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Background: Cardiovascular disease (CVD) is the leading cause of death in Western countries and is highly prevalent in patients with kidney disease. Traditional risk factors for CVD often accompany kidney dysfunction, and chronic kidney disease per se is considered an additional risk factor. Risk stratification for CVD remains suboptimal even after the introduction of global risk assessment by various scores. This has prompted the search for novel markers of cardiovascular risk, and several biomarkers have been suggested as candidates, together with C-reactive protein (CRP). The objective of the present study was to investigate the relationship between novel biomarkers of vascular inflammation (soluble form of the receptor for advanced glycation end products [sRAGE] and eotaxin-3) with CRP in a population of hypertensive patients at high cardiovascular risk. Methods: Plasma sRAGE, high-sensitivity CRP (hs- CRP) and eotaxin-3 were measured in 399 hypertensive patients (265 men, mean age 58 ± 8 years)with diabetes mellitus, metabolic syndrome or organ damage. Results: Plasma concentrations of sRAGE, eotaxin-3 and hs-CRP were not different between diabetic and nondiabetic subjects. Univariate analysis showed that plasma levels of sRAGE and eotaxin-3 were not associated with hs-CRP in either subgroup. Conclusion: Our study confirms the robust and widely studied role of CRP as an important marker of vascular inflammation. We also postulate the possible involvement of sRAGE and eotaxin, 2 novel biomarkers, in CVDs. On the basis of our results, we can put forward the hypotheses that hs-CRP, s-RAGE and eotaxin are reliable but unrelated cardiovascular risk markers. © 2012 Società Italiana di Nefrologia - ISSN 1121-8428.

Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and coronary syndromes. Atherosclerosis is a complex multifactorial disorder. Data indicate that the complement proteins play a crucial role in the link between inflammation and atherogenesis. Thus, there is evidence supporting the role of complement activation in atherogenesis. Complement receptor 1 (CR1) is a membrane protein found on different cells involved in various activities of the complement system. We demonstrated the possible involvement of CR1 in atherosclerosis studying the allele and genotype frequencies of the CR1 Pro1827Arg, CR1 His1208Arg exon 22 and int27 HindIII polymorphisms in a sample of patients with angiographically documented coronary artery disease (CAD) (n=550) and in healthy controls (n=380) matched for age, gender and ethnicity. Our data showed no significant deviations between the two groups with regard to either allele or genotype frequencies. After stratification according to risk factors, our analysis revealed a reduced frequency of the GG genotype of the Pro1827Arg polymorphism in patients with CAD and dyslipidemia vs the controls (p=0.031) and of the GG and LL genotypes in CAD patients with dyslipidemia vs CAD patients without dyslipidemia regarding the Pro1827Arg and CR1 HindIII intron 27 polymorphisms (GG, p=0.019; LL, p=0.184). We analyzed the haplotype frequencies of CR1. A decrease in CAD patients carrying the CAC haplotype compared to controls (p=0.043) and a decrease in the CAC haplotype in CAD patients with hypertension vs healthy controls (p=0.029) were demonstrated. Our data showed a possible involvement of CR1 gene polymorphisms in the predisposition to the development of this disease.

Upregulation of the receptor for advanced glycation end products (RAGE) may play a crucial role in neointimal formation upon vessel injury. The −374T/A variant of the RAGE gene promoter, which has been associated with an altered expression of the cell-surface receptor, could exert a protective effect toward the development of vascular disease. The aim of this study is to determine the impact of this common genetic variant in the occurrence of clinical in-stent restenosis after coronary stent implantation. The −374T/A polymorphism of the RAGE gene promoter was evaluated by PCR-RFLPs in 267 patients with coronary artery disease who underwent coronary stent implantation and a subsequent coronary angiography 6–9 months later for suspected restenosis. In-stent restenosis was assessed by means of quantitative angiography. Carriers of the-374AA genotype showed a significantly reduced risk of developing restenosis after percutaneous transluminal intervention than non-carriers. To determine whether the protective effect of the homozygous AA genotype toward clinical restenosis was independent of potential confounders, we performed multivariable logistic regression analysis. After allowance for clinical and biochemical risk factors and stent length, the AA genotype remained significantly associated with a reduced prevalence of in-stent restenosis. No relation was evident between the RAGE genotype and established cardiovascular risk factors. In conclusion, the −374AA genotype of the RAGE gene promoter could be associated with a reduced risk of in-stent restenosis after coronary stent implantation.

The pulmonary circulation is a high-flow/low-pressure system, coupled with a flow generator chamber–the right ventricle–, which is relatively unable to tolerate increases in afterload. A right heart catheterization, using a fluid-filled, balloon-tipped Swan-Ganz catheter allows the measurement of all hemodynamic parameters characterizing the pulmonary circulation: the inflow pressure, an acceptable estimate the outflow pressure, and the pulmonary blood flow. However, the study of the pulmonary circulation as a continuous flow system is an oversimplification and a thorough evaluation of the pulmonary circulation requires a correct understanding of the load that the pulmonary vascular bed imposes on the right ventricle, which includes static and dynamic components. This is critical to assess the prognosis of patients with pulmonary hypertension or with heart failure. Pulmonary compliance is a measure of arterial distensibility and, either alone or in combination with pulmonary vascular resistance, gives clinicians the possibility of a good prognostic stratification of patients with heart failure or with pulmonary hypertension. The measurement of pulmonary arterial compliance should be included in the routine clinical evaluation of such patients.

Inflammation plays a key role in atherosclerosis. Galectin-3 is a macrophage- and endothelium-derived mediator actively involved in the regulation of many aspects of inflammatory cell behaviour. The aim of this study is to quantify plasma Galectin-3 in patients with coronary artery disease (CAD) and different clinical manifestation at the moment of observation in order to verify whether Galectin-3 could be a useful biomarker of atherosclerotic state. We enrolled 125 patients affected by CAD, angiographically documented (70 stable, 55 unstable). They underwent accurate examinations and anamnestic data was collected. The most important traditional risk factors, such as age, hypertension, and body mass index, were reported. Plasma Galectin-3 was quantified using an ELISA kit. Unstable patients (n = 55) had a higher plasma Galectin-3 levels in respect to the stable subjects (27.75 ng/mL (19.27–39.09) vs 6.48 ng/ml (4.88–8.83), p