Normal Level of Cholesterol /The level of cholesterol plays a vital role in the cardiovascular disease process. A high level of lipids, including cholesterol and triglycerides in the serum, which also termed hyperlipidemia, leads to a higher risk of developing atherosclerotic cardiovascular disease (CVD).

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 the cardiovascular disease process. A high level of lipids, including cholesterol and triglycerides in the serum, which also termed 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,

  • Total cholesterol
  • High-density lipoprotein (HDL) cholesterol
  • Low-density lipoprotein (LDL) cholesterol
  • Triglycerides

Specimen Collection

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, the  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:

  • The estimated LDL-C level is not accurate in patients with hypertriglyceridemia(up to 4.5mmol/l or 400 mg/dL) – such a setting warrants ultracentrifugal single spin analysis or immunoprecipitation technique
  • There is an underestimation of LDL-C level in patients with lower LDL-C (less than 25 mg/dL or 0.6 mmol/L)
  • There is an underestimation of intermediate-density lipoprotein(IDL), and some VLDL remnants which are considered atherogenic

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.

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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.

Apolipoproteins

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

Indications for screening or obtaining lipid profile varies between adults and children.

  • The National Health and Nutrition Examination Survey (NHANES) for 1999 to 2006 reports a 20% prevalence rate of dyslipidemia among adolescents with a statistically significant higher level of lipids in higher BMI adolescents. Among those adolescents with dyslipidemia, only 0.8% of them might need pharmacological treatment. The guideline by the United States National Heart, Lung, and Blood Institute (NHLBI) expert panel in 2011 recommend that all children should be screened for dyslipidemia to identify children with familial hypercholesterolemia (FH). FH patients are at higher risk for morbidity and early mortality. Fasting lipid test is the recommendation for children with cardiovascular risks, such as hypertension, obesity, diabetes, and family history; non-fasting lipid test is preferable for those without known cardiovascular risks.
  • In adults, the most common indications are:

    • Screening due to a family history of lipid disorder, such as familial hypercholesterolemia
    • Establish the risk of 10-year cardiovascular disease, such as the 2008 Framingham general cardiovascular risk score or JBS3 risk score
    • Pancreatitis
    • Management for atherosclerotic cardiovascular diseases
    • Evaluation for lipid-lowering therapy

Potential Diagnosis

Dyslipidemias

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).

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According to the Adult Treatment Panel III (ATP III), the standard levels per guideline as following

Fasting triglyceride level

  • Normal: less than 150 mg/dL
  • Mild hypertriglyceridemia: 150 to 499 mg/dL
  • Moderate hypertriglyceridemia: 500 to 886 mg/dL
  • Very high or severe hypertriglyceridemia: greater than 886 mg/dL

LDL-C level

  • Optimal: less than 100 mg/ dL
  • Near optimal/above optimal:100 to 129 mg/dL
  • Borderline high: 130 to 159 mg/dL
  • High: 160 to 189 mg/dL
  • Very high: greater than 190 mg/dL
HDL level

  • Low: less than 40
  • High: greater than or equal to 60

Metabolic syndrome There are five definitions of metabolic syndrome:

  • The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III), 2005
  • International Diabetes Federation(IDF), 2006
  • Group for the Study of Insulin Resistance (EGIR), 1999
  • World Health Organization, 1999
  • American Association of Clinical Endocrinologists (AACE), 2003;

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:

  • HDL cholesterol – less than 1.0 mmol/L (40 mg/dL) (men); less than 1.3 mmol/L (50 mg/dL) (women) or pharmaceutical treatment for low HDL cholesterol, i.e., treatment with one or more of niacin or fibrates
  • Triglycerides – greater than or equal to 1.7 mmol/L (150 mg/dL) or drug treatment for elevated triglycerides, i.e., treatment with one or more of niacin or fibrates
  • Glucose – greater than or equal to 5.6 mmol/L (100 mg/dL) or drug treatment for elevated blood glucose
  • Obesity – Waist greater than or equal to 102 cm (men) or 88 cm (women)
  • Blood pressure – greater than or equal to 130/85 mmHg or drug treatment for hypertension

Atherosclerotic Cardiovascular disease (ASCVD)

  • Coronary heart disease presents as myocardial infarction, angina pectoris, heart failure, or coronary death
  • The cerebrovascular disease presents as a stroke or transient ischemic attack
  • Peripheral artery disease, such as intermittent claudication
  • Aortic atherosclerosis and thoracic or abdominal aortic aneurysm, the diseases as mentioned earlier are often generalized as the term cardiovascular disease(CVD)

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.

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Several factors are taken into account in 10-year risk cardiovascular assessment as following,

  • Age (between 20 to 79)
  • Sex
  • Race
  • Systolic blood pressure
  • Diastolic blood pressure
  • Total cholesterol  

    1. LDL cholesterol  
    2. HDL cholesterol  
  • History of diabetes
  • On hypertension treatment?
  • On a statin?
  • On aspirin therapy?

The 10-year risk for ASCVD falls into the following categories:

  • Low-risk (less than 5%)
  • Borderline risk (5% to 7.4%)
  • Intermediate risk (7.5% to 19.9%)
  • High risk (greater than or equal to 20%)

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.

References

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