Early inflammation and risk of long-term development of heart failure and mortality in survivors of acute myocardial infarction predictive role of C-reactive protein.

OBJECTIVES: We aimed to study the relationship between C-reactive-protein (CRP), obtained within 12 to 24 h of symptoms onset, and long-term risk of death and heart failure (HF) in survivors of acute myocardial infarction (MI). BACKGROUND: A robust inflammatory response is an integral component of the response to tissue injury during MI. The magnitude of the early inflammatory response to ischemic injury might be an important determinant of long-term outcome. METHODS: We prospectively studied 1,044 patients admitted with acute MI and discharged from hospital in stable condition. RESULTS: During a median follow-up of 23 months (range, 6 to 42 months), 113 patients died and 112 developed HF. In a multivariable Cox regression model adjusting for clinical variables and predischarge ejection fraction, compared with patients in the first CRP quartile, the adjusted hazard ratios (HRs) for death progressively increased with higher quartiles of CRP (second quartile 1.4 [95% confidence interval (CI) 0.6 to 2.9]; third quartile 2.3 [95% CI 1.2 to 4.6]; fourth quartile 3.0 [95% CI 1.5 to 5.7]; for trend, p = 0.0002). Compared with patients in the first CRP quartile, the adjusted HRs for HF were: second quartile, 1.1 (95% CI 0.5 to 2.3); third quartile, 1.9 (95% CI 1.0 to 3.6); and fourth quartile, 2.1 (95% CI 1.2 to 3.9) (for trend, p = 0.005). CONCLUSIONS: C-reactive-protein is a marker of long-term development of HF and mortality in patients with acute MI and provides prognostic information beyond that provided by conventional risk factors and the degree of left ventricular systolic dysfunction.     

Admission B-type natriuretic peptide levels and in-hospital mortality in acute decompensated heart failure.

OBJECTIVES: This study was designed to determine whether admission B-type natriuretic peptide (BNP) levels are predictive of in-hospital mortality in acute decompensated heart failure (HF). BACKGROUND: Levels of BNP have been demonstrated to facilitate the diagnosis of HF and predict mortality in chronic systolic HF. METHODS: B-type natriuretic peptide levels within 24 h of presentation were obtained in 48,629 (63%) of 77,467 hospitalization episodes entered in ADHERE (Acute Decompensated Heart Failure National Registry). In-hospital mortality was assessed by BNP quartiles in the entire cohort and in patients with reduced (n = 19,544) as well as preserved (n = 18,164) left ventricular systolic function using chi-square and logistic regression models. RESULTS: Quartiles (Q) of BNP were Q1 (<430), Q2 (430 to 839), Q3 (840 to 1,729), and Q4 (> or =1,730 pg/ml). The BNP levels were <100 pg/ml in 3.3% of the total cohort. Patients in Q1 versus Q4 were younger, more likely to be women, and had lower creatinine and higher left ventricular ejection fraction. There was a near-linear relationship between BNP quartiles and in-hospital mortality: Q1 (1.9%), Q2 (2.8%), Q3 (3.8%), and Q4 (6.0%), p < 0.0001. B-type natriuretic peptide quartile remained highly predictive of mortality even after adjustment for age, gender, systolic blood pressure, blood urea nitrogen, creatinine, sodium, pulse, and dyspnea at rest, Q4 versus Q1 (adjusted odds ratio 2.23 [95% confidence interval 1.91 to 2.62, p < 0.0001]). The BNP quartiles independently predicted mortality in patients with reduced and preserved systolic function. CONCLUSIONS: An elevated admission BNP level is a significant predictor of in-hospital mortality in acute decompensated HF with either reduced or preserved systolic function, independent of other clinical and laboratory variables. (Registry for Acute Decompensated Heart Failure Patients; http://www.clinicaltrials.gov/show/NCT00366639; NCT00366639).     

Predictive value of high sensitivity C-reactive protein in patients with ST-elevation myocardial infarction treated with percutaneous coronary intervention.

AIMS: To evaluate the predictive value of high sensitivity (hs) C-reactive protein levels on long-term survival in patients with ST-elevation myocardial infarction (STEMI) treated with primary PCI. METHODS AND RESULTS: We conducted a retrospective analysis of 758 STEMI patients (from January 2003 to December 2005), with STEMI onset <12 h and hs-C-reactive protein determination on admission. Patients were classified into four groups [I (hs-C-reactive protein < 0.48 mg/dL), II (hs-C-reactive protein > or = 0.48 to <1.2 mg/dL), III (hs-C-reactive protein > or = 1.2 to <3.1 mg/dL), IV (hs-C-reactive protein > or = 3.1 mg/dL)] according to quartiles of hs-C-reactive protein serum level. The IV quartile hs-C-reactive protein group had a higher incidence of in-hospital mortality and cumulative adverse events. At a mean follow-up of 724 +/- 376 days (range 0-1393), the IV quartile hs-C-reactive protein group showed lower estimated survival, lower estimated myocardial infarction-free survival and lower estimated event-free survival. At multivariable analysis hs-C-reactive protein appeared to be an independent predictor of long-term mortality (HR: 1.04, 95% CI: 1.01-1.07, P = 0.003), long-term mortality and re-infarction (HR: 1.03, 95% CI: 1.01-1.06, P = 0.008) and adverse events (HR: 1.03, 95% CI: 1.01-1.05, P = 0.03). CONCLUSION: Evaluation of hs-C-reactive protein on admission in STEMI patients undergoing primary PCI allows reliable risk stratification of these patients.     

Mineralocorticoid receptor antagonist initiation during admission is associated with improved outcomes irrespective of ejection fraction in patients with acute heart failure

Aims

Heart failure (HF) guidelines recommend initiation and optimization of guideline-directed medical therapy, including mineralocorticoid receptor antagonists (MRAs), before hospital discharge. However, scientific evidence for this recommendation is lacking. Our objective was to determine whether initiation of MRA prior to hospital discharge is associated with improved outcomes.

Methods and results

We performed a secondary analysis of 6197 patients enrolled in the RELAX-AHF-2 study. Patients were divided into four groups according to MRA therapy at baseline and discharge. At baseline 30% of patients received MRA therapy, which increased to 50% of patients at discharge. In-hospital initiation of an MRA was observed in 1690 (27%) patients, 1438 (23%) patients remained on MRA therapy, 418 (7%) patients discontinued MRA treatment, and 2651 (43%) patients did not receive an MRA during hospital stay. Compared with patients who did not receive MRA therapy, in-hospital initiation of an MRA was independently associated with lower risks of mortality (multivariable hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.60–0.96; p = 0.02), cardiovascular death (HR 0.77, 95% CI 0.59–1.01; p = 0.06), hospitalization for HF or renal failure (HR 0.72, 95% CI 0.60–0.86; p = 0.0003) and the composite endpoint of cardiovascular death and/or rehospitalization for HF or renal failure (HR 0.71, 95% CI 0.61–0.83; p < 0.0001) at 180 days. These results were independent of baseline left ventricular ejection fraction.

Conclusion

In patients hospitalized for acute HF, in-hospital initiation of an MRA was associated with improved post-discharge outcomes, independent of left ventricular ejection fraction and other potential confounders.     

Lower admission blood pressure as an independent predictor of 1-year mortality in elderly patients experiencing a first hospitalization for acute heart failure

BackgroundSystolic blood pressure (SBP) is an acknowledged prognostic factor in patients with heart failure (HF). Admission SBP should be a risk factor for 1-year mortality even in elderly patients experiencing a first admission for HF, and this risk may persist in the oldest subset of patients.DesignMethods: We reviewed the medical records of 1031 patients aged 70 years or older admitted within a 3-year period for a first episode of acute heart failure (AHF). The cohort was divided according to admission SBP values in quartiles. We analyzed all-cause mortality as a function of these admission SBP quartiles.ResultsMean age was 82.2 ± 6 years; their mean admission SBP was 138.6 ± 25 mmHg. A statistically significant association was present between mortality at 30 (p < 0.0001), 90 (p < 0.0001), and 365 days (p < 0.0001) after hospital discharge and lower admission SBP quartiles. One-year mortality ranged from 14.7% for patients within the upper SBP quartile to 41.4% for those in the lowest quartile. The multivariate analysis confirmed this association (HR: 0.884; 95% CI: 0.615-0.76; p = 0.0001), which remained significant when admission SBP was evaluated as a continuous variable (HR: 0.980; 95% CI: 0.975–0.985; p = 0.0001). The association between SBP and 1-year mortality remained when the sample was divided into old (70–82 years) and “oldest-old” (>82 years) patients.ConclusionsLower SBP at admission is an independent predictor of midterm postdischarge mortality for elderly patients experiencing a first admission for AHF.     

An international perspective on heart failure and left ventricular systolic dysfunction complicating myocardial infarction: the VALIANT registry.

AIMS: We analysed the contemporary incidence, outcomes, and predictors of heart failure (HF) and/or left ventricular systolic dysfunction (LVSD) before discharge in patients with acute myocardial infarction (MI). The baseline presence of HF or LVSD, or its development during hospitalisation, increases short- and long-term risk after MI, yet its incidence, predictors, and outcomes have not been well described in a large, international, general MI population. METHODS AND RESULTS: The VALIANT registry included 5573 consecutive MI patients at 84 hospitals in nine countries from 1999 to 2001. A multivariable logistic survival model was constructed using baseline variables to determine the adjusted mortality risk for those with in-hospital HF and/or LVSD. Baseline variables were also tested for associations with in-hospital HF and/or LVSD. Of the 5566 patients analysed, 42% had HF and/or LVSD during hospitalisation. Their in-hospital mortality rate was 13.0% compared with 2.3% for those without HF and/or without LVSD. After adjustment for other baseline risk factors, in-hospital HF and/or LVSD carried a hazard ratio for in-hospital mortality of 4.12 (95% confidence interval: 3.08-5.56). Patients with HF and/or LVSD also had disproportionately higher rates of other cardiovascular events. CONCLUSIONS: HF and/or LVSD is common in the general contemporary MI population and precedes 80.3% of all in-hospital deaths after MI. Survivors of early MI-associated HF and/or LVSD have more complications, longer hospitalisations, and are more likely to die during hospitalisation. Although baseline variables can identify MI patients at highest risk for HF and/or LVSD, such patients are less likely to receive indicated procedures and medical therapies.     

Precipitating Factors for Acute Heart Failure Hospitalization and Long-Term Survival

Heart failure (HF) patients have frequent exacerbations leading to high consumption of medical services and recurrent hospitalizations.Different precipitating factors have various effects on long-term survival.We investigated 2212 patients hospitalized with a diagnosis of either acute HF or acute exacerbation of chronic HF. Patients were divided into 2 primary precipitant groups: ischemic (N = 979 [46%]) and nonischemic (N = 1233 [54%]). The primary endpoint was all-cause mortality.Multivariate analysis demonstrated that the presence of a nonischemic precipitant was associated with a favorable in-hospital outcome (OR 0.64; CI 0.43–0.94), but with a significant increase in the risk of 10-year mortality (HR 1.12; CI 1.01–1.21). Consistently, the cumulative probability of 10-year mortality was significantly higher among patients with a nonischemic versus ischemic precipitant (83% vs 90%, respectively; Log-rank P value <0.001). Subgroup analysis showed that among the nonischemic precipitant, the presence of renal dysfunction and infection were both associated with poor short-term outcomes (OR 1.56, [P < 0.001] and OR 1.35 [P < 0.001], respectively), as well as long-term (HR 1.59 [P < 0.001] and HR 1.24 [P < 0.001], respectively).Identification of precipitating factors for acute HF hospitalization has important short- and long-term implications that can be used for improved risk stratification and management.     

Relation of serum total cholesterol, C-reactive protein levels, and statin therapy to survival in heart failure

Although increased cholesterol levels predict mortality in patients with coronary artery disease, it is unclear whether hypercholesterolemia is associated with adverse survival in patients with heart failure. A cohort of subjects derived from the Intermountain Heart Collaborative Study Registry (1993 to 2003) who had ejection fractions < or = 40% or clinical diagnoses of heart failure and long-term follow-up for death were studied (n = 1,646). Total cholesterol (TC) was divided into quartiles: quartile 1, < 141.3 mg/dl; quartile 2, 141.3 to 167.9 mg/dl; quartile 3, 168.0 to 201.0 mg/dl; and quartile 4, > 201.0 mg/dl. Multivariate Cox regression models were used to evaluate the associations of cholesterol, statin therapy, and C-reactive protein to mortality. The mean age was 65.5 years; 65% of the subjects were men and 65% had coronary artery disease. Although 53% were using statins, statin use was not different across TC quartiles. Average time to death was 2.4 years (maximum 10). Mortality for quartile 4 versus quartile 1 was not different (hazard ratio [HR] 1.12, p = 0.52); mortality was reduced for quartile 3 versus quartile 1 (HR 0.66, p = 0.027) and tended to be reduced for quartile 2 versus quartile 1 (HR 0.77, p = 0.14). Subanalysis of patients not using statins (n = 737, death = 20.2%) found no association between TC and survival (for quartile 3 vs quartile 1, HR 0.97, p = 0.89), but for patients using statins (n = 848, death = 16.3%), the effect was even greater for quartile 3 versus quartile 1 (HR 0.40, p = 0.002) than in the overall population. Nonsurvivors had higher levels of C-reactive protein than survivors. In conclusion, elevated TC appears to be associated with improved survival. The effect was stronger in patients receiving statin therapy, but the cause of this differential effect is uncertain.     

Association between blood glucose and long-term mortality in patients with acute coronary syndromes in the OPUS-TIMI 16 trial

Hyperglycemia in the context of acute coronary syndrome (ACS) is a common observation, and existing data suggest that high glucose levels are associated with increased in-hospital mortality. We assessed the relation between random glucose and long-term mortality in 9,020 patients with ACS who were enrolled in the OPUS-TIMI 16 trial. A significant relation between glucose level and 10-month mortality was observed (2.7% in quartile 1 vs 7.0% in quartile 4, p <0.0001). After multivariable adjustment for co-morbidity, which included history of diabetes, this relation remained significant (quartile 4 vs 1, hazard ratio 1.70, 95% confidence interval 1.16 to 2.50, p = 0.006). These observations were similar in the TACTICS-TIMI 18 trial. In addition, we observed that B-type natriuretic peptide and troponin I levels increased across glucose quartiles in the OPUS-TIMI 16 trial (p values for trend = 0.002 and 0.0001, respectively) and the TACTICS-TIMI 18 trial (p values for trend = 0.006 and 0.0001, respectively). High blood glucose during ACS is an independent predictor of long-term mortality and is significantly correlated with prognostic biomarkers. Glucose levels during ACS may be an important addition to the risk stratification of patients with ACS and a potentially important target for therapy.     

Hyperuricaemia and long-term outcome after hospital discharge in acute heart failure patients

BACKGROUND: Uric acid (UA) may be involved in chronic heart failure (HF) pathogenesis, entailing a worse outcome. The purpose of this study was to examine the role of hyperuricaemia as a prognostic marker after hospital discharge in acute HF patients. METHODS: We studied 212 patients consecutively discharged after an episode of acute HF with LVEF<40%. Blood samples for UA measurement were extracted in the morning prior to discharge. The evaluated endpoints were death and new HF hospitalization. RESULTS: Mean UA levels were 7.4+/-2.4 mg/dl (range 1.6 to 16 mg/dl), with 127 (60%) of patients being within the range of hyperuricaemia. Hyperuricaemia was associated with a higher risk of death (n=48) (HR 2.0, 95% CI 1.1-3.9, p=0.028), new HF readmission (n=67) (HR 1.8, 95% CI 1.1-3.1, p=0.023) and the combined event (n=100) (HR 1.9, 95% CI 1.2-2.9, p=0.004). At 24 months, cumulative event-free survival was lower in the two higher UA quartiles (36.9% and 40.7% vs. 63.5% and 59.5%, log rank=0.006). After adjustment for potential confounders, hyperuricaemia remains an independent risk factor for adverse outcomes (HR 1.6, 95% CI 1.1-2.6, p=0.02). CONCLUSIONS: In hospitalized patients with acute HF and LV systolic dysfunction, hyperuricaemia is a long-term prognostic marker for death and/or new HF readmission.     

Usefulness of noninvasive estimate of pulmonary vascular resistance to predict mortality, heart failure, and adverse cardiovascular events in Patients With stable coronary artery disease (from the Heart and Soul Study)

Pulmonary vascular resistance (PVR) is an important hemodynamic variable that affects prognosis and therapy in a wide range of cardiovascular and pulmonary conditions. We sought to determine whether a noninvasive estimate of PVR predicts adverse outcomes in patients with stable coronary artery disease. Using Doppler echocardiography we measured the estimated PVR (defined as the ratio of the tricuspid regurgitant velocity [TRV] to the velocity-time integral [VTI] of the right ventricular outflow tract [RVOT]) in 795 ambulatory patients with stable coronary artery disease. Participants were categorized by quartiles of the TRV/VTI RVOT ratio. Hazard ratios (HRs) and 95% confidence intervals were calculated for all-cause mortality, heart failure hospitalization, and adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or stroke). After 4.3 years of follow-up there were 161 deaths, 44 deaths from cardiovascular causes, 103 heart failure hospitalizations, and 120 adverse cardiovascular events. Compared with patients in the lowest TRV/VTI RVOT quartile, those in the highest quartile were at increased risk of all-cause mortality (unadjusted HR 1.8, 95% confidence interval 1.3 to 2.5), heart failure hospitalization (unadjusted HR 2.9, 95% confidence interval 2.0 to 4.3), and adverse cardiovascular events (unadjusted HR 2.0, 95% confidence interval 1.4 to 2.9). After multivariate adjustment, patients in the highest quartile were at increased risk of heart failure hospitalizations (adjusted HR 2.5, 95% confidence interval 1.3 to 4.7). In conclusion, a noninvasive estimate of PVR (TRV/VTI RVOT ratio) predicts mortality, heart failure hospitalization, and adverse cardiovascular events in patients with stable coronary artery disease.     

Relationship between heart-type fatty acid-binding protein levels and the risk of death in patients with serious condition on arrival at the emergency department

OBJECTIVE: Although heart-type fatty acid-binding protein (H-FABP) is a cardiac marker useful for early diagnosis of acute myocardial infarction (AMI), few data are available on its prognostic value. The objective of this study is to clarify the prognostic value of H-FABP in patients with a serious condition. METHODS AND PATIENTS: We conducted a prospective study of 617 patients who presented to the emergency department with a serious condition. The H-FABP levels on arrival at the emergency department were divided into four groups using their quartiles. The endpoint was death from any causes in-hospital. RESULTS: H-FABP ranged from 1.2 to 2,300 ng/ml, with a median of 19.9 ng/ml, a 25%-value of 6.7 ng/ml and 75%-value of 54.0 ng/ml. The unadjusted rate of the mortality increased progressively with increasing H-FABP quartile point (11% for quartile-I, 22% for quartile-II, 36% for quartile-III, and 38% for quartile-IV; p<0.001). After adjustment for age, gender, systolic blood pressure and the presence or absence of cardiovascular disease, H-FABP was the independent factor to predict the mortality. CONCLUSION: H-FABP has proven to be an independent factor for prognosis in patients with a serious condition on arrival at the emergency department.     

The prognostic value of estimated creatinine clearance alongside functional capacity in ambulatory patients with chronic congestive heart failure

OBJECTIVES: The goal of this study was to determine the prognostic significance of estimated creatinine clearance (CrCl) in relation to 6-min walk distance in ambulatory patients with congestive heart failure (HF). BACKGROUND: Although measurement of renal function is integral to the management of chronic congestive HF, its prognostic implications are not well described and have not been formally evaluated relative to measures of functional capacity. METHODS: We analyzed outcomes of the 585 participants of the 6-min walk substudy of the Digitalis Investigation Group (DIG) trial. The CrCl was estimated using the Cockcroft-Gault equation. Predictors of all-cause mortality were identified using semiparametric Cox proportional hazards regression and completely parametric hazard analyses. RESULTS: Most subjects (85%) were New York Heart Association functional class II and III. Mean age was 65 (+/-12) years and mean ejection fraction (EF) 35% (+/-13%). There were 153 (26%) deaths during a median of 2.6 years of follow-up. Mortality by increasing quartiles of estimated CrCl was 37% (18 to 48 ml/min), 29% (47 to 64 ml/min), 18% (64 to 86 ml/min), and 21% (86 to 194 ml/min) with corresponding hazard ratios (HRs) relative to the top quartile of 2.1 (95% confidence interval [CI], 1.4 to 3.3), 1.6 (95% CI, 1.0 to 2.5), and 0.9 (95% CI, 0.5 to 1.5), respectively. In Cox regression analyses, independent predictors of mortality were estimated CrCl (adjusted HR [quartile 1:quartile 4] 1.5; 95% CI, 1.1 to 2.1), 6-min walk distance < or =262 m [adjusted HR, 1.63; 95% CI, 1.12 to 2.27]), EF, recent hospitalization for worsening HF, and need for diuretic treatment. Parametric (hazard) analysis confirmed consistent effects of estimated CrCl on mortality in several subgroups including that of patients with EF >45%. CONCLUSION: In ambulatory patients with congestive HF, estimated CrCl predicts all-cause mortality independently of established prognostic variables.     

Does previous hypertension affect outcome in acute heart failure?

Background

The effect of previous long-term hypertension on mortality in acute heart failure (HF), regardless of blood pressure values, has not been well studied.

Methods

Acute Heart Failure Database (AHEAD) — Czech HF registry enrolled 4153 consecutive patients with acute HF. We excluded severe forms (cardiogenic shock, pulmonary oedema, right HF) and analysed 2421 patients with known presence or absence of previous hypertension. Demographic, clinical and laboratory profile, treatment and mortality rates were assessed and predictors of outcome were identified.

Results

Patients with previous hypertension (71.5%) were older, more of female gender, with worse pre-hospitalisation NYHA class, increased incidence of co-morbidities and higher left ventricular ejection fraction (LVEF). Although in-hospital mortality was similar in both cohorts (2.6%), survival at 1, 2 and 3-year was worse in the hypertensive group (75.6%, 65.9% and 58.7% vs. 80.7%, 74.2% and 69.8%; P < 0.001). Nevertheless, hypertension was not associated with mortality in multivariate analysis and stronger predictors of outcome were identified (P < 0.05): new-onset acute HF [hazard ratio (HR) 0.62] and increased body mass index (HR 0.68) proved to have a protective role. Advanced age (HR 1.86), diabetes (HR 1.45), lower LVEF (HR 1.28) and admission blood pressure (HR 1.54), elevated serum creatinine (HR 1.63), hyponatremia (HR 1.77) and anaemia (HR 1.40) were associated with worse survival.

Conclusion

Antecedent hypertension is frequent in patients with acute HF and contributes to organ and vascular impairment. However its presence has no independent influence on short- and medium-term mortality, which is influenced by other related co-morbidities.     

Association of uric acid with mortality in patients with stable coronary artery disease

ObjectiveThe association between uric acid and cardiovascular disease is poorly studied. We undertook this study to assess whether uric acid level predicts clinical outcome in patients with stable coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI).Materials/MethodsThis study included 8149 patients with stable CAD who underwent PCI. Uric acid was measured before angiography. The primary end point was 1-year mortality. Quartiles of quartiles of uric acid were: 1.49 to < 5.49 mg/dl (1st quartile; n=2032 patients), 5.49 to < 6.40 mg/dl (2nd quartile; n=1981 patients), 6.40 to < 7.50 mg/dl (3rd quartile; n=2093 patients) and 7.50 to 21.90 mg/dl (4th quartile; n=2043 patients).ResultsThere were 196 deaths during the 1-year follow-up. The numbers of deaths (Kaplan-Meier estimates) according to uric acid quartiles were: 35 deaths (1.8%) in the 1st quartile, 30 deaths (1.6%) in the 2nd quartile, 45 deaths (2.2%) in the 3rd quartile and 86 deaths (4.3%) in the 4th quartile (unadjusted hazard ratio [HR]=1.60, 95% confidence interval [CI] 1.38-1.86, P < 0.001 for each standard deviation [SD] increase in the logarithmic scale). After adjustment for traditional cardiovascular risk factors, renal function and inflammatory status, the association between uric acid and 1-year mortality remained significant (adjusted HR=1.26, 95% CI 1.07-1.48; P=0.005 for each standard deviation increase in the logarithmic scale). Uric acid improved predictivity of the multivariable model regarding mortality (P=0.040).ConclusionsElevated level of uric acid is an independent predictor of 1-year mortality in patients with stable CAD treated with PCI.     

Heart rate variability in long-term risk assessment in middle-aged women with coronary heart disease: The Stockholm Female Coronary Risk Study

OBJECTIVES: Low heart rate variability (HRV) is associated with poor prognosis after acute coronary events in men. In women, the prognostic impact is not well documented. The objective of this study was to assess the long-term predictive power of HRV on mortality amongst middle-aged women with coronary heart disease (CHD). DESIGN, SETTINGS AND SUBJECTS: Consecutive women below 65 years hospitalized for an acute coronary syndrome during a 3-year period in Stockholm were examined for cardiovascular prognostic factors including HRV, and followed for a median of 9 years. An ambulatory 24-h electrocardiograph was recorded during normal activities, 3-6 months after hospitalization. SDNN index (mean of the standard deviations of all normal to normal intervals for all 5-min segments of the entire recording) and the following frequency domain parameters were assessed: total power, high-frequency (HF) power, low-frequency (LF) power, very-low frequency (VLF) power and LF/HF ratio. Using Cox proportional hazards regression, the hazard ratios (HR) for each 25% decrease of the HRV parameters were assessed. RESULTS: After controlling for the independent, significant predictors of mortality amongst the clinical variables, the following HRV parameters were found to be significant predictors of all-cause mortality: SDNN index [HR 1.56, 95% confidence intervals (CI) 1.19-2.05], total power (HR 1.21, 95% CI 1.08-1.35), VLF power (HR 1.22, 95% CI 1.09-1.36), LF power (HR 1.18 95%, CI 1.07-1.30) and HF power (HR 1.18, 95% CI 1.05-1.33). The results were essentially the same when cardiovascular mortality was used as end-points. The HRV parameters were stronger predictors of mortality in the first 5 years following the index event. CONCLUSION: Low HRV is a predictor of long-term mortality amongst middle-aged women with CHD when measured 3-6 months after hospitalization for an acute coronary syndrome, even after controlling for established clinical prognostic markers.     

Effect of revascularization on mortality associated with an elevated white blood cell count in acute coronary syndromes

Inflammation is increasingly recognized as having an important role in patients with acute coronary syndromes. We sought to determine whether an elevated white blood cell (WBC) count would predict subsequent mortality and whether revascularization would have a protective effect. We analyzed data from 10,480 patients with acute coronary syndromes enrolled in the PURSUIT trial who had a WBC count measured on admission. WBC count values were stratified by quartiles, and death rates at 6 months were examined in univariate and multivariate analyses. Propensity analysis was performed to assess the effect of revascularization on the relation between WBC count and mortality. In the lowest quartile of WBC count, mortality was 4.0%; it was 5.8% in the second quartile, 6.7% in the third quartile, and 8.0% in the fourth quartile (p <0.001). In a multivariable model incorporating baseline demographic and clinical variables, an increasing WBC count was a significant predictor of death, with a hazard ratio of 1.07 per 1,000/microl increment in WBC count (p <0.001). Furthermore, the interaction term between mortality due to an elevated WBC count and benefit of in-hospital revascularization was significant (hazard ratio 0.94, p = 0.032), suggesting that the excess risk due to an elevated WBC count was attenuated by revascularization. An elevated WBC count at hospital admission, although only a crude index of inflammation, nevertheless is an independent predictor of death at 6 months in patients with acute coronary syndromes. This finding supports a pivotal role for inflammation in acute coronary syndromes. Importantly, this study suggests that in-hospital revascularization may mitigate some of the excess risk due to inflammation.     

Carotid plaque and intima-media thickness and the incidence of ischemic events in patients with atherosclerotic vascular disease

We aimed to evaluate whether carotid intima-media thickness (CIMT) or the presence of plaque can confer additional predictive value of future cardiovascular (CV) ischemic events in patients with pre-existing atherosclerotic vascular disease. We identified 2317 patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry who had atherosclerotic vascular disease and baseline CIMT measurements. The entire range of CIMT was divided into quartiles and the fourth quartile (≥ 1.5 mm) was defined as carotid plaque. Mean ± standard deviation baseline CIMT was 1.31 ± 0.65 mm. Associated CV ischemic events and vascular-related hospitalizations were evaluated over a 2-year follow-up. There was a positive increase in adjusted hazard ratios (HRs) for all-cause mortality (p = 0.04 for trend) and the quadruple endpoint (CV death, myocardial infarction (MI), stroke, hospitalization for CV events) with increasing quartiles of CIMT (p = 0.0008 for trend), which was mainly driven by the fourth quartile (carotid plaque). HRs for all-cause mortality, CV death, CV death/MI/stroke and the quadruple endpoint comparing the highest (carotid plaque) with the lowest CIMT quartile were 2.09 (95% CI, 1.07-4.10; p = 0.03); 2.49 (1.10-5.67; p = 0.03); 1.71 (1.10-2.67; p = 0.02); and 1.73 (1.31-2.27; p = 0.0001). In conclusion, our analyses suggest that the presence of carotid plaque, rather than the thickness of intima-media, appears to be associated with increased risk of CV morbidity and mortality, but confirmation of these findings in other population and prospective studies is required.     

Admission blood glucose level and mortality among hospitalized nondiabetic patients with heart failure

BACKGROUND: The significance of admission blood glucose level in nondiabetic patients with heart failure (HF) is unknown. We examined the possible association between admission glucose levels and outcome in a large cohort of hospitalized patients with HF. METHODS: We analyzed the data of 4102 patients with HF, who were hospitalized during a prospective national survey. The present study focuses on a subgroup of 1122 nondiabetic patients with acute HF who were admitted because of acute HF or exacerbation of chronic HF. RESULTS: In-hospital mortality was twice as high in patients with admission blood glucose levels in the third tertile (7.2%) compared with the first (3%) and second (4%) tertiles (P = .02). Furthermore, mortality risk was correlated with admission glucose levels; each 18-mg/dL (1-mmol/L) increase in glucose level was associated with a 31% increased risk of in-hospital mortality (adjusted odds ratio, 1.31; 95% confidence interval, 1.10-1.57; P = .003) and a 12% increase in 60-day mortality (adjusted hazard ratio, 1.12; 95% confidence interval, 1.01-1.25; P = .04). Admission blood glucose levels remained an independent predictor of in-hospital and 60-day mortality even after the exclusion of 315 patients (28%) with acute myocardial infarction and HF. The 6- and 12-month mortality rates were similar in patients with and without abnormal admission blood glucose levels. CONCLUSIONS: Elevated admission blood glucose levels are associated with increased in-hospital and 60-day mortality, but not 6-month or 1-year mortality, in nondiabetic patients hospitalized because of HF.     

Increased Plasma Concentrations of Soluble ST2 Independently Predict Mortality but not Cardiovascular Events in Stable Coronary Heart Disease Patients: 13-Year Follow-up of the KAROLA Study

Purpose

sST2 (soluble suppression of tumorigenicity 2), a member of the interleukin-1 family, has been suggested to play a role in cardiac remodeling and inflammatory signaling. We assessed the association between sST2 in patients with stable coronary heart disease (CHD) with multiple cardiovascular outcomes and total mortality, simultaneously controlling for a large number of potential confounders.

Methods

Plasma concentrations of sST2 (ELISA, Critical Diagnostics) were measured at baseline in a cohort of 1081 patients. The Cox-proportional hazards model was used to determine the prognostic value of sST2 on a combined cardiovascular disease (CVD) endpoint, on cardiovascular death, and on total mortality after adjustment for covariates.

Results

The median sST2 level was 28.9 ng/mL (IQR 23.8, 35.1) (mean age at baseline 58.9 years, 84.6% male). sST2 concentration was positively correlated with inflammatory markers and emerging risk factors, e.g., cystatin C, N-terminal probrainnatriuretic peptide (NT-proBNP), high-sensitivity (hs)-Troponin T and I, mid-regional pro-atrial natriuretic peptide (MR-proANP), and growth differentiation factor 15 (GDF-15). Results after short- and long-term (4.5 and 12.3 years, respectively) follow-up (FU) displayed no statistically significant association with the combined endpoint of non-fatal and fatal CVD events when the top quartile (Q4) of sST2 concentration was compared to the bottom quartile (Q1). A relationship during long-term FU was seen with CVD mortality even after multivariable adjustments including clinical risk variables (HR 1.65; 95% CI 1.02–2.86), but not in a fully adjusted model whereas, in contrast, it was still highly significant after short-term FU (HR (5.97 (95%CI 1.32–27.06)). In addition, the sST2 concentration was still strongly associated with total mortality in the fully adjusted model including clinical variables and cystatin C based estimated glomerular filtration rate, NT-proBNP, hsCRP and hs-TnI comparing Q4 vs Q1 during long-term FU (HR of 1.48 (95% CI 1.03–2.13)) and short-term FU (HR 3.06 (95% CI 1.29–7.24)).

Conclusions

Elevated levels of sST2 concentration in stable CHD patients may independently predict short- and long-term risk for fatal CVD events and total mortality but not non-fatal CVD events.