Radial artery flow-mediated dilatation in heart failure patients: effects of pharmacological and nonpharmacological treatment.

Congestive heart failure (CHF) is associated with an impaired flow-mediated vasodilation that reflects an impaired endothelial function. Limited information is available, however, on whether and to what extent this impairment is improved by pharmacological or nonpharmacological treatment. We measured radial artery diameter and blood flow by an echo-tracking Doppler device both at baseline and after 4 minutes of hand ischemia, which increases diameter through NO secretion mediated by an increase in flow and shear stress. Data were collected from 44 CHF patients (New York Heart Association class I to III) under standard treatment (diuretic, digitalis, and enalapril, 20 mg/d), in whom CHF severity was assessed by a cardiopulmonary stress test, and from 16 age- and sex-matched controls. CHF patients were then randomized to maintain for (A) 2 months of standard treatment (n=11), (B) treatment with double the ACE inhibitor dose (n=11), (C) standard treatment with an angiotensin II antagonist (losartan, 50 mg/d; n=11), or (D) standard treatment with bicycle training for 30 minutes, 3 times a week (n=11). At baseline, radial artery diameter and flow were similar in CHF patients and controls; CHF patients had a modest although significant impairment in flow increase (-36%) and a striking impairment (-78%) in diameter increase following the 4 minutes of ischemia. After 2 months, baseline diameter and flow remained unaltered in the 4 groups. After the 4 minutes of ischemia, radial artery flow and diameter increased as before in the group under standard treatment (A), whereas in the other 3 groups, the increase was significantly (P<0.05) and, for diameter, markedly (B, 83%; C, 92%; and D, 95%) greater. The vasodilatation induced by trinitroglycerin was similar in CHF and control subjects and not affected by treatments. In CHF, radial artery shows a marked reduction in flow-mediated vasodilation, reflecting impairment of endothelial function. This impairment can be markedly improved by treatments that effectively block the renin-angiotensin system either at ACE or at ACE plus angiotensin receptor level. This is the case also with nonpharmacological treatment of CHF.

Local effects of atherosclerotic plaque on arterial distensibility.

Hypertension, diabetes, and hypercholesterolemia are characterized by a reduction in arterial distensibility and by accelerated atherosclerosis. Whether arterial stiffening is an inherent feature of these conditions or just the consequence of the atherosclerotic clinical or subclinical lesions is not known, however. Our aim was to obtain information on this issue by directly measuring, in humans, arterial distensibility both at the site of an atherosclerotic lesion and at the proximal normal site. In 10 patients (8 men; mean+/-SEM age, 65.2+/-3.4 years) affected by monolateral hemodynamic significant internal carotid artery stenosis, we measured arterial distensibility (Wall Track System; PIE Medical) bilaterally, both at the internal carotid artery and at the common carotid artery level. In the common carotid artery, measurements were made 3 cm below the bifurcation. In the affected internal carotid artery, measurements were made at the plaque shoulder (wall thickness of 2 mm). Measurements were made in the contralateral internal carotid artery at a symmetrical level. Arterial wall thickness was measured in the same site of arterial distensibility. Arterial distensibility was less in the internal than in the common carotid artery, with a marked reduction at the plaque internal carotid artery level compared with the corresponding contralateral site (-45%, P<0.01). It was also less, however, in the common carotid artery branching into the atherosclerotic internal carotid artery than in the contralateral common carotid artery (-25%, P<0.05). Wall thickness was similar in the 2 common carotid arteries and obviously greater in the affected internal carotid artery than in the contralateral artery. Arterial distensibility was markedly less in the internal carotid artery where there was a plaque compared with the intact contralateral internal carotid artery; it was also less, however, in the common carotid artery of the affected side in comparison with the contralateral common carotid artery. This provides evidence that the effect of a plaque on arterial mechanical properties is not limited to the actual plaque site but rather extends to a considerable degree in a proximal direction.

Progression of functional and structural cardiac alterations in young normotensive uncomplicated patients with type 1 diabetes mellitus.

OBJECTIVE: We have recently observed that in young, normotensive patients with a type I diabetes mellitus and no macro or microvascular complications, large artery structure and function are already altered. This study has been done to assess whether this condition is also characterized by early alterations in cardiac structure and function, and whether these alterations progress with time. DESIGN AND METHODS: In 56 insulin-treated, normotensive uncomplicated type I diabetic patients (age 35.0 +/- 2 years, means +/- SE) in good metabolic control, left ventricular wall thickness and diameter were measured by echocardiography together with left ventricular ejection fraction and diastolic function E/A (ratio between early and late ventricular filling), before and after 23 +/- 1 months. The same measurements were made in 20 age and sex-matched subjects who served as controls (C). RESULTS: Compared to C, diabetic patients had a significant increase in left ventricular wall (septal plus posterior wall) thickness (+ 8.4%), left ventricular mass index (+ 11%) and h/r ratio (left ventricular wall thickness/ventricular end diastolic diameter, + 16.0%) whereas they showed a reduction of E/A (-6%). In C, all echocardiographic values were unchanged after 2 years. This was the case also for diabetic patients, except for left ventricular ejection fraction and diastolic diameter which showed a significant reduction (-7.2%) and increase (+ 3.8%), respectively, with a reduction of ratio between LV wall thickness and diameter, h/r (-6.8%). CONCLUSIONS: Uncomplicated type I diabetes mellitus is characterized by early structural and functional cardiac alterations. Some of these alterations show a measurable progression within a relatively short time span.

Progression of large artery structural and functional alterations in Type I diabetes.

AIMS/HYPOTHESIS: Type I (insulin-dependent) diabetes mellitus is accompanied by reduced arterial distensibility and increased arterial wall thickness even in normotensive subjects with no micro-macrovascular complications. It is not known whether, and how fast, these subclinical markers of vascular damage develop over time. METHODS: We measured arterial wall distensibility in radial, common carotid artery and abdominal aorta in 60 normotensive patients (aged 35.0 +/- 1.2 years, means +/- SE) with Type I diabetes with no microvascular or macrovascular complications and in 20 healthy control subjects matched for age. Arterial distensibility was determined by continuous measurements of arterial diameter through echotracking techniques and by using either the Langewouters (radial artery) or the Reneman formula (carotid artery and aorta). The same echotracking techniques allowed us to ascertain the radial and carotid artery wall thickness. Data were collected before and after 23 +/- 1 months. RESULTS: In the first study, carotid artery distensibility was similar but radial artey and aortic distensibility was less (p < 0.01) in patients with diabetes than in control subjects (-39 % and 25 % respectively). This was accompanied by an increase (p < 0.01) in both radial (42 %) and carotid artery wall thickness (46 %). After 23 +/- 1 months diabetic subjects showed a further reduction in arterial distensibility (radial-12 %, p < 0.05; carotid-8 %, NS; aorta-20% p < 0.05) and an increase in arterial wall thickness (radial + 15 %; carotid 14%, p < 0,05). No change in distensibility and wall thickness values occurred in control subjects. CONCLUSION/INTERPRETATION: The early reduction in arterial distensibility and increase in arterial wall thickness characterizing uncomplicated normotensive Type I diabetes patients shows a measurable worsening over the short term.

Effects of physical training of the dominant arm on ipsilateral radial artery distensibility and structure.

BACKGROUND: Exercise training induces cardiovascular changes that are both generalized and restricted to the microcirculation of the tissues more actively involved in the exercise itself. Whether the local effect of exercise extends to larger arteries is unknown, however. METHODS: In the right and left upper limb of 17 right-handed subjects performing an asymmetric training of the upper limbs (hammer throwers and baseball players) and 16 age-matched sedentary controls, we continuously measured radial artery diameter, distensibility and wall thickness by an echotracking and a beat-to-beat finger blood pressure device. Arterial distensibility was calculated by the arctangent model of Langewouters and expressed as continuous values from diastolic to systolic blood pressure. Measurements were made: (1) in baseline conditions; (2) after release from prolonged proximal ischaemia; and (3) after an increase in radial artery blood flow caused by a short (4 min) distal ischaemia to determine the endothelial involvement in the training-induced change in arterial distensibility. RESULTS: In athletes the radial artery distensibility was markedly greater in the right than in the left arm, the latter showing values slightly greater than those seen in the two arms of sedentary subjects. In both arms and groups radial artery distensibility increased markedly after prolonged ischaemia, the between arm and group differences being preserved, however. The radial artery response to distal short ischaemia was, on the other hand, similar in the two arms of the athletes, although greater in these subjects than in the sedentary ones. Radial artery wall thickness was greater in the trained than in the untrained arm of athletes, both values being greater than in sedentary subjects. CONCLUSIONS: Asymmetrical training of the upper limbs is accompanied by a greater distensibility of the middle-sized arteries of the more trained side. This is not associated with asymmetrical changes in endothelial structure or function. It is associated with a greater wall thickness in the trained side, suggesting that, at least in part, a training-induced asymmetrical change in wall structure (possibly with a predominance of more distensible tissues such as elastine and smooth muscle) is responsible.

Radial artery wall alterations in genetic hemochromatosis before and after iron depletion therapy.

Iron overload is believed to have an adverse influence on the cardiovascular system and animal studies have shown that iron may be involved in the events that lead to atherosclerosis via an enhancement of smooth muscle cell proliferation, lipid oxidation, and free radical production. There are no data on the effect of iron overload on arterial structural and mechanical properties in humans. We measured wall thickness and distensibility (D) by ultrasonography of the radial artery in 12 patients with uncomplicated genetic hemochromatosis (GH) who were normotensive and without atherosclerotic plaques. Twelve age- and sex-matched patients were taken as controls. Nine patients were evaluated also after iron depletion. Wall thickness was greater in patients with GH than in controls (+50%, P <.01) whereas D was slightly reduced in the former group compared with the latter group, though the difference was not statistically significant. After iron depletion, a significant reduction of wall thickness and a significant increase in D were observed (-24% and +33%, P <.05 for both). Thus, in patients with hemochromatosis, arterial wall thickness is increased before the onset of cardiovascular complications. This alteration is reverted by iron depletion, which also can improve the initial and modest radial artery wall stiffening associated with this condition. Thus, functional and structural alterations in midsize muscle arteries may be an early abnormality of hemochromatosis.

Pharmacological improvement of large arteries properties.

Arterial distensibility reflects mechanical properties of the arterial wall and have, thus a clearcut clinical relevance. This because an arterial distensibility reduction is associated with an increased pulse pressure, an increased cardiac work and a reduced diastolic vital organ perfusion. In recent years it has been demonstrated that arterial distensibility is reduced in marked and mild hypercholesterolemia, in a manner independent from arterial blood pressure values. Arterial mechanical properties are also impaired in heart failure, this leading to a further cardiac damage. This important vascular properties however, can be improved by appropriate treatment, while the time needed for that can be extremely long.

Early impairment of large artery structure and function in type I diabetes mellitus.

AIMS/HYPOTHESIS: Diabetes mellitus is associated with an increased incidence of atherosclerosis. How early functional and structural alterations of large arteries that may preceded atherosclerosis occur in the course of this disease has, however, never been conclusively documented. METHODS: We evaluated arterial wall distensibility in the radial artery, common carotid artery and abdominal aorta in 133 patients (aged 35.4 +/- 0.9 years, means +/- SEM) with Type I (insulin-dependent) diabetes mellitus and no macrovascular complications. Arterial distensibility was derived from continuous measurements of arterial diameter through echotracking techniques and use of either the Langewouters (radial artery) or the Reneman (carotid artery and aorta) formula. The same echotracking techniques enabled us to obtain radial artery and carotid artery wall thickness. Data were compared with those from 70 age-matched normotensive control subjects. RESULTS: In diabetic patients arterial distensibility was consistently less (p < 0.01) than in control subjects, the reduction averaging 26%, 14% and 25% for the radial artery, carotid artery and aorta, respectively. This was accompanied by an increase (p < 0.01) in both radial and carotid artery wall thickness. The changes were more pronounced in patients with microalbuminuria, retinopathy or neuropathy or both. They were evident also in those without microvascular complications. This was the case also when subjects in whom diabetes was associated with hypertension (n = 30) were excluded from data analysis. Carotid and aortic wall abnormalities showed a relation with the duration of disease and blood pressure whereas radial artery abnormalities showed a relation with glycated haemoglobin. CONCLUSION/INTERPRETATION: Type I diabetes is characterised by diffuse arterial wall stiffening and thickening which progress with the severity of the disease but can clearly be seen also in the absence of any diabetic-related complication. This suggests that in diabetes stiffening and thickening are an early marker of vascular damage.

Sympathetic tone restrains arterial distensibility of healthy and atherosclerotic subjects.

BACKGROUND: Sympathetic activation induced by cold pressor test or cigarette smoking is accompanied by a marked reduction of radial artery distensibility. It is not known, however, whether arterial distensibility is under tonic sympathetic restraint, or whether this restraint involves arteries greater than the radial one in both normal and pathological conditions. METHODS: We studied the distensibility of radial artery by continuous ultrasonographic assessment of the changes in arterial diameter over the diasto-systolic pressure range (finger pressure measurement) in eight patients with a Dupuytren disease before and 20 min after ipsilateral brachial plexus anaesthesia. We also studied ultrasonographic distensibility of femoral artery in seven subjects before and 20 min after ipsilateral subarachnoid anaesthesia, performed before arthroscopic surgery, and in five patients with claudicatio intermittens before and 1 month after ipsilateral removal of the lumbar sympathectomy chain. In all three conditions, the contralateral artery served as control. RESULTS: The three interventions did not cause any significant alteration in blood pressure and heart rate. Radial artery distensibility was markedly increased by ipsilateral anaesthesia of the brachial plexus (+36%, P<0.01). This was the case also for femoral artery distensibility both following ipsilateral subarachnoid anaesthesia in healthy subjects (+47%, P<0.05) or ipsilateral sympathetic gangliectomy in patients with peripheral artery disease (+26%, P<0.05). In all three instances, the distensibility of the contralateral artery remained unaffected. CONCLUSIONS: These data indicate that the sympathetic nervous system exerts a marked tonic restraint of arterial distensibility. This restraint involves medium-size and large muscular arteries and can also be seen in subjects with peripheral artery disease. This stiffening influence may increase the traumatic effect of intravascular pressure on the vessel wall and favour atherosclerosis.

Fluctuations of radial artery distensibility throughout the menstrual cycle.

Estrogen administration has a number of favorable cardiovascular effects, and recent evidence suggests that these include an increase in arterial distensibility. Whether this is also the case for the physiological changes in estrogen production during the menstrual cycle has never been determined, however. In 21 premenopausal healthy women, we continuously measured radial artery diameter and blood pressure by an echo-tracking device and a beat-to-beat finger device, respectively. Arterial distensibility was calculated as distensibility/blood pressure curve. The measurements were made during the follicular, ovulatory, and luteal phases of the menstrual cycle. As expected, compared with the follicular phase, plasma estradiol, follicle-stimulating hormone, luteinizing hormone, and prolactin were increased in the ovulatory phase, whereas progesterone was increased in the luteal phase, together with antidiuretic hormone. Radial artery distensibility was increased in the ovulatory and reduced in the luteal phase, the changes being independent of the small, concomitant blood pressure changes. The arterial wall stiffening seen in the luteal phase was associated with a reduction in the flow-dependent endothelial dilatation of the radial artery as assessed by the hyperemia after short-term ischemia of the hand. Thus, the natural menstrual cycle is characterized by alterations in radial artery distensibility. The mechanisms responsible for this phenomenon remain to be clarified. It is possible, however, that the greater arterial distensibility of the ovulatory phase is due to an estrogen-dependent reduction in vascular smooth muscle tone, whereas the arterial stiffening of the luteal phase depends on vascular smooth muscle contraction due to more complex hormonal phenomena, ie, an endothelial impairment due to estrogen reduction but also to an increase in progesterone and antidiuretic hormone levels.

Effects of prolonged immobilization of the limb on radial artery mechanical properties.

Physical training is associated with an increase in arterial distensibility. Whether the effect of training on this variable is evident also for ordinary levels of exercise or no exercise is unknown, however. We have addressed this issue by investigating the effect on radial artery distensibility of prolonged monolateral immobilization of the ipsilateral limb versus the following resumption of normal mobility. We studied 7 normotensive subjects (age, 25.4+/-3.0 years; systolic/diastolic blood pressure, 119+/-9/68+/-6 mm Hg, mean+/-SE) in whom 1 limb had been immobilized for 30 days in plaster because of a fracture of the elbow. At both the day after plaster removal and after 45 days of rehabilitation, radial artery distensibility was evaluated by an echo-tracking device (NIUS-02), which allows arterial diameter to be measured noninvasively and continuously over all pressures from diastole to systole (finger monitoring), with the distensibility values being continuously derived from the Langewouters formula. In both instances, the contralateral arm was used as control. Immediately after removal of the plaster, radial artery distensibility was markedly less in the previously immobilized and fractured limb compared with the contralateral limb (0.4+/-0.1 versus 0.8+/-0.1, 1/mm Hg 10(-3), P<0.05). After rehabilitation, the distensibility of the radial artery was markedly increased in the previously fractured limb (0.65+/-0.1 1/mm Hg 10(-3), P<0.05), whereas no change was seen in the contralateral limb. Thus, complete interruption of physical activity is associated with a marked reduction of arterial distensibility, indicating that even an ordinary level of activity plays a major role in modulation of arterial mechanical properties.

Present and future role of combination treatment in hypertension.

Both in clinical practice and in drug trials, combination treatment of hypertension plays a fundamental role. This article reviews the features that make combined therapy with two drugs valuable, i.e., additive antihypertensive efficacy, different mechanisms of action, and reciprocal side-effect minimization. Also examined are the advantages and disadvantages of a fixed combination, emphasizing that a major advantage is simplification of the treatment schedule. This is clinically relevant because complexity of treatment negatively affects patient compliance, which in hypertensive patients is poor, leading to poor long-term blood pressure control in the hypertensive fraction of the population.

Effects of cigarette smoking on carotid and radial artery distensibility.

OBJECTIVE: Cigarette smoking acutely induces a marked increase of blood pressure and heart rate. This is accompanied by a marked reduction of radial artery distensibility. Whether this reflects an alteration of arterial mechanics of large elastic arteries as well is not established, however. DESIGN AND METHODS: In this study we addressed the acute effects of smoking on the stiffness of a peripheral medium-sized muscular artery and a large elastic vessel. We studied seven healthy normotensive smokers (age 28+/-7 years, mean+/-SEM), in the absence of smoking for at least 24 h. Radial artery (NIUS 02) and carotid artery diameter (WTS) were concomitantly acquired beat-to-beat in the 5 min before, during and after smoking of a cigarette containing 1.2 mg of nicotine. Blood pressure and heart rate were concomitantly recorded by a Finapres device. Radial and carotid artery distensibility were calculated according to the Langewouters and Reneman formulae, respectively. Data were collected for consecutive 30 s periods. Statistical comparisons were performed between the three different phases and, within each phase, between 30 s periods. In five subjects the protocol was repeated after 1 week using a stran rather than a cigarette to obtain data under sham smoking. RESULTS: Smoking increased systolic blood pressure by 14%, diastolic blood pressure by 10% and heart rate by 27%. Radial artery diameter was reduced during smoking (-3.7%) and more so after smoking (-14.8%), while carotid artery diameter did not change significantly either during or after smoking. Radial artery distensibility was also significantly reduced only after smoking (-41.3%, P < 0.01), while carotid artery distensibility was significantly reduced both during (-33.3%) and after smoking (-27.2%) (P < 0.01 versus before). No changes in blood pressure, heart rate and arterial wall mechanics were induced by sham smoking. CONCLUSIONS: Acute cigarette smoking reduces distensibility not only in medium-sized but also in large elastic arteries, therefore causing a systemic artery stiffening. The mechanisms of these effects remain to be determined. However, it is likely that adrenergic mechanisms are responsible for the arterial distensibility alterations.