Naoko Miyagawa

Impact of metabolic syndrome on the risk of cardiovascular disease mortality in the united states and in Japan

The United States has a higher prevalence of metabolic syndrome (MS) and cardiovascular disease (CVD) mortality than Japan, but it is unknown how much of the difference in MS accounts for the mortality difference. The aim of this study was to examine the impact of MS on the excess CVD mortality in the United States compared with that in Japan. Data from the United States Third National Health and Nutrition Examination Survey (NHANES III; n = 12,561) and the Japanese National Integrated Project for Prospective Observation of Noncommunicable Disease and Its Trends in Aged (NIPPON DATA; n = 7,453) were analyzed. MS was defined as ≥3 of 5 risk factors (obesity, high blood pressure, decreased high-density lipoprotein cholesterol, elevated glycosylated hemoglobin, and elevated triglycerides). The results show that after a median of 13.8 years of follow-up in the United States, 1,683 patients died from CVD (11.75 per 1,000 person-years), and after a median of 15 years of follow-up in Japan, 369 patients died from CVD (3.56 per 1,000 person-years). The age-adjusted prevalence of MS was 26.7% in the United States and 19.3% in Japan. Of 5 MS factors, obesity, high blood pressure, elevated triglycerides, and glycosylated hemoglobin in the United States, and high blood pressure and elevated glycosylated hemoglobin in Japan were significant risk factors for CVD mortality. Estimates of 13.3% and 44% of the excess CVD mortality for the United States could be explained by the higher prevalence of MS and MS plus baseline CVD history than in Japan. In conclusion, the present study is the first to quantitatively demonstrate that MS and MS plus baseline CVD history may significantly contribute to the explanation of excess CVD mortality in the United States compared with Japan.

Long-term risk of BP values above normal for cardiovascular mortality: a 24-year observation of Japanese aged 30 to 92 years.

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-chain n-3 polyunsaturated fatty acids intake and cardiovascular disease mortality risk in Japanese: A 24-year follow-up of NIPPON DATA80

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.

Fruit and vegetable intake and mortality from cardiovascular disease in Japan: a 24-year follow-up of the NIPPON DATA80 Study

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.

Six random specimens of daytime casual urine on different days are sufficient to estimate daily sodium/potassium ratio in comparison to 7-day 24-h urine collections.

The objective of this study was to determine the optimal number and type of casual (spot) urine specimens required to estimate an individual’s urinary sodium/potassium (Na/K) ratio. A total of 48 participants, 25 men and 23 women, aged between 25 and 59 years, was recruited from healthy volunteers. The Na/K ratio in each casual urine and 7-day 24-h urine sample was measured. Correlation analysis and the quality of agreement by the Bland and Altman method between casual urine and 24-h urine were analyzed. The mean Na/K ratio of 7-day 24-h urine was 4.3. The mean Na/K ratio of six random specimens of daytime (collected between 09 and 17 hours) casual urine correlated most strongly with the Na/K ratio of 7-day 24-h urine (r=0.87). The bias for the mean Na/K ratio between 7-day 24-h urine and daytime casual urine was almost negligible (0.03), and the quality of agreement for the mean of the six random, daytime casual urine specimens on different days was similar to that of the 2-day 24-h urine samples for estimating 7-day 24-h values. Our findings show that the mean Na/K ratio of six random daytime casual urine specimens on different days was a good substitute for the 2-day 24-h urine Na/K ratio.

Low-carbohydrate diets and cardiovascular and total mortality in Japanese: a 29-year follow-up of NIPPON DATA80.

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.

Secular trends of the impact of overweight and obesity on hypertension in Japan, 1980–2010

The prevalence of overweight (body mass index (BMI)=25.0–29.9 kg m−2) and obesity (⩾30.0 kg m−2) has been increasing over the last several decades in Japan. We examined trends of the impact of overweight and obesity on hypertension (systolic/diastolic blood pressure ⩾140/90 mm Hg or antihypertensive drugs use) using four national surveys in Japan, from which the participants were randomly sampled from the entire population. Study participants aged 30–79 years were selected for each survey (10 370 in 1980, 8005 in 1990, 5327 in 2000 and 2547 in 2010). The results showed that the impact of overweight and obesity on hypertension had increased significantly (P=0.040 and 0.006 in men and women, respectively). From 1980 to 2010, the multivariable-adjusted odds ratios for hypertension, comparing overweight and obesity with normal weight (BMI =18.5–24.9 kg m−2), went from 1.94 (95% confidence intervals: 1.64, 2.28) to 2.82 (2.07, 3.83) in men, and from 2.37 (2.05, 2.73) to 3.48 (2.57, 4.72) in women. Most of the association was observed in overweight participants, as only 3% of the Japanese were obese. In addition to the relationship between excessive BMI and other adverse health conditions, the rise in the association with hypertension increases the urgency in addressing weight control. We need to address the overweight and obesity epidemic.

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.