Apo AI comprises 65% of the apolipoprotein of high density lipoprotein (HDL), providing the structural scaffold for its formation. It is also a co-factor for lecithin cholesterol acyl transferase (LCAT), required for esterification of cholesterol to cholesteryl esters.
HDL-cholesterol is involved in the reverse transport of cholesterol from peripheral tissues to the liver, from where it can be excreted. Hence apo A1 deficiency confers increased risk of coronary artery and peripheral vascular disease, even in the absence of other coronary risk factors. Patients with significant arteriosclerosis generally have lower plasma Apo A1 concentrations than a normal population.
Specific genetic abnormalities of the apo A1 gene may be associated with reduced levels of apo A1 and HDL. These are not all associated with increased coronary risk.
Reduced apo AI values are also associated with smoking, diets rich in carbohydrates and/or polyunsaturated fats, dyslipoproteinaemias (eg familial hypo-alphalipoproteinaemia), uncontrolled diabetes, liver disease, chronic renal failure, and some therapies (beta blockers, diuretics, progestins, androgens).
Raised apo A1 concentrations are associated with pregnancy, familial hyperalphalipoproteinaemia, and with drugs such as carbamazepine, phenytoin, phenobarbitone, oestrogens, oral contraceptives, ethanol, niacin, fibrates and statins.
Most genetic hypoalphalipoproteinaemias are caused by mutations in enzymes, and transporters involved in reverse cholesterol transport. Mutations in apoA-I are rare and associated with amyloidosis, peripheral neuropathy and both increased and decreased risks of atherosclerosis.
Serum apo A1 and apo B levels are increasingly recognised as better indicators of atherosclerotic risk than cholesterol and triglycerides alone. Atherosclerotic patients are better distinguished from normal individuals by the finding of increased plasma apo B or decreased plasma apo A1 than by a raised LDL- and low HDL-cholesterol. The ratio of apo A1 to apo B may provide a better index of cardiovascular risk than the individual values.
Clinical Indications:
Apo A1 measurements can be used to characterise patients with genetic disorders which lead to low HDL-Cholesterol levels. There are few prospective studies of apo A1 in cardiovascular risk prediction and in some, HDL-Cholesterol was superior.
Apo A1 assays are theoretically more accurate and precise than HDL-cholesterol methods.
Approximate reference range:
0.8 -1.9g/L
(See individual laboratory report)
Patient preparation:
Patients should follow their normal diet for 3 weeks prior to sampling. A fasting sample is preferred, but non-fasting is acceptable. Standardise posture to reduce effect of change in plasma volume – seat the patient for 5 minutes before sampling. Avoid venous stasis – apply tourniquet briefly before inserting needle and release before drawing the sample.
Sample details:
EDTA plasma or serum (min. vol. 0.5ml).
Stable 4 days at 4°C, 2months at -20°C
Transport – First Class Post (avoid weekends)
Information required:
Age, sex, NHS/Hospital No.
Medication
HDL-cholesterol (if available)
References:
Wald NJ, Law M, Watt HC et al. Apolipoproteins and ischaemic heart disease; implications for screening. Lancet 1994; 343: 75-79
Sniderman AD, Cianflone K. Measurement of apoproteins; time to improve the diagnosis of atherogenic dyslipidaemias Clin Chem 1996; 42: 489-91