Oral Mycobiome Differences in Various Spatial Niches With and Without Severe Early Childhood Caries

Purpose: Severe early childhood caries (S-ECC) is a microbe-mediated disease with tooth hard tissue destruction. However, the role of the fungal community in various ecological niches of deciduous dental caries has not been fully elucidated. This study aimed to analyze the differences of mycobiome in diverse spatial niches with and without S-ECC.Method: A total of 48 samples were obtained from 8 S-ECC children (SE group) and 8 caries-free children (CF group) aged 4–5 years. Unstimulated saliva (S), healthy supragingival plaque (FMIX), mixed plaque from decayed teeth (SMIX) and carious lesion (DMIX) samples were collected. The ITS2 region of the fungi was amplified and sequenced using the Ion S5™XL platform.Results: A total of 281 species were identified. Candida albicans showed relatively higher abundance in S-ECC children, while Alternaria alternata and Bipolaris sorokiniana were more enriched in CF group. In this study, the relative abundance of C. albicans in CF.FMIX (0.4%), SE.FMIX (12.5%), SE.SMIX (24.0%), and SE.DMIX (37.2%) increased successively. Significant differences of fungal species richness and diversity were observed between SE.FMIX-SE.SMIX, SE.FMIX-SE.DMIX (P < 0.05).Conclusions: The diversity of fungal communities in S-ECC children showed significant differences in various spatial niches of primary teeth. The richness of C. albicans was closely related to the caries states and depth, suggesting that it may play a crucial role in caries pathogenicity.

The Effect of Vitamin D on Coronary Atherosclerosis: A Propensity Score Matched Case–Control Coronary CTA Study

Background: Vitamin D supplementation may be associated with lower cardiovascular (CV) events, but the data are controversial. It remains speculative whether vitamin D supplementation has a direct effect on coronary atherosclerosis. We therefore set out to assess the influence of vitamin D supplementation on the coronary atherosclerosis profile quantified by coronary computed tomography angiography (CTA) in a retrospective case–control cohort study. Methods: 176 patients (age: 62.4 ± 10.4) referred to coronary CTA for clinical indications were included. A total of 88 patients receiving vitamin D supplementation (mean duration 65.3 ± 81 months) were 1:1 propensity score matched with 88 controls for age, gender, smoking, arterial hypertension, positive family history, dyslipidemia, and diabetes. Coronary stenosis severity (CAD-RADSTM), mixed plaque burden (weighted for non-calcified), high-risk-plaque (HRP) features, and plaque density (HU) were quantified by CTA. Serum 25-hydroxyvitamin D (OH)-levels were measured in 138 patients and categorized into four groups (0: <20 ng/mL; 1: 20–40 ng/mL; 2: 40–60 ng/mL; and 3: >60 ng/mL) and compared with CTA. Results: The prevalence of atherosclerosis by CTA was similar in both groups (75.6% versus 74.3%, p = 0.999), >50% coronary stenosis was slightly higher in controls (p = 0.046), but stenosis severity score (CAD-RADS) was not different (p = 0.106). Mixed plaque burden (weighted for non-calcified) was lower in patients receiving vitamin D supplementation (p = 0.002) and high-risk-plaque prevalence was markedly lower (3.8% versus 32%, p < 0.001). CT plaque density (HU) was higher (p < 0.001) in the vitamin D group. Patients with serum vitamin D (OH) levels >60 ng/mL had higher plaque density (p = 0.04), indicating more calcified and less vulnerable plaque. Conclusions: In this retrospective case–control cohort study, vitamin D supplementation was associated with less high-risk plaque, less non-calcified plaque burden, and a higher calcified plaque independent of CV risk factors.

POS0216 GREATER HIGH-DENSITY LIPOPROTEIN LEVELS OVER TIME ARE LINKED TO DECREASED CORONARY PLAQUE FORMATION AND REGRESSION AND STABILIZATION OF HIGH-RISK LESIONS IN RHEUMATOID ARTHRITIS

Background:The relationship between serum lipoproteins and cardiovascular disease risk in rheumatoid arthritis (RA) is complex1. Their levels and function may vary based on disease activity and medication use. Beneficial effects on high-density lipoprotein (HDL-C) levels, structure and behavior, in response to treatment have been described. However, the impact of HDL-C levels over time on coronary atherosclerosis progression in RA is unknown.Objectives:We here evaluated the influence of HDL-C levels over time on long-term coronary plaque formation and progression in patients with RA.Methods:One hundred one RA patients without symptoms or history of cardiovascular disease who participated in a computed tomography angiography study of coronary atherosclerosis had repeat assessments after 6.9±0.3 years to evaluate plaque progression. Clinical, laboratory and medication data were recorded at baseline and regular outpatient follow-up visits thereafter. Time-averaged HDL-C was calculated for each patient using available consecutive HDL measurements between baseline and follow-up. Robust logistic regression assessed the association between time-averaged HDL-C and likelihood of new plaque formation in segments without plaque at baseline, and transition of prevalent mixed plaque to calcified plaque. Robust multinomial logistic regression evaluated the effect of time-averaged HDL-C on likelihood of new non-calcified, mixed or calcified plaque formation in segments without plaque (compared to remaining without plaque), and non-calcified plaque regression or transition to mixed or calcified plaque at follow-up (compared to remaining non-calcified). All models accounted for clustering of coronary segments within patients and adjusted for Framingham D’Agostino risk score, proximal segment location, time-averaged CRP, cumulative prednisone dose, bDMARD duration, statin duration, waist-to-height ratio, and time-averaged triglycerides.Results:Participants were mostly female (n=87, 86.1%), with a mean ± standard deviation (SD) age of 51.5±10.3 years and time-averaged HDL-C of 51.7±13.9. Ninety-seven new plaques formed in segments without plaque at baseline; 20 were noncalcified, 21 were mixed, and 56 were calcified. Time-averaged HDL-C had no effect on new total plaque formation (adjusted odds ratio-OR 0.88 [95% CI 0.64-1.21]). However, each 1-SD increase in time-averaged HDL-C associated with a 44% reduced likelihood of new non-calcified plaque formation at follow-up (adjusted OR 0.56 [95% CI 0.35-0.92], Figure 1). In contrast, there was no effect of time-averaged HDL-C on new mixed or calcified plaque formation. Of 98 non-calcified plaques at baseline, 42 did not change at follow-up, 32 regressed (disappeared), 16 transitioned to mixed and 8 to calcified plaques. Each SD increase in time-averaged HDL-C yielded a 2.2-fold greater likelihood of non-calcified plaque regression (adjusted OR 2.21 [95% CI 1.02-4.83]). Sixteen of 52 mixed plaques present at baseline transitioned to more stable calcified lesions, and time-averaged HDL-C (per 1-SD increment) predicted a 3.5-fold increased likelihood of transition of mixed to fully calcified plaque (adjusted OR 3.56 [95% CI 1.25-10.17]).Conclusion:Higher HDL-C over time predicted regression of existing and decreased formation of new higher-risk non-calcified plaque. It also associated with transition of vulnerable mixed plaque to more stable fully calcified plaque. These effects were independent of RA treatment duration, prednisone dose and statin exposure.References:[1]Toms TE et al. Curr Vasc Pharmacol. 2010;8:301–326.Figure 1.Impact of HDL-C over time on coronary plaque progression in RADisclosure of Interests:George Karpouzas Speakers bureau: Sanofi/Genzyme/Regeneron, Consultant of: Sanofi/Genzyme/Regeneron, Grant/research support from: Pfizer, Sarah Ormseth: None declared, Elizabeth Hernandez: None declared, Matthew Budoff: None declared

Coronary atherosclerosis profile in patients with end-stage liver disease prior to liver transplantation due to alcoholic fatty liver: a coronary CTA study

Objectives To assess the coronary atherosclerosis profile by coronary computed tomography angiography (CTA) in patients with end-stage liver disease (ESLD) due to alcohol-related liver disease (ARLD) evaluated for liver transplantation (LT), in a retrospective matched case-controlled cohort study. Methods One hundred forty patients (age 60.6 years ± 9.8, 20.7% females) who underwent coronary CTA were included. Seventy patients with ESLD due to ARLD (ESLD-alc) were propensity score (1:1) matched for age, gender, and the major 5 cardiovascular risk factors with healthy controls. CTA analysis included the following: stenosis severity according to CAD-RADS as (0) = no, (1) minimal < 25%, (2) mild 25–50%, (3) moderate 50–70%, and (4) severe > 70% stenosis, total mixed plaque burden weighted for non-calcified component (G-score) and high-risk plaque criteria (Napkin-Ring, low attenuation plaque, spotty calcification, positive remodeling). Results Prevalence of coronary artery disease (CAD) was high (84.4%) in the ESLD-alc group but similar to controls. Stenosis severity was similar (CAD-RADS, 1.9 vs. 2.2, p = 0.289). High-grade stenosis (> 70%) was observed in 12.5% of ESLD-alc patients. High-risk plaques were less frequent in the ESLD-alc cohort as compared to controls (4.5% vs. 37.5%, p < 0.001), and total mixed plaque burden was lower (G-score, 4.9 versus 7.4, p = 0.001). Plaque density was lower in controls (56.6HU ± 3.2 vs. 91.3HU ± 4.5, p = 0.007) indicating more lipid-rich in controls, but higher mixed fibro-calcific plaque component in those with alcohol-related ESLD. Conclusion Patients with alcohol-related ESLD exhibit more mixed fibro-calcified plaques but less plaque with high-risk features and less fibro-fatty plaque burden, while total CAD prevalence is high. Key Points • Patients with ESLD prior to LT have a high total prevalence of CAD and stenosis severity, which is similar to those of healthy controls with an identical cardiovascular risk profile. • Patients with ESLD prior to LT due to alcohol abuse have more calcific but less fibro-fatty plaque and less high-risk plaque. • CTA seems to be a useful imaging technique for risk stratification prior to LT.

4182Sex specific patterns in the onset and manifestation of coronary atherosclerotic plaque; insights from the multi-center CCTA CONFIRM registry

Background Pathobiologic data support varied atherosclerotic plaque characteristics which uniquely define risk in women as compared to men (i.e., plaque erosion versus rupture). The advent of noninvasive coronary computed tomographic angiography (CCTA) allows for further exploration as to a sex-specific signature of atherosclerotic plaque features unique to women and different from that of men. In this analysis, we compared sex differences in the age of onset of coronary atherosclerosis and varied plaque findings between women and men. Methods From the multicenter CONFIRM registry, the Leiden CCTA score (based on segmental plaque extent, location, severity, and composition) was calculated in women and men without prior CAD, with imputation for missing plaque data. First, women and men were matched on the Leiden CCTA score to allow assessment of differences in atherosclerotic profile. Second, the earliest age of women and men to display a median Leiden CCTA score >0, >2, >6, >8 was evaluated. Third, the prognostic value of previously established thresholds of the Leiden CCTA score was examined for all-cause mortality with Cox-proportional hazard analysis, and specifically a sex interaction. Results In total, 11,678 women (age 58.5±12.4 years) and 13,272 men (age 55.6±12.5 years) were included. Of the patient subset matched on Leiden CCTA score (10,266 women, score 4.1±6.0 and 10,266 men, Leiden score 4.1±6.0, P=0.589), women were characterized by less obstructive CAD (≥50% stenosis) (17.5% vs 19.1%, P=0.003), more frequent non-obstructive left main plaque (10.1% vs 8.9%, P=0.004) and a lower number of segments with non-calcified or mixed plaque, but an equal number of calcified plaques. The earliest age when women and men have a median Leiden CCTA score above 0, 2, 4, 6, or 8 was consistently 14 to 16 years later for women. A visual representation of the CAD development delay is shown in Figure 1. Adjusted for age, the hazard ratio for death (827 events) for a score 6–20, and >20 (compared with 0–6) was 1.95 (95% CI 1.56–2.42), and 3.44 (95% CI 2.40–4.93) for women, respectively, and 1.63 (95% CI 1.31–2.03), 2.22 (95% CI 1.64–3.00) for men, respectively (P-interaction 0.006). Despite the low number of events, women <50 years with a score >20 were at 12.8 (95% CI 3.58–45.73) times increased risk. Conclusion There is an approximate 15-year delay in onset of coronary atherosclerosis for women compared to men. The burden of atherosclerotic plaque is associated with a higher relative hazard for death among women than men. The pattern of more nonobstructive CAD, especially in the left main coronary artery, but also less non-calcified plaque supports a sex-specific plaque signature which may uniquely define risk among women as compared to men. Acknowledgement/Funding The research reported in this manuscript was funded, in part, by the National Institute of Health (Bethesda, MD, USA) under award number R01 HL115150.

The efficacy and safety of Shenzhu Guanxin Recipe Granules for treatment of patients with coronary artery disease: protocol for a double-blind, randomized controlled trial

Background Coronary artery disease (CAD) is one of the most common types of the cardiovascular diseases, previous pilot trials suggested that Traditional Chinese Medicine brought clinical benefits for patients with CAD. We will conduct this trial to determine the efficacy and safety of Shenzhu Guanxin Recipe Granules for treatment of patients with coronary artery disease. Patients and Methods This randomized controlled trial recruited 194 patients who were diagnosed CAD by clinical manifestations and examinations, in which coronary computed tomography angiography (CCTA) showed 50-70% of stenosis, with soft or mixed plaque. The included participants were randomly assigned to the case group and control group with a 1:1 allocation ratio; patients in the case group received SGR and usual care, and those in the control group received placebo (6 g/day for 6 months) and usual care. The endpoint of the study included calcium coverage score (CCS), C-Reactive protein (CRP), and the levels of blood lipids, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and ATP-binding membrane cassette transporter A1 (ABCA1) were calculated before recruiting at6th month. The indicators were Seattle Angina Questionnaire (SAQ) and TCM syndrome questionnaire scores at 0th, 3rd, and 6th months. Discussion This clinical trial may provide a reliable evidence regarding the clinical effectiveness and safety of SGR therapy for patients with CAD by clinical manifestations and examinations, in which coronary computed tomography angiography (CCTA) showed 50-70% of stenosis, with soft or mixed plaque.

The efficacy and safety of Shenzhu Guanxin Recipe Granules for treatment of patients with coronary artery disease: protocol for a double-blind, randomized controlled trial

Background Coronary artery disease (CAD) is one of the most common types of the cardiovascular diseases, previous pilot trials suggested that Traditional Chinese Medicine brought clinical benefits for patients with CAD. We will conduct this trial to determine the efficacy and safety of Shenzhu Guanxin Recipe Granules for treatment of patients with coronary artery disease. Patients and Methods This randomized controlled trial recruited 194 patients who were diagnosed CAD by clinical manifestations and examinations, in which coronary computed tomography angiography (CCTA) showed 50-70% of stenosis, with soft or mixed plaque. The included participants were randomly assigned to the case group and control group with a 1:1 allocation ratio; patients in the case group received SGR and usual care, and those in the control group received placebo (6 g/day for 6 months) and usual care. The endpoint of the study included calcium coverage score (CCS), C-Reactive protein (CRP), and the levels of blood lipids, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and ATP-binding membrane cassette transporter A1 (ABCA1) were calculated before recruiting at6th month. The indicators were Seattle Angina Questionnaire (SAQ) and TCM syndrome questionnaire scores at 0th, 3rd, and 6th months. Discussion This clinical trial may provide a reliable evidence regarding the clinical effectiveness and safety of SGR therapy for patients with CAD by clinical manifestations and examinations, in which coronary computed tomography angiography (CCTA) showed 50-70% of stenosis, with soft or mixed plaque.

The efficacy and safety of Shenzhu Guanxin Recipe Granules for treatment of patients with coronary artery disease: protocol for a double-blind, randomized controlled trial

Background Coronary artery disease (CAD) is one of the most common types of the cardiovascular diseases, previous pilot trials suggested that Traditional Chinese Medicine brought clinical benefits for patients with CAD. We will conduct this trial to determine the efficacy and safety of Shenzhu Guanxin Recipe Granules for treatment of patients with coronary artery disease. Patients and Methods This randomized controlled trial recruited 194 patients who were diagnosed CAD by clinical manifestations and examinations, in which coronary computed tomography angiography (CCTA) showed 50-70% of stenosis, with soft or mixed plaque. The included participants were randomly assigned to the case group and control group with a 1:1 allocation ratio; patients in the case group received SGR and usual care, and those in the control group received placebo (6 g/day for 6 months) and usual care. The endpoint of the study included calcium coverage score (CCS), C-Reactive protein (CRP), and the levels of blood lipids, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and ATP-binding membrane cassette transporter A1 (ABCA1) were calculated before recruiting at6th month. The indicators were Seattle Angina Questionnaire (SAQ) and TCM syndrome questionnaire scores at 0th, 3rd, and 6th months. Discussion This clinical trial may provide a reliable evidence regarding the clinical effectiveness and safety of SGR therapy for patients with CAD by clinical manifestations and examinations, in which coronary computed tomography angiography (CCTA) showed 50-70% of stenosis, with soft or mixed plaque.

The efficacy and safety of Shenzhu Guanxin Recipe Granules for treatment of patients with coronary artery disease: protocol for a double-blind, randomized controlled trial

Background Coronary artery disease (CAD) is one of the most common types of the cardiovascular diseases, previous pilot trials suggested that Traditional Chinese Medicine brought clinical benefits for patients with CAD. We will conduct this trial to determine the efficacy and safety of Shenzhu Guanxin Recipe Granules for treatment of patients with coronary artery disease. Patients and Methods This randomized controlled trial recruited 190 patients who were diagnosed CAD by clinical manifestations and examinations, in which coronary computed tomography angiography (CCTA) showed 50-70% of stenosis, with soft or mixed plaque. The included participants were randomly assigned to the case group and control group with a 1:1 allocation ratio; patients in the case group received SGR and usual care, and those in the control group received placebo (6 g/day for 6 months) and usual care. The endpoint of the study included calcium coverage score (CCS), C-Reactive protein (CRP), and the levels of blood lipids, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and ATP-binding membrane cassette transporter A1 (ABCA1) were calculated before recruiting at6th month. The indicators were Seattle Angina Questionnaire (SAQ) and TCM syndrome questionnaire scores at 0th, 3rd, and 6th months. Discussion This clinical trial may provide a reliable evidence regarding the clinical effectiveness and safety of SGR therapy for patients with CAD by clinical manifestations and examinations, in which coronary computed tomography angiography (CCTA) showed 50-70% of stenosis, with soft or mixed plaque.

Abstract 17172: Ethnic Differences in Prevalence of Coronary Artery Calcification and Plaque Composition Among Whites and African Americans

Introduction: Racial differences in the prevalence of coronary artery calcification (CAC) are well documented. African Americans (AA) tend to have a lower prevalence of CAC despite greater coronary risk factors and according to some reports higher cardiovascular disease (CVD) morbidity and mortality Hypothesis: We hypothesize despite a lower prevalence of CAC; AA would have similar or higher burden of non-calcified plaque (NCP). Methods: We retrospectively evaluated data from 4280 (3886 whites and 482 AA) consecutive patients, who underwent non-contrast and contrast cardiac computed tomography at our center. We used the 17-segment American Heart Association classification for assessment of coronary arteries. We quantified the amount of plaque in each segment as mild (score of 1), moderate (score of 2), or severe (score of 3) using a previously described method. We calculated total plaque score (TPS) by summation of the amount of plaque of each coronary segment. The non-calcified plaque score (NCPS) and mixed plaque score (MPS) were similarly calculated by summing the plaque scores in each segment separately. The segment involvement score (SIS), ranging from 0 to 17, was calculated as the total number of segments with any plaque; the segment stenosis score (SSS), was obtained by grading the stenosis severity of each segment with plaque, as was previously described in literature. Results: Prevalence of CAC>0 was 77% in whites versus 61% in AA (median Interquartile range]:190[13-780] versus 38[0-275];P<0.001). After adjustment for age, diabetes, BMI, family history of CAD, chest pain, hyperlipidemia, HTN and smoking, there was no significant difference in NCPS (β(Se) = 0.1 (0.4), P=0.731) and MPS (β(Se) = -0.4 (0.8), p=0.590) in AA compared with whites. TPS (β(Se) = -1.6 (0.4), P<0.001), SSS (B(Se)=-1.5(0.5), p<0.001 and Segment involvement score (B(Se)= 0.9 (0.2), P<0.001) were significantly lower in AA compared with whites. Conclusion: Despite the significantly lower prevalence of CAC in AA, the burden of NCP and mixed plaque were similar in AA compared with whites. Further studies would be needed to elucidate whether the higher burden of NCP burden despite a lower prevalence of CAC is responsible for higher CVD mortality in AA.