Daniel R. Kaiser

Clinical applications of arterial stiffness, Task Force III: recommendations for user procedures

In vivo arterial stiffness is a dynamic property based on vascular function and structure. It is influenced by confounding factors like blood pressure (BP), age, gender, body mass index, heart rate, and treatment. As a consequence, standardization of the measurement conditions is imperative. General and method/device-specific user procedures are discussed. The subjects conditions should be standardized before starting measurements. These conditions include a minimal resting period of 10 min in a quiet room. It also includes prohibitions on smoking, meals, alcohol, and beverages containing caffeine before measurements. The position of the subject and time of measurements should be standardized. In comparative studies, corrections should be made for confounding factors. Repeated measurements are done preferably by the same investigator, and if available validated with user-independent automated procedures. As it is not feasible to discuss all methods or devices measuring arterial stiffness in one article, more attention is given to user procedures of commercially available devices, because these devices are of interest for a wider group of investigators. User procedures of methods/devices are discussed according to the nature of arterial stiffness measured: systemic, regional, or local arterial stiffness. Each section discusses general or method/device-specific user procedures and is followed by recommendations. Each recommendation discussed during the First International Consensus Conference on the Clinical Applications of Arterial Stiffness is quoted with the level of agreement reached during the conference. Also proposals for future research are made.

In Vivo Human Brachial Artery Elastic Mechanics Effects of Smooth Muscle Relaxation

BACKGROUND The effects of smooth muscle relaxation on arterial wall mechanics are controversial. We used a new, in vivo, noninvasive technique to measure brachial artery wall mechanics under baseline conditions and following smooth muscle relaxation with nitroglycerin (NTG). METHODS AND RESULTS Eight healthy, normal subjects (6 male, 2 female; age 30+/-3.1 years) participated in the study. The nondominant brachial artery was imaged through a water-filled blood pressure cuff using an external ultrasound wall-tracking system at baseline and following 0.4 mg sublingual NTG. Simultaneous radial artery pressure waveforms were recorded by tonometry. Transmural pressure (TP) was reduced by increasing water pressure in the cuff. Brachial artery area, unstressed area, compliance, stress, strain, incremental elastic modulus (Einc), and pulse wave velocity (PWV) were measured over a TP range from 0 to 100 mm Hg. Baseline area versus TP curves generated 30 minutes apart were not significantly different. NTG significantly shifted area versus TP (P<0.0001) and compliance versus TP (P<0.001) curves upward, whereas the Einc versus TP (P<0.05) and PWV versus TP (P<0. 01) curves were shifted downward. NTG also significantly shifted stress versus strain (P<0.01) and Einc versus strain (P<0.01) curves to the right. CONCLUSIONS We conclude that brachial artery elastic mechanics can be reproducibly measured over a wide range of TP and smooth muscle tone using a new noninvasive ultrasound technique. Smooth muscle relaxation with NTG increases isobaric compliance and decreases isobaric Einc and PWV in the human brachial artery.

Smooth Muscle Relaxation: Effects on Arterial Compliance, Distensibility, Elastic Modulus, and Pulse Wave Velocity

Compliance, distensibility, incremental elastic modulus (E(inc)), and pulse wave velocity are all terms used to describe the mechanical properties of arteries. Previous studies assessing the effects of smooth muscle relaxation on each of these parameters have produced conflicting results. Our laboratory has previously demonstrated that intrabrachial infusion of nitroglycerin in normal human subjects results in a large increase in brachial artery compliance without changing arterial wall stiffness as measured by E(inc). In the present study, the relationships among compliance, distensibility, E(inc), and pulse wave velocity under different levels of vascular tone are shown using data acquired by intravascular ultrasound as well as theoretical curves. We demonstrate that the effects of smooth muscle relaxation can be depicted as 2 separate steps: (1) a rightward shift to a new theoretical curve describing the relationship between 2 of the above elastic parameters that is solely due to changes in vessel geometry and (2) a shift along the new curve that is dependent on changes in wall stiffness.

Relationships of Cardiac Autonomic Function With Metabolic Abnormalities in Childhood Obesity

Objective: The objective was to examine cardiovascular autonomic (cANS) function and its potential relationships with leptin resistance, insulin resistance, oxidative stress, and inflammation in a pediatric sample with varying levels of obesity.

Rosiglitazone improves endothelial function and inflammation but not asymmetric dimethylarginine or oxidative stress in patients with type 2 diabetes mellitus

We compared the vascular effects of rosiglitazone versus glyburide and evaluated asymmetric dimethylarginine (ADMA) and oxidative stress as potential mechanisms associated with changes in vascular health in patients with type 2 diabetes mellitus (T2DM). Patients were randomized to 6 months of either rosiglitazone (n = 20) or glyburide (n = 16) in addition to metformin. The following variables were measured pre- and post-treatment: glucose, insulin, homeostasis model assessment (HOMA), hemoglobin A1c (HbA1c), C-peptide, blood pressure, lipids, C-reactive protein (CRP), ADMA, 8-isoprostane, oxidized LDL cholesterol, brachial artery flow-mediated dilation (FMD), endothelium-independent dilation (EID), and brachial and carotid artery stiffness. Rosiglitazone and glyburide treatment resulted in significant and equivalent decreases in glucose (p < 0.0001) and HbA1c (p < 0.0001), with a trend toward decreased HOMA (p = 0.09). Rosiglitazone significantly decreased C-peptide (p < 0.01) with a strong trend toward decreased fasting insulin (p = 0.05). Rosiglitazone reduced CRP compared with glyburide (p = 0.001), but no differences were observed between groups for ADMA or the markers of oxidative stress. Rosiglitazone significantly improved FMD (p < 0.05) with trends toward improvements in carotid artery distension (p = 0.099) and distensibility (p = 0.078). In conclusion, compared with glyburide, rosiglitazone improves endothelial function and CRP in patients with T2DM. These improvements are not associated with reductions in ADMA or markers of oxidative stress.

The effects of quinapril and atorvastatin on the responsiveness to sildenafil in men with erectile dysfunction

Phosphodiesterase-5 (PDE-5) inhibitors are an effective therapy for the majority of men with erectile dysfunction (ED). However, many men with ED still report a suboptimal or partial response even after an adequate trial of oral PDE-5 therapy. Since ED is associated with impaired vascular function and both atorvastatin and quinapril have been previously shown to improve vascular function, we examined the effects of adjunctive treatment with these medications in men with vasculogenic ED who were suboptimal responders to 100 mg of sildenafil. Men with ED and suboptimal response to sildenafil were randomly assigned to 3 months of treatment with atorvastatin 40 mg (n = 12), quinapril 10 mg (n = 10), or placebo (n = 13), along with continued adjunctive sildenafil use. Measured variables included: International Index of Erectile Function (IIEF) questionnaire, brachial artery flow-mediated dilation (FMD), endothelium-independent dilation (EID) via nitroglycerin, penile Doppler blood flow, blood pressure (BP), lipids, and C-reactive protein (CRP). Compared to placebo, quinapril (p < 0.01) significantly improved symptoms of ED as measured by the IIEF-5 questionnaire. There was a trend toward a significant improvement in IIEF-5 with atorvastatin. Similarly, quinapril significantly improved the IIEF ED Domain (p < 0.05). Other peripheral and penile vascular parameters were unchanged with drug therapy as compared to placebo. In conclusion, treatment with quinapril, in combination with sildenafil, improved ED in men with suboptimal response to sildenafil alone. Atorvastatin demonstrated a trend toward improved ED in this group.

Role of nitric oxide deficiency and its detection as a risk factor in pre-hypertension.

Systemic inhibition of nitric oxide (NO) synthesis raises blood pressure, and endothelial dysfunction with reduced NO bioactivity is a precursor of atherosclerosis. Pre-hypertensive blood pressures place patients at increased risk for cardiovascular morbid events. Whether NO deficiency contributes to this increased risk has not been explored. Constitutive NO release was inhibited by infusion of the substituted arginine NG-nitro-L-arginine-methyl ester (L-NAME) in 10 normal volunteers. Hemodynamics, radial artery pulse contour analysis, brachial artery ultrasound, and aortic pulse wave velocity were monitored as well as plasma neurohormone levels. A modest rise in blood pressure within the normotensive range (113/65 to 124/77 mm Hg, P < .01) was accompanied by a rise in estimated systemic vascular resistance (1193 to 1514 dyne-sec-cm-5, P < .001). Pulse contour analysis revealed a fall to abnormal levels in systemic small artery elasticity (diastolic decay) (9.8 to 6.4 ml/mm Hg, P < .001) and a less consistent but significant increase in the second pressure peak in systole (P < .05). Large artery elasticity index, brachial artery caliber, and brachial artery compliance were unchanged. Flow-mediated brachial artery dilation was blunted slightly (5.29% to 4.47%, P = .06), and aortic pulse wave velocity increased slightly but significantly (8.25 to 8.98 m/s, P = .04), probably as a result of the rise in pressure. The magnitude of effect of L-NAME on small artery elasticity (-31.2% +/- 18.4%) was significantly greater and more consistent than its effect on other vascular measurements. Circulating neurohormonal vasoconstrictor levels fell or were unchanged after L-NAME, and a significant reduction in plasma norepinephrine was closely inversely correlated with the rise in blood pressure. Nitroglycerin infusion in 4 additional subjects produced selective relaxation in small arteries, whereas norepinephrine constricted both small and large arteries. A hemodynamic state consistent with pre-hypertension was induced by NO synthase inhibition in normal volunteers. Reduction in small artery compliance was a sensitive marker for this induced endothelial dysfunction and may serve as a useful marker for pre-hypertensive patients at risk for cardiovascular morbid events.

Intramural dyssynchrony from acute right ventricular apical pacing in human subjects with normal left ventricular function.

Ventricular pacing causes early myocardial shortening at the pacing site and pre-stretch at the opposing ventricular wall. This contraction pattern is energetically inefficient and may lead to decreased cardiac function. This study was designed to describe the acute effects of right ventricular apical (RVa) pacing on dyssynchrony and systolic function in human subjects with normal left ventricular (LV) function and compare these effects to pacing from alternate ventricular sites. Patients (n = 26) undergoing an electrophysiology evaluation were studied during atrial pacing (AAI) and dual chamber pacing from the RVa, left ventricular free wall (LVfw), and the combination of RVa and LVfw (BiV). Tissue Doppler imaging was used to measure intramural dyssynchrony by utilizing an integrated cross-correlation synchrony index (CCSI) from the apical 4-chamber view. RVa and BiV pacing significantly reduced systolic function as measured by longitudinal systolic contraction amplitude (SCAlong) (p < 0.05) and LV velocity time integral (VTI) (p < 0.05) compared to AAI and LVfw pacing. RVa (and to a lesser extent BiV) pacing resulted in septal and lateral intramural dyssynchrony as indicated by significantly (p < 0.05) lower CCSI values as compared to AAI. CCSI was significantly (p < 0.05) worse during RVa than LVfw pacing. In patients with normal LV function, acute ventricular pacing in the RVa alone, or in conjunction with LVfw pacing (BiV), results in impaired regional and global LV systolic function and intramural dyssynchrony as compared to LVfw pacing alone.

Intramural dyssynchrony and response to cardiac resynchronization therapy in patients with and without previous right ventricular pacing

Right ventricular (RV) pacing is an iatrogenic cause of heart failure (HF) that has not been well studied. We assessed whether HF patients paced from the right ventricle (RVp) adversely remodel and respond to cardiac resynchronization therapy (CRT) in a similar way to HF patients without right ventricular pacing (nRVp).

Diet revision in overweight children: effect on autonomic and vascular function

In an effort to determine the effect of a 5-month dietary modification on measures of vascular and cardiac autonomic (cANS) function in overweight (OW) children, 15 OW children had standard non-invasive measures of vascular and cANS function assessed pre- and post-intervention. Body fat percentage and cANS, but not vascular, function changed significantly after the intervention. Changes in body composition in OW children due to dietary modification alone can result in modest improvements in indices of cardiac risk.