Circulation, Volume 150, Issue Suppl_1, Page A4139135-A4139135, November 12, 2024. Background:Stroke associated with atrial fibrillation (AF) is a significant cause of mortality. This CDC analysis delves into mortality trends due to stroke in AF patients aged ≥ 25 years, from 1999 to 2020. By analyzing extensive datasets we scrutinized how factors such as gender, race, region of residence, and level of urbanization intersect with mortality rates.Methods:Death data from 1999 to 2020 was analyzed using the Centers for Disease Control and Prevention database, employing ICD codes I48 for AF and I64 for stroke. Age-adjusted mortality rate (AAMR) per 100,000 people with 95% confidence intervals was calculated for the total population, stratified by gender, race, urban/rural status, and census region. The Joinpoint regression software was used to calculate annual percentage change (APC) trend for each stratification.Results:In the U.S. between 1999 and 2020, total of 331,106 deaths occurred among adults due to AF associated with stroke. Deaths occurred predominantly in medical facilities (43.2%). The overall AAMR for AF associated stroke decreased from 26.8 per 100,000 in 1999 to 18.4 in 2020, with an AAPC of -2.05 (p value < 0.000001). Additionally, AAMR declined significantly from 1999 to 2018 (APC: -2.65, p value = 0.012398), followed by an increase from 2018 to 2020 (APC: 3.90, p value = 0.220356). Women had slightly higher AAMRs compared to men (men: 6.6; women: 7.1). The AAMR for women reduced substantially from 1999 to 2020 than for men. AAMRs varied among racial/ethnic groups, with White patients having the highest AAMR (7.4), followed by Blacks (5.4), American Indian or Alaska Natives (4.6), Asian or Pacific Islanders (4.5), and Hispanic population (4.1). AAMRs decreased for all races except for Black population. Geographically, AAMRs ranged from 4.3 in Nevada to 11.9 in Vermont, with the Western region showing the highest mortality (AAMR: 7.9). Nonmetropolitan areas had slightly higher AAMRs than metropolitan areas, with both experiencing a decrease over the study period.Conclusion:This analysis depicts significant disparities in mortality rates attributed to stroke associated with AF and underscores the need for larger population-based studies to further understand the primary factors influencing the observed geographical, racial, and gender differences. Targeted interventions and equitable healthcare access are crucial to mitigate these disparities and improve outcomes for this population.
Risultati per: Caratterizzazione dell'asma in base all'età di insorgenza: uno studio di coorte multi-database
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Abstract 4144512: Impact of Nutritional Status on Transcatheter Edge-to-Edge Repair Outcomes in Mitral Regurgitation: Insights from a National Database Analysis
Circulation, Volume 150, Issue Suppl_1, Page A4144512-A4144512, November 12, 2024. Introduction:Transcatheter edge-to-edge repair of the mitral valve with the MitraClip has offered a less invasive percutaneous alternative to surgical repair in select candidates with mitral regurgitation. Various factors impact the outcomes of MitraClip. We investigated the impact of nutritional status on the outcomes of MitraClip.Methods:Utilizing the nationwide inpatient sample data for years from January 1, 2016, and December 31, 2021, patients who underwent MitraClip were identified. They were categorized based on obesity and protein energy malnutrition (PEM). Statistical significance was assigned at p
Abstract 4144560: Phase 2 Open-label, Single-arm, Multi-center Clinical Trial to Evaluate the Efficacy and Safety of Camostat Mesylate in Patients with Protein-losing Enteropathy after Fontan Operation-Preliminary Outcome
Circulation, Volume 150, Issue Suppl_1, Page A4144560-A4144560, November 12, 2024. Introduction:Protein-losing enteropathy (PLE) is a multifaceted condition that profoundly affects the systemic health and quality of life of Fontan patients. Despite medical progress, the treatment of PLE remains a significant challenge. This study investigates the efficacy and safety of Camostat Mesylate for managing PLE patients who have undergone the Fontan operation.Hypothesis:We hypothesize that Camostat Mesylate will enhance the gut environment, resulting in increase of serum albumin levels and decrease of stool alpha-1 antitrypsin levels in PLE patients following Fontan operation.Methods:This phase 2, multicenter, open-label, single-arm trial included patients over 4 years old diagnosed with PLE following Fontan operation. Camostat Mesylate was added to conventional treatments, with follow-up assessments at 1, 3, and 6 months, and a final evaluation one month after discontinuation. Efficacy was measured by changes in serum albumin, stool alpha-1 antitrypsin levels, and PLE symptoms such as diarrhea, edema, weight changes, and ascites.Results:Nineteen patients were enrolled in the study, of whom fifteen patients completed follow-up as per protocol. The median age was 15 years (interquartile range, 12.0-21.3). The median time between the Fontan operation and PLE diagnosis was 2.4 years. Serum albumin levels increased from 2.5 to 2.6 g/dL (p=0.504), and stool alpha-1 antitrypsin levels decreased significantly from 280.0 to 172.1 mg/dL (p=0.033). Notably, patients with diarrhea at baseline showed substantial improvement in both parameters, with increased serum albumin levels from 1.8 to 2.2 g/dL and decreased stool alpha-1 antitrypsin levels from 220.3 to 80.2 mg/dL. No serious adverse events were reported during study period.Conclusions:Camostat Mesylate demonstrated safety and efficacy, reducing stool alpha-1 antitrypsin in PLE patients after Fontan operation, especially those with diarrhea at baseline. Therefore, Camostat Mesylate could be considered as an additional treatment option for patients with PLE following Fontan operation.Key words:Camostat mesylate; protein-losing enteropathy; Fontan operationSource of Funding:This research was funded by SNUH Lee Kun-hee Child Cancer&Rare Disease Project, Republic of Korea.
Abstract 4144555: Atrial Fibrillation Catheter Ablation among Patients with Mediastinal Radiation; Insight from The National Inpatient Database (2015-2020)
Circulation, Volume 150, Issue Suppl_1, Page A4144555-A4144555, November 12, 2024. Introduction/Background:Radiation therapy (RT) is one of the most common treatment modalities for mediastinal cancers. RT has multiple adverse cardiovascular effects and it has been identified as an independent risk factor for atrial fibrillation (AF). The efficacy of catheter ablation in AF is well established, however there is limited data on procedural safety and outcomes in patients with mediastinal cancers and history of radiationMethods:The National Inpatient Sample (NIS) was analyzed from 2015-2020 to identify admissions for AF catheter ablation among patients with previous history of mediastinal radiation exposure using the 10-PCS (International Classification of Diseases, procedure coding system) codes. Baseline characteristics were compared between the two groups and multivariate logistic regression was used to analyze hospitalization outcomes.Results:We identified 257,240 admissions for AF catheter ablation of which 1720 patients (0.67%) had a history of mediastinal radiation exposure. In the adjusted analysis, the odds of in-hospital mortality (aOR 0.639, 95% CI 0.34-1.20, p 0.1637), major complications (aOR 0.876, 95% CI 0.73-1.05, p 0.1443), any gastrointestinal or hematological complication (aOR 0.853, 95% CI 0.63-1.15, p 0.3017), renal complications (aOR 1.017, 95% CI 0.88-1.18, p 0.0509) were similar in both cohorts. The odds of any cardiovascular complication (aOR 0.825, 95% CI 0.70-0.97, p 0.0208) was lower and odds of any pulmonary complication (aOR 1.433, 95% CI 1.27-1.62, p
Abstract 4143265: Unveiling Gender Disparities in Chagas Disease patients with cardiac involvement: Insights from the NIS Database
Circulation, Volume 150, Issue Suppl_1, Page A4143265-A4143265, November 12, 2024. Background:Chagas disease (CD) is caused by a protozoan named Trypanosoma cruzi, in its chronic stage it may present with organ involvement, including the heart. Previous studies suggest that being a male is associated with increased mortality in CD. Understanding gender disparities associated with this condition is imperative for better patient management.Hypothesis:Gender has an impact on the outcome of CD with cardiac involvement.Aim:To investigate if gender has an impact on the clinical outcomes of CD with cardiac involvement.Methods:We examined the National Inpatient Sample data from 2016-2020, and conducted a retrospective descriptive study. We included all patients 18 years and older, male and female, diagnosed with CD with cardiac involvement. We excluded patients who were younger than 18 years of age. Baseline socio-demographic characteristics, comorbidities, and outcomes of the two groups were described. Hypothesis testing for categorical variables was performed using Chi-Square. Continuous variables were tested with a Student t-test. Statistical significance was defined as a two-tailed p-value of
Abstract 4119535: Aspirin Use and Cardiovascular Disease Incidence in Adults with High Lipoprotein(a): A Multi-Cohort Study
Circulation, Volume 150, Issue Suppl_1, Page A4119535-A4119535, November 12, 2024. Introduction:There is an active debate about who may benefit from taking aspirin to reduce their incidence of cardiovascular disease (CVD). Some prior cohort studies with small sample size suggest that aspirin use may be associated with a lower incidence of CVD or coronary heart disease (CHD) in adults with Lp(a) ≥50 mg/dL but not in those with Lp(a)
Abstract 4143225: Carotid Artery Ultrasound Grayscale and Incident Dementia: The Multi-Ethnic Study of Atherosclerosis (MESA)
Circulation, Volume 150, Issue Suppl_1, Page A4143225-A4143225, November 12, 2024. Introduction:Vascular contributions to cognitive impairment and dementia are potentially modifiable. Early detection of reversible arterial injury may improve dementia risk stratification and provide an opportunity for treatment monitoring. We hypothesized that carotid ultrasound grayscale-median (GSM), a novel imaging biomarker of early arterial injury, would predict incident all-cause dementia in the Multi-Ethnic Study of Atherosclerosis (MESA).Methods:The MESA enrolled adults aged 45-84 years old who were free of atherosclerotic cardiovascular disease at baseline. Common carotid artery GSM (grayscale units) was measured at baseline. Incident all-cause dementia events were identified by hospital and death records. Adjusted Cox proportional hazards models with natural cubic splines allowing for non-linear effects investigated the associations of baseline GSM and incident all-cause dementia.Results:The 1,788 participants were a mean (standard deviation) 63.1 (10.3) years old (53% female). Over a median of 13.7 years, 157 all-cause dementia events occurred. Lower (worse) carotid GSM independently predicted incident all-cause dementia (Hazard Ratio [HR] 1st to 3rd tertile, 1.39 [95% Confidence Intervals, 1.08-1.80], p =0.04). In models adjusting additionally for carotid IMT there was no attenuation of the association of GSM and incident all-cause dementia (HR 1.63 [95% CI 1.13-2.35], p=0.033) (Figure 1).Conclusions:Lower GSM predicts incident all-cause dementia independent of carotid intima-media thickness, suggesting it may serve as an early marker of dementia risk.
Abstract 4131228: Where Adults with Advanced Heart Failure Die: Insights from the CDC-WONDER Database
Circulation, Volume 150, Issue Suppl_1, Page A4131228-A4131228, November 12, 2024. Background:Adults with heart failure (HF) are becoming more and more prevalent. The location of death and related disparities in these patients are poorly understood.Aim:The purpose of the study was to look at the locations of adult deaths from HF and identify any age, race, or ethnicity-related variations over a 25-year period.Methods:The Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Database provided death certificate data and the National Center for Health Statistics provided individual-level mortality data for the trend-level analysis of adults aged (20-64 and 65+ years) conducted from 1999-2023. Hospital, home, hospice and nursing home/long-term care were the categories for the places of death.Results:Between 1999 and 2023, a total of 7,644,759 adult deaths from HF were recorded (87.9% White, 53.4% female). HF-related deaths decreased from 1999 (3.60% and 143.6 AAMR) to 2010 (3.47% and 123.1 AAMR). From 2010 onwards, a gradual rise is seen, with the rate of HF deaths reaching 5.18% and 168.1 AAMR in 2023. Notably, deaths at home increased from 18.41% (50,648 of 275,132) in 1999 to 33.47% (132,470 of 395,826) in 2023 and deaths in hospice/nursing homes increased from 30.95% (85,144 of 275,132) in 1999 to 34.71% (116,634 of 336,014) in 2017 and then sudden fall was observed until 2023 to 29.54% (116,931 of 395,826). Older adults (65+) were more likely to die in inpatient facilities. Gender, ethnicity, and urbanization influenced the place of death, with males, whites, and those residing in large metropolitan areas more likely to die in medical facilities.Conclusion:Prioritize end-of-life planning for HF patients with poor prognosis, regardless of age, to improve quality of life and death.
Abstract 4140981: In-Hospital Outcomes of Left Atrial Appendage Occlusion (LAAO) among patients with Atrial Fibrillation and Hematological Malignancy; Insight from The National Inpatient Database (2015-2020)
Circulation, Volume 150, Issue Suppl_1, Page A4140981-A4140981, November 12, 2024. Introduction/Background:Patients with hematological malignancies are at a higher risk of developing atrial fibrillation. Additionally, it can predispose to an increased risk of bleeding limiting anticoagulation for stroke prevention. LAAO has been successfully utilized among patients with atrial fibrillation and contraindication to anticoagulation.Research Question:What are the outcomes and in-hospital complications of left atrial appendage occlusion (LAAO) among patients with atrial fibrillation and hematological malignancy?Methods:The National Inpatient Sample (NIS) was analyzed from 2015-2020 to identify admissions for LAAO among patients with and without a hematological malignancy. Baseline characteristics were compared between the two groups and multivariate logistic regression was used to analyze hospitalization outcomes.Results:We identified 89,920 weighted admissions for LAAO procedures of which 1,665 patients (1.85%) had a hematological malignancy. In the adjusted analysis, the odds of MACCE (aOR 1.86, 95% CI 1.10-3.14, p 0.0205), cardiogenic shock (aOR 3.76, 95% CI 1.95-7.24, p
Abstract 4146540: Clinical characteristics and mortality outcomes in a multi-ethnic cohort of Asian patients with myocarditis
Circulation, Volume 150, Issue Suppl_1, Page A4146540-A4146540, November 12, 2024. Background:Myocarditis is an inflammatory disease of the myocardium associated with numerous adverse outcomes such as arrhythmias, heart failure, cardiac arrest as well as death. Clinical characteristics and mortality outcome data in myocarditis specific to Asian patients is limited.Research Question:To evaluate characteristics and mortality outcome amongst a multi-ethnic cohort of Asian patients diagnosed with myocarditis.Methods:This retrospective, single-center cohort study involved consecutive patients diagnosed with myocarditis between 2010 and 2021 in a tertiary academic center. Patient respective clinical profile, diagnostic results and outcomes were detailed. Categorical variables were compared between mortality groups using the chi-squared test, and continuous variables with t-tests or Mann-Whitney U tests.Results:A total of 203 patients (mean age 41.8, 40.9% female) diagnosed with myocarditis were included in the study. The prevalence of fulminant myocarditis, acute non-fulminant myocarditis and chronic inflammatory cardiomyopathy in this cohort was 31%, 67.2% and 5.5% respectively. Over a mean follow up period of 4.7 years (SD 3.5), the all-cause mortality was 17.7% (36 patients) (p=
Abstract 4140013: Sleep Disparities Across Demographics and Cardiometabolic Disorders in the NIH All of Us Fitbit Database
Circulation, Volume 150, Issue Suppl_1, Page A4140013-A4140013, November 12, 2024. Background:Prior research has noted disparities in sleep duration among demographic groups and those with cardiometabolic disorders. However, these are mostly based on self-reported data. The NIH All of Us Fitbit database offers a new method for objective and reliable sleep assessment.Goals:The study aimed to objectively assess sleep duration using the All of Us Fitbit database across various demographic variables and cardiometabolic disorders.Methods:All of Us participants with at least one year of Fitbit data were identified. Fitbit’s “minutes asleep” parameter was extracted daily over the first year of Fitbit use and averaged. The average total minutes asleep (TMA) was compared across self-reported age, sex and race groups. For those individuals who also shared their electronic health record (EHR) data, TMA was compared between those with and without hypertension, diabetes, and sleep apnea. T-test and ANOVA were used for comparisons.Results:The first year of Fitbit data for 13,039 participants (51 [16]* years, 69% female, 82% White) was analyzed, with sleep information available for 330 [104] days (90% complete data). TMA decreased with age, with the 18-44, 45-64, and 65+ groups averaging 366 [64], 348 [72], and 339 [85] minutes respectively (p
Abstract 4139978: Multi-Modality Imaging Characteristics and Survivals By Aortic Stenosis Subtypes In Patients Undergoing Transcatheter Aortic Valve Replacement
Circulation, Volume 150, Issue Suppl_1, Page A4139978-A4139978, November 12, 2024. Background:Discrepant transthoracic echocardiography (TTE) parameters are not infrequently observed in patients with significant aortic stenosis (AS), however, there is limited literature regarding their computed tomography (CT) characteristics and prognostic implications.Aims:We compared the multi-modality imaging characteristics and outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) by AS subtype.Methods:Patients with severe AS (defined as aortic valve area
Abstract 4142110: Coronary Artery Calcium Scans Powered by Artificial Intelligence (AI-CAC) Predicts Atrial Fibrillation and Stroke Comparably to Cardiac Magnetic Resonance Imaging: The Multi-Ethnic Study of Atherosclerosis (MESA)
Circulation, Volume 150, Issue Suppl_1, Page A4142110-A4142110, November 12, 2024. Background:Coronary artery calcium (CAC) scans contain more actionable information than the Agatston CAC score. We have previously shown in the Multi-Ethnic Study of Atherosclerosis (MESA) that AI-enabled left atrial (LA) volumetry in CAC scans (AI-CAC) enabled prediction of atrial fibrillation (AF) as early as one year. Furthermore, we have recently shown adding AI-CAC LA volumetry to CHA2DS2-VASc risk score improved stroke prediction in MESA. In this study we evaluated the performance of AI-CAC LA volumetry versus LA measured by human experts using cardiac magnetic resonance imaging (CMRI) for predicting AF and stroke, and compared them with CHARGE-AF risk score, Agatston score, and NT-proBNP.Methods:We used 15-year outcomes data from 3552 asymptomatic individuals (52.2% women, age 61.7±10.2 years) who underwent both CAC scans and CMRI in the MESA baseline examination. We have applied the AutoChamberTM(HeartLung.AI, Houston, TX) component of AI-CAC to 3552 CAC scans. CMRI LA volume was previously measured by human experts. Data on NT-proBNP, CHARGE-AF risk score and the Agatston score were obtained from MESA. Discrimination was assessed using the time-dependent area under the curve (AUC).Results:Over 15 years follow-up, 562 cases of AF and 140 cases of stroke accrued. The AUC for 15-yearAF predictionby AI-CAC LA volume (0.801) was comparable to CMRI LA volume (0.797) and significantly higher than Agatston CAC Score (0.687) and NT-proBNP (0.704). Similarly, the AUC for 15-yearstrokepredictionfor AI-CAC volumetry (0.761) was comparable to CMRI volumetry (0.751) and significantly higher than NT-proBNP (0.631) and Agatston CAC Score (0.646). AI-CAC LA volume outperformed CHARGE AF over 1-3 years for incident AF (p
Abstract 4143199: The Multi-omic, Multi-tissue Response to Acute Endurance and Resistance Exercise: Results from the Molecular Transducers of Physical Activity Consortium
Circulation, Volume 150, Issue Suppl_1, Page A4143199-A4143199, November 12, 2024. Introduction:Exercise is critical to cardiovascular health. However, the underlying molecular mechanisms are not well described. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) seeks to create a detailed molecular map of the response to exercise. Described here is the first human cohort of MoTrPAC, enrolled prior to the COVID-19 shutdown (N=175).Methods:Healthy, sedentary adults were randomized to an 8-exercise circuit of resistance exercise (RE, N=73), a 40 minute submaximal endurance exercise bout (EE, N=65), or to non-exercising control (N=37). Blood, muscle, and adipose tissue were sampled at 4-7 time points relative to exercise, depending on tissue/modality. Samples were deep phenotyped across multiple omic domains including chromatin accessibility, transcriptomics, proteomics, phosphoproteomics, and metabolomics.Results:The cohort was 72% female, with a mean±sd age of 41±15 years and BMI of 27.1±4.0 kg/m2. Exercise affected over 34,000 molecular features in ≥1 tissue/time point including a high proportion of transcriptomic and phosphoproteomic features (Figure A). Molecular signatures were compared between EE and RE: enrichment analysis of muscle phosphoproteomics showed a greater activation of MAP kinases in RE compared to EE at all time points. To identify plausible exerkines (secreted molecules signaling an acute exercise bout), differentially abundant features in any sampled tissue cells were compared to temporally-matched cognate protein levels in plasma, yielding 110 features. A known exerkine, CX3CL1 (fractalkine) was identified, in addition to novel candidates, such as cellular communication network factor 1 (CCN1), a secreted extracellular matrix protein linked to plasma triglyceride levels, which showed increased abundance early post exercise (Figure B). Network analysis across tissues and omes identified novel transcription factor “hubs” as candidate master regulators of exercise response.Conclusions:These first MoTrPAC data represent an unparalleled multi-tissue, multi-omic, multi-time point, multi-modality map of acute exercise, enhancing our understanding of the molecular transducers that may link exercise and cardiovascular health.
Abstract 4146424: Evaluating reported ethnicity, genetic ancestry and three-way local-ancestry admixture with preeclampsia in GenPE, a multi-center case-control study of Colombian women
Circulation, Volume 150, Issue Suppl_1, Page A4146424-A4146424, November 12, 2024. The role of genetic ancestry (GA) in hypertensive pregnancy disorders in Latin-American women is poorly understood.Using data from amulti-center case-control study (GenPE) of preeclampsia (PE) in young Colombian women(median age = 19) of predominantly low socioeconomic status (2364 controls and 1811 cases), who identify as Afro-Caribbean (AFR-C), White Hispanic (HISP), Amerindian, and Mixed ethnicity,we evaluated associations between 1) reported ethnicity, and 2) empirically estimated GA, with PE. We performed 3-way admixture mapping using European (EUR), African (AFR) and Amerindian (AMR) ancestry references from the Human Genome Diversity Project using the FLARE software to estimate local and global ancestry in GenPE samples. Statistical significance threshold, for three-way local ancestry analyses, was empirically estimated using STEAM (P = 3.45×10-6).In multivariable logistic regression modelsfor reported ethnicity,AFR-C were 33% more likely to have PE (OR = 1.33; P = 0.02) than HISP women.In models evaluating empirically estimated global GA,AFR was positively associated (OR per 10% increase in ancestry = 1.05; P = 0.002), while AMR (OR = 0.91; P = 0.035) and EUR (OR = 0.95; P = 0.009) were inversely associated with PE. Additionally,adjusting for reported ethnicity in models evaluating global GA and PEchanged estimates only marginally for AFR (OR = 1.04; P = 0.025) and EUR (OR = 0.92; P = 0.009).Evaluation of GA and PE in a subset of women who reported AFR-C ethnicity, showed stronger estimates for all global ancestries: AFR (OR = 1.11; P = 0.013, EUR (OR = 0.82; P = 0.026), and AMR (OR = 0.83; P = 0.01).Association analyses with AFR local GA identified three loci associated with PE.The top locusat chromosome 11, rs2021740 (a smooth muscle enhancer inOTOG1and nearMYOD1), each additional allele of AFR origin associated with 27% increased odds of PE (OR = 1.27; P = 1.13×10-7).The A-allele for this variantis found in greater frequency in AFR reference populations (22%) than in EUR (5%).Subgroup analyses with HELLP syndrome(279 cases and 2364 controls) shows intriguingly opposite findings with increased risk for global AMR and EUR ancestry and decreased risk for AFR ancestry.Using a genetically diverse hispanic population, we showgenetic ancestry is associated with PE independent of reported ethnicityand further demonstrate thepower of admixture mapping to identify a candidate locus for PE.
Abstract 4127990: Inactive Matrix Gla Protein and Cardiovascular Outcomes: the Multi-Ethnic Study of Atherosclerosis
Circulation, Volume 150, Issue Suppl_1, Page A4127990-A4127990, November 12, 2024. Background:Matrix Gla protein (MGP) inhibits arterial calcification. Higher inactive MGP, dephosphorylated-uncarboxylated (dp-ucMGP), is positively associated with vascular calcification, possibly portending cardiovascular events. The objective was to determine the association of dp-ucMGP with incident cardiovascular disease (CVD) events and mortality in the Multi-Ethnic Study of Atherosclerosis (MESA).Methods:MESA is a cohort study of 45-84 year-old individuals enrolled between 2000-02 with adjudicated outcomes through 2019. Dp-ucMGP was measured at baseline in n=2663 participants with cardiac computed tomography at Exams 1 (2000-02) and 5 (2010-12). Using age-stratified Cox proportional hazard models, adjusted for sex, race-ethnicity, body mass index, systolic blood pressure, statin use, anti-hypertensive medication use, smoking status, physical activity, alcohol use, diabetes, high density lipoprotein, low density lipoprotein, triglycerides, phosphate, and estimated glomerular filtration rate, we determined the association of dp-ucMGP with risk of all CVD (mean follow-up 16+4 years), hard CVD (17+3 years), hard CHD (17+3 years), and all-cause mortality (18+2 years).Results:The youngest age quartile (45-53-years-old) with higher dp-ucMGP levels (520-2934 pmol/L) had an increased risk of all CVD (HR 3.01 [95% CI 1.56, 5.80], p=0.001), hard CVD (HR 2.78 [95% CI 1.29, 6.02], p=0.009), hard CHD (HR 3.37 [95% CI 1.29, 8.81], p=0.013) and all-cause mortality (HR 2.69 [95% CI 1.06, 6.79], p=0.037) compared to dp-ucMGP levels between 150-519 pmol/L in maximally adjusted models. There was no relationship with any outcomes for the other age quartiles (Table).Conclusions:Middle aged individuals with elevated dp-ucMGP levels ( >520 pmol/L) had an increased risk of incident CVD, CHD, and all-cause mortality.