Vascular Disease Prevention (Discontinued) - Volume 3, Issue 2, 2006

Background: Inadequate lifestyles (LS) in young women may be related to the increasing population that migrate to the cities. Objective: To compare the LS in rural and urban women and to assess their relation with educational levels and cardiovascular risk factors. Material and methods: Four hundred and eleven women (233 from rural and 178 from urban areas) aged 20 - 44 years were studied using the McMaster University questionnaire 'Do you have to fantastic lifestyle?'. Results : The mean age was similar in both groups (30.9 ± 7.2 years for rural vs 29.6 ± 7.3 for urban). Of the interviewed subjects, the rural women had a lower education level (47.2% had more than 8 years of study vs 73.6%; p<0.0001) and had a partner more frequently (68.3% vs 53.4%; p<0.04). The LS were better in the rural area (70.4 ± 12.4 vs 66.7 ± 14.0, p<0.01) and this was determined by less consumption of alcohol and drugs, more physical activity and higher family support. A higher level of schooling was related to better LS. Additionally, the women who had good LS had a lower body mass index. Conclusion: The urban women have worse LS than the rural ones. In both groups, the educational level was associated with healthier LS and less obesity, well-known risk factors for chronic diseases.

Women have a slower cardiac repolarization than men, which manifests as longer heart rate corrected QT interval (QTc) on the ECG. This study was undertaken to identify cyclical variations of QTc and to detect whether it can further be modulated by handgrip exercise. ECG changes were recorded before and after handgrip exercise during different phases of menstrual cycle in 30 healthy women (25-40 yrs) with a regular menstrual cycle. The different menstrual cycle phases were assigned on the basis of dates and confirmed by plasma levels of estrogen and progesterone. Daily basal body temperature was recorded to confirm the ovulatory phase. ECG parameters (in lead II) were recorded before and immediately after release of handgrip. During the menstrual phase, the basal RR interval was 0.765 ± 0.03 sec and after handgrip exercise, it increased to 0.829 ± 0.02 sec (p<0.05). The QTc interval was maximal in the menstrual phase (0.44 ± 0.007). There was a significant decrease in QTc interval in the menstrual phase (0.41 ± 0.009 sec, p<0.05) after handgrip exercise. This study confirms the cyclic variation of the QTc interval. The prolonged QTc interval during the menstrual phase is likely to produce arrhythmias if women are exposed to agents which further prolong the refractory period. A fall in the QTc interval was seen after handgrip exercise during the menstrual phase, females may be advised to engage themselves in isometric activities so as to decrease their susceptibility to arrhythmias.

Coronary surgery includes the majority of cardiac surgery interventions in industrialised countries and represents the most common complex surgery in the world with a trend towards an increase. Every year approximately 800,000 patients worldwide undergo Coronary Artery By-pass Grafting (CABG) with a peri-operative mortality of 1-3%. Over the years, the indications for CABG have changed and remain in continuous evolution not only because of the development of innovative diagnostic and surgical techniques, but also because of the introduction of new non-surgical strategies that can manage cases that in the past were referred to cardiac surgeons. A notable example of this is the Percutaneous Coronary Interventions (PCI), and the subsequent introduction of always more sophisticated stents, which have substantially contributed to the modification of the population of patients undergoing CABG. As a result, patients undergoing cardiac surgery are increasingly aged and with more serious coronary artery involvement. For these reasons, the mean surgical risk expected for cardiac surgical patients has increased in recent years. This review summarises the developments in coronary surgery, tracing a parallel with interventional cardiology and provides a vision of future trends.

Human urotensin II (U-II), the most potent vasoconstrictor peptide identified to date, and its receptor (UT) are involved in atherosclerosis. U-II is expressed in endothelial cells, macrophages, macrophage-derived foam cells, and myointimal and medial vascular smooth muscle cells (VSMCs) of atherosclerotic human coronary arteries. UT receptors are present in VSMCs of human coronary arteries, thoracic aorta and cardiac myocytes. Lymphocytes are the most active producers of U-II, whereas monocytes and macrophages are the major cell types expressing UT receptors, with relatively little receptor expression in foam cells, lymphocytes, human carotid arteries or aorta. Peripheral infusion of U-II causes vasoconstriction in the human forearm, and U-II also stimulates VSMC proliferation and shows synergistic interactions with oxidised LDL, hydrogen peroxide and serotonin. U-II also accelerates foam cell formation by up-regulation of acylcoenzyme A:cholesterol acyltransferase-1 in human monocyte-derived macrophages, up-regulates type 1 collagen expression and down-regulates matrix metalloproteinase-1 expression in human endothelial cells, and activates NADPH oxidase and plasminogen activator inhibitor-1 in human VSMCs, leading to progression of atherosclerotic plaque. Clinical studies demonstrated elevated plasma U-II concentrations in patients with hypertension or diabetes mellitus, and positive correlations with systolic and diastolic blood pressure, body weight and fasting plasma glucose levels, while experimental studies indicated that U-II inhibits glucose-induced insulin release from pancreatic β cells in rats, promotes food intake in mice and hyperlipidaemia by channelling glucose to free fatty acid synthesis in fish. These findings suggest that U-II plays key roles in metabolic syndrome.

Thrombin-mediated fibrinogen conversion to fibrin and fibrin monomer cross-linking by activated factor (F)XIII result in the formation of a clot, which is relatively resistant to mechanical and enzymatic degradation. Clot structure, characterized by clot porosity and fiber thickness, plays a role in atherothrombotic vascular disease. In patients with advanced coronary artery disease, reduced fibrin clot permeability was first documented in 1992. Dense clot fiber networks have been found in survivors of myocardial infarction aged <50 years and in their first-degree relatives. Altered fibrin clot architecture has also been reported in dyslipidemia and in diabetes. There is evidence that a number of genetic and environmental factors affect fibrin clot architecture and clot resistance to lysis. Elevated inflammatory markers have been associated with decreased clot permeability and lower clot susceptibility to fibrinolysis. A similar effect exerts hiperhomocysteinemia. Favorable changes in fibrin clot structure can be induced by drug administration. Acetylsalicylic acid (aspirin) at therapeutic doses has been reported to increase clot permeability and enhance clot lysability. Recently, we have shown that lipid-lowering agents (statins, fibrates) and angiotensin-converting enzyme inhibitors alter fibrin clot structure similarly to aspirin. The most probable mechanisms underlying altered clot architecture in patients at risk of cardiovascular disease are a decrease/increase in fibrinogen or thrombin levels, or nonenzymatic modification of the fibrinogen molecules such as oxidation or glycation. Despite substantial experimental evidence, it remains to be determined to what extent fibrin clot properties influence the prevention and treatment of cardiovascular disease.

Background: Cholesterol-induced cytotoxicity is a major cause of death of macrophages in atherosclerotic lesions. Apoptosis, or programmed cell death, plays an important role in atherogenesis. A deficiency of endogenous heparin activity is said to result in hypertriglyceridemia, hypercholesterolemia and enhanced atherogenesis, which is corrected on injecting exogenous heparin. In the current study, a low-molecular-weight heparin (LMWH), certoparin was tested for its influence on lipid anomalies and apoptotic damage in early atherogenesis. Methods and results: Two groups of male Wistar rats (140 ± 10 g) were fed an atherogenic diet comprising of normal rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil (CCT diet) for two weeks. One group was left untreated, the other was administered certoparin (300 μg/day/rat) commencing on day 8 and continued for a week. At the end of the two-week experimental period, we found significant elevation in plasma free cholesterol, free fatty acids and phospholipids (p< 0.001) and abnormal accumulation of cholesterol, triglycerides and phospholipids in the cardiac, hepatic and renal tissues of the untreated animals. Administration of LMWH subcutaneously corrected the lipid anomalies partly by restoring the altered activities of lipid metabolizing enzymes including total lipase, lipoprotein lipase, lecithin: cholesterol acyl transferase, cholesterol ester synthetase and hydrolase. Protein aggregation and cross- linking were observed in the cardiac microsomes of the untreated hypercholesterolemic group, along with significantly high malondialdehyde levels (p< 0.001); LMWH treatment afforded considerable protection against this oxidative damage. DNA fragmentation analysis and comet assay revealed marked DNA damage in the cardiovascular tissue from the untreated hypercholesterolemic group that was minimized by subcutaneous LMWH treatment. Conclusion: The LMWH, certoparin favorably modulates lipid disturbances in cardiac, hepatic and renal tissues, exerts a beneficial effect on oxidative changes and the structural integrity of cardiac microsomal membranes, and protects against apoptotic DNA damage in the cardiovascular tissue, thereby proving to be potentially anti-atherogenic.

The functional changes of endothelium can be detected by ultrasound (US) parameter flow-mediated vasodilation (FMD). The carotid intima-media thickness (IMT) reflects the structural changes of arterial wall. The combination of previous mentioned methods with the inflammatory markers may provide more complex information concerning the changes of arterial wall as every method allows alone. Significantly reduced, FMD has been found in subjects with coronary artery disease (CAD) compared to the control group (C group) (CAD group: 96.47 ± 13.4%, C group: 108.27 ± 7.1%). Endothelium-independent vasodilation (EID) was also significantly reduced. Mean diameters of the brachial artery at rest, the common carotid artery (CCA) and the internal carotid artery (ICA) were significantly larger in subjects with CAD. The mean carotid IMT of the near and the far wall was significantly higher. There were observed elevated levels of soluble receptor RI of tumor necrosis factor-a (sTNF-RI) in these subjects, too. A significant has been found correlation between soluble receptor RII of tumor necrosis factor-α (sTNF-RII) and carotid IMT of the near wall, and the slight correlation between sTNF-RI and the diameter of brachial artery at rest. According to the multivariate analysis, a relationship was determined between sTNF-RII, diameter of CCA and carotid IMT of the near wall. Conclusions: We have found significant reduced FMD and activation of sTNF-RI in patients with CAD in mild stage of CHF. The relationships between mean diameter of CCA, carotid IMT of the near wall and sTNF-RII may be explained via the arterial remodeling.

The first cause of mortality in the dialysis population is cardiovascular disease. Accelerated atherosclerosis and vascular calcifications play a key role in the pathogenesis of cardiovascular disease in chronic kidney disease (CKD) patients. Mineral metabolism disorders and increased serum calcium-phosphate product have recently been investigated as factors inducing vascular calcification. Cardiovascular disease in renal failure appears to be associated with bone metabolism alterations. Hyperphosphatemia has been investigated as an inducing factor for cardiovascular morbidity in this population. Recent in vitro studies showed how vascular smooth muscle cells calcify when incubated in a medium containing elevated concentration of inorganic phosphate. Together with classical passive precipitation of calcium-phosphate in soft tissues, inorganic phosphate may cause extraskeletal calcification through "ossification" of the tunica media in the vasculature of CKD patients. In addition, the treatment of hyperphosphatemia and secondary hyperparathyroidism with calcium-based phosphate binders and calcitriol has increased the risk of vascular calcification in dialysis patients. "Second generation" therapy of hyperphosphatemia with free-calcium and aluminum phosphate binders, new vitamin D metabolites, and calcimimetics may prevent extraskeletal mineralization in uremic subjects, reducing both cardiovascular morbidity and mortality.

The foramen ovale is an ellipsoidal-shaped tunnel in the interatrial septum of the foetal heart allowing a rightto- left shunt between the two atria. It generally closes soon after birth but remains permeable in about 30% of adults. The frequency of this patent foramen ovale (PFO) in stroke patients is higher than among the general population, particularly in individuals with stroke of unknown aetiology (cryptogenic stroke) and in younger patients. Three theories have been proposed to explain the role of PFO in cryptogenic stroke: the paradoxical embolism theory, the arrhythmogenic theory and the thrombogenic theory. None have as yet been irrefutably confirmed. However, several secondary stroke prevention strategies have been developed in these patients: antiplatelet agents, oral anticoagulants, percutaneous closure and surgical repair. Secondary stroke prevention in these patients is presently one of the most controversial issues among cerebrovascular disease experts. We present a state-of-the-art review of secondary stroke prevention evidence in patients with cryptogenic stroke and PFO.

It has been known that vascular inflammatory reactions, such as adherence and infiltration of monocytes and lymphocytes into the vascular endothelium, play an important role in the pathogenesis of atherosclerosis. In this process, the expression of adhesion molecules and chemokines is responsible in the vascular endothelium. In human and animal athero- sclerotic tissues, the expression of thromboxane A2 (TXA2) and F2-isoprostane, ligands of TXA2 receptors, is potentiated, suggesting the involvement of these factors in atherosclerosis. Several in vitro studies suggest that stimulation of TXA2 receptors in vascular endothelial cells may augment expression of adhesion molecules and chemokines. TXA2 receptor antagonists may prevent the exacerbation of inflammation by blocking these responses. Recent reports using experimental animal models of atherosclerosis indicated that the induction of adhesion molecule and chemokine expression by TXA2 receptor stimulation is significantly involved in the process of inflammatory cell infiltration in the formation of atherosclerotic lesions. It is understood that TXA2 receptor antagonists inhibit the formation of this lesion by blocking the process. It has been clinically proven that low-dose aspirin, a cyclooxygenase inhibitor and an agent to inhibit TXA2 formation, prevents cardiovascular events following an intervention. However, low-dose aspirin do not inhibit the production of F2- isoprostanes by oxidative stress in the atherosclerotic lesions. In this regard, potent TXA2 receptor antagonists are capable of blocking the actions of TXA2 and F2-isoprostane, thus may offer a more potent effect in the prevention of atherosclerotic vascular diseases.

Objective: The aim of the study is to investigate whether chaotic phenomena affect the process of atherosclerosis (ATH). Methods: Modeling the major elements in the initiation of atherosclerosis, that is to say, oxLDL, macrophages (MAC) and foam cells (FCE), a set of three first order differential equations has been developed and studied in phase-space (x,y,z). Results: The elementary equilibrium points in three dimensional phase portrait analysis, including attractors, saddles and repellors. Conclusions: Attractors indicate a stable equilibrium point, which attenuates the evolution of ATH,while the saddles and particularly the repellors correspond to an unstable dynamic system, which promotes the formation of ATH-plaques.Among other mechanisms, chaotic phenomena also seem to regulate in a particular way the ATH-process, that calls for further theoretical and experimental research.

Dual antiplatelet treatment with aspirin and a thienopyridine (either ticlopidine or clopidogrel) is currently recommended after percutaneous coronary intervention with stent implantation (PCI-S). This regimen has been proven superior to the combination of oral anticoagulation (OAC) and aspirin, which at present, has therefore little role in this setting. In patients undergoing PCI-S with an indication for long-term OAC, because of atrial fibrillation, mechanical heart valve, previous thromboembolism, etc., the optimal antithrombotic treatment is currently unknown. The limited available evidence shows substantial variability in the management of these patients, who are treated according to standardized protocols only in 54% of cases. The adopted strategies include, either selected or systematic, substitution of OAC for dual antiplatelet therapy in 25 to 54% of cases, addition to OAC of a single antiplatelet agent in 12 to 25% and institution of triple therapy with OAC, aspirin and a thienopyridine in about 60%. OAC is systematically aimed at a lower intensity in 33% of cases only, whereas in another 29% this is pursued when a high hemorrhagic risk is perceived. In 69% of patients having exchanged OAC for dual antiplatelet administration, the original treatment is resumed after 1 to 3-6 months, with longterm association of an antiplatelet agent in most cases. Both efficacy and safety of the various antithrombotic regimens were suboptimal in the small series reported, with a 30-day occurrence of thrombotic and major bleeding complications of 4% and 3 to 7%, respectively. For current practice, stratification of medium-term risk of thrombo-embolism upon OAC interruption is warranted. In low-risk patients (i.e. lone atrial fibrillation, venous thromboembolism > 6 months, etc.), preprocedural OAC interruption and substitution for dual antiplatelet treatment, to be continued for the following 1 to 6 months, is appropriate. In medium- to high-risk patients (i.e. mitral or multiple mechanical valves, recent arterial or venous thromboembolism, etc.), medium-term triple therapy with OAC, aspirin and a thienopyridine should be adopted. In both risk groups, drug-eluting stents should be avoided as much as possible, due to the prolonged need for dual antiplatelet treatment. In the absence of strongly supportive evidence however, large scale registries and clinical trials are warranted to confirm the currently suggested strategies and to evaluate alternative antithrombotic regimens in patients with and indication for OAC undergoing PCI-S, whose number is likely to progressively increase over the next years.