Japanese K6 as an indicator of stress and defined K6≧5 points as a high-stress group and K6<5 points as a low-stress group. A four-year follow-up survey (2014, 2015) was conducted on 1,004 people (follow-up rate of 90%). We excluded 39 participants with missing values, and 185 people whose K6 score was higher than 5 points at baseline. A final total of 780 participants' scores were examined for: gender, age, living situation, physical activity level, average sleep time, as well as the K6 score, the Japanese Hearing Handicap Inventory for Elderly (HHIE-S), and the Japanese Oswestry Disability Index (ODI). We conducted a logistic regression analysis using K6≧5 points at the four-year follow-up survey as the dependent variable and each factor at the baseline survey as the independent variable.Results　Of the 780 subjects analyzed, 132 (16.9%) were highly stressed (K6≧5 points) at the four-year follow-up point. A logistic regression analysis found age (40s/70s) (odds ratio 3.38, 95% confidence interval 1.45-7.86), living situation (single/living together) (odds ratio 1.98, 95% confidence interval 1.07-3.68), and ODI scores (every 1%) (odds ratio 1.05, 95% confidence interval 1.01-1.09), to all be significantly associated with high stress.Conclusion　This study suggests that age, living situation, and ODI scores are related to future stress.

Development of a Cardiovascular Disease Risk Prediction Model Using the Suita Study, a Population-Based Prospective Cohort Study in Japan.

AIM: To construct a risk prediction model for cardiovascular disease (CVD) based on the Suita study, an urban Japanese cohort study, and compare its accuracy against the Framingham CVD risk score (FRS) model. METHODS: After excluding participants with missing data or those who lost to follow-up, this study consisted of 3,080 men and 3,470 women participants aged 30-79 years without CVD at baseline in 1989-1999. The main outcome of this study was incidence of CVD, defined as the incidence of stroke or coronary heart disease. Multivariable Cox proportional hazards models with stepwise selection were used to develop the prediction model. To assess model performance, concordance statistics (C-statistics) and their 95% confidence intervals (CIs) were calculated using a bootstrap procedure. A calibration test was also conducted. RESULTS: During a median follow-up period of 16.9 years, 351 men and 241 women developed CVD. We formulated risk models with and without electrocardiogram (ECG) data that included age, sex, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, diabetes mellitus, smoking, and urinary protein as risk factors. The C-statistics of the Suita CVD risk models with ECG data (0.782; 95% CI, 0.766-0.799) and without ECG data (0.781; 95% CI, 0.765-0.797) were significantly higher than that of the FRS model (0.768; 95% CI, 0.750-0.785). CONCLUSIONS: The Suita CVD risk model is feasible to use and improves predictability of the incidence of CVD relative to the FRS model in Japan.

Daily Habit of Water Intake in Patients with Cerebral Infarction before its Onset; Comparison with a Healthy Population: A Cross-Sectional Study.

BACKGROUND: While water intake is frequently recommended to prevent cerebral infarction (CI), only few studies have been published on this topic. OBJECTIVES: This study retrospectively estimated the daily non-alcohol drink (NAD) intake in CI patients before CI onset and compared it with NAD in healthy subjects. METHODS: We performed a cross-sectional study on CI patients in 3 hospitals and healthy subjects in the Kobe Orthopedic and Biomedical Epidemiologic (KOBE) study. Data from 1,287 subjects (274 CI patients and 1,013 healthy subjects) were used for the analyses. By dividing the CI patients into "increased", "unchanged", and "decreased" groups according to their current NAD intake, we compared the NAD intake between these 3 groups and healthy subjects by analyses of covariance and the post hoc test, adjusting for sex, age, surveyed month, body mass index, alcohol drinking history, and smoking history. Under the assumption that the NAD intake in the "unchanged" group was equal to the NAD intake before CI onset, the OR of less NAD intake for CI adjusting for the relevant variables in the "unchanged" group and the healthy subjects was calculated; the cut-off point was chosen using Youden's index. RESULTS: The mean age (mean ± SD) of the participants was 62.8 ± 9.3 years. One hundred and fifty-one patients (36 women) were included in the "increased" group; 105 (30 women), in the "unchanged" group; 18 (2 women), in the "decreased" group; and 1,013 (706 women), in the "healthy" group. The mean NAD intake was 1,702.5 ± 670.2 mL in the "increased" group, 1,494.2 ± 611.2 mL in the "unchanged" group, 1,268.0 ± 596.1 mL in the "decreased" group, and 1,720.6 ± 686.0 mL in the "healthy" group. After adjusting for the relevant variables, a significant difference in NAD intake between the groups was observed (F = 6.1, p < 0.001), and a post hoc test demonstrated significant differences (p < 0.05) in NAD intake between the "healthy" and "unchanged" groups, and between the "increased" and "unchanged" groups. The OR of less NAD intake (<1,570 mL/day, chosen using Youden's index) for CI was 2.48 (95% CI 1.52-4.07). CONCLUSION: This study showed that daily NAD intake before CI onset in CI patients was less than that in healthy persons, indicating that sufficient intake of NAD may be protective for CI.

Prevalence of RNF213 p.R4810K Variant in Early-Onset Stroke With Intracranial Arterial Stenosis.

Background and Purpose- The ring finger protein 213 gene ( RNF213) is a susceptibility gene for moyamoya disease and large-artery ischemic stroke in East Asia. We examined the prevalence and correlates of the RNF213 p.R4810K variant in patients with early-onset ischemic stroke in a Japanese single-center cohort. Methods- We analyzed 70 early-onset stroke patients with intracranial arterial stenosis who developed a noncardioembolic stroke or transient ischemic attack from 20 to 60 years of age. Patients with moyamoya disease were excluded. Results- The RNF213 p.R4810K variant was found in 17 patients (24%), and more often in women than men (38% versus 16%, odds ratio 3.3; 95% CI, 1.1-10.2, P=0.04). The variant was identified in 35% of patients with stenosis in the M1 segment of the middle cerebral artery or the A1 segment of the anterior cerebral artery (odds ratio, 25.0; 95% CI, 1.4-438; P<0.01) but in only one patient (9%) with intracranial posterior circulation stenosis. Conventional atherosclerotic risk factors did not differ between variant carriers and noncarriers. Conclusions- The RNF213 p.R4810K variant is common in early-onset ischemic stroke with anterior circulation stenosis in Japan. Further investigation of the RNF213 gene will provide new insights into pathogenetic mechanisms of early-onset stroke.

Higher serum uric acid level is inversely associated with renal function assessed by cystatin C in a Japanese general population without chronic kidney disease: the KOBE study.

BACKGROUND: Although several epidemiological studies have suggested that high serum uric acid (SUA) levels are related to a decline in kidney function, only a few studies have investigated using cystatin C to calculate estimated glomerular filtration rate (eGFR). We aimed to clarify the relationship between SUA levels and kidney function assessed by cystatin C in a Japanese general community population without chronic kidney disease (CKD). METHODS: We conducted a community-based cross-sectional study that included 1086 healthy participants, aged 40-74 years, without CKD and not undergoing treatment of hyperuricemia, who had participated in the baseline survey of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study. The preconditions for participation in this study were no past histories of cardiovascular disease or cancer, and not undergoing treatment for diabetes, hypertension, or dyslipidemia. We classified the participants into quartiles stratified by sex according to their SUA level and then examined the relationship with eGFR. The odds ratios for having a low eGFR, defined as the lowest quartile of eGFR (i.e., ≤78.4 mL/min/1. 73m2) was estimated according to SUA quartiles (men, Q1 ≤ 5.0, Q2 5.1-5.9, Q3 6.0-6.6, and Q4 ≥ 6.7; women, Q1 ≤ 3.8, Q2 3.9-4.3, Q3 4.4-4.9, and Q4 ≥ 5.0 mg/dL) after adjustment for age, body mass index, systolic blood pressure, HbA1c, high and low density lipoprotein cholesterol, and smoking and drinking habits. The adjusted mean of each quartile was also calculated. RESULTS: Multivariable-adjusted means of eGFR showed a graded decrease in higher SUA quartiles (men, Q1 90.5, Q2 88.0, Q3 83.5, and Q4 82.0; women, Q1 95.7, Q2 91.3, Q3 89.2, and Q4 86.7). In addition, the multivariable-adjusted odds ratios for having a lower eGFR (95% confidence interval) for each SUA quartile compared with Q1 was Q2 2.29 (0.98, 5.35), Q3 4.94 (2.04, 11.97), and Q4 8.01 (3.20, 20.04) for men, and was Q2 2.20 (1.12, 4.32), Q3 2.68 (1.39, 5.20), and Q4 4.96 (2.62, 9.41) for women. CONCLUSIONS: There was a graded inverse relationship between mild elevations in SUA levels and eGFR assessed by cystatin C in an apparently healthy Japanese population without CKD. This association was similar in both men and women.

Detection of Subclinical Peripheral Artery Ischemia in Healthy Male Smokers by an Ankle-Brachial Index After Exercise: Sasayama Study.

We investigated the relationship between smoking and the risk of nonnormal (≤0.99) ankle-brachial index (ABI) at rest and after ankle plantar flexion exercise in healthy male community dwellers. A cross-sectional study was performed including 228 Japanese men aged 40 to 64 years without a history of cardiovascular diseases. Participants were classified as never, ex-, and current smokers. We estimated the multivariate-adjusted odds ratios (ORs) for nonnormal ABI of ex- and current smokers in relation to never smokers after adjusting for age and other confounding factors. At rest, the prevalence of nonnormal ABI was not significantly different by smoking status. After exercise, the prevalence of nonnormal ABI increased from 1.8% to 11.5% in ex-smokers and from 3.8% to 17.0% in current smokers, while the prevalence did not significantly change in never smokers. The multivariate-adjusted OR for nonnormal ABI after ankle plantar flexion exercise, in relation to never smokers, was 3.85 (95% confidence interval [CI]: 0.79-18.9) for ex-smokers and 6.97 (95% CI: 1.32-36.7) for current smokers. Our results suggest that ABI after ankle plantar flexion exercise is useful for early detection of subclinical peripheral artery ischemia in male smokers without typical symptoms.

Development of a Basic Risk Score for Incident Atrial Fibrillation in a Japanese General Population　- The Suita Study.

BACKGROUND: An atrial fibrillation (AF) risk score for a non-Western general population has not been established.Methods and Results:A total of 6,898 participants (30-79 years old) initially free of AF have been prospectively followed for incident AF since 1989. AF was diagnosed when AF or atrial flutter was present on ECG at a biannual health examination; was indicated as a current illness; or was in the medical records during follow-up. Cox proportional hazard ratios were analyzed after adjusting for cardiovascular risk factors at baseline. During the 95,180 person-years of follow-up, 311 incident AF events occurred. We developed a scoring system for each risk factor as follows: 0/-5, 3/0, 7/5, and 9/9 points for men/women in their 30 s-40 s, 50 s, 60 s, and 70 s, respectively; 2 points for systolic hypertension, overweight, excessive drinking, or coronary artery disease; 1 point for current smoking; -1 point for moderate non-high-density lipoprotein-cholesterol; 4 points for arrhythmia; and 8, 6, and 2 points for subjects with cardiac murmur in their 30 s-40 s, 50 s, and 60 s, respectively (C-statistic 0.749; 95% confidence interval, 0.724-0.774). Individuals with score ≤2, 10-11, or ≥16 points had, respectively, ≤1%, 9%, and 27% observed probability of developing AF in 10 years. CONCLUSIONS: We developed a 10-year risk score for incident AF using traditional risk factors that are easily obtained in routine outpatient clinics/health examinations without ECG.

Does the flushing response modify the relationship between alcohol intake and hypertension in the Japanese population? NIPPON DATA2010.

The influence of alcohol intake on hypertension may vary depending on the flushing response, but this relationship has not been confirmed. The relationship between alcohol intake and hypertension was examined according to the flushing response in a representative sample of the Japanese population. Participants in the National Health and Nutrition Survey in 2010 were asked to participate in the baseline survey of NIPPON DATA2010. Here, we investigated the relationship between alcohol intake and hypertension according to the flushing response. Statistical analyses were performed in a cross-sectional manner using multiple logistic regression models after adjusting for age, body mass index, smoking status, present illness of diabetes mellitus and present illness of dyslipidemia. Of the 1139 men and 1263 women, 659 and 463, respectively, had hypertension. Among the men, alcohol intake was positively associated with hypertension, regardless of the flushing response (P for linear trend both <0.05). This positive relationship was observed for both users and non-users of antihypertensive drugs. No interaction with the flushing response was observed (P for interaction=0.360). In women, although the direction differed between flushers and non-flushers, the association between alcohol intake and hypertension was not significant, regardless of flushing response. In conclusion, In Japanese men, alcohol intake was positively associated with hypertension in a manner that was not influenced by the flushing response.

Association between serum long-chain n-3 and n-6 polyunsaturated fatty acid profiles and glomerular filtration rate assessed by serum creatinine and cystatin C levels in Japanese community-dwellers.

BACKGROUND: Plasma concentration of n-3 polyunsaturated fatty acids (PUFAs) has been reported to be associated with renal function in Western populations. However, few studies have investigated the association between serum long-chain n-3 and n-6 PUFA profiles and renal function in a Japanese population with high marine-derived long-chain n-3 PUFA intake. METHODS: A cross-sectional study was performed in 549 Japanese rural community-dwellers aged 40 to 64 years. In adjusted analysis of covariance, we assessed the relationship between estimated glomerular filtration rate (eGFR) and tertiles of serum long-chain n-3 and n-6 PUFA profiles ([eicosapentaenoic acid {EPA} + docosahexaenoic acid {DHA}]:arachidonic acid [AA]). GFR was estimated by Japanese specific equations using serum creatinine and cystatin C (eGFRcre and eGFRcys). Using multivariate-adjusted linear regression models, we also assessed the relationships between eGFRs and several n-3 and n-6 PUFAs, which have been suggested to be associated with renal function. RESULTS: In all participants, higher dietary fish intake as assessed by a semi-quantitative questionnaire was associated with higher serum value of (EPA+DHA):AA. Participants in the higher (EPA+DHA):AA tertiles had non-significantly higher eGFRcre and significantly higher eGFRcys (P = 0.016). In addition, eGFRcys in T2+T3 of (EPA+DHA):AA was significantly higher than that in T1 (adjusted mean eGFRcys, T1: 87 ml/min/1.73 m(2), T2+T3: 91 ml/min/1.73 m(2); P < 0.01). Among the PUFAs, only (EPA+DHA) was significantly associated with eGFRcys. CONCLUSIONS: Serum (EPA+DHA):AA, which reflects an individual's fish intake, might be associated with eGFRcys in Japanese community-dwellers.

The Relationship between Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Ligands Containing Apolipoprotein B and the Cardio-Ankle Vascular Index in Healthy Community Inhabitants: The KOBE Study.

AIMS: Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 ligands containing apolipoprotein B (LAB) and lectin-like oxidized LDL receptor-1 (LOX-1) are known as LOX-1-related modified LDL indicators. These indicators play an important role in the early phase atherosclerosis, but the relationship between these indicators and subclinical atherosclerosis, as represented by the cardio-ankle vascular index (CAVI), has not been assessed. We herein investigated the association of LOX-1- related modified LDL indicators and the CAVI in healthy, Japanese urban community inhabitants who were considered to be at low risk for cardiovascular disease (CVD). METHODS: The participants were 515 healthy Japanese (310 men and 205 women) without a history of CVD, cancer or the use of medication for hypertension, diabetes or dyslipidaemia. To estimate the association between LOX-1-related modified LDL indicators (LAB, soluble form of LOX-1 (sLOX-1)) and the CAVI, we performed multivariable linear regression analyses with possible confounders such as the serum LDL cholesterol level. RESULTS: The plasma LAB showed a positive association with the CAVI in men (standardized coefficient: 0.11, p = 0.04). This relationship was not observed in women. On the other hand, no clear association was observed between the CAVI and the plasma sLOX-1 level in either sex. CONCLUSIONS: The plasma LAB levels may represent a useful marker for detecting potential atherosclerosis in healthy individuals considered to be at low risk for atherosclerosis and CVD. Further studies are needed to confirm the present findings.

Blood pressure, low-density lipoprotein cholesterol, and incidences of coronary artery disease and ischemic stroke in Japanese: the Suita study.

BACKGROUND: Blood 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. METHODS: Individuals 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. RESULTS: There 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). CONCLUSIONS: The 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.

The relationship between waist circumference and the risk of stroke and myocardial infarction in a Japanese urban cohort: the Suita study.

BACKGROUND AND PURPOSE: Body mass index is most commonly used as the obesity index. Recently, waist circumference (WC) has been shown to be associated with the risk of cardiovascular disease (CVD). However, no studies have observed an association between WC and CVD in Japan. We examined the relationships of WC and body mass index with CVD in a Japanese urban population. METHODS: We studied 5474 Japanese individuals (aged 30 to 79 years without CVD at baseline) who completed a baseline survey and received follow-up through December 2005. WC was measured at the umbilical level of participants in the standing position to the nearest 1 cm. The Cox proportional hazard ratios for CVD according to the quartiles of WC were calculated after adjustment for age, smoking, and drinking status. RESULTS: During a mean follow-up of 11.7 years, 207 strokes and 133 myocardial infarctions were documented. In women, compared with the lowest quartile (WC <70 cm), the hazard ratio (95% CIs) after adjusting for age, smoking, and drinking in the highest quartile (WC >or=84 cm) were 1.85 (1.03 to 3.31) for CVD and 2.64 (1.16 to 6.03) for stroke. However, no such relationships of WC with CVD or stroke risk were observed in men. After further adjustment of hypertension, diabetes, and hypercholesterolemia, all of the mentioned relationships were not statistically significant. No associations of body mass index with CVD or strokes were observed. CONCLUSIONS: WC may be a better predictor for CVD or stroke in Japanese women.