Antibody responses in arthritic and uncomplicatedYersinia enterocolitica infections

Concentrations of antiyersinia antibody isotypes IgG1, IgG2, IgG3, IgG4, IgA and IgM were measured in 33 patients with yersiniosis using a solid-phase radioimmunoassay. Sixteen patients had a complicating reactive arthritis. Throughout the observation period IgG1 and IgM antibodies both constituted approximately one-third of the total antibodies, while IgA accounted for 10%, IgG3 accounted for 1%, and IgG4 antibodies could not be detected. IgG1, IgM, and IgA antibodies (and the total titer) had reached their peak at the beginning of the observation period (ca. day 20 after the onset of symptoms). The levels then gradually decreased; the total titers averaged 40 times the background at the beginning of the observation period and 4 times the background on day 350. IgM antibodies could be detected as late as a year after the infection. The concentration of IgG2 antibodies varied greatly from patient to patient. In most patients it increased until a plateau was reached approximately 2 months after the onset of symptoms. A decline was observed later. Five arthritic but no nonarthritic patients had a pronounced IgG2 response (more than half of the IgG antibodies were IgG2 in one or several samples).     

Carotid artery intima-media thickness in Finnish families with familial combined hyperlipidemia

BACKGROUND: Familial combined hyperlipidemia (FCHL) is the most common hereditary lipid disorder that predisposes the patients to premature coronary heart disease. Members of FCHL families are categorised as affected or unaffected according to serum lipid levels. This study is aimed to evaluate whether there is a difference in carotid artery wall thickness between asymptomatic FCHL family members who are affected and those who are unaffected according to the currently used lipid criteria. METHODS AND RESULTS: Carotid artery ultrasonography with intima-media thickness (IMT) measurements was performed for 148 members of 39 Finnish FCHL families. Study subjects who had no history of coronary heart disease or stroke were divided into two groups according to their serum total cholesterol and/or triglyceride levels. The average carotid IMT of the affected subjects (0.75+/-0.15 mm) was not significantly different from that of their unaffected relatives (0.73+/-0.13 mm), P=0.90. In multivariate analysis, age, gender, and pulse pressure, but no lipid variables, contributed significantly to the variation of carotid IMT. CONCLUSIONS: The IMT findings in FCHL family members indicate that the current lipid criteria alone are of limited value in predicting long-term risk of cardiovascular disease in asymptomatic members of FCHL families.     

Cholesterol Efflux Capacity In Vitro Predicts the Severity and Extent of Coronary Artery Disease in Patients with and without Type 2 Diabetes

Objective - To investigate the relation between severity and extent of coronary artery disease (CAD) and in vitro cholesterol efflux capacity. Design - This study consisted of 46 type 2 diabetic, and 42 nondiabetic men undergoing coronary angiography. Quantitative coronary angiography was used to estimate the severity, extent, and overall "atheroma burden" of CAD. The capacity of patient plasma to induce cholesterol efflux from cultured Fu5AH rat hepatoma cells was measured in vitro. Results - In the combined study population (n = 88), there was a significant inverse correlation between efflux and global atheroma burden (r = -0.23, p < 0.05). In the diabetic group, the global atheroma burden index was independently associated both with cholesterol efflux and with LpA-I levels. However, in the nondiabetic CAD group this association was lost when efflux and LpA-I levels were included in the same model. Conclusion - The present study demonstrated that efflux capacity was inversely associated with the severity and extent of CAD. In the diabetic group this association was independent of LpA-I levels, suggesting impaired antiatherogenic potential of these particles in type 2 diabetic patients.     

Apolipoprotein E polymorphism is associated with both carotid and coronary atherosclerosis in patients with coronary artery disease

Background and aimsApolipoprotein E (apoE) polymorphism plays a significant role in the development of atherosclerosis and cardiovascular disease. Therefore, the aim of the present study was to examine the association between apoE polymorphism and carotid intima-media thickness (IMT), and severity and extent of coronary artery disease (CAD).Methods and resultsB-mode ultrasound and quantitative coronary angiography (QCA) were used to assess carotid, and coronary artery atherosclerosis in 91 patients with clinically suspected CAD referred for cardiac catheterization. Two apoE phenotype groups were defined: apoE3 (E3/E3) and apoE4 (including E4/E3, E4/E4 phenotypes). Maximum IMT was higher in the apoE4 group than in the apoE3 group (p = 0.022). The global atheroma burden index was similarly higher in the apoE4 group than in the apoE3 group (p = 0.033). ApoE4 subjects had higher levels of apolipoprotein B (apoB) (p = 0.008), triglycerides (p = 0.006), remnant lipoprotein-cholesterol (RLP-C) (p = 0.023), and lipoprotein(a) [(Lp(a)] (p = 0.041) than apoE3 subjects. The mean LDL particle size was smaller in the apoE4 group than in the apoE3 group (p = 0.041).ConclusionsApoE polymorphism was associated with both carotid and coronary atherosclerosis. Patients with the apoE4 isoform had an increased carotid IMT and a more severe and extensive CAD than patients with the apoE3 isoform.     

Diabetic dyslipidemia

By the year 2025, there will be more than 300 million type 2 diabetes sufferers worldwide. This epidemic will be followed by a wave of cardiovascular disease. Diabetes is in fact a serious vascular disease with poor prognosis, and not only a disease characterized by elevated blood glucose. If adequate attention were paid to this, it would be much easier to relieve the burden of cardiovascular disease in type 2 diabetes patients. One important cardiovascular risk factor in type 2 diabetic people is dyslipidemia. This is characterized by low HDL-cholesterol, high serum VLDL-triglycerides, and a preponderance of small, dense LDL. Even slight elevations of LDL-cholesterol in type 2 diabetic patients are associated with a substantial increase in cardiovascular risk. The composition of lipid particles in diabetic dyslipidemia is more atherogenic than in dyslipidemia in general. This means in turn that normal lipid concentrations are more atherogenic in diabetic than in non-diabetic patients. Retrospective analyses show that, in terms of protection from cardiovascular endpoints, the benefit of lipid lowering in type 2 diabetic patients is at least as great as in the non-diabetic population. Lowering of LDL-cholesterol is a very attractive target for the reduction of coronary heart disease in type 2 diabetic people.     

Reduced IGFBP-1 is associated with thickening of the carotid wall in type 2 diabetes

OBJECTIVE: The aim of the present study was to assess the role of the insulin-like growth factor (IGF) system and lipids in predicting the carotid intima-media thickness (IMT) in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 239 type 2 diabetic participants in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study (76 women) aged 50-75 years were examined before fenofibrate intervention. Patients underwent carotid ultrasonography for determination of IMT. IGF-I, IGF binding protein 1 (IGFBP-1), IGFBP-3, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein B (apoB), lipoprotein(a) (Lp(a)), glucose, HbA(1c), and C-peptide were measured in fasting samples. Patients were divided in groups without (n = 168) and with (n = 71) clinical cardiovascular disease (CVD). RESULTS: Partial correlations adjusted for age, sex, BMI, and diabetes duration showed an inverse association of IGFBP-1 with C-peptide (r = -0. 24, P = 0.018) and with maximal IMT (r = -0.42, P < 0.001), whereas IGF I and IGFBP-3 correlated positively with several risk-promoting lipid parameters. In linear regression analysis controlling for age, sex, BMI, diabetes duration, and presence or absence of oral antihyperglycemic or insulin medication, determinants of IMT were age, IGFBP-1, pulse pressure, Lp(a), diabetes duration, and insulin treatment. IGFBP-1 persisted in the model for subjects with CVD. CONCLUSIONS: In summary, a decrease in IGFBP-1 is a marker of carotid IMT thickening in patients with type 2 diabetes.     

Fatty liver,insulin resistance,and dyslipidemia

After recently being recognized as a feature of the metabolic syndrome, fatty liver has evolved as a key player in the pathogenesis of dyslipidemia. Development of nonalcoholic fatty liver disease comes from an imbalance between the influx and production of fatty acids and the use of fatty acids for oxidation or secretion as very low density lipoprotein (VLDL) triglycerides. Previously, we have shown a strong relationship between increased liver fat and overproduction of large VLDL particles. We observed recently that in patients with high liver fat, insulin was unable to regulate VLDL production. The result is increased concentrations of VLDL particles in the circulation. Consequently, changes are seen in the metabolism of other lipoproteins that interact with VLDL particles, the net result being decreased high-density lipoprotein cholesterol and increased formation of small, dense low-density lipoprotein. In this article, we review recent findings on the development of fatty liver and its role in the diabetic dyslipidemia pathogenesis.