ADD1 460W allele associated with cardiovascular disease in hypertensive individuals

High blood pressure is a predictor of cardiovascular disease. Hence, genes contributing to essential hypertension may play a role in the etiology of cardiovascular disease. For this reason, we examined the association between the alpha-adducin (ADD1) G460W and G-protein beta3 subunit (GNB3) 825C>T polymorphisms and the prevalence of peripheral arterial disease (PAD) and incidence of coronary heart disease (CHD) in non-Hispanic whites from the Atherosclerosis Risk in Communities (ARIC) Study. PAD prevalence was defined by an ankle-brachial index, ie, the ratio of ankle systolic blood pressure to brachial artery systolic blood pressure, of 相似文献   

IL-4 VNTR gene polymorphism in chronic polyarthritis. The rare allele is associated with protection against destruction

OBJECTIVE: To evaluate the occurrence of variants of the interleukin 4 (IL-4) and IL-4 receptor (IL-4R) genes in patients with rheumatoid arthritis (RA) and their possible contribution to joint destruction. METHODS: Allelic frequencies for polymorphisms in the IL-4 [variable number of tandem repeat (VNTR) polymorphism in intron 3] and IL-4 receptor alpha chain (transition at nucleotide 1902) genes were assessed in 335 RA patients and 104 controls. Clinical indices of disease activity, disability and joint destruction and plasma levels of IL-1beta, IL-1Ra and sCD23 were assessed to evaluate a possible functional effect. RESULTS: Carriage of the rare IL-4(2) allele was higher in patients with non-destructive RA (40%) than in those with destructive RA (22.3%; odds ratio = 1.9, 95% confidence interval 1. 1-3.5, P = 0.0006) and in controls (26%, P = 0.002). Patients positive for this rare allele had significantly less joint destruction, assessed by the Larsen wrist index (P = 0.004) and a lower erythrocyte sedimentation rate (P = 0.04). A significantly higher carriage rate of IL-4(2) was seen in HLA-DR4/DR1(-) patients with non-destructive RA than in those with destructive RA. The IL-4 receptor polymorphism was not over-represented. Plasma levels of IL-1beta, IL-1Ra and sCD23, known to be modified by IL-4, were not different in individuals having different alleles. CONCLUSION: This IL-4 VNTR gene polymorphism may be a protective factor for severe joint destruction in RA that could be used as a prognostic marker early in the course of the disease.     

Non-alcoholic fatty liver disease is associated with cardiovascular disease risk markers

Recognition of the link between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) has boosted research in this area. The main objective of this paper is to review the literature on NAFLD in the context of CVD, focussing on underlying mechanisms and treatment. Besides excessive fatty acid influx, etiologic factors may include components of the metabolic syndrome, cytokines and mitochondrial dysfunction. NAFLD is associated with both hepatic and systemic insulin resistance. In the case of NAFLD, the liver overproduces several atherogenic factors, notably inflammatory cytokines, glucose, lipoproteins and coagulation factors, and factors increasing blood pressure. Intervention studies on diet and laparoscopic surgery revealed improvements of hepatic fat content and CVD risk profile. Pharmacological approaches with potential benefit have been developed as well, but effects are often confounded by weight change. NAFLD is associated with an increased CVD risk profile (and hepatic risk). In order to improve CVD risk profile, prevention and treatment of NAFLD seem advisable. However, well-designed intervention studies, randomized clinical trials and long-term follow-up studies are scarce.     

Thrombocytopenia in falciparum malaria is associated with high concentrations of IL-10

Over the last decade, a number of observations have suggested that platelets may play a role in the pathophysiology of severe malaria. However, somewhat paradoxically, thrombocytopenia is not associated clearly with outcome. We studied the relationship between thrombocytopenia and cytokines in Kenyan children with severe malaria and showed that thrombocytopenia (platelet count < 150 x 10(9)/L) strongly correlates with high levels of interleukin (IL)-10. Several studies have shown that high levels of IL-10 are associated with a favorable outcome in severe malaria. Taken together, these data suggest why thrombocytopenia has a complex relationship with severe disease and suggest one mechanism whereby IL-10 may modify the outcome of severe disease.     

SLE, atherosclerosis and cardiovascular disease

Atherosclerosis is an inflammatory disease and the major cause of cardiovascular disease (CVD) in general. Atherosclerotic plaques are characterized by the presence of activated immune competent cells, but antigens and underlying mechanisms causing this immune activation are not well defined. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are important clinical problems but may in addition also shed light on how immune reactions are related to premature atherosclerosis and atherothrombosis. A combination of traditional and nontraditional risk factors, including dyslipidaemia (and to a varying degree hypertension, diabetes and smoking), inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. Premature atherosclerosis in some form leading to atherothrombosis is likely to be a major underlying mechanism, though distinctive features if any, of SLE-related atherosclerosis when compared with 'normal' atherosclerosis are not clear. One interesting possibility is that factors such as inflammation or aPL make atherosclerotic lesions in autoimmune disease more prone to rupture than in 'normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients remains to be demonstrated. Treatment of SLE patients should also include a close monitoring of traditional risk factors for CVD. In addition, attention should also be paid to nontraditional risk factors such as inflammation and SLE-related factors such as aPL. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation and immune reactions present in atherosclerotic lesions.     

Fatty liver disease is associated with underlying cardiovascular disease in HIV-infected persons(*)

Background

Cardiovascular disease is an increasing concern among HIV‐infected persons and their providers. We determined if fatty liver disease is a marker for underlying coronary atherosclerosis among HIV‐infected persons.

Methods

We performed a cross‐sectional study in HIV‐infected adults to evaluate the prevalence of and factors, including fatty liver disease, associated with subclinical coronary atherosclerosis. All participants underwent computed tomography for determination of coronary artery calcium (CAC; positive defined as a score >0) and fatty liver disease (defined as a liver‐to‐spleen ratio <1.0). Factors associated with CAC were determined using multivariate logistic regression models.

Results

We included in the study 223 HIV‐infected adults with a median age of 43 years [interquartile range (IQR) 36–50 years]; 96% were male and 49% were Caucasian. The median CD4 count was 586 cells/μL and 83% were receiving antiretroviral medications. Seventy‐five (34%) had a positive CAC score and 29 (13%) subjects had fatty liver disease. Among those with CAC scores of 0, 1–100 and >100, the percentage with concurrent fatty liver disease was 8, 18 and 41%, respectively (P=0.001). In the multivariate model, CAC was associated with increasing age [odds ratio (OR) 4.3 per 10 years; P<0.01], hypertension (OR 2.6; P<0.01) and fatty liver disease (OR 3.8; P<0.01).

Conclusions

Coronary atherosclerosis as detected using CAC is prevalent among young HIV‐infected persons. The detection of fatty liver disease among HIV‐infected adults should prompt consideration of assessment for underlying cardiovascular disease and risk factor reduction.     

The APOE ɛ2 allele is associated with increased plasma apolipoprotein E levels in patients with coronary artery disease

AimsWe sought to evaluate the influence of APOE polymorphisms (ɛ2-rs7412, ɛ4-rs429358) on plasma levels of apolipoprotein E in patients with confirmed coronary artery disease.MethodsA total of 94 patients with coronary artery disease were included in our study. Genotypisation for rs429358 and rs7412 in APOE was performed and plasma levels of apolipoprotein E, lipids, and hs-CRP were measured.ResultsSignificantly higher plasma levels of APOE were found in the ɛ2 carriers compared to the normal ɛ3/ɛ3 genotype (40.4 mg/mL vs. 22.9 mg/mL, P = 0.018). There was no difference in APOE levels between the ɛ4 allele and ɛ3/ɛ3 allele carriers. Significantly higher HDL cholesterol levels (1.55 mmol/L vs. 1.16 mmol/L, P = 0.001) were found in the ɛ2 carriers, and significantly lower levels of hs-CRP (1.07 mg/L vs. 2.14 mg/L, P = 0.035) in the ɛ4 carriers compared to the normal ɛ3/ɛ3 genotype.ConclusionsIn CAD patients, the ɛ2 APOE allele is associated with significantly higher plasma levels of APOE and HDL cholesterol, whereas the ɛ4 allele is associated with significantly lower levels of hsCRP.     

Circulating heat shock protein 60 is associated with early cardiovascular disease

The phylogenetically conserved nature of heat shock proteins (Hsp) has led to the proposition that they may provide a link between infection and the inflammatory component to vascular disease. Hypertension is associated with atherosclerosis. Here, we measured circulating heat shock protein and heat shock protein antibody levels in association with borderline hypertension. Seventy-two men with borderline hypertension patients and 75 normotensive control subjects (diastolic blood pressure 85 to 94 and <80 mm Hg, respectively) were selected from a population-screening program. The levels of Hsp60; Hsp70; and anti-human Hsp60, anti-human Hsp70, and anti-mycobacterial Hsp65 antibodies were determined with enzyme immunoassay. The presence of carotid atherosclerosis and the intima-media thickness values were determined with ultrasonography. A major novel observation in this report was the detection of circulating Hsp60, which was present at a significantly enhanced level in patients with borderline hypertension. Furthermore, serum Hsp60 was associated with intima-media thicknesses (P<0.01). Anti-Hsp65 antibody levels were higher in borderline hypertension (P<0.001), whereas Hsp70 and anti-Hsp70 antibody levels did not differ. In contrast to anti-Hsp65 antibody, anti-Hsp60 antibody levels were lower in borderline hypertension (P<0.03), although the difference was quantitatively small. None of the parameters evaluated were associated with atherosclerosis, metabolic factors, or smoking. We identified elevated Hsp60 levels in patients with borderline hypertension and an association between early atherosclerosis and Hsp60 levels. The physiological role of Hsp60 release has yet to be defined, but given the proinflammatory properties, these proteins could be involved in the induction/progression of both hypertension and atherosclerosis, as well as being markers for early cardiovascular disease.     

Serum cystatin C is associated with other cardiovascular risk markers and cardiovascular disease in elderly men

Renal dysfunction is associated with increased cardiovascular morbidity and mortality. The aim of this cross-sectional study was to investigate the relationship between the glomerular filtration marker cystatin C and other cardiovascular risk markers and morbidity in elderly males. Cystatin C was measured in a group of 77-year-old males (n=792) and compared cystatin C with other known risk markers for cardiovascular disease. Cystatin C values were significantly increased in individuals with diabetes (p=0.05) and cardiovascular diseases (p<0.0001). There were significant correlations between cystatin C values and body mass index, HbA1c, insulin, triglycerides and hsCRP.     

The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: A systematic review

Objective

To perform a systematic review of the literature regarding the epidemiology of the association between systemic lupus erythematosus (SLE) and atherosclerotic cardiovascular disease (CVD), including the increased risk for CVD, as well as the risk factors responsible for development of CVD in patients with SLE.

Methods

We followed the PRISMA guidelines to systematically search the PubMed database from inception to June 2012. Studies were selected using predefined eligibility criteria, and 2 authors independently extracted data. The risk of bias was measured for each study using a domain-based assessment.

Results

We report on 28 studies that met criteria for inclusion in our analysis. We found strong epidemiologic evidence that SLE patients have an increased relative risk of CVD compared to controls. There is limited information regarding relative CVD mortality risks among SLE patients. Traditional CVD risk factors, including age, male sex, hyperlipidemia, smoking, hypertension, and CRP, are associated with CVD risk among SLE patients. Several SLE-specific factors, including disease activity and duration, and possibly specific manifestations and therapies, further increase risk. Several risk factors, such as disease activity and glucocorticoid use, are closely associated, making it difficult to disentangle their effects.

Conclusions

CVD risk among SLE patients compared to the general population is at least doubled. While older SLE patients appear to have the highest absolute risks of CVD, young women have alarmingly high relative risks, given the rarity of CVD in the comparison general population. Both traditional and SLE-specific risk factors are important, although there are discrepancies within the literature.     

Cytomegalovirus infection is associated with elevated interleukin-10 in coronary artery disease

Previous studies show that cytomegalovirus (CMV) infection could increase the production of inflammatory cytokines in coronary artery disease (CAD). However, little is known about the influence of CMV infection on interleukin-10 (IL-10) levels in CAD. We attempted to investigate the relationships between CMV infection and serum IL-10 levels in patients with CAD. CMV IgG and serum levels of IL-10 were measured with ELISA in patients with CAD (n=463) and smooth coronary artery controls documented by coronary arteriography (n=125). Subjects were dichotomized according to calculated median level of IL-10 (6.84 pg/ml) in different groups or subgroups. The seropositivity of CMV IgG was more frequently found in the high IL-10 group than the low IL-10 group (46.8% versus 30.4%, P<0.001). The prevalence of CMV infection was significantly higher in the high IL-10 group than the low IL-10 group among the patients with CAD (48.1% versus 28.6%, P<0.001), but among the controls (40.4% versus 35.6%, P=0.588). On multiple logistic regression analysis, the adjusted odds ratio (95% confidence intervals) of high IL-10 associated with CMV infection was 2.3 (1.6-3.4, P<0.001) in the patients with CAD, and 1.1 (0.5-2.5, P=0.83) in the controls. We found a significant association of CMV infection with elevated IL-10 in the patients with CAD; therefore, we propose that changes in the immune response to CMV are a compounding factor in CAD.     

Light wine consumption is associated with a lower odd for cardiovascular disease in chronic kidney disease

Aims

To examine the association between wine consumption and the prevalence of chronic kidney disease (CKD) and cardiovascular disease (CVD).

The IL-6 -174G>C polymorphism is associated with cardiovascular diseases and mortality in 80-year-old humans

Chronic low-grade elevations in circulating levels of interleukin (IL)-6 act as a marker of subclinical cardiovascular diseases (CVD) and provide an independent predictor of increased mortality in elderly populations. The purpose of the present study was to test the hypothesis that the IL-6 -174G>C promoter polymorphism was associated with a high prevalence of CVD and acted as an independent predictor of mortality in a longitudinal study of 324 relatively healthy 80-year-old people with a history of CVD in 18% of the cases. The C allele was associated with elevated serum levels of IL-6 at baseline and the CC genotype had a high prevalence of CVD. A Cox regression model was used to explore the effect of the polymorphism on survival in the following six years. A significant interaction was found between smoking status and the polymorphism. Thus, C allele carrier status was associated with increased all-cause mortality risk in non-smokers independently of sex, body mass index, co-morbidity, and low-grade elevations in serum levels of IL-6. This effect was not detected among smokers. We conclude that the IL-6 -174G>C polymorphism was an independent predictor of all-cause mortality in octogenarians but the effect was complex and interacted with the smoking status.     

Apolipoprotein E genotype is not associated with cardiovascular disease in heterozygous subjects with familial hypercholesterolemia

Background

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein cholesterol levels and premature cardiovascular disease (CVD). There are important differences in the presence of CVD among heterozygous subjects with FH. Some of this variability can be explained by genetic factors, and the apolipoprotein (apo) E genotype has been proposed as a useful marker.

Methods

We analyzed the apo E genotype in 706 non-related subjects who were heterozygous for FH from Spain. CVD was present in 198 subjects (28%), 132 men (41%) and 66 women (17%).

Results

Apo E allele frequencies for the ε3, ε4, and ε2 alleles were 0.89, 0.09, and 0.02 respectively. Age, body mass index, smoking status, high blood pressure, diabetes mellitus, presence of tendon xanthomas, total cholesterol level, triglyceride levels, high-density lipoprotein cholesterol level, low-density lipoprotein cholesterol level, and Lp(a) did not differ among genotypes. The incidence of CVD and the age of onset of CVD did not differ among genotypes either. In the multivariant analysis, apo E genotype did not contribute significantly to CVD.

Conclusions

Heterozygous men with FH have a very high risk of coronary disease in a Mediterranean country, and the apo E genotype in this large group of adults with FH is not associated either with CVD or lipid values, in contrast with the established effect in the general population.