Lower Reactive Hyperemia Index Research Articles

The impact of prediabetes and diabetes on endothelial function in a large population-based cohort

Background Diabetes and prediabetes are well-recognized risk factors for cardiovascular disease (CVD) and are marked by vascular endothelial dysfunction (ED). However, there is a scarcity of thorough population-based studies examining ED in individuals with diabetes/prediabetes free from manifest CVD. Here, we examined the association between ED assessed by reactive hyperaemia index (RHI) in the finger and diabetes/prediabetes in a large middle-aged population cohort. Methods Within the Malmö Offspring Study, following the exclusion of participants <30 years and participants with prevalent CVD, 1384 participants had complete data on all covariates. The RHI was calculated using pulse amplitude tonometry. ED was defined as RHI < 1.67. Multivariable logistic and linear regression models were conducted to investigate associations between ED and RHI with diabetes and prediabetes. Results The study population had a mean age of 53.6 ± 7.6 years (53% women). In study participants with manifest diabetes (n = 121) and prediabetes (n = 514), ED was present in 42% and 25% respectively, compared to 23% in those with normal glucometabolic status. In multivariable logistic regression analyses, prevalent diabetes was significantly associated with ED (OR 1.95; 95%CI 1.57-3.39; p = 0.002), as well as with lower RHI (β-coeff. -0.087; p = 0.002). However, prediabetes showed no association with neither ED nor RHI. Conclusion In a population free from CVD, vascular endothelial dysfunction was primarily associated with manifest diabetes, but not with prediabetes, implying that finger ED may develop when diabetes is established, rather than being an early sign of glucose intolerance. Further research is needed to explore whether addressing glucose intolerance could potentially delay or prevent vascular ED onset.

Prognostic value of peripheral endothelial function on major adverse cardiovascular events above traditional risk factors.

This study aims to identify whether adding peripheral microvascular dysfunction (PMED), a marker of atherosclerosis to established risk scores has an incremental prognostic value for major adverse cardiovascular events (MACE). This is a retrospective study of patients who underwent measuring peripheral arterial tonometry from 2006 to 2020. The optimal cut-off value of the reactive hyperaemia index (RHI) that had maximal prognostic value associated with MACE was calculated. Peripheral microvascular endothelial dysfunction was defined as the RHI lower than the cut-off. Traditional cardiovascular risk factors such as age, sex, congestive heart failure, hypertension, diabetes, stroke, and vascular disease were determined to calculate the CHA2DS2-Vasc score. The outcome was MACE defined as myocardial infarction, heart failure hospitalization, cerebrovascular events, and all-cause mortality. A total of 1460 patients were enrolled (average age 51.4 ± 13.6, 64.1% female). The optimal cut-off value of the RHI was 1.83 in the overall population and in females and males was 1.61 and 1.8, respectively. The risk of MACE during 7 [interquartile range (IQR): 5,11] years of follow-up was 11.2%. Kaplan-Meier analysis showed that lower RHI is associated with worse MACE-free survival (P < 0.001). Multivariate Cox proportional hazard analysis, controlling for classic cardiovascular risk factors or risk scores such as CHA2DS2-Vasc and Framingham risk score revealed that PMED is an independent predictor of MACE. Peripheral microvascular dysfunction predicts cardiovascular events. Non-invasive assessment of peripheral endothelial function may be useful in early detection and improving the stratification of high-risk patients for cardiovascular events.

Clinical value of the platelet and inflammatory factor activation in vascular endothelial injury in essential hypertension.

To investigate the clinical value of platelet and inflammatory factor activation in vascular endothelial injury in hypertension. A total of 120 hypertension patients diagnosed in our hospital from December 2019 to June 2021 were enrolled as study objects (Hypertension group); besides, another cohort of 60 healthy people undergoing physical examination at the same period were recruited as the controls (Control group). Next, the baseline clinical characteristics of subjects in the two groups were recorded and compared. Specifically, a hematology analyzer was adopt for detecting the mean platelet volume (MPV), platelet distribution width (PDW) and platelet hematocrit (PCT); ELISA for the level of IL-6, IL-8 and TNF-α; PHILIPS EPIQ 7 C (a device assessing endothelial vasodilator function in a non-invasive fashion) for reactive hyperemia index (RHI); univariate and multivariate regression analysis for risk factors triggering endothelial dysfunction; and Spearman correlation analysis for the correlation of platelet activation indicators and inflammatory factor level with vascular endothelial function. Compared with the Control group, the patients in the Hypertension group exhibited higher levels of MPV, PDW, PCT, inflammatory factors (IL-6, IL-8 and TNF-α) and lower RHI. Moreover, Spearman correlation analysis showed a significant negative correlation of MPV, PDW, PCT, IL-6, IL-8 and TNF-α level with RHI level. In addition, univariate and multivariate regression analysis presented that MPV, PCT, IL-8 and TNF-α were risk factors for vascular endothelial dysfunction. The activation of platelet and inflammatory factor is closely related to vascular endothelial function injury in patients with hypertension. To be specifically, platelet and inflammatory factor activation can effectively reflect the vascular endothelial function injury in patients with hypertension and has high clinical value.

Abstract P407: Sex Differences in Microvascular Response to Mental Stress and Adverse Cardiovascular Events Among Patients With Ischemic Heart Disease

Introduction: Microvascular dysfunction during acute mental stress may be an important determinant of major adverse cardiovascular outcomes (MACE) especially among middle-aged women survivors of an acute myocardial infarction (MI). Hypothesis: There are sex differences in the association between microvascular dysfunction and MACE. Methods: The Myocardial Infarction and Mental Stress Study 2 enrolled individuals who had been hospitalized for an MI in the past 8 months at the age of 60 years or younger, with an oversampling of women. Reactive hyperemia index (RHI) was used to measure digital microvascular function before and 30 minutes after a public-speaking mental stress task. This assessment was contrasted with macrovascular endothelial function at the brachial artery through flow-mediated dilation (FMD). Participants were followed for 5-years, and MACE was defined as a composite of cardiovascular death, first/recurring events for nonfatal MI, and hospitalizations for heart failure. Cox proportional hazards models were used to examine vascular response to stress (difference between post-stress and resting values) and MACE adjusting for demographics, clinical risk factors, medications, psychological factors, and mental stress ischemia. Lower RHI and FMD values are indicative of greater microvascular and endothelial dysfunction, respectively. Results: Of 263 participants, the mean age was 51 years and 48% were women. There were 64 patients with 141 adverse cardiovascular events (first and repeated). In the overall sample, there was no significant association between microvascular response to stress and MACE, but there was a significant interaction with sex (p = 0.03). Each standard deviation decrease in RHI response to stress was associated with 50% greater risk of MACE (HR: 1.50, 95% CI: 1.05, 2.13) among women only, while no association was observed in men (HR 0.93, 95% CI: 0.69, 1.26). Transient endothelial dysfunction in response to stress (for each standard deviation decrease in FMD) was associated with 35% greater risk of MACE (HR: 1.35; 95% CI: 1.07, 1.71), and was similar in women and men. Conclusions: Peripheral microvascular dysfunction with mental stress is associated with MACE among women but not among men. In contrast, brachial artery endothelial dysfunction is similarly related to MACE among both men and women. These results suggest that microvascular dysfunction is a female-specific mechanism linking psychological stress to adverse outcomes.

Endothelial function measured by peripheral arterial tonometry in patients with chronic myeloid leukemia on tyrosine kinase inhibitor therapy: a pilot study

BackgroundArterial occlusive events are an emerging problem in patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitor (TKI) therapy. Endothelial cell damage is thought to play an important role in the development of vascular events. Measurement of the peripheral vasodilator response by peripheral arterial tonometry (PAT) has reportedly been useful in the non-invasive assessment of endothelial dysfunction. To date, no studies have assessed endothelial function using PAT in patients with CML receiving TKIs.MethodWe measured the reactive hyperemia index (RHI) using PAT in young patients with CML (men aged ≤ 55 years and women aged ≤ 65 years) receiving TKIs.ResultsThirty patients with CML were examined (mean age, 43.5 ± 9.8 years; men, 57%). The median RHI was 1.81. Among these patients, 16.7% and 83.3% were taking imatinib and second- or third-generation TKIs, respectively. There were no differences in the baseline characteristics between the low RHI (< 1.67, n = 10), borderline RHI (≥ 1.67 and < 2.10, n = 14), and normal RHI (≥ 2.10, n = 6) groups. Serum uric acid (UA) levels and the RHI were significantly negatively correlated (r = -0.40, p = 0.029).ConclusionOne-third of young patients with CML receiving TKI therapy were classified as having a low RHI. The RHI was negatively correlated with serum UA level. Larger prospective studies are necessary to examine whether the RHI predicts cardiovascular events in such patients.

Prognostic value of reactive hyperemia index using peripheral artery tonometry in patients with heart failure

Given the high prevalence and poor prognosis of heart failure (HF), finding prognostic factors for patients with HF is crucial. This study investigated the prognostic value of reactive hyperemia index (RHI), a measure of endothelial function, in HF. A total of 90 HF patients (mean age, 63.7 ± 13.2 years; female, 25.6%) with a history of hospitalization for HF treatment were prospectively enrolled. RHI was measured using digital arterial tonometry in a stable condition. Clinical events, including all-cause death and HF admission, were assessed. During the median follow-up of 3.66 years (interquartile range, 0.91–4.94 years), 26 clinical events (28.9%) occurred. Although there were no significant differences in risk factors and laboratory findings according to the occurrence of clinical events, the RHI value was significantly lower in patients with clinical events than in those without (1.21 ± 0.34 vs. 1.68 ± 0.48; P < 0.001). Kaplan–Meier survival analysis showed that a lower RHI value (< 1.48) was associated with a significantly higher incidence rate of clinical events (log-rank P < 0.001). In multivariable cox regression analysis, a low RHI value (< 1.48) was associated with an increased risk of clinical events (hazard ratio, 14.09; 95% confidence interval, 3.61–54.99; P < 0.001) even after controlling for potential confounders. Our study showed that reduced RHI was associated with an increased risk of adverse clinical outcomes in HF. This suggests that endothelial dysfunction may be an important prognostic marker in patients with HF.

Endothelial function testing before conditioning therapy is useful for predicting transplant-related complications after allogeneic hematopoietic cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is a useful tool for the treatment of hematologic malignancies. However, transplantation-related complications are the main cause of non-relapse mortality. Previous reports suggest that endothelial damage is related to early complications after HSCT. Non-invasive reactive hyperemia peripheral arterial tonometry (RH-PAT) was performed to evaluate endothelial function as a predictive marker for these complications. The reactive hyperemia index (RHI) obtained from RH-PAT was evaluated before the conditioning regimen. The relationship between the RHI and the appearance of engraftment syndrome, thrombotic microangiopathy, and acute graft-versus-host disease (aGVHD) was assessed. Receiver operating characteristic curve analysis showed that an RHI value of 1.58 was the optimal cut-off for predicting transplantation-related complications. In total, 49 patients (22 acute myelogenous leukemia, 7 acute lymphocytic leukemia, 6 myelodysplastic syndrome, 6 adult T-cell leukemia, 6 non-Hodgkin lymphoma, and 2 others) were enrolled; 34 had a normal RHI (≥ 1.59), and 15 had an abnormally low RHI (≤ 1.58). Thrombotic microangiopathy (20.2% vs 0.0%, P = 0.025) and aGVHD (80.0% vs 41.2%, P = 0.015) were significantly more frequent in patients with a low RHI. Endothelial dysfunction assessed by RH-PAT before HSCT was able to predict transplantation-related complications.

Hypothalamic‐pituitary‐adrenal axis activity and vascular function in healthy adults

The objective of this study is to assess the relationship between hypothalamic-pituitary-adrenal (HPA) axis activity, vascular function and insulin sensitivity in healthy adults. Open observational study. Thirty healthy adults were studied at the Endocrine Research Unit, Repatriation General Hospital, Adelaide, SA, Australia. HPA activity was assessed from the serum cortisol 30 min after 1 µg ACTH1-24 (Novartis Pharmaceuticals). Subjects with a cortisol below (n = 15) and above (n = 15) the median were categorized as low and high responders, respectively. Reactive hyperaemia index (RHI) was measured fasting to estimate endothelial function. Matsuda index was calculated from glucose and insulin concentrations collected fasting and 30 minutely for 2 h after a mixed meal (10 kcal/kg, 45% carbohydrate, 15% protein, 40% fat). The primary endpoint was the difference in RHI between low and high responders. There were no significant differences in age (61 ± 9 vs. 64 ± 7 years, p = .19), body mass index (BMI; 26 ± 3 vs. 24 ± 4 kg/m2 , p = .25) and sex (p = .71) between low and high responders. High responders had a lower RHI (2.1 ± 0.2 vs. 2.6 ± 0.2, p = .04) than low responders and there was a negative association between RHI and peak cortisol post ACTH1-24 (β = -.56, p < .01). There were no significant differences in Matsuda index (15.0 ± 2.4 vs. 22.7 ± 5.2, p = .19) between high and low responders. In healthy adults, endothelial dysfunction is likely to contribute to the association between HPA hyperactivity and increased cardiovascular risk. As insulin sensitivity was not different in high and low responders, endothelial dysfunction is not primarily secondary to insulin resistance.

Arsenic exposure from drinking water and endothelial dysfunction in Bangladeshi adolescents

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, with ∼80% of CVD-related deaths occurring in low- and middle-income countries. Growing evidence suggests that chronic arsenic exposure may contribute to CVD through its effect on endothelial function in adults. However, few studies have examined the influence of arsenic exposure on cardiovascular health in children and adolescents. To examine arsenic's relation to preclinical markers of endothelial dysfunction, we enrolled 200 adolescent children (ages 15–19 years; median 17) of adult participants in the Health Effects of Arsenic Longitudinal Study (HEALS), in Araihazar, Bangladesh. Participants' arsenic exposure was determined by recall of lifetime well usage for drinking water. As part of HEALS, wells were color-coded to indicate arsenic level (<10 μg/L, 10–50 μg/L, >50 μg/L). Endothelial function was measured by recording fingertip arterial pulsatile volume change and reactive hyperemia index (RHI) score, an independent CVD risk factor, was calculated from these measurements. In linear regression models adjusted for participant's sex, age, education, maternal education, land ownership and body weight, individuals who reported always drinking water from wells with >50 μg/L arsenic had a 11.75% lower level of RHI (95% CI: −21.26, −1.09, p = 0.03), as compared to participants who drank exclusively from wells with ≤50 μg/L arsenic. Sex-stratified analyses suggest that these associations were stronger in female participants. As compared to individuals who drank exclusively from wells with ≤50 μg/L arsenic, the use of wells with >50 μg/L arsenic was associated with 14.36% lower RHI (95% CI: −25.69, −1.29, p = 0.03) in females, as compared to 5.35% lower RHI (95% CI: −22.28, 15.37, p = 0.58) in males for the same comparison. Our results suggest that chronic arsenic exposure may be related to endothelial dysfunction in adolescents, especially among females. Further work is needed to confirm these findings and examine whether these changes may increase risk of later adverse cardiovascular health events.

Abstract 12986: Association of Gestational Diabetes With Subclinical Cardiovascular Disease on Echocardiogram and Endothelial Function Testing

Introduction: Gestational diabetes mellitus (GDM) increases risk for cardiovascular disease (CVD). The subclinical cardiovascular structural and functional changes that contribute to long-term cardiovascular risk are unclear. Hypothesis: We hypothesized that GDM is associated with adverse cardiovascular remodeling, diastolic function abnormalities, and endothelial dysfunction at approximately a decade after delivery, thereby increasing CVD risk. Methods: We conducted a cross-sectional analysis of women from an existing cohort with abstracted clinical pregnancy data. Women attended a follow-up visit at a median of 9 years after delivery. Echocardiograms, Peripheral Arterial Tonometry (EndoPAT), glycocalyx analysis (GlycoCheck) and laboratory testing were conducted at the follow-up visit. Results: Among 217 women who attended the follow-up visit, 53 (24%) had history of GDM. After adjusting for age, race, preeclampsia history or preterm delivery, women with prior Compared to women without GDM, women with prior GDM had higher interventricular septal and left ventricular (LV) posterior wall thickness and lower septal e’ velocity ( Table ; Model 2). They also had worse endothelial function with lower reactive hyperemia index (RHI) and adverse GlycoCheck parameters. Measures of hypertrophy were attenuated by additional adjustment for body mass index, hypertension, and diabetes (Model 3), but findings of adverse LV diastology, RHI and GlycoCheck parameters remained significant. Conclusions: Women with GDM were more likely to have increased LV wall thickness, adverse diastology and endothelial dysfunction nearly a decade postpartum. Adjusting for traditional cardiovascular risk factors attenuated some but not all parameters. These findings suggest that subclinical structural and functional cardiac and vascular changes may be a mechanism by which GDM causes increased risk of CVD.

Does overnight duty affect vascular endothelial function?

BackgroundThe reactive hyperemia index (RHI), which is obtained from the measurement of peripheral arterial tonometry (PAT), is highly associated with the percentage change in the end-diastolic arterial diameter (%flow-mediated dilatation) at reactive hyperemia. Low RHI is reported to be a mortality risk in patients with a high risk of cardiovascular (CV) disease. CV events are thought to be induced by physical and mental stress, including long-term fatigue and lack of sleep. However, the relationship between fatigue, lack of sleep, and endothelial function has not yet been established.MethodsHealthy hospital workers (n = 13, 6 men and 7 women) with an average age of 31.6 years were assigned to this study after they provided written informed consent. During the study period, we conducted 72 measurements of reactive hyperemia-peripheral arterial tonometry (RH-PAT) in the morning before or after their duty. At each measurement of the RH-PAT, we recorded the participants’ hours of sleep and evaluated their degree of fatigue using a visual analog scale (VAS).ResultsAlthough the VAS was significantly less (36 ± 16% and 64 ± 12%, p < 0.001) and the hours of sleep were longer (6.0 ± 1.1 h and 2.3 ± 1.0 h, p < 0.001) before duty compared to those after duty, the RHI was comparable between them (2.12 ± 0.53 vs. 1.97 ± 0.50, p = 0.21). The VAS score was significantly higher in participants with low RHI (< 1.67) than in those with normal RHI (≥ 2.07) (59 ± 13% and 46 ± 21%, respectively, p < 0.05). However, binary logistic regression showed no significant association between low RHI and the VAS when adjusted for systemic blood pressure (SBP) and heart rate variability (HRV). In a simple regression analysis, the RHI was significantly correlated with the VAS score but not with sleep duration. A multiple linear regression analysis also showed no significant association between the RHI and VAS scores after adjustment for SBP and HRV.ConclusionsVascular endothelial function was not associated with overnight duty, hours of sleep, or degree of fatigue in healthy young adults. Since the RHI may be decreased in severe fatigue conditions through autonomic nerve activity, one should consider the physical and mental conditions of the examinee when evaluating the RH-PAT results.

Endothelial Dysfunction and Diabetes Related Complications in Adolescents with Type 1 Diabetes

Introduction: Patients with Type 1 Diabetes (T1D) are at high risk of developing vascular complications. Endothelial Dysfunction (ED) is the early reversible stage of vascular disease. Aim: Poor Diabetic control is associated with ED. Based on a hypothesis we aimed to determine the relationship between metabolic control and endothelial function in a cohort of adolescents with T1D. Methods: 42 adolescents with T1D were recruited. Weights, heights and BMI were recorded. Blood pressure was measured, followed by assessment of Reactive hyperaemia index (RHI) by Endo-PAT. Fasting blood samples were taken for evaluation of HbA1c, liver, renal function, lipid profile. Inflammatory markers (adiponectin, leptin, thrombomodulin, serum Intravascular Adhesion Molecules (sICAM), E-Selectin and p-Selectin) were measured in 20 patients. Urinary microalbumin to creatinine ratio measured. Participants completed a physical activity questionnaire. Baseline data included the date of diagnosis, duration of diabetes, current insulin dose, insulin regimen, daily screen time and relevant family history of early cardiovascular disease. Results: Reactive hyperaemia index correlated with age. Thirteen adolescents (31%) had low RHI, suggesting relatively impaired endothelial function. Lower RHI correlated with higher diastolic blood pressure (r=-0.34) and p-Selectin level (r=-0.3) suggesting impairment in vascular health. Poor metabolic control was associated with impaired lipid profile (r=0.55), higher diastolic blood pressure (r=0.38) and higher level of inflammatory markers Pselectin (r=0.55). Active life style was associated with improved blood pressure (r=-0.35) and lipid profile (r=-0.39).

Water arsenic exposure and endothelial dysfunction in Bangladeshi adolescents

BACKGROUND AND AIM: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, with ~80% of CVD-related deaths occurring in low- and middle-income countries. Growing evidence suggests that chronic arsenic (As) exposure may contribute to CVD through its effect on endothelial dysfunction in adults. However, few studies have examined the influence of As exposure on cardiovascular health in children and adolescents. METHODS: To examine As’s relation to preclinical markers of endothelial dysfunction, we enrolled 200 adolescent children (ages 15-19 years; median: 17) of adult participants in the Health Effects of Arsenic Longitudinal Study (HEALS), in Araihazar, Bangladesh. Participant’s water As exposure was determined by recall of lifetime well usage. Wells are color coded to indicate As level (10 µg/L, 10-50 µg/L, 50 µg/L As). Endothelial function was measured by recording fingertip arterial pulsatile volume change using Endo-PAT2000 (Itamar Medical) and reactive hyperemia index (RHI) score, an independent CVD risk factor, was calculated from these measurements. RESULTS:In linear regression models adjusted for sex, age, education and weight at the time of RHI measurement, individuals who reported always using wells with ≥50 µg/L As had a lower level of RHI by 11.62% (95% CI: -20.94, -1.16, p=0.03), as compared to participants who drank exclusively from wells with 50 µg/L As. Sex-stratified analyses suggest that these associations were stronger in female participants. The use of wells with ≥50 µg/L As was associated with 14.87% lower RHI (95% CI: -25.59, -2.60, p=0.02) in females, as compared to 5.05% lower RHI (95% CI: -21.81, 15.29, p=0.60) in males for the same comparison. CONCLUSIONS:Our results suggest that chronic As exposure may be related to endothelial dyfunction and vascular reactivity in adolescents, with potential differences by sex. Further work is needed to confirm these findings and examine whether these changes may increase risk of later adverse cardiovascular health effects. KEYWORDS: Arsenic, adolescents, cardiovascular health, endothelial function, Bangladesh

Peripheral Artery Tonometry Reveals Impaired Endothelial Function before Percutaneous Coronary Intervention in Patients with Periprocedural Myocardial Injury.

Background Periprocedural myocardial injury (PMI) is a most common complication of percutaneous coronary intervention (PCI). Microembolization and inflammation underlying PMI could lead to coronary microvascular dysfunction (CMD) and vice versa. Reactive hyperemia index (RHI) assessed by peripheral artery tonometry (PAT) has been considered as a noninvasive method to assess endothelial function and CMD, which could be useful to predict PMI. Methods 268 patients suspected with stable coronary artery disease (CAD) and scheduled for elective coronary angiography were enrolled. RHI was measured by using the Endo-PAT2000™ device before angiography. The association among RHI, PMI, and cardiovascular events was further assessed. Results In this cohort, 189 patients (70.5%) were diagnosed with CAD and 119 patients (44.4%) underwent drug-eluting stent (DES) implantation. Compared with patients without CAD, CAD patients had lower RHI (1.88 ± 0.55 vs. 2.02 ± 0.58, P < 0.05). Patients with PMI had a lower RHI before angiography (1.75 ± 0.37 vs. 1.95 ± 0.50, P < 0.05). Receiver operating characteristic curve analysis of RHI revealed an area under the curve (AUC) of 0.61, with a sensitivity of 62.7% and specificity of 50.0% to predict PMI. Moreover, we found that CAD patients with RHI ≤ 1.81 had a higher incidence of composite cardiac events after stenting (adjusted hazard ratio (HR) 3.31, 95% confidence interval (CI) 1.07–10.22, P < 0.05). Conclusions RHI assessment through PAT could be a promising method to predict PMI before the procedure. RHI is associated with increased risk of long-term adverse cardiac events after DES implantation.

Is endothelial function impaired among women with placenta-mediated fetal growth restriction? Evidence from a prospective cohort study using peripheral artery tonometry

IntroductionWomen with pregnancies complicated by IUGR are at increased risk for future cardiovascular disease. Nevertheless, it is unknown whether endothelial function of women with pregnancies complicated by IUGR is already impaired during pregnancy. Hence, we evaluated maternal endothelial function in pregnancies complicated by IUGR due to placental dysfunction. MethodsProspective cohort study assessing systemic endothelial function of women with singleton pregnancies and estimated fetal weight (EFW) below 10th percentile and abnormal umbilical artery flow (n = 15). Control group included women with singleton pregnancies and normal EFW (n = 22). Endothelial function was assessed using EndoPAT™ device which evaluates the change in peripheral vascular tone in reaction to temporal ischemia, a process called reactive hyperemia. The ratio of the readings before and after ischemia is used to assess endothelial function and called reactive hyperemia index (RHI). Low RHI values indicate endothelial dysfunction. ResultsThe median gestational age at endoPAT examination was comparable between the IUGR and control groups (32; IQR 31,33; p = 0.18). The median RHI was significantly lower in the IUGR group compared to the control group (1.3 vs 1.5, p = 0.02). Median gestational age at delivery and mean neonatal birth weight were lower in the IUGR group compared to the control group (36.7 (35.6,37.2) vs 37.7 (35.3, 39.3), p = 0.04 and 1647 ± 414 g vs 2785 ± 587 g, p < 0.001). Discussion-Pregnant women with IUGR due to placental dysfunction are characterized by impaired systemic endothelial function.

Abstract 14230: Integration of Vascular Phenotyping With Metabolomic Profiling in Black Subjects With Heart Failure With Reduced Ejection Fraction

Introduction: Impaired vascular function in blacks contributes to a higher risk of heart failure (HF) compared to other race/ethnicities. Hypothesis: Black patients with HF with reduced ejection fraction (HFrEF) will have worse digital microvascular function measured using peripheral arterial tonometry (PAT). High resolution metabolomics profiling will identify novel biomarkers of vascular function. Methods: PAT was used to estimate the reactive hyperemia index (RHI) in blacks and whites with HFrEF (N=154, age: 53.7 ± 13.0 yrs, 48.7% female, 61.0% black) and healthy controls (N=200, age: 43.2 ± 14.0 yrs, 47.0% female, 27.0% black). Linear regression was used to determine if race was associated with RHI after adjustment for traditional CV risk factors. High-resolution plasma metabolomics profiling and pathway analysis, followed by metabolite confirmation with mass spectrometry were used to derive a metabolomics score (MS) from metabolites that were significantly associated with RHI, different between blacks and whites, and attenuated the association of black race with RHI. Results: Black subjects were younger in both the HFrEF and control cohorts. Blacks with HFrEF were more likely to have nonischemic HF and hypertension, more likely to be on hydralazine-nitrates and diuretics. RHI was lower in blacks than whites both in subjects with HFrEF (1.8 ± 0.5 vs. 2.0 ± 0.5, P=0.02) and in healthy controls (2.1 ± 0.5 vs. 2.4 ± 0.5, P=0.003). Black race was independently associated with lower RHI (adjusted β=-0.221, P=0.03). MS comprising metabolites representative of cardiac cachexia (3-Methyl-Histidine, L-Histidine, Creatinine), vascular collagen turnover (4-hydroxyproline), purine metabolism and oxidative stress (uric acid) attenuated the association of black race with RHI by 49.8%. Conclusion: Integration of vascular phenotyping with metabolomic profiling reveals a novel MS that attenuates the association of black race with impaired microvascular function.

Correction: The Relationship Between the Impairment of Endothelial Function and Thyroid Antibodies in Hashimoto's Thyroiditis Patients with Euthyroidism.

Endothelial dysfunction is the important early step in the development of atherosclerosis. Hypothyroidism caused by Hashimoto’s thyroiditis and other thyroid disease is one of the risk factors of endothelial dysfunction. The present study tried to investigate the endothelial function and its associated factors in Hashimoto thyroiditis with euthyroidism. A total of 95 newly diagnosed Hashimoto’s thyroiditis patients with euthyroidism and 45 healthy controls were studied. Hashimoto’s patients were divided into 3 subgroups namely, single thyroglobulin antibody (TGAb) positive subgroup, single thyroid peroxidase antibody (TPOAb) positive subgroup, and both TGAb and TPOAb positive subgroup. Endothelial function was tested by the reactive hyperemia index (RHI). Hashimoto’s thyroiditis patients had lower RHI than healthy controls (1.73±0.42 vs 1.96±0.51, p<0.05). Hashimoto’s thyroiditis with single TGAb positive patients had higher RHI than single TPOAb positive (1.98±0.57 vs. 1.69±0.33, p<0.05) and TGAB + TPOAb positive patients (1.98±0.57 vs. 1.68±0.42, p<0.05). RHI were negatively associated with total cholesterol (TC, r=−0.215, p<0.05), low density lipoprotein cholesterol (LDL-C, r=−0.268, p<0.05), triglyceride (TG, r=−0.192, p<0.05), and TPOAb (r=−0.288, p<0.05). In the regression analysis, LDL-C (β=−0.146, p<0.05), TG (β=−0.034, p<0.05) and TPOAb (β=−0.001, p<0.05) were independently associated with RHI. Hashimoto’s patients had poor endothelial function. TPOAb levels were negatively associated with endothelial function.

Cardiovascular Outcomes in Young Adulthood in a Population-Based Very Low Birth Weight Cohort

To assess differences in left heart structure and function, and endothelial function in a national cohort of very low birth weight (VLBW) young adults and term-born controls. The New Zealand VLBW study is a prospective, population-based, longitudinal cohort study which included all infants born <1500g in 1986. The VLBW cohort (n=229; 71% of survivors) and term-born controls (n=100), were assessed at age 26-30years. Measures of left heart structure and function were evaluated by echocardiography, vascular function was assessed using blood pressure, reactive hyperemia index, and arterioventricular coupling by calculating left ventricular (LV) and arterial elastance. Compared with controls, those born VLBW had smaller LVs, even when indexed for body surface area (mean LV mass, 89.7±19.3g/m2 vs 95.0±22.3g/m2 [P=.03]; LV end-diastolic volume, 58.3±10.9mL/m2 vs 62.4±12.4mL/m2 [P=.002]; and LV end-systolic volume, 20.8±4.9mL/m2 vs 22.6±5.8mL/m2 [P=.004]). VLBW participants had lower stroke volume (median, 37.2mL/m2 [IQR, 33-42mL/m2] vs median, 40.1mL/m2 [IQR, 34-45mL/m2]; P=.0059) and cardiac output (mean, 4.8±1.2 L/min vs 5.1±1.4 L/min; P=.03), but there was no difference in ejection fraction. The VLBW group had higher LV elastance (3.37±0.88mm Hg/mL vs 2.86±0.75mm Hg/mL; P<.0001) and arterial elastance (1.84±0.4 vs 1.6±0.4; P<.0001) and lower reactive hyperemia index (0.605±0.28 vs 0.688±0.31; P=.041). These measures were influenced by birth weight and sex, but we found limited associations with other perinatal factors. Being born preterm and VLBW is associated with differences in cardiovascular structure and function in adulthood. This population may be more vulnerable to cardiovascular pathology as they age. Australian Clinical Trials Registry ACTRN12612000995875.

The Relationship Between the Impairment of Endothelial Function and Thyroid Antibodies in Hashimoto's Thyroiditis Patients with Euthyroidism.

Endothelial dysfunction is the important early step in the development of atherosclerosis. Hypothyroidism caused by Hashimoto's thyroiditis and other thyroid disease is one of the risk factors of endothelial dysfunction. The present study tried to investigate the endothelial function and its associated factors in Hashimoto thyroiditis with euthyroidism. A total of 95 newly diagnosed Hashimoto's thyroiditis patients with euthyroidism and 45 healthy controls were studied. Hashimoto's patients were divided into 3 subgroups namely, single thyroglobulin antibody (TGAb) positive subgroup, single thyroid peroxidase antibody (TPOAb) positive subgroup, and both TGAb and TPOAb positive subgroup. Endothelial function was tested by the reactive hyperemia index (RHI). Hashimoto's thyroiditis patients had lower RHI than healthy controls (1.73±0.42 vs 1.96±0.51, p<0.05). Hashimoto's thyroiditis with single TGAb positive patients had higher RHI than single TPOAb positive (1.98±0.57 vs. 1.69±0.33, p<0.05) and TGAB + TPOAb positive patients (1.98±0.57 vs. 1.68±0.42, p<0.05). RHI were negatively associated with total cholesterol (TC, r=-0.215, p<0.05), low density lipoprotein cholesterol (LDL-C, r=-0.268, p<0.05), triglyceride (TG, r=-0.192, p<0.05), and TPOAb (r=-0.288, p<0.05). In the regression analysis, LDL-C (β=-0.146, p<0.05), TG (β=-0.034, p<0.05) and TPOAb (β=-0.001, p<0.05) were independently associated with RHI. Hashimoto's patients had poor endothelial function. TPOAb levels were negatively associated with endothelial function.

Peripheral endothelial function changes during HER2-directed therapy differ based on whether or not a patient receives anthracycline.

1044 Background: Trastuzumab is well-demonstrated to be associated with cardiotoxicity (typically reduced ejection fraction), most commonly in patients who also receive anthracycline. The vascular effects of trastuzumab and anthracycline are understudied; we aimed to compare change in endothelial function during and after trastuzumab and to assess how anthracycline receipt affects this. Methods: This is an observational prospective study of women with newly diagnosed HER2-positive breast cancer. All participants underwent baseline evaluation of endothelial function testing by use of the EndoPAT2000 device approximately every three months over the subsequent 18 months after the initiation of HER2-directed therapy +/- anthracycline. The primary endpoint was change in endothelial function over time using the reactive hyperemia index (RHI). Framingham Risk Score (FRS) and lower RHI are both known to be independent predictors of future cardiovascular events in the general population. RHI deterioration was defined as a 20% reduction from baseline RHI to any available follow-up RHI assessment. Univariate analyses assessed if age, FRS, baseline RHI, and RHI deterioration differed between recipients and non-recipients of anthracycline using the Wilcoxon test. A multivariate logistic model evaluated FRS, age, and anthracycline receipt as possible independent predictors of RHI deterioration. Results: Among 38 eligible patients who consented and completed baseline assessments in addition to at least one follow-up assessment, 17 (45%) subsequently received anthracycline. 145 total follow-up RHI assessments were available overall (5 per patient on average). There were no differences between recipients and non-recipients of anthracyclines with regard to age [mean 49 years (SD 12) vs 53 years (SD 11); p=0.25], baseline FRS [mean 1.0 (SD 1.0) vs 1.5 (SD 1.4); p= 0.28] or baseline RHI [mean 2.4 (SD 0.6) vs 2.1 (SD 0.7); p=0.09]. RHI deterioration was more common for anthracycline recipients (mean 43% vs 21%; p=0.004), and in the multivariate model, anthracycline use was the only independent predictor of RHI deterioration (odds ratio: 2.8; 95% confidence interval: 1.35-6.07; p=0.006). Conclusions: This study suggests that endothelial dysfunction is more common after combined anthracycline and HER2-directed therapy than after HER2-directed therapy alone. RHI should be further studied as a possible early biomarker of cardiovascular toxicity in patients receiving treatment for breast cancer.