bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P309: N-3 Polyunsaturated Fatty Acids and Subclinical Atherosclerosis in Mexican Women
Authors: Monge Adriana , Ortiz-Panozo Eduardo , Yunes Elsa , Cantu-Brito Carlos , Catzin-Khulmann Andres , Lopez-Ridaura Ruy , Harris William S , Lajous Martin
Published: July 2021

Introduction:
Long chain n-3 polyunsaturated fatty acids (n-3 PUFAs) may affect cardiovascular risk through various biological pathways. There is limited evidence of the relation with subclinical atherosclerosis (SA).

Hypothesis:
N-3 PUFAs is inversely associated with SA.

Methods:
We evaluated the cross-sectional association between whole blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and common carotid intima media thickness (cIMT) in 490 disease-free without self-reported hypertension, diabetes, hypercholesterolemia, stroke, myocardial infarction, and/or peripheral arterial disease women in the Mexican Teachers’ Cohort from Chiapas and Yucatan. Between 2012 and 2013, neurologists assessed cIMT with an ultrasound and we measured whole blood EPA+DPA through HPLC in dried blood spots and expressed values as % of total identified fatty acids. In a reproducibility study we observed an intraclass correlation coefficient of 0.89 (n=52). We categorized whole blood EPA+DHA in quartiles and defined SA as cIMT ≥0.8mm or presence of plaque. Mean adjusted differences and multivariable odds ratios with the lowest category as a reference were estimated using linear and logistic regression.

Results:
Mean (±SD) age was 46.5 (±7.7) and the prevalence of SA was 18.8% (n=92). Mean %EPA+DHA was 3.65±0.83 and the prevalence of low %EPA+DHA (below 4%) was 71%. In multivariable analyses (Table), we observed a suggestion of an inverse relation with %DHA but results were not statistically significant. The mean adjusted difference (95%CI) comparing extreme quartiles of %DHA was -0.018(-0.039 - 0.003), p-trend 0.17. The OR(95%CI) comparing extreme quartiles of %DHA was 0.59(0.27-1.27).

Conclusions:
In a population of middle-aged Mexican women whole blood EPA and DHA were not associated to intima-media thickness. The narrow distribution of N-3 PUFA levels in this population may have limited our ability to detect an association.
Abstract P315: Tomato Consumption by Form and Its Relationship to Total Vegetable Intake in the US: Implications for Healthier Dietary Patterns
Authors: Reimers Kristin J , Keast Debra R
Published: July 2021

Despite public health efforts to decrease risk of cardiovascular disease by promoting healthier dietary patterns, Americans persistently under-consume vegetables. Discovering feasible, achievable strategies to increase vegetable intake can contribute to improved dietary patterns and health outcomes. Tomatoes are the most consumed non-starchy vegetable in the US and also contribute the greatest porportion of vegetables to the USDA Food Pattern (MyPlate). Despite tomatoes’ dietary importance, little is known about tomato consumption by form. Tomato forms and amounts consumed in the US were determined by examining the intakes of adults 19 years and older (n = 16,252) in the National Health and Nutrition Examination Survey, 2005-06, 2007-08, and 2009-10. The forms of tomatoes in foods participants reported were divided into two categories: tomato products and raw. Foods containing tomato products were further divided into four subgroups: 1) canned tomatoes as main ingredients, 2) canned tomatoes as minor ingredients, 3) juice and 4) condiments. Tomato products comprised approximately 63% of total tomato consumption, primarily as main ingredients (33%) of foods such as pasta with tomato sauce, with smaller amounts contributed from minor ingredients (12%), condiments (10%) and juice (7%). Raw tomatoes accounted for the remaining 37%. Participants who consumed the most tomatoes, defined as those who met or exceeded the MyPlate tomato target amount (0.65 cup equivalents/d), consumed 67% of their tomatoes as tomato products and 33% as raw. These heavy tomato consumers’ total vegetable intake was 2.48 cup equivalents/d, which approximated the 2.5 cup equivalent MyPlate total vegetable target amount. Increasing the awareness and importance of the contribution of tomato intake by form, and the relationship between tomato intake and total vegetable intake targets can inform future strategies to achieve greater vegetable intake and thus improve dietary patterns for Americans.
Abstract P325: Quantifying the UK Social and Economic Benefits of Potential Policies to Reduce dietary Trans Fats: Modelling Study.
Authors: Pearson-Stuttard Jonathan , Allen Kirk , Hooton William , Diggle Peter , Capewell Simon , O'Flaherty Martin
Published: July 2021

Background:
Industrial trans fatty acids (TFAs) are commonly added to processed foods as a cheap way to increase shelf-life and enhance palatability. Natural TFA are found in small quantities in meat and dairy products. TFA substantially increase the risk of Coronary Heart Disease (CHD). The UK burden of CHD remains large, and unequal across socio-economic groups. TFA intake is also unequal, with largest intake in the most deprived groups.

Methods:
We modelled three policy options for reducing TFA in the English diet; a) increased labelling requirements resulting in partial voluntary reformulation; b) a ban on TFA in all restaurant & take-away food, and c) a total TFA ban in all processed foods.

We quantified health benefits for the period 2015-2020 for each policy (deaths prevented and life-years-gained -LYG). Analyses were stratified by age, gender, and socioeconomic quintiles (IMDQ). Mortality gains were linked to economic cost and benefits: direct healthcare costs, productivity loss averted, and informal care; government costs comprising legislative and monitoring; and costs to industry. Results were tested in a probabilistic sensitivity analysis.

Results:
The most effective UK policy in reducing CHD mortality from 2015-2020, would be a total TFA ban resulting in approximately 8,600 fewer CHD deaths [95% confidence interval 3,400 - 14,700] with a substantial inequality reduction of some 3,300 deaths [1,300 - 6,000]. Labelling with partial voluntary reformulation might result in approximately 2,500 fewer CHD deaths [1,100 - 4,600]; and an inequality reduction of some 800 deaths [300 - 1,400]. Whilst a TFA ban in restaurant and take-away food could yield approximately 2,200 fewer CHD deaths [900 - 3,800]; and an inequality reduction of some 700 [300 - 1,200]).

All policies would be cost-saving for the government due to big reductions in health care costs. A total ban could achieve annual societal savings of approximately £96 million The labelling and restaurant and take-away bans might gain £12 - £14 million savings for, representing £8,600 to £3,700-£4,800 per QALY. Industry costs might reach some £210 million if extensive reformulations were required, but could be negligible if reformulations were absorbed into natural product reformulation cycles.

Conclusions:
Policies to reduce TFA consumption in the English population are a priority public health measure. As both TFA consumption and CHD burden are higher deprived groups, any TFA reduction will reduce inequalities in CHD mortality. A total ban on TFA in ALL processed foods would have the greatest coverage across social groups. It would also represent a good investment from a societal perspective. Policies with less comprehensive coverage would be correspondingly less effective at reducing mortality, inequalities and cost effective, but would still yield substantial health, and economic gains.
Abstract P331: Ethnic Differences in Glycoslation Indices in Non-Diabetic Adults: The Diabetes, Heart and Health Survey
Authors: Metcalf Patricia A , Sundborn Gerhard , Jackson Rod T
Published: July 2021

Objective:
We examined whether there were ethnic differences in glycosylated haemoglobin concentrations, the glycation gap and haemoglobin glycation index in non-diabetic adults.

Research design and methods: We studied 3,318 non-diabetic adults aged 35 to 74 years. Glycoslylated haemoglobin (HbA1c) levels were compared in 1,589 Europeans, 825 Maori, 689 Pacific and 226 Asians. The glycation gap was calculated using the residuals from the regression of HbA1c on mean fasting and 2 hour glucose levels and the haemoglobin glycation index using the residuals from the regression of HbA1c on fructosamine.

Results:
Mean ± SD HbA1c was 38.0 ± 4.57 mmol/mol. After adjusting for age and gender, mean (se) HbA1c was higher in Maori (38.6 mmol/mol (0.14)), Pacific (40.8 (0.16)) and Asians (37.9 (0.27)) compared with Europeans (36.5 (0.10)) (all P < 0.0001 vs. Europeans). In contrast, there was little difference in fructosamine levels between ethnic groups with 231.5 (0.63) μmol/L in Europeans, 230.7 (0.44) in Maori, 237.8 (1.16) in Asians (both P > 0.05 versus Europeans), and 232.7 (0.16) in Pacific (P < 0.05). After adjusting for age, sex, education, body mass index (BMI), systolic and diastolic blood pressure, fasting and post-glucose load glucose levels, cholesterol, triglycerides, HDL-cholesterol, physical exercise levels, total calorie intake and socioeconomic status, HbA1c levels were 37.0 (0.10) mmol/mol in Europeans, and remained higher in Maori (38.4 (0.13)), Pacific (40.0 (0.15)) and Asians (38.1 (0.25)) (all P < 0.001) compared to Europeans. The mean (se) age and gender adjusted glycation gap (based on fructosamine) was -1.50 (0.10) mmol/mol for Europeans, 0.66 (0.14) mmol/mol for Maori, 2.77 (0.16) mmol/mol for Pacific (Both (P < 0.0001 vs. Europeans), and -0.37 (0.27) mmol/mol in Asians (P =0.001 vs. Europeans. Similarly, the mean haemoglobin glycation index (based on mean glucose) was -1.34 (0.10) in Europeans, 0.41 (0.13) in Maori, 2.63 (0.15) in Pacific (both P < 0.0001 versus Europeans) and -0.45 (0.25) in Asians (P = 0.001 vs. Europeans).

Conclusion:
There were differences in HbA1c, the glycation gap and the haemoglobin glycation index between Europeans and Maori, Pacific and Asian non-diabetic adults, but there was little difference between ethnic groups for fructosamine. These differences could be due to heritable factors that may vary between the ethnic groups or may be related to high or low glycators.
Abstract P335: High-sensitive C-reactive Protein and Risk of Undiagnosed and Incident Diabetes: The Singapore Chinese Health Study
Authors: Pan An , Yuan Jian-Min , Koh Woon-Puay
Published: July 2021

Introduction:
There has been growing evidence that elevated levels of C-reactive protein (CRP), as a biomarker of inflammation, are associated with increased risk of diabetes. However, previous prospective studies were mostly conducted among Caucasians, and few were done in Chinese. Thus, we assessed the hypothesis that elevated CRP levels are related to increased risk of type 2 diabetes among Chinese adults residing in Singapore.

Methods:
The Singapore Chinese Health Study (SCHS) is a population-based cohort that recruited 63,257 Chinese adults aged 45-74 years during 1993 and 1998, and morning blood samples were collected from about 32,000 participants during the first follow-up visit (1999-2004). In this diabetes case-control study nested within SCHS, all eligible participants were free of diagnosed diabetes, cardiovascular disease and cancer at blood collection, and 571 cases subsequently reported to have diabetes at the follow-up II visit (2006-2010), while 571 controls were matched to cases for age (±3 years) and date (±6 months) of blood collection, sex and dialect group and remained free of diabetes, cardiovascular disease at the follow-up II visit. Plasma high-sensitive CRP (hs-CRP) concentrations were assayed, and conditional logistical regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs).

Results:
The mean (SD) concentrations of hs-CRP was 2.79 (2.65) and 1.86 (2.03) mg/L, respectively, in cases and controls (P<0.001). After controlling for matching factors, education level, smoking status, alcohol intake, physical activity, baseline hypertension, fasting status, body mass index, triglycerides and HDL cholesterol, the ORs (95% CIs) across quartiles of hs-CRP were 1.00 (ref), 1.25 (0.79-1.98), 1.23 (0.78-1.95), and 1.73 (1.11-2.69; P for trend=0.01). Among the cases, there were 279 subjects who had HbA1C ≥6.5% at the time of blood collection and thus classified as undiagnosed diabetes, and the other 292 subjects had HbA1C <6.5% at blood collection and were classified as incident diabetes. In the undiagnosed diabetes case-control sets, the ORs (95% CIs) across quartiles of hs-CRP were 1.00 (ref), 1.23 (0.59-2.56), 2.26 (1.10-4.66), and 2.46 (1.26-4.83; P for trend=0.009); while in the incident diabetes case-control sets, the ORs (95% CIs) were 1.00 (ref), 1.22 (0.63-2.36), 0.73 (0.38-1.41), and 1.25 (0.65-2.42; P for trend=0.39).

Conclusions:
In this prospective nested case-control study of Chinese adults, elevated CRP levels are not independently associated with increased risk of incident diabetes. The positive association between CRP and undiagnosed diabetes suggests that CRP may parallel with hyperglycemia. Our results do not support the independent role of CRP in the development of type 2 diabetes in Chinese population.
Abstract P342: Periodontal Bacteria, Prevalent Prediabetes and Plasma Glucose Progression: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS)
Authors: Demmer Ryan T , Jacobs David R , Singh Richa , Zuk Aleksandra , Rosenbaum Michael , Papapanou Panos N , Desvarieux Moïse
Published: July 2021

Introduction:
Periodontal infections have been hypothesized as a cardiometabolic risk factor. The relationship between periodontal microbiota and early diabetes risk has not been studied.

Hypothesis:
We hypothesized that periodontopathic bacteria would be associated with both prevalent pre diabetes and accelerated longitudinal plasma glucose progression among diabetes-free adults.

Methods:
The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 300 diabetes-free adults (77% female) aged 20-55 years (mean=34±10). Prevalent prediabetes was defined as: i) 5.6%<HbA1C<6.5%; or ii) 99 mg/dL<fasting plasma glucose (FPG)<126 mg/dL. In 1,188 subgingival plaque samples, 11 bacterial species including Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Treponema denticola (Td), Tannerella forsythia (Tf) and Actinomyces naeslundii (An) were assessed at baseline. Modified Poisson regression evaluated prediabetes prevalence across bacterial tertiles. Risk ratios (RR), 95% confidence intervals (CI) for 3rd vs. 1st tertile are presented. Follow-up is ongoing but longitudinal FPG was available for interim analysis among the first n=100 recall-eligible participants (mean follow-up time=2±0.3 years). Mixed-effects regressions evaluated FPG time trends across baseline bacterial levels. All analyses were adjusted for cardiometabolic risk factors.

Results:
Prediabetes prevalence was 18% (54 of 300). RRs(95%CI) summarizing associations between bacteria and pre diabetes were as follows: Aa=2.48[1.34,4.58], p=0.004; Pg=3.41[1.78,6.58], p=0.0003; Td=1.99[0.992,4.00], p=0.052 and Tf=1.95[1.0,3.84], p=0.05; An=0.46[0.25,0.85], p=0.01. Among participants with high baseline values of Pg or Tf, FPG increased by ~2.5 mg/dl during follow-up (all p-values<0.05) while no FPG progression was observed among participants with low baseline bacterial levels.

Conclusion:
Periodontopathic microbiota are associated with both prevalent prediabetes and longitudinal plasma glucose increase among diabetes-free adults.
Abstract P354: The “Afro-Cardiac Study” Identifies High Burden of Cardiovascular Disease Risk in West African Immigrants in the United States
Authors: Commodore-Mensah Yvonne Y , Berko Charles A , Sampah Maame E , Cudjoe Joycelyn , Himmelfarb Cheryl D
Published: July 2021

Introduction:
The African immigrant population grew 40-fold between 1960 and 2007, from 35,355 to 1.4 million with one third coming from West Africa, primarily Ghana and Nigeria. African immigrants have been understudied and, traditionally, lumped into the racial category of Black/African-American. We have examined the prevalence of CVD risk factors (hypertension, overweight/obesity, diabetes, hyperlipidemia, current smoking and physical inactivity), assessed global CVD risk and identified independent predictors of increased CVD risk by sex in West African immigrants (WAI).

Methods:
Cross-sectional study of WAI (Ghanaians and Nigerians) aged 35-74 years recruited from churches in the Baltimore/ Washington, DC metropolitan area. CVD risk factors were determined per AHA guidelines. Descriptive statistics were performed on participant’s Pooled Cohort Equations (PCE) scores and CVD risk factors with comparison by sex. Participants with PCE scores ≥7.5% and ≥3 CVD risk factors were deemed high risk. A multivariable logistic regression was fitted to identify independent predictors of high CVD risk.

Results:
The mean age of the 253 participants was 49.5±9.2 years and 58% were female. Males were more likely to be employed than females (90% vs. 72%; p=0.001). Only 52% of participants had health insurance. The majority [54% [137/253)] had ≥3 CVD risk factors and 28% had PCE score ≥7.5%. Smoking was the least prevalent (<1%) and overweight/obesity the most prevalent (88%) risk factor. Although females (64%) were more likely to be treated for hypertension than males (36%), there was no difference in hypertension control by sex. Diabetes was identified in 16% of the participants. Mean total cholesterol (TC) was 180.9±33.9mg/dL and 32% had TC level ≥200mg/dL. In addition, 44% were found to be physically inactive (<150minutes/week of moderate or <75minutes/week of vigorous physical activity). In females, employment [0.18 AOR, 95%CI: 0.075-0.44)] and health insurance [0.35 AOR, 95%CI 0.14-0.87)] were associated with a PCE score ≥7.5%. In males, higher social support was associated with a 0.92 (95%CI: 0.84-0.98) odds of having ≥3 CVD risk factors.

Conclusion:
The high prevalence of CVD risk among relatively young WAIs is worrisome and suggests that the “healthy immigrant effect” may no longer hold for 21st century African immigrants. Employment and health insurance were protective against high CVD risk in females with social support protective against high CVD risk in males. CVD prevention strategies must be tailored to the unique needs of the WAI with consideration of socioeconomic status and sex.
Abstract P357: Genome-Wide Association Study of the PR Interval in Hispanic Populations
Authors: Seyerle Amanda A , Lin Henry J , Gogarten Stephanie M , Soliman Elsayed Z , Heckbert Susan R , Kerr Kathleen F , Kooperberg Charles , Rodriguez Carlos J , Guo Xiuqing , Ryckman Kelli K , Yao Jie , Sotoodehnia Nona , Taylor Kent D , Whitsel Eric , Rotter Jerome I , Laurie Cathy , Avery Christy L
Published: July 2021

BACKGROUND:
The PR interval (PR) is an electrocardiographic measure of atrial and atrioventricular nodal conduction. PR prolongation has been associated with atrial fibrillation, pacemaker implantation, heart failure, and all-cause mortality. Although Hispanic/Latino (HL) populations have high burdens of cardiovascular morbidity and mortality, they remain a chronically understudied population, with previous genome-wide association studies of PR limited to European (EU), African (AA), and Asian (AS) descent populations.

METHODS:
We included 13,507 participants of HL ancestry from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and Women’s Health Initiative clinical trials (WHI). PR was automatically measured from digital electrocardiogram tracings recorded using standardized methods in all participants. Genotype data were imputed to the 1000 Genomes Phase 1 reference panel, and associations were examined using linear regression assuming an additive genetic model and adjusting for global ancestry, study center or region, clinical covariates (age, sex, heart rate, height, body mass index, systolic blood pressure, beta blocker use), and study weights (HCHS/SOL only). Study-specific results were combined using a fixed-effects, inverse variance weighted meta-analysis. Linkage disequilibrium (LD) patterns were examined using LocusZoom, and r2 values were calculated using 1000 Genomes reference populations.

RESULTS:
We identified six loci associated with PR in HL populations at genome-wide significant levels: SLC8A1, SCN5A, SCN10A, ARHGAP24, CAV1/CAV2, and SOX5. At these loci, index SNPs had important effects (β range: 2-4 ms) and common minor allele frequencies (MAF range: 13-40%). Of note, five of the six identified loci were previously associated with PR in EU populations, and four in AA populations; however, the association with SLC8A1 has been found only in AS populations. Whereas the SLC8A1 index SNP, rs17026148, is common in AS (MAF = 50%), AA (MAF = 15%), and HL populations (MAF = 17%), it is rare in EU populations (MAF < 5%). Interestingly, SLC8A1 LD patterns are similar across AS, EU, and HL populations in this region.

CONCLUSIONS:
Our results suggest that genetic determinants of PR are consistent across race/ethnicity but that previous studies in EU populations were either underpowered to detect the SLC8A1 locus or that it resides on an Asian/American Indian haplotype, thus underscoring the importance of conducting genetic studies in diverse populations.
Abstract P362: Association of DNA Methylation Age With Risk of Type 2 diabetes: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Roetker Nicholas S , Pankow James S , Nelson Heather H , Guan Weihua , Hicks Chindo , Mosley Thomas
Published: July 2021

Introduction:
It has been proposed that DNA methylation patterns can be used to characterize rate of aging, but it is not known whether methylation age associates with aging-related diseases and conditions independently of chronological age and other risk factors.

Hypothesis:
There is a positive association between age acceleration (defined as the difference between DNA methylation age and chronological age) and risk of type 2 diabetes (T2D).

Methods:
We estimated DNA methylation age in African American men and women of the Atherosclerosis Risk in Communities Study using two published predictors. Incident T2D was identified from follow-up visits and telephone interviews. Logistic and Cox proportional hazards regression models were used to estimate the association of age acceleration with incident T2D, modeling age acceleration both continuously and categorically in three percentile groups (0-25th, 25-75th, 75-100th). Regression models were adjusted for chronological age, sex, white blood cell distribution, education, smoking, alcohol, sport index, body mass index, waist to hip ratio, blood pressure, antihypertensive and lipid-lowering medication, HDL and LDL cholesterol, and triglycerides.

Results:
After adjustment for chronological age, sex, and white blood cell type proportions, those with greater age acceleration were more likely to have prevalent T2D (p-trend ≤ 0.003 across percentile categories of age acceleration for both DNA methylation predictors). Among 1,547 participants who were free of T2D at baseline (mean age: 56 years, range: 47-70), there were 170 incident cases of T2D over a mean 5.4 years of follow-up. T2D incidence was not associated with age acceleration in either crude or risk factor-adjusted models. In the fully-adjusted logistic regression models, odds ratios (95% confidence intervals) for T2D across the percentile categories of age acceleration were 1 (ref.), 0.92 (0.58, 1.45), and 1.42 (0.84, 2.40); and 1 (ref.), 0.87 (0.55, 1.39), and 0.93 (0.52, 1.64), respectively, for the two DNA methylation age predictors.

Conclusion:
In conclusion, DNA methylation age acceleration, proposed as a marker of the rate of aging, was associated cross-sectionally with prevalent diabetes, but did not predict risk of T2D independently of chronological age. Additional prospective studies are needed to explore relationships with development of other chronic conditions in order to determine if DNA methylation age can serve as a useful proxy for rate of aging.
Abstract P389: Effects of Dietary Patterns on Vitamin D and Other Markers of Bone-Mineral Metabolism: Results From the Dash Trial
Authors: Hassoon Ahmed , Appel Lawrence , Miller Edgar
Published: July 2021

Background:
The relationship of CVD with vitamin D levels and other markers of bone-mineral metabolism is of substantial interest. The Dietary Approaches to Stop Hypertension (DASH) diet effectively lowers blood pressure and is now recommended to promote CV health. The effects of the DASH diet on vitamin D and other markers of bone-mineral metabolism is unknown.

Objective:
To determine the effect of dietary patterns on blood levels of vitamin D, PTH, and ionized calcium, and urinary excretion of calcium and phosphate.

Methods:
Data on study outcomes were available in 334 participants from the original DASH trial. Baseline levels were obtained from blood and urine collected at the end of the run-in while on the control diet. Participants were then randomized to control diet (37% kcal total fat); fruits & vegetable diet (also 37% kcal total fat); or the DASH diet (27% kcal total fat). Follow-up levels were obtained during the last week of the eight-week intervention period.

Results:
Mean (±SD) baseline blood levels of vitamin D, PTH , and ionized calcium were 15.1±3.7ng/ml, 46.1±18.5 ng/ml and 1.3±0.06 mmol/l, respectively. For urinary calcium and phosphate were 126.8±45.3mg/dl and 715.0±277.3 mg/dl, respectively. See table for within-diet changes. The DASH diet, net of control, reduced vitamin D by -1.29ng/ml (P= 0.005). In stratified analyses, the reduction in vitamin D appeared more prominent in blacks, but the p-value for interaction (race*diet) was non-significant (P=0.21). Otherwise, the DASH diet had no significant effect on the other markers, net of control. Compared to control, the fruit & vegetable diet reduced urinary calcium and phosphorus excretion.

Conclusion:
The DASH diet modestly reduced vitamin D levels among all participants, with potentially larger effects in blacks. The reduction in vitamin D levels might have resulted from the lower fat content of the DASH diet. Overall, during the eight-weeks of intervention, no major harm or benefit of the DASH diet was documented on biomarkers related to bone-mineral metabolism.
Abstract 106: Utility of Ferritin as a Predictor of the Patients with Kawasaki Disease Refractory to Intravenous Immunoglobulin Therapy
Authors: Yamamoto Noboru , Sato Kaoru , Hoshina Takayuki , Kojiro Masumi , Kusuhara Koichi , Kusuhara Koichi
Published: July 2021

Purpose:
Several scoring systems for prediction of non-responsiveness to initial course of intravenous immunoglobulin (IVIG) therapy have been available in the patients diagnosed as Kawasaki disease (KD). However, all non-responders cannot be identified completely by these scoring systems. The aim of this study is to investigate whether ferritin can be a useful marker as a predictor of the patients with KD refractory to IVIG therapy.

Materials and Methods:
This retrospective study enrolled 63 patients with KD hospitalized at Kitakyushu General Hospital during 2010 to 2013. These patients were divided into IVIG responders (n= 41) and non-responders (n=22). Serum ferritin levels and the scoring systems for prediction of non-responsiveness to initial IVIG treatment were compared between these two groups.

Results:
Serum ferritin level was significantly elevated in non-responders (p=0.01). The area under the receiver-operating-characteristics curve was 0.698, and the sensitivity and specificity in more than 215 ng/ml of serum ferritin levels was 54.5% and 85.4%, respectively. Two of the three scoring systems for prediction of non-responsiveness to initial IVIG treatment in non-responders were also significantly higher scores than that in responders, but many non-responders had a low score of these scoring systems. Approximately half of the patients with low score of these scoring systems had high serum ferritin level (≧ 215 ng/ml).

Conclusion:
Serum ferritin level can be a useful marker for the prediction of non-responsiveness to initial IVIG treatment and may be an important complementary marker to the scoring systems for prediction of non-responsiveness to initial IVIG treatment.
Abstract 136: A Case of Complex Congenital Heart Disease with Postoperative Complications of Impaired Consciousness and Several Arrhythmias due to Encephalitis in the Acute Stage of Kawasaki Disease
Authors: Nakagawa Naomi , Kamada Masahiro , Ishiguchi Yukiko , Moritoh Yuji , Okamoto Kenji
Published: July 2021

Background:
In addition to muscular and medium arteries, Kawasaki disease causes inflammation in nerves and the myocardium. However, arrhythmia severe enough to be problematic is rare. Patient: At age 1 day, the patient was in a state of shock and was diagnosed with Taussig-Bing anomaly and aortic arch coarctation. At age 4 days, he underwent aortic arch reconstruction and pulmonary arterial banding. At age 2 months, he underwent arterial switch operation and ventricular septal defect closure. No significant arrhythmias were observed. At age 5 years 6 months, he had a fever, and 5 days later, he developed rash, conjunctival hyperemia, and redness of the lips and fingertips. Kawasaki disease was diagnosed on day 7 after symptom onset. The patient presented with disorientation, so electroencephalography and magnetic resonance imaging were performed and revealed overall slow-wave activity and cerebral edema, respectively, indicating complicated encephalitis. Sinoatrial block and sinus arrest were also observed. The patient received ultrahigh-dose γ-globulin therapy and steroid pulse therapy for encephalitis. The fever resolved at a total γ-globulin dose of 4 g/kg. The other main Kawasaki disease symptoms also disappeared. By day 18, his consciousness completely recovered but the sinus arrest remained. On day 20, an atrial flutter developed from tachycardia that was treated with electric shocks. Sinus arrest at a maximum of 5.7 s was observed at that time, and bradycardia-tachycardia syndrome was suspected. On the same day, the sinus arrest improved gradually and largely disappeared 3 days later. The atrial flutter also disappeared. Discussion: Severe arrhythmia that requires treatment is rare in Kawasaki disease. Our patient underwent surgery for a complex cardiac anomaly. Thus, the requisites for arrhythmia were present when the Kawasaki disease caused myocardial inflammation, which is thought to cause severe symptoms.
Abstract 137: Efficacy Of Raise Protocol For Children With Incomplete Kawasaki Disease
Authors: Naoi Kazuyuki , Asami Yuji , Takatsuki Shinichi , Seki Mitsuru , Ikehara Satoshi , Nakayama Tomotaka , Matsuura Hiroyuki , Kobayashi Tohru , Arakawa Hirokazu , Saji Tsutomu
Published: July 2021

Background:
Although RAISE study demonstrated that intravenous immunoglobulins (IVIG) plus prednisolone (PSL) therapy for refractory Kawasaki disease (KD) reduced coronary artery aneurysm, the study population included a few incomplete KD. The aim of study was to evaluate the efficacy of RAISE protocol for incomplete KD.

Methods:
Children with incomplete KD which have 4 or less major symptoms of KD were enrolled. Using Kobayashi score, children were divided into low and high risk for IVIG resistance. Children with low risk group received IVIG monotherapy, whereas IVIG plus PSL therapy administrated for high risk group. Retrospectively, we assessed initial treatment response and coronary artery abnormalities (CAAs).

Results:
Overall, 63 incomplete KD (age; median and range 17 months (1-115 months), sex ratio; boys:girls 37:26) were enrolled. Median day of illness at diagnosis was 5 day of illness (2-10 days). Low risk group included 52 cases (83%) and the remaining 11 cases were high risk group. In low risk group, 87% of children (45 cases) were initial treatment responders. All 7 non-responders were responded to additional methylprednisolone steroid pulse therapy. All 11 children with high risk group were responders to the initial treatment. Five cases have equal to greater than 2.5 of Z-Score, which were all low risk group. All CAAs regressed to normal coronary diameter within 1 month.

Conclusions:
RAISE protocol was useful for the treatment of incomplete KD without any CAAs.
Abstract 146: Third Intravenous Immunoglobulin Is An Effective Option For Kawasaki disease Patients Resistant To Cyclosporin A
Authors: Suzuki Hiroyuki , Suenaga Tomohiro , Kakimoto Nobuyuki , Takeuchi Takashi , Yoshikawa Norishige , Shibuta Shoichi , Terai Masaru , Hamada Hiromichi , Onouchi Yoshihiro , Hata Akira
Published: July 2021

Background:
About 10-20% of patients with Kawasaki Disease (KD) who fail to respond to IVIG, show a high prevalence of CAL. The new guideline (2012) has proposed several options for second- and third-line therapy for patients resistant to IVIG. However, there are still no definite treatment options for refractory KD. We have reported that cyclosporin A (CsA) is a well tolerated, safe and promising option for patients resistant to IVIG. However, certain subgroups of such patients may also be resistant to CsA. In this study, we examined if a third course IVIG might be effective for patients resistant to CsA.

Patients and Methods:
Between April 2008 and May 2014, 42 Japanese patients who met the diagnostic criteria for KD and received CsA treatment were enrolled as study subjects.

All patients were resistant to both initial (2 g/kg for 24 hours) and additional IVIG, and were then administered CsA orally (Neoral[[Unable to Display Character: Ⓡ]], oral solution, Novartis Pharma Co. Ltd., Tokyo, Japan). The initial dose of CsA was 4mg/kg/day, and it was divided into two equal daily doses every 12 hours. The dose of CsA was adjusted to between 4 and 8 mg/kg/day to maintain a trough level of 60-200 ng/ml by reference to clinical and laboratory data such as body temperature and C-reactive protein level. After the start of CsA treatment, if patients remained febrile for more than 5 days, or if fever returned after an afebrile period within 5 days, CsA treatment was judged to be ineffective, and the patients were then given a third course of IVIG. We analyzed some laboratory data between CsA effective group and CsA resistant group.

Results:
CsA treatment was judged to be ineffective in 14 of 42 (33%) patients. Eleven of those 14 patients received a third IVIG, and then, 8 (72.7%) patients of them became afebrile within 24hours. The other three patients became afebrile after a fourth IVIG. The serum levels of AST and soluble interleukin-2 receptor before the start of CsA treatment were significantly lower in CsA effective group than in CsA resistant group.

Conclusion:
A third course of IVIG is an effective option for KD patients who are resistant to CsA .
Abstract 156: Serial Evaluations of Coronary Artery Abnormalities in Kawasaki Disease Patients Should Include Assessment for the Development of Luminal Myofibroblastic Proliferation and Chronic Thromboses: a Preliminary Echocardiographic Study
Authors: Carr Michael , Rowley Anne , Orenstein Jan M , Shulman Stanford , Duffy Elise
Published: July 2021

Introduction:
We recently reported that luminal myofibroblastic proliferation (LMP) is an active process of smooth muscle-cell derived myofibroblasts and their matrix products that can cause progressive coronary artery (CA) stenoses in KD patients. Serial echocardiography to assess for high risk CA changes, with periodic cardiac functional assessments in selected patients, is the current standard of care for monitoring patients with CA abnormalities. Monitoring for LMP/chronic thromboses is not routinely performed.

Hypothesis:
We hypothesized that echocardiographic images from KD children with severe CA abnormalities could suggest the presence of LMP and/or chronic thromboses, indicating the potential for progression to CA stenoses.

Methods:
We reviewed echocardiographic studies from a convenience sample of 28 KD patients with multiple aneurysms/giant aneurysms, to determine whether LMP and/or thrombosis could be identified on serial imaging.

Results:
In 12 of the 28 patients, images were highly suggestive of LMP and/or thromboses. This could only be assessed in the proximal segments of the left main, circumflex, left anterior descending and right CAs. Detection was enhanced by optimizing the depth and sector width for the coronary artery segment of interest and use of magnification on the review station. Variations in echocardiographic techniques such as low frequency probes, harmonics, persistence, excessive compress or low gain settings made the assessment difficult. 4 patients in this cohort required CA bypass and 1 died from myocardial infarction due to progressive LMP. Distal vessel occlusion could not be visualized by echocardiography.

Conclusions:
Images highly suggestive of LMP/chronic thromboses were evident in at least a third of patients with severe CA disease, including one patient who died of progressive LMP stenosis documented at autopsy. Echocardiography could not distinguish between LMP and chronic thrombosis as the cause of CA stenoses. Our study highlights the need for improved serial imaging for ongoing LMP/thromboses in AHA risk group IV. Patients with these complications may require more frequent cardiac functional assessments than are routinely recommended, to avoid adverse outcomes.
Abstract 163: Regressed Coronary Aneurysm after Kawasaki Disease: What are they hiding? An Optical Coherence Tomography (OCT) study
Authors: Dionne Audrey , Fournier Anne , Ibrahim Ragui , Gebhard Catherine , Dahdah Nagib
Published: July 2021

Background:
Coronary artery aneurysms (CAA) are a serious complication of Kawasaki disease (KD). Regression of CAA occurs in 50% of the cases on follow up. Actual imaging techniques often described these segments as normal, whereas studies have shown significant endothelial and smooth muscle dysfunction.

Method:
KD patients scheduled for angiographic follow-up between June 2013 and August 2014 underwent OCT imaging. We compared coronary intimal changes in coronary artery segments with no history of CAA to segments with regressed CAA, and segments with persistent CAA. The intima was measured in sections adjacent to the CAA for the segments with persistent CAA, at the former CAA and adjacent sections for those who regressed, and at various corresponding sections for segments with no history of CAA.

Results:
OCT was performed on 18 patients at 12.4 ± 5.5 years. Overall 14/18 (77.7%) had a history of CAA. Of those, 7/14 (50.0%) had regressed CAA at time of OCT. Data was analyzed according to echocardiographic and angiographic progress of CAA segments. Accordingly, all 18/18 persistent CAA segments and 11/11 regressed CAA segments had significant intimal hyperplasia, compared to 1/13 with no history of segmental CAA (P<0.001). The intensity of intimal hyperplasia is displayed in Table 1.

Conclusion:
Despite normal angiographic features, regressed CAA segments displayed significant intimal hyperplasia, similarly to those with persistent CAA. These features may present a risk of adverse coronary events.
Abstract 175: Dual source 128-slice computed tomography coronary angiography: A low radiation paradigm in evaluation of Kawasaki disease at Chandigarh, North India
Authors: Singhal Manphool , Gupta Pankaj , Singh Surjit , Gupta Anju , Rohit Manoj K , Arora Suman , Khandelwal Niranjan
Published: July 2021

Objective:
To evaluate the feasibility of low dose computed tomography coronary angiography (CTCA) on a dual source scanner in children on follow up for Kawasaki disease (KD).

Methods:
A prospective study comprising 20 consecutive children with KD was conducted from November 2013 to August 2014 on 128-dual source second generation Siemens Definition Flash with either prospective or retrospective electrocardiographic (ECG) gating. A radiologist blinded to the clinical profile and echocardiography (ECHO)/ stress thallium data evaluated each scan. Peak Kilovolts (KVp), milliampere (mA) and radiation dose (dose length product-mGycm and effective dose milliSieverts-mSv) were recorded. Another radiologist correlated CTCA data with clinical/ other imaging data.

Results:
Demographic/ clinical data and scan parameters are given in Table. Mean effective dose was 1.25 mSv (range 0.22 to 2.74), with prospective ECG gating in 8 patients, it was even lower (0.22 to 0.91 mSv). Six of the 20 patients showed abnormalities including ectasia (n=3), aneurysm (n=2) and stenosis (n=3). More than one abnormality was seen in 2 patients. Four children with normal ECHO had abnormalities detected on CTCA. Stress thallium scintiscan had been performed in 16 patients with mild/ moderate reversible perfusion defects detected in 14. Six of 14 patients with moderate perfusion abnormalities had an abnormal CTCA.

Conclusion:
In our experience, dual source CTCA is a feasible low radiation dose modality in evaluation in patients with KD.

Future impact:
Dual source CTCA has potential to be standard of care for evaluation of coronary artery abnormalities in KD.
Abstract 19: Epidemiologic Surveillance of Kawasaki Disease in Manitoba and Northwestern Ontario 2000-2010
Authors: Pepelassis Dionysios , Lautatzis Maria E , Schantz Daryl , Hyman Jeff , Soni Reeni , Buffo Ilan
Published: July 2021

Objective:
The purpose of this study is to determine the incidence of persistent coronary artery sequelae due to KD between the First Nation/Metis (FN/M) and non First Nation children (n-FN) in the province of Manitoba and Northwestern Ontario, Canada.

Methods:
This is a 10-year (2000-2010) retrospective chart review study of all patients < 18 years of age identified with KD and persistent coronary artery aneurysms. The data was obtained from the Children’s Hospital of Winnipeg medical records and the Electronic Echocardiography data based at the Variety Heart Centre.

Results:
A total of 103 children and adolescents with KD and with at least 3 echocardiography studies were enrolled. Complete or incomplete presentation of KD was determined according to the fulfillment for the disease classic criteria on diagnosis. Age at diagnosis ranged between 2 months to 4 years (median 0.5 years) with 2 patients diagnosed during their early infancy (age< 90 days). The median follow up period was 4 years (1.3 to 6.3 years). Persistent coronary artery aneurysms were detected in 10 children (M/F ratio 3:1). Nine (9) of the studied subjects account for the FN/M children group and the remaining 1 is of Asian origin. We observed no n-FN children with permanent cardiac sequelae secondary to KD.

Conclusion:
There is a significantly higher occurrence of permanent coronary artery lesions due to KD among the FN/M children in the province of Manitoba and Northwestern Ontario. However, this study does not imply direct association of any risk factor, which might be related with our findings. Socio-environmental or even genetic factors might contribute to these findings. Nevertheless, these speculations are beyond the scope of this study. We suggest that a strategy of early, diagnosis and treatment of KD based on the latest AHA guidelines, when we deal with patients of these ethnic/racial groups, should be implemented.
Abstract 190: Continuous Vascular Remodeling Related To Development Of Arteriosclerosis Or Atherosclerosis In Kawasaki Disease ~ Immunohistochemical Study using an Animal Model ~
Authors: Hamaoka Kenji , Fujii Maiko , Kuchitsu Yuki , Yoshioka Ayako , Okamoto Akiko , Suzuki Chinatsu , Yahata Tomoyo , Nakamura Akihiro , Ikeda Kazuyuki
Published: July 2021

Background:
Atherosclerotic coronary heart disease has recently emerged as a clinical issue among young individuals with a history of Kawasaki disease (KD), which is a systemic vasculitis unique to children. However, whether or not and how KD promotes atherosclerosis remains unclear. We hypothesized that, analogous to the pathogenesis of arteriosclerosis or atherosclerosis, endothelial injury and the resultant intimal thickening are induced in coronary arteries after attenuation of vasculitis.

Methods:
We used a rabbit model of KD developed by Onouchi et al. and performed histopathological analysis of the coronary arteries at acute (1, 3, 5, and 7 days) and chronic (3 months) phases of the disease.

Results:
In these rabbit models, a pan-arteritis with significant intimal cellular hypertrophy was histologically detected in the acute phase, and arterial intimal thickening was observed during the chronic phase. Immunohistochemical analysis of the coronary arteries revealed that the thickened intimal lesions observed during the chronic phase comprised abundant α-smooth muscle actin (α-SMA)-positive cells, most of which concomitantly expressed vascular cell adhesion molecule-1 and nuclear factor-κB. Although macrophages positive for RAM11 were barely detected, macrophage colony stimulating factor was strongly expressed in migrating smooth muscle cells in the intimal layer. In addition, the accumulation of proteoglycan as extracellular matrix was distinctly visible in the thickened intima, indicating progressive accumulation of lipids and proliferation of smooth muscle cells within the lesion.

Conclusions:
These findings suggest that, in KD-associated vasculitis, the migration of α-SMA-positive cells into the thickened intima might induce continuous vascular inflammation and remodeling, which might progress to coronary arteriosclerosis or atherosclerosis.
Abstract 205: Over 5 Years Follow-up of Kawasaki Disease with Atopic Bronchial Asthma
Authors: Nakamura Toshimi , Nakamura Tsuneyuki , Ko Giyo , Yamashita Yoko , Akita Chisato , Saikawa Yutaka
Published: July 2021

Background:
Recent epidemiological studies have suggested that some patients with Kawasaki disease (KD) have an atopic tendency. However, it is not clear what the long-term prognosis will be for KD-patient with allergic disease. We aim to investigate the long-term prognosis of KD-patient with allergic disease.

Subjects & Methods:
We studied a cohort of KD-patient (n=58, follow-up age; 9.95±1.84 years), in whom we examined total serum IgE and specific IgE at KD-onset (onset age; 2.13±1.84 years). Using retrospective patient medical record analysis, we evaluated the prevalence of bronchial asthma at onset and follow-up of KD. In addition, we examined the hospitalization rate, medical history and family history in pediatric bronchial asthma after KD-onset.

Results:
In our study, KD-patient had markedly higher total serum IgE and prevalence of bronchial asthma at onset of KD than the general children’s population, as reported by Japanese national government (Table 1). The prevalence of bronchial asthma at follow-up was similar to the general children’s population. 9 children had already had a diagnosis of a bronchial asthma at KD-onset. 8 children had subsequently developed bronchial asthma after KD-onset. In these 2 groups, however, 6 and 8 children, respectively, had remitted during follow-up. Nobody was hospitalized for asthmatic exacerbation after KD-onset.

Conclusions:
These findings demonstrate that KD-patient with atopic bronchial asthma at onset have not developed severe allergic reaction. There results provide that the pathogenic mechanism of KD might weakly or transiently provoke an elevation of total IgE and the developing of allergies.