RESUMO
OBJECTIVE: To describe enrollment characteristics of youth in the Cascade Screening for Awareness and Detection of FH Registry. STUDY DESIGN: This is a cross-sectional analysis of 493 participants aged <18 years with heterozygous familial hypercholesterolemia recruited from US lipid clinics (n = 20) between April 1, 2014, and January 12, 2018. At enrollment, some were new patients and some were already in care. Clinical characteristics are described, including lipid levels and lipid-lowering treatments. RESULTS: Mean age at diagnosis was 9.4 (4.0) years; 47% female, 68% white and 12% Hispanic. Average (SD) highest Low-density lipoprotein cholesterol (LDL-C) was 238 (61) mg/dL before treatment. Lipid-lowering therapy was used by 64% of participants; 56% were treated with statin. LDL-C declined 84 mg/dL (33%) among those treated with lipid-lowering therapy; statins produced the greatest decline, 100 mg/dL (39% reduction). At enrollment, 39% had reached an LDL-C goal, either <130 mg/dL or ≥50% decrease from pre-treatment; 20% of those on lipid-lowering therapy reached both goals. CONCLUSIONS: Among youth enrolled in the Cascade Screening for Awareness and Detection of FH Registry, diagnosis occurred relatively late, only 77% of children eligible for lipid-lowering therapy were receiving treatment, and only 39% of those treated met their LDL-C goal. Opportunities exist for earlier diagnosis, broader use of lipid-lowering therapy, and greater reduction of LDL-C levels.
Assuntos
Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/terapia , Adolescente , Anticolesterolemiantes/uso terapêutico , Criança , LDL-Colesterol/sangue , Doença da Artéria Coronariana/prevenção & controle , Estudos Transversais , Suplementos Nutricionais , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/sangue , Estilo de Vida , Masculino , Sistema de Registros , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Lower pulmonary artery acceleration time (PAcT) is correlated with higher pulmonary artery pressure. The aim of this study was to test the hypothesis that PAcT measured in young adulthood would be associated with future cardiovascular outcomes. METHODS: In the Coronary Artery Risk Development in Young Adults year 5 examination (1990-1991), PAcT was measured as the time interval from onset to peak flow velocity at the pulmonary valve annulus on Doppler echocardiography. The primary outcome was a composite of fatal or nonfatal cardiovascular disease events: myocardial infarction, non-myocardial infarction acute coronary syndrome, coronary revascularization, congestive heart failure, stroke, transient ischemic attack, carotid artery disease, and peripheral arterial disease. RESULTS: PAcT was obtained in 4,171 participants (mean age, 30 ± 4 years, 55% women, 51% white). PAcT groups obtained using linear spline methodology were as follows: group I, PAcT ≥ 196 msec (n = 122); group II, PAcT < 196 and ≥115 msec (n = 3,195); and group III, PAcT < 115 msec (n = 854). During follow-up (median, 24.9 years), the primary outcome occurred in 216 participants (5.2%); 66 of 854 (7.7%) of those with PAcT < 115 msec, 149 of 3,195 (4.7%) of those with intermediate PAcT level, and one of 122 (0.8%) of those with PAcT ≥ 196 msec. In a fully adjusted model, the lowest and intermediate PAcT groups had hazard ratios of 8.3 (95% CI, 1.1-62.1; P = .04) and 6.8 (95% CI, 0.9-50.5; P = .06), respectively, in comparison with the highest PAcT group. CONCLUSIONS: PAcT is useful for better identifying young adults at higher risk for cardiovascular events, who may benefit from a strict control of modifiable cardiovascular risk factors.
Assuntos
Doenças Cardiovasculares/fisiopatologia , Vasos Coronários/fisiopatologia , Ecocardiografia Doppler/métodos , Artéria Pulmonar/fisiopatologia , Adolescente , Adulto , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Incidência , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Artéria Pulmonar/diagnóstico por imagem , Medição de Risco/métodos , Fatores de Risco , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OBJECTIVES: To test whether youth with Down syndrome have aortic stiffness indices, as measured by pulse wave velocity (PWV), that differ from youth without Down syndrome and to compare reference-based age-adjusted (age-PWV-Z) and height-adjusted (Ht-PWV-Z) in youth with and without Down syndrome. STUDY DESIGN: Cross-sectional study of PWV in 129 adolescents with Down syndrome and 97 youth of comparable age, sex, race/ethnicity, and body mass index (BMI). PWV, age-PWV-Z, and Ht-PWV-Z were compared. Regression models were developed to test for associations with PWV. RESULTS: Youth with Down syndrome and controls were comparable in BMI-Z (1.4 [-1.5 to 2.8] vs 1.2 [-2.0 to 2.8], P = .57) but not Ht-Z (-2.3 [-4.7 to 0.8] vs 0.4 [-2.0 to 2.6], P < .0001). PWV (m/s, 5.0 [3.1-7.9] vs 5.0 [3.6-8.0], P = .5) and mean arterial pressure (MAP, mm Hg) (78 [61-102] vs 74 [64-97], P = .09) were not different between groups. In adjusted analyses confined to Down syndrome, PWV was associated only with BMI, but not age, black race, or MAP (R2 = 0.11). In contrast, BMI, age, black race, and MAP were all positively associated with and better explained PWV in controls (R2 = 0.50). PWV was not associated with height in youth with or without Down syndrome. Although age-PWV-Z was not different in Down syndrome (-0.36 [-2.93 to 3.49]) vs -0.15 [-2.32 to 3.22]), Ht-PWV-Z was greater in Down syndrome (0.32 [-2.28 to 4.07] vs -0.08 [-2.64 to 2.64], P = .002), and Ht-PWV-Z was greater than age-PWV-Z in Down syndrome (P < .0001). CONCLUSIONS: The lack of relationship of PWV, an independent predictor of adult cardiovascular events, with its traditional determinants including MAP suggests Down syndrome-specific phenomena may alter such relationships in this population. In youth with Down syndrome, Ht-adjusted PWV may overestimate aortic stiffness. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01821300.
Assuntos
Síndrome de Down/fisiopatologia , Rigidez Vascular , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Análise de Onda de Pulso/métodos , Adulto JovemRESUMO
OBJECTIVES: Data regarding atherogenic dyslipidemia and the inflammation profile in youth with type 2 diabetes is limited and the effect of insulin therapy on these variables has not previously been studied in youth. We determined the impact of insulin therapy on lipid and inflammatory markers in youth with poorly controlled type 2 diabetes. STUDY DESIGN: In the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) multicenter trial, 285 participants failed to sustain glycemic control on randomized treatment (primary outcome, glycated hemoglobin A1c [HbA1c] at ≥8% for 6 months); 363 maintained glycemic control (never reached primary outcome). Statins were used for a low-density lipoprotein cholesterol of ≥130 mg/dL. Upon reaching the primary outcome, insulin was started. Changes in lipids and inflammatory markers (slopes over time) were examined. RESULTS: Progression of dyslipidemia was related to glycemic control. In those with the primary outcome, insulin therapy impacted HbA1c modestly, and dampened the increase in total cholesterol, low-density lipoprotein cholesterol, and total apolipoprotein B, although statin use increased from 8.6% to 22% year after the primary outcome. The increase in triglycerides and plasma nonesterified fatty acids stabilized after insulin was started, independent of HbA1c. There was an increase in high-sensitivity C-reactive protein that continued after insulin initiation, related to HbA1c and percent overweight. CONCLUSIONS: Worsening dyslipidemia and inflammation over time raise concern regarding premature development of atherosclerosis in youth with type 2 diabetes. Insulin therapy has a limited benefit in the absence of glycemic control. Strategies to achieve better glycemic control are needed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00081328.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Dislipidemias/sangue , Insulina/uso terapêutico , Lipídeos/sangue , Adolescente , Glicemia/análise , Criança , LDL-Colesterol/sangue , Progressão da Doença , Feminino , Hemoglobinas Glicadas/análise , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inflamação , MasculinoRESUMO
OBJECTIVES: To examine cardiac biomarkers over time in youth-onset type 2 diabetes, and relate serum concentrations to cardiovascular disease risk factors, and left ventricular structure and function. STUDY DESIGN: TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) was a multicenter randomized trial of 3 treatments including 521 participants with type 2 diabetes, aged 10-17 years, and with 2-6 years of follow-up. Participants were 36% male, obese, and ethnically diverse. Annual serum concentrations of brain natriuretic peptide, troponin, tumor necrosis factor (TNF)-α, receptors 1 and 2 were related to blood pressure, body mass index, hemoglobin A1c, and left ventricular ejection fraction, diastolic function, relative wall thickness, and mass. RESULTS: Elevated concentrations of brain natriuretic peptide (≥100 pg/mL), TNF-α (≥5.6 pg/mL) and troponin (≥0.01 ng/mL), were present in 17.8%, 18.3%, and 34.2% of the cohort, respectively, at baseline, and in 15.4%, 17.1%, and 31.1% at the end of the study, with wide variability over time, without persistence in individuals or clear relationship to glycemia or cardiovascular structure/function. TNF receptors concentrations were increased at baseline and not significantly different from end-of-study concentrations. Adverse echocardiographic measures were more likely in the highest TNF receptor tertile (all P < .05): higher left ventricular mass (39.3 ± 9.0 g/m2.7), left atrial internal dimension (3.7 ± 0.4 cm) and E/Em ratio, a measure of diastolic dysfunction (6.2 ± 1.9). After adjustment for body mass index, these relationships were no longer significant. CONCLUSIONS: Elevated serum concentrations of cardiac biomarkers were common in youth with type 2 diabetes, but their clinical significance is unclear and will require further long-term study. TRIAL REGISTRATION: ClinicalTrials.govNCT00081328.