Future Cardiovascular Outcomes Research Articles

The Role of Troponin testing in patients with Supraventricular Tachycardia, Systematic Review and Meta-Analysis

Background: Supraventricular tachycardia (SVT) is commonly evaluated in the emergency department (ED). While troponin has been shown to be elevated in SVT, its usefulness for predicting coronary artery disease and future adverse cardiovascular outcomes has not been shown. Objectives: We aimed to evaluate the prognostic utility of troponin measurement as part of SVT management in the ED. Methods: We performed a literature search in the PubMed and Scopus databases from inception to August 30, 2023, including all studies reporting troponin measurements in adult patients (age >18 years) presenting to the ED with supraventricular tachycardia. The primary outcome of interest for this study was the prevalence of elevated troponin in patients with SVT. Secondary outcomes included the prevalence of major adverse cardiac events (MACE) and additional cardiac testing with significant findings. Results: We included 7 studies (500 patients) in our analysis. Six studies reported the number of patients with SVT and elevated troponin, with a pooled prevalence of 46% (95% CI 27%-66%, I2 93%). The pooled prevalence of all MACE in our study was 6% (95% CI 1%-25%), while the prevalence for MACE among patients with elevated serum troponin levels was 11% (95% CI 4%-27%). Conclusions: Troponin levels are frequently ordered for ED patients with SVT and are often elevated. However, this review suggests that they have low prognostic value in predicting MACE.

Association of single-point insulin sensitivity estimator index (SPISE) with future cardiovascular outcomes in patients with type 2 diabetes.

To investigate the association of single-point insulin sensitivity estimator (SPISE) index with future cardiovascular outcomes in patients with type 2 diabetes. SPISE index (= 600 × high-density lipoprotein cholesterol [mg/dL]0.185/triglycerides [mg/dL]0.2 × body mass index [kg/m2]1.338) was calculated in 10 190 participants. Cox proportional hazard regression models were applied to evaluate the association between SPISE index and future cardiovascular outcomes. Restricted cubic spline analyses and two-piecewise linear regression models were employed to explore the nonlinear association and to determine the threshold value. Subgroup and interaction analyses were conducted to test the robustness of the results. After fully adjusting for well-established metabolic confounders, higher SPISE index was significantly associated with lower risk of future cardiovascular outcomes in patients with type 2 diabetes (major adverse cardiovascular event [MACE]): hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.90-0.98, p = 0.0026; overall mortality: HR 0.90, 95% CI 0.86-0.93, p < 0.0001; cardiovascular disease [CVD] mortality: HR 0.85, 95% CI 0.79-0.92, p < 0.0001; congestive heart failure (CHF): HR 0.72, 95% CI 0.67-0.78, p < 0.0001; major coronary events: HR 0.91, 95% CI 0.87-0.95, p < 0.0001. There was a nonlinear association between SPISE index and future cardiovascular outcomes (the threshold value was 5.68 for MACE, 5.71 for overall mortality, 4.64 for CVD mortality, 4.48 for CHF, and 6.09 for major coronary events, respectively). Higher SPISE index was independently associated with lower risk of future cardiovascular outcomes in type 2 diabetes patients after full adjustment for well-established metabolic confounders.

Chronic pain-mental health comorbidity and excess prevalence of health risk behaviours: a cross-sectional study.

Chronic musculoskeletal pain and anxiety/depression are significant public health problems. We hypothesised that adults with both conditions constitute a group at especially high risk of future cardiovascular health outcomes. To determine whether having comorbid chronic musculoskeletal pain and anxiety/depression is associated with the excess prevalence of selected known cardiovascular health risk behaviours. A cross-sectional survey of adults aged 35+ years randomly sampled from 26 GP practice registers in West Midlands, England. Respondents were classified into four groups based on self-reported presence/absence of chronic musculoskeletal pain (pain present on most days for six months) and anxiety or depression (Hospital Anxiety and Depression Score 11+). Standardised binomial models were used to estimate standardised prevalence ratios and prevalence differences between the four groups in self-reported obesity, tobacco smoking, physical inactivity, and unhealthy alcohol consumption after controlling for age, sex, ethnicity, deprivation, employment status and educational attainment. The excess prevalence of each risk factor in the group with chronic musculoskeletal pain-anxiety/depression comorbidity was estimated. Totally, 14519 respondents were included, of whom 1329 (9%) reported comorbid chronic musculoskeletal pain-anxiety/depression, 3612 (25%) chronic musculoskeletal pain only, 964 (7%) anxiety or depression only, and 8614 (59%) neither. Those with comorbid chronic musculoskeletal pain-anxiety/depression had the highest crude prevalence of obesity (41%), smoking (16%) and physical inactivity (83%) but the lowest for unhealthy alcohol consumption (18%). After controlling for covariates, the standardised prevalence ratios and differences for the comorbid group compared with those with neither chronic musculoskeletal pain nor anxiety/depression were as follows: current smoking [1.86 (95% CI 1.58, 2.18); 6.8%], obesity [1.93 (1.76, 2.10); 18.9%], physical inactivity [1.21 (1.17, 1.24); 14.3%] and unhealthy alcohol consumption [0.81 (0.71, 0.92); -5.0%]. The standardised prevalences of smoking and obesity in the comorbid group exceeded those expected from simple additive interaction.

3-Tesla cardiac magnetic resonance imaging in primary dilated cardiomyopathy.

Cardiac magnetic resonance imaging (CMR) is an excellent non-invasive imaging tool in the assessment of patients with dilated cardiomyopathy (DCM). Few studies have analysed the findings in primary (idiopathic) DCM. To study the CMR features in primary DCM. We conducted a descriptive observational study on 20 adult patients with suspected or confirmed primary DCM. Each patient underwent a dedicated 3-Tesla CMR scan, and the findings were evaluated. Seventeen patients had systolic dysfunction with a reduced ejection fraction and elevated end-diastolic volume, 19 patients had contractile dysfunction in the form of global left ventricular hypokinesia, 13 patients showed no abnormal delayed contrast enhancement with gadolinium administration, and 7 patients showed abnormal late gadolinium enhancement patterns. In patients with primary DCM, CMR is a powerful diagnostic tool that can definitively establish the diagnosis, assess the severity of the disease, predict the risk of future adverse cardiovascular outcomes, check for complications, and assist in future follow-ups. What the study adds. Cardiac magnetic resonance imaging (CMR) is an excellent non-invasive imaging tool in the assessment of patients with primary dilated cardiomyopathy (DCM). Findings include global ventricular enlargement, systolic dysfunction (ejection fraction <40%), and elevated end-diastolic (≥140 mL) and end-systolic volumes. Global abnormal wall contractility is often seen. In DCM there is either no abnormal gadolinium enhancement or curvilinear mid-myocardial or subepicardial late gadolinium enhancement, unrelated to a coronary artery distribution.Implications of the findings. In patients with primary DCM, CMR provides powerful diagnostic and prognostic information. Enhanced awareness and understanding of this relatively uncommon condition among clinicians and radiologists would be of benefit in patient management and treatment.

Sex and age differences of major cardiovascular events in patients after percutaneous coronary intervention.

Women usually have higher risk after receiving percutaneous coronary interventions (PCIs) than men with coronary artery disease (CAD). The aim of this study was to investigate the association of sex differences with future outcomes in CAD patients undergoing PCI, to assess the role of age, and to extend observed endpoints to stroke and congestive heart failure. Six thousand six hundred forty-seven patients with CAD who received successful PCIs. The associations between clinic outcomes and sex were analyzed. The primary outcome was major cardiovascular events (MACE), including cardiac death, nonfatal myocardial infraction, and nonfatal stroke. The secondary outcome was MACE and hospitalization for heart failure (total CV events). During a mean of 52.7 months of follow-up, 4833 men and 1614 women received PCI. Univariate and multivariate analyses showed that women were independently associated with an increased risk of cardiac death (HR, 1.78; 95% CI, 1.32-2.41), hospitalization for heart failure (HR, 1.53; 95% CI, 1.23-1.89), MACE (HR, 1.34; 95% CI, 1.10-1.63), and total CV events (HR, 1.39; 95% CI, 1.20-1.62). In the subgroup analysis, women aged under 60 years had higher cardiovascular risks than men of the same age category. Women with CAD after successful PCI had poorer cardiovascular outcomes than men. Additionally, younger women (aged <60 years) were especially associated with a higher risk of developing future adverse cardiovascular outcomes.

Stratification of diabetes in the context of comorbidities, using representation learning and topological data analysis

Diabetes is a heterogenous, multimorbid disorder with a large variation in manifestations, trajectories, and outcomes. The aim of this study is to validate a novel machine learning method for the phenotyping of diabetes in the context of comorbidities. Data from 9967 multimorbid patients with a new diagnosis of diabetes were extracted from Clinical Practice Research Datalink. First, using BEHRT (a transformer-based deep learning architecture), the embeddings corresponding to diabetes were learned. Next, topological data analysis (TDA) was carried out to test how different areas in high-dimensional manifold correspond to different risk profiles. The following endpoints were considered when profiling risk trajectories: major adverse cardiovascular events (MACE), coronary artery disease (CAD), stroke (CVA), heart failure (HF), renal failure (RF), diabetic neuropathy, peripheral arterial disease, reduced visual acuity and all-cause mortality. Kaplan Meier curves were plotted for each derived phenotype. Finally, we tested the performance of an established risk prediction model (QRISK) by adding TDA-derived features. We identified four subgroups of patients with diabetes and divergent comorbidity patterns differing in their risk of future cardiovascular, renal, and other microvascular outcomes. Phenotype 1 (young with chronic inflammatory conditions) and phenotype 2 (young with CAD) included relatively younger patients with diabetes compared to phenotypes 3 (older with hypertension and renal disease) and 4 (older with previous CVA), and those subgroups had a higher frequency of pre-existing cardio-renal diseases. Within ten years of follow-up, 2592 patients (26%) experienced MACE, 2515 patients (25%) died, and 2020 patients (20%) suffered RF. QRISK3 model’s AUC was augmented from 67.26% (CI 67.25–67.28%) to 67.67% (CI 67.66–67.69%) by adding specific TDA-derived phenotype and the distances to both extremities of the TDA graph improving its performance in the prediction of CV outcomes. We confirmed the importance of accounting for multimorbidity when risk stratifying heterogenous cohort of patients with new diagnosis of diabetes. Our unsupervised machine learning method improved the prediction of clinical outcomes.

DNA methylation patterns at birth predict health outcomes in young adults born very low birthweight

BackgroundIndividuals born very low birthweight (VLBW) are at increased risk of impaired cardiovascular and respiratory function in adulthood. To identify markers to predict future risk for VLBW individuals, we analyzed DNA methylation at birth and at 28 years in the New Zealand (NZ) VLBW cohort (all infants born < 1500 g in NZ in 1986) compared with age-matched, normal birthweight controls. Associations between neonatal methylation and cardiac structure and function (echocardiography), vascular function and respiratory outcomes at age 28 years were documented.ResultsGenomic DNA from archived newborn heel-prick blood (n = 109 VLBW, 51 controls) and from peripheral blood at ~ 28 years (n = 215 VLBW, 96 controls) was analyzed on Illumina Infinium MethylationEPIC 850 K arrays. Following quality assurance and normalization, methylation levels were compared between VLBW cases and controls at both ages by linear regression, with genome-wide significance set to p < 0.05 adjusted for false discovery rate (FDR, Benjamini-Hochberg). In neonates, methylation at over 16,400 CpG methylation sites differed between VLBW cases and controls and the canonical pathway most enriched for these CpGs was Cardiac Hypertrophy Signaling (p = 3.44E−11). The top 20 CpGs that differed most between VLBW cases and controls featured clusters in ARID3A, SPATA33, and PLCH1 and these 3 genes, along with MCF2L, TRBJ2-1 and SRC, led the list of 15,000 differentially methylated regions (DMRs) reaching FDR-adj significance. Fifteen of the 20 top CpGs in the neonate EWAS showed associations between methylation at birth and adult cardiovascular traits (particularly LnRHI). In 28-year-old adults, twelve CpGs differed between VLBW cases and controls at FDR-adjusted significance, including hypermethylation in EBF4 (four CpGs), CFI and UNC119B and hypomethylation at three CpGs in HIF3A and one in KCNQ1. DNA methylation GrimAge scores at 28 years were significantly greater in VLBW cases versus controls and weakly associated with cardiovascular traits. Four CpGs were identified where methylation differed between VLBW cases and controls in both neonates and adults, three reversing directions with age (two CpGs in EBF4, one in SNAI1 were hypomethylated in neonates, hypermethylated in adults). Of these, cg16426670 in EBF4 at birth showed associations with several cardiovascular traits in adults.ConclusionsThese findings suggest that methylation patterns in VLBW neonates may be informative about future adult cardiovascular and respiratory outcomes and have value in guiding early preventative care to improve adult health.

Prevalence and prognostic implications of hypertensive response to exercise in patients with hypertrophic cardiomyopathy

ObjectiveHypertensive response to exercise (HRE) is observed in patients with hypertrophic cardiomyopathy (HCM) with normal resting blood pressure (BP). However, the prevalence or prognostic implications of HRE in HCM remain unclear. MethodsIn this study, normotensive HCM subjects were enrolled. HRE was defined as systolic BP > 210 mmHg in men or >190 mmHg in women, or diastolic BP > 90 mmHg, or an increase in diastolic BP > 10 mmHg during treadmill exercise. All participants were followed for subsequent development of hypertension, atrial fibrillation (AF), heart failure (HF), sustained ventricular tachycardia/fibrillation (VT/VF), and all-cause death. Six hundred and eighty HCM patients were screened. Results347 patients had baseline hypertension, and 333 patients were baseline normotensive. 132 (40%) of the 333 patients had HRE. HRE was associated with female sex, lower body mass index and milder left ventricular outflow tract obstruction. Exercise duration and metabolic equivalents were similar between patients with or without HRE, but the HRE group had higher peak heart rate (HR), better chronotropic response and more rapid HR recovery. Conversely, non-HRE patients were more likely to exhibit chronotropic incompetence and hypotensive response to exercise. After a mean follow-up of 3.4 years, patients with and without HRE had similar risks of progression to hypertension, AF, HF, sustained VT/VF or death. ConclusionHRE is common in normotensive HCM patients during exercise. HRE did not carry higher risks of future hypertension or cardiovascular adverse outcomes. Conversely, the absence of HRE was associated with chronotropic incompetence and hypotensive response to exercise.

The deep learning algorithm estimates chest radiograph-based sex and age as independent risk factors for future cardiovascular outcomes.

Chest X-rays (CXRs) convey much illegible physiological information that deep learning model (DLM) has been reported interpreting successfully. Since the electrocardiogram age established by DLM was revealed as a heart biological marker, we hypothesize that CXR age has similar potential to describe the heart and lung states. Therefore, we developed a DLM to predict sex and age through CXR and analyzed its relation with future cardiovascular diseases (CVD). A total of 90,396 CXRs aged 20 to 90 were collected and separated into a development set with 53,102 CXRs and demographic information pairs, a tuning set with 7073 pairs, an internal validation set with 17,364 pairs, and an external validation set with 12,857 pairs. The study trained DLM with development set for estimating age and sex and compared them to actual information. The mean absolute errors of predicted age were 4.803 and 4.313 years in the internal and external validation sets, respectively. The area under the curve of sex analysis was 0.9993 and 0.9988 in the internal and external validation sets, respectively. Patients whose CXR age was 5 years older than chronologic age lead to higher risk of all-cause mortality (hazard ratio (HR): 2.42, 95% confidence interval (CI): 2.00-2.92), cardiovascular (CV)-cause mortality (HR: 7.57, 95% CI: 4.55-12.60), new-onset heart failure (HR: 2.07, 95% CI: 1.56-2.76), new-onset chronic kidney disease (HR: 1.73, 95% CI: 1.46-2.05), new-onset acute myocardial infarction (HR: 1.80, 95% CI: 1.12-2.92), new-onset stroke (HR: 1.45, 95% CI: 1.10-1.90), new-onset coronary artery disease (HR: 1.26, 95% CI: 1.04-1.52), and new-onset atrial fibrillation (HR: 1.43, 95% CI: 1.01-2.02). Using DLM to predict CXR age provided additional information for future CVDs. Older CXR age is an accessible risk classification tool for clinician use.

Abstract 12093: Inter-Reader Reliability of Coronary Calcium Estimation From Non-Gated Chest Computed Tomography Scans Using a Semi-Quantitative Scoring Method

Introduction: Coronary artery calcium (CAC) is strongly associated with cardiovascular risk. CAC burden can be qualitatively estimated from non-gated chest computed tomography (CT) imaging and may be used to predict future cardiovascular outcomes. We evaluated whether resident physician trainees can reliably estimate CAC burden from existing non-gated chest CTs using a semi-quantitative scoring method. Methods: A group of 4 resident physicians without formal training in CT image interpretation underwent a training session to qualitatively estimate CAC burden from non-gated, contrast and non-contrast CT scans. CAC was estimated for each coronary artery as absent, mild (1-24% vessel length), moderate (25-49% vessel length) and severe (&gt;50% vessel length). All Chest CTs were reviewed by two physicians, each blinded to the interpretations of the other reviewer, to assess (a) the presence or absence of CAC, (b) the presence or absence of moderate-severe CAC, and (c) a semi-quantitative CAC index, at a per-patient level and by vessel. Inter-reader reliability (IRR) was assessed by percent agreement, Cohen's kappa coefficient, and the intraclass correlation coefficient (ICC). Results: Using a semi-quantitative scoring system to estimate an index of overall CAC burden, the ICC was 0.96 (CI 0.94-0.98). The percent agreement for the presence of any CAC was 74% (kappa 0.82) and 89% for moderate-to-severe CAC (kappa 0.85). The IRR stratified for each coronary vessel is shown in Table 1. CAC estimated from both contrast and non-contrast scans was associated with substantial agreement between readers ( Table 1 ). Conclusions: With a single training session, resident physicians can quickly and reliably estimate CAC burden from non-gated chest CT imaging. This may facilitate cardiovascular risk stratification in patients without dedicated cardiac testing. 1b

Predictive value of novel circulating biomarkers in Chagas disease: The Brazilian Chagas disease cohort

Abstract Introduction Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is the leading causes of non-ischemic heart failure and premature cardiac deaths in Latin America. Identifying predictive biomarkers of morbidity and progression of Chagas cardiomyopathy (CCC) is important to deciphering novel pathways and aid in early identification of patients at highest risk for future adverse cardiovascular (CV) outcomes. Objectives To determine the association of novel circulating biomarkers with CCC and disease survival. Methods Serum levels of 184 unique cardiometabolic and inflammation proteins were measured using proximity extension immunoassay using age- and sex- matched patients without history of any other cardiovascular or infectious diseases as well as diabetes mellitus, who were identified and selected at the referral outpatient center for Chagas Disease at a clinical hospital in Brazil. Univariable linear regression using standardized protein levels were compared between patients with and without CCC. All p-values were adjusted for multiple testing and in findings with p value&amp;lt;0.0002 were considered statistically significant. Proteins that reached significance level were further compared between disease mortalities and survival. We also performed network analysis using STRING-DB on overexpressed proteins to determine its interaction. Results We used data from 44 with CCC and 44 with asymptomatic T. cruzi-positive patients (indeterminate). Among individuals with CCC, 22 patients had a fatal cardiovascular event during follow-up period of 4.1 (SD ±1.4) years. In linear regression analyses, we identified 45 candidate biomarkers associated with chronic CC (all p values &amp;lt;0.0002). Among these, only three proteins (IL33, CD40, REG1A) were significantly different between individuals with CCC who died vs survived over a period of 4.1 years. We used 38 overexpressed proteins in network analysis. THBS4, marker of cardiac remodeling, was overexpressed in CCC. CXCL11 were seen co-expressed with CXCL9 and CXCL10, all are known activators of CD4+ Th1 cells in CCC. Conclusion We identified 45 novel cardiometabolic and inflammatory markers that are associated with chronic Chagas cardiomyopathy. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Leading House of Latin America of the Swiss State Secretariat for Education, Research and Innovation (SERI)

The Fourth Trimester: a Time for Enhancing Transitions in Cardiovascular Care.

Purpose of ReviewThe “fourth trimester” concept, defined as the first 12 weeks after delivery (and beyond), is a critical window of time for clinicians to intervene to optimize women’s cardiovascular health after pregnancy. A timely and comprehensive postpartum cardiovascular assessment should be performed in all women following delivery in order to (1) follow up medical conditions present prior to conception, (2) evaluate symptoms and signs of common postpartum complications, and (3) identify risk factors and prevent future adverse cardiovascular outcomes. In this review, we aim to discuss major maternal cardiovascular risk factors such as hypertensive disorders of pregnancy, gestational diabetes mellitus, postpartum weight retention, and postpartum depression, as well as lactation as a potential protective risk modifying factor. Additionally, we will review effectiveness of outpatient interventions to enhance transitions in cardiovascular care during the fourth trimester.Recent FindingsA seamless hand-off from obstetric to primary care, and potentially cardiology, is needed for early detection and management of hypertension, weight, glycemic control, stress and mood, and long-term cardiovascular risk. Additionally, the use of telemedicine, blood pressure self-monitoring, remote activity monitoring, and behavioral health coaches are potentially feasible modalities to augment clinic-based care for cardiovascular risk factors and weight management, but additional studies are needed to study their long-term effectiveness.SummaryDevelopment of a comprehensive postpartum care plan with careful consideration of each patient’s risk profile and access to resources is critical to improve maternal morbidity and mortality, reduce health disparities, and achieve long-term cardiovascular health for women. Supporting postpartum well-being of women during this transition period requires a multidisciplinary approach, especially primary care engagement, and planning should start before delivery.

Blood pressure control measures and cardiovascular outcomes: a prospective hypertensive cohort

Purpose We investigated whether blood pressure (BP) control measures, visit-to-visit BP variability, and time in therapeutic range (TTR) are associated with future cardiovascular outcomes in hypertensive patients. Materials and Methods Among 1,408 hypertensive patients without cardiovascular disease, we prospectively evaluated the incident major cardiovascular events over 6 years. In newly diagnosed patients, antihypertensive drug treatment was initiated. We estimated two markers of on-treatment BP control, (1) visit-to-visit BPV as the coefficient of variation of office systolic BP (BP-CV), and (2) TTR calculated as the percentage of office systolic BP measurements within 120–140mmHg across visits. Results The hypertensive cohort (672 males, mean age 60 years, 31% newly diagnosed) had a mean systolic/diastolic BP of 142/87 mmHg. The mean number of visits was 4.9 ± 2.6, while the mean attained systolic/diastolic BP during follow-up was 137/79 mmHg using 2.7 ± 1.1 antihypertensive drugs. The BP-CV and TTR were 9.1 ± 4.1% and 45 ± 29%, respectively, and the incidence of the composite outcome was 8.3% (n = 117). After adjustment for relevant confounders and standardization to z-scores, BP-CV and TTR were associated with a 43% (95% CI, 27–62%) increase and a 33% (95% CI, 15–47%) reduction in the outcome. However, the joint evaluation of TTR and BP-CV in a common multivariable model indicated that a standardized change of TTR was associated with the outcome to a greater extent than BP-CV (mean hazard ratios of 30% vs. 24%, respectively). When combined with the higher BP standardized-CV quartile, the lower TTR quartile predicted the outcome by 2.3 times (95% CI, 1.1–5.4) compared to the inverse TTR and BP-CV quartile pattern. Conclusion High BP-CV or low TTR was associated with future cardiovascular events in a cohort of treated hypertensive patients. As a determinant, the extent of TTR value appears greater than BP-CV when these measures are considered in the same multivariable model.

Are cardiovascular health measures heritable across three generations of families in Soweto, South Africa? A cross-sectional analysis using the random family method

ObjectivesCardiovascular disease is increasing in many low and middle-income countries, including those in Africa. To inform strategies for the prevention of cardiovascular disease in South Africa, we sought to determine...

Arterial stiffness and nocturnal hypertension in preterm children and adolescents.

Preterm birth has been associated with increased risk for developing hypertension and other chronic diseases during childhood and adulthood. The aim of the current prospective case-control study was to investigate the associations of preterm birth with ambulatory blood pressure (BP) levels and arterial stiffness during childhood and adolescence. The study population included 52 children and adolescents born preterm and 26 healthy children born full term with similar age. The participants underwent ambulatory BP monitoring (ABPM) and assessment of carotid-femoral pulse wave velocity (PWV). Preterm children presented higher night SBP z score values compared to controls, but did not differ in other ABPM parameters, office peripheral and central SBPs. Nocturnal hypertension was found in 78% (7/9) of ex-preterm children with ambulatory BP hypertension. Preterm birth was an independent predictor of PWV z score adjusted for heart rate. Estimated marginal means for PWV z score adjusted for age, sex, presence of kidney disease at birth, office BPs, night BPs, central SBP, and BMI z scores were significantly higher in preterm individuals compared to controls (0.703, 95% confidence interval [CI] 0.431-0.975 versus -0.19, 95% CI -0.574-0.536, respectively, P = 0.027). Preterm children who were overweight presented the highest values of night SBP and PWV z score. Preterm birth is associated with higher nocturnal BP and increased arterial stiffness in childhood and adolescence. Increased awareness for detection of hypertension and prevention of obesity in childhood could prevent future adverse cardiovascular outcomes in preterm individuals.

Prognostic Value of Exercise Stress Echocardiography in Pediatric Cardiac Transplant Recipients

Cardiac allograft vasculopathy (CAV) is a leading cause of long-term morbidity and mortality in pediatric heart transplant (HTx) recipients. Exercise stress echocardiography (ESE) has been shown to be useful in the detection of angiographically confirmed coronary artery disease in children. However, the prognostic utility of ESE for prediction of cardiac events in HTx survivors is unknown. We aim to assess whether an abnormal (positive) ESE is be associated with a higher risk of future cardiovascular (CV) outcomes in pediatric HTx recipients. We conducted a retrospective review of CV outcomes in a cohort of 95 pediatric HTx recipients who underwent 188 ESEs over a 10-year period. A composite endpoint for CV events including myocardial infarction, hospitalization for nonrejection heart failure, coronary revascularization, need for repeat transplantation, and death was used. Based on the interpretation of the ESE results, each ESE study was classified for this study as either positive (abnormal) or negative (normal) for ischemia. Results of the coronary angiograms performed near the time of ESE were also assessed and classified for this study as positive (abnormal) or negative (normal) for CAV according to standard HTx criteria for CAV. Fifty-one (27%) ESEs were positive for ischemia. There was a total of 35 CV events in 23 patients. A positive ESE was associated with increased risk of any CV event (hazard ratio=3.55; 95% CI, 1.52, 8.28), as well as an increased risk of CV death (hazard ratio=3.19; 95% CI, 1.23, 8.28). Freedom from composite CV outcome at 1, 2, and 3years following a positive ESE was 89.9% (95% CI=77.3%, 95.7%), 81.5% (95% CI=65.9%, 90.5%), and 63.2% (95% CI=41.9%, 78.5%), respectively. Freedom from composite CV outcome at 1, 2, and 3years following a negative ESE was 99.3% (94.8, 99.9), 98.4% (93.6, 99.6), and 97.0% (90.6, 99.1), respectively. No patient died within 1year of a negative ESE. In this largest study of ESE in pediatric HTx recipients, a positive or abnormal ESE is associated with increased future CV morbidity and mortality. Conversely, a negative ESE can help predict CV event-free survival. Even in the setting of a normal coronary angiogram, our pilot data show that an abnormal ESE may still be clinically important. Use of ESE in follow-up may improve risk stratification and management of pediatric HTx recipients.

Predictive value of the apolipoprotein B/A1 ratio in intracerebral hemorrhage outcomes.

Background and AimsThe apolipoprotein B (apoB)/apolipoprotein A1 (apoA1) ratio is a key indicator in predicting future cardiovascular outcomes. However, it is still unclear whether the ratio of apoB/apoA1 is a better predictor of the outcomes after intracerebral hemorrhage (ICH). Therefore, we aimed to assess the relationships between the ratio of apoB/apoA1 and functional outcomes, all‐cause mortality, and stroke recurrence in ICH patients.MethodsTwo hundred and sixteen Chinese ICH patients participated in this study from December 2018 to December 2019. Laboratory routine tests including hematology analysis, coagulation tests, and lipid levels were examined. The clinical outcomes included functional outcomes evaluated by the modified Rankin Scale score (mRS), all‐cause death, and stroke recurrence 1 year after discharge. Associations between the apoB/apoA1 ratio and the outcomes were evaluated using logistic regression analysis. Based on multivariate analysis, we constructed a nomogram. Univariate survival analysis was performed by the Kaplan–Meier method and log‐rank test. All the patients were classified into two groups by the median value of the apoB/apoA1 ratio: B1 < 0.8 and B2 ≥ 0.8.ResultsOf the 216 patients, 107 had an apoB/apoA1 ratio ≥ 0.8. Eighty‐five patients had poor functional outcomes (mRS ≥ 3), and 32 patients had severe functional outcomes (mRS ≥ 4). During the 1‐year follow‐up, a total of 18 patients died, and 13 patients had apoB/apoA1 ratio levels ≥0.8 during the 1‐year follow‐up period. Moreover, 16 recurrent strokes were recorded. Adjustments for age, sex, smoking, alcohol, body mass index, lipid levels, and hematoma site and volume showed that a high apoB/apoA1 ratio was significantly related to adverse functional outcomes and all‐cause mortality. The ORs for B2 versus B1 were 3.76 (95% CI: 1.37 to 10.40, p = 0.010), 22.74 (95% CI: 1.08 to 474.65, p = 0.044), and 7.23 (95% CI: 1.28 to 40.88, p = 0.025) for poor functional outcomes with mRS ≥ 3, mRS ≥ 4, and all‐cause mortality, respectively.ConclusionAn increased apoB/apoA1 ratio at admission was independently related to poor functional outcome and all‐cause mortality in ICH patients at the 1‐year follow‐up.

Circulating PCSK9 Linked to Dyslipidemia in Lebanese Schoolchildren.

In adults, elevated levels of circulating Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) have been associated with increased Low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and worse cardiovascular outcomes. However, few studies analyzed the relation between PCSK9 and lipid parameters in pediatric populations. The aim of our study is to evaluate the distribution and the correlation of serum PCSK9 levels with lipid parameters in a sample of Lebanese school children. Using an immunofluorescence assay, we measured serum PCSK9 levels in 681 school children recruited from ten public and private Lebanese schools. We analyzed the association between PCSK9 and age, sex, Body Mass Index (BMI), and lipid parameters (total cholesterol (TC), LDL-C, TG, High-density lipoprotein cholesterol (HDL-C), non-HDL-C, and lipoprotein (a) (Lp(a)). Serum PCSK9 levels were significantly correlated with TC, LDL-C, and non-HDL-C (p value < 0.0001) but not with TG, HDL-C, and Lp(a). PCSK9 levels were also significantly higher in children with high TC, LDL-C, and non-HDL-C (p values = 0.0012, 0.0002, 0.001, respectively). No significant gender differences in PCSK9 were found. In addition, no significant associations between PCSK9 and both age and BMI percentiles were observed. In girls, no difference in PCSK9 values was observed according to menarche while in boys, testosterone levels were not significantly associated with PCSK9. Serum PCSK9 levels were significantly correlated with TC, LDL-C, and non-HDL-C levels. Further studies are needed to find if PCSK9 measurements have an additional value to predict future cardiovascular outcomes in pediatric populations.

Bone Marrow Cells Improve Coronary Flow Reserve in Ischemic Nonrevascularized Myocardium: A MiHeart/IHD Quantitative Perfusion CMR Substudy

ObjectivesThis study investigated whether intramyocardial bone marrow–derived hematopoietic progenitor cells (BMCs) increase coronary flow reserve (CFR) in ischemic myocardial regions where direct revascularization was unsuitable. BackgroundPatients with diffuse coronary artery disease frequently undergo incomplete myocardial revascularization, which increases their risk for future adverse cardiovascular outcomes. The residual regional ischemia related to both untreated epicardial lesions and small vessel disease usually contributes to the disease burden. MethodsThe MiHeart/IHD study randomized patients with diffuse coronary artery disease undergoing incomplete coronary artery bypass grafting to receive BMCs or placebo in ischemic myocardial regions. After the procedure, 78 patients underwent cardiovascular magnetic resonance (CMR) at 1, 6, and 12 months and were included in this cardiac magnetic resonance substudy with perfusion quantification. Segments were classified as target (injected), adjacent (surrounding the injection site), and remote from injection site. ResultsOf 1,248 segments, 269 were target (22%), 397 (32%) adjacent, and 582 (46%) remote. The target had significantly lower CFR at baseline (1.40 ± 0.79 vs 1.64 ± 0.89 in adjacent and 1.79 ± 0.79 in remote; both P < 0.05). BMCs significantly increased CFR in target and adjacent segments at 6 and 12 months compared with placebo. In target regions, there was a progressive treatment effect (27.1% at 6 months, P = 0.037, 42.2% at 12 months, P = 0.001). In the adjacent segments, CFR increased by 21.8% (P = 0.023) at 6 months, which persisted until 12 months (22.6%; P = 0.022). Remote segments in both the BMC and placebo groups experienced similar improvements in CFR (not significant at 12 months compared with baseline). ConclusionsBMCs, injected in severely ischemic regions unsuitable for direct revascularization, led to the largest CFR improvements, which progressed up to 12 months, compared with smaller but persistent CFR changes in adjacent and no improvement in remote segments.

Type 1 Diabetes Patients With Different Residual Beta-Cell Function but Similar Age, HBA1c, and Cardiorespiratory Fitness Have Differing Exercise-Induced Angiogenic Cell Mobilisation.

BackgroundMany individuals with type 1 diabetes retain residual beta-cell function. Sustained endogenous insulin and C-peptide secretion is associated with reduced diabetes related complications, but underlying mechanisms remain unclear. Lower circulating numbers of endothelial and hematopoietic progenitor cells (EPCs and HPCs), and the inability to increase the count of these cells in response to exercise, are also associated with increased diabetes complications and cardiovascular disease. It is unknown whether residual beta-cell function influences HPCs and EPCs. Thus, this study examined the influence of residual beta-cell function in type 1 diabetes upon exercise-induced changes in haematopoietic (HPCs) and endothelial progenitor cells (EPCs).MethodsParticipants with undetectable stimulated C-peptide (n=11; Cpepund), 10 high C-peptide (Cpephigh; >200 pmol/L), and 11 non-diabetes controls took part in this observational exercise study, completing 45 minutes of intensive walking at 60% . Clinically significant HPCs (CD34+) and EPCs (CD34+VEGFR2+) phenotypes for predicting future adverse cardiovascular outcomes, and subsequent cell surface expression of chemokine receptor 4 (CXCR4) and 7 (CXCR7), were enumerated at rest and immediately post-exercise by flow cytometry.ResultsExercise increased HPCs and EPCs phenotypes similarly in the Cpephigh and control groups (+34-121% across phenotypes, p<0.04); but Cpepund group did not significantly increase from rest, even after controlling for diabetes duration. Strikingly, the post-exercise Cpepund counts were still lower than Cpephigh at rest.ConclusionsResidual beta-cell function is associated with an intact exercise-induced HPCs and EPCs mobilisation. As key characteristics (age, fitness, HbA1c) were similar between groups, the mechanisms underpinning the absent mobilisation within those with negative C-peptide, and the vascular implications, require further investigation.