Connie E McCoy

Youth With Obesity and Obesity-Related Type 2 Diabetes Mellitus Demonstrate Abnormalities in Carotid Structure and Function

Background— Adults with obesity or type 2 diabetes mellitus (T2DM) are at higher risk for stroke and myocardial infarction. Increased carotid intima-media thickness (cIMT) and stiffness are associated with these adverse outcomes. We compared carotid arteries in youth who were lean, were obese, or had T2DM. Methods and Results— Carotid ultrasound for cIMT measurement was performed, the Young elastic modulus and beta stiffness index were calculated, and anthropometric and laboratory values and blood pressure were measured in 182 lean, 136 obese, and 128 T2DM youth (aged 10 to 24 years). Mean differences were evaluated by ANOVA. Independent determinants of cIMT, Young elastic modulus, and beta stiffness index were determined with general linear models. Cardiovascular risk factors worsened from lean to obese to T2DM groups. T2DM subjects had greater cIMT than that in lean and obese subjects for the common carotid artery and bulb. For the internal carotid artery, cIMT measurements in both obese and T2DM groups were thicker than in the lean group. The carotid arteries were stiffer in obese and T2DM groups than in the lean group. Determinants of cIMT were group, group×age interaction, sex, and systolic blood pressure for the common carotid artery (r2=0.17); age, race, and systolic blood pressure for the bulb (r2=0.16); and age, race, sex, systolic blood pressure, and total cholesterol for the internal carotid artery (r2=0.21). Age, systolic blood pressure, and diastolic blood pressure were determinants of all measures of carotid stiffness, with sex adding to the Young elastic modulus (r2=0.23), and body mass index Z score, group, and group×age interaction contributing to the beta stiffness index (r2=0.31; all P<0.0001). Conclusions— Youth with obesity and T2DM have abnormalities in carotid thickness and stiffness that are only partially explained by traditional cardiovascular risk factors. These vascular changes should alert healthcare practitioners to address cardiovascular risk factors early to prevent an increase in the incidence of stroke and myocardial infarction.

Cardiac and Vascular Consequences of Pre‐Hypertension in Youth

Hypertension is associated with increased left ventricular mass (LVM) and carotid intima‐media thickness (cIMT), which predict cardiovascular (CV) events in adults. Whether target organ damage is found in pre‐hypertensive youth is not known. The authors measured body mass index, blood pressure, fasting glucose, insulin, lipids and C‐reactive protein, LVM/height2.7 (LVM index), diastolic function, cIMT, carotid stiffness, augmentation index, brachial artery distensibility, and pulse wave velocity (PWV) in 723 patients aged 10 to 23 years (29% with type 2 diabetes mellitus). Patients were stratified by blood pressure level (normotensive: 531, pre‐hypertensive: 65, hypertensive: 127). Adiposity and CV risk factors worsened across blood pressure group. There was a graded increase in cIMT, arterial stiffness, and LVM index and decrease in diastolic function from normotension to pre‐hypertension to hypertension. In multivariable models adjusted for CV risk factors, status as pre‐hypertension or hypertension remained an independent determinant of target organ damage for LVM, diastolic function, internal cIMT, and carotid and arterial stiffness. Pre‐hypertension is associated with cardiovascular target organ damage in adolescents and young adults.

Triglyceride to HDL-C Ratio and Increased Arterial Stiffness in Children, Adolescents, and Young Adults

BACKGROUND AND OBJECTIVE: Lipid levels are linked to early atherosclerosis. Risk stratification may be improved by using triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), which relates to arterial stiffness in adults. We tested whether TG/HDL-C was an independent predictor of arterial stiffness in youth. METHODS: Subjects 10 to 26 years old (mean 18.9 years, 39% male, 56% non-Caucasian, n = 893) had laboratory, anthropometric, blood pressure, and arterial stiffness data collected (brachial distensibility, augmentation index, carotid-femoral pulse-wave velocity). Subjects were stratified into tertiles of TG/HDL-C (low, n = 227; mid, n = 288; high, n = 379). RESULTS: There was a progressive rise in cardiovascular (CV) risk factors and arterial stiffness across TG/HDL-C ratio. The high TG/HDL-C ratio group had the stiffest vessels (all P < .03 by analysis of variance). TG/HDL-C as a continuous variable was an independent determinant of brachial distensibility in CV risk factor adjusted model and for carotid-femoral pulse-wave velocity in obese subjects, with trend for higher augmentation index. CONCLUSIONS: TG/HDL-C, an estimate of small, dense low-density lipoprotein cholesterol, is an independent determinant of arterial stiffness in adolescents and young adults, especially in obese youth. These data suggest that use of TG/HDL-C may be helpful in identifying young adults requiring aggressive intervention to prevent atherosclerotic CV diseases.

Relationship between Elevated Arterial Stiffness and Increased Left Ventricular Mass in Adolescents and Young Adults

OBJECTIVE To determine whether arterial stiffness relates to left ventricular mass (LVM) in adolescents and young adults. STUDY DESIGN Demographic, anthropometric, laboratory, echo, carotid ultrasound and arterial stiffness data were obtained in 670 subjects 10 to 24 years of age (35% male, 62% non-Caucasian). Global stiffness index (GSI) was calculated from five measures of carotid artery stiffness, augmentation index, brachial distensibility, and pulse wave velocity (1 point if ≥95th% for subjects with body mass index <85th%). Stiff arteries (S = 73) were defined as GSI ≥95th%. Differences between flexible (F = 597) and S groups were evaluated by t tests. Models were constructed to determine whether GSI was an independent determinant of LVM index or relative wall thickness (RWT). RESULTS The S group had more adverse cardiovascular risk factors, higher LVM index and RWT (P ≤ .05) with a trend for abnormal cardiac geometry. Independent determinants of LVM index were higher GSI, age, body mass index, systolic blood pressure, heart rate, glycated hemoglobin A1c, male sex, and sex-by-heart rate interaction (r(2) = 0.52; P ≤ .05). GSI was also an independent determinant of RWT. CONCLUSIONS Increased arterial stiffness in adolescents and young adults is associated with LVM index independently of traditional cardiovascular risk factors. Screening for arterial stiffness may be useful to identify high risk adolescents and young adults.

Adiposity has no direct effect on carotid intima-media thickness in adolescents and young adults: Use of structural equation modeling to elucidate indirect & direct pathways

BACKGROUND Carotid intima-media thickness (cIMT) is associated with CV events in adults. Thicker cIMT is found in youth with CV risk factors including obesity. Which risk factors have the most effect upon cIMT in youth and whether obesity has direct or indirect effects is not known. We used structural equation modeling to elucidate direct and indirect pathways through which obesity and other risk factors were associated with cIMT. METHODS We collected demographics, anthropometrics and laboratory data on 784 subjects age 10-24 years (mean 18.0 ± 3.3 years). Common, bulb and internal carotid cIMT were measured by ultrasound. Multivariable regression analysis was performed to assess independent determinants of cIMT. Analyses were repeated with structural equation modeling to determine direct and indirect effects. RESULTS Multivariable regression models explained 11%-22% of variation of cIMT. Age, sex and systolic blood pressure (BP) z-score were significant determinants of all cIMT segments. Body mass index (BMI) z-score, race, presence of type 2 diabetes mellitus (T2DM), hemoglobin A1c (HbA1c) and non-HDL were significant for some segments (all p = 0.05). The largest direct effect on cIMT was age (0.312) followed by BP (0.228), Blood glucose control (0.108) and non-HDL (0.134). BMI only had a significant indirect effect through blood glucose control, BP & non-HDL. High sensitivity C-reactive protein (CRP) had a small indirect effect through blood glucose control (all p = 0.05). CONCLUSIONS Age and BP are the major factors with direct effect on cIMT. Glucose and non-HDL were also important in this cohort with a high prevalence of T2DM. BMI only has indirect effects, through other risk factors. Traditional CV risk factors have important direct effects on cIMT in the young, but adiposity exerts its influence only through other CV risk factors.

Comparison of mercury sphygmomanometry blood pressure readings with oscillometric and central blood pressure in predicting target organ damage in youth.

ObjectiveHypertension (HT) is an important risk factor for target organ damage (TOD). New methods for measuring BP are replacing mercury sphygmomanometry in many clinics. We examined the utility of different BP measurement techniques in predicting subclinical TOD in adolescents and young adults. MethodsParticipants in a study of the cardiovascular effects of obesity and type 2 diabetes were evaluated (N=677, 18±3.3 years, 35% male, 60% non-White, 30% with type 2 diabetes). We measured adiposity, laboratory data, left ventricular mass, carotid intima-media thickness, and pulse wave velocity. BP was measured three times by mercury sphygmomanometry (BPm), using an oscillometric device (BPo), and by arterial tonometry to measure central aortic BP (BPc). Participants were stratified as normotensive, prehypertensive, or hypertensive. ResultsThe prevalence of HT in this cohort with a mean BMI of 31 was the highest on BPo measurement (16%), followed by BPm (11%) and BPc (9%; P⩽0.001) measurements. BPm was the most consistent in differentiating left ventricular mass and pulse wave velocity among participants in the prehypertensive group as compared with the normotensive and hypertensive groups. Mercury BP measurement was also more sensitive and specific at predicting greater left ventricular mass, pulse wave velocity, and carotid thickness compared with other BP measurement techniques in logistic regression. ConclusionWe conclude that mercury sphygmomanometry should remain the gold standard for evaluation of HT and the risk for TOD in adolescents and young adults.

Tefillin Use Induces Remote Ischemic Preconditioning Pathways in Healthy Males

The present study assessed whether tefillin use (tight, nonocclusive, wrapping of the arm) elicits a remote ischemic preconditioning (RIPC)-like effect in subjects with both acute and chronic use. RIPC, created by short bursts of ischemia-reperfusion, has not been successfully taken to the bedside. Several large population studies have found that Orthodox Jewish men (who wear tefillin almost daily) have decreased cardiovascular mortality compared with non-Orthodox counterparts. We hypothesized that tefillin use is a relevant component in triggering a preconditioning effect. Jewish men ( n = 20) were enrolled; 9 men were daily tefillin users (conditioned) and 11 men were nonusers of tefillin as controls (naïve). Subjects were evaluated for adherence to traditional Jewish practice, had vital signs measured, blood drawn for analysis of circulating cytokines and monocyte function, and underwent brachial flow-mediated dilation to evaluate vascular reactivity at baseline (basal) and after 30 min of using tefillin (acute treatment). Under basal conditions, both groups had similar peak systolic velocity (SV), diameter, and flow volume, although the conditioned group had higher SV at 120 s postdeflation ( P = 0.05). Acute tefillin use augmented artery diameter and flow volume in both groups, with conditioned subjects experiencing higher SV than control subjects at 90 and 120 s postdeflation ( P = 0.03 and P = 0.02, respectively). Conditioned subjects had decreased inflammation, monocyte migration and adhesion, and endothelial activation compared with control subjects at baseline. Acute use of tefillin did not significantly alter monocyte function in either group. In this pilot study, acute tefillin use improves vascular function, whereas chronic tefillin use is associated with an anti-inflammatory RIPC-like phenotype. NEW & NOTEWORTHY We hypothesized that tefillin use among Orthodox Jewish men (who practice a nonocclusive leather banding of their nondominant arm) will induce a remote ischemic preconditioning phenotype. Chronic use of tefillin in Orthodox Jewish men was associated with increased systolic velocity and attenuated inflammation and monocyte chemotaxis and adhesion versus Jewish men who do not wear tefillin. Acute use of tefillin in both populations augmented brachial artery diameter and blood flow but not inflammatory profiles compared with baseline.The present study assessed whether tefillin use (tight, nonocclusive, wrapping of the arm) elicits a remote ischemic preconditioning (RIPC)-like effect in subjects with both acute and chronic use. RIPC, created by short bursts of ischemia-reperfusion, has not been successfully taken to the bedside. Several large population studies have found that Orthodox Jewish men (who wear tefillin almost daily) have decreased cardiovascular mortality compared with non-Orthodox counterparts. We hypothesized that tefillin use is a relevant component in triggering a preconditioning effect. Jewish men ( n = 20) were enrolled; 9 men were daily tefillin users (conditioned) and 11 men were nonusers of tefillin as controls (naïve). Subjects were evaluated for adherence to traditional Jewish practice, had vital signs measured, blood drawn for analysis of circulating cytokines and monocyte function, and underwent brachial flow-mediated dilation to evaluate vascular reactivity at baseline (basal) and after 30 min of using tefillin (acute treatment). Under basal conditions, both groups had similar peak systolic velocity (SV), diameter, and flow volume, although the conditioned group had higher SV at 120 s postdeflation ( P = 0.05). Acute tefillin use augmented artery diameter and flow volume in both groups, with conditioned subjects experiencing higher SV than control subjects at 90 and 120 s postdeflation ( P = 0.03 and P = 0.02, respectively). Conditioned subjects had decreased inflammation, monocyte migration and adhesion, and endothelial activation compared with control subjects at baseline. Acute use of tefillin did not significantly alter monocyte function in either group. In this pilot study, acute tefillin use improves vascular function, whereas chronic tefillin use is associated with an anti-inflammatory RIPC-like phenotype. NEW & NOTEWORTHY We hypothesized that tefillin use among Orthodox Jewish men (who practice a nonocclusive leather banding of their nondominant arm) will induce a remote ischemic preconditioning phenotype. Chronic use of tefillin in Orthodox Jewish men was associated with increased systolic velocity and attenuated inflammation and monocyte chemotaxis and adhesion versus Jewish men who do not wear tefillin. Acute use of tefillin in both populations augmented brachial artery diameter and blood flow but not inflammatory profiles compared with baseline.

Age, Race, and Gender Influence Internal Carotid Artery Doppler Velocities in Children

Introduction Few data are available describing internal carotid artery pulsed-wave Doppler velocities in children. Therefore, mean values were obtained in healthy children and correlates of peak systolic (PSV) and end diastolic (EDV) velocities were determinants. Methods As part of an ongoing longitudinal study of cardiovascular risk factors in children, bilateral PSV and EDV were obtained in 115 subjects (age 17.0 ± 3.8 years; 37% Caucasian, 63% African American; 43% male, 57% female). Standard carotid duplex imaging was performed with a GE Vivid 7, 7–12 MHz linear array transducer. Velocities were acquired in the proximal 2 cm of each artery, placing the angle of insonation parallel to vessel wall resulting in angles of ≥50 degrees and ≤60 degrees. All velocities were measured in triplicate. Means and standard deviations of all significant variables were calculated and differences tested with t-testing. Pearson correlation coefficients between PSV, EDV, and covariates (age < or ≥ 18 years, height (HT), weight (WT), gender, systolic blood pressure) were determined. General linear models were constructed to elucidate significant determinants of velocities. Results Mean values for PSV and EDV differed significantly by age and race. PSV values differed by gender (all p < 0.02). Age and race correlated with PSV and EDV, whereas gender correlated only with PSV measures. In general linear models, when stratified by age groups, age and race were significant determinates of both velocities and HT only a determinate for PSV. Younger subjects had greater velocities. When stratified by race, results were similar, with Caucasians having increased velocities. When stratified by gender, no models were significant. Conclusion Normal PSV and EDV values are greater in children than adults and in Caucasians versus African-Americans. These may be influenced by age and race differences in HT. Proximal internal carotid pulsed Doppler velocities in children should be interpreted based by age and race.