Classical Risk Factors For Atherosclerosis Research Articles

Chlamydia pneumoniae infection acts as an endothelial stressor with the potential to initiate the earliest heat shock protein 60-dependent inflammatory stage of atherosclerosis

We identified increased expression and redistribution of the intracellular protein 60-kDa human heat shock protein (hHSP60) (HSPD1) to the cell surface in human endothelial cells subjected to classical atherosclerosis risk factors and subsequent immunologic cross-reactivity against this highly conserved molecule, as key events occurring early in the process of atherosclerosis. The present study aimed at investigating the role of infectious pathogens as stress factors for vascular endothelial cells and, as such, contributors to early atherosclerotic lesion formation. Using primary donor-matched arterial and venous human endothelial cells, we show that infection with Chlamydia pneumoniae leads to marked upregulation and surface expression of hHSP60 and adhesion molecules. Moreover, we provide evidence for an increased susceptibility of arterial endothelial cells for redistribution of hHSP60 to the cellular membrane in response to C. pneumoniae infection as compared to autologous venous endothelial cells. We also show that oxidative stress has a central role to play in endothelial cell activation in response to chlamydial infection. These data provide evidence for a role of C. pneumoniae as a potent primary endothelial stressor for arterial endothelial cells leading to enrichment of hHSP60 on the cellular membrane and, as such, a potential initiator of atherosclerosis.

Psoriasis: a Skin Disease Associated With Increased Cardiovascular Risk

Psoriasis and psoriatic arthritis are associated with increased risk of cardiovascular events and cardiovascular mortality. Alongside classic risk factors for atherosclerosis, the severity of psoriatic skin disease also influences cardiovascular risk in these patients. In both cases, endothelial dysfunction and increased intima-media thickness in the carotid artery are indicators of subclinical cardiovascular disease. Active treatment of the psoriasis and management of traditional cardiovascular risk factors are essential in order to reduce cardiovascular morbidity in these patients. Clinical practice guidelines on the management of cardiovascular risk will define a new integrated approach to the care of patients with psoriasis and psoriatic arthritis.

Patients with chronic gastrointestinal ischemia have a higher cardiovascular disease risk and mortality

ObjectivesWe determined the prevalence of classical risk factors for atherosclerosis and mortality risk in patients with CGI. MethodsA case–control study was conducted. Patients referred with suspected CGI underwent a standard work-up including risk factors for atherosclerosis, radiological imaging of abdominal vessels and tonometry. Cases were patients with confirmed atherosclerotic CGI. Controls were healthy subjects previously not known with CGI. The mortality risk was calculated as standardized mortality ratio derived from observed mortality, and was estimated with ten-year risk of death using SCORE and PREDICT. ResultsBetween 2006 and 2009, 195 patients were evaluated for suspected CGI. After a median follow-up of 19 months, atherosclerotic CGI was diagnosed in 68 patients. Controls consisted of 132 subjects. Female gender, diabetes, hypercholesterolemia, a personal and family history of cardiovascular disease (CVD), and current smoking are highly associated with CGI. After adjustment, female gender (OR 2.14 95% CI 1.05–4.36), diabetes (OR 5.59, 95% CI 1.95–16.01), current smoking (OR 5.78, 95% CI 2.27–14.72), and history of CVD (OR 21.61, 95% CI 8.40–55.55) remained significant. CGI patients >55 years had a higher median ten-year risk of death (15% vs. 5%, P = 0.001) compared to controls. During follow-up of 116 person-years, standardized mortality rate was higher in CGI patients (3.55; 95% CI 1.70–6.52). ConclusionsPatients with atherosclerotic CGI have an increased estimated CVD risk, and severe excess mortality. Secondary cardiovascular prevention therapy should be advocated in patients with CGI.

Role of arterial stiffness in cardiovascular disease

Propagation of the pressure wave along the arterial tree (pulse wave velocity [PWV]) is related to the intrinsic elasticity of the arterial wall. PWV is increased in stiffer arteries and, when measured over the aorta, is an independent predictor of cardiovascular morbidity and mortality. Given the predictive power of PWV, identifying strategies that prevent or reduce stiffening may be important in prevention of cardiovascular events. One view is that aortic stiffness occurs as a result of atherosclerosis along the aorta. However, there is little or no association between PWV and classical risk factors for atherosclerosis, other than age and blood pressure. Furthermore, PWV does not increase during early stages of atherosclerosis, as measured by intima-media thickness and non-calcified atheroma, but it does increase in the presence of aortic calcification that occurs within advanced atherosclerotic plaque. Age-related widening of pulse pressure is the major cause of age-related increase in prevalence of hypertension and has been attributed to arterial stiffening. This review summarizes the methods of measuring aortic stiffness in humans, the pathophysiological mechanisms leading to aortic stiffness, including its association with atherosclerosis, and the haemodynamic consequences of increased aortic stiffness.

Kynurenic acid – a new tool in the treatment of hiperhomocysteinemia and its consequences?

Atherosclerosis together with its cardiovascular consequences is the most common and significant cause of death, particularly in highly developed countries. The process of atherogenesis begins as soon as in childhood and depends on classical risk factors. Atherosclerosis also results from a chronic inflammatory-immune process which takes place in the vascular walls. Furthermore, it has been known for a number of years that the development of atherosclerotic lesions is closely connected with the concentration of homocysteine in serum. Homocysteine is a sulfur amino acid originating from methionine. An increased concentration of homocysteine in blood harmfully influences blood vessels, leading to a higher risk of ischemic heart disease and stroke. Since tackling classical atherosclerosis risk factors is not efficient enough when it comes to protecting the cardiovascular system from diseases, new substances possessing anti-atherogenic properties, especially endogenous ones, are sought. Recently, researchers have paid attention to a connection between homocysteine and an endogenous tryptophan derivative, kynurenic acid. Recently, it was revealed that kynurenic acid counteracts the harmful effects of homocysteine on endothelium cells in vitro. The hypothesis assuming homocysteine-kynurenate interplay suggests the existence of a new mechanism of atherogenesis and gives us an opportunity to use this knowledge in both prevention and treatment of cardiovascular diseases.

Efeito da terapia antirretroviral e dos níveis de carga viral no complexo médio-intimal e no índice tornozelo-braço em pacientes infectados pelo HIV

OBJETIVOS: Identificar precocemente a prevalência de aterosclerose, por causa do espessamento do complexo médio-intimal das carótidas comuns e do índice tornozelo-braço. Essas medidas foram relacionadas com os fatores de risco clássicos de aterosclerose e os específicos dos infectados pelo HIV (tempo de doença, tempo de tratamento, tipo de tratamento, tipo de terapia antirretroviral utilizada, CD4 e carga viral). MÉTODOS: Setenta casos infectados com o HIV foram avaliados pela medida automática do complexo médio-intimal nas carótidas e do índice tornozelo-braço. Consideraram-se os fatores de risco clássicos de aterosclerose (idade, sexo, hipertensão arterial sistêmica, tabagismo, hipercolesterolemia, hipertrigliceridemia, obesidade e história familiar de evento cardiovascular), as medidas antropométricas e as variáveis relacionadas ao HIV. O nível de significância assumido foi de 5%. RESULTADOS: O tempo médio de diagnóstico do HIV foi de 104,9 meses e de tratamento foi de 97,9 meses. Quanto ao tipo de tratamento, 47 (67,1%) fizeram uso de inibidor de protease por mais de seis meses e 36 (51,4%) estão em uso atualmente. O índice tornozelo-braço estava aumentado em um único paciente (0,7%) e não se evidenciou espessamento do complexo médio-intimal em nenhum indivíduo. Não existiu associação significante da medida do complexo médio-intimal da carótida comum direita com nenhuma das variáveis analisadas. CONCLUSÕES: Indivíduos jovens, sob o uso de terapia antirretroviral por cinco anos ou mais, não apresentaram espessamento do complexo médio-intimal ou aumento do índice tornozelo-braço. Não houve diferença do espessamento do complexo médio-intimal associada ao tipo de esquema antirretroviral utilizado ou nível de carga viral.

Relationship between coronary artery calcification and various biomarkers in type 2 diabetic patients

Abstract Aim. Cardiovascular disease is the most common made of mortality in type 2 diabetes mellitus. This study investigated the relationship between the presence of calcification in coronary artery and biochemical parameters alone with the classic risk factors of atherosclerosis in patients with type 2 diabetes. Methods. Forty one (27 female and 14 male) patients with type 2 diabetes without symptomatic coronary artery disease (CAD) or previous myocardial infarction and with normal kidney functions were included in the study. Multislice Computerized Tomography (MSCT) was used for coronary artery calcium scoring (CACS). Patients were classifed into two groups as CACS=0 and CACS>0. Results. In 12 (29.3%) patients coronary artery calcification was noted. Waist circumference, systolic blood pressure, total cholesterol, low-density lipoprotein, and triglyceride levels were significantly different between those with (CACS>0) and without (CACS=0) (p 0 olarak 2 gruba ayrildi. Bulgular. 12 (%29,3) hastada koroner arterlerde kalsifikasyon saptandi. Bel cevresi, sistolik kan basinci, total kolesterol, dusuk dansiteli lipoprotein ve trigliserid seviyeleri ile KAKS arasindaki iliski onemli bulundu (p<0,05). Sonuc. Diyabetik hastalarda koroner arter kalsifikasyonu aterosklerozla iliskilidir. Anahtar sozcukler: Tip 2 diabetes mellitus, ateroskleroz, koroner arter kalsifikasyonu

Association of fetuin-A and heat shock protein 70 with arterial calcification in patients with peripheral vascular disease

Abstract Atherosclerosis may present with arterial calcification, which is associated with increased cardiovascular morbidity and mortality. Fetuin-A plays a role in the inhibition of extraosseal calcification, and heat shock protein 70 (Hsp70) is elevated in peripheral artery disease. The aim of our study was to examine the potential role of fetuin-A and Hsp70 in the inhibition of arterial calcification in atherosclerotic patients. Classical risk factors of atherosclerosis as well as the severity of arterial calcification and atherosclerosis were assessed by ultrasound, angiography, and serum analysis in a cross-sectional study of patients with carotid stenosis, aortic aneurysm, and lower extremity atherosclerosis. We demonstrate that there is an inverse correlation between serum fetuin-A levels and the severity of arterial calcification in patients with chronic atherosclerotic lower extremity disease without renal disease or infection. Our data suggest that it is not end-stage renal disease and dialysis that explains the earlier reported association of low fetuin-A level and arterial calcification. The novel finding of our study is the significantly different serum fetuin-A levels in patients with aortic aneurysm of different etiologies (atherosclerosis and Marfan syndrome). Our results suggest that there is an association between serum fetuin-A levels and the severity of arterial calcification also in patients without renal failure.

Effects of bench step exercise on arterial stiffness in post-menopausal women: Contribution of IGF-1 bioactivity and nitric oxide production

ObjectiveTo examine the effect of bench step exercise on arterial pulse wave velocity (PWV) and the associated contribution of insulin-like growth factor (IGF)-1 bioactivity and nitric oxide (NO). DesignTwenty-six elderly (post-menopausal) women were randomly allocated to a bench step exercise group or a control group. The participants in the bench step exercise group practiced a 12-week home-based bench step exercise for 10–20min, 3 times daily (i.e., for a total of 140min/week at the intensity level of lactate threshold (LT)). In addition to conventional risk factors of atherosclerosis, PWV, IGF-1/IGF binding protein (IGFBP)-3 molar ratio (an index for IGF-1 bioactivity), and urinary nitrite/nitrate (NOx) excretion were measured before and after the intervention. ResultsBMI, systolic blood pressure, fasting plasma glucose, low-density lipoprotein cholesterol, LT, and PWV were significantly improved in the bench step exercise group. A significant positive correlation between changes in PWV and IGF-1/IGFBP-3 molar ratio, and a significant negative correlation between changes in IGF-1/IGFBP-3 molar ratio and urinary NOx excretion were found in the bench step exercise group. ConclusionThe bench step exercise leads to improvements in not only the classical risk factors of atherosclerosis but also the arterial stiffness in elderly women, partly through NO production via IGF-1 bioactivity.

Atherosclerosis in juvenile idiopathic arthritis.

Atherosclerosis is a chronic inflammatory disease of the arteries. Clinical consequences of the atherosclerotic process occur in the adult population, however atherosclerotic process begins in childhood. The classic risk factors for atherosclerosis include obesity, dyslipidaemia, age, gender or family history. In recent years, attention has been drawn to the similarity between atherosclerotic inflammatory processes and inflammatory changes in the course of systemic connective tissue disease, in particular systemic lupus etythematosus (SLE) or rheumatoid arthritis (RA). There is also observed the similarity of the pathogenetic background of development of atherosclerosis and juvenile idiopathic arthritis (JIA). Elevated levels of pro-inflammatory cytokines are observed in the course of juvenile idiopathic arthritis. Also homocysteine concentrations, which may play a significant role in the development of atherosclerotic lesions, are observed higher in patients with JIA. Some studies revealed higher carotid intima-media thickness (IMT) index values in children with JIA. In view of the fact that atherosclerotic process begins as early as in childhood, the introduction of appropriate preventive measures in children is a matter of utmost importance.

Aterosclerose em indivíduos infectados com o HIV

Objective: To compare the measurements of the ankle-arm index and the intima-media complex of the femoral and subclavian carotids in patients with HIV on antiretroviral therapy in relation to the Control Group. Methods: Seventy patients with HIV who had been on antiretroviral therapy for at least five years and 70 individuals who are not infected with HIV, paired by gender and age, aged until 50 years, were assessed by the measurement of the ankle-arm index and the intima-media complex of the common, internal, femoral and right subclavian carotids. In common carotids, the manual and automatic measurement of the intima-media complex were perform, and the automatic measurement of the common carotid was considered as the gold standard, regarding the thick intimamedia complex when it is >0.8 mm. The group homogeneity was analyzed at a 5% significance level, and automatic and manual measurements were compared; for the carotids, Bland-Altman graphs were used. Results: A patient from the case group (0.7%) presented an increased ankle-arm index (>1.3 bilaterally with no signs of calcification), and no changes were observed in the control group. The automatic average of the intima-media complex in common carotids was not thick in any individual. There was no significant different between the groups as to the ankle-arm index, the intima-media complex and the presence of atheromatous Tese de doutorado desenvolvida no Hospital das Clinicas da Universidade Federal de Pernambuco (UFPE) e no Hospital Agamenon Magalhaes, pelo programa de Pos-Graduacao em Cirurgia do Centro de Ciencias da Saude da UFPE, apresentada em 04.03.2010. Orientador: Prof. Dr. Carlos teixeira Brandt e Profa. Dra. Heloisa Ramos Lacerda de Melo Banca examinadora: Prof. Dr. Alvaro Antonio Bandeira Ferraz, Prof. Dr. Jose Lamartine de Andrade Aguiar, Prof. Dr. Silvio da Silva Caldas Neto, Prof. Dr. Silvio Romero de Barros Marques e Prof. Dr. Luiz Claudio Arraes de Alencar * Doutorado em Cirurgia pela Universidade Federal de Pernambuco (UFPE); Especialista em Angiologia pela Sociedade Brasileira de Angiologia e Cirurgia Vascular (SBACV); Especialista em Ultrassonografia Doppler pelo Colegio Brasileiro de Radiologia (CBR) e pela Universidade Paul Sabatier-Toulouse – Franca; Socia Titular da SBACV e Membro Coligado do CBR. Conflitos de interesse: nada a declarar. Submetido em: 25.03.11. Aceito em 31.08.11. J Vasc Bras. 2011;10(4):336-337. Aterosclerose em individuos infectados com o HIV Godoi ETAM J Vasc Bras 2011, Vol. 10, No 4 337 plaques. Mean age was 40.5 years in the case group, and 40.8 years in the control group. Both groups were similar as to smoking and systemic arterial hypertension. Cholesterol and triglycerides were higher in the case group, but the body mass index and the abdominal circumference had a higher normality percentage in this group. When comparing the automatic average right common carotid (RCC) with other locations (subclavian origin, medium segment and common femoral), the difference was statistically and clinically significant in the origin of the right subclavian (RCC=0.51 versus 0.91 mm; p<0.001). Conclusion: People who have HIV do not present a higher risk for atherosclerosis than the control population, considering the classic risk factors of atherosclerosis and the specific characteristics of the HIV. By comparing the automatic average of RCC with other locations, the difference was statistically and clinically significant in the origin of the right subclaian.

Dyslipidemia, Statins, and Venous Thromboembolism

Venous thromboembolism (VTE) is one of the most frequent and serious vascular diseases. Although the major risk factors of VTE are well recognized, the pathology often develops in subjects without any obvious precipitating factor. Recent evidence suggests a link between arterial and venous thrombosis, particularly in patients with idiopathic venous thrombosis. Therefore, similar or identical risk factors may play a role in the development of both diseases. A positive association between classical risk factors of atherosclerosis, including dyslipidemia, and VTE has been reported. Recent studies demonstrated an association between hypercholesterolemia and objectively verified VTE. Circulating lipids have been shown to have both prothrombotic- and endothelium-deteriorating properties. Studies suggested a greater generation of thrombin, endothelial dysfunction, and higher platelet activity in hyperlipidemic blood. By impeding these mechanisms, statins may protect against VTE. Observational, controlled studies and two meta-analyses showed that statins significantly reduced VTE risk, most likely in a process independent from cholesterol lowering, through mechanisms related to the pleiotropic effects of these drugs. Currently, it is unknown whether VTE prevention is a class-effect of statins, or if statins differ in their antithrombotic efficacy, and it is also unknown if statin benefit is dose-dependent. However, there are also opposite findings about the efficacy of statins in prevention of VTE. Therefore, the use of statins for prophylaxis of VTE cannot be generally recommended at this stage. Further studies are needed to identify those patients who could eventually benefit maximally from treatment with statins for prevention of VTE.

Subclinical hypothyroidism and risk to carotid atherosclerosis

The aim of this study was to assess whether subclinical hypothyroidism (SCH) is associated with carotid atherosclerosis, as well as dyslipidemia, and arterial hypertension. The study included 69 consecutive patients with newly diagnosed SCH, and 30 matched healthy controls. Body mass index (BMI), TSH, fT4, antibodies to thyroid peroxidase (TPOabs), lipids, blood pressure, mean and maximum carotid intima-media thickness (CIMT) were determined in all participants. Mean values of CIMT, triglycerides, and total cholesterol/HDL-C ratio were significantly different in SCH patients versus matched controls. Linear multiple regression analysis demonstrated that TSH, diastolic blood pressure and triglycerides were independent predictors of mean CIMT, fT4 for maximum CIMT; and that TSH, fT4, age, and total cholesterol/HDL-C ratio were independent predictors of the presence of carotid plaques. Our data revealed that SCH is associated with increase in CIMT and presence of carotid plaques, independent of classical risk factors for atherosclerosis.

The autoimmune concept of atherosclerosis

This review summarizes the recent data on the 'Autoimmune Concept of Atherosclerosis', according to which the first stage of this disease is due to an autoimmune reaction against arterial endothelial cells expressing heat shock protein 60 (HSP60) and adhesion molecules when stressed by classical atherosclerosis risk factors. Special emphasis is put on oxidized low-density lipoproteins as early endothelial stressors. Plasma cholesterol and LDL levels considered 'normal' by the medical community are possibly too high from an evolutionary viewpoint. The proinflammatory milieu at sites of early atherosclerotic lesions could be conducive to oxidation of LDL in situ. LDL oxidation can also take place at nonvascular sites or in the circulation under general proinflammatory conditions explaining its proatherosclerotic role in 'normocholesterolemic' individuals. We hypothesize that the plasma cholesterol and LDL levels currently considered normal are evolutionarily too high. Cholesterol and/or oxidized low-density lipoprotein, even as a mild HSP60-inducing endothelial stressor, function as a ubiquitous risk factor. If this hypothesis is true, most members of developed societies might be at risk to develop atherosclerotic plaques at anti-HSP60-immunity-triggered intimal inflammatory foci, irrespective of the primary risk-factor(s).

Atherosclerosis and rheumatoid arthritis: relationships between intima-media thickness of the common carotid arteries and disease activity and disabilty

To investigate the intima-media thickness of the common carotid arteries (IMT-CCA) in patients with Rheumatoid Arthritis (RA), and its relationships with classical atherosclerosis risk factors and disease features i.e. duration, activity and disability. 48 RA patients (35 F, 13 M; age ed 26-69 years median 55; disease duration 1-18 years, median 8), and 22 controls (16 F, 6 M; age 28-66, median 50) matched for classical atherosclerosis risk factors, i.e. age, sex, smoking, blood pressure, body mass index, diabetes, familiarity, and for postmenopausal status, were studied. IMT and plaques were measured in the left and right common carotid arteries. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apoliporotein AI, apolipoprotein B, and rheumatoid factor were determined in patients and controls. The DAS28, the HAQ-DI and disease duration were considered as clinical parameters reflecting disease status. The IMT-CCA (mean +/- SD) was significantly greater in the 48 RA patients than in the 22 controls subjects (1.00+/-0.25 vs. 0.78+/-0.21; p=0.0007). In the 70 subjects investigated CCA-IMT resulted to be significantly correlated with diastolic blood pressure, body mass index, triglyceride and RA status. In the 48 RA patients no correlation was detected with either disease duration or activity or disability. our study confirms an increased IMT in RA patients without any clinically evident manifestation of cardiovascular disease. It supports the existence of subclinical atherosclerosis in RA.

211 Circulating vegf concentrations are independently predictive of coronary artery disease severity measured by quantitative coronary angiography in patients with stable angina

VEGF is hypothesized to be implicated in the development and progression of atherosclerotic plaques by promoting intra-plaque vascularisation and hamorrhage. However, clinical data regarding the value of VEGF as a biomarker of atherosclerosis have been contradicting. We sought to evaluate the association between VEGF and the severity of coronary artery disease assessed by quantitative coronary angiography (QCA). In this cross-sectional study, serum VEGF serum concentrations were measured in 168 patients undergoing angiography for acute coronary syndrome (ACS) (n = 112) or for stable angina (n = 56). QCA was used to determine the cumulative coronary stenosis score (CCSS), which is calculated by adding all percent diameter stenoses. A higher score reflects more severe disease. Patients with an ACS had lower VEGF serum concentrations than patients with stable angina (182 pg/ml (95% CI 152-211 pg/ml) vs 288 pg/ml (95% CI 232-343 pg/ml),P = 0.001). We observed a significant and robust correlation between VEGF concentrations and the CCSS in patients with stable angina (r = 0.423 P = 0.001). This relationship was not seen in patients with ACS (r = 0.010 P = 0.920). In a multivariate analysis of patients with stable angina that included classical atherosclerosis risk factors, VEGF remained an independent predictor of the CCSS (P = 0.001). Our study supports the role of VEGF as a potential biomarker of atherosclerosis in patients with stable coronary artery disease

Heat Shock Protein 60 and Immune Inflammatory Responses in Atherosclerosis

Hallmarks of inflammation in various cardiovascular diseases, notably atherosclerosis, have been observed for a long time. However, evidence for an (auto)antigen-driven process at these sites of inflammation has come forward only recently. Heat shock proteins (HSPs) have been identified as playing either immunologically mediated disease promoting or protective roles. HSP60 has been shown to trigger innate and adaptive immune responses that initiate the earliest still reversible inflammatory stage of atherosclerosis. HSP60 is structurally highly conserved and abundantly expressed by prokaryotic and eukaryotic cells under stressful conditions. Beneficial protective immunity to microbial HSP60 acquired by infection or vaccination and bona fide autoimmunity to biochemically altered autologous HSP60 is present in all humans. In vitro and in vivo experiments have demonstrated that classical atherosclerosis risk factors can act as endothelial stressors that provoke the simultaneous expression of adhesion molecules and of HSP60 in mitochondria, in cytoplasm, and on the cell surface, where it acts as a "danger signal" for cellular and humoral immune reactions. Hence, protective, preexisting anti-HSP60 immunity may have to be "paid for" by harmful (auto)immune cross-reactive attack on arterial endothelial cells maltreated by atherosclerosis risk factors. These experimentally and clinically proven findings are the basis for the autoimmune concept of atherosclerosis.

Tumornecrosis-Factor-α 308 GA Polymorphism in Atherosclerotic Patients

The development of the atherosclerosis is a multifactorial process, where the clinical pattern is determined by environmental and genetic factors. Except for the classical risk factors of atherosclerosis (hypertension, lipid-metabolic disorders, diabetes, smoking) the clinical signs can be influenced by the genetic variants (polymorphisms) of the enzymes, which are responsible for the endothelial cell function and for the thrombotic factors. In our examination our aim was to define the TNF-α 308GA polymorphisms in atherosclerotic diabetic, atherosclerotic non-diabetic and healthy patients. We found correlation of the frequency of myocardial infarction and stroke in atherosclerotic diabetic and atherosclerotic non-diabetic patients. We proved that among patients with mutant TNF-α AA genotype the occurrence of cardiovascular events is significantly higher: Mutant AA homozygous genotype: control group 1, 6%, MI group 10,7%, p < 0,005, OR: 8,17 versus Normal GG allele: control group 76,7%, MI group 61,3%. The TNF-α AA genotype can have a clinical importance as a prognostic and therapeutic marker, although further studies are needed to confirm this hypothesis.

Effects of standard treatment on the dynamics of matrix metalloproteinases gene expression in patients with acute coronary syndromes

Inflammation plays a critical role in the pathology of acute coronary syndrome (ACS). Matrix metalloproteinases (MMP) – proteolytic enzymes participating in plaque destabilization – are the crucial effectors of proinflammatory mechanisms leading to plaque rupture. Numerous reports have confirmed the significance of these factors both in circulating blood and locally in the plaque. There is, however, a lack of information on the molecular mechanisms leading to these disturbances, and the effect of standard treatment for ACS on these processes. The aim of the study was to assess the gene expression of MMP-2, -9 and TIMP-2, and the effect of standard treatment on the expression of the studied genes.The study was conducted in 32 patients with ACS and 15 healthy subjects (control group). Monocytes were isolated using Rosette-Sep kits. Gene expression of MMP-2, MMP-9 and TIMP-2 was evaluated on days 1 and 5in the studied group and once in controls. Total mRNA was extracted from monocytes and the number of mRNA copies was assessed by QRT-PCR.Monocytes of ACS patients present with significantly higher gene expression of MMP-2, -9 and TIMP-2 compared to healthy controls (0.0915 ±0.037 vs. 0.001 ±0.0002, p<0.01; 0.81±0.279 vs. 0.10±0.057, p<0.05; 0.84±0.140 vs. 0.42±0.126, p<0.05, respectively). After the 5-day standard treatment, a significant decrease in MMP-2 gene expression was observed. Other studied genes did not show relevant changes during the observation period. No significant correlation was found between classical atherosclerosis risk factors and the expression of the studied genes.Monocytes of ACS patients significantly overexpressed MMP-2, MMP-9 and TIMP-2. Five days of standard treatment resulted in down-regulation of the MMP-2 gene. MMP gene overexpression appears to be an independent factor concerning the pathogenesis of ACS.

Carotid intima-media thickness, hs-CRP and TNF-α are independently associated with cardiovascular event risk in patients with atherosclerotic occlusive disease

This prospective study aimed to determine whether carotid intima-media thickness (CIMT) and biomarkers can enhance the predictive value of classic atherosclerosis risk factors (RFs) for cardiovascular (CV) event risk in patients with confirmed atherosclerosis. MethodsBaseline levels of hs-CRP, Tumor Necrosis Factor alpha (TNF-α), Transforming Growth Factor beta (TGF-β), Interleukin-6 (IL-6), Interleukin-10 (IL-10) and Nt-proBNP were measured in 304 subjects (189 men) aged 64.2±9.4 years, with confirmed atherosclerotic occlusive disease. Maximum CIMT values of common, bulb and internal carotid arteries were measured and expressed as mean CIMT value. The incidences of CV death, myocardial infarction (MI), ischemic stroke (IS) and symptomatic lesion progression were recorded. ResultsDuring 44.7±12.1 months of follow-up, CV events occurred in 61 (20.1%) patients. Age (odds ratio: OR=1.04; p=0.013), diabetes (OR=2.01; p=0.007), LDL-cholesterol>3.35mmol/L (OR=2.03; p=0.007), previous MI (OR=2.14; p=0.003) and previous IS (OR=3.35; p<0.001) were found independent CV event RFs. Adding biomarkers or CIMT to classic RFs revealed that levels of TNF-α>6pg/mL (OR=1.77; p=0.024), hs-CRP>6mg/L (OR=1.69; p=0.009) or CIMT>1.25mm (OR=5.11; p<0.001) were independently associated with CV event risk. While Nt-proBNP was found RF of CV death (OR=1.19; p=0.003) and MI (OR=1.19; p=0.002). In patients with RFs plus TNF-α>6pg/mL and hs-CRP>6mg/L, a 2- and 5-year event-free survival was 8% and 4%, respectively, as compared to 42% and 33% in those with RFs but lower TNF-α and hs-CRP levels. While, CIMT<1.25mm increased a 2- and 5-year CV event-free survival probability to 79% and 73%, respectively, despite classic RFs presence. ConclusionAdditive value of TNF-α, hs-CRP and CIMT to classic RFs in CV risk stratification was found in patients with confirmed atherosclerosis. Nt-proBNP was found an independent risk factor of CV death and MI.