Biomarker-associated Monocyte Inflammatory Signaling in Myocardial Infarction

Abstract Background: Monocytes are essential components in inflammatory signaling, and their recruitment is crucial in the signaling pathway, which directs and determines cell adhesion to the activated endothelium. A better understanding of the correlation between monocyte subsets and inflammatory signaling in patients with atherosclerotic disease in acute coronary syndrome (ACS) is essential for the development of more effective therapies for the prevention and treatment of cardiovascular diseases. Objective: To analyze differences between biomarkers and monocyte activation in the setting of ischemic heart disease. Methods: This was a case-control study comparing biomarkers and monocyte subsets between patients with ACS with and without ST-segment elevation and individuals without coronary stenosis. The nonparametric Kruskal-Wallis test was used to assess differences between groups, and Dunn's post hoc test was used to identify which groups were different. Cuzick's test for ordered group trends was used to assess falling or rising trends. Participants were classified into 3 groups: control (0); non-ST-elevation myocardial infarction (NSTEMI) (1); ST-elevation myocardial infarction (STEMI) D1 (2). Results: Forty-seven patients with ACS and 19 controls with no obstructive lesions on coronary angiography were recruited. Monocyte profile assessment was statistically different regarding time of symptom onset and the presence or absence of atherosclerotic disease (Kruskal-Wallis, p = 0.0009). Dunn's post hoc test showed a significant difference between the control group and the STEMI D1 (p = 0.0014), STEMI D3 (p = 0.0036), and STEMI D7 (p = 0.0195) groups, corresponding to a 2-fold increase in classical (p = 0.0022) and nonclassical (p = 0.0031) monocytes compared with controls. For classical monocytes, there was a difference between the control group and all STEMI groups and between the NSTEMI group and the STEMI D1, D3, and D7 groups. For nonclassical monocytes, there was a difference between the control group and the STEMI D7 group (p = 0.0056) and between the NSTEMI group and the STEMI D7 group (p = 0.0166). Conclusion: This study found that there was an increase in total and classical monocyte mobilization at the time of acute myocardial infarction in patients with ACS.

Predictors of Hospitalization in Vitamin K Antagonist Users Presenting with Bleeding at the Emergency Department

Abstract Background Vitamin K antagonists (VKA) are indicated for the prevention of thromboembolic events and reduction of mortality in patients with atrial fibrillation and patients with valvular prostheses. However, their use is associated with bleeding complications and hospitalizations. Predictors of hospital admission for bleeding in these patients are poorly known. Objectives To define the predictors for hospitalization of VKA users who seek emergency care due to bleeding. Methods Single-center, cross-sectional study, with retrospective analysis of electronic medical records from 03/01/2012 to 02/27/2017. Clinical and laboratory variables were compared between patients who were hospitalized and those who were not. A logistic regression model as used, in which the variables were included using the Backward stepwise method, with a p value of 0.05 as the input criterion, a removal value of 0.20 and a confidence interval of 95%. The p-value was considered statistically significant when <0.05. Results A total of 510 patients with bleeding were included, of whom 158 were hospitalized. Predictors of hospitalization were: INR at supratherapeutic levels (OR 3.45; P <0.01; 95% CI 1.58 - 7.51), gastrointestinal bleeding (OR 2.36; P <0.01; CI 95% 1.24 - 4.50), drop in hemoglobin (OR 6.93; P <0.01; 95% CI 3.67 - 13.07), heart failure (OR 1.96; P 0.01; 95% CI 1.16 - 3.30) and need for blood transfusion (OR 8.03; P <0.01; 95% CI 2.98 - 21.64). Conclusion Drop in hemoglobin, heart failure, INR at supratherapeutic levels, gastrointestinal bleeding and need for blood transfusion were associated with hospitalization. Identification of these factors in the initial evaluation would help to define which patients will demand more intensive care.

Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension and diabetes mellitus: results from the PREVER-treatment randomized controlled trial.

AIMS: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of JNC 7 Stage I hypertension in patients with type 2 diabetes mellitus. METHODS: In an a priori subgroup analysis of a randomized, double-blind, controlled trial, volunteers aged 30-70 years, with stage I hypertension and diabetes mellitus, were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 47) or 50 mg of losartan (N = 50), and followed for 18 months in 21 clinical centers. If BP remained uncontrolled after three months, study medication dose was doubled, and if uncontrolled after six months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg BID) were added as open label drugs in a progressive fashion. RESULTS: Systolic BP decreased to a greater extent in participants allocated to diuretics compared to losartan (P < 0.001). After 18 months of follow-up, systolic BP was 128.4 ± 10.3 mmHg in the diuretic group versus 133.5 ± 8.0 in the losartan group (P < 0.01). In the diuretic group, 36 out of 43 participants (83.7%) had a JNC 7 normal BP, compared to 31/47 (66%) in the losartan group (P = 0.089). Serum cholesterol was higher in the diuretic arm at the end of the trial. Other biochemical parameters and reports of adverse events did not differ by treatment. CONCLUSIONS: Treatment of hypertension based on a combination of chlorthalidone and amiloride is more effective for BP lowering compared to losartan in patients with diabetes mellitus and hypertension. TRIAL REGISTRATION: Clinical trials registration number: NCT00971165.

Is there an association between the nutritional and functional parameters and congestive heart failure severity?

BACKGROUND & AIMS: The association between markers of nutritional status (handgrip strength [HGS] and adductor pollicis muscle thickness [APMT]) and clinical markers of congestive heart failure (CHF) severity is currently unclear. The objective of this study was to evaluate the association between HGS, APMT, as markers of nutritional status and CHF severity. METHODS: APMT and muscle strength was measured in 500 CHF patients bilaterally. Nutritional status was assessed by Subjective Global Assessment (SGA). Functional classification was performed according to guidelines provided by the New York Heart Association (NYHA) and ejection fraction (EF) was measured to classify CHF severity. Poisson regression, adjusted for sex and age, was performed to verify the association between nutritional factors and CHF severity markers. RESULTS: The majority of patients (75.8%) were ≥60 years old and 53.6% were either overweight or obese. SGA identified 42.2% of the patients as malnourished, 12.6% with low APMT, and 29.0% with low HGS. Most of the patients were classified as NYHA III/IV (56.8%) and almost one third of patients (31.1%) had EF ≤ 40%. HGS and APMT were significantly lower in malnourished male patients and in male patients with a lower EF or worse NYHA classification. Even after controlling for the EF, malnourished patients showed a 2.5-fold increased risk of CHF severity by NYHA classification and for each kilogram of increase in the HGS, there was a significant decrease of 2% in the risk (RR: 0.98 p < 0.001). Malnourished patients presented a 52% higher risk (RR: 1.52 p = 0.016) of having a low EF, whereas for each APMT increase, there was a 5% decrease in the risk (RR: 0.95 p < 0.001), even after controlling for NYHA classification. CONCLUSIONS: Malnutrition is highly prevalent among patients with CHF and it is associated with the functional class and the severity of the disease. Objective markers of strength (HGS) and muscle (APMT) are independently associated with the CHF severity, assessed by NYHA classification and EF, respectively, even after adjustment for other confounding variables. Thus, the implementation of these nutritional assessment methods in hospital routines, either by SGA or by objective methods, such as HGS and APMT, can configure effective measurements for early detection of malnutrition in patients at higher risk, and possibly a way to avoid their further functional decline.

Adductor pollicis muscle and nutritional status in heart failure patients: Is there an association?

OBJECTIVES: Adductor pollicis muscle thickness (APMT) has been used as a simple index for muscle mass for the assessment of nutritional status among hospitalized patients to identify malnutrition. The aim of this study was to evaluate the association between APMT and nutritional status in clinical patients diagnosed with congestive heart failure (CHF). METHODS: APMT was measured in 500 patients with CHF on the dominant side. Nutritional status was assessed means of by the Subjective Global Assessment (SGA). Functional classification was performed according to guidelines provided by the New York Heart Association (NYHA), which establishes four categories of CHF severity. Poisson regression was used to verify the association of APMT, malnutrition, and severity of CHF. P ≤ 0.05 was considered statistically significant. RESULTS: The malnutrition prevalence varied from 1.5% in patients with functional class I CHF to 96.2% in patients classified as functional class IV (P ≤ 0.001). In both sexes, APMT values were significantly lower in patients who were malnourished (P< 0.001). The proportion of patients with CHF and malnutrition was higher among women than men (47.2 versus 37.4%, P = 0.027). Malnutrition was slightly more common among patients ≥60 y of age compared with other age groups (48.3%, P ≤ 0.001). APMT is a significant protective factor for malnutrition even after controlling for sex, age, body mass index, and CHF functional class. CONCLUSIONS: Malnutrition is highly prevalent among patients with CHF and is associated with functional class. APMT may be used as a simple index for muscle mass for the assessment of nutritional status in these patient populations, and is also associated with malnutrition in these patients, even after controlling for other risk factors.

Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment)

ABSTRACT: The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy.

Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment).

The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01643434.