How Do Apolipoproteins ApoB and ApoA-I Perform in Patients with Acute Coronary Syndromes

Abstract

Acute coronary syndromes are the leading cause of hospitalization and death. Results from recent stu - dies suggest that apolipoprotein measurement and apoB: apoA-I are superior to traditional lipids in the estimation of coro nary risk. We compared apolipoprotein concentrations and apoB:apoA-I with traditional lipid measures and athe ro - genic indices in patients diagnosed with acute coronary syndromes (ACS) within 6 hrs from the onset of chest pain. A study group consisted of 227 patients diagnosed with ACS (STEMI=60, NSTEMI=66 and UA=105). Clinically healthy volunteers (n=85) served as controls. Measure ments of cardiac TnI, lipid profile, hsCRP, apolipoprotein A-I and apoB100 were performed and apoB:apoA-I, TC-HDL-C, LDL-C:HDL-C ratios were calculated. Patients had increased LDL-C (>3.0 mmol/L) and non-HDL-C (>3.4 mmol/L). Triglycerides were below the cut-off value, but patients had significantly higher TG concentrations and lower HDL-C compared to controls (p<0.001). Apo B and apoA-I con - cen tration in patients remained within the accepted range. Atherogenic indices TC:HDL-C, LDL-C:HDL-C and apoB: apoA-I were significantly increased in patients. ApoB:apoA-I ratio in ACS males was within low risk whereas in females corresponded to medium risk. ApoB:apoA-I and LDL-C:HDLC ratios were of good diagnostic utility for discrimination between patients and controls (AUC 0.71 and 0.79; respec - tively). ApoB:apoA-I and LDL-C:HDL-C were of very good diagnostic utility for discrimination between STEMI patients and controls (AUC 0.80 and 0.84). We could not show the superiority of apoB:apoA-I over LDL-C:HDL-C as the discr i - Introduction According to data published in the National Reg - istry of Acute Coronary Syndromes (PL-ACS) every year in Poland 140.000 subjects are diagnosed with acute coronary syndromes (ACS) (1). Acute coronary syndromes are a group of disorders developing as a consequence of atherosclerosis and characterized by changes in the coronary circulation, whose common feature is the significant reduction or cessation of blood flow in the coronary arteries. The most com - mon cause of circulatory disorders is a blood clot formed at the rupture of atherosclerotic plaque. No vel cardiac biomarkers are used to identify patients with ACS even when there is no evidence of cardio my ocyte damage (myeloperoxidase, ischemia-modi fied albu - min, heart-fatty acid binding protein). Simi la rly, novel biomarkers are assessed that may be re gar ded as risk discriminators of cardiovascular disease (CVD) with a predictive value for future events. Apolipoprotein B (apo B) and apolipoprotein A-I (apo A-I), either sepa - rately or together as a cal cu lated apoB:apoA-I ratio, may predict CVD risk more accurately than traditional lipid pro file measurement. Each proatherogenic lipoprotein fraction: VLDL, IDL, and LDL contains one apo B molecule per par - ticle, therefore the serum concentration of apo B re - flects the total number of atherogenic particles (2). HDL is the only antiatherogenic lipoprotein and its major structural protein is apo A-I. This protein pro - duced both in the liver and intestine is involved in reverse cholesterol transport carrying excess choles - terol from peripheral tissues back to the liver for ex - cretion (3). In spite of the availability of standardized com - mer cial assays, apo B and/or apoA-I are not yet widely measured in routine medical laboratory prac tice. Data sug gest that measurement of apo B po ten tially could pro vide several advantages over the con ventional measu re ment of LDL-cholesterol (LDL-C) and non- HDL-C as a cardiovascular disease risk in dex. Apo B can be mea sured directly and with a high accuracy and pre cision in the nonfasting state (4). The reliability and reproducibility of apo B assays are comparable to those expected for non-HDL-C, a meas ure of all the cholesterol in atherogenic lipo proteins (5). The optimal value for LDL-cholesterol (LDL-C) is <2.6 mmol/L, for non-HDL-C it is <3.4 mmol/L and the opti mal apo B concentration is <0.9 g/L (6). Results above these values indicate an increased risk of CVD including acute coronary syndromes. Even the most accurate determinations of LDL-C or non- HDL-C, obta ined after calculation of other para me - ters, do not fully reflect the proatherogenic impact of apo B containing lipoproteins. Studies showed that in sub jects with normal or slightly increased concen - trations of LDL-C, apo B is a better indicator of CVD risk. This comes from the fact that even with a slightly elevated concentration of LDL-C in the blood, with conco mittant hypertriglyceridemia and low HDL-C, very often an increase of small dense LDL particles occurs (7). Small dense LDL have up to 25% lower cho lesterol content per one apo B molecule than large LDL particles (8). Cardiovascular risk is more directly related to the number and size of atherogenic parti cles than to their cholesterol concentration (4, 7, 9). The concentration of apo AI in the circulation is approximately 1–1.3 g/L, and the majority of this protein (99%) is a part of HDL. Concentration of apo A-I below 1.2 g/L is related to greater risk of CVD (10). The cholesterol content of HDL particles is influ enced by blood triglyceride concentration and in, general, hypertriglyceridemia is associated with low HDL-C and low apo A-I values (11, 12). The most use ful as a predictor of CVD risk seems to be the cal culated apoB:apoA-I ratio (13). Previous reports have shown that an apoB:apoA-I ratio of <0.7 and <0.6 for men and women respectively is associated with low risk for cardiovascular disease. ApoB:apoA-I corresponds to the relationship between proathero genic apo B-con - taining lipoproteins and anti-athero genic HDL fraction (13). The advantage of calcula ting this ratio is that the concentrations of both apo lipoproteins are not influ - enced by a nonfasting state and during daytime. In addi tion, with regard to the tests performed after acute coronary syndromes have occurred, it does not matter how much time has elap sed since the blood collection. This is a valuable piece of information, because in pa - tients sus pected with ACS the credibility of lipid mea - surement is questioned if the blood was collected within 24 hours after the incident. Results from recent studies suggested that the se rum concentration of apo B and apo A-I as well as the apoB:apoA-I ratio are related to the occurrence of ACS in different ethnic populations (8). We aimed to com pare apolipoprotein concentrations and the apoB: apoA-I ratio with the traditional lipid measures in patients diag nosed with acute coronary syndromes. 238 Sypniewska et al.: Apolipoproteins B and A-I in acute coronary syndromes mination power of both was almost identical. Determination of apolipoproteins should not be recommended for routine clinical use, however, incorporating apoB and apoB:apoA-I into risk assessment could provide additional important information on cardiovascular risk.