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Background: The prevalence of obesity among people of reproductive age has steadily increased. The rates of both maternal/parental and fetal adverse outcomes increased significantly with higher BMI. In this study, we examined the national estimates of adverse maternal/parental and fetal outcomes among pregnant individuals with pre-pregnancy obesity using a nationally representative database. Methods: This was a retrospective observational analysis of data retrieved from the Nationwide Inpatient Sample database (2010-2014). The primary outcomes of this study were various adverse maternal/parental and fetal outcomes. Delivery related hospitalizations and all outcomes were identified using the ICD-9 codes. Additionally, propensity-score matching analysis was conducted. Results: There were a total of 18,687,217 delivery-related hospitalizations, of which 1,048,323 were among people with obesity. The mean age of pregnant persons with obesity was 28.5 years while among those without obesity was 28.0 years. Between both groups, most pregnant persons were White, followed by Hispanic and Black. Pregnant persons with obesity were more likely to have labor inductions (AOR: 1.51; 95% CI: 1.42, 1.60), cesarean deliveries (1.70; 1.62, 1.79), and greater length of stay after both cesarean deliveries (1.14; 1.08, 1.36) and vaginal deliveries (1.48; 1.23, 1.77). They were also more likely to have risk factors for adverse obstetrical outcomes such as gestational hypertension (2.17; 2.06, 2.29), preeclampsia (2.06; 1.42, 2.99), gestational diabetes (2.75; 2.60, 2.90), premature rupture of membranes (1.17; 1.08, 1.27), chorioamnionitis (1.39; 1.25, 1.55), and venous thromboembolism (1.63; 1.34, 1.99). Additionally, pregnant persons with obesity were more likely to have adverse fetal outcomes such as excessive fetal growth (3.18; 2.96, 3.43) and fetal distress (1.28; 1.21, 1.35). Conclusion: Pregnant persons with obesity had significantly greater risk for adverse obstetrical outcomes. Risk stratification of pregnant individuals based on obesity can inform obstetrical providers’ clinical decision-making and potentially improve patient outcomes and decrease costs. There is an opportunity to address these risks with pre-conception interventions. Future studies could examine the effect of pre-conception interventions such as counseling on pre-pregnancy weight management, lifestyle modifications addressing nutrition and activity, and pre-pregnancy bariatric surgery.

Introduction: Prior research has shown that hospital outcomes such as mortality among COVID-19 patients receiving methylprednisolone and dexamethasone differed despite having similar anti-inflammatory effect. In this study, we compared mortality rate among three groups (usual care with no steroids [NS], methylprednisolone [MP], or dexamethasone [DE]) of COVID-19 patients. Methods: Data was collected retrospectively from a large healthcare system in the South Florida region. All eligible COVID-19 patients from April 1 to Dec 31, 2020 were included in this study. Propensity scores (PS) was utilized to match patients on their demographics and acuity scores (Age Group, Ethnicity, Gender, APR risk of mortality, and APR severity of illness, etc.). All-cause mortality was compared among the three groups after accounting for demographics, length of stay (hospital and ICU), days on MP or DE, ventilator status, days on ventilator, other medication history (HCQ, Tocilizumab, etc.), pO2, and lab values (hCRP, Ferritin, Glucose, etc.). Multivariate Logistic regression and Survival analysis was utilized for the analysis. Results: There were a total of 2445 eligible COVID-19 cases. After PS matching, 292 cases in each group (n = 876) were included in the analysis. There were 42% females and the majority of participants were White Hispanic (81%). The average age (SD) of the PS matched cohort was 64 (17.1) years, and there was a significant difference between LOS among the three groups with MP being the highest (Mean: 12.4; SD: 12.1). All-cause mortalities in the NS, MP, and DE groups were about 6%, 19% and 7% (p < 0.0001) respectively. Logistic regression showed that the odds of mortality among NS (AOR: 1.9, 95% CI: 0.10, 41.8) group were higher, and DE (AOR: 0.15, 95% CI: 0.04, 0.57) group were significantly lower than MP group respectively. Similar results were observed in the survival analysis after accounting for total hospital length of stay. The adjusted hazard ratios suggest that patients who were in the DE group had lower mortality as compared to MP group but, the effect was not significant (HR: 0.70, p < 0.18). In a subgroup survival analysis among patients who were ventilated (n = 69) in the matched cohort, mortality was higher in DE group compared to MP group however the effect was not significant (HR: 1.8, 95% CI: 0.82, 4.0). Conclusions: Among hospitalized COVID-19 cases, preliminary results show that patients who received DE had lower mortality as compared to those who received MP. Among COVID-19 patients who require mechanical ventilation, sufficiently dosed MP may lead to a decreased mortality as compared to DE. However more in depth analysis with higher number of patients and better characterization of variables such as dosage of the drugs, are needed to confirm these findings.

Background: FGF-23 is an endocrine regulator of phosphate metabolism as well as also a potent biomarker that mediates cardiovascular remodeling, with markedly elevated plasma concentration associated with the occurrence of morbid cardiovascular events such as myocardial infarction. This association usually indicates risk of developing further adverse cardiovascular events in individuals that are already susceptible to repeat morbid cardiovascular outcomes. This cross-sectional epidemiological study aims at investigating the risk association between FGF-23 and individuals in the 8 th year cohort of the Boston Puerto Rican Health Study (BPRHS) that have self-reported clinical cardiovascular disease in the form of myocardial infarction. Methods: FGF-23 plasma concentration was measured by ELISA in 496 participants of the fourth wave of the Boston Puerto Rican Health Study (BPRHS). Multivariate logistic regressions were used to analyze the cross-sectional association of plasma FGF-23 quartile distribution with self-reported clinical diagnosis of myocardial infarction (MI). Results: The crude model for the association between FGF-23 and MI showed increased risk across the 2 nd , 3 rd and 4 th quartiles, OR (95% CI); 1.27 (0.48-3.34), 1.13 (0.42-3.04), and 3.13 (1.33-7.33), respectively. The relationship with the highest vs lowest quartile remained significant after adjusting for age, sex and BMI, OR (95% CI); 2.91 (1.15-7.36). With further adjustment for diabetes, smoking, plasma total cholesterol, HDL cholesterol and triglycerides, results were attenuated, and the latter comparison was no longer statistically significant, OR (95% CI); 2.15 (0.79-5.79). The test for trend across the quartiles yielded a p value of 0.03. Conclusion: Within this population of older Puerto Rican adults, FGF-23 was not significantly associated with increased likelihood of self-reported history of myocardial infarction. Longitudinal studies, using clinical parameters that objectively measure the progression of cardiovascular disease are needed to assess the prognostic value of FGF-23 for future cardiovascular outcomes.

Introduction: Statins use for secondary cardiovascular disease (CVD) prevention is associated with better health outcomes and lower cost among adults with ASCVD. We aimed to examine the prevalence of statin use among adults with ASCVD in the US and to assess for gender and racial differences in statin use. Methods: We identified adults aged 40-75 years with ASCVD (defined using ICD codes and self-reported history) from the 2008-17 Medical Expenditure Panel Survey (MEPS) data. We estimated the trends in statin use among them, and used joint point regression (JPR) to estimate the annual percentage change in statin use. Logistic regression was used to assess the racial variation in statin use. We applied the weights in the MEPS complex survey design to estimate population sizes, so all results are nationally representative. Results: Between 2008 and 2017, 24896 adults aged 40-75 years with ASCVD were identified. In 2017, there were 2445 patients with ASCVD (equivalent to 24.5 million adults). In 2017, the mean age [SE] was 62.2 [0.3] years, and 42.9% were females. The overall proportion of adults with ASCVD using statin increased from 50.0% in 2008 to 58.7% in 2017, with an average annual percentage change of 0.95% between 2010 and 2017 ( p= 0.01). As shown in Figure 1a , among those with ASCVD, statin use was persistently lower in women than in men. In 2017, compared to White adults with ASCVD, Blacks (OR=0.69; 95% CI: 0.51-0.92) and Hispanics (OR=0.62; 95% CI: 0.45-0.85) were less likely to be on statin. Each year, over 3 million women with ASCVD were not on statin, and majority of them were Blacks and Hispanics. (Figure 1b) Conclusion: Millions of adults with ASCVD are not on statins in the US while gender and racial inequalities in statin use remains, despite persistent guideline recommendations. Herein lies an opportunity to improve CVD-related outcomes and cost by intensifying efforts to use statins for the secondary prevention of CVD and closing gender and racial gaps, especially with the 2030 sustainable development goals in view.

Background: Major adverse cardiovascular and cerebrovascular events (MACCE) are significant causes of perioperative morbidity and mortality but, the incidence and effects following cancer surgeries are unknown. The aims of this study were to evaluate national trends in MACCE after major cancer surgeries and to identify cancer types associated with cardiovascular events using a large national database. Methods: Patients who had major cancer surgeries from 2005 to 2014 were identified from the National Inpatient Sample database. Hospitalizations for surgeries for cancer of prostate, bladder, esophagus, pancreas, lung, liver, breast, colon and rectum were identified by ICD9 diagnosis and procedure codes. The main outcome was perioperative MACCE, defined as in-hospital, all-cause death, acute myocardial infarction (AMI), or acute ischemic stroke, and was evaluated over time. Results: Among 2,854,810 hospitalizations for major cancer surgeries, perioperative MACCE occurred in 67,316 hospitalizations (2.4%). Mean (SE) age of patients was 65.4 (0.07) years and 54.2% were male patients. MACCE occurred most frequently in patients undergoing surgeries for lung (6.8%), pancreatic (4.5%), and colorectal (3.3%) cancers. Between 2005 and 2014, the frequency of MACCE declined from 2.7% to 2.2% ( P P P = 0.002). However, no significant changes were observed for acute ischemic stroke ( P = 0.6) during the study period. Conclusion: Perioperative MACCE occurs in 1 out of every 42 hospitalizations for major cancer surgeries. Despite reductions in the rate of death and AMI among patients undergoing major cardiac surgeries, perioperative ischemic stroke remained constant over time. The lack of improvements in perioperative ischemic stroke rate is concerning and requires additional interventions. Significant efforts should be directed towards improving cardiovascular care during the perioperative period of cancer surgeries.

Introduction: Cardiometabolic syndrome consists of a cluster of metabolic dysfunctions such as impaired glucose tolerance, insulin resistance, dyslipidemia, central adiposity, and hypertension. According to the latest estimates, globally, nearly 25% of all adults have cardiometabolic syndrome. Both cardiometabolic syndrome and cancer pathophysiology commonly involve inflammation and oxidative stress. The objective of this systematic review was to evaluate existing evidences that support the association between cardiometabolic syndrome and risk of developing cancer. Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Scopus for relevant articles published from the database inception until October 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for this review. Using the Oxford Center for Evidence-Based Medicine guidelines individual studies were evaluated. A total of 59 articles were included in this study. Results: Our review showed that cardiometabolic syndrome was associated with increased risk for colorectal, hepatic, endometrial, breast, and bladder cancers. These associations showed variations for sex and geographical locations. For example, the associations were stronger for pancreatic and rectal cancers among women. The strength of these associations was also stronger for sex specific cancers such as breast and endometrial cancers. Studies on European populations showed that these associations were stronger for colorectal cancer among women. However, one study showed that presence of cardiometabolic syndrome contributed protective effects to prostate cancer among American men. In general, strongest associations were found for colorectal cancer among both men and women and hepatic cancer among men. Among cardiometabolic factors, impaired glucose tolerance and central adiposity were the greatest contributors towards increased risk for cancers. Conclusion: Given these results, there should be greater focus on primary prevention to identify and treat cardiometabolic risk factors. In addition, patients with greater cardiometabolic risk factors should be screened earlier and more frequently for cancers. A number of gender and geographical gaps identified in this review could be targeted for improvements as per the goals of 2030 sustainable development initiatives. Future studies should consider cardiometabolic syndrome and cancer together and develop effective interventions for decreasing the incidence and morbidity associated with both the conditions.

Background: In August 2019, FDA approved TAVR for low-risk patients, a paradigm shift in the field of Cardiology. This approval will pave the way for TAVR to rapidly become mainstream, and it will be a preferred procedure for patients with symptomatic aortic stenosis in the coming years. In this study, we considered creating a useful tool to assess the risk of 30-day readmission after TAVR. Methods: We utilized data from ACS National Surgical Quality Improvement Program (ACS NSQIP) between 2015 and 2017. We selected 35 past medical history (such as history of CHF, COPD, etc.) and preoperative lab (such as BUN, WBC count, etc.) variables. A binary variable for 30-day readmission was created. Elastic net, random forest, and gradient boosted classification trees machine learning models were run and best performing model was selected based on the AUROC. Variables were plotted according to the importance. We created a nomogram using logistic regression by including important variables. Methods: About 594 patients underwent TAVR between 2015 and 2017; 56% patients were 80 years or older; and 45% were females. Majority of patients (62.8%) were Non-Hispanic White, had BMI ≥ 25 (71%), and took antihypertensive medication (82%). History of CHF was reported by 26%, and COPD by 17%. There were 68 (11.4%) patients who were readmitted within 30-days for any cause. Gradient boosted classification performed best. Top 15 variables were selected for logistic regression analysis to construct a nomogram. Five of the top variables were Total hospital LOS, pre-op platelet count, pre-op serum sodium, general anesthesia, pre-op BUN. Conclusion: In the US, 1 in 6 patients with TAVR could be readmitted within 30-days due to any cause after TAVR. We presented an interpretable model based on past medical history and pre-operative variables, which can be used to identify high risk patients so that their hospital readmission risk and can be reduced. This will also lower financial burden among patients.

Objective: The accuracy and applicability of various cardiovascular disease (CVD) risk calculators may not be same in different populations. Wecompared 5 RFS for CVD risk on patients from Bosnia and Herzegovina to explore relations between different RFS and estimate use of theircombination. Methods: We utilized demographic, medical history, and lipid profile data gathered from patients seen in primary care clinic in 2013. FiveRFS namely, 10 year Framingham CHD score, QRISK 2, AHA/ACC ASCVD risk score, Framingham ATP III score, and EU SCORE were calculatedusing demographic, history of diabetes and hypertension, taking any hypertension medication, and lipid profile variables. Additionally, we entered these scores as dimensions in hierarchical cluster analysis to group people based on their risk of developing CVD. Results: There were 1277 patients in thisstudy and majority (65%) were women. The mean (SD) age of the sample was 56.2 (11.4) years. Correlation between these scores are presented inTable 1. We obtained 4 clusters with significant different cluster centers. Clusters were ordered from lowest to highest risk; cluster 1 containing patients with lowest and cluster 4 with highest mean RFS. Cluster centers, which represents mean values for all the RFS are given in Table 2. Conclusion: All risk scores performed well in this population. Only EU SCORE correlated less with other RFS. Obtained clusters are more homogenous and were ableto classify patients better. This novel method of using calculated RFCs as dimensions in clustering produced very good estimates of patient’s risk ofdeveloping CVD by combining several RFS, even in a case where originally RFS were created for and from different population.

Background— Free radical scavengers have failed to improve patient outcomes, promoting the concept that clinically important oxidative stress may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of nonf ree radical mediated oxidative stress with clinical outcomes. Methods and Results— Plasma levels of reduced (cyst ei ne and glutathione) and oxidized (cyst i ne and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7±2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death ( P +1 SD and Conclusions— A high burden of oxidative stress, quantified by the plasma aminothiols, cystine, glutathione, and their ratio, is associated with mortality in patients with coronary artery disease, a finding that is independent of and additive to the inflammatory burden. Importantly, these data support the emerging role of nonfree radical biology in driving clinically important oxidative stress.

Introduction: Every year more than 75 million adults are diagnosed with HTN in the US. Despite spending $50 billion/ year to lower mortality related to HTN, only about 54% of patients have this condition managed. In 2014, mortality due to HTN or related complications was 410,000. AMI is a more severe manifestation of coronary artery disease with 735,000 people diagnosed yearly. It is estimated that hospitals lose $4493-$7940 per patient due to AMI. We studied costs for events associated with HTN and AMI in MEPS. Methods: Individuals aged ≥20 in MEPS (2014) were included. Hierarchical clustering was used for analysis. Age, sex, education status, race, Hispanic ethnicity, US citizenship status, family income, insurance, people who reported HTN and/ or AMI events were entered as dimensions. Cluster and descriptive analyses were adjusted for survey weights. Results: About 236 million weighted individuals were eligible for the analysis (Female: 51.7%; White: 79.1%; High school or above: 61%; Any private insurance: 66%; and Income≥ 400% of poverty line: 41%). Out of these, about 4.9 million participants reported costs/ events related to AMI and 61.8 million related to HTN. Five groups were identified based on similarity within each cluster (Table 1). The maximum number of participants were present in cluster 1 (weighted n = 101 million) with the most number of participants (21.5%) who reported HTN among all cluster groups. In general, cluster 5 had the lowest annual total of direct health care payments and events. Selected medical history is described in Table 2. Conclusion: Results show insights into the cost of HTN and AMI events, and their relationship with other comorbid conditions. Being computationally demanding, clustering methodologies are rarely utilized in survey data analysis. This could be the first example of clustering approach applied to data from MEPS. Once clustering methods are improved in weighted survey data, estimates will be more reliable.

Background: Each year in the USA, more than 75 million adults are diagnosed with hypertension (HTN), but less than 54% have it condition under control. Mortality due to HTN or related complications was 410,000 in 2014 and resulted in close to $50 billion spent. Acute Myocardial Infarction (AMI) is the most dramatic manifestation of coronary artery disease. Every year, about 735,000 people are diagnosed with AMI and it is estimated that hospitals lose $4493-$7940 per AMI patient on hospitalization. We studied interplays of expenditures for all events associated with HTN and AMI in the US in 2014. Methods: We used all available subsets from Medical Expenditure Panel Survey (MEPS; 2014) to extract all cost and utilization events related to HTN and AMI, following procedures for complex surveys as described in MEPS specifications to define population influenced by HTN and AMI, number of events, and related costs. Patients were included in this analysis if they were ≥20 years. Results: In 2014, there were about 236 million weighted participants in MEPS. Out of these, about 4.9 million participants reported costs related to AMI and 61.8 million related to HTN. About 3.9 million people reported both. Out of 61 million with HTN, 4 million reported AMI, whereas out of 174 million without HTN, only 1 million had AMI (OR: 11.1; 7.9-15.5). Those who had events associated with AMI, with an average cost of $5328/event, adding to total expenditures of $26.6 billion. Cost of AMI, HTN and both were $6.8 billion, $4.1 billion, and $2.7 billion, respectively. The total cost of hospitalization due to both HTN and AMI was 31.4% of the total healthcare expenditure among these participants. Conclusion: Burden of AMI includes almost 5 million people who live and die with AMI, and pay a high cost to manage this condition. Evidence from this study suggests that there is a significant disparity between the cost of hospitalization due to AMI between people with HTN and without HTN, which has potential implications on outcomes, quality of care, and hospital sustainability for AMI population. Symptom management at primary care settings may decrease the number of AMI events resulting in lower spending and cost savings by hospitals.

Introduction: According to the National Institute on Drug Abuse, lifetime cocaine use has remained stable since 2009. An estimated 1.5 million individuals aged ≥12 years reported cocaine use in 2014. Cocaine use is a significant risk factor for acute myocardial infarction (AMI), especially in the age group 18-45 years. Hence, we examined trends in hospitalizations due to cocaine-induced AMI in the United States. Methods: The current study was a retrospective analysis of the National Inpatient Sample, collected during the period 2005-2014. Participants between 18 and 45 years were included in the analysis. Cocaine-induced AMI hospitalizations were identified using ICD-9-CM codes 304.2X and 305.6X for cocaine dependence or abuse, and 410.XX for AMI diagnosis. We used Cochran Armitage test for categorical variables and Cuzick nonparametric test for trends for continuous variables. Results: A total of 49,715 weighted cocaine-induced AMI hospitalizations were reported during the study period. Cocaine-induced AMI hospitalizations increased from 4,619 in 2005 to 5,065 in 2014 (relative increase, 9.7%, P trend =0.124). Majority of the patients were non-White (55.3%), men (79.3%), in the age group 41-45 years (83.1%), and with Medicare/Medicaid coverage (51.2%). Highest change in trend was observed for non-White population and Medicare/Medicaid payers. Conclusion: Our study showed that cocaine-induced AMI hospitalizations remained stable during the years 2005-2014. Initial results point towards structural and racial disparities in such hospitalizations, especially among non-White men and population with Medicare/Medicaid coverage. Effective interventions to reduce cocaine use are needed, and treatment must be based on 2008 AHA guidelines for cocaine-associated chest pain and myocardial infarction.

Introduction: As number of elderly Americans is projected to double by 2050, population aged ≥65 years will have the highest impact on Medicare spending. The prevalence of elderly population with hypertension (HTN) is around 65% and if patients receive good primary care or an early intervention, these HTN related hospitalizations could be prevented saving millions in Medicare spending. Our objective was to examine the trends in hospitalizations related to HTN and total cost over 10 years among aged ≥65 years. Methods: Using data from Nationwide Inpatient Sample database from 2005-2014, we explored the existence of trends in HTN admission rates and corresponding hospitalization costs among adults ≥65 years vs other age groups. Weighted estimates for rates and mean total cost were reported using SUDAAN after adjusting for complex survey design. Results: Overall, hospitalizations due to HTN increased by 26% in 2014 from 2005. Hospitalizations were highest among patients ≥65 years (57.8%) followed by 40-64 (32.6%) and 18-39 years (9.6%). During 2005-2014, hospitalization rates among ≥65 years increased significantly (10.7%, p p Conclusion: Hospitalizations and costs associated with HTN, especially Medicare, have increased over the past 10 years among elderly. Although these trends are alarming, these events could be prevented through symptom management at primary care, medication adherence, care coordination, or modifying care-seeking behavior resulting in potential savings of 851M over a year. This would reduce burden of Medicare spending, which is projected to surpass the rate of growth in federal revenues.

Objectives: Extensive data suggests that lesbian, gay and bisexual (LGB) adults are more likely to experience adverse cardiovascular outcomes relative to heterosexuals. However, evidence regarding cardiovascular health (CVH) disparities and sexual orientation is scarce. The aim of this study was to examine the distribution of CVH metrics in a US nationally representative population of heterosexual (HT), and LGB adults. Methods: This cross-sectional study analyzed 2445 participants (representing 115 million) adults aged 18 or over years in the 2011-2012 NHANES survey. The CVH factors of smoking, body mass index (BMI), physical activity (PA), diet, blood pressure (BP), total cholesterol (TC) and glucose (GLU) were measured. Each CVH factor was then classified as ideal; intermediate; or poor. Ideal CVH was defined as presence of >=5 ideal CVH metrics. Results: 95.1% of the weighted sample self-identified as HT (95% CI: 93.5%, 96.6%) compared to 4.9% (95%: 3.3%, 6.5%) LGB. The figure illustrates the distribution of each of the 7 CVH categories according to sexual orientation. In age, gender, and race adjusted analysis, LGB individuals were 36% (AOR: 0.64; 95%: 0.29, 1.4; p > 0.05) less likely to have ideal CVH compared to HT. These proportions go higher after adjusting for age. Conclusions: The results suggest that LGB individuals face a higher risk of being in the category for poor cardiovascular health compared to heterosexuals. Evidence suggests that there are sexual orientation disparities among adults. If confirmed in other studies, results point towards disproportionately higher risk for cardiovascular disease among sexual-minority populations. Figure

Introduction: Higher education and income can modify behavioral risk factors for lifetime cardiovascular disease (CVD) risk. The aim of this study was to observe ethnic differences in the CV health, as measured by inadequate cardiovascular health index (CVHI) category, among a cohort of females with high family income, education, and BMI. We also examined differences in perception about self-reported weight and attitudes toward weight loss and exercise. Methods: Adult non-pregnant females aged 20 years or older from the 2011-2012 NHANES were included in the study. Participants were at least college educated, had a poverty to income ratio of 350% or above, and BMI (≥ 30). Weighted regression was adjusted for demographics, PHQ-9 score, perception about weight, if participant tried to lose weight last year, and history of CVD, angina, or heart attack. Results: The sample represented 2,990,456 eligible females in the US. About 13.2% Hispanic perceived their weight to be about right as compared to 10% Black, and 3.3% White. About 89% Hispanics tried to lose weight in past year compared to 71% White and Black. Weighted regression showed that Hispanic (β: -2.47, 95% CI: -4.44, -0.50) and Black (β: -0.74, 95% CI: -1.93, 0.45) had low CVHI score as compared to White. Higher PHQ9 score (β: -0.12, p > 0.05) and those who did not try to lose weight (β: -1.55, p < 0.01) were associated with lower, and those with positive attitude towards their weight were associated with higher CVHI score (β: 0.38, p > 0.05). Our study suggests huge variations in these characteristics by country of birth and citizenship with corroborated ambiguity in definitions. Conclusion: Previous research is inconclusive about existence of Hispanic paradox in cardiovascular health domain. Our study suggests that Hispanic ethnicity was a significant predictor of negative CVHI, when socioeconomic status (SES) was high among all obese females. There was higher prevalence of history of weight management and low CVHI score among Hispanic females; Hispanic females belonging to higher SES may be at a higher risk for CVD related adverse events. In our study, effect of education and income diminished and SES was not associated with participant’s willingness to lose weight despite being obese. Health disparities expressed as differences in CVHI exist despite high education and family income.

Introduction: Psychological factors including stress are associated with adverse cardiovascular (CV) disease outcomes. Gender differences exist in both the perception of stress and the magnitude of the stress response. We hypothesize that self-perceived psychological stressors would have a greater impact on women compared to men as measured by the American Heart Association Life’s Simple Seven (LS7) health metrics. Methods: This was a cross-sectional study conducted among employees of BHSF. The LS7 metrics (smoking, physical activity, diet, body mass index, blood pressure, cholesterol and glucose) were each scored as ideal (2), intermediate (1), or poor (0), with composite scores ranging from 0 to 14. Total scores were categorized as optimal (11-14), average (9-10) and inadequate (0-8). We used multinomial logistic regression to compare psychological factors obtained by questionnaire (self-perceived stress, life satisfaction, hopelessness, sadness, depression, anxiety) with the LS7 score (inadequate score served as reference). The model was stratified by gender and adjusted for age, ethnicity, and education level. Results: Of the 9,056 participants, 74% were female, 17% white, 57% Hispanic, 16% black, with a mean age of 43±12 years. Self-perceived adverse psychological factors were associated with being less likely to achieve adequate and optimal LS7 scores (Table). For example both women and men, respectively, with self-perceived stress were less likely to have optimal LS7 metrics [OR 0.47 (95% CI 0.40-0.56) vs. 0.50 (0.36-0.69)]. There were some interactions by gender (P Conclusions: In an ethnically diverse population, participants with negative self-perceived psychological factors are more likely to have inadequate CV health as measured by LS7. Contrary to our hypothesis, in general, men and women were similarly affected by adverse psychological factors. Addressing psychological stressors may be one mechanism to improve CV health.

Free radical scavengers have failed to improve patient outcomes, promoting the concept that clinically important oxidative stress may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of nonfree radical mediated oxidative stress with clinical outcomes.Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7 ± 2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (P0.001 both) before and after adjustment for covariates. High cystine and low glutathione levels (+1 SD and-1 SD, respectively) were associated with higher mortality (adjusted hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.19-2.21; HR, 2.19; 95% CI, 1.50-3.19; respectively) compared with those outside these thresholds. Furthermore, the ratio of cystine/glutathione was also significantly associated with mortality (adjusted HR, 1.92; 95% CI, 1.39-2.64) and was independent of and additive to high-sensitivity C-reactive protein level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction.A high burden of oxidative stress, quantified by the plasma aminothiols, cystine, glutathione, and their ratio, is associated with mortality in patients with coronary artery disease, a finding that is independent of and additive to the inflammatory burden. Importantly, these data support the emerging role of nonfree radical biology in driving clinically important oxidative stress.

Background: Recent study demonstrated paradoxical relationship between body mass Index (BMI) and all cause mortality in patients with acute decompensated heart Failure (ADHF), where higher BMI was associated with decreased mortality. We sought to test whether this relationship exists between BMI and ADHF readmissions Methods: Consecutive patients presented to the emergency department from March 2014 to July 2015 with the diagnosis of ADHF were analyzed in a retrospective cohort study. Cohort was grouped in to prespecified BMI categories; normal weight (BMI 30 Kg/m2 and above). Primary endpoints were incidence of 30 day ADHF readmission and time to first ADHF readmission from the index hospitalization. Patients with end stage COPD on home O2, cirrhosis and end stage renal failure on dialysis were excluded. Unplanned hospitalizations due to other cause than ADHF were excluded. ADHF hospitalizations were adjudicated by an independent blinded clinician Results: Cohort (N=188) consisted 51(27.1%) normal weight, 61 (32.4%) over weight and 76 (40.4%) obese patients. Females were 63% (N=119), patients with heart failure with preserved ejection fraction were 47% (N=90), Obese [BMI 31(28-38) Kg/m2; Median (IQR)] patients were younger (median age; 77 years vs 83 years; P=0.002), whereas other covariates were similar between groups. In median follow up of 1.2 years, total 30 day ADHF readmissions were 32 and total ADHF admissions were 214. Incidence of both 30 day and total ADHF readmissions were similar in all 3 BMI categories; ANOVA P=0.18 (30 day ADHF readmissions) and P= 0.62 (total ADHF readmissions). Obesity was neither associated with risk for 30 day readmission; OR=0.64 (CI: 0.20 - 2.0; P= 0.45) nor with the time to first ADHF readmission from the index hospitalization; log rank P=0.5 (Figure 1) Conclusions: Higher BMI is not protective against ADHF readmissions in patients with ADHF. Further studies are needed in larger data sets to validate our findings.

Introduction: In 2010, the American Heart Association set 2020 national goals for promoting cardiovascular health (CVH), emphasizing measurement of reproducible health behaviors and health factors and attaining ideal CVH status. In recent years, significant emphasis has been placed on adopting these metrics globally to monitor strategies to improve CVH. In this study, we synthesize available data to compare distribution of CVH metric metrics detailed in national representative cohorts a focus on presence of ideal CVH (ICVH). Method: A MEDLINE database search was conducted using relevant free text terms such as “life’s simple 7”, “AHA 2020”, “American Heart Association 2020” and “Ideal cardiovascular health”. Ideal CVH was defined as 6-7 ideal factors; conversely poor ICVH was considered as 0-1 ideal factors. Results: The pooled data comprised of 7 cross-national cohorts with a total of 152289 participants from India, United States, China, Spain, Korea, Luxembourg and Republic of Srpska. Significant variations in individual ideal CVH metrics were noted. Across population cohorts, diet metric consistently appeared suboptimal apart from Korea in which 55% participants reported ideal diet status. Overall majority population in each of the 7 cross-national cohorts lied in the range having 2-5 ideal CV health metrics (79-88%). A very small percentage of each population had 0-1 METRICS, with Spain, USA and Republic of Srpska having the highest percentage (18%) of reported poor ICVH. On the other hand, only representative cohorts from China and Korea reported ideal CVH status in more than 10% population. Conclusion: Overall suboptimal proportion of national representative cohorts have reported ideal CVH status. Significant efforts are needed to streamline current policies for enhancing CVH and sharpening focus interventions that will yield the greatest sustainable improvement in population CVH status.

Non-alcoholic fatty liver disease (NAFLD) is considered an independent risk factor for increased cardiovascular disease (CVD). Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) cohort enrolled 6814 adults without prior CVD. We excluded 2,692 participants who had missing variables, heavy drinkers, history of steroid use and chronic liver disease. NAFLD was defined using non-contrast cardiac CT and a liver/spleen attenuation ratio (L/S) < 1. Arterial compliance and stiffness, was expressed as Distensibility coefficient and Young’s modulus. Common and internal carotid intima media thickness (IMT) and coronary artery calcium (CAC) > 0 were used as markers of subclinical CVD. A multivariate robust linear regression and logistic regression analysis was done to evaluate the association of NAFLD and this subclinical CVD markers. RESULTS: Our analysis of 4,123 participants showed a NAFLD prevalence 17% (n=665), 55% were female with a mean age of 63 (±10) years, 39% white, 10% Chinese, 28% African American, and 23% were Hispanic. Individuals with NAFLD had Distensibility coefficient (10 -3 mmHg -1 ) of 2.4 vs. 2.5 without NAFLD, p=0.05. CIMT (mm) was 0.88 in NAFLD vs. 0.87 without NAFLD, p=0.003. Multivariate linear regression analysis showed the presence of NAFLD was associated with both the common carotid and internal carotid IMT and logCAC. Logistic analysis only showed an independent association with CAC>0 (OR 1.44 95% CI 1.18, 1.75) and CIMT >1mm (OR 1.30 95% 1.08, 1.56). When stratified by race the association with CIMT >1mm was only significant among Caucasian whites (OR 1.37 95% 1.00, 1.90) and Hispanic (OR 1.53 95% 1.08, 2. 17) and CAC>0 was only significant among Hispanics (OR 1.52 95% 1.06, 2.19). Conclusion: NAFLD is independently associated with Carotid IMT and coronary artery calcification in a multi-ethnic population. This study reaffirms the role of NAFLD in early atherosclerosis and provides opportunity to explore strategies for early screening for subclinical CVD and aggressive preventive therapies.

Background: Ethnic differences in obesity are well documented; however, the epidemiological evidence of the impact of socioeconomic and educational status on its relationship is sparse. We sought to assess the impact of educational attainment, as a proxy of socioeconomic status, on the association between ethnicity and morbid obesity (MO) among employees of Baptist Health South Florida (BHSF), a large nonprofit healthcare organization. Methods: Data was collected from employees participating in an annual Health Risk Assessment in 2014. Educational attainment was self-reported while weight, height and other biometric measures were measured in person. MO was categorized using eligibility criteria for bariatric surgery as outlined by the 1991 NIH consensus guidelines for surgery for the obese. Results: Data was collected for 9361 participants (mean age 42.8 ± 12.1 years, 74% females, 63% Hispanic). Overall, 7% meet criteria for MO (Non-Hispanic White [NHW]: 5%; Hispanics: 6%; Non-Hispanic Black [NHB]: 12%). A lower education was associated with a greater prevalence of morbid obesity (Post graduate/ professional: 4.2%; completed college: 5.2%; some college or lower: 9.8%) The highest (18%) and lowest (4%) prevalence of MO were observed in NHB with some college education or lower (SCL), and in Hispanics with post-graduate or professional educational (PG) attainment respectively. Among PG, compared to NHW, the odd ratios (95% CI) for presence of MO among NHB was 1.3 (0.6 - 2.5). Conversely, the respective MO risk for NHB vs. NHW was 4 fold higher (2.5 - 6.4) among those with SCL. Interaction of ethnicity and educational attainment for predicting MO was significant (p Conclusion: Underlying differences in educational status significantly impact ethnic disparities in morbid obesity. The co-existing influence of education and racial disparities should be jointly addressed to maximize yield of future wellness efforts aimed at optimizing CV health.

Background: The AHA’s 2020 Strategic Goals emphasize the value of favorable modifiable risk factor (MRF) profile to reduce the burden of CVD morbidity and mortality. In this study we aimed to quantify the overall and incremental impact of MRF on health care expenditure in the U.S among those with and without CVD. Methods: The study population was derived from the 2012 Medical Expenditure Panel Survey (MEPS), a nationally representative adult sample (≥ 40 years). Direct costs were calculated for all-cause health care resource utilization. Variables of interest included CVD diagnoses (coronary artery disease, stroke, peripheral artery disease, dysrhythmias or heart failure), ascertained by ICD-9-CM codes, and MRF (hypertension, diabetes mellitus, hypercholesterolemia, smoking, physical activity and/or obesity). Two-part econometric models were utilized to study cost data; a generalized linear model with gamma distribution and link log was used to assess expenditures, taking into consideration the survey’s complex design. Results: The final study sample consisted of 15,651 MEPS participants (57 ± 12 years, 52% female). Overall, 6,231 (39%) had 0-1, 7,429 (49%) had 2-3, and 1,991 (12%) had ≥ 4 MRF, translating to 55.5, 69.9 and 17.9 million adults ≥ 40 years in U.S, respectively. Generally, there was a direct decrease in health expenditures with favorable MRF across CVD status (Table). These differences persisted after taking into account demographics, insurance status and comorbid conditions. Among those without established CVD, the average medical expenditure was $4,013 (95% CI 5,117, 2,910) and $2,696 (95% CI 4,416, 977) lower for those with 0-1 & 2-3 MRF, as compared to those with ≥ 4 MRF. Conclusion: Favorable MRF profile is associated with significantly lower medical expenditure among individuals with and without established CVD. Our study provides robust estimates for potential healthcare savings with nationwide policies focusing on preventing and managing modifiable CV risk factors.

Background: The concept of Life’s Simple 7 (LS7) metrics was introduced by the American Heart Association to assess and promote cardiovascular health. Individuals with favorable LS7 scores have a lower incidence of cardiovascular disease. In this study, we examined the association between the LS7 metrics and incident heart failure (HF) Methods: We analyzed data from the Multi-Ethnic Study of Atherosclerosis, a multicenter cohort study that included 6,814 participants free of established cardiovascular disease, between the ages of 45 and 84. The components of the LS7 metrics (smoking, physical activity, body mass index, diet, blood pressure, total cholesterol and blood glucose) were graded on a scale of 0-2, with 2 indicating “ideal” status, 1 indicating “intermediate” status and 0 indicating “poor” status. These scores were summed for each participant, thus, the LS7 score created ranged from 0 to 14. Hazard ratios and incidence rates of HF per 1000 person-years were calculated Results: After exclusion of participants with incomplete data, the final study population was 6,506 (53% female mean age 62 ±10 years). In a median follow up of 10.2 years, 181 (2.8%) participants developed HF. The incidence of HF decreased as the number of ideal LS7 metrics increased 6.5 per 1000 person-years for participants with 0-1 ideal metrics compared to 1.3 per 1000 person-years for those with 5 ideal metrics (Table). No HF event was reported in participants with 6-7 ideal metrics at baseline. In comparison to participants with 0-1 ideal metrics, having 2, 3, 4, and 5 ideal metrics was associated with an 11%, 36%, 59% and 76% lower hazard for HF respectively. In addition, optimal and average LS7 scores were associated with an 80% and 51% lower hazard for HF, respectively Conclusion: The American Heart Association LS7 metrics was associated with a lower incidence of HF in a follow up extending up to 10 years. These findings suggest that efforts to achieve ideal cardiovascular health metrics favorably reduce the risk of HF, a major source of morbidity and mortality

Background: Although studies have described an inverse relationship between sleep duration and obesity, there is limited knowledge about the association between sleep duration and severe obesity in the work place. In this study, we evaluated the relationship between self-reported sleep duration and severe obesity in a large, healthcare employee population. Methods: Employees of Baptist Health South Florida (BHSF), a large nonprofit healthcare organization participated in an annual Health Risk Assessment in 2014, from which data for this study was obtained. Average sleep duration was self-reported while weight, height and other biometric measures were captured in person. Obesity status was categorized as BMI 8 hours). Results: A total of 10363 participants (mean age 42.8 ± 12.1 years, 75% females, 57% Hispanic) had complete information on the variables of interest. Almost one-quarter (24%) of employees who slept less than 6 hours a day were severely obese, compared to about 13% and 14% of employees who sleep between 6-8 hours and 8 or more hours of sleep respectively. Compared to those who slept for 6 - 8 hours, persons who slept for less than 6 hours had almost a 2-fold increase in odds of severe obesity (OR= 1.9; 1.6 - 2.2). Conclusion: In this large diverse employee population, short sleep duration is associated with a significantly increased risk of severe forms of obesity. Workplace-based programs should be encouraged to place more emphasis on adequate sleep as an important factor associated with weight control and cardiovascular health. Further studies are needed to define a temporal relationship between sleep duration and obesity severity.

Background: Atherosclerotic Cardiovascular disease (ASCVD) remains the leading cause of deaths and costs in the US. Despite advancements in therapies, no study has evaluated drivers of pharmaceutical expenditures among individuals with ASCVD. We aimed to assess the economic impact of modifiable risk factors (MRF) on overall pharmaceutical expenditures among ASCVD patients. Methods: We studied the 2012 Medical Expenditure Panel Survey (MEPS) data of adults aged ≥40 years with Body Mass Index ≥18.5Kg/m2 and ICD-9 diagnosis of ASCVD (410, 413, 414, 433, 434, 435, 436, 437, 440, 443, and 447). Using total pharmacy expenditure variable in MEPS as our primary outcome, marginal and actual expenditures associated with predictors were estimated using a two-part econometric model with probit and glm, family(gamma) link (log). Results: Based on the 2012 MEPS, an estimated 140.7 million people in US are aged ≥40 years. An estimated 15.4 million had ASCVD (69±15 years; 41% female). Overall, total pharmaceutical expenditure among those with ASCVD was $52.7 billion (95% CI: $44.2-62.0 billion), which accounted for 33.7% of total pharmaceutical expenditures. Individuals with ASCVD had $1,847 (95% CI: $1,655 - 2,038) incremental pharmaceutical expenditure vs. those without it (p Conclusion: Our study results suggest attainment of favorable modifiable risk status as delineated in AHA 2020 Impact goals can have a beneficial impact on pharmaceutical costs, which accounts for significant proportion of overall healthcare expenditure.

Background: Studies have shown that individuals with higher levels of Ideal Cardiovascular Health (ICVH) metrics have favorable health outcomes. However, none of these studies quantify the reduction in the risk of death per unit increase in ICVH. In this study, we estimated the reduction in CVD and all-cause mortality attributable to per unit improvement in ICVH. Methods: Five studies identified through a literature search were included. Major differences in the re-categorization of the 7 ICVH metrics were noted, with studies having between 3-6 groups. Reference groups also ranged from 0 to ≤2 ideal CVH metrics. Because of these differences, risk reduction per unit increase in ICVH was not comparable across studies. To overcome these challenges, we quantified association between ICVH metrics and all-cause/CVD mortality using a dose-response meta-analysis, so all exposure categories contribute to a defined pooled association and heterogeneity is reduced by accounting for values assigned to these qualitative metrics. Results: Original data and meta-analysis model of studies assessing CVD mortality are shown in the figure. There was a significant linear trend ( p < 0.001) with moderate heterogeneity (Q test = 12, p = 0.02 and I2 = 66 %). Each unit increase in ICVH metric was associated with 18% (95% CI: 12, 23) reduction in HR. In all-cause mortality analysis (graph not shown), there was also a significant linear trend (p < 0.001) with moderate heterogeneity (Q test = 18, p = 0.003, and I2 = 72 %). Each unit increase in ICVH metric was associated with a 10% (95% CI: 6, 13) reduction in HR for all cause mortality. Conclusion: Our study is the first meta-analysis to demonstrate a dose-response impact of ICVH on mortality. The novel dose-response design allowed us to investigate strength, direction and type of association as well as overcomes challenges posed by heterogeneity ICVH metrics categorization while preserving the statistical control for confounding variables that was conducted in the individual studies.

Background: Physical activity (PA) is an established factor for favorable cardiovascular disease (CVD) outcomes and quality of life. However, to date little is available on PA’s independent impact on healthcare cost. In this study, we aimed to estimate this effect on medical expenditure from a nationally representative cohort with and without CVD. Methods: The 2012 Medical Expenditure Panel Survey data was analyzed. Our study population was limited to non-institutionalized adults ≥ 40 years of age. Variables of interest were CVD (coronary artery disease, stroke, heart failure, dysrhythmias or peripheral artery disease), modifiable risk factors (MRF; hypertension, diabetes mellitus, hypercholesterolemia, smoking, and/or obesity), and PA (dichotomous variable: defined as moderate-vigorous exercise of ≥ 30 minutes, 5 times/week). Two-part econometric models were utilized to study cost data; a generalized linear model with gamma distribution and link log was used to assess expenditures per capita, taking into consideration the survey’s complex design. Results: Our final study sample consisted of 15,651 surveyed individuals (mean age: 58.5 ± 12 years, 46% male). Overall, 46% engaged in at least moderate exercise, translating to 21 million physically active adults in the U.S. Of those with CVD, 34% reported PA, vs. 47% without CVD. In those without CVD, a higher prevalence of PA was noted with lower MRF burden (≥ 3: 35%, 2: 44%, 0-1: 53%). Generally, participants reporting moderate-vigorous PA incurred significantly lower healthcare costs, seen both in those with and without CVD. Among those without CVD, those engaged in moderate-vigorous PA with 0-1 & ≥ 3 MRF had $1,038 & $1,785 less healthcare expenditure, respectively, than their less physically active counterparts. Conclusion: In addition to tremendously improving CVD risk, moderate-vigorous PA is also associated with significantly less healthcare spending. Our findings further reinforce the importance of physical activity in health promotion and CVD prevention.

Background— The Mediterranean diet is protective against cardiovascular disease; a proposed mechanism is through a reduction in systemic inflammation. It is unknown to what extent the association between the Mediterranean diet and inflammation is due to genetic or other familial factors. Methods and Results— We administered the Willett food frequency questionnaire to 345 middle-aged male twins and assessed adherence to the Mediterranean diet using a published adherence score. Fasting plasma levels of interleukin-6, C-reactive protein, and known cardiovascular risk factors were measured. Mixed-effect regression analyses were used to examine the relationship between diet score and inflammatory biomarkers after accounting for known cardiovascular risk factors. Adherence to the Mediterranean diet was associated with reduced levels of interleukin-6 ( P P =0.10) after adjustment for total energy intake, other nutritional factors, known cardiovascular risk factors, and use of supplements and medications. When the overall association of adherence to the diet with interleukin-6 levels was partitioned into between- and within-pair effects, the between-pair effect was not significant ( P =0.9) and the within-pair effect was highly significant ( P Conclusions— Shared environmental and genetic factors are unlikely to play a major role in the association between adherence to the Mediterranean diet and systemic inflammation. These results support the hypothesis that reduced inflammation is an important mechanism linking Mediterranean diet to reduced cardiovascular risk.

Background: Healthcare disparities are a major public health concern. It is known that ethnicity and educational status independently predict health outcomes. Higher numbers of the American Heart Association's (AHA) ideal Life’s Simple 7 metrics (LS7) are associated with better cardiovascular health. In this study, we investigated the interplay of ethnicity and education on the attainment of ideal cardiovascular health (ICH) among employees of Baptist Health South Florida (BHSF), a large nonprofit health care organization. Methods: The data collected during BHSF annual voluntary wellness examination included age, gender, race, ethnicity and education. We assessed cardiovascular health using the LS7 metrics. Components of the LS7 metrics (smoking, physical activity, body mass index, diet, total cholesterol, blood pressure, and blood glucose) were categorized into ideal, intermediate and poor, according to AHA criteria. Study participants who met 6-7 ideal metrics were considered to have attained ICH. Results: The study population consisted of 9056 individuals (Mean age 43 ± 12 years, 74% women). Among employees with postgraduate education, 12% of white employees met the ideal for 6-7 LS7 metrics, 15% for Hispanic and 4% for Black employees. For employees with college degrees, the prevalence of 6-7 ideal LS7 metrics was 14%, 16% and 8% for white, Hispanic and black employees respectively (Figure). Overall, the odds of meeting 6-7 ideal LS7 metrics was lower for Hispanic and black employees compared to white employees of similar education (Table). These differences were especially large in those with high school education or less. Conclusion: Minorities are at an increased risk of poor cardiovascular health particularly those with the lowest educational achievement. Comprehensive workplace wellness programs that target these groups will improve cardiovascular health and employee productivity, in addition to saving health care costs.

Introduction: We aim to evaluate cost-effectiveness of recent FDA advisory committee recommended PCSK9 inhibitors for reducing cardiovascular disease (CVD) risk from societal & U.S. third-party payer perspective. Methods: A Markov model was used to evaluate costs and effects associated with addition of PCSK9 inhibitor to standard of care (SOC) based on a) estimated 53% 1-year relative risk reduction (SOC 1 year CVD event rate: 2.18%, PCSK9 inhibitor+SOC: 0.95%), b) indirect annual CVD reduction probability (using Framingham risk) via mean 61% LDL lowering among at CV risk patients. The model considers cycles of 1 year. Post CVD events last 5 years, after that time individuals go back to treatment state if no subsequent CVD observed. Health state costs were derived from published evidence. Survival probabilities >1 year were transformed to annual probabilities assumed on survival models. From societal perspective, cost per Quality-Adjusted Life Years (QALYs) gained are presented. We estimated payer’s perspective on net benefit balancing treatment vs. avoided cost and premium revenues over patient lifespan. Results: The table highlights societal gains and payer’s net benefit across range of estimated annual drug cost. At willingness-to-pay threshold of $100,000/QALY, PCSK9 inhibitors appear cost-effective if priced annually at $2500. At annual cost of $10,000, cost/QALY gained with PCSK9 inhibitor is nearly $400,000. From payer’s perspective, approximate net benefit was -$11,000 to -$51,000 per patient treated across annual drug cost range. Net benefits were only positive if treatment priced around $500/year. Conclusion: This study provides insights to facilitate discussion among healthcare stakeholders for considering future PCSK9 inhibitor’s utility balancing estimated benefits while accounting need for additional financial resources. Gaps between social & private benefits need to be aligned for appropriate PCSK9 inhibitors adoption in U.S.

Introduction: There has been increased focus on the relationship between sleep duration and cardiovascular disease, however, there is limited understanding of the association of sleep duration with cardiovascular health (CVH). In this study we examine the relationship between sleep duration and the American Heart Association’s ideal CVH in a large employee population. Methods: Data for this study was collected from participants at the 2014 health risk assessment in which they reported their average hours of sleep, their dietary patterns. In person, participants were weighed and their heights were measured. They also had blood pressure, blood glucose, total cholesterol measurements as well as breath carbon monoxide tests for smoking. The ideal for each CVH metric was estimated for each of the 7 metrics. Sleep duration was grouped into less than 6 hours, 6 to 7.9 hours and 8 or more hours. Ideal CVH was classified as presence of 6-7 ideal metrics. Results: A total of 9700 participants (mean age 43yrs, 74% female) completed the 2014 health risk assessment and had complete data on the variables of interest. Overall, more females and persons without college degrees slept for less than 6 hours. Compared to those with less than 6 hours of sleep, those with 8 or more hours of sleep had 1.6 times the odds of ideal diet (95% CI: 1.1-2.6), 1.7 times the odds of having ideal BMI (95% CI: 1.4-2.1), 1.3 times the odds of having ideal BP (95% CI: 1.1-1.5) and 2.4 times the odds of achieving ideal physical activity (95% CI: 2.4 - 2.9) after controlling for age, sex and educational levels. Comparing to those with less than 6 hours of sleep and with a reference of 0-2 ideal metrics, participants with 8 or more hours of sleep were 2.7 times as likely to have ideal CVH (see figure). Conclusions: Our study findings underscore the importance of promoting sleep health for optimizing ideal CVH. Further studies are needed to determine generalizability of our results.

BACKGROUND: Obesity is strongly related to chronic health problems and concomitant increased healthcare costs for employers. The aim of the study is to explore the distribution of obesity categories and estimate associated health costs among self-insured employees of Baptist Health South Florida (BHSF), a large not-for-profit health care organization. METHODS: Distribution of BMI categories was determined among individuals participating in a voluntary health risk assessment (HRA) available to employees eligible for health benefits. The potential estimates of obesity related costs to BHSF were imputed using CDC's Obesity Cost Calculator based on data from NHIS and MEPS (http://www.cdc.gov/leanworks/costcalculator/disclaimer.html). RESULTS: Overall 9996 (aged 43.1±12.1 years, 75% females, 75% Hispanic, 35% hypertensive, 4% diabetic) employees participated in 2013 annual HRA and wellness fair. The age-adjusted mean BMI was 29.3 (95% CI, 29.1-29.5) for men and 28.3 (95% CI, 28.15-28.45) kg/m2 for women. The table describes distribution of BMI categories according to gender and age groups. The age-adjusted prevalence of obesity (BMI>30 kg/m2) was 36% (95% CI, 34%-37%) among men and 32% (95% CI, 31%-33 %) among women. In BHSF employee population, 6% (n=581) were classified as morbidly obese (BMI>=40) and 7% (n=748) individuals met criteria for bariatric surgery. Total annual estimated cost attributable to high BMI (>25) were $8.05 million (74% medical and 26% work lost) of which 41% were contributed by 14% employees with BMI>35. The average attributable cost per high BMI employee ranged from $598 among those with BMI 25-29.9 to $2695 with BMI>=40. CONCLUSIONS: One third of employees (predominantly female and Hispanic) in a large health care organization (BHSF) were obese. Given the significant financial burden imposed by obesity large self-insured organizations like BHSF have a lot to gain by introducing evidence-driven weight reduction programs, and tracking the success of these programs in the workforce.

Introduction: With the development of new health metrics to define ideal cardiovascular health (CVH), several studies have examined the distribution of the American Heart Association (AHA) 2020 ideal CVH metrics both within and outside the United States (US). In this meta-analysis of proportions, we synthesized available data on ideal CVH metrics distribution in US cohorts and compared them with non-US populations. Methods: A MEDLINE database search was conducted using relevant free text terms such as “life’s simple 7”, “AHA 2020”, “American Heart Association 2020” and “ideal cardiovascular health” between January 2000 and October 2014. Studies were included in the meta-analysis if the proportions achieving ideal for 0, 1, 2, 3, 4, 5 or ≥6 ideal CVH metrics were known or could be estimated. A meta-analysis of proportions was conducted for US and non-US studies using a random effect model (REM). REM models were chosen because of the significant heterogeneity among studies. Results: Overall the pooled data consisted of 10 US cohorts with a total population of 94,761 participants and 6 non-US cohorts with a total of 130,242 participants. The table shows the pooled prevalence of ideal CVH factors in this population. Overall the pooled estimates of US cohorts showed 15% had 0-1 ideal CVH metrics (inter-study range: 7-22%), while 3% (inter-study range: 1-10%) had 6-7 ideal CVH metrics. This is comparable to 12% (inter-study range 1-17%) and 2% (inter-study range: 1-12%) for 0-1 and 6-7 ideal CVH metrics in the non-US studies. Conclusion: The proportion of persons achieving 6 or more ideal CVH metrics in both US and non-US cohorts is very low and the distribution of CVH metrics is similar in both US and non-US populations. Considering the strong association with worse outcomes, a coordinated global effort at improving CVH should be considered a priority.

Introduction: Fibroblast Growth Factor 23 (FGF23) is bone-derived hormone regulating phosphate homeostasis as part of a newly described bone-kidney axis. Several studies have demonstrated that elevated circulating FGF23 levels are independently associated with cardiovascular mortality. Methods: A systematic review was conducted according to Meta-analysis of Observational Studies in Epidemiology Group guidelines. Six databases (PubMed-Central, Ovid-MEDLINE, EMBASE, Web of Science, BIOSIS and Cochrane Database of Systematic Reviews) were searched for articles published between 2000 and 2014 examining the longitudinal association between FGF23 and CVD mortality among populations without prior CVD, Chronic Kidney Disease, or Diabetes. The review yielded 1,961 articles, of which 982 met the inclusion criteria. About 893 abstracts were excluded during the title and abstract screen, and an additional 92 after full text review. Only three articles met the review criteria and were included in the meta-analysis. Data from selected articles were abstracted and independently assessed for quality by two reviewers. Summary estimates and associated 95% confidence intervals were included in fixed and random-effects models. The presence of heterogeneity was evaluated using a Q-statistic with a conservative p-value of 0.10. All analyses were performed using R library meta. Results: Data for 15,379 participants were included in the meta-analysis. The hazard ratio for quartiles two and four when compared with quartile one,the reference category, were 1.29 (1.06- 1.58; p=0.01) and 1.31 (1.077-1.59; p=0.0068) respectively. There was no significant difference in CVD mortality between the third and first quartile. There was also no evidence of heterogeneity observed (I2 = 0%, p = 0.611). Conclusions: This study found a U-shaped association between FGF23 and CVD mortality suggesting that either low or high serum levels increase risk for CVD mortality. Current strategies focus on lowering high levels of circulating FGF23, but little attention has been given to understanding optimal levels necessary to prevent CVD mortality. If this U-shaped relationship between FGF23 and CVD mortality is real, the possible links, causes, and mechanisms require additional research.

Introduction: A family history (FH) of premature coronary artery disease (CAD) is an important prognostic risk factor. Emerging evidence suggests that CAD location as well as severity may be heritable. We sought to investigate the association between a FH of premature CAD with the location and severity of angiographically phenotyped CAD. Methods: 2854 patients undergoing coronary angiography were enrolled from the Emory Cardiovascular Biobank. A FH of CAD was defined as having any male or female relative with history of CAD at age ≤55 or ≤65 year old respectively. Coronary angiograms were phenotyped using a 17 segment AHA model. Proximal disease was defined as having ≥70% lesion in the left main or proximal portion of any of the three major epicardial arteries, while CAD severity was assessed by counting the number of vessels with ≥70% stenosis. Results: Among this population (mean age 63±12, male 67%, diabetes 33%), 21% reported a positive FH of premature CAD. After adjustment for age, gender, and traditional cardiovascular risk factors, those with a positive FH were more likely to have significant CAD than those without a positive FH (OR 1.3 (1.1-1.7)). They were 40% more likely to have single vessel (OR 1.4(1.1-1.7)) and up to 80% more likely to have multi-vessel disease (OR 1.8 (1.4-2.4)). In addition, they were also much more likely to have left main (OR 1.9 (1.3-2.8)) and proximal vessel involvement (OR 1.5 (1.2 - 1.9)), but not distal vessel stenosis (OR 1.1 (0.9-1.4)). Conclusions: A FH of CAD is associated with a greater likelihood of multi-vessel and proximal anatomical disease. Whether site specific disease is genetically mediated remains to be explored.

Introduction: Metabolic syndrome, the clustering of multiple cardiovascular risk factors, is established as a risk factor for CVD. Shorter or longer sleep duration has been reported to be associated with increased risk of metabolic syndrome (MS) and diabetes mellitus (DM) through increased insulin resistance (IR). However, it is not known if impaired sleep alters IR in a high-risk population with known MS/DM. Methods: The Baptist Employee Healthy Heart Study is an ongoing lifestyle intervention study examining the effects of web-based interventions on reducing CVD risk in individuals with MS/DM. Sleep duration was self reported by the participants. Daily sleep duration was categorized into sleep 8 hours (long). Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting insulin and fasting glucose level. Results: The population consisted of 182 participants (74% women, 49% Hispanic, mean age 52 ± 9 years). In this study the mean sleep duration was 7±5 hours and mean HOMA-IR was 5.2 ± 5.6 units. Systolic and diastolic blood pressure, BMI, waist circumference, total cholesterol level and LDL cholesterol level did not apparently differ across the groups. Both short and long sleepers tended to have lower HDL cholesterol level and higher triglyceride level (p8hrs (9.52±10.7), p Conclusions: In this study of high metabolic risk individuals, sleep duration was associated with increased insulin resistance and highlights the importance of improving sleep hygiene in the clinical management of high risk individuals with MS and DM.

INTRODUCTION: A recent meta-analysis demonstrated that Lipoprotein-associated phospholipase A 2 (LpPLA 2 ) activity is associated with CVD events. However, the mechanisms which mediate this risk are poorly established. This study aims to assess the cross-sectional association between LpPLA 2 and components of an advanced lipid panel, subclinical CVD and markers of inflammation. METHODS: The Baptist Employee Healthy Heart Study (BEHHS) is an ongoing study examining the effect of web-based interventions on reducing CVD risk in individuals with metabolic syndrome & type II diabetes mellitus. Cardio IQ™ Ion Mobility lipoprotein fractionation was utilized for advanced lipid subclass measurement resulting in direct quantification of particles in each lipoprotein sub-class fraction. Endothelial function was assessed using endoPAT2000 (Itamar, Israel) and individuals older than 35 years had CT scan for coronary artery calcium (CAC). LpPLA 2 was measured by Enzyme-linked Immunosorbent Assay (ELISA). RESULTS: The population consisted of 182 individuals, 74% female with a mean age of 51±10 years (range 25 - 72). Overall the median plasma LpPLA 2 level was 199 ng/mL. In univariate analyses, there was a significant association with several lipid subclasses and with hs-CRP. After adjusting for risk factors, LpPLA 2 was independently associated with LDL-c and LDL particle size, Large LDL subclass A, small IDL, small, medium and large VLDL, and with hs-CRP. On the other hand there was no association between LpPLA 2 mass and HOMA-IR, reactive hyperemia index or presence of CAC. CONCLUSIONS: LpPLA 2 is significantly associated with several lipoprotein sub-classes and with systemic inflammation without affecting vascular endothelial function or atherosclerosis. Further studies are required to determine if lifestyle interventions affect LpPLA2 and how this may translate to reduced systemic inflammation and an improvement in cardiometabolic profile.

BACKGROUND: Bariatric surgery among the morbidly obese is recommended as an option to mitigate future risk of cardiovascular disease, diabetes and hypertension. To date there is little evidence on the effect of extensive lifestyle interventions among these high-risk groups in reducing the need for such procedures in extended periods. METHODS: The purpose of the present study is assess efficacy of an intensive lifestyle workplace intervention on significant body weight across the spectrum of obesity in a worksite wellness program, called “My Unlimited Potential (MyUP)” conducted at Baptist Health South Florida. Changes in BMI are being measured from baseline to 12 months follow up, along with corresponding improvements in cardio-metabolic risk. In addition, the decrease in participants meeting criteria for bariatric surgery over the study period is examined at 6 and 12 months. Bariatric surgery criteria were defined as BMI≥40 or BMI between 35 and 40 and at least one of the following co-morbidities: diabetes, hypertension, or high cholesterol. RESULTS: The study population consisted of 272 individuals (48±9 years, 78% female) with BMI≥27 at baseline. Complete data at 12-month follow up was available for 141 individuals (52%). A total of 21(14%) and 14 (10%) participants had lost at least 10 % of their body weight by 6 months and 12 months respectively. Forty-six participants (32%) initially met criteria for bariatric surgery. At six month follow-up 43% (20 of 46, p CONCLUSIONS: This worksite wellness program effectively obviated the need for bariatric surgery in approximately half of those who were initially eligible at 1 year of follow up. Replication of this program with a larger cohort with stricter attention to attrition is needed to asses the utility of our program and its implications as a larger corporate wellness strategy.

Introduction: Visceral adiposity is associated with increased CVD risk. Ectopic fat deposition is linked with lipotoxicity, metabolic derangement, insulin resistance, and atherosclerosis. The lipoprotein(LP) subclasses are established risk markers for CVD mortality. We evaluated for the association of ectopic visceral fat measures [pericardial (PCF), Epicardial (EPC)], traditional adiposity measures [waist: hip ratio (WHR), Body Mass index (BMI), waist circumference (WC)] and the LP subclasses. Methods: The Baptist Employee Healthy Heart Study (BEHHS) an ongoing study examines the effect of web based interventions on reducing CVD risk in subjects with metabolic syndrome and type II diabetes mellitus. We measured PCF and EPC adipose tissue volumes from the 16-slice multi-detector computed tomography (MDCT) (GE AWW 3D Workstation). Cardio IQ™ Ion Mobility LP fractionation was utilized for advanced lipid subclass measurement resulting in direct quantification of particles in each LP sub-class fraction. Results: The population had 182 participants, 74% women, 49% Hispanic, mean age of 52 ± 9 years. The median PCF volume was 130 (97-166) cc, EPC volume 112(78-265) cc, mean WC 105±15 cm, BMI 34±6 kg/m2 ,WHR was 0.94 (SD 0.09). There was no correlation between BMI, and WC with any of the LP. WHR was significantly correlated with LDL particle size LDL large (A), , IDL small, and HDL large, see table 1. These associations were not significant in multivariate regression analysis. On the other hand PCF and ECP were significantly correlated with a wide spectrum of the LPs. After an adjusted robust regression, they remained significantly associated with IDL(large), LDL(total), VLDL(small), VLDL(medium) and VLDL(large). Conclusion: This demonstrates association between the ectopic adiposity and LP subclasses compared to traditional obesity measures. Further follow-up is needed to assess the interplay of lifestyle intervention in improving cardiometabolic profile

Introduction: Several individual ECG parameters are predictive of cardiovascular disease (CVD) mortality, and when combined in a score, may improve risk prediction. Hypothesis: We hypothesized that an ECG risk score (based on automated measures available on many modern ECG machines) can effectively predict CVD mortality, and augment risk classification when added to traditional risk factors (TRF). Methods: We examined 6786 individuals aged 40-79 years without known CVD in NHANES III (1988-1994) followed 10 years for CVD mortality. Six pre-specified ECG variables (“ECG model”), were evaluated including P, R, T axes, QT interval, QRS width, and heart rate. Three risk scores were developed for variables containing: 1) TRF only, 2) ECG factors (including age, sex, and race), and 3) TRF+ECG combined. Validation was performed using a cohort aged 40-74 years from NHANES I (n=3773), enrolled in 1971-1974. Age stratification was performed with cutoff of 65 years because of increased competing risks in older individuals. Results: During 10 years of follow up, 384 CVD deaths occurred. Frontal QRS-T angle, T-axis, wide QRS interval (cutoff 120 ms), heart rate-corrected QT interval, and heart rate were found to be significant predictors (p Conclusion: A risk score based on routinely reported automated ECG variables and TRF predicts risk of 10-year CVD death better than TRF alone in a cohort age < 65 years without known CVD.

Background: Studies have demonstrated that improving physical fitness is associated with weight loss and improvement in cardio-metabolic risk profile. However, the effect of improvement in aerobic fitness on metabolic risk in the absence of significant weight loss in a high risk working population is poorly understood. We examined efficacy of both weight reduction and increased aerobic fitness on metabolic syndrome in an ongoing multicomponent lifestyle intervention improvement program (My Unlimited Potential (myUP)), among employees of Baptist Health South Florida (BHSF). Methods: The study population included 158 participants who had at least 2 metabolic risk factors at baseline. An advanced nurse practitioner, registered dietician, exercise physiologist, certified diabetic educator, and registered nurse met with participants to provide one-on-one counseling and fitness training. During the first 12 weeks the multidisciplinary team rigorously supervised participants. Results: Over the 12 week period, there was a significant increase in METS (median difference 2.7; IQR 1.4 to 3.4 p Conclusion: Improvements in respiratory fitness as can be seen with exercise, even in the absence of significant weight loss, is associated with significant reduction in cardiometabolic risk. In an intensive lifestyle modification interventional program aimed at CVD risk reduction, emphasis should be placed at increasing physical fitness, not only on weight loss.

Background: With about 59% of the entire US population currently in the work force, American Heart Association has emphasized worksite-based interventions to improve cardiovascular health among the working population. The primary aim of this study was to assess the short-term (12 weeks) efficacy of an ongoing multi-component, behavioral intervention improvement program (My Unlimited Potential (myUP), among employees of Baptist Health South Florida (BHSF), a large not-for-profit health care system. Methods: BHSF employees with two or more Cardio-metabolic risk factors, such as total cholesterol ≥ 200 mg/dl, systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, hemoglobin A1C ≥ 6.5%, and body mass index (BMI) ≥ 30 were considered for the study. Behavioral interventions were focused on diet and physical activity modifications. Results: Overall 202 (48±10 years, 78% females) employees enrolled in myUP wellness program. The retention of subjects was high with 89% (n=181) of subjects following up at 12 weeks. The figure below demonstrates the baseline, follow-up and estimated mean change in anthropometric, exercise capacity on treadmill test and CM participants. BMI reduction >5% was noted in 38% of the participants. Significantly higher, clinically meaningful, endpoints, especially in attaining blood pressure goals and exercise capacity (>10 METS), during the short-term follow-up in this behavioral intervention program (figure), were achieved. Conclusion: These findings suggest that an intensive behavioral modification intervention program, delivered to employees in a health care setting, results in significant short term benefit in weight reduction, increase fitness level and concomitantly improve cardio-metabolic risk profile. Further follow-up is in progress to ascertain whether these benefits are sustainable over a longer duration.

Negative impact of CVD as the leading cause of death in the US is worsened by the significant burden of obesity and associated morbidity and concerns about the growing population inactivity. The American Heart Association has emphasized worksite-based interventions to improve CV health. We evaluated the benefits of improved physical activity(PA) and weight loss(WL) among employees of the Baptist Health South Florida enrolled in a wellness intervention program. Methods: Employees with two or more Cardio-metabolic risk factors , such as total cholesterol ≥ 200 mg/dl, systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, hemoglobin A1C ≥ 6.5%, and body mass index (BMI) ≥ 30 were enrolled in an intervention program themed “My unlimited potential”. Interventions were focused on diet and PA modifications. We defined improved physical activity as the difference in the metabolic equivalents (METs) at 12 weeks follow-up and at baseline. WL (lbs) was the difference in weight at follow-up. The relationship between WL and changes in METs was explored in an ordered logistic regression. Results: Overall 203 (48±10 years, 78% females) employees were enrolled with a retention rate of 89% (n=181) at 12 weeks follow-up. At baseline the median weights was 211 lbs., and mean METs- 8.6, while at follow-up the median weight was 200 lbs, and the mean METs 11. At 12 weeks follow up 38% had significant WL (lost >5% of baseline weight). The median WL was 8.4 (IQR 4.8-13.0) lbs and the mean change in METs was 2.4±1.8. Median WL increased with increasing tertiles of METs change; tertile1- 6.5(4-11) lbs., tertile2- 9(6-13)lbs. tertile3- 11(7-15)lbs. Increased PA was related to increased WL across BMI categories adjusting for age, gender and baseline weight. Conclusion: This study points strongly toward the benefit of increasing PA among other lifestyle modification interventions in controlling weight. Although further follow-up of this population to evaluate sustainability of change is needed, our results clearly relate improved PA and health.

Background: In this study we aim to assess the short term effects of clinically significant Blood Pressure (BP) reduction after a behavioral intervention on systemic inflammation, measured by elevated high sensitivity c-reactive protein (HSCRP), in a high cardiovascular disease (CVD) risk cohort. Methods: The study was conducted among 180 employees of Baptist Health South Florida who had 2 or more CVD risk factors such as obesity, diabetes, hypertension or elevated total cholesterol and was involved in a three-month workplace lifestyle intervention. The intervention focused on nutritional and physical activity modifications. At baseline and at 3 months follow-up, anthropometric, clinical, and laboratory measures were obtained. Significant BP reduction was defined as systolic blood pressure (SBP) reduction ≥ 10mmHg or diastolic blood pressure (DBP) reduction ≥ 5mmHg at 3 months of follow-up. A HSCRP >3mg/L was considered elevated. Results: Over the 3-month study period the median SBP decline was 16mmHg (IQR 4 -23mmHg) while the median reduction in DBP was 10mmHg (IQR 6 -16mmHg). 87% (156 participants) experienced significant BP reduction. Among those without significant BP reduction, the prevalence of elevated HSCRP at baseline was 58% and at follow-up it was 75% (p = 0.125). However, among those who had significant BP reduction, there was significant reduction in the prevalence of elevated HSCRP from 66.7% to 57.1% (p Conclusion: Clinically significant reduction in blood pressure over a short period in a high cardiovascular disease risk working population is independently associated with markedly diminished risk of elevate hs-CRP. Longer follow-up intervention studies are required to further understand if these effects are sustained.

Background: Deaths from early-onset coronary heart disease (CHD) translate into a large number of potential life-years lost with substantial impact on families and society. Although overall CHD mortality has declined in the past few decades, the extent to which such decline applies to early CHD mortality and to specific racial groups and urbanization levels has not been examined. We sought to describe the pattern and magnitude of racial and urban-rural variations in early-onset CHD mortality in the United States. Methods: We used data from the National Center for Health Statistics to examine trends in CHD death rates (ICD-10 codes I20-I25) between 1999 and 2007. Early-onset CHD mortality was defined as death due to CHD in men less than 55 yrs or women less than 65 yrs. Rate changes were calculated in the overall population and by race (blacks vs whites) and urbanization (rural vs. urban). Poisson regression was used to model the data. Results: Between 1999 and 2007, there were approximately 400,000 deaths due to early-onset CHD. There was an overall 25% decline in age-adjusted early-onset CHD mortality rates from 79 per 100,000 to 59 per 100,000 but this decline varied by gender, race, and urbanization. Women had a greater decline (27%) compared with men (19%) and blacks had slightly more decline (27%) compared to whites (25%). Urban areas (30%) had twice the decline compared to rural areas (16%). In this period early CHD deaths was higher in blacks than whites and higher in rural than urban areas (Figure). Blacks in rural areas had the highest early-onset CHD mortality, followed by blacks in large metros, while urban whites had the lowest rate. Black-white differences remained similar in urban and rural areas over this time period. Conclusion: The overall decline in early-onset CHD mortality is encouraging, but there are important differences by race and urbanization. Blacks in rural areas have the highest early-onset CHD mortality rates. Early-onset CHD can be used to identify and target groups with high risk in order to reduce disparities.

Background— There is a paucity of randomized trials regarding diagnostic testing in women with suspected coronary artery disease (CAD). It remains unclear whether the addition of myocardial perfusion imaging (MPI) to the standard ECG exercise treadmill test (ETT) provides incremental information to improve clinical decision making in women with suspected CAD. Methods and Results— We randomized symptomatic women with suspected CAD, an interpretable ECG, and ≥5 metabolic equivalents on the Duke Activity Status Index to 1 of 2 diagnostic strategies: ETT or exercise MPI. The primary end point was 2-year incidence of major adverse cardiac events, defined as CAD death or hospitalization for an acute coronary syndrome or heart failure. A total of 824 women were randomized to ETT or exercise MPI. For women randomized to ETT, ECG results were normal in 64%, indeterminate in 16%, and abnormal in 20%. By comparison, the exercise MPI results were normal in 91%, mildly abnormal in 3%, and moderate to severely abnormal in 6%. At 2 years, there was no difference in major adverse cardiac events (98.0% for ETT and 97.7% for MPI; P =0.59). Compared with ETT, index testing costs were higher for exercise MPI ( P P =0.0008). Overall, the cumulative diagnostic cost savings was 48% for ETT compared with exercise MPI ( P Conclusions— In low-risk, exercising women, a diagnostic strategy that uses ETT versus exercise MPI yields similar 2-year posttest outcomes while providing significant diagnostic cost savings. The ETT with selective follow-up testing should be considered as the initial diagnostic strategy in symptomatic women with suspected CAD. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00282711.

Background— Functional tricuspid regurgitation (TR) is increasingly recognized as a source of morbidity. Current repair strategies focus on annular remodeling because annular dilatation is common in patients with TR. Although papillary muscle (PM) displacement is recognized in functional mitral regurgitation, its role in TR is less well characterized. The objective of this in vitro study was to further clarify the mechanisms by which TR occurs as an effect of annular dilatation and PM displacement. Methods and Results— Porcine tricuspid valves (n=16) were studied in an in vitro right heart simulator. The valve dynamics were quantified with isolated annular dilatation starting with a normal annular size (6 cm 2 ) and incrementally dilated up to 100%, isolated PM displacement, and a combination of the 2. All valves lost competence at 40% dilatation, resulting in a TR of 7.9±3.4 mL ( P ≤0.05) compared with baseline and central residual leaflet length of 0.5±0.2 cm. Multidirectional displacement of the anterior and posterior/septal PMs and all PMs significantly ( P ≤0.05) increased TR, with normal annular area. Malcoaptation was observed where the 3 leaflets joined with all significant levels of TR. The anterior leaflet had the greatest percent change in residual leaflet length, whereas PM displacement caused a reduction in residual leaflet length for the septal leaflet for all conditions. Conclusions— This study shows that although annular dilatation alone leads to TR, isolated PM displacement can also cause TR; annular remodeling strategies should be tailored in the setting of severe PM displacement.

On behalf of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Investigators, we wish to thank Drs Joshi, Tarantini, and colleagues for their letters to the editor regarding our article.1 Many excellent comments were made that serve to clarify the COURAGE nuclear substudy. It is important to note that this study was devised to compare treatment effectiveness using nuclear quantification of ischemia as a surrogate outcome. The design of the substudy was based on the prognostic findings from observational registries of tens of thousands of patients undergoing stress myocardial perfusion single photon emission computed tomography (SPECT).2–4 Importantly, no published data were available previously to suggest that significant relative risk reduction would be seen in patients with ischemia reduction. Therefore, this study was not powered to examine differences in prognosis but was designed to determine whether percutaneous coronary intervention (PCI) resulted in a greater reduction of objective ischemia than did optimal medical therapy alone, extending prior, small series that found serial changes in …

Introduction. Major depressive disorder (MDD) is associated with coronary heart disease, but the underlying mechanisms are unclear. Coronary flow reserve (CFR) in response to adenosine is an index of coronary microvascular dysfunction which predisposes to myocardial ischemia. We examined the relationship between MDD and CFR in a genetically informative sample. Methods. We studied 141 twin pairs drawn from the Vietnam Era Twin Registry who were born between 1946 and 1956 (mean age 54). For all twins, a lifetime history of MDD was determined with the Structured Clinical Interview for Psychiatry Disorders; 53 pairs were discordant for MDD and 88 pairs were free of MDD. Standard cardiovascular risk factors were obtained by interview and examination. We performed myocardial perfusion imaging and blood flow quantitation with [13N] ammonia positron emission tomography at rest and after adenosine stress. A perfusion defect score summed the number and severity of defects across 20 myocardial regions. CFR was measured as the ratio of maximum flow to baseline flow at rest. Mixed-effect and GEE models were used to conduct matched-pair analyses. Results. There was no difference in the distribution of abnormal scans, in summed rest or stress defect scores, and in heart rate/blood pressure responses to adenosine between twins with and without MDD. Among the DZ twin pairs discordant for MDD, the mean CFR was lower in twins with MDD than their brothers without MDD (2.36 ± 0.66 vs 2.75 ± 0.90; p=0.03); no significant difference in mean CFR was found in MZ discordant pairs (2.90±0.78 vs 2.64±0.64, p=0.13). The zygosity by MDD interaction was significant (p=0.01). Results did not change substantially after adjusting for cardiovascular disease risk factors and antidepressant use (adjusted interaction p=0.007). There were no differences in myocardial perfusion comparing twins in discordant pairs with twins in healthy pairs. Conclusions. MDD is associated with lower CFR in spite of no differences in visible perfusion defects, suggesting microvascular dysfunction. This association is largely due to shared genetic liability between depression and CFR, suggesting a common underlying pathophysiological process linking depression and coronary microvascular dysfunction. This research has received full or partial funding support from the American Heart Association, AHA National Center.