Atherosclerotic cardiovascular disease (ASCVD) is one of the worldwide leading cause of cardiovascular morbidity and mortality. In 2013 coronary artery disease and cerebrovascular disease were the first and third causes of death, which attributed to 84.5% cardiovascular death and 28.2% of all-cause mortality, respectively. Experts predict these numbers to increase in the future due to the transformation of the human lifestyle, particularly fast-food diet, and sedentary living. It also contributed to substantial morbidity because coronary heart disease (CHD) is one of the most important etiology of heart failure, specifically ischemic cardiomyopathy. Due to better healthcare systems and technology, many CHD patients that experienced acute ischemic events survived but later developed heart failure. The relationship between cholesterol and heart disease is well-established. Therefore, following appropriate guidelines for screening is of paramount importance.
Cholesterol is a sterol compound found in most human body tissues. From a physiologic standpoint, cholesterol and its derivatives are vitally crucial for cell membranes and myriad metabolic processes in the body. Also, cholesterol is used to make hormones, fat-soluble vitamins, and bile acids. The primary source of cholesterol is from animal-based foods, such as eggs, dairy, and cheese. Based on density, cholesterol can classify as high-density lipoproteins (HDL), low-density lipoproteins (LDL), or very-low-density lipoproteins (VLDL). Triglycerides are also part of the blood-lipid profile. Of note, LDL, VLDL, and triglycerides have been correlated to increased risk of CHD, while the reverse appears to be true for HDL. Thus, higher HDL levels confer a protective effect on CHD and all-cause mortality.
Traditionally, when patients were scheduling for cholesterol testing, they needed to fast for more than eight hours. The reason behind this laboratory routine is to avoid triglyceride elevation postprandially. However, recently, routine fasting is not mandatory for every patient before cholesterol testing. Nevertheless, some circumstances require patients to fast. Thus, the decision to fast or not to fast depends on the clinical question being asked by the respective physician, as outlined below:
Then, patients will undergo a venous blood sampling of 0.5 to 1 mL, mostly through their antecubital vein. The container for the specimen must be a gel-barrier transport, green-top (heparin) tube, or lavender-top (EDTA) tube. Then, the serum must be separated from other blood components within 45 minutes of collection. Samples should be stored at room temperature.
The LDL cholesterol estimation can proceed with two distinct methods; indirect and direct. The former approach utilizes the Friedewald cholesterol estimation formula. On the other hand, the latter method utilizes homogeneous assays. In unreliable conditions, such as triglyceride >400 mg/dL, the direct methods can be used to supplement the Friedewald calculation, which has shown to able to meet the standard requirements set by National Cholesterol Education Program (NCEP) for LDL-C testing. When used for non-fasting samples, the direct method was precise and accurate (CV <4% and bias <4%).
Nonetheless, there were several limitations to direct methods. A study of comparison between direct and indirect methods with the reference method of the ultracentrifugation in HIV patients, which hypertriglyceridemia are common, found that no adequate agreement between these two tests with the ultracentrifugation. When TG is more than 400 mg/dL, the direct method tends to overestimate the actual LDL, whereas the indirect method tends to underestimate the actual LDL levels.
There are many major clinical practice guidelines set by several colleges and societies with their subtle differences between them. However, the primary goals of these clinical practice guidelines are all the same, which are cholesterol testing to prevent CAD in healthy populations or primary prevention and to provide early detection and slow down the progression of diseases or secondary prevention.
Cholesterol screening is an integral part of primary and secondary prevention of ASCVD. It can detect a vulnerable population that may be asymptomatic but with a high risk of ASCVD due to genetic predispositions. Additionally, it can detect cholesterol elevations secondary to other diseases, such as diabetes, chronic kidney disease, and HIV infection, or due to drug usage, such as oral contraceptive drugs and others. Furthermore, abnormally high levels of cholesterol components might indicate familial hypercholesterolemia.
Occasionally, when screening for cardiovascular disease by cholesterol test, the result might reveal low or even untraceable levels of LDL-C. When the LDL is < 80 mg/dL, hypobetalipoproteinemia might be suspected, whereas an undetected level of LDL signifies abetalipoproteinemia.
*When non-fasting triglycerides concentration exceeds 5mmol/L (440 mg/dL), obtaining a fasting plasma sample may be considered.
The NCEP has also set the LDL-C concentrations and their respective labels in adult >18 years old, with <100, 100 - 129, 130 - 159, 160 - 189, and >= 190 mg/dL identified as desirable, above desirable, borderline high, high, and very high, respectively. For children and adolescents, cholesterol concentrations of <110mg/dL, 110 - 129 mg/dL, and >= 130 mg/dL were deemed acceptable, borderline high, and high, respectively.
The original Friedewald equation is total cholesterol (TC) = HDL + LDL + Triglycerides( TG)/5, and it is comparable to the ultracentrifuge method of lipoprotein quantification. However, three conditions preclude the use of this equation, explain as follows:
Therefore, a new estimation method is proposed by Martin et al. Their estimation is more accurate because it does not use fix ratio between TG and VLDL, but it incorporates adjustable factors for the ratios of triglyceride and VLDL. Consequently, when the LDL is very low, or the TG is very high, i.e.,>400 mg/dL, this new estimation gives more accurate results. This equation has also shown to be superior compared to the Friedewald equation for non-fasting samples.
LDL-C and HDL-C levels are essential for calculating the 10-year risk of ASCVD derived from the Lloyd-Jones et al. study, which is applicable for men and women, age 40 to 79, and African American/Non-Hispanic White. However, for other ethnicities, Non-Hispanic White is used. Nonetheless, it can overestimate or underestimate the risk.
Another risk-estimation tool identified as heart score, which is adopted by the European Society of Cardiology, also incorporates total cholesterol and HDL levels. It derives from a study by Conroy et al., which involved 12 European cohort studies, 250,000 patient-data sets, with 3 million person-years of observation, and 7000 fatal cardiovascular events.
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