Search

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. [ABSTRACT FROM PUBLISHER]

Aims: Continued low mortality from coronary heart disease in Japan, despite deleterious changes in traditional risk factors, remains unexplained. Since aortic calcification (AC) was an early predictor of cardiovascular mortality, we compared the progression and incidence of AC between Japanese in Japan, white Americans, and third-generation Japanese Americans in the ERA JUMP cohort. We examined whether higher blood levels of marine-derived n-3 fatty acids (FAs) in Japanese than in Americans accounted for the difference., Methods and Results: Men (n=700) aged 40-49 years (252 Japanese in Japan, 238 white, and 210 Japanese Americans) were examined at baseline and 4-7 years later. AC was evaluated from the aortic arch to the iliac bifurcation with computed tomography and quantified by the Agatston method. Robust linear regression and linear mixed models were used to compare the progression of AC. Multivariable logistic regression models were fitted to compare the incidence of AC (AC≥50 at follow-up) among those with baseline AC<50. Japanese in Japan had a significantly slower progression of AC than white and Japanese Americans after adjusting for age, baseline AC, follow-up time, and traditional risk factors. White Americans had a significantly higher incidence of AC than Japanese in Japan (OR=4.61 [95%CI, 1.27-16.82]). Additional adjustment for blood levels of n-3 FAs accounted for the difference in AC incidence but not progression., Conclusion: Japanese in Japan had a significantly slower progression and lower incidence of AC than white Americans. High levels of marine-derived n-3 FAs in Japanese in Japan partly accounted for the difference in incidence., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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., Competing Interests: This work was supported by a grant from the Kao Research Council for the Study of Healthcare Science (Tokyo, Japan); by the Uehara Memorial Foundation (Tokyo, Japan); by grant numbers A13307016, A17209023, A21249043, A23249036, A25253046, A15H02528, A18H04074, 17K15827, and 25893097 from the Ministry of Education, Culture, Sports, Science and Technology Japan; and by a grant (HL068200) from the National Institutes of Health. All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

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., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Computed tomography (CT) can directly provide information on body compositions and distributions, compared to anthropometric indices. It has been shown that various obesity indices are associated with carotid intima-media thickness (IMT). However, whether CT-based obesity indices are stronger than anthropometric indices in association with atherosclerosis remains to be determined in a general population., Methods: We cross-sectionally assessed carotid IMT using ultrasound in 944 community-dwelling Japanese men free of stroke and myocardial infarction. CT image at the L4-L5 level was obtained to compute areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Anthropometric measures assessed included body mass index (BMI), waist circumference, and waist-to-hip ratio. Using multivariable linear regression, slopes of IMT per 20 th to 80 th percentile of each index were compared. We also compared the slope of index with simultaneous adjustment for BMI in the same model., Results: Areas of VAT and SAT were positively associated with IMT, but not stronger than those of anthropometric indices in point estimates. Among all obesity indices, BMI was strongest in association with IMT after adjusting for age and lifestyle factors or further adjusting for metabolic factors. In simultaneous adjustment models, BMI, but not CT-based indices, remained significant and showed the strongest association., Conclusions: In community-dwelling Japanese men, anthropometric obesity indices, BMI in particular, were more strongly associated with carotid atherosclerosis than CT-based obesity indices. The association of general obesity with carotid atherosclerosis was strong and adding CT-based obesity measure did not considerably influence in the association.

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 cm 3 (IQR, 47.2-90.0 cm 3 ) to 73.6 cm 3 (IQR, 53.3-98.1 cm 3 ; 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.

Aim: The clinical significance of coronary artery calcification (CAC) is not fully determined in general East Asian populations where background coronary heart disease (CHD) is less common than in USA/Western countries. We cross-sectionally assessed the association between CAC and estimated CHD risk as well as each major risk factor in general Japanese men., Methods: Participants were 996 randomly selected Japanese men aged 40-79 y, free of stroke, myocardial infarction, or revascularization. We examined an independent relationship between each risk factor used in prediction models and CAC score ≥100 by logistic regression. We then divided the participants into quintiles of estimated CHD risk per prediction model to calculate odds ratio of having CAC score ≥100. Receiver operating characteristic curve and c-index were used to examine discriminative ability of prevalent CAC for each prediction model., Results: Age, smoking status, and systolic blood pressure were significantly associated with CAC score ≥100 in the multivariable analysis. The odds of having CAC score ≥100 were higher for those in higher quintiles in all prediction models (p-values for trend across quintiles ＜0.0001 for all models). All prediction models showed fair and similar discriminative abilities to detect CAC score ≥100, with similar c-statistics (around 0.70)., Conclusions: In a community-based sample of Japanese men free of CHD and stroke, CAC score ≥100 was significantly associated with higher estimated CHD risk by prediction models. This finding supports the potential utility of CAC as a biomarker for CHD in a general Japanese male population.

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.

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.

Aim: To examine whether the inflammatory markers C-reactive protein (CRP) and fibrinogen are associated with biomarkers of atherosclerosis [carotid intima-media thickness (IMT) and coronary artery calcification (CAC)] in the general male population, including Asians., Methods: Population-based samples of 310 Japanese, 293 Japanese-American and 297 white men 40-49 years of age without clinical cardiovascular disease underwent measurement of IMT, CAC and the CRP and fibrinogen levels as well as other conventional risk factors using standardized methods. Statistical associations between the variables were evaluated using multiple linear or logistic regression models., Results: The Japanese group had significantly lower levels of inflammatory markers and subclinical atherosclerosis than the Japanese-American and white groups (P-values all ＜0.001). The mean level of CRP was 0.66 vs. 1.11 and 1.47 mg/L, while that of fibrinogen was 255.0 vs. 313.0 and 291.5 mg/dl, respectively. In addition, the mean carotid IMT was 0.61 vs. 0.73 and 0.68 mm, while the mean prevalence of CAC was 11.6% vs. 32.1% and 26.3%, respectively. Body mass index (BMI) showed significant positive associations with both the CRP and fibrinogen levels. Although CRP showed a significant positive association with IMT in the Japanese men, this association became non-significant following adjustment for traditional risk factors or BMI. In all three populations, CRP was not found to be significantly associated with the prevalence of CAC. Similarly, fibrinogen did not exhibit a significant association with either IMT or the prevalence of CAC., Conclusions: The associations between inflammatory markers and subclinical atherosclerosis may merely reflect the strong associations between BMI and the levels of inflammatory markers and incidence of subclinical atherosclerosis in both Eastern and Western populations.

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