ApoA-1 (apolipoprotein A-1) is the main component of HDL (high-density lipoprotein) and stabilizes PON-1 (paraoxonase-1), which prevents lipid peroxidation and oxLDL (oxidized low-density lipoprotein) formation. Autoantibodies against apoA-1 [anti-(apoA-1) IgG] have been found in antiphospholipid syndrome and systemic lupus erythematosous, two diseases with an increased risk of thrombotic events, as well as in ACS (acute coronary syndrome). OxLDL levels are also elevated in these diseases. Whether anti-(apoA-1) IgGs exist in other prothrombotic conditions, such as APE (acute pulmonary embolism) and stroke, has not been studied and their potential association with oxLDL and PON-1 activity is not known. In the present study, we determined prospectively the prevalence of anti-(apoA-1) IgG in patients with ACS ( n =127), APE ( n =58) and stroke ( n =34), and, when present, we tested their association with oxLDL levels. The prevalance of anti-(apoA-1) IgG was 11% in the ACS group, 2% in the control group and 0% in the APE and stroke groups. The ACS group had significantly higher median anti-(apoA-1) IgG titres than the other groups of patients. Patients with ACS positive for anti-(apoA-1) IgG had significantly higher median oxLDL values than those who tested negative (226.5 compared with 47.7 units/l; P <0.00001) and controls. The Spearman ranked test revealed a significant correlation between anti-(apoA-1) IgG titres and serum oxLDL levels ( r =0.28, P <0.05). No association was found between PON-1 activity and oxLDL or anti-(apoA-1) IgG levels. In conclusion, anti-(apoA-1) IgG levels are positive in ACS, but not in stroke or APE. In ACS, their presence is associated with higher levels of oxLDL and is directly proportional to the serum concentration of oxLDL. These results emphasize the role of humoral autoimmunity as a mediator of inflammation and coronary atherogenesis.

PPAR (peroxisome-proliferator-activated receptor) is a nuclear receptor. Activation of PPARγ by its ligands could modulate gene transcription, thereby leading to multiple anti-atherogenic and fibrinolytic effects. However, the association between the 161T allele in exon 6 of the PPARγ gene and premature AMI (acute myocardial infarction) is not clear. We recruited 146 patients with premature AMI (onset age ≤50 years) and 146 controls. The C161T polymorphism was examined using PCR and restriction-fragment-length polymorphism. Plasma levels of Ab-ox-LDL (antibody against oxidized low-density lipoprotein) were measured in 27 male smokers, whose genotypes have been identified. The frequency of the PPARγ TT genotype among patients with AMI was significantly higher than that in controls [13% compared with 5.5%; OR (95% CI) 2.7, (1.1–6.5), where OR and CI are odds ratio and confidence interval respectively]. This association was not observed in CC or CT genotypes. Using multivariate logistic regression analyses, we found that the homozygous TT genotype [OR (95% CI), 3.1 (1.2–7.9)], smoking [OR (95% CI), 3.5, (2.1–6.0)], hypertension [OR (95% CI), 3.6, (1.9–6.9)] and diabetes mellitus [OR (95% CI), 3.5 (1.5–8.4)] were independent risk factors for premature AMI. Plasma levels of Ab-ox-LDL were significantly higher in healthy volunteers with the TT genotype compared with those with the CC genotype (49.3±18.1 compared with 24.2±15.2 units/l respectively; P =0.02). Therefore in our study we observed an association between the PPARγ 161 TT genotype and premature AMI. Lipid peroxidation was significantly influenced by the 161T allele.

Oxidized low-density lipoprotein (OxLDL) and autoantibodies to OxLDL (aOxLDL) are implicated in the development of atherosclerosis. The objective of this study was to determine the importance of these factors in hypertension, a major risk factor for atherosclerosis. Samples were obtained from 111 men with established hypertension (diastolic pressure >95 mmHg) from the Swedish component of an ongoing hypertension study (European Lacidipine study on Atherosclerosis, ELSA) and from 75 normotensive control men, who were from a Swedish population-screening programme (diastolic pressure <80 mmHg). The presence of carotid atherosclerosis and the intima-media thicknesses were determined by ultrasonography. A monoclonal antibody to OxLDL, EO6, was used to determine oxidation epitopes in LDL. aOxLDL of IgG and IgM subclass were tested by ELISA against OxLDL. Hypertensive men had increased OxLDL levels compared with normotensives ( P =0.002), whereas autoantibodies tested were largely similar between groups. There was no association between the antibodies tested, or OxLDL and carotid atherosclerosis. Age was not associated with OxLDL or aOxLDL measurements. Taken together, our findings indicate that OxLDL is elevated in hypertensive men, which may predispose to atherosclerosis in hypertension. In contrast, aOxLDL levels were unchanged and the role of aOxLDL may depend on disease stage and/or type.

Results from several recent reports have linked high serum C-reactive protein (CRP) levels to atherosclerotic disease and its complications. The aims of the present study were to investigate the relationship between CRP levels and subclinical atherosclerosis, as measured by ultrasound in the carotid and femoral arteries; and also to examine whether CRP levels are associated with antibodies to oxidized low-density lipoprotein (Ox-LDL). The study group ( n = 391) consisted of clinically healthy 58-year-old men recruited from the general population. CRP and antibody titres to Ox-LDL were measured by ELISA. The results showed an association between CRP and ultrasound-assessed subclinical atherosclerosis in the femoral artery ( r = 0.14, P = 0.010), and also between CRP and systolic blood pressure, diastolic blood pressure, heart rate, triglycerides, high-density lipoprotein, body mass index, waist-to-hip ratio (WHR), blood glucose, cigarette-years and antibody titres to ox-LDL ( r = 0.19, P < 0.001). In this clinically healthy population of 58-year-old men, CRP levels were associated with both intima-media thickness and plaque occurrence in the femoral artery. The association between CRP and femoral atherosclerosis was not independent of smoking, serum LDL cholesterol, or systolic blood pressure. CRP levels were independently related to abdominal obesity measured as WHR, smoking and antibody titres to Ox-LDL.

1. In this study we compared the 500 MHz 1 H-NMRs from native and oxidized low-density lipoproteins. 2. The measurements revealed a characteristic pattern of three resonances in spectra from oxidized, but not from native low-density liprotein at 1.17 p.p.m., 1.18 p.p.m. and 1.20 p.p.m. (relative to 3-trimethylsilyl-[2,2,3,3- 2 H 4 ]-propionate). 3. A quantitative comparison between these resonances in sera from patients with coronary heart disease and healthy control subjects revealed that the intensity was significantly higher in patients with coronary heart disease (1.17 p.p.m.: 0.026±0.014 versus 0.015±0.019; 1.18 p.p.m.: 0.032±0.011 versus 0.017±0.021; 1.20 p.p.m.: 0.030±0.066 versus 0.010±0.005; P < 0.05 compared with healthy control subjects for each resonance). 4. Fractionation of sera from patients with coronary heart disease revealed that the resonances equal to those obtained from experimentally oxidized low-density lipoprotein are indeed caused by the low-density lipoprotein fraction of the sera. 5. When the NMRs from sera were calibrated with oxidized low-density lipoprotein prepared by Cu 2+ oxidation, a concentration of 66.5±28.6 ; μ g/ml and 36.3±23.7 ; μ g/ml ( P < 0.05) was estimated in patients with coronary heart disease and healthy subjects respectively. Elevated levels of oxidized low-density lipoprotein also occurred in those patients with normal serum concentrations of total low-density lipoprotein. 6. The study shows a simple method to measure oxidized low-density lipoprotein in human serum and may gain interest to assess the cardiovascular risk factor profiles more completely.