Peripheral augmentation index as a biomarker of vascular aging: an invasive hemodynamics approach.

We compared two measures of vascular function obtained from digital volume waveforms with measures of target organ damage and novel invasive measures of vascular function as they relate to vascular aging. Aortic pulse pressure amplification, pulsatility, form factor and extent of coronary atherosclerosis (modified Gensini score) were obtained invasively in 59 patients undergoing left heart catheterization. Digital volume waveforms were captured via peripheral arterial tone (PAT) and used to derive augmentation index (AIx) and the pulse wave amplitude-reactive hyperemia index (PWA-RHI). AIx was associated with age (r = 0.50, p < 0.05) and aortic pulsatility (r = 0.45, p < 0.05) and inversely associated with estimated glomerular filtration rate (-0.29, p < 0.05) aortic pulse pressure amplification (r = -0.28, p < 0.05) and aortic form factor (r = -0.38, p < 0.05). AIx was slightly higher in patients with left ventricular hypertrophy (LVH) versus those without left ventricular hypertrophy (30 vs. 14%, p = 0.058). There was no association between AIx and Gensini score. PWA-RHI was not associated with age, estimated glomerular filtration rate or invasive vascular parameters and did not differ in patients with versus without LVH (p = ns). PWA-RHI was inversely associated with Gensini score (r = -0.32, p < 0.05). AIx derived from PAT is correlated with age-associated changes in vascular function and target organ damage but not coronary atherosclerotic burden. PWA-RHI is associated with coronary atherosclerotic burden but is not associated with target organ damage or other measures of vascular aging assessed in this study. Each parameter provides distinct insight into systemic vascular aging and target organ damage.

Endothelium-dependent vasodilation is associated with exercise capacity in smokers and non-smokers.

Smoking is an established cardiovascular risk factor that impairs endothelial function and reduces exercise capacity. Peripheral vascular endothelial function correlates with exercise capacity, but whether this association prevails in smokers is unknown. The purpose of this investigation was to examine the association between endothelial function and exercise capacity in chronic smokers and non-smoking controls. Brachial artery flow-mediated dilation (FMD, endothelium-dependent) following 5 minutes of upper arm occlusion was compared in 26 smokers (age 58 +/- 2 years; 15 female; BMI (body mass index) = 28 +/- 1) and 39 non-smokers (age 58 +/- 2 years; 24 female; BMI = 28 +/- 1) using ultrasound. Exercise treadmill time (ETT) was recorded from a standard Bruce protocol during symptom limited stress testing. There was found to be a significant positive association between FMD and ETT in smokers (r = 0.60, p < 0.05) and non-smokers (r = 0.28, p < 0.05). FMD was significantly lower in smokers versus non-smokers (8.9 +/- 0.9 vs 12.6 +/- 0.7%, p < 0.05). ETT was significantly lower in smokers (425 +/- 35 seconds) versus non-smokers (522 +/- 25 seconds, p < 0.05). After adjusting for FMD, there were no longer group differences in ETT. When patients were matched according to FMD, there were no differences in ETT between smokers and non-smokers. In conclusion, peripheral endothelial dysfunction is a correlate of low exercise capacity in smokers and non-smokers alike. Future research is needed to examine if improving endothelial function will lead to concomitant increases in exercise capacity in chronic smokers.

Peripheral Augmentation Index is Associated With the Ambulatory Arterial Stiffness Index in Patients With Hypertension.

BACKGROUND: Vascular dysfunction is highly prevalent if not ubiquitous in patients with hypertension. We compared two different measures of vascular function obtained from digital volume waveforms with measures of ventricular-vascular load derived from 24-hour blood pressure (BP) recordings in patients with hypertension. METHODS: Digital pulsatile volume waveforms were captured via plethysmography (peripheral arterial tone, PAT) and used to derive augmentation index (a measure of ventricular-vascular coupling) and the pulse wave amplitude-reactive hyperemia index (a measure of microvascular reactivity). Ambulatory arterial stiffness index (AASI) and the BP variability ratio (BPVR) were derived from 24-hour ambulatory BP recordings. RESULTS: There was a positive association between PAT-AIx and AASI (r = 0.52, P < 0.05). There was also a positive association between PAT-AIx and BPVR (r = 0.37, P < 0.05). PAT-AIx was not associated with PWA-RHI (r = -0.14, P > 0.05). PWA-RHI was not associated with AASI or BPVR (P > 0.05). CONCLUSIONS: PAT-AIx is associated with ambulatory measures of vascular function and may offer clinical insight into vascular burden and cardiovascular disease risk in patients with hypertension independent of information obtained from PWA-RHI.

Effect of atenolol vs metoprolol succinate on vascular function in patients with hypertension.

BACKGROUND: We evaluated the effect of atenolol vs metoprolol succinate on vascular function in patients with essential hypertension. HYPOTHESIS: Given intrinsic differences between these agents, we hypothesized that atenolol and metoprolol succinate would have disparate effects on vascular function. METHODS: This study included 24 patients with hypertension (age 56 ± 2 years, 8 female, body mass index 28 ± 1) and featured a randomized, double-blind, crossover design. Each ß-blocker (atenolol or metoprolol succinate) was taken by patients once daily for a 4-week period. Measures of vascular function included peripheral augmentation index (AIx) and pulse wave amplitude reactive hyperemia index from peripheral arterial tonometry, and brachial artery flow-mediated dilation from ultrasound. RESULTS: There were similar reductions in mean arterial pressure following treatment with atenolol and metoprolol succinate. Compared with metoprolol succinate, there was a significant increase in peripheral AIx following atenolol therapy (P < 0.05). There were no changes in brachial artery flow-mediated dilation or pulse wave amplitude reactive hyperemia index following either drug treatment. CONCLUSIONS: Although atenolol and metoprolol succinate have similar effects on blood-pressure reduction, they have different effects on vascular function. Compared with metoprolol succinate, atenolol increases peripheral AIx. Neither drug has an effect on vascular endothelial function. These findings may have clinical implications, depending on the indication for treatment in an individual patient.

Utility of the neutrophil to lymphocyte ratio in predicting long-term outcomes in acute decompensated heart failure.

Neutrophil-to-lymphocyte ratio (NLR) has been associated with poor outcomes in patients with acute coronary syndromes. However, its role for risk stratification in acute decompensated heart failure (ADHF) has not been well described. In this study, 1,212 consecutive patients admitted with ADHF who had total white blood cell and differential counts measured at admission were analyzed. The patients were divided into tertiles according to NLR. The association between NLR and white blood cell types with all-cause mortality was assessed using Cox regression analysis. During a median follow-up period of 26 months, a total of 284 patients (23.4%) had died, and a positive trend between death and NLR was observed; 32.8%, 23.2%, and 14.2% of deaths occurred in the higher, middle, and lower tertiles, respectively (p <0.001). After adjusting for confounding factors, multivariate analysis demonstrated that patients in the higher NLR tertile had the highest mortality (adjusted hazard ratio 2.23, 95% confidence interval (CI) 1.63 to 3.02, p <0.001), followed by those in the middle tertile (adjusted hazard ratio 1.62, 95% CI 1.16 to 2.23, p = 0.001). Furthermore, tertiles of NLR were superior in predicting long-term mortality compared with white blood cell, neutrophil, and relative lymphocyte counts. Patients in the higher NLR tertile (adjusted odds ratio 3.46, 95% CI 2.11 to 5.68, p <0.001) had a significantly higher 30-day readmission rate. In conclusion, higher NLR, an emerging marker of inflammation, is associated with an increased risk for long-term mortality in patients admitted with ADHF. NLR is a readily available inexpensive marker to aid in the risk stratification of patients with ADHF.

Relation of pulse pressure to blood pressure response to exercise in patients with hypertrophic cardiomyopathy.

Almost one third of patients with hypertrophic cardiomyopathy (HC) will have an abnormal blood pressure response (ABPR) to exercise, and this has been associated with a greater risk of sudden cardiac death. In the present study, we examined the association between the steady (mean arterial pressure) and pulsatile (pulse pressure) blood pressure components as they relate to ABPR in patients with HC (n = 70). All patients completed a standard Bruce protocol during symptom-limited stress testing with concurrent hemodynamic measurements. Pulse pressure (PP) was significantly greater in patients with HC with an ABPR (n = 19) than in the patients with HC without an ABPR to exercise (p <0.05). According to binary logistic regression analysis, PP at rest was a significant predictor of ABPR in patients with HC (p <0.05). Mean arterial pressure was not significantly different between the 2 groups, nor was it a predictor of an ABPR in the presence of HC. Those within the greatest tertile of PP at rest were 4.8 times more likely to have an ABPR than those within the lowest PP tertile (95% confidence interval 1.24 to 18.2, p <0.05). In conclusion, elevations in PP at rest might identify patients with HC at a greater risk of having an ABPR during exercise.

L-arginine as a nutritional prophylaxis against vascular endothelial dysfunction with aging.

With advancing age, peripheral conduit and resistance arteries lose the ability to effectively dilate owing to endothelial dysfunction. This vascular senescence contributes to increased risk of cardiovascular disease (CVD) with aging. L-arginine plays a role in numerous physiological processes including nitrogen detoxification, immunocompetence, growth hormone (GH) secretion, and insulin secretion. Recently, a considerable amount of attention has been placed on the ability of this amino acid to affect vascular endothelial function. The purpose of this review will be to examine the use of L-arginine as a novel nutritional strategy to potentially stave progression of vascular dysfunction with aging and CVD. Emphasis will be placed on the ability of L-arginine to modulate the vascular inflammatory and systemic hormonal milieu, which in turn may have a positive effect on vascular endothelial function.

Elevated augmentation index derived from peripheral arterial tonometry is associated with abnormal ventricular-vascular coupling.

BACKGROUND: Although typically derived from the contour of arterial pressure waveform, augmentation index (AIx) may also be derived from the digital pulse volume waveform using finger plethysmography (peripheral arterial tonometry, PAT). Little is known regarding the physiologic correlates of AIx derived from PAT. In this study, we investigated the relation of PAT-AIx with measures of ventricular-vascular coupling. METHODS: Pulse volume waves were measured via PAT and used to derive AIx. Using 2-dimensional echocardiography, effective arterial elastance index (EaI) was estimated as end-systolic pressure/stroke volume index. Left ventricular (LV) end-systolic elastance index (E(LV)I) was calculated as end-systolic pressure/end-systolic volume index. Ventricular-vascular coupling ratio was defined as EaI/E(LV)I. RESULTS: Given the bi-directional nature of ventricular-vascular uncoupling as measured by echocardiography, patients were separated into three groups: low EaI/E(LV)I (<0.6, n = 21), optimal EaI/E(LV)I (mean 0.6-1.2, n = 16) and high EaI/E(LV)I (>1.2, n = 10). Adjusting for potential confounders (age, mean arterial pressure, height and heart rate), patients with optimal EaI/E(LV)I had lower AIx (1 +/- 4%, P<0.05) compared to those with low EaI/E(LV)I (13 +/- 4%) and high EaI/E(LV)I (19 +/- 5%). CONCLUSIONS: Abnormal ventricular-vascular coupling, arising from either increased effective arterial elastance or increased ventricular elastance, is associated with increased AIx as measured by PAT. Additional research is needed to examine other vascular correlates of PAT-AIx.

Assessment of vascular endothelial function with peripheral arterial tonometry: information at your fingertips?

Endothelial dysfunction is an important component in the pathogenesis of atherosclerosis. The ability to assess the endothelium in a meaningful manner has been the subject of intense investigation over decades. Since the function of endothelial cells is a gauge of vascular health, assessment of vascular function is emerging as a useful tool for predicting cardiovascular risk and as a surrogate outcome measure for cardiovascular reduction intervention studies. This review highlights techniques for assessing endothelial function, focusing on a novel method of determining peripheral vascular reactivity via arterial tonometry.

Peripheral arterial tonometry for risk stratification in men with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) risk is not fully revealed by traditional risk factors. Identification of a simple, noninvasive tool that allows for detection of high-risk CAD patients and can be applied in large populations and clinical settings would prove valuable. HYPOTHESIS: We sought to test the hypothesis that peripheral arterial tonometry (PAT) would be associated with residual risk in men with CAD. METHODS: In this study, finger PAT was used to measure pulse wave amplitude (PWA) during reactive hyperemia (RH) and taken as a measure of microvascular endothelial function in 42 men with stable CAD and well controlled low-density lipoprotein cholesterol (LDL-C) levels. Plasma levels of high-sensitivity C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA(2)) were measured and used to reclassify men into high-risk (elevated hs-CRP and Lp-PLA(2)), moderate-risk (either elevated hs-CRP or Lp-PLA(2)), or low-risk (low hs-CRP and Lp-PLA(2)) groups. RESULTS: PWA-RH was significantly lower in the high-risk group (1.3 +/- 0.04) compared to the moderate-risk (1.6 +/- 0.07, P < 0.05) and low-risk (2.0 +/- 0.1, P < 0.05) groups. According to binary logistic regression, PWA-RH was a significant predictor of high-risk status among men with CAD (P < 0.05). CONCLUSION: Measurement of peripheral microvascular endothelial function with PAT may be able to distinguish high-risk men from moderate- and low-risk men with stable CAD and well-controlled LDL-C levels and thus aid in residual risk stratification in this at risk cohort.

Peripheral vascular endothelial function in patients with hypertrophic cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HC) have coronary microvascular dysfunction, which is an independent predictor of adverse left ventricular remodeling, systolic dysfunction, and mortality in these patients. Whether these defects in vasomotor function are localized to the coronary arteries or whether systemic vasomotor dysfunction is present in patients with HC has not yet been adequately examined. The aim of this study was to test the hypothesis that patients with HC have altered peripheral vascular endothelial function. Subjects without coronary artery disease (CAD) and those with CAD served as negative and positive controls, respectively. Conduit artery endothelium-dependent vasomotion was assessed with ultrasound by measuring flow-mediated dilation of the brachial artery. Flow-mediated dilation was lower in patients with HC compared with those without CAD (p <0.05) but was similar in patients with CAD (p = NS). In conclusion, vasomotor dysfunction in HC is not restricted to the coronary vasculature. Patients with HC have impaired peripheral conduit vessel endothelial function, and the magnitude of impairment is similar to that seen in older patients with advanced CAD.