Vascular Disease Prevention (Discontinued) - Volume 3, Issue 1, 2006

Disseminated intravascular coagulation (DIC) is frequently associated with severe bleeding tendency and organ failure; the outcome of DIC is often poor. The difference in mortality, laboratory data and pathological state in DIC due to various underlying diseases was examined. Mortality associated with DIC due to infection, solid cancers (SC), organ failure (OF) and acute non-lymphocytic leukemia (ANLL) was more than 30%, but that due to aneurysms, acute promyelocytic leukemia (APL) and acute lymphocytic leukemia (ALL) was low. In International Society of Thrombosis and Haemostasis (ISTH) scoring system, DIC score point of fibrin related marker was high in all underlying diseases and that of platelet count was usually high in leukemia. DIC score pattern was similar in various underlying diseases excepting abdominal aortic aneurysms. DIC in leukemia is caused by tissue factor (TF) and plasminogen activator (PA), while that in sepsis is caused by activated leukocytes. Hemostatic abnormalities in infections are different from those in leukemia; relatively high fibrinogen and low antithrombin levels in sepsis and high D-dimer and low fibrinogen levels in leukemia. Diagnosis of the early phase DIC is important for treatment but it might be necessary to use different DIC diagnostic criteria for infections or leukemia.

Objective: To study the vibration adaptation of the aortic wall, after experimentally-induced stenosis in pig descending thoracic aorta. Methods: A 5 mm length, circumferential, rigid, symmetric constriction was created surgically, in eight healthy pigs, producing approximately a 15-20 mmHg pressure drop. Pressure Tip Catheters were used to monitor the pressure drop. Blood flow waveforms were recorded via a Bi-Directional Doppler Flow-meter at pre-A and post-B stenotic areas. Measurements were carried out before, 10 min after and 90 days after the creation of stenosis. The oscillating force acting on the aorta at regions A and B was approximated with the help of blood pressure waveforms. Euthanasia was performed after 90 days and the descending thoracic aorta removed. Eight sham-operated pigs were used as controls. Results: Pressure waveforms were recorded at both A and B sites and maintained until euthanasia. Also, vibration analysis proved that the oscillation frequency of the applied force at A and B regions was greater than that of the control tissues (p<0.05). Conclusions: A minor experimental stenosis located at the level of the descending thoracic aorta increased the oscillating frequency of the vessel. This elevation may act as a "vibration-like disease" to endothelium, to the vasavasorum or even to gene expression of the underlying cells through the developed fatigue or tuning.

Objective: To observe the risk factors of vascular thrombotic diseases in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: From February of 2003 to April of 2005 24 patients with moderate and severe OSAHS (OSAHS group) and 19 healthy adults (control group) were recruited. Their blood samples were drawn at 6:00 and 16:00 respectively for testing hemocrit, platelet aggregation (PAG), whole blood viscosity (WBV), prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen (Fng) and endothelin (ET). Results: There was a significantly higher hemocrit, WBV, Fng and ET as well as a significant shortening of PT and APTT at 6:00 than that at 16:00 in OSAHS group. However, there was no significant difference in all testing items between 6:00 and 16:00 in control group. The hemocrit, WBV, PAG, plasma Fng and ET were significantly higher, and PT and APTT were obviously shorter at 6:00 in OSAHS group than those at 6:00 in control group. A higher hemocrit, PAG, plasma Fng and ET, a longer PT and APTT were observed at 16:00 in OSAHS group, compared with those at 16:00 in control group. Conclusions: In OSAHS patients there were striking risk factors of thrombosis, which is more remarkable in the early morning than in the afternoon.

It is well-established practice to use thromboprophylaxis for patients undergoing surgical procedures due to their moderate to high risk of incidence of venous thromboembolic disease (VTE). However, many patients hospitalised for medical diagnoses also have a moderate to high incidence of VTE. This is due to several factors related to the patient type as well as disease specific factors. The purpose of this review is to summarise the risk of VTE in different subgroups of medical disease. The risk however, is not the same for all types of medical patients and thus the method and frequency of prophylaxis should be stratified according to patient risk. There continues to be exciting developments in the field of thromboprophylaxis, with the use of new anticoagulants in clinical trials involving medical patients. The safety and effectiveness of such pharmaceutical agents are described.

Radiation to the head and neck region has recently been established as a significant risk factor for the development of extracranial carotid stenosis. The underlying pathophysiology is similar to non-radiation induced atherosclerosis. However, the extent of involvement, the rapid progression as compared with patients without irradiation suggests that this is a unique disease entity, which warrants close surveillance, especially for patient with relatively good prognosis. Surgical intervention could be difficult in this group of patients who suffered from fibrosis related to radiation. Carotid stenting has recently served as a safe and effective alternative treatment for the disease.

Chymase forms angiotensin II (Ang II) which plays a crucial role in vascular diseases. In dog grafted veins, chymase activity and Ang II concentration along with vascular proliferation were significantly increased, while they were completely suppressed by a chymase inhibitor. After balloon injury in dog arteries, vascular chymase activity was significantly increased, and a chymase inhibitor and an Ang II receptor blocker were effective in preventing the vascular proliferation, but an angiotensin-converting enzyme inhibitor was ineffective. In clinical studies, an Ang II receptor blocker was successful in preventing restenosis after percutaneous coronary intervention, but an Ang II-converting enzyme inhibitor was not. In human and animal atherosclerosis, chymase activity was significantly increased, and a chymase inhibitor prevented experimental atherosclerosis. These observations suggest chymase may promote vascular proliferation and atherosclerosis. Chymase also activates matrix metalloproteinase-9 which promotes aortic aneurysm and angiogenesis. In human aortic aneurysms, chymase activity was significantly higher than in the normal aortas. In a hamster aneurysm model, chymase activity was also higher in the aneurysmal aortas than in the normal aortas, whereas a chymase inhibitor significantly prevented the aortic aneurysm. Chymase also acts as a pro-angiogenic factor, because the injections of the chymase gene or of purified chymase into implanted sponges strongly facilitate angiogenesis in hamsters. The mechanism of chymase- induced angiogenesis may depend not only on Ang II formation but also on activation of matrix metalloproteinase- 9. In this review, we propose chymase inhibitors as a novel therapeutic strategy for anti-vascular remodeling.

Abdominal aortic aneurysms are associated with increased morbidity and mortality. Wide controversy exists as to whether the detection of such conditions should be followed by immediate surgical management or, instead, a more conservative approach ("watchful waiting") should be adopted. Statin therapy has been demonstrated not only to prevent expansion, but also to reduce aneurysmal size. These potential advantages require further investigation and guidelines concerning the routine use of statins as additional therapeutic tools for the management of abdominal aortic aneurysms.

Recently short-term power spectral analysis of heart rate variability (HRV) has been used also to stratify the risk of sudden death in subjects with chronic heart failure (CHF). Short-term spectral analysis of RR variability in normotensive healthy subjects shows two distinct components of HRV: high-frequency power (HF), which synchronizes with breathing and therefore reflects vagal modulation of the sinus node, and low-frequency power (LF) oscillating around 0.1 Hz influenced also, though not solely, by sympathetic modulation of the sinus node. Among factors that strongly influence autonomic control of the sinus node and HRV are aging, hypertension and CHF. CHF, markedly reduces both spectral components of HRV and the paradoxical LF reduction is a risk factor for sudden death. It is reasonable that, in a next future, LF could become a useful tool to identify more precisely subjects at high risk of sudden death in various cardiovascular conditions.

During periodontitis, dental plaque microorganisms may disseminate through the blood to infect the vascular endothelium and contribute to the occurrence of atherosclerosis and risk of myocardial ischemia and infarction. Aggregation of platelets is induced by the platelet aggregation-associated protein (PAAP) expressed on plaque bacteria, including Streptococcus sanguis and Porphyromonas gingivalis. Findings from the Dental Atherosclerosis Risk in Communities study also indicate that periodontal disease is associated with carotid intima media wall thickness, a measure of subclinical atherosclerosis. Inflammation is increasingly recognized as a major component of atherosclerosis, especially in plaques associated with acute coronary syndromes, as often demonstrated at necropsy. Chronic infection is now recognized as one of the possible causes of chronic inflammation that could lead to atherogenesis and plaque instability. Periodontitis is an inflammatory reaction (to Gram-negative, anaerobic bacterial infections) of the surrounding tooth, including the periodontal ligament, cementum, and alveolar and supporting bone. The next step will be to determine whether periodontitis could be an inflammatory-infectious trigger to endothelial dysfunction and vascular inflammation (leading to atherosclerosis), and whether proper management would improve endothelial dysfunction and vascular inflammation and thus, prevent atherogenesis.

Systemic Lupus Erythematosus (SLE) is a chronic inflammatory disease of unknown cause which can affect any organs, characterized by a wide range of auto-antibodies. Studies of several large cohorts of SLE patients have reported an increased prevalence of symptomatic of sub-clinical coronary artery disease (CAD). It is currently believed that accelerated atherosclerosis in SLE results from a combination of numerous risk factors. In addition to a high prevalence of traditional risk factors, inflammatory processes in SLE are considered to be important in atherogenesis. Chronic activation or damage to the endothelium in SLE may trigger the inflammatory cascade and thereby promoting atherogenesis. Several forms of endothelial insult are being recognized in SLE, including hypercholesterolaemia, hyperhomocysteinaemia, mechanical stress from hypertension, increased oxidative stress and immunological injury as a result of immune complex deposition. Furthermore, autoantibodies directed against oxidised lipoproteins, along with chronic secretion of proinflammatory cytokines and suppression of fibrinolytic pathways may also contribute to atherosclerosis. SLE patients may also be more susceptible to the deleterious effects of the CAD risk factors due to pre-existing inflammation-induced vascular injury. This review updates the modifiable risk factors in SLE. The main focus is on the potential utility of these risk factors. The putative mechanisms of accentuated risk as a result of underlying inflammation, and evidence for association with premature atherosclerosis are discussed. Strategies which may be useful in preventing the development of progression of atheroma in this population include close monitoring and aggressive treatment of the traditional risk factors as in patients with high risk of CAD. The role of antioxidant and immunomodulators are also explored.

Elevated levels of plasma homocysteine (Hcy) appear to be associated with a higher risk of occlusive vascular disease as well as a number of other clinical conditions. The exact mechanism involved is not fully understood. Recently, it has been shown that Thymoquinone, the most active component in Nigella Sativa (NiSa) seeds, as well as the seed's oil, caused almost complete protection against methionine-induced hyperhomocysteinemia (HHcy) in the plasma of rats as well as the oxidative stress associated with this state. Here Hcy levels in blood serum of rats fed a methionine-enriched diet (with deficient levels of folate, vitamins B6 and B12) for 7 weeks together with NiSa (at 250 mg/kg/day; oral suspension) led to 72.1 ± 3.35% protection against HHcy induced by the same diet without the seeds. There was no significant change in Hcy levels in control groups fed a standard diet with or without the seeds. Furthermore, the seeds imparted a 90.0 ± 4.0% protection against the rise in liver Hcy levels, and reduced the control levels by 28.0% ± 0.4%. The degree of protection in brain tissue homogenates reached a level of 29.0 ± 2.0%. In addition, there was no significant rise in Hcy levels in heart tissue under the excess methionine conditions, nor was there any significant effect by the NiSa on the levels on heart tissue Hcy under these conditions. NiSa treatment, however, significantly reduced the levels of Hcy in the control heart tissue by 43 ± 8%. On the other hand, the NiSa provided full protection against the rise in serum triglyceride levels (approx 3.0 fold) as well as the drop (24.2 ± 1.5%) in serum Superoxide Dismutase (SOD) antioxidant enzyme activity without causing any significant effect against the decrease in the total antioxidant status under the excess methionine conditions used. These results demonstrate the effective protection by NiSa against induced HHcy in serum, liver, and brain tissues together with its ability to reduce Hcy level in heart tissue.