Acute coronary syndromes in the absence of significant coronary artery disease

Abstracts

OBJETIVO: Avaliar as características clínicas, a evolução e as complicações intra-hospitalares de pacientes com síndromes coronarianas agudas (SCA) na ausência de doença arterial coronariana (DAC) obstrutiva significativa. MÉTODOS: Estudo transversal envolvendo pacientes internados, de agosto/96 a março/02, com síndromes coronarianas agudas, com e sem supradesnivelamento ST, analisando as características clinicas, demográficas e complicações intra-hospitalares nos casos com (>50%) e sem (< 50%) estenose coronariana significativa. RESULTADOS: Dos 1351 pacientes admitidos com síndrome coronariana aguda, 28% apresentavam supradesnivelamento ST e 72% não o demonstravam. Os pacientes com a síndrome coronariana aguda sem supradesnivelamento do segmento ST, na ausência de obstrução coronariana significativa, eram mais jovens, predominantemente mulheres, e apresentavam menor freqüência de dislipidemia, doença arterial coronariana prévia, diabetes mellitus, tabagismo e hipertensão arterial sistêmica, quando comparados àqueles com lesão obstrutiva significativa. Entre os indivíduos com síndrome coronariana aguda e supradesnivelamento ST, tabagismo foi o fator de risco com maior prevalência nos pacientes com lesão obstrutiva não significativa. Quanto às complicações, houve menor freqüência de isquemia recorrente, insuficiência cardíaca congestiva e arritmias em pacientes com síndrome coronariana aguda sem supradesnivelamento ST na ausência de lesão coronariana obstrutiva significativa. CONCLUSÃO: Pacientes com síndrome coronariana aguda sem supradesnivelamento ST com lesões coronarianas obstrutivas não significativas são mais jovens, predominantemente mulheres, com menor freqüência de fatores de risco para doença arterial coronariana e menor incidência de complicações, em relação aos pacientes com lesão coronariana obstrutiva significativa.

doença arterial coronariana; características clínicas; estenose coronariana

ORIGINAL ARTICLE

Acute coronary syndromes in the absence of significant coronary artery disease

Maria das Graças Viana Pinheiro; Alvaro Rabelo Jr.; Rogerio Santos de Jesus; Luciana Cunha Nascimento; Ursula Maria Moreira Costa

Salvador, BA - Brazil

Unidade de Cardiologia e Cirurgia Cardiovascular- Fundação Bahiana de Cardiologia

^{Correspondence}

ABSTRACT

OBJECTIVE: To assess the clinical characteristics, evolution, and in-hospital complications of patients with acute coronary syndromes (ACS) in the absence of significant obstructive coronary artery disease (CAD).

METHODS: Cross-sectional study of patients hospitalized from August 1996 to March 2002 with acute coronary syndrome, with or without an elevation in the ST segment, and with (= 50%) or without (<50%) significant coronary stenosis. Their clinical and demographic characteristics and their in-hospital complications were analyzed.

RESULTS: Of the 1351 patients admitted with acute coronary syndrome, 28% had an elevation in the ST segment and 72% had no elevation. The patients with acute coronary syndrome with no elevation in the ST segment and no significant coronary obstruction were younger, predominantly females, and had a lower frequency of dyslipidemia, previous coronary arterial disease, diabetes mellitus, smoking, and systemic arterial hypertension, when compared with those with significant obstructive lesion. Among the individuals with acute coronary syndrome and an elevation in the ST segment, smoking was the most prevalent risk factor in patients with nonsignificant obstructive lesion. In regard to complications, recurring ischemia, congestive heart failure, and arrhythmias were more frequent in patients with acute coronary syndrome with no elevation in the ST segment and no significant obstructive coronary lesion.

CONCLUSION: Patients with acute coronary syndrome with no elevation in the ST segment and with nonsignificant obstructive coronary lesions are younger, predominantly females, have a greater frequency of risk factors for coronary arterial disease, and a lower incidence of complications as compared with patients with significant obstructive coronary lesion.

Keywords: coronary arterial disease, clinical characteristics, coronary stenosis

Acute coronary syndromes are usually caused by coronary obstruction due to an interaction of thrombotic and vasospastic phenomena and coronary atherosclerotic lesions, which can manifest as different clinical findings, such as unstable angina, acute myocardial infarction, or sudden death ¹. Initially, only the atheromatous plaques with significant obstruction, reducing the lumen of the vessel by more than 50%, were considered to have a potential for rupture, subsequent thrombosis, and vascular occlusion ². Recent studies, however, have challenged the old paradigm and shown that, even plaques with no significantly obstructive lesions, ie, with lumen reduction lower than 50%, also have a thrombogenic potential ³.

The association of acute coronary syndrome and nonsignificant coronary obstruction began to be reported in the 70s ⁴. Since then, several studies have shown some differences in the prognosis and distribution of the risk factors in that group of patients, comparing those patients with others with acute coronary syndrome and significant obstructive lesions ⁵. However, those studies had varied results and used different definitions and inclusion criteria. Therefore, a controversy persisted in regard to the aspects characterizing patients with acute coronary syndrome in the absence of significant obstructive coronary arterial disease.

This study aimed at defining the clinical characteristics and short-term evolution of patients with acute coronary syndrome with and without an elevation in the ST segment, comparing the individuals without significant obstructive lesion with those with significant coronary artery obstruction.

Methods

This was a retrospective cross-sectional study with patients admitted with acute coronary syndrome between August 1996 and March 2002. The acute coronary syndromes with an elevation in the ST segment were defined as follows: chest pain lasting more than 30 minutes; an elevation in the creatine phosphokinase isoenzyme (CK-total) and its myocardial fraction (CK-MB) of at least twice the basal value. The electrocardiographic alterations in this group included an elevation in the ST segment > 1 mm in 2 contiguous leads of the same ventricular wall in the peripheral leads, or an elevation in the ST segment > 2 mm in at least 2 contiguous leads in the horizontal plane, or both, associated or not with the recent appearance of left bundle-branch block ⁶. Acute coronary syndromes with no elevation in the ST segment comprise acute myocardial infarction with no elevation in the ST segment and unstable angina. The individuals with unstable angina had precordial pain at rest, depression in the ST segment > 1 mm in 2 contiguous leads of the same ventricular wall, and inversion of the T wave or spiked T wave, both symmetric. Infarction with no elevation in the ST segment affected individuals with chest pain and no elevation in the ST segment, but with an increase in the biochemical markers of myocardial necrosis (total CK and CK-MB) ⁷.

The following patients were excluded from the study: those who did not undergo coronary angiography during hospitalization; those who were transferred to another institution within less than 48 hours; and those who underwent previous coronary artery bypass grafting.

The patients were distributed into 2 groups according to the visual assessment of the severity of the coronary arterial lesions identified on coronary angiography in one or more of the 3 major coronary arteries, or their major branches, or both. The criterion of the BARI study ⁸ was used for defining the significant obstructive coronary lesion: the group with a significant obstructive coronary lesion had coronary stenosis = 50%, and the group without a significant obstructive coronary lesion had coronary stenosis <50%, including normal coronary arteries. The coronary angiographies were performed during the patient's hospitalization and interpreted by more than 2 hemodynamicists.

The severity of the coronary lesion (lesion > 50% and < 50%) found on coronary angiography was used for the comparative analysis of the clinical and demographic characteristics and complications of the individuals with acute coronary syndrome with and without an elevation in the ST segment.

The patients with acute coronary syndrome without an elevation in the ST segment received the conventional therapy, which consisted of rest, oxygen therapy, nitrate, antiplatelet agent, beta-blocker or calcium channel blocker, or both, in the case of vasospasm, and plain heparinization, if no contraindication existed. The patients with an elevation in the ST segment, who were admitted to the emergency unit within the first 12 hours of pain onset, underwent thrombolysis or were referred for primary angioplasty, depending on the availability of the service.

The clinical and demographic variables of the patients were stored in the Epidemiology of the Acute Coronary Syndromes (EPICOR) databank, which represents the recording of all admissions due to acute myocardial infarction or unstable angina at the Coronary Unit of the Cardiology and Cardiovascular Surgery Unit of the Fundação Bahiana de Cardiologia ⁹. The follow-up of patients proceeded from admission until hospital discharge, and all therapeutic and diagnostic interventions adopted were recorded, as were the complications and outcomes of the patients with the syndromes studied during the in-hospital phase.

The definitions of risk factors for coronary arterial disease were those used by the II Brazilian Consensus on Dyslipidemia ¹⁰. The following variables were analyzed: sex, age, systemic arterial hypertension, diabetes mellitus, sedentary lifestyle, dyslipidemia, obesity, familial history, previous coronary artery disease, and smoking. During hospitalization, the 5 major cardiovascular complications assessed were as follows: 1) recurring myocardial ischemia, translated by the reappearance of angina or acute myocardial infarction; 2) congestive heart failure defined by signs and symptoms of pulmonary congestion, requiring the use of specific therapy, such as diuretics, vasodilators, or digitalis, or both; 3) cardiogenic shock defined as systolic blood pressure < 90 mm Hg for more than 30 minutes, requiring the use of vasopressors; 4) arrhythmias requiring pharmacological treatment, electrical cardioversion or use of pacemaker; and 5) death.

The continuous variables were expressed as mean value ± standard deviation, and the categorical variables were expressed as proportions. The chi-square test or the Fisher exact test was used for testing the differences between the proportions after checking whether the data were in accordance with the premises for those tests. The continuous variables of the individuals with and without an elevation in the ST segment were compared by use of the Student t test for independent samples. The prevalence ratios were used with their respective 95% confidence intervals (95% CI), as an estimate of the measure of association between the coronary lesion and its possible or eventual predictors, in individuals with and without an elevation in the ST segment. Values lower than 5% (P < 0.05) were considered statistically significant.

Multiple logistic regression was used for identifying the possible independent predictors for the syndrome with and without an elevation in the ST segment in individuals with no significant coronary artery obstructions. The odds ratios (OR) and their respective 95% confidence intervals (95% CI) were used as estimates of the prevalence ratios of the risks of the association between the variables.

Results

From August 1996 to March 2002, 1866 patients were admitted with acute coronary syndrome. Of those, 515 patients were excluded from the study because they had not undergone coronary angiography, which resulted in a study with 1351 patients [722 (57.1%) men and 579 (42.9%) women]. Of the patients admitted with acute coronary syndrome, 374 (28%) had an elevation in the ST segment, and 977 (72%) had no elevation in that segment.

The analysis of the coronary angiographies showed that 182 (13.5%) patients had a 0 to 25% lesion, 39 (2.9%) patients had a 25% to 50% lesion, and 1130 (83.6%) had a lesion > 50%. Of the individuals with no elevation in the ST segment, 21% had a lesion < 50% and 79% had a lesion > 50%. Of the individuals with an elevation in the ST segment, 5% had a lesion < 50%, while 95% of the patients had a lesion > 50% (fig. 1).

In regard to the age group of the patients with acute coronary syndrome with no elevation in the ST segment, we observed that those with nonsignificant obstructive coronary lesions were, on average, 4 years younger than those with significant obstructive lesions (57 ± 12 versus 61 ± 11; P < 0.05). These individuals also had a lower incidence of systemic arterial hypertension, diabetes mellitus, dyslipidemia, smoking, and previous coronary artery disease, as compared with those with significant obstructive lesion. In regard to the remaining risk factors, no statistically significant difference was observed between the groups.

The demographic characteristics of the individuals with acute coronary syndrome with an elevation in the ST segment obtained on admission showed that, although the patients with lesion <50% were younger than individuals with significant obstructive coronary lesions (45 versus 59 years; P < 0.0001), no difference in sex distribution was found, or in the prevalence of risk factors between the groups. Smoking, however, was the only risk factor with a greater prevalence in individuals with coronary obstruction < 50% (tab. I).

Of the clinical and demographic characteristics assessed in multivariate analysis, the most important predictive factors for acute coronary syndrome with an elevation in the ST segment in individuals with a nonsignificant obstructive coronary lesion were as follows: female sex, age < 60 years, and no previous coronary arterial disease. In individuals with acute coronary syndrome with an elevation in the ST segment, the most important predictive factor for a nonsignificant obstructive coronary lesion was age <60 years (tab. II).

In patients with acute coronary syndrome with an elevation in the ST segment, no difference was found in the incidence of complications, such as congestive heart failure, cardiogenic shock, arrhythmias, recurring ischemia, and sudden death between individuals with and without a significant obstructive lesion. Neither cardiogenic shock nor sudden death was reported in the group with a lesion < 50%.

In the group with acute coronary syndrome and no elevation in the ST segment, the patients with a nonsignificant obstructive coronary lesion had a lower incidence of recurring ischemia (22.9% versus 9.5%; P < 0.0001), cardiogenic shock (1.9% versus 0%; P = 0.04), and arrhythmias (3.3% versus 0%; P = 0.009), and no in-hospital mortality was observed (tab. III). They also had a shorter length of hospital stay when compared with the patients with significant obstructive coronary lesions (4.9 ± 3.08 versus 7.8 ± 4.3 days; P < 0.05). The individuals with acute coronary syndrome with an elevation in the ST segment had no statistically significant difference in regard to complications when individuals with and without a significant obstructive lesion were compared. However, those with lesions < 50% had a shorter length of hospital stay (6.0 ± 2.3 versus 8.8 ± 4.2; P < 0.05).

Discussion

The atherosclerotic lesion is usually responsible for acute coronary syndromes, whose clinical spectrum comprises unstable angina, acute myocardial infarction, and sudden death. In the last 40 years, studies with coronary angiography have identified patients without significant coronary obstruction in up to 20% of the patients admitted with acute coronary syndrome.

Recent studies have challenged the old paradigm based on the idea that the coronary syndromes resulted from the gradual and progressive luminal obstruction caused by the growth of the atherosclerotic plaque. In the new paradigm, the risk of rupture is directly related to the intrinsic characteristics of the plaque associated with local thrombogenesis and extrinsic triggers. These factors are more important than the degree of stenosis and size of the plaque, determining the most lethal clinical manifestations of coronary atherosclerosis ³.

In accordance with data in the literature ^11,12, in our study, 16.3% of the patients admitted with acute coronary syndrome had nonsignificant obstructive coronary lesions. On admission, those individuals had predominantly the clinical manifestations of acute coronary syndrome without an elevation in the ST segment (72.3%), while only 27.7% had clinical findings of that syndrome with an elevation in the ST segment.

Some studies have shown contradictory results regarding the clinical and demographic characteristics in patients with acute coronary syndrome and coronary arteries without significant obstructive lesions. In regard to demographic characteristics in our case series, women predominated (58.8%) among the patients without an elevation in the ST segment, differing from individuals with an elevation in the ST segment, in whom no difference in sex distribution was observed in the groups with and without a significant obstructive lesion.

Unlike the report by Diver et al ¹², Roe et al ¹³, and the present study, Costa et al ¹⁴ reported a greater frequency of men among the patients with acute coronary syndrome in the absence of significant coronary obstruction. On the other hand, Raymond et al ¹⁵ showed no difference in sex distribution between both groups. However, the latter 2 studies assessed only acute myocardial infarction, and analyzed patients with and without an elevation in the ST segment.

In regard to the mean age of patients with an elevation in the ST segment, our study, similarly to that of Roe et al ¹³, found that patients without a significant obstructive lesion belong to a younger age group than patients with significant obstructive lesions. However, in the TIMI IIIA study, Diver et al ¹² reported a similar mean age in both groups.

In the group with an elevation in the ST segment, we also observed a lower mean age in individuals with a nonsignificant obstructive lesion when compared with that of patients with an obstructive lesion > 50%.

In individuals with acute coronary syndrome with no elevation in the ST segment and with no significant obstructive coronary lesion, our study found a lower frequency of systemic arterial hypertension, diabetes mellitus, smoking, dyslipidemia, and coronary artery disease when compared with the findings in patients with significant coronary lesions. These results are in accordance with those reported by Roe et al ¹³ and Costa et al ¹⁴, who confirmed the low incidence of risk factors in that subgroup of individuals.

In patients with acute coronary syndrome with an elevation in the ST segment, this study found no difference in the distribution of risk factors in the groups with and without a significant obstructive coronary lesion, except for smoking, which was the most prevalent factor in individuals with a lesion < 50%. Zimmerman et al ¹⁶ and Fournier et al ¹⁷ reported an association between smoking, acute myocardial infarction, and coronary arteries without significant obstructions in younger individuals.

The most important independent predictors for acute coronary syndrome with no elevation in the ST segment in the absence of significant obstruction assessed in our study and in that of Roe et al ¹³ were as follows: female sex, age < 60 years, and absence of previous coronary artery disease.

The determining factors of worse prognosis during the in-hospital phase are related to recurring ischemia and left ventricular dysfunction ¹⁸. Some researchers ^11,12 , studying patients who evolve with acute coronary syndrome without an elevation in the ST segment, have reported a low incidence of complications in the acute phase of the ischemic event, such as arrhythmias, congestive heart failure, and hypotension, as compared with that of individuals with acute coronary syndrome and an elevation in the ST segment. In our case series, the patients with acute coronary syndrome and nonsignificant obstructive coronary lesion, with or without an elevation in the ST segment, had a shorter length of hospital stay as compared with that of patients with significant obstructive coronary lesions, probably due to the low incidence of complications.

The studies with patients with acute coronary syndrome and no significant obstructive coronary lesions are case series with a small number of individuals, in which most information is based on retrospective studies with varied results, and using different definitions and inclusion criteria. The lack of uniformity in defining significant obstructive coronary lesions leads to a variation in the prevalence of acute coronary syndrome in individuals with no significant obstructive coronary lesions, which in the literature corresponds to 1 to 20% of the individuals. Roe et al ¹³ and Raymond et al ¹⁵ have considered coronary stenosis < 50%, including normal coronary arteries, as nonsignificant obstructive coronary lesions. On the other hand, Zimmerman et al ¹⁶, considered only patients with completely normal coronary arteries.

The inclusion of patients with atypical chest pain, mainly women, whose cardiac catheterization showed the absence of coronary artery disease and no need for a routine coronary arteriography according to the recommendation of the attending physician, may have led to selection bias, therefore, hindering data analysis. Another limitation regards the limited angiographic information, which does not include the characteristics of the lesions. In this way, the method used for quantifying the severity of coronary lesions was visual assessment; however, quantitative angiography is known to be a more accurate method for assessing the degree of coronary stenosis ¹⁹.

Our results have shown that patients with acute coronary syndrome, an elevation in the ST segment, and nonsignificant obstructive coronary lesions were younger and had a greater prevalence of smoking when compared with individuals with significant obstructive coronary lesions. In regard to the individuals with acute coronary syndrome without an elevation in the ST segment, those with a nonsignificant obstructive coronary lesion were predominantly of the female sex, belonged to a younger age group, and had a lower frequency of risk factors when compared with individuals with a significant obstructive coronary lesion.

The individuals without a significant obstructive coronary lesion also had a lower rate of complications, which resulted in a shorter length of hospital stay in that group. In individuals with acute coronary syndrome and an elevation in the ST segment, no statistically significant difference was observed in the in-hospital evolution of those with or without a significant obstructive lesion.

References

Recebido para publicação em 20/3/03

Aceito em 17/3/04

English version by Stela Maris Costalonga

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Publication Dates

• Publication in this collection
  14 Feb 2005
• Date of issue
  Jan 2005

History

• Accepted
  17 Mar 2004
• Received
  20 Mar 2003