All patients with a deficient PF activity had high Lp(a) values. While the prevalence of PF deficiency ranges about 1-2%, in 7 (19%) patients with clinically manifested atherosclerosis and 3 (19%) healthy adults with elevated Lp(a) this defect was found. The findings demonstrate an association between PF deficiency and Lp(a), indicating a biochemical interaction.
PAPS patients with cerebrovascular insults had recurrence of cerebrovascular episodes, measurement of apo(a) concentrations will help in the follow-up of those patients and thus in the prediction of future episodes.
Elevated plasma levels of Lp(a) were found in patients with APS compared to 22 healthy controls (). Patients with APS with maximal elevation of Lp(a) showed a lower fibrinolytic activity (lower D-dimer and higher plasminogen activator inhibitor) than patients whose Lp(a) was within a normal range. These findings suggest that Lp(a) may represent a marker of APS and that Lp(a) has a negative effect on the fibrinolytic system that might contribute to the thrombotic tendency of APS.
Existence of autoantibodies against MDA-Lp(a). The presence of antibodies reacting not only against MDA-LDL but also against MDA-Lp(a) supports the hypothesis of a role for oxidative phenomena in the pathogenesis of APS and atherosclerosis.
A number of factors can be encountered in the pathogenesis of the accelerated arterial disease seen in patients with antiphospholipid (Hughes) syndrome (APS) and systemic lupus erythematosus (SLE). Among these, high levels of Lp(a) have been described in both and increasing evidence indicates that patients with antiphospholipid antibodies (aPL) are under oxidative stress. Recent studies suggest that the so-called “oxidation theory of atherosclerosis” may also be applied to Lp(a).
Beta2-glycoprotein I (beta2GPI) is a glycoprotein of unknown physiological function. It is the main target antigen for antiphospholipid antibodies in patients with antiphospholipid syndrome (APS). beta2GPI binds with high affinity to the atherogenic lipoprotein Lp(a) which shares structural homology with plasminogen, a key molecule in the fibrinolytic system. Impaired fibrinolysis has been described in APS.
Patients with aPL are in hypercoagulable state. High levels of Lp(a) in plasma may impair the fibrinolytic system resulting in thromboses, especially in the arterial system.
The mean serum Lp(a) level was significantly higher () in the RA patients (27.5 mg/dL) than in the controls (15.0 mg/dL) possibly partly because of S3 phenotype predominance.
These data indicated that synovial fluid apo(a) originates from circulating Lp(a) and that diffusion of Lp(a) through synovial tissue is facilitated in inflammatory types of arthritis. In synovial tissues, apo(a) co-localized with fibrin. In humans, apo(a) may modulate locally the fibrinolytic activity and may thus contribute to the persistence of intra-articular fibrin in inflammatory arthritis.
Analysis of the six studies showed Lp(a) level was higher and HDL level was lower in RA patients than in healthy controls. Patients with RA may have altered lipid profiles from one country to another one. Especially in Turkey, higher serum Lp(a), lower HDL-C and higher TG levels may be found in RA patients instead of some findings of other countries showing different results. Ethnicity may be a reason for these findings.
In this paper additional results of interleukin determinantions in relation to HLA type and Lp(a) levels are presented and discussed. It is suggested that an autoimmune process, perhaps triggered by a concomitant intracellular infection may occur, especially in patients with inherited high Lp(a) levels in combination with certain inherited HLA class II genotypes.
The associations found between LP(a) and insulin release, rheumatoid arthritis and renal diseases suggest that Lp(a) may be involved in immunological mechanisms. In a new hypothesis it is suggested that an autoimmune process might especially occur in individuals with inherited high Lp(a) levels and certain HLA class II genotypes, triggered by a concurrent infection.
Certain HLA class II DR genotypes in combination with high Lp(a) levels and C. pneumoniae titers occurred more frequently in both male and female patients than in controls.
In the RA and control groups, serum Lp(a) levels were mg/dL and mg/dL, respectively (). CRP levels were positively correlated with Lp(a), HDL-C level were negatively correlated with Lp(a) (, ).
Sera of patients showed higher TC ( versus mmol/L, ), LDL-c ( versus mmol/L, ), Lp(a) ( versus mmol/L, ) and lower HDL-c ( versus mmol/L, ). Apo A-1 was correlated to Lp(a) (, ). Corticoid dose was not associated to dyslipidaemia, but in multiple regression models, corticoid dose may be negatively related to some atherogenic markers, in particular non-HDL-c. Tunisian patients with markedly active RA experience substantially reduced serum HDL-c and increased TC, LDL-c and Lp(a) concentrations as well as increased TC/HDL-c, LDL-c/HDL-c and non-HDL-c/HDL-c ratios.
Nine (42.3%) of 21 RA patients and 6 (31.6%) of 19 controls had high Lp(a) levels (>30 mg/dL) and the Lp(a) level was higher in RA patients compared with controls ( versus mg/dL) without significant difference ().
Our study suggests that patients with untreated active RA have altered lipoprotein and apolipoprotein patterns that may possibly expose them to higher risk of atherosclerosis. The inflammatory condition of RA may affect the metabolism of HDL-cholesterol and apo A1.
Lipoprotein(a), (Lp(a)), an independent atherogenic factor, was significantly increased in 93 patients with classical, seropositive rheumatoid arthritis of median disease activity. In the patients with Lp(a) concentrations above the upper reference value of 480 mg/L there was a significant correlation between Lp(a) and the concentration of orosomucoid, erythrocyte sedimentation rate, and the platelet count.
Inhibition of IL-6 signalling improves insulin sensitivity in humans with immunological disease suggesting that elevated IL-6 levels in type 2 diabetic subjects might be causally involved in the pathogenesis of insulin resistance. Furthermore, our data indicate that inhibition of IL-6 signalling decreases Lp(a) serum levels, which might reduce the cardiovascular risk of human subjects.
Lp(a) levels were highest in active RA mg/dL) modest in controls ( mg/dL) and lowest in inactive RA ( mg/dL). Lp(a) concentrations were found positively correlated with ox-Lp(a) (, Pb 0.001) and Lp(a)-IC (, Pb 0.001) concentrations respectively. Ox-Lp(a) concentrations were also related with Lp(a)-IC concentrations (, Pb 0.001).
Serum beta(2)-GPI-Lp(a) ( U/mL versus U/mL, ) and beta(2)-GPI-ox-LDL ( U/mL versus U/mL, ) concentrations in RA were both significantly higher than those of controls. Ox-Lp(a) ( mg/L versus mg/L, ) and ox-LDL ( mg/L versus mg/L, ) were also higher in RA than in controls.
Coagulation was significantly activated in Ssc patients (increase in F1 + 2, ; TAT, ; and Lp(a), ). Endothelial injury reduces endothelial function, as suggested by impairment of fibrinolysis and activation of the coagulative pathway.
SSc patients had statistically significant differences when compared to healthy controls in median and 25–75th percentile distribution of Lp(a) (110 mg/L, 51–389 mg/L versus 79 mg/L, 29–149 mg/L; ). When compared to current NCEP/AHA/ACC goals, the values distributions and the relative percentage of patients with undesirable or abnormal vales were statistically different for Lp(a) (29% versus 3%) and Hs-CRP (42% versus 12%) (both ). Lp(a) measurement might be useful in SSc to identify and eventually treat subsets of patients more predisposed to develop thrombotic complications.
AD patients (SLE) are at high risk of CVD. Nontraditional risk factors like OxLDL, oxLDL autoantibodies, phospholipids, and inflammation could lead to new therapeutic strategies and insight into disease mechanisms.
Patients with SLE and venous thrombosis had higher levels of beta2GPI-IC when compared with thrombosis-free patients or with healthy controls (). Patients with higher Lp(a) levels (>50 mg/dL) possessed higher levels of beta2GPI-IC as compared with patients with lower Lp(a) concentration (<20 mg/dL) ().
Our study is the first to reveal that hypoalbuminemia appearing during disease flare plays an important role in increasing the serum Lp(a) levels in lupus patients with renal disease and shows that corticosteroid treatment reduced the elevated serum Lp(a) levels almost to original levels.
Existence of autoantibodies against MDA-Lp(a). The presence of antibodies reacting not only against MDA-LDL but also against MDA-Lp(a) supports the hypothesis of a role for oxidative phenomena in the pathogenesis of APS and atherosclerosis.
Serum Lp(a) levels are significantly higher () in patients with SLE, these patients have a risk of developing cardiovascular disease and atherosclerosis and should be followed up.
Lp(a) ( mg/L versus mg/L) and ox-Lp(a) ( mg/L versus mg/L) concentrations were higher in SLE patients than in controls (). Beta(2)-GPI-Lp(a) complexes were detectable in both controls and with higher levels in SLE patients.
Antigenic stimuli in the pathogenesis of atherosclerosis: oxLDLs, beta2glycoprotein1 (beta2GP1), LP(a), heat shock proteins (HSPs), extracellular matrix components (collagen and fibrinogen), and foreign antigens including bacteria.
