Is There a Role for Imaging Youth at Risk of Atherosclerosis?

PURPOSE OF REVIEW: Cardiovascular (CV) risk factors such as dyslipidemia, hypertension, diabetes, and obesity are associated with an increased risk for CV events in adults. Noninvasive measures of vascular health are associated with these CV events and can potentially help risk stratify children with CV risk factors. The purpose of this review is to summarize recent literature regarding vascular health in children with cardiovascular risk factors. RECENT FINDINGS: Adverse changes in pulse wave velocity, pulse wave analysis, arterial distensibility, and carotid intima-media thickness are seen in children with CV risk factors supporting potential utility in risk stratification. Assessing vascular health in children can be challenging due to growth-related changes in vasculature, multiple assessment modalities, and differences in normative data. Vascular health assessment in children with cardiovascular risk factors can be a valuable tool for risk stratification and help identify opportunities for early intervention. Future areas of research include increasing normative data, improving conversion of data between different modalities, and increasing longitudinal studies in children linking childhood risk factors to adult CV outcomes.

Obese and Type 2 Diabetic Youth Have Increased Forward and Backward Wave Reflections.

OBJECTIVE: Pulse wave analysis estimates arterial wave reflections relating to left ventricular dysfunction and cardiovascular event risk in adults. Forward and backward waves (Pf and Pb) may improve risk stratification for cardiovascular events. Data in youth are lacking. We hypothesized that a significant difference in wave reflections would be identified in young subjects with adverse cardiovascular risk factors. Approach and Results: Vital signs and labs were obtained in 551 patients aged 10 to 24 years who were lean (L=199), obese (O=173), or had type 2 diabetes (T=179). Wave separation was performed. Differences in cardiovascular risk factors and wave reflections were assessed using ANOVA. General linear models were constructed to elucidate independent predictors of wave reflections. O and T subjects had an adverse cardiovascular risk profile versus L. O and T subjects had higher Pf and Pb versus L (P≤0.05). When adjusted for adiposity and other cardiovascular risk factors, reflection magnitude increased from L to O to T with higher T versus L values (P≤0.05) and near-significant O versus L values (P=0.06). Adiposity and blood pressure were major determinants of wave reflections. Pb influenced log left ventricular mass index, log E/e', and log composite carotid intima-media thickness. CONCLUSIONS: Adolescents and young adults with obesity and type 2 diabetes have altered forward and backward wave reflections versus lean controls related to adiposity, BP, and insulin levels. These parameters may help risk stratify patients with adverse cardiovascular risk factors.

Hypertension in children.

PURPOSE OF REVIEW: Hypertension is a common finding in children, and increases the risk for future cardiovascular events. This review focuses on recent advances in pediatric hypertension research including changes in hypertension guidelines, epidemiology, predictors of hypertension, blood pressure (BP) measurement, effects on target organs, and treatment of hypertension. RECENT FINDINGS: Changes in the 2017 hypertension guidelines by the American Academy of Pediatrics (AAP) have resulted in increased prevalence of elevated BP and hypertension in the United States, and there is no international consensus on these changes. Despite rising pediatric overweight and obesity in China, hypertension prevalence is stable, suggesting multifactorial effects on childhood BP. Maternal diabetes and exposure to particulate matter are associated with higher childhood BP, and body size in infancy and early childhood is a determinant of adult high BP. Children with elevated BP have evidence of target organ damage with altered retinal vasculature and pulse wave velocity parameters compared to normotensive patients. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be the best antihypertensive medications for the pediatric population even for African-American patients. SUMMARY: Research continues to illuminate contributors to pediatric hypertension and demonstrates opportunities for further study on the effects of hypertension and its management in children.

Outcomes of Trauma "Walk-Ins" in the American College of Surgeons Trauma Quality Program Database.

BACKGROUND: Outcomes of trauma "walk-in" patients (using private vehicles or on foot) are understudied. We compared outcomes of ground ambulance vs walk-ins, hypothesizing that delayed resuscitation and uncoordinated care may worsen walk-in outcomes. METHODS: A retrospective analysis 2020 American College of Surgeons Trauma Quality Programs (ACS-TQP) databases compared outcomes between ambulance vs "walk-ins." The primary outcome was in-hospital mortality, excluding external facility transfers and air transports. Data was analyzed with descriptive statistics, bivariate, multivariable logistic regression, including an Inverse Probability Weighted Regression Adjustment with adjustments for injury severity and vital signs. The primary outcome for the 2019 (pre-COVID-19 pandemic) data was similarly analyzed. RESULTS: In 2020, 707,899 patients were analyzed, 556,361 (78.59%) used ambulance, and 151,538 (21.41%) were walk-ins. We observed differences in demographics, hospital attributes, medical comorbidities, and injury mechanism. Ambulance patients had more chronic conditions and severe injuries. Walk-ins had lower in-hospital mortality (850 (.56%) vs 23,131 (4.16%)) and arrived with better vital signs. Multivariable logistic regression models (inverse probability weighting for regression adjustment), adjusting for injury severity, demographics, injury mechanism, and vital signs, confirmed that walk-in status had lower odds of mortality. For the 2019 (pre-COVID-19 pandemic) database, walk-ins also had lower in-hospital mortality. DISCUSSION: Our results demonstrate better survival rates for walk-ins before and during COVID-19 pandemic. Despite limitations of patient selection bias, this study highlights the need for further research into transportation modes, geographic and socioeconomic factors affecting patient transport, and tailoring management strategies based on their mode of arrival.

Pediatric Primary Hypertension: An Underrecognized Condition: A Scientific Statement From the American Heart Association.

The overall prevalence of hypertension in childhood is 2% to 5%, and the leading type of childhood hypertension is primary hypertension, especially in adolescence. As in adults, the leading risk factors for children with primary hypertension are excess adiposity and suboptimal lifestyles; however, environmental stress, low birth weight, and genetic factors may also be important. Hypertensive children are highly likely to become hypertensive adults and to have measurable target organ injury, particularly left ventricular hypertrophy and vascular stiffening. Ambulatory and home blood pressure monitoring may facilitate diagnosis. Primordial prevention of hypertension through public health implementation of healthier diet and increased physical activity will reduce the prevalence of primary hypertension, and evidence-based treatment guidelines should be implemented when hypertension is diagnosed. Further research to optimize recognition and diagnosis and clinical trials to better define outcomes of treatment are needed.

Hypertriglyceridemia-induced acute pancreatitis in children: A mini-review.

Severe hypertriglyceridemia (HTG) is a known metabolic cause of acute pancreatitis (AP) in pediatric patients. The incidence of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is less well established in pediatric compared to adult patients. Studies in adults suggest that higher risk of AP occurs when triglyceride levels (TG) are >1,000 mg/dL. Most common etiologies for severe HTG in pediatric patients are either from primary hypertriglyceridemia, underlying genetic disorders of lipid and TG metabolism, or secondary hypertriglyceridemia, separate disease or exposure which affects TG metabolism. Most common theories for the pathophysiology of HTG-AP include hydrolysis of TG by pancreatic lipase to free fatty acids leading to endothelial and acinar cell damage and ischemia, as well as hyperviscosity related to increased chylomicrons. Though there are varying reports of HTG-AP severity compared to other causes of AP, a steadily growing body of evidence suggests that HTG-AP can be associated with more severe course and complications. Therapeutic interventions for HTG-AP typically involve inpatient management with dietary restriction, intravenous fluids, and insulin; select patients may require plasmapheresis. Long term interventions generally include dietary modification, weight management, control of secondary causes, and/or antihyperlipidemic medications. Though some therapeutic approaches and algorithms exist for adult patients, evidence-based management guidelines have not been well established for pediatric patients.

Association of Blood Pressure-Related Increase in Vascular Stiffness on Other Measures of Target Organ Damage in Youth.

BACKGROUND: Hypertension-related increased arterial stiffness predicts development of target organ damage (TOD) and cardiovascular disease. We hypothesized that blood pressure (BP)-related increased arterial stiffness is present in youth with elevated BP and is associated with TOD. METHODS: Participants were stratified by systolic BP into low- (systolic BP <75th percentile, n=155), mid- (systolic BP ≥80th and <90th percentile, n=88), and high-risk BP categories (≥90th percentile, n=139), based on age-, sex- and height-specific pediatric BP cut points. Clinic BP, 24-hour ambulatory BP monitoring, anthropometrics, and laboratory data were obtained. Arterial stiffness measures included carotid-femoral pulse wave velocity and aortic stiffness. Left ventricular mass index, left ventricular systolic and diastolic function, and urine albumin/creatinine were collected. ANOVA with Bonferroni correction was used to evaluate differences in cardiovascular risk factors, pulse wave velocity, and cardiac function across groups. General linear models were used to examine factors associated with arterial stiffness and to determine whether arterial stiffness is associated with TOD after accounting for BP. RESULTS: Pulse wave velocity increased across groups. Aortic distensibility, distensibility coefficient, and compliance were greater in low than in the mid or high group. Significant determinants of arterial stiffness were sex, age, adiposity, BP, and LDL (low-density lipoprotein) cholesterol. Pulse wave velocity and aortic compliance were significantly associated with TOD (systolic and diastolic cardiac function and urine albumin/creatinine ratio) after controlling for BP. CONCLUSIONS: Higher arterial stiffness is associated with elevated BP and TOD in youth emphasizing the need for primary prevention of cardiovascular disease.

Rationale and Best Practices for Pediatric Cardiology Prevention Programs.

Atherosclerotic cardiovascular diseases are the most common cause of death in North America, and a significant number of children have conditions such as inherited dyslipidemias, overweight/obesity, and hypertension, placing them at increased risk for future cardiovascular events and other comorbidities. Training in cardiovascular prevention is an important tool to help pediatric cardiologists address these issues in children. We describe a model for training pediatric cardiologists in primary and secondary prevention strategies. A multidisciplinary team approach is needed for robust training in dyslipidemias, hypertension, insulin resistance and type 2 diabetes mellitus, and other obesity-related comorbidities. Research is a significant component of training and necessary for translating science into practice. Ongoing education is also necessary, and certification is available through associations such as the National Lipid Association, the American Diabetes Association, The Obesity Society, and the American Hypertension Specialist Certification Program. Knowledge of primordial, primary, and secondary cardiovascular prevention strategies is essential for pediatric cardiologists to accomplish the goal of helping children lead healthier lives long into adulthood.

Obesity across the lifespan in congenital heart disease survivors: Prevalence and correlates.

BACKGROUND: Congenital heart disease (CHD) survivors are at risk for cardiovascular comorbidities exacerbated by obesity. OBJECTIVES: Determine relationships between overweight/obesity and medical factors across the lifespan of CHD. METHODS: Lesion severity, weight, blood pressure, cardiac and other comorbidities, and cardiac medications were abstracted from the medical records of 3790 CHD patients, aged ≥6 years, who attended CHD care in the Midwestern U.S. RESULTS: The proportion of patients with overweight/obesity increased across the lifespan, with 73% of adults affected by overweight/obesity. Obesity was more prevalent among patients with moderate lesions (29%). Overweight/obesity was associated with elevated blood pressure across age and lesion severity. Young adults with obesity and simple or moderate lesions had more comorbidities (simple: IRR = 3.1, moderate: IRR = 2.3) and cardiac medications (simple: IRR = 2.2, moderate: IRR = 1.7). CONCLUSIONS: Obesity and its cardiovascular correlates are present across the lifespan for CHD survivors, highlighting the need for early prevention and intervention.

Subclinical Systolic and Diastolic Dysfunction Is Evident in Youth With Elevated Blood Pressure.

Hypertension is associated with cardiovascular events in adults. Subclinical changes to left ventricular strain and diastolic function have been found before development of decreased left ventricular ejection fraction and cardiovascular events. Our objective was to study effects of blood pressure (BP) on ventricular function in youth across the BP spectrum. Vital signs and labs were obtained in 346 participants aged 11 to 19 years who had BP categorized as low-risk (N=144; systolic BP <75th percentile), mid-risk (N=83; systolic BP ≥80th and <90th percentile), and high-risk (N=119; systolic BP ≥90th percentile). Echocardiography was performed to assess left ventricular strain and diastolic function. Differences between groups were analyzed by ANOVA. General linear models were constructed to determine independent predictors of systolic and diastolic function. Mid-risk and high-risk participants had greater adiposity and more adverse metabolic labs (lower HDL [high-density lipoprotein], higher glucose, and higher insulin) than the low-risk group. Mid-risk and high-risk participants had significantly lower left ventricular ejection fraction and peak global longitudinal strain than the low-risk group (both P≤0.05). The E/e' ratio was higher in the high-risk group versus the low-risk and mid-risk groups, and the e'/a' ratio was lower in the high-risk versus the low-risk group (both P≤0.05). BP and adiposity were statistically significant determinants of left ventricular systolic and diastolic function. Subclinical changes in left ventricular systolic and diastolic function can be detected even at BP levels below the hypertensive range as currently defined.

Dallas MegaShelter Medical Operations Response to Hurricane Harvey.

On August 25, 2017, Hurricane Harvey made landfall near Corpus Christi, Texas. The ensuing unprecedented flooding throughout the Texas coastal region affected millions of individuals.1 The statewide response in Texas included the sheltering of thousands of individuals at considerable distances from their homes. The Dallas area established large-scale general population sheltering as the number of evacuees to the area began to amass. Historically, the Dallas area is one familiar with "mega-sheltering," beginning with the response to Hurricane Katrina in 2005.2 Through continued efforts and development, the Dallas area had been readying a plan for the largest general population shelter in Texas. (Disaster Med Public Health Preparedness. 2019;13:33-37).

Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice.

Huntington's disease (HD) is an inherited neurodegenerative disorder with no disease-modifying treatment. Expansion of the glutamine-encoding repeat in the Huntingtin (HTT) gene causes broad effects that are a challenge for single treatment strategies. Strategies based on human stem cells offer a promising option. We evaluated efficacy of transplanting a good manufacturing practice (GMP)-grade human embryonic stem cell-derived neural stem cell (hNSC) line into striatum of HD modeled mice. In HD fragment model R6/2 mice, transplants improve motor deficits, rescue synaptic alterations, and are contacted by nerve terminals from mouse cells. Furthermore, implanted hNSCs are electrophysiologically active. hNSCs also improved motor and late-stage cognitive impairment in a second HD model, Q140 knockin mice. Disease-modifying activity is suggested by the reduction of aberrant accumulation of mutant HTT protein and expression of brain-derived neurotrophic factor (BDNF) in both models. These findings hold promise for future development of stem cell-based therapies.

Neonatal immune-tolerance in mice does not prevent xenograft rejection.

Assessing the efficacy of human stem cell transplantation in rodent models is complicated by the significant immune rejection that occurs. Two recent reports have shown conflicting results using neonatal tolerance to xenografts in rats. Here we extend this approach to mice and assess whether neonatal tolerance can prevent the rapid rejection of xenografts. In three strains of neonatal immune-intact mice, using two different brain transplant regimes and three independent stem cell types, we conclusively show that there is rapid rejection of the implanted cells. We also address specific challenges associated with the generation of humanized mouse models of disease.

Peripheral ocular aberrations in mild and moderate keratoconus.

PURPOSE: To investigate the influence of keratoconus on peripheral ocular aberrations. METHODS: Aberrations in seven mild and five moderate keratoconics were determined over a 42° horizontal × 32° vertical visual field, with a modified aberrometer. Control data were obtained from an emmetropic group. RESULTS: Most aberrations in the keratoconics showed field dependence, predominately along the vertical meridian. Mean spherical equivalent M, oblique astigmatism J(45), and regular astigmatism J(180) refraction components and total root mean square aberrations (excluding defocus) had high magnitudes in the inferior visual field. The rates of change of aberrations were higher in the moderate than in the mild keratoconics. Coma was the dominant peripheral higher-order aberration in both the emmetropes and the keratoconics; for the latter, it had high magnitudes in the center and periphery of the visual field. CONCLUSIONS: Greater rates of change in aberrations across the visual field occurred in the keratoconus groups than in the emmetropic control group. The moderate keratoconics had more rapid changes in, and higher magnitudes of, aberrations across the visual field than did the mild keratoconics. The dominant higher-order aberration for the keratoconics across the visual field was vertical coma.