Vascular Disease Prevention (Discontinued) - Volume 5, Issue 3, 2008

Lipoprotein(a), Lp(a), represents a class of lipoproteins characterized by having a single mole of poB100 covalently linked to a single mole of apolipoprotein(a), apo(a), a multikringle structure with close homology to lasminogen. High plasma levels of Lp(a) have been associated with an increased incidence of atherosclerotic cardiovascular disease by mechanisms yet poorly defined. The structural and functional properties of Lp(a) have directed early attention to the. proatherogenic and prothrombotic properties of this lipoprotein. However, recent studies have uncovered an additional mechanism dealing with oxidative-derived post-translational changes promoting the chemical linkage of apo(a) to proinflammatory oxidized phosphatidylcholine (ox-PC). The scope of this review is to critically examine the available information on this subject in the context of the overall cardiovascular pathogenicity of Lp(a) taking into account the underlying notion of atherosclerosis as a chronic inflammatory process and also comment on the potential therapeutic implications of these new findings.

We review extensive data in patients with coronary heart disease demonstrating the benefits of exercise training (ET) programs with cardiac rehabilitation on various cardiovascular (CV) factors, including exercise capacity, plasma lipids, obesity indices, diabetes mellitus/metabolic syndrome, inflammation, blood rheology, autonomic function, indices of ventricular repolarization dispersion, psychological risk factors, quality of life, and overall major CV morbidity and mortality. In addition, we discuss the positive outcomes of ET programs in patients with peripheral arterial disease, including benefits on objective assessments of claudication and walking distance, as well as CV risk factors and overall morbidity and mortality.

Internal jugular vein (IJV) thrombosis is exceedingly rare and it is typically the result of head and neck infections or trauma, intravenous drug abuse or long-standing central venous catheters. Malignancies are also a cause of IJV thrombosis. We present a case of bilateral IJV thrombosis in a 48-year-old man. Additional investigations revealed a malignancy of the stomach. Based on a search of the literature, we suggest that patients with spontaneous and/or recurrent IJV thrombosis should undergo thorough investigation to prevent overlooking an occult malignancy.

Objective: We carried out a retrospective cohort study to examine the influence of personal and disease characteristics at the time of admission on the 30-day mortality of acute myocardial infarction (AMI) among Chinese subjects. Methods: All 1440 patients with transmural AMI admitted to the coronary care unit of a major regional hospital in Hong Kong from 1991 to 2001 were included and followed up for at least 30 days. Cox's proportional hazard regression model was used to examine the independent effects of various personal and disease characteristics on 30-day mortality. Results: 253 patients (17.6%) died within 30 days of symptom onset. Significant predictors of 30-days mortality were older age, pre-morbid New York Heart Association (NYHA) functional class Grade II to IV (vs Grade I), anterior AMI (vs inferior/ posterior AMI), use of diuretics before admission and thrombolytic therapy after admission (protective). Conclusion: The predictors identified would assist clinicians in characterizing the mortality risks of patients at the time of admission for AMI, so that appropriate strategy for management can be planned.

In recent years, the role of C-reactive protein (CRP) in cardiovascular disease has been a lively topic of debate. The reasons for this interest can be summarized as follows. First, CRP has been identified as a powerful cardiovascular risk marker. Second, CRP may not only be a cardiovascular risk marker but also a risk factor, i.e., it may be causally involved in atherogenesis and its sequelae. Third, if it is indeed a cardiovascular risk factor, CRP may be a therapeutic target for primary or secondary prevention of cardiovascular disease. The medical and economic impact of these possibilities is evident. However, despite considerable research, the key questions concerning the role of CRP in cardiovascular disease remain unanswered.

Background and objective: Insulin resistance is thought to be central to the pathogenesis of abdominal obesitylinked metabolic syndrome (MetS). Colestimide, a 2-methylimidazole-epichlorohydrin polymer, is a new bile-acidsequestering resin used to lower LDL cholesterol. In recent reports, bile acid-controlled signaling pathways have shown promise as novel drug targets to treat metabolic disorders, such as obesity, type 2 diabetes, hyperlipidemia, and atherosclerosis. The aim of this study was to evaluate the efficacy of colestimide on weight loss in MetS patients. Methods: Sixty-one patients with MetS who had cardiovascular risk factors were randomized to receive lifestyle counseling with or without colestimide treatment. The primary endpoint was achieved when the reduction in body weight is ≥5%. Additionally, differences in the waist circumference and metabolic-associated profiles between the colestimide group and the control group, which received lifestyle modifications alone, were analyzed. Results: The numbers of participants who achieved ≥5% weight loss significantly favored the colestimide group over the non-colestimide group (71.4% vs. 33.3%; p < 0.01). The mean reduction in waist circumference during the study period (average 22 weeks) was greater with colestimide than without it (10.1 ± 5.4 vs. 7.1 ± 5.2 cm, p < 0.05). Conclusions: The colestimide treatment together with lifestyle intervention was associated with reduction in body weight and waist circumference over a relatively short term in obese subjects. The combination of colestimide and lifestyle intervention may be useful for weight management in MetS patients with cardiovascular risk factors.

Unfractionated heparin (UFH) and Low Molecular Weight Heparins (LMWHs) represent the mainstay of agents available for the management of venous and arterial thrombosis. LMWHs represent the agents of choice for the prevention and treatment of venous thromboembolism because they have improved pharmacological and pharmacokinetic advantages. LMWHs are derived from UFH by chemical or enzymatic depolymerization; they have a mean molecular weight of 4,000 to 5,000 d. The LMWHs include dalteparin, enoxaparin, nadroparin and certoparin. They can be used inhospital or out-of-hospital because they can be administered subcutaneously without the need for laboratory monitoring and they have better bioavailability and cause less platelet activation. Several randomized trials suggested that patients with symptomatic or asymptomatic pulmonary embolism, symptomatic deep venous thrombosis can be treated with LMWH instead of UFH. Compared with UFH, LMWHs have a more predictable dose-response relationship (obviates the need for laboratory monitoring), a longer half-life (allows once-daily or twice-daily administration) and a lower risk for immune-mediated thrombocytopenia or osteoporosis. This is partly due to more targeted action: UFH acts on both thrombin and factor Xa about equally, whereas LMWHs are more active against factor Xa.

Objective: Drug eluting stents have recently been associated with the increased risk of adverse thrombogenic events and/or late luminal loss, which is highly associated with incomplete re-endothelialization. The increased risks behoove the design of alternative delivery modalities and/or drugs that do not compromise the re-endotheliaization process. The objective of the present study is to elucidate the biological mechanism(s) by which non-stent-based delivery modalities for the anti-proliferative lipid metabolite, C6-ceramide, could lead to a reduction in arterial injury after angioplasty. Results: Immunohistochemical studies in rabbit and porcine models suggest that C6-ceramide-coated balloon catheters limit arterial stenosis without inhibiting endothelial wound healing responses. Specifically, C6-ceramide-coated balloon catheters reduce internal elastica injury with a corresponding reduction in medial fracture length in a 28-day porcine coronary artery stretch model. In addition, C6-ceramide decreases the formation of the fibrin matrix to possibly augment the subsequent wound healing response. We hypothesized that differential metabolism of exogenous ceramide by coronary endothelial and smooth muscle cells could explain the apparent discrepancy between the anti-proliferative actions of ceramide and the pro-wound healing responses of ceramide. Human coronary artery endothelial cells (HCAEC), in contrast to human coronary artery smooth muscle cells (HCASMC), preferentially express ceramide kinase and form ceramide-1- phosphate, which promotes endothelial cell survival. Conclusion: Differential metabolism of ceramide between HCASMC and HCAEC offers a mechanism by which ceramide preferentially limits smooth muscle cell growth, in the presence of active wound healing. The combinatorial ability of ceramide to limit vascular smooth muscle proliferation and promote re-endothelialization, offers the potential for C6- ceramide-coated catheters to serve as adjuncts to stent-based modalities or as a stand-alone treatment.