Dyslipidemia in American Indian Adolescents and Young Adults: Strong Heart Family Study.

BACKGROUND: Although many studies on the association between dyslipidemia and cardiovascular disease (CVD) exist in older adults, data on the association among adolescents and young adults living with disproportionate burden of cardiometabolic disorders are scarce. METHODS AND RESULTS: The SHFS (Strong Heart Family Study) is a multicenter, family-based, prospective cohort study of CVD in an American Indian populations, including 12 communities in central Arizona, southwestern Oklahoma, and the Dakotas. We evaluated SHFS participants, who were 15 to 39 years old at the baseline examination in 2001 to 2003 (n=1440). Lipids were measured after a 12-hour fast. We used carotid ultrasounds to detect plaque at baseline and follow-up in 2006 to 2009 (median follow-up=5.5 years). We identified incident CVD events through 2020 with a median follow-up of 18.5 years. We used shared frailty proportional hazards models to assess the association between dyslipidemia and subclinical or clinical CVD, while controlling for covariates. Baseline dyslipidemia prevalence was 55.2%, 73.6%, and 78.0% for participants 15 to 19, 20 to 29, and 30 to 39 years old, respectively. Approximately 2.8% had low-density lipoprotein cholesterol ≥160 mg/dL, which is higher than the recommended threshold for lifestyle or medical interventions in young adults of 20 to 39 years old. During follow-up, 9.9% had incident plaque (109/1104 plaque-free participants with baseline and follow-up ultrasounds), 11.0% had plaque progression (128/1165 with both baseline and follow-up ultrasounds), and 9% had incident CVD (127/1416 CVD-free participants at baseline). Plaque incidence and progression were higher in participants with total cholesterol ≥200 mg/dL, low-density lipoprotein cholesterol ≥160 mg/dL, or non-high-density lipoprotein cholesterol ≥130 mg/dL, while controlling for covariates. CVD risk was independently associated with low-density lipoprotein cholesterol ≥160 mg/dL. CONCLUSIONS: Dyslipidemia is a modifiable risk factor that is associated with both subclinical and clinical CVD, even among the younger American Indian population who have unexpectedly high rates of significant CVD events. Therefore, this population is likely to benefit from a variety of evidence-based interventions including screening, educational, lifestyle, and guideline-directed medical therapy at an early age.

Health Equity and Policy Considerations for Pediatric and Adult Congenital Heart Disease Care among Minoritized Populations in the United States.

Achieving health equity in populations with congenital heart disease (CHD) requires recognizing existing disparities throughout the lifespan that negatively and disproportionately impact specific groups of individuals. These disparities occur at individual, institutional, or system levels and often result in increased morbidity and mortality for marginalized or racially minoritized populations (population subgroups (e.g., ethnic, racial, social, religious) with differential power compared to those deemed to hold the majority power in the population). Creating actionable strategies and solutions to address these health disparities in patients with CHD requires critically examining multilevel factors and health policies that continue to drive health inequities, including varying social determinants of health (SDOH), systemic inequities, and structural racism. In this comprehensive review article, we focus on health equity solutions and health policy considerations for minoritized and marginalized populations with CHD throughout their lifespan in the United States. We review unique challenges that these populations may face and strategies for mitigating disparities in lifelong CHD care. We assess ways to deliver culturally competent CHD care and to help lower-health-literacy populations navigate CHD care. Finally, we review system-level health policies that impact reimbursement and research funding, as well as institutional policies that impact leadership diversity and representation in the workforce.

Diversity, Equity, and Inclusion, Child Health, and the Pediatric Subspecialty Workforce.

Using multiple metrics, the diversity of the pediatric population in the United States is increasing. However, recent data suggest significant disparities in both the prevalence and management of child health conditions cared for by pediatric subspecialists. These inequities occur across multiple dimensions of diversity, including race and ethnicity, country of origin, socioeconomic status, sex and gender, and disability. Research also suggests that attending to diversity, equity, and inclusion in the medical workforce may positively affect health outcomes. High-quality pediatric subspecialty care thus requires knowledge of these data, attention to the effects of social drivers, including racism and discrimination, on health and wellbeing, and interventions to improve pediatric health equity through educational, practice, policy, and research innovations. In this article, we review data on the diversity of the pediatric population and pediatric subspecialty workforce, suggest potential strengths, weaknesses, opportunities, and threats of current diversity, equity, and inclusion initiatives in academic pediatrics, and provide recommendations across 4 domains: education and training, practice, policy, and future research. The ultimate goal of pediatrics is to improve health equity for all infants, children, adolescents, and young adults cared for in the United States by pediatric subspecialists.

Diet Quality and Kidney Outcomes in Adolescent and Adult American Indians: the Strong Heart Family Study.

BACKGROUND: The burden of kidney disease is exceedingly high among American Indians (AIs). We sought to examine the relationship of diet quality, a modifiable risk factor, and kidney outcomes in AI adolescents and adults, hypothesizing that healthier diets are associated with lower odds of incident albuminuria and eGFR decline. METHODS: This is an analysis from the Strong Heart Family Study, a longitudinal study of cardiovascular disease and its risk factors among AIs from Arizona, North and South Dakota, and Oklahoma (n = 1720, mean age 39 + / - 16 years, 16% adolescents at baseline). Participants completed two exams (baseline: 2001-2003; follow-up: 2007-2009). The primary exposure was diet quality, expressed as the Alternative Healthy Eating Index 2010 (AHEI), on a 110-point scale (assessed using a 119-item Block food frequency questionnaire). The primary outcomes were as follows: 1) incident albuminuria (albumin to creatinine ratio 30 mg/g or greater); and 2) eGFR decline of 30% or greater. Generalized estimating equations were used to examine the association of AHEI (in quartiles) with outcomes. RESULTS: Ten percent of participants (6% of adolescents) had incident albuminuria and 2% of participants (2% of adolescents) had eGFR decline. For those with normal fasting glucose levels, the odds ratio (OR) for incident albuminuria comparing extreme quartiles of diet quality (least healthy [reference] versus healthiest quartiles) was 0.48 (95% CI 0.28, 0.81) after adjustment for demographics and comorbidities. CONCLUSIONS: For American Indians with normal fasting glucose, higher diet quality decreases the odds of developing albuminuria. These findings inform future efforts to prevent CKD in American Indian adolescents and young adults.

Status of Maternal Cardiovascular Health in American Indian and Alaska Native Individuals: A Scientific Statement From the American Heart Association.

Cardiovascular disease is the leading cause of pregnancy-related death in the United States. American Indian and Alaska Native individuals have some of the highest maternal death and morbidity rates. Data on the causes of cardiovascular disease-related death in American Indian and Alaska Native individuals are limited, and there are several challenges and opportunities to improve maternal cardiovascular health in this population. This scientific statement provides an overview of the current status of cardiovascular health among American Indian and Alaska Native birthing individuals and causes of maternal death and morbidity and describes a stepwise multidisciplinary framework for addressing cardiovascular disease and cerebrovascular disease during the preconception, pregnancy, and postpartum time frame. This scientific statement highlights the American Heart Association's factors for cardiovascular health assessment known collectively as Life's Essential 8 as they pertain to American Indian and Alaska Native birthing individuals. It summarizes the impact of substance use, adverse mental health conditions, and lifestyle and cardiovascular disease risk factors, as well as the cascading effects of institutional and structural racism and the historical trauma faced by American Indian and Alaska Native individuals. It recognizes the possible impact of systematic acts of colonization and dominance on their social determinants of health, ultimately translating into worse health care outcomes. It focuses on the underreporting of American Indian and Alaska Native disaggregated data in pregnancy and postpartum outcomes and the importance of engaging key stakeholders, designing culturally appropriate care, building trust among communities and health care professionals, and expanding the American Indian and Alaska Native workforce in biomedical research and health care settings to optimize the cardiovascular health of American Indian and Alaska Native birthing individuals.

Plasma lipidomic profile of depressive symptoms: a longitudinal study in a large sample of community-dwelling American Indians in the strong heart study.

Dyslipidemia has been associated with depression, but individual lipid species associated with depression remain largely unknown. The temporal relationship between lipid metabolism and the development of depression also remains to be determined. We studied 3721 fasting plasma samples from 1978 American Indians attending two exams (2001-2003, 2006-2009, mean ~5.5 years apart) in the Strong Heart Family Study. Plasma lipids were repeatedly measured by untargeted liquid chromatography-mass spectrometry (LC-MS). Depressive symptoms were assessed using the 20-item Center for Epidemiologic Studies for Depression (CES-D). Participants at risk for depression were defined as total CES-D score ≥16. Generalized estimating equation (GEE) was used to examine the associations of lipid species with incident or prevalent depression, adjusting for covariates. The associations between changes in lipids and changes in depressive symptoms were additionally adjusted for baseline lipids. We found that lower levels of sphingomyelins and glycerophospholipids and higher level of lysophospholipids were significantly associated with incident and/or prevalent depression. Changes in sphingomyelins, glycerophospholipids, acylcarnitines, fatty acids and triacylglycerols were associated with changes in depressive symptoms and other psychosomatic traits. We also identified differential lipid networks associated with risk of depression. The observed alterations in lipid metabolism may affect depression through increasing the activities of acid sphingomyelinase and phospholipase A2, disturbing neurotransmitters and membrane signaling, enhancing inflammation, oxidative stress, and lipid peroxidation, and/or affecting energy storage in lipid droplets or membrane formation. These findings illuminate the mechanisms through which dyslipidemia may contribute to depression and provide initial evidence for targeting lipid metabolism in developing preventive and therapeutic interventions for depression.

Subclinical atherosclerosis in adolescents and young adults and the risk of cardiovascular disease: The Strong Heart Family Study (SHFS).

BACKGROUND AND AIMS: Rates of cardiovascular disease (CVD) among American Indians (AI) have been increasing. Although we have observed an association between atherosclerosis and CVD in older adults, the potential association among young AI is unclear. Therefore, we aim to describe the prevalence of atherosclerosis among young AI and determine its association with CVD and all-cause mortality. METHODS AND RESULTS: We evaluated AI participants from the Strong Heart Family Study (SHFS), who were <40 years old and CVD free at the baseline examination, 2001-2003 (n = 1376). We used carotid ultrasound to detect baseline atherosclerotic plaque. We identified CVD events and all-cause mortality through 2019, with a median follow-up of 17.8 years. We used shared frailty Cox Proportional Hazards models to assess the association between atherosclerosis and time to CVD event or all-cause mortality, while controlling for covariates. Among 1376 participants, 71 (5.2%) had atherosclerosis at baseline. During follow-up, 120 (8.7%) had CVD events and 104 (7.6%) died from any cause. CVD incidence was higher in participants who had baseline atherosclerosis (13.51/1000 person-years) than in those who did not (4.95/1000 person-years, p = 0.0003). CVD risk and all-cause mortality were higher in participants with atherosclerosis, while controlling for covariates (CVD HR = 1.85, 95%CI = 1.02-3.37, p = 0.0420; all-cause mortality HR = 2.04, 95%CI = 1.07-3.89, p = 0.0291). CONCLUSIONS: Among young AI, atherosclerosis was independently associated with incident CVD and all-cause mortality later in life. Thus, atherosclerosis begins early in life and interventions in adolescents and young adults to slow the progression of disease could prevent or delay CVD events later in life.

Belhassen Tachycardia in a Pediatric Patient: A Simulation for Pediatric Emergency Medicine Fellows.

Ventricular tachycardia in pediatric emergency department patients is a high-risk, low-frequency event well suited for education through simulation. This technical report describes a simulation-based curriculum for Pediatric Emergency Medicine fellows and senior residents involving the evaluation and management of a 10-year-old female presenting with palpitations who is ultimately diagnosed with Belhassen tachycardia. The curriculum highlights the features that differentiate Belhassen tachycardia (idiopathic left posterior fascicular ventricular tachycardia) from supraventricular or other tachycardias, building upon foundational pediatric resuscitation skills and Pediatric Advanced Life Support (PALS) algorithms for advanced learners.

Caring for American Indian and Alaska Native Children and Adolescents.

American Indian and Alaska Native (AI/AN) populations have substantial health inequities, and most of their disease entities begin in childhood. In addition, AI/AN children and adolescents have excessive disease rates compared with the general pediatric population. Because of this, providers of pediatric care are in a unique position not only to attenuate disease incidence during childhood but also to improve the health status of this special population as a whole. This policy statement examines the inequitable disease burden observed in AI/AN youth, with a focus on toxic stress, mental health, and issues related to suicide and substance use disorder, risk of and exposure to injury and violence in childhood, obesity and obesity-related cardiovascular risk factors and disease, foster care, and the intersection of lesbian, gay, bisexual, transgender, queer, and Two-Spirit and AI/AN youth. Opportunities for advocacy in policy making also are presented.

Stress and Cardiometabolic Disease Risk for Indigenous Populations throughout the Lifespan.

BACKGROUND: Indigenous people experience the greatest cardiometabolic disease disparity in the Unites States, yet high cardiometabolic disease risk factors do not fully explain the extent of the cardiometabolic disease disparity for Indigenous people. Stress, trauma, and racism occur at high rates within Indigenous communities and have not been well explored as significant contributors to cardiometabolic disease disparities despite emerging literature, and therefore will be described here. METHODS: This descriptive study explores the relationship between cardiometabolic disease risks and Indigenous-specific stressors (e.g., early childhood stress and trauma, adulthood stress and trauma, and historical and intergenerational trauma) using current literature. Indigenous-specific protective factors against cardiometabolic disease are also reviewed. RESULTS: Increasing research indicates that there is a relationship between Indigenous-specific stressful and traumatic life experiences and increased cardiometabolic disease risk. Mental health and psychophysiology play an important role in this relationship. Effective interventions to reduce cardiometabolic disease risk in Indigenous communities focus on ameliorating the negative effects of these stressors through the use of culturally specific health behaviors and activities. CONCLUSIONS: There is increasing evidence that cultural connection and enculturation are protective factors for cardiometabolic disease, and may be galvanized through Indigenous-led training, research, and policy change.

Long-term azithromycin use is not associated with QT prolongation in children with cystic fibrosis.

Chronic Azithromycin (AZM) is a common treatment for lung infection. Among adults at risk of cardiac events, AZM use has been associated with cardiovascular harm. We assessed cardiovascular safety of AZM among children with CF, as a secondary analysis of a placebo-controlled, clinical trial, in which study drug was taken thrice-weekly for a planned 18 months. Safety assessments using electrocardiogram (ECG) occurred at study enrollment, and then after 3 weeks and 18 months of participation. Among 221 study participants with a median of 18 months follow-up, increased corrected QT interval (QTc) of ≥30 msec was rare, at 3.4 occurrences per 100 person-years; and incidence of QTc prolongation was no higher in the AZM arm than the placebo arm (1.8 versus 5.4 per 100 person-years). No persons experienced QTc intervals above 500 msec. Long-term chronic AZM use was not associated with increased QT prolongation.

Association between race/ethnicity, illness severity, and mortality in children undergoing cardiac surgery.

OBJECTIVE: Prior studies demonstrate an association between nonwhite race/ethnicity, insurance status, and mortality after pediatric congenital heart surgery. The influence of severity of illness on that association is unknown. We examined the relationship between race/ethnicity, severity of illness, and mortality in congenital cardiac surgery, and whether severity of illness is a mechanism by which nonwhite patients experience increased surgical mortality. METHODS: We performed a retrospective cohort study of children younger than age 18 years old undergoing cardiac surgery admitted to the intensive care unit (n = 40,545) between 2009 and 2016 from the Virtual Pediatric Systems (VPS, LLC, Los Angeles, Calif) database. Multivariate regression models were constructed to examine the role of severity of illness as a mediator between race/ethnicity and mortality in children undergoing cardiac surgery. RESULTS: In multivariate models examining severity of illness scores, African-American patients had statistically significant higher severity of illness scores when compared with their white counterparts. In multivariate models of intensive care unit mortality after adjustment for covariates, African-American patients had a higher odds of postoperative mortality (odds ratio, 1.40, 95% confidence interval, 1.04-1.89) when compared with white children. This increased odds of mortality was mediated through higher severity of illness, because adjustment for severity of illness removed this survival disadvantage for black patients. CONCLUSIONS: Although African-American children undergoing cardiac surgery had higher postoperative mortality, this survival difference appears to be mediated via severity of illness. Preoperative and intraoperative factors may be drivers for this survival disparity.

Cardiovascular Risk Factors Associated With Venous Thromboembolism.

Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. Exposures: A panel of several established cardiovascular risk factors. Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). Results: Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated with higher VTE risk.

Pediatric Emergency Medicine Simulation Curriculum: Cardiac Tamponade.

Introduction: Cardiac tamponade is an uncommon presentation to the pediatric emergency department and requires early recognition and emergent intervention. Methods: We developed this patient simulation case to simulate a low-frequency, high-acuity scenario for pediatric emergency medicine fellows and resident physicians in emergency medicine, pediatrics, and family medicine. We ran the case in a pediatric emergency department using a high-fidelity pediatric mannequin and equipment found in the clinical environment, including a bedside ultrasound machine. The case involved a 10-year-old patient with Hodgkin lymphoma who presented with fever, neutropenia, and shock and was found to have a pericardial effusion with tamponade after evaluation. The providers were expected to identify signs and symptoms of shock, as well as cardiac tamponade, and demonstrate appropriate emergent evaluation and management. Required personnel included a simulation technician, instructors, and a nurse. Debriefing tools tailored specifically for this scenario were created to facilitate a formal debriefing and formative learner assessment at the end of the simulation. Results: This case has been implemented with 10 pediatric emergency medicine fellows during two 3-year cycles of fellow education. Session feedback reflected a high level of satisfaction with the case and an increased awareness of bedside ultrasound in the identification of cardiac tamponade. Discussion: This resource for teaching the critical components for diagnosing and managing unstable cardiac tamponade in the pediatric patient, including use of bedside ultrasound, was well received by pediatric emergency medicine fellows.