**10. Meta-analysis of studies on CV risk**

In 2006 Thomson and Danesh published a meta-analysis based on data from 23 relevant prospective studies in which apoB, apoA-I and the apo-ratio were associated with risk of MI (8). They compared risk in the top versus the bottom tertile of baseline values. The relative risks were; apoB 1.86 (95% CI 1.55-2.22, cases n = 6,320), apoA-I 1.62 (1.43-1.83, cases n = 6,333), and the apo-ratio 1.86 (1.55-2.22, cases n = 3,730). ApoB and the apo-ratio were directly related to risk, whereas apoA-I was protective. In that study no results were given for any lipids.

In 2009 the Emerging Risk Factor Collaboration (ERFC) published an extended metaanalysis in which they included 302,430 men and women without previous vascular disease from 68 long-term prospective studies, mostly in Europe and North America (10). During 2.79 million person-years of follow-up, there were 8,857 nonfatal MI, 3,928 coronary heart disease deaths, 2,534 ischemic strokes, 513 hemorrhagic strokes, and 2,536 unclassified strokes. Half of the studies included less than 100 events, and the largest study (ARIC) included 871 cases. In 22 studies on risk of MI and in 8 studies on risk of ischemic stroke they had also measured apoB, apoA-I and the apo-ratio. In 91,307 individuals with 4,499 MI and in 8 studies with 60,571 individuals and 1,192 cases they could compare how well the TC/HDL-C ratio and apoB, apoA-I and the apo-ratio were related to these CV events. In all of these comparisons non-HDL-C, HDL-C, the non-HDL-C/HDL-C ratio, apoB, apoA-I and the apo-ratio, adjusted for age and sex, were significantly related to risk of both MI and ischemic stroke. When additionally adjusted also for blood pressure, smoking, BMI, hypertension, and other lipid markers the HR was 1.50 (95%CI, 1.38-1.62) for the non-HDL-C/HDL-C ratio and 1.49 (1.39-1.60) for the apo-ratio. Interestingly, adjusting for these confounders changed the HR only marginally. These data show that the lipid- and aporatios give similar and significant prediction of risk. Furthermore they also found that apoB had similar risk as non-HDL-C, and apoA-I had similar risk as HDL-C. The ERFC authors concluded that both lipid- and apo-ratios can be used even in the non-fasted state since the apo-ratio and the lipid ratio give similar information. Furthermore, they also discuss that there may be important advantages for using apolipoproteins.

Importantly, the ERFC did not include the three largest studies on risk of MI and stroke related to lipids, apos and the apo-ratio. These are the studies; AMORIS, n = 6,794 first cases of AMI (88), and n = 4,470 first ischemic stroke (101), INTERHEART, cases n = 15, 152 for first MI (59), n = 2,337 for first stroke (108), and the ISIS study, n = 3,510 for first MI (60). These studies were excluded because a complete set of confounding variables were not available (AMORIS), or that two studies were case-control studies (INTERHEART and ISIS). The findings in ERFC are therefore restricted to the results based on only prospective studies with many fewer number of events (total n = 5,691) compared to these much larger studies also covering a world-wide population (AMORIS, INTERHEART, INTERSTROKE and ISIS) (total n = 32,263). So adding all these results to those obtained in the ERFC studies the advantages of the apo-ratio as risk predictor may be even more compelling. Such advantages for clinical use are commented in several sections below and are summarized in the discussion. Results from a recent ERFC publication are also included and discussed in page 39.
