Luc M. Van Bortel

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.

Short and long-term effects of smoking on arterial wall properties in habitual smokers

OBJECTIVESnThis study investigated the short-term effects of smoking on hemodynamic function and distensibility and compliance of large arteries in habitual smokers. In addition, the effect of smoking was not measured in nonsmokers, but vessel wall properties were compared between smokers and nonsmokers (basal state).nnnBACKGROUNDnSmoking is a well known risk factor for atherosclerosis. Loss of distensibility and compliance of large arteries may play a role in the onset of atherosclerosis.nnnMETHODSnThe distensibility and compliance coefficients of the common carotid and brachial arteries were determined from the arterial wall displacement during systole and the end-diastolic diameter by using a vessel wall movement detector and from the pulse pressure as assessed in the upper arm. Cardiac function (cardiac output, stroke volume) was measured with Doppler echocardiography. Systemic vascular resistance was calculated as mean arterial pressure divided by cardiac output.nnnRESULTSnIn habitual smokers, smoking one cigarette caused a sharp increase in blood pressure (6%) and heart rate (14%). Cardiac index increased (16%), mainly because of the marked increase in heart rate. Stroke and systemic vascular resistance indexes did not change significantly. Smoking enhanced forearm blood flow after wrist occlusion (17%), but total forearm blood flow was unchanged, suggesting an increase in muscle blood flow and a decrease in skin flow. Because of higher blood pressure, the diameter of the elastic common carotid artery increased by 3% (passive phenomenon). Distensibility of the carotid artery decreased (7%), and as a result, carotid compliance was preserved. In contrast, despite higher blood pressure, the diameter of the muscular brachial artery did not change, suggesting an increased vascular tone. Brachial distensibility and compliance decreased (18% and 19%, respectively). Habitual smokers were comparable to nonsmokers with regard to blood pressure, cardiac function, vascular resistance and vessel wall properties of large arteries. Heart rate was higher in habitual smokers (14%).nnnCONCLUSIONSnThese data indicate that in habitual smokers, smoking one cigarette causes short-term increases in arterial wall stiffness that might be harmful to the artery and increase the risk for plaque rupture. Except for a higher heart rate, no obvious long-term effect of smoking was observed on hemodynamic variables and arterial stiffness. Because acute cardiovascular events are mainly due to plaque rupture, the short-term effects of smoking might be a more important risk than long-term effects for these acute ischemic events.

Resistance and conduit arteries following converting enzyme inhibition in hypertension.

Alterations in the structure of resistance and conduit arteries are a characteristic hallmark in hypertension. Studies carried out in hypertensive rats and in humans suggest that angiotensin I-converting enzyme inhibition has an effect on arterial structure of resistance arteries. In hypertensive rats the reduction of the media to lumen ratio is dose-dependent and significantly different from the effects of other antihypertensive agents at doses causing an equal degree of blood pressure reduction. In large conduit arteries, hypertrophy of the vessels is reversed by converting enzyme inhibition both in hypertensive rats (studies on central arteries) and in human (studies on peripheral arteries) hypertension. The reduction of hypertrophy is associated with a decrease in arterial stiffness, partly independent of blood pressure reduction. These findings suggest that regression of structural vascular changes may contribute to both the decrease in the arteriolar resistance and the improvement in the buffering function of large arteries. The decrease in arteriolar resistance and the improvement of large artery compliance may participate in blood pressure reduction and an improvement in pulse pressure amplification produced by converting enzyme inhibition.

Effects of antihypertensive agents on local arterial distensibility and compliance.

Distensibility and compliance are important vessel wall properties. Distensibility is related to elastic properties of the arterial wall, and compliance reflects the buffering function of the artery. Distensibility is a determinant of stress on the vessel wall. A decreased distensibility might increase the risk of arterial wall damage. Therefore, a preserved local distensibility might be important in protecting the arterial wall of each particular artery and especially of those arteries that are more susceptible to vascular disease. Local distensibility and compliance of various large arteries can be measured noninvasively with echo tracking techniques. Studies on local distensibility and compliance revealed that with the calcium antagonist verapamil and the angiotensin-converting enzyme inhibitor perindopril arterial compliance increased mainly because of an increase in distensibility, with only a minor effect on arterial diameter. In contrast, the nitrate compound isosorbide dinitrate increased compliance mainly by increasing arterial diameter, without an increase in distensibility. This indicates that an increase in arterial compliance does not automatically imply an increase in arterial distensibility. The effect of antihypertensive drugs may also depend on the vascular territory. The diuretic amiloride/hydrochlorothiazide increased brachial artery compliance but not common carotid artery compliance. During angiotensin-converting enzyme inhibition the effect on arterial compliance was smaller at the carotid than the femoral artery. However, the opposite held for the nitrate compound. These distinctive effects of antihypertensive drugs on arterial distensibility and compliance and on vascular territories may be relevant to pharmacological prevention and management of arterial disease.

Effects of hypervolemia on interdialytic hemodynamics and blood pressure control in hemodialysis patients

The influence of hypervolemia on hemodynamics and interdialytic blood pressure, as well as in relation to vascular compliance, was investigated in 10 hemodialysis patients who were not receiving vasoactive medication. All subjects were studied during a relative normovolemic interdialytic period (from 1 kg below dry weight postdialytic until dry weight predialytic) and a hypervolemic interdialytic period (from 1 kg above dry weight postdialytic until 3 kg above dry weight predialytic). Interdialytic blood pressure was measured with an ambulatory blood pressure monitor. Cardiac output was echographically measured and total peripheral resistance calculated postdialytic, mid-interdialytic, and predialytic. At the same time, a blood sample was drawn for analyzing vasoactive hormones, sodium, and hematocrit. In all patients, ideal dry weight was estimated by echography of the caval vein. Arterial and venous compliance were measured with an ultrasound vessel wall movement detector system and a strain-gauge plethysmograph. After fluid load, an increase in intravascular volume, an increase in caval vein diameter and cardiac output, and a decrease in peripheral resistance was observed. No significant influence of a 3-L fluid load was found on interdialytic blood pressure course (153+/-24 mm Hg/90+/-19 mm Hg in the hypervolemic period and 146+/-27 mm Hg/89+/-22 mm Hg in the normovolemic period). Sodium and osmolality were similar in the hypervolemic and normovolemic interdialytic periods. After fluid load, a decrease in arginine vasopressin and angiotensin II was observed, which probably contributed to the decreased systemic vascular resistance. Catecholamines were not influenced by fluid load, but increased during the interdialytic period, suggesting accumulation after dialysis. Three of the 10 patients had higher systolic but not diastolic blood pressures after fluid load (159+/-13 mm Hg/81+/-22 mm Hg in the hypervolemic period and 135+/-16 mm Hg/81+/-22 mm Hg in the normovolemic period). No correlation could be found between arterial or venous compliance and blood pressure changes. We concluded that a 3-L interdialytic fluid load does not result in higher blood pressure in most hemodialysis patients.

Vascular effects of 5-HT1B/1D-receptor agonists in patients with migraine headaches

Second‐generation triptans are believed to have fewer cardiovascular effects than sumatriptan. This was investigated in vivo by comparing the vascular effects of equipotent therapeutic dosages of selective 5‐HT1B/1D‐receptor agonists.

Is it possible to develop drugs that act more selectively on large arteries

BACKGROUNDnPatients with high pulse pressures have an increased risk for cardiovascular events. Drugs that selectively decrease high pulse pressure may be of interest for these patients. Such drugs have a more pronounced effect on large arteries than on resistance vessels.nnnOBJECTIVEnTo compare the selectivity to large arteries of the new nitric oxide donor sinitrodil with the classic nitrate isosorbide dinitrate in healthy young men in order to investigate whether it is possible to develop drugs that act more selectively on large arteries.nnnDESIGNnThe study had a double-blind, 5-way cross-over design. In randomized order, subjects received a single oral dose of 10 mg sinitrodil, 20 mg sinitrodil, 40 mg sinitrodil, isosorbide dinitrate and placebo. Measurements were performed before and 45 min after administration of the drugs. Between each drug administration, at least 3 days of wash-out was allowed.nnnMETHODSnThe effects of the drugs on large arteries and resistance vessels were assessed by their effects on brachial artery compliance and total peripheral resistance, respectively.nnnRESULTSnBrachial artery compliance increased gradually with increasing doses of sinitrodil (by 10, 20 and 27% with 10, 20 and 40 mg sinitrodil, respectively). Total peripheral resistance index decreased with isosorbide dinitrate (by 11%) and 40 mg sinitrodil (by 7%), while it remained unchanged with 10 mg and 20 mg sinitrodil.nnnCONCLUSIONSnThe results of this study show that it may be possible to develop drugs with a higher selectivity for large arteries. Such drugs may be good candidates to decrease high pulse pressure without substantially decreasing mean and diastolic blood pressures.

Does B-mode common carotid artery intima-media thickness differ from M-model?

An increased intima-media thickness of the common carotid artery is thought to be an early sign of atherosclerosis. Both B- and M-mode ultrasonographic techniques are used to measure the intima-media thickness of the common carotid artery (B-IMT and M-IMT, respectively). The present study compares intima-media thickness of the common carotid artery measured with the two techniques. Intima-media thickness was measured in a random population sample of 250 subjects. Comparison was made by mean and 95% confidence intervals of differences between B-IMT and M-IMT, by linear regression analysis, and by intraclass and concordance correlation coefficients. M-IMT was + 0.011 +/- 0.091 mm (95% confidence intervals: -0.167 to + 0.188 mm) larger than B-IMT, which was 0.661 +/- 0.136 mm (range: 0.380 to 1.120 mm). Intraclass and concordance correlation coefficients were 0.802 and 0.801, respectively. In conclusion, acceptable agreement exists between the two methods and there was no important systematic difference between B-IMT and M-IMT.

Disparate effects of antihypertensive drugs on large artery distensibility and compliance in hypertension

Distensibility and compliance are large artery properties, that may be important in cardiovascular disease. Distensibility is a determinant of the pulsatile stress on the vessel wall and is thought important in ageing and atherosclerotic disease. Compliance reflects the buffering capacity of the arteries and is a major determinant of the afterload on the heart. In hypertension large arteries are getting stiffer, resulting in a decreased distensibility and compliance. Decrease in blood pressure by itself can improve large artery properties. Despite a decrease in blood pressure, not all antihypertensive drugs improve large artery properties. Compliance is improved by firstline antihypertensive drugs such as angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, beta-blockers with vasodilating properties, selective beta 1-blockers and some diuretics. Recent data suggest that ACE inhibitors such as perindopril improve distensibility and compliance of large arteries more than diuretics such as amiloride/hydrochlorothiazide. Apart from the indirect effect (decrease in blood pressure), this makes a direct effect of perindopril on large artery properties very likely. ACE inhibitors such as perindopril decrease the afterload on the heart more than diuretics such as amiloride/hydrochlorothiazide by both a more pronounced decrease in systemic vascular resistance and an increase in large artery compliance.

Assessment of regional vascular distensibility in diseased iliofemoral arteries by intravascular ultrasound.

The influence of atherosclerosis on distensibility of iliac and superficial femoral arteries was assessed retrospectively in 28 patients using intravascular ultrasound. Distensibility was related to lesion morphology, lesion geometry, percentage area stenosis, effect of balloon angioplasty, hypertension and patients age. In 10 patients, free lumen area remained unchanged during the cardiac cycle. From the remaining 18 patients, a total of 135 cross-sections underwent qualitative and quantitative analysis. Cross-sections without a lesion were compared with those showing; soft/hard and eccentric/concentric lesions. At normal sites, iliac arteries showed greater distensibility than femoral arteries (6.5 +/- 2.4% vs. 3.5 +/- 0.9%; p < or = 0.05). Hard lesions in iliac arteries were less distensible than lesions; in femoral arteries this difference was less pronounced. Lesion geometry did not influence arterial distensibility. Intravascular ultrasound revealed no difference in distensibility when normal cross-sections were compared with those having a < 50% or a 50% to 90% area stenosis. In contrast, a significant decrease in femoral artery distensibility was found in the presence of > 90% stenosis (0.4%). Comparison of cross-sections before and after balloon angioplasty revealed a marked increase in distensibility of iliac arteries following intervention; in the femoral artery, there was practically no change in distensibility. Hypertension and increasing age proved to have no significant influence on arterial distensibility. This study demonstrates that intravascular ultrasound is potentially a powerful tool to assess arterial distensibility and the influence of atherosclerosis on vascular dynamics.