Prepared by: Mark O'Doherty and Maria Hughes, UKCRC Centre of Excellence for Public Health, Queens University Belfast, United Kingdom
Details of collected information about apolipoprotein assessment in CHANCES cohorts are displayed in the attached Excel tables for ApoA1 and ApoB.
ApoB is the primary structural component of the atherogenic LDL particles, and is essential for the binding of LDL particles to the LDL receptor for the absorption and catabolism of LDL cholesterol. An excessive number of ApoB-containing particles are one of the main triggers in the atherogenic process, as it is the ApoB molecule in each particle that leads to entrapment of the atherogenic lipoprotein in the arterial wall (Walldius & Jungner, 2004). ApoA1 interacts with HDL receptor and stimulates lecithin-cholesterol acyltransferase enzyme resulting in esterification of cholesterol, the essential step in the process of reverse cholesterol transport. ApoA1 also manifests anti-inflammatory and antioxidant effects (Walldius & Jungner, 2004). Additionally, the ratio of ApoB/ApoA1 is predictive of cardiac risk. This ratio suggests that the higher the value of ApoB/ApoA1, the more cholesterol is likely to be deposited in the arterial wall, thereby provoking atherogenesis and hence also increasing CVD risk (Walldius & Jungner, 2004). McQueen et al. reported that the nonfasting ApoB/ApoA1 ratio was superior to any of the cholesterol ratios for estimation of the risk of acute myocardial infarction in all ethnic groups, in both sexes, and at all ages, and it should be introduced into worldwide clinical practice (McQueen et al, 2008). This makes ApoA1 and ApoB important within CHANCES because conventional lipid measures tend to lose predictive power in elderly patients (Moller et al, 2006).
However, only three cohorts can provide data: MORGAM, RES and SENECA, with no repeated measurements. RES (RSI) and Seneca have both measurements at baseline, and MORGAM has measurements within a subsample of participants in the Biomarker Sub Study.
Most cohorts have used fasting samples (e.g. overnight), but this is variable between the cohorts participating within the MORGAM Biomarker Sub Study (see http://www.thl.fi/publications/morgam/qa/baseline/chol/table3.htm). However, as with cholesterol measurements, studies have shown that lipid profiles change minimally in response to normal food intake (Langsted et al, 2008; Mora et al, 2008), and nonfasting lipid profiles may predict increased risk of cardiovascular events (Langsted et al, 2008). All three cohorts have used serum for the measurement of ApoA1 and ApoB.
As explained in an earlier section, the delay between sample collection and analysis varies across the cohorts. RES stored samples at -20°C, whereas SENECA stored samples at -80 °C. MORGAM cohorts vary but freezing is acceptable if at a temperature of -20°C for 1 year or at a temperature of -60°C for a longer period. Vials should be kept tightly closed. This was important within MORGAM as some analyses did not occur until several years from baseline, within the Biomarker Sub Study.
Table 4. ApoA1 and ApoB
| Cohort BL | ApoA1 | ApoB |
|---|---|---|
| MORGAM | 25,119 | 25,118 |
| RES (RS-1) | ~7000 | ~7000 |
| SENECA | 2146 | 2146 |
| Total | ~ 34,265 | ~ 34,264 |
References
Langsted A, Freiberg JJ, Nordestgaard BG. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction. Circulation. 2008;118:2047-56.
McQueen MJ, Hawken S, Wang X, et al. Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study. Lancet. 2008;372:224-33.
Moller CS, Zethelius B, Sundstrom J, et al. Impact of follow-up time and re-measurement of the electrocardiogram and conventional cardiovascular risk factors on their predictive value for myocardial infarction. J Intern Med. 2006;260:22-30.
Mora S, Rifai N, Buring JE, et al. Fasting compared with nonfasting lipids and apolipoproteins for predicting incident cardiovascular events. Circulation. 2008;118:993--1001.
Walldius G, Jungner I. Apolipoprotein B and apolipoprotein A-I: risk indicators of coronary heart disease and targets for lipid-modifying therapy. J Intern Med 2004; 255: 188--205.
