Heart failure during acute coronary syndrome and the long-term cancer risk: the ABC-9 Study on heart disease.

AIMS: A higher risk of cancer among patients with heart failure (HF) has been suggested in recent community-based studies. This study aimed to investigate the impact of HF during hospitalization with acute coronary syndrome (ACS) on the long-term cancer risk. METHODS AND RESULTS: The study included 572 patients admitted with ACS to three Italian hospitals, discharged cancer-free, and prospectively followed for 24 years or until death. All but three patients completed the follow-up, which represented 6440 person-years (mean age: 66 ± 12 years; 70% males). Baseline HF was diagnosed in 192 (34%) patients. A total of 129 (23%) patients developed cancer (103 without HF and 26 with HF), and 107 (19%) patients died due to it (81 without HF and 26 with HF). The incidence rates for cancer onset and cancer death were not different according to HF status. Cox regression analysis revealed no association between HF or left ventricular ejection fraction (LVEF) and cancer risk. In addition, no difference in cancer risk was observed among patients with HF with preserved ejection fraction, HF with mildly reduced ejection fraction, and HF with reduced ejection fraction. In competing risk regression analysis, the risk of cancer onset associated with HF was sub-hazard ratio (SHR) 0.47 [95% confidence interval (CI): 0.30-0.72; P = 0.001] and SHR 1.02 (95% CI: 1.01-1.04; P = 0.002) with LVEF. Results were the same in the adjusted model. Yet the fully adjusted model showed an attenuated association between cancer death and HF (SHR: 0.63; 95% CI: 0.37-1.05; P = 0.08) and LVEF (SHR: 1.02; 95% CI: 0.99-1.06; P = 0.08). Consistent results were obtained after using propensity score matching analysis that created 192 pairs. A negative interaction between age and HF and a positive interaction between age and LVEF for cancer risk have also been found. CONCLUSIONS: An inverse association between baseline HF and long-term cancer risk has been observed among the ABC Study on heart disease patients who were followed for 24 years after ACS.

Healthy overweight and obesity in the young: Prevalence and risk of major adverse cardiovascular events.

AIMS: To investigate the prevalence of metabolically healthy overweight/obesity and to study its longitudinal association with major adverse cardiovascular and renal events (MARCE). METHODS AND RESULTS: The study was conducted in 1210 young-to-middle-age subjects grouped according to their BMI and metabolic status. The risk of MARCE was evaluated during 17.4 years of follow-up. Forty-eight-percent of the participants had normal weight, 41.9% had overweight, and 9.3% had obesity. Metabolically healthy status was found in 31.1% of subjects with normal weight and in 20.0% of those with overweight/obesity. During the follow-up, there were 108 MARCE. In multivariate Cox analysis adjusted for confounders and risk factors, no association was found between MARCE and overweight/obesity (p = 0.49). In contrast, metabolic status considered as a two-class variable (0 versus at least one metabolic abnormality) was a significant predictor of MARCE (HR, 2.11; 95%CI, 1.21-3.70, p = 0.009). Exclusion of atrial fibrillation from MARCE (N = 87) provided similar results (HR, 2.11; 95%CI, 1.07-4.16, p = 0.030). Inclusion of average 24 h BP in the regression model attenuated the strength of the associations. Compared to the group with healthy metabolic status, the metabolically unhealthy overweight/obesity participants had an increased risk of MARCE with an adjusted HR of 2.33 (95%CI, 1.05-5.19, p = 0.038). Among the metabolically healthy individuals, the CV risk did not differ according to BMI group (p = 0.53). CONCLUSION: The present data show that the risk of MARCE is not increased in young metabolically healthy overweight/obesity suggesting that the clinical approach to people with high BMI should focus on parameters of metabolic health rather than on BMI.

Microalbuminuria during acute coronary syndrome: Association with 22-year mortality and causes of death. The ABC-8* study on heart disease. (*ABC is an acronym for Adria, Bassano, Conegliano, and Padova Hospitals).

BACKGROUND: Microalbuminuria is associated with adverse outcomes in acute coronary syndrome (ACS) patients. METHODS: To evaluate the very long-term association between Microalbuminuria and the overall mortality and causes of death in this clinical setting, we prospectively studied 579 unselected ACS patients admitted to three hospitals. The baseline albumin-to-creatinine ratio (ACR) was measured on days 1, 3, and 7 in 24-h urine samples. Patients were followed for 22 years or until death. RESULTS: Virtually all patients completed follow-up; 449(78%) had died: 41% due to non-sudden cardiac death (non-SCD), 19% sudden cardiac death (SCD), 40% due to non-cardiac (non-CD) death. Using unadjusted Cox regression analysis, ACR was a significant predictor of all-cause mortality (hazard ratio [HR] 1.26;95%confidence interval [CI] 1.22-1.31; p˂0.0001) and the three causes of death (HR 1.40;95%CI 1.32-1.48; p˂0.0001), (HR 1.22;95%CI 1.12-1.32; p˂0.0001) and (HR 1.16;95%CI 1.09-1.23; p˂0.0001) for non-SCD, SCD and non-CD respectively. Using a fully adjusted model, ACR was a significant independent predictor of all-cause mortality (HR 1.12; 95%CI 1.08-1.16; p˂0.0001) and only non-SCD (HR 1.21; 95%CI 1.14-1.29; p˂0.0001). There was a positive interaction between ACR level and history of AMI (HR 1.15; 95%CI 1.03-1.29; p = 0.01) and the presence of heart failure at admission (HR 1.11; 95%CI 1.01-1.24; p = 0.04), and negative interaction with higher than median LVEF (HR 0.89; 95%CI 0.80-0.99; p = 0.03) for all-cause mortality at the multivariable level. CONCLUSION: Based on the present analysis, baseline urinary albumin excretion during ACS is a strong independent predictor of the very long-term mortality risk, chiefly due to non-sudden cardiac death.

Differences in Cancer Death Risk Long After ACS Among Selected Urban and Rural Areas in North Italy: The ABC-7a Study on Heart Disease.

BACKGROUND: An increased risk of cancer death has been demonstrated for patients diagnosed with acute coronary syndrome (ACS). We are investigating possible geographic risk disparities. METHODS: This prospective study included 541 ACS patients who were admitted to hospitals and discharged alive in three provinces of Italy's Veneto region. The patients were classified as residing in urban or rural areas in each province. RESULTS: With 3 exceptions, all patients completed the 22-year follow-up or were followed until death. Urban (46%) and rural (54%) residents shared most of their baseline demographic and clinical characteristics. Pre-existing malignancy was noted in 15 patients, whereas 106 patients developed cancer during the follow-up period, which represented 6232 person-years. No difference in the cancer death risk was found between the urban and rural areas or between southern and northern provinces (hazard ratio [HR] 1.1; 95% confidence interval [CI] 0.7-1.7; p = 0.59 and HR 1.1; 95% CI 0.9-1.4; p = 0.29, respectively) according to the unadjusted Cox regression analysis. Geographic areas, however, showed a strong positive interaction, with risk increasing from the urban to rural areas from southern to northern provinces (HR 1.9; 95% CI 1.1-3.0; p = 0.01). The fully adjusted Cox regression and Fine-Gray competing risk regression models provided similar results. Interestingly, these results persisted, and even strengthened, after exclusion of the 22 patients who developed malignancy and survived to the end of follow-up. We did not observe an urban/rural difference in non-neoplastic death risk or a significant interaction between the geographic areas. CONCLUSION: Our analysis reveals that the cancer death risk among unselected ACS patients in Italy's Veneto region significantly differs by geography. The northern rural area has the highest risk. These results highlight the importance of implementing a preventive policy based on area-specific knowledge.

Risk of malignancy long after acute coronary syndrome in selected urban and rural areas and comparison with smoking risk: the ABC-7* study on Heart Disease.

BACKGROUND: Increased cancer risk has been reported in patients with acute coronary syndrome (ACS). OBJECTIVES: To investigate geographic differences in risk malignancy long after ACS. METHODS: We enrolled 586 ACS patients admitted to hospitals in three provinces in the Veneto region of Italy in this prospective study. Patient's residency was classified into three urban and three nearby rural areas. RESULTS: All (except for 3) patients completed the follow-up (22 years or death) and 54 % were living in rural areas. Sixteen patients had pre-existing malignancy, and 106 developed the disease during follow-up. Cancer prevalence was 17 % and 24 % (p = 0.05) and incidence of malignancy was 16 and 21/1000 person-years for urban and rural areas, respectively. In unadjusted logistic regression analysis, cancer risk increased from urban to rural areas (odds ratio [OR] 3.4;95 % confidence interval [CI] 1.7-7.1; p = 0.001), with little change from north to south provinces (OR 1.5;95 % CI 1.0-2.2; p = 0.06). Yet, we found a strong positive interaction between urban-rural areas and provinces (OR 2.1;95 % CI 1.2-3.5; p = 0.003). These results kept true in the fully adjusted model. Unadjusted Cox regression analysis revealed increasing hazards ratios (HRs) for malignancy onset from urban to rural areas (HR 3.0;95 % CI 1.5-6.2; p = 0.02), but not among provinces (HR 1.3;95 % CI 1.0-2.0; p = 0.14). Also, we found a strong positive interaction between geographic areas (HR 2.1;95 % CI 1.3-3.5; p = 0.002), even with a fully adjusted model. CONCLUSIONS: The results in unselected real-world patients demonstrate a significant geographic difference in malignancy risk in ACS patients, with the highest risk in the north-rural area.

Baseline plasma lipid levels in patients with acute coronary syndrome: Association with 20-year mortality. The ABC-5a* Study on Heart Disease.

BACKGROUND: The relationship between baseline plasma lipid levels during acute coronary syndrome and the outcome has clinical relevance. METHODS: To evaluate their long-term prognostic value, we examined 589 patients admitted with acute coronary syndrome at three hospitals. Baseline plasma lipids were assessed on days 1 and 7. Patients were followed for 20 years or until death. RESULTS: Virtually, all patients completed follow-up; 437 (74%) had died: 24% from coronary artery disease/heart failure (CAD/HF), 21% sudden cardiac death (SCD), 16% from other cardiovascular causes and 39% had non-cardiac death. The incidence rate (IR) of all-cause mortality was not different among patients with baseline plasma lipids less or greater than the median value. The IR of CAD/HF mortality was not significantly higher among patients with greater than median low-density lipoprotein (LDL) cholesterol and triglyceride (TG) levels. The IR of non-cardiac death tended to be lower among patients with greater than median total cholesterol (TC) and LDL levels. Using three levels of adjusted Cox survival models, baseline plasma lipids had no consistent independent or inverse association with all-cause mortality, even after excluding patients who received statins. Competitive risk survival models for each cause of death revealed that the only hazard of non-cardiac death was consistently higher among patients with less than or equal to median TC and LDL levels. CONCLUSION: In the present prospective long-term study, after acute coronary syndrome, baseline plasma lipid levels seem not to be associated with long-term global mortality. Only an independent inverse association between TC and LDL and non-cardiac death has been observed.

Association between plasma lipid levels during acute coronary syndrome and long-term malignancy risk. The ABC-4* study on heart disease.

BACKGROUND: Emerging evidence suggests that patients with coronary artery disease carry an increased risk of developing malignancy, with deleterious effects on long-term prognosis. Our aim was to ascertain whether baseline plasma lipid levels during acute coronary syndrome (ACS) are associated with malignancy in long-term. METHODS: This study included 589 patients admitted with ACS to three centers and discharged alive. Plasma lipid levels were assessed on the first morning after admission. Patients were followed for 17 years or until death. RESULTS: Five hundred seventy-one patients were free from malignancy at enrollment, of them 99 (17.3%) developed the disease during follow-up and 75 (13.1%) died due to it. Compared to patients without malignancy, those with malignancy showed lower plasma levels of total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TG). The groups showed similar statin use rates at any time in follow-up. The incidence rate of neoplasia and neoplastic mortality was higher in patients with baseline TC or LDL values ≤ median; they showed 85 and 72% increased incidence rate of developing malignancy and 133 and 122% increased incidence rate of neoplastic death respectively. No differences were observed relative to HDL and TG levels. In survival analysis using Cox regression with parsimonious models, patients with baseline TC or LDL values > median, respectively, showed risks of 0.6(95% CI 0.4-0.9; p = 0.01) and 0.6(95%CI 0.4-0.9; p = 0.02) for malignancy onset, and 0.5(95% CI 0.3-0.8; p = 0.005) and 0.5(95% CI 0.3-0.8; p = 0.004) for neoplastic death. Similar results were obtained using competitive risk analysis with parsimonious models. CONCLUSIONS: This long-term prospective study of an unselected real-world patient sample showed that neoplasia onset and mortality are independently associated with low plasma TC and LDL levels at admission for ACS.

Neoplastic disease after acute coronary syndrome: incidence, duration, and features: the ABC-4* Study on Heart Disease.

AIM: To investigate the clinical features and incidence of malignant neoplasia during 17 years of follow-up in an unselected sample of patients with acute coronary syndrome (ACS). METHODS: The Adria, Bassano, Conegliano, and Padova Hospital-4 Study on Heart Disease is an ongoing, prospective study of an unbiased population of patients with ACS. Baseline clinical and laboratory data were obtained during the first 7 days of hospitalization at three different intensive coronary care units. The current study included data from 589 patients with ACS. RESULTS: At enrollment, 19 patients had confirmed neoplasia. During follow-up, 99 additional patients developed malignant neoplastic disease. The incidence rate was 17.8 cases per 1000 person-years, which was about three times higher than that observed in the general population. Patients had a shorter duration of neoplasia when they developed it after enrollment compared with those with preexisting neoplasia [hazard ratio = 2.0 (1.5-2.6), P = 0.001]. Patients with neoplasia who died during follow-up had an earlier onset of neoplasia [hazard ratio = 1.8 (1.1-2.9), P = 0.01] and shorter duration than survivors [hazard ratio = 4.1 (2.4-7.0), P < 0.0001]. The estimated time to diagnosis of neoplasia indicated elderly patients had a significantly higher risk than younger people during the 17 years of follow-up. After the onset of neoplasia, survival time declined more sharply in the elderly than younger people. CONCLUSION: The long-term prospective study showed that patients with ACS have a higher incidence of malignancy than the general population. Those who develop neoplasm after being diagnosed with ACS have a worse prognosis than patients with a preexisting neoplasia.

Heart failure in women and men during acute coronary syndrome and long-term cardiovascular mortality (the ABC-3* Study on Heart Disease) (*Adria, Bassano, Conegliano, and Padova Hospitals).

AIMS: We investigated the gender-based differences in the association between heart failure (HF) during acute coronary syndrome (ACS) and post-discharge, long-term cardiovascular (CV) mortality. METHODS AND RESULTS: The present study included 557 patients enrolled in three intensive coronary care units and discharged alive. HF during ACS was evaluated by Killip class and left ventricular ejection fraction (LVEF). Interaction between gender and HF after 15years of follow up was studied using Cox models including a formal interaction term. Median age was 67 (interquartile range [IQR], 59-75) years, 29% were females, 37% had non-ST elevation myocardial infarction and 32% Killip class>1, and median LVEF was 53% (IQR 46-61). All but five patients were followed up to 15years, representing 5332 person-years. Of these, 40.2% died of CV-related causes. Crude CV mortality rate was higher among women (52.2%) than men (35.3%; P<0.0001). At a univariable level, a negative interaction between female gender and Killip class for CV mortality was found [hazard ratio (HR)=0.51 (0.34-0.77), P=0.002]. In five multivariable models after controlling for age, main CV risk factors, clinical features, post-discharge medical treatment, and mechanical coronary reperfusion, the interaction was significant across all models [HR=0.63 (0.42-0.95), P=0.02 in the fully adjusted model]. LVEF showed no significant hazard associated with female gender on univariable analysis [HR=1.4 (0.9-0.2.0), P=0.11] but did so in all adjusted models [HR=1.7 (1.2-2.5), P=0.005 in the fully adjusted model]. CONCLUSION: Gender is a consistent, independent effect modifier in the association between HF and long-term CV mortality after ACS.

Long-term effect of continuing sports activity in competitive athletes with frequent ventricular premature complexes and apparently normal heart.

The long-term outcome of athletes with frequent ventricular premature complexes (VPCs) and apparently normal heart has not been fully clarified. To evaluate the clinical and prognostic significance of VPCs and the influence of continuing sports activity during follow-up, we studied 120 healthy athletes (96 men; median age 16 years) in whom frequent VPCs (>100 VPCs/24 hours) were discovered by chance during preparticipation screening. All athletes were followed up for a median of 84 months. During follow-up, 96 underwent serial 24-hour Holter recording and 62 underwent serial echocardiography. The median number of VPCs/24 hours on basal Holter was 3,760. During follow-up, 81 athletes continued sports activity, whereas 39 did not. No athlete died or developed overt heart disease. The median number of VPCs/24 hours decreased in both athletes who continued sports activity and those who did not (from 3,805 to 1,124, p <0.0001 and from 5,787 to 1,298, p <0.0001, respectively). During follow-up, left ventricular ejection fraction slightly decreased to <55% in 9 of 62 athletes who, in respect to the remaining 53, had more VPCs/24 hours both in the basal state (12,000 vs 3,880) and during follow-up (10,702 vs 1,368), and a longer follow-up (95 vs 36 months). In conclusion, (1) frequent VPCs in athletes without heart disease have a long-term benign prognostic significance, (2) sporting activity does not modify this benign outcome, (3) during follow-up, the burden of VPCs decreases whether or not subjects continue sports activity, and (4) in 14.5% of athletes, ejection fraction slightly decreases over time.

Does long-lasting sports practice increase the risk of atrial fibrillation in healthy middle-aged men? Weak suggestions, no objective evidence.

BACKGROUND: Some authors have suggested that sports activity can increase the risk of atrial fibrillation in healthy middle-aged men. Therefore, sport activity, although it prevents coronary artery disease, might be the cause of a potentially dangerous arrhythmia. METHODS: To verify this assumption, we critically analyzed the current literature including original articles, reviews and meta-analyses. RESULTS AND CONCLUSIONS: All published articles showed several limitations. The data provided by published studies support the following conclusions: the incidence of atrial fibrillation in sporting middle-aged men is rare (<0.5% per year); a possible facilitating effect on atrial fibrillation is limited to vigorous endurance exercise, not to less vigorous sports; there are no convincing data to demonstrate that sport itself may be the cause of atrial fibrillation in healthy middle-aged men; and a facilitating effect of long-lasting sport cannot be excluded in middle-aged individuals with cardiovascular disorders. Nevertheless, the beneficial effects of exercise should offset this supposed risk, which, albeit increased, remains low.

Predictors of ten-year event-free survival in patients with acute myocardial infarction (from the Adria, Bassano, Conegliano, and Padova Hospitals [ABC] study on myocardial infarction).

The long-term event-free survival (EFS) after acute myocardial infarction (AMI) is largely uninvestigated. We analyzed noninvasive clinical variables in association with long-term EFS after AMI. The present prospective study included 504 consecutive patients with AMI at 3 hospitals from 1995 to 1998 (Adria, Bassano, Conegliano, and Padova Hospitals [ABC] study). Thirty-seven variables were examined, including demographics, cardiovascular risk factors, in-hospital characteristics, and blood components. The end point was 10-year EFS. Logistic and Cox regression models were used to identify the predictive factors. We compared 3 predictive models according to the goodness of fit and C-statistic analyses. At enrollment, the median age was 67 years (interquartile range 58 to 75), 29% were women, 38% had Killip class >1, and the median left ventricular ejection fraction was 51% (interquartile range 43% to 60%). The 10-year EFS rate was 19%. Both logistic and Cox analyses identified independent predictors, including young age (hazard ratio 1.2, 95% confidence interval 1.1 to 1.3, p = 0.0006), no history of angina (hazard ratio 1.4, 95% confidence interval 1.1 to 1.8, p = 0.009), no previous myocardial infarction (hazard ratio 1.4, 95% confidence interval 1.1 to 1.7, p = 0.01), high estimated glomerular filtration rate (hazard ratio 0.8, 95% confidence interval 0.7 to 0.9, p = 0.001), low albumin/creatinine excretion ratio (hazard ratio 1.2, 95% confidence interval 1.1 to 1.3, p <0.0001), and high left ventricular ejection fraction (hazard ratio 0.8, 95% confidence interval 0.7 to 0.9, p = 0.006). These variables had greater predictive power and improved the predictive power of 2 other models, including Framingham cardiovascular risk factors and the recognized predictors of acute heart damage. In conclusion, 10-year EFS was strongly associated with 4 factors (ABC model) typically neglected in studies of AMI survival, including estimated glomerular filtration rate, albumin/creatinine excretion ratio, a history of angina, and previous myocardial infarction. This model had greater predictive power and improved the power of 2 other models using traditional cardiovascular risk factors and indicators of heart damage during AMI.

[Risk stratification in Brugada syndrome]. / Stratificazione del rischio nella sindrome di Brugada.

Individuals with type 1 Brugada ECG pattern may suffer from malignant ventricular arrhythmias (Brugada syndrome). Patients with Brugada syndrome and documented cardiac arrest should receive an implantable cardioverter-defibrillator. In the remaining subjects, the best management is controversial. Many data suggest that patients with syncope, particularly if they have a spontaneous type 1 ECG pattern, have a significant risk. In the remaining population of asymptomatic subjects, the risk is lower but not negligible. How to manage these latter cases is an unsolved issue. The usefulness of the electrophysiological study (EPS) in risk stratification, i.e. inducibility of sustained ventricular tachycardia/fibrillation, is controversial. Indeed, some authors strongly support the prognostic value of EPS, while others completely deny its usefulness. We recently published our experience concerning the usefulness of a combined approach that considered both clinical data and EPS results; 320 patients (258 males, mean age 43 years) with type 1 ECG were enrolled. No patient had previous cardiac arrest; 54% of patients had a spontaneous and 46% a drug-induced type 1 ECG. One third had syncope, two thirds were asymptomatic; 245 patients underwent EPS; 110 patients received an implantable defibrillator. Patients were followed up for 40 months. During follow-up, 17 patients had major arrhythmic events (MAE) (14 resuscitated ventricular fibrillations and 3 sudden deaths). Both spontaneous type 1 ECG and syncope significantly increased the risk (8.6% and 10.4% event rates vs 2.8% and 1.3%). MAE occurred in 14% of subjects with positive EPS, in no subjects with negative EPS, and in 5.3% of subjects without EPS. All MAE occurred in subjects who had ≥ 2 risk factors (syncope, family history of sudden death and positive EPS). Among these patients, those with spontaneous type 1 ECG had a 30% event rate. In subjects with drug-induced type 1 MAE were rare. In conclusion, 1) in subjects with the Brugada type 1 ECG neither a single clinical risk factor nor EPS alone are able to identify subjects at the highest risk; 2) a multiparametric approach (including syncope, family history of sudden death and positive EPS) helps to identify populations at the highest risk; 3) subjects at the highest risk are those with a spontaneous type 1 ECG and ≥ 2 risk factors; 4) the remainder is at low risk.

Risk stratification in individuals with the Brugada type 1 ECG pattern without previous cardiac arrest: usefulness of a combined clinical and electrophysiologic approach.

AIMS: Risk stratification in individuals with type 1 Brugada electrocardiogram (ECG) pattern (type 1 ECG) for primary prevention of sudden death (SD). METHODS AND RESULTS: Three hundred and twenty patients (258 males, median age 43 years) with type 1 ECG were enrolled. No patient had previous cardiac arrest. Fifty-four per cent of patients had a spontaneous and 46% a drug-induced type 1 ECG. One-third had syncope, two-thirds were asymptomatic. Two hundred and forty-five patients underwent electrophysiologic study (EPS) and 110 patients received an implantable cardiac defibrillator (ICD). During follow-up [median length 40 months (IQ20-67)], 17 patients had major arrhythmic events (MAE) (14 resuscitated ventricular fibrillation (VF) and three SD). Both a spontaneous type 1 ECG and syncope significantly increased the risk (2.6 and 3.0% event rate per year vs. 0.4 and 0.8%). Major arrhythmic events occurred in 14% of subjects with positive EPS, in no subjects with negative EPS and in 5.3% of subjects without EPS. All MAE occurred in subjects who had at least two potential risk factors (syncope, family history of SD, and positive EPS). Among these patients, those with spontaneous type 1 ECG had a 30% event rate. CONCLUSION: (1) In subjects with the Brugada type 1 ECG, no single clinical risk factor, nor EPS alone, is able to identify subjects at highest risk; (2) a multiparametric approach (including syncope, family history of SD, and positive EPS) helps to identify populations at highest risk; (3) subjects at highest risk are those with a spontaneous type 1 ECG and at least two risk factors; (4) the remainder are at low risk.

Comparison of C-reactive protein and albumin excretion as prognostic markers for 10-year mortality after myocardial infarction.

BACKGROUND: C-reactive protein (CRP) is an established prognostic marker in the setting of acute coronary syndromes. Recently, albumin excretion rate also has been found to be associated with adverse outcomes in this clinical setting. Our aim was to compare the prognostic power of CRP and albumin excretion rate for long-term mortality following acute myocardial infarction (AMI). HYPOTHESIS: To determine whether albumin excretion rate is a better predictor of long-term outcome than CRP in post-AMI patients. METHODS: We prospectively studied 220 unselected patients with definite AMI (median [interquartile] age 67 [60-74] y, female 26%, heart failure 39%). CRP and albumin-to-creatinine ratio (ACR) were measured on day 1, day 3, and day 7 after admission in 24-hour urine samples. Follow-up duration was 10 years for all patients. RESULTS: At survival analysis, both CRP and ACR were associated with increased risk of 10-year all-cause mortality, also after adjusting for age, hypertension, diabetes mellitus, prehospital time delay, creatine kinase-MB isoenzyme peak, heart failure, and creatinine clearance. CRP and ACR were associated with nonsudden cardiovascular (non-SCV) mortality but not with sudden death (SD) or noncardiovascular (non-CV) death. CRP was not associated with long-term mortality, while ACR was independently associated with outcome both in short- and long-term analyses. At C-statistic analysis, CRP did not improve the baseline prediction model for all-cause mortality, while it did for short-term non-SCV mortality. ACR improved all-cause and non-SCV mortality prediction, both in the short and long term. CONCLUSIONS: ACR was a better predictor of long-term mortality after AMI than CRP.

Acute-phase inflammatory markers during myocardial infarction: association with mortality and modes of death after 7 years of follow-up.

BACKGROUND: The relationship between acute-phase inflammatory markers in the setting of acute myocardial infarction (AMI) and long-term outcomes is largely unexplored. OBJECTIVES: The aim of the study was to investigate the predictive power of acute-phase inflammatory markers following AMI for short-term and long-term mortality separately and modes of death. METHODS: In 220 unselected patients with AMI [median age 67 (interquartile range 60-74) years, women 26%], blood neutrophil granulocytes, erythrocyte sedimentation rate, C-reactive protein, and alpha1-acid glycoprotein were measured 1, 3 and 7 days after admission. All patients completed 7 years of follow-up. Endpoints were 1-year (short-term) and 2- to 7-year (long-term) mortality and modes of death, classified as nonsudden cardiovascular, sudden, and noncardiovascular death. RESULTS: The short-term mortality rate was 18%. The long-term mortality rate was 26%. The short-term mortality risk was higher in patients in whom the markers were in the upper tertile. Fully adjusted hazard ratios (and 95% confidence interval) were 3.2 (1.4-7.9), 3.5 (1.7-7.9), 3.5 (1.6-8.6), and 6.1 (2.3-19.1) for neutrophil granulocyte, erythrocyte sedimentation rate, C-reactive protein, and alpha1-acid glycoprotein, respectively. The excess mortality was chiefly due to nonsudden cardiovascular mortality [fully adjusted hazard ratios were 4.6 (1.7-14.7), 4.7 (1.9-13.7), 5.9 (2.0-21.3) and 5.5 (2.0-17.6), respectively], whereas no association was found with sudden death or noncardiovascular modes of death. In the long term, the association with mortality and modes of death was no longer significant. CONCLUSION: The acute-phase inflammatory markers tested following AMI are independently and concordantly associated with short-term mortality and their prediction is associated only with nonsudden cardiovascular modes of death. These markers are not associated with long-term mortality.