Background: Platelet function testing remains a challenge in evaluation of bleeding disorders. The literature suggests a highly variable rate of qualitative platelet defects (QPDs) among individuals with bleeding symptoms. However, diagnosis of platelet disorders is complicated by the need for testing fresh platelets and the requirement of specialized expertise and equipment for performing the assays. Thus, typically only tertiary care centers have the ability to perform comprehensive platelet testing. Platelet testing may be especially difficult in pediatrics, when required blood volume and challenging phlebotomy may limit the age at which patients can be tested. Thus, a test that would allow effective screening of patients without the need for specialized expertise would be of benefit, especially if testing could be accomplished on a smaller quantity of blood. Multiple electrode aggregometry (MEA) is a whole blood, impedance based platelet function assay using standardized reagents and automated pipetting. Indeed, MEA is currently utilized as point-of-care testing for both ASA and P2Y12 inhibitors. MEA has the further advantage of requiring significantly less blood volume for aggregation testing.

Dyslipidemia is a major risk factor for CVD. Previous studies on lipid heritability have largely focused on white populations assessed after the obesity epidemic. Given secular trends and racial differences in lipid levels, this study explored whether lipid heritability is consistent across time and between races. African American and white nuclear families had fasting lipids measured in the 1970s and 22–30 years later. Heritability was estimated, and bivariate analyses between visits were conducted by race using variance components analysis. A total of 1,454 individuals (age 14.1/40.6 for offspring/parents at baseline; 39.6/66.5 at follow-up) in 373 families (286 white, 87 African American) were included. Lipid trait heritabilities were typically stronger during the 1970s than the 2000s. At baseline, additive genetic variation for LDL was significantly lower in African Americans than whites (P = 0.015). Shared genetic contribution to lipid variability over time was significant in both whites (all P < 0.0001) and African Americans (P ≤ 0.05 for total, LDL, and HDL cholesterol). African American families demonstrated shared environmental contributions to lipid variation over time (all P ≤ 0.05). Lower heritability, lower LDL genetic variance, and durable environmental effects across the obesity epidemic in African American families suggest race-specific approaches are needed to clarify the genetic etiology of lipids.

Objective To evaluate the relationships of adiponectin levels at age 16 years in obese schoolgirls to metabolic syndrome and its components at age 23 years.Study design Seven-year prospective study of 381 females.Results In 144 white and 129 black non-obese 16-year old girls (body mass index < 24.6 kg/m(2)), race-specific median adiponectin levels (white 12 mg/L, black 11) was used to identify paradoxically high adiponectin levels in obese girls. Of 34 white and 74 black obese girls, 12 (35%) and 19 (26%) had paradoxically high adiponectin levels. In these 108 obese girls, adiponectin levels at age 16 years independently predicted high-density lipoprotein cholesterol (positive) and waist (negative), insulin (negative), and glucose (negative) at age 23 years; paradoxically high adiponectin levels at age 16 years was a negative independent predictor for waist, homeostatic model assessment-insulin resistance, and for the number of abnormal components of the metabolic syndrome at age 23 years. In 31 pairs of obese girls with and without paradoxically high adiponectin levels, matched by race and age 16 body mass index, adiponectin levels at age 16 years was a negative predictor for the number of abnormal metabolic syndrome components at age 23 years.Conclusion Paradoxically high adiponectin levels in obese 16 year old girls protects against metabolic syndrome and its components at age 23 years. (J Pediatr 2011; 158: 208-14).

OBJECTIVE:To determine to what degree annual reports from ages 14 to 19 years of menstrual cycles ≥42 days would be associated with increased body mass index (BMI), waist circumference, glucose, insulin, and homeostasis model assessment insulin resistance (HOMA-IR) at ages 14-25 years. DESIGN:Prospective 11-year follow-up from ages 14 to 25 years. SETTING:Urban-suburban schools, post-high school. PATIENT(S):A total of 370 schoolgirls. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):BMI, waist, insulin, glucose, HOMA-IR. RESULT(S):From ages 14 to 19 years, 269 girls had 0/6 annual reports of menstrual cycles ≥42 days, 74 had 1, 19 had 2, and 8 had ≥3. Among these four categories, girls with ≥3 annual reports had highest free T and DHEAS at age 14, highest BMI and waist at ages 14, 19, and 25, highest insulin at age 25, and highest glucose and HOMA-IR at age 24 years. The number of annual reports of menstrual cycles ≥42 days was positively related to change in BMI and waist and inversely with change in high-density lipoprotein cholesterol from ages 14 to 25 years. CONCLUSION(S):Three or more annual reports of menstrual cycles ≥42 days during ages 14-19 are associated with high BMI, waist circumference, insulin, glucose, and HOMA-IR at ages 14-25 years.

OBJECTIVE:We hypothesized that oligomenorrhea (menstrual cyclicity ≥42 days), hyperandrogenism, low levels of sex hormone-binding globulin (SHBG), childhood insulin, and metabolic syndrome (MetS) at age 14 years would predict MetS and class III obesity (body mass index ≥40 kg/m(2)) at age 24 years.STUDY DESIGN:In this prospective study of schoolgirls, at age 14 years, the girls were categorized as regularly cycling (n = 375), oligomenorrheic (n = 18), or oligomenorrhea plus biochemical hyperandrogenism (polycystic ovary syndrome [PCOS]; n = 12), together designated PCOS.RESULTS:Significant explanatory variables for MetS at age 24 years included childhood insulin, MetS, and PCOS category (all positive) and SHBG (negative) at age 14 years. Using categorical data, top decile of childhood insulin, MetS at age 14, bottom decile of SHBG, and PCOS category were significant positive predictors for MetS at age 24. SHBG (negative), black race (positive), and oligomenorrhea (positive) were significant explanatory variables for class III obesity at age 24. Using categorical data, black race, MetS at age 14, bottom decile of SHBG, PCOS category, and top decile of childhood insulin were positive explanatory variables for class III obesity at age 24 years.CONCLUSIONS:Oligomenorrhea, PCOS (a subcohort of oligomenorrhea), hyperandrogenism, low SHBG, MetS, and childhood insulin at age 14 years may represent a critical, reversible pathway for the development of MetS and class III obesity in young adulthood.

Objective To evaluate the relationships of adiponectin levels at age 16 years in obese schoolgirls to metabolic syndrome and its components at age 23 years. Study design Seven-year prospective study of 381 females. Results In 144 white and 129 black non-obese 16-year old girls (body mass index < 24.6 kg/m), race-specific median adiponectin levels (white 12 mg/L, black 11) was used to identify paradoxically high adiponectin levels in obese girls. Of 34 white and 74 black obese girls, 12 (35%) and 19 (26%) had paradoxically high adiponectin levels. In these 108 obese girls, adiponectin levels at age 16 years independently predicted high-density lipoprotein cholesterol (positive) and waist (negative), insulin (negative), and glucose (negative) at age 23 years; paradoxically high adiponectin levels at age 16 years was a negative independent predictor for waist, homeostaticmodel assessment– insulin resistance, and for the number of abnormal components of the metabolic syndrome at age 23 years. In 31 pairs of obese girls with and without paradoxically high adiponectin levels, matched by race and age 16 body mass index, adiponectin levels at age 16 years was a negative predictor for the number of abnormal metabolic syndrome components at age 23 years. Conclusion Paradoxically high adiponectin levels in obese 16 year old girls protects against metabolic syndrome and its components at age 23 years. (J Pediatr 2011;158:208-14).

Objective. We assessed adolescent anthropometry, lipids, insulin, glucose, and blood pressures to identify factors associated with high-sensitivity C-reactive protein (hsCRP) and its tracking in young adults. Methods. Ten-year prospective study of 589 schoolgirls, 321 black, 268 white. Results. HsCRP did not differ (P > .08) by race or oral contraceptive use. HsCRP tracked from age 16 to 25 (r = 0.77), 16 to 26 (r = 0.50), 24 to 26 (r = 0.66), and 25 to 26 (r = 0.71), all P ≤ .02. By stepwise regression, at age 16, waist circumference accounted for 44.8% of hsCRP variance; BMI accounted for 33.1%, 34.4%, and 31.1% at ages 24, 25, and 26, P < .0001 for all. Changes in cholesterol and BMI were associated with change in hsCRP from age 24–26 (partial R 2 = 12.3%  P < .0001, 6.6%  P = .0012). Changes in BMI and triglyceride (partial R 2 = 8.5%  P = .0001, 3.3%, P = .0045) were associated with change in hsCRP from age 25 to 26. Conclusions. HsCRP tracks from age 16 to 26, with BMI, waist circumference, and cholesterol as major determinants.

Although adiponectin is correlated inversely with obesity, some obese adults without metabolic complications of obesity have paradoxically high adiponectin. Therefore, we assessed adiponectin risk factor relations in 133 obese 16-year-old school girls from a cohort of 448, focusing on paradoxically high adiponectin-risk in obesity and the healthy obese phenotype. Median adiponectin (11.9 mg/L) in nonobese girls (body mass index (BMI) < 24.6 kg/m(2)) was selected as a cutpoint to identify high adiponectin in obese girls. Of 90 black and 43 white obese girls (BMI >= 24.6), 25 black (28%) and 13 white (30%) girls had paradoxically high adiponectin (>11.9). The 38 obese girls with adiponectin >11.9 versus the 95 obese girls with adiponectin <= 11.9 had higher median high-density lipoprotein (HDL) cholesterol (54 vs 46 mg/dL, P = 0.0007) and apolipoprotein A1 (ApoA1) (181 vs 164 mg/dL, P = 0.011) and had lower insulin (14 vs 20 uU/mL, P = 0.0006). In the 133 obese girls, through stepwise regression, the adiponectin category (>11.9, 5 11.9 mg/L) was a significant independent positive determinant of HDL cholesterol (partial r(2) = 8.4%, P = 0.001), ApoA1 (partial r(2) = 4.1%, P = 0.025), and it was associated inversely with fasting serum insulin (partial r(2) = 5.4%, P = 0.0074). By stepwise logistic regression in the 133 obese girls, the adiponectin category (high vs low) was a significant inverse explanatory variable for metabolic syndrome (odds ratio 0.20, 95% confidence intervals 0.04-0.95, P = 0.043). We conclude that paradoxically high adiponectin is associated with the healthy obese phenotype in obese adolescent black and white girls. (Translational Research 2010;156:302-308)

Adolescent girls with polycystic ovary syndrome (PCOS) have increased levels of factors constituting the metabolic syndrome: centripetal obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), and hyperinsulinemia. Given the strong association reported between early, persistent obesity and development of metabolic syndrome 10 years later in girls, we speculated that if adolescent girls without PCOS had obesity measures similar to girls with PCOS, they would exhibit similar metabolic syndrome-cardiovascular disease risk factors. Within this context, we compared 37 adolescent girls with PCOS and 2 samples of normal, regularly cycling adolescent girls (controls) of similar ages, selected from the Cincinnati Clinic of the National Heart, Lung, and Blood Institute Growth and Health Study. The first sample included 157 controls selected using a stratified random sample based on age. As expected, girls with PCOS had higher body mass index (BMI), waist circumference, insulin, systolic blood pressure (SBP) and diastolic blood pressure, triglycerides (TGs), lower HDL-C, and higher low-density lipoprotein cholesterol (LDL-C) and free testosterone (FT) than controls. A second sample consisted of girls matched one to one with girls with PCOS for BMI and age. Comparisons of group differences were not significant for insulin, lipids, or blood pressure; girls with PCOS had a trend toward higher values for waist circumference (median, 92.7 vs 87.5 cm; P = .07) and much higher median FT (4.25 vs 1.42 ng/mL, P = .0001). After matching for BMI and age, by conditional regression analysis, we showed that the groups were not differentiated (P > .15) by insulin, HDL-C, LDL-C, TG, SBP, or diastolic blood pressure, but were differentiated by higher FT (P = .0024) and waist circumference (P = .0024) in PCOS than in controls. Prospective longitudinal analyses of NHGS controls showed that changes in BMI from ages 9 to 10 years to ages 15 to 16 years were positively associated with changes in waist circumference (P < .0001), LDL-C (P = .01), TG (P = .008), and SBP (P = .002). These findings suggest that if adolescent girls achieve adiposity equal to girls with PCOS, they then acquire major components of the metabolic syndrome, and excluding high FT and waist circumference, comparable increased cardiovascular disease risk.