Leeza Salowich‐Palm

Background Anticardiolipin antibodies (aCL) have been associated with an increased risk of stroke and thrombo-occlusive events. Little is known about the influence of aCL on recurrent thrombo-occlusive events. Methods Consecutively identified patients (n=132) with focal cerebral ischemia [stroke=112, transient ischemic attack (TIA)=20] harboring aCL of at least 10 GPL units at the time of their index event were prospectively followed to estimate the effect of aCL titer on time to and risk of subsequent thrombo-occlusive events (stroke, TIA, deep venous thrombosis, pulmonary embolism, myocardial infarction) and death. On the basis of prior literature, we divided patients into those with aCL ≤40 GPL (n=111; mean age, 63±14 years; mean follow-up, 1.95 years) and those with aCL >40 GPL (n=21; mean age, 54±20 years; mean follow-up, 1.50 years). Results There was no difference between groups for prevalence of hypertension, diabetes mellitus, cigarette smoking, atrial fibrillation, prior TIA, or sex. The GPL >40 group was younger (54±20 versus 63±14 years; P =.055), had more prior strokes [9/21 (48%) versus 27/111 (20%); P =.030], more frequent subsequent thrombo-occlusive events and death [15/21 (71%) versus 51/111 (48%); P =.030], and a shorter median time (years) to event (0.15 versus 0.61, log rank P =.005). The risk ratio for recurrent event and death with GPL >40 obtained from Cox proportional hazards models, adjusted for prior strokes, prior TIAs, hypertension, diabetes mellitus, atrial fibrillation, and cigarette smoking was 1.9 (95% confidence interval, 1.0 to 3.5; P =.051). Conclusions Our data suggest that subsequent thrombo-occlusive events and death after focal cerebral ischemia associated with IgG aCL may occur sooner and more frequently with GPL >40.

We prospectively studied 81 consecutively identified patients with antiphospholipid antibodies (aPLs) who developed focal cerebral ischemia over a 7-year period. The mean age of this cohort was approximately a decade younger than the average atherothromboembolic stroke victim and women were more commonly involved than men. The frequency of conventional stroke risk factors was lowest in the group of stroke patients with the highest levels of IgG cardiolipin immunoreactivity. Other serological abnormalities associated with aPL (false-positive Venereal Disease Research Laboratory test, thrombocytopenia, prolonged activated partial thromboplastin time [aPTT]) were more common in the group with over 100 GPL units (high positive). Patients with the highest IgG anticardiolipin titers had the shortest times to subsequent thrombo-occlusive events. The most common recurrent event was cerebral infarction, often occurring within the first year of follow-up during a mean prospective follow-up of 3 years. Over one-half of the cohort had at least one recurrent thrombo-occlusive event during follow-up. This distinct syndrome of cerebral ischemia should be recognized for its younger age at onset, predominance of women, high risk of recurrent thrombo-occlusive events, and the possible use of the IgG anticardiolipin antibody titer for prognosis.

OBJECTIVE: To investigate associations between cerebrovascular risk factors and anticardiolipin (aCL) immunoreactivity. BACKGROUND: High titers of aCL immunoreactivity, mainly the immunoglobulin (Ig) G isotype, were shown to predict aCL-related thrombo-occlusive complications. METHODS: aCL antibodies, and IgG and IgM isotypes were measured by a validated assay in a single laboratory, run in duplicate, in 749 individuals with first ischemic stroke (n = 300) and patients with other CNS disease or undergoing diagnostic procedures. RESULTS: Age varied according to aCL categories, with a mean of 61.8 years among patients with negative aCL (< 10 IgG phospholipid units [GPL]) to 62.3, 64.9, and 69.9 years in patients with immunoreactivity 10 to 20, 20 to 40, and >40 GPL respectively (p = 0.02). History of atrial fibrillation, congestive heart failure, or valvular heart disease was associated with significantly higher rates of positive IgG aCL (>10 GPL) and with higher immunoreactivity. IgG aCL immunoreactivity increased significantly, in a dose-response manner, as a function of the number of cerebrovascular risk factors present. In patients with first ischemic stroke, rates of 10 to 20, 20 to 40, and >40 GPL were 14%, 7%, and 0% among those with no risk factors versus 20%, 12%, and 12% respectively among patients with four or more risk factors (p = 0.007). No significant associations were identified, however, between IgM isotype aCL and any of the risk factors or increasing number of risk factors. CONCLUSION: The presence of multiple cerebrovascular risk factors is associated with substantially higher rates of positive IgG isotype aCL, and with higher immunoreactivity. These findings should caution against overdiagnosis of the antiphospholipid syndrome, and consequent changes in management among patients with multiple cerebrovascular risk factors.

The purpose of the present prospective observational study was to assess whether or not the presence of anticardiolipin antibodies (aCL) in unselected first ischemic stroke patients is associated with adverse outcome. Consecutive patients (n = 300; mean age 64 years; 48% males) presenting with a first acute ischemic stroke were evaluated for IgG aCL and were systematically followed up. During a median follow-up of 21 months, 58 patients (19%) died. Mortality rates were higher in patients with aCL >20 IgG phospholipid units (GPL) [33 vs. 18%; relative risk (RR) 1.94, 95% confidence interval (CI) 1.02-3.67; p = 0.042] or >40 GPL (40 vs. 19%; RR 2.46, 95% CI 1.05-5.75; p = 0.037). Elevated aCL did not confer an increased risk during follow-up of a combined end point of stroke, myocardial infarction and vascular death or of nonfatal thrombo-occlusive events. Rates of malignancy detected during follow-up were higher among patients with aCL >20 GPL (19 vs. 5%, p = 0.007) and >40 GPL (27 vs. 6%, p = 0.01). The excess mortality associated with elevated aCL was eliminated after adjustment for age, cardiovascular risk factors and malignancy. These results demonstrate that aCL above 20-40 GPL among consecutive ischemic stroke patients is a marker of increased mortality during follow-up, but older age and higher rates of cardiovascular risk factors and malignancy detected during follow-up account for the higher mortality.