The occurrence of acute ST-segment elevation myocardial infarction (STEMI) in the youth is complex and multifactorial; however, many researches have proposed that impaired lipid metabolism plays a major role in the development of cardiovascular (CVS) diseases . Apolipoprotein A (ApoA) is one of the largest structural protein components of the lipid, and mainly, of high-density lipoprotein. Besides its antioxidant and anti-inflammatory properties, it is responsible for stimulating the reverse cholesterol transport, removing the excess cholesterol from the tissues, and relocating it to the liver [2,3]. The diagnostic and therapeutic strategies of assessing such lipoproteins may be useful, and even more sensitive than traditional lipids, for the management and prevention of STEMI, especially in young patients with near-normal LDL levels [4,5]. Given the magnitude of the coronary artery disease (CAD) in the young ages all over the world, particularly in Iraq, and the limited available data on the role of ApoA in early onset STEMI, we conducted this study to both estimate the levels of ApoA in patients diagnosed with early onset STEMI and to assess its relation with CVS risk factors [6,7].
Method and materials
This case-control study was performed at the Azadi Teaching Hospital in Duhok Province, Kurdistan Region, Iraq, between 2018 and 2019. The study included 50 young patients presented with acute STEMI and 40 healthy individuals with the same age and sex and without a history of CAD. Patients aged older than 50 were excluded. For both groups, the major CVS risk factors, namely diabetes mellitus, arterial hypertension, current smoking, dyslipidemia and family history of CAD were recorded. Hypertension was defined as blood pressure in excess of the threshold of 140/90 mmHg, or antihypertensive therapy use. Diabetes mellitus was defined as fasting serum glucose in excess of 126 mg/dl (7 mmol/l) on two occasions, or anti-diabetic therapy use. Hyperlipidemia, and for the purposes of this study, was defined as a fasting serum cholesterol in excess of 200 mg/dl (5.2 mmol/l), LDL more than 100 mg/dl (2.6 mmol/l), HDL less than 40 mg/dl (1 mmol/l) or serum triglyceride in excess of 150 mg/dl (1.7 mmol/l), or the use of statins. Chronic kidney disease referred to level of serum creatine more than 1.2 mg/dl (110 mmol/l) in males and more than 1.0 mg/dl (90 mmol/l) in females. Positive family history of CAD strictly encountered males with ages of 45 years and less and females with ages of 55 years and less [8–12]. These risk factors were defined based on standardized definitions [8–12]. An approximate 5 ml of blood was drawn from patients after a12-hour fasting for estimation of ApoA, lipid profile, serum creatinine and blood glucose. Serum ApoA was estimated by Immunoturbidimetric assay. In the sample of the test, the Anti-apolipoprotein A-1 antibodies react with the antigen to form antigen/antibody complexes by Roche/Hitachi Cobas C systems (Roche Diagnostics, Mannheim, Germany). Other investigations were carried out for all subjects by using commercially available kits on fully auto analyzer (Cobas C 311 analyzer; Diagnostics Roche, Germany). The normal range of ApoA was (104-202 mg/dl). This study was approved by the ethical committee at the Kurdistan Board of Medical Specializations in Erbil, Kurdistan Region, Iraq. All participants were informed about the aim of the study and written consents were given. Data were analyzed using the Statistical Package for Social Sciences (SPSS, version 16.0; IBM, Chicago, Illinois, USA). Continuous variables were calculated as mean ± SD, and categorical variables were presented as counts and percentages. A Chi-square and Fisher exact tests were used to compare categorical variables. A one-way analysis of variance or unpaired t-test was used for continuous variables. A linear regression test was used to identify risk factors of early onset STEMI. P-value <0.05was regarded as significant.
Regarding the association of CVS risk factors with the low ApoA level, Table 1 showed significant associations between low levels of ApoA with smoking and dyslipidemia with P values of 0.025 and 0.007, respectively. Family history of CAD did not achieve significant level. No significant difference in the levels of ApoA between cases and controls was found.
Assessing the mean levels of ApoA, Table 2 showed that the males, current smokers and the dyslipidemia had significantly lower levels of ApoA with P values of 0.014, 0.036 and 0.016, respectively.
Considering ApoA as a dependent variable in linear regression model, independent risk factors among early onset STEMI were the male (P < 0.001) and the dyslipidemia (P ≤ 0.030) as in Table 3
The main findings of this study are the following; first, there was no significant difference in levels of ApoA between patients with early onset STEMI and the healthy age-sex matched individuals; and, second, there was a clear relation between low levels of ApoA and the male, the dyslipidemia and current smokers. This mean that this apolipoprotein is related to the clustering of conventional CVS risk factors in young patients.
The trend of the early onset CAD, including the acute STEMI in developing countries, is alarming. According to recently available data from our area, based on a study conducted in Iraqi Kurdistan by Ameen et al., the prevalence of documented early onset CAD was 31%; which was quite higher than the rates in other parts of the world. That study also showed a clustering of conventional CVS risk factors like smoking, male sex and dyslipidemia among such cases .
In convergence with data by Guerra et al. , this study and the Dallas heart study found no consistent independent relationship between plasma levels of ApoA and coronary artery disease and coronary calcium in whites or blacks’ patients with CAD. In contrast, Barbir et al. showed a positive association between abnormal levels of ApoA and confirmed cases of CAD. It was independent of levels of serum lipids of patients, a situation that refers to the superior sensitivity of ApoA as an indicator of ischemia compared with lipids .
Furthermore, Rahim et al. suggested that serum ApoA might have higher sensitivity in predicting CAD than the serum HDL, and even more, the ApoA-1 is an earlier indicator of CAD especially in younger patients. The higher sensitivity of Apo according to Rahim study may impact the morbidity and mortality of CAD in the long-term .
Despite the absence of a significant relation between low levels of ApoA and positive family of CAD in this study, Freedan et al.  study found that offspring of patients with myocardial infarction had abnormal low serum levels of ApoA and considered them at risk of CAD in the future. However, since the scope of this study is limited by the small sample size, we concluded that ApoA is significantly lower in patients having clusters of CVS risk factors, and based on this conclusion, we do recommend the measurement of ApoA levels in young individuals with multiple CVS risk factors and the application of policies of controlling this factor. Further studies are warranted to see the direct effect of ApoA in the occurrence of early onset STEMI in patients with and without conventional CVS risk factors and evaluate the sensitivity of this indicator in predicting ischemia, particularly in young patients with normal or near-normal serum lipid levels.
Conflicts of interest
There are no conflicts of interest.
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