Digital Arterial Tonometry Research Articles

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.

Impact of metabolic syndrome and systemic inflammation on endothelial function in postmenopausal women.

Data on the impact of metabolic syndrome (MetS) and systemic inflammation on endothelial function remains scarce. In this study, we aimed to investigate the combined effects of MetS and systemic inflammation on endothelial function in postmenopausal women. We identified 423 postmenopausal women from February 2019 through July 2020. MetS was diagnosed according to the International Diabetes Federation (IDF) criteria, and high sensitivity C-reaction protein (hs-CRP) was measured to assess the degree of underlying inflammation. The measurement of endothelial function was using digital arterial tonometry by assessing reactive hyperemia-induced vasodilation in one arm and adjusting for changes in the contralateral arm (reactive hyperemia index, RHI). There were 156 patients with MetS and 267 without MetS. Compared to the group without MetS, patients with MetS had significantly lower natural logarithmic RHI (0.66±0.29 versus 0.91±0.31; p<0.001), but higher levels of hs-CRP (0.98 [0.31, 3.54] versus 0.53 [0.20, 2.14]; p<0.001). In sequential multivariable analysis, the presence of hs-CRP (ΔR2=0.047, p=0.004) had a significant and independent influence on natural logarithmic RHI. Furthermore, the interaction of hs-CRP*MetS was synergistically associated with endothelial dysfunction even in the fully adjusted model (β=-0.107, 95% CI [-0.161~-0.053], p=0.009). MetS and systemic inflammation are synergistically associated with endothelial dysfunction in postmenopausal women. Postmenopausal women with both these conditions appear to be at a significantly higher risk for adverse cardiovascular events.

Effect of prolonged treatment with phosphodiesterase-5-inhibitors on endothelial dysfunction in vascular diseases and vascular risk conditions: A systematic review analysis and meta-analysis of randomized double-blind placebo-controlled trials.

To challenge the argument that continuous use of phosphodiesterase-5-selective inhibitors may reduce endothelial cell dysfunction in patients with vascular diseases or vascular risk conditions. This study included systematic reviews and meta-analysis of randomized double-blind placebo-controlled trials dealing with the prolonged use of phosphodiesterase-5-selective inhibitors. The risk of bias and quality of trials were assessed by the Cochrane algorithm. Fixed or random effect models, standardised mean differences and heterogeneity were estimated in the study. Systematic search for randomized double-blind placebo-controlled trials was done in PubMed, Scopus, CINAHL, Science direct and the Cochrane Library. Randomized double-blind placebo-controlled trials reporting measures of endothelial cell dysfunction and/or endothelial cell activation were included. On the whole, 469 subjects were allocated to the phosphodiesterase-5-selective inhibitor group, while 463 were assigned to the placebo group in 13 randomized double-blind placebo-controlled trials. Flow-mediated dilation of the brachial artery was found to improve after the administration of phosphodiesterase-5-selective inhibitors (P<0.0001). The results were questioned by the elevated and uncorrectable heterogeneity (I2 =92%) and the asymmetry of the funnel plot suggested a publication bias. Phosphodiesterase-5-selective inhibitors have no effect on endothelial cell dysfunction, as assessed in the resistance vessels by digital arterial tonometry. The blood level of endothelin-1 was observed to be decreased in phosphodiesterase-5-selective inhibitors arm (P=0.03), although the effect disappeared once the publication bias and heterogeneity were corrected. The effect of phosphodiesterase-5-selective inhibitors on biomarkers of endothelial cell activation was found to be inconsistent. The results on the benefits of a prolonged use of phosphodiesterase-5-selective inhibitors, with the objective of lowering endothelial cell dysfunction in patients with vascular diseases or vascular risk conditions are not convincing. This is because of the overall low quality of evidence, giving an unclear scientific support to this treatment. Systematic review registration: PROSPERO registration: CRD42017055399.

Increased CVD Risk Burden Diminishes the Protective Effect of Remote Ischemic Preconditioning Against Endothelial Ischemia‐Reperfusion Injury in Humans

PurposeA powerful treatment against endothelial ischemia‐reperfusion injury is remote ischemic preconditioning, which can trigger tissue protection by exposing a limb to small cycles of vascular occlusion. However, animal models of aging, diabetes, hyperlipidemia, and obesity indicate that the protective benefits of ischemic preconditioning are weakened. The extent to which a clinically relevant burden of CVD risk factors interferes with remote preconditioning in humans is not clear. The purpose of the present study was to determine the influence of CVD risk factor burden on the capacity of remote ischemic preconditioning to prevent endothelial reperfusion injury in adults.MethodsTwenty‐two (age: 45±14 yr) sedentary adults (12 lower burden: 0–2 risk factors; &lt;1% 10‐year FRS; 10 raised burden: 3–5 risk factors: ≥1% 10‐year FRS) were studied using a 2×2 randomized cross‐over design. Digital arterial tonometry (EndoPAT 2000, Itamar Medical Inc.) was used to assess endothelial vasodilation during reactive hyperemia before and after 65 min of left arm endothelial ischemia‐reperfusion injury (20 min brachial artery ischemia followed by 45 min reperfusion) that was preceded by remote ischemic preconditioning (right arm brachial artery: 3×5 min ischemia/reperfusion) or sham. Experiments were conducted in accordance with the Declaration of Helsinki for protection of human subjects.Statistical AnalysisRepeated measures ANOVA was used to assess group differences between the reactive hyperemia index (RHI) before and after endothelial reperfusion injury in the absence and presence of remote ischemic preconditioning.ResultsIn lower burden subjects, remote preconditioning was able to prevent endothelial reperfusion injury (from baseline: 2.1±0.4 to post endothelial injury: 2.5±0.5, P=0.072). In contrast, in the raised burden subjects the RHI (baseline: 2.3±0.9) was significantly reduced by 25% despite attempts to induce protection by remote preconditioning (1.8±0.7; P&lt;0.05). The capacity of remote ischemic preconditioning to protect against endothelial reperfusion injury was inversely related (r=−0.61; P=0.004) to CVD risk burden.ConclusionsEndothelial reperfusion injury was prevented when preceded by remote ischemic preconditioning in the lower burden subjects but failed to provide protection in the raised risk burden subjects. CVD risk factors appear to disrupt the protective properties of remote ischemic preconditioning in humans. These findings provide important critical insight to explain why the large‐scale multi‐center RIPHeart and ERICCA randomized trials of remote ischemic preconditioning failed to show reductions in postoperative clinical events in patients undergoing elective cardiac surgery.

The association of endothelial function and tone by digital arterial tonometry with MRI left ventricular mass in African Americans: the Jackson Heart Study

Peripheral vascular endothelial dysfunction assessed by digital peripheral arterial tonometry (PAT) has been associated with risk for adverse cardiovascular events. We examined the relations of peripheral microvascular dysfunction and left ventricular mass in a community-based cohort of African Americans. We examined participants of the Jackson Heart Study who had PAT and cardiac magnetic resonance imaging evaluations between 2007 and 2013. Consistent with pertinent literature, left ventricular mass index (LVMI) was adjusted for body size by indexing to height2.7. Pearson's correlation and general linear regression analyses were used to relate reactive hyperemia index, baseline pulse amplitude (BPA), and augmentation index (markers of microvascular vasodilator function, baseline vascular pulsatility, and relative wave reflection, respectively) to LVMI after adjusting for traditional cardiovascular risk factors. A total of 440 participants (mean age 59 ± 10 years, 60% women) were included. Age- and sex-adjusted Pearson's correlation analysis suggested that natural log transformed LVMI was negatively correlated with reactive hyperemia index (coefficient: −0.114; P = .02) and positively correlated with BPA (coefficient: 0.272; P < .001). In multivariable analyses, higher loge LVMI was associated with higher BPA (β: 0.210; P = .03) after accounting for age, sex, body mass index, diabetes, hypertension, ratio of total cholesterol and high-density lipoprotein cholesterol, smoking, and history of cardiovascular disease. In a community-based sample of African Americans, higher baseline pulsatility measured by PAT was associated with higher LVMI by cardiac magnetic resonance imaging after adjusting for traditional risk factors.

Comparison of the Effect of the Metabolic Syndrome and Multiple Traditional Cardiovascular Risk Factors on Vascular Function

ObjectiveTo assess the effect of the metabolic syndrome (MetS) on endothelial function and compare these findings to those in individuals with a similar burden of traditional cardiovascular (CV) risk factors (≥3) without MetS. Patients and MethodsBoth MetS and multiple CV risk factors were identified from 1103 individuals who underwent the evaluation of endothelial function at the Mayo Clinic, in Rochester, Minnesota, from July 1, 2000, through July 31, 2011. Endothelial function was measured using digital arterial tonometry by assessing reactive hyperemia–induced vasodilation in one arm and adjusting for changes in the contralateral arm (reactive hyperemia index [RHI]). ResultsA total of 316 individuals with MetS and 210 with multiple risk factors were assessed. Endothelial dysfunction was more pronounced in the MetS group compared with the multiple risk factor group (mean ± SD natural logarithmic RHI, 0.61±0.25 and 0.68±0.28, respectively; P=.006). Leukocyte count (7.00±1.89 × 109/L vs 6.41±1.76 × 109/L, respectively; P=.001) and high-sensitivity C-reactive protein level (1.78±1.53 mg/L vs 1.48±1.42 mg/L, respectively; P=.01) were higher in the MetS group compared with the multiple risk factor group. After adjustment for covariates and 6 traditional CV risk factors in a multivariate regression model, MetS had a significant and independent influence on natural logarithmic RHI (β=−.11; P=.01). ConclusionThe current study found that individuals with MetS have a higher degree of endothelial dysfunction and inflammation compared with individuals with multiple CV risk factors and may therefore have an increased CV risk beyond the contributions of multiple traditional risk factors.

Abstract P099: The Relation of Kidney Disease to Measures of Digital Arterial Tonometry in the Jackson Heart Study

Background: The presence of chronic kidney disease is greater in African Americans than in non-Hispanic whites. Though there is data to show a relation between endothelial dysfunction and end-stage kidney disease, the relation to mild and moderate chronic kidney disease (particularly in African Americans) is unclear. Methods and Results: Digital arterial tonometry was performed during Exam 2 and 3 of the Jackson Heart Study using the endoPAT2000. Data from digital arterial tonometry included baseline pulse wave amplitude (BPA) as a measure of endothelial tone and reactive hyperemic index (F-RHI) as a measure of endothelial function. For this study, the estimated glomerular filtration rate (eGFR) was calculated using the MDRD equation. Those participants with eGFR &lt; 60 ml/min/1.73m2 were defined as having CKD. Participants with eGFR &lt; 15 ml/min/1.73m2 were excluded from the analysis. Microalbuminuria in this study was defined as a urinary albumin:creatinine ratio ≥ 17mg/g in men and ≥ 25 mg/g in women. We compared the differences in least square means adjusted for age and sex, and adjusted for multiple traditional clinical covariates using a generalized linear model. Results: There were 834 participants in the study population (mean age 58.5 years, 61% women); 87 (10.4%) participants with CKD and 108 (13.0%) with microalbuminuria. In age and sex adjusted samples, we found that both BPA and F-RHI were significantly associated with CKD in the pooled samples. However in multivariable adjusted analysis the relation was no longer significant in either the pooled or sex-specific samples. In the multivariable adusted analysis,BPA was significantly (P=0.036) associated with microalbuminuria in men and F-RHI was weakly significantly (P=0.08) associated with microalbuminuria in women. Conclusion: We found that endothelial dysfunction as measured by digital arterial tonometry is not significantly associated with chronic kidney disease. There is an association of endothelial tone in men and endothelial dysfunction in women with microalbuminuria.