Dyslipidemia

Professor M. Nazrul Islam
MBBS, FCPS, FRCP (Edin), FCCP, FACC
Professor of Cardiology
Head of the Department, Department of Cardiology
Dhaka Medical College, Dhaka, Bangladesh

INTRODUCTION

In the developed societies the major cause of death and premature disability is Atherosclerosis. Moreover, current prediction estimate that by the year 2020 atherosclerotic cardiovascular diseases, notably atherosclerosis, will become the leading global cause of total disease burden. There are 11.8 million deaths per year in the world from cardiovascular diseases, almost double that from cancer. Dyslipidemia plays a vital role in atherosclerotic cardiovascular diseases.

Dyslipidemia is a disorder of lipoprotein metabolism, including lipoprotein overproduction or deficiency. It may be manifested by elevation of the total cholesterol, the low-density lipoprotein (LDL) and the triglyceride (TG) concentrations (hyperlipidemia) and a decrease in the high density lipoprotein (HDL) concentration (hypolipidemia) in the blood. It is also termed as Dyslipoproteinemia.

EPIDEMIOLOGY

Dyslipidemia prevalence is similar in Black and Hispanic Americans and non-Hispanic whites but the latter were significantly less likely to be treated and to have lipid control. These differences are mostly explained by differences in socioeconomic and health care access. Chinese Americans has the lowest prevalence of dyslipidemia which could be related to dietary and other cultural differences that result in lower total and LDL concentrations.The prevalence of some common forms of dyslipidemia is shown in the table 1.

PHYSIOLOGY

Lipid & Lipoproteins in Blood
Cholesterol and triglyceride are the two main lipids in blood. They are carried in lipoproteins, globular particles that also

contain proteins known as apoproteins. Cholesterol is an essential element of all animal cell membranes & myelin sheaths. It also serves as a precursor for steroid hormones and bile acids. Triglycerides also known as triacylglycerols or triacylglycerides are glycerides in which the glycerol is esterified with three fatty acids. They are important in transferring energy from food into cells. Lipoproteins are usually classified on the basis of density which is determined by the amounts of triglyceride (which makes them less dense) and apoproteins (which makes them more dense). The higher the ratio of protein to lipid content the higher the density (Table 2). The lipoproteins are named VLDL (very low density lipoproteins), LDL (low density lipoproteins), HDL (high density lipoproteins) and IDL (intermediate density lipoproteins). VLDL particles transfer endogenously synthesized cholesterol and triglycerides to cells and they eventually become LDL particles. Excess LDL particles are then excreted into the bile. HDL particles are made in liver & intestine and appear to facilitate the transfer of apoproteins. They also participate in reverse cholesterol transport. The least dense particles known as chylomicron, they are normally found in the blood only after eating fat containing foods. TG and cholesterol are packaged to form chylomicron in the intestine and travel via the portal vein into liver & via thoracic duct into circulation.

Digestion

After taking lipid food items lingual lipase hydrolyzes one bond from triglycerides to form diglycerides and fatty acids. In the stomach, Gastric lipase hydrolyzes fat and mixes with water and acid. In the small intestine CCK (cholecystokinin, enzyme secreted from Pancreas) signals gallbladder to release bile for emulsification of fat. Pancreatic lipase enters from pancreas through the pancreatic duct & breaks down triglycerides to a monoglyceride or occasionally to a glycerol. Intestinal lipase also acts on triglycerides with pancreatic lipase. Bile is either reabsorbed and recycled or trapped by dietary fiber and excreted. If excreted; liver must make more bile from cholesterol & thus effectively lowers blood cholesterol. There are four major clinically significant physiologic steps in the lipid metabolism cascade from VLDL to LDL namely; VLDL assembly, hydrolysis by Lipoprotein lipase (LPL), remnant catabolism and LDL catabolism. Defects at any step in the cascade can lead to dyslipidemia.