Dyslipidemia Disease Background

Introduction

Dyslipidemia is an abnormality in lipoprotein metabolism that results in elevations of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and/or non-high-density lipoprotein cholesterol (non-HDL-C) levels, or significantly reduced high-density lipoprotein cholesterol (HDL-C) levels. An increase in serum concentration of TC, LDL, TG, or non-HDL-C is equivalent to an increased risk for cardiovascular diseases (CVD). 

Dyslipidemia_Disease Background

Epidemiology

The prevalence of an abnormality in one or more lipid fractions would depend on the population being studied, highest in those with premature coronary heart disease (CHD). Aside from those with CHD, the prevalence of dyslipidemia also increases with age, and strongly influenced by factors such as diet (ie saturated fat and cholesterol content) and obesity. In 2008, the World Health Organization (WHO) estimated that the global prevalence of hypercholesterolemia was 39%, much higher in females (37% for males and 40% in for females). Hypercholesterolemia is notably a feature of wealthy western countries, being highest in Europe (53.7%) and America (47.7%). However, recent studies show a decreasing trend in total cholesterol in these regions largely due to a decline in non-HDL cholesterol and an increase in mean HDL.  

In Southeast Asia, based on WHO, the overall prevalence of dyslipidemia is much lower than its western counterparts at 30.3%. However, the prevalence of dyslipidemia across the Asia Pacific region is highly variable, ranging from 9% in Indonesia to around 46% in the Philippines. The estimated prevalence of hypercholesterolemia in Malaysia is around 38%, similar in both rural and urban populations). High prevalence of hypercholesterolemia was also reported in Malaysian young adults aged 30-34 at 27.9%.

Pathophysiology

All lipids circulate in the blood in the form of lipoproteins, which have 5 types. These include chylomicrons, VLDL, intermediate-density lipoprotein (IDL), LDL, and HDL. Among these, chylomicrons are the largest of the lipoproteins and are the ones responsible for transporting dietary lipids from the intestine to the liver where they are metabolized into smaller and denser remnants, IDL. VLDL particles, which are formed in the liver, carry endogenous triglycerides and, to a lesser extent, 10-15% of the total cholesterol. These VLDL particles serve as precursors to LDL. LDL is the primary atherogenic lipoprotein associated with increased risk for CVD, carrying as much as 60-70% of the total cholesterol to the periphery. VLDL particles may also be atherogenic independent of LDL when levels exceed 200 mg/dL. In contrast, HDL is protective against CVD.  

Etiology

Dyslipidemia is one of the top 5 risk factors for coronary heart disease and myocardial infarction. It may have roots in one or more of the following mechanisms: Dietary causes, secondary causes, and genetic causes. Excessive dietary intake of saturated and trans fat is an important cause or contributor to elevated LDL-C. Additionally, excessive intake of refined carbohydrates and simple sugars increases triglyceride levels. Refined carbohydrates and sugars are also associated with insulin resistance and have adverse effects on LDL-C, LDL-C size, VLDL, HDL-C, HDL functionality, vascular inflammation, oxidative stress, and vascular immune function.  

With regards to secondary causes, many specific diseases and conditions are associated with dyslipidemia such as cholestatic liver disease, diabetes mellitus, renal diseases (eg nephrotic syndrome, chronic renal disease), hypothyroidism, and obesity. In addition, tobacco use, medications (eg beta-blockers, thiazide diuretics, glucocorticoids, estrogen therapy), heavy metals, and toxins also induce dyslipidemia.   

Lastly, genetic causes may include monogenic and polygenic defects. Among those suffering from hypertriglyceridemia, polygenic determinants are much more common than monogenic disorders. In the case of familial combined hyperlipidemia (FCHL), there is hepatic overproduction of apoB-100-containing particles (ie VLDL and LDL), thus resulting in increased total cholesterol, LDL-C, triglycerides, and apolipoprotein B (apoB) levels. 

Classification

Hypercholesterolemia  

Hypercholesterolemia is defined if the patient has increased LDL, TC, and LDL-C.    

Hypertriglyceridemia  

Hypertriglyceridemia is a state where very-low-density lipoproteins (VLDL) and TG are significantly increased. The desirable level of TG is <1.7 mmol/L (<150 mg/dL). Moderate or high hypertriglyceridemia is when the TG level is 1.7-5.6 mmol/L (150-499 mg/dL). Severe or very high hypertriglyceridemia is when the TG level is >5.6 mmol/L (≥500 mg/dL).  

Etiologic factors include heredity, obesity, type 2 diabetes mellitus (T2DM), high carbohydrate diet, renal disease, and medications (eg corticosteroids, Tamoxifen, Ciclosporin, estrogens, protease inhibitors, Isotretinoin).  

Combined Dyslipidemia  

Combined dyslipidemia is defined if the patient has increased LDL, VLDL, TC, LDL-C, and TG.