Prognostication of long-term outcomes for patients with ischemic heart disease

Cardiovascular disease, including coronary heart disease (CHD), is the leading cause of death among elderly adults across many European countries. In 2005, the Clinic of Cardiology, Hospital of Lithuanian University of Health Sciences (former Kaunas University of Medicine), started to gather the clinical data of patients with acute and chronic coronary syndromes according to the standards set by the Cardiology Audit and Registration Data Standards Project. The aim of our study was to evaluate one-year mortality after inpatient treatment for acute and chronic coronary syndromes in different risk groups. Material and methods. A total of 3268 patients who were treated for coronary heart disease acute myocardial infarction, unstable angina, stable angina – at the Clinic of Cardiology, Hospital of Lithuanian University of Health Sciences (former Kaunas University of Medicine) in 2005 were randomly selected. Clinical data of the patients were collected by means of a standardized questionnaire. After one year, 1908 patients were reexamined, and predominant symptoms, treatment during one-year period, outcomes were evaluated. Results. Multiple logistic regression analysis revealed that one-year mortality after acute coronary syndromes was most influenced by age of 70–80 years, history of stroke, Killip class III-IV, and reduced high-density lipoprotein cholesterol levels. For patients who were treated for chronic coronary syndromes, reduced EF (<40%) and increased heart rate (>70 beats per minute) were the strongest independent predictors of one-year mortality. Conclusion. A scoring system for the assessment of mortality risk within one year for patients with acute and chronic coronary syndromes was constructed, which could be useful for cardiologists as well as family physicians for risk evaluation in inpatient and outpatient settings.


Introduction
Cardiovascular disease (CVD), including coronary heart disease (CHD), is the main cause of global mortality in most European countries that leads to about 17 million deaths annually (1).Although overall mortality from CHD in Western Europe has declined, the absolute number of people who died from CHD in these countries has not decreased and the incidence of CHD, with aging population, even has increased.Mortality from many chronic noninfectious diseases in Lithuania is higher than in other European countries.In 2008, age-standardized ischemic heart disease mortality rates in Lithuania were 3 times greater than on average across EU countries (449 per 100 000 population for men and 240 per 100 000 population for women) (2).Survival prolongation in patients with CHD depends on effective primary and secondary prevention, new medical treatments and interventional methods.
Epidemiological studies on CHD that include CHD registry and health checkups in a random population have been carried out in Kaunas, Lithuania, since 1970 (3).In 2005, the Clinic of Cardiology, Hospital of Lithuanian University of Health Sciences (former Kaunas University of Medicine), started to gather the clinical data of patients with acute and chronic coronary syndromes according to the standards set by the Cardiology Audit and Registration Data Standards (CARDS) Project.This standardized system of clinical data collection has been launched with the aim to develop expert consensus on data standards (variables, defi nitions, and coding) that could allow comparing the prevalence of individual symptoms and disease expression of patients with acute and chronic coronary syndromes at hospital, and evaluation of patient survival during one year.The aim of this study was to evaluate one-year patient mortality after inpatient treatment of acute and chronic coronary syndromes in different risk groups.

Material and methods
A total of 3268 patients who were treated for coronary heart disease -acute myocardial infarction, unstable angina, stable angina -at the Clinic of Cardiology, Hospital of Lithuanian University of Health Sciences (former Kaunas University of Medicine) in 2005 were randomly selected.Their data were collected by a standardized questionnaire.Medical history data, comorbidities, status on admission, drug and interventional treatment, rehabilitation therapy, and recommended treatment after discharge were analyzed.A total of 1908 patients were reexamined after one year: predominant symptoms, applied treatment, and outcomes during one year were evaluated.Risk factors for CHD were evaluated during this study.Arterial hypertension was diagnosed with a history of BP ≥140/90 mm Hg or if antihypertensive medications were prescribed for a patient.Dyslipidemia was diagnosed as an increase in low-density lipoprotein cholesterol (LDL-Ch) levels in blood serum (≥ 3 mmol/L) and total cholesterol (TCh) levels (>5.2 mmol/L), and a decrease in high-density lipoprotein cholesterol levels (HDL-Ch) (<1.2 mmol/L for women and <1.0 mmol/L for men).Hyperglycemia was defi ned as plasma glucose value exceeding ≥5.6 mmol/L.Myocardial infarction was diagnosed according to the WHO guidelines: angina pain and equivalent, ischemic signs of ECG (Q wave, ST and T changes), and an increase in troponin I level (>0.05 μg/L).The diagnosis of unstable angina was confi rmed with the angina syndrome, ischemic changes on ECG without increased enzyme levels in blood, and angiography assessment of the coronary artery.Coronary artery angiography was performed by the Judkins technique.Severe stenosis of 1, 2, or 3 vessels was defi ned as a narrowing of the coronary artery (≥50%).Stable angina was determined according to the standard clinical picture and fi ndings of ECG, exercise test, and angiography.The patients with acute myocardial infarction (MI) were ranked according to the Killip classifi cation.Cardiovascular functional capacity was classifi ed according to the recommendations of the New York Heart Association (NYHA FC I-IV).
Statistical analysis.The statistical analysis was performed using SPSS (Statistical Package for Social Science) version 13 and Microsoft Offi ce Excel 2003 statistical programs.Descriptive statistics was used for the analysis of continuous data.Categorical data were summarized as frequencies and percentages, and for comparisons, the chi-square test was used.Univariate and multivariate logistic regression analysis was employed for the risk assessment.Oneyear mortality risk was evaluated by isolated and standardized odds ratios with 95% confi dence intervals (CI).A risk factor was considered informative for one-year mortality if its standardized risk was signifi cant.Complex one-year mortality risk was evaluated by risk score, summing informative risk factors multiplied with the weighted scores proportional to standardized risk ratio.

Results
A total of 3268 randomly selected patients who were treated for acute and chronic coronary syndromes at the Clinic of Cardiology, Lithuanian University of Health Sciences (former Kaunas University of Medicine), were examined.After one year, 1908 patients (739 women and 1169 men) were reexamined.The majority of the participants were men (61.3%), mostly aged 51-80 years.More than one-third (n=660, 34.6%) of the participants were smokers, 12.8% (244 patients) had diabetes, and 78.3% (1494 patients) had a history of hypertension (Table 1).
Majority of the patients complained of chest pains.Angiotensin-converting enzyme (ACE) inhibitors, β-blockers, statins, and anticoagulants (aspirin) were prescribed for more than 80% of patients during the hospitalization and for 50% to 70% patients at home.Interventional therapy was more frequently applied for 40-70-year-old patients: 40-60-year olds underwent angioplasty more frequently and 50-70-year olds -surgical treatment.Interventional treatment was more often applied for men than women (by 11.5%) and for those with severe stenosis (>50%) of 1 to 3 coronary arteries.
Previous heart failure, stroke, and chronic obstructive pulmonary disease, atrial fi brillation (AF) at admission, Killip class III or IV at admission, age of 70-80 years, ejection fraction (EF) of <40%, and dyslipidemia (HDL-Ch <1.0 mmol/L for males and <1.2 mmol/L for females) were among the factors found to be independent predictors of one-year mortality for the patients with acute coronary syndromes (Table 2).Interventional treatment (performed percutaneous transluminal coronary angioplasty and coronary artery bypass grafting) signifi cantly reduced the risk of death within oneyear period (Table 2).
Heart rate of ≥70 beats per minute at admission, age of ≥80 years, EF of <40%, dyslipidemia (HDL-Ch <1.0 mmol/L for males and <1.2 mmol/L for females), and chronic AF were among the factors found to be independent predictors of one-year mortality for the patients with chronic coronary syndromes (Table 3).
Selected informative signs for one-year mortality for the patients with acute and chronic coronary syndromes were evaluated by a scoring system, refl ecting mortality risk (Tables 4 and 5).
According to the score, a patient can be attributed to the groups of low, moderate, and high risk of death within one-year period.Moderate-and high-risk patients with acute coronary syndromes were approximately 5 and 10 times, respectively, more likely to die within one year as compared to low-risk patients (Table 6).For high-risk patients with chronic coronary syndromes, the risk of death within one year was nearly 13 times greater than for low-risk patients (Table 7).

Discussion
Comparison of the prevalence of risk factors in our target population with the data of other studies revealed that our study population was older (50-70 years).The prevalence of the most common risk factors in our study population was similar to that in other European countries, except for much higher prevalence of hypertension (4).
The impact of different risk factors on mortality was compared across different clinical registries and Prognostication of long-term outcomes for patients with ischemic heart disease studies.Signifi cant risk factors for one-year mortality in our study corresponded to risk factors most commonly reported in literature (3).Integrated one-year mortality analysis showed that age of 70-80 years, history of stroke, Killip class III or IV, and decreased HDL-Ch levels in blood had the greatest impact on mortality within one year in patients with acute coronary syndromes.For patients with chron-ic coronary syndromes, one-year mortality was signifi cantly associated with reduced EF (<40%) and heart rate (>70 bpm).Heart failure leads to a signifi cant risk of death in patients with acute coronary syndromes as shown in the Candesartan in Heart failure-Assessment of Reduction in Mortality and Morbidity (CHARM), Euro Heart Survey II studies, and Studies of Left Ventricular Dysfunction (SOLVD).The results of these studies have shown that a history of heart failure (EF <40%) also contributes to a poor prognosis of patients with chronic coronary syndromes, because the most common cause of heart failure is myocardial infarction (5,6).The GRACE registry suggests that acute heart failure 3 to 4 times increased risk of death after MI during 6-month period (7), and by data of other studies, the risk of death was even greater after MI and unstable angina, complicated with heart failure, during an 18-month period (8,9).Our data show that Killip class III or IV is one of the major risk factor for one-year mortality.According to literature data, a history of stroke is an independent factor signifi cantly increasing mortality from acute coronary syndromes (10), and some authors reported that after ischemic stroke, the 5-year risk of MI or cardiovascular death was increased to 17.4%, and coronary artery disease along with AF was associated with a 75% increase in the risk of MI or vascular death (11).AF is a signifi cant risk factor contributing to mortality in patients with chronic ischemic syndromes and associated with the risk of heart failure and stroke (12).The BEAUTIFUL study showed the prognostic signifi cance of heart rate for patients with chronic coronary syndromes (13).Higher risk of one-year mortality was found in patients with unstable angina as compared with patients with chronic coronary syndromes in the National Heart, Lung, and Blood Institute Dynamic Registry (4.4%  (15).However, in our study, this parameter insignifi cantly increased the risk of one-year mortality.Studies reported that adequate HDL-Ch levels protect against future cardiovascular events and affect atherosclerotic regression (16).Our data confi rmed that a decrease in HDL-Ch levels in blood signifi cantly increased the risk of death within one year both for patients with acute and chronic coronary syndromes.
Recently, many researchers are trying to develop models for risk stratifi cation in patients with acute or chronic coronary syndromes (17)(18)(19).In the Euro Heart Survey, a simple scoring system was constructed that allowed discrimination between lowand high-risk groups of patients with chronic ischemic disease during a one-year period.This study showed that previous myocardial infarction ( (20).Long duration of chest pain (>6 months) reduced the risk of death (0.48; 95% CI, 0.3-0.77;P=0.002) (20).The Global Registry of Acute Coronary Events study reported that ACS patients who experienced any adverse cardiovascular event were more likely to have a history of hyperlipidemia, smoking, MI, stroke, Killip class II-IV heart failure, cardiac arrhythmias (AF, ventricular tachycardia, ventricular fi brillation), higher heart rate, angioplasty, and to be older (21).ACS, complicated with ventricular arrhythmias, significantly increased in-hospital mortality and mortality during 6 months after hospitalization (22,23).
Our proposed risk scoring system makes it possible to identify and discriminate patients at high risk of death during one-year period according to medical history and clinical data, and can be easily used individualizing patient care and treatment by cardiologists and family physicians.

Conclusion
A scoring system for the assessment of mortality risk within one year for patients with acute and chronic coronary syndromes was constructed, which could be useful for cardiologists as well as family physicians for risk evaluation in inpatient and outpatient settings.

Table 3 .
Independent predictors of one-year mortality for patients with chronic coronary syndromes

Table 4 .
Integrated one-year death risk, expressed as a standardized risk ratio, for patients with acute coronary syndromes

Table 5 .
Integrated one-year death risk, expressed as a standardized risk ratio, for patients with chronic coronary syndromes

Table 6 .
One-year mortality risk groups for patients with acute ischemic syndromes

Table 8 .
One-year mortality rate for patients with acute coronary syndromes

Table 7 .
One-year mortality risk groups for patients with chronic ischemic syndromes