Journal of the American Heart Association

BackgroundPlacental function is associated with congenital heart defects (CHD), frequently presenting with malperfusion lesions and small-for-gestational-age size. However, placental villous vasculature in the setting of CHD is understudied. This study evaluated differences in placental, neonatal, and maternal outcomes among maternal/infant dyads with versus without CHD. MethodsWe conducted a gestational age- and fetal sex-matched retrospective case control study using specimens prospectively collected by a local biobank. Neonatal outcomes included birthweight, placental weight, and their ratio (placental efficiency). We estimated the proportion of placental villous tissue comprised of fetal vascular endothelial cells (%FVE) using anti-CD34 immunohistochemistry and a pixel count algorithm. Placental weight multiplied by %FVE estimated the grams of placental tissue comprised of villous vasculature (placental vascular index). Maternal outcomes included hypertensive disorders of pregnancy and gestational diabetes. We compared cases and controls using linear and logistic regression adjusted for maternal smoking and cold ischemia time. Stratified analyses examined associations by preterm birth status. ResultsDyads (n=34 with CHD, n=34 without CHD) had maternal age of 29.4{+/-} 4.9 years and were 35.6{+/-}4.0 gestational weeks at delivery. Groups had similar placental, neonatal, and maternal parameters. Among preterm neonates, we observed small-to-moderate effect sizes indicating lower placental weight, %FVE, and placental vascular index, and higher placental efficiency, in CHD cases. Among term neonates, moderate effect sizes suggested lower birthweight, placental weight, and placental vascular index in CHD cases. ConclusionsThough differences between groups were not significant, moderate effect sizes suggested that placental vascularization was lower among preterm neonates with CHD.

Background: Resting electrocardiogram (ECG) is not currently recommended as part of cardiovascular disease (CVD) risk assessment, although accumulating evidence suggests a potential role. Objective: To examine the association between ECG abnormalities and incident CVD events as assessed by the 2023 Predicting Risk of Cardiovascular Disease Events (PREVENT) equations. Design: Secondary data analysis from the REasons for Geographic And Racial Differences in Stroke (REGARDS) prospective cohort, including study participants without a baseline CVD. Exposure: ECG abnormalities were classified by Minnesota Code (MC) as normal, any minor, or major abnormality at baseline (2003-2007). Outcome: Participants were followed for expert adjudicated incident CVD events through December 31, 2021. Results: Among 19,173 participants (mean age at baseline of 63.7 years; 57.8% were female). According to the PREVENT risk equations, 39.4% were classified as <7.5% 10-year risk CVD risk, 44.6% as 7.5-20% risk, and 16.0% as >20% risk. Overall, 47.0% had normal ECG, 44.0% had any minor abnormality, and 9.0% had any major abnormality. During follow-up, CVD events occurred in 12.4% of participants with normal ECG, 17.0% of those with any minor abnormality, and 25.4% of those with any major abnormality. Compared to those without ECG abnormality, the adjusted HR for incident CVD were 1.19 (95% CI 1.10-1.29) for any minor abnormality, and 1.53 (1.36-1.72) for any major ECG abnormality. In the <7.5% risk group, 43.6% had at least one ECG abnormality; in this risk group compared to those without ECG abnormality, the HR for incident CVD associated with any major ECG abnormality, present in 5.0% of the <7.5% risk group, was 1.87 (95% CI 1.34-2.62), The HR for any minor ECG abnormalities, present in 38.6% was 1.13 ( 95% CI 0.93 - 1.37). Conclusion: ECG abnormalities were associated with risk of CVD events across PREVENT risk groups. A substantial proportion of low-risk participants (according to the PREVENT equation) had ECG abnormalities and associated elevated risk. This supports the potential for using ECG to identify a subgroup of low-risk patients who may benefit from more aggressive primary prevention especially with major ECG abnormalities. Addition of electrocardiographic evaluation to the PREVENT risk equations may improves cardiovascular risk discrimination.

Background: The manifestations of cardiovascular disease (CVD) among people with HIV (PWH) differ by region globally. While HIV disease is associated with increased atherosclerotic CVD risk in the global North, non-ischemic heart failure (HF) is more common in sub-Saharan Africa, the global HIV epicenter. We estimated the effect of treated HIV on the frequency and phenotype of HF and its cardiac precursors in South Africa (SA). Methods: In an observational study, we recruited PWH on antiretroviral therapy (ART), age [&ge;]40 years and people without HIV (PWoH) with similar distributions of age, sex, ethnicity, and hypertension, from a community clinic in Khayelitsha (Cape Town, SA). Procedures included a clinical assessment, echocardiography (Echo), and b-type natriuretic peptide (BNP) measure. Echo parameters defined structural abnormalities, left ventricle (LV) filling pressure, and LV systolic and diastolic dysfunction (DD). HF was defined by symptoms and/or BNP [&ge;]35pg/mL and LV dysfunction, subcategorized as reduced, mildly reduced, or preserved ejection fraction (HFrEF, HFmrEF, and HFpEF). Comparisons by HIV status were adjusted for age, sex, hypertension, smoking, obesity, diabetes, elevated LDL-cholesterol, and hazardous alcohol use. Results: Between September 2022 and August 2025, we enrolled 1008 PWH and 500 controls [median (Q1-Q3) age 48 years (43-53), 77% female]. Among PWH and controls respectively, 37% and 39% had hypertension, 21% and 25% were current smokers, 40% and 45% were obese, and 9% and 17% had diabetes. LV systolic dysfunction (1%) and HFrEF (1%) were rare, and undiagnosed HFpEF (8%) was the predominant HF phenotype. Compared to controls, PWH had higher odds of elevated LV mass index (LVMI) (OR 2.1; 95%CI 1.5-3.0) and DD (OR 1.4; 95%CI 1.0-2.0). Risk for elevated LVMI and DD was greatest among women with HIV, who also had an increased risk for undiagnosed HFpEF (OR 1.9; 95%CI 1.2-3.2), compared to women without HIV; effects which were not seen among men (p=0.051 for HIV*Sex interaction). Conclusions: In a peri-urban SA community with a high burden of cardiometabolic risk factors, the frequency of abnormal structural and functional cardiac precursors of HFpEF was greater amongst ART-treated PWH. This was most pronounced amongst women with HIV, who also had increased risk of undiagnosed HFpEF.

Abstract Background Cardiogenic shock (CS) is a heterogeneous syndrome with diverse etiologies, treatment pathways, and outcomes. Prior studies of sex differences in CS have largely focused on acute myocardial infarction-related CS or evaluated CS as a single entity. Whether sex-based differences in outcomes and treatment utilization vary across distinct CS phenotypes remains incompletely defined. Methods We performed a retrospective cohort study using the National Inpatient Sample, a nationally representative all-payer database of United States hospitalizations. Adult hospitalizations with CS were identified using ICD-10-CM code R57.0 and categorized into clinically relevant phenotypes, including acute myocardial infarction (AMI), heart failure (HF), arrhythmia-related shock, myocarditis/Takotsubo, valvular disease, and other etiologies. Survey-weighted analyses accounting for the complex sampling design were used for primary analyses. The primary outcome was in-hospital mortality. Secondary outcomes included use of mechanical circulatory support (MCS) and mechanical ventilation. Propensity score-matched analyses were performed as sensitivity analyses. Results Among 254,691 weighted CS hospitalizations, 158,747 (62.3%) occurred in men and 95,896 (37.7%) in women. In survey-weighted analyses, women had higher in-hospital mortality in AMI-related CS (36.1% versus 31.3%; OR, 1.24; 95% CI, 1.19-1.28), HF-related CS (30.5% versus 25.8%; OR, 1.27; 95% CI, 1.23-1.30), and arrhythmia-related CS (37.3% versus 31.6%; OR, 1.28; 95% CI, 1.20-1.38). Women were less likely to receive ECMO (2.4% versus 2.9%), IABP/Impella (13.1% versus 18.9%), or any MCS (14.6% versus 20.4%), but were more likely to receive mechanical ventilation (44.9% versus 42.9%). In propensity-matched analyses, mortality differences were attenuated but persisted in AMI-related, HF-related, and valvular CS. Conclusions Sex differences in CS outcomes and treatment utilization are strongly phenotype dependent. Women experienced higher mortality in major CS phenotypes while receiving less advanced mechanical circulatory support. These findings support early recognition, rapid phenotype classification, and sex-conscious but non-delayed escalation strategies for women with CS.

Objective To evaluate the associations between maternal history of psychiatric disorders and the risk cardiovascular disease (CVD) in offspring. Design Population based cohort study. Setting Nationwide health registers in Sweden. Participants All 4 171 005 liveborn singletons in Sweden from 1973 to 2014. Follow-up started at birth and ended until the first diagnosis of CVD, death, emigration, or December 31st, 2023, whichever occurred first. Exposures for observational studies Maternal psychiatric disorders diagnosed before delivery (n=208,680, 5.0%). Main outcome measures The primary outcome was the first diagnosis of CVD in offspring, identified through hospital registers. Additional outcomes included specific CVD subtypes. To address potential familial confounding, a cousin comparison was performed, comparing the risk of CVD in offspring born to mothers who were biological sisters. Mediation analyses examined the roles of congenital heart disease, small for gestational age, and preterm birth. Results During up to 51 years of follow-up, 307 596 (7.4%) offspring had a diagnosis of CVD. Maternal history of psychiatric disorders was associated with a higher risk of overall CVD both in the full cohort (hazard ratio 1.19, 95% confidence interval 1.17 to 1.21) and the cousin-comparison cohort (n=1 577 113; 1.08, 1.03 to 1.13). In disease-specific analyses, a prominent association with heart failure was robustly observed in both the full cohort (1.59, 1.37 to 1.85) and the cousin comparison cohort (1.51, 1.06 to 2.17). Mediation analyses indicated that congenital heart disease mediated 9.5% of the association between maternal psychiatric disorders and offspring CVD risk. Preterm birth and small for gestational age contributed minimally (<3%) to the observed associations. Conclusions Maternal history of psychiatric disorders was associated with an increased risk of CVD up to early middle-age in offspring. Congenital heart disease partly mediated this association.

BackgroundHypertension is the most potent modifiable risk factor for recurrent intracerebral hemorrhage (ICH), yet blood pressure (BP) control after ICH remains suboptimal, particularly among disadvantaged racial and socioeconomic groups. To what extent post-ICH BP disparities reflect pre-existing hypertension inequities versus differences in post-ICH management is unknown. We examined disparities in BP control before and after ICH, assessed whether post-ICH care differentially improves BP across groups and whether post-ICH disparities persist after accounting for pre-existing BP differences. MethodsWe performed a case-only study in the All of Us Research Program, identifying ICH survivors using electronic health record diagnosis codes. Mean systolic BP was calculated for pre-ICH (1-365 days before) and post-ICH (30-365 days after) windows. Neighborhood deprivation tertiles were calculated using 3-digit ZIP codes. The primary outcome was uncontrolled BP ([&ge;]140 mmHg). Logistic regression estimated odds of uncontrolled BP, and mediation analysis estimated the proportion of post-ICH disparities explained by pre-ICH BP. ResultsAmong 2,226 ICH survivors (mean age 60; 50.6% female), 1,760 had pre-ICH and 1,852 had post-ICH BP data. Uncontrolled BP was more common in Black than White survivors both pre-ICH (38.9% vs 21.4%; p<0.001) and post-ICH (34.3% vs 16.3%; p<0.001), and in Deprived versus Privileged neighborhoods post-ICH (23.7% vs 15.8%; p<0.001). In adjusted models, Black race (OR 3.51; 95% CI 2.55-4.83; p<0.001) and Deprived neighborhoods (OR 1.38; 95% CI 1.00-1.91; p=0.048) were associated with uncontrolled post-ICH BP. Among survivors uncontrolled before ICH, 67% of White but only 45% of Black survivors achieved control afterward (p=0.001). Adjusting for pre-ICH BP control status only modestly attenuated the Black-White disparity (OR 4.05 to 2.95; P<0.001). In mediation analyses, pre-ICH BP explained only 27% of the racial (P<0.001) and 26% of the deprivation (P=0.014) disparity. ConclusionsRacial and socioeconomic disparities in BP control persist after ICH, but most post-ICH disparities are not explained by pre-existing inequalities. More advantaged populations achieve greater BP improvement, suggesting effective post-ICH management exists but does not reach all patients equitably. Targeted interventions addressing barriers to post-ICH BP control in disadvantaged populations may substantially reduce persistent disparities.

BackgroundFetal alcohol spectrum disorders (FASDs) impact up to 5% of U.S. school age children; however, the burden of congenital and acquired cardiovascular disease (CVD) in adults with FASDs remains poorly defined. We investigated associations between FASDs, cardiometabolic abnormalities, and CVD using electronic health record (EHR) data. MethodsWe performed a retrospective cohort study of adults ([&ge;]18 years) receiving ambulatory care with a FASD diagnosis (n = 208, mean age 38.4{+/-}14.5, 50% female) and age- and sex-matched control patients without FASD (n = 824, mean age 41.6{+/-}14.5, 50% female). Cardiometabolic outcomes were overweight/obesity, dyslipidemia, and diabetes mellitus. Cardiovascular outcomes were congenital heart defects (CHDs), heart murmur, hypertension, conduction defects, arrhythmias, structural heart remodeling, systolic and diastolic dysfunction, heart failure, myocardial infarction (MI), stroke, and thromboembolic events. Associations were assessed using age-adjusted logistic and Poisson regression, with sex-by-diagnosis interaction testing. Multivariable logistic regression was then used to estimate the odds of cardiovascular outcomes with additional adjustment for cardiometabolic conditions. Associations between CHD and CVD outcomes were evaluated using Fishers exact tests. ResultsAdults with FASDs had a higher prevalence (p<0.05) of cardiometabolic abnormalities, including dyslipidemia, type 2 diabetes, and the co-occurrence of multiple cardiometabolic abnormalities (overweight/obese, HDL cholesterol < 40 mg/dL, and type 2 diabetes mellitus). Overweight/obesity was more prevalent in females with FASDs but not males. CHDs were significantly more common in individuals with FASDs than controls (6% vs 1%, p < 0.001). Compared with controls, the FASD cohort had a higher incidence of systolic and diastolic dysfunction (6% vs. 2%), structural heart remodeling (11% vs 5%), MI (6% vs. 2%), stroke (4% vs 1%), and thromboembolic events (4% vs 1%; all p < 0.05). Significant sex-by-diagnosis interactions were observed for hypertension, arrhythmia, and heart failure, with elevated rates specific to FASD females. In individuals with FASDs, CHD diagnosis was associated with an increased incidence of conduction defects, arrhythmias, heart remodeling, heart failure, and systolic and diastolic dysfunction. Increased CVD burden in FASD adults remained significant after adjustment for BMI, composite cardiometabolic abnormalities, and hyperlipidemia. ConclusionsAdults with FASDs exhibit an increased burden of CVD not fully explained by conventional cardiometabolic risk factors. These findings support enhanced cardiovascular screening in individuals with FASDs.

The purposes of this study were to determine whether adverse childhood family environment (ACFE) exposure is associated with altered hemodynamic responses to graded exercise in young adulthood, and whether this association was modified by sex and race in a large, population-based cohort. We hypothesized that ACFE exposure would be associated with an exaggerated exercise pressor response in young adulthood, independent of resting BP. We further hypothesized that the association between ACFE and the hemodynamic response to exercise would be stronger in females than males, and in Black versus White participants. MethodsExercising blood pressure (BP) and heart rate (HR) responses were recorded during graded exercise testing and ACFE exposure was assessed among 3,417 young adults (mean age = 25 {+/-} 4 y; 44% female; 46% Black). Linear mixed-effects models that included participant-specific random intercepts and random slopes were used to assess the relation between ACFE exposure and exercising systolic (SBP), diastolic, and mean BP, pulse pressure (PP), pulse pressure index (PPI), heart rate (HR), and rate pressure product (RPP). All models were adjusted for resting values of the hemodynamic outcome, as well as age, sex, race, study center, body mass index, current hypertension medication use, smoking status, and alcohol consumption. ResultsGraded exercise hemodynamic responses were analyzed in 3,346-3,417 participants in the final models, providing 15,372-17,481 observations. Higher ACFE exposure was associated with lower SBP ({beta} = -0.304 mmHg/ACFE, p = 0.033), HR ({beta} = -0.485 bpm/ACFE, p<0.001), and RPP ({beta} = -83.404 bpm{middle dot}mmHg/ACFE, p=0.002) at the lowest workload, but steeper workload-related increases in SBP (interaction {beta} = 0.044 mmHg{middle dot}MET-{superscript 1}{middle dot}ACFE-{superscript 1}, p=0.029), HR ({beta} = 0.061 bpm{middle dot}MET-{superscript 1}{middle dot}ACFE-{superscript 1}, p<0.001), RPP ({beta} = 10.16 bpm{middle dot}mmHg{middle dot}MET-{superscript 1}{middle dot}ACFE-{superscript 1}, p=0.025), and PP ({beta} = 0.052 mmHg{middle dot}MET-{superscript 1}{middle dot}ACFE-{superscript 1}, p=0.038) and PPI ({beta} = 0.000232 units{middle dot}MET-{superscript 1}{middle dot}ACFE-{superscript 1}, p=0.018). These findings were robust to additional adjustment for central adiposity, exercise capacity, and maximal heart rate and heart rate recovery. ConclusionOur findings add nuanced evidence revealing that early adversity is associated with a demand-dependent shift in cardiovascular regulation, with attenuated responses at low demand, but more dramatic increases in pulsatile and myocardial load responses during progressive physiological stress.

Background: Resting electrocardiogram (ECG) are associated with heart failure (HF) events, even though it is not currently recommended in risk assessment. Objective: To examine the association between ECG abnormalities and incident HF events according to the 2023 PREVENT HF equation. And identify a subgroup of individuals who are misclassified as being at low risk. Design: Secondary data analysis from the REasons for Geographic And Racial Differences in Stroke (REGARDS) prospective cohort, including study participants without baseline HF. Exposure: ECG abnormalities were classified by Minnesota Code (MC) as normal, only minor, or any major abnormality at baseline (2003-2007). Outcome: Participants were followed for expert adjudicated incident HF hospitalizations/ deaths through December 2021. Results: Among 20,923 participants (mean age at baseline 63.6 years, 53.7% female), 26.0% of the sample was classified as low risk (<3%), 17.5% as borderline risk (3-<5%), 27.5% as intermediate risk (5%-<10%), and 29.0% as high risk (10%). Compared to those without ECG abnormality, the adjusted HR for incident HF was 1.56 (95% CI 1.35-1.80) for any minor abnormality and 2.56 (2.18-3.00) for any major abnormality. 43.5% of the population were in the less than 5% risk by PREVENT among whom 45.8% had any ECG abnormalities. The fully adjusted HR for only minor ECG abnormalities in the <3% was 1.47 (95% CI 0.72-3.01), and the fully adjusted HR for any major ECG abnormality was 5.22 (95% CI 2.42-11.30). In the borderline risk group, the fully adjusted HR for only minor ECG abnormalities was 1.37 (95% CI 0.89 - 2.11), and the fully adjusted HR for any major ECG abnormality was stronger than the HR in the intermediate and high-risk groups; 3.05 (95% CI 1.85 - 5.03). Conclusion: ECG abnormalities were common and associated with HF events across all PREVENT risk groups, especially in the low/borderline risk groups with major ECG abnormalities.

Sex specific differences in stroke are recognized. Whether differences in incident stroke risk persists in recent periods needs further elucidation to aid public health preventive efforts. AimTo determine long-term sex specific trends in stroke and stroke risk factors at different epochs among Framingham Heart Study participants. MethodsWe examined age-adjusted 10-year stroke incidence using Cox regression in women and men in five epochs: 1962-1969 (epoch 1, reference), 1971-1976 (epoch 2), 1987-1991 (epoch 3), 1998-2005 (epoch 4), 2015-2021 (epoch 5). We compared stroke incidence by sex across epochs, estimated decade-wise linear trends overall and by sex. We compared risk factors in successive epochs to the first, and estimated sex-specific trends in risk factors. Interactions between baseline risk factors with epoch and trends were assessed by sex. Secondary analyses were repeated in participants <60 years old. ResultsIncident stroke occurred in 4.5% (178/3996) in epoch 1, 3.9% (227/5786) in epoch 2, 3.9% (199/5137) in epoch 3, 2.7% (207/7642) in epoch 4, 2.2% (119/5534) in epoch 5. Men had higher risk of incident stroke in each epoch with significant difference in epochs 2 (HR 1.41, 95% CI [1.08, 1.84]) and 4 (HR 1.46, 95% CI [1.11, 1.91]) overall, and in epoch 4 (HR 2.13, 95% CI [1.17, 3.87]) among those <60 years. Stroke incidence declined by 16% per decade in men (HR 0.84, 95% CI [0.79, 0.89]) and 19% per decade in women (HR 0.81, 95% CI [0.76, 0.86]). Among those <60 years, stroke incidence declined by 22% per decade in women (HR 0.78, 95% CI [0.67, 0.95]). Hypertension declined by 8% per decade in women only ([OR] 0.92, 95% CI [0.90, 0.94]), while Atrial fibrillation and diabetes increased in both. ConclusionStroke incidence continues to decline in recent periods for women and men. Among participants <60 years, decline was observed only in women, possibly related to decline in hypertension in women.

BackgroundIndividuals with spinal cord injury (SCI) experience accelerated atherosclerotic cardiovascular disease that is not fully explained by traditional risk factors. Endothelial dysfunction is a key mechanism in atherosclerosis. We tested the hypothesis that endothelium-dependent vasodilation is impaired in adults with SCI and is due, at least in part, to oxidative stress. MethodsTwenty-four adults (age:19-58 yr) free of overt cardiometabolic disease were studied: 12 non-injured adults (9 M/3 F) and 12 adults with chronic SCI (8 M/4 F; time since injury 1.5 - 25 years). Forearm blood flow was determined (FBF; via strain-gauge plethysmography) in response to intra-arterial infusion of acetylcholine and isoproterenol in the absence and presence of the antioxidant vitamin C as well as the FBF response to sodium nitroprusside. ResultsAdults with SCI demonstrated significantly lower vasodilator response to acetylcholine (from 4.1{+/-}0.6 to 10.7{+/-}2.6 mL/100 mL tissue/min vs 4.1{+/-}1.1 to 15.7{+/-}3.4 mL/100 mL tissue/min) and isoproterenol (4.0{+/-}0.6 to 11.2{+/-}2.2 mL/100 mL tissue/min vs 4.3{+/-}1.0 to 15.0{+/-}2.6 mL/100 mL tissue/min) compared with non-injured adults. FBF response to sodium nitroprusside was not significantly different between the groups. Co-infusion of vitamin C significantly increased the vasodilator response to acetylcholine (~45%) and isoproterenol (~25%) in the adults with SCI to levels comparable with non-injured adults. ConclusionsChronic SCI is associated with endothelial-dependent vasodilator dysfunction. Impaired vasodilation across two distinct endothelial agonists suggests that chronic SCI is associated with endothelial dysfunction not confined to a specific receptor or intracellular signaling pathway. Moreover, oxidative stress is a contributing factor underlying SCI-related endothelial vasodilator dysfunction. NCT06443151 CLINICAL PERSPECTIVEO_LIThe novel finding of this study is that individuals with SCI demonstrate impaired endothelial vasodilator function in absence of traditional cardiovascular risk factors. C_LIO_LIOxidative stress is a contributing factor to SCI-related endothelial vasodilator dysfunction. C_LIO_LIFuture studies are needed to determine the efficacy of therapeutic interventions, either lifestyle or pharmacologic, in improving endothelial function in order to mitigate the elevated ASCVD risk after SCI. C_LI

BackgroundNeighborhood social vulnerability may shape cardiovascular health (CVH), but its association with Lifes Essential 8 (LE8), and whether changes in vulnerability track with changes in CVH during midlife, are unclear. We examined cross-sectional and longitudinal associations of the Social Vulnerability Index (SVI) with LE8 and assessed differences by SVI domain, LE8 component, race, and sex. MethodsWe analyzed CARDIA participants at Year 15 (Y15; 2000-2001; n = 3,168; mean age 40 years) and Year 30 (Y30; 2015-2016; n = 2,267; mean age 55 years). Residential addresses were geocoded and linked to 2000 and 2016 SVI. Participants were stratified by SVI quartiles. CVH scores were calculated from LE8 metrics (range 0-100; higher is better CVH), excluding sleep. Using multivariable linear regression adjusted for age, sex, race, and educational attainment, we estimated LE8 differences across SVI quartiles and associations of 15-year SVI change/residential mobility with change in LE8. Cox models estimated incident CVD associations. ResultsHigher SVI was associated with lower LE8 at both exams. Adjusted Q4 vs Q1 differences in overall LE8 were -5.34 points (95% CI, -6.90 to -3.78) at Y15 and -4.60 points (95% CI, -6.51 to -2.69) at Y30. Among the four SVI domains, SES and household characteristics drove most of the disparity in LE8 scores (Y30 Q4 vs. Q1: SES {Delta} = -6.98; household {Delta} = -6.56 points). Component-level differences across quartiles of SVI were largest for nicotine exposure at Y15 (-13.09 points) and physical activity at Y30 (-13.09 points). Changes in SVI and residential mobility were not significantly associated with change in LE8. ConclusionHigher social vulnerability was associated with significantly lower CVH. Socioeconomic and household factors, along with behavioral gaps in nicotine exposure and physical activity, may be key targets for community-level interventions to improve cardiovascular health equity.

Background: Children with congenital heart disease (CHD) require specialized care and may face worse outcomes if they experience food insecurity (FI). FI is associated with poor nutrition, hospitalizations, and developmental delays, compounding cardiac risks. Limited research evaluated impact of FI on health status among children with CHD. This study examines socioeconomic factors and the relationship between FI and health status in children with CHD. Methods: 2023 National Survey of Children?s Health (NSCH) data were used to compare rates of FI between children ages < 17 years with and without CHD and to assess overall health status of those with CHD. Descriptive, univariate, and multivariable logistic regression were utilized. Results: Among 53,477 children, 1,233(2%) had CHD. FI was reported in 35% of children with CHD vs. 27% without CHD(p=0.005). After adjustment, children with CHD had higher odds of FI (OR 1.49; 95% CI: 1.05?2.12). Hispanic ethnicity, residence in Midwest or South, lower household education, and lower poverty index were significantly associated with FI. Households receiving food assistance had higher FI. Living in grandparent household was associated with lower odds of FI. Within the CHD subgroup, 5% reported fair or poor health. Children with CHD experiencing FI had greater odds of fair or poor health than those without FI (OR 3.91, 95% CI 1.70?9.02; p=0.001). Conclusions: Children with CHD face higher odds of FI, which is strongly associated with worse reported health. Addressing socioeconomic vulnerability and FI may improve outcomes and reduce disparities in this high-risk population through targeted screening and intervention strategies nationwide. Keywords: Congenital Heart Disease, Food Insecurity Screening, National Survey of Children?s Health (NSCH), Health Disparities

BackgroundVaping among adolescents and young adults (AYA) could affect cardiovascular health. While pulmonary outcomes of vaping are well-documented, the link between vaping and abnormalities of heart rhythm remains unclear. We conducted a retrospective cohort study to test the hypothesis that the risk of heart rhythm abnormalities is increased in AYA who vape. MethodsWe used data from the TriNetX network to identify two cohorts of AYA (11 to 24 years old). The first cohort included individuals who vaped, and the second cohort was a comparison of individuals who did not report vaping. Individuals in the vaping cohort were matched 1:1 with those in the comparison cohort using propensity scores. The primary outcome was the association between vaping and diagnoses of heart rhythm abnormalities. The study analyzed data from 114,404 patients (57,202 in each cohort) with no significant differences in baseline characteristics. ResultsPatients who vaped had 82% higher odds of being diagnosed with heart rhythm abnormalities compared to those who did not vape (OR: 1.82, 95% CI: 1.74-1.91, p < 0.001). Furthermore, the hazard of developing heart rhythm abnormalities was approximately twice as high among vapers compared to those who did not (HR: 1.97, 95% CI: 1.88-2.06, p < 0.001). ConclusionThis study shows a significant association between e-cigarette use and an increased risk of heart rhythm abnormalities in AYA. These findings highlight the potentially harmful cardiac electrophysiological outcomes of vaping in this population and underscore the importance of health interventions and surveillance.

Patients with Fontan circulation face evolving risk for cardiovascular morbidity and mortality, yet the interplay between cardiac function, vascular properties, and circulating proteins is incompletely defined. We hypothesized that biochemical biomarkers and multimodal cardiovascular profile differ significantly between Fontan patients and controls, and that selected markers may serve as predictors of reduced single ventricle function. We conducted a prospective observational study at a tertiary pediatric heart center including 31 individuals with Fontan circulation and 52 matched controls. Cardiac function was assessed by echocardiography; vascular phenotyping included carotid intima-media thickness, central and peripheral blood pressure, augmentation index corrected for heart rate, carotid-femoral pulse wave velocity, aging index, and reactive hyperemia index. Compared to controls, the Fontan group had increased pulse wave reflection and central systolic pressure as well as decreased echocardiographic markers of systolic and diastolic function, while pulse wave velocity and other vascular parameters were not significantly different between the groups. Levels of 92 circulating cardiovascular biomarkers were quantified in a subset of 25 of the Fontan cohort and 81 controls using a proximity extension assay. Twenty-two biomarkers differed significantly in the Fontan group compared to controls, including FGF23, REN, HAOX1, and IL17D. Levels of several of these biomarkers correlated with patient age. Most importantly, HAOX1 (a peroxisomal oxidase linked to redox metabolism) and FGF23 (a bone-derived hormone regulating phosphate and vitamin D homeostasis) correlated negatively with ejection fraction within the Fontan group. By contrast, BNP was not associated with cardiac function in the Fontan group. None of the biomarkers correlated with central arterial parameters. In summary, central arterial hemodynamics and biomarkers such as FGF23 and HOAX1 may improve monitoring of cardiovascular function in single ventricle patients with Fontan circulation.

IntroductionPreterm pre-eclampsia is associated with increased risk of later cardiovascular disease. This study examines cardiometabolic health 3-6 years post-preterm pre-eclampsia and explores whether early postnatal cardiovascular phenotypes relate to later cardiovascular morbidity. MethodsPICk-UP trial participants who experienced preterm pre-eclampsia underwent assessments including anthropometry, blood pressure (BP), arteriography, echocardiography, biomarkers and cardiac magnetic resonance (CMR) imaging 3-6 years postpartum. The primary outcome was hypertension prevalence, with secondary outcomes including cardiac fibrosis, remodelling, and function, obesity, and lipid abnormalities. Associations between baseline, pregnancy and postnatal characteristics with the primary and secondary outcomes were explored. ResultsForty-five women were included; 37 underwent echocardiography and 20 had CMR. At 3-6 years, 53% had hypertension, 32% developed de novo hypertension, 30% had adverse left ventricular (LV) remodelling, 49% had diastolic dysfunction, and 27% were obese. Myocardial fibrosis was detected in 35% of CMR participants. No cardiovascular measures changed from 6 months postpartum to 3-6 years. Women who developed hypertension demonstrated higher BP and LV mass index, from 6 weeks postpartum, with distinct postnatal BP trajectories. Women with myocardial fibrosis exhibited higher sFlt and CRP concentrations from 6 weeks postpartum, with sFlt correlating with native T1 at 3-6 years. DiscussionWomen with prior preterm pre-eclampsia show significant cardiometabolic morbidity 3-6 years postpartum. Early postnatal phenotypes indicate long-term cardiovascular risk. Persistent anti-angiogenic imbalance and inflammation may contribute to myocardial fibrosis. Early BP, weight, and biomarker measurement may help identify at-risk women, warranting further studies on optimising postnatal care to mitigate cardiovascular risk after preterm pre-eclampsia.

CaMKII{delta} is the dominant isozyme of Ca2+/calmodulin-dependent protein kinase II in the heart. Under certain pathological conditions, it can be oxidized, causing a constitutive activation that can lead to cardiac failure. We recently showed that, in purified CaMKII{delta} exposed to oxidative conditions, a disulfide link formed between Cys273 and Cys290 causes this autonomous activation. Cys273 has a low pKa that facilitates the oxidation of its thiol to a sulfenic acid at physiological pH. Does this matter in vivo? To answer that question, we created a transgenic mouse with Cys273 mutated to serine (CaMKII{delta}C273S) to prevent disulfide formation. We conducted a detailed assessment of cardiac function at rest and in a dobutamine stress test. We found that the CaMKII{delta} Cys273Ser mutation does not have deleterious effects on cardiac physiology. Then, we assessed whether the mutation would protect the heart from ischemia-reperfusion in the Langendorff model. The CaMKII{delta}C273S mouse had improved cardiac function and decreased infarct size compared to the wild-type mouse. We conclude that blocking disulfide formation at Cys273 protects the heart against ischemia-reperfusion injury. Drugs that specifically target Cys 273 may be therapeutic in human cardiac disease.

The epidermal growth factor receptor (EGFR) family network comprises 4 receptors (EGFR, ERBB2, ERBB3, ERBB4) and numerous ligands, and is dysregulated in many cancers. Since anti-cancer drugs that target these receptors are cardiotoxic for some patients, it is important to understand the network in cardiac cells. Data from the Human Protein Atlas established that EGFR family members and their ligands are differentially expressed in cardiac cell types. Ligand expression was altered in human failing hearts and may contribute to disease. These ligands stimulated extracellular signal-regulated kinases 1/2 (ERK1/2) and Akt in rat cardiomyocytes but to different degrees. Afatinib (at a concentration to inhibit all EGF family receptors) was used to assess the role of the network in a mouse model of cardiac hypertrophy induced by angiotensin II (AngII). Echocardiography and segmental strain analysis demonstrated that afatinib reduced AngII-induced cardiac hypertrophy and caused cardiac dysfunction. This was associated with loss of cardiomyocyte hypertrophy, enhanced cardiac fibrosis, and reduced expression of Nrg1. NRG1 binds to ERBB4 in cardiomyocytes which homodimerizes or heterodimerises with ERBB2. The role of ERBB2 in the cardiomyocyte response to NRG1 compared with EGF was dissected using tucatinib (a selective ERBB2 inhibitor) and mRNA expression profiling. Most, but not necessarily all, of the response to NRG1 required ERBB2 signalling; most, but not all, of the response to EGF did not. Thus, the EGFR family network plays an important role in the heart. Understanding this network may identify therapeutic approaches to avoid cardiotoxicity associated with EGFR family anti-cancer drugs. Clinical perspectivesO_LIAnti-cancer drugs that target the epidermal growth factor receptor (EGFR) family are cardiotoxic for some patients; it is therefore important to understand the network in cardiac cells. C_LIO_LIThe EGFR family and their ligands are differentially expressed in cardiac cells with changes in ligand expression in heart failure; inhibition of all receptors in a mouse model of hypertrophy reduces cardiac hypertrophy and causes cardiac dysfunction with attenuation of cardiomyocyte hypertrophy and enhanced cardiac fibrosis and loss of neuregulin 1 (NRG1); in rat cardiomyocytes, NRG1 signalling to gene expression is largely mediated via ERBB2. C_LIO_LIThe EGFR family network plays an important role in the heart; understanding this network may identify therapeutic approaches to avoid cardiotoxicity associated with anti-cancer drugs targeted against it. C_LI

Objectives To examine the acute effects of a single bout of high-intensity interval training (HIIT) on fetal blood flow distribution during the third trimester of pregnancy. Methods Thirty-four healthy pregnant participants (mean age 31.6 years, standard deviation (SD) 4.1; gestational week 33.8 (SD 0.4) completed eight 30-second high-intensity cycling work-bouts interspersed with 2-minute rest periods. Fetal heart rate (FHR), maternal blood pressure, and Doppler-derived blood flow indices in the middle cerebral artery, umbilical artery and vein, and ductus venosus were assessed before and after exercise. We estimated fetal liver blood flow and the ratio of umbilical vein flow to ductus venosus. Maternal heart rate (HR) and FHR were recorded throughout exercise. Paired t-tests compared pre- and post-exercise values. Results No significant changes were observed in fetal blood flow indices or distribution following exercise. Average maternal HR and FHR during the work-bouts were 158 bpm (SD 16) and 152 bpm (SD 12), respectively. Following HIIT, maternal systolic blood pressure increased by 5 mmHg (95% CI 1 to 8, p=.014), maternal HR by 22 bpm (95% CI 15 to 28, p<.001), and FHR by 13 bpm (95% CI 10 to 17, p<.001). We recorded 16 instances of FHR above normal range during HIIT. Conclusion A single HIIT session in late pregnancy increased maternal blood pressure and HR and transiently elevated FHR but did not affect fetal blood flow indices or distribution. Brief episodes of fetal tachycardia were observed but appeared to be clinically insignificant. Future research should investigate the effects of repeated HIIT exposure during pregnancy.

Background:Stroke continues to be one of the major causes of death and long-term disability worldwide, with a greater impact in low-and middle-income countries. In India, there is limited evidence examining stroke burden and its changes over time and across regions. Therefore, we aimed to assess the burden of stroke in India from 1990 to 2023 using the latest data from the Global Burden of Disease (GBD) Study, along with projections up to 2035. Methods:We used estimates from the GBD 2023 study to examine stroke incidence, prevalence, mortality, and disability-adjusted life years (DALYs) in India from 1990 to 2023. Age-standardized rates were analyzed to understand how these measures have changed over time. We also conducted state-level analyses to explore regional differences in stroke burden. The contributions of all major modifiable risk factors were assessed using population-attributable fractions. In addition, we projected future trends in stroke burden up to 2035. Results:From 1990-2023, the percentage change in overall stroke burden in India showed minimal variation across key indicators. Incidence remained largely stable (0.00%[-0.04 to 0.05]), while prevalence showed a slight increase(0.06%[0.03 to 0.10]). Mortality (-0.11%[-0.36 to 0.20]) and DALYs (-0.17%[-0.38 to 0.12]) demonstrated modest declines over the study period. Notable regional disparities were evident, with states such as Chhattisgarh, Assam, and Jharkhand bearing the highest burden. High systolic blood pressure remained the leading risk factor in 2023, contributing the largest share of stroke-related deaths, followed by dietary risks, air pollution, tobacco use, and high body mass index. Future projections indicate that by 2035, stroke prevalence is likely to increase, while incidence, mortality, and DALYs are expected to show only modest changes. Conclusions: Stroke remains a major and growing public health challenge in India with a continuing increase in burden despite slight improvements in age-standardized rates over time. Addressing this challenge will require stronger prevention efforts, better control of key risk factors, and focused strategies to reduce regional disparities in stroke burden nationwide.