Several epidemiological and clinical studies have constantly and reliably documented that LDL-C constitutes the chief atherogenic lipoprotein for evolving ACS. Substantially, it is viewed as the principal target for lipid-lowering therapies if we targeted to cardiovascular-disease prevention and treatment [9, 10]. Surprisingly, many individuals with ACS may have normal or even low LDL-C concentrations so there was a compelling evidence of developing the prediction of cardiovascular risk by measuring numerous forms of apolipoproteins [11]. ApoB/ApoA1 ratio was recommended as an accountable risk marker of acute myocardial infarction, unlike the TC/HDLc ratio [7].
Our study included 90 patients admitted with ACS. They were divided according to their presentation into 3 groups: STEMI, NSTEMI, and unstable angina. All the patients underwent coronary angiography and were further subclassified according to their Gensini scores into 3 groups: high Gensini score > 47, intermediate Gensini score (24–47), and low Gensini score < 24. Serum Apo B and Apo A1 levels were measured and compared with their Gensini scores.
We found a strong positive correlation of both Apo B and ApoB/ApoA1 in predicting high Gensini scores (scores ≥ 47) in patients who suffered from acute coronary syndromes (P value <0.001). Patients with NSTEMI and STEMI had significantly higher Apo B/Apo A 1 ratio and Apo B levels than those with UA (P value <0.05). On the contrary, no significant correlation between Apo A and Gensini scores was found (P value >0.05). It is known that each particle of the atherogenic lipoproteins like low-density lipoprotein, very-low-density lipoprotein, intermediate-density lipoprotein, and lipoprotein (a) carries a single ApoB100 molecule. Hence, the plasma ApoB100 concentrations notably reflect proatherogenic potentials. On the other hand, ApoA is the key apolipoprotein component of high-density lipoprotein which represents the ApoA serum content whereby antiatherogenic potentials are witnessed. Thus, the ApoB100/ApoA1 ratios represent the balance between the harmful and beneficial potentials. The higher the ApoB100/ApoA1 ratio, the more developed atherogenic potentials we get and/or the less antiatherogenic potentials we attain [12].
Similarly, Tian et al. studied 2256 patients presented with CAD, and they reported a significant association between ApoB/ApoA1 ratios and Gensini scores among these patients [13]. Another study conducted by Song et al. on 792 angiographically defined CAD patients argued that the ApoB/ApoA1 ratios could be a convenient predictor for the coronary stenosis severity in CAD patients [12].
In an evaluation of 170 thousand Swedish subjects, the AMORIS study (Apolipoprotein-related Mortality Risk) showed that Apo B/Apo A-1 ratios were identified as a single variable which was closely associated with attributable risk of fatal MI, predominantly when lipid levels fall within the range of desirable values [5].
Additionally, the INTERHEART study examined about 30 thousand individuals in 52 countries and concluded that the Apo B/Apo A-1 ratios were associated strongly with the prediction of MI than other traditional risk factors as hypertension, smoking, and diabetes regardless of gender, age, and ethnic group [14].
Moreover, Gensini scores presented in this study were significantly elevated in diabetic than non-diabetic patients (P value <0.05). These findings come in agreement with a previous study by Du et al. [8] which was carried on 380 diabetic patients, and they concluded that the baseline ApoB/ApoA-1 was typically superior to other lipid and lipoprotein parameters in predicting high GS (scores ≥ 47) in diabetic patients with newly diagnosed CAD. The best cutoff value of ApoB/ApoA-1 in predicting for high GS in DM patients with CAD was 0.72 (with 61.2% sensitivity and 62.1% specificity). In our study, the best cutoff value of ApoB/ApoA-1 was 0.8 (with a sensitivity of 90% and a specificity of 70%).
Similar to our results, Walldius et al. suggested cutoff points for the Apo B/Apo A-1 ratios of 0.8 and stated that the high values could represent an increased hazard of cardiovascular events [15].
Saputri et al. studied 182 patients with ACS and declared that the high Apo B/Apo A-1 ratios ≥ 0.865 resemble an independent predictor of major cardiovascular events with a three-folds risk increase if compared to Apo B/Apo A-1 group ratio < 0.865 during the follow-up [16].
Moreover, Kaneva et al. investigated 157 apparently healthy men with normolipidemia and concluded that the subjects with ApoB/ApoA-1 higher than 0.90 had more atherogenic lipid profile. Thus, the ApoB/ApoA-1 ratio could be classified as a sensitive marker for atherogenic risks [17]. Additionally, Cunanan et al. investigated 95 patients with ACS and revealed the existence of elevated Apo B levels [18].
The Quebec Cardiovascular Study studied 2155 Canadian men to assess superiority of Apo B on other conventional lipid parameters for increased cardiovascular risks. After a 13-year follow-up period, the study remarked the increased Apo B levels as an independent risk factor for ischemic event prediction even with desirable levels of LDL-C [19].
In the study carried out by Hong et al. on 280 patients with NSTEMI who underwent PCI; Apo B and Apo B/Apo A1 ratios were associated with the total occlusion of infarction-related artery in the cases [20]. More recently, Rebecca et al. conducted research on 75 cases with ACS and 69 controls, and they suggested that adding ApoB and ApoB/ApoA1 to the traditional lipid profile would be more helpful in predicting early onset ACS [21].
In a large-scale study, 1414 males and 1436 females with no history of MI were evaluated for 13 years. The results confirmed the strong association between high Apo B levels and increased risk of MI, whereas increased Apo A1 levels were insignificantly associated with low risks of MI. However, the multivariate analysis displayed that the Apo B/Apo A1 ratios were associated strongly with the MI risks, even after age, body mass index, smoking, diabetes mellitus, and hypertension considerations [22].
Hong et al. demonstrated that the ratio of apoB/apoA-1 might confer as the best discriminator for the severity of CAD in diabetic patients; moreover, the higher ratios of apoB/apoA-1 were associated with more severe the CAD would be when assessed with GS [23].
In our study, no significant difference in Apo A1 levels between the studied patients was found (P value >0.05). Similarly the Quebec study and the Northwick Park Heart study did not find any significant association between ApoA and CAD risks in multivariable analysis [19]. On the contrary, the AMORIS study concluded that ApoA-1 had an important protecting role against fatal MI. The suggestion retained its close predictive power even if added to a total cholesterol and triglyceride model [5].
One explanation for the lack of statistical significance of Apo-A may be the fact that the present study and several other studies were smaller in sample sizes than AMORIS in which 175,000 participants were included. Thus, such smaller studies might not be eligible enough to express a moderate protective power of ApoA-1 [5].
Study limitations
There are some limitations of our study that must be addressed: (1) the small number of study population, the full lipid profile was not taken to compare the predictive power of Apo B, and Apo B/Apo A1 ratios with LDL and triglycerides in detection of severe coronary artery disease, we failed to exclude patients who were already on statin therapy before presentation with ACS and lastly there was no follow-up for the patients with higher levels of ApoB and ApoB/ApoA ratios in order to detect early and late cardiovascular events.
