Association of cardiovascular risk profile with premature all-cause and cardiovascular mortality in US adults: findings from a national study.

OBJECTIVE: To assess the association between cardiovascular risk factor (CRF) profile and premature all-cause and cardiovascular disease (CVD) mortality among US adults (age < 65). METHODS: This study used data from the National Health Interview Survey from 2006 to 2014, linked to the National Death Index for non-elderly adults aged < 65 years. A composite CRF score (range = 0-6) was calculated, based on the presence or absence of six established cardiovascular risk factors: hypertension, diabetes, hypercholesterolemia, smoking, obesity, and insufficient physical activity. CRF profile was defined as "Poor" (≥ 3 risk factors), "Average" (1-2), or "Optimal" (0 risk factors). Age-adjusted mortality rates (AAMR) were reported across CRF profile categories, separately for all-cause and CVD mortality. Cox proportional hazard models were used to evaluate the association between CRF profile and all-cause and CVD mortality. RESULTS: Among 195,901 non-elderly individuals (mean age: 40.4 ± 13.0, 50% females and 70% Non-Hispanic (NH) White adults), 24.8% had optimal, 58.9% average, and 16.2% poor CRF profiles, respectively. Participants with poor CRF profile were more likely to be NH Black, have lower educational attainment and lower income compared to those with optimal CRF profile. All-cause and CVD mortality rates were three to four fold higher in individuals with poor CRF profile, compared to their optimal profile counterparts. Adults with poor CRF profile experienced 3.5-fold (aHR: 3.48 [95% CI: 2.96, 4.10]) and 5-fold (aHR: 4.76 [3.44, 6.60]) higher risk of all-cause and CVD mortality, respectively, compared to those with optimal profile. These results were consistent across age, sex, and race/ethnicity subgroups. CONCLUSIONS: In this population-based study, non-elderly adults with poor CRF profile had a three to five-fold higher risk of all-cause and CVD mortality, compared to those with optimal CRF profile. Targeted prevention efforts to achieve optimal cardiovascular risk profile are imperative to reduce the persistent burden of premature all-cause and CVD mortality in the US.

Cumulative social disadvantage and health-related quality of life: national health interview survey 2013-2017.

BACKGROUND: Evidence for the association between social determinants of health (SDoH) and health-related quality of life (HRQoL) is largely based on single SDoH measures, with limited evaluation of cumulative social disadvantage. We examined the association between cumulative social disadvantage and the Health and Activity Limitation Index (HALex). METHODS: Using adult data from the National Health Interview Survey (2013-2017), we created a cumulative disadvantage index by aggregating 47 deprivations across 6 SDoH domains. Respondents were ranked using cumulative SDoH index quartiles (SDoH-Q1 to Q4), with higher quartile groups being more disadvantaged. We used two-part models for continuous HALex scores and logistic regression for poor HALex (< 20th percentile score) to examine HALex differences associated with cumulative disadvantage. Lower HALex scores implied poorer HRQoL performance. RESULTS: The study sample included 156,182 respondents, representing 232.8 million adults in the United States (mean age 46 years; 51.7% women). The mean HALex score was 0.85 and 17.7% had poor HALex. Higher SDoH quartile groups had poorer HALex performance (lower scores and increased prevalence of poor HALex). A unit increase in SDoH index was associated with - 0.010 (95% CI [-0.011, -0.010]) difference in HALex score and 20% higher odds of poor HALex (odds ratio, OR = 1.20; 95% CI [1.19, 1.21]). Relative to SDoH-Q1, SDoH-Q4 was associated with HALex score difference of -0.086 (95% CI [-0.089, -0.083]) and OR = 5.32 (95% CI [4.97, 5.70]) for poor HALex. Despite a higher burden of cumulative social disadvantage, Hispanics had a weaker SDoH-HALex association than their non-Hispanic White counterparts. CONCLUSIONS: Cumulative social disadvantage was associated with poorer HALex performance in an incremental fashion. Innovations to incorporate SDoH-screening tools into clinical decision systems must continue in order to accurately identify socially vulnerable groups in need of both clinical risk mitigation and social support. To maximize health returns, policies can be tailored through community partnerships to address systemic barriers that exist within distinct sociodemographic groups, as well as demographic differences in health perception and healthcare experience.

Low educational attainment is associated with higher all-cause and cardiovascular mortality in the United States adult population.

INTRODUCTION: Educational attainment is an important social determinant of health (SDOH) for cardiovascular disease (CVD). However, the association between educational attainment and all-cause and CVD mortality has not been longitudinally evaluated on a population-level in the US, especially in individuals with atherosclerotic cardiovascular disease (ASCVD). In this nationally representative study, we assessed the association between educational attainment and the risk of all-cause and cardiovascular (CVD) mortality in the general adult population and in adults with ASCVD in the US. METHODS: We used data from the 2006-2014 National Death Index-linked National Health Interview Survey for adults ≥ 18 years. We generated age-adjusted mortality rates (AAMR) by levels of educational attainment (< high school (HS), HS/General Education Development (GED), some college, and ≥ College) in the overall population and in adults with ASCVD. Cox proportional hazards models were used to examine the multivariable-adjusted associations between educational attainment and all-cause and CVD mortality. RESULTS: The sample comprised 210,853 participants (mean age 46.3), representing ~ 189 million adults annually, of which 8% had ASCVD. Overall, 14.7%, 27%, 20.3%, and 38% of the population had educational attainment < HS, HS/GED, Some College, and ≥ College, respectively. During a median follow-up of 4.5 years, all-cause age-adjusted mortality rates were 400.6 vs. 208.6 and 1446.7 vs. 984.0 for the total and ASCVD populations for < HS vs ≥ College education, respectively. CVD age adjusted mortality rates were 82.1 vs. 38.7 and 456.4 vs 279.5 for the total and ASCVD populations for < HS vs ≥ College education, respectively. In models adjusting for demographics and SDOH, < HS (reference = ≥ College) was associated with 40-50% increased risk of mortality in the total population and 20-40% increased risk of mortality in the ASCVD population, for both all-cause and CVD mortality. Further adjustment for traditional risk factors attenuated the associations but remained statistically significant for < HS in the overall population. Similar trends were seen across sociodemographic subgroups including age, sex, race/ethnicity, income, and insurance status. CONCLUSIONS: Lower educational attainment is independently associated with increased risk of all-cause and CVD mortality in both the total and ASCVD populations, with the highest risk observed for individuals with < HS education. Future efforts to understand persistent disparities in CVD and all-cause mortality should pay close attention to the role of education, and include educational attainment as an independent predictor in mortality risk prediction algorithms.

Delayed medical care due to transportation barriers among adults with atherosclerotic cardiovascular disease.

BACKGROUND: In patients with atherosclerotic cardiovascular disease (ASCVD), barriers related to transportation may impair access to care, with potential implications for prognosis. Although few studies have explored transportation barriers among patients with ASCVD, the correlates of delayed care due to transportation barriers have not been examined in this population. We aimed to examine this in U.S. patients with ASCVD using nationally representative data. METHODS: Using data from the 2009-2018 National Health Interview Survey, we estimated the self-reported prevalence of delayed medical care due to transportation barriers among adults with ASCVD, overall and by sociodemographic characteristics. Logistic regression was used to examine the association between various sociodemographic characteristics and delayed care due to transportation barriers. RESULTS: Among adults with ASCVD, 4.5% (95% CI; 4.2, 4.8) or ∼876,000 annually reported delayed care due to transportation barriers. Income (low-income: odds ratio [OR] 4.43, 95% CI [3.04, 6.46]; lowest-income: OR 6.35, 95% CI [4.36, 9.23]) and Medicaid insurance (OR 4.53; 95% CI [3.27, 6.29]) were strongly associated with delayed care due to transportation barriers. Additionally, younger individuals, women, non-Hispanic Black adults, and those from the U.S. South or Midwest, had higher odds of reporting delayed care due to transportation barriers. CONCLUSIONS: Approximately 5% of adults with ASCVD experience delayed care due to transportation barriers. Vulnerable groups include young adults, women, low-income people, and those with public/no insurance. Future studies should analyze the feasibility and potential benefits of interventions such as use of telehealth, mobile clinics, and provision of transportation among patients with ASCVD in the U.S.

Team-based strategies to prevent heart failure.

PURPOSE OF REVIEW: The burden of heart failure (HF) in the United States and worldwide is projected to rise. Prevention of HF can curb the burden of this chronic syndrome, but current approaches are limited. This review discusses team-based strategies aimed to prevent HF. RECENT FINDINGS: Individuals at high risk for developing HF can be identified using HF risk scores, biomarkers, and cardiac imaging. Electronic medical records (EMR) can integrate clinical data to estimate HF risk and identify individuals who may benefit most from preventive therapies. Team-based interventions can lead to enhanced adherence to medications, optimization of medical management, and control of risk factors. Multifaceted interventions involve EMR-based strategies, pharmacist- and nurse-led initiatives, involvement of community personnel, polypills, and digital solutions. SUMMARY: Team-based strategies aimed to prevent HF incorporate a broad group of personnel and tools. Despite implementation challenges, existing resources can be efficiently utilized to facilitate team-based approaches to potentially reduce the burden of HF.

Glucagon-Like Peptide 1 Receptor Agonists: A Medication for Obesity Management.

PURPOSE OF REVIEW: The burden of obesity worldwide is high and projected to rise. Obesity increases the risk of several cardiovascular diseases and cardiometabolic risk factors; hence, utilizing effective long-term therapies for obesity is of utmost importance. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as effective therapies that achieve substantial weight loss and improve cardiometabolic risk. The purpose of this review is to discuss the role of GLP-1RAs in obesity management. RECENT FINDINGS: Two subcutaneous GLP-1RAs, liraglutide and semaglutide, have been evaluated in several clinical trials for weight loss. Liraglutide achieves a mean weight loss of 4-7 kg, and more than 50% of treated individuals achieve 5% or more weight loss. Semaglutide has a greater impact on weight loss, with a mean weight loss of 9-16 kg, and more than 50% of treated individuals achieve 10-15% or more weight loss. These results led to regulatory approval of these agents for weight loss in individuals with obesity, regardless of diabetes status. In addition to weight loss, the benefits of GLP-1RAs extend to other risk factors, such as glycemic control and blood pressure. Gastrointestinal symptoms are the most frequently encountered adverse events with incidences between 5 and 30%. Finally, the cost remains one of the most critical challenges that limit GLP-1RAs use. GLP-1RAs have robust weight loss benefits and are expected to have a critical role in the management of obesity in the coming years. Upcoming studies will evaluate the durability of weight loss achieved with GLP-1RAs and the impact on cardiovascular outcomes.

Implementation of Cardiometabolic Centers and Training Programs.

PURPOSE OF REVIEW: Type 2 diabetes is frequently accompanied by obesity, nonalcoholic fatty liver disease, chronic kidney disease, and cardiovascular disease, which collectively contribute to the high burden of cardiometabolic disease. This review discusses cardiometabolic disease management, strategies to implement cardiometabolic centers to deliver care, and dedicated programs to train the next generation of cardiometabolic experts. RECENT FINDINGS: Sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and a nonsteroidal mineralocorticoid receptor antagonist have demonstrated beneficial effects across cardiometabolic conditions. However, utilization of effective pharmacotherapies is low in clinical practice, in part due to clinical inertia and traditional sharp delineation in clinical responsibilities of specialists. Multidisciplinary clinics and population-health models can provide comprehensive care but require investment in physical and information technology infrastructure as well as in training and accreditation. Post-internal medicine residency cardiometabolic health training programs have been proposed. Implementing cardiometabolic centers in health systems involves reshaping current practices. Training programs focused on cardiometabolic health are needed to address the growing burden of disease and specific training needs in this ever-expanding area.

Impact of Laparoscopic Sleeve Gastrectomy on Cardiovascular Pharmacotherapy in Left Ventricular Assist Device Patients.

ABSTRACT: Left ventricular assist device (LVAD) implantation is increasingly utilized in patients with advanced heart failure and morbid obesity. Laparoscopic sleeve gastrectomy (LSG) can facilitate weight loss in this population and can ultimately change the pharmacokinetics of heart failure therapeutics. In this study, we aimed to explore the changes in cardiovascular pharmacotherapy post LSG intervention. We conducted a retrospective observational cohort study of morbidly obese LVAD patients between 2013 and 2019 at the University of Florida with available pharmacotherapeutic data at 1 and 6 months. Thirteen post-LSG patients and 13 control subjects were included in the final analysis. In the post-LSG group, the mean body mass index decreased significantly (44 ± 5 vs. 34 ± 4.9, P < 0.001), and 7 patients were successfully bridged to cardiac transplantation. Only 3 patients required adjustment of their LVAD speed. Mean return to flow decreased by 8 mm Hg, despite a 45% reduction in the mean number of vasodilators per patient (1.2 vs. 0.7, P = 0.03). Mean weekly warfarin dose decreased by 35% after 6 months (32.9 ± 20.9 vs. 50.7 ± 26.6, P = 0.01). The use of diuretics, vasodilators, and beta-blockers was significantly reduced by 50%, 45%, and 35%, respectively. None of these changes were observed in the control group at 6-month follow-up post LVAD. In this single-center experience, weight loss post LSG is associated with decreased vasodilator, diuretic, and anticoagulant medication requirements in LVAD patients.

Identification of MicroRNA-124 as a Major Regulator of Enhanced Endothelial Cell Glycolysis in Pulmonary Arterial Hypertension via PTBP1 (Polypyrimidine Tract Binding Protein) and Pyruvate Kinase M2.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by abnormal growth and enhanced glycolysis of pulmonary artery endothelial cells. However, the mechanisms underlying alterations in energy production have not been identified. METHODS: Here, we examined the miRNA and proteomic profiles of blood outgrowth endothelial cells (BOECs) from patients with heritable PAH caused by mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene and patients with idiopathic PAH to determine mechanisms underlying abnormal endothelial glycolysis. We hypothesized that in BOECs from patients with PAH, the downregulation of microRNA-124 (miR-124), determined with a tiered systems biology approach, is responsible for increased expression of the splicing factor PTBP1 (polypyrimidine tract binding protein), resulting in alternative splicing of pyruvate kinase muscle isoforms 1 and 2 (PKM1 and 2) and consequently increased PKM2 expression. We questioned whether this alternative regulation plays a critical role in the hyperglycolytic phenotype of PAH endothelial cells. RESULTS: Heritable PAH and idiopathic PAH BOECs recapitulated the metabolic abnormalities observed in pulmonary artery endothelial cells from patients with idiopathic PAH, confirming a switch from oxidative phosphorylation to aerobic glycolysis. Overexpression of miR-124 or siRNA silencing of PTPB1 restored normal proliferation and glycolysis in heritable PAH BOECs, corrected the dysregulation of glycolytic genes and lactate production, and partially restored mitochondrial respiration. BMPR2 knockdown in control BOECs reduced the expression of miR-124, increased PTPB1, and enhanced glycolysis. Moreover, we observed reduced miR-124, increased PTPB1 and PKM2 expression, and significant dysregulation of glycolytic genes in the rat SUGEN-hypoxia model of severe PAH, characterized by reduced BMPR2 expression and endothelial hyperproliferation, supporting the relevance of this mechanism in vivo. CONCLUSIONS: Pulmonary vascular and circulating progenitor endothelial cells isolated from patients with PAH demonstrate downregulation of miR-124, leading to the metabolic and proliferative abnormalities in PAH ECs via PTPB1 and PKM1/PKM2. Therefore, the manipulation of this miRNA or its targets could represent a novel therapeutic approach for the treatment of PAH.

High circulating angiopoietin-2 levels exacerbate pulmonary inflammation but not vascular leak or mortality in endotoxin-induced lung injury in mice.

BACKGROUND: Elevated plasma levels of angiopoietin-2 (ANGPT2) have been reported in patients with acute lung injury (ALI); however, it remains unclear whether this increase contributes to, or just marks, the underlying vasculopathic inflammation and leak associated with ALI. Here we investigated the biological consequences of inducing high circulating levels of ANGPT2 in a mouse model of endotoxin-induced ALI. METHODS: Transgenic mice (ANGPT2OVR) with elevated circulating levels of ANGPT2, achieved through conditional hepatocyte-specific overexpression, were examined from 3 to 72 hours following lipopolysaccharide (LPS)-induced ALI. An aptamer-based inhibitor was used to neutralise the effects of circulating ANGPT2 in LPS-exposed ANGPT2OVR mice. RESULTS: Total cells, neutrophils and macrophages, as well as inflammatory cytokines, were significantly higher in bronchoalveolar lavage (BAL) of ANGPT2OVR versus littermate controltTA mice at 48 hours and 6 hours post-LPS, respectively. In contrast, LPS-induced vascular leak, evidenced by total BAL protein levels and lung wet/dry ratio, was unchanged between ANGPT2OVR and controlstTA, while BAL levels of IgM and albumin were decreased in ANGPT2OVR mice between 24 hours and 48 hours suggesting a partial attenuation of vascular leak. There was no significant difference in LPS-induced mortality between ANGPT2OVR and controlstTA. An ANGPT2-neutralising aptamer partially attenuated alveolar cell infiltration while exacerbating vascular leak in LPS-exposed ANGPT2OVR mice, supported by underlying time-dependent changes in the lung transcriptional profiles of multiple genes linked to neutrophil recruitment/adhesion and endothelial integrity. CONCLUSIONS: Our findings suggest that high circulating ANGPT2 potentiates endotoxin-induced lung inflammation but may also exert other pleiotropic effects to help fine-tune the vascular response to lung injury.

Estradiol shifts interactions between the infralimbic cortex and central amygdala to enhance fear extinction memory in female rats.

There is growing evidence that estradiol (E2) enhances fear extinction memory consolidation. However, it is unclear how E2 influences the nodes of the fear extinction network to enhance extinction memory. This study begins to delineate the neural circuits underlying the influence of E2 on fear extinction acquisition and consolidation in female rats. After fear conditioning (day 1), naturally cycling female rats underwent extinction learning (day 2) in a low-E2 state, receiving a systemic administration of either E2 or vehicle prior to extinction training. Extinction memory recall was then tested 24 hr later (day 3). We measured immediate early gene c-fos expression within the extinction network during fear extinction learning and extinction recall. During extinction learning, E2 treatment increased centrolateral amygdala c-fos activity and reduced lateral amygdala activity relative to vehicle. During extinction recall, E2-treated rats exhibited reduced c-fos expression in the centromedial amygdala. There were no group differences in c-fos expression within the medial prefrontal cortex or dorsal hippocampus. Examining c-fos ratios with the infralimbic cortex (IL) revealed that, despite the lack of group differences within the IL, E2 treatment induced greater IL activity relative to both prelimbic cortex and central amygdala (CeA) activity during extinction memory recall. Only the relationship between IL and CeA activity positively correlated with extinction retention. In conclusion, E2 appears to modify interactions between the IL and the CeA in females, shifting from stronger amygdalar modulation of fear during extinction learning to stronger IL control during extinction recall. © 2016 Wiley Periodicals, Inc.

Marked Strain-Specific Differences in the SU5416 Rat Model of Severe Pulmonary Arterial Hypertension.

We assessed the pulmonary hemodynamic response to vascular endothelial growth factor receptor, type 2, inhibition using SU5416 (SU) with and without chronic hypoxia (CH) in different background strains and colonies of rats. A single subcutaneous injection of SU (20 mg/kg) or vehicle was administered to different substrains of Sprague-Dawley (SD) rats, and they were compared with Lewis and Fischer rats, with and without exposure to CH (10% O2 for 3 wk). Remarkably, a unique colony of SD rats from Charles River Laboratories, termed the SD-hyperresponsive type, exhibited severe pulmonary arterial hypertension (PAH) with SU alone, characterized by increased right ventricular systolic pressure, right ventricular/left ventricular plus septal weight ratio, and arteriolar occlusive lesions at 7-8 weeks (all P < 0.0001 versus vehicle). In contrast, the other SD substrain from Harlan Laboratories, termed SD-typical type, as well as Fischer rats, developed severe PAH only when exposed to SU and CH, whereas Lewis rats showed only a minimal response. All SD-typical type rats survived for up to 13 weeks after SU/CH, whereas SD-hyperresponsive type rats exhibited mortality after SU and SU/CH (35% and 50%, respectively) at 8 weeks. Fischer rats exposed to SU/CH exhibited the greatest mortality at 8 weeks (78%), beginning as early as 4 weeks after SU and preceded by right ventricle enlargement. Of note, a partial recovery of PAH after 8 weeks was observed in the SD-typical type substrain only. In conclusion, variation in strain, even between colonies of the same strain, has a remarkable influence on the nature and severity of the response to SU, consistent with an important role for genetic modifiers of the PAH phenotype.

Occlusive lung arterial lesions in endothelial-targeted, fas-induced apoptosis transgenic mice.

Pulmonary arterial hypertension (PAH) is a lethal disease that is characterized by functional and structural abnormalities involving distal pulmonary arterioles that result in increased pulmonary vascular resistance and ultimately right heart failure. In experimental models of pulmonary hypertension, endothelial cell (EC) apoptosis is a necessary trigger for the development of obliterative lung arteriopathy, inducing the emergence of hyperproliferative and apoptosis-resistant vascular cells. However, it has not been established whether EC apoptosis is sufficient for the induction of complex lung arteriolar lesions. We generated a conditional transgenic system in mice to test the hypothesis that lung endothelial cell apoptosis is sufficient to induce a PAH phenotype. The Fas-induced apoptosis (FIA) construct was expressed under the control of endothelial-specific Tie2 promoter (i.e., EFIA mice), and administration of a small molecule dimerizing agent, AP20187, resulted in modest pulmonary hypertension, which was associated with obliterative vascular lesions localized to distal lung arterioles in a proportion of transgenic mice. These lesions were characterized by proliferating cells, predominantly CD68 macrophages. Although endothelial cell apoptosis was also seen in the kidney, evidence of subsequent arteriopathy was seen only in the lung. This model provides direct evidence that lung endothelial cell apoptosis acts as a trigger to initiate a PAH phenotype and provides initial insight into the potential mechanisms that underlie a lung-specific arterial response to endothelial injury.

Role of thromboelastography and rapid thromboelastography to assess the pharmacodynamic effects of vitamin K antagonists.

Thromboelastography (TEG) measures the effects of antithrombotic agents by assessing global functional clotting status by evaluating the viscoelastic properties of in vitro clot formation. Recently, rapid TEG (r-TEG), which uses tissue factor in addition to standard kaolin to accelerate activation of the clotting cascade, has been proposed to obtain more immediate results. The correlation between results of TEG or r-TEG with international normalized ratio (INR) in patients on vitamin K antagonist (VKA) therapy has not been explored and represents the aim of this study. Patients on chronic therapy with VKAs (n = 100) were included in an observational prospective pharmacodynamic study. The correlation between TEG parameters, in particular markers of thrombus generation [Reaction time (R), maximum rate of thrombus generation (MRTG), and time to maximum rate of thrombus generation (TMRTG)], and INR values as well as the concordance between these parameters and therapeutic INR ranges were evaluated. In addition, in a subgroup of subjects (n = 17), the correlation of r-TEG parameters with TEG parameters and INR values was also assessed. No correlation was found between INR and TEG parameters of thrombus generation, in particular between INR and R (r = 0.189, p = 0.06), MRTG (r = -0.027, p = 0.79), and TMRTG (r = 0.188, p = 0.06). Further, no concordance was found between these parameters and recommended INR ranges. Significant Spearman correlations were found between INR and activated clotting time (rS = 0.546, p < 0.001), r-R (rS = 0.572, p = 0.017), and r-TMRTG (rS = 0.510, p = 0.037), but not r-MRTG (rS = 0.131, p = 0.617). Results were obtained in 24 ± 6 versus 12 ± 4 min with TEG and r-TEG, respectively (p < 0.001). In patients on chronic VKA therapy, TEG is not a useful tool to evaluate VKA anticoagulant effect, compared with standard INR measurements. However, r-TEG parameters of thrombus generation correlate with INR levels, suggesting a possible role of this assay for measuring more expeditiously anticoagulant treatment effects.

Condyloma lata of the umbilicus: A case report highlighting the present syphilis emergency.

Syphilis is an ancient sexually transmitted infection that plagues communities across the United States and the world. Cutaneous syphilis has a wide variety of manifestations and presentations, and is notoriously difficult to identify clinically as a result. In this report, we describe the case of a 30-year-old patient with condyloma lata on the umbilicus, an extremely rare site for the presentation of these lesions. With the recent surge in syphilis infections nationwide, including congenital infections, this case underscores the urgent necessity for heightened syphilis awareness and suspicion among clinicians.

Social disadvantage, coronary artery calcium, and their interplay in the prediction of atherosclerotic cardiovascular disease events.

BACKGROUND AND AIMS: Social determinants of health (SDOH) are key for the identification of populations at increased risk of atherosclerotic cardiovascular disease (ASCVD). However, whether at the individual level SDOH improve current ASCVD risk prediction paradigms beyond traditional risk factors and the coronary artery calcium (CAC) score, is unknown. We evaluated the interplay between CAC and SDOH in ASCVD risk prediction. METHODS: MESA is a prospective study of US adults free of clinical ASCVD at baseline. We used an SDOH index inclusive of 14 determinants from 5 domains. The index ranged 0-1 and was divided into quartiles, with higher ones representing worse SDOH. Cox regression was used to evaluate the adjusted associations between CAC, SDOH, their interplay, and ASCVD events. The C-statistic was computed to assess improvement in risk discrimination for prediction of ASCVD events. RESULTS: We included 6479 MESA participants (50% with CAC = 0, 24% CAC>100). ASCVD incidence increased with increasing CAC scores across SDOH quartiles. The lowest incidence was noted in those with CAC = 0 and favourable SDOH (2/1000 person-years) and highest in those with CAC>100 and most unfavourable SDOH (20.6/1000 person-years). While CAC was strongly associated with ASCVD across SDOH quartiles, SDOH was weakly associated with ASCVD across CAC strata. CAC improved the discriminatory ability of all prediction models beyond traditional risk factors, the improvement in C-statistic ranging +0.02 - +0.05. Improvements with SDOH were smaller, and were none on top of CAC. CONCLUSIONS: CAC improves ASCVD risk stratification across the spectrum of social vulnerability, while SDOH fail to improve risk prediction beyond traditional RFs and CAC.

Hemotympanum as a Complication of a Valsalva Maneuver during Childbirth.

Background: Hemotympanum may occur due to otic barotrauma secondary to Valsalva maneuver during the second phase of labor. A pressure differential across the tympanic membrane (TM) of about five psi can cause rupture. The increased intrathoracic and intraabdominal pressure spikes repeatedly manifested by "pushing" during second-stage labor easily approach (and may exceed) this level. Clinical Presentation. This case report describes a healthy thirty-seven-year-old multipara patient admitted for the 40-weeks' gestational age routine follow-up that proceeded to active labor followed by an aural fullness and bloody otorrhea. Otoscopic examination with a light microscope confirmed the hemotympanum of the right tympanic membrane. Conclusion: Forceful Valsalva can cause hemotympanum. Investigating the benefits and disadvantages of the pushing methods could help reduce such complications in the future. A prompt evaluation of an otolaryngologist should be requested in the event of a new postpartum hearing disturbance or bloody otorrhea.

Body Mass Index and All-Cause and Cardiovascular Mortality in United States Adults With and Without Atherosclerotic Cardiovascular Disease: Findings from the National Health Interview Survey.

In a nationally representative population-based study of US adults, the authors sought to examine the association between body mass index (BMI) and all-cause and cardiovascular disease (CVD) mortality in a nationally representative sample of adults with and without atherosclerotic cardiovascular disease (ASCVD), and further stratified by age, sex, and race/ethnicity. The study used data from 2006 to 2015 National Health Interview Survey and categorized participants into the following BMI categories: normal weight (20-24.9), overweight (25-29.9), obesity class 1 (30-34.9), obesity class 2 (35-39.9), and obesity class 3 (≥40 kg/m2). Multivariable Cox proportional hazards models were used to assess the risk of all-cause and CVD mortality across successively increasing BMI categories overall, and by sociodemographic subgroups. A total of 210,923 individuals were included in the final analysis. In the population without ASCVD, the risk of all-cause and CVD mortality was lower in overweight and higher in obesity classes 2 and 3, compared with normal weight, with the highest risk observed in the young adult (age 18-39) population. Elderly adults (65 and above) and populations with ASCVD exhibited a BMI-mortality paradox. In addition, Hispanic individuals did not show a relationship between BMI and mortality compared with non-Hispanic White and Black adults. In conclusion, being overweight was associated with decreased risk, whereas obesity class 3 was consistently associated with increased risk of all-cause and CVD mortality in adults without ASCVD, particularly young adults. BMI-mortality paradox was noted in ASCVD, elderly, and non-Hispanic adults.

Social Determinants of Cardiovascular Risk, Subclinical Cardiovascular Disease, and Cardiovascular Events.

Background Although there is research on the impact of social determinants of health (SDOHs) on cardiovascular health, most existing evidence is based on individual SDOH components. We evaluated the impact of cumulative SDOH burden on cardiovascular risk factors, subclinical atherosclerosis, and incident cardiovascular disease events. Methods and Results We included 6479 participants from the MESA (Multi-Ethnic Study of Atherosclerosis). A weighted aggregate SDOH score representing the cumulative number of unfavorable SDOHs, identified from 14 components across 5 domains (economic stability, neighborhood and physical environment, community and social context, education, and health care system access) was calculated and divided into quartiles (quartile 4 being the least favorable). The impact of cumulative SDOH burden on cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking, and obesity), systemic inflammation, subclinical atherosclerosis, and incident cardiovascular disease was evaluated. Increasing social disadvantage was associated with increased odds of all cardiovascular risk factors except dyslipidemia. Smoking was the risk factor most strongly associated with worse SDOH (odds ratio [OR], 2.67 for quartile 4 versus quartile 1 [95% CI, 2.13-3.34]). Participants within SDOH quartile 4 had 33% higher odds of increased high-sensitivity C-reactive protein (OR, 1.33 [95% CI, 1.11-1.60]) and 31% higher risk of all cardiovascular disease (hazard ratio, 1.31 [95% CI, 1.03-1.67]), yet no greater burden of subclinical atherosclerosis (OR, 1.01 [95% CI, 0.79-1.29]), when compared with those in quartile 1. Conclusions Increasing social disadvantage was associated with more prevalent cardiovascular risk factors, inflammation, and incident cardiovascular disease. These findings call for better identification of SDOHs in clinical practice and stronger measures to mitigate the higher SDOH burden among the socially disadvantaged to improve cardiovascular outcomes.