Severity of angiographic coronary obstruction and the apolipoprotein E polymorphism in acute coronary syndromes

Abstracts

FUNDAMENTO: Existem evidências de associação entre o polimorfismo da apolipoproteína E (APOE) e a doença coronariana, entretanto há controvérsias. OBJETIVO: Avaliar a associação entre o número de vasos coronarianos acometidos por obstrução significativa definida por angiografia, o polimorfismo da APOE e as variáveis clínicas. MÉTODOS: Estudo transversal multicêntrico que envolveu 207 pacientes (138 homens) com síndrome coronariana aguda (SCA) em Niterói (RJ - Brasil), os quais realizaram angiografia coronariana e determinação do genótipo para o polimorfismo APOE *2*3*4, pelo método de Restriction Fragment Length Polymorphism (RFLP). RESULTADOS: A frequência dos alelos APOE *2 foi de 6,8%, *3 foi de 82,5%, e *4 foi de 10,7%. Quanto ao número de vasos lesados, 27% dos pacientes apresentavam obstrução uniarterial, 33,8%, biarterial, e 39,1%, triarterial ou de tronco da coronária esquerda. O grau de lesão multivascular não se relacionou com a presença do alelo *4 (p = 0,78), mas com a idade > 55 anos (p = 0,025), o ex-tabagismo (p = 0,004) e a dislipidemia (p = 0,05) na análise multivariada e com doença arterial coronariana prévia (p = 0,05), diabete (p = 0,038) e síndrome metabólica (p = 0,021) na análise univariada. A prevalência de dislipidemia, diabete e hipertensão arterial sistêmica (HAS) foi elevada em relação a estudos semelhantes, com aumento progressivo da prevalência de HAS (p = 0,59) e de diabete (p = 0,06), de acordo com o número de vasos lesados. CONCLUSÃO: O polimorfismo da APOE não se associou ao número de vasos coronarianos com obstrução significativa em qualquer faixa etária. Por outro lado, a idade > 55 anos, o ex-tabagismo e a dislipidemia associaram-se à lesão multivascular.

Apolipoproteína E2; síndrome coronariana aguda; polimorfismo genético; angiografia coronariana

FUNDAMENTO: Hay evidencias de asociación entre el polimorfismo de la apolipoproteína E (APOE) y la enfermedad coronaria, sin embargo hay controversias. OBJETIVO: Evaluar la asociación entre el número de vasos coronarios afectados por obstrucción significativa definida por angiografía, el polimorfismo de la APOE y las variables clínicas. MÉTODOS: Estudio transversal multicéntrico que implicó a 207 pacientes (138 varones) con síndrome coronario agudo (SCA) en la ciudad de Niterói (RJ - Brasil), los que realizaron angiografía coronaria, y determinación del genotipo para el polimorfismo APOE *2*3*4 mediante el método de Restriction Fragment Length Polymorphism (RFLP). RESULTADOS: La frecuencia de los alelos APOE *2 fue del 6,8%, *3 fue del 82,5%, y *4 fue del 10,7%. En cuanto al número de vasos lesionados, el 27% de los pacientes presentaban obstrucción uniarterial, el 33,8%, biarterial, y el 39,1%, triarterial o de tronco de la coronaria izquierda. El grado de lesión multivascular no se relacionó con la presencia del alelo *4 (p = 0,78), sino con la edad > 55 años (p = 0,025), el ex tabaquismo (p = 0,004) y la dislipidemia (p = 0,05) en el análisis multivariado y con la enfermedad arterial coronaria previa (p = 0,05), la diabetes (p = 0,038) y el síndrome metabólico (p = 0,021) en el análisis univariado. La prevalencia de dislipidemia, diabetes e hipertensión arterial sistémica (HAS) fue elevada con relación a estudios semejantes, con aumento progresivo de la prevalencia de HAS (p = 0,59) y de diabetes (p = 0,06), según el número de vasos lesionados. CONCLUSIÓN: El polimorfismo de la APOE no se asoció al número de vasos coronarios con obstrucción significativa en cualquier grupo de edad. Por otro lado, la edad > 55 años, el ex tabaquismo y la dislipidemia se asociaron a la lesión multivascular.

Apolipoproteína E2; síndrome coronario agudo; polimorfismo genético; angiografía coronaria

ORIGINAL ARTICLE

Severity of angiographic coronary obstruction and the apolipoprotein E polymorphism in acute coronary syndromes

Arlisa Monteiro de Castro Dias; Amália Faria dos Reis; Claudia Guerra Murad Saud; Maria das Graças Leitão Chilinque; Rafaela Ferreira Leite; Rosemery Nunes Cardoso Abdalah; Mariana Ferreira Fiqueiredo; Georgina Severo Ribeiro; Carlos Augusto Cardozo de Faria

Hospital Universitário Antonio Pedro (HUAP) da Faculdade de Medicina da Universidade Federal Fluminense (UFF), Niterói, RJ - Brazil

Mailing address

SUMMARY

BACKGROUND: There is evidence of the association between the apolipoprotein E (APOE) and coronary disease; however, there are controversies.

OBJECTIVE: To evaluate the association between the number of coronary vessels with significant obstruction defined by angiography, the APOE polymorphism and clinical variables.

METHODS: This was a cross-sectional, multicenter study with 207 patients (138 men), with acute coronary syndrome (ACS), in the city of Niteroi, state of Rio de Janeiro, Brazil, who underwent coronary angiography and genotype determination for the APOE *2*3*4 polymorphism by the Restriction Fragment Length Polymorphism (RFLP) method.

RESULTS: The frequency of the alleles was APOE *2 - 6.8%, *3 - 82.5%, *4 - 10.7%. Regarding the number of affected vessels, 27% of patients presented monoarterial obstruction, 33.8% biarterial and 39.1% triarterial and/or left coronary trunk. The degree of multivascular lesion did not correlate with the presence of the *4 allele (p= 0.78), but with age > 55 years (p=0.025), being an ex-smoker (p=0.004) and dyslipidemia (p=0.05) at the multivariate analysis and also with previous coronary artery disease (CAD) (p=0.05), diabetes (p=0.038) and metabolic syndrome (p=0.021) at the univariate analysis. The prevalence of dyslipidemia, diabetes and systemic arterial hypertension (SAH) was elevated regarding similar studies, with progressive increases in the prevalence of SAH (p=0.59) and diabetes (p=0.06), according to the number of affected vessels.

CONCLUSION: The APOE polymorphism was not associated with the number of coronary vessels with significant obstruction at any age range. On the other hand, age > 55 years, being an ex-smoker and dyslipidemia associated with the multivascular lesion.

Key words: Apolipoprotein E2; acute coronary syndrome; polymorphism, genetic; coronary angiography.

Introduction

The apolipoprotein E (APOE), a plasma protein that comprises the structure of several lipoproteins (kilomicron, VLDL-cholesterol, IDL-cholesterol and HDL-cholesterol), acts as a receptor-binding factor. It has an acknowledged role in the transportation of cholesterol and other lipids from peripheral tissues to the liver, so they can be metabolized¹.

The most studied isoforms are the three first described ones: apolipoprotein E2, E3 and E4, codified by the alleles (epsilon 2, 3 an 4). The frequency of the *2, *3, *4 alleles is estimated as being around 11%, 72% and 17% in the general population, respectively¹. The *4 allele has been found with higher prevalence in the African populations², and has been associated to higher plasma levels of total cholesterol and LDL-cholesterol and lower serum levels of APOE¹; therefore, due to these influences, it has been studied as a possible risk factor for coronary disease³.

In spite of the ethnical differences in the studied populations, Wilson et al³ and Song et al⁴ found, in their meta-analyses, increased risk for significant coronary artery disease (CAD) in the presence of *4 allele. However, when certain populations are studied separately, as demonstrated in the studies by Kolovou et al^5,6 in Greece and Muros & Ferrer⁷ in Spain, the association between the presence of the *4 allele and CAD can be negative. Recently, an important study published by Morgan et al⁸ evaluated 84 genetic polymorphisms in acute myocardial infarction (AMI) and did not report any significant association with APOE polymorphism.

Two Brazilian studies^9,10 did not find any association between the presence of *4 allele and CAD; however, Salazar et al¹¹ observed an association between the *4 allele and CAD in young women. These case-control studies were carried out in the state of Sao Paulo. Up to the start of the present study, we did not find any publications that had evaluated genetic polymorphisms and acute coronary syndrome (ACS) in the state of Rio de Janeiro (RJ). As the degree of miscegenation is very high in our country and there is heterogeneity among the geographical regions, it is important that the studies be carried out in different states, for comparison of the results.

We chose to study this subject in the city of Niteroi, as it was the only city in the state of Rio de Janeiro where the rate of mortality due to ischemic coronary disease was higher than the one by cerebrovascular disease, from 1980 to 2000¹² and due to the fact that circulatory diseases were the main cause of death and hospital admission in the last ten years¹³.

With the objective of evaluating the existence of an association between this APOE polymorphism, clinical variables and the number of affected coronary vessels with significant obstruction defined by coronary angiography, we selected all patients that had undergone coronary angiography during hospital admission due to ACS in the city of Niteroi (RJ) from a prospective cohort study carried out in partnership between the Universidade Federal Fluminense (UFF) and the Universidade Federal do Rio de Janeiro (Federal University of Rio de Janeiro)¹³. One of the objectives of this cohort study, of which methodology and epidemiological aspects were published by Reis et al¹³, was to study the association of APOE polymorphisms, angiotensin- and angiotensinogen-converting-enzyme with clinical and laboratory outcomes that had been pre-defined in patients with ACS, given the small number of Brazilian publications that have reported on these aspects. This research group has dedicated since 2003 to the study of epidemiological and genetic aspects of the ACS in cities of the state of Rio de Janeiro, within the lines of research of the Post-Graduation course in Cardiovascular Sciences at UFF. The results of the other analyses carried out with this cohort study population will be published subsequently, as they are not part of the objective of the present study.

Methods

Three public hospitals and two private ones in the city of Niteroi, state of Rio de Janeiro, Brazil, participated in the prospective cohort study, with patients' enrollment occurring between June 2004 and June 2005. This study was approved in 2003 by Ethics Committee in Research of the School of Medicine of UFF and the National Commission on Ethics in Research. All patients signed the Free and Informed Consent Form. Men and women aged > 20 years, consecutively admitted with a diagnosis of ACS: AMI with or without ST-segment elevation or unstable angina were included in the study¹³. This was a cross-sectional study that selected the 234 patients from the original prospective study, who had undergone coronary angiography during hospital stay. Of these, 207 presented at least one coronary artery with significant obstruction (> 70%), who were selected for the statistical analysis of the present study.

The collected blood samples were sent to the Laboratory of PCR and Molecular Biology of the Service of Clinical Pathology of Hospital Universitário Antonio Pedro (UFF) for laboratory analyses and identification of the genetic polymorphism of APOE.

The samples were collected in tubes with EDTA for genomic DNA isolation, which was carried out through the saline precipitation method¹⁴. After the extraction, the integrity of the samples was analyzed by submarine electrophoresis (BIO RAD electrophoresis system) in 0.8% agarose gel with TBE 1X buffer (90 Mm Tris-HCl, 90 mM boric acid and 2 mM EDTA), stained with ethidium bromide and stored at 4°C for posterior polymorphism analysis. The DNA samples were submitted to the Polymerase-Chain Reaction (PCR) and evaluated by electrophoresis in a 2% agarose gel. The APOE genotype determination was carried out through the Restriction Fragment Length Polymorphism (RFLP) method¹⁵.

The 220 bp amplicon obtained from the PCR was treated with a unit of HhaI restriction enzyme, according to the manufacturer's instructions, producing DNA fragments of different sizes and allowing the identification of the genotypes.

After the digestion, the samples were evaluated in a 10% polyacrylamide gel in a Hoefer SE 400 vertical electrophoresis system by Amersham Biosciences. As size indicator, a 25 base-pair (bp) marker was used, applied together with the samples, to help the visualization of the fragments of 91, 83, 72, 48, 38 and 34 bp. The identification of the APOE genotypes was based on the following profile: E2E2 – fragments of 91, 83, 38 bp; E3E3 – 91,48, 38, 34 bp; E4E4 – 72, 48, 38, 34 bp; E2E3 – 91, 83, 48, 38, 34 bp ; E2E4 – 91, 83, 72, 48, 38 bp; E3E4 – 91, 72, 48, 38, 34 bp.

The coronary angiography results were discussed with the hemodynamicists and cardiologists from the teams responsible for the hospital admission units, who were blinded to the results of the genetic analysis. As the number of patients that had undergone coronary angiography and presented coronary obstruction < 70% or that presented normal results was small (11.5%), and as they could be joined in a single group, we chose to exclude them from the statistical analysis.

Arterial obstruction > 70%, was considered a significant lesion, quantified or estimated by angiography¹⁶ and multivascular disease stenosis > 70% in two or more coronary systems¹⁷ or left coronary trunk lesion > 50%.

We considered a vessel each one of the systems¹⁸: 1) Descending Artery System: (DA and branches); 2) Circumflex System: (CX and branches); 3) Right Coronary System: (RC and branches). It was considered monoarterial when only one of the systems above was affected with lesions > 70%; biarterial if two systems were affected and triarterial if there were lesions > 70% in the three systems.

As the trunk lesion and the trivascular lesion are independent risk factors for intra-hospital adverse events¹⁶, these two groups were evaluated together in some statistical analyses.

The diagnosis of metabolic syndrome was defined by the criteria of the World Health Organization, which allows the use of the body mass index (BMI) to evaluate obesity¹⁹.

The criteria for the diagnosis of dyslipidemia were: a) Dyslipidemia (1) – cholesterol > 200 or LDL > 130 or TG > 150 mg/dl or history of previous dyslipidemia (lipid profile values above the normal range) associated to the previous use of hypolipemiant drugs; b) Dyslipidemia (2) – HDL < 40 or TG > 150 or LDL >130 or Cholesterol > 200 mg/dl or previous use of hypolipemiant drugs.

The criteria for the diagnosis of ACS and the definition of left ventricular failure were based on the European and American Directives and Consensus (ACC/AHA), Cardiology textbooks and scientific articles, having been detailed in a previously published article¹³.

Statistical analysis

Statistical significance was set at 5% and the statistical analysis was performed with the SAS^® software, version 6. The analysis of the association between the qualitative variables and the degree of affected vessels was carried out by the χ² test and the adjusted χ² test. Tukey's multiple comparisons test was used to identify which degrees of coronary lesions differed among them, at a 5% level.

The analysis of association between the degree of the affected vessels and the presence of the *4 allele in the general sample and at the age range < 65 years was carried out by the χ² test and by Fisher's exact test. The χ² test was also used to perform the statistical analysis of the correlation between coronary obstruction and the presence of metabolic syndrome.

The Logistic Regression analysis was carried out to identify the independent variables, including the APOE polymorphism, which simultaneously influenced the degree of the obstructed vessels according to the coronary angiography. The selected variables were: presence of *4 allele, age 55 years, age 60 years, male sex, BMI (kg/m²), history of previous CAD, history of CAD in first-degree relatives, smoking, diagnosis of diabetes mellitus, ACS type, diagnosis of dyslipidemia (1) and left ventricular failure (LVF) during hospital stay. The process of factor selection was the stepwise one, at the level of 5% and 10%. Regarding age, the model was tested with age 55 years and later with age 60 years, to evaluate which one of them had a better explicative power in association with the other variables.

Results

The prevalence of the studied variables in the 207 patients according to gender is shown in Table 1. The distribution of the APOE polymorphism genotypic frequencies in the sample (Table 2) was in Hardy-Weinberg equilibrium. For the statistical analysis, the genotypes were grouped in three groups: E2E2, E2E3 (*2 allele present), E3E3 (*3 allele present), E2E4, E3E4, E4E4 (*4 allele present). The patients that did not harbor the *4 allele represent the addition of the two first groups.

The APOE polymorphism (Table 3) was not statistically associated with the degree of the affected vessels (p=0.80), not even when the *4 allele and the *2 allele were evaluated separately (p=0.78 and p=0.52, respectively).

A significant association as observed between age 55 years with the degree of affected vessels (p=0.045). The percentage of patients aged 55 years at the monoarterial degree (64.3%) was significantly lower than in the biarterial (81%) and triarterial + trunk (80%).

There was a significant association between smoking and the degree of affected vessels (p=0.023). The percentage of ex-smokers at the triarterial degree + trunk (50.6%) and biarterial (45.7%) was significantly higher than in the monoarterial degree (28,6%).

The group of patients with triarterial degree + trunk (55.6%) presented a LVF proportion at hospital admission that was significantly higher than the monoarterial degree (35.7%), with p=0.043.

The diagnosis of diabetes mellitus increased progressively when correlated with the degree of affected vessels: 31% at the monoarterial, 43% at the biarterial and 51.9% at the triarterial + trunk (p=0.06). The diagnosis of systemic arterial hypertension (SAH) followed a similar pattern: 78% at the monoarterial, 84.3% at the biarterial and 92.6% at the triarterial + trunk (p=0.059).

The diagnosis of dyslipidemia (1) and (2), total cholesterol increase, low HDL-cholesterol and increase in triglycerides did not present a significant association with the number of affected vessels.

Metabolic syndrome presented a significant association with the degree of affected vessels, being more prevalent in the triarterial + trunk group, than in the monoarterial group (p=0.012).

A new analysis was carried out with the objective of comparing the monoarterial with the multivascular groups (biarterial + triarterial + trunk) and verifying whether they were statistically different under the point of view of the analyzed variables (Table 4). When the classification was performed with two degrees of coronary obstruction severity (Table 4), the multivascular degree presented a significant association with the variables age > 55 years (p=0.025), presence of previous CAD (p=0.05), ex-smokers (p=0.004), diabetes mellitus (p=0.038) and dyslipidemia (1) (p=0.05). However, the degree of affected vessels still did not present a significant association with APOE polymorphism.

Differently from what was observed at the analysis with three degrees of affected vessels (Table 3), in this analysis there was no significant association between the mono and multivascular degrees and the metabolic syndrome variable (p=0.12). The diagnosis of SAH increased proportionally to the degree of the angiographic lesion severity (univascular = 78.6% and multivascular = 88.7%), although it did not reach statistical significance (p=0.061).

As shown in Table 5, when the subgroup of patients aged < 65 years was analyzed, no association was observed between the degree of affected vessels and the presence of *4 allele, in cases with three degrees of severity (p=0.80) , as well as with two degrees (p=0.66).

Tables 6 and 7 present the parameters for the significant variables selected by the Logistic Regression method at the level of 5% and 10%, respectively. The parameters are: coefficient, standard error, p value and relative risk (RR), with its respective 95% confidence interval (CI) for the occurrence of multivascular lesion.

When the variables are analyzed simultaneously according to the Logistic Regression, it was observed that the ex-smoker (RR 3.86) and the diagnosis of dyslipidemia (1) (RR 2.14) were significant to explain the multivascular degree at the level of 5% (Table 6). The non-smokers also presented a significantly higher risk than the current smokers (RR = 2.45). The other variables did not present an independent contribution to explain the multivascular degree.

When analyzing at the level of 10% (table 7), we observed that the ex-smoker (RR 3.37), diagnosis of dyslipidemia (1) (RR 2.11) and age 55 years (RR 1.96) were significant to explain the degree of multivascular lesion, whereas the non-smoker presented a borderline p value.

Discussion

In this studied population, there was a predominance of the male sex (66.7%), mean age was 63 years, the most frequent type of ACS was acute myocardial infarction (62%), the most prevalent degree of lesion was the multivascular one (72.9%) and the percentage of patients with previous CAD was 40.1%. In a Brazilian study carried out in São Paulo²⁰, which evaluated 1,413 patients with unstable angina submitted to coronary angioplasty, the predominance of the male sex was also observed (62%), with a mean age of 61 years; however, the frequency of multivascular lesions was lower (42%). Other authors in a study carried out in patients with Ami in the city of Niteroi²¹ found almost the same percentage of male sex patients (66.8%), also with a lower percentage of multivascular disease (54.9% in men and 63.3% in women). In the present study, the percentages of the coronary obstruction type did not significantly differ regarding sex (Table 4).

The high prevalence of multivascular lesion (72.9%), found in patients that underwent coronary angiography in the present study demonstrates the correct indication of the examination. On the other hand, the low percentage of patients with univascular lesion might have influenced the results, considering that the influence of the APOE polymorphism might not have been demonstrated due to the lack of of a representative group of patients with a lower extension of the disease.

In the present study, 43.4% of the patients met the diagnostic criteria of diabetes mellitus and 86% of SAH. These findings characterize a population with a high prevalence of the mentioned diseases, considering the findings of other studies with CAD patients Duarte et al²² observed a prevalence of 56% of SAH in patients with ACS that presented adverse events during hospital admission and of 62% in patients without events. At the Afirmar²³ study, which evaluated risk factors in ACS in 1,279 Brazilian patients, the prevalence of SAH was even lower (54.34%), as well as of diabetes (21.6%).

The diagnosis of dyslipidemia (2) showed a prevalence of 88.6%, much higher than the one observed by Duarte et al²², also in a Brazilian study with similar criterion (60.5%).

Regarding the current smoking, the prevalence found (31,5%) was similar to the prevalence observed in the study by Peixoto et al²¹ (34.1%) and lower than the prevalence of 41.5% described by Piegas et al²³.

The metabolic syndrome was diagnosed in 44.9% of the total sample and in 47.6% of the patients aged < 65 years. These results are a little higher than the ones found in another Brazilian study related to ACS, in which 40% f the patients were classified as having metabolic syndrome²⁴.

We observed that the most significant variables to explain the multivascular degree at the logistic regression analysis were: 1) ex-smoker and dyslipidemia (1) at the level of significance of 5% and 2) ex-smoker, dyslipidemia (1) and age > 55 years at the level of 10%. The ex-smoker was more significant than the current smoker, which might be explained by the fact that ex-smokers are older and probably stopped smoking due to a previous diagnosis of CAD or other pathologies that contraindicate smoking, whereas the current smoker, due to the fact of being younger, has not been exposed long enough to risk factors to develop multivascular lesions.

In this studied population, the prevalence of the *4 allele (10.7%) was similar to the prevalence of the allele in healthy populations such as the Portuguese (9%)²⁵, the Italian (10%), the Mexican (10.2%)²⁶, the Spanish (9%)², the elderly population of Rio Grande do Sul that descends from Italians (11%)²⁷, as well as the patients with CAD in Sao Paulo (9%)¹⁰. On the other hand, the frequency of the allele was lower than the one observed in northern European countries, such as Ireland (22%)²⁸ and lower than the one found in the town of Ouro Preto, state of Minas Gerais, Brazil (20%)²⁹, where the African contribution for the formation of the population was higher.

No association was found in the present study between the presence of the *4 allele and a higher angiographic severity. These findings differ from the ones found by Lehtinen et al³⁰, Wang et al³¹ and Ye et al³², who also evaluated the APOE genotype regarding the number of vessels with significant lesions and observed an increase in the frequency of the *4 allele in cases with multivascular lesions. It is worth mentioning that Wang (op. cit.) evaluated only three individuals aged < 65 years.

Even when the subgroup of younger individuals ( 65 years) was analyzed separately, the severity of the coronary lesions did not present a significant association with the presence of the *4 allele. The study by Salazar et al¹¹ in São Paulo found different results; however, the population was younger, with a mean age of around 48 years and consisted of women, only. In our sample, only 6 (2.8%) of the women aged < 65 years harbored the *4 allele. Thus, it was not possible to establish comparisons.

The outcome of our study, in relation to the fact that the APOE polymorphism was not considered an independent risk factor for the severity of the angiographic lesions in both sexes, was similar to the case-control studies carried out in the state of Sao Paulo by Mansur et al⁹ and Souza et al¹⁰. The study by Mansur et al.⁹ also compared within the group with coronary disease (with or without AMI), uni- and multivascular lesion, similar to present study. The lack of association observed in the present study could be explained, in part, by the fact that the frequency of this allele was low in our sample (10.7%), as also occurred in the study by Souza et al (9%)¹⁰. The analysis of the outcomes of these Brazilian studies together allows us to conclude that even associations that have been well-established in the literature might not be confirmed due to population differences.

The exposition to classic risk factors starts to have a higher influence on the individual tendency to present significant coronary obstruction with aging³³. The high prevalence of risk factors observed in this study probably contributed to the high percentage of multivascular lesion found in it and it also might have exercised a higher influence on the degree of angiographic lesion than the APOE polymorphism, due to the percentage of elderly individuals in the present study (45% aged > 65 years). As multivascular lesions are independent risk factors for intra-hospital adverse events¹⁶, the results of the present study point out to the need for establishing more effective public health policies that will allow a better control of coronary risk factors, as well as the decrease in the high morbimortality due to ACS observed in this population studied in the city of Niteroi, RJ, Brazil, as previously reported by Reis et al¹³.

Considering the aforementioned facts, this APOE polymorphism had little influence on the population of the present study. The predisposition for CAD is determined by multiple genetic and environmental factors, and it is unlikely that a single genetic polymorphism is capable of causing a significant increase in the risk of developing it³³. The negative result of the present study corroborates the existing idea in the current scientific literature, of the importance of the simultaneous study of several polymorphisms, mainly in polygenic and multifactorial diseases such as the coronary disease.

We believe that the publication of these negative results is important, as they call attention to the variations that exist in different geographic regions of Brazil and the world, regarding the genetic profile and the prevalence of environmental risk factors, which, when associated, will lead to a higher or lower prevalence of CAD. These different results also indicate the need for adequacy to the local reality of risk scores, as genetic and environmental factors will influence or not the risk of CAD or its prognosis, depending on the complex inter-relation among these factors in that population.

The lack of a control group was considered one of the main limitations of the present study. However, the study data were obtained from a larger, prospective study that included patients admitted at the hospital with a diagnosis of ACS and it would not have been ethical to program a hemodynamic study in patients in whom the diagnosis of ACS had not been confirmed, or in those with ACS considered as low clinical risk. Additionally, the study was an observational one and the research team had no influence regarding the performance or not of the hemodynamic study.

Conclusion

The apolipoprotein E polymorphism did not show an association with a higher degree of coronary lesion severity in the total sample or in the subgroup of patients aged < 65 years.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Sources of Funding

This study was partially funded by Instituto Biossocial de Volta Redonda.

Study Association

This article is part of the thesis of Master submitted by Arlisa Monteiro de Castro, from Universidade Federal Fluminense.

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Publication Dates

• Publication in this collection
  22 Oct 2009
• Date of issue
  Sept 2009

History

• Reviewed
  10 Aug 2008
• Received
  27 Apr 2008
• Accepted
  09 Sept 2008