Predictor Of All-cause Death Research Articles

GW24-e0064 Should Coronary Chronic Total Occlusion be Recanalised in Diabetic Patients?

ObjectivesAlthough there are increasing data suggesting that patients could get survival advantage from the recanalising procedure of coronary chronic total occlusion (CTO) as compared with optimal medical treatment (OMT) alone,...

Comparison of predictive performance of various fatty acids for the risk of cardiovascular disease events and all-cause deaths in a community-based cohort

BackgroundThe issue of whether saturated fats and trans fats are superior predictors of all-cause death and cardiovascular disease than n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), remains a matter of contention. Furthermore, few studies have examined the relationship between fatty acids and the outcomes of cardiovascular disease (CVD) in Asian populations. The aim of this study was to compare the effectiveness of various plasma fatty acids as predictors for all-cause death and CVD events in an ethnic Chinese population. MethodsThis study assembled a community-based prospective cohort, comprising 1833 participants (60.6 ± 10.5 yrs, 44.5% women) who underwent a comprehensive evaluation of fatty acids in blood using gas chromatography. None of the subjects had a history of CVD at the time of recruitment. ResultsA total of 568 individuals died and 275 individuals developed CVD during the follow-up period (median of 9.6 years; interquartile range of 8.9–10.5 years). Following adjustment for established cardiovascular risk factors, the relative risk of all-cause death in the highest quartile, compared with the lowest quartile, was 1.33 for saturated fats (95% confidence interval [CI], 1.01–1.75, test for trend, P = 0.015), 1.71 for trans fats (95% CI, 1.27–2.31, test for trend, P = 0.0003), 0.77 for EPA (95% CI, 0.59–1.00, test for trend, P = 0.048), and 0.89 for DHA (95% CI, 0.68–1.18, test for trend, P = 0.354). Similar patterns were observed for CVD events. Trans fats presented the largest area under the receiver operator characteristic curve (0.740, 95% CI, 0.716–0.766) for the prediction of all-cause death. A mutually adjusted two-marker model indicated that saturated fats and trans fats were significant predictors of all-cause death and CVD; however, the other fatty acids were not. In addition, trans fats presented the greatest improvement in net reclassification for all-cause death (7.7%, P = 0.003), followed by EPA (3.8%, P = 0.033). Saturated fats presented the greatest improvement in net reclassification for CVD events (5.6%, P = 0.039). ConclusionsOur data provides strong evidence to support that plasma saturated fats and trans fats can predict all-cause death and CVD more effectively than other fatty acid markers.

Patterns of ectopy leading to increased risk of fatal or near-fatal cardiac arrhythmia in patients with depressed left ventricular function after an acute myocardial infarction

To identify potential new markers for assessing the risk of sudden arrhythmic events based on a method that captures features of premature ventricular complexes (PVCs) in relation to sinus RR intervals in Holter recordings (heartprint). Holter recordings obtained 6 weeks after acute myocardial infarction from 227 patients with reduced ventricular function (left ventricular ejection fraction ≤ 40%) were used to produce heartprints. Measured indices were: PVCs per hour, standard deviation of coupling interval (SDCI), and the number of occurrences of the most prevalent form of PVCs (SNIB). Predictive values, survival analysis, and Cox regression with adjustment for clinical variables were performed based on primary endpoint, defined as an electrocardiogram-documented fatal or near-fatal arrhythmic event, death from any cause, and cardiac death. High ectopy (PVCs per hour ≥10) was a predictor of all endpoints. Repeating forms of PVCs (SNIB ≥ 83) was a predictor of primary endpoint, hazard ratio = 3.5 (1.3-9.5), and all-cause death, hazard ratio = 2.8 (1.1-7.3), but not cardiac death. SDCI ≤ 80 ms was a predictor of all-cause death and cardiac death, but not of primary endpoint. High ectopy, prevalence of repeating forms of PVCs, and low coupling interval variability are potentially useful risk markers of fatal or near-fatal arrhythmias after myocardial infarction.

Calcium Affects on Vascular Endpoints (CAVE) Retrospective Cohort Trial

Purpose The goal of this study was to examine the association of calcium supplements with coronary artery disease and survival. Our initial hypothesis was that when adjusted for risk factors, calcium supplements would not affect overall survival outcomes or coronary artery disease prevalence in a community population followed by a large cardiovascular practice. Methods Data was retrospectively collected for 5 years and 8 months (1/1/2004to 10/8/2009) from the electronic medical record at a large cardiovascular practice at a university. Only patients ≥ age 50 were included in our analysis Results The baseline characteristics of the 8060 study subjects. For the entire study population the mean age was 65 +/– 10 years, 71% were women. On multivariable logistic regression analysis, calcium supplementation was not an independent predictor of all-cause death, nor was calcium supplementation an independent predictor of the diagnosis of coronary artery disease. Survival analysis showed no survival differences for patients on calcium supplements (p = NS). Hazard ratios using the Cox proportional hazards model were calculated, showing that calcium supplementation was not an independent predictor of reduced survival. Conclusion This study suggests that there was no association between calcium supplementation and coronary artery disease as well as overall survival in a large retrospective cohort of patients greater than 50 with high rates of significant cardiovascular risk factors.

Effects of smoking in patients treated with cardiac resynchronization therapy

Smoking is associated with increased morbidity and mortality in cardiac patients. However, data on the prognostic impact of smoking in heart failure (HF) patients on cardiac resynchronization therapy with defibrillator (CRT-D) are absent. We investigated the effects of smoking on all-cause mortality and on a composite endpoint (all-cause death/appropriate device therapy), appropriate and inappropriate device therapy, in 649 patients with HF who underwent CRT-D between January 2003 and October 2011 in 6 Centers (4 in Italy and 2 in USA). 68 patients were current smokers, 396 previous-smokers (patients who had smoked in the past but who had quit before the CRT-D implant), and 185 had never smoked. The risk of each endpoint by smoking status was evaluated with both Kaplan-Meier and Cox proportional-hazard analysis. After adjusting for age, left ventricular ejection fraction, QRS width and ischemic etiology, both current and previous smoking were independent predictors of all-cause death [HR=5.07 (95% CI 2.68-9.58), p<0.001 and HR=2.43 (95% CI 1.38-4.29), p=0.002, respectively) and of composite endpoint [HR=1.63 (1.04-2.56); p=0.033 and HR=1.46 (1.04-2.04) p=0.027]. In addition, current smokers had a significantly higher rate of inappropriate device therapy compared to never smokers [HR=21.74 (4.53-104.25), p=0.005]. Our study indicates that in patients with HF who received a CRT-D device, current and previous smoking increase the event rate per person-time of death and of appropriate and inappropriate ICD therapy more than other known negative prognostic factors such as age, left ventricular dysfunction, prolonged QRS duration and ischemic etiology.

Association Between Abnormal Myocardial Fatty Acid Metabolism and Cardiac-Derived Death Among Patients Undergoing Hemodialysis: Results From a Cohort Study in Japan

Detecting myocardial ischemia in hemodialysis patients is crucial given the high incidence of silent ischemia and the high cardiovascular mortality rates. Abnormal myocardial fatty acid metabolism as determined by imaging with (123)I-labeled BMIPP (β-methyl iodophenyl-pentadecanoic acid) might be associated with cardiac-derived death in hemodialysis patients. Prospective observational study. Asymptomatic hemodialysis patients with one or more cardiovascular risk factors, but without known coronary artery disease, were followed up for 3 years at 48 Japanese hospitals (406 men, 271 women; mean age, 64 years). Baseline BMIPP summed scores semiquantified using a 17-segment 5-point system (normal, 0; absent, 4). Cardiac-derived death, including cardiac and sudden death. HRs were estimated using a Cox model for associations between BMIPP summed scores and cardiac-derived death, adjusting for potential confounders of age, sex, body mass index, dialysis duration, and cardiovascular risk factors. Rates of all-cause mortality and cardiac-derived death were 18.5% and 6.8%, respectively. Cardiac-derived death (acute myocardial infarction [n = 10], congestive heart failure [n = 13], arrhythmia [n = 2], valvular heart disease [n = 1], and sudden death [n = 20]) accounted for 36.8% of all-cause deaths. Cardiac-derived death (n = 46) was associated with age, history of heart failure, and BMIPP summed scores of 4 or higher (HR, 2.9; P < 0.001). Three-year cardiac-derived death-free survival rates were 95.7%, 90.6%, and 78.8% when BMIPP summed scores were 3 or lower, 4-8, and 9 or higher, respectively. BMIPP summed score also was a predictor of all-cause death (HR, 1.6; P = 0.009). Sudden death of unknown cause was considered to have been cardiac derived, although a coronary origin was not confirmed. Abnormal myocardial fatty acid metabolism is associated with cardiac-derived death in hemodialysis patients. BMIPP single-proton emission computed tomography appears clinically useful for predicting cardiac-derived death in this population.

Mid-regional pro-atrial natriuretic peptide as a prognostic marker for all-cause mortality in patients with symptomatic coronary artery disease

In the present study, we investigated the prognostic value of MR-proANP (mid-regional pro-atrial natriuretic peptide). We consecutively evaluated a catheterization laboratory cohort of 2700 patients with symptomatic CAD (coronary artery disease) [74.1% male; ACS (acute coronary syndrome), n=1316; SAP (stable angina pectoris), n=1384] presenting to the Cardiology Department of a large primary care hospital, all of whom underwent coronary angiography. Serum MR-proANP and other laboratory markers were sampled at the time of presentation or in the catheterization laboratory. Clinical outcome was assessed by hospital chart analysis and telephone interviews. The primary end point was all-cause death at 3 months after enrolment. Follow-up data were complete in 2621 patients (97.1%). Using ROC (receiver operating characteristic) curves, the AUC (area under the curve) of 0.73 [95% CI (confidence interval), 0.67-0.79] for MR-proANP was significantly higher compared with 0.58 (95% CI, 0.55-0.62) for Tn-I (troponin-I; DeLong test, P=0.0024). According to ROC analysis, the optimal cut-off value of MR-proANP was at 236pmol/l for all-cause death, which helped to find a significantly increased rate of all-cause death (n=76) at 3 months in patients with elevated baseline concentrations (≥236pmol/l) compared with patients with a lower concentration level in Kaplan-Meier survival analysis (log rank, P<0.001). The predictive performance of MR-proANP was independent of other clinical variables or cardiovascular risk factors, and superior to that of Tn-I or other cardiac biomarkers (all: P<0.0001). MR-proANP may help in the prediction of all-cause death in patients with symptomatic CAD. Further studies should verify its prognostic value and confirm the appropriate cut-off value.

Usefulness of β-Trace Protein and Cystatin C for the Prediction of Mortality in Non ST Segment Elevation Acute Coronary Syndromes

Beta-trace protein (BTP) is a low-molecular mass protein belonging to the lipocalin protein family, which is more sensitive than serum creatinine for detecting impaired renal function. The aims of the present study were to evaluate whether plasma BTP improves the risk stratification of patients with non-ST-segment elevation acute coronary syndromes and to compare it to cystatin C (CysC), serum creatinine, and estimated glomerular filtration rate. Two hundred twenty-six consecutive patients with non-ST-segment elevation acute coronary syndromes were prospectively included. Blood samples were obtained within 24 hours of hospital admission to measure BTP, CysC, and creatinine. The study end point was all-cause death. Over a median follow-up period of 859 days (interquartile range [IQR] 524 to 1,164), 24 patients (10.6%) died. Decedents had higher concentrations of BTP (1.03 mg/L [IQR 0.89 to 1.43] vs 0.74 mg/L [IQR 0.61 to 0.92], p <0.001), CysC (1.16 mg/L [IQR 0.91 to 1.59] vs 0.90 mg/L [IQR 0.76 to 1.08], p = 0.001), and serum creatinine (1.10 mg/L [IQR 0.87 to 1.46] vs 0.94 mg/L [IQR 0.80 to 1.10], p = 0.004) and a lower mean estimated glomerular filtration rate (60 ± 20 vs 80 ± 24 ml/min/1.73 m(2), p <0.001). After multivariate adjustment, BTP and CysC were predictors of all-cause death, while estimated glomerular filtration rate and serum creatinine concentrations did not achieve statistical significance. In stratified analyses according to kidney function, elevated BTP and CysC were associated with a higher risk for all-cause death. Reclassification analyses showed that BTP and CysC added complementary information to Global Registry for Acute Coronary Events (GRACE) risk score. In conclusion, BTP and CysC levels were associated with all-cause death risk and modestly improved prognostic discrimination beyond the GRACE risk score in patients with non-ST segment elevation acute coronary syndromes.

The Association of Geriatric Nutritional Risk Index and Total Lymphocytes Count with Mortality in Korean Hemodialysis Patients

Background: Our objective was to examine the association between the Geriatric Nutritional Risk Index (GNRI) and Total lymphocytes count (TLC) with mortality in Korean Hemodialysis Patients. Methods: We examined the GNRI and TLC of 120 maintenance hemodialysis patients and followed these patients for 120 months. Predictors for all-cause death were examined using life table analysis and the Cox proportional hazards model. Results: Life table analysis revealed that subjects with a GNRI P = 0.048), but subjects with a TLC 3 (n = 76)had a similar survival rate compared those with a TLC ≥ 1500/mm 3 (n = 44) (Wilcoxon test, P = 0.500). Multivariate Cox proportional hazards analyses demonstrated that the GNRI was a significant predictor of mortality [hazard ratio (HR) 9.315, 95% confidence interval (CI) 1.161–74.753, P = 0.036], after adjusting for age, sex, presence of type 2 diabetes mellitus, Kt/V, nPCR and TLC. The association of a GNRI ≥ 90 with a TLC ≥ 1500/mm 3 seemed to exclude the occurring of complications with moderate reliability. Conclusion: These results demonstrate that the GNRI may be a significant predictor of mortality in Korean hemodialysis patients. However, the use of TLC might improve the evaluation of nutritional risk and the identification of patients at risk of malnutrition.Figure 1. Total lymphocytes count and 120-month survival of hemodialysis patients. In both groups, survival rate during the follow-up period was similar. (life table analysis, P = 0.500). Download full-size image

Elevated resting heart rate is an independent predictor of all-cause death and cardiovascular events in Japanese ambulatory hemodialysis patients

Elevated heart rate (HR) is an independent risk factor for all-cause death or cardiovascular events in non-hemodialysis subjects; however, the clinical significance of elevated HR in hemodialysis patients is not well studied. We prospectively evaluated the relationship between HR and adverse outcome in a total of 229 ambulatory hemodialysis patients (57% men; mean age 62.2years) recruited from two dialysis clinics in 2009. Mean (SD) HR of this cohort was 74.1 (11.0) beats per minute (bpm). Receiver operating characteristic curves identified an HR cut-off level of ≥80bpm for increased adverse outcome. After a mean follow-up of 525days (range 7-760days) a total of 30 primary endpoints (21 all-cause deaths, 4 acute coronary syndromes and 8 strokes) and 38 secondary endpoints (30 primary endpoints, 8 congestive heart failures, and 5 other cardiovascular events) were detected. Cox regression analysis revealed that HR >80bpm was not an independent predictor of primary endpoints [hazard ratio 1.81, 95% confidence interval (CI) 0.79-4.11, p=NS], but of secondary endpoints (hazard ratio 2.01, 95% CI 1.01-4.22, p<0.05) after adjusting for age, sex, hemodialysis duration, and cardiovascular risks. Elevated HR is an independent predictor of all-cause death and cardiovascular events in Japanese ambulatory hemodialysis patients.

Geriatric Nutritional Risk Index May Be a Significant Predictor of Mortality in Korean Hemodialysis Patients: A Single Center Study

Our objective was to examine the association between the Geriatric Nutritional Risk Index (GNRI) and mortality in Korean hemodialysis (HD) patients. We examined the GNRI of 120 maintenance HD patients and followed these patients for 120 months. Predictors for all-cause death were examined using life table analysis and the Cox proportional hazards model. Life table analysis revealed that subjects with a GNRI < 90 (n = 19) had a marginally lower survival rate than did those with a GNRI ≥ 90 (n = 101) (Wilcoxon test, P = 0.048). Multivariate Cox proportional hazards analyses demonstrated that the GNRI was a significant predictor of mortality (hazard ratio 0.966, 95% confidence interval 0.945-0.995, P = 0.018), after adjusting for age, sex, presence of diabetes mellitus, and body weight. These results demonstrate that the GNRI may be a significant predictor of mortality in Korean HD patients.

Impact of Body Mass Index on Clinical Outcome in Patients Hospitalized With Congestive Heart Failure

Obesity has recently been shown to have a favorable effect on the prognosis of patients with congestive heart failure (CHF), but only a few such studies are available in Japan. The purpose of the present study was to investigate whether the obesity paradox is still present after adjusting for CHF characteristics. A total of 219 patients hospitalized with CHF were reviewed, and the impact of body mass index (BMI) on prognosis was examined. Patients were divided into 4 groups according to BMI quartiles. The endpoint was defined as all-cause death or unplanned CHF hospitalization. According to univariate analysis, a higher BMI was associated with better outcomes. High-BMI patients were younger, likely to be male, and had a higher prevalence of hypertension and diabetes. The plasma B-type natriuretic peptide (BNP) levels and blood urea nitrogen (BUN) levels were lower, while the serum hemoglobin and sodium levels were higher in high-BMI patients. The prevalence of atrial fibrillation was lower in high-BMI patients. Predictors for all-cause death or CHF hospitalization based on univariate analysis were age, prior CHF hospitalization, estimated glomerular filtration rate, plasma BNP levels, BUN levels, and serum hemoglobin and sodium levels. According to multivariate analysis, a high BMI was still associated with better outcomes. High BMI was associated with better clinical outcomes in Japanese CHF patients.

Cardiac troponin T concentrations above the 99th percentile value as measured by a new high-sensitivity assay predict long-term prognosis in patients with acute coronary syndromes undergoing routine early invasive strategy

A recently developed immunoassay for high-sensitivity measurement of cardiac troponin T (hsTnT) allows measurement at the 99th percentile for a normal population with an assay imprecision <10%. It is unclear whether such a low cutpoint (14ng/L) is helpful for long-term risk stratification of patients with an acute coronary syndrome (ACS) undergoing routine early invasive strategy. Consecutive patients with ACS admitted to a chest pain unit were studied. The usefulness of hsTnT for early diagnosis of myocardial infarction (MI) and prediction of all-cause death or death/MI over a median of 271days following presentation was compared against the fourth generation cTnT at the 99th percentile cutpoint. Of 1,384 patients with ACS enrolled, 47.8% had non-ST-segment elevation MI (NSTEMI), 26.4% unstable angina, 21.8% STEMI and 4% had non-ACS. Adjusted risk for all-cause death [adjusted HR 8.26 (95%CI: 1.13-66.33), p=0.038] and death/MI [adjusted HR 2.71 (95% CI: 1.15-6.38), p=0.023] were significantly higher with hsTnT above the 99th percentile. In particular, among patients with a standard fourth generation cTnT result below the 99th percentile cutoff (0.01ng/mL), hsTnT improved risk assessment. Mortality risk associated with an elevated hsTnT was present across the spectrum of ACS, as well as in conditions with hsTnT elevations not related to ACS. hsTnT at the 99th percentile cutoff is useful for the diagnostic evaluation of patients with ACS, and provides strong and independent predictive power for adverse long-term outcomes even after early invasive strategy.

Prognostic Factors Affecting Clinical Outcomes after Coronary Artery Bypass Surgery: Analysis of Patients with Chronic Kidney Disease after 5.9 Years of Follow-Up

Coronary artery bypass grafting (CABG) is a highly successful treatment for prolonging the lives of selected patients; however, preoperative and postoperative renal dysfunction has been an important predictor of adverse cardiovascular events. Concerns have recently grown regarding chronic kidney disease (CKD), which is an independent risk factor for cardiovascular diseases. In the present study we examined the significance of renal function on the basis of the estimated glomerular filtration rate (eGFR) and analyzed other factors as predictors of long-term clinical outcomes after CABG. The subjects were 195 patients who underwent CABG from July 1996 through September 2008 at our hospital. Patients who received preoperative dialysis or who died during hospitalization or both were excluded. The patients were divided into 2 groups based on eGFR at the time of discharge (eGFR ≥60 mL/min/1.73 m(2): non-CKD group; or eGFR <60 mL/min/1.73 m(2): CKD group), and long-term outcomes were compared between the groups. The effects of other risk factors on long-term morbidity and mortality were also examined. The mean age of patients was 64.6 ± 9.3 years, and the mean duration of follow-up was 69.5 ± 44.5 months. There were no significant differences in either deaths from all causes or cardiovascular deaths between the CKD group and the non-CKD group. Multivariate analysis using the Cox proportional hazards model revealed that age (hazard ratio, 1.044; p=0.001) was a predictor of all-cause death and that age (hazard ratio, 1.154; p<0.001), diabetes mellitus (hazard ratio, 3.122; p=0.046), unstable angina (hazard ratio, 5.012; p=0.003), and proteinuria (hazard ratio, 7.982; p<0.001) were predictors of cardiovascular death. conclusions: Our study demonstrates that age, diabetes mellitus, unstable angina, and proteinuria are factors that affect long-term prognosis after CABG, whereas eGFR <60 mL/min/1.73 m(2) is not a predictive risk factor for either all-cause death or cardiovascular death. Although the predictive value of eGFR <60 mL/min/1.73 m(2) is generally accepted, analysis of our own data with receiver operating characteristic curves shows that eGFR <50 mL/min/1.73 m(2) is a more sensitive predictor of long-term outcome.

Ten-year risk of all-cause mortality: assessment of a risk prediction algorithm in a French general population

While assessment of global cardiovascular risk is uniformly recommended for risk factor management, prediction of all-cause death has seldom been considered in available charts. We established an updated algorithm to predict absolute 10-year risk of all-cause mortality in apparently healthy subjects living in France, a country with high life expectancy. Analyses were based on the Third French MONICA Survey on cardiovascular risk factors (1995-1996) carried out in 3,208 participants from the general population aged 35-64. Vital status was obtained 10 years after inclusion and assessment of determinants of mortality was based on multivariable Cox modelling. One-hundred-fifty-six deaths were recorded. Independent determinants of mortality were living area (Northern France), older age, male gender, no high-school completion, smoking, systolic blood pressure ≥ 160 mmHg, LDL-cholesterol ≥ 5.2 mmol/l, and diabetes. Score sheets were developed to easily estimate 10-year risk of death. For example, a non diabetic, heavy smoker, 46-year old man, living in South-Western France, who did not complete high-school, with LDL-cholesterol ≥ 5.2 mmol/l and systolic blood pressure < 160 mmHg, has a 17% probability of death in the ten coming years. The C-statistic of the prediction model was 0.76 [95% CI: 0.72-0.80] with a degree of overoptimism estimated at 0.0058 in a bootstrap sample. Calibration was satisfying: P value for Hosmer-Lemeshow χ(2) test was 0.483. This prediction algorithm is a simple tool for guiding practitioners towards a more or less aggressive management of risk factors in apparently healthy subjects.

112 Inability to exercise or a non-diagnostic exercise test identify a higher risk sub-set of patients in those with an intermediate pretest probability of coronary artery disease:

Introduction The Rapid Access Chest Pain (RACP) service model aims to fast-track all patients with suspected cardiac chest pain using exercise electrocardiography. However, in those with an intermediate pre-test probability of coronary artery disease, guidelines recommend non-invasive stress imaging as the preferred first line investigation. The non-invasive functional imaging techniques include stress echocardiography and radionuclide myocardial perfusion imaging, but in many centres these investigations are not readily available and so the exercise ECG remains the mainstay investigation. Aims This was a study of patients attending the RACP service with an intermediate pre-test probability of CAD (Int-CAD). The aims were to compare the demographic characteristics of those with and without a non-diagnostic exercise ECG and to determine the independent predictors of all-cause death in this group of patients Methods We retrospectively studied consecutive patients who attended the RACP service from January 2004 to December 2006. The variables analysed included age, gender, ethnicity, diabetes, hypertension, hypercholesterolaemia, smoking and exercise ECG findings. Three year follow-up data on all-cause death were collected from the hospital system and central register. Results The study cohort consisted of 1174 patients with an intermediate pretest probability of CAD. The patients were divided into two groups; group 1 consisted of those with a diagnostic exercise ECG (either positive or negative), and group 2 were those without a diagnostic test (either an equivocal result or unable to exercise). Comparative data of the two groups are shown below: Group 2 patients were significantly older, had a higher proportion of women, higher prevalence of diabetes, hypertension and hypercholesterolaemia and a higher pre-test probability of CAD. Over a mean follow up period of 39.4±9.9 months, the death rate in group 1 was 1.5% and in group 2 was 7.5%. Multivariate analysis showed that age (p Conclusion In conclusion, a non-diagnostic exercise ECG identifies a higher risk sub-set of patients (29% of patients) in the intermediate pretest probability group with a fivefold increased risk of death at 3 years. This latter sub-set of patients, in particular, is not adequately well served by the RACP service model based on the exercise ECG. Future models of care need to incorporate early and increased access to pharmacological stress imaging.

The prognostic value of circulating markers of collagen turnover after acute myocardial infarction

Background We assessed the time profiles and prognostic utility of circulating markers of collagen turnover (CTO) following acute myocardial infarction (MI). In contrast to previous studies, no patient had been pre-treated with inhibitors of the renin-angiotensin-aldosterone system (RAAS) at the time of initial assessment. Methods Plasma levels of N-terminal fragment of type I collagen (PINP), carboxy-terminal telopeptide of type I collagen (ICTP), N-terminal fragment of type III collagen (PIIINP), matrix metalloproteinase-1(MMP-1) and tissue inhibitor of MMPs type-1 (TIMP-1) were assessed in 233 patients following acute MI. The CTO markers were initially assessed prior to treatment by either captopril or losartan, at a median of 3 days following MI. In addition, blood samples were acquired at 1 month, 1 year and 2 years following MI. Development of heart failure symptoms, all-cause and cardiovascular death were recorded as endpoints during two years of follow-up. Results With the exception of PIIINP, all CTO markers demonstrated significant longitudinal changes following MI. At baseline, ICTP (p < 0.0001) and TIMP-1 (p = 0.01) levels were significantly elevated in patients who later died compared with survivors. In multivariable analysis only ICTP reached statistical significance as predictor of all cause death (p = 0.048). In patients developing symptoms of heart failure during follow-up, ICTP was the only significantly elevated CTO marker (p < 0.01). Conclusion The present study supports a prognostic role for ICTP in both the acute and chronic phase following MI.

Geriatric Nutritional Risk Index, a simplified nutritional screening index, is a significant predictor of mortality in chronic dialysis patients

Malnutrition is a common complication in haemodialysis patients. Recently, the Geriatric Nutritional Risk Index (GNRI) has been reported as a simple and accurate tool to assess nutritional status of haemodialysis patients. Our objective was to examine the association between GNRI and mortality in chronic haemodialysis patients. We examined the GNRI of 490 maintenance haemodialysis patients (60 ± 12 years, 293 males and 197 females) and followed up these patients for 60 months. Predictors for all-cause death were examined using Kaplan-Meier analysis and Cox proportional analyses. The GNRI was 98.0 ± 6.0, and was significantly and negatively correlated with age and haemodialysis duration. During the 60-month follow-up period, 129 patients died. According to the highest positive likelihood and risk ratios, the cutoff value of GNRI for mortality was set at 90. Kaplan-Meier analysis revealed that patients with a GNRI <90 (n = 50) had a significantly lower survival rate, compared to those with GNRI ≥90 (n = 440) (log-rank test, P < 0.0001). Multivariate Cox proportional hazards analyses demonstrated that GNRI was a significant predictor for mortality [hazard ratio (HR) 0.962, 95% confidence interval (CI) 0.931-0.995, P < 0.05], after adjustment for age, gender, C-reactive protein, presence of diabetes and haemodialysis duration. These results demonstrated that GNRI is a significant predictor for mortality in haemodialysis patients. The simple method of GNRI is considered to be a clinically useful marker for the assessment of nutritional status in haemodialysis patients.

Abstract 5811: Dual Function of Bone Morphogenetic Protein-2 in the Progression of Atherosclerotic Lesion and Atherosclerotic Intimal Calcification in vivo

Vascular calcification is one of the most important risk factor for the cardiovascular diseases as well as a predictor of all-cause death. Recent findings suggest that bone calcification regulatory factors, locally expressed in blood vessels, play unique roles in the formation of vascular calcification. However, detailed molecular mechanisms, that regulate the intimal calcification associated with atherosclerosis, remain unclear. We first investigated the potential role of de-differentiated VSMCs in the formation of atherosclerotic intimal calcification. In vitro studies revealed that bone morphogenetic protein-2 (BMP-2), a potent initiator for osteoblastic differentiation was markedly up-regulated in the de-differentiated VSMCs comparing to the differentiated VSMCs. We therefore generated the BMP-2 transgenic mice in which BMP-2 expression was driven by α SMA-promoter, and mated them with ApoE-knockout mice to obtained BMP-2-Tg/ApoE-KO mice. After 8 weeks of high fat diet, atherosclerotic intimal calcification was not detectable even in BMP-2-Tg/ApoE-KO mice. Somewhat unexpectedly, atherosclerosis was significantly attenuated in BMP-2-Tg/ApoE-KO mice as compared to ApoE-KO mice. The number of α SMA-positive VSMCs and macrophages in the atherosclerotic intima was significantly reduced in BMP-2-Tg/ApoE-KO. Also, we found that BMP-2 inhibits the uptake of acetylated LDL in macrophage, and protects endothelial cells from apoptosis in vitro. Of note, when fed with high fat diet for 30 weeks, atherosclerotic intimal calcification was greater in BMP-2-Tg/ApoE-KO than in ApoE-KO mice, whereas the size of atherosclerotic lesion was not different between them. In conclusion, we revealed the dual function of BMP-2 in the atherosclerosis anti-atherogenic function in the early atherosclerotic lesion, presumably through reducing the proliferation of VSMCs inhibiting the lipid-uptake in macrophage protecting endothelial cells from apoptosis, and pro-calcification function in the advanced atherosclerotic intima.

Neurohormones as Predictors of Outcome in an Elderly Heart Failure Population Naive of Neurohormonal Blockers Results from the CIBIS III Neurohormonal Substudy

Objectives: Although neurohormones have a well-established prognostic value in patients with chronic heart failure (CHF), little is known about this in CHF patients untreated with angiotensin-converting enzyme (ACE)-inhibitors, angiotensin-receptor blockers (ARBs) and beta-blockers. Methods: Baseline N-terminal pro atrial natriuretic peptide (NT-pro-ANP), N-terminal pro B-type natriuretic peptide (NT- pro-BNP), big endothelin (big-ET) and arginine-vasopressin (AVP) were tested for prognostic importance to predict the primary endpoint (death or hospitalisation) in 109 patients participating in the third Cardiac Insufficiency BIsoprolol Study(CIBIS III). Minimum follow-up time was 12 months (6 months monotherapy followed by 6 months combina- tiontherapy). Results: On average, patients had moderate elevation of all neurohormones tested. In univariate analysis, both below- median NT-pro-BNP (HR 0.37, 95% confidence interval (CI) 0.17-0.81, p=0.013) and below-median big-ET (HR 0.39, 95% CI 0.18-0.86, p=0.02) predicted decreased risk of all-cause death or hospitalisation, compared with above-median values. NT-pro-BNP lost its predictive power in multivariate analysis, while big-ET above median as well as body mass index (BMI) below median and presence of ischemic heart disease were predictive of increased risk of death or hospitali- sation. Using Cox stepwise regression analysis, only BMI (p=0.011) and big-ET (p=0.003) remained significant predictors of death or hospitalisation. Conclusion: In a cohort of elderly CHF patients naive of ACE-inhibitors, ARBs and beta-blockers, the best predictors of all-cause death or hospitalisation were a low BMI and elevated levels of big-endothelin.