Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake.

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.

Loci for insulin processing and secretion provide insight into type 2 diabetes risk.

Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.

Evaluation of the electronic stethoscope (FONODOC) as a cardiac screening tool during the preoperative evaluation of children.

Background and Aims: An electronic stethoscope with an inbuilt phonocardiogram is a potentially useful tool for paediatric cardiac evaluation in a resource-limited setting. We aimed to compare the acoustic and electronic stethoscopes with respect to the detection of murmurs as compared to the transthoracic echocardiogram (TTE). Methods: This was an observational study. Fifty children aged 0-12 years with congenital heart diseases (CHDs) and 50 without CHD scheduled for echocardiography were examined using both stethoscopes. The findings were corroborated with clinical findings and compared with the echocardiography report. Results: Among the 50 cases without CHD, no murmur was detected using either of the stethoscopes. This was in agreement with TTE findings. The calculated specificity of both stethoscopes was 100%. Amongst the 50 cases with CHD, the electronic stethoscope picked up murmurs in 32 cases and missed 18 cases. The acoustic stethoscope picked up murmurs in 29 cases and missed 21 cases. Thus, the sensitivity of electronic and acoustic stethoscopes as compared to TTE was calculated to be 64% and 58%, respectively. The positive predictive value of the electronic stethoscope as compared to TTE was 100% while the negative predictive value was 73%. The kappa statistic was 0.93 suggesting agreement in 93%. Mc-Nemar's test value was 0.24 suggesting that the electronic stethoscope did not offer any advantage over the acoustic stethoscope for the detection of CHD in children. Conclusion: A comparison of the electronic stethoscope with an acoustic stethoscope suggests that the rate of detection of CHD with both stethoscopes is similar and echocardiography remains the gold standard.

Association of equol producing status with aortic calcification in middle-aged Japanese men: The ERA JUMP study.

BACKGROUND: Equol, an isoflavone (ISF)-derived metabolite by the gut microbiome in certain individuals termed as equol-producers, might be the key anti-atherogenic component of ISFs. Our objective was to determine the association between equol-producing status and aortic atherosclerosis assessed as aortic calcification (AC). METHODS: This population-based study of 302 Japanese men aged 40-49, free of cardiovascular disease, examined serum levels of equol and ISFs, AC in the entire aorta by electron-beam computed tomography with Agatston method, and cardiovascular risk factors. We defined equol-producers as individuals with serum levels of equol ≥20 nM and prevalent AC as an AC score ≥ 10. We analyzed the association between equol-producing status and AC using Tobit and logistic regressions. We performed age-stratified analyses since age was a significant effect-modifier. RESULTS: The 70th to 90th percentile AC scores were 4 to 243 in equol-producers and 15 to 444 in non-producers, respectively. Overall, equol-producers (41% of the sample) had lower AC scores (-209, [95% confidence interval (CI): -455, 36]) and odds of AC (odds ratio (OR): 0.7 [95% CI: 0.4, 1.3]), although not statistically significant, compared to non-producers after controlling for cardiovascular risk factors. Among men aged 46-49, equol-producers had significantly lower AC scores (-428 [95% CI: -827, -29]). Furthermore, there were null associations between serum levels of ISFs and both AC score and the odds of AC. CONCLUSION: In middle-aged Japanese men, equol-producers had a non-significantly lower burden of aortic atherosclerosis than non-producers whereas ISFs had a null association. Studies with larger sample sizes in both sexes are warranted.

Accuracy of 1-Hour Plasma Glucose During the Oral Glucose Tolerance Test in Diagnosis of Type 2 Diabetes in Adults: A Meta-analysis.

OBJECTIVE: One-hour plasma glucose (1-h PG) during the oral glucose tolerance test (OGTT) is an accurate predictor of type 2 diabetes. We performed a meta-analysis to determine the optimum cutoff of 1-h PG for detection of type 2 diabetes using 2-h PG as the gold standard. RESEARCH DESIGN AND METHODS: We included 15 studies with 35,551 participants from multiple ethnic groups (53.8% Caucasian) and 2,705 newly detected cases of diabetes based on 2-h PG during OGTT. We excluded cases identified only by elevated fasting plasma glucose and/or HbA1c. We determined the optimal 1-h PG threshold and its accuracy at this cutoff for detection of diabetes (2-h PG ≥11.1 mmol/L) using a mixed linear effects regression model with different weights to sensitivity/specificity (2/3, 1/2, and 1/3). RESULTS: Three cutoffs of 1-h PG, at 10.6 mmol/L, 11.6 mmol/L, and 12.5 mmol/L, had sensitivities of 0.95, 0.92, and 0.87 and specificities of 0.86, 0.91, and 0.94 at weights 2/3, 1/2, and 1/3, respectively. The cutoff of 11.6 mmol/L (95% CI 10.6, 12.6) had a sensitivity of 0.92 (0.87, 0.95), specificity of 0.91 (0.88, 0.93), area under the curve 0.939 (95% confidence region for sensitivity at a given specificity: 0.904, 0.946), and a positive predictive value of 45%. CONCLUSIONS: The 1-h PG of ≥11.6 mmol/L during OGTT has a good sensitivity and specificity for detecting type 2 diabetes. Prescreening with a diabetes-specific risk calculator to identify high-risk individuals is suggested to decrease the proportion of false-positive cases. Studies including other ethnic groups and assessing complication risk are warranted.

Data on alcohol consumption and coronary artery calcification among asymptomatic middle-aged men for the ERA-JUMP study.

Data presented in this article are supplementary data to our primary article 'Association of Alcohol Consumption and Aortic Calcification in Healthy Men Aged 40-49 Years for the ERA JUMP Study' [1]. In this article, we have presented supplementary tables showing the independent association of alcohol consumption with coronary artery calcification using Tobit conditional regression and ordinal logistic regression.

Comparison of carotid plaque burden among healthy middle-aged men living in the US, Japan, and South Korea.

BACKGROUND: Carotid plaque has emerged as a marker of coronary heart disease (CHD) risk. Comparison of carotid plaque burden between different race/ethnic groups may provide a relative estimate of their future CHD risk. METHODS: We conducted a population-based study among apparently healthy middle-aged men aged 40-49 years (ERA JUMP study (n = 924)) and recruited 310 Whites in Pittsburgh, US, 313 Japanese in Otsu, Japan, and 301 Koreans in Ansan, South Korea. The number of carotid plaque and CHD risk factors was assessed using a standardized protocol across all centers. The burden of carotid plaque was compared between race/ethnic groups after adjustment for age and BMI, and after multivariable adjustment for other CHD risk factors using marginalized zero-inflated Poisson regression models. Cross-sectional associations of risk factors with plaque were examined. RESULTS: Whites (22.8%) had more than four-fold higher prevalence (p < 0.01) of carotid plaque than Japanese men (4.8%) while the prevalence among Koreans was 10.6%. These differences remained significant after adjustment for age, BMI as well as other risk factors - incidence density ratio (95% confidence interval) for plaque was 0.13 (0.07, 0.24) for Japanese and 0.32 (0.18, 0.58) for Koreans as compared to Whites. Age, hypertension and diabetes were the only risk factors significantly associated with presence of carotid plaque in the overall population. CONCLUSION: Whites have significantly higher carotid plaque burden than men in Japan and Korea. Lower carotid plaque burden among Japanese and Koreans is independent of traditional CVD risk factors.

Association of alcohol consumption and aortic calcification in healthy men aged 40-49 years for the ERA JUMP Study.

BACKGROUND AND AIMS: Several studies have reported a significant inverse association of light to moderate alcohol consumption with coronary heart disease (CHD). However, studies assessing the relationship between alcohol consumption and atherosclerosis have reported inconsistent results. The current study was conducted to determine the relationship between alcohol consumption and aortic calcification. METHODS: We addressed the research question using data from the population-based ERA-JUMP Study, comprising of 1006 healthy men aged 40-49 years, without clinical cardiovascular diseases, from four race/ethnicities: 301 Whites, 103 African American, 292 Japanese American, and 310 Japanese in Japan. Aortic calcification was assessed by electron-beam computed tomography and quantified using the Agatston method. Alcohol consumption was categorized into four groups: 0 (non-drinkers), ≤1 (light drinkers), >1 to ≤3 (moderate drinkers) and >3 drinks per day (heavy drinkers) (1 drink = 12.5 g of ethanol). Tobit conditional regression and ordinal logistic regression were used to investigate the association of alcohol consumption with aortic calcification after adjusting for cardiovascular risk factors and potential confounders. RESULTS: The study participants consisted of 25.6% nondrinkers, 35.3% light drinkers, 23.5% moderate drinkers, and 15.6% heavy drinkers. Heavy drinkers [Tobit ratio (95% CI) = 2.34 (1.10, 4.97); odds ratio (95% CI) = 1.67 (1.11, 2.52)] had significantly higher expected aortic calcification score compared to nondrinkers, after adjusting for socio-demographic and confounding variables. There was no significant interaction between alcohol consumption and race/ethnicity on aortic calcification. CONCLUSIONS: Our findings suggest that heavy alcohol consumption may be an independent risk factor for atherosclerosis.

Long chain n-3 polyunsaturated fatty acids are not associated with circulating T-helper type 1 cells: Results from the Multi-Ethnic Study of Atherosclerosis (MESA).

T-helper type 1 (Th1) cells are pro-inflammatory and provide signals to immune cells. Animal models and in vitro human cell culture experiments have indicated that long chain n-3 polyunsaturated fatty acids (LCn3PUFAs) reduce Th1 cell levels; however, the association is unknown in healthy humans. We hypothesized that circulating levels and dietary intake of LCn3PUFAs have an inverse association with circulating levels of Th1 cells and studied 895 participants in the Multi-Ethnic Study of Atherosclerosis (age 61 ± 10 years at exam 1, 52% women, 44% white, 21% African-American, 24% Hispanic-American, 11% Chinese-American). Phospholipid LCn3PUFAs (% of total fatty acids), measured by gas chromatography, and intake of LCn3PUFAs, evaluated by food frequency questionnaire, were evaluated at exam 1 (2000-02) and defined as the sum of eicosapentaenoic and docosahexaenoic acids. Th1 cells were measured by flow cytometry at exam 4 (2005-07), expressed as a percentage of CD4+ lymphocytes that were interferon-γ+ (%Th1: CD4+IFN-γ+). Median (interquartile range) plasma LCn3PUFA, dietary LCn3PUFA, and %Th1 levels were 4.31% (3.40-5.82%), 0.09 (0.05-0.16) g/day, and 14.4% (9.8-20.0%), respectively. When the association of LCn3PUFA-quartiles with %Th1 was analyzed using general linear models, neither plasma nor dietary LCn3PUFAs were significantly associated with %Th1 (P-trend = 0.58 and 0.80, respectively), which remained even after adjusting for demographics, lifestyle factors, lipids, season, and cytomegalovirus titers. In this multi-ethnic U.S. population, circulating levels and dietary intake of LCn3PUFAs were not significantly associated with Th1 cell levels. Further research is needed to assess potential benefits of supplementation and much higher dietary consumption of LCn3PUFAs on Th1 cells.

Vitamin D and Blood Pressure Among U.S. Adults: A Cross-sectional Examination by Race/Ethnicity and Gender.

INTRODUCTION: The cross-sectional association of serum vitamin D levels with blood pressure and hypertension status among a representative sample of U.S. adults was examined. METHODS: Participants of the National Health and Nutrition Examination Survey from 2001 to 2010 were included in these analyses. Harmonizing of the vitamin D levels from 2001 to 2006 with vitamin D measurement from 2007 to 2010 was done using regression equations released by the Centers for Disease Control and Prevention. Use of vitamin D supplements was assessed for all participants. Statistical analyses included examination of linear association of vitamin D levels with blood pressure and non-linear cubic splines with hypertension in overall population, by gender, and by race/ethnicity. RESULTS: With every 10 nmol/L higher vitamin D, systolic blood pressure decreased by 0.19 mmHg in this population (p<0.01). In fully adjusted stratified analyses, this association was present among females (-0.25 mmHg, p<0.01) and non-Hispanic whites (0.22 mmHg, p<0.01). After race/ethnic and gender stratification, this association was observed among non-Hispanic white females (0.26 mmHg, p=0.01), non-Hispanic black females (0.65 mmHg, p=0.02), and marginally significant among Hispanic males (0.33 mmHg, p=0.07). Non-parametric assessment with cubic splines show that vitamin D has an inverse association with odds of hypertension up to 100 nmol/L with no apparent benefit at higher levels in overall population, and even lower threshold levels of vitamin D in non-Hispanic blacks (50 nmol/L) and Hispanic Americans (70 nmol/L). CONCLUSIONS: Significant race/ethnic and gender differences exist in the association of vitamin D and systolic blood pressure. Odds for hypertension are reduced significantly at higher vitamin D levels, but this benefit plateaus at very high vitamin D levels.

Significant inverse association of equol-producer status with coronary artery calcification but not dietary isoflavones in healthy Japanese men.

Equol, a metabolite of the dietary isoflavone daidzein, is produced by the action of gut bacteria in some individuals who are termed as equol-producers. It is proposed to have stronger atheroprotective properties than dietary isoflavones. We examined a cross-sectional association of dietary isoflavones and equol-producer status with coronary artery calcification (CAC), a biomarker of coronary atherosclerosis, among men in Japan. A population-based sample of 272 Japanese men aged 40-49 years recruited from 2004 to 2007 was examined for serum isoflavones, serum equol, CAC and other factors. Equol-producers were classified as individuals having a serum level of equol >83 nm. The presence of CAC was defined as a coronary Ca score ≥10 Agatston units. The associations of dietary isoflavones and equol-producers with CAC were analysed using multiple logistic regression. The median of dietary isoflavones, equol and CAC were 512·7 (interquartile range (IQR) 194·1, 1170·0), 9·1 (IQR 0·10, 33·1) and 0·0 (IQR 0·0, 1·0) nm, respectively. Prevalence of CAC and equol-producers was 9·6 and 16·0 %, respectively. Dietary isoflavones were not significantly associated with CAC. After multivariable adjustment, the OR for the presence of CAC in equol-producers compared with equol non-producers was 0·10 (95 % CI 0·01, 0·90, P<0·04). Equol-producers had significantly lower CAC than equol non-producers, but there was no significant association between dietary isoflavones and CAC, suggesting that equol may be a key factor for atheroprotective properties of isoflavones in Japanese men. This finding must be confirmed in larger studies or clinical trials of equol that is now available as a dietary supplement.

The role of initial and longitudinal change in blood pressure on progression of arterial stiffness among multiethnic middle-aged men.

OBJECTIVE: A few studies have examined the longitudinal association of blood pressure (BP) with arterial stiffness progression, and the results were inconsistent. The objective of this study was to investigate the roles of initial BP and its longitudinal change on the progression of arterial stiffness measured using brachial-ankle pulse wave velocity (baPWV). METHOD: Study participants (n = 656) were from population-based samples of healthy men aged 40-49 years at baseline (213 White Americans, 47 African-Americans, 152 Japanese Americans and 244 Japanese in Japan). BP measures, baPWV and other factors were examined at baseline and 4-7 years later. General linear regression was applied for statistical analyses. RESULT: Annual change in SBP (standardized coefficient: 0.33, P < 0.001), but not its baseline level (standardized coefficient: 0.03, P = 0.495), had a positive significant association with the progression of baPWV after adjusting for a wide range of standard cardiovascular risk factors. Similarly, annual changes in DBP (standardized coefficient: 0.35, P < 0.001), pulse pressure (standardized coefficient: 0.15, P = 0.001) and mean arterial pressure (standardized coefficient: 0.37, P < 0.001) were positively associated with the progression of baPWV. None of the baseline measures were related to the progression of baPWV. CONCLUSION: Our findings imply that, regardless of initial BP, effective monitoring and controlling of BP is important to slow down arterial wall stiffening and hence reduce cardiovascular risk.

Increased Aortic Calcification Is Associated With Arterial Stiffness Progression in Multiethnic Middle-Aged Men.

Arterial stiffness is established as an independent predictor of cardiovascular morbidity and mortality. The objective was to prospectively evaluate association of aortic calcification burden with progression of arterial stiffness in population-based samples of healthy middle-aged men from ERA JUMP cohort (Electron-Beam Computed Tomography and Risk Factor Assessment in Japanese and US Men in the Post-World War II Birth Cohort). Men (n=635) aged 40 to 49 years (207 white American, 45 black American, 142 Japanese American, and 241 Japanese in Japan) were examined at baseline and 4 to 7 years later. Aortic calcification was evaluated from level of aortic arch to iliac bifurcation. Arterial stiffness progression was measured as annual change in brachial-ankle pulse wave velocity. Multivariable-adjusted general linear models were applied to investigate associations of longitudinal change in aortic calcification with arterial stiffness progression in participants overall, as well as in subgroups without or with prevalent aortic calcification at baseline. Annual change in aortic calcification was positively and significantly associated with arterial stiffness progression. In participants with annual changes in aortic calcium score of ≤0, 1 to 10, 11 to 100, and >100, the adjusted means (SD) for the annual change in brachial-ankle pulse wave velocity were 3.8 (2.2), 7.2 (2.2), 12.2 (1.8), and 15.6 (2.6) cm/s, respectively (P for trend <0.01) adjusted for baseline aortic calcification, arterial stiffness, and standard cardiovascular risk factors. Arterial stiffness was associated with the incidence of aortic calcification over the follow-up period among participants without aortic calcification (n=297) and with an increase in aortic calcification among participants with prevalent aortic calcification at baseline (n=388). Our findings suggest aortic calcification may be causally linked to arterial stiffness.

Progression of coronary artery calcium in Japanese American men and white men in the ERA JUMP study.

BACKGROUND: Progression of coronary artery calcium (CAC) is associated with increased risk of coronary heart disease (CHD) and is reported to be greater in whites than blacks, Hispanics, and Chinese in the US. Our objective was to compare progression of CAC between Japanese Americans and whites. METHODS: Population-based sample of 303 Japanese American men and 310 white men aged 40-49years, free of clinical cardiovascular disease at baseline, were examined for CAC at baseline (2004-2007) and follow-up (2008-2013). Progression of CAC was defined as change in coronary calcium scores (CCS) in participants with baseline CCS>0 and incident CAC in participants with baseline CCS=0. Multiple linear regression and relative risk regression were used to compare change in CCS scores and incident CAC between the two races, respectively. RESULTS: Japanese American men had significantly greater annual change in CCS than white men (median [interquartile range]: 11.3 Agatston units [1.4, 24.9] vs 2.5 [-0.22, 14.5]) in the unadjusted analyses. After adjusting for cardiovascular risk factors and follow-up time, change in CCS (beta±CI) and incidence rate ratio of CAC was similar in Japanese American men and white men: -0.12 (-0.34, 0.15) and (0.87 [95% CI: 0.20, 3.9]), respectively. CONCLUSIONS: In contrast to previously reported greater progression of CAC in whites than other races, we found a similar progression of CAC in Japanese American men as white men. Our study identifies Japanese American men as a target group for prevention of CHD. Large prospective studies are warranted to confirm these findings.

The impact of equol-producing status in modifying the effect of soya isoflavones on risk factors for CHD: a systematic review of randomised controlled trials.

Recent studies suggest that the ability to produce equol, a metabolite of the soya isoflavone daidzein, is beneficial to coronary health. Equol, generated by bacterial action on isoflavones in the human gut, is biologically more potent than dietary sources of isoflavones. Not all humans are equol producers. We investigated whether equol-producing status is favourably associated with risk factors for CHD following an intervention by dietary soya isoflavones. We systematically reviewed randomised controlled trials (RCT) that evaluated the effect of soya isoflavones on risk factors for CHD and that reported equol-producing status. We searched PubMed, EMBASE, Ovid Medline and the Cochrane Central Register for Controlled Trials published up to April 2015 and hand-searched bibliographies to identify the RCT. Characteristics of participants and outcomes measurements were extracted and qualitatively analysed. From a total of 1671 studies, we identified forty-two articles that satisfied our search criteria. The effects of equol on risk factors for CHD were mainly based on secondary analyses in these studies, thus with inadequate statistical power. Although fourteen out of the forty-two studies found that equol production after a soya isoflavone intervention significantly improved a range of risk factors including cholesterol and other lipids, inflammation and blood pressure variables, these results need further verification by sufficiently powered studies. The other twenty-eight studies primarily reported null results. RCT of equol, which has recently become available as a dietary supplement, on CHD and its risk factors are awaited.

A Significant Positive Association of Vitamin D Deficiency with Coronary Artery Calcification among Middle-aged Men: For the ERA JUMP Study.

OBJECTIVE: Although a significant positive association of vitamin D deficiency with coronary heart disease has been demonstrated in cross-sectional as well as prospective studies, only a few studies have examined the association of vitamin D deficiency with subclinical atherosclerosis. We examined whether vitamin D deficiency is associated with subclinical atherosclerosis, as measured by coronary artery calcification (CAC) in asymptomatic adults. METHODS: In a population-based cross-sectional study, 195 men aged 40 to 49 years without cardiovascular disease were randomly selected (98 Caucasian and 97 Japanese American men). Liquid chromatography-tandem mass spectrometry was utilized to measure serum vitamin D. CAC was examined by electron beam computed tomography using standardized protocols and read centrally at the University of Pittsburgh using Agatston's methods. To investigate an association between vitamin D deficiency (defined as 25-hydroxyvitamin D [25(OH)D] < 20 ng/mL) and CAC (defined as Agatston score ≥ 10), we utilized multivariable logistic regression models. RESULTS: Prevalence of CAC and vitamin D deficiency was 27.2% and 10.3%, respectively. Participants with CAC were significantly older, had significantly higher body mass index (BMI), and had higher rates of smoking. Those with CAC were 3.31 times likely to be vitamin D deficient, after adjusting for traditional cardiovascular risk factors (odds ratio [OR] = 3.31, 95% confidence interval [CI], 1.12-9.77). CONCLUSIONS: In this population-based study of healthy middle-aged men, vitamin D deficiency had a significant positive association with the presence of CAC.

Significantly Greater Progression of Intima-Media Thickness of the Carotid Artery in Japanese American Men Than in White Men: The ERA JUMP Study.

BACKGROUND: Although a westernized lifestyle was associated with increased coronary heart disease (CHD), morbidity, and mortality in first- and second-generation Japanese Americans, CHD mortality was reported to be lower in this population than in whites. The risk profile of CHD for third- and fourth-generation Japanese Americans is not known. We compared the progression of carotid intima-media thickness (CIMT) between third- or fourth-generation Japanese Americans and whites. METHODS: Population-based samples of 473 men (Japanese Americans, 227; whites, 246) aged 40-49 years at baseline and free of clinical cardiovascular disease were examined for CIMT at baseline (2004-2007) and follow-up (2007-2013). CIMT was determined centrally at the University of Pittsburgh, Pittsburgh, Pennsylvania. Analysis of covariance was used to compare annualized progression of CIMT between Japanese Americans and whites, adjusting for cardiovascular risk factors and baseline CIMT. RESULTS: Progression of CIMT was significantly greater in Japanese Americans than in whites both before and after adjusting for covariates: mean, 14.4 µm/y; 95% confidence interval [CI],12.3-16.4 vs 9.8 µm/y; 95% CI, 7.8-11.7; P < 0.05 and 15.1 µm/y; 95% CI, 13.1-17.1 vs 9.1 µm/y; 95% CI, 7.2-11.0; P < 0.05, respectively. Age, total cholesterol/high-density lipoprotein cholesterol, and diabetes in Japanese Americans and age, hypertension, and lipid medication in whites were significantly associated with progression of CIMT. CONCLUSIONS: The significantly greater progression of CIMT in Japanese Americans than in whites might suggest a higher future burden of CHD in Japanese Americans than in whites. The current study identifies Japanese Americans as an important target group for prevention of CHD. Future research assessing carotid plaque in addition to CIMT is warranted.

Brachial-ankle pulse wave velocity is associated with coronary calcification among 1131 healthy middle-aged men.

BACKGROUND: Brachial-ankle pulse wave velocity (baPWV) is a simple and reproducible measure of arterial stiffness and is extensively used to assess cardiovascular disease (CVD) risk in eastern Asia. We examined whether baPWV is associated with coronary atherosclerosis in an international study of healthy middle-aged men. METHODS: A population-based sample of 1131 men aged 40-49 years was recruited - 257 Whites and 75 Blacks in Pittsburgh, US, 228 Japanese-Americans in Honolulu, US, 292 Japanese in Otsu, Japan, and 279 Koreans in Ansan, Korea. baPWV was measured with an automated waveform analyzer (VP2000, Omron) and atherosclerosis was examined as coronary artery calcification (CAC) by computed-tomography (GE-Imatron EBT scanner). Association of the presence of CAC (defined as ≥ 10 Agatston unit) was examined with continuous measure as well as with increasing quartiles of baPWV. RESULTS: As compared to the lowest quartile of baPWV, the multivariable-adjusted odds ratio (95% Confidence Interval [CI]) for the presence of CAC in the combined sample was 1.70 (0.98, 2.94) for 2nd quartile, 1.88 (1.08, 3.28) for 3rd quartile, and 2.16 (1.19, 3.94) for 4th quartile (p-trend = 0.01). The odds for CAC increased by 19% per 100 cm/s increase (p < 0.01), or by 36% per standard-deviation increase (p < 0.01) in baPWV. Similar effect-sizes were observed in individual races, and were significant among Whites, Blacks and Koreans. CONCLUSION: baPWV is cross-sectionally associated with CAC among healthy middle-aged men. The association was significant in Whites and Blacks in the US, and among Koreans. Longitudinal studies are needed to determine its CVD predictive ability.