Published papers

Background: Dietary intake of long-chain n-3 PUFA (LCn3FA) among Japanese is generally higher than that in Western populations. However, little is known whether an inverse association of LCn3FA with cardiovascular disease (CVD) risk exists in a population with higher LCn3FA intake. Objective: To investigate the association between LCn3FA intake and the long-term risk of CVDs in a Japanese general population. Methods: We followed-up a total of 9190 individuals (56.2% women, mean age 50.0 years) randomly selected from 300 areas across Japan and free from CVDs at baseline. Dietary LCn3FA intake was estimated using household weighed food records. Cox models were used to calculate multivariate-adjusted hazard ratios (HR) and confidence intervals (CI) according to sex specific quartiles of LCn3FA intake. Results: During 24-year follow-up (192,897 person-years), 879 cardiovascular deaths were observed. The median daily intake of LCn3FA was 0.37% kcal (0.86 g/day). Adjusted HR for CVD mortality was lower in the highest quartile of LCn3FA intake (HR 0.80; 95% CI 0.66-0.96) compared with the lowest quartile, and the trend was statistically significant (P = 0.038). The similar but statistically non-significant trends were observed for coronary heart disease death and stroke death. In analyses by age groups, the inverse associations of LCn3FA intake with the risk of total CVD death and stroke death were significant in younger individuals (30-59 years at baseline). Conclusion: LCn3FA intake was inversely and independently associated the long-term risk of total CVD mortality in a representative sample of Japanese with high LCn3FA intake. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Objective: In Western populations, blood pressure (BP) measured at baseline has been reported to predict long-term (over 20 years) risk of mortality from cardiovascular diseases (CVDs). However, corresponding evidence is scarce in Asia where stroke is dominant. We investigated the association between baseline BP and 24-year mortality risk due to CVD, in a representative Japanese general population. Methods: We followed up a nationwide sample of 8592 Japanese, aged 30 years or above without a history of CVD and antihypertensive medication at baseline, for 24 years. Hazard ratios for CVD mortality in BP categories defined according to JCN7 criteria were estimated using Cox model adjusted for potential confounding factors with normal BP treated as the reference category. Results: We observed 689 CVD deaths. Hazard ratios for CVD mortality were progressively and significantly increased from the category of prehypertension. Population-attributable fraction (PAF) demonstrated that 43 and 48% of CVD and stroke deaths were explained by non-normal BP at baseline. Hazard ratios and PAF were remarkably higher in younger participants (aged 30-59 years) than those in the elderly (aged 60 years or above). Particularly, in younger men, 81% of CVD deaths were explained by non-normal BP. In sensitivity analysis, participants with antihypertensive medication showed the highest hazard ratio for CVD morality compared with the other categories. Conclusions: BP levels above normal at baseline retained significant relative and absolute risks of CVD and stroke mortality during 24 years. Long-lasting burden of non-normal BP particularly in younger individuals suggests the importance of primary prevention of high BP from younger generation.

Long-term safety of consuming low-carbohydrate diets (LCD) in Asian populations, whose carbohydrate intake is relatively high, is not known. In the present study, the association of LCD with CVD and total mortality was assessed using data obtained in the NIPPON DATA80 (National Integrated Project for Prospective Observation of Non-communicable Disease and Its Trends in the Aged 1980) during 29 years of follow-up. At baseline in 1980, data were collected from study participants aged >= 30 years from randomly selected areas in Japan. LCD scores were calculated based on the percentage of energy as carbohydrate, fat and protein, estimated by 3 d weighed food records. A total of 9200 participants (56% women, mean age 51 years) were followed up. During the follow-up, 1171 CVD deaths (52% in women) and 3443 total deaths (48% in women) occurred. The multivariable-adjusted hazard ratio (HR) for CVD mortality using the Cox model comparing the highest v. lowest deciles of LCD score was 0 60 (95% CI 0 38, 0 94; P-trend = 0 021) for women and 0 78 (95% CI 0 58, 1 05; P-trend = 0 079) for women and men combined; the HR for total mortality was 0 74 (95% CI 0 57, 0 95; P-trend = 0 029) for women and 0 87 (95% CI 0 74, 1 02; P-trend = 0 090) for women and men combined. None of the associations was statistically significant in men. No differential effects of animal-based and plant-fish-based LCD were observed. In conclusions, moderate diets lower in carbohydrate and higher in protein and fat are significantly inversely associated with CVD and total mortality in women.

Background and Objectives: Total fat intake is linked to the intake of other nutrients. Little data are available on the extent to which total fat affects diet quality in Japanese people. We investigated the relationship between total fat intake and other nutrient intake using INTERLIPID/INTERMAP data on Japanese people living in Japan. Methods and Study Design: The participants included 371 men and 401 women with a healthy body mass index and between the ages of 40 and 59 from 4 population samples in Japan. Nutrient intake data were based on four in-depth 24-hour dietary recalls per person. Results: Analysis of covariance adjusted for age revealed that total fat intake was positively related to intakes of calcium, thiamine, riboflavin, meat, eggs, and milks and dairy products for both sexes. Total fat intake was inversely associated with carbohydrate and cereals intake for both sexes. On average, men with total fat intake between 25.0 and 27.4% of total energy had saturated fatty acids above 7%, which is the upper limit recommended for preventing lifestyle-related diseases. Men with total fat intake less than 20% of total energy had a higher risk of not meeting the Dietary Reference Intakes for Japanese (2015) for some nutrients. Conclusions: Total fat intake was positively associated with calcium, thiamine, and riboflavin intakes and inversely associated with carbohydrate intake. Our results suggest that in 40-59-year-old men with a healthy body mass index, total fat intake between 20 and 27% of total energy may best support adequate intake of other nutrients.

Background: Non-high-density lipoprotein (HDL) cholesterol level, generally less affected by fasting status or serum triglyceride levels, may be useful for predicting future cardiovascular events in daily clinical practice. This study aimed to investigate the role of non-HDL cholesterol in the development of fatal coronary events and stroke in the general Japanese population. Methods and results: From the NIPPON DATA 90 prospective cohort study, 8383 participants were followed up for 20 years since 1990. After exclusion of 666 cases without lipid or covariates data, 561 cases who were 75 years old or older, 274 cases with history of cardiovascular disease, and 181 cases with lipid-lowering treatment, 6701 participants were included in this analysis. Non-HDL cholesterol was defined as total cholesterol minus HDL cholesterol. Outcomes were death from coronary heart disease and stroke. During the period, 69 participants died from coronary heart disease and 112 from stroke. Compared with participants with non-HDL cholesterol level b3.9 mmol/L, age- and sex-adjusted hazard ratios for mortality by coronary heart disease in those with non-HDL cholesterol levels of 3.9-4.3 mmol/L, 4.4-4.8 mmol/L and >= 4.9 mmol/L were 1.27 (95% confidence interval [CI] 0.65-2.49), 1.81 (95% CI 0.92-3.55) and 2.40 (95% CI 1.30-4.43), respectively (P trend = 0.010). This association remained significant even after adjusting for other cardiovascular risk factors (P trend = 0.010). There was no clear association between non-HDL cholesterol levels and mortality by stroke (P trend= 0.052). Conclusions: Among the general Japanese population, non-HDL cholesterol levels were clearly associated with future mortality by coronary heart disease, but not by stroke. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Purpose Low-carbohydrate diets (LCD) are a popular dietary strategy for weight reduction. The effects of LCD on long-term outcome vary depending on type of LCD, possibly due to the fact that effects on cardiometabolic risk factors may vary with different types of LCD. Accordingly, we studied these relations. Methods We assessed serum concentrations of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), high-sensitivity C-reactive protein (CRP), total cholesterol, glycated hemoglobin, and uric acid, and nutrient intakes by standardized methods in men and women ages 40-59 years from four population samples of Japanese in Japan (553 men and 544 women, combined). For people consuming usual, animal-based, and plant-based LCDs, we calculated LCD scores, based on relative level of fat, protein, and carbohydrate, by modifying the methods of Halton et al. Instead of calculating scores based on animal or vegetable fat, we used saturated fatty acids (SFA) or monounsaturated fatty acids (MUFA) + polyunsaturated fatty acids (PUFA). Results In multivariate regression analyses with adjustment for site, age, sex, BMI, smoking, alcohol intake, physical activity, and years of education, all three LCD scores were significantly positively related to HDLc (all P < 0.001), but not to LDLc. The plant-based LCD score was significantly inversely related to log CRP (coefficient = -0.010, P = 0.018). Conclusions All three LCD scores were significantly positively related to HDLc. The plant-based LCD score was significantly inversely related to CRP. Carbohydrate intake below 50 % of total energy with higher intakes of vegetable protein and MUFA + PUFA, and lower intakes of SFA may be favorable for reducing cardiometabolic risk factors.

BACKGROUND: Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C. METHODS: Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10-8) were selected from the GWAS catalog, and seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF). RESULTS: We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively. CONCLUSIONS: The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking.

OBJECTIVE: This study aimed to investigate the incidence rates and predictors of lower limb fractures in a general Japanese population. METHODS: NIPPON DATA is a nationwide, long-term, prospective cohort study of individuals who participated in the National Cardiovascular Survey Japan and the National Nutrition Survey in 1990. Overall, 3,134 individuals (1,827 women, 1,307 men) who participated in follow-up assessments in 1995, 2000, and/or 2006 were included in the present analysis. The outcomes of this study were lower limb fractures (including proximal femur fractures). RESULTS: The mean age at baseline was 63.8 years in women and 63.1 years in men. The average body mass index (BMI) was 23.3 kg/m2 in women and 22.9 kg/m2 in men. During a mean follow-up of 12.1 years, 271 total lower limb fractures were observed. In women, older age, lower BMI, and less intake of vegetables were associated with increased risks of proximal femur fractures. With regard to the outcome of total lower limb fractures, less intake of vegetables and regular exercise were significant predictors in women. Calcium intake was not significantly associated with proximal femur or total lower limb fractures. There were no significant predictors of proximal femur or total lower limb fractures in men, except for age. CONCLUSIONS: Aging was a significant risk factor for proximal femur and total lower limb fractures in both men and women. With regard to modifiable risk factors, low BMI and low intake of vegetables were associated with increased risks of proximal femur and/or total lower limb fractures in the general population of Japanese women.

BACKGROUND/OBJECTIVES: There have been few studies on the association of fruit and vegetable (FV) intake with cardiovascular disease (CVD) risk in Asian populations where both dietary habits and disease structure are different from western countries. No study in Asia has found its significant association with stroke. We examined associations of FV intake with mortality risk from total CVD, stroke and coronary heart diseases (CHDs) in a representative Japanese sample. METHODS: A total of 9112 participants aged from 24-year follow-up data in the NIPPON DATA80, of which baseline data were obtained in the National Nutrition Survey Japan in 1980, were studied. Dietary data were obtained from 3-day weighing dietary records. Participants were divided into sex-specific quartiles of energy adjusted intake of FV. Multivariate-adjusted hazard ratios (HRs) were calculated between strata of the total of FV intake, fruit intake and vegetable intake. The adjustment included age, sex, smoking, drinking habit and energy adjusted intakes of sodium and some other food groups. RESULTS: Participants with higher FV intake were older, ate more fish, milk and dairy products and soybeans and legumes and ate less meat. Multivariate-adjusted HR (95% confidence interval; P; P for trend) for the highest versus the lowest quartile of the total of FV intake was 0.74 (0.61-0.91; 0.004; 0.003) for total CVD, 0.80 (0.59-1.09; 0.105; 0.036) for stroke and 0.57 (0.37-0.87; 0.010; 0.109) for CHD. CONCLUSIONS: The results showed that higher total intake of FVs was significantly associated with reduced risk of CVD mortality in Japan.

Plasma amino acids (AAs) have emerged as promising biomarkers for metabolic disorders, yet their causality remains unclear. We aimed to investigate the genetic determinants of AA levels in a cohort of 10,333 individuals and their causal effects on cardiometabolic traits using Mendelian randomization (MR). Plasma levels of 20 AAs were quantified using capillary electrophoresis mass spectrometry. Genome-wide association studies were conducted using BOLT-LMM and heritability estimation via LDSC analysis. Causal effects of AAs on 11 cardiometabolic traits were examined using two-sample MR analyses. We identified 85 locus-metabolite associations across 43 genes for 18 AAs, including 44 novel loci linked to metabolic genes. Heritability for AAs was estimated at 16%. MR analysis demonstrated cystine to positively associate with systolic blood pressure (SBP) (β = 0.056, SE = 0.010), while serine indicated protective effects on SBP (β = − 0.040, SE = 0.011), diastolic BP (β = − 0.044, SE = 0.010), and coronary artery disease (odds ratio 0.888, SE = 0.028). We identified potentially novel genetic loci associated with AA levels and demonstrated robust causal associations between several AAs and cardiometabolic traits. These findings reinforce the importance of AAs as potential biomarkers and therapeutic targets in cardiometabolic health.

BACKGROUND: The trend of association between overweight and high serum total cholesterol (TC) among the elderly is unclear. In addition, there is little evidence of risk of underweight for high TC. Therefore, we examined the trend of association of overweight or underweight with high TC among Japanese elderly people using nationwide population-based data. METHODS: Data of the National Survey on Circulatory Disorders and National Health and Nutrition Survey for 1980, 1990, 2000, and 2010 were used in the analysis. High TC was defined as 220 mg/dL and above. For participants aged ≥50 years, sex-specific odds ratios (ORs) of overweight or underweight compared with normal body mass index participants for high TC were calculated using a logistic regression model adjusted for age, smoking, drinking, exercise, food, and treatment of hyperlipidemia. RESULTS: A total of 5,734, 4,673, 5,059, and 2,105 participants enrolled in these surveys in 1980, 1990, 2000, and 2010, respectively. Although overweight was positively and significantly associated with high TC in 1980, the association has gradually weakened since (ORs in 1980 and 2010 were 2.44; 95% confidence interval [CI], 1.83-3.24 and 0.92; 95% CI, 0.66-1.27 among men and 1.43; 95% CI, 1.18-1.72 and 1.08; 95% CI, 0.81-1.44 among women, respectively). While underweight was inversely and significantly associated with high TC in 1980, the association also gradually weakened among women (ORs in 1980 and 2010 were 0.28; 95% CI, 0.12-0.60 and 0.37; 95% CI, 0.10-1.28 among men and 0.39; 95% CI, 0.26-0.57 and 0.96; 95% CI, 0.58-1.57 among women, respectively). CONCLUSIONS: These findings provide evidence that high TC prevention efforts must expand the target to not only overweight but also to normal and underweight people.

Background & aim: Although dietary soy intake is linked with health benefits, a relation with stroke has not been established. The present study examined the association between the intake of tofu, the richest source of dietary soy, with stroke mortality in a general population cohort of Japanese men and women. Methods: Data comprise 9244 Japanese enrolled in the National Nutrition Survey of Japan in 1980. Participants were free of cardiovascular disease and followed for 24 years. Dietary intake was estimated from 3-day weighed food records. Multivariable Cox regression models were used to estimate hazard ratios across levels of tofu intake. Results: During follow-up, there were 417 deaths due to stroke (88 cerebral hemorrhage [CH], 245 cerebral infarction [CI], and 84 of other subtypes). Among all men, and in women aged 65 years or more, tofu intake was unrelated to each form of stroke. For young women (< 65 years of age), a significantly lower risk of CH in the top versus bottom quartile of tofu intake was observed (Multivariable-adjusted HR = 0.26, 95% CI: 0.08–0.85). Conclusions: In this large prospective study with long follow-up of Japanese men and women, consumption of tofu was unrelated to the risk of stroke except for CH in women < 65 years of age. Whether the association in younger women is real or due to chance alone warrants further study.

BACKGROUND: The relationships among socioeconomic status and lifestyle improvements have not yet been examined in a representative Japanese population. METHODS: We analyzed data from 2,647 participants (1,087 men and 1,560 women) who participated in NIPPON DATA2010. This survey inquired about lifestyle improvements and socioeconomic status. Education was categorized as low (≤9 years), middle (10-12 years), and high (≥13 years). Marital status was categorized as married, divorced, widowed, and never married/other. A multivariable logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of lifestyle improvements with the intention of preventing cardiovascular diseases for educational attainment and marital status, with adjustments for age and awareness of cardiovascular disease risk factors. RESULTS: Overall, 1,507 (56.9%) participants practiced prevention and improvements in hypertension, diabetes, elevated cholesterol, and metabolic syndrome, and the OR of lifestyle improvements was significantly higher with a high education than with a low education in men (OR 2.86; 95% CI, 1.96-4.17) and women (OR 2.36; 95% CI, 1.67-3.33). The number of participants who practiced prevention and improvements in hypertension, diabetes, elevated cholesterol, and metabolic syndrome was significantly lower in divorced than in married men (OR 0.46; 95% CI, 0.22-0.95) and women (OR 0.53; 95% CI, 0.33-0.86). CONCLUSIONS: Specific differences caused by educational attainment and marital status may exist in lifestyle improvements.

Background: Reducing the urinary sodium-to-potassium ratio is important for reducing both blood pressure and risk of cardiovascular disease. Among free-living Japanese individuals, we carried out a randomized trial to clarify the effect of lifestyle modification for lowering urinary sodium-to-potassium ratio using a self-monitoring device.Methods: This was an open, prospective, parallel randomized, controlled trial. Ninety-two individuals were recruited from Japanese volunteers. Participants were randomly allocated into intervention and control groups. A month-long dietary intervention on self-monitoring urinary sodium-to-potassium ratio was carried out using monitors (HEU-001F, OMRON Healthcare Co., Ltd., Kyoto, Japan). All participants had brief dietary education and received a leaflet as usual care. Monitors were handed out to the intervention group, but not to the control group. The intervention group was asked to measure at least one spot urine sodium-to-potassium ratio daily, and advised to lower their sodium-to-potassium ratio toward the target of less than 1. Outcomes included changes in 24-hour urinary sodium-to-potassium ratio, sodium excretion, potassium excretion, blood pressure, and body weight in both groups.Results: Mean measurement frequency of monitoring was 2.8 times/day during the intervention. Changes in urinary sodium-to-potassium ratio were −0.55 in the intervention group and −0.06 in the control group (P = 0.088); respective sodium excretion changes were −18.5 mmol/24 hours and −8.7 mmol/24 hours (P = 0.528); and corresponding potassium excretion was 2.6 mmol/24 hours and −1.5 mmol/24 hours (P = 0.300). No significant reductions were observed in either blood pressure or body weight after the intervention.Conclusions: Providing the device to self-monitor a sodium-to-potassium ratio did not achieve the targeted reduction of the ratio in “pure self-management” settings, indicating further needs to study an effective method to enhance the synergetic effect of dietary programs and self-monitoring practice to achieve the reduction. However, we cannot deny the possibility of reducing sodium-to-potassium ratio using a self-monitoring device.

Several studies demonstrated that visit-to-visit variability of blood pressure (BP) predicted future events of total death, stroke and cardiovascular disease. Little is known about factors associated with visit-to-visit BP variability in different countries. We recruited participants aged 40-59 years from four countries (Japan, the People's Republic of China [PRC], the United Kingdom [UK] and the United States [US]). At each study visit, BP was measured twice by trained observers using random zero sphygmomanometers after five minutes resting. We defined visit-to-visit BP variability as variation independent of mean (VIM) by using average systolic BP of 1st and 2nd measurement across four study visits. Data on 4680 men and women were analyzed. Mean ± standard deviation of VIM values among participants in Japan, the PRC, the UK and the US were 5.44 ± 2.88, 6.85 ± 3.49, 5.65 ± 2.81 and 5.84 ± 3.01, respectively; VIM value in the PRC participants was significantly higher. Sensitivity analyses among participants without antihypertensive treatment or past history of cardiovascular disease yielded similar results. Higher VIM value was associated with older age, female gender, lower pulse rate and urinary sodium excretion and use of antihypertensive agents such as angiotensin converting enzyme inhibitors, beta blockers and calcium channel blockers. The difference of visit-to-visit BP variability between PRC and other countries remained significant after adjustment for possible confounding factors. In this large international study across four countries, visit-to-visit BP variability in the PRC was higher than in the other three countries. Reproducibility and mechanisms of these findings remain to be elucidated.

BACKGROUND: Few studies have compared factors related to cognitive function among people with similar genetic backgrounds but different lifestyles. OBJECTIVE: We aimed to identify factors related to lower cognitive scores among older Japanese men in two genetically similar cohorts exposed to different lifestyle factors. METHODS: This cross-sectional study of community-dwelling Japanese men aged 71-81 years included 2,628 men enrolled in the Kuakini Honolulu-Asia Aging Study based in Hawaii and 349 men in the Shiga Epidemiological Study of Subclinical Atherosclerosis based in Japan. We compared participant performance through Cognitive Abilities Screening Instrument (CASI) assessment in Hawaii (1991-1993) and Japan (2009-2014). Factors related to low cognitive scores (history of cardiovascular disease, cardiometabolic factors, and lifestyle factors) were identified with questionnaires and measurements. Multivariable logistic regression analysis was used to calculate the adjusted odds ratios (ORs) of a low (< 82) CASI score based on different factors. RESULTS: CASI scores were lower in Hawaii than in Japan [21.2%(n = 556) versus 12.3%(n = 43), p < 0.001], though this was not significant when adjusted for age and educational attainment (Hawaii 20.3%versus Japan 17.9%, p = 0.328). History of stroke (OR = 1.65, 95%confidence interval = 1.19-2.29) was positively associated with low cognitive scores in Hawaii. Body mass index ≥25 kg/m2 tended to be associated with low cognitive scores in Japan; there was a significant interaction between the cohorts. CONCLUSION: Cognitive scores differences between cohorts were mostly explained by differences in educational attainment. Conversely, cardiovascular diseases and cardiometabolic factors differentially impacted cognitive scores among genetically similar older men exposed to different lifestyle factors.

Background: An early repolarization pattern, characterized by an elevation of the QRS-ST junction (J-point) on 12-lead electrocardiography (ECG) is associated with cardiac and sudden death. However, little is known about the prognostic significance of J-point elevation for various disease-specific cardiovascular outcomes, including coronary artery disease (CAD). Methods and Results: To investigate the association between the presence of J-point elevation ≥0.1 mV and various disease-specific cardiovascular outcomes, we conducted a 15-year prospective study in a representative general Japanese population of 7,630 individuals (41% men, mean age 52.4 years) who participated in the National Survey of Circulatory Disorders. Cox models were used to estimate the hazard ratios (HRs) adjusted for possible confounding factors. J-point elevation was present in 264 individuals (3.5%) and was associated with an increased risk of cardiac death (adjusted HR, 2.54 95% confidence interval [CI] 1.40-4.58 P=0.002) and death from CAD (adjusted HR, 4.66 95% CI 2.30-9.46 P< 0.001). In a subgroup analysis by age, the association between J-point elevation and cardiovascular outcomes was more remarkable in middle-aged (< 60 years) than in older individuals (≥60 years) (all P for interaction < 0.05). Conclusions: J-point elevation on standard 12-lead ECG was an independent predictor of cardiac death and death from CAD in a representative sample of the general Japanese population, particularly among the middle-aged.

Aim: Pulse wave velocity (PWV) is a simple and valid clinical method for assessing arterial stiffness. Coronary artery calcification (CAC) is an intermediate stage in the process leading to overt cardiovascular disease (CVD) and an established determinant of coronary artery disease. This study aimed to examine the association between PWV and CAC in a population-based sample of Japanese men. Methods: This is a cross-sectional study of 986 randomly selected men aged 40-79 years from Shiga, Japan. CVD-free participants were examined from 2006 to 2008. Brachial-ankle PWV (baPWV) was measured using an automatic waveform analyzer. CAC was assessed using computed tomography. Agatston scores >= 10 were defined as the presence of CAC. Results: Prevalence of CAC progressively increased with rising levels of baPWV: 20.6%, 41.7%, 56.3%, and 66.7% across baPWV quartiles < 1378, 1378-1563, 1564-1849, and > 1849 cm/s (P < 0.001 for trend). Associations remained significant after adjusting for age and other factors, including body mass index, systolic blood pressure, pulse rate, total and high-density lipoprotein cholesterol, hemoglobin A1c, drinking, smoking and exercise status, and the use of medication to treat hypertension, dyslipidemia and diabetes (P = 0.042 for trend). The optimal cutoff level of baPWV to detect CAC was 1612 cm/s using receiver operating characteristic curve analysis. Conclusions: Arterial stiffness as defined by an elevated baPWV is associated with an increased prevalence of CAC in a general population-based setting among Japanese men.

Aim: In animals, dietary energy restriction is reported to increase longevity, whereas in humans, all cohort studies from Western countries have not shown an association between the low energy intake and longevity. We examined the association between total energy intake and longevity in Japan where dietary pattern is different from that in the West. Methods: A total of 7,704 Japanese aged 30-69 years were followed from 1980 to 2009. Participants were divided into the quintiles of total energy (kcal/day) based on data collected from the National Nutrition Survey. Hazard ratios and 95% confidence intervals (CIs) were derived through the use of Cox proportional hazards models to compare the risk of death across and between the quintiles. Results: There was a significant association between increased energy intake and all-cause mortality risk in only men (P for linear trend 0.008). In cause-specific analysis, compared with the lowest quintile, there was rise in coronary heart disease (CHD) mortality among men (HR; 2.63, 95% CI; 0.95-7.28, P for linear trend 0.016) and women (HR; 2.91, 95% CI; 1.02-8.29, P for linear trend 0.032) and cancer mortality among men (HR; 1.50, 95% CI; 0.999-2.24, P for linear trend 0.038) in the top quintile. Conclusion: We observed significant associations of high energy intake with all-cause and cancer mortality among men and with CHD mortality among men and women. Further studies are needed to confirm the benefits of caloric restriction.

BACKGROUND: Low-density lipoprotein particle (LDL-P) has recently been found to be a stronger predictor of cardiovascular disease (CVD) than LDL-cholesterol (LDL-C). OBJECTIVES: Whether LDL-P is associated with subclinical atherosclerosis, independent of LDLC, as well as other lipid measures has not been fully examined. We aimed to analyze LDL-P associations with measures of subclinical atherosclerosis. METHODS: We examined 870 Japanese men randomly selected from Kusatsu City, Shiga, Japan, aged 40-79 years from 2006-2008, free of clinical CVD and not using lipid-lowering medication. Cross-sectional associations of lipid measures with carotid intima-media thickness (cIMT) and coronary artery calcification (CAC; >0 Agatston score) were examined. RESULTS: LDL-P was significantly positively associated with cIMT and maintained this association after adjustments for LDL-C and other lipid measures. Although these lipid measures were positively associated with cIMT, model adjustment for LDL-P removed any significant relationships. Higher LDL-P was associated with a significantly higher odds ratio of CAC and further adjustment for LDL-C did not affect this relationship. In contrast, the LDL-C association with CAC was no longer significant after adjustment for LDL-P. Other lipid measures attenuated associations of LDL-P with CAC. Likewise, associations of these measures with CAC were attenuated when model adjustments for LDL-P were made. CONCLUSIONS: In a community-based sample of Japanese men, free of clinical CVD, LDL-P was a robust marker for subclinical atherosclerosis, independent of LDL-C and other lipid measures. Associations of LDL-C and other lipid measures with either cIMT or CAC were generally not independent of LDL-P. (C) 2016 National Lipid Association. All rights reserved.