The gut microbiota and coronary artery calcification in Japanese men.

BACKGROUND: The gut microbiota differs between patients with coronary artery disease (CAD) and healthy controls; however, it currently remains unclear whether these differences exist prior to the onset of CAD. We herein investigated the gut microbiota associated with subclinical coronary artery calcification (CAC) in a Japanese population. METHODS: A total of 663 Japanese men were enrolled in this cross-sectional study. Computed tomography and gut microbiology tests were performed, and CAC scores were calculated using the Agatston method. Participants were categorized into 4 groups based on their CAC scores: CAC = 0, 0

Proteinuria and Reduced Estimated Glomerular Filtration Rate are Independently Associated With Lower Cognitive Abilities in Apparently Healthy Community-Dwelling Elderly Men in Japan: A Cross-sectional Study.

BACKGROUND: The association of proteinuria and reduced estimated glomerular filtration rate (eGFR) with cognition needs more clarification. We cross-sectionally examined whether proteinuria and reduced eGFR, even in moderate stages, were independently associated with lower cognition in a community-based sample of elderly men. METHODS: Our cohort initially comprised 1,094 men aged 40-79 years from a random sample from Shiga, Japan in 2006-2008. Of 853 men who returned for the follow-up examination (2009-2014), we analyzed 561 who were ≥65 years, free of stroke, and completed the Cognitive Abilities Screening Instrument (CASI) at follow-up (higher CASI scores [range 0 to 100] indicate better cognition). Proteinuria was assessed via dipstick. eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration Equation. Participants were divided into three groups either by eGFR (≥60, 59-40, and <40 mL/min/1.73 m2) or by proteinuria (no, trace, and positive), considered normal, moderate, and advanced, respectively. Using linear regression, we computed mean CASI score, with simultaneous adjustment for proteinuria and eGFR in addition to other potential confounders. RESULTS: Significant trends of lower cognition were observed across the groups of worse proteinuria and lower eGFR independently: multivariable-adjusted mean CASI scores were 90.1, 89.3, and 88.4 for proteinuria (Ptrend = 0.029), and 90.0, 88.5, and 88.5 for eGFR (Ptrend = 0.015) in mutual-adjustment model. CONCLUSIONS: Proteinuria and reduced eGFR, even in their moderate stages, were independently associated with lower cognition in a community-based sample of elderly men. The results suggest the importance of proteinuria and low eGFR for early detection and prevention of cognitive decline.

Association of Alcohol Consumption With Fat Deposition in a Community-Based Sample of Japanese Men: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA).

BACKGROUND: Excessive alcohol intake has been shown to be associated with cardiovascular disease via metabolic pathways. However, the relationship between alcohol intake and obesity has not been fully elucidated. We aimed to examine the association of alcohol consumption with fat deposition and anthropometric measures. METHODS: From 2006-2008, we conducted a cross-sectional study in a population-based sample of Japanese men aged 40 through 79 years. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography imaging. Based on a questionnaire, we classified participants into five groups according to weekly alcohol consumption, excluding former drinkers: non-drinkers (0 g/week), 0.1-160.9, 161-321.9, 322-482.9, and ≥483 g/week. Multivariable linear regression was used to estimate adjusted means of obesity indices for each group. RESULTS: We analyzed 998 men (mean age and body mass index [BMI], 63.8 years and 23.6 kg/m2, respectively). Higher weekly alcohol consumption was strongly and significantly associated with higher abdominal VAT area, percentage of VAT, and VAT-to-SAT ratio (all P for trend <0.001), and also with waist circumferences and waist-to-hip ratio (P for trend = 0.042 and 0.007, respectively). These associations remained significant after further adjustment for BMI, whereas alcohol consumption had no significant association with abdominal SAT area. CONCLUSIONS: Higher alcohol consumption was associated with higher VAT area, VAT%, and VAT-to-SAT ratio, independent of confounders, including BMI, in general Japanese men. These results suggest that alcohol consumption may have a potential adverse effect on visceral fat deposition.

Change in Pericardial Fat Volume and Cardiovascular Risk Factors in a General Population of Japanese Men.

BACKGROUND: Pericardial fat volume (PFV), defined as the volume of ectopic fat in and around the heart, is associated with the atherosclerotic process in coronary arteries. The magnitude of change in PFV over time and the factors affecting this change in a general population, however, have not been investigated. Methods and Results: Cardiac computed tomography (CT) was carried out at baseline and at follow-up in 623 Japanese men aged 40-79 years without a history of cardiovascular disease who were selected randomly in Kusatsu (Shiga, Japan). PFV was measured on cardiac CT in a qualified laboratory. Age, heart rate, triglycerides, and obesity measurements (weight, body mass index, and waist circumference) were significantly and positively associated with PFV at baseline. Over an average interval of 4.7 years, median PFV increased significantly from 64.1 cm3 (IQR, 47.2-90.0 cm3) to 73.6 cm3 (IQR, 53.3-98.1 cm3; P<0.001). Current smoking and heart rate were significantly and independently associated with changes in PFV (B=3.336, P<0.001 and B=6.409, P=0.003, respectively). CONCLUSIONS: PFV increased significantly over time in a population-based observational study of Japanese men. PFV change was significantly and independently associated with smoking status and heart rate, suggesting that quitting smoking might help reduce PFV, which could be expected to decrease the risk of coronary artery disease.

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.

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 men's 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 men's 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.

Association of Anthropometric and CT-Based Obesity Indices with Subclinical Atherosclerosis.

AIM: Few studies have compared the strength in the associations of anthropometric and computed tomography (CT)-based obesity indices with coronary artery calcification (CAC), aortic artery calcification (AoAC), and aortic valve calcification (AVC). METHODS: We assessed cross-sectcional associations of anthropometric and CT-based obesity indices with CAC, AoAC, and AVC. Anthropometric measures included body mass index (BMI), waist circumference, hip ircumference, waist-to-hip circumference ratio, and waist-to-height ratio in 931 men (mean age, 63.7 years) from a population-based cohort. CT images at the L4/5 level were obtained to calculate the areas of abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), total adipose tissue (TAT), VAT-to-SAT ratio (VSR), and VAT-to-TAT ratio (VTR). CAC, AoAC, and AVC were quantified using the Agatston score based on CT scanning. RESULTS: CAC, AVC, and AoAC were present in 348 (62.6%), 173 (18.6%), and 769 (82.6%) participants, respectively. In multivariable models adjusting for age, lifestyle factors, and CT types (electron beam CT and multidetector row CT), anthropometric and CT-based obesity indices were positively associated with CAC (p＜0.01). Conversely, VAT-to-SAT ratio and VAT-to-TAT ratio were positively associated with AoAC (p＜0.01). Any obesity indices were not associated with AVC. CONCLUSIONS: The strength of the associations of obesity indices with subclinical atherosclerosis varied according to the anatomically distinct atherosclerotic lesions, among men.

Heart Rate Fragmentation, Ambulatory Blood Pressure, and Coronary Artery Calcification: A Population-Based Study.

Background: Little is known regarding whether ultra-rapid patterns of heart rate variability (eg, heart rate fragmentation [HRF]) are associated with coronary artery calcification (CAC) in a general population. Objectives: This study aimed to assess the association between HRF and CAC, and whether these associations are independent of systolic blood pressure (SBP) levels. Methods: From SESSA (the Shiga Epidemiological Study of Subclinical Atherosclerosis), we used data from 24-hour ambulatory blood pressure monitoring to identify awake and asleep SBP levels, and data from concurrent 24-hour Holter monitoring to quantify HRF using the awake and asleep percentage of inflection points (PIP). CAC on computed tomography scanning was quantified using an Agatston score. We used multivariable binomial logistic regression to assess the associations of PIP and ambulatory SBP with the presence of CAC, as defined by Agatston score >0. Results: Of the 508 participants in this study (mean age: 66.5 ± 7.3 years), 325 (64%) had CAC and 183 (36%) did not. In fully adjusted models of prevalent CAC that also included office SBP, the ORs with 95% CIs for awake PIP, awake SBP, asleep PIP, and asleep SBP were 1.23 (95% CI: 0.99-1.54), 1.40 (95% CI: 1.11-1.77), 1.31 (95% CI: 1.05-1.62), and 1.28 (95% CI: 1.02-1.60), respectively. There was no evidence of interaction between PIP and ambulatory SBP in association with CAC. Results were similar when other HRF indices instead of PIP were used. Conclusions: Higher HRF and SBP levels during sleep are each associated with the presence of CAC in a general male population.

Association of step counts with cognitive function in apparently healthy middle-aged and older Japanese men.

Background: Increasing physical activity may prevent cognitive decline. Previous studies primarily focused on older adults and used self-reported questionnaires to assess physical activity. We examined the relationship between step count, an objective measure of physical activity, and cognitive function in community-based middle-aged and older Japanese men. Methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis randomly recruited community-dwelling healthy men aged 40-79 years from Shiga, Japan, and measured their step counts over 7 consecutive days using a pedometer at baseline (2006-2008). Among men who returned for follow-up (2009-2014), we assessed their cognitive function using the Cognitive Abilities Screening Instrument (CASI) score. We restricted our analyses to those with valid 7-day average step counts at baseline and those who remained free of stroke at follow-up (n = 676). Using analysis of covariance, we calculated the adjusted means of the CASI score according to the quartiles of the average step counts. Results: The mean (standard deviation) of age and unadjusted CASI score were 63.8 (9.1) years and 90.8 (5.8), respectively. The CASI score was elevated in higher quartiles of step counts (90.2, 90.4, 90.6, and 91.8 from the lowest to the highest quartile, respectively, [p for trend = 0.004]) in a model adjusted for age and education. Further adjustment for smoking, drinking, and other cardiovascular risk factors resulted in a similar pattern of association (p for trend = 0.005). Conclusion: In apparently healthy middle-aged and older Japanese men, a greater 7-day average step count at baseline was associated with significantly higher cognitive function score.

Significant inverse associations of serum n-6 fatty acids with plasma plasminogen activator inhibitor-1.

Epidemiological studies suggested that n-6 fatty acids, especially linoleic acid (LA), have beneficial effects on CHD, whereas some in vitro studies have suggested that n-6 fatty acids, specifically arachidonic acid (AA), may have harmful effects. We examined the association of serum n-6 fatty acids with plasminogen activator inhibitor-1 (PAI-1). A population-based cross-sectional study recruited 926 randomly selected men aged 40-49 years without CVD during 2002-2006 (310 Caucasian, 313 Japanese and 303 Japanese-American men). Plasma PAI-1 was analysed in free form, both active and latent. Serum fatty acids were measured with gas-capillary liquid chromatography. To examine the association between total n-6 fatty acids (including LA and AA) and PAI-1, multivariate regression models were used. After adjusting for confounders, total n-6 fatty acids, LA and AA, were inversely and significantly associated with PAI-1 levels. These associations were consistent across three populations. Among 915 middle-aged men, serum n-6 fatty acids had significant inverse associations with PAI-1.

A Comparison of Segment-Specific and Composite Measures of Carotid Intima-Media Thickness and their Relationships with Coronary Calcium.

AIMS: The utility of carotid intima-media thickness (cIMT) as a marker for coronary heart disease is under heavy debate. This is predominantly due to the lack of a standard definition of cIMT, leading to inconsistent results. We investigated and compared the relationships of five different measures of cIMT with coronary calcium. METHODS: Japanese men aged 40-79y ( n=869) from Shiga Epidemiological Study of Subclinical Atherosclerosis were examined. Mean cIMT was measured in three segments of the carotid arteries: common carotid artery (CCAmean), internal carotid artery (ICAmean) and bifurcation (Bifmean). Mean cIMT of average values (Mean cIMT) and mean cIMT of maximum values (Mean-Max cIMT) of all segments combined were assessed. Coronary calcium was assessed as coronary artery calcification (CAC). Ordinal logistic regression was used to determine the odds ratio (OR) of higher CAC per 1 standard deviation higher cIMT measure. Analyses were adjusted for cardiovascular covariates and stratified by age quartiles. RESULTS: All cIMT measures had positive associations with CAC (p＜0.001): [OR, 95% Confidence Interval]: ICAmean [1.23, 1.07-1.42], CCAmean [1.27, 1.08-1.49], Bifmean [1.33, 1.15-1.53], Mean cIMT [1.42, 1.22-1.66], and Mean-Max [1.50, 1.28-1.75]. In age-stratified analyses, only Mean-Max cIMT maintained a significant relationship with CAC in every age quartile (p＜0.05), while CCAmean had some of the weakest associations among age quartiles. CONCLUSIONS: Mean-Max cIMT had consistently stronger associations with coronary calcium, independent of important confounders, such as age. The most oft-used measure, CCAmean, was no longer associated with coronary calcium after age-adjustment and stratification.

Relationship between Kidney Function and Subclinical Atherosclerosis Progression Evaluated by Coronary Artery Calcification.

AIMS: The roles of urinary albumin, eGFRcystatin (eGFRcys), and eGFRcreatinine (eGFRcre) in the progression of coronary artery calcification (CAC) remain unclear. Therefore, the present study investigated the relationship between kidney function and CAC progression. METHODS: A total of 760 Japanese men aged 40-79 years were enrolled in this population-based study. Kidney function was measured using eGFRcre, eGFRcys, and the urine albumin-to-creatinine ratio. CAC scores were calculated using the Agatston method. CAC progression was defined as an annual increase of ＞10 Agatston units (AU) among men with 0＜CAC＜100 AU at baseline, that of ＞10% among those with CAC ≥ 100 AU, and any progression for those with CAC=0 at baseline. The relative risk (RR) of CAC progression based on kidney function was assessed using a robust Poisson regression model. RESULTS: The mean follow-up period was 4.9 years. CAC progression was detected in 45.8% of participants. Positive associations between CAC progression and albuminuria (＞30mg/g) (RR: 1.29; 1.09 to 1.53; p=0.004) and low eGFRcys (＜60ml/min/1.73m2) (RR: 1.27; 1.05 to 1.53; p=0.012) remained significant after adjustments for age, the follow-up time, and computerized tomography type. Following further adjustments for hypertension, diabetes mellitus, dyslipidemia, C-reactive protein, and lifestyle factors, CAC progression was associated with albuminuria (RR: 1.20; 1.01 to 1.43; p=0.04) and low eGFRcys (RR: 1.19; 0.99 to 1.43; p=0.066), but not with eGFRcre. CONCLUSION: CAC progression was associated with albuminuria; however, its relationship with eGFRcys was weakened by adjustments for risk factors.

Difficulty in controlling heavy menstrual bleeding at menarche in a patient with Glanzmann's thrombasthenia.

Glanzmann's thrombasthenia is a rare inherited autosomal recessive bleeding disorder caused by platelet dysfunction. Adolescent girls with Glanzmann's thrombasthenia may experience problematic heavy menstrual bleeding beginning at menarche; this can be difficult to manage. Here, we report the case of an 11-year-old girl with Glanzmann's thrombasthenia who presented with heavy menstrual bleeding at menarche, which was difficult to control. The vaginal bleeding persisted and did not respond to a treatment with packed red blood cells (16 U total), platelet concentrates (70 U total), or administration (>50 doses) of recombinant activated factor VII (rFVIIa). Eventually, a combination of rFVIIa and hormonal therapy (a combined oral contraceptive pill) was introduced. The bleeding stopped at nearly 1 month from onset of menarche. Thereafter, the condition was managed by monthly subcutaneous administration of a GnRH agonist. Management of severe menorrhagia in adolescent patients with Glanzmann's thrombasthenia requires close collaboration with gynecologists or adolescent medicine specialists. More clinical studies are required to identify an effective combination of rFVIIa and hormonal therapy for this condition.

Congenital Hypofibrinogenemia in a Neonate with a Novel Mutation in the FGB Gene.

Detection of severe hypofibrinogenemia (<50 mg/dL) in a neonate soon after birth is alarming because of the risk of hemorrhage. A female neonate was noted to be hypofibrinogenemic (<50 mg/dL) on day 0 of birth; she showed no thrombocytopenia/coagulopathy or hemorrhagic symptoms. Considering the possibility of afibrinogenemia, which may cause bleeding, fresh frozen plasma (FFP) was initiated twice a week to maintain her plasma fibrinogen level at 50-100 mg/dL. Thereafter, we found hypofibrinogenemia in her father and elder sister and plasma fibrinogen levels, determined by clot formation and immunological methods, showed similarly reduced values in both the neonate (proband) and her father. Based on a presumed diagnosis of congenital hypofibrinogenemia, sequencing of the fibrinogen genes was performed, revealing a novel heterozygous mutation of FGB (Genbank NG008833); a p.403Try>Stop. The neonate was treated with repeat FFP infusions until two months of age, when treatment was stopped because she remained asymptomatic.

Differences between home blood pressure and strictly measured office blood pressure and their determinants in Japanese men.

Conventional office blood pressure (OBP) and home blood pressure (HBP) measurements are often inconsistent. The purpose of this research was (1) to test whether strictly measured OBP values with sufficient rest time before measurement (st-OBP) is comparable to HBP at the population level and (2) to ascertain whether there are particular determinants for the difference between HBP and st-OBP at the individual level. Data from a population-based group of 1056 men aged 40-79 years were analyzed. After a five-min rest, st-OBP was measured twice. HBP was measured after a 2-min rest every morning for seven consecutive days. To determine factors related to ΔSBP (HBP minus st-OBP measurements), multiple linear regression analyses and analyses of covariance were performed. While st-OBP and HBP were comparable (136.5 vs. 137.2 mmHg) at the population level, ΔSBP varied with a standard deviation of 13.5 mmHg. Smoking was associated with a larger ΔSBP regardless of antihypertensive usage, and BMI was associated with a larger ΔSBP in participants using antihypertensive drugs. The adjusted mean ΔSBP in the highest BMI tertile category was 4.6 mmHg in participants taking antihypertensive drugs. st-OBP and HBP measurements were comparable at the population level, although the distribution of ΔSBP was considerably broad. Smokers and obese men taking antihypertensive drugs had higher HBP than st-OBP, indicating that their blood pressure levels are at risk of being underestimated. Therefore, this group would benefit from the addition of HBP measurements.

Associations of D-dimer and von Willebrand factor with atherosclerosis in Japanese and white men.

OBJECTIVE: D-dimer and von Willebrand factor (vWF) are associated with atherosclerosis. We recently reported that in a post-World War II birth cohort, Japanese men in Japan had lower levels of atherosclerosis than white men in the United States (U.S.). We examined whether the differences in D-dimer and vWF levels are associated with differences in atherosclerosis between the two populations. METHODS AND RESULTS: Population-based samples of 99 Japanese and 100 white American men aged 40-49 years were examined for coronary artery calcification (CAC), carotid intima-media thickness (IMT), D-dimer, vWF, and other factors using a standardized protocol. When compared to white American men,Japanese had similar levels of D-dimer (0.22 +/- 0.28 vs. 0.19 +/- 0.24 microg/L, respectively, P = 0.39) but significantly higher levels of vWF (124.1 +/- 36.6 vs. 91.3 +/- 48.8%, respectively, P < 0.01). Japanese as compared to white American men had significantly lower prevalence of CAC (13.1 vs. 28.0%, P < 0.01, respectively) and significantly lower IMT (0.61 +/- 0.07 vs. 0.66 +/- 0.08 mm, P < 0.01, respectively). Japanese men had a significant positive association of D-dimer with the prevalence of CAC and a negative association of vWF with IMT, whereas white American men did not have any significant associations. CONCLUSIONS: In men aged 40-49 years, Japanese as compared to white Americans had similar levels of D-dimer and higher levels of vWF although Japanese had a significantly lower prevalence of CAC and IMT. These haemostatic factors are unlikely to explain the difference in atherosclerosis in these populations.

Liver fat accumulation assessed by computed tomography is an independent risk factor for diabetes mellitus in a population-based study: SESSA (Shiga Epidemiological Study of Subclinical Atherosclerosis).

AIMS: Ectopic fat accumulation is related to insulin resistance and diabetes mellitus (DM). However, the effect of fatty liver on DM in non-obese individuals has not been clarified. We investigated whether liver fat accumulation assessed by computed tomography (CT) is associated with the incidence of DM. METHODS: In a prospective population-based study, 640 Japanese men were followed up for 5 years. The liver to spleen (L/S) ratio of the CT attenuation value was used as the liver fat accumulation index. We calculated the odds ratio (OR) and 95% confidence interval (CI) for the DM incidence of per 1 standard deviation (SD) lower L/S and those of L/S < 1.0 compared with L/S ≥ 1.0, using logistic regression models. RESULTS: Both per 1 SD lower L/S and L/S < 1.0 were significantly associated with a risk for DM incidence (1 SD lower L/S: OR = 1.57, 95%CI = 1.14-2.16; L/S < 1.0: OR = 2.27, 95%CI = 1.00-5.14). The relationship between L/S and incidence of DM was consistent in the obese and non-obese groups, with thresholds of BMI 25 kg/m2, waist circumference 85 cm, or visceral adipose tissue 100 cm2. CONCLUSIONS: Liver fat accumulation assessed by CT was associated with the incidence of DM.

Smoking habits and progression of coronary and aortic artery calcification: A 5-year follow-up of community-dwelling Japanese men.

BACKGROUND AND AIMS: To examine whether smoking habits, including smoking amount and cessation duration at baseline, are associated with atherosclerosis progression. METHODS: At baseline (2006-08, Japan), we obtained smoking status, amount of smoking and time since cessation for quitters in a community-based random sample of Japanese men initially aged 40-79 years and free of cardiovascular disease. Coronary artery calcification (CAC) and aortic artery calcification (AAC) as biomarker of atherosclerosis was quantified using Agatston's method at baseline and after 5 years of follow-up. We defined progression of CAC and AAC (yes/no) using modified criteria by Berry. RESULTS: A total of 781 participants was analyzed. Multivariable adjusted odds ratios (ORs) of CAC and AAC progression for current smokers were 1.73 (95% CI, 1.09-2.73) and 2.47 (1.38-4.44), respectively, as compared to never smokers. In dose-response analyses, we observed a graded positive relationship of smoking amount and CAC progression in current smokers (multivariable adjusted ORs: 1.23, 1.72, and 2.42 from the lowest to the highest tertile of pack-years). Among the former smokers, earlier quitters (≥10.7 years) had similar ORs of the progression of CAC and AAC to that of participants who had never smoked. CONCLUSIONS: Compared with never smokers, current smokers especially those with greater pack-years at baseline had higher risk of atherosclerosis progression in community-dwelling Japanese men. Importantly, the residual adverse effect appears to be present for at least ten years after smoking cessation. The findings highlight the importance of early avoidance or minimizing smoking exposure for the prevention of atherosclerotic disease.

Differences Between Coronary Artery Calcification and Aortic Artery Calcification in Relation to Cardiovascular Disease Risk Factors in Japanese Men.

AIMS: Calcification in the coronary and aortic arteries has been linked to cardiovascular morbidity and mortality. The pathophysiological influence of aortic artery calcification (AAC) differs from that of coronary artery calcification (CAC). We aimed to compare the relationships between CAC and AAC and cardiovascular disease (CVD) risk factors. METHODS: We examined a random sample of 1035 Japanese men aged 40-79 years. CAC and AAC were measured by computed tomography and scored according to the Agatston method. Using a logistic regression, we calculated the odds ratio (OR) as being in the highest quintile (Q5) of the calcification score compared to the lower quintiles (Q1-Q4) per 1 standard deviation higher CVD risk factor. Models were simultaneously adjusted for age, body mass index (BMI), systolic blood pressure, smoking (pack-year), alcohol intake, hemoglobin A1c, uric acid, estimated glomerular filtration rate (eGFR), serum lipids, and C-reactive protein. Differences in ORs were investigated using a generalized estimating equation. We performed a multiple linear regression using log-transformed CAC and AAC values as dependent variables. RESULTS: CAC and AAC were independently associated with age (OR, 95% CI: 2.30 [1.77-2.98] for CAC and 3.48 [2.57-4.73] for AAC), p for difference ＜0.001), systolic blood pressure (1.29 [1.08-1.53] and 1.28 [1.07-1.54], p for difference=0.270), and smoking (1.22, [1.04-1.43] and 1.34 [1.13-1.58]) p for difference=0.071). Alcohol correlated with AAC only (1.17 [0.97-1.41] for CAC and 1.42 [1.16-1.73] for AAC, p for difference= 0.020). CONCLUSIONS: CAC and AAC were associated with similar CVD risk factors. The strength of association slightly differed between CAC and AAC.