High HDL Cholesterol (Hyperalphalipoproteinemia) Workup

Updated: Jul 15, 2021
  • Author: Basma Abdulhadi, MD; Chief Editor: George T Griffing, MD  more...
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Laboratory Studies

Several studies have found that the vascular effects of high-density lipoprotein (HDL) vary widely and do not always correlate with HDL concentrations in blood. In contrast to healthy individuals’ HDL, research found that HDL in patients with CHD, kidney disease, or diabetes demonstrated no protective vascular effects and was even thought to have some harmful effects. In acute and chronic diseases, the HDL composition itself changes, undergoing modification in complex ways. This needs to be remembered when interpreting lipid panel results, as it may be misleading to assume an equivalence between HDL levels and “good cholesterol.” [2] Currently available blood assays cannot determine the functionality of HDL cholesterol (HDL-C) but can only quantify it in plasma; they may in future be replaced by assays that can assess the composition and functionality of HDL-C.

Prior consumption of food has little effect on the determination of HDL, with postprandial blood samples usually yielding results that can be well interpreted. [2, 15]

Plasma fasting lipid profile

A plasma fasting lipid profile measures low-density lipoprotein (LDL), HDL, total cholesterol, and triglyceride levels.

Lipids in plasma and in isolated lipoprotein fractions are quantified by enzymatic methods. HDL cholesterol levels are determined using a phosphotungstic/magnesium chloride reagent to precipitate the apo B–containing lipoproteins; cholesterol is enzymatically measured in the supernatant. LDL cholesterol levels are calculated using the Friedewald formula or may be measured directly using enzymatic methods.

Plasma HDL apolipoproteins

Studies of HDL apolipoproteins are not routinely performed clinically, but they may be useful research assays. Some clinicians use ratios of apo A-I to apo B-100 for risk assessment, but these measurements are quite expensive and have proven to be no more accurate than the measurement of the ratio of total cholesterol to HDL cholesterol. Measurement of apo C, apo D, and apo E concentrations is not clinically useful.

Apo A lipoproteins include apo A-I, apo A-II, and apo A-IV. Apo C lipoproteins include apo C-I, apo C-II, and apo C-III.

Other apolipoproteins

Other apolipoproteins include apo D and apo E.


Imaging Studies

Whether or not imaging studies are appropriate depends on the clinical manifestations associated with hyperalphalipoproteinemia (HALP), if any. Patients with HALP-related corneal opacification may require ophthalmoscopic examination and corneal or intraocular imaging.


Other Tests

Studies to assess CTEP or hepatic lipase activity are not routinely performed clinically, but they may be useful research assays.

Density ultracentrifugation can be used to isolate and measure high-density lipoprotein (HDL) levels directly.

Nuclear magnetic resonance measurements of HDL levels are used in some specialized laboratories. HDL2 and HDL3 subfraction measurements can also be performed in the specialized laboratories involved in research studies.

A study by Minhas et al suggested that in patients with hyperalphalipoproteinemia, evaluation of cardiovascular disease risk using the QRISK2 calculator be performed using standard population mean HDL values rather than actual measured HDL to avoid underestimation of disease risk. The report found a statistically significant difference between scores using the two types of measurements. [40]



No procedures are usually required.


Histologic Findings

In rare cases of hyperalphalipoproteinemia in which patients have multiple lipomatosis syndrome, histologic examinations may be performed on biopsy specimens. The findings are usually consistent with lipoma.