Patrícia Lourenço

Prognostic Value of High-Sensitivity C-Reactive Protein in Heart Failure: A Systematic Review

BACKGROUND Several studies have suggested that high-sensitivity C-reactive protein (hsCRP) is a strong independent predictor of acute myocardial infarction and cardiovascular death. In the specific heart failure (HF) context, a low-grade inflammatory state can contribute to HF progression. AIMS To perform a systematic review on the current knowledge about low-grade inflammation, as assessed by hsCRP, in the prediction of HF in general and in high-risk populations as well as its prognostic value in established HF. METHODS We used a computerized literature search in the Medline database using the following key words: C-Reactive Protein, Heart Failure, Cardiomyopathy, Cardiac Failure, Prognosis, and Death. Articles were selected if they had measurements of hsCRP in different patient samples and reference to outcomes in terms of morbidity and mortality. RESULTS hsCRP is associated with incident HF in general and high-risk populations and provides prognostic information in HF patients. In almost all studies, the association of hsCRP with clinical events was independent of other baseline variables known to influence morbidity and mortality. Very different cutoffs have been proposed in each context across studies. CONCLUSIONS The prognostic power of hsCRP, whether we consider incident HF or adverse outcomes in established HF, is consistent in different patient populations.

Chronic obstructive pulmonary disease in heart failure. Prevalence, therapeutic and prognostic implications.

BACKGROUND Patients with heart failure (HF) frequently have comorbidities. Frequency, prognostic, and therapeutic implications of chronic obstructive pulmonary disease (COPD) in HF are largely unknown. We aimed to assess the prevalence and prognostic implications of COPD in a sample of stable patients with HF and to determine the frequency of beta-blocker (bB) use and rate of withdrawal according to COPD coexistence. METHODS We conducted a retrospective cohort study including 186 patients followed in an outpatient HF clinic. All patients had left ventricular systolic dysfunction and a spirometry result. Patients were classified according to the GOLD guidelines. Treatment was instituted at the discretion of the attending physicians. Prognosis was compared between groups using Cox proportional hazards regression. The primary end point was death or all-cause hospitalization. RESULTS The prevalence of COPD was 39.2% (73/186). No difference was detected between the COPD and non-COPD groups in the rate of bB use (86.3% vs 87.6%, P = .97) and withdrawal (11.1% and 8.1%, P = .71). Mean follow-up was 14.2 +/- 8.8 months. The primary end point occurred in 71 (38.2%) patients--32 in the COPD group and 39 in the remaining (43.8% and 34.5%, respectively; hazard ratio 1.40, 95% CI 0.88-2.24). Severe COPD (GOLD stages III and IV) was associated with an adverse outcome (hazard ratio 2.10, 95% CI 1.05-4.22). CONCLUSIONS We observed a high COPD prevalence in stable patients with HF. Severe COPD predicted worse prognosis. Rates of bB use were high and rates of bB withdrawal were low; both were independent of COPD.

Neutrophil Gelatinase-Associated Lipocalin in the Diagnosis of Type 1 Cardio-Renal Syndrome in the General Ward

BACKGROUND AND OBJECTIVES The early identification of acute heart failure (HF) patients with type 1 cardio-renal syndrome should be the first step for developing prevention and treatment strategies for these patients. This study aimed to assess the performance of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C in the early detection of type 1 cardio-renal syndrome in patients with acute HF. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS One-hundred nineteen patients admitted with acute HF were studied. NGAL and creatinine were measured in the first hospitalization morning; creatinine was also measured at least after 48 to 72 hours. Physicians were blinded to NGAL and cystatin C levels. Type 1 cardio-renal syndrome was defined as an increase in the creatinine level of at least 0.3 mg/dl or 50% of basal creatinine. RESULTS Type 1 cardio-renal syndrome developed within 48 to 72 hours in 14 patients (11.8%). Admission NGAL levels were higher in these patients: 212 versus 83 ng/dl. At a cutoff value of 170 ng/L, NGAL determined type 1 cardio-renal syndrome with a sensitivity of 100% and a specificity of 86.7%. The area under the receiver-operating characteristic curve of NGAL was 0.93 and that of cystatin C was 0.68. CONCLUSIONS Above a cutoff value of 170 ng/L, NGAL predicts 48- to 72-hour development of type 1 cardio-renal syndrome with a negative predictive value of 100% and a positive predictive value of 50%. NGAL independently associates with type 1 cardio-renal syndrome and might be a useful biomarker in the early recognition of these patients.

Prognostic value of neutrophil gelatinase-associated lipocalin in acute heart failure

BACKGROUND The identification of patients at risk for worse outcome is still a challenge. We hypothesized that cystatin C, a marker of renal function, and neutrophil gelatinase-associated lipocalin (NGAL), a marker of acute renal injury, would have a role in the prognostic stratification of these patients. METHODS We prospectively evaluated 121 patients admitted for acute HF. Serum NGAL and cystatin C levels were measured on the first morning after admission. The outcome measures used were the occurrence of death from all causes, and the combined endpoint defined as the first occurrence of either death or hospital admission. Patients were followed for up to 3 months. RESULTS The variables associated with a higher occurrence of death in a univariate approach were older age and higher levels of BNP, cystatin C and NGAL, and those associated with the occurrence of the combined endpoint were older age, Diabetes mellitus, lower GFR, type 1 cardio-renal syndrome, BNP, cystatin C and NGAL. BNP and NGAL remained independent predictors of the occurrence of both all-cause death and the combined endpoint. NGAL levels in the 75th percentile (>167.5 ng/mL) were associated with a 2.7-fold increase in the risk of death and a 2.9-fold increase in the risk of the first occurrence of either death or hospitalization. CONCLUSIONS Serum NGAL, a marker of acute renal injury, is an independent predictor of worse short term prognosis in patients with acute HF. This suggests a role of renal damage, apart from renal function, in the prognosis of these patients.

Adiponectin is increased in cardiac cachexia irrespective of body mass index

Cardiac cachexia (CC) is a complication of chronic heart failure (CHF). Little is known about the mechanisms leading to CC. Adiponectin, leptin, and ghrelin are important regulators of energy metabolism and body weight. Previous studies of CHF and CC had great differences in body mass index (BMI) between cachectic and non‐cachectic patients. To assess serum adiponectin, leptin, and ghrelin concentrations in cachectic and non‐cachectic patients.

Nutritional markers and prognosis in cardiac cachexia

BACKGROUND Cachexia frequently complicates chronic heart failure (CHF) and predicts an ominous prognosis. Hormonal and inflammatory environment differ between cachectic and non-cachectic patients. Nutritional markers of cardiac cachexia and prognostic predictors in this context are not completely understood. OBJECTIVES To study biochemical markers of nutritional status in cardiac cachexia and to investigate variables associated with worse prognosis. METHODS A total of 94 ambulatory patients--38 cachectics and 56 non-cachectics--were recruited. Cardiac cachexia was defined as a weight loss of ≥ 7.5%. An anthropometric evaluation was performed in all patients and blood was collected for several laboratory determinations: haemoglobin, lymphocytes, albumin, transferrin, pre-albumin, cholesterol and triglycerides. Patients were included in a prospective cohort study. RESULTS Cachectics had lower albumin and pre-albumin levels. They also had lower haemoglobin, lymphocytes and triglycerides. Levels of high-sensitivity C-reactive protein, and catabolic hormones were higher in the cachectic group. Low pre-albumin was the only nutritional marker independently associated with cardiac cachexia. (OR = 1.08, CI: 1.01-1.17). During a follow-up of 16.2 ± 5.2 months, 15 (39.4%) cachectic patients and 6 (10.7%) non-cachectics died. In the cachectic group, lower cholesterol was independently associated with worse outcome (HR = 1.32, CI: 1.11-1.57). CONCLUSIONS Pre-albumin seems to be the best laboratory marker of undernutrition in CHF. Low cholesterol independently associates with worse outcome in cardiac cachexia.

Low prealbumin is strongly associated with adverse outcome in heart failure

Objective Prealbumin is one of the best indicators of nutritional status. We previously showed that prealbumin predicted in-hospital mortality in heart failure (HF) patients. We evaluated if a low discharge prealbumin after admission with acute HF would predict morbidity and mortality. Methods We conducted a prospective observational study. Patients admitted with a primary diagnosis of HF were studied. Follow-up was up to 6 months. Endpoints analysed were: all-cause and HF-death; all-cause and worsening HF hospitalisation. Patients with discharge prealbumin ≤15.0 mg/dL and those with prealbumin >15 mg/dL were compared. A Cox-regression analysis was used to evaluate the prognostic impact of low prealbumin. Results We studied 514 patients. Mean age was 78 years and 45.7% were male. During follow-up, 101 patients died (78 for HF) and 209 patients were hospital readmitted (140 for worsening HF). Median prealbumin was 20.1 (15.3–25.3) mg/dL. Patients with lower prealbumin were more often women, older aged and with non-ischaemic HF; they had lower albumin, haemoglobin and total cholesterol; and higher glomerular filtration rate, C-reactive protein, B-type natriuretic peptide and length of hospital stay. Lower prealbumin associated with less β-blocker and statin use. Patients with discharge prealbumin ≤15 mg/dL had a multivariate adjusted HR of 6-month all-cause and HF death of 1.67 (1.00 to 2.80) and 2.12 (1.19 to 3.79) respectively and of all-cause and HF readmission of 1.47 (1.01 to 2.14) and 1.58 (1.01 to 2.47). Conclusions Patients with discharge prealbumin ≤15 mg/dL have an higher risk of 6 months morbidity and mortality. The unbalance between protein–energy demands and its availability predicts ominous HF outcome.

Higher C-Reactive Protein Predicts Worse Prognosis in Acute Heart Failure Only in Noninfected Patients

The prognostic role of C‐reactive protein (CRP) in acute heart failure (HF) is not fully understood, and the impact of an infectious process in its risk‐stratification power was not previously evaluated.

Diagnostic value of patterns of symptoms and signs of heart failure: application of latent class analysis with concomitant variables in a cross-sectional study

Objective The diagnosis of heart failure (HF) requires a compatible clinical syndrome and demonstration of cardiac dysfunction by imaging or functional tests. Since individual symptoms and signs are generally unreliable and have limited value for diagnosing HF, the authors aimed to identify patterns of symptoms and signs, based on findings routinely collected in current clinical practice, and to evaluate their diagnostic value, taking into account the a priori likelihood of HF. Design Cross-sectional evaluation. Participants 1115 community participants aged ≥45 years from Porto, Portugal, in 2006–2008. Main outcomes measures Patterns were identified by latent class analysis, using concomitant variables to predict class membership. Patterns used 11 symptoms/signs, covering dimensions of congestion and hypoperfusion. Sex, age, education, obesity, diabetes and history of myocardial infarction or HF were included as concomitants. Results Bayesian information criteria supported a solution with three patterns: 10.1% of participants followed a pattern with symptoms of troubled breathing and signs of congestion (pattern 1), 27.8% a pattern characterised mainly by signs of congestion (pattern 2) and 62.1% were essentially asymptomatic (pattern 3); model fit was best when including concomitant variables. The likelihood ratio of patterns 1, 2 and 3 for left ventricular systolic dysfunction was 3.4, 1.1 and 0.6, and for left ventricular diastolic dysfunction 3.5, 1.4 and 0.5, respectively. Conclusions The use of concomitant variables can improve the diagnostic value of the symptoms and signs patterns and, consequently, improve the usefulness of the symptoms and signs for diagnosis and as an outcome measure. The potential for application in other settings of complex diagnoses is very high. These models were shown to be useful to standardise and quantify the probabilistic reasoning in clinical diagnosis, upon which decisions of further investigation and even treatment need to be made.

Dipeptidyl peptidase IV and mortality after an acute heart failure episode.

Background: Dipeptidyl peptidase IV (DPP IV) is a key enzyme in B-type natriuretic peptide processing. DPP IV was never studied in human heart failure (HF). We aimed to measure DPP IV concentration in acute HF and determine its association with mortality. Methods and Results: Patients hospitalized with acute HF were eligible. We excluded patients with acute coronary syndromes. A discharge blood sample was collected from all patients and they were followed for a 6-month period. Outcome was HF death. Patients were compared across DPP IV quartiles. A Cox regression analysis was used to assess the prognostic power of DPP IV. We studied 164 patients. Median age was 78 years, 48.8% were men, and 63 had type 2 diabetes and 59.1% had left ventricular systolic dysfunction. Quartiles of DPP IV were <215.2; ≥215.2 and <269.3; ≥269.3 and <348.6; and ≥348.6 ng/mL; groups were homogenous between them. Seventeen patients died. Patients with DPP IV in the last quartile had a hazard ratio of HF death up to 6 months of 2.89, 95% confidence interval, 1.11–7.46. Association was B-type natriuretic peptide independent. Conclusions: Discharge DPP IV ≥348.6 ng/mL conferred an approximately 3-fold higher risk of 6-month HF death. Further studies would be important to understand the role of DPP IV in HF.