Invasive Forearm Technique Research Articles

Endothelium-dependent vasodilation, insulin resistance and the metabolic syndrome in an elderly cohort: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

Background Only a few previous studies have investigated endothelium-dependent vasodilation in the metabolic syndrome (MetS). In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, different techniques to assess vasodilation in conduit and resistance arteries were evaluated in relation to the MetS and insulin resistance. Methods In this population-based study, 1016 subjects aged 70 were evaluated by the invasive forearm technique with acetylcholine (EDV), brachial artery ultrasound to assess flow-mediated vasodilation (FMD) and pulse wave analysis with a beta-2 receptor agonist challenge, terbutaline. Results EDV was lower in subjects with the MetS (NECP/ATP III-criteria, prevalence 23%) compared to those without ( p < 0.0001), and declined with increasing number of MetS criteria ( p < 0.0001), after adjustment for coronary heart disease, stroke and cardiovascular medication. Also a reduced pulse wave response ( p = 0.015), but not FMD ( p = 0.64), was seen in those with the MetS. EDV and the pulse wave response, but not FMD, were inversely related to insulin resistance evaluated by the HOMA index. Also endothelium-independent vasodilation (EIDV) induced by intra-brachial infusion of sodium nitroprusside was impaired in subjects with MetS and in insulin resistance. Conclusions Vasodilation evaluated with the invasive forearm technique and pulse wave analysis with a beta-2 agonist, but not FMD, was reduced in elderly subjects with the MetS and was related to insulin resistance. Also EIDV showed the same pattern, suggesting a general deterioration in vasoreactivity mainly in resistance arteries in elderly subjects with the MetS.

Vasodilation and visceral fat in elderly subjects: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

Background Although obesity has long been recognised as a cardiovascular risk factor, only in recent years has the role of visceral adipose tissue (VAT) been evaluated. In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, we related VAT and other obesity indices to endothelium-dependent vasodilation in both capacitance and resistance arteries. Methods and results In this population-based study, 1016 subjects aged 70 were evaluated by the invasive forearm technique with acetylcholine (EDV) and brachial artery ultrasound to assess flow-mediated vasodilation (FMD). Intra-abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) were determined by magnetic resonance imaging in a random sample of 287 subjects. EDV, but not FMD, was inversely related to VAT, SAT, BMI and the waist/hip ratio ( r = −0.23, −0.16, −0.21 and −0.11, respectively, p = 0.05–0.001 after adjustment for gender). In multiple regression analysis however, only VAT was an independent predictor of EDV. Similar results were obtained for endothelium-independent vasodilation (EIDV, infusion of sodium nitroprusside in the brachial artery). Conclusions Both endothelium-dependent and independent vasodilation in the forearm resistance arteries, but not FMD in the brachial artery, was reduced in elderly subjects with increased intra-abdominal adipose tissue mass. This finding suggests deterioration in general vasoreactivity mainly in resistance arteries in elderly subjects with intra-abdominal obesity.

Systolic and diastolic hypertension impair endothelial vasodilatory function in different types of vessels in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

Endothelium-dependent vasodilation (EDV) is known to be impaired in middle-aged hypertensive individuals, but less is known regarding hypertension in the elderly. In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, different techniques to evaluate EDV in resistance and conduit arteries were applied in elderly subjects and were related to the type of hypertension. In this population-based study, 1016 subjects aged 70 years were evaluated by the invasive forearm technique with acetylcholine (EDV), brachial artery ultrasound to assess flow-mediated dilatation (FMD) and pulse wave analysis with a beta-2 receptor agonist challenge, terbutaline. Those without antihypertensive treatment were divided into three groups: normotensive individuals (n = 256), and those with isolated systolic hypertension (n = 309) or combined systolic/diastolic hypertension (n = 79). Compared with normotensive individuals, EDV was reduced in those with combined systolic/diastolic hypertension only (P = 0.0019), whereas FMD was mainly reduced in those with isolated systolic hypertension (P = 0.013). Furthermore, in regression analysis, EDV was related to diastolic blood pressure only (r = -0.10, P = 0.017), whereas FMD was mainly related to systolic blood pressure (r = -0.13, P = 0.0023). The pulse wave-based method to analyse vasoreactivity was not consistently affected by hypertension. In elderly subjects, systolic hypertension mainly impairs conduit artery endothelial vasodilatory function, whereas diastolic hypertension mainly induces dysfunction in resistance arteries.

Vasodilation in resistance arteries is related to the apolipoprotein B/A1 ratio in the elderly – The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

Background Recent studies have shown the apolipoprotein B to apolipoprotein A1 ratio (apoB/A1) to be superior to LDL-cholesterol measurements to predict cardiovascular events. The present study aims to relate apoB/A1 to endothelium-dependent vasodilation, an early marker of atherosclerosis, in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study. Methods and results In this population-based study, 1016 subjects aged 70 years were evaluated by the invasive forearm technique with acetylcholine (EDV), brachial artery ultrasound to assess flow-mediated vasodilation (FMD) and pulse wave analysis with a beta-2 receptor agonist challenge, terbutaline. EDV and the pulse wave response, but not FMD, were related to apoB/A1 levels ( r = −0.11, p = 0.0038 for EDV, r = −0.16, p < 0.0001 for the pulse wave analysis and r = 0.01, p = 0.65 for FMD). Neither LDL-cholesterol, nor non-HDL-cholesterol, was significantly related to the measurements of endothelium-dependent vasodilation. Also endothelium-independent vasodilation (EIDV) evaluated by the invasive forearm technique with sodium nitroprusside was related to apoB/A1 levels ( r = −0.12, p < 0.0016). Conclusion The apoB/A1 levels, but not LDL-cholesterol, were inversely related to endothelium-dependent vasodilation evaluated by EDV and pulse wave analysis, but not by FMD. Also EIDV showed the same pattern, suggesting a general deterioration in vasoreactivity mainly in resistance arteries in elderly subjects with high apoB/A1 levels.

Arterial compliance influences the measurement of flow-mediated vasodilation, but not acetylcholine-mediated forearm blood flow: The prospective investigation of the vasculature in uppsala seniors (PIVUS) study

Objectives Flow-mediated vasodilation (FMD) is low even in healthy elderly and therefore relations between FMD and cardiovascular risk factors might be hard to evaluate in the elderly. Using data from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, we investigated if a reduced arterial distensibility could influence FMD measurements. Methods In the population-based PIVUS study (1016 subjects aged 70), assessments of arterial distensibility by ultrasound in the carotid artery (CCA) and FMD were performed. Endothelium-dependent vasodilation was also evaluated with the invasive forearm technique with acetylcholine (EDV) and by pulse wave analysis following terbutaline injection. A poor CCA distensibility was defined as <25th percentile in the healthy part of the population ( n = 131). Results FMD was significantly related to the Framingham risk score only in those with a good CCA distensibility ( r = −0.16, p = 0.0081 versus r = −0.06, p = 0.17 in those with a poor CCA distensibility, p = 0.0001 for difference). In contrast, the relationship between EDV and coronary risk was not affected by CCA distensibility ( r = −0.11, p = 0.018 versus r = −0.13, p = 0.027). Conclusions A reduced CCA distensibility could in part explain the low FMD values in the elderly. FMD correlated to the Framingham risk score only in those with a good CCA distensibility, exemplifying a limitation of the use of FMD in elderly populations. On the contrary, EDV was not affected by arterial stiffness.

A Comparison of Three Different Methods to Evaluate Endothelium-Dependent Vasodilation in the Elderly

Three different techniques to evaluate endothelium-dependent vasodilation in the peripheral circulation have been described but not simultaneously tested in a large-scale population-based setting. This study aimed to evaluate the feasibility and usefulness of these techniques in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. In the population-based PIVUS study (1016 subjects aged 70 years), the invasive forearm technique with acetylcholine given in the brachial artery (EDV), the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD), and the pulse wave analysis method with beta-2-agonist (terbutaline) provocation were successfully used in 87%, 97%, and 86% of the sample, respectively. The results of EDV and pulse wave analysis were interrelated (r=0.12, P=0.0013), but no relationships were found with FMD measurements. All 3 techniques were correlated to the Framingham risk score (r=0.10 to 0.12, P=0.0007 to 0.001). In multiple regression analysis, however, only EDV and FMD were independently associated with the Framingham score. All 3 evaluated techniques were feasible to perform in a general elderly population. Both the invasive forearm technique and FMD were independently associated with increased coronary risk, suggesting that information on conduit artery and resistance artery endothelial function carry different, but important, information in the elderly. If the invasive technique cannot be used, the pulse wave based technique is an alternative.

Evaluation of four different methods to measure endothelium-dependent vasodilation in the human peripheral circulation

At present, several techniques exist that claim to evaluate endothelium-dependent vasodilation (EDV) in the human peripheral circulation. The present study aims to evaluate the relationships between four of these techniques. A group of 24 young, healthy subjects underwent measurements of EDV and endothelium-independent vasodilation (EIDV) in predominately resistance vessels in the forearm using the invasive forearm technique with local infusion of methacholine and sodium nitroprusside, evaluation of flow-mediated vasodilation (FMD) in the conduit brachial artery measured by ultrasound, with or without the addition of ischaemic hand exercise, and evaluation of the reduction in the relative height of the inflection point of the radial pulse wave following beta(2)-adrenergic receptor stimulation. The reduction in the relative height of the inflection point following beta(2)-adrenergic receptor stimulation was significantly related to both EDV and EIDV in the forearm (r=-0.41 and r=-0.42 respectively; both P<0.05), but not to the EDV/EIDV ratio (r=-0.10). However, FMD, with or without the addition of ischaemic hand exercise, was not significantly related to the results obtained using the other two techniques (r=-0.18 to +0.13). In conclusion, the reduction in the relative height of the inflection point of the pulse wave following beta(2)-adrenergic receptor stimulation was related to both EDV and EIDV measured by the invasive forearm technique, indicating that the pulse wave technique does not measure EDV specifically. FMD in the brachial artery, with or without ischaemic hand exercise, was not significantly related to values obtained using the other two techniques, indicating that endothelial function differs between conduit and resistance arteries, and that both of these measurements should be evaluated in future studies.