Faculty Bibliography

Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are emerging as epidemics of the 21st century and are important components of the metabolic syndrome (MS). Evidence demonstrates a relationship between HTN, T2DM, and several vascular and metabolic abnormalities that are components of the MS. HTN affects nearly 70 million Americans and over one billion worldwide; likewise, the MS affects 44% of the US population above the age of 60 years and is rapidly increasing. HTN associated with the MS has certain pathophysiologic characteristics that provide clinical challenges. There is growing evidence that tissue activation of the renin-angiotensin system contributes to endothelial dysfunction, microalbuminuria, insulin resistance, and subsequent increased risk for cardiovascular and chronic kidney disease. The notion that HTN is a metabolic as well as a vascular disease provides a new treatment paradigm.

Thromboembolic events contribute significantly to the morbidity and mortality in cancer. Effective and safe anticoagulation - mainstay in prevention and treatment of thrombosis - remains very challenging clinical task in oncology patients - population of high rate of treatment failure, bleeding complications and thromboembolic events recurrences. Prospective randomized clinical studies have documented that with advent of low molecular weight heparins new possibilities for thrombosis treatment and long-term prevention with more convenient and safe anticoagulation have emerged. Considerable advances have been achieved at present time in our understanding of the pathobiology of thrombogenesis in human malignancies, particularly of the interactions between coagulation cascade reactions and processes of tumor growth and dissemination. This builds up a new challenge for modern oncology - appreciation of the hypothesis of anti-malignant effects of anticoagulants, which could influence the outcome of human cancer. Antineoplastic effects of antithrombotic drugs have been reported in various experimental models. Heparins have been the most extensively studied and have been shown to reduce the primary tumour growth and its metastatic spread. Joint evidence from fundamental research and from several randomized clinical trials, observing beneficial impact of low molecular weight heparins therapy on cancer patients survival, dictate the need for further scientific steps to confirm biological effects of heparins in human malignancies. The evidence is started to accumulate, that clinically approved heparins have different abilities to influence some processes of metastasis spread. The experimental work towards development of heparin derivates with low anticoagulant activity, but with potential inhibitory effects on tumor cells migration is in progress.

Primarily statin drugs inhibit hepatic 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is responsible for the reduction in circulating low-density lipoprotein (LDL) cholesterol. Several findings from recent research studies indicate that statins have multiple actions that favorably influence key factors involved in the atherogenic process. These so-called pleiotropic properties affect various aspects of cell function, inflammation, coagulation, and vasomotor activity. These effects are mediated either indirectly through LDL cholesterol reduction or via a direct effect on cellular functions. Such actions may contribute to the early cardiovascular benefit observed in several outcome trials with statin drugs therapy. Although many of the pleiotropic properties of statins may be a class effect, some may be unique to certain agents and account for differences in their pharmacological activity. This review summarise the results of the major outcome trials of statins and non-statins therapy and the possible mechanisms beyond lipid lowering contributing to plaque stability.