Vicente Bertomeu-González

Improvement in risk stratification with the combination of the tumour marker antigen carbohydrate 125 and brain natriuretic peptide in patients with acute heart failure

AIM Elevated brain natriuretic peptide (BNP) and tumour marker antigen carbohydrate 125 (CA125) levels have shown to be associated with higher risk for adverse outcomes in patients with acute heart failure (AHF). Nevertheless, no attempt has been made to explore the utility of combining these two biomarkers. We sought to assess whether CA125 adds prognostic value to BNP in predicting 6-month all-cause mortality in patients with AHF. METHODS AND RESULTS We analysed 1111 consecutive patients admitted for AHF. Antigen carbohydrate 125 (U/mL) and BNP (pg/mL) were measured at a median of 72 +/- 12 h after instauration of treatment. Antigen carbohydrate 125 and BNP were dichotomized based on proposed prognostic cutpoints, and a variable with four categories was formed (BNP-CA125): C1 = BNP < 350 and CA125 < 60 (n = 394); C2 = BNP > or = 350 and CA125 < 60 (n = 165); C3 = BNP < 350 and CA125 > or = 60 (n = 331); and C4 = BNP > or = 350 and CA125 > or = 60 (n = 221). The independent association between BNP-CA125 and mortality was assessed with the Cox regression analysis, and their added predictive ability tested by the integrated discrimination improvement (IDI) index. At 6 months, 181 deaths (16.3%) were identified. The cumulative rate of mortality was lower for patients in C1 (7.8%), intermediate for C2 and C3 (17.8% and 16.9%, respectively), and higher for C4 (37.2%), and P-value for trend <0.001. After adjusting for established risk factors, the highest risk was observed when both biomarkers were elevated (C4 vs. C1: HR = 4.05, 95% CI = 2.54-6.45; P < 0.001) and intermediate when only one of them was elevated: (C2 vs. C1: HR = 1.71, 95% CI = 1.00-2.93; P = 0.050) and (C3 vs. C1: HR = 2.10, 95% CI = 1.30-3.39; P = 0.002). Moreover, when CA125 was added to the clinical model + BNP, a 10.4% (P < 0.0001) improvement in the IDI (on the relative scale) was found. CONCLUSION In patients admitted with AHF, CA125 added prognostic value beyond the information provided by BNP, and thus, their combination enables better 6-month risk stratification.

Frailty and other geriatric conditions for risk stratification of older patients with acute coronary syndrome.

BACKGROUND Geriatric conditions may predict outcomes beyond age and standard risk factors. Our aim was to investigate a wide spectrum of geriatric conditions in survivors after an acute coronary syndrome. METHODS A total of 342 patients older than 65 years were included. At hospital discharge, 5 geriatric conditions were evaluated: frailty (Fried and Green scores), physical disability (Barthel index), instrumental disability (Lawton-Brody scale), cognitive impairment (Pfeiffer questionnaire), and comorbidity (Charlson and simple comorbidity indexes). The outcomes were postdischarge mortality and the composite of death/myocardial infarction during a 30-month median follow-up. RESULTS Seventy-four (22%) patients died and 105 (31%) suffered from the composite end point. Through univariable analysis, all individual geriatric indexes were associated with outcomes, mainly mortality. Of all of them, frailty using the Green score had the strongest discriminative accuracy (area under the receiver operating characteristic curve 0.76 for mortality). After full adjustment including clinical and geriatric data, the Green score was the only independent predictive geriatric condition (per point; mortality: hazard ratio 1.25, 95% CI 1.15-1.36, P = .0001; composite end point: hazard ratio 1.16, 95% CI 1.09-1.24, P = .0001). A Green score ≥ 5 points was the strongest mortality predictor. The addition of the Green score to the clinical model improved discrimination (area under the receiver operating characteristic curve 0.823 vs 0.846) and significantly reclassified mortality risk (net reclassification improvement 26.3, 95% CI 1.4-43.5; integrated discrimination improvement 4.0, 95% CI 0.8-9.0). The incremental predictive information was even greater over the GRACE score. CONCLUSIONS Frailty captures most of the prognostic information provided by geriatric conditions after acute coronary syndromes. The Green score performed better than the other geriatric indexes.

Carbohydrate Antigen 125: An Emerging Prognostic Risk Factor in Acute Heart Failure?

Objective: To assess whether circulating levels of carbohydrate antigen 125 (CA125) predict subsequent 6-month all-cause mortality in patients after the index hospitalisation for acute heart failure (HF). Design and setting: Prospective cohort study at a single teaching centre in Spain. Methods: 529 consecutive patients with acute HF admitted in a single university centre were analysed. In addition to the traditional clinical information, CA125 (U/ml) was measured during the early course of hospitalisation. The independent association between baseline CA125 and mortality was assessed with Cox regression analysis. The follow-up was limited to 6 months. Results: 349 (66%) patients showed serum levels of CA125 >35 U/ml (established cut-off point value). At a 6-month follow-up, 89 (16.8%) deaths were identified. A positive trend between mortality and CA125 quartiles was observed; 3.8%, 15.2%, 22% and 26.5% of deaths occurred from quartile 1 to 4 of CA125 (p<0.001). Likewise, a monotonic, ascending trend in the risk ratios was estimated from the multivariable Cox model. Compared with the first quartile of CA125, the HRs (95% CI) for the second, third and fourth quartiles were 3.25 (1.20 to 8.79), 4.91 (1.88 to 12.85) and 8.41 (3.24 to 21.79), respectively. Conclusions: Serum levels of CA125 obtained in patients admitted with a diagnosis of acute HF was shown to be an independent predictor of mortality up to the 6-month follow-up.

Erectile Dysfunction in High-Risk Hypertensive Patients Treated with Beta-Blockade Agents

BACKGROUND Erectile dysfunction (ED) is a multifactorial disease related to age, vascular disease, psychological disorders, or medical treatments. Beta-blockade agents are the recommended treatment for hypertensive patients with some specific organ damage but have been outlined as one of leading causes of drug-related ED, although differences between beta-blockade agents have not been assessed. METHODS Cross-sectional and observational study of hypertensive male subjects treated with any beta-blockade agent for at least 6 months. ED dysfunction was assessed by the International Index of Erectile Dysfunction (IIEF). RESULTS 1.007 patients, mean age 57.9 (10.59) years, were included. The prevalence of any category of ED was 71.0% (38.1% mild ED; 16.8% moderate ED; 16.1% severe ED). Patients with ED had longer time since the diagnosis of hypertension and higher prevalence of risk factors and comorbidities. The prevalence of ED increased linearly with age. ED patients received more medications and were more frequently treated with carvedilol and less frequently with nebivolol. Patients treated with nebivolol obtained higher scores in every parameter of the IIEF questionnaire. The multivariate analysis identified independent associations between ED and coronary heart disease (OR: 1.57), depression (OR: 2.25), diabetes (OR: 2.27), atrial fibrillation (OR: 2.59), and dyhidopiridines calcium channel blockers (OR: 1.76); treatment with nebivolol was associated to lower prevalence of ED (OR: 0.27). CONCLUSION ED is highly prevalent in hypertensive patients treated with beta-blockade agents. The presence of ED is associated with more extended organ damage and not to cardiovascular treatments, except for the lower prevalence in nebivolol-treated patients.

Factores asociados a la falta de control de la hipertensión arterial en pacientes con y sin enfermedad cardiovascular

INTRODUCTION AND OBJECTIVES Hypertension is one of the most prevalent and poorly controlled risk factors, especially in patients with established cardiovascular disease (CVD). The aim of this study was to describe the rate of blood pressure (BP) control and related risk factors. METHODS Multicenter, cross-sectional and observational registry of patients with hypertension recruited from cardiology and primary care outpatient clinics. Controlled BP defined as <140/90 mmHg. RESULTS 55.4% of the 10 743 patients included had controlled BP and these had a slightly higher mean age. Patients with uncontrolled BP were more frequently male, with a higher prevalence of active smokers, obese patients, and patients with diabetes. The rate of controlled BP was similar in patients with or without CVD. Patients with uncontrolled BP had higher levels of blood glucose, total cholesterol, low density lipoproteins and uric acid. Patients with uncontrolled BP were receiving a slightly higher mean number of antihypertensive drugs compared to patients with controlled BP. Patients with CVD were more frequently receiving a renin-angiotensin-aldosterone axis inhibitor: 83.5% vs. 73.2% (P<.01). Multivariate analysis identified obesity and current smoking as independently associated with uncontrolled BP, both in patients with or without CVD, as well as relevant differences between the two groups on other factors. CONCLUSIONS Regardless of the presence of CVD, 55% of hypertensive patients had controlled BP. Lifestyle and diet, especially smoking and obesity, are independently associated with lack of BP control. Full English text available from: www.revespcardiol.org.

Quality of Anticoagulation With Vitamin K Antagonists

Vitamin K antagonists (VKA) have a narrow therapeutic range, and literature analysis reveals poor quality of anticoagulation control. We sought to assess the prevalence of poor anticoagulant control in patients under VKA treatment in the prevention of stroke for atrial fibrillation (AF).

Differential prognostic effect of systolic blood pressure on mortality according to left‐ventricular function in patients with acute heart failure

To evaluate the relationship between systolic blood pressure (SBP) and long‐term mortality in patients with acute heart failure (AHF) stratified by ejection fraction (LVEF): reduced (≤40%) vs. preserved (≥50%).

Antigen carbohydrate 125 and brain natriuretic peptide serial measurements for risk stratification following an episode of acute heart failure

BACKGROUND The prognostic utility of combining serial measurements of brain natriuretic peptide (BNP) and antigen carbohydrate 125 (CA125) is largely unknown. The aim of this work is to assess the prognostic utility of serial measurements of BNP, CA125, and their optimal combination for predicting long-term mortality, following a hospitalization for acute heart failure (AHF). METHODS AND RESULTS We analyzed 293 consecutive patients admitted with AHF where CA125 and BNP were measured at discharge (T1) and at the first ambulatory visit (T2: median 31 days after discharge). Biomarkers were evaluated as snapshot determinations or as serial changes in absolute, relative or categorical changes and related to subsequent mortality with Cox regression analysis. The incremental prognostic value added by each biomarker was evaluated by the integrated discrimination improvement (IDI) index. During a median follow-up of 18 months, 91 deaths (31.1%) were identified. From the different metrics tested, the categorical changes in CA125 (Normalization: decreasing to≤35 U/ml at T2; Decreasing but not normalization: decreasing but T2>35 U/ml; small-increase: increasing but T2≤35 U/ml and; high-increase: increasing and T2>35 U/ml) showed the best discriminative accuracy. For BNP none of the serial changes metrics tested were superior to a single determination at T2 (BNP≥100 pg/ml). Adding these two biomarkers characterization to the clinical model, resulted in a 9.21% (p<0.001) gain in IDI index. CONCLUSIONS In patients discharged for AHF, CA125 modeled as a pre-post categorical change, and BNP as a single determination at T2, resulted in the best marker combination for predicting all-cause mortality.

Las concentraciones bajas de colesterol unido a las lipoproteínas de alta densidad se asocian de manera independiente a enfermedad coronaria aguda en pacientes que ingresan por dolor torácico

INTRODUCTION AND OBJECTIVES The role of high-density lipoproteins in the context of acute chest pain has not been well characterized. The objective of this study was to determine the relative contribution of lipid profile to the risk of acute coronary syndrome in patients admitted to a cardiology ward for chest pain. METHODS We included all consecutive admissions in a single cardiology department over a period of 10 months and 1-year follow-up was performed. RESULTS In total, 959 patients were included: 457 (47.7%) were diagnosed with non-ischemic chest pain, 355 (37%) with non-ST-elevation acute coronary syndrome, and 147 (15.3%) with ST-elevation acute coronary syndrome. Prevalence of high-density lipoproteins <40 mg/dL was 54.6%, and was higher in patients with acute coronary syndrome (69.4% vs 30.6%; P<.01). The prevalence of acute coronary syndrome increased with reductions in mean high-density lipoproteins. Age, active smoking, diabetes, fasting glucose >100 mg/dL, and high-density lipoproteins <40 mg/dL were independently associated with acute coronary syndrome, and low high-density lipoproteins was the main associated factor (odds ratio, 4.11; 95% confidence interval, 2.87-5.96). Survival analysis determined that, compared with non-ischemic chest pain, the presence of acute coronary syndrome was associated with significantly greater risk of all-cause and cardiovascular mortality. CONCLUSIONS Low levels of high-density lipoproteins cholesterol (≤40 mg/dL) were independently associated with a diagnosis of acute coronary syndrome in patients hospitalized for chest pain, with an inverse relationship between lower levels of high-density lipoproteins and prevalence of acute coronary syndrome.

Differential mortality association of loop diuretic dosage according to blood urea nitrogen and carbohydrate antigen 125 following a hospitalization for acute heart failure

Recent observations in chronic stable heart failure suggest that high‐dose loop diuretics (HDLDs) have detrimental prognostic effects in patients with high blood urea nitrogen (BUN), but recent findings have also indicated that diuretics may improve renal function. Carbohydrate antigen 125 (CA125) has been shown to be a surrogate of systemic congestion. We sought to explore whether BUN and CA125 modulate the mortality risk associated with HDLDs following a hospitalization for acute heart failure (AHF).