Peripheral Arterial Tonometry Ratio Research Articles

Epicardial Fat Volume Is Associated with Endothelial Dysfunction, but not with Coronary Calcification: From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

The increase in epicardial fat volume (EFV) is related to coronary artery disease (CAD), independent of visceral or subcutaneous fat. The mechanism underlying this association is unclear. Coronary artery calcium (CAC) score and endothelial dysfunction are related to coronary events, but whether EFV is related to these markers needs further clarification. To evaluate the association between automatically measured EFV, cardiovascular risk factors, CAC, and endothelial function. In 470 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) with measures of EFV, CAC score and endothelial function, we performed multivariable models to evaluate the relation between cardiovascular risk factors and EFV (response variable), and between EFV (explanatory variable) and endothelial function variables or CAC score. Two-sided p <0.05 was considered statistically significant. Mean age was 55 ± 8 years, 52.3% of patients were men. Mean EFV was 111mL (IQ 86-144), and the prevalence of CAC score=0 was 55%. In the multivariable analyses, increased EFV was related to female sex, older age, waist circumference, and triglycerides (p<0.001 for all). Higher EFV was associated with worse endothelial function: as compared with the first quartile, the odds ratio for basal pulse amplitude were (q2=1.22, 95%CI 1.07-1.40; q3=1.50, 95%CI 1.30-1.74; q4=1.50, 95%CI 1.28-1.79) and for peripheral arterial tonometry ratio were (q2=0.87, 95%CI 0.81-0.95; q3=0.86, 95%CI 0.79-0.94; q4=0.80, 95%CI 0.73-0.89), but not with CAC score>0. Higher EFV was associated with impaired endothelial function, but not with CAC. The results suggest that EFV is related to the development of CAD through a pathway different from the CAC pathway, possibly through aggravation of endothelial dysfunction and microvascular disease.

Picturing Vascular Health in Patients with Type 2 Diabetes Mellitus: Review based on the Special Lecture 2021

Professor Hamburg's lecture focuses on understanding what is happening to the endothelium in patients with diabetes. The many previous cohort studies have shown that vascular dysfunction predicts cardiovascular disease and that it really reflects an early event in the pathogenesis of therosclerosis, myocardial dysfunction, hypertension, and stroke. According to her own studies and the recent researches reveal that there is a particular association between diabetes mellitus and microvascular dysfunction reflected by abnormal Peripheral Arterial Tonometry ratio and reactive hyperemia. And further, she carried out a series of studies using the ability to collect endothelial cells from patients to show that endothelial phenotype is altered in patients with diabetes, with loss of insulin signaling, loss of nitric oxide, and activation of inflammation. And it is suggested that this is a platform to understand how interventions might benefit the endothelial cells in patients with diabetes at cardiovascular standpoint.

Digital Peripheral Arterial Tonometry and Cardiovascular Disease Events: The Framingham Heart Study.

Novel noninvasive measures of vascular function are emerging as subclinical markers for cardiovascular disease (CVD) and may be useful to predict CVD events. The purpose of our prospective study was to assess associations between digital peripheral arterial tonometry (PAT) measures and first-onset major CVD events in a sample of FHS (Framingham Heart Study) participants. Using a fingertip PAT device, we assessed pulse amplitude in Framingham Offspring and Third Generation participants (n=3865; mean age, 55±14 years; 52% women) at baseline and in 30-second intervals for 4 minutes during reactive hyperemia. The PAT ratio (relative hyperemia index) was calculated as the post-to-pre occlusion pulse signal ratio in the occluded arm, relative to the same ratio in the control (nonoccluded) arm, and corrected for baseline vascular tone. Baseline pulse amplitude and PAT ratio during hyperemia are measures of pressure pulsatility and microvascular function in the finger, respectively. We used Cox proportional hazards regression to relate PAT measures in the fingertip to incident CVD events. During follow-up (median, 9.2 years; range, 0.04–10.0 years), 270 participants (7%) experienced new-onset CVD events (n=270). In multivariable models adjusted for cardiovascular risk factors, baseline pulse amplitude (hazard ratio [HR] per 1 SD, 1.04 [95% CI, 0.90–1.21]; P=0.57) and PAT ratio (HR, 0.95 [95% CI, 0.84–1.08]; P=0.43) were not significantly related to incident composite CVD events, including myocardial infarction or heart failure. However, higher PAT ratio (HR, 0.76 [95% CI, 0.61–0.94]; P=0.013), but not baseline pulse amplitude (HR, 1.15 [95% CI, 0.89–1.49]; P=0.29), was related to lower risk for incident stroke. In a sensitivity analysis by stroke subtype, higher PAT ratio was related to lower risk of incident ischemic stroke events (HR, 0.68 [95% CI, 0.53–0.86]; P=0.001). Novel digital PAT measures may represent a marker of stroke risk in the community.

Relations of arterial stiffness and endothelial dysfunction with incident venous thromboembolism

IntroductionAssociation between arterial vascular dysfunction and risk of venous thromboembolism (VTE) is uncertain. We determined the associations between comprehensive measures of arterial vascular function and risk of incident VTE in a community-based cohort study with robust longitudinal follow-up. Materials and methodsIn the Framingham Heart Study Original, Offspring, Third Generation, and Omni cohorts, we measured carotid-femoral pulse wave velocity and central pulse pressure (n = 8261, age 51.5 ± 15.5 years, 54% women), flow-mediated dilation and hyperemic velocity (n = 6540, age 47.9 ± 14.1 years, 54% women), and peripheral arterial tonometry ratio (n = 4998, age 54.3 ± 16.0 years, 52% women). Deep venous thrombosis and pulmonary embolism were diagnosed with imaging studies and adjudicated by three Framingham Heart Study physicians. Results and conclusionsThe rate of incident VTE was 1.6–2.1 per 1000 person-years during mean follow-up of 8.5–11.2 years. In age- and sex-adjusted Cox proportional hazards regression models, carotid-femoral pulse wave velocity was associated with increased risk of VTE (HR 1.32, 95% CI 1.05–1.66, p = 0.02), however the association was no longer statistically significant after multivariable adjustment (HR 1.24, 95% CI 0.96–1.61, p = 0.10). None of the other vascular variables were associated with the risk of VTE in any of the models. In our comprehensive examination of arterial vascular function and risk of VTE, we did not observe any association between select arterial function measures and risk of VTE after multivariable adjustment.

Non-invasive peripheral vascular function, incident cardiovascular disease, and mortality in the general population.

Aims Evidence suggests that peripheral vascular function is related to cardiovascular disease (CVD) and mortality. We evaluated the associations of non-invasive measures of flow-mediated dilatation and peripheral arterial tonometry with incident CVD and mortality.Methods and results In a post-hoc analysis of the community-based Gutenberg Health Study, median age 55 years (25th/75th percentile 46/65) and 49.5% women, we measured brachial artery flow-mediated dilatation (N=12 599) and fingertip peripheral arterial tonometry (N=11 125). After a follow-up of up to 11.7 years, we observed 595 incident CVD events, 106 cardiac deaths, and 860 deaths in total. Survival curves showed decreased event-free survival with higher mean brachial artery diameter and baseline pulse amplitude and better survival with higher mean flow-mediated dilatation and peripheral arterial tonometry ratio (all Plog rank <0.05). In multivariable-adjusted Cox regression analyses only baseline pulse amplitude was inversely related to mortality [hazard ratio (HR) per standard deviation increase, 0.86, 95% confidence interval (95% CI), 0.79–0.94; P=0.0009]. After exclusion of individuals with prevalent CVD the association was no longer statistically significant in multivariable-adjusted models (HR 0.91, 95% CI 0.81–1.02; P=0.11). None of the vascular variables substantially increased the C-index of a model comprising clinical risk factors.Conclusions In our cohort, non-invasive measures of peripheral vascular structure and function did not reveal clinically relevant associations with incident CVD or mortality. Whether determination of pulse amplitude by peripheral arterial tonometry improves clinical decision-making in primary prevention needs to be demonstrated.

Abstract 13062: Epicardial Fat Associates With Endothelial Dysfunction, but Not With Coronary Calcium Score: From the Elsa-brasil Cohort Study

Introduction: Epicardial fat has been related to coronary artery disease (CAD) independent of visceral or subcutaneous fat. The mechanism responsible for this association has not yet been elucidated. Our objective was to evaluate the association between automatically measured epicardial fat volume (EFV), cardiovascular risk factors, coronary artery calcium (CAC) and endothelial function in participants of ELSA-Brasil. Methods and Results: The sample comprised 470 (mean age 55± 8y, 52.3% men) participants from ELSA-MG, one of the Investigation Centers of the cohort, who had valid computed tomography scans and endothelial function evaluated by peripheral arterial tonometry (PAT). The mean EFV was 111 (IQ 86-144) mL. CAC=0 was detected in 55% of participants. In the multivariable analyses between cardiovascular risk factors and EFV, the following associations were observed with higher EFV: female sex; and increased age, waist circumference and triglycerides (p &lt;0.001 for all). In multivariable analyses, higher EFV remained associated with worse endothelial function - basal pulse amplitude (q2=1.22, CI95% 1.07-1.40, p=0.004; q3=1.50, CI95% 1.30-1.74, p&lt;0.001; q4=1.50, CI95% 1.28-1.79, p&lt;0.001) and PAT ratio (q2=0.87, CI95% 0.81-0.95, p&lt;0.001; q3=0.86, CI95% 0.79-0.94, p&lt;0.001; q4=0.80, CI95% 0.73-0.89, p&lt;0.001), but not with CAC. Conclusions: Higher EFV was associated with impaired endothelial function, but not with higher CAC. Our results suggest that the mechanism by which epicardial fat deposits relates to CAD may be different from the pathway of CAC, which relates to calcified plaques. A possible mechanism may be through the enhancement of endothelial dysfunction, microvascular disease and predominantly lipidic non-calcified plaques.

Noninvasive peripheral vascular function and atrial fibrillation in the general population

Arterial stiffness is a strong predictor of atrial fibrillation in the community. Whether noninvasively measured conduit artery function and peripheral vascular reactivity are related to atrial fibrillation remains unknown. In 15 010 individuals of the population-based Gutenberg Health Study, mean age 55 ± 11 years, 50.5% men, we determined noninvasive vascular function by flow-mediated dilation (FMD) and peripheral arterial tonometry (PAT) in relation to manifest atrial fibrillation (N = 466). Patients with atrial fibrillation exhibited a higher mean brachial artery diameter [4.81 mm (4.17, 5.33) in atrial fibrillation vs. 4.31 mm (3.67, 4.93)] and baseline pulse amplitude in arbitrary units [6.35 (5.76, 6.78) in atrial fibrillation vs. 6.09 (5.36, 6.71)] as well as a reduced FMD in arbitrary units [1.29 (1.26, 1.33) in atrial fibrillation vs. (1.31 (1.26, 1.37)] and PAT ratio [0.42 (0.19, 0.77) in atrial fibrillation vs. 0.67 (0.33, 0.94)] compared with individuals without atrial fibrillation (all PWilcoxon rank-sum test). In age-adjusted and sex-adjusted logistic regression analyses, only baseline brachial artery diameter [odds ratio (OR) per standard deviation 1.19; 95% confidence interval (CI), 1.04-1.37; P = 0.012] and PAT ratio (OR 0.83; 0.74-0.94; P = 0.0029) were associated with atrial fibrillation. In risk factor and heart rate-adjusted models, there was no statistically significant correlation of atrial fibrillation and brachial artery diameter, FMD and PAT ratio while baseline pulse amplitude was reduced in individuals with atrial fibrillation (OR 0.81; 95% CI 0.71-0.93; P = 0.0034). In our large contemporary cohort, peripheral vascular function was compromised in individuals with atrial fibrillation. However, observed associations were mediated by age and classical risk factors. Noninvasive vascular function measures did not improve discriminatory ability for atrial fibrillation.

Endothelial dysfunction and cellular repair in heart failure with preserved ejection fraction: response to a single maximal exercise bout

Endothelial dysfunction and cellular repair in heart failure with preserved ejection fraction: response to a single maximal exercise bout

Brain correlates of stress-induced peripheral vasoconstriction in patients with cardiovascular disease.

The influence of acute psychological stress on cardiovascular disease is an emerging public health concern. Identification of brain mechanisms underlying this may aid in the discovery of possible treatments. Acute psychological stress may induce arteriolar vasoconstriction and reduce blood flow to vital organs. We hypothesized that functional changes in brain regions involved with memory and autonomic/emotional regulation are implicated in the vasoconstrictive stress response, including the medial prefrontal cortex (anterior cingulate), insula, and dorsolateral prefrontal cortex. Subjects with a history of coronary artery disease (N=59) underwent measurement of microvascular vasomotor tone with the EndoPAT device and O-15 positron emission tomography (PET) imaging of the brain during exposure to mental stress and control conditions. The peripheral arterial tonometry (PAT) ratio was calculated as the mean peripheral vasomotor tone during stress divided by the mean tone during rest. Whole brain contrasts were performed between groups above and below the median PAT ratio, and significant contrasts were defined with cutoff p<0.005. Stress-induced peripheral vasoconstriction (below median PAT ratio) was associated with increased stress activation in insula and parietal cortex, and decreased activation in the medial prefrontal cortex with stress tasks compared to control tasks. These findings demonstrate that stress-induced vasoreactivity is associated with changes in brain responses to stress in areas involved in emotion and autonomic regulation. These findings have important implications on possible treatments for mental stress-induced vascular toxicity.

Arterial elasticity as a risk factor for early cardiovascular disease among testicular cancer survivors treated with platinum-based chemotherapy: a cross-sectional pilot study.

PurposeTesticular cancer survivors who have received platinum-based chemotherapy are at risk for premature cardiovascular disease. The etiology of this risk is not well understood. This pilot study explores the impact of platinum-based chemotherapy on endothelial function.MethodsTesticular cancer survivors <30 years old at the time of diagnosis who received platinum-based chemotherapy between 2002 and 2012, as well as 17 similarly aged male controls, were identified. Consented subjects underwent vascular assessment using the HDI/PulseWave CR-2000 Cardiovascular Profiling System and the Endo-PAT2000 system. Biomarkers and functional test markers were compared among cases, controls, and a group of historical controls using two sided two-sampled t-tests and Wilcoxon rank-sum tests.ResultsThirteen survivors with a median age of 30.2 years and body mass index of 27.3 were enrolled, along with 17 healthy controls with a median age of 27.1 years and body mass index of 24.8. Median time from chemotherapy was 4.7 (range: 0.8–14) years. There was no statistical difference in reactive hyperemia peripheral arterial tonometry ratio between cases and controls (p = 0.574). There was no statistical difference in small or large artery elasticity between cases and controls (p = 0.086) or between cases and historical controls (p = 0.729). There was also no statistical difference in the blood levels of circulating endothelial cells, von Willebrand factor, and vascular cell adhesion molecules. There was a trend toward increased metabolic syndrome in cases (15%) as compared to recruited controls (6%), though this difference was not statistically significant (p = 0.565).ConclusionTesticular cancer survivors have no clinically significant difference in endothelial function compared to controls 4 years after the completion of chemotherapy. Further research is needed to explore the secondary modifiable causes that may contribute to the risk of premature cardiovascular disease.

Abstract P294: Greater Peripheral Vasoconstriction During Mental Stress Predicts Adverse Cardiovascular Outcomes

Introduction: Peripheral arterial vasoconstriction during mental stress (MS) has been associated with mental stress-induced myocardial ischemia, which in turn has been linked with worse cardiovascular outcomes. It is unknown whether the magnitude of peripheral vasoconstriction with MS is predictive of long term outcomes. Hypothesis: We hypothesized that greater peripheral arterial vasoconstriction during MS would be associated with adverse events among patients with coronary artery disease (CAD). Methods: Four hundred sixty-three patients with stable CAD and normal left ventricular function, (age 63±9, 75% male, 27% Black, EF 60±8 %) underwent MS testing with a standardized public speaking stressor. Digital pulse wave amplitude was continuously measured at baseline and during MS using peripheral arterial tonometry (PAT), and the PAT ratio of pulse wave amplitude (during mental stress/ baseline) was calculated. Cox proportional hazard models were calculated to examine the association between the PAT ratio and outcomes. Results: Median PAT ratio during MS was 0.68, indicating 32% average constriction with MS compared to rest. Subjects with greater peripheral constriction [low (&lt;median) PAT ratio] were more likely to be male (80% vs. 70%, P=0.008) compared to those with PAT ratio ≥median, but their risk factor profiles were similar. During 2.8±0.5 year follow-up, 64 patients had adverse cardiac events including 7 cardiovascular deaths, 19 MI, and 54 revascularization events. After adjusting for age, sex, race, hypertension, diabetes, current smoking status, and prior MI, those with low PAT ratio had a greater risk of CV death/MI (HR[hazard ratio] 2.49, 95% CI [1.04-5.99]) and CV death/MI/revascularization (HR 1.77, 95% CI [1.03-3.04]) compared to those with high PAT ratio. Conclusion: Greater peripheral arterial vasoconstriction with MS is associated with a higher risk of adverse cardiovascular outcomes in patients with CAD.

Mental stress peripheral vascular reactivity is elevated in women with coronary vascular dysfunction: Results from the NHLBI-sponsored Cardiac Autonomic Nervous System (CANS) study.

Women with chest pain, ischemia, and no obstructive coronary artery disease often have coronary vascular dysfunction (CVaD). Peripheral vascular reactivity to mental stress may contribute mechanistic understanding of stress-induced ischemia in women with CVaD. 62 women (41 CVaD and 21 controls) underwent mental stress testing (MST) with anger recall, mental arithmetic, and forehead cold pressor (COP) challenge. Emotional arousal was measured (Likert scale). Reactive hyperemia index (RHI) was calculated before and after MST by peripheral arterial tonometry (PAT). Stress PAT ratio (SPR) of pulse amplitude during stress to rest was obtained to measure vasoconstriction. Wilcoxson rank sum test was used for analysis. Mean age of CVaD and control groups was 58±9 and 55±10years (p=0.73). Baseline RHI correlated with coronary endothelial function (r=0.36, p=0.03) and inversely with RHI change post-MST (r=-0.51, p<0.001). During MST, 10% of controls reported chest pain vs. 41% of CVaD subjects (p=0.01). RHI did not change significantly after MST in either group. CVaD subjects had lower SPR vs. controls during mental arithmetic (0.54 [0.15, 1.46] vs. 0.67 [0.36, 1.8], p=0.039), not evident in the other tasks. Vasoconstriction inversely correlated with anxiety (r=-3.4, p=0.03), frustration (r=-0.37, p=0.02), and feeling challenged (r=-0.37, p=0.02) in CVaD but not controls. Mental stress peripheral vascular reactivity is elevated in women with CVaD compared to controls. Elevated vascular reactivity may be one contributor to stress-induced chest pain in CVaD. Interventions that modulate vasoconstrictive responses may be of benefit and should be tested in clinical trials in women with CVaD.

Hemodynamic, catecholamine, vasomotor and vascular responses: Determinants of myocardial ischemia during mental stress

AimsMental stress-induced myocardial ischemia (MSIMI) in patients with coronary artery disease (CAD) is associated with adverse cardiovascular outcomes. We aim to assess hemodynamic, neuro-hormonal, endothelial, vasomotor and vascular predictors of MSIMI. Methods and resultsWe subjected 660 patients with stable CAD to 99mTc sestamibi myocardial perfusion imaging at rest, with mental (speech task) and with conventional (exercise/pharmacological) stress. Endothelium-dependent flow-mediated dilation (FMD), microvascular reactivity [reactive hyperemia index (RHI)] and arterial stiffness [pulse wave velocity (PWV)] were measured at rest and 30-min after mental stress. The digital microvascular vasomotor response during mental stress was assessed using peripheral arterial tonometry (PAT). A total of 106(16.1%) patients had MSIMI. Mental stress was accompanied by significant increases in rate-pressure-product (heart rate x systolic blood pressure; RPP), epinephrine levels and PWV, and significant decreases in FMD and PAT ratio denoting microvascular constriction. In comparison to those with no MSIMI, patients with MSIMI had higher hemodynamic and digital vasoconstrictive responses (p<0.05 for both), but did not differ in epinephrine, endothelial or macrovascular responses. Only presence of ischemia during conventional stress (OR of 7.1, 95%CI of 4.2, 11.9), high hemodynamic response (OR for RPP response≥vs<ROC cutoff of 1.8, 95%CI of 1.1, 2.8), and high digital vasoconstriction (OR for PAT ratio<vs≥ROC cutoff of 2.1, 95%CI of 1.3, 3.3) were independent predictors of MSIMI. ConclusionIschemia during conventional stress testing and hemodynamic and vasoconstrictive responses to mental stress can help predict subjects with CAD at greater risk of developing MSIMI.

The relation of digital vascular function to cardiovascular risk factors in African-Americans using digital tonometry: the Jackson Heart Study

Digital vascular tone and function, as measured by peripheral arterial tonometry (PAT), are associated with cardiovascular risk and events in non-Hispanic whites. There are limited data on relations between PAT and cardiovascular risk in African-Americans. PAT was performed on a subset of Jackson Heart Study participants using a fingertip tonometry device. Resting digital vascular tone was assessed as baseline pulse amplitude. Hyperemic vascular response to 5 minutes of ischemia was expressed as the PAT ratio (hyperemic/baseline amplitude ratio). Peripheral augmentation index (AI), a measure of relative wave reflection, also was estimated. The association of baseline pulse amplitude (PA), PAT ratio, and AI to risk factors was assessed using stepwise multivariable models. The study sample consisted of 837 participants from the Jackson Heart Study (mean age, 54 ± 11 years; 61% women). In stepwise multivariable regression models, baseline pulse amplitude was related to male sex, body mass index, and diastolic blood pressure (BP), accounting for 16% of the total variability of the baseline pulse amplitude. Age, male sex, systolic BP, diastolic BP, antihypertensive medication, and prevalent cardiovascular disease contributed to 11% of the total variability of the PAT ratio. Risk factors (primarily age, sex, and heart rate) explained 47% of the total variability of the AI. We confirmed in our cohort of African-Americans, a significant relation between digital vascular tone and function measured by PAT and multiple traditional cardiovascular risk factors. Further studies are warranted to investigate the utility of these measurements in predicting clinical outcomes in African-Americans.

Abstract 536: Poor Correlation Between FMD and PAT-Ratio in Patients With Metabolic Syndrome

Background: Flow mediated dilatation (FMD) and peripheral arterial tonometry (PAT) are commonly used methods for assessing endothelial function in a research setting but it is unclear how well they correlate. The aim of this study is to compare and correlate these methods in patients with metabolic syndrome. Methods: The study involved 105 subjects (mean age68±10 years) with metabolic syndrome. Based on the results of coronary angiography, they were divided into 2 groups: a study group with coronary lesions (n=68) and a control group without coronary lesions (n=37). Flow mediated vasodilatation (FMD) and nitroglycerine-induced vasodilatation (NID) in the brachial artery was measured by using UNEXEF18G (UNEX CO, Japan). At the same time, PAT ratio was measured by using Endo-PAT 2000 (Itamar Medical, Israel) Results: FMD was not correlated with PAT ratio by Spearman`s analysis. FMD was significantly impaired in the study group compared to that in the control group (3.9±1.8% vs. 2.6±1.5%, respectively; P&lt;0.001). However, NID and PAT ratio had no deference in the two groups. Multivariable analysis revealed that FMD (odds ratio: 0.53, 95% confidence interval [CI]: 0.31-0.90) were independent variables for CAD in metabolic syndrome patients. Conclusion: This study showed that poor correlation between FMD and PAT in patients with metabolic syndrome. PAT may not be used as a substitute for FMD as a measure of endothelial function

Abstract 302: The PAT Ratio is Reduced by Beta-blockers

Background: Flow-mediated dilatation (FMD) of the brachial artery and Peripheral arterial tonometry (PAT) are both methods for assessing endothelial vascular function. FMD measures predominantly nitric oxide mediated vasodilation whereas PAT measures a more complex range of mechanisms. The recent study showed that the sympathetic nervous system plays a significant role in this response. Methods: The study involved 176 subjects (mean age66 ±12 years). Based on the medication of beta-blockers, they were divided into 2 groups: beta-blocker group (n=37) and control group (n=139). Flow mediated vasodilatation (FMD) and nitroglycerine-induced vasodilatation (NID) in the brachial artery was measured by using UNEXEF18G (UNEX CO, Japan), and nitroglycerin mediated vasodilatation (NMD) was used as a control test for FMD. At the same time, PAT ratio was measured by using Endo-PAT 2000 (Itamar Medical, Israel) Results: PAT ratio was significantly impaired in beta-blocker group compared to that in control group (1.5±0.4% vs. 1.9±0.6%, respectively; P&lt;0.05). However, FMD and NMD had no deference in both groups. Multivariable analysis revealed that blood sugar and medication of beta-blockers were independent variables for PAT ratio. Conclusion: These result show that beta-blockers is associated with a tendency towards reduced PAT ratio. PAT needs to be further studied, including the assessment of non-endothelial factor

Abstract 13036: Relations of Metabolically Healthy and Unhealthy Obesity and to Digital Vascular Function in Three Community-based Cohorts: A Meta-Analysis

Introduction: Obesity and metabolic risk factors induce microvascular dysfunction, a marker of early vascular disease that predicts cardiovascular events. Whether obese individuals with a metabolically healthy profile have impaired microvascular function remains unclear. Objectives: The aim of this study was to evaluate the relation of obesity phenotypes stratified by metabolic status to microvascular function. Methods: We meta-analyzed aggregate data from 3 large cohorts (Brazilian Longitudinal Study of Adult Health, the Framingham Heart Study and the Gutenberg Heart Study; N= 16830 participants, age range 19-90, 48.7% women). Regression slopes between cardiovascular risk factors and microvascular function, measured by peripheral arterial tonometry (PAT), were calculated for each cohort. Individuals were classified as normal-weight, overweight or obese by body mass index (BMI) and further stratified by healthy or unhealthy metabolic status based on metabolic syndrome defined by the ATP-III criteria. Results: Male sex, BMI and the presence of metabolic risk factors were associated with more impaired PAT measures ( P &lt;0.0001 for baseline pulse amplitude, P &lt;0.01 for PAT ratio). There was stepwise impairment of vascular measures from normal weight to obesity in both metabolic status strata (all P &lt;0.0001). Metabolically healthy obese had more impaired vascular function than metabolically healthy normal-weight individuals (baseline pulse amplitude 6.12±0.017 vs. 5.61±0.010; PAT ratio 0.58±0.008 vs. 0.76±0.005, respectively, all P &lt;0.0001). Within the same BMI category, metabolically healthy individuals had better vascular function than their metabolically unhealthy counterparts (all P &lt;0.0001). Conclusion: Metabolically healthy obese individuals have impaired microvascular function, though the degree of impairment is less marked than in metabolically unhealthy obese individuals. Our findings suggest that obesity is detrimental to vascular health irrespective of metabolic status.

The Impact of Obstructive Sleep Apnea and Tobacco Smoking on Endothelial Function

Background: Endothelial dysfunction has been recognized to occur in the context of obstructive sleep apnea (OSA) or tobacco smoking. However, the deleterious effect on vascular function with concurrence of both conditions is largely unknown. Objective: To investigate whether the concurrence of OSA and smoking poses an additive detriment to endothelial dysfunction. Methods: Chinese men without a history of chronic medical illness were invited to complete a questionnaire including smoking pack-year exposure, polysomnography and peripheral arterial tonometry (PAT) for endothelial function. Serum 8-isoprostane, advanced oxidation protein products (AOPP) and monocyte chemo-attractant protein-1 (MCP-1) were measured. Results: 114 men were successfully enrolled. PAT ratio, adjusted for age and body mass index, correlated inversely with overall severity of OSA: apnea-hypopnea index (AHI), r = -0.160 (p = 0.092); oxygen desaturation index, r = -0.214 (p = 0.024); duration of oxygen saturation <90%, r = -0.219 (p = 0.020); and minimum oxygen saturation, r = 0.250 (p = 0.008). The PAT ratio decreased with increasing pack-year group (p = 0.018). It was lower with concurrent smoking history and moderate-severe OSA (AHI ≥15/h) compared to having one or neither factor (p = 0.011). Serum levels of 8-isoprostane and AOPP were positively related to severity of OSA, while MCP-1 correlated with smoking quantity. Multiple linear regression analyses showed that severity of intermittent hypoxia, MCP-1 and pack-year exposure were independent predictors of PAT ratio. Conclusion: While OSA, in particular intermittent hypoxemia, and tobacco smoking were independent risk factors, the concurrence of moderate-severe OSA and smoking was associated with the most severe impairment in endothelial function.

Influence of Postprandial Hyperglycemic Conditions on Arterial Stiffness in Patients With Type 2 Diabetes.

Patients with type 2 diabetes (T2D) are at an increased risk of cardiovascular disease. The objective of the study was to determine whether postprandial hyperglycemia affects arterial function in T2D. A single-center, open-label study of three groups of men were studied: 1) T2D patients with albuminuria (n = 22), 2) T2D patients without albuminuria (n = 24), and 3) nondiabetic controls (n = 25). Patients were randomized to a two-period crossover study schedule, ingesting breakfast, with or without insulin lispro (to induce low or high postprandial glycemia). Arterial stiffness was assessed by calculating pulse wave velocity (PWV) and augmentation index using applanation tonometry, and endothelial dysfunction was assessed using peripheral arterial tonometry, 30 minutes before breakfast and up to 240 minutes after breakfast. At baseline, arterial stiffness was increased in patients. When adjusted for age and body mass index, in a combined group of patients with and without albuminuria, brachial PWV was higher during low (P = .032) and high (P = .038) postprandial glycemia vs controls. These differences were driven by the albuminuria group vs controls during low (P = .014) and high (P = .018) postprandial glycemia. No differences were observed in aortic PWV, augmentation index, or peripheral arterial tonometry ratio between patients and controls. Endothelin-1 and IL-6 were higher, and superoxide dismutase was lower, during postprandial hyperglycemia in T2D patients vs controls. In patients with T2D and albuminuria, brachial PWV was higher under postprandial hyperglycemic conditions, relative to controls. These data suggest that hyperglycemia induces an increase in stiffness of intermediate-sized arteries. We found no changes in other parts of the arterial bed.

Abstract 17413: Influence of Endothelial Function and Rho-Associated Kinase Activity in Patients With Primary Aldosteronism

Background: Primary aldosteronism (PA) is a most common cause of secondary hypertension and patients are divided into two subtypes in clinically, aldosterone producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). Hypertension is associated with endothelial dysfunction. It is well known that endothelial dysfunction is an independent predictor of cardiovascular events. Rho-associated kinases (ROCKs), one of the first downstream targets of the small GTP-binding protein Rho A, mediate various cellular physiologic functions. It has been reported that an increase in ROCK activity is associated with cardiovascular diseases, including hypertension. However, there is little information on the relationship between subtype of PA and the grade of atherosclerosis. The purpose of this study was to evaluate the vascular function and ROCK activity in patients with PA. Methods: Vascular function, including peripheral arterial tonometry (PAT) and ROCK activity in peripheral leukocytes were evaluated in 18 patients with APA group (49.5±15.5 years, 7 males), 14 patients with IHA group (56.1±11.0 years, 8 males), and 23 age-, gender-, and blood pressure-matched EH group (55.6 ± 9.9 years, 13 males). Results: PAT ratio was significantly lower in the APA and IHA groups than in the EH group (0.62±0.23 vs. 0.62±0.24 and 0.79±0.28, P&lt;0.05, respectively), whereas there was no significant difference in PAT ratio between the APA group and IHA group. ROCK activity was significantly higher in the APA group than in the IHA group and EH group (1.36±0.58 vs. 0.95±0.51 and 0.80±0.39, P&lt;0.05 and P&lt;0.001, respectively), whereas there was no significant difference in ROCK activity between the IHA group and EH group. PAT ratio correlated with plasma aldosterone concentration (PAC) (r=-0.36, P&lt;0.01) and plasma renin activity ratio (ARR) (r=-0.26, P=0.05). ROCK activity correlated with serum potassium (r=-0.27, P=0.05), PAC (r=0.39, P&lt;0.01) and ARR (r=0.49, P&lt;0.01). Conclusions: APA and IHA were associated with endothelial dysfunction and APA increased ROCK activity compared with those in IHA and EH. These findings suggest that APA may have a higher risk of future cardiovascular events.