Takayasu arteritis (TAK) and systemic lupus erythematosus (SLE) are inflammatory diseases that primarily affect young women. TAK is a rare vasculitis that affects the aorta and its main branches, whereas SLE is a chronic autoimmune disease that effects multiple organs. Both diseases are associated with premature cardiovascular disease (CVD), and a wish to understand these associations prompted the studies of this thesis.

The macrocirculation, microcirculation and vascular haemodynamics were studied in patients with TAK (N=25 in Paper I, N=17 in Paper II) and SLE (N=60 in Papers III and IV), and compared with age- and gender-matched controls. Vessel wall thickness (intima-media thickness (IMT)), vessel wall appearance, and occurrence of atherosclerotic plaques were evaluated in multiple vascular areas using high-frequency ultrasound (US). Microcirculation in the skin was studied after induced ischaemia employing a new method that combines laser Doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS). The measured microcirculatory value was defined as the peak oxygen saturation (OxyP). Pulse wave analysis was used for calculation of the central augmentation index (AIx). Cerebrovascular reserve capacity (CVR) was analysed using transcranial Doppler (TCD).

Paper I

In this study, TAK patients were examined with US, including follow-up studies. Clinically active cases of TAK showed significantly increased IMT compared to stable patients with TAK and healthy controls. The arteries of patients with active disease showed signs of intra-mural micro-vessels, oedema, or increased vessel diameter, whereas these signs were not seen in cases of stable disease. The Takayasu US index (based on the summation of the IMT in three arterial areas) was higher in active disease than in stable disease, and was valuable for the assessment of relapse.

Paper II

In this study of vascular haemodynamics in patients with TAK we observed impaired microcirculation, as compared with controls. CVR was preserved regardless of proximal arterial stenosis. The AIx, reflecting arterial stiffness, was increased, also in the arms without proximal stenosis or occlusion.

Papers III and IV

Increased IMT with predominantly medium echogenicity was observed in multiple arteries of the 60 patients with SLE, predominantly in vascular areas that are not usually part of the IMT measurements. The patients with SLE developed plaques more frequently and earlier in life compared to the controls. Correlation with traditional cardiovascular risk factors was observed, indicating atherosclerotic mechanisms rather than inflammation. The patients with SLE had higher AIx values and lower OxyP levels, even at younger ages, and both these methods correlated with the IMT and plaque occurrence.

Conclusions

For patients with TAK, US can be valuable both for the diagnosis of the disease and for distinguishing between the active and stable disease forms. The microcirculation and degree of arterial stiffness in the arms are affected also in patients with TAK without proximal stenosis/occlusion, indicating a more widespread arterial wall dysfunction.

In patients with SLE, increased IMT, an affected microcirculation, increased arterial stiffness, and premature atherosclerotic plaques indicate vascular affection coupled with increased risk for cardiovascular disease. All these evaluated methods may be used for longitudinal studies with or without intervention.

Background Takayasu arteritis (TA) is a rare large-vessel arteritis that primarily affects the aorta and its major branches. The aim of this study was to describe the value of high frequency ultrasound for monitoring of inflammatory activity. Methods Twenty-five patients, range 11-71 years, diagnosed with TA were investigated with duplex ultrasound (DUS) including follow-up studies. Twenty-five healthy controls were also investigated. Nine patients had newly diagnosed active TA. Sixteen patients had stable/inactive disease at baseline DUS, and TA was diagnosed median 4 center dot 5 years previously. Intima-media thickness (IMT), vessel and lumen diameter were measured in the carotid arteries, central neck arteries and the aortic arch. The vessel walls were studied qualitatively. The Takayasu ultrasound index was created for inflammatory activity scoring. Results Intima-media thickness in common carotid artery (CCA) was (median and 25-75 percentile parenthetic) 2 center dot 3 mm (1 center dot 7-2 center dot 9) in clinically active TA, 1 center dot 2 mm (1 center dot 1-1 center dot 6) in clinically stable TA (Pamp;lt;0 center dot 001) and 0 center dot 5 mm (0 center dot 5-0 center dot 6) in healthy controls (Pamp;lt;0 center dot 001). Clinically active TA had prominent increase in IMT and/or increased vessel diameter, and/or intramural arteries, and/or hypoechogenic areas interpreted as oedema in the vessel wall. TA in clinical remission was characterized by increased IMT with medium to high echogenicity with or without fibrotic stripes. The Takayasu ultrasound index was higher in patients with active disease versus treated disease, 2 center dot 55 (1 center dot 60-3 center dot 05) versus 1 center dot 30 (1 center dot 00-1 center dot 58), (P = 0 center dot 003). Conclusion DUS is an excellent tool to monitor inflammatory changes in the vessel wall in TA. Further DUS studies in larger patient populations are warranted.

OBJECTIVE: The aim of this study was to evaluate an extended protocol of the large vessels using high-frequency duplex ultrasound (DUS) for detection of vessel wall inflammation.

METHODS: Fifty-eight patients performed a DUS examination where arteritis could not be excluded. All DUS examinations were performed using ACUSON S2000 TM ultrasound system (Siemens Medical Solutions USA, Inc.). High-frequency linear transducers were used (18L6 MHz, 9L4MHz) or curve linear for the aortic arch (6C2 MHz). Carotid, vertebral, central neck arteries (subclavian, axillary, innominate) arteries, aortic arch and femoral arteries were studied. Circumferential, homogenous wall thickening, with or without a hyperechogenic stripe lining the innermost layer, were regarded as typical signs of arteritis. Intima-media thickness (IMT) was measured in the patients and a normal control group. The latest clinical updated diagnosis was assessed at least 6 months after DUS.

RESULTS: The DUS findings showed normal vessels (n = 14), arteritis and atherosclerosis (n = 13), atherosclerosis (n = 15) and arteritis (n = 16). The latter group had a significant increased IMT in the common femoral artery and the common carotid artery (mean 1·0 ±  SD 0·3 mm versus 0·6 ± 0·2 mm in the normal group (n = 37), P<0·00001, 1·2 ± 0·5 mm versus 0·8 ± 0·2 mm in the normal group (n = 40), P<0·00001). In the groups with sonographic signs implying arteritis (n = 29), 20 patients had a clinical diagnosis of arteritis, whereas eight patients had another main diagnosis such as malignancy/other inflammatory or infectious disease complicated by inflammation of the vessel wall. One patient had multiple diagnoses and was not possible to classify.

CONCLUSION: An extended ultrasound protocol for central neck and leg arteries could be of value for diagnosis of arteritis. In case of atypical vessel wall inflammation, other main diagnoses should be considered.

A method for computer-aided assessment of blood vessel geometries based on shape-fitting algorithms from metric vision was evaluated. Acoustic images of cross sections of the radial artery and cephalic vein were acquired, and medical practitioners used a computer application to measure the wall thickness and nominal diameter of these blood vessels with a caliper method and the shape-fitting method. The methods performed equally well for wall thickness measurements. The shape-fitting method was preferable for measuring the diameter, since it reduced systematic errors by up to 63% in the case of the cephalic vein because of its eccentricity.