Cranial ischemic complications (CICs) are the most dreaded manifestations of giant cell arteritis (GCA). The incidence of vision loss in most recent studies is around 15%, although rates as high as 49% and as low as 6% have been reported1,12-15,19,23-25. In most patients with vision loss it is secondary to anterior ischemic optic neuropathy or central retinal artery occlusion. Cerebrovascular accidents (CVAs) are less common, reported in 3%-4% of the patients2,13. Other ischemic complications, such as scalp necrosis or tongue necrosis, are rare8,16.
Most frequently, CICs are among the presenting manifestations of GCA. Yet a substantial number of patients develop CICs at a later stage, despite treatment with steroids. Data from 2 large-scale studies1,24 that together included 430 patients showed that 2%-6% of the patients developed vision loss within the first year of steroid therapy. In a 2002 multicenter prospective study19 of 98 GCA patients, this figure was even higher: 8% of the patients had new vision loss at 1 year.
Similarly, patients may present with CVA as a primary manifestation of GCA, but, not infrequently, patients will develop CVAs soon after starting steroid therapy. Gonzalez-Gay et al13 reported on 239 GCA patients: 7 of the 8 patients who had CVAs had been on steroid therapy for at least 3 days at the time of the stroke. The median interval between the start of steroid treatment and the stroke was 10 days.
Therefore, it seems important to identify those patients at risk of developing late CICs. Identifying such high-risk patients would be of significant clinical value, as more aggressive therapy may prove beneficial in these cases. On the other hand, identifying patients with a low risk of developing late CICs could result in less aggressive therapy with lower doses of prednisone, decreasing the rate of drug-related adverse effects. In recent years there have been some attempts to evaluate individual risk factors for CICs in GCA patients, by several groups of researchers. Most of these studies have focused on CICs at presentation. In the current report we aim to delineate risk factors for CICs, both at presentation and particularly during the follow-up period, and to review and evaluate the current data on this issue.
We reviewed charts of all patients in the 4 general hospitals in Jerusalem with the diagnosis of GCA between 1980 and 2000. In 152 patients, the diagnosis was proven by biopsy; 23 other cases were included as they met the American College of Rheumatology (ACR) criteria for GCA classification20. Follow-up data were available either from outpatient clinic files or from the patients' primary care physicians. Patients with less than 3 months' follow-up data were excluded. Altogether, admission data were available for 175 patients and follow-up data for 166 patients.
Admission data included the patient's age, gender, symptoms at presentation and their duration, concomitant diseases and medications, significant findings on physical examination (including ophthalmologic and neurologic examinations, when relevant), and results of laboratory tests-erythrocyte sedimentation rate (ESR), blood chemistry panel, and blood counts. Follow-up data included the starting dose of prednisone, other medications used by the patient, and disease-related symptoms including the development of CICs. Patients were considered as having hypertension, hyperlipidemia, or diabetes when these diagnoses were included in their hospital's discharge summary.
In patients presenting with CICs, GCA was diagnosed when ACR criteria were fulfilled. Likewise, CICs developing within 2 weeks of GCA diagnosis were also considered to be GCA related. CICs developing later, during tapering of steroid dose or following discontinuation of steroids, were considered GCA related only when associated with at least 1 of the other GCA-related signs or symptoms, or laboratory evidence of acute-phase reaction (elevation of C-reactive protein or ESR).
Associations between CICs and explanatory variables were tested by the Fisher exact test. Variables associated with CICs with a level of significance of p < 0.09 in univariate analysis were entered into a multivariate analysis. This higher level was determined in order not to omit borderline univariate association that might prove significant when adjusting for other variables. Multivariate analysis was performed with multiple logistic regression models. Analyses were done with SPSS for Windows v11.
CICs at Presentation
Of the 175 patients, 43 (24.6%) presented with CICs: 32 (18.3%) had acute loss of vision (26 had anterior ischemic optic neuropathy and 6 had central retinal artery occlusion) and 13 (7.4%) had CVAs. Two of those patients had both CVAs and anterior ischemic optic neuropathy occurring simultaneously (within 24 hours of each other). In 6 of the 13 CVA patients, the strokes were in the posterior distribution. Only 11 (34.4%) of the patients with vision loss had GCA symptoms unrelated to the eyes at the time of diagnosis. In contrast, 10 (77%) of the patients with CVA had other GCA-related symptoms at the time of diagnosis. Amaurosis fugax or transient ischemic attacks were reported by 7 of the patients with vision loss and 3 patients with CVAs. Diplopia preceded vision loss in 2 patients. Visual hallucinations preceded loss of vision in 5 patients. Altogether, such transient cerebro-ophthalmic ischemic episodes (COIEs) were reported by 33 patients; 17 of them (51.5%) eventually presented with CICs.
Associations between CICs and several variables at presentation are shown in Table 1. Based on a univariate logistic regression, the major risk factors for CICs were male sex, transient COIEs, and jaw claudication, while the presence of polymyalgia rheumatica symptoms, systemic symptoms (temperature >38°C, fatigue, or anorexia), and the use of low-dose aspirin (100 mg/d) were associated with a lower risk (see Table 1). There was no significant association between CICs and the presence of cardiovascular risk factors (diabetes, hypertension, or hyperlipidemia), the patient's age, platelet counts, hemoglobin levels, and ESR. Following multivariate analysis, risk factors that remained significant were transient COIEs (odds ratio [OR] 4.3) and male sex (OR 2.5), while the presence of systemic symptoms remained a significant "protective" factor (OR 0.3). Among the systemic symptoms, the presence of fever was more significantly associated with lower CICs risk. The use of low-dose aspirin was also protective (OR 0.3), with borderline significance (see Table 1).
Following GCA diagnosis and initiation of steroid therapy, 14 of 166 patients (8.4%) developed late CICs: 8 had vision loss (4.8%) and 6 had CVAs (3.6%), 3 of them in the posterior distribution. In 5 patients (36%) the late CICs developed within the first 2 weeks of steroid therapy; in 6 other patients they developed in the first year (together, 79%); and in 3 patients they occurred later, up to 30 months following initiation of steroids. Five patients developed CICs while on full doses of prednisone (60-80 mg/d). In 3 patients CICs developed while they were tapering the dose (mean dose at the time of CICs was 13 mg/d; range, 5-25 mg/d). In 6 patients CICs occurred following discontinuation of steroids: 3 of them had unplanned steroid discontinuation, which was decided by the patient (mostly due to steroid-related adverse effects) without consulting the treating physician. The mean time from steroid discontinuation to CICs was 6 weeks (range, 2-10 wk).
Seven of the 8 patients with loss of vision (87.5%) had already had vision loss in 1 eye at presentation. Two of the 6 patients developing CVA (33.3%) had also lost vision in 1 eye at presentation. Altogether, 9 of the 42 patients (21.4%) with CICs at presentation developed late CICs despite steroid therapy. In comparison, only 5 of the 124 patients (4%) without CICs at presentation developed late CICs, during the follow-up period (Table 2).
During follow-up, 8 patients experienced transient COIEs (3 had transient ischemic attacks, 4 had amaurosis fugax, and 1 had transient diplopia): 4 of these patients (50%) developed CICs (permanent vision loss in 3 and CVA in 1 patient). In comparison, only 6.3% (10 of 158) of patients without transient COIEs during the follow-up period eventually developed CICs (see Table 2). Despite the small number of patients with transient COIEs, COIEs were strongly and significantly associated with developing CICs in univariate analysis (OR 14.8; 95% confidence interval [CI] 3.2-68.1; see Table 2). However, due to the small number of patients with COIEs, this factor was not included in the multivariate analysis.
CICs developing during the follow-up period were not significantly associated with the patient's age, gender, cardiovascular risk factors (diabetes, hyperlipidemia, or hypertension), systemic symptoms at presentation, ESR, hemoglobin or platelet levels at presentation, or starting dose of prednisone (see Table 2).
Following multivariate analysis, the risk factor that remained significant for developing late CICs during the follow-up period was CICs at presentation (OR 8.3), while the use of low-dose aspirin was significantly associated with a decreased rate of late CICs (OR 0.2) (see Table 2).
DISCUSSION AND LITERATURE REVIEW
In the current report we separated the risk factors for CICs at presentation from those for CICs developing during steroid therapy or following steroid discontinuation. It appears that transient COIEs, lack of systemic symptoms (especially fever), male sex, and non-use of low-dose aspirin were associated with CICs at presentation. Factors associated with CICs developing later in the course of the disease were CICs at presentation, transient COIEs during follow-up, and non-use of aspirin.
In recent years, several groups of researchers have tried to evaluate the relationship between several disease-related clinical and laboratory parameters and the risk of developing CICs in GCA. In most of the studies, data included CICs occurring at presentation or soon after the diagnosis was made.
Systemic Manifestations and Inflammatory Response
Cid et al5 evaluated the impact of potential risk factors in a retrospective study of 200 patients. Thirty-two patients had CICs: 28 had vision loss, 3 had strokes (1 of them had concomitant vision loss), and 2 had permanent diplopia. One of the patients with vision loss also had scalp necrosis. A univariate analysis showed that systemic signs of inflammatory response-fever and weight loss-were significantly less common in patients with CICs. ESR was significantly decreased, while mean hemoglobin was higher in patients with CICs. Although multivariate analysis to evaluate the interrelationships among the different variables was not reported in that study, it seemed that augmented inflammatory or systemic response was associated with a protective effect against developing CICs. Patients who did not have such symptoms (fever and weight loss) and had a relatively minor degree of inflammation (ESR < 85 mm/h and hemoglobin > 11 g/dL) were at significantly increased risk of developing CICs (OR 5.0; 95% CI 2.0-12.2).
Gonzalez-Gay et al13 also found that absence of constitutional symptoms (weight loss of 4 kg or more, or temperature of 38°C or more) was associated with increased risk for permanent vision loss among 239 GCA patients. However, laboratory parameters of inflammation did not differ significantly between those with visual loss and those without it.
Constitutional symptoms (temperature of 38°C or more for at least a week, severe asthenia, or weight loss of more than 5% of body weight) were associated with decreased incidence of vision loss in the study of Liozon et al23. In this prospective study, 23 of 174 patients developed visual loss. OR for vision loss in patients with constitutional symptoms was 0.14 (95% CI 0.02-0.77; p = 0.01). Patients with vision loss also had significantly lower levels of C-reactive protein; however, ESR and hemoglobin levels did not differ from patients without vision loss.
Hayreh et al15 also found that fever was associated with lower incidence of ocular involvement: fever was present in 14% of their patients with ocular involvement (most of them had vision loss), compared with 33% of the patients without ocular involvement (p = 0.006). Differences in the frequency of malaise and anorexia were not significant. In contrast to the study of Cid et al5, patients with ocular involvement had lower ESR (80 vs 92 mm/h; p = 0.016), but there were no differences in C-reactive protein levels or the prevalence of anemia.
Our data are in agreement with these studies. The presence of systemic symptoms was associated with a protective effect against CICs occurring at presentation (see Table 1). When the impact of each of these symptoms was analyzed separately, it appeared that fever was the most significant. As with most other studies, we did not find an association between CICs and levels of laboratory parameters of inflammation. In this context, it seems reasonable that fever would be the most reliable factor regarding an inflammatory response: most individuals have baseline temperatures below 37.5°C. Thus temperatures of 38°C or more clearly differentiate normal from abnormal. In contrast, baseline hemoglobin and ESR levels vary significantly among elderly individuals, and many have levels considered to be "abnormal" before GCA presentation. As pre-GCA levels are not available in most cases, it is difficult to evaluate the disease-related increment or decrement. The other clinical parameters are also difficult to evaluate accurately: anorexia and fatigue or malaise are self-reported by the patients and are not quantifiable. Weight loss is also self-reported for the most part, and may not be quantified by many patients.
The reason for this fever-associated "protection" against CICs is not clear. It is possible that some inflammatory cytokines, causing elevation of temperatures, may also protect against ischemia by some unknown mechanism, possibly antiplatelet or anticoagulant effects, or by decreasing intimal hyperplasia of the inflamed arteries or preserving endothelial function, keeping the lumen patent. In assays of temporal artery tissue, it appeared that in cases with local ischemia the levels of interleukin (IL)-1β and interferon γ mRNA were high, while in patients with fever the level of IL-1β mRNA was variable and interferon γ mRNA was low29. In another report, GCA patients with ischemic events had lower IL-6 mRNA tissue expression and lower circulating IL-6 levels, while, compared to patients without ischemia, no significant differences were found for IL-1β and tumor necrosis factor17. IL-6 is known to be associated with fever18,22. In addition, angiogenesis in temporal artery sections was more prominent in patients with strong acute phase response, and in those without ischemic complications6. It was suggested that angiogenic activity of IL-6 could be a potential protective mechanism, as elevated production of IL-6 was associated with a lower incidence of ischemic events in GCA17. Another potential mechanism of protection against ischemic events could be an anticoagulant effect of the systemic inflammatory response, mediated by endothelium-dependent release of tissue plasminogen activator4.
In 1991 Espinoza et al11 reported an association between severe vascular complications in polymyalgia rheumatica-GCA and anticardiolipin antibodies (aCL). This prospective study included 30 polymyalgia rheumatica patients and 20 GCA patients: 8 of the GCA patients had aCL, 2 of them (25%) developed CICs (1 had blindness and 1 CVA), and 3 had transient ischemic symptoms. None of the 12 GCA patients with negative aCL developed CICs. Three of the 30 polymyalgia rheumatica patients and 2 of 50 control subjects had aCL, and none developed CICs. Chakravarty et al3 reported that 14 of 44 GCA patients (with or without polymyalgia rheumatica) had aCL, and 3 of them (21%) developed CICs (2 had CVAs and 1 had anterior ischemic optic neuropathy). In contrast, none of the 30 GCA patients without aCL developed CICs. In a larger-scale study, Duhaut et al9 reported data of 129 biopsy-positive GCA patients: 8 patients had blindness, 4 of them (50%) had aCL, while 35 of 121 (29%) without blindness had aCL. They found that aCL was associated with thrombotic complications in univariate (but not multivariate) analysis.
In contrast, other studies found no association between aCL and CICs: Manna et al26 reported data on their group of 33 patients: 17 were aCL positive and 16 were aCL negative. Eight patients in each group developed CICs (6 anterior ischemic optic neuropathy and 2 with cerebral ischemia). Another prospective study reported that 2 of 10 GCA patients with IgG aCL developed CICs, compared to 1 of 10 with negative IgG aCL21. Espinosa et al10 found no relationship between ischemic manifestations and the presence of aCL, anti β2glycoprotein-I, lupus anticoagulant, or antiprothrombin antibodies in 66 GCA patients. In our group sera from 40 patients were tested for antiphospholipid antibodies: 12 were positive (30%). Two of these patients developed CICs (17%), compared to 5 of the 28 (18%) without antiphospholipid antibodies.
Antiphospholipid antibodies may harbor some risk for developing CICs in GCA patients, but these conflicting data make it impossible to draw definite conclusions.
De Keyser et al7 reported an association between thrombocytosis and CICs in a retrospective study of 56 GCA patients: 18 developed transient or permanent CICs. Eleven of these patients (61%) had thrombocytosis, (platelet count > 400 × 109/L), compared to 10 of 38 without CICs (26%). The difference was statistically significant (p < 0.01). In a larger-scale, prospective study of 174 patients, Liozon et al23 reported that 48 patients had ischemic visual symptoms. Of the 87 patients with thrombocytosis, 37% developed visual ischemic symptoms, compared to 16 (18%) of those without thrombocytosis. Permanent vision loss occurred in 23 patients. This was also associated with elevated platelet counts: the mean platelet count in patients with vision loss was 489 ± 172 × 109/L, compared to 409 ± 133 × 109/L in patients without vision loss (OR 3.7; 95% CI 1.8-7.9; p < 0.001). In addition, there was correlation between the degree of thrombocytosis and the risk of permanent vision loss: 33% of patients with platelet counts above 600 × 109/L developed permanent vision loss, compared to 23% and 16% of patients with platelet counts above 500 and 400 × 109/L, respectively.
In contrast, 2 large-scale studies found no association between thrombocytosis and CICs in GCA: Gonzalez-Gay et al14 found similar platelet counts in 161 biopsy-proven GCA patients with or without visual manifestations or permanent vision loss. Cid et al5 reported that the mean platelet count in 200 biopsy-proven GCA patients with irreversible CICs was even lower than in patients without CICs (337 × 109/L compared to 375 × 109/L), but this difference was not statistically significant. Similarly, in our study there was no significant difference between platelet counts in patients with or without CICs (445 × 109/L compared to 452 × 109/L, respectively). CICs were present in 27% of GCA patients with thrombocytosis, compared to 21% of patients with normal platelet counts.
Thrombocytosis may harbor some risk for developing CICs in GCA patients, but these conflicting data make it impossible to draw definite conclusions.
Font et al12 studied 146 GCA patients; 23 had vision loss: 65% of them had premonitory visual symptoms before vision loss for an average of 8 days. These included amaurosis fugax, blurry vision, partial field defects, and diplopia. Similar figures were reported by Liu et al24: half of the patients with vision loss had premorbid visual symptoms, the most common of which was amaurosis fugax.
Cid et al5 reported that 32% of patients with CICs had had amaurosis fugax, compared to only 6% in patients without CICs. Transient diplopia was also more common in patients developing CICs (16% vs 4%; p = 0.02). Gonzalez-Gay et al14 found that 12 of 24 patients (50%) with permanent visual loss had had amaurosis fugax, while only 11 of 137 (8%) without visual sequelae had had amaurosis fugax. In other words, of the 23 patients with amaurosis fugax, 12 (52%) developed permanent loss of vision. The calculated OR was 12.6 (95% CI 4.4-36.1; p < 0.001). Hayreh et al15 reported similar figures: permanent vision loss developed in 64% of the 33 eyes with amaurosis fugax. Lower figures were reported by Aiello et al1: 25% of patients with amaurosis fugax or transient diplopia developed visual loss.
The strongest predictor of permanent vision loss in the study of Liozon et al23 was a history of transient visual ischemic symptoms, mainly amaurosis fugax (OR 6.3; 95% CI 1.8-7.9; p = 0.02). Such symptoms preceded vision loss in 10 of 23 patients (43%), with an average delay of 3 days.
The impact of transient ischemic attacks as a risk factor for developing CICs in GCA patients had not been thoroughly evaluated. Cid et al5 reported that 6.3% of patients with irreversible CICs had had transient ischemic attacks, while only 2.3% without CICs had had transient ischemic attacks, but the difference was not statistically significant.
In the current study transient COIEs were also strongly associated with developing CICs, both at presentation and during the course of the disease. The chance of developing CICs at presentation was 51.5% for patients with transient COIEs, and only 18.3% for patients without these transient ischemic symptoms (see Table 1). Similarly, the chance of developing late CICs was 50% for patients with transient COIEs occurring during the follow-up period, compared to only 6.3% of the patients without transient COIEs during this period (see Table 2).
This type of jaw pain also has been considered a warning sign for developing CICs. Aiello et al1 reported its presence in 55% of 34 patients with vision loss compared to 32% of patients without loss of vision (p < 0.02). Gonzalez-Gay et al13 reported that jaw claudication was predictive of both permanent visual loss and CVA (OR 1.8 and 3.5, respectively).
Other studies did not find an association between jaw claudication and CICs. Cid et al5 and Hayreh et al15 reported that about half of the patients with or without CICs had jaw claudication. Liozon et al23 also did not find differences in the rate of this symptom between patients with or without visual loss.
In our patients jaw claudication was less frequent: only 31 GCA patients (18%) reported this symptom at presentation. Of these 31 patients, 39% developed CICs, compared to only 21% of patients without jaw claudication (OR 2.3; p = 0.06). However, this association was not significant following multivariate analysis. Thus, it seems that the presence of jaw claudication may harbor some risk for developing CICs in GCA patients, but the conflicting data of these studies make it impossible to draw definite conclusions.
Previous CICs as Risk Factors for New CICs
A small fraction of GCA patients develop CICs despite steroid therapy during the course of the disease (late CICs). As shown in our data, most of these patients (9 of 14, 64%) had had previous CICs at presentation. Of the 42 patients with CICs at presentation who were included in the follow-up evaluation, 9 (21.4%) developed another GCA-related CIC during follow-up. In comparison, only 4% (5 of 124) of patients without CICs at presentation developed CICs during follow-up (p = 0.001) (see Table 2).
Gonzalez-Gay et al13 reported that all 4 patients who developed vision loss after starting steroid therapy had had vision loss in the other eye at presentation. In addition, they found that the best predictor of CVA (mostly occurring after commencing steroid therapy) was the presence of permanent vision loss (OR 7.6; 95% CI 1.6-37.0; p = 0.01), and the best predictor for irreversible vision loss was CVA (OR 26; 95% CI 2.3-304; p = 0.008)13,14.
In another study, 3 of the 9 patients who developed vision loss after the start of steroid therapy had had anterior ischemic optic neuropathy at presentation24. All but 1 were on steroids at the time of vision loss. A similar rate was reported by Aiello et al1: 5 patients developed vision loss after starting steroid therapy, 3 of them had had vision loss in the other eye at presentation. Data from these 2 large-scale studies show that 2%-6% of GCA patients developed visual loss within the first year of steroid therapy, but the risk was augmented in the subgroup of patients who had presented with visual loss in 1 eye: 8%-16% of these patients lost vision in the fellow eye, mostly within a few weeks. The risk rate was similar in the prospective study of Hoffman et al19: 3 of the 17 patients (18%) who had already had 1 episode of vision loss at study entry experienced additional vision loss during the first year after enrollment.
Other Factors Associated With CICs
Age was associated with an increased rate of ocular symptoms in 1 study only15. In that report, patients with ocular involvement were older than patients without visual manifestations (mean age, 76.2 yr and 73.8 yr, respectively; p = 0.026). In our study, patients who developed late CICs tended to be younger than those who did not (70.5 yr and 74.2 yr, respectively), but this difference did not reach statistical significance (see Table 2).
Gender was associated with CICs at presentation only in Israeli patients. In our report, the OR for CICs in males was 2.5 (95% CI 1.1-5.4; p = 0.02) (see Table 1). Nir-Paz et al28 also found increased occurrence of blindness in men compared to women among 71 Israeli GCA patients: 25.9% of men, but only 9.1% of women, had complete blindness. It should be noted that some of our patients were included in that study. The reason for this increased risk among Israeli men with GCA is not clear. Smoking, 1 of the possible confounding factors, was not taken into consideration due to lack of reliable information regarding smoking history in many of the cases, a result of the retrospective nature of our study. As smoking is more prevalent in men, it could explain the varied results in regard to other studies. In the current study, the risk for developing late CICs, during the course of the disease, was similar among men and women (see Table 2).
Polymyalgia rheumatica was associated with reduced rates of CICs in GCA patients in some studies. Liozon et al23 found a strong protective effect of polymyalgia rheumatica: 30% of patients with no vision loss had polymyalgia rheumatica, compared to only 4% of patients with permanent vision loss (OR 0.04; 95% CI 0.01-0.5; p = 0.02). Gonzalez-Gay et al13 also found that 38% of patients with ocular symptoms had polymyalgia rheumatica, compared to 51% of patients without ocular symptoms. This difference was close to reaching statistical significance (p = 0.06). In our patients there was a trend toward lower rates of CICs in patients with polymyalgia rheumatica: 16% of 63 patients with polymyalgia rheumatica had CICs, compared to 29% of 112 without polymyalgia rheumatica. The OR, based on univariate analysis, was 0.45 (95% CI 0.21-0.99, p < 0.05), but this significance level did not hold following multivariate analysis.
In contrast, Cid et al5 did not find significant differences between the rates of polymyalgia rheumatica in GCA patients with or without CICs (47% and 50%, respectively), and Aiello et al1 reported no significant difference regarding visual findings in patients presenting with polymyalgia rheumatica.
Thus, it is possible that the presence of polymyalgia rheumatica symptoms may harbor some protective effect against developing CICs in GCA patients, but the varied data of these studies make it impossible to draw definite conclusions.
Elevation of Liver Enzymes
Elevation of liver enzymes was associated with a decreased chance of developing CICs in some studies. Gonzalez-Gay et al13 reported that GCA patients with elevated liver enzymes had a decreased chance of developing CICs (OR 0.33; 95% CI 0.12-0.88; p = 0.02). Cid et al5 also found a trend toward increased alkaline phosphatase levels in patients without CICs compared to patients with CICs, but this did not reach statistical significance. Similarly, Liozon et al23 found that 53% of patients with no vision loss had hepatic abnormalities, compared to 35% of patients with permanent vision loss, but the difference was not statistically significant. It is possible that the liver abnormalities are part of the acute-phase reaction, and thus might be associated with the presumed protective effect mentioned above.
Homocysteine levels were evaluated in only 1 report of 17 GCA and 39 polymyalgia rheumatica patients27. Plasma levels were significantly higher in GCA-polymyalgia rheumatica patients compared to age-matched controls. Homocysteine levels in GCA patients were higher than in polymyalgia rheumatica patients, but the difference was not statistically significant. It is noteworthy that homocysteine levels increased in GCA patients following steroid treatment. Ten of the GCA patients had ischemic manifestations. Although these patients had higher levels of homocysteine compared to GCA patients without ischemic manifestations (15 μM vs 11.6 μM), this difference did not reach statistical significance. Further studies are needed to evaluate the role of homocysteine in developing GCA-related CICs, especially because levels increase with steroid therapy.
In conclusion, several variables have been shown to be associated with increased risk for CICs in GCA patients (Table 3). Accordingly, patients may be stratified into high-risk and low-risk groups in regard to developing CICs. Future studies can be done to determine whether high-risk patients might benefit from a more aggressive treatment approach, with higher doses of steroids initially and the possible addition of antiplatelet medications27a or folic acid; and whether lower doses of prednisone would be sufficient for low-risk patients.
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