Complications of Coronary Syndrome and Stroke in Cohort Study

Thrombus formation can cause acute events such as acute myocardial infarction (AMI) and angina or extend to peripheral artery disease or stroke. Patients with acute symptoms of a vascular bed, such as AMI, are at high risk of developing events in another vascular beds, such as ischemic cerebrovascular disease2. Understanding that Internacional Journal of Cardiovascular Sciences. 2015;28(5):377-384


Introduction
The components of acute coronary syndrome (ACS) and stroke are among the main diseases of the circulatory system and both, in their etiology, present the involvement of atherothrombotic process.
Acute manifestations of atherothrombotic disease include acute coronary syndrome (unstable angina, acute myocardial infarction without ST-segment elevation, acute myocardial infarction with ST-segment elevation), stroke/transient ischemia and symptomatic peripheral arterial disease 1 .
Thrombus formation can cause acute events such as acute myocardial infarction (AMI) and angina or extend to peripheral artery disease or stroke.Patients with acute symptoms of a vascular bed, such as AMI, are at high risk of developing events in another vascular beds, such as ischemic cerebrovascular disease 2 .Understanding that these diseases are consequences of the same underlying vascular process has been a breakthrough toward the development of new therapeutic interventions can help identify patients at risk and prevent manifestations of atherothrombosis 3 .
Despite the observed decrease in mortality due to diseases of the circulatory system 4 , the components of ACS and stroke remain among the leading causes of death and present relevant prevalence 5 .The complications of ischemic heart diseases include reinfarction 6 , heart failure 7 and the possibility of cerebrovascular disease 8 , or serious medical conditions that can lead to death 9,10 .Case-control multicenter study including patients with ACS and ischemic brain disease showed that risk factors for both diseases were similar and most of them are modifiable, which would increase the comprehensiveness of primary prevention measures 11 .
In turn, epidemiological information from cohort studies can provide important insights about the characteristics of patients most likely to complications.This manuscript aims to verify the incidence of complications of acute coronary syndrome or stroke and its risk factors in a cohort over one-year follow-up.

Methods
An epidemiological study deriving from the Project "Prospective cohort of patients with acute coronary syndrome," from May 2009 to May 2011, was conducted on patients aged ≥ 30, of both sexes, diagnosed with ACS or stroke, admitted to a large-size hospital located in Porto Alegre, state of Rio Grande do Sul, and followed up at 30 days, six months and one year after discharge from hospital.
Patients who lived outside of Rio Grande do Sul, who did not have a phone number to be contacted, whose diagnoses have changed while in hospital to another diagnosis not included in the inclusion criteria, those unable to answer the questionnaire and those whose parents were not accessible in the hospital after three attempts of contact for data collection were excluded from the study.
The sample size was calculated considering the confidence index of 95%, power of 80%, unexposed ratio: exposed 1:2, outcome frequency between the unexposed 20% and relative risk of 2.0, requiring 181 participants.Added losses and requirements of adjusted analysis required the selection of 226 participants.
Pilot study was conducted during the first 30 days of research in order to assess the quality of data collection instruments and to check the logistics of fieldwork.Quality control was conducted in a random sample of 5% of people included in the study in order to assess the internal validity of the research.
For data collection, four models of standardized precoded questionnaires were used.The initial data were extracted from a questionnaire given to the patients and from their medical records.During follow-up, three questionnaires were given through telephone contact at 30 days, six months and one year after discharge from hospital.Data collection was conducted by interviewers undergoing training program.
The study outcome was the presence of complications of ACS or stroke up to one year after hospital discharge.The following complications were considered: new episode of stroke, acute myocardial reinfarction, heart failure or death.Note that to build the outcome, only one complication was considered, that is, if any individual presented more than one event, only one would be counted.
The emergence of a new episode of stroke, reinfarction, heart failure and death were analyzed on three occasions in follow-ups up to 30 days, six months and one year after discharge.
The independent variables investigated were classified as demographic, socioeconomic, behavioral and morbidities.The demographic variables included age, sex, self-reported skin color and marital status (married or in a de facto relationship; widowed, single or separated).
The socioeconomic variables were education in terms of full years of study (≥12 years; 11.9 years; 8-5 years; ≤4 years) and monthly family income categorized into tertiles.
Behavioral variables were represented by smoking (nonsmoker, former smoker > 10 years, former smoker < 10 years and smoker); nutritional status, physical activity and alcohol consumption.

• ACS -acute coronary syndrome • AMI -acute myocardial infarction • BMI -body mass index
Nutritional status was classified by body mass index (BMI) calculated by dividing weight (kg) by height (m) squared (kg/m 2 ), both self-reported by the participants.
Physical activity was analyzed according to the frequency and duration in leisure.The participants were classified as physically active when they performed activities lasting ≥150 minutes per week.
For alcohol consumption, any quantities considered to represent risk for cardiovascular diseases were considered.According to the World Health Organization, risk is considered when daily consumption of alcohol is greater than two drinks for men and one drink for women.One drink corresponds to a can of beer, a glass of wine or standard shot of distilled drink.
Morbidities variables collected at study entry were the presence of hypertension and diabetes mellitus, both reported by the patients.
Data were double entered in the Program Epi Info, detecting any typos.
Statistical analysis was performed using the software SPSS 17 (Statistical Package for the Social Sciences) and Stata 10.The analysis described the incidences of complications in each follow-up period.Later, descriptive analyzes were conducted to characterize the population included in the study.Gross analysis of incidence in the period of complications was carried out upon presentation of hazard ratios, confidence intervals and statistical tests.We used Poisson regression with robust variance in the adjusted analysis.For the adjusted analysis, variables with p-value of up to 0.20 in the gross analysis were selected.The entry of the variables followed a hierarchical model.The model adopted was based on the principle that demographic and socioeconomic variables were distally located determining the behavioral variables arranged on an intermediate level which, in turn, influenced the morbidities, all related to the outcome.
The incidences of complications were observed in isolation in each follow-up period.The most frequent incidences were deaths, with greater frequency in the first 30 days following the occurrence of heart failure, with greater frequency in one-year follow-up.The incidences of reinfarction and new episode of stroke were very low in all periods analyzed (Table 1).
In the gross analysis, a higher incidence of complications in individuals aged >80, non-white skin color, widowed, single or separated individuals, in those with a poorer education and former smokers <10 years was found.Among the participants who reported diabetes mellitus, the occurrence of complications was 33.0% higher, although with a threshold significance (Table 2).
The gross analysis showed no statistically significant differences in sex, family income, BMI, physical activity, alcohol consumption and high blood pressure that were extracted from the model (Table 2).
After adjustment between demographic and socioeconomic variables, it was found that individuals aged ≥80 and those of non-white skin color had higher prevalence of complications.In the second level adjustment, former smokers <10 and smokers were associated with the outcome.Former smokers had a higher magnitude than smokers.Participants who reported diabetes mellitus also showed a higher incidence of complications after adjustment for age, skin color and smoking (Table 3).

Discussion
The incidence of complications in individuals with ACS or stroke was 27.6%, which is considered high, because follow-up lasted only one year.The diseases of inclusion in this study confirmed their severity, and the occurrence of deaths was the most frequent complication in the follow-ups.Other cohort studies have also shown a high occurrence of deaths 12,13 resulting from AMI.
In a cohort of five years, Fox et al. 14 observed that late consequences of ACS, such as death, myocardial infarction and stroke were substantially higher in the later period than during the hospital stay.
Another event of high incidence after one year of followup was heart failure.The study by Ezekowitz et al. 12 also showed a high incidence of heart failure.However, it included elderly individuals followed for five years, that is, longer observation time.
A cohort study conducted in a Brazilian tertiary care hospital, including 760 patients with ACS found no incidence of non-fatal stroke in 1.1% in 30-day follow-up and 1.5% at six months 15 .
In this study, the incidence of stroke was low.It is known that the incidence of stroke after ACS has ranged from 0.18% to 1.5%, even in over long periods of follow-up 16 .
It considered the low incidence of reinfarction in all follow-up.A higher incidence in the first 30 days was expected, as studies have shown high incidence of reinfarction in the first ten days after the acute event 17 .
This study was conducted in a highly complex hospital upon admission of private or insured patients with a mean age > 70, with high income and education levels.
Another study involving the same population showed that even when hospitalized because of recognizably serious illnesses, the individuals have not changed their habits of life and were exposed to a number of risk factors 18 , which may point to the difficulties of changes in lifestyle.The presence of complications was associated with increased age, non-white skin color, smoking, and diabetes mellitus.These factors are well discussed in the literature.
It should be noted that the risk factors associated with cerebrovascular disease may have different behavior from those associated with the CSA, such as high blood pressure.The impact of treatment is more relevant in stroke than in ACS 19 .
Age is a recognized risk factor for the onset of complications 12,20,21 .In addition to being a risk factor for hospitalizations and deaths 22 , older individuals may be at increased frequency of comorbidities such as chronic obstructive pulmonary disease, another vascular disease and kidney disease, as well as greater exposure to risk factors such as hypertension and diabetes 12,23 .
In this study, non-white skin color was another independent variable associated with the occurrence of complications.Race/ethnicity classified as non-white was identified among the risk factors for the incidence of stroke and after acute myocardial infarction, in a metaanalysis involving 22 studies 8 .Other studies have shown increased incidence of heart failure among black individuals 24,25 .It is known that left ventricular hypertrophy affects mainly black peoples, which is supported by the high prevalence of uncontrolled blood pressure among people of black ethnicity leading to the occurrence of cardiac failure 24 .
The analysis pointed out as significant the association two modifiable factors: smoking and diabetes mellitus.
Smoking has been considered the main cause of preventable death around the world by the World Health Organization.Many observational and multicenter studies have clarified the risk factors for coronary artery disease, including smoking 26,27 .In this study, after adjustment for age and skin color, there was a higher incidence of complications among former smokers and smokers, respectively.This finding may add one more contribution to the set of harms related to tobacco, since in the classic study of Doll et al. 28 , using a healthy population, smoking cessation reduced the cardiovascular risk to levels similar to those of nonsmokers.
Several studies have pointed out diabetes mellitus as a risk factor for the occurrence of complications in diseases of the circulatory system 26,29,30 .The presence of diabetes has caused twice the risk for coronary artery disease, stroke and deaths attributed to other vascular causes.
The presence of the disease has been strongly related to fatal AMI due to more severe forms of coronary lesions in people with diabetes, so that about 20.0% of vascular deaths would be attributable to its occurrence.With the increasing rates of obesity worldwide, it is likely that the absolute risk for diabetes mellitus and vascular diseases will increase as well 30 .The study showed the importance of diabetes mellitus determining the occurrence of complications, even controlling for age, skin color and smoking.
The main limitation to evaluate the findings of this manuscript was a consequence of inclusion criteria.Patients diagnosed with ACS and stroke have been accepted regardless of the first episode.Patients who were included in the study could have presented some diagnosis of interest.Another problem in the study design was the non-distinction between ACS components that could indicate more severe forms of the disease.However, the study design was appropriate, the number of losses was smaller than 10% and data were rigorously collected.

Conclusions
The two groups of diseases involved in the study (ACS and stroke) confirmed their condition of severity, so much so that the occurrence of deaths was the most frequent complication in the follow-ups.There was a significant association of diabetes mellitus and smoking with the occurrence of complications, even controlling for age and skin color.

Potential Conflicts of Interest
This study has no relevant conflicts of interest.

Table 2 Demographic, socioeconomic, behavioral variables and morbidities of the studied population and incidence of complications
HR -hazard ratio; sing -single; sep -separated; BMI -body mass index

Table 3 Incidence of acute coronary syndrome complications in relation to the variables selected: adjusted analysis
This study was partially funded by the National Council for Scientific and Technological Development (Notice MCT/CNPq 14/2009 Range B).Association This manuscript is part of the Masters' Dissertation of Rosangela Uebel in the Graduate Program in Collective Health of Universidade do Vale do Rio dos Sinos.