Anticardiolipin antibodies in Lyme disease

Sera from 28 patients with Lyme disease were tested for the presence of anticardiolipin antibodies (ACLA). Seven serum samples had elevated levels of IgM ACLA, and 4 had elevated levels of IgG ACLA. Higher IgM ACLA positivity tended to be associated with neurologic disease, and IgM ACLA levels correlated with the specific IgM response to the infecting spirochete (P less than 0.01). Absorption experiments indicated that ACLA and antispirochete antibodies are largely separate populations. Thus, ACLA may occur in patients with Lyme disease, particularly in those with neurologic abnormalities, and the production of these antibodies seems to be linked to the specific IgM response.     

Anticardiolipin antibodies and coronary heart disease.

Arterial or venous thrombotic events have been described as complications in patients with positive anticardiolipin antibodies (aCL), affecting various organs including the heart. In order to see whether aCL could be, among others, a predisposing factor for coronary artery occlusions and whether it could serve as a prognostic marker for coronary heart disease, 232 patients enrolled in the European Concerted Action on Thrombosis Angina Pectoris Study were studied. aCL and various other haemostatic parameters were determined at time of admittance in order to see whether a relationship existed between haemostasis at baseline and extent or prognosis of the cardiovascular disease. A follow-up at 12 and 24 months after angiography included information about relapsing coronary or other thrombotic events, treatment and outcome of the disease. aCL were not found to be a marker of either progressive cardiovascular disease or recurrent thrombotic events. No correlation was found, either in aCL positive or in aCL negative patients, between high levels of haemostasis activation markers, such as beta-thromboglobulin, platelet factor 4 or fibrinopeptide A and recurrent cardiovascular disease.     

Anticardiolipin antibodies in patients with liver disease

OBJECTIVE: Our aim was to test the hypothesis that anticardiolipin antibodies (aCL) may cause an antiphospholipid syndrome and thrombotic events in patients with liver disease. METHODS: aCL were measured in 116 healthy controls and 372 patients with liver disease of different stage and etiology: 136 cases secondary to hepatitis C virus (HCV) infection, 139 due to hepatitis B virus (HBV) infection, 69 with alcoholic liver damage, and 28 cryptogenic in origin. Prior thrombotic events were recorded. The results were related to age, gender, stage, severity, and etiology of the liver disease, as well as to the occurrence of organ- and nonorgan-specific autoantibodies. RESULTS: aCL were positive in 4.4% of controls and in 18.8% of patients (p < 0.0002). Patients with aCL were more frequently men with an advanced cirrhosis and simultaneous occurrence of anti-smooth-muscle antibodies (ASMA) in serum (p < 0.0006); their liver damage was often secondary to HBV (37.3%) or alcohol abuse (18.5%). At conditional logistic regression analysis, only the presence of ASMA (odds ratio [OR] = 3.02, 95% confidence interval [CI] 1.7-5.5, p = 0.0003), HBV (OR = 3.4, 95% CI 1.6-7.2, p = 0.0013), or alcoholic liver disease (OR = 5.3, 95% CI 2.3-12.2, p = 0.0001) were independently associated with aCL. Thrombosis was encountered in 24 patients (6.4%). At conditional logistic regression analysis, thrombosis was significantly associated with advanced age (OR = 1.07, 95% CI 1.0-1.1, p = 0.0094), development of hepatocellular carcinoma (OR = 17.8, 95% CI 1.6-196.0, p = 0.01), HBV etiology (OR = 6.3, 95% CI, 1.6-24.6, p = 0.0076), or cryptogenic liver disease (OR = 54.8, 95% CI 5-599.9, p = 0.001). Of the five patients with newly documented portal thrombosis during the follow-up, only one tested positive for aCL. CONCLUSIONS: In patients with nonautoimmune liver disease, aCL production is an epiphenomenon of the liver damage and is not associated with thrombotic complications. These data do not support the hypothesis that HCV is a cause of the antiphospholipid syndrome.     

Anticardiolipin antibodies as a risk factor of atherosclerosis in intermittent claudication

Anticardiolipin antibodies have been associated as a risk factor of atherosclerosis. The aim of this study was to evaluate the association between anticardiolipin antibodies and intermittent claudication. Forty consecutive patients (33 men, 7 women; age range: 45-84 years, mean 65.5) who were seen in the angiology and vascular surgery department with intermittent claudication were evaluated. Exclusion criteria included prior revascularization, angioplasty, or a history of thrombosis of a lower limb. Forty individuals (23 men, 17 women; age range: 58-82 years, mean 67.1) who attended a support group for senior citizens and who were apparently healthy formed the control group. Anticardiolipin antibodies were evaluated by means of enzyme-linked immunosorbent assay (ELISA) for quantitative measurement of immunoglobulin G (IgG) and IgM antibodies against cardiolipins in serum. IgG levels were considered normal when < 7, borderline from 7 to 10, and elevated at > 10 GPL units/mL; IgM levels were normal when < 4, borderline from 4 to 7, and elevated at > 7 MPL, as recommended by the test manufacturers. Statistical analysis used the relative risk test with a confidence interval of 95%. Twenty-three patients from the study group and 6 individuals from the control group were found to have elevated levels of anticardiolipin antibodies giving a relative risk of 3.833 (ranging from 1.749 to 8.4; p value < 0.0001). In conclusion, patients who have elevated levels of anticardiolipin antibodies present a 3.8 times greater risk of developing intermittent claudication.     

Anticardiolipin antibodies in a patient with Crohn's disease and thrombosis.

Thrombosis is an uncommon though well recognized complication of inflammatory bowel disease, for which various coagulation alterations have been described as possible causes. Antiphospholipid syndrome (APS) is defined as the association of thrombosis, fetal loss and thrombocytopenia with anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA). We describe a case of a 21-year-old female with recurrent thrombosis associated with aCL who went on to develop Crohn's disease. Tissue typing done in this patient revealed the presence of the HLA-DR7, DRw53, which previous studies have shown to be found in increased frequencies in APS patients. To our knowledge, this is the first report of an association between these two clinical conditions and, in this particular case, aCL may be implicated in the thrombotic events.     

Novel risk factors for peripheral arterial disease in young women

PURPOSE: To investigate traditional and novel risk factors (homocysteine and C-reactive protein levels, and exposure to infections) for peripheral arterial disease in young women. SUBJECTS AND METHODS: In a multicenter, population-based, case-control study, 212 young women (mean [+/- SD] age, 48.2 +/- 7.0 years) with peripheral arterial disease and 475 healthy control women (mean age, 45.5 +/- 8.1 years) completed a standardized questionnaire and provided blood samples. Peripheral arterial disease was angiographically confirmed if a stenotic lesion (more than 50% reduction of the lumen) was present in at least one major peripheral artery. Hyperhomocysteinemia was defined as a nonfasting plasma homocysteine level exceeding the 90th percentile of the control group. History of infectious diseases was determined by questionnaire. RESULTS: Elevated C-reactive protein levels were associated with an increased likelihood of peripheral arterial disease (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 1.8 to 8.5 for women in the third quartile; OR = 3.1; 95% CI: 1.4 to 6.8 for women in the fourth quartile; both comparisons with women in the first quartile). Hyperhomocysteinemia was not associated with a significantly increased risk of peripheral arterial disease (OR = 1.6; 95% CI: 0.9 to 3.0). A history of chickenpox, shingles, mumps, pneumonia, chronic bronchitis, peptic ulcer, or periodontitis was independently related to peripheral arterial disease, with adjusted odds ratios varying from 1.7 (95% CI: 1.0 to 3.1) for mumps to 3.4 (95% CI: 1.5 to 7.7) for peptic ulcer. The risk of peripheral arterial disease increased with the number of these infections; exposure to five or more infections increased the odds 3.7-fold (95% CI: 1.7 to 8.2). This association was not affected by the level of C-reactive protein. CONCLUSION: Our results do not support a strong relation between homocysteine and peripheral arterial disease in young women. However, an elevated C-reactive protein level and several types of symptomatic infection were associated with peripheral arterial disease.     

Cardiovascular disease in young women: a population at risk

Ischemic heart disease (IHD) is a leading cause of morbidity in the United States and worldwide. In women, it is the leading cause of death in all age groups except young women who rarely have clinically evident disease. However, when young women less than age 50 develop IHD, they are at high risk for mortality. This may be due in part to delay in diagnosis or less aggressive treatment. Young women may be less aggressively treated with medical therapies and percutaneous or surgical interventions despite studies that have shown benefit in women as well as men. Young women are an especially important population to target for treatment and study since prevention of IHD during this stage of life can have great personal and societal health consequences. Epidemiological studies, including the INTERHEART study, have identified risk factors including hypertension, diabetes, metabolic syndrome, smoking, and sedentary lifestyle that explain much of IHD in women. Several factors, including diabetes, metabolic syndrome, and tobacco use, are stronger predictors of IHD in young women as compared with older women. Healthcare practitioners who encounter young women should aggressively treat risk factors, maintain an appropriate index of suspicion for IHD, and treat acute coronary syndromes promptly and intensively to reduce the burden of IHD in young women.     

Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis.

OBJECTIVE: To determine whether the presence of anticardiolipin antibodies is a risk factor for ischemic stroke and venous thrombosis in healthy adult men. DESIGN: A nested, case-control study in a prospective cohort. SETTING: A nationwide study of physicians. PARTICIPANTS: The study sample was drawn from the Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in 22,071 male physicians. At entry, 68% of the participants submitted plasma samples that were subsequently frozen at -80 degrees C. During 60.2 months of follow-up, follow-up for nonfatal outcomes was 99.7% complete and ascertainment of fatal outcomes was 100% complete. We identified men with documented ischemic stroke, deep venous thrombosis of the leg, or pulmonary embolus and for whom a plasma sample was available. A control was matched by age, smoking history, and length of follow-up to each of the 100 patients with ischemic stroke and the 90 patients with deep venous thrombosis or pulmonary embolus. MEASUREMENTS: Plasma samples were assessed for IgG anticardiolipin antibodies by enzyme-linked immunosorbent assay. The mean anticardiolipin antibody titers of the case patients in the two diagnostic groups (ischemic stroke; venous thrombosis or pulmonary embolus) were compared with those of the control groups, and relative risks were calculated for patients in increasing percentile categories of anticardiolipin antibodies by conditional logistic regression. RESULTS: The anticardiolipin antibody titers were higher in case patients with deep venous thrombosis and pulmonary embolus than in their matched controls (P = 0.01). Persons with anticardiolipin antibody titers above the 95th percentile had a relative risk for developing deep venous thrombosis or pulmonary embolus of 5.3 (95% CI, 1.55 to 18.3; P = 0.01). The anticardiolipin antibody titers in case patients with ischemic stroke and controls were not significantly different (P > 0.2), and no clear trend of higher risks among those with elevated levels of anticardiolipin antibodies was observed. CONCLUSION: An anticardiolipin antibody level above the 95th percentile is an important risk factor for deep venous thrombosis or pulmonary embolus but not for ischemic stroke in healthy adult men.     

Anticardiolipin antibodies in ischaemic heart disease: marker or myth?

OBJECTIVES--To assess the incidence and significance of anticardiolipin antibodies after myocardial infarction and in unstable angina. DESIGN--A prospective study of all patients under 60 admitted to the coronary care unit over a 12 month period with a diagnosis of acute myocardial infarction who were followed up for a further 12 months. Patients admitted with unstable angina were similarly assessed but not followed up. Anticardiolipin antibody concentrations were compared with those of age matched controls. SETTING--A district general hospital. PATIENTS--307 patients with acute myocardial infarction and 160 patients with unstable angina. RESULTS--Anticardiolipin antibody concentrations in the two patient groups did not differ significantly from those in the control groups. Antibody concentrations were not related to a history of angina or myocardial infarction nor were they related to subsequent cardiovascular complications. CONCLUSION--This study shows no significant association between anticardiolipin antibody concentrations and either myocardial infarction or unstable angina.     

Anticardiolipin antibodies are not associated with rheumatic heart disease.

The aim of this study was to examine the prevalence of anticardiolipin antibodies in rheumatic valve heart disease. Serum samples of 31 consecutive patients with rheumatic heart disease and documented valve involvement, as well as six patients with acute rheumatic fever were tested for IgG anticardiolipin antibodies by a validated ELISA. No anticardiolipin antibodies were found when a cut-off point set at mean +/- 5 s.d. was applied. We can conclude that anticardiolipin antibodies are not present in rheumatic heart disease patients and, as suggested by several observations, these antibodies do not appear to have a pathogenic role in this particular disease.     

Anticardiolipin antibodies in HIV-negative and HIV-positive haemophiliacs

Anticardiolipin antibodies (ACA) were determined in 72 heavily transfused haemophiliacs, 43 HIV-positive and 29 HIV-negative. The presence of ACA was detected in 10 patients, all of them infected by HIV: 8 in CDC II, 1 in CDC III and 1 in CDC IV. The comparison with alterations of other laboratory markers in HIV-infected patients did not show any statistically significant difference between ACA-negative and -positive patients. In summary, ACA were found only in HIV-infected haemophiliacs. In this subgroup of patients the presence of ACA was not associated with progression to AIDS.     

Anticardiolipin antibodies in autoimmune thrombocytopenic purpura

Using a recently devised solid phase radioimmunoassay to detect anticardiolipin antibodies, we report the presence of these antibodies in 30 of 96 patients with chronic autoimmune thrombocytopenic purpura (AITP). IgG anticardiolipin antibody levels were elevated in 14 patients and IgM anticardiolipin antibody levels were elevated in 27 patients. We suggest that these antibodies may mediate peripheral platelet destruction by binding to phospholipids in the platelet membrane. It is also conceivable that the presence of anticardiolipin antibodies may select a subpopulation of patients with chronic AITP who may go on to develop other autoimmune disorders, such as systemic lupus erythematosus.     

Anticardiolipin antibodies in acquired immunodeficiency syndrome

We undertook a prospective study of IgG and IgM anticardiolipin antibodies (ACAs) to determine their clinical significance in patients with acquired immunodeficiency syndrome (AIDS). IgG ACAs were found in 24 (92.3%) of 26 patients with AIDS who were hospitalized for pulmonary complaints (group 1) and in 13 (93%) of 14 patients with AIDS-related complex (group 2). In addition, 17 (94%) of 18 patients with AIDS (group 3) who had coagulation tests and were studied retrospectively had IgG ACAs. The prevalence of IgG ACAs in these three groups was significantly higher than in healthy controls, but was comparable to that in 31 consecutive patients with systemic lupus erythematosus (67.7%). The mean titer of IgG ACAs in group 1 was higher than in groups 2 and 3 but was not different from that in the patients with systemic lupus erythematosus. The frequency and titer of IgM ACAs in group 1 (7.6%) or group 2 (14.3%) were not significantly different from those in normal controls (4.7%). In contrast, half of the patients in group 3 had low-titer IgM ACAs. The serum titer of IgG ACAs in patients with AIDS with thrombocytopenia was significantly higher than it was in those with normal platelet counts. There was no association between ACAs and Pneumocystis carinii pneumonia or other infections, cancer, thrombosis, positive VDRL test, or presence of the lupus anticoagulant. The prevalence and titer of IgG or IgM ACAs were not associated with abnormal results of any coagulation test. Although we found IgG ACAs to be associated with thrombocytopenia in AIDS, their presence does not carry exactly the same clinical significance as it does in systemic lupus erythematosus. The high prevalence of ACAs in AIDS, in AIDS-related complex, and in otherwise healthy contacts with antibodies to human immunodeficiency virus suggests that their occurrence may be related to the underlying human immunodeficiency virus infection.