Recent Advances in the Management of Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening and progressive disease characterized by pulmonary vascular remodeling that leads to increased pulmonary vascular resistance and pulmonary arterial pressure, most often resulting in right-sided heart failure. Originally considered to be a disorder of vasoconstriction and vasodilatation, it has become clear that the predominant characteristic of PAH is abnormal cellular proliferation leading to progressive obliteration of the pulmonary vasculature. Current PAH-specific therapies target one of three major pathways involved in development and progression of PAH: 1) The endothelin pathway targeted by the endothelin receptor antagonists (ERAs); 2) the prostacyclin pathway, targeted by prostacyclin analogs and 3) the nitric oxide (NO) pathway, targeted by the phosphodiesterase type 5 (PDE-5) inhibitors.

Status of HDL in Current Scenario.

Cardiovascular disease is a leading cause of death worldwide. Coronary heart disease (CHD) caused by atherosclerosis is the most common cause of morbidity and mortality. Prevention, stabilization and regression of atherosclerotic plaques may have a major impact on reducing the risk of acute coronary events. Low-density lipoprotein-cholesterol (LDL-C) lowering agents, primarily the statins, are the current mainstay in the pharmacologic management of dyslipidemia. Epidemiologic and observational studies have shown that high-density lipoprotein-cholesterol (HDL-C) is also a strong independent predictor of CHD, suggesting that raising HDL-C levels might afford clinical benefit in the reduction of cardiovascular risk. HDL particles have key atheroprotective functions—including the capacity to efflux cellular cholesterol—in addition to having antioxidative, anti-inflammatory, antiapoptotic, antithrombotic and vasodilatory actions. Therapeutic approaches to raise HDL-C levels can target one or more of several mechanisms, including the production of apolipoprotein A-I (apoA-I) or modification of intravascular remodeling of HDL particles. However, the landscape of HDL-raising therapies is now littered with failed therapies, including niacin and the negative results with the cholesteryl ester transfer protein (CETP) inhibitors. This is attributed to potential adverse effects of CETP inhibition such as the generation of HDL particles that have deficient biological activities and a deleterious impact on reverse cholesterol transport and steroid metabolism. Normalization of both defective HDL function and diminished HDL levels should, therefore, be the focus of pharmacological HDL-raising in future studies.