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.

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.

Thinking Back about a Positive Event: The Impact of Processing Style on Positive Affect.

The manner in which individuals recall an autobiographical positive life event has affective consequences. Two studies addressed the processing styles during positive memory recall in a non-clinical sample. Participants retrieved a positive memory, which was self-generated (Study 1, n = 70) or experimenter-chosen (i.e., academic achievement, Study 2, n = 159), followed by the induction of one of three processing styles (between-subjects): in Study 1, a "concrete/imagery" vs. "abstract/verbal" processing style was compared. In Study 2, a "concrete/imagery," "abstract/verbal," and "comparative/verbal" processing style were compared. The processing of a personal memory in a concrete/imagery-based way led to a larger increase in positive affect compared to abstract/verbal processing in Study 1, as well as compared to comparative/verbal thinking in Study 2. Results of Study 2 further suggest that it is making unfavorable verbal comparisons that may hinder affective benefits to positive memories (rather than general abstract/verbal processing per se). The comparative/verbal thinking style failed to lead to improvements in positive affect, and with increasing levels of depressive symptoms it had a more negative impact on change in positive affect. We found no evidence that participant's tendency to have dampening thoughts in response to positive affect in daily life contributed to the affective impact of positive memory recall. The results support the potential for current trainings in boosting positive memories and mental imagery, and underline the search for parameters that determine at times deleterious outcomes of abstract/verbal memory processing in the face of positive information.

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.

C-reactive protein in acute myocardial infarction: association with heart failure.

BACKGROUND: High C-reactive protein (CRP) levels have been associated with higher mortality rate in patients with acute myocardial infarction (AMI). However, it is not known whether inflammation plays a role in the time-course of heart failure (HF) in this clinical setting. Our aim was to study the nature of the relationship between CRP and HF during AMI. METHODS: This prospective study was carried out in 269 subjects admitted to the hospital for suspected AMI. Of these, 220 had evidence of AMI. The other 49 subjects were studied as controls. CRP was assessed on the first, third, and seventh day after admission. RESULTS: CRP was significantly higher in the patients with AMI than in the control patients (P =.001) and peaked on the third day. Among the patients with AMI, CRP was higher in patients with HF than in patients without HF (adjusted P =.008, P =.02 and P =.03 on 1st, 3rd, and 7th day, respectively). Prevalence of HF on admission was slightly higher in the subjects with first-day CRP >or=15 mg/L than in those with CRP <15 mg/L, and the between-group difference progressively increased from the first to the seventh day (P <.0001). At multivariable regression analysis, first-day log-CRP was shown to be a strong independent predictor of both HF progression (P <.0001) and left ventricular ejection fraction (P <.0001). One-year total mortality and HF-mortality rates turned out to be higher in the patients with CRP >or=85 mg/L than in those with CRP below that level (P <.0001), and log-third-day CRP was independently associated with 1-year mortality at multivariable analysis (P =.0001). CONCLUSIONS: CRP on admission to hospital is suitable for predicting the time-course of HF in patients with AMI. Peak CRP value is a strong independent predictor of global and HF-mortality during the following year.

Heart rate during myocardial infarction: relationship with one-year global mortality in men and women.

BACKGROUND: Elevated heart rate (HR) has been found to be related to an increased death rate in patients with acute myocardial infarction (AMI), but sex differences and optimal timing for HR measurement have not been sufficiently investigated. OBJECTIVES: To verify the predictive value of HR for one-year mortality in a cohort of subjects hospitalized for AMI, with men and women considered separately. PATIENTS AND METHODS: HR was measured in 424 patients (303 men and 121 women) with constant sinus HR, on the first, third and seventh days after hospital admission for AMI. Clinical and laboratory data were obtained on the same days. All patients were followed up for one year. RESULTS: Among the men, the one-year mortality rate was 5% for the subjects with a seven-day HR of less than 80 beats/min, and the one-year mortality rate was 39% for patients with a seven- day HR of 80 beats/min or more (P<0.0001). Among the women, the differences in mortality related to HR were not significant. In a multivariate Cox regression analysis, the relative risks of mortality in men who had an HR of 80 beats/min or more were 3.1 (CI=1.4 to 7.0, P=0.003) on the first day, 4.1 (CI=1.8 to 9.8, P=0.001) on the third day and 8.6 (CI=2.9 to 27.0, P<0.0001) on the seventh day. In the 203 men in whom echocardiographic left ventricular ejection fraction was measured, an interactive effect of high HR with depressed ejection fraction on mortality was found. Beta-blocking therapy influenced HR during AMI but did not influence the HR-mortality association. CONCLUSIONS: The results of the present prospective study show that HR measured during the first week after admission for AMI is an important predictor of mortality in men. The predictive power of HR increased from the first to the seventh day after AMI.