Of a total of 576 persons approached, 92 declined and 14 were excluded due to their inability to speak either English or French. Four hundred and seventy (470) persons provided informed consent. Of these, 208 aCL/LAC-tested individuals were age-, gender- and referral center-matched to 208 CBC-tested individuals. Forty-eight CBC-tested and six aCL/LAC-tested individuals could not be matched and were not studied further.
Description of confirmed events at baseline
One hundred twenty-eight TE were confirmed in 69 participants: 13 with CVA, 5 with TIA, 15 with MI, 9 with angina, 32 with DVT, 14 with PE, 2 with amaurosis fugax and 6 with other thrombotic events. The number of events per person were as follows: CVA (nine with one, three with two, one with four); TIA (one each); DVT (22 with one, five with two, three with three, and two with four); PE (twelve with one, two with two); amaurosis fugax (one each); and other thrombotic events (two with a lacunar infarct, two with renal thrombosis, one with three femoral arterial occlusions, and one with Budd-Chiari and a ureteral artery infarct).
Characteristics of the cohort
Characteristics of the cohort of 416 participants are shown in . The mean age was 46.5 years and 83% were female. No clinically important differences in education or ethnic group were seen between the aPL-request and the CBC-request groups. Smoking was reported in 28% of the cohort, HBP in 16%, DM in 6%, SLE in 20%, and FMH in 48%. As expected, prednisone, hydroxychloroquine, aspirin, and warfarin use were higher in the aPL-request group. There was also a clinically relevant difference in the number of people in each group with confirmed thrombotic events, multiple thrombotic events, and reported obstetrical events, with the percent risk being higher for the aPL-request group and the 95% CI for the percent risk difference excluding zero.
Demographic characteristics, cardiovascular risk factors, medications, and previous thrombotic and obstetrical events at baseline.
shows the number and percentage of individuals who tested positive for aPL. As expected, the percentage of individuals who tested positive for aPL was higher in the aPL-request group for all aPL except aβ2GPI IgM. The frequency of aCL IgG and LA were highest among all of the aPL and similar within each group (~15–16% in the aPL-request group and ~8–10% in the CBC-request group). The percentage of individuals with aβ2GPI IgG was low (4.3% in the aPL-request group and 2.7% in the CBC-request group). Seventy-five (18%) of all participants had at least one aPL. Of these, 26 had aCL only, 20 had LA only, 6 had aβ2GPI only, 3 had both aCL and aβ2GPI, 12 had both LA and aCL, and 8 were positive for all three aPL (data not shown). None of the subjects were positive for LA and aβ2GPI, and aβ2GPI status was unknown for one subject who was otherwise aPL-negative. When aPL-positive and aPL-negative study participants were compared, regardless of original request group, a higher proportion of aPL-positive participants were found to have HBP, SLE, and FMH (results not shown).
Number and percentage of individuals testing positive for aPL.
shows the proportions of confirmed TE and reported obstetrical events by study group and, within each study group, by aPL antibody status. The percent risk difference [95% CI] for TE in the aPL-request group was 23.3 [9.0 to 37.5], well into the range of clinically relevant difference. In contrast, the percent risk difference was shifted towards a less clinically relevant range for the CBC-request group (7.3 [−9.3 to 23.8]). For the pooled population, the percent risk difference was 25.3 [13.8 to 36.7], and the entire 95% CI was in the clinically relevant range. Similarly, more obstetric events were reported in aPL-positive subjects in the aPL-request group (percent risk difference [95% CI] = 15.8 [0.1 to 30.9]), with the difference reaching clinical relevance. A smaller difference was observed in the CBC-request group (percent risk difference [95% CI] = 2.9 [−16.1 to 21.9]).
Percentage risk differences in individuals with thrombotic and obstetric events.
Association of aCL with thrombosis
shows the adjusted odds ratios (OR) and 95% CI for the associations between aCL IgG or IgM and ATE, VTE, or TE, for all 416 subjects. When the associations were modeled with the aCL IgG titre as a dichotomous variable, the ORs and their 95% CIs were in a clinically relevant range for VTE and TE. Similarly, the associations between aCL IgG titre, as a continuous variable, and ATE, VTE, or TE were all clinically relevant. For aCL IgM, the ORs were closer to 1 than those for aCL IgG, when aCL IgM presence was modelled as a dichotomous variable, and were similar to those for aCL IgG, when aCL IgM presence was modelled as a continuous variable. However, the confidence intervals were wider and included values that were outside the range of clinical relevance when either the dichotomous or continuous variable was used. Presence of aCL, regardless of isotype, was associated with both VTE and TE. Similar results were found when the analysis was restricted to those in the aPL-request group (results not shown).
Association of aCL IgG or IgM and thrombosis in the pooled population (N = 416).
Association of the number of different aPL present, and aPL profiles, with thrombosis
shows the estimated adjusted ORs and 95% CI for the associations of ATE, VTE, or TE with the presence of each additional aPL, and with specific aPL combinations, for the pooled population. One subject in the CBC-request group was excluded from this analysis because his or her aβ2GPI status was not available. The ORs for a 1-antibody increase were 1.5, 1.7, and 1.7 for the models with ATE, VTE, and TE as the outcome, respectively. As the 95% CI excluded 1.0 in the models with either VTE or TE as the outcome, these values can be considered to be within the clinically relevant range. In these regression models, the type of aPL antibody involved was not taken into account.
Association of the number of different aPL present, and aPL profiles, with thrombosis for the pooled population (N = 415).
In the regression models with aPL combinations as the main variables, ORs and 95% CIs could not be accurately estimated for the subgroup with aβ2GPI alone (n = 6), due to the lack of thromboses. For the same reason, ORs and 95% CIs could not be estimated for the subgroup with aCL and aβ2GPI in models with VTE as the outcome (n = 3), and the OR estimates for this subgroup lacked precision in the other models. aCL with LAC was the combination with the highest OR for TE. Comparatively equivalent OR were found for aCL only, LAC only, aCL and aβ2GPI, and all three aPL. Similar results were found when the analysis was restricted to the aPL-request group (data not shown).