Brachial Distensibility Research Articles

0757 Associations between Objective Sleep Health and Cardiovascular Health in Adolescents with Type 1 Diabetes

Abstract Introduction Adolescents with type 1 diabetes (T1D) are at risk for early-onset cardiovascular disease due to increased arterial stiffness, decreased endothelial function, and early-stage hypertension compared to healthy peers. Poor sleep health has been associated with greater glycemic variability, increased insulin resistance, and poorer cardiovascular health; however, the relationship between sleep and vascular health has not been studied in adolescents with T1D. The aim of this study was to evaluate associations between objectively measured sleep and cardiovascular health in this population. We hypothesized that better sleep health would correlate with better cardiovascular health. Methods Twenty-four adolescents with T1D completed the study during the academic year. Sleep was monitored for one week at home with actigraphy. Watchpat-assessed apnea hypopnea index (AHI) and vascular measures were obtained during an overnight study visit. EndoPAT estimated reactive hyperemia index (RHI) and augmentation index (AI). Dynapulse measured systolic and diastolic blood pressure (SBP, DBP), mean arterial pressure (MAP), heart rate (HR), pulse wave velocity (PWV), and brachial distensibility and resistance (BrachD, BrachR). Correlations between sleep and vascular measures were examined. Results Participants were an average age of 15.5±1.1 years (54.2% female, 83.3% White non-Hispanic, BMI 58.8 ±25.8%ile, HbA1c 7.5±1.2%). Average school night (weekday) sleep duration was 6.7±0.8 hours and average sleep efficiency (SE) was 82.8±6.9%. The majority (87.5%) of participants slept less than the clinical recommendation of 8-10 hours per night. Worse actigraphy-estimated SE was associated with higher DBP (r=-0.52, p=0.02; mean= 59.2±6.7mmHg) and MAP (r=-0.46, p=0.04; mean= 79.5±7.5mmHg). Higher AHI was associated with higher BrachR (r=0.81, p< 0.001). No significant associations were identified between sleep variables and RHI, AI, HR, PWV, or BrachD (all p>0.05). Conclusion Poorer SE and higher AHI were associated with poorer indicators of vascular health in adolescents with T1D, consistent with prior literature linking poorer sleep health with risk factors for hypertension in adults with T1D. Further research is needed to determine if improving sleep can improve cardiovascular comorbidities in adolescents with T1D. Support (if any) JDRF 2-SRA-2019-848-S-B; JDRF 2-SRA-2022-1144-M-B; Ludeman Center for Women’s Health Research COVID-19 Relief Supplemental Grant; Colorado Clinical & Translational Research Center Maternal & Child Health Pilot Award; CTSA UL1 TR002535

Relationship between Arterial Stiffness and Subsequent Cardiac Structure and Function in Young Adults with Youth-Onset Type 2 Diabetes: Results from the TODAY Study

Higher arterial stiffness may contribute to future alterations in left ventricular systolic and diastolic function. We tested this hypothesis in individuals with youth-onset type 2 diabetes from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Arterial stiffness (pulse wave velocity [carotid-femoral, femoral-foot, and carotid-radial], augmentation index, brachial distensibility) was measured in 388 participants with type 2 diabetes (mean age, 21years; diabetes duration, 7.7±1.5years). To reflect overall (composite) vascular stiffness, the five arterial stiffness measures were aggregated. An echocardiogram was performed in the same cohort 2years later. Linear regression models assessed whether composite arterial stiffness was associated with left ventricular mass index or systolic and diastolic function, independent of age, sex, race/ethnicity, current cigarette smoking, and long-term exposure (time-weighted mean values over 9.1years) of hemoglobin A1c, blood pressure, and body mass index. Interactions among arterial stiffness and time-weighted mean hemoglobin A1c, blood pressure, and body mass were also examined. After adjustment, arterial stiffness remained significantly associated with left ventricular mass index and diastolic function measured by mitral valve E/Em, despite attenuation by time-weighted mean body mass index. A significant interaction revealed a greater adverse effect of composite arterial stiffness on mitral valve E/Em among participants with higher levels of blood pressure over time. Arterial stiffness was unrelated to left ventricular systolic function. The association of higher arterial stiffness with future left ventricular diastolic dysfunction suggests the path to future heart failure may begin early in life in this setting of youth-onset type 2 diabetes. ClinicalTrials.gov NCT00081328.

Longitudinal changes in vascular stiffness and heart rate variability among young adults with youth-onset type 2 diabetes: results from the follow-up observational treatment options for type 2 diabetes in adolescents and youth (TODAY) study.

(1) To describe changes in arterial stiffness and heart rate variability (HRV) over a 5-year interval, (2) examine changes by sex and race-ethnicity, and (3) evaluate the risk factors associated with the longitudinal changes in arterial stiffness and HRV. Participants with youth-onset type 2 diabetes enrolled in the observational follow-up phase of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial had arterial stiffness [(pulse wave velocity, augmentation index, brachial distensibility] and six indices of HRV measured 5 years apart. Multivariable linear regression models assessed risk factors associated with changes in the outcomes over time. At initial vascular assessment, the 304 participants were a mean age of 21 years, 34% male, and had a mean diabetes duration of 8 years. In more than half the cohort pulse wave velocity, augmentation index and HRV increased over 5 years (p<0.01). Brachial distensibility did not change. There were no differences in the 5-year change by race/ethnicity except for a single HRV measure, where non-Hispanic Blacks had greater worsening of parasympathetic function compared to non-Hispanic Whites, p = 0.008. Blood pressure was related to greater worsening in augmentation index and pulse wave velocity. Higher hemoglobin A1c over time was related to worsening pulse wave velocity and HRV. Arterial stiffness and HRV worsened over 5 years. Blood pressure and glycemic control may be potential targets to influence adverse changes in arterial stiffness and HRV in young adults with youth-onset type 2 diabetes. ClinicalTrials.gov NCT00081328.

Dietary sodium intake and sodium load is associated with arterial stiffness in children and young adults.

The aim of this study was to examine the association of sodium intake (g/day) and sodium load (Na-L; mg/kcal/day) on arterial stiffness in youth. A cross-sectional analysis of 723 youth enrolled in a study evaluating the cardiovascular effects of obesity and type 2 diabetes mellitus (T2DM). Three measures of arterial stiffness were evaluated: brachial distensibility (BrachD), carotid-femoral pulse wave velocity (PWVcf) and augmentation index (AIx). Three-day diet histories yielded mean daily sodium and calorie intake. Youth were divided into Na-L tertiles: Low (≤1.67 mg/kcal per day); Medium (1.68--1.98 mg/kcal per day) and High (>1.98 mg/kcal per day). General linear models adjusting for demographics, % body fat, T2DM and SBP z-score evaluated the independent association of Na-L with arterial stiffness. Mean age was 17.9 years (10-24 years), 35% male, 59% nonwhite and 31% T2DM. Mean (±standard deviation) dietary intake was calories = 2074 (±797) kcal/day; Na = 3.793 (±1567) g/day; Na- = 1.86 (±0.753) mg/kcal per day. With higher levels of dietary Na intake and Na-L, measures of arterial stiffness worsened: BrachD decreased (Na intake: beta = -0.09, P = 0.003; Na-L: beta = -0.28, P < 0.0001), PWVcf increased (Na intake: beta = 0.07, P = 0.007; Na-L: beta = 0.21, P < 0.0001) but AIx did not change (Na intake: beta = -0.4, P = 0.2; Na-L: beta = 0.89, P = 0.11). In multivariable analysis, High Na-L was independently associated with BrachD, PWVcf and AIx (P < 0.05 for all), with age modifying the association of High Na-L with PWVcf and AIx. Sodium intake and load are associated with arterial stiffness, a preclinical measure of CVD, among a paediatric population. Paediatricians should stress healthy dietary choices to reduce accelerated vascular ageing.

18-OR: Longitudinal Changes in Vascular Stiffness and Heart Rate Variability (HRV) in Young Adults with Type 2 Diabetes (T2D): The TODAY Study

Little is known about how arterial stiffness and HRV progress in young adults with youth-onset T2D. We examined changes in pulse wave velocity (PWV), augmentation index (AIx), brachial distensibility and HRV over 5-years in young adults with T2D (n=304, 34% male, first assessment at mean age 21 years, mean diabetes duration 8 years) who participated in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial. Changes by sex, race/ethnicity, and the risk factors associated with the changes in arterial stiffness and HRV were assessed. PWV carotid-femoral, AIx and HRV worsened over 5-years (p<0.0001), Table. There were no differences in the 5-year change by race/ethnicity. In multivariable models, female sex (β=2.9, p=0.03) and mean arterial pressure (β=1.9 per 10 mmHg, p< 0.001) related to greater worsening in AIx. Mean arterial pressure related to PWV carotid-femoral (β=0.4 per 10 mmHg, p<0.0001). Higher time-weighted mean HbA1c, a measure of cumulative glycemic exposure, was related to worsening of both PWV carotid-femoral and HRV (β=0.1, p=0.03 and β=-3.8, p<0.0001, per 1% respectively). Targeting improvements in blood pressure and glycemic control may favorably influence the progression of arterial stiffness and HRV in T2D.View largeDownload slideView largeDownload slide DisclosureA. S. Shah: None. S. A. Arslanian: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk, Other Relationship; Self; AstraZeneca, Research Support; Self; Eli Lilly and Company, Novo Nordisk. E. M. Urbina: None. L. El ghormli: None. S. Gidding: None. K. S. Hughan: None. L. E. Katz: None. D. Koren: None. J. B. Tryggestad: None. F. Bacha: None. B. H. Braffett: None.FundingNational Institute of Diabetes and Digestive and Kidney Diseases (U01DK61212, U01DK61230, U01DK61239, U01DK61242, U01DK61254)

Abstract 17051: Bromocriptine Improves Central Aortic Stiffness in Adolescents With Type 1 Diabetes Mellitus: Arterial Health Results From the BCQR-T1D Study

Introduction: The presence of global vascular dysfunction is a well-recognized feature in youth with type 1 diabetes (T1D). This predisposes young patients to the life-long exposure and increased incidence of cardiovascular events. Therapeutic strategies to mitigate vascular dysfunction are urgently needed. Hypothesis: We hypothesized that bromocriptine quick release (BCQR) therapy would improve vascular health in youth with T1D. Methods: This was a placebo-controlled, random-order, double-blinded, cross-over study investigating BCQR as adjunct therapy on central aortic stiffness as measured by phase-contrast MRI. Participants also underwent flow mediated dilation test and brachial distensibility evaluation using tonometry. Adolescents with T1DM were randomized 1:1 to phase-1 of 4-week BCQR (minimum dose 1.6 mg daily) or placebo therapy after which all vascular measurements were performed. Following a 4-week washout period, phase 2 was performed in identical fashion with the alternate treatment. Results: Forty-two adolescents (mean age 15.9 yrs, HbA1c 8.6%, BMI %ile 71.4, TD duration 5.8 yrs) with T1D were enrolled. BCQR therapy decreased systolic (Δ = -5 mmHg, p &lt; 0.001) and diastolic blood pressure (Δ = -2 mmHg, p = 0.039). BCQR therapy reduced ascending aortic PWV (Δ = -0.4 m/s, p = 0.005), and increased RAC (Δ = -2.6%, p = 0.022), and distensibility (Δ = 0.08 %/mmHg, p = 0.010). In the thoraco-abdominal aorta, BCQR decreased PWV (Δ = -0.2 m/s, p = 0.013) and increased distensibility (Δ = 0.05 %/mmHg, P = 0.032) (FIGURE). In contrast, BCQR decreased RHI (Δ = -0.34, p = 0.006). Conclusions: BCQR therapy improved central aortic stiffness and pressure hemodynamics in adolescents with T1D over 4 weeks. However, BCQR decreased peripheral RHI. BCQR therapy might serve as a potential clinical intervention to attenuate accelerated aortic stiffness in youth with T1D supporting future longer-term studies.

Abstract P137: Women Experience A Greater Decline In Brachial Artery Distensibility With Age Than Men

Introduction: Brachial artery distensibility is reduced in type 1 diabetes and can predict future coronary artery disease (CAD). Although women generally have reduced cardiovascular risk as compared with men, type 1 diabetes increases cardiovascular risk to a greater degree in women such that their cardiovascular risk matches that in men. Sex differences in arterial distensibility may contribute to the increased cardiovascular risk in women with type 1 diabetes. Hypothesis: We tested the hypothesis that brachial distensibility differed by sex and by diabetes status in a cohort of adults with and without type 1 diabetes. Methods: We measured brachial distensibility via DynaPulse instrument (PulseMetric, San Diego, CA) in 268 adults with type 1 diabetes (mean age 44±9 years) and 373 adults without diabetes (mean age 47 ±8 years) who completed clinical study visits 8±0.89 years apart. A linear mixed model was used to calculate mean brachial distensibility by age at the study visits in men and women by diabetes status. This model was adjusted for age, sex, diabetes status, and visit number. An age group*sex*diabetes interaction was used to calculate least squares means (LSmeans) brachial distensibility and examine trends in each stratum of interest. Results: Brachial distensibility decreases with increasing age (Figure 1). This reduction is greatest for women with type 1 diabetes and smallest for men without diabetes, with decreases from the oldest to youngest age group of 2.6 %/mmHg and 0.98 %/mmHg, respectively. Prior to the age of 40 years, women have better brachial distensibility than men regardless of diabetes status, while men have better brachial distensibility than women beginning in the 40-45 years age group. Conclusions: Women experience a steeper decline in their brachial distensibility than men regardless of diabetes status. Rapid reduction in brachial distensibility may contribute to the increases in cardiovascular risk in women with type 1 diabetes.

Role of peribrachial fat as a key determinant of brachial artery dilatation for successful arteriovenous fistula maturation in hemodialysis patients

The functional quality of the inflow artery is one of the most important determinants of arteriovenous fistula (AVF) success. We evaluated the association of early optimal brachial arterial dilatation with a successful AVF maturation and assessed the role of peribrachial adipose tissue in determining brachial arterial distensibility. All patients underwent a preoperative vascular mapping with Doppler ultrasound (US), and only patients who had suitable vessels for AVF creation were enrolled (n = 162). Peribrachial fat thickness was measured using US. To evaluate the degree of brachial dilatation, follow-up US was performed at 1 month after surgery, and early brachial artery dilation was defined as the change in postoperative arterial diameter compared to the preoperative value. The primary outcome was failure to achieve a clinically functional AVF within 8 weeks. Nonfunctional AVF occurred in 21 (13.0%) patients, and they had a significantly lower brachial dilatation than patients with successful AVF during early period after surgery (0.85 vs. 0.43 mm, p = 0.003). Patients with a brachial dilatation greater than median level showed a 1.8-times higher rate of achieving a successful AVF than those without. Interestingly, the early brachial dilatation showed significant correlations with diabetes (r = −0.260, p = 0.001), peribrachial fat thickness (r = −0.301, p = 0.008), and the presence of brachial artery calcification (r = −0.178, p = 0.036). Even after adjustments for demographic factors, comorbidities, and baseline brachial flow volume, peribrachial fat thickness was an independent determinant for early brachial dilatation (β = −0.286, p = 0.013). A close interplay between the peri-brachial fat and brachial dilatation can be translated into novel clinical tools to predict successful AVF maturation.

Metformin Improves Insulin Sensitivity and Vascular Health in Youth With Type 1 Diabetes Mellitus.

Cardiovascular disease is the leading cause of mortality in type 1 diabetes mellitus (T1DM) and relates strongly to insulin resistance (IR). Lean and obese adolescents with T1DM have marked IR. Metformin improves surrogate markers of IR in T1DM, but its effect on directly measured IR and vascular health in youth with T1DM is unclear. We hypothesized that adolescents with T1DM have impaired vascular function and that metformin improves this IR and vascular dysfunction. Adolescents with T1DM and control participants underwent magnetic resonance imaging of the ascending (AA) and descending aorta to assess pulse wave velocity, relative area change, and maximal (WSSMAX) and time-averaged (WSSTA) wall shear stress. Participants with T1DM also underwent assessment of carotid intima-media thickness by ultrasound, brachial distensibility by DynaPulse, fat and lean mass by dual-energy x-ray absorptiometry, fasting laboratories after overnight glycemic control, and insulin sensitivity by hyperinsulinemic-euglycemic clamp (glucose infusion rate/insulin). Adolescents with T1DM were randomized 1:1 to 3 months of 2000 mg metformin or placebo daily, after which baseline measures were repeated. Forty-eight adolescents with T1DM who were 12 to 21 years of age (40% body mass index [BMI] ≥90th percentile; 56% female) and 24 nondiabetic control participants of similar age, BMI, and sex distribution were enrolled. Adolescents with T1DM demonstrated impaired aortic health compared with control participants, including elevated AA and descending aorta pulse wave velocity, reduced AA and descending aorta relative area change, and elevated AA and descending aorta WSSMAX and WSSTA. Adolescents with T1DM in the metformin versus placebo group had improved glucose infusion rate/insulin (12.2±3.2 [mg·kg-1·min-1]/μIU/μL versus -2.4±3.6 [mg·kg-1·min-1]/μIU/μL, P=0.005; 18.6±4.8 [mg·lean kg-1·min-1]/μIU/μL versus -3.4±5.6 [mg·lean kg-1·min-1]/μIU/μL, P=0.005) and reduced weight (-0.5±0.5 kg versus 1.6±0.5 kg; P=0.004), BMI (-0.2±0.15 kg/m2 versus 0.4±0.15 kg/m2; P=0.005), and fat mass (-0.7±0.3 kg versus 0.6±0.4 kg; P=0.01). Glucose infusion rate/insulin also improved in normal-weight participants (11.8±4.4 [mg·kg-1·min-1]/μIU/μL versus -4.5±4.4 [mg·kg-1·min-1]/μIU/μL, P=0.02; 17.6±6.7 [mg·lean kg-1·min-1]/μIU/μL versus -7.0±6.7 [mg·lean kg-1·min-1]/μIU/μL, P=0.02). The metformin group had reduced AA WSSMAX (-0.3±0.4 dyne/cm2 versus 1.5±0.5 dyne/cm2; P=0.03), AA pulse wave velocity (-1.1±1.20 m/s versus 4.1±1.6 m/s; P=0.04), and far-wall diastolic carotid intima-media thickness (-0.04±0.01 mm versus -0.00±0.01 mm; P=0.049) versus placebo. Adolescents with T1DM demonstrate IR and impaired vascular health compared with control participants. Metformin improves IR, regardless of baseline BMI, and BMI, weight, fat mass, insulin dose, and aortic and carotid health in adolescents with T1DM. Metformin may hold promise as a cardioprotective intervention in T1DM. URL: https://www.clinicaltrials.gov . Unique identifier: NCT01808690.

Prevalence of arterial stiffness in adolescents with type 2 diabetes in the TODAY cohort: Relationships to glycemic control and other risk factors

AimsWe aimed to determine the prevalence of arterial stiffness in young adults with youth-onset type 2 diabetes who previously participated in the TODAY clinical trial and whether arterial stiffness is influenced by their prior diabetes treatment assignment or glycemic control. MethodsWe measured arterial stiffness by femoral, radial, and foot pulse wave velocity (PWV), augmentation index (AIx), and brachial distensibility (BrachD) in 453 TODAY participants (age 20.8 ± 2.5 years, diabetes duration 7.6 ± 1.5 years, 36.4% male, BMI 36.7 ± 8.2 kg/m2) at a mean of 7.6 years post-randomization. Increased arterial stiffness in TODAY youth was defined compared with data from lean controls. We assessed whether glycemic control over time or diabetes treatment in TODAY was associated with arterial stiffness. ResultsArterial stiffness was identified in up to 50% of TODAY participants. Prior diabetes treatment assignment was not associated with higher arterial stiffness. Glycemic control over time was associated with PWV radial and foot only. Age, race-ethnicity, sex, higher blood pressure and BMI were also associated with higher arterial stiffness. ConclusionsNearly half of TODAY youth have increased arterial stiffness. Targeting blood pressure and perhaps obesity and glycemic control may positively impact arterial health in adolescents with type 2 diabetes.Trial registration: ClinicalTrials.govNCT00081328.

Arterial Thickness and Stiffness Are Independently Associated with Left Ventricular Strain

The aim of this study was to examine the association between myocardial strain and arterial thickness and stiffness in young adults. Increased common carotid artery intima media thickness and peripheral arterial stiffness are known to precede coronary artery disease and cardiovascular (CV) events such as myocardial infarction and congestive heart failure. However, subclinical cardiac dysfunction can be detected in high-risk adults by myocardial strain echocardiography. The authors hypothesized that increased carotid artery intima media thickness would be associated with abnormal myocardial strain in young subjects who had obesity and type 2 diabetes mellitus. CV risk factors were collected in 338 young adults participating in a prospective, cross-sectional study. The CV parameters collected included intima-media thickness, peripheral arterial stiffness by brachial distensibility, and myocardial strain and strain rate. General linear models were constructed to determine if vascular structure and function measures were independently associated with myocardial strain and strain rate. A linear relationship was found between global longitudinal strain obtained from the four-chamber view and global strain rate in systole and carotid intima-media thickness (four-chamber global longitudinal strain: β=3.0, CV risk factor-adjusted R2=0.34; global strain rate in systole: β=0.0053, R2=0.21; P≤.0001) and between four-chamber global longitudinal strain and lower brachial distensibility (β=-0.42, R2=0.22; P<.001). Adverse changes in vascular structure and function are simultaneously present with reduced myocardial systolic function.

Abstract P032: Cardiovascular Risk Factors and Brachial Distensibility in Children

Introduction: Our previous cross-sectional studies demonstrated a relationship between elevated cardiovascular risk factors and arterial stiffness in adolescents. Other investigators showed longitudinal associations between cardiovascular risk factors at age 9 and adult arterial stiffness. Therefore we sought to determine if risk factor-related increase in arterial stiffness could be demonstrated even earlier in childhood. Hypothesis: In 10-year-old children, elevated blood pressure and BMI will be associated with less brachial distensibility (greater arterial stiffness). Methods: A community sample of 232 children (age 9.6 ± 0.5 years, 52% male, 83% white) in follow up from a longitudinal study were enrolled and had the following measures collected: height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), brachial distensibility (BrachD, PulseMetric, San Diego, CA). Pearson correlation coefficients were calculated and general linear modeling was performed to evaluate the relationships between cardiovascular risk factors and arterial stiffness. Results: Participants had a mean BMI of 18.6 ± 3.4 kg/m^2, waist-to-hip ratio (WHR) of 0.9 ± 0.05, BMI z-score of 0.5 ± 1.1, SBP of 96 ± 9 mm Hg, DBP of 53 ± 11 mm Hg, SBP z-score of -0.5 ± 0.8, DBP z-score of -0.7 ± 1, and BrachD of 7.4 ± 2.2 percent change per mm Hg. The following cardiovascular risk factors were significantly associated with BrachD: WHR (r = -0.19, p = 0.005), BMI z-score (r = -0.16, p = 0.01), and SBP z-score (r = -0.14, p = 0.04). Modeling revealed both WHR and BMI z-score but not SBP z-score were associated with BrachD independent of age, sex, and race. After reducing a model simultaneously adjusting for all multiple risk factors and demographic variables, WHR, race, and age remained independently associated with BrachD. Conclusions: Associations between multiple cardiovascular risk factors (WHR, BMI, SBP) and arterial stiffness (brachial distensibility) are present in children as young as 10 years old, with WHR maintaining an independent association in a model adjusted for multiple covariates. These findings build on previous evidence that early exposure to cardiovascular risk factors can affect vascular health and support the contention that threats to cardiovascular health should be met aggressively in childhood.

Low Serum Vitamin D Levels Are Associated With Increased Arterial Stiffness in Youth With Type 2 Diabetes

OBJECTIVEAdult studies demonstrate that low vitamin D (25[OH]D) is an independent risk factor for arterial stiffness. Similar studies have not been conducted in youth with type 2 diabetes mellitus (T2DM). The objective was to elicit the association between 25[OH]D and arterial stiffness in obese youth with and without T2DM. We hypothesized that 25[OH]D would be inversely correlated with arterial stiffness indices, including pulse wave velocity (PWV), augmentation index (AIx), and brachial distensibility (BrachD).RESEARCH DESIGN AND METHODSCross-sectional analysis was conducted in Cincinnati, OH, from 2004 to 2010. 25[OH]D, PWV, AIx, and BrachD were measured in 190 youth with T2DM, 190 obese control subjects without T2DM, and 190 lean control subjects without T2DM. Multivariate analyses were conducted to elicit the independent association between 25[OH]D and arterial stiffness indices by group.RESULTSThe mean age was 17.9 ± 3.4 years, 55% were African American, and 34% were male. The mean 25[OH]D levels were 21.27, 14.29, and 14.13 ng/mL in lean individuals, obese individuals, and obese individuals with T2DM, respectively (P < 0.01). PWV, AIx, and BrachD worsened from lean to obese to T2DM (P < 0.01). General linear models found that 25[OH]D level was independently associated with PWV in lean individuals and with AIx in the group with T2DM such that a 3 ng/mL increase in 25[OH]D was associated with an AIx decrease of 1% (baseline AIx = 5.7 ± 12.0%).CONCLUSIONS25[OH]D is inversely associated with some measures of arterial stiffness in lean adolescents and obese adolescents with T2DM but not in obese normoglycemic adolescents. Future studies are needed to determine if supplemental 25[OH]D is important for cardiovascular health.

Severe Obesity in Adolescents and Young Adults Is Associated With Subclinical Cardiac and Vascular Changes.

Severe obesity is the fastest growing subgroup of obesity in youth. We sought to explore the association between severe obesity and subclinical measures of cardiac and vascular structure and function in adolescents and young adults. This was a cross-sectional comparison of 265 adolescents and young adults with severe obesity (defined as body mass index [BMI] ≥120% of the 95th percentile) to 182 adolescents and young adults with obesity (defined as BMI ≥100-119th of the 95th percentile) at tertiary medical center. Noninvasive measures of cardiac and vascular structure and function were assessed. Participants were a mean age of 17.9 years, 62% were non-Caucasian, and 68% were female. Systolic blood pressure, fasting insulin, C-reactive protein, IL-6, and frequency of type 2 diabetes were higher in participants with severe obesity (all P < .05). Arterial thickness and stiffness, cardiac structure, and diastolic function were also significantly worse in youth with severe obesity as measured by higher left ventricular mass index, worse diastolic function, higher carotid intima media thickness, and pulse wave velocity and lower brachial distensibility (all P < .05). Regression modeling showed that severe obesity (compared with obesity) was independently associated with each of the above outcomes after adjustment for age, race, sex, blood pressure, lipids, and inflammatory markers (P < .05). Adolescents and young adults with severe obesity have a more adverse cardiovascular risk profile and worse cardiac and vascular structure and function. More importantly, severe obesity is independently associated with these subclinical cardiac and vascular changes.

Arterial stiffness in adolescents and young adults with and without type 1 diabetes: the SEARCH CVD study.

Arterial stiffness is a useful parameter to predict future cardiovascular disease. We sought to compare arterial stiffness in adolescents and young adults with and without type 1 diabetes (T1D) and explore the risk factors associated with the differences observed. Carotid-femoral pulse wave velocity (PWV), augmentation index (AI75), and brachial distensibility (BrachD) were measured in 402 adolescents and young adults with T1D (age 18.8 ± 3.3 yr, T1D duration 9.8 ± 3.8 yr) and 206 non-diabetic controls that were frequency-matched by age, sex, and race/ethnicity in a cross-sectional study. General linear models were used to explore variables associated with an increase in arterial stiffness after adjustment for demographic and metabolic covariates. T1D status was associated with a higher PWV (5.9 ± 0.05 vs. 5.7 ± 0.1 m/s), AI75 (1.3 ± 0.6 vs. -1.9 ± 0.7%), and lower BrachD (6.2 ± 0.1 vs. 6.5 ± 0.1%Δ/mmHg), all p < 0.05. In multivariate models, age, sex, race, adiposity, blood pressure, lipids, and the presence of microalbuminuria were found to be independent correlates of increased arterial stiffness. After adjustment for these risk factors, T1D status was still significantly associated with arterial stiffness (p < 0.05). Peripheral and central subclinical vascular changes are present in adolescents and young adults with T1D compared to controls. Increased cardiovascular risk factors alone do not explain the observed differences in arterial stiffness among cases and controls. Identifying other risk factors associated with increased arterial stiffness in youth with T1D is critical to prevent future vascular complications.

Abstract P059: Arterial Thickness and Stiffness are Independent Predictors of Myocardial Strain

Vascular dysfunction is associated with cardiac dysfunction, a precursor of CV events (MI,CHF) in adults. We hypothesized that abnormalities in vascular structure and function are associated with cardiac systolic dysfunction as measured by cardiac strain and strain rate in young adults. Carotid ultrasound and echocardiography were performed on 338 subjects (22.2 + 3.7 years; 38% male (M); 63% non-white (NW); 33% lean, 36% obese and 31% T2DM). CIMT was traced along the far wall of the distal CCA, bulb, and proximal ICA. Stiffness measures included carotid-femoral pulse wave velocity (PWVf), brachial distensibility (BrachD) and Peterson’s Elastic Modulus in the CCA (PEM). LV systolic function was assessed by global longitudinal (4-chamber) strain (GS) and strain rate in systole (GSRs). Anthropometry, BP, HR, fasting lipids, CRP, and glucose were collected. Correlations were calculated between vascular measures and cardiac strain. General linear models were constructed to determine if vascular measures were independent predictors of GS and GSRs. Covariates included age, sex, race, BMI z-score, MAP, group, TG, HDL, LDL, insulin, glucose, and CRP. GS and GSRs correlated with peripheral arterial stiffness (lower BrachD, higher PEM, higher PWVf) and structure (thicker CIMT), all p&lt;.01 (Figure). After adjusting for other risk factors, BrachD was an independent predictor of poorer GSRs: GSRs=-1.1611 -.13*BrachD + .05 (if M) + .06 (if NW) + .004*MAP - .0003*glucose + .07*Insulin. CCA IMT independently predicted both GS and GSRs: GS=-.26 + 4.6* CCA + .92 (if M) + .58*BMIZ + .56*MAP- .03*HDL + 1.06*insulin; GSRs= -1.4 + .26*CCA+ .05 (if M) + .03*BMIZ + .003*MAP - .0003*glucose + .06*Insulin. All factors were significant at p&lt;.05 in these models. We conclude that adverse pre-clinical vascular and cardiac findings are present in youth simultaneously and may increase risk for future CV events. Assessment of vascular structure and function may add incremental benefit in stratifying risk in young adults for future CV events.

Arterial stiffness is increased in young normotensive subjects with high central blood pressure

Information on high central blood pressure (CBP; HCP) in normotensive subjects (NT) and its relation to target organ damage (TOD) is not well established in young subjects. This study aimed to elucidate determinants of HCP and its relation with TOD. Anthropometrics, lab, brachial, and CBP were obtained on 430 normotensive subjects (NT; 16–24 years, 34% male, 44% Caucasian, 27% type 2 diabetes). HCP was defined as elevated CBP, with normal brachial BP. Subjects with HCP (prevalence, 16%) were more frequently female and African American, and had a higher prevalence of obesity and diabetes, a more adverse metabolic profile, higher levels of inflammation, brachial BP, central pulse pressure, and heart rate compared with NT. HCP also had evidence for TOD with a significant higher carotid intima media thickness, left ventricular mass, augmentation index, pulse wave velocity, and lower brachial distensibility than NT. HCP is related to early cardiac and vascular dysfunction and remain an independent predictor of TOD even after adjusting for cardiovascular risk factors.

Treatment: special conditions: Co-existing heart disease: atrial fibrillation

Information on high central blood pressure (CBP; HCP) in normotensive subjects (NT) and its relation to target organ damage (TOD) is not well established in young subjects. This study aimed to elucidate determinants of HCP and its relation with TOD. Anthropometrics, lab, brachial, and CBP were obtained on 430 normotensive subjects (NT; 16–24 years, 34% male, 44% Caucasian, 27% type 2 diabetes). HCP was defined as elevated CBP, with normal brachial BP. Subjects with HCP (prevalence, 16%) were more frequently female and African American, and had a higher prevalence of obesity and diabetes, a more adverse metabolic profile, higher levels of inflammation, brachial BP, central pulse pressure, and heart rate compared with NT. HCP also had evidence for TOD with a significant higher carotid intima media thickness, left ventricular mass, augmentation index, pulse wave velocity, and lower brachial distensibility than NT. HCP is related to early cardiac and vascular dysfunction and remain an independent predictor of TOD even after adjusting for cardiovascular risk factors.

Achieving International Society for Pediatric and Adolescent Diabetes and American Diabetes Association clinical guidelines offers cardiorenal protection for youth with type 1 diabetes.

Most youth with type 1 diabetes do not meet the American Diabetes Association (ADA) and International Society for Pediatric and Adolescent Diabetes (ISPAD) targets for hemoglobin A1c (HbA1c), blood pressure (BP), lipids, and body mass index (BMI). We hypothesized that ISPAD/ADA goal achievement at baseline would be associated with cardiorenal risk factors at baseline and 2 yr follow-up in adolescents with type 1 diabetes. We assessed the cross-sectional and longitudinal relationships between ISPAD/ADA goal achievement at baseline and cardiorenal health at baseline and 2-yr follow-up (n = 297; 15.4 ± 2.1 yr at baseline) in adolescents with type 1 diabetes. Goal achievement was defined as HbA1c < 7.5%, BP < 90th percentile for age, sex, and height, low density lipoprotein-cholesterol (LDL-C) <100 mg/dL, high density lipoprotein-cholesterol (HDL-C) >35 mg/dL, triglycerides (TG) <150 mg/dL and BMI <85th percentile for age and sex. Cardiorenal outcomes included pulse-wave velocity (PWV), brachial distensibility (BrachD), augmentation index (AIx), and epidermal growth factor receptor (eGFR) continuously and categorically as hyperfiltration (eGFR ≥ 135 mL/min/1.73 m(2)). Adolescents with type 1 diabetes who met 1-3 goals, had significantly greater (P < 0.05) baseline PWV (5.1 ± 0.1 vs. 5.4 ± 0.1 m/s), follow-up PWV (5.5 ± 0.1 vs. 5.7 ± 0.1 m/s), greater follow-up eGFR (104 ± 2 vs. 116 ± 3 mL/min/1.73 m(2)), and greater odds of renal hyperfiltration at follow-up (odds ratio (OR): 20.0, 95% confidence interval (CI): 3.8-105.2) compared to those who met 4-6 goals after adjusting for Tanner stage, sex, age, and diabetes duration. No statistically significant differences in the cardiorenal outcomes were observed between adolescents with type 1 diabetes who met 4-6 goals and non-diabetic controls (n = 96). In adolescents with type 1 diabetes, baseline ADA/ISPAD goal achievement was associated with cardiorenal protection at baseline and 2-yr follow-up.

Associations of dietary intake patterns identified using reduced rank regression with markers of arterial stiffness among youth with type 1 diabetes.

Youth with type 1 diabetes (T1DM) are at substantially increased risk for adverse vascular outcomes, but little is known about the influence of dietary behavior on cardiovascular disease (CVD) risk profile. We aimed to identify dietary intake patterns associated with CVD risk factors and evaluate their impact on arterial stiffness (AS) measures collected thereafter in a cohort of youth with T1DM. Baseline diet data from a food frequency questionnaire and CVD risk factors (triglycerides, low density lipoprotein-cholesterol, systolic blood pressure, hemoglobin A1c, C-reactive protein and waist circumference) were available for 1153 youth aged ⩾10 years with T1DM from the SEARCH for Diabetes in Youth Study. A dietary intake pattern was identified using 33 food groups as predictors and six CVD risk factors as responses in reduced rank regression (RRR) analysis. Associations of this RRR-derived dietary pattern with AS measures (augmentation index (AIx75), n=229; pulse wave velocity, n=237; and brachial distensibility, n=228) were then assessed using linear regression. The RRR-derived pattern was characterized by high intakes of sugar-sweetened beverages (SSB) and diet soda, eggs, potatoes and high-fat meats and low intakes of sweets/desserts and low-fat dairy; major contributors were SSB and diet soda. This pattern captured the largest variability in adverse CVD risk profile and was subsequently associated with AIx75 (β=0.47; P<0.01). The mean difference in AIx75 concentration between the highest and the lowest dietary pattern quartiles was 4.3% in fully adjusted model. Intervention strategies to reduce consumption of unhealthy foods and beverages among youth with T1DM may significantly improve CVD risk profile and ultimately reduce the risk for AS.