Sayuki Torii

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.

Lifetime cigarette smoking is associated with abdominal obesity in a community-based sample of Japanese men: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA)

Studies from Western countries suggest that smokers tend to display greater abdominal obesity than non-smokers, despite showing lower weight. Whether this holds true in a leaner population requires clarification. Using indices of abdominal obesity including visceral adipose tissue, we examined whether lifetime cigarette smoking is associated with unfavorable fat distribution among Japanese men. From 2006 to 2008, we conducted a cross-sectional investigation of a community-based sample of Japanese men at 40–64 years old, free of cardiovascular diseases and cancer. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography. We divided participants into four groups: never-smokers; and tertiles of pack-years of smoking among ever-smokers. Using multivariable linear regression, we calculated adjusted means of obesity indices (VAT, SAT, VAT-SAT ratio [VSR], and waist-hip ratio [WHR]) for each group, and mean differences between consecutive groups. We analyzed 513 men (median age, 58.2 years; current smokers, 40.1%). Two-thirds showed body mass index (BMI) < 25 kg/m2 (median, 23.5 kg/m2). Overall, greater lifetime smoking group was associated with greater WHR and VSR. On average, one higher smoking group was associated with 0.005 higher WHR (95% CI, 0.001–0.008; P = 0.005) and 0.041 greater VSR (95% CI, 0.009–0.073; P = 0.012) after adjustment for potential confounders, including BMI. In this sample of relatively lean Japanese men, greater lifetime smoking was associated with a metabolically more adverse fat distribution. Although smoking is commonly associated with lower BMI, minimizing the amount of lifetime smoking should be advocated.

Four to seven random casual urine specimens are sufficient to estimate 24-h urinary sodium/potassium ratio in individuals with high blood pressure.

This study was done to clarify the optimal number and type of casual urine specimens required to estimate urinary sodium/potassium (Na/K) ratio in individuals with high blood pressure. A total of 74 individuals with high blood pressure, 43 treated and 31 untreated, were recruited from the Japanese general population. Urinary sodium, potassium and Na/K ratio were measured in both casual urine samples and 7-day 24-h urine samples and then analyzed by correlation and Bland–Altman analyses. Mean Na/K ratio from random casual urine samples on four or more days strongly correlated with the Na/K ratio of 7-day 24-h urine (r=0.80–0.87), which was similar to the correlation between 1 and 2-day 24-h urine and 7-day 24-h urine (r=0.75–0.89). The agreement quality for Na/K ratio of seven random casual urine for estimating the Na/K ratio of 7-day 24-h urine was good (bias: −0.26, limits of agreements: −1.53–1.01), and it was similar to that of 2-day 24-h urine for estimating 7-day 24-h values (bias: 0.07, limits of agreement: −1.03 to 1.18). Stratified analyses comparing individuals using antihypertensive medication and individuals not using antihypertensive medication showed similar results. Correlations of the means of casual urine sodium or potassium concentrations with 7-day 24-h sodium or potassium excretions were relatively weaker than those for Na/K ratio. The mean Na/K ratio of 4–7 random casual urine specimens on different days provides a good substitute for 1–2-day 24-h urinary Na/K ratio for individuals with high blood pressure.

Relationship of Insulin Resistance to Prevalence and Progression of Coronary Artery Calcification Beyond Metabolic Syndrome Components: Shiga Epidemiological Study of Subclinical Atherosclerosis

Objective—The association between insulin resistance (IR) and coronary artery calcification (CAC) has been uncertain after adjustment for metabolic syndrome components. We aimed to evaluate whether IR is associated with CAC prevalence or progression independently of metabolic syndrome components. Approach and Results—We conducted a population-based study in a random sample of Japanese men aged 40 to 79 years and determined IR using the homeostasis model assessment of insulin resistance (HOMA-IR). The associations of HOMA-IR and other diabetic parameters per 1-SD increase with CAC prevalence and progression were evaluated using multivariable logistic regression. Of 1006 total participants at baseline (mean age, 64±10 years), CAC prevalence was observed in 646 (64.2%), and of 789 participants at follow-up (mean duration, 4.9±1.3 years), CAC progression was observed in 365 (46.3%). After adjustment for covariates including metabolic syndrome components, higher HOMA-IR was independently associated with CAC prevalence (adjusted odds ratio 1.34, 95% confidence interval 1.10–1.63; P=0.003) and progression (odds ratio 1.32, 95% confidence interval 1.09–1.60; P=0.004). In participants without diabetes mellitus, positive associations were similarly observed (prevalence: odds ratio 1.29, 95% confidence interval 1.04–1.60; P=0.022; and progression: odds ratio 1.25, 95% confidence interval 1.01–1.55; P=0.042), whereas glucose and hemoglobin A1c were not associated with CAC prevalence and progression. Conclusions—Higher IR was associated with CAC prevalence and progression independently of metabolic syndrome components in Japanese men and also in those without diabetes mellitus. Among diabetic measures, IR and fasting insulin, but not glucose and hemoglobin A1c, predicted CAC progression in men without diabetes mellitus.

Association between Pulse Wave Velocity and Coronary Artery Calcification in Japanese men.

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.

Diurnal variation of urinary sodium-to-potassium ratio in free-living Japanese individuals

High sodium-to-potassium ratios are associated with elevated blood pressure levels and an increased risk of cardiovascular diseases. We aimed to determine whether urinary sodium-to-potassium ratios fluctuate diurnally during the day to understand measured values of casual urinary sodium-to-potassium ratios. A total of 13,277 casual urine specimens were collected under free-living conditions from 122 Japanese normotensive and hypertensive individuals. Participants collected all casual urine samples in aliquot tubes, reported urine volumes and the time at each voiding for 10–22 days. Then, specimens were classified into hourly data. Diurnal patterns of urinary sodium-to-potassium ratios and urinary concentrations of sodium and potassium were evaluated. Overall mean values of hourly urinary sodium-to-potassium ratios were highest (4.1–5.0) in the early morning, lower (3.3–3.8) in the daytime and higher (4.0–4.4) toward evening hours. The mean urinary sodium and potassium concentrations were the lowest (90–110 and 24–32 mmol l−1, respectively) during the early morning and higher (110–140 and 35–43 mmol l−1, respectively) after mid-morning. Diurnal variability of potassium concentrations was larger than for sodium concentrations. Diurnal variations in urinary sodium-to-potassium ratios were comparable between normotensive and hypertensive individuals, between hypertensive individuals with and without antihypertensive medications, and among age and gender-specific subgroups. Overall mean hourly urinary sodium-to-potassium ratios fluctuated diurnally under free-living conditions and were higher during the morning and evening and lower during the daytime compared with 24-h urinary sodium-to-potassium ratios. Diurnal variation in urinary sodium-to-potassium ratios should be considered to understand actual daily dietary levels and avoid over- and under-estimation in clinical practice.

Effectiveness of a Self-monitoring Device for Urinary Sodium-to-Potassium Ratio on Dietary Improvement in Free-Living Adults: a Randomized Controlled Trial

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.

The Influence of the Japanese Nationwide Cardiovascular Prevention System Health Guidance on Smoking Cessation Among Smokers: A Propensity Score Matching Analysis

Aim: We investigated whether 2 types of personalized health guidance (repeated and single counseling) in the Japanese nationwide cardiovascular prevention system promoted smoking cessation among smokers. Methods: The study included 47,745 Japanese smokers aged 40 to 74 years classified into 2 personalized health guidance schemes. After a 1-year follow-up, we compared the rates of smoking cessation between individuals who had received counseling (“supported”) and those who had not received counseling (“unsupported”). Using propensity score matching analysis, we estimated the average treatment effect (ATE) of each approach on smoking cessation after balancing out the characteristics between the supported and unsupported groups. The propensity score regression model included age, medical insurance type, weight gain since the age of 20 years, exercise, eating habits, alcohol intake, quality of sleep, readiness to modify lifestyle, willingness to receive support, and body mass index. Results: In the repeated counseling scheme, the age-adjusted rates of smoking cessation in the supported and unsupported groups were 8.8% and 6.3% for males, and 9.8% and 9.1% for females respectively. In the single counseling scheme, the corresponding rates were 8.4% and 7.3% for supported and unsupported males, and 11.0% and 11.7% for supported and unsupported females respectively. The ATE of repeated counseling was + 2.64% (95% confidence interval: + 1.51% to + 3.77%) for males and + 3.11% (−1.85% to +8.07%) for females. The ATE of single counseling was +0.61% (−1.17% to +2.38%) for males and −1.06% (−5.96% to +3.85%) for females. Conclusions: In the Japanese cardiovascular prevention system, repeated counseling may promote smoking cessation among male smokers.

Self-reported Sleep Duration and Subclinical Atherosclerosis in a General Population of Japanese Men

Aim: There are few data regarding associations between sleep duration and subclinical atherosclerosis in Japan. The aim of this study was to evaluate associations of self-reported sleep duration with calcification in the coronary arteries (CAC) and carotid intima media thickness (IMT) in Japanese men. Methods: This was a cross-sectional survey of 1093 randomly selected men from Kusatsu City, Japan. Average sleep duration on weekdays was estimated through questionnaire; CAC by computed tomography; and carotid IMT by ultrasonography. Results: The prevalence of CAC was 50.0% for participants with sleep duration < 5.5 h, 43.9% with 5.5–6.4 h, 50.0% with 6.5–7.4 h, 49.3% with 7.5–8.4 h, and 62.5% with ≥ 8.5 h. In univariate analysis, participants with sleep duration ≥ 8.5 h had significantly higher prevalence of CAC than those with 6.5–7.4 h (p = 0.043). After adjustment for age and other risk factors, however, the association was not significant (p = 0.776). The average IMT was 0.85 mm for participants with sleep duration < 5.5 h, 0.83 mm with 5.5–6.4 h, 0.85 mm with 6.5–7.4 h, 0.88 mm with 7.5–8.4 h, and 0.90 mm with ≥ 8.5 h. None of the differences in IMT observed in crude or multivariable-adjusted analyses was significant (all p > 0.1). Conclusion: Self-reported sleep duration was not associated with increased CAC or carotid IMT in a general population of Japanese men.