Vertebral Tortuosity Is Associated With Increased Rate of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome.

Background Arterial tortuosity is associated with adverse events in Marfan and Loeys-Dietz syndromes but remains understudied in Vascular Ehlers-Danlos syndrome. Methods and Results Subjects with a pathogenic COL3A1 variant diagnosed at age <50 years were included from 2 institutions and the GenTAC Registry (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions). Height-adjusted vertebral artery tortuosity index (VTI-h) using magnetic resonance or computed tomography angiography was calculated. Associations between VTI-h and outcomes of (1) cardiovascular events (arterial dissection/rupture, aneurysm requiring intervention, stroke), or (2) hollow organ collapse/rupture at age <50 years were evaluated using receiver operator curve analysis (using outcome by age 30 years) and mixed-effects Poisson regression for incidence rate ratios. Of 65 subjects (54% male), median VTI-h was 12 (interquartile range, 8-16). Variants were missense in 46%, splice site in 31%, and null/gene deletion in 14%. Thirty-two subjects (49%) had 59 events, including 28 dissections, 5 arterial ruptures, 4 aneurysms requiring intervention, 4 strokes, 11 hollow organ ruptures, and 7 pneumothoraces. Receiver operator curve analysis suggested optimal discrimination at VTI-h ≥15.5 for cardiovascular events (sensitivity 70%, specificity 76%) and no association with noncardiovascular events (area under the curve, 0.49 [95% CI, 0.22-0.78]). By multivariable analysis, older age was associated with increased cardiovascular event rate while VTI-h ≥15.5 was not (incidence rate ratios, 1.79 [95% CI, 0.76-4.24], P=0.185). However, VTI-h ≥15.5 was associated with events among those with high-risk variants <40 years (incidence rate ratios, 4.14 [95% CI, 1.13-15.10], P=0.032), suggesting effect modification by genotype and age. Conclusions Increased arterial tortuosity is associated with a higher incidence rate of cardiovascular events in Vascular Ehlers-Danlos syndrome. Vertebral tortuosity index may be a useful biomarker for prognosis when evaluated in conjunction with genotype and age.

Competitive Sports Participation is Associated with Decreased Risk of Obesity in Children with Bicuspid Aortic Valve.

Individuals with bicuspid aortic valve (BAV) have historically been advised to avoid contact sports and isometric exercise for risk of increasing aortic dilation and valve disease. There is mounting evidence that current sports participation guidelines qualify children for a high rate of sports exclusion, and that this population is at increased risk of obesity. The primary aim of this study was to evaluate relationship between sports participation and aortic dilation in children with bicuspid aortic valve and secondarily the relationship between competitive sports participation and obesity. We performed a review of children between the ages of 8 and 17 years with isolated BAV followed at Oregon Health & Science University. We excluded those with other congenital heart diseases, genetic conditions, prior cardiac intervention, and inability to ambulate independently. Parents completed a phone survey detailing their child's level of daily activity and participation in competitive sports. Demographic information and most recent echo findings were collected from the electronic medical record. We found no difference between the aortic diameters of athletes vs non-athletes. We also found that sports participation and daily activity were both associated with a decreased likelihood of obesity (OR 0.24, 95% CI 0.078-0.73 and OR 0.24, 95% CI 0.081-0.71 respectively). In summary, in our sample population, competitive sports participation was associated with a decreased risk of obesity. Competitive sports participation does not appear to be associated with an increased risk of aortic dilation in our population.

Emergency vascular surgical care in populations with unique physiologic characteristics: Pediatric, pregnant, and frail populations.

Vascular surgical emergencies are common in vascular surgical care and require complex decision making and multidisciplinary care. They are especially challenging when they occur in patients with unique physiological characteristics, such as pediatric, pregnant, and frail patients. Among the pediatric and pregnant population, vascular emergencies are rare. This rarity challenges accurate and timely diagnosis of the vascular emergency. This landscape review summarizes these three unique populations' epidemiology and emergency vascular considerations. Understanding the epidemiology is the foundation for accurate diagnosis and subsequent management. Considering each population's unique characteristics is crucial to the emergent vascular surgical interventions decision making. Collaborative and multidisciplinary care is vital in gaining expertise in managing these special populations and achieving optimal patient outcomes.

EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis.

EMILIN1 (elastin-microfibril-interface-located-protein-1) is a structural component of the elastic fiber network and localizes to the interface between the fibrillin microfibril scaffold and the elastin core. How EMILIN1 contributes to connective tissue integrity is not fully understood. Here, we report bi-allelic EMILIN1 loss-of-function variants causative for an entity combining cutis laxa, arterial tortuosity, aneurysm formation, and bone fragility, resembling autosomal-recessive cutis laxa type 1B, due to EFEMP2 (FBLN4) deficiency. In both humans and mice, absence of EMILIN1 impairs EFEMP2 extracellular matrix deposition and LOX activity resulting in impaired elastogenesis, reduced collagen crosslinking, and aberrant growth factor signaling. Collagen fiber ultrastructure and histopathology in EMILIN1- or EFEMP2-deficient skin and aorta corroborate these findings and murine Emilin1-/- femora show abnormal trabecular bone formation and strength. Altogether, EMILIN1 connects elastic fiber network with collagen fibril formation, relevant for both bone and vascular tissue homeostasis.

Development of consensus recommendations for the management of post-operative chylothorax in paediatric CHD.

OBJECTIVE: A standardised multi-site approach to manage paediatric post-operative chylothorax does not exist and leads to unnecessary practice variation. The Chylothorax Work Group utilised the Pediatric Critical Care Consortium infrastructure to address this gap. METHODS: Over 60 multi-disciplinary providers representing 22 centres convened virtually as a quality initiative to develop an algorithm to manage paediatric post-operative chylothorax. Agreement was objectively quantified for each recommendation in the algorithm by utilising an anonymous survey. "Consensus" was defined as ≥ 80% of responses as "agree" or "strongly agree" to a recommendation. In order to determine if the algorithm recommendations would be correctly interpreted in the clinical environment, we developed ex vivo simulations and surveyed patients who developed the algorithm and patients who did not. RESULTS: The algorithm is intended for all children (<18 years of age) within 30 days of cardiac surgery. It contains rationale for 11 central chylothorax management recommendations; diagnostic criteria and evaluation, trial of fat-modified diet, stratification by volume of daily output, timing of first-line medical therapy for "low" and "high" volume patients, and timing and duration of fat-modified diet. All recommendations achieved "consensus" (agreement >80%) by the workgroup (range 81-100%). Ex vivo simulations demonstrated good understanding by developers (range 94-100%) and non-developers (73%-100%). CONCLUSIONS: The quality improvement effort represents the first multi-site algorithm for the management of paediatric post-operative chylothorax. The algorithm includes transparent and objective measures of agreement and understanding. Agreement to the algorithm recommendations was >80%, and overall understanding was 94%.

Cardiovascular Outcomes in Aortopathy: GenTAC Registry of Genetically Triggered Aortic Aneurysms and Related Conditions.

BACKGROUND: The GenTAC (Genetically Triggered Thoracic Aortic Aneurysm and Cardiovascular Conditions) Registry enrolled patients with genetic aortopathies between 2007 and 2016. OBJECTIVES: The purpose of this study was to compare age distribution and probability of elective surgery for proximal aortic aneurysm, any dissection surgery, and cardiovascular mortality among aortopathy etiologies. METHODS: The GenTAC study had a retrospective/prospective design. Participants with bicuspid aortic valve (BAV) with aneurysm (n = 879), Marfan syndrome (MFS) (n = 861), nonsyndromic heritable thoracic aortic disease (nsHTAD) (n = 378), Turner syndrome (TS) (n = 298), vascular Ehlers-Danlos syndrome (vEDS) (n = 149), and Loeys-Dietz syndrome (LDS) (n = 121) were analyzed. RESULTS: The 25% probability of elective proximal aortic aneurysm surgery was 30 years for LDS (95% CI: 18-37 years), followed by MFS (34 years; 95% CI: 32-36 years), nsHTAD (52 years; 95% CI: 48-56 years), and BAV (55 years; 95% CI: 53-58 years). Any dissection surgery 25% probability was highest in LDS (38 years; 95% CI: 33-53 years) followed by MFS (51 years; 95% CI: 46-57 years) and nsHTAD (54 years; 95% CI: 51-61 years). BAV experienced the largest relative frequency of elective surgery to any dissection surgery (254/33 = 7.7), compared with MFS (273/112 = 2.4), LDS (35/16 = 2.2), or nsHTAD (82/76 = 1.1). With MFS as the reference population, risk of any dissection surgery or cardiovascular mortality was lowest in BAV patients (HR: 0.13; 95% CI: 0.08-0.18; HR: 0.13; 95%: CI: 0.06-0.27, respectively). The greatest risk of mortality was seen in patients with vEDS. CONCLUSIONS: Marfan and LDS cohorts demonstrate age and event profiles congruent with the current understanding of syndromic aortopathies. BAV events weigh toward elective replacement with relatively few dissection surgeries. Nonsyndromic HTAD patients experience near equal probability of dissection vs prophylactic surgery, possibly because of failure of early diagnosis.

Fetal counseling for congenital heart disease: is communication effective?

PURPOSE: To assess the accuracy of maternal understanding of fetal cardiac defects following initial fetal counseling. METHODS: Pregnant women with a fetal diagnosis of congenital heart disease (CHD) were surveyed regarding understanding of their fetus's heart defect. The survey asked: (1) for a description of the heart condition; (2) how confident they were in the diagnosis; (3) whether their fetus would require heart surgery. Two fetal cardiologists evaluated the maternal qualitative description. Partners were excluded from the study. RESULTS: Fifty-one participants consented and 39 completed the survey. Mean age was 31 years, 60% had some college level or post-graduate education, 48% had Medicaid insurance, and 81% were Caucasian. More than three-quarters of participants, stated they had either "quite a bit" or "very much" understanding of their fetus's diagnosis. Maternal assessment matched the physician's assessment of accuracy with 77% (N = 30) demonstrating either "quite a bit" or a "very accurate" description of the diagnosis. All women correctly understood if their fetus would require heart surgery. Highest level of maternal education positively correlated with the accuracy of diagnosis (regression coefficient 0.48, p < .002). However, confidence in the diagnosis was independent of both education (0.30, p = .167) and maternal age (-0.03, p = .234). CONCLUSIONS: Fetal counseling is effective in conveying anatomy and the need for surgery; however, accuracy amongst women with lower levels of education and maternal confidence in understanding can be improved.

Sports participation, activity, and obesity in children who have undergone the Fontan procedure.

BACKGROUND: Children with CHD are at risk for obesity and low levels of activity. These factors are associated with an increased risk of poor outcome. Participation in organised sports is an important avenue for children to maintain physical activity, though the relationship between sports participation and obesity has not been examined in the Fontan population. METHODS: We performed a cross-sectional study of children aged 8-18 who had been evaluated between January 1, 2015 and October 1, 2019 at the Doernbecher Children's Hospital outpatient paediatric cardiology clinic and had previously undergone a Fontan. Patients were excluded if they were unable to ambulate independently or if they had undergone a heart transplant. Patient characteristics were recorded from the electronic medical record. Parents were interviewed via a telephone survey and asked to describe their child's activity levels and sports participation. RESULTS: Our final cohort included 40 individuals, 74% were male. The overall prevalence of obesity (CDC BMI >95% for sex/age) in the cohort (23%) was significantly higher in non-athletes (33%) than athletes (0) (p = 0.02). There was no difference in cardiac complications or comorbidities between athletes and non-athletes. Athletes were more likely to meet daily activity recommendations (p = 0.05). CONCLUSION: Fontan patients who do not participate in sports are significantly more likely to be obese and less likely to be active than those who do. This is the first study to demonstrate the association between competitive sports participation and decreased likelihood of obesity in the Fontan population.

Sports Participation and Exercise Restriction in Children with Isolated Bicuspid Aortic Valve.

Our study was to apply the 2015 American Heart Association/American College of Cardiology Athletic Participation Guidelines to a group of otherwise healthy school age children and young adults with bicuspid aortic valve (BAV) and describe the potential competitive sports restriction as they age. We performed a retrospective chart review of children and young adults aged 5 to 22 years with isolated BAV with at least two echocardiograms between 2000 and 2013. Using task force guidelines, exercise restriction was recommended for any of the following: (1) any dilation of the aortic root, (2) any dilation of the ascending aorta, (3) moderate aortic stenosis, (4) severe aortic regurgitation; (5) left ventricular dilation or (6) reduced shortening fraction. Of the 345 patients with isolated BAV, 202 were considered restricted at study entry. The final cohort included 123 children and young adults. Over the course of follow up, 36% (44 of 123) met restriction criteria. The most likely cause for restriction was aortic dilation (34%). Progression of aortic valve disease occurred in a minority of patients (3%). There were no reports of death, dissection or catheter or surgical based intervention. In conclusion, we found that strict adherence to current guidelines would result in restriction of more than 1/3 of school age children and young adults with BAV from some form of competitive athletics during school age years. Strict application of the current guidelines in this age group may lead to over-restriction of youths from competitive sports.

The Utility of Echocardiography in Pediatric Patients with Structurally Normal Hearts and Suspected Endocarditis.

The objective of this study was to evaluate the utility of transthoracic echocardiography (TTE) in children with structurally normal hearts suspected of having infective endocarditis (IE). We hypothesized that the diagnostic yield of TTE is minimal in low-risk patients with normal hearts. We performed a retrospective chart review of TTEs performed for concern for endocarditis at a pediatric tertiary care referral center in Portland, Oregon. Three hundred patients met inclusion criteria (< 21 years old, completed TTE for IE from 2005 to 2015, no history of congenital heart disease or endocarditis). We recorded findings that met the modified Duke criteria (MDC) including fever, positive blood culture, and vascular/immunologic findings; presence of a central line; whether or not patients were diagnosed with IE clinically; and if any changes to antibiotic regimens were made based on TTE. Ten patients (3%) had echocardiograms consistent with IE. When compared to the clinical diagnosis of IE, the positive predictive value (PPV) of one positive blood culture without other major/minor MDC was 0. Similarly, the PPV of two positive blood cultures without other major/minor criteria was 0.071. Patients should be evaluated using the MDC to assess the clinical probability of IE prior to performing a TTE. Patients with a low probability for IE should not undergo TTE as it has a low diagnostic yield and patients are unlikely to be diagnosed with disease.

Determination of right ventricular function with adjusted systolic to diastolic duration ratio after transannular patch repair of tetralogy of Fallot.

BACKGROUND: Early detection of right ventricular dysfunction after transannular patch for tetralogy of Fallot (TOF-TAP) is essential for management. OBJECTIVES: To evaluate echocardiographic metrics of ventricular function correlate with functional MRI measurements, in patients with TOF-TAP. METHODS: A retrospective review of patients with TOF-TAP between 2007 and 2017 who had an echocardiogram and MRI within six months were analyzed. Systolic to diastolic ratio (SD ratio) was measured from the tricuspid regurgitation and adjusted for heart rate. Tricuspid Annular Plane Systolic Excursion (TAPSE), Fractional Area Change (FAC), and shortening fraction (SF) were additionally measured. Echocardiographic measurements were correlated with MRI assessment of right ventricular ejection fraction (RVEF), left ventricular ejection fraction (LVEF), right ventricular end-diastolic volume index (RVEDi), and right to left ventricle volume ratio (RV/LV). RESULTS: Of the 53 patients (mean age 12.8 years) that met inclusion criteria, 45 (85%) had available TR jets for SD ratio analysis. The HR adjusted SD ratio negatively correlated with RVEF (r = -.359, P = .016), LVEF (r = -.317, P = .038) and positively with RV/LV EDV ratio (r = .347, P = .024). TAPSE, FAC, and SF measurements did not show significant correlation. CONCLUSION: In patients with TOF-TAP, there is a moderate negative correlation between heart rate adjusted SD ratio and MRI metrics of ventricular function, suggesting that decreased filling time is a marker for reduced right ventricular function. The SD ratio may be a useful echocardiographic tool for serial evaluation of in this population.

Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations.

PURPOSE: Smooth muscle dysfunction syndrome (SMDS) due to heterozygous ACTA2 arginine 179 alterations is characterized by patent ductus arteriosus, vasculopathy (aneurysm and occlusive lesions), pulmonary arterial hypertension, and other complications in smooth muscle-dependent organs. We sought to define the clinical history of SMDS to develop recommendations for evaluation and management. METHODS: Medical records of 33 patients with SMDS (median age 12 years) were abstracted and analyzed. RESULTS: All patients had congenital mydriasis and related pupillary abnormalities at birth and presented in infancy with a patent ductus arteriosus or aortopulmonary window. Patients had cerebrovascular disease characterized by small vessel disease (hyperintense periventricular white matter lesions; 95%), intracranial artery stenosis (77%), ischemic strokes (27%), and seizures (18%). Twelve (36%) patients had thoracic aortic aneurysm repair or dissection at median age of 14 years and aortic disease was fully penetrant by the age of 25 years. Three (9%) patients had axillary artery aneurysms complicated by thromboembolic episodes. Nine patients died between the ages of 0.5 and 32 years due to aortic, pulmonary, or stroke complications, or unknown causes. CONCLUSION: Based on these data, recommendations are provided for the surveillance and management of SMDS to help prevent early-onset life-threatening complications.

Echocardiographic Screening of Rheumatic Heart Disease in American Samoa.

While rheumatic heart disease (RHD) is a treatable disease nearly eradicated in the United States, it remains the most common form of acquired heart disease in the developing world. This study used echocardiographic screening to determine the prevalence of RHD in children in American Samoa. Screening took place at a subset of local schools. Private schools were recruited and public schools underwent cluster randomization based on population density. We collected survey information and performed a limited physical examination and echocardiogram using the World Heart Federation protocol for consented school children aged 5-18 years old. Of 2200 students from two private high schools and two public primary schools, 1058 subjects consented and were screened. Overall, 133 (12.9%) children were identified as having either definite (3.5%) or borderline (9.4%) RHD. Of the patients with definitive RHD, 28 subjects had abnormal mitral valves with pathologic regurgitation, three mitral stenosis, three abnormal aortic valves with pathologic regurgitation, and seven borderline mitral and aortic valve disease. Of the subjects with borderline disease, 77 had pathologic mitral regurgitation, 12 pathologic aortic regurgitation, and 7 at least two features of mitral valve disease without pathologic regurgitation or stenosis. Rheumatic heart disease remains a major cause of morbidity and mortality worldwide. The prevalence of RHD in American Samoa (12.9%) is to date the highest reported in the world literature. Echocardiographic screening of school children is feasible, while reliance on murmur and Jones criteria is not helpful in identifying children with RHD.

Bicuspid and unicuspid aortic valves: Different phenotypes of the same disease? Insight from the GenTAC Registry.

BACKGROUND: Unicuspid aortic valve (UAV) is a rare disorder, often difficult to distinguish from bicuspid aortic valve (BAV). BAV and UAV share valve pathology such as the presence of a raphe, leaflet fusion, aortic stenosis, aortic regurgitation, and/or ascending aortic dilatation, but a comprehensive echocardiographic comparison of patients with UAV and BAV has not been previously performed. METHODS: We investigated UAV and BAV patients at an early stage of disease included in GenTAC, a national registry of genetically related aortic aneurysms and associated cardiac conditions. Clinical and echocardiographic data from the GenTAC Registry were compared between 17 patients with UAV and 17 matched-controls with BAV. RESULTS: Baseline characteristics including demographics, clinical findings including family history of BAV and aortic aneurysm/coarctation, and echocardiographic variables were similar between BAV and UAV patients; aortic stenosis was more common and more severe in patients with UAV. This was evidenced by higher mean and peak gradient, smaller aortic valve area, and more advanced valvular degeneration (all P < .05). There were no significant differences in aortic dimensions, with a similar pattern of enlargement of the ascending aorta. CONCLUSIONS: The similar baseline characteristics with more accelerated aortic valve degeneration and stenosis suggest that UAV represents an extreme in the spectrum of BAV syndromes. Therefore, it is reasonable to consider application of recommendations for the management of patients with BAV to those with the rarer UAV.

Associations of Age and Sex With Marfan Phenotype: The National Heart, Lung, and Blood Institute GenTAC (Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions) Registry.

BACKGROUND: The associations of age and sex with phenotypic features of Marfan syndrome have not been systematically examined in a large cohort of both children and adults. METHODS AND RESULTS: We evaluated 789 Marfan patients enrolled in the National Heart, Lung, and Blood Institute GenTAC (Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions) Registry (53% male; mean age 31 [range: 1-86 years]). Females aged ≥15 and males aged ≥16 years were considered adults based on average age of skeletal maturity. Adults (n=606) were more likely than children (n=183) likely to have spontaneous pneumothorax, scoliosis, and striae but were comparable in revised Ghent systemic score, ectopia lentis, and most phenotypic features, including prevalence of aortic root dilatation. Prophylactic aortic root replacement and mitral valve surgery were rare during childhood versus adulthood (2% versus 35% and 1% versus 9%, respectively, both P<0.0001). Adult males were more likely than females to have aortic root dilatation (92% versus 84%), aortic regurgitation (55% versus 36%), and to have undergone prophylactic aortic root replacement (47% versus 24%), all P<0.001. Prevalence of previous aortic dissection tended to be higher in males than females (25% versus 18%, P=0.06); 44% of dissections were type B. Type B dissection was strongly associated with previous prophylactic aortic root replacement. CONCLUSIONS: Pulmonary, skeletal, and aortic complications, but not other phenotypic features, are more prevalent in adults than children in Marfan syndrome. Aortic aneurysms and prophylactic aortic surgery are more common in men. Aortic dissection, commonly type B, occurs in an appreciable proportion of Marfan patients, especially in men and after previous prophylactic aortic root replacement.

The Need for Standardized Methods for Measuring the Aorta: Multimodality Core Lab Experience From the GenTAC Registry.

OBJECTIVES: This study sought to evaluate variability in aortic measurements with multiple imaging modalities in clinical centers by comparing with a standardized measuring protocol implemented in a core laboratory. BACKGROUND: In patients with aortic disease, imaging of thoracic aorta plays a major role in risk stratifying individuals for life-threatening complications and in determining timing of surgical intervention. However, standardization of the procedures for performance of aortic measurements is lacking. METHODS: To characterize the diversity of methods used in clinical practice, we compared aortic measurements performed by echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI) at the 6 GenTAC (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions) clinical centers to those performed at the imaging core laboratory in 965 studies. Each center acquired and analyzed their images according to local protocols. The same images were subsequently analyzed blindly by the core laboratory, on the basis of a standardized protocol for all imaging modalities. Paired measurements from clinical centers and core laboratory were compared by mean of differences and intraclass correlation coefficient (ICC). RESULTS: For all segments of the ascending aorta, echocardiography showed a higher ICC (0.84 to 0.93) than CT (0.84) and MRI (0.82 to 0.90), with smaller mean of differences. MRI showed higher ICC for the arch and descending aorta (0.91 and 0.93). In a mixed adjusted model, the different imaging modalities and clinical centers were identified as sources of variability between clinical and core laboratory measurements, whereas age groups or diagnosis at enrollment were not. CONCLUSIONS: By comparing core laboratory with measurements from clinical centers, our study identified important sources of variability in aortic measurements. Furthermore, our findings with regard to CT and MRI suggest a need for imaging societies to work toward the development of unifying acquisition protocols and common measuring methods.

Association Between Adiposity and Left Ventricular Mass in Children With Hypertension.

Left ventricular hypertrophy (LVH) is prevalent among hypertensive children; however, blood pressure (BP) does not predict its presence. The authors conducted a 1-year prospective cohort study to examine the hypothesis that obesity-related risk factors are associated with left ventricular mass index (LVMI) in hypertensive children, and the association between adiposity and LVMI is mediated by BP-dependent and -independent pathways. A total of 49 hypertensive children were enrolled: 51% were overweight/obese and 41% had LVH at baseline. Children overweight/obese at baseline and follow-up had a greater LVMI increase than those of healthy weight at each visit: mean change of 6.4 g/m(2.7) vs 0.95 g/m(2.7) . Baseline body mass index z score was independently associated with LVMI change (ß=4.08, 1.54-6.61; P=.002). Only pulse pressure and serum aldosterone partially mediated this relationship. Hypertensive youth manifest multiple cardiovascular disease risk factors that worsen over time despite treatment. Of these, adiposity is most associated with LVH and increasing LVMI.

Elevated uric acid and obesity-related cardiovascular disease risk factors among hypertensive youth.

BACKGROUND: Uric acid (UA) is associated with high blood pressure in adolescents and with left ventricular hypertrophy (LVH) and cardiovascular disease (CVD) in adults. We sought to determine if UA is independently associated with CVD risk factors and left ventricular mass (LVM) over time in hypertensive youth. METHODS: This was a 1-year prospective observational study of hypertensive children aged 3-19 years. Cross-sectional and longitudinal associations of serum UA with CVD risk factors and LVM were explored. RESULTS: Of the 49 children who completed both the baseline and 12-month assessments, at baseline the mean age was 13.8 years and mean UA was 5.5 mg/dL; 24% had elevated UA, 51% were overweight/obese and 39% had LVH. Measures of adiposity, low high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, LVM and LVH were all significantly associated with elevated UA at baseline, but not with change over time. Each 1 mg/dL increase in baseline UA was associated with a 2.5 g/m(2.7) increase in the LVM index at follow-up (95% confidence interval 0.64, 4.39; p = 0.01); after adjustment for age, sex, race, body mass index z-score, change in UA, time, blood pressure and medication use, this association was no longer significant. CONCLUSIONS: Hypertensive children with elevated UA have a higher prevalence of obesity-related CVD risk factors. Among hypertensive children, UA may be a marker of adiposity and not an independent CVD risk factor.