Hypolipidemic Therapy and HDL

Statins significantly reduce cardiovascular events by reducing low-density-lipoprotein cholesterol (LDL-C). However, despite achieving the LDL goals, a substantial residual risk remains. It appears that low levels of high-density lipoprotein cholesterol (HDL-C) constitute another independent risk factor for coronary artery disease (CAD). Therefore, raising HDL levels appears an attractive target to further reduce the cardiovascular risk. However, classical HDL-reducing drugs (nicotinic acid derivatives, fibrates) are not well tolerated and newer agents (torcetrapid), which seemed effective in doing that, had to be withdrawn due to increased mortality. Nevertheless, due to the importance of HDL in influencing the cardiovascular risk, efforts in developing safer drugs are continuing. Such pharmacological developments, as well as the nonpharmacological approaches to increase HDL, and other HDL-targeted therapies are discussed in this overview. I N T R O D U C T I O N Cardiovascular disease remains the leading cause of morbidity and mortality in the developed countries. Over the last two decades we have witnessed an impressive reduction in cardiovascular risk mainly with the use of 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins), which are directed to reduce low-density-lipoprotein cholesterol (LDL-C). The use of these drugs has resulted in a 21% reduction in the risk of major cardiovascular (CV) events, for every 39 mg/dl (1 mmol/l) decrease in LDL-C. More aggressive LDL lowering using high-dose statins has led to even greater reductions in the risk of future CV events. However, despite achieving the LDL goals recommended by ATP III guidelines, a substantial residual risk remains, and it appears that an approximate 70% of coronary events have not been prevented in statin trials. On the other hand, early epidemiological data showed that low levels of high-density lipoprotein cholesterol (HDL-C) constitute an independent risk factor for coronary artery disease (CAD). Therefore, raising HDL levels appears an attractive target in the effort of further reducing cardiovascular risk. E P I D E M I O L O G Y From the 1970s, the Framingham study showed that low HDL levels were associated with increased risk of cardiovascular events. More recent data confirm these observations, suggesting that a 2-3% increase in CV risk results from every 1mg/dl decrease in HDL-C. The inverse relationship between HDL and CAD was also demonstrated in ATHENS CARDIOLOGY UPDATE 2010 First Department of Cardiology, Evagelismos General Hospital of Athens, Athens, Greece HOSPITAL CHRONICLES 2010, SUPPLEMENT: 184–192