Therapeutic Advances in Cardiovascular Disease

For many years, the cyclic blood pressure (BP) curve was described exclusively from two specific points of this curve, the highest, called systolic blood pressure, and the lowest, called diastolic blood pressure, both dominating the basis of cardiovascular (CV) hypertensive epidemiology. Nowadays, it is largely admitted that the BP curve should be characterized from pulsatile arterial hemodynamics, thus leading to the definition of novel indices in CV epidemiology. The present chapter details these new aspects.

Recent studies have revealed the clinical usefulness of central blood pressure (BP) as an index of risk for cardiovascular disease. The arterial pulse waveform is the sum of the forward pressure wave generated by left ventricular ejection and a backward propagating wave that is subsequently reflected from the peripheral site, and the time point at which these forward and backward propagating waves merge and the amplitude of the reflected (backward) wave affect the level of central BP. The augmentation index (AIx) has been proposed as a measure of the wave reflection, and its clinical usefulness has also been evaluated. In the process, the non-linear relationship between age and AIx, the prognostic value of AIx, and the various effects of antihypertensive drugs on AIx have been shown. However, the clinical usefulness of AIx has not been established, and several questions about its use remain. Future studies will be needed to address these questions, and may contribute to important changes in the management of cardiovascular disease. In this review, we present recent findings on the AIx and discuss the role of this parameter in clinical practice.

Type 2 Diabetes Mellitus confers an excess risk of cardiovascular disease. The mechanisms involved in the development of the disease are an active field of research, and prompt the development of newer and safer therapeutics with implications for cardiovascular disease. Currently there is increasing awareness of the role of platelet dysfunction, low-grade chronic inflammation and thrombogenesis in the pathophysiology of insulin resistance, T2DM, as well as type 1 diabetes mellitus and cardiovascular disease. This new evolving knowledge has allowed a better understanding of the role of aspirin, an old medication with proven beneficial effects on patients with established cardiovascular disease. The influence of salicylates on insulin resistance, glucose homeostasis, platelet function and inflammatory pathways, in particular related to the activation of the NFκB pathway, is a promising field of active research, and will help in the management of both diabetes mellitus and atherosclerotic-related cardiovascular disease.

Drug-eluting stents (DES) in percutaneous coronary interventions significantly reduce rates of restenosis and the need for new revascularizations compared with bare metal stents. However, as the use of DES has increased dramatically, questions have been raised about their long-term safety. Concerns about an increased risk of late stent thrombosis, particularly beyond the first year of treatment, have arisen and have been exacerbated by sparse and conflicting information, and boosted an intense debate between cardiologists. In this article, we reviewed the most recent information to clarify the conundrum of late stent thrombosis and the long-term safety of DES.

The non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) and cyclooxygenase-2 (COX-2) inhibitors are commonly utilized agents for musculoskeletal conditions. The harmful cardiorenal effects of some nsNSAIDs are well described and thought to be related to inhibition of prostanoid synthesis. Since the non-specific inhibition of both cyclooxygenase enzymes was associated with a higher incidence of gastrointestinal side effects, the selective targeting of the COX-2 enzymes with the COX-2 inhibitors promised and delivered a lower incidence of gastrointestinal side effects. However, the COX-2 inhibitors have not been found to be bereft of cardiorenal side effects. Indeed, some of these agents lead to increased blood pressure, an excessive risk of congestive heart failure and pro-thrombotic effects, especially in high risk populations. These deletrious effects, however, may not be class-specific and possibly related to pharmacokinetics, enzyme specificity and endothelium effects. This article also reviews the body of literature linking the nsNSAIDs and COX-2 inhibitors with important adverse cardiorenal effects and their putative mechanisms.