Dyslipidemia Diagnostics

Lipid profile is obtained from an individual with diabetes mellitus, cardiovascular disease (CVD), cerebrovascular disease, or other cardiovascular disease risk factor(s) or from an individual with a family history or clinical evidence of familial hypercholesterolemia. Clinically significant atherosclerotic cardiovascular diseases (ASCVD) include coronary heart disease (CHD), acute coronary syndrome (myocardial infarction [MI], unstable angina), coronary insufficiency, angina, ischemic stroke, hemorrhagic stroke, transient ischemic attack (TIA), peripheral artery disease (PAD), abdominal aortic aneurysm, and heart failure. Improvement in the lipid profile can result from the treatment of the underlying cause of secondary dyslipidemia.  

In order to diagnose dyslipidemia, it is important to measure plasma lipids such as TC, HDL-C, non-HDL-C computed as (TC - HDL-C), and TG. LDL-C is derived from the Friedewald formula: LDL-C (mmol/L) = TC - HDL-C - (TG x 0.45) or LDL-C (mg/dL) = TC - HDL-C - (TG x 0.2).  

Considerations  

Fasting or a non-fasting plasma lipid profile can be used in screening and in risk estimation. Non-fasting samples can be used to document baseline lipid levels before initiation of statin therapy in patients with clinical ASCVD. Fasting lipid profile is recommended for an initial evaluation in patients with a family history of premature ASCVD, or genetic hyperlipidemia, or for follow-up of patients with hypertriglyceridemia. TC and HDL-C can be measured accurately at any time of the day. TG levels are affected by food resulting in a higher plasma level of about 0.3 mmol/L (27 mg/dL), by alcohol intake within 24 hours prior to measurement, and by smoking during the fasting state. Non-HDL cholesterol can be computed even from a non-fasting lipid profile.  

Friedewald formula can only be used if TG is <4.5 mmol/L (<400 mg/dL) but is only recommended for use during fasting states. In patients with a TG of >4.5 mmol/L (>400 mg/dL), a non-HDL-C of >3.37 mmol/L (>130 mg/dL) should be the alternative primary target of treatment. Non-HDL-C may be considered as a secondary target of therapy in patients with combined hyperlipidemias, diabetes, chronic kidney disease (CKD), or cardiometabolic risk. If TG is >2.3 mmol/L (>200 mg/dL), non-HDL-C is a better indicator of total atherogenic burden.  

Plasma measurement of cholesterol is 3% lower than serum measurements. Levels will be affected by recent acute illness (eg fever, surgery, stroke) and drugs (eg beta-blockers, steroids, thiazides). If possible, measure lipids within 24 hours of myocardial infarction. ≥1 measurement is needed to make a hyperlipidemic diagnosis because of the biological variability.  

Dyslipidemia Screening Tests  

Lipid Profile  

A lipid profile includes plasma or serum TC, LDL-C, HDL-C, and TG.  It is used to ensure that the most accurate lipid assessment is achieved. For lipid screening, both fasting and non-fasting specimens may be utilized. Fasting LDL-C measurement is recommended for patients with high TG levels.    

LDL-C  

LDL-C measurement is recommended as the primary lipid analysis method for screening, diagnosis, and management of dyslipidemia. The direct measurement of LDL-C in certain high-risk patients (eg patients with diabetes mellitus, vascular disease, fasting TG level of >2.9 mmol/L or >250 mg/dL) is recommended. Estimation by Friedewald equation is valid only for values obtained in the fasting state and is largely inaccurate in TG levels of >2.3 mmol/L (>200 mg/dL) and is invalid when TG levels are 4.5 mmol/L (>400 mg/dL).  

HDL-C  

An HDL-C of >1.6 mmol/L (>60 mg/dL) is an independent negative risk factor for dyslipidemia in both sexes. In women, very low HDL-C (<1.03 mmol/L or <40 mg/dL) is an independent risk factor for the development of CVD and mortality, even in the presence of a normal LDL-C and/or TG levels or TC level of <5.2 mmol/L (<200 mg/dL). Women with low HDL-C have a CVD risk elevated to almost 3-fold (as compared with women with high HDL-C).  

It is considered an alternative risk marker, especially in combined hyperlipidemia, diabetes, metabolic syndrome, or chronic kidney disease.  

Non-HDL-C (TC minus HDL-C)  

In patients with moderately increased TG (2.3-5.6 mmol/L or 200-500 mg/dL), diabetes mellitus, obesity, metabolic syndrome, and/or established CVD, or if insulin resistance is suspected, measure non-HDL-C. It provides a better cardiovascular risk assessment than LDL-C alone in patients with moderately elevated TG levels. It shows the total atherogenic burden including particles contained within VLDL, intermediate-density lipoproteins (IDL), LDL, chylomicron remnants, and lipoprotein(a) [Lp(a)]. It can be considered as an additional therapeutic target for residual cardiovascular risk reduction after the LDL-C has been reached.    

Triglycerides  

TG levels of ≥1.7 mmol/L (≥150 mg/dL) may help identify those at risk for insulin resistance syndrome. Persistent TG levels of ≥175 mg/dL may point to a significant increase in the risk for CVD. A very high TG level is associated with an increased risk of pancreatitis.  

Apolipoprotein B  

Target apolipoprotein B (apo B) level to <90 mg/dL (<0.9 g/L) for those at risk of CVD (including those with diabetes mellitus). Target apo B level to <80 mg/dL (<0.8 g/L) for those with established CVD or those with diabetes mellitus who have ≥1 additional risk factor.  

Apo B may help evaluate the success of LDL-C-lowering therapy. It can be considered as an additional therapeutic target to further reduce cardiovascular events in individuals on statin therapy who have achieved their LDL-C goal. It is recommended for risk assessment in patients with high TG levels, diabetes mellitus, obesity, metabolic syndrome, or very low LDL-C levels. It is considered as an alternative risk marker, especially in combined hyperlipidemia, diabetes, metabolic syndrome, or chronic kidney disease.  

Apo B and/or Apo B/Apo A1 ratio calculation and the evaluation in patients with TG of ≥150, HDL-C of <40, prior ASCVD event, type 2 diabetes mellitus, and/or insulin resistance syndrome may help in determining the best treatment strategy. Apo B reflects LDL particle number and is considered a more potent measure of CVD risk as compared with LDL-C and LDL particle size. The measurement of apo B-100 provides a more accurate evaluation of atherogenicity since all atherogenic particles (VLDL, IDL, LDL) contain one apo B-100 molecule.  

Lipoprotein(a) [Lp(a)]  

Lipoprotein(a) is an LDL particle with an Apo(a) moiety that has pro-atherogenic effects attributed to its pro-coagulant and pro-inflammatory effects. It should be measured at least once in a person’s lifetime to identify people who have inherited an elevated Lp(a) level of ≥430 nmol/L (≥180 mg/dL) and have a very high lifetime risk of ASCVD. It should be considered in patients with an estimated 10-year risk of ASCVD that is near the threshold between high and moderate risk.  

Other Diagnostic Tests  

A high-sensitivity C-reactive protein of ≥2 mg/dL and an ankle-brachial index of <0.9 are associated with an increased risk of ASCVD.