Current Vascular Pharmacology - Volume 5, Issue 2, 2007

Evidence is emerging that disturbances in sleep and sleep disorders play a role in the morbidity of chronic conditions. However, the relationship between sleep processes, disease development, disease progression and disease management is often unclear or understudied. Numerous common medical conditions can have an affect on sleep. For example, diabetes or inflammatory conditions such as arthritis can lead to poor sleep quality and induce symptoms of excessive daytime sleepiness and fatigue. It has also been suggested that poor sleep may lead to the development of cardiovascular disease for which an underlying inflammatory component has been proposed. It is therefore important that the development and progression of such disease states are studied to determine whether the sleep effect merely reflects disease progression or whether it may be in some way causally related. Sleep loss can also have consequences on safety related behaviours both for the individuals and for the society, for example the increased risk of accidents when driving while drowsy. Sleep is a complex phenotype and as such it is possible that there are numerous genes which may each have a number of effects that control an individual's sleep pattern. This review examines the interaction between sleep (both quantity and quality) and parameters of cardiovascular risk. We also explore the hypothesis that inflammation plays an essential role in cardiovascular disease and that a lack of sleep may play a key role in this inflammatory process. Aim: To review current evidence regarding the endocrine, metabolic, cardiovascular and immune functions and their interactions with regard to sleep, given the current evidence that sleep disturbances may affect each of these areas.

Despite the recent advances in medical therapy and coronary revascularization procedures, coronary artery disease (CAD) remains the major cause of morbidity and mortality in the developing countries. In patients with severe CAD, persistent myocardial ischemia in hibernated myocardium resulted in progressive loss of cardiomyocytes with development of heart failure. As a result, therapeutic approaches to enhance neovascularization are being underwent intensive investigation. Recent experimental studies have demonstrated adult bone marrow (BM) can induce neovascularization in ischemic myocardium can improve heart function. These findings have prompted the development of different cellular transplantation approaches for heart diseases refractory to conventional therapy after myocardial infarction. Although the initial pilot clinical trials have shown potential clinical benefit of BM therapy for therapeutic angiogenesis, the long-term safety, the optimal timing and treatment strategy remains unclear. Furthermore, in order to acquire more optimized quality and quantity of BM derived stem cell for myocardial regeneration, several issues remain to be addressed, such as the development of a more efficient method of stem cells identification, purification and expansion. Emerging, rationally designed, randomized clinical trials are required to assess the clinical implication of BM derived stem cells therapy in treatment of CAD.

Wall shear stress is a fluid dynamic quantity that is gradually emerging as a potentially important factor of coronary atherosclerosis. Methods, therefore, of estimation of shear stress in the arterial system are of clinical relevance. The purpose of this review is to define wall shear stress, review the various methods that have been used for its assessment in human circulation, and examine the methodological limitations and applicability of each method in clinical practice.

Anticoagulant drugs are traditionally administered for the prevention and treatment of thrombosis. Besides multi-targeted, traditional anticoagulants, such as coumarins or heparins, the search for the optimal antithrombotic efficacy to bleeding risk ratio has prompted the development of a novel armamentarium of anticoagulant drugs, which is expected to be introduced in the market. These emerging drugs are mainly targeted to suppress the propagation of the coagulation cascade (thrombin burst), by direct thrombin inhibition or selective inhibition of activated factor X. Therefore, thrombin or activated factor X antagonists would produce an efficient anticoagulation while minimizing the risk of bleeding, the most common adverse events of conventional anticoagulants. No routine monitoring, favorable form of administration and better compliance are additional advantages of these innovative drugs, which are already in advanced development or already licensed for clinical use. The aim of this article is to provide an overview on the mechanisms of action, clinical applications, cost-effectiveness and side effects of these emerging anticoagulant strategies.

Persistent pulmonary hypertension (PPHN) is a disease characterised by the disruption of the transition from fetal to neonatal circulation with the persistence of high pulmonary vascular resistances and right-to left shunting. This condition, occurring in about 1-2 newborns per 1000 live births, causes severe hypoxemia. Despite significant improvements in treatment, the mortality of PPHN varies from 10 to 20 % of affected newborns. Pulmonary hypertension is frequently observed in some cardiac malformation and in congenital diaphragmatic hernia, in meconium aspiration syndrome, neonatal sepsis, podalic presentation and male sex. Maternal risk factors are tobacco smoking, cesarean section, low socioeconomic conditions, diabetes and urinary infections. Another predisposing condition is antenatal or postnatal exposure to some drugs. The medications involved in drug-induced pulmonary hypertension and the mechanisms involved are reviewed.

Dual antiplatelet therapy (aspirin plus clopidogrel) is mandatory in patients treated with coronary stent implantation. This strategy is highly effective in prevention of stent thrombosis until its struts are covered with endothelium. However, a substantial number of patients still suffer from recurrent ischemic coronary events despite adequate antiplatelet therapy. These events fall into three categories: stent thrombosis, in stent restenosis and events related to other nonstented coronary lesions. Some data suggest that beside other local and systemic factors resistance to aspirin and clopidogrel may be a possible cause of stent thrombosis and ischemic events in patients after coronary interventions. Several mechanisms of antiplatelet drug resistance have been reported including poor compliance, interactions with other drugs, genetic polymorphism or increased platelet turnover. More research is needed to adequately assess the clinical significance and prognostic value of antiplatelet drug resistance detected by laboratory tests in patients undergoing percutaneous intervention. We review published data on mechanisms and the clinical significance of aspirin and clopidogrel resistance in patients after coronary interventions.

Obesity and metabolic syndrome are increasing dramatically worldwide, contributing to cardiovascular morbidity and mortality. There are currently few safe and efficacious therapeutics for obesity and most strategies are focused on appetite suppression. Thyroid hormones reduce adiposity via increased metabolic rate, but unfortunately they cause large changes in metabolic rate and direct cardiac acceleration, making them useless for treating obesity. Thyroid hormone receptors (TRs) work as transcription factors and two subtypes exist: TRβ and TRβ . TRβ mediates tachycardia and much of the metabolic rate effect, while TRβ mediates cholesterol and TSH lowering effects of thyroid hormones. TR activation modestly increases metabolic rate such that a therapeutic window of 5-10 fold increases in metabolic rate can be seen without tachycardia. This was initially studied in TRα 1 -/- mice. Recent structure activity work has resulted in the discovery of several TRβ selective thyromimetics such as KB-141. Studies with KB-141 show that it has a 10-fold window in which therapeutic increases in metabolic rate are seen without tachycardia or cardiac hypertrophy. This agent lowers cholesterol in rats and primates. In primates, KB-141 causes significant weight and cholesterol reduction in addition to the independent risk factor Lp(a). These effects were seen without any effect on heart rate, unlike thyroid hormone (T3). Further work with TR selective agents is warranted and recent work suggests the possibility of developing compounds that selectively penetrate different tissues which may have an even more desirable therapeutic window. Selective thyromimetics, therefore, may be useful as adjunctive therapy to appetite suppressants along with exercise and diet restriction.

The “pleiotropic” effects of statins have been the centre of a considerable research activity. Among the numerous experimental and clinical studies of this field, some focused on the effects of statins on blood pressure (BP), while others reported data on BP together with other parameters. Some of the animal or human studies do not show an association between statin treatment and BP changes, whereas others usually report mild but significant reductions. Among the latter, all clinical studies using ambulatory BP recordings show a significant drop in both systolic and diastolic BP in hypertensive patients. In addition, accumulating evidence has identified a number of statin actions that may be involved in BP lowering. Overall, current evidence suggests that statins can be associated with a mild beneficial effect on BP, but further research is needed to clarify the exact magnitude of this action, as well as its clinical relevance.

Omega-3 fatty acids are essential substances for the development and function of human organism. They cannot be synthesized in humans, and consequently have to be acquired from food, almost exclusively from fish. Omega-3 fatty acids exert potent anti-inflammatory and anti-atherosclerotic actions by interfering with the metabolism of arachidonic acid, modifying lipid composition (mainly lowering triglycerides), improving hemodynamics and reducing cardiac hypertrophy. Recently, clinical and experimental studies demonstrated an anti-arrhythmic effect and a significant impact on survival after myocardial infarction (MI). It follows that omega-3 fatty acids have been widely accepted for clinical use in patients with dyslipidemia or with atherosclerotic disease and in survivors of acute MI. This review briefly explores the metabolic mechanisms and the clinical effects of this class of substances and considers their use in patients with cardiovascular disease.