Perfluoroalkyl substances (PFAS) and lead (Pb) as "cardiovascular disruptors" in 9-11-year-old children living in Syracuse, New York, United States.

OBJECTIVE: Per- and polyfluoro-alkyl substances (PFAS) and lead (Pb) are ubiquitous environmental toxicants with apparent impact on cardiovascular disease (CVD) risk. As one possible mechanism for this increased risk, we have previously demonstrated an association between Pb exposure and heightened cardiovascular reactivity to acute psychological stress, a CVD risk factor. The present study expands this approach and considers both PFAS and Pb exposures (and the possible interaction). METHODS: We assessed 14 serum PFAS and whole blood Pb concentrations in a sample of 9-11 year-old children (N = 291; 43.2% White, 56.8% Black; 53.5% female). We measured cardiovascular functioning at rest and during psychological stress as well as multiple indicators of subclinical CVD including resting blood pressure (BP), carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass (LVM). Data analysis included general linear modeling as well as a non-parametric approach to study metal mixtures, specifically Bayesian Kernel Machine Regression (BKMR). RESULTS: Significant interactions between different PFAS and with Pb suggest the importance of considering toxicant mixtures when assessing potential disruption of the cardiovascular system. The pattern of findings suggests that greater "vascular reactivity" (elevated BP and vascular resistance during acute psychological stress) was associated with higher concentrations of perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and Pb, but only when perfluorooctanoic acid (PFOA) was concurrently elevated. With respect to subclinical outcomes, increasing perfluorodecanoic acid (PFDA) was associated with greater cIMT (ß = 0.21, p = 0.010). CONCLUSION: To our knowledge this is the first study to consider how PFAS exposures might affect cardiovascular functioning and subclinical disease. Although a complex pattern of associations emerged, it does appear that PFAS and Pb can be classified as "cardiovascular disruptors" in children. Further research is needed to replicate these novel findings and determine whether these disruptions produce future cardiovascular disease.

Exposure to Arsenic and Subclinical Cardiovascular Disease in 9- to 11-Year-Old Children, Syracuse, New York.

Importance: Studies in adults have demonstrated associations between arsenic exposure and clinical and subclinical cardiovascular disease (CVD). No studies to date have considered potential associations in children. Objective: To examine the association between total urinary arsenic levels in children and subclinical indicators of CVD. Design, Setting, and Participants: This cross-sectional study considered 245 children, a subset from the Environmental Exposures and Child Health Outcomes (EECHO) cohort. Children from the Syracuse, New York, metropolitan area were recruited from August 1, 2013, until November 30, 2017, with enrollment throughout the year. Statistical analysis was performed from January 1, 2022, to February 28, 2023. Exposures: Total urinary arsenic was measured using inductively coupled plasma mass spectrometry. Creatinine concentration was used to adjust for urinary dilution. In addition, potential exposure routes (eg, diet) were measured. Main Outcomes and Measures: Three indicators of subclinical CVD were assessed: carotid-femoral pulse wave velocity, carotid intima media thickness, and echocardiographic measures of cardiac remodeling. Results: The study sample included 245 children aged 9 to 11 years (mean [SD] age, 10.52 [0.93] years; 133 [54.3%] female). The geometric mean of the creatinine-adjusted total arsenic level in the population was 7.76 µg/g creatinine. After adjustment for covariates, elevated total arsenic levels were associated with significantly greater carotid intima media thickness (ß = 0.21; 95% CI, 0.08-0.33; P = .001). In addition, echocardiography revealed that elevated total arsenic was significantly higher for children with concentric hypertrophy (indicated by greater left ventricular mass and greater relative wall thickness; geometric mean, 16.77 µg/g creatinine; 95% CI, 9.87-28.79 µg/g) relative to the reference group (geometric mean, 7.39 µg/g creatinine; 95% CI, 6.36-8.58 µg/g). With respect to exposure source, significant geographic clustering of total arsenic was found in 1 urban area of Syracuse, New York. Conclusions and Relevance: These findings suggest a significant association between arsenic exposure and subclinical CVD in children. Elevated total arsenic levels were found in an area of Syracuse with known elevations of toxic metals from industrial waste, suggesting historical pollution as a possible source. Given the novelty and potential importance of this association, further research is needed to confirm our findings. Any potential effect of urinary arsenic exposure in childhood on actual clinical CVD outcomes in adulthood remains to be determined.

Association of Sleep Quality With Greater Left Ventricular Mass in Children Aged 9 to 11 Years.

OBJECTIVE: Research has consistently found associations between sleep characteristics and cardiovascular disease risk in children, adolescents, and adults. Although primarily investigated in clinical samples (e.g., in those with sleep disorders), greater left ventricular mass is associated with poor sleep quality in nonclinical adult populations as well; however, this has not been evaluated in children or adolescents. Our study aim was to consider the relationship between objectively measured sleep characteristics and left ventricular mass in children. METHODS: We assessed sleep and cardiac structure in a biracial sample of 9- to 11-year-old children (n = 176; 41% White, 59% Black; 50% female). Sleep was assessed with actigraphy for five nights. Cardiac dimensions were assessed using echocardiography. RESULTS: After adjusting for covariates, we found that poor sleep quality was associated with significantly greater left ventricular mass (ß = 0.13, t(167) = 2.14, p = .034, Cohen d = 0.16, for activity during sleep; ß = 0.15, t(167) = 2.43, p = .016, Cohen d = 0.18, for sleep fragmentation). Other cardiac dimensions (namely, relative wall thickness and right ventricular dimension) were also significantly associated with sleep characteristics. Notably, associations did not differ as a function of sex or race. CONCLUSIONS: The present findings are novel and unique because no prior reports have systematically documented the association between poor sleep quality with potentially detrimental cardiac remodeling in a nonclinical sample of children. However, the novelty and importance of these findings require additional research for confirmation.

Racial Differences in Left Ventricular Mass and Wave Reflection Intensity in Children.

The burden of heart failure is disproportionately higher in African Americans, with a higher prevalence seen at an early age. Examination of racial differences in left ventricular mass (LVM) in childhood may offer insight into risk for cardiac target organ damage (cTOD) in adulthood. Central hemodynamic load, a harbinger of cTOD in adults, is higher in African Americans. The purpose of this study was to examine racial differences in central hemodynamic load and LVM in African American and non-Hispanic white (NHW) children. Two hundred sixty-nine children participated in this study (age, 10 ± 1 years; n = 149 female, n = 154 African American). Carotid pulse wave velocity (PWV), forward wave intensity (W1) and reflected wave intensity (negative area, NA) was assessed from simultaneously acquired distension and flow velocity waveforms using wave intensity analysis (WIA). Wave reflection magnitude was calculated as NA/W1. LVM was assessed using standard 2D echocardiography and indexed to height as LVM/[height (2.16) + 0.09]. A cutoff of 45 g/m (2.16) was used to define left ventricular hypertrophy (LVH). LVM was higher in African American vs. NHW children (39.2 ± 8.0 vs. 37.2 ± 6.7 g/m (2.16), adjusted for age, sex, carotid systolic pressure and socioeconomic status; p < 0.05). The proportion of LVH was higher in African American vs. NHW children (25 vs. 12 %, p < 0.05). African American and NHW children did not differ in carotid PWV (3.5 ± 4.9 vs. 3.3 ± 1.3 m/s; p > 0.05). NA/W1 was higher in African American vs. NHW children (8.5 ± 5.3 vs. 6.7 ± 2.9; p < 0.05). Adjusting for NA/W1 attenuated racial differences in LVM (38.8 ± 8.0 vs. 37.6 ± 7.0 g/m (2.16); p = 0.19). In conclusion, racial differences in central hemodynamic load and cTOD are present in childhood. African American children have greater wave intensity from reflected waves and higher LVMI compared to NHW children. WIA offers novel insight into early life origins of racial differences in central hemodynamic load and cTOD.

Neurodevelopmental Delay After the Neonatal Repair of Coarctation and Arch Obstruction.

BACKGROUND: Although single ventricle physiology and cyanosis are known risk factors for neurodevelopmental delay (NDD), the impacts of isolated coarctation (Iso CoA) repair or arch reconstruction (AR) are less understood. METHODS: The Vineland Adaptive Behavior Scales, third edition, prospectively evaluated children without a genetic syndrome. An overall composite score, normalized to age and sex, was generated from individual domain scores. NDD was defined as a composite or domain score at least 1 SD less than the established mean. Iso CoA was repaired using a left thoracotomy, whereas AR was performed using a sternotomy and cardiopulmonary bypass. Children with a structurally normal heart and without previous surgery were used as control patients. RESULTS: Of 60 children, 50 required neonatal repair (12 for Iso CoA, 38 for AR), and 10 were control patients. From the entire cohort of children who required neonatal coarctation repair (Iso CoA + AR) composite (93.9 ± 15.9 vs 105.0 ± 7.4; P = .004) and all domain scores were significantly lower than control patients. NDD was present in 25 of 50 children after repair and in 0 of 10 control patients (P = .003). Similarly, the prevalence of NDD was significantly greater after Iso CoA repair (58.3% vs 0%; P = .005) and AR (47.3% vs 0%; P = .007) than in the control population, but no significant difference was found between the Iso CoA and AR groups (P = .74). CONCLUSIONS: In this small cohort, half of the neonates who required either Iso CoA repair or AR exhibit NDD at an intermediate-term follow-up.

Racial Differences in Aortic Stiffness in Children.

OBJECTIVE: To investigate racial differences in central blood pressure and vascular structure/function as subclinical markers of atherosclerotic cardiovascular disease in children. STUDY DESIGN: This cross-sectional study recruited 54 African American children (18 female, 36 male; age 10.5 ± 0.9 years) and 54 white children (27 female, 26 male; age 10.8 ± 0.9 years) from the Syracuse City community as part of the Environmental Exposures and Child Health Outcomes study. Participants underwent blood lipid and vascular testing on 2 separate days. Carotid artery intima-media thickness and aortic stiffness were measured by ultrasonography and carotid-femoral pulse wave velocity, respectively. Blood pressure was assessed at the brachial artery and estimated in the carotid artery using applanation tonometry. RESULTS: African American children had significantly higher pulse wave velocity (4.8 ± 0.8 m/s) compared with white children (4.2 ± 0.7 m/s; P < .05), which remained significant after adjustment for confounding variables including socioeconomic status. African American children had significantly higher intima-media thickness (African American 0.41 ± 0.06, white 0.39 ± 0.05 mm), and carotid systolic blood pressure (African American 106 ± 11, white 102 ± 8 mm Hg; P < .05) compared with white children, although these racial differences were no longer present after covariate adjustments for height. CONCLUSIONS: Racial differences in aortic stiffness are present in childhood. Our findings suggest that racial differences in subclinical cardiovascular disease occur earlier than previously recognized.