The Contributions of Knee Extension Strength and Hand Grip Strength to Factors Relevant to Physical Frailty: The Tanno-Sobetsu Study.

Sarcopenia is the core factor of frailty. This study specifically focused on lower limb muscle strength and examined muscle indices that indicate the risk of frailty or pre-frailty in older adults. The study included 327 community-dwelling individuals aged ≥65 years (43.7% male) who participated in the cohort. Frailty was defined based on five symptoms: weight loss, low activity level, exhaustion, weakness and slowness. Participants were classified into frail (three or more applicable), pre-frail (one to two applicable) and non-frail groups. Muscle strength (knee extension strength, toe grip strength and hand grip strength) were assessed, and appendicular muscle mass was assessed via a bioelectrical impedance analysis. The adjusted odds ratio (OR) of muscle indices for with frailty (frail group vs. pre-frail group) or pre-frailty (pre-frail group vs. non-frail group) were calculated. The prevalence of frail and pre-frail was 7% and 40%, respectively. Adjusted for age, sex, albumin and medical history, knee extension strength was significantly associated with frailty (odds ratio 0.95, 95% CI 0.92-0.98), while hand grip strength was associated with pre-frailty (odds ratio 0.92, 95% CI 0.88-0.97) but not with other muscle indices. This study is significant for identifying knee extension strength as a factor relevant to frailty in older adults considered pre-frailty, emphasizing the importance of this specific muscle measure in predicting and managing frailty.

Preserved Lower Limb Muscle Mass Prevents Insulin Resistance Development in Nondiabetic Older Adults.

OBJECTIVE: To investigate roles of sarcopenia indexes in prediction of development of insulin resistance in nondiabetic older adults. DESIGN: A 2-year follow-up cohort. SETTING AND PARTICIPANTS: The Tanno-Sobetsu study, a prospective observational cohort, included 194 community-dwelling nondiabetic older adults during 2017-2019. METHODS: Lower limb, upper limb, appendicular, and trunk muscle masses by a bioelectrical impedance analysis, grip strength, knee extension torque, and walking speed were measured in study participants aged ≥65 years (79 men and 115 women) at baseline. Muscle mass and strength were divided by the weight, and then multiplied by 100 to calculate the weight ratio (%). Insulin resistance was assessed by homeostasis model (HOMA-IR) at baseline, and the study participants whose HOMA-IR was less than 1.73 at baseline were followed for a maximum of 2 years. The study endpoint was development of insulin resistance defined as HOMA-IR ≥1.73. The adjusted hazard ratio (HR) of each sarcopenia component for development of insulin resistance was calculated. RESULTS: Lower limb muscle mass (HR 0.88, 95% CI 0.79-0.98) and appendicular muscle mass (HR 0.89, 95% CI 0.81-0.99), but not other sarcopenia components, were associated with the development of insulin resistance, independently of sex and age, HOMA-IR, and waist circumference at baseline. CONCLUSIONS AND IMPLICATIONS: The loss of lower limb muscle mass is a significant risk factor for development of insulin resistance independently of obesity in nondiabetic older adults. The lower limb muscle mass may be a novel target of interventions for the prevention of diabetes in older adults.

Circulating plasma phospholipid fatty acid levels as a biomarker of habitual dietary fat intake: The INTERMAP/INTERLIPID Study.

BACKGROUND: Accurate assessment of fat intake is essential to examine relationships between diet and disease risk. However, estimating individual intakes of fat quantity by dietary assessment is difficult. OBJECTIVE: We assessed the association of plasma phospholipid fatty acid levels with dietary intake of fatty acids in the INTERMAP/INTERLIPID study, conducted with a standardized protocol. METHODS: The study participants were 1339 men and women ages 40-59 years from five Japanese populations one from Hawaii; four from Japan. Fatty acid intake was estimated from four standardized 24-hour dietary recalls. Plasma phospholipid fatty acid composition was analyzed by gas chromatography. We illustrated the relationship between intake and circulating fatty acid levels using Spearman's rank-correlation coefficients, mean, and median values. RESULTS: Spearman's rank-correlation coefficients between intake (g/d) and circulating fatty acid levels (µg/ml) were -0.03 to 0.21 for saturated fatty acids and monounsaturated fatty acids and -0.04 to 0.32 for trans fatty acids. The coefficients for essential n-3 and n-6 fatty acids were moderate to high, especially for eicosapentaenoic acid (EPA), 0.60; docosahexaenoic acid (DHA), 0.41; and EPA+DHA, 0.51. The circulating levels and intake of marine-derived n-3 fatty acids showed a linear association, at least for the intake of EPA+DHA up to 2.1 g/d. CONCLUSION: We observed high correlation between intake and circulating levels of marine-derived n-3 fatty acids in participants from Japanese and Japanese-American populations with high and low fish intake. Plasma phospholipid marine-derived n-3 fatty acid measurements are a simple and reliable biomarker for assessing dietary intake.

Small High-Density Lipoprotein and Omega-3 Fatty Acid Intake Differentiates Japanese and Japanese-Americans: The INTERLIPID Study.

AIM: To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii, in the absence of possible genetic confounders, and cross-sectionally examine the associated modifiable lifestyle factors. METHODS: Overall, 1,241 (aged 40-59 years) Japanese living in Japan and Japanese-Americans in Hawaii were included. We quantified 130 serum lipid profiles (VLDL 1-5, IDL, LDL 1-6, high-density lipoprotein [HDL] 1-4, and their subfractions) using Bruker's 1H-nuclear magnetic resonance spectrometer for the primary outcome. Modifiable lifestyle factors included body mass index (BMI), physical activity, alcohol and smoking habits, and 70 nutrient parameters. We evaluated the different lipids between the groups using partial least squares-discriminant analysis and association between extracted lipids and lifestyle factors using multivariable linear regression analysis. RESULTS: Concentrations of HDL4, HDL with the smallest particle size, were lower in Japanese than in Japanese-Americans of both sexes. Higher fish-derived omega-3 fatty acid intake and lower alcohol intake were associated with lower HDL4 concentrations. A 1% higher kcal intake of total omega-3 fatty acids was associated with a 9.8-mg/dL lower HDL4. Fish-derived docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid intake were inversely associated with HDL4 concentration. There was no relationship between country, sex, age, or BMI. CONCLUSIONS: Japanese and Japanese-Americans can be differentiated based on HDL4 concentration. High fish intake among the Japanese may contribute to their lower HDL4 concentration. Thus, HDL particle size may be an important clinical marker for coronary artery diseases or a fish consumption biomarker.

Investigation of the urinary sodium-to-potassium ratio target level based on the recommended dietary intake goals for the Japanese population: The INTERMAP Japan.

Growing epidemiological evidence has shown an association of the urinary sodium (Na) to potassium (K) ratio (Na/K ratio) with blood pressure and cardiovascular diseases. However, no clear cutoff level has been defined. We investigated the cutoff level of the urinary Na/K ratio under different dietary guidelines for Japanese individuals, especially that endorsed by the 2020 revised Japanese Dietary Reference Intakes (DRIs). A population of 1145 Japanese men and women aged 40 to 59 years from the INTERMAP study was examined. Using high-quality standardized data, the averages of two 24 h urinary collections and four 24 h dietary recalls were used to calculate the 24 h urinary and dietary Na/K ratios, respectively. Associations between the urinary and dietary Na/K ratios were tested by sex- and age-adjusted partial correlation. The optimal urinary Na/K ratio cutoff level was determined by receiver operating characteristic (ROC) curves and sex-specific cross tables for recommended dietary K and salt. Overall, the average molar ratio of 24 h urinary Na/K was 4.3. We found moderate correlations (P < 0.001) of the 24 h urinary Na/K ratio with 24 h urinary Na and K excretion (r = 0.52, r = -0.49, respectively) and the dietary Na/K ratio (r = 0.53). ROC curves showed that a 24 h urinary Na/K ratio of approximately 2 predicted Na and K intake that meets the dietary goals of the Japanese DRIs. The range of urinary Na/K ratios meeting the dietary goals of the Japanese DRIs for both Na and K was 1.6‒2.2 for men and 1.7‒1.9 for women. Accomplishing a urinary Na/K ratio of 2 would be desirable to achieve the DRIs dietary goals for both Na and K simultaneously in middle-aged Japanese men and women accustomed to Japanese dietary habits. This observational study is registered at www.clinicaltrials.gov as NCT00005271.

Toe Grip strength declines earlier than hand grip strength and knee extension strength in community-dwelling older men: a cross sectional study.

BACKGROUND: The aim of this study is to examine the age-related changes in the toe grip strength and its differences from hand grip strength and knee extension strength using cross-sectional data. METHODS: Of participants aged 65 years over who underwent health checkups for lifestyle-related diseases in 2018, 307 men and women met the criteria. Toe grip strength, hand grip strength, and knee extension strength were also measured as optional tests. The participants were divided into five groups categorized by every 5 years of age (Group 65-85). The data were analyzed with multiple comparisons using the linear mixed multilevel model to examine the following categories: association between age and muscle strength, differences in the pattern of change, and gender, using the 65-69 years group as a reference. RESULTS: In men, there were interaction effects between the factors of age and muscle, but in women there were not. Toe grip strength was significantly lower in Group 70, 75, 80, and 85 in men, lower in Group 85 than in 65 in women. Hand grip strength was significantly lower in Group 85 than in 65 in both men and women. There was no significant difference in knee extension strength among the age groups for both men and women. CONCLUSIONS: The decline in toe grip strength may occur earlier and in a different pattern from hand grip strength and knee extension strength in men.

Plasma Tsukushi Concentration Is Associated with High Levels of Insulin and FGF21 and Low Level of Total Cholesterol in a General Population without Medication.

Tsukushi (TSK) is a member of the small leucine-rich proteoglycan family that controls developmental processes and organogenesis. TSK was also identified as a new hepatokine, which is mainly expressed in the liver, and is secreted by hepatocytes, to regulate energy and glycolipid metabolism in response to nonalcoholic fatty liver disease. However, the role of plasma TSK, especially its role in the general population, has not been fully addressed. We investigated the associations between plasma TSK concentration and several metabolic markers, including fibroblast growth factor 21 (FGF21), a hepatokine, and adiponectin, an adipokine, in 253 subjects (men/women: 114/139) with no medication in the Tanno−Sobetsu Study, which employed a population-based cohort. There was no significant sex difference in plasma TSK concentration, and the level was positively correlated with the fatty liver index (FLI) (r = 0.131, p = 0.038), levels of insulin (r = 0.295, p < 0.001) and levels of FGF21 (r = 0.290, p < 0.001), and was negatively correlated with the total cholesterol level (r = −0.124, p = 0.049). There was no significant correlation between the TSK level and body mass index, waist circumference, adiponectin, high-density lipoprotein cholesterol or total bile acids. The multivariable regression analysis showed that high levels of insulin and FGF21 and a low level of total cholesterol were independent determinants of plasma TSK concentration, after adjustment for age, sex and FLI. In conclusion, plasma TSK concentration is independently associated with high levels of insulin and FGF21, a hepatokine, and a low level of total cholesterol, but not with adiposity and adiponectin, in a general population of subjects who have not taken any medications.

Circulating level of fatty acid-binding protein 4 is an independent predictor of metabolic dysfunction-associated fatty liver disease in middle-aged and elderly individuals.

AIMS/INTRODUCTION: Metabolic dysfunction-associated fatty liver disease (MAFLD), defined as hepatosteatosis with type 2 diabetes mellitus, overweight/obesity or metabolic dysregulation, has been proposed as a new feature of chronic liver disease. Fatty acid-binding protein 4 (FABP4) is expressed in adipose tissue, and secreted FABP4 is associated with the development of insulin resistance and atherosclerosis. However, the relationship between MAFLD and FABP4 has not been fully addressed. MATERIALS AND METHODS: Associations of MAFLD with metabolic markers, including FABP4, fibroblast growth factor 21 and adiponectin, were investigated in 627 individuals (men/women 292/335) in the Tanno-Sobetsu Study, a population-based cohort. RESULTS: The mean age was 65 years (range 19-98 years, median [interquartile range] 68 [56-76] years). Hepatosteatosis was determined by the fatty liver index (FLI), and FLI ≥35 for men and FLI ≥16 for women were used for detection of fatty liver, as previously reported using 14,471 Japanese individuals. FLI was positively correlated with systolic blood pressure and levels of FABP4 (r = 0.331, P < 0.001), fibroblast growth factor 21, homeostasis model assessment of insulin resistance as an insulin resistance index and uric acid, and was negatively correlated with levels of high-density lipoprotein cholesterol and adiponectin. FABP4 concentration was independently associated with FLI after adjustment of age, sex, systolic blood pressure and levels of uric acid, high-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21 in multivariable regression analysis. Logistic regression analysis showed that FABP4 was an independent predictor of MAFLD after adjustment of age, sex, presence of diabetes mellitus, hypertension and dyslipidemia, and levels of uric acid, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21. CONCLUSIONS: FABP4 concentration is independently associated with FLI and is an independent predictor of MAFLD in middle-aged and elderly individuals.

Circulating PCSK7 Level is Independently Associated with Obesity, Triglycerides Level and Fatty Liver Index in a General Population without Medication.

AIM: Dyslipidemia and altered iron metabolism are typical features of non-alcoholic fatty liver disease (NAFLD). Proprotein convertase subtilisin/kexin type 7 (PCSK7), a transmembrane-anchored endonuclease, is associated with triglycerides level and processing of transferrin receptor 1. However, the significance of circulating PCSK7 has not been fully addressed, though prosegment PCSK7 is secreted from cells. We investigated the associations of plasma PCSK7 level with several parameters. METHODS: Plasma PCSK7 concentration was measured in 282 subjects (male/female: 126/156) without medication of the Tanno-Sobetsu Study, a population-based cohort study. RESULTS: There was no significant sex difference in PCSK7 level. Current smoking habit, but not alcohol drinking habit, was associated with increased PCSK7 level. PCSK7 concentration was negatively correlated with age and blood urea nitrogen and was positively correlated with body mass index (BMI) and levels of γ-glutamyl transpeptidase (γGTP), triglycerides and fatty liver index (FLI), which is calculated by BMI, waist circumference and levels of γGTP and triglycerides, as a noninvasive and simple predictor of NAFLD. There were no significant correlations of PCSK7 level with levels of iron and plasma PCSK9, a secreted PCSK family member and a regulator of low-density lipoprotein cholesterol level. Multivariable regression analyses after adjustment of age, sex and current smoking habit showed that PCSK7 concentration was independently associated with BMI (ß=0.130, P=0.035), triglycerides (ß=0.141, P=0.027) or FLI (ß=0.139, P=0.030). CONCLUSIONS: Plasma PCSK7 concentration is independently associated with chronic liver disease including obesity and elevated triglycerides level in a general population of individuals who had not regularly taken any medications.

Prediction of Lifetime Risk of Cardiovascular Disease Deaths Stratified by Sex in the Japanese Population.

Background Lifetime risk is an informative estimate for driving lifestyle and behavioral changes especially for young adults. The impact of composite risk factors for cardiovascular disease on lifetime risk stratified by sex has not been investigated in the Japanese population, which has a much lower mortality of coronary heart disease compared with the Western population. We aimed to estimate lifetime risk of death from cardiovascular disease attributable to traditional risk factors. Methods and Results We analyzed pooled individual data from the Evidence for Cardiovascular Prevention from Observational Cohorts in a Japanese cohort study. A modified Kaplan-Meier approach was used to estimate the remaining lifetime risk of cardiovascular death. In total, 41 002 Japanese men and women with 537 126 person-years of follow-up were included. The lifetime risk at the index-age of 45 years for those with optimal risk factors (total cholesterol <4.65 mmol/L, systolic blood pressure <120 mm Hg, diastolic blood pressure <80 mm Hg, absence of diabetes, and absence of smoking habit) was lower compared with the highest risk profile of ≥2 risk factors (6.8% [95% CI, 0%-11.9%] versus 19.4% [16.7%-21.4%] for men and 6.9% [1.2%-11.5%] versus 15.4% [12.6%-18.1%] for women). Conclusions The magnitude and the number of risk factors were progressively associated with increased lifetime risk even in individuals in early adulthood who tend to have low short-term risk. The degree of established cardiovascular risk factors can be converted into lifetime risk. Our findings may be useful for risk communication in the early detection of future cardiovascular disease risk.

Independent Association of Fatty Liver Index With Left Ventricular Diastolic Dysfunction in Subjects Without Medication.

Nonalcoholic fatty liver disease has been reported to be potentially linked to cardiovascular disease. Fatty liver index (FLI) is a noninvasive and simple predictor of nonalcoholic fatty liver disease. However, little is known about the relationship between FLI and cardiac function, especially in a general population. We investigated the relationships of FLI with echocardiographic parameters in 185 subjects (men/women: 79/106) of the Tanno-Sobetsu Study, a population-based cohort, who were not being treated with any medication and who underwent echocardiography. FLI was negatively correlated with high-density lipoprotein cholesterol and peak myocardial velocity during early diastole (e'; r = -0.342, p <0.001), an index of left ventricular (LV) diastolic function, and ratio of peak mitral velocities during early and late diastole (E/A) and was positively correlated with age, systolic and diastolic blood pressures, creatinine, uric acid, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein, ratio of mitral to myocardial early diastolic peak velocity (E/e'), left atrial volume index and LV mass index. No significant correlation was found between FLI and LV ejection fraction. Stepwise multivariable regression analysis showed that FLI was independently and negatively associated with e' after adjustment of age, gender, high-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance, and high-sensitivity C-reactive protein. Conversely, e' was independently and negatively associated with FLI after adjustment of age, gender, systolic blood pressure, and LV ejection fraction. In conclusion, elevated FLI is independently associated with LV diastolic dysfunction in a general population without medication. FLI would be a novel marker of LV diastolic dysfunction as an early sign of myocardial injury.

Distinct Regulation of U-ACE2 and P-ACE2 (Urinary and Plasma Angiotensin-Converting Enzyme 2) in a Japanese General Population.

[Figure: see text].

Independent association of plasma xanthine oxidoreductase activity with hypertension in nondiabetic subjects not using medication.

Xanthine oxidoreductase (XOR), a rate-limiting and catalyzing enzyme of uric acid formation in purine metabolism, is involved in reactive oxygen species generation. Plasma XOR activity has been shown to be a novel metabolic biomarker related to obesity, liver dysfunction, hyperuricemia, dyslipidemia, and insulin resistance. However, the association between plasma XOR activity and hypertension has not been fully elucidated. We investigated the association of hypertension with plasma XOR activity in 271 nondiabetic subjects (male/female: 119/152) who had not taken any medications in the Tanno-Sobetsu Study, a population-based cohort. Males had higher plasma XOR activity than females. Plasma XOR activity was positively correlated with mean arterial pressure (r = 0.128, P = 0.036). When the subjects were divided by the presence and absence of hypertension into an HT group (male/female: 34/40) and a non-HT group (male/female: 85/112), plasma XOR activity in the HT group was significantly higher than that in the non-HT group (median: 39 vs. 28 pmol/h/mL, P = 0.028). There was no significant difference in uric acid levels between the two groups. Multivariable logistic regression analysis showed that plasma XOR activity (odds ratio: 1.091 [95% confidence interval: 1.023-1.177] per 10 pmol/h/mL, P = 0.007) was an independent determinant of the risk for hypertension after adjustment for age, sex, current smoking and alcohol consumption, estimated glomerular filtration rate, brain natriuretic peptide, and insulin resistance index. The interaction of sex with plasma XOR activity was not significant for the risk of hypertension. In conclusion, plasma XOR activity is independently associated with hypertension in nondiabetic individuals who are not taking any medications.

Relationships of Alcohol Consumption with Coronary Risk Factors and Macro- and Micro-Nutrient Intake in Japanese People: The INTERLIPID Study.

Several studies have reported a J-shaped relationship between alcohol consumption and coronary heart disease (CHD) risk. However, the mechanisms of this relationship remain unclear. This study aimed to evaluate the relationships of alcohol consumption with established CHD risk factors and with macro-/micro-nutrient intake among Japanese people. Participants were 1,090 Japanese men and women aged 40-59 y enrolled in the INTERLIPID study, excluding former drinkers. Based on two 7-d alcohol records, participants were classified as non-drinkers (0 g/wk), light-drinkers (<100 g/wk), moderate-drinkers (100-299 g/wk), or heavy-drinkers (≥300 g/wk). Detailed macro-/micro-nutrient intake was evaluated using four in-depth 24-h dietary recalls and adjusted for total energy intake excluding alcohol. We analyzed the associations of CHD risk factors and nutrient intake with alcohol consumption. Serum high-density lipoprotein cholesterol and blood pressure were higher and low-density lipoprotein cholesterol was lower among those with higher alcohol consumption. J-shaped relationships with alcohol consumption were observed for the proportion of current smokers, number of cigarettes smoked, and prevalence of hypertension; these risk factors were lowest among light-drinkers. Carbohydrate and total fiber intakes were lower and protein and dietary cholesterol intakes were higher among those with higher alcohol consumption. These associations were similar for men and women. Alcohol consumption was related to nutrient intake as well as established CHD risk factors. Non-drinkers were higher on some CHD risk factors than were light-drinkers. These findings may influence the J-shaped relationship between alcohol consumption and CHD risk.

Elevated circulating FABP4 concentration predicts cardiovascular death in a general population: a 12-year prospective study.

Fatty acid-binding protein 4 (FABP4) is secreted from adipose tissue and acts as an adipokine, and an elevated circulating FABP4 level is associated with metabolic disorders and atherosclerosis. However, little is known about the causal link between circulating FABP4 level and mortality in a general population. We investigated the relationship between FABP4 concentration and mortality including cardiovascular death during a 12-year period in subjects of the Tanno-Sobetsu Study, a population-based cohort (n = 721, male/female: 302/419). FABP4 concentration at baseline was significantly higher in female subjects than in male subjects. All-cause death occurred in 123 (male/female: 74/49) subjects, and 34 (male/female: 20/14) and 42 (male/female: 26/16) subjects died of cardiovascular events and cancer, respectively. When divided into 3 groups according to tertiles of FABP4 level at baseline by sex (T1-T3), Kaplan-Meier survival curves showed that there were significant differences in rates of all-cause death and cardiovascular death, but not cancer death, among the groups. Multivariable Cox proportional hazard model analysis with a restricted cubic spline showed that hazard ratio (HR) for cardiovascular death, but not that for all-cause death, significantly increased with a higher FABP4 level at baseline after adjustment of age and sex. The risk of cardiovascular death after adjustment of age, sex, body mass index and levels of brain natriuretic peptide and high-sensitivity C-reactive protein in the 3rd tertile (T3) group (HR: 4.96, 95% confidence interval: 1.20-22.3) was significantly higher than that in the 1st tertile (T1) group as the reference. In conclusion, elevated circulating FABP4 concentration predicts cardiovascular death in a general population.

A Combination of Blood Pressure and Total Cholesterol Increases the Lifetime Risk of Coronary Heart Disease Mortality: EPOCH-JAPAN.

AIM: Lifetime risk (LTR) indicates the absolute risk of disease during the remainder of an individual's lifetime. We aimed to assess the LTRs for coronary heart disease (CHD) mortality associated with blood pressure (BP) and total cholesterol levels in an Asian population using a meta-analysis of individual participant data because no previous studies have assessed this risk. METHODS: We analyzed data from 105,432 Japanese participants in 13 cohorts. Apart from grade 1 and 2-3 hypertension groups, we defined "normal BP" as systolic/diastolic BP ＜130/＜80 mmHg and "high BP" as 130-139/80-89 mmHg. The sex-specific LTR was estimated while considering the competing risk of death. RESULTS: During the mean follow-up period of 15 years (1,553,735 person-years), 889 CHD deaths were recorded. The 10-year risk of CHD mortality at index age 35 years was ≤ 0.11%, but the corresponding LTR was ≥ 1.84%. The LTR of CHD at index age 35 years steeply increased with an increase in BP of participants with high total cholesterol levels [≥ 5.7 mmol/L (220 mg/dL)]. This risk was 7.73%/5.77% (95% confidence interval: 3.53%-10.28%/3.83%-7.25%) in men/women with grade 2-3 hypertension and high total cholesterol levels. In normal and high BP groups, the absolute differences in LTRs between the low and high total cholesterol groups were ≤ 0.25% in men and ≤ 0.40% in women. CONCLUSIONS: High total cholesterol levels contributed to an elevated LTR of CHD mortality in hypertensive individuals. These findings could help guide high-risk young individuals toward initiating lifestyle changes or treatments.

Impact of hypertension stratified by diabetes on the lifetime risk of cardiovascular disease mortality in Japan: a pooled analysis of data from the Evidence for Cardiovascular Prevention from Observational Cohorts in Japan study.

Lifetime risk is an informative estimate to motivate people to change lifestyle behaviors, especially from a younger age, in public health education. The impact of the combination of hypertension and diabetes on the lifetime risk of cardiovascular mortality has not been investigated in Asian populations. A pooled analysis of individual data from nine cohorts was performed. A total of 57,339 Japanese men and women were eligible for the analysis. We used the modified Kaplan-Meier approach and estimated the remaining lifetime risk of cardiovascular mortality starting from the index age of 35 years. Participants were classified into four categories defined by hypertension and diabetes. The lifetime risk was increased in the order of those without either risk, those without hypertension but with diabetes, those with hypertension but without diabetes, and those with both risks. The lifetime risk of cardiovascular mortality at the 35-year index age was as follows: 7.8% in men and 6.2% in women for those without either hypertension or diabetes, 13.2% in men and 9.5% in women for those without hypertension but with diabetes, 17.2% in men and 11.7% in women for those with hypertension but without diabetes, and 19.4% in men and 15% in women for those with both risks. These findings reinforce the need for a life-course perspective in the management of hypertension and diabetes from a younger age.

Food Sources of Dietary Potassium in the Adult Japanese Population: The International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP).

A lower-than-recommended potassium intake is a well-established risk factor for increased blood pressure. Although the Japanese diet is associated with higher sodium intake and lower potassium intake, few studies have examined the source foods quantitatively. Studies on dietary patterns in association with potassium intake will be useful to provide dietary advice to increase potassium intake. Twenty-four-hour (hr) dietary recall data and 24-hr urinary potassium excretion data from Japanese participants (574 men and 571 women) in the International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) were used to calculate food sources of potassium and compare food consumption patterns among quartiles of participants categorized according to 24-hr urinary potassium excretion per unit of body weight (UK/BW). The average potassium intake was 2791 mg/day per participant, and the major sources were vegetables and fruits (1262 mg/day), fish (333 mg/day), coffee and tea (206 mg/day), and milk and dairy products (200 mg/day). Participants in the higher UK/BW quartile consumed significantly more vegetables and fruits, fish, and milk and dairy products, and ate less rice and noodles. Conclusion: Advice to increase the intake of vegetables and fruits, fish, and milk may be useful to increase potassium intake in Japan.

Differential regulation of hypoxanthine and xanthine by obesity in a general population.

AIMS/INTRODUCTION: Uric acid is synthesized by oxidation of hypoxanthine and xanthine using a catalyzing enzyme, xanthine oxidoreductase (XOR), which can be a source of reactive oxygen species. Plasma XOR activity is a metabolic biomarker associated with obesity, hyperuricemia, liver dysfunction and insulin resistance. However, it has recently been reported that XOR activity in fat tissue is low in humans, unlike in rodents, and that hypoxanthine is secreted from human fat tissue. MATERIALS AND METHODS: The associations of obesity with hypoxanthine, xanthine and plasma XOR activity were investigated in 484 participants (men/women: 224/260) of the Tanno-Sobetsu Study. RESULTS: Levels of hypoxanthine, xanthine and plasma XOR activity were significantly higher in men than in women. In 59 participants with hyperuricemia, 11 (men/women: 11/0) participants were being treated with an XOR inhibitor and had a significantly higher level of xanthine, but not hypoxanthine, than that in participants without treatment. In all of the participants, hypoxanthine concentration in smokers was significantly higher than that in non-smokers. Stepwise and multivariate regression analyses showed that body mass index, smoking habit and xanthine were independent predictors of hypoxanthine after adjustment of age, sex and use of antihyperuricemic drugs. Whereas, alanine transaminase, hypoxanthine and plasma XOR activity were independent predictors for xanthine, and alanine transaminase, triglycerides and xanthine were independent predictors for plasma XOR activity. CONCLUSIONS: The concentration of hypoxanthine, but not that of xanthine, is independently associated with obesity and smoking habit, indicating differential regulation of hypoxanthine and xanthine in a general population.