Dietary nitrate intake and net nitrite-generating capacity of the oral microbiome interact to enhance cardiometabolic health: Results from the Oral Infections Glucose Intolerance and Insulin Resistance Study (ORIGINS).

Background: We investigated the association between dietary nitrate intake and early clinical cardiometabolic risk biomarkers, and explored whether the oral microbiome modifies the association between dietary nitrate intake and cardiometabolic biomarkers. Methods: Cross-sectional data from 668 (mean [SD] age 31 [9] years, 73% women) participants was analyzed. Dietary nitrate intakes and alternative healthy eating index (AHEI) scores were calculated from food frequency questionnaire responses and a validated US food database. Subgingival 16S rRNA microbial genes (Illumina, MiSeq) were sequenced, and PICRUSt2 estimated metagenomic content. The Microbiome Induced Nitric oxide Enrichment Score (MINES) was calculated as a microbial gene abundance ratio representing enhanced net capacity for NO generation. Cardiometabolic risk biomarkers included systolic and diastolic blood pressure, HbA1c, glucose, insulin, and insulin resistance (HOMA-IR), and were regressed on nitrate intake tertiles in adjusted multivariable linear models. Results: Mean nitrate intake was 190[171] mg/day. Higher nitrate intake was associated with lower insulin, and HOMA-IR but particularly among participants with low abundance of oral nitrite enriching bacteria. For example, among participants with a low MINES, mean insulin[95%CI] levels in high vs. low dietary nitrate consumers were 5.8[5.3,6.5] vs. 6.8[6.2,7.5] (p=0.004) while respective insulin levels were 6.0[5.4,6.6] vs. 5.9[5.3,6.5] (p=0.76) among partcipants with high MINES (interaction p=0.02). Conclusion: Higher dietary nitrate intake was only associated with lower insulin and insulin resistance among individuals with reduced capacity for oral microbe-induced nitrite enrichment. These findings have implications for future precision medicine-oriented approaches that might consider assessing the oral microbiome prior to enrollment into dietary interventions or making dietary recommendations.

Clinical attachment loss is cross-sectionally associated with elevated glucose among adults without diabetes.

AIM: We investigated whether periodontal measures are cross-sectionally associated with prediabetes and cardiometabolic biomarkers among non-diabetic younger adults. MATERIALS AND METHODS: One thousand seventy-one participants (mean age = 32.2 years [SE = 0.3]; 73% female) from the Oral Infections, Glucose Intolerance and Insulin Resistance Study were enrolled. Full-mouth clinical attachment loss (fm-CAL), probing depth (fm-PD) and bleeding on probing were ascertained. Interproximal CAL (i-CAL) and probing depths (i-PD) served as our primary exposures. Glucose, HbA1c, insulin and insulin resistance (HOMA-IR) outcomes were assessed from fasting blood. Prediabetes was defined per American Diabetes Association guidelines. Prediabetes prevalence ratios (PR [95% CI]) and mean [SE] cardiometabolic biomarkers were regressed on periodontal variables via multivariable robust variance Poisson regression or multivariable linear regression. RESULTS: Prevalence of prediabetes was 12.5%. Fully adjusted prediabetes PR in Tertiles 3 versus 1 of mean i-CAL was 2.42 (1.77, 3.08). Fully adjusted fasting glucose estimates across i-CAL tertiles were 83.29 [0.43], 84.31 [0.37], 86.48 [0.46]; p for trend <.01. Greater percent of sites with i-PD ≥3 mm showed elevated natural-log-HOMA-IR after adjustment (0%-12% of sites = 0.33 [0.03], 13%-26% of sites = 0.39 [0.03], ≥27% of sites = 0.42 [0.03]; p for trend = .04). CONCLUSIONS: i-CAL (vs. fm-CAL) was associated with elevated fasting glucose and prediabetes, whereas i-PD (vs. fm-PD) was associated with insulin resistance. Future studies are needed to examine periodontal disease and incident prediabetes.

The impact of pre-existing hematologic disorders on morbidity and mortality following heart transplantation: Focus on early graft dysfunction.

BACKGROUND: Heart transplantation (HT) is the gold standard therapy for advanced heart failure, providing excellent long-term outcomes. However, postoperative outcomes are limited by bleeding, infections, and primary graft dysfunction (PGD) that contribute to early mortality after HT. HT candidates with pre-existing hematologic disorders, bleeding, and clotting, may represent a higher risk population. We assessed the short- and long-term outcomes of patients with pre-existing hematologic disorders undergoing HT. METHODS AND RESULTS: Medical records of all adult patients who received HT from January 2010 to December 2019 at our institution were retrospectively reviewed. Hematologic disorders were identified via chart review and adjudicated by a board-certified hematologist. Inverse probability weighting and multivariable models were used to adjust for potential pretransplant confounders. Four hundred and ninety HT recipients were included, of whom 29 (5.9%) had a hematologic disorder. Hematologic disorders were associated with severe PGD requiring mechanical circulatory support (aOR 3.15 [1.01-9.86]; p = .049), postoperative infections (aOR 2.93 [1.38-6.23]; p = .01), and 3-year acute cellular rejection (ACR) (≥1R/1B) (aSHR 2.06 [1.09-3.87]; p = .03). There was no difference in in-hospital mortality (aOR 1.23 [.20-7.58], p = .82) or 3-year mortality (aHR 1.58 [.49-5.12], p = .44). CONCLUSIONS: Patients with hematologic disorders undergoing HT are at increased risk of severe PGD, postoperative infections, and ACR, while in-hospital and 3-year mortality remain unaffected.

Periodontal Status, C-Reactive Protein, NT-proBNP, and Incident Heart Failure: The ARIC Study.

BACKGROUND: Periodontal disease (PD), resulting from inflammatory host response to dysbiotic subgingival microbiota, has been linked to cardiovascular disease; however, its relationship to heart failure (HF) and its subtypes (heart failure with reduced ejection fraction [HFrEF] and heart failure with preserved ejection fraction [HFpEF]) is unexplored. OBJECTIVES: The authors hypothesize that the presence of PD is associated with increased risk of incident HF, HFpEF, and HFrEF. METHODS: A total of 6,707 participants (mean age 63 ± 6 years) of the ARIC (Atherosclerosis Risk In Communities) study with full-mouth periodontal examination at visit 4 (1996-1998) and longitudinal follow-up for any incident HF (visit 4 to 2018), or incident HFpEF and HFrEF (2005-2018) were included. Periodontal status was classified as follows: healthy, PD (as per Periodontal Profile Classification [PPC]), or edentulous. Multivariable-adjusted Cox proportional hazards models were used to calculate HRs and 95% CIs for the association between PPC levels and incident HF, HFpEF, or HFrEF. Additionally, biomarkers of inflammation (C-reactive protein [CRP]) and congestion (N-terminal brain natriuretic peptide [NT-proBNP]) were assessed. RESULTS: In total, 1,178 incident HF cases occurred (350 HFpEF, 319 HFrEF, and 509 HF of unknown type) over a median of 13 years. Of these cases, 59% had PD, whereas 18% were edentulous. PD was associated with an increased risk for HFpEF (HR: 1.35 [95% CI: 0.98-1.86]) and significantly increased risk for HFrEF (HR: 1.69 [95% CI: 1.18-2.43]), as was edentulism: HFpEF (HR: 2.00 [95% CI: 1.37-2.93]), HFrEF (HR: 2.19 [95% CI: 1.43-3.36]). Edentulism was associated with unfavorable change in CRP and NT-proBNP, whereas PD was associated only with CRP. CONCLUSIONS: Periodontal status was associated with incident HF, HFpEF, and HFrEF, as well as unfavorable changes in CRP and NT-proBNP.

Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS.

Background The enterosalivary nitrate-nitrite-nitric oxide (NO3-NO2-NO) pathway generates NO following oral microbiota-mediated production of salivary nitrite, potentially linking the oral microbiota to reduced cardiometabolic risk. Nitrite depletion by oral bacteria may also be important for determining the net nitrite available systemically. We examine if higher abundance of oral microbial genes favoring increased oral nitrite generation and decreased nitrite depletion is associated with a better cardiometabolic profile cross-sectionally. Methods and Results This study includes 764 adults (mean [SD] age 32 [9] years, 71% women) enrolled in ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study). Microbial DNA from subgingival dental plaques underwent 16S rRNA gene sequencing; PICRUSt2 was used to estimate functional gene profiles. To represent the different components and pathways of nitrogen metabolism in bacteria, predicted gene abundances were operationalized to create summary scores by (1) bacterial nitrogen metabolic pathway or (2) biochemical product (NO2, NO, or ammonia [NH3]) formed by the action of the bacterial reductases encoded. Finally, nitrite generation-to-depletion ratios of gene abundances were created from the above summary scores. A composite cardiometabolic Z score was created from cardiometabolic risk variables, with higher scores associated with worse cardiometabolic health. We performed multivariable linear regression analysis with cardiometabolic Z score as the outcome and the gene abundance summary scores and ratios as predictor variables, adjusting for sex, age, race, and ethnicity in the simple adjusted model. A 1 SD higher NO versus NH3 summary ratio was inversely associated with a -0.10 (false discovery rate q=0.003) lower composite cardiometabolic Z score in simple adjusted models. Higher NH3 summary score (suggestive of nitrite depletion) was associated with higher cardiometabolic risk, with a 0.06 (false discovery rate q=0.04) higher composite cardiometabolic Z score. Conclusions Increased net capacity for nitrite generation versus depletion by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.

Early microbial markers of periodontal and cardiometabolic diseases in ORIGINS.

Periodontitis affects up to 50% of individuals worldwide, and 8.5% are diagnosed with diabetes. The high-comorbidity rate of these diseases may suggest, at least in part, a shared etiology and pathophysiology. Changes in oral microbial communities have been documented in the context of severe periodontitis and diabetes, both independently and together. However, much less is known about the early oral microbial markers of these diseases. We used a subset of the ORIGINS project dataset, which collected detailed periodontal and cardiometabolic information from 787 healthy individuals, to identify early microbial markers of periodontitis and its association with markers of cardiometabolic health. Using state-of-the-art compositional data analysis tools, we identified the log-ratio of Treponema to Corynebacterium bacteria to be a novel Microbial Indicator of Periodontitis (MIP), and found that this MIP correlates with poor periodontal health and cardiometabolic markers early in disease pathogenesis in both subgingival plaque and saliva.

Probiotic Use in Celiac Disease: Results from a National Survey.

BACKGROUND AND AIMS: Patients with celiac disease (CD) commonly use supplements for perceived health benefits despite scant evidence. We aimed to characterize the prevalence and predictors of probiotic use among CD patients. METHODS: We analyzed data from iCureCeliac®; a patient-powered research network questionnaire distributed by the Celiac Disease Foundation. We included adults with self-reported CD who answered questions regarding demographics, diagnosis, symptoms, and treatment. We compared probiotic users versus probiotic non-users and subsequently performed multivariable logistic regression, assessing for independent predictors of probiotic use. RESULTS: 4,909 patients met the criteria for inclusion in the study. Of these, 1,160 (23.6%) responded to a question regarding probiotic use. The mean age of participants was 38.8 years and 82% were female. 381 patients (33%) reported using probiotics. More probiotic users sought nutritional counseling at time of diagnosis (36% vs. 30%, p=0.05) and remained symptomatic despite a gluten-free diet (40% vs. 25%, p <0.001). Probiotic users had lower scores on the pain subscale of the SF36 (63.7±21.6 vs. 69.5±22.1, p=0.006). On multivariable analysis, patients diagnosed after age 50 (OR=2.04, 95%CI: 1.37-3.04), and those with persistent symptoms despite a gluten-free diet (OR=1.94, 95%CI: 1.44-2.63) were more likely to use probiotics. CONCLUSION: In this large study of a national CD registry, roughly one-third of CD patients reported using probiotics. Patients diagnosed later in life were more likely to use probiotics and those who remained symptomatic despite a gluten-free diet were twice as likely to take probiotics. Patients may be seeking additional means of treatment for persistent symptoms.

A Virtual Cardiovascular Care Program for Prevention of Heart Failure Readmissions in a Skilled Nursing Facility Population: Retrospective Analysis.

BACKGROUND: Patients with heart failure (HF) in skilled nursing facilities (SNFs) have 30-day hospital readmission rates as high as 43%. A virtual cardiovascular care program, consisting of patient selection, initial televisit, postconsultation care planning, and follow-up televisits, was developed and delivered by Heartbeat Health, Inc., a cardiovascular digital health company, to 11 SNFs (3510 beds) in New York. The impact of this program on the expected SNF 30-day HF readmission rate is unknown, particularly in the COVID-19 era. OBJECTIVE: The aim of the study was to assess whether a virtual cardiovascular care program could reduce the 30-day hospital readmission rate for patients with HF discharged to SNF relative to the expected rate for this population. METHODS: We performed a retrospective case review of SNF patients who received a virtual cardiology consultation between August 2020 and February 2021. Virtual cardiologists conducted 1 or more telemedicine visit via smartphone, tablet, or laptop for cardiac patients identified by a SNF care team. Postconsult care plans were communicated to SNF clinical staff. Patients included in this analysis had a preceding index admission for HF. RESULTS: We observed lower hospital readmission among patients who received 1 or more virtual consultations compared with the expected readmission rate for both cardiac (3% vs 10%, respectively) and all-cause etiologies (18% vs 27%, respectively) in a population of 3510 patients admitted to SNF. A total of 185/3510 patients (5.27%) received virtual cardiovascular care via the Heartbeat Health program, and 40 patients met study inclusion criteria and were analyzed, with 26 (65%) requiring 1 televisit and 14 (35%) requiring more than 1. Cost savings associated with this reduction in readmissions are estimated to be as high as US $860 per patient. CONCLUSIONS: The investigation provides initial evidence for the potential effectiveness and efficiency of virtual and digitally enabled virtual cardiovascular care on 30-day hospital readmissions. Further research is warranted to optimize the use of novel virtual care programs to transform delivery of cardiovascular care to high-risk populations.

Diet quality and periodontal disease: Results from the oral infections, glucose intolerance and insulin resistance study (ORIGINS).

AIMS: This study examined the cross-sectional association between diet quality and periodontal disease. MATERIALS AND METHODS: In the Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS), 923 individuals completed the National Cancer Institute's validated Diet History Questionnaire 1, from which the Alternative Healthy Eating Index (AHEI) scores and A Priori Diet Quality Scores (APDQS) were calculated. Mean probing depth (MPD), mean clinical attachment loss (MAL) and % of sites bleeding on probing (%BOP) were derived from full-mouth periodontal exams. Multivariable adjusted linear and logistic regression models assessed the associations between diet quality and MPD, MAL, %BOP, and the odds of periodontitis (defined via the CDC/AAP classification). RESULTS: Alternative Healthy Eating Index and APDQS were not associated with MPD, MAL, or periodontitis. While AHEI was also not associated with %BOP, the APDQS was associated with %BOP (p = .03). Higher nut consumption was related to lower MPD (p = .03) and periodontitis odds (p = .03). Higher red meat consumption was associated with higher MPD (p = .01) and %BOP (p = .05). Higher trans-fatty acid consumption was also associated with increased %BOP (p = .05). CONCLUSION: Overall diet quality scores were not associated with periodontal status. Future studies are necessary to replicate the associations observed in this study to minimize the risk of false discovery.

Cardiovascular disease risk factors among transgender women in Chiang Mai, Thailand.

Transgender individuals take hormone therapy (HT) for transitioning secondary sexual characteristics, especially by transgender women assigned male at birth (AMAB). The transgender drug is a relatively new field in health care, but limited data exist to inform the cardiovascular risk factor profile among younger individuals undergoing HT. Therefore, this study was to evaluate the relationship between HT and cardiovascular (CVD) risk factors in Thai transgender women. A cross-sectional study was conducted from October 1st 2018-November 30th 2018 in 100 transgender women not receiving HT (Control group) and 100 transgender women receiving HT (HT group) in Chiang Mai, Thailand. Demographic data were recorded for each consenting subject. Non-invasive arterial examinations were undertaken, including carotid intima-media thickness (CIMT), ankle-brachial index (ABI), and cardio-ankle vascular index (CAVI). CVD risk factors including lipid profiles, fasting plasma glucose (FPG), C-reactive protein (CRP), cardiovascular risk markers (pro b-type natriuretic peptide (proBNP) and cardiac troponin I), and sex hormone levels were determined. The average age in both groups was 24±5.1 years. The average time of HT use was 6.65±0.52 years in the HT group. Mean waist circumference was significantly lower in the HT group compared with the control group (77.50±14.00 vs. 81.20±12.90 cm; P=0.004) while CRP (3.44±6.82 vs. 3.28±5.80 mg/L; P=0.031) and cardiac troponin I (0.029±0.051 vs. 0.014±0.014 ng/mL; P=0.040) values were greater in HT group than the control group. Mean CIMT was lower in the HT group vs. the control group (P=0.094). Among transgender women, receiving HT was associated with enhanced levels of a subset of CVD risk factors. More research is necessary to inform the need for novel CVD prevention and treatment strategies in transgender women.

Predictors of Outcomes in Endoscopies for Foreign Body Ingestion: A Cross-Sectional Study.

BACKGROUND: As foreign body ingestion/food impaction is one of the less common indications for upper endoscopy in adults, few studies have investigated outcomes. We aimed to determine the distribution of ingested items warranting endoscopy and to identify factors associated with successful endoscopic retrieval. METHODS: We conducted a retrospective, cross-sectional study, identifying all endoscopies performed between June 2006 and June 2018 for foreign body ingestion or food impaction. We performed univariate and multivariate analyses to identify variables associated with endoscopic foreign body visualization and successful removal from the mouth. RESULTS: Of the 168 endoscopies identified, the ingested item was visualized in 131 (78%) and was removed from the mouth in 88 (52.4%). 6.5% of cases required surgery and 2.4% of cases had a perforation noted. The two most common foreign bodies were food boluses (51.2%) and bones (28.6%). Older patients were more likely to have their ingested foreign body visualized during endoscopy (age ≥ 70 compared to 18-29 adjusted odds ratio [aOR] 8.78; 95% CI 1.62-47.70) and more likely to have it removed from the mouth (aOR 5.57; 95% CI 1.34-22.85). Bones were less likely to be visualized on endoscopy (aOR 0.16; 95% CI 0.04-0.57) but not less likely to be removed successfully (aOR 0.85; 95% CI 0.42-1.72). Foreign bodies visible on radiography were more likely to be identified on endoscopy (aOR 9.07; 95% CI 2.71-30.37) and more likely to be successfully removed (aOR 2.82; 95% CI 1.26-6.32). CONCLUSIONS: Factors such as age, radiographic visibility, and the suspected foreign body may affect the likelihood that it can be visualized and removed. Future studies should focus on further characterizing complications of foreign body ingestions and the types of patients and objects most at risk.