Lipids are circulating as lipoproteins, consisting of unesterified cholesterol, triglycerides, phospholipids, and protein. There are five major lipoproteins in blood: (1) chylomicrons; (2) very low-density lipoprotein (VLDL); (3) intermediate-density lipoprotein (IDL); (4) low-density lipoprotein (LDL); and (5) high-density lipoprotein (HDL). Each of these classes of lipoproteins transports cholesterol and triglyceride to its designated destinations.
The level of cholesterol plays a vital role in cardiovascular diseases process. A high level of lipids, including cholesterol and triglycerides in the serum, which also termed as hyperlipidemia, leads to a higher risk of developing atherosclerotic cardiovascular disease (CVD). Clinically, obtaining a lipid profile assists in the screening, diagnosing, and managing diseases. Here, we will discuss the indications for testing, the role of lipid profiles, and the relevant health care issues. Generally, a lipid profile or lipid panel consists of the following,
Cholesterol level measurement is from serum. A non-fasting lipid test can be done anytime without fasting; a fasting lipid test requires a 12-hour fast except for water. Total and HDL cholesterol are measured directly from serum. First developed in the 1960s, Friedewald equation has been used widely to estimate LDL-C which is (total cholesterol) – (high-density lipoprotein cholesterol [HDL-C]) – (triglycerides/5) in mg/dL for research as well as clinical purpose. A fixed factor of 5 for the ratio of fasting triglyceride level(up to 4.5mmol/l ) to very low-density lipoprotein cholesterol(TG: VLDL-C) is the assumption from the equation. Optimizing LDL-C level has been the main target for current guidelines, including the European Society of Cardiology, European Atherosclerosis Society, and the American Heart Association and American College of Cardiology. There are several limitations of the Friedewalk equation as follows:
In an extensive cross-sectional analysis, Martin SS et al. proposed a novel calculation that is more accurate than the Friedewald equation regardless of fasting/nonfasting blood samples.
Fasting or non-fasting
While fasting LDL-C is still the standard for initiating lipid-lowering therapy, there has been a heated debate over fasting or non-fasting lipid profile among specialists. The rationale behind the discussion of fasting or non-fasting is because the triglycerides level can be affected by the last intake and the limitations of the Friedewald equation per se. Advantages of the non-fasting lipid profile are its accessibility clinically, simplicity for both patients and medical practitioners; whereas the fasting lipid profile is inconvenient for patients and clinicians as it requires an additional visit. Also, the accuracy of the fasting lipid profile depends on patients' compliance.
Many current guidelines propose that nonfasting LDL-C holds similar significance to that of fasting LDL-C. A fasting lipid panel is a strong recommendation for patients with type 2 diabetes, obesity, medications that may affect lipid levels, such as thiazides and beta blockers, and excessive intake of alcohol.
The 2010 American College of Cardiology Foundation/American Heart Association guideline does not recommend measurement of apolipoproteins, size of lipid particles, and density for cardiovascular risk assessment. (Level III)
Indications for screening or obtaining lipid profile varies between adults and children.
Primary disorders of lipid metabolism such as familial hypercholesterolemia (FH), chylomicronemia, familial combined hyperlipidemia, familial dysbetalipoproteinemia classify according to Fredrickson phenotype. Secondary dyslipidemia can result from diabetes mellitus, hypothyroidism, obstructive liver diseases, chronic renal failure, drugs that increase LDL-C including retinoids, cyclosporine A, and phenothiazines and drugs that decrease HDL-C including progestins, androgens, beta-blockers, and anabolic steroids.
Based on the types of lipid abnormalities, dyslipidemias can be categorized into high total cholesterol (TC), High low-density lipoprotein cholesterol (LDL-C), High non-high-density lipoprotein cholesterol (non-HDL-C), High triglycerides (TG), and Low high-density lipoprotein cholesterol (HDL-C). According to the Adult Treatment Panel III (ATP III), the standard levels per guideline as following:
There are five definitions of the metabolic syndrome:
Among these, The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) is the most widely used. Parameters for the definitions of metabolic syndrome are triglycerides, HDL cholesterol, glucose, hypertension, and obesity, and metabolic syndrome is diagnosed when three or more the followings are abnormal:
Atherosclerotic Cardiovascular disease (ASCVD)
Atherosclerosis is the major culprit in most of the coronary heart disease. Lipids and lipoproteins are established risk factors for developing atherosclerotic cardiovascular diseases(ASCVD). Large clinical trials reported lipid-lowering therapy to reduce the risk of ASCVD events.
Several factors are taken into account in 10-year risk cardiovascular assessment as following,
The 10-year risk for ASCVD falls into the following categories:
Risk-enhancing factors such as family history of premature ASCVD, metabolic syndrome, chronic kidney disease, premature menopause, chronic inflammatory disorders, high-risk ethnic groups (e.g., South Asian), persistent elevations of LDL-C greater than or equal to 160 mg/dL or triglycerides greater than or equal to 175 mg/dL, high-sensitivity C-reactive protein greater than or equal to 2.0 mg/L, and ankle-brachial index less than 0.9.
For dyslipidemia, obtaining a detailed family history is crucial. By identifying family members with any abnormal deposits of cholesterol in the skin or eyes, premature CHD, or those who have elevated cholesterol during childhood assist in establishing a diagnosis. Perform physical examination with attention to abnormal deposits of cholesterol in the skin or eyes, such as tendon xanthomata which mostly present in the Achilles tendons and dorsum of the hands, and xanthelasmas, which are soft and yellow plaques that often present on the eyelids. Fasting lipid profile revealed the majority of the abnormalities. However, an evaluation for causes resulted in secondary hyperlipidemia is warranted. The clinician can offer genetic testing of LDLR, APOB, and PCSK9 gene mutations, even though the benefits are still not well-established.
First and foremost, it is essential to educate individuals on a heart-healthy lifestyle. LDL-C is one of the major culprits in the development of atherosclerotic heart disease. The target level of LDL-C is between 50 to 70mg/dl to prevent plaque formation in the blood vessels. Patients should undergo evaluation for 10-year risk and those with more than 10 percent risk; guidelines strongly recommend statin therapy. Low levels of HDL-C are related to an increased risk of CVD; however, according to recent studies, HDL-C raising therapy showed no clinical benefit; therefore, routine use is not recommended.
Primary prevention recommendations for adults age between 40 to 75 years old With an LDL Level of 70 to 189 mg/dL. High levels of low-density lipoprotein-cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C) are risk factors for coronary heart disease. Large clinical trials have shown that lowering LDL-C levels significantly reduce cardiovascular events and mortality rate; whereas, according to current consensus, HDL-C is not a target for primary prevention in coronary artery diseases(CAD). Nevertheless, recent studies proposed the prognostic value of serum cholesterol efflux capacity in patients with coronary artery disease.
According to the 2018 Guideline on the Management of Blood Cholesterol,, clinicians should target at lowering LDL-C levels by more than 50% with maximally tolerated statin therapy in ASCVD. In very high-risk ASCVD individuals who are already under statin therapy and remain an increased LDL-C level (more than 70mg/dL); clinicians should then initiate additional non-statin therapy such as ezetimibe. Furthermore, individuals on maximally tolerated statin along with ezetimibe, a PCSK9 inhibitor should then be considered. Ezetimibe is preferred before initiating a PCSK9 inhibitor due to its cost and convenience. Begin high-intensity statin therapy despite 10-year ASCVD risk in severe hypercholesterolemia( LDL-C level greater than or equal to 190 mg/dL ). Start moderate-intensity statin therapy regardless of 10-year ASCVD risk in 40 to 75-year-old diabetic patients with a level of LDL-C greater than or equal to 70 mg/dL; for those non-diabetic patients with a level of LDL-C greater than or equal to 70 mg/dL and a 10-year ASCVD risk more than 7.5%, consider a moderate-intensity statin.
Moderate-intensity statin therapy is expected to have a 30 to 50 percent LDL-C reduction, as following,
High-intensity statin therapy is expected to have a greater than or equal to 50 percent LDL-C reduction, as following,
In most of the cases, do not intensify statin therapy for patients who are on moderate-intensity statin therapy. The efficacy of statin therapy should undergo evaluation in six to eight weeks after the initiation. Statin therapy management should take place when statin-induced muscle adverse events, elevated aminotransferase, or renal dysfunction such as proteinuria have developed. However, routine monitoring of serum creatine kinase (CK) levels is not currently a reocmmendation for patients on statins. For medical practitioners, obtaining a baseline CK level should be considered before initiating statin therapy. Education on lifestyle modification, medication compliance, and awareness of new onset of muscle discomforts or weakness is crucial.
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