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We read with great interest the article by Medina et al about atherosclerosis in primary antiphospholipid syndrome (APS).1 They showed that the intima-media thickness (IMT) of carotid arteries from patients with primary APS was greater than that of age and sex matched controls.
We wish to comment on their methodology and findings. For the ultrasound technique Medina et al did not define the area where the measurement of IMT was taken, nor did they specify whether the anterior or posterior carotid wall was measured. The anterior or near wall is prone to reverberation artefact, making placement of the callipers difficult. IMT should be measured at a site away from atheromatous plaques. The figures provided by Medina et al show that colour and power Doppler were used to define the lumen of the vessel, but there is no mention of how these were standardised. The gain, pulse repetition frequency, prioritisation of colour versus grey scale, use of contrast agents, angle of insonation, and the velocity of blood flow (systole or diastole) will all affect the position of the border of the colour echo in the image and hence affect the readings taken. Their fig 2B shows that the colour echo does not conform to the “white line” of the intimal-luminal interface. Furthermore, the placement of the measurement callipers in figs 2B and 3B is not correct. Here most workers advise that the image be magnified to facilitate accurate calliper placement. Also, the effect of laminar or plug flow patterns may influence readings. With their technique even IMT readings in their controls are far higher than those reported in the world literature (reviewed by Aminbakhsh and Mancini2).
We would have liked to see the antiphospholipid antibody (aPL) titre of the their patients and how they ranked if entered in their regression model in table 3.
A previous study identified IgG anticardiolipin antibody (aCL) as an independent predictor of carotid IMT, suggesting a possible dose effect of IgG aCL on IMT.3 Therefore aPL titres at the lower end of the medium range (20–80 GPL) may be less atherogenic than those at the higher end of the same range.
To confuse matters further, most of their patients with primary APS had other significant conventional risk factors for atherosclerosis, whether in isolation or combination. The prevalence of hypertension, hyperlipidaemia, and obesity was 36%, 54%, and 25%, respectively, in their cohort with several patients having more than one risk factor.
We question the author’s conclusion of atherosclerosis in primary APS. As it stands, their scanning technique overestimates IMT readings, and other conventional cardiovascular risk factors are overrepresented in their cohort, potentially masking the atherogenic potential of aPL.
We thank Dr Ames et al for their interest in our study and for their comments about our methodology and findings of atherosclerosis in primary antiphospholipid syndrome (APS).1
We agree about the difficulties of anterior carotid wall measurements. Therefore our intima-media thickness (IMT) measurements were performed on the posterior wall, as is shown in fig 2B. Our patients did not have atheromatous plaques, consequently this artefact did not alter the IMT measurement. The colour and power Doppler ultrasound were standardised in our hospital according to the method of Cantú-Brito et al. Briefly, the sensitivity and specificity of the method were 91.3 and 92.7%, respectively.2 A composite measure that combined the maximal common carotid artery IMT and maximal internal carotid artery IMT was obtained by averaging these two measurements after standardisation with subtraction of the mean and division by the standard deviation for the measurement.
Colour Doppler cannot define the “white line”, but this technique does define the intimal-luminal interface. The position of the callipers in fig 2B is correct for IMT measurement, but in fig 3B the callipers are showing the indentations in the lumen vessel.
The carotid artery IMT in our controls was 1.2 (0.44) mm. This value is higher than that reported in other studies but, however, only 7/28 controls had an IMT >1 mm. The mean IMT in these seven controls was 1.65 mm (range 1.1–2). The explanation of these results is that the controls also had other cardiovascular risk factors and they were hospital workers. In other studies performed in Mexico, IMT was detected in more than 60% of people from the general population.3
In our regression model we did not include the titres of anticardiolipin antibodies, because we did not determine them simultaneously with the carotid artery IMT study. We have only historical data of antiphospholipid antibodies. We are currently analysing the association of antiphospholipid antibodies and other new risk factors with carotid artery IMT.
In relation to conventional risk factors for atherosclerosis, we agree that these are confusing variables, but the logistic regression analysis controlled for these factors. Certainly, it is very difficult to have patients and controls who do not have traditional risk factors for atherosclerosis.
In view of all the above mentioned information, we think that our patients with primary APS had a significantly greater IMT of the carotid arteries than the controls.
The results are not overestimated because all ultrasound scanning was performed under similar conditions in both groups, by a single experienced radiologist who was unaware of the clinical information, and using the same sonograph equipment.
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