Lipoprotein Biomarkers: Apolipoprotein A-1 (Apo A-1)

Optimal Takeaways

Apolipoprotein A-1 is the protein component of HDL. It contributes to HDL’s beneficial effects, such as cholesterol processing, blood clotting moderation, and prostacyclin stabilization. Low levels are associated with CVD, MI, diabetes, and kidney dysfunction. Higher levels are beneficial and are associated with reduced risk of atherosclerosis, cardiovascular disease, peripheral vascular disease, and diabetic complications.

Standard Range: 94.00 - 176.00 mg/dL (0.94 - 1.76 g/L)

The ODX Range: 150 – 210 mg/dL (1.50 – 2.10 g/L)

Low Apo A-1 is associated with acute inflammation (Bardagjy 2019), atherosclerosis, CVD, myocardial infarction, uncontrolled diabetes, nephrotic syndrome, chronic renal failure, hemodialysis, cholestasis, Tangier disease, fish eye disease, familial hypoalphalipoproteinemia, smoking, and excess carbohydrate or polyunsaturated fat intake. Drugs that may decrease Apo A-1 include androgens, diuretics, beta-blockers, and progestins (Pagana 2021).

High Apo A-1 is considered cardioprotective but can also be seen with pregnancy, weight reduction, exercise, and familial hyperalphalipoproteinemia. Drugs that increase Apo A-1 include ethanol, lovastatin, pravastatin, simvastatin, carbamazepine, niacin, phenobarbital, estrogens, and oral contraceptives (Pagana 2019). A higher Apo A-1 is also associated with a reduced risk of insulin resistance and anti-inflammatory and anti-tumorigenic effects (Rahim 2016).

Overview

Apolipoproteins are the protein components of lipoprotein carriers that transport lipids through the blood and lymphatic systems. Several factors, including diet, hormones, and medications, influence hepatic synthesis of apolipoproteins. Apo A-1, the protein component of HDL, is considered protective against heart disease and peripheral artery disease (Pagana 2021). Measurement of apolipoproteins is direct and not calculated, and test preparation does not require fasting (As 2013).

Potential functions of Apo A-1 include activation of the lecithin-cholesterol acyltransferase enzyme that helps HDL esterify and retain cholesterol, stabilization of prostacyclin, and moderation of blood clotting. Low Apo A-1 is considered an independent risk factor for CVD. Apo A-1 was significantly lower in individuals with atherosclerosis in a study of 200 subjects. Mean Apo A-1 was 90.69 mg/dL in patients versus 207.2 mg/dL in controls. Apo A-1 had a substantially higher sensitivity for identifying CAD atherosclerosis than HDL (Rahim 2016).

A higher Apo A-1 level suggests a reduced risk of atherosclerosis. In a cross-sectional study of 90 subjects with acute coronary syndrome, the highest Apo A-1, with a mean of 118.44 mg/dL, was associated with the lowest Gensini score (GS), reflecting the severity of atherosclerosis (Yaseen 2021).                          

In 785 elderly men, Apo A-1 was considered the best predictive marker for CVD and ischemic heart disease mortality. Survivors had a mean Apo A-1 of 151 mg/dL, while those who died of ischemic heart disease had a mean of 133 mg/dL. Researchers concluded that the predictive value of Apo A-1 was superior to that of HDL-C, LDL-C, Apo B, and Apo B/Apo A1 ratio with regard to cardiovascular risk (Florvall 2006).

Meta-analysis of 17 case-control studies suggests that a lower Apo A-1 is also significantly associated with premature coronary artery disease in younger subjects, i.e., in men younger than 55 and women younger than 65, a significant cause of death in this group (Haji 2021). In a cross-sectional study of 50 stroke patients 30-70 years of age, the mean Apo A-1 level in cases was 87.1 mg/dL, while the mean value in controls was significantly higher at 158.9 mg/dL. Notably, HDL-C was reduced significantly, and total cholesterol, LDL-C, and triglycerides were significantly elevated in stroke patients (As 2013).

A decreasing Apo A-1 level is associated with the severity of diabetic retinopathy (DR) as well and may be used in the early detection of the disease. Mean Apo A-1 was 148.86 mg/dL in mild DR, 124.39 mg/dL in moderate DR, and 110.30 mg/dL in severe DR. (Ankit 2017).

References

Ankit, B S et al. “Stronger relationship of serum apolipoprotein A-1 and B with diabetic retinopathy than traditional lipids.” Indian journal of endocrinology and metabolism vol. 21,1 (2017): 102-105. doi:10.4103/2230-8210.196030

As, Shilpasree et al. “A study of serum apolipoprotein A1, apolipoprotein B and lipid profile in stroke.” Journal of clinical and diagnostic research : JCDR vol. 7,7 (2013): 1303-6. doi:10.7860/JCDR/2013/5269.3123

Bardagjy, Allison S, and Francene M Steinberg. “Relationship Between HDL Functional Characteristics and Cardiovascular Health and Potential Impact of Dietary Patterns: A Narrative Review.” Nutrients vol. 11,6 1231. 30 May. 2019, doi:10.3390/nu11061231

Florvall, Gösta et al. “Apolipoprotein A1 is a stronger prognostic marker than are HDL and LDL cholesterol for cardiovascular disease and mortality in elderly men.” The journals of gerontology. Series A, Biological sciences and medical sciences vol. 61,12 (2006): 1262-6. doi:10.1093/gerona/61.12.1262

Haji Aghajani, Mohammad et al. “The association between apolipoprotein A-1 plasma level and premature coronary artery disease: A systematic review and meta-analysis.” International journal of clinical practice vol. 75,11 (2021): e14578. doi:10.1111/ijcp.14578

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Rahim, Salma et al. “Serum Apo A-1 and Its Role as a Biomarker of Coronary Artery Disease.” Cureus vol. 8,12 e941. 24 Dec. 2016, doi:10.7759/cureus.941

Yaseen, Rehab Ibrahim et al. “The relation between Apo B/ApoA-1 ratio and the severity of coronary artery disease in patients with acute coronary syndrome.” The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology vol. 73,1 24. 16 Mar. 2021, doi:10.1186/s43044-021-00150-z