Adverse Cardiovascular Disease Outcomes Research Articles

Risk of Adverse Cardiovascular Outcomes in Postmenopausal Women with Inflammatory Bowel Disease.

Individuals with inflammatory bowel disease (IBD) who lack traditional cardiovascular disease (CVD) risk factors, such as young females, are observed to experience adverse CVD outcomes. Whether women with IBD have increased CVD risk after the menopause transition is unclear. We conducted a survival analysis of Women's Health Initiative (WHI) participants and excluded those with missing IBD diagnosis, model covariate data, follow-up data, or a baseline history of the following CVD outcomes: coronary heart disease (CHD), ischemic stroke, venous thromboembolism (VTE), peripheral arterial disease (PAD). Risk of outcomes between IBD and non-IBD women was performed using Cox proportional hazard models, stratified by WHI trial and follow-up. Models were adjusted for age, socio-demographics, comorbidities (e.g., hypertension, diabetes, hypercholesterolemia, etc.), family history, and lifestyle factors (e.g., smoking, alcohol, physical activity, body mass index, etc.). Of 134,022 WHI participants meeting inclusion criteria, 1367 (1.0%) reported IBD at baseline. Mean baseline age was 63.4 years. After adjusting for age and other confounders, no significant difference was observed between IBD and non-IBD women for the risk of CHD (HR 0.96, 95% CI 0.73-1.24), VTE (HR 1.11, 95% CI 0.81-1.52) or PAD (HR 0.64, 95% CI 0.28-1.42). After adjusting for age, risk of ischemic stroke was significantly higher (HR 1.41, 95% CI 1.06-1.88) in IBD than non-IBD women. With further adjustment, the excess risk of ischemic stroke among IBD women was attenuated and no longer statistically significant (HR 1.31, 95% CI 0.98-1.76). Among postmenopausal women with IBD, risk of ischemic stroke may be higher than in non-IBD women.

Implications of Cardiopulmonary Risk for the Management of COPD: A Narrative Review.

Chronic obstructive pulmonary disease (COPD) constitutes a major global health burden and is the third leading cause of death worldwide. A high proportion of patients with COPD have cardiovascular disease, but there is also evidence that COPD is a risk factor for adverse outcomes in cardiovascular disease. Patients with COPD frequently die of respiratory and cardiovascular causes, yet the identification and management of cardiopulmonary risk remain suboptimal owing to limited awareness and clinical intervention. Acute exacerbations punctuate the progression of COPD in many patients, reducing lung function and increasing the risk of subsequent exacerbations and cardiovascular events that may lead to early death. This narrative review defines and summarises the principles of COPD-associated cardiopulmonary risk, and examines respiratory interventions currently available to modify this risk, as well as providing expert opinion on future approaches to addressing cardiopulmonary risk.

Abstract P115: Urban Greenspace and All-Cause, Cardiovascular Disease-Specific, and Breast Cancer-Specific Mortality Among Older Women With Breast Cancer in the United States: Regional Variations Within the Surveillance, Epidemiology, and End Results and Medicare Linked Database

Background: Cardiovascular disease (CVD) and cancer are leading causes of morbidity and mortality in the US. Cancer survivors are at increased risk for adverse CVD outcomes due to multiple factors, including cardiotoxicity. Research suggests that greenspace contributes to better health outcomes, including CVD and breast cancer (BC). Objective: To explore relationships between urban greenspace and all-cause (ACM), CVD-specific (CVDSM), and BC-specific (BCSM) mortality and explore regional differences among older women diagnosed with BC in the US SEER-Medicare database. Methods: The 2011 national landcover database was linked to the 2010 census tracts and the 2010-2017 SEER-Medicare BC cohort. Women were included if they were 66+ years at diagnosis, had invasive BC, enrolled in Medicare Part A and Part B for 12 months before diagnosis, and had a census tract match for greenspace. Independent variable ‘greenspace’ was census tract percent tree canopy quartiles. Outcomes were all-cause, CVD, and BC-specific survival. Censoring was determined by the end of the study date, 12/31/2018. Covariates included age and comorbidity at BC diagnosis, race/ethnicity, dual enrollment in both Medicare and Medicaid eligibility, neighborhood social vulnerability, and tumor stage. Results: Regional variations in association between greenspace and BC survival were observed (Table 1). Greenspace is protective for ACM and BCSM in California, Washington, New Jersey, and Michigan, while no significant associations were observed in Georgia or Louisiana. For CVDSM, greenspace is protective in CA, while no significant differences were observed in Washington, Louisiana, and Michigan. An inverse relationship is observed for CVDSM in Georgia and New Jersey. Discussion: Our findings warrant more studies to investigate why greenspace is protective in some areas (i.e., CA, NJ, MI) or hazardous in other areas (i.e., GA). There is a need to identify critical factors and pathways contributing to these greenspace-survival differences.

Association of neutrophil-to-lymphocyte ratio and risk of cardiovascular and all-cause mortality in hypertension patients

Background and objectiveHypertension affects over a billion people worldwide and is often associated with poor prognoses. The neutrophil-to-lymphocyte ratio (NLR) has become a significant marker, showing a connection to adverse outcomes in cardiovascular diseases (CVDs). The objective of this study is to examine the relationship between the NLR and outcomes in patients with hypertension. MethodsThe study included hypertensive individuals who were surveyed in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. Mortality status was determined using the data from National Death Index (NDI). To investigate the dose-response relationship, restricted cubic spline (RCS) models were used. This study employed adjusted cox proportional hazards regression models to compute hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) for all-cause and cardiovascular mortality. The predictive accuracy of the NLR for survival outcomes was assessed utilizing time-dependent receiver operating characteristic (ROC) curve analysis. ResultsA total of 13,724 participants were included in the final analysis, including 7073 males and 6651 females. The cohort was stratified into higher (>2.0) and lower (≤2.0) NLR groups according to the median value. Over a median follow-up of 64 months, there were 1619 all-cause deaths and 522 cardiovascular deaths among participants. The RCS analysis indicated a non-linear relationship between NLR and the risk of mortality. The adjusted model showed that the group with a higher NLR had a significantly higher risk of all-cause (HR 1.47, 95% CI 1.22–1.77) and cardiovascular mortality (HR 2.08, 95% CI 1.52–2.86). ROC analysis showed that the area under the curves (AUCs) of 0.692, 0.662, 0.644, and 0.625 for predicting all-cause mortality, and 0.712, 0.692, 0.687, and 0.660 for cardiovascular mortality at 1, 3, 5, and 10 years. ConclusionElevated NLR is associated with increased risk of cardiovascular and all-cause mortality, and NLR may independently predict outcomes in individuals with hypertension.

Disparities in Cardiovascular Disease-Related Outcomes Among Cancer Survivors in the United States: A Systematic Review of the Literature

Cancer and cardiovascular disease (CVD) are major causes of morbidity and mortality in the United States (US). Cancer survivors have increased risks for CVD and CVD-related mortality due to multiple factors including cancer treatment-related cardiotoxicity. Disparities are rooted in differential exposure to risk factors and social determinants of health (SDOH), including systemic racism. This review aimed to assess SDOH's role in disparities, document CVD-related disparities among US cancer survivors, and identify literature gaps for future research. Following the Peer Review of Electronic Search Strategies (PRESS) guidelines, MEDLINE, PsycINFO, and Scopus were searched on March 15, 2021, with an update conducted on September 26, 2023. Articles screening was performed using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, a pre-defined Population, Exposure, Comparison, Outcomes, and Settings (PECOS) framework, and the Rayyan platform. A modified version of the Newcastle-Ottawa Scale was used to assess the risk of bias, and RAW Graphs for alluvial charts. This review is registered with PROSPERO under ID #CRD42021236460. Out of 7,719 retrieved articles, 24 were included, and discussed diverse SDOH that contribute to CVD-related disparities among cancer survivors. The 24 included studies had a large combined total sample size (n=7,704,645; median=19,707). While various disparities have been investigated, including rural-urban, sex, socioeconomic status, and age, a notable observation is that non-Hispanic Black cancer survivors experience disproportionately adverse CVD outcomes when compared to non-Hispanic White survivors. This underscores historical racism and discrimination against non-Hispanic Black individuals as fundamental drivers of CVD-related disparities. Stakeholders should work to eliminate the root causes of disparities. Clinicians should increase screening for risk factors that exacerbate CVD-related disparities among cancer survivors. Researchers should prioritise the investigation of systemic factors driving disparities in cancer and CVD and develop innovative interventions to mitigate risk in cancer survivors.

Real-World Systolic and Diastolic Blood Pressure Levels and Cardiovascular Mortality in Patients With Type 2 Diabetes-Results From a Large Registry Cohort in Asia.

Elevated blood pressure (BP) is associated with increased risk of cardiovascular mortality. However, there is ongoing debate whether intensive BP lowering may paradoxically increase the risk of cardiovascular disease (CVD), especially in patients with type 2 diabetes (T2D). We investigated the association of BP with risk of CVD mortality in patients with T2D. We used data on 83 721 patients with T2D from a multi-institutional diabetes registry in Singapore from 2013 to 2019. BP was analyzed as categories and restricted cubic splines using Cox multivariable regression analysis stratified by preexisting CVD and age (<65 years versus ≥65 years). The primary outcome was CVD mortality, determined via linkage with the national registry. Among 83 721 patients with T2D (mean age 65.3 years, 50.6% women, 78.9% taking antihypertensive medications), 7.6 per 1000 person-years experienced the primary outcome. Systolic BP had a graded relationship with a significant increase in CVD mortality at levels >120 to 129 mm Hg. Diastolic BP levels >90 mm Hg were significantly associated with CVD mortality in those aged ≥65 years. In addition, diastolic BP <70 mm Hg was associated with a significantly higher risk of CVD mortality in all patients. In patients with T2D, clinic systolic BP levels ≥130 mm Hg or diastolic BP levels ≥90 mm Hg are associated with higher risk of CVD mortality. Diastolic BP <70 mm Hg is also associated with the risk of adverse CVD outcomes, although reverse causality cannot be ruled out.

Mid-Regional Proadrenomedullin in COVID-19—May It Act as a Predictor of Prolonged Cardiovascular Complications?

The rising prevalence of cardiovascular disease (CVD) and the impact of the SARS-CoV-2 pandemic have both led to increased mortality rates, affecting public health and the global economy. Therefore, it is essential to find accessible, non-invasive prognostic markers capable of identifying patients at high risk. One encouraging avenue of exploration is the potential of mid-regional proadrenomedullin (MR-proADM) as a biomarker in various health conditions, especially in the context of CVD and COVID-19. MR-proADM presents the ability to predict mortality, heart failure, and adverse outcomes in CVD, offering promise for improved risk assessment and treatment strategies. On the other hand, an elevated MR-proADM level is associated with disease severity and cytokine storms in patients with COVID-19, making it a predictive indicator for intensive care unit admissions and mortality rates. Moreover, MR-proADM may have relevance in long COVID, aiding in the risk assessment, triage, and monitoring of individuals at increased risk of developing prolonged cardiac issues. Our review explores the potential of MR-proADM as a predictor of enduring cardiovascular complications following COVID-19 infection.

Abstract 18447: Comparative Seasonal Variation in Outcomes Among Patients Hospitalized for Heart Failure in Cold- and Warm-Climate States

Background: Despite emerging evidence that extreme heat and air pollution exposure are linked to adverse cardiovascular disease outcomes, paradoxical seasonal trends in heart failure hospitalizations and deaths have been observed, with peaks occurring in winter months. This study aimed to explore how seasonal variations in heart failure admissions differ among individuals hospitalized in cold-climate and warm-climate states. Methods: Population-level, state-wide data were used to explore outcomes among all individuals hospitalized for heart failure in Texas (1999-2016) and New York (1994-2007). Seasonal variation was assessed using time of discharge (January-March, April-June, July-September, October-December). Multivariable logistic and linear regression were used to explore the relationship between time of discharge and the primary outcomes of interest: mortality and length of stay (LOS). Analyses were adjusted for age, sex, race, ethnicity, and comorbidities (hypertension, hyperlipidemia, diabetes, CAD, arrhythmias, anemia, COPD, tobacco use). Results: Among individuals hospitalized for heart failure in both Texas and New York, mortality and LOS were significantly increased during winter months compared to spring, summer, and early fall (Table). While similar seasonal trends were observed across states, the observed effect sizes were smaller in the Texas population. Conclusions: Among patients hospitalized for heart failure in Texas and New York, there is an increase in mortality and LOS during winter months. However, the differences in effect sizes after controlling for traditional risk factors suggests that other variables (i.e., temperature fluctuations) may affect these seasonal trends and warrants further exploration.

Recent advancement in regulatory requirements on hypertension in India as per CDSCO in comparison with south Africa

Hypertension is a significant health issue in India and KwaZulu-Natal, South Africa, and it is associated with a considerable reduction in adverse cardiovascular disease outcomes. The India Hypertension Control Initiative (IHCI) was launched to accelerate access to treatment services and reduce hypertension prevalence by 25% by 2025. The IHCI project was designed to improve hypertension control in public sector clinics, and it was launched in the 2018–2019 in 26 districts across five states of India: Punjab, Madhya Pradesh, Kerala, Maharashtra, and Telangana. Both India and KwaZulu-Natal, South Africa, face significant public health issues related to hypertension, with 29.8% of adults suffering from the condition. India has made significant progress in addressing hypertension and refining regulatory measures. The overall occurrence of hypertension in India is 29.8%. There was a vital difference in the prevalence between urban and rural areas and among certain demographic groups in both countries. In rural areas, awareness, treatment, and control were significantly lower among men compared to women. Hypertension prevalence was higher in urban than rural areas in all studies that covered both types of area in the country. Awareness and treatment are especially important in the rural areas. It appears that hypertension is a significant issue in both countries, with higher prevalence rates in urban areas and among certain demographic groups. In this paper, we review and focus on the comparison on regulatory requirements on hypertension in both the countries.

Vascular Age Assessed From an Uncalibrated, Noninvasive Pressure Waveform by Using a Deep Learning Approach: The AI-VascularAge Model.

Aortic stiffness, assessed as carotid-femoral pulse wave velocity, provides a measure of vascular age and risk for adverse cardiovascular disease outcomes, but it is difficult to measure. The shape of arterial pressure waveforms conveys information regarding aortic stiffness; however, the best methods to extract and interpret waveform features remain controversial. We trained a convolutional neural network with fixed-scale (time and amplitude) brachial, radial, and carotid tonometry waveforms as input and negative inverse carotid-femoral pulse wave velocity as label. Models were trained with data from 2 community-based Icelandic samples (N=10 452 participants with 31 126 waveforms) and validated in the community-based Framingham Heart Study (N=7208 participants, 21 624 waveforms). Linear regression rescaled predicted negative inverse carotid-femoral pulse wave velocity to equivalent artificial intelligence vascular age (AI-VA). The AI-VascularAge model predicted negative inverse carotid-femoral pulse wave velocity with R2=0.64 in a randomly reserved Icelandic test group (n=5061, 16%) and R2=0.60 in the Framingham Heart Study. In the Framingham Heart Study (up to 18 years of follow-up; 479 cardiovascular disease, 200 coronary heart disease, and 213 heart failure events), brachial AI-VA was associated with incident cardiovascular disease adjusted for age and sex (model 1; hazard ratio, 1.79 [95% CI, 1.50-2.40] per SD; P<0.0001) or adjusted for age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, prevalent diabetes, hypertension treatment, and current smoking (model 2; hazard ratio, 1.50 [95% CI, 1.24-1.82] per SD; P<0.0001). Similar hazard ratios were demonstrated for incident coronary heart disease and heart failure events and for AI-VA values estimated from carotid or radial waveforms. Our results demonstrate that convolutional neural network-derived AI-VA is a powerful indicator of vascular health and cardiovascular disease risk in a broad community-based sample.

Comparison of Atherosclerotic Cardiovascular Risk Factors and Cardiometabolic Profiles Between Current and Never Users of Marijuana.

The relationship between marijuana use and cardiovascular health remains uncertain, with several observational studies suggesting a potential association with increased adverse atherosclerotic cardiovascular disease (ASCVD) outcomes. This study examined the relationship between marijuana use, ASCVD risk factors, and cardiometabolic risk profiles. US adults (18-59 years) without cardiovascular disease were identified from the National Health And Nutrition Examination Survey (2005-2018) based on self-reported marijuana use. Current users (used within the past month) and never users were compared with assess the burden and control of traditional ASCVD risk factors and biomarkers, using inverse probability of treatment weighting to adjust for sociodemographic and lifestyle factors, including tobacco use. Of the 13 965 participants identified (mean age, 37.5; 51.2% female; 13% non-Hispanic Black), 26.6% were current users. Current users were predominantly male, low-income, and more likely to be concurrent tobacco users. Inverse probability of treatment weighting analysis showed no significant differences in the burden and control of hypertension (19.3% versus 18.8%, P=0.76; 79.8% versus 77.8%, P=0.75), dyslipidemia (24.0% versus 19.9%, P=0.13; 82% versus 75%, P=0.95), diabetes (4.8% versus 6.4%, P=0.19; 52.9% versus 50.6%, P=0.84), obesity (35.8% versus 41.3%, P=0.13), and physical activity levels (71.9% versus 69.3%, P=0.37) between current and never users. Likewise, mean 10-year ASCVD risk scores (2.8% versus 3.0%, P=0.49), 30-year Framingham risk scores (22.7% versus 24.2%, P=0.25), and cardiometabolic profiles including high-sensitivity C-reactive protein (3.5 mg/L versus 3.7 mg/L, P=0.65), neutrophil-lymphocyte ratio (2.1 versus 2.1, P=0.89), low-density lipoprotein (114.3 mg/dL versus 112.2 mg/dL, P=0.53), total cholesterol (191.2 mg/dL versus 181.7 mg/dL, P=0.58), and hemoglobin A1C (5.4% versus 5.5%, P=0.25) were similar between current and never users. This cross-sectional study found no association between self-reported marijuana use and increased burden of traditional ASCVD risk factors, estimated long-term ASCVD risk, or cardiometabolic profiles. Further studies are needed to explore potential pathways between adverse cardiovascular disease outcomes and marijuana use.

Prevalence of anemia and associated factors among adult hypertensive patients in Referral Hospitals, Amhara Regional State

Anemia is a risk factor for adverse cardiovascular disease outcomes in hypertensive patients. Chronic anemia increases preload, reduces afterload, and leads to increased cardiac output in hypertension patients. In the long term, this may result in maladaptive left ventricular hypertrophy, which in turn is a well-recognized risk factor for cardiovascular disease outcomes and all-cause mortality in hypertension. Low hemoglobin and hematocrit levels might be strongly indicate hypertensive end-organ damage, specifically kidney failure. Therefore, this study determined the prevalence of anemia and associated factors among hypertensive patients in Referral Hospitals, Amhara Regional State, Ethiopia, in 2020. An institution-based cross-sectional study was conducted in Amhara Regional Referral Hospitals from February 20 to April 30, 2020. Random and systemic sampling techniques were used to select 428 study participants. Data were entered and coded in to Epi data version 3.0 and then exported into STATA 14 for analysis. In bivariable logistic regression, variables with a p-value of < 0.25 were included in multivariable logistic regression. Using a 95% confidence interval, variables having a p-value ≤ 0.05 in multivariable logistic regression were declared as statistically significant variables. In this study, a total of 428 study participants were involved with 99.5% response rate. The prevalence of anemia among hypertensive patients was 17.6%, with a 95% CI (14.3–21.5%). Estimated glomerular filtration rate (eGFR) < 90 ml/min (AOR = 2.77, 95% CI 1.56- 4.92)], duration of hypertension (HTN) ≥ 5 years (AOR = 2.37, 95% CI 1.36–4.15), uncontrolled blood pressure (AOR = 1.91, 95% CI 1.08–3.35), and higher pulse pressure (AOR = 1.05 (95% CI 1.02–1.08) were significantly associated with anemia. Nearly one out of five hypertensive patients had anemia. Impaired estimated glomerular filtration rate, duration of HTN, blood pressure status, and pulse pressure were the independent predictors of anemia among hypertensive patients. Screening hemoglobin level at a regular interval is recommended for the hypertensive patients to take an appropriate intervention.

Protein Glycosylation Influences Soluble Urokinase Plasminogen Activator Receptor (suPAR) Measurements

Elevated plasma levels of the biomarker soluble urokinase plasminogen activator receptor (suPAR) are prognostic of adverse outcomes in cardiovascular disease (CVD). This novel inflammatory protein has five known N-linked glycosylation sites, but the contribution of glycosylation to disease progression is unknown. This study aimed to assess the impact of glycosylation on suPAR measurements. Bio-banked plasma samples from healthy volunteers and patients with CVD were treated with deglycosylation enzymes. suPAR was measured for all treated and untreated samples using the Virogates suPARnostic ELISA. Percentage change in suPAR concentrations following treatment were compared using paired t-test, and differences between patient cohorts were examined using the Mann-Whitney test. In healthy subjects, suPAR concentrations increased after pre-treatment with deglycosylation enzymes (median 1.8 vs 2.4 ng/mL; p<0.001; n=15). In patients diagnosed with myocardial infarction (MI), a percentage increase in suPAR concentrations was also obtained after deglycosylation treatment, and this increment was higher than acute chest pain patients without MI (58% vs 44%; p=0.02; n=15). In patients with acute decompensated heart failure, a higher percentage change in suPAR concentrations was also observed following deglycosylation, compared with that of healthy subjects (38% vs 30%; p=0.04; n=33). suPAR immunoreactivity increased for the ViroGates ELISA after removal of protein glycosylation, as demonstrated by higher concentrations observed after treatment. This suggests that the current clinical assay for suPAR is influenced by its N-linked glycosylation. As glycosylation alterations are associated with CVD, further investigations are required to assess this implication with respect to the prognostic accuracy of suPAR in cardiovascular disease progression.

Immunologic profiles in patients with chronic limb-threatening ischemia undergoing endovascular revascularization.

Inflammation and immune dysregulation have been associated with adverse outcomes in cardiovascular disease. There is limited understanding of the association of different profiles of white blood cell (WBC) subsets and red cell distribution width (RDW) in patients with chronic limb-threatening ischemia (CLTI). Patients with CLTI undergoing endovascular revascularization in our single-center, tertiary care hospital from 2017 to 2019, who had a preceding complete blood count (CBC) with WBC differentials (n =213), were included in the analysis. Patient characteristics, laboratory values, and clinical outcomes were collected. Cox proportional hazards regression models were used to assess for associations between all-cause mortality and leukocyte subset; multivariate analysis was used to account for confounders. Kaplan-Meier curves were generated to depict survival censored at 1 year postrevascularization using baseline CBC indices. Adjusting for confounders, elevated RDW was associated with increased mortality (continuous per % increase, adjusted hazard ratio [HR] 1.33, p < 0.001). Baseline lymphopenia was associated with mortality in univariate analysis. Other leukocyte subtypes were not associated with mortality outcomes in our population. Exploratory analysis showed negative deflections in ∆WBC from pre- to postprocedure day 1 were affiliated with increased mortality when adjusted for age, sex, race, chronic kidney disease, and baseline hemoglobin (∆WBC HR 1.16, p = 0.004). Further exploratory analysis showed an association between RDW and all-comers readmission. The utilization of a periprocedural WBC subset differential can be a useful adjunct to risk-stratify patients with CLTI undergoing endovascular revascularization. Further studies are needed to understand potential ways to modulate immune dysregulation so as to improve mortality outcomes.

The Relationship Between the Neutrophil Percentage-to-Albumin Ratio and Rates of 28-Day Mortality in Atrial Fibrillation Patients 80 Years of Age or Older.

Atrial fibrillation (AF) is the most common cardiac arrhythmia among the older patients (≥ 80 years) in clinical practice. The index of neutrophil percentage-to-albumin ratio (NPAR) is a reliable predictor of adverse outcomes in cardiovascular diseases. There is scarce evidence regarding the association between NPAR and mortality among the older patients with AF. The research was conducted among 1141 patients with AF between January 2015 and June 2020, hospitalized at Huadong Hospital affiliated with Fudan University. The primary outcome were 28-day all-cause and cardiovascular mortality. Cox regression analysis and Kaplan-Meier survival curves were used to explore the correlation between NPAR and 28-day all-cause or cardiovascular mortality. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) were performed for the predictive values of NPAR on prognosis. The 28-day death rate from cardiovascular disease and all-causes were 3.3% and 8.7%, respectively. Continuous NPAR levels were positively associated with all-cause (HR 1.13, 95% CI 1.09, 1.16) and cardiovascular (HR 1.16, 95% CI 1.10, 1.23) mortality after adjustment for confounding variables. Relative to patients in the T1 group, those in higher NPAR tertiles also exhibit elevated risks of all-cause (P < 0.001) and cardiovascular mortality (P < 0.001). Furthermore, both all-cause and cardiovascular mortality rates rose with increasing NPAR in all analyzed subgroups. NPAR values are consistently positively related to 28-day all-cause and cardiovascular mortality rates in patients ≥80 years of age with AF.

Abstract 13: Circadian Misalignment is Associated With Impaired Heart Rate Variability in Adolescents

Introduction: Adequate sleep has been recognized by AHA as part of Life’s Essential 8 in the prevention of cardiovascular disease (CVD). The circadian system, which governs the sleep-cycle, is also involved in cardiac, metabolic and autonomic regulation. Heart rate variability (HRV), a marker of cardiac autonomic modulation (CAM), is known to predict CVD. As a result, circadian misalignment of the sleep-wake cycle, which is highly prevalent in adolescents, may impact CAM and be a potential risk factor for adverse CVD outcomes in early life. Hypothesis: We hypothesize that deviations in the circadian timing of sleep are associated with blunted HRV in adolescents. Methods: We analyzed data from 337 population-based randomly-selected adolescents from the Penn State Child Cohort (median 16 years; 47% female; 21% racial/ethnic minority) who had at least 3-night at-home actigraphy (ACT), in-lab 9-h polysomnography (PSG) and 24-h Holter-monitoring heart rate variability (HRV) data. ACT-sleep duration and sleep midpoint (SM) were calculated as the intra-individual mean total sleep time and midpoint of the sleep period, respectively. ACT-sleep variability and sleep regularity (SR) were calculated as the intra-individual standard deviation of sleep duration and sleep midpoint across nights, respectively. Frequency and time-domain HRV indices, including HR oscillations at high frequencies (HF), standard deviation between normal heart beats or R-R intervals (SDNN), and root mean square of successive differences between normal heartbeats (RMSSD), were primary outcomes. Linear regression models tested SM and SR as predictors of HRV indices, while accounting for sex, race/ethnicity, age, body mass index, ACT-sleep duration, ACT-sleep variability, and PSG-apnea/hypopnea index. Results: While there were no meaningful associations between SM or SR with daytime HRV, there were significant associations between SM with nighttime HRV. A later SM was associated with lower nighttime Log-HF, SDNN and RMSSD, yet higher nighttime LF/HF (all p&lt;0.03). For each standard deviation increase in SM (i.e., 1.5 hours later), there was a decrease of -5.50ms (1.92) in nighttime RMSSD (p=0.004). More specifically, the nighttime RMSSD of adolescents with a SM at 5:30 (i.e., sleep onset at 2:00, sleep offset at 9:00), was 18.2ms (6.7) lower (p=0.007) than that of adolescents with a SM at 2:30 (i.e., sleep onset at 23:00, sleep offset at 6:00). Conclusions: A delayed sleep phase is associated with impaired CAM in adolescents. These data support that circadian misalignment of the sleep-wake cycle may independently contribute to CVD risk.

Comparison of Body Mass Index (Four Categories) to In-Hospital Outcomes in Patients Who Underwent Transcatheter Aortic Valve Implantation

Although obesity is often associated with adverse outcomes in cardiovascular diseases, studies have demonstrated a beneficial effect on patients who underwent transcatheter aortic valve implantation (TAVI), coining the term "obesity paradox." We sought to determine if the obesity paradox is valid when patients are studied in body mass index (BMI) groups versus simplified classification of obese and nonobese. We examined the National Inpatient Sample database from 2016 to 2019 for all patients who underwent TAVI >18 years of age using the International Classification of Diseases, 10th edition procedure codes. Patients were grouped by BMI categories of underweight, overweight, obese, and morbidly obese. They were compared with normal-weight patients to assess the relative risk of in-hospital mortality, cardiogenic shock, ST-elevation myocardial infarction, bleeding complications requiring transfusions, and complete heart blocks requiring permanent pacemaker. A logistic regression model was constructed to account for potential confounders. Of the 221,000 patients who underwent TAVI, 42,315 patients with appropriate BMI designation were stratified into BMI groups. Compared to the normal-weight group, overweight, obese, and morbid-obese TAVI patients were associated with a lower risk of in-hospital mortality (relative risk [RR] 0.48, confidence interval [CI] 0.29 to 0.77, p <0.001), (RR 0.42, CI 0.28 to 0.63, p <0.001), (RR 0.49, CI 0.33 to 0.71, p <0.001 respectively), cardiogenic shock (RR 0.27, CI 0.20 to 0.38, p <0.001), (RR 0.21, CI 0.16 to 0.27, p <0.001), (RR 0.21, CI 0.16 to 0.26, p <0.001), and blood transfusions (RR 0.63, CI 0.50 to 0.79, p <0.001), (RR 0.47, CI 0.39 to 0.58, p <0.001), (RR 0.61, CI 0.51 to 0.74, p <0.001). This study indicated that obese patients were at a significantly lower risk of in-hospital mortality, cardiogenic shock, and bleeding complications requiring transfusions. In conclusion, our study supported the existence of the obesity paradox in TAVI patients.

Obstructive Sleep Apnea and Cardiovascular Disease: Where Do We Stand?

Obstructive sleep apnea is common in adults with cardiovascular disease. Accumulating evidence suggests an association between obstructive sleep apnea and cardiovascular disease independent of the traditionally recognized cardiovascular disease risk factors. Observational studies indicate that obstructive sleep apnea is a risk factor for development of cardiovascular disease and that alleviation of obstructive events with positive airway pressure may improve cardiovascular disease outcomes. However, recent randomized controlled trials have not supported the beneficial effect of positive airway pressure in cardiac populations with concomitant obstructive sleep apnea. Some evidence suggests that the relationship between obstructive sleep apnea and traditionally recognized cardiovascular disease risk factors is bidirectional, suggesting that patients with cardiovascular disease may also develop obstructive sleep apnea and that efficient treatment of cardiovascular disease may improve obstructive sleep apnea. Recent data also indicate that the apnea-hypopnea index, which is commonly used as a diagnostic measure of obstructive sleep apnea severity, has limited value as a prognostic measure for cardiovascular disease outcomes. Novel markers of obstructive sleep apnea-associated hypoxic burden and cardiac autonomic response seem to be strong predictors of adverse cardiovascular disease outcomes and response to treatment of obstructive sleep apnea. This narrative review and position paper from the Turkish Collaboration of Sleep Apnea Cardiovascular Trialists aims to update the current evidence about the relationship between obstructive sleep apnea and cardiovascular disease and, consequently, raise awareness for health professionals who deal with cardiovascular and respiratory diseases to improve the ability to direct resources at patients most likely to benefit from treatment of obstructive sleep apnea and optimize treatment of the coexisting cardiovascular diseases. Moreover, the Turkish Collaboration of Sleep Apnea Cardiovascular Trialists aims to contribute to strengthening the efforts of the International Collaboration of Sleep Apnea Cardiovascular Trialists in this context.

Abstract 15192: Neighborhood Social Vulnerability Predicts Cardiovascular Disease Outcomes Through Pro-Inflammatory Risk Factors

Introduction: Emerging evidence suggests that neighborhood adverse characteristics are linked to nationwide disparities in cardiovascular disease (CVD) incidence and mortality. However, it is unclear if this association is linked to disease progression and outcomes in people with established CVD. Hypothesis: We hypothesized that in patients with CVD, neighborhood social adversity, measured as social vulnerability index (SVI) predicts incident cardiovascular events at least partly through pro-inflammatory. Methods: A total of 4150 participants enrolled in the Emory Cardiovascular Biobank, residential addresses were geocoded according to the census tract and SVI was determined using the Center for Disease Control data. Serum hs-C-reactive protein (hsCRP) levels were measured during enrollment and participants were followed up for incident myocardial infarction (MI) and cardiovascular death. Subdistribution hazard models were used to investigate the association between SVI and the study endpoint. A mediation analysis was performed to evaluate whether hsCRP levels underly this association. Results: Mean age was 63 years, 24% Black, and 64% were women. During a median 5 year follow-up, there were 904 (22%) adverse events. SVI and hsCRP were correlated (r=0.12, P&lt;0.001). After adjustment for age, race, sex,hypertension, diabetes mellitus, body mass index, prior MI, prior heart failure, renal function, smoking, statin and aspirin use, participants in the highest SVI quartile (most socially vulnerable), had a 31% (95%CI, 4%,64%) higher risk of CV death/MI compared to those in the lowest quartile. The risk was attenuated and became insignificant after adjusting for the hsCRP 23% (CI -3%, 54%). Serum hsCRP levels mediated 61% of the association between SVI and adverse events. Conclusions: Neighborhood social vulnerability is an independent risk factor for adverse outcomes in CVD, that is at least in part mediated through increased systemic inflammation. Neighborhood social vulnerability may explain some of the residual risk observed in patients with CVD.

Abstract 13132: Uncontrolled Diabetes is Associated With Adverse Cardiovascular Disease Outcomes in Those With Stage B Heart Failure

Background: Among persons with stage B heart failure (HF) (subclinical cardiac dysfunction), diabetes is associated with markedly increased risk of progression to clinical HF. Whether stage B HF indicates greater risk for other cardiovascular disease (CVD) outcomes in the presence of diabetes is unknown. Methods: We included ARIC Visit 5 (2011-13) participants without clinical HF who met criteria for stage A (HF risk factors) or stage B (subclinical cardiac dysfunction by echocardiogram or elevated cardiac biomarkers) HF. Across HF stages A and B, we calculated incidence rates and their differences and used Cox models to estimate hazard ratios for overall mortality, CVD mortality, coronary heart disease (CHD), and HF associated with controlled diabetes (HbA1c &lt;7%) and uncontrolled diabetes (HbA1c ≥ 7%), compared to no diabetes. Results: 4,774 participants (mean age 75.4, 58.3% women, 20.2% black) were followed for a median 7.3 years, with 867 deaths, 237 CVD deaths, 228 CHD events, and 470 HF events. There were significant additive interactions (increased absolute risk) associated with uncontrolled diabetes (vs. no diabetes) for total mortality, CVD death, CHD, and HF for stage B, but not stage A (Table). The incidence rate differences (per 1000 person-years) associated with uncontrolled diabetes (vs. no diabetes) were greater in stage B vs stage A for all outcomes (Table). In multivariable adjusted models, uncontrolled diabetes (vs. no diabetes) was associated with statistically significant hazard ratios (increased relative risk) for all CVD outcomes in stage B, but did not have significant associations with any CVD outcomes in stage A (Table). Conclusion: In stage B HF, diabetes is associated with global CVD risk. Intensive preventive efforts to avert various forms of CVD may be indicated for those with diabetes and subclinical cardiac dysfunction.