Isolated low high density lipoprotein-cholesterol (HDL-C): implications of global risk reduction. Case report and systematic scientific review

Abstract

Background: The importance of low high-density lipoprotein cholesterol (HDL-C), elevated non HDL-C (as part of the metabolic syndrome, prediabetes, and type 2 diabetes mellitus), and an isolated low HDL-C is rapidly emerging. The antiatherosclerotic roles of reverse cholesterol transport and the pleiotropic antioxidant--anti-inflammatory mechanistic effects of HDL-C are undergoing rapid exponential growth.

Case presentation: In 1997 a 53-year-old Caucasian male presented with a lipoprotein profile of many years duration with an isolated low HDL-C and uric acid levels in the upper quintile of normal. He developed an acute myocardial infarction involving the right coronary artery and had percutaneous transluminal coronary angioplasty with stenting of this lesion. He also demonstrated a non-critical non-flow limiting lesion of the proximal left anterior descending coronary artery at the time of this evaluation. Following a program of global risk reduction this patient has done well over the past 7 years and remains free of any clinical signs and symptoms of atherosclerosis. His HDL-C and uric acid levels are currently in the normal physiological range.

Conclusion: Low HDL-C and isolated low HDL-C constitute an important risk factor for atherosclerosis. Therapies that lead to a return to normal physiologic range of HDL-C may result in the delay of atherosclerotic progression.

Figure 1

Reverse Cholesterol Transport. This figure demonstrates the process of reverse cholesterol transport. It begins in the arterial vessel wall and with the assistance of the ATP binding cassette transporter A-1 (ABCA-1) and in collaboration with the Apo A-1 protein attached to the outer shell of the nascent HDL-C lipoprotein particle free cholesterol is internalized within the HDL-C lipoprotein particle. The enzyme lecithin cholesterol acyltransferase (LCAT) esterifies free cholesterol (FC) via a lipidation process and internalizes it within the HDL-3, which matures to a larger HDL-2 lipoprotein particle. From this point in time the HDL-3 and 2 particles can enter the hepatic cycle via the Scavenger Receptor B-1 and subsequently excreted in the bile. The alternative pathway is for the larger HDL-C apoA-1 lipoprotein particles to undergo a transference of the cholesterol esters through an exchange process with triglycerides via cholesterol ester transfer protein (CETP) to the ApoB-100 lipoprotein particles and enter the liver for further metabolism via the low density lipoprotein receptor (LDLR) to be subsequently excreted in the bile.

Figure 2

The Atherosclerotic Kitchen Sink. This image portrays the importance of the HDL-C drain in maintaining a certain level of atherogenic lipoproteins within the arterial vessel wall to prevent accumulation and the undesirable possibility of an acute event with overflow or acute coronary syndromes. This simple analogy of homeostasis points to an important concept: That being the frequent need for combination therapy in order to control the various components of the atherogenic lipoprofile. Isolated low HDL-C is certainly a red flag regarding the development of atherosclerosis and CHD and additionally the elevation of low HDL-C levels may have a DRANO-LIKE effect to open a clogged drain in an atherosclerotic arterial vessel wall.