Sayaka Kadowaki

Long chain n-3 polyunsaturated fatty acids and incidence rate of coronary artery calcification in Japanese men in Japan and white men in the USA: population based prospective cohort study

Objective To determine whether serum concentrations of long chain n-3 polyunsaturated fatty acids (LCn3PUFAs) contribute to the difference in the incidence rate of coronary artery calcification (CAC) between Japanese men in Japan and white men in the USA. Methods In a population based, prospective cohort study, 214 Japanese men and 152 white men aged 40–49 years at baseline (2002–2006) with coronary calcium score (CCS)=0 were re-examined for CAC in 2007–2010. Among these, 175 Japanese men and 113 white men participated in the follow-up exam. Incident cases were defined as participants with CCS≥10 at follow-up. A relative risk regression analysis was used to model the incidence rate ratio between the Japanese and white men. The incidence rate ratio was first adjusted for potential confounders at baseline and then further adjusted for serum LCn3PUFAs at baseline. Results Mean (SD) serum percentage of LCn3PUFA was >100% higher in Japanese men than in white men (9.08 (2.49) vs 3.84 (1.79), respectively, p<0.01). Japanese men had a significantly lower incidence rate of CAC compared to white men (0.9 vs 2.9/100 person-years, respectively, p<0.01). The incidence rate ratio of CAC taking follow-up time into account between Japanese and white men was 0.321 (95% CI 0.150 to 0.690; p<0.01). After adjusting for age, systolic blood pressure, low density lipoprotein cholesterol, diabetes, and other potential confounders, the ratio remained significant (0.262, 95% CI 0.094 to 0.731; p=0.01). After further adjusting for LCn3PUFAs, however, the ratio was attenuated and became non-significant (0.376, 95% CI 0.090 to 1.572; p=0.18). Conclusions LCn3PUFAs significantly contributed to the difference in the incidence of CAC between Japanese and white men.

Association of serum n−6 and n−3 polyunsaturated fatty acids with lipids in 3 populations of middle-aged men

BACKGROUND The association of serum polyunsaturated fatty acids (PUFAs) with lipids in different populations is not known. OBJECTIVE Our aim was to examine the association of serum n-6 (omega-6) or n-3 (omega-3) PUFAs with triglycerides or HDL-cholesterol concentrations in 261 white, 285 Japanese, and 212 Japanese American men aged 40-49 y. DESIGN We used a population-based cross-sectional study. Of the original sample (n = 926), those taking lipid-lowering medications or who had diabetes (n = 168) were excluded. Serum fatty acids were analyzed by capillary gas-liquid chromatography. Multiple regression models as a function of tertile groups of each PUFA were used. RESULTS Serum n-6 PUFAs were significantly inversely associated with triglycerides across populations after adjustment for age, body mass index, pack-years of smoking, and ethanol consumption [beta = -0.39 (P < 0.001), -0.38 (P < 0.001), and -0.33 (P < 0.001) in whites, Japanese, and Japanese Americans, respectively]. Marine n-3 PUFAs were significantly inversely associated with triglycerides across populations [beta = -0.15 (P < 0.001), -0.22 (P < 0.001), and -0.13 (P < 0.001) in whites, Japanese, and Japanese Americans, respectively]. n-6 PUFAs were significantly positively associated with HDL cholesterol in whites (beta = 4.49, P < 0.001) and Japanese (beta = 3.73, P < 0.01). Marine n-3 PUFAs were significantly positively associated with HDL cholesterol in Japanese (beta = 2.15, P < 0.05), and eicosapentaenoic acid was significantly positively associated with HDL cholesterol in whites (beta = 2.68, P < 0.01). CONCLUSION Serum n-6 and n-3 PUFAs are inversely associated with triglycerides across populations.

Visceral and Subcutaneous Adiposity and Adiponectin in Middle-aged Japanese Men: The ERA JUMP Study

Adiponectin is reduced in obesity and has been suggested to play an important role in modulation of atherosclerosis. We studied the relationship between visceral (VAT) and subcutaneous (SAT) adipose tissue and serum adiponectin concentrations in Japanese men. Participants were 304 randomly selected community‐based Japanese men aged 40–49 without a prior history of cardiovascular disease. Participants were grouped according to tertiles of serum adiponectin. In multiple linear regression analysis including age, pack years of smoking, and alcohol intake as covariates, log‐transformed adiponectin was inversely associated with both VAT and SAT when these two obesity measures were included separately in the models. However, log‐transformed adiponectin was inversely associated with VAT (standardized β estimate = −0.465; P < 0.0001) and positively associated with SAT (standardized β estimate = 1.277; P = 0.03), when these were included concomitantly in the model. In conclusion, VAT and SAT had differential associations with serum adiponectin concentrations.

Higher liver fat content among Japanese in Japan compared with non-Hispanic whites in the United States

Among Asians, including Japanese, obesity is related to dyslipidemia and insulin resistance at a lower level of body mass index (BMI) compared with non-Hispanic whites (NHW). We hypothesize that this ethnic difference in the relationship between BMI and metabolic risks is partly associated with the ethnic difference in fat distribution, namely, liver fat as well as visceral adipose tissue. To compare liver fat content among Japanese vs NHW men, regional computed tomographic images were taken to measure liver computed tomographic density in population-based samples of 313 Japanese and 288 NHW men aged 40 to 49 years, along with the assessment of metabolic parameters. Liver fat content was higher in Japanese than NHW men (liver to spleen attenuation ratio [lower value means higher liver fat content]: 1.01 +/- 0.16 vs 1.07 +/- 0.15, respectively; P < .01), despite a lower mean BMI in Japanese men (BMI: 23.6 +/- 2.9 vs 27.8 +/- 4.2 kg/m(2), P < .01). Moreover, Japanese men had a greater disposition for fatty liver with a small increase in BMI than NHW (P < .01), whereas both groups had a similar relationship between visceral adipose tissue and BMI. In both groups, liver fat content correlated with triglycerides, homeostasis model assessment of insulin resistance, and C-reactive protein. Liver fat content is higher among Japanese than NHW; and this ethnic difference becomes more robust with a small increase in BMI, suggesting that fatty liver is a sensitive marker for the failure of the adipose tissue to expand to accommodate an increased energy influx, and is associated with similar metabolic risk in Japanese despite lower BMI compared with NHW men.

Cross-Sectional Comparison of Coronary Artery Calcium Scores Between Caucasian Men in the United States and Japanese Men in Japan The Multi-Ethnic Study of Atherosclerosis and the Shiga Epidemiological Study of Subclinical Atherosclerosis

The incidence of coronary heart disease in the United States has declined, and prevalences of several coronary disease risk factors have become comparable to those in Japan. Therefore, the burden of coronary atherosclerosis may be closer among younger persons in the 2 countries. We aimed to compare prevalences of coronary atherosclerosis, measured with coronary artery calcium scores, between men in the 2 countries by age group (45-54, 55-64, or 65-74 years). We used community-based samples of Caucasian men in the United States (2000-2002; n = 1,067) and Japanese men in Japan (2006-2008; n = 832) aged 45-74 years, stratifying them into groups with 0, 1, 2, or ≥3 of the following risk factors: current smoking, overweight, diabetes, dyslipidemia, and hypertension. We calculated adjusted odds ratios of US Caucasian mens having Agatston scores of ≥10, ≥100, and ≥400 with reference to Japanese men. Overall, the odds of Caucasian men having each Agatston cutoff point were greater. The ethnic difference, however, became smaller in younger age groups. For example, adjusted odds ratios for Caucasian mens having an Agatston score of ≥100 were 2.05, 2.43, and 3.86 among those aged 45-54, 55-64, and 65-74 years, respectively. Caucasian men in the United States had a higher burden of coronary atherosclerosis than Japanese men, but the ethnic difference was smaller in younger age groups.

A cross-sectional association of obesity with coronary calcium among Japanese, Koreans, Japanese Americans, and US Whites

AIMS Conflicting evidence exists regarding whether obesity is independently associated with coronary artery calcium (CAC), a measure of coronary atherosclerosis. We examined an independent association of obesity with prevalent CAC among samples of multi-ethnic groups whose background populations have varying levels of obesity and coronary heart disease (CHD). METHODS AND RESULTS We analysed a population-based sample of 1212 men, aged 40-49 years free of clinical cardiovascular disease recruited in 2002-06; 310 Japanese in Japan (JJ), 294 Koreans in South Korea (KN), 300 Japanese Americans (JA), and 308 Whites in the USA (UW). We defined prevalent CAC as an Agatston score of ≥10. Prevalent CAC was calculated by tertile of the body mass index (BMI) in each ethnic group and was plotted against the corresponding median of tertile BMI. Additionally, logistic regression was conducted to examine whether an association of the BMI was independent of conventional risk factors. The median BMI and crude prevalence of CAC for JJ, KN, JA, and UW were 23.4, 24.4, 27.4, and 27.1 (kg/m2); 12, 11, 32, and 26 (%), respectively. Despite the absolute difference in levels of BMI and CAC across groups, higher BMI was generally associated with higher prevalent CAC in each group. After adjusting for age, smoking, alcohol, hypertension, lipids, and diabetes mellitus, the BMI was positively and independently associated with prevalent CAC in JJ, KN, UW, but not in JA. CONCLUSION In this multi-ethnic study, obesity was independently associated with subclinical stage of coronary atherosclerosis among men aged 40-49 years regardless of the BMI level.

Lipoprotein-associated phospholipase A2 is related to risk of subclinical atherosclerosis but is not supported by Mendelian randomization analysis in a general Japanese population

OBJECTIVE Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme predominantly bound to low-density lipoprotein (LDL). Lp-PLA2 is recognized as playing a key role in inflammatory processes and the development of atherosclerosis. This study aimed to investigate whether Lp-PLA2 is related to subclinical atherosclerosis, independently from traditional risk factors, in a general Japanese population by analyses of both the observational study and Mendelian randomization using V279F polymorphism. METHODS AND RESULTS We cross-sectionally examined community-based sample of 929 Japanese men aged 40-79 years, without statin treatment, who were randomly selected from the resident registration. Multiple regression analyses of Lp-PLA2 activity and concentration were undertaken separately for men aged 40-49 years and 50-79 years, to clarify interactions of age and Lp-PLA2. Lp-PLA2 activity for men aged 50-79 years was significantly and positively related to intima-media thickness (IMT) (P = 0.013) and plaque index (P = 0.008) independent of traditional risk factors including small LDL particles, but not to coronary artery calcification (CAC) score. Associations with Lp-PLA2 concentration were qualitatively similar to those of activity. Corresponding relationships were not observed in men aged 40-49 years. Mendelian randomization analyses based on V279F genotype did not show any significant associations with subclinical atherosclerosis, although the homozygote and heterozygote of V279F showed low Lp-PLA2 activity and concentration. CONCLUSIONS Lp-PLA2 activity in Japanese men aged 50-79 years was associated significantly and positively with IMT and plaque in the carotid artery but Mendelian randomization did not support that Lp-PLA2 is a causative factor for subclinical atherosclerosis.

Smoking, Smoking Cessation, and Measures of Subclinical Atherosclerosis in Multiple Vascular Beds in Japanese Men

Background Smoking is an overwhelming, but preventable, risk factor for cardiovascular diseases (CVD), although smoking prevalence remains high in developed and developing countries in East Asia. Methods and Results In a population‐based sample of 1019 Japanese men aged 40 to 79 years, without CVD, we examined cross‐sectional associations of smoking status, cumulative pack‐years, daily consumption, and time since cessation, with subclinical atherosclerosis at 4 anatomically distinct vascular beds, including coronary artery calcification, carotid intima‐media thickness (CIMT) and plaque, aortic artery calcification (AoAC), and ankle‐brachial index. Current, former, and never smoking were present in 32.3%, 50.0%, and 17.7%, respectively. Compared to never smokers, current smokers had significantly higher risks of subclinical atherosclerosis in all 4 circulations (eg, odds ratios for coronary artery calcification >0, 1.79 [95% CIs, 1.16–2.79]; CIMT >1.0 mm, 1.88 [1.02–3.47]; AoAC >0, 4.29 [2.30–7.97]; and ankle‐brachial index <1.1, 1.78 [1.16–2.74]) and former smokers did in carotid and aortic circulations (CIMT >1.0 mm, 1.94 [1.13–3.34]; and AoAC >0, 2.55 [1.45–4.49]). Dose–response relationships of pack‐years and daily consumption, particularly with CIMT, carotid plaque, AoAC, and ankle‐brachial index, were observed among both current and former smokers, and even a small amount of pack‐years or daily consumption among current smokers was associated with coronary artery calcification and AoAC, whereas time since cessation among former smokers was linearly associated with lower burdens of all atherosclerotic indices. Conclusions Cigarette smoking was strongly associated with subclinical atherosclerosis in multiple vascular beds in Japanese men, and these associations attenuated with time since cessation.

Lipoprotein particle profiles compared with standard lipids in association with coronary artery calcification in the general Japanese population

OBJECTIVE The utility of lipoprotein particle profiles measured by nuclear magnetic resonance (NMR) spectroscopy beyond standard serum lipids remains inconclusive. Furthermore, few studies have compared NMR measurements with standard lipids in association with coronary artery calcification (CAC) in Japanese, where the coronary atherosclerotic burden is low. We examined whether NMR-based lipoprotein particle profiles are associated with CAC, and compared them with standard lipid and lipid ratios in the Japanese general population. METHODS AND RESULTS We conducted a cross-sectional study in 851 men aged 40-79 years without cardiovascular diseases and lipid-lowering therapies. Adjusted odds ratios (ORs) (95% confidence intervals) for the top versus the bottom quartile of NMR-measured particle concentrations were 2.01 (1.24-3.23) for low-density lipoprotein (LDL-P), 1.04 (0.62-1.75) for high-density lipoprotein (HDL-P), 1.82 (1.13-2.95) for very-low-density lipoprotein (VLDL-P), and 1.92 (1.18-3.17) for LDL-P/HDL-P ratio. Similarly adjusted ORs of NMR-measured particle sizes were 0.59 (0.36-0.97) for LDL-P, 0.66 (0.40-1.10) for HDL-P, and 0.67 (0.40-1.12) for VLDL-P. The corresponding ORs were 1.82 (1.14-2.90) for total cholesterol (TC), 2.06 (1.28-3.30) for low-density lipoprotein cholesterol (LDL-C), 0.56 (0.34-0.91) for high-density lipoprotein cholesterol (HDL-C), 2.02 (1.24-3.29) for triglycerides, 2.08 (1.29-3.36) for non-high-density lipoprotein cholesterol (non-HDL-C), 2.27 (1.37-3.78) for TC/HDL-C ratio, and 1.73 (1.06-2.85) for LDL-C/HDL-C ratio. After mutual adjustment for total LDL-P concentration and TC/HDL-C ratio or non-HDL-C, LDL-P was no longer associated, whereas TC/HDL-C ratio remained significantly associated with CAC. CONCLUSIONS In community-based Japanese men, the overall association of CAC with NMR-measured lipoprotein indices is comparable, but not superior, to that with standard lipids.

Alcohol intake and 19-year mortality in diabetic men: NIPPON DATA80

Although moderate alcohol intake in diabetic Caucasians is associated with a reduction in coronary heart disease mortality, no study in Japanese with diabetes has examined the association between alcohol intake and mortality outcomes. We analyzed the relationship between alcohol intake and all-cause and cause-specific mortality using the database from NIPPON DATA80. At the baseline in 1980, data on history, lifestyle, and physical examinations were collected on study participants aged 30 years and older from randomly selected areas in Japan. After excluding participants with comorbidities, we followed 4,018 male participants (3,614 nondiabetics, 195 with impaired glucose tolerance and 209 diabetic) for 19 years. During the 19 years of follow-up, there were 990 deaths; 328 were from cardiovascular disease and 157 from all-heart diseases. With the never-drinking category serving as a reference, the Cox multivariate-adjusted hazard ratios for non-daily and daily drinkers for cardiovascular mortality were 0.43 (95% confidence intervals: 0.19-0.95) and 0.45 (0.25-0.80), respectively, and 0.33 (0.12-0.91) and 0.31 (0.15-0.67) for all-heart disease mortality in the combined impaired glucose tolerance and diabetic Japanese men. Alcohol drinking in men with glucose intolerance was associated with a significant reduction in cardiovascular and all-heart disease mortality as seen in the general population in Japan.