natriuretic-peptide--brain and Calcinosis

Cardiac biomarkers, such as cardiac troponin T (cTnT), brain natriuretic peptide (BNP), and N-terminal-pro-BNP (NT-pro-BNP), are commonly used to diagnose acute coronary syndrome and congestive heart failure exacerbation in symptomatic patients. Levels of these biomarkers are frequently chronically elevated in asymptomatic patients with ESRD who are receiving maintenance dialysis. Other imaging biomarkers commonly encountered in nephrologists' clinical practice, such as coronary artery calcium measured by computed tomography, left ventricular hypertrophy, and carotid intima-media thickness, are also frequently abnormal in asymptomatic patients with ESRD. This article critically reviews the limited observational data on associations between cTnT, BNP, NT-pro-BNP, coronary artery calcium, left ventricular hypertrophy, and carotid intima-media thickness with cardiovascular events and death in non-dialysis-dependent patients with CKD. Although sufficient evidence suggests that these biomarkers may be used for prognostication, the diagnostic utility of cTnT, BNP, and NT-pro-BNP remain challenging in patients with CKD. Decreased renal clearance may affect the plasma levels of these biomarkers, and upper reference limits were originally derived in patients without CKD. Until better data are available, higher cutoffs, or a rise in level compared with previous values, have been proposed to help distinguish acute myocardial infarction from chronic elevations of cTnT in symptomatic patients with CKD. Additionally, it is not known whether these biomarkers are modifiable and amenable to interventions that could change hard clinical outcomes in patients with CKD not yet undergoing long-term dialysis.

Topics: Biomarkers; Calcinosis; Carotid Intima-Media Thickness; Coronary Artery Disease; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Tomography, X-Ray Computed; Troponin T; Ventricular Dysfunction, Left

Topics: Ankle Brachial Index; Anti-Obesity Agents; Arteriosclerosis; Biomarkers; C-Reactive Protein; Calcinosis; Coronary Disease; Diabetes Mellitus; Diagnostic Imaging; Dyslipidemias; Endarterectomy; Fibrinolytic Agents; Genetic Markers; Glycated Hemoglobin; Health Behavior; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Life Style; Lipids; Metabolic Syndrome; Natriuretic Peptide, Brain; Obesity; Risk Assessment; Risk Factors; Smoking Cessation; Stents; Stroke; Thrombosis; Troponin I

The risk of cardiovascular disease is tremendously high in dialysis patients. Dialysis patients treated with vitamin D analogs show decreased cardiovascular morbidity and mortality compared with untreated patients. We examined the influence of two common vitamin D analogs, alfacalcidol and paricalcitol, on important cardiovascular biomarkers in hemodialysis patients. Anti-inflammatory effects and the influence on regulators of vascular calcification as well as markers of heart failure were examined.. In 57 chronic hemodialysis patients enrolled in a randomized crossover trial comparing paricalcitol and alfacalcidol, we examined the changes in osteoprotegerin, fetuin-A, NT-proBNP, hs-Crp, IL-6 and TNF-α, during 16 weeks of treatment.. NT-proBNP and osteoprotegerin increased comparably in the paricalcitol and alfacalcidol-treated groups. Fetuin-A increased significantly in the alfacalcidol-treated group compared with the paricalcitol-treated group (difference 32.84 μmol/l (95% C.I.; range 0.21-67.47)) during the first treatment period. No difference was found between the groups during the second treatment period, and IL-6, TNF-α and hs-Crp were unchanged in both treatment groups.. Paricalcitol and alfacalcidol modulate regulators of vascular calcification. Alfacalcidol may increase the level of the calcification inhibitor fetuin-A. We did not find any anti-inflammatory effect or difference in changes of NT-proBNP.. ClinicalTrials.gov NCT00469599 May 3 2007.

Topics: Aged; Aged, 80 and over; Biomarkers; Calcinosis; Cross-Over Studies; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Vitamin D

The study aims were to test the effect of rosuvastatin on the progression of left ventricular (LV) diastolic function in patients with aortic stenosis (AS), and to evaluate the use of beta-natriuretic-peptide (BNP) as a marker of diastolic dysfunction in this condition.. Sixty-one hypercholesterolemic, consecutive new referrals with moderate AS were administered rosuvastatin (Crestor) 20 mg/day for 18 months, while a further 60 subjects with normal cholesterol levels remained untreated. The LV diastolic function was determined using conventional Doppler echocardiography, tissue Doppler imaging (TDI); BNP plasma levels were monitored when subjects entered the study and then assessed prospectively at six-month intervals until the study end.. After an 18-month (mean 73 +/- 24 weeks) period of treatment with rosuvastatin (Tx group), patients showed a significantly better diastolic function than untreated subjects (uTx group), as indicated by an isovolumic relaxation time (IVRT) (Tx 102.0 +/- 42.8 versus 97.2 +/- 19.1; p < 0.001; uTx 99.7 +/- 21.7 versus 95.2 +/- 21.8 ms; p = 0.032), E/A ratio (Tx 1.0 +/- 0.6 versus 0.9 +/- 0.3, p = 0.52; uTx 1.2 +/- 0.40 versus 0.9 +/- 0.30 versus, p = 0.006), and E/E' ratio (Tx 11.4 +/- 1.5 versus 11.4 +/- 1.8, p = 0.19; uTx 15.4 +/- 1.2 versus 12.3 +/- 1.5, p < 0.001). Similarly, at study end, plasma levels of BNP were significantly lower in the Tx group than in the uTx group [median (1st-3rd quartiles): 37.0 pg/ml (20.1-65.2 pg/ml) versus 57.1 pg/ml (46.9-98.2 pg/ml); p = 0.017].. The results of this prospective follow up study of asymptomatic patients showed that rosuvastatin treatment delays the progression of diastolic dysfunction in moderate AS when assessed using hemodynamic echocardiographic parameters or by the release of plasma physiological markers. Hence, the benefits of statin treatment in AS, which are known to affect the valve endothelium, also extend to changes affecting myocardial function itself.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Calcinosis; Diastole; Disease Progression; Echocardiography; Female; Fluorobenzenes; Follow-Up Studies; Heart Failure, Diastolic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Treatment Outcome; Ventricular Dysfunction, Left

Recent trials have failed to show that statin therapy halts the progression of calcific aortic stenosis (AS). We hypothesized that statin therapy in younger patients with congenital AS would be more beneficial, because the valve is less calcified. In the present double-blind, placebo-controlled trial, 63 patients with congenital AS (age 18 to 45 years) were randomly assigned to receive either 10 mg of rosuvastatin daily (n = 30) or matched placebo (n = 33). The primary end point was the progression of peak aortic valve velocity. The secondary end points were temporal changes in the left ventricular mass, ascending aortic diameter, and N-terminal pro-brain natriuretic peptide (NT-proBNP). The median follow-up was 2.4 years (interquartile range 1.9 to 3.0). The mean increase in peak velocity was 0.05 ± 0.21 m/s annually in the rosuvastatin group and 0.09 ± 0.24 m/s annually in the placebo group (p = 0.435). The annualized change in the ascending aorta diameter (0.4 ± 1.7 mm with rosuvastatin vs 0.5 ± 1.6 mm with placebo; p = 0.826) and left ventricular mass (1.1 ± 15.8 g with rosuvastatin vs -3.7 ± 30.9 g with placebo; p = 0.476) were not significantly different between the 2 groups. Within the statin group, the NT-proBNP level was 50 pg/ml (range 19 to 98) at baseline and 21 pg/ml (interquartile range 12 to 65) at follow-up (p = 0.638). NT-proBNP increased from 40 pg/ml (interquartile range 20 to 92) to 56 pg/ml (range 26 to 130) within the placebo group (p = 0.008). In conclusion, lipid-lowering therapy with rosuvastatin 10 mg did not reduce the progression of congenital AS in asymptomatic young adult patients. Interestingly, statins halted the increase in NT-proBNP, suggesting a potential positive effect of statins on cardiac function in young patients with congenital AS.

Topics: Adolescent; Adult; Aortic Valve; Aortic Valve Stenosis; Belgium; Blood Flow Velocity; Calcinosis; Disease Progression; Double-Blind Method; Echocardiography, Doppler; Female; Fluorobenzenes; Follow-Up Studies; Heart Valve Prosthesis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Prospective Studies; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Young Adult

The aim of the prospective, randomized, placebo-controlled Tyrolean Aortic Stenosis Study (TASS) was to characterize the natural history and risk factors and their possible modulation by new-onset atorvastatin treatment (20 mg/day vs placebo) in patients with asymptomatic calcified aortic stenosis. Forty-seven patients without previous lipid-lowering therapy or indications for it according to guidelines at study entry were randomized to atorvastatin treatment or placebo and prospectively followed for a mean study period of 2.3 +/- 1.2 years. Patients' prognoses were worse than expected, with 24 (51%) experiencing major adverse clinical events, in most cases the new onset of symptoms followed by aortic valve replacement. In multivariate regression analysis, independent risk factors for worse clinical outcomes were aortic valve calcification, as assessed by multidetector computed tomography, and plasma levels of C-reactive protein. In univariate analysis, mean systolic pressure gradient or an increased N-terminal-pro-B-type natriuretic peptide plasma level allowed the prediction of major adverse clinical events as well, whereas concomitant coronary calcification, age, and the initiation of atorvastatin treatment had no significant prognostic implication. As shown in a subgroup of 35 patients (19 randomly assigned to atorvastatin and 16 to placebo), annular progression in aortic valve calcification and hemodynamic deterioration were similar in both treatment groups. In conclusion, TASS could demonstrate a poor clinical outcome in patients with asymptomatic calcified aortic stenosis which can be predicted by new risk factors such as strong AVC or increased plasma levels of CRP or NT-proBNP. The study does not support the concept that treatment with a HMG-CoA reductase inhibitor (20 mg atorvastatin once daily) halts the progression of calcified aortic stenosis.

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Atorvastatin; C-Reactive Protein; Calcinosis; Cholesterol; Disease Progression; Female; Heart Valve Prosthesis; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Pyrroles; Risk Factors; Tomography, X-Ray Computed

Enhanced risk stratification of patients with aortic stenosis (AS) is necessary to identify patients at high risk for adverse outcomes, and may allow for better management of patient subgroups at high risk of myocardial damage. The objective of this study was to identify plasma biomarkers and multimarker profiles associated with adverse outcomes in AS.. We studied 708 patients with calcific AS and measured 49 biomarkers using a Luminex platform. We studied the correlation between biomarkers and the risk of (i) death and (ii) death or heart failure-related hospital admission (DHFA). We also utilized machine-learning methods (a tree-based pipeline optimizer platform) to develop multimarker models associated with the risk of death and DHFA. In this cohort with a median follow-up of 2.8 years, multiple biomarkers were significantly predictive of death in analyses adjusted for clinical confounders, including tumour necrosis factor (TNF)-α [hazard ratio (HR) 1.28, P < 0.0001], TNF receptor 1 (TNFRSF1A; HR 1.38, P < 0.0001), fibroblast growth factor (FGF)-23 (HR 1.22, P < 0.0001), N-terminal pro B-type natriuretic peptide (NT-proBNP) (HR 1.58, P < 0.0001), matrix metalloproteinase-7 (HR 1.24, P = 0.0002), syndecan-1 (HR 1.27, P = 0.0002), suppression of tumorigenicity-2 (ST2) (IL1RL1; HR 1.22, P = 0.0002), interleukin (IL)-8 (CXCL8; HR 1.22, P = 0.0005), pentraxin (PTX)-3 (HR 1.17, P = 0.001), neutrophil gelatinase-associated lipocalin (LCN2; HR 1.18, P < 0.0001), osteoprotegerin (OPG) (TNFRSF11B; HR 1.26, P = 0.0002), and endostatin (COL18A1; HR 1.28, P = 0.0012). Several biomarkers were also significantly predictive of DHFA in adjusted analyses including FGF-23 (HR 1.36, P < 0.0001), TNF-α (HR 1.26, P < 0.0001), TNFR1 (HR 1.34, P < 0.0001), angiopoietin-2 (HR 1.26, P < 0.0001), syndecan-1 (HR 1.23, P = 0.0006), ST2 (HR 1.27, P < 0.0001), IL-8 (HR 1.18, P = 0.0009), PTX-3 (HR 1.18, P = 0.0002), OPG (HR 1.20, P = 0.0013), and NT-proBNP (HR 1.63, P < 0.0001). Machine-learning multimarker models were strongly associated with adverse outcomes (mean 1-year probability of death of 0%, 2%, and 60%; mean 1-year probability of DHFA of 0%, 4%, 97%; P < 0.0001). In these models, IL-6 (a biomarker of inflammation) and FGF-23 (a biomarker of calcification) emerged as the biomarkers of highest importance.. Plasma biomarkers are strongly associated with the risk of adverse outcomes in patients with AS. Biomarkers of inflammation and calcification were most strongly related to prognosis.

Topics: Aortic Valve Stenosis; Biomarkers; Calcinosis; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

The presence of coronary artery calcification (CAC) and its severity predict future cardiovascular events and is used for risk stratification. However, the association of CAC with heart failure (HF) in patients without a history of coronary artery disease (CAD) remains unclear. This study aimed to determine the correlations of CAC with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and HF events in patients without a history of CAD or HF.. From June 2010 to June 2013, a total of 487 patients without a history of CAD and HF were enrolled. All of the patients underwent plane multi-detector computed tomography. They were divided into four categories according to CAC scores: ≤10, 11-100, 101-400, and ≥401.. The proportion of patients with high NT-proBNP levels increased with CAC categories (p<0.0001). The CAC score was associated with NT-proBNP levels ≥400pg/ml, with an odds ratio of 2.901 (95% confidence interval: 1.368-6.151, p=0.0055) for CAC scores ≥401 compared with CAC scores of 0-10 after adjustment for confounding factors. During the follow-up period of 497±315 days, nine patients were admitted for HF. Kaplan-Meier analysis showed that patients with CAC scores ≥401 had a lower rate of freedom from admission for HF with cumulative incidences of 0.4%, 1%, 2%, and 8% for CAC scores of 0-10, 11-100, 101-400, and ≥401, respectively (p<0.0001). Increasing CAC scores were associated with an increase in incidence of admission for HF, with a hazard ratio of 10.371 for CAC scores ≥401 (95% CI: 1.062-101.309, p=0.0443) compared with CAC scores of 0-10 after adjustment for risk factors.. Severe CAC is an independent determinant of high NT-proBNP levels and a predictor of admission for HF in a population without a history of CAD or HF.

Topics: Aged; Aged, 80 and over; Calcinosis; Coronary Artery Disease; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Proportional Hazards Models; Risk Factors; Severity of Illness Index; Tomography, X-Ray Computed

We investigated the relationship of the Syntax Score (SS) and coronary artery calcification (CAC), with plasma levels of biomarkers related to cardiovascular damage and mineral metabolism, as there is sparse information in this field.. We studied 270 patients with coronary disease that had an acute coronary syndrome (ACS) six months before. Calcidiol, fibroblast growth factor-23, parathormone, phosphate and monocyte chemoattractant protein-1 [MCP-1], high-sensitivity C-reactive protein, galectin-3, and N-terminal pro-brain natriuretic peptide [NT-proBNP] levels, among other biomarkers, were determined. CAC was assessed by coronary angiogram as low-grade (0-1) and high-grade (2-3) calcification, measured with a semiquantitative scale ranging from 0 (none) to 3 (severe). For the SS study patients were divided in SS<14 and SS≥14. Multivariate linear and logistic regression analyses were performed.. MCP-1 predicted independently the SS (RC = 1.73 [95%CI = 0.08-3.39]; p = 0.040), along with NT-proBNP (RC = 0.17 [95%CI = 0.05-0.28]; p = 0.004), male sex (RC = 4.15 [95%CI = 1.47-6.83]; p = 0.003), age (RC = 0.13 [95%CI = 0.02-0.24]; p = 0.020), hypertension (RC = 3.64, [95%CI = 0.77-6.50]; p = 0.013), hyperlipidemia (RC = 2.78, [95%CI = 0.28-5.29]; p = 0.030), and statins (RC = 6.12 [95%CI = 1.28-10.96]; p = 0.013). Low calcidiol predicted high-grade calcification independently (OR = 0.57 [95% CI = 0.36-0.90]; p = 0.013) along with ST-elevation myocardial infarction (OR = 0.38 [95%CI = 0.19-0.78]; p = 0.006), diabetes (OR = 2.35 [95%CI = 1.11-4.98]; p = 0.028) and age (OR = 1.37 [95%CI = 1.18-1.59]; p<0.001). During follow-up (1.79 [0.94-2.86] years), 27 patients developed ACS, stroke, or transient ischemic attack. A combined score using SS and CAC predicted independently the development of the outcome.. MCP-1 and NT-proBNP are independent predictors of SS, while low calcidiol plasma levels are associated with CAC. More studies are needed to confirm these data.

Topics: Aged; Biomarkers; Calcifediol; Calcinosis; Chemokine CCL2; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Vascular Calcification

Several biomarkers including B-type natriuretic peptide (BNP) have been suggested to improve prediction of coronary events and all-cause mortality. Moreover, coronary artery calcium (CAC) as marker of subclinical atherosclerosis is a strong predictor for cardiovascular mortality and morbidity. We aimed to evaluate the predictive ability of BNP and CAC for all-cause mortality and coronary events above traditional cardiovascular risk factors (TRF) in the general population.. We followed 3782 participants of the population-based Heinz Nixdorf Recall cohort study without coronary artery disease at baseline for 7.3 ± 1.3 years. Associations of BNP and CAC with incident coronary events and all-cause mortality were assessed using Cox regression, Harrell's c, and time-dependent integrated discrimination improvement (IDI(t), increase in explained variance).. Subjects with high BNP levels had increased frequency of coronary events and death (coronary events/mortality: 14.1/28.2% for BNP ≥100 pg/ml vs. 2.7/5.5% for BNP < 100 pg/ml, respectively). Subjects with a BNP ≥100 pg/ml had increased incidence of hard endpoints sustaining adjustment for CAC and TRF (for coronary events: hazard ratio (HR) (95% confidence interval (CI)) 3.41(1.78-6.53); for all-cause mortality: HR 3.35(2.15-5.23)). Adding BNP to TRF and CAC increased measures of predictive ability: coronary events (Harrell's c, for coronary events, 0.775-0.784, p = 0.09; for all-cause mortality 0.733-0.740, p = 0.04; and IDI(t) (95% CI), for coronary events: 2.79% (0.33-5.65%) and for all-cause mortality 1.78% (0.73-3.10%).. Elevated levels of BNP are associated with excess incident coronary events and all-cause mortality rates, with BNP and CAC significantly and complementary improving prediction of risk in the general population above TRF.

Topics: Aged; Biomarkers; Calcinosis; Cause of Death; Coronary Angiography; Coronary Artery Disease; Female; Follow-Up Studies; Germany; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Population Surveillance; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Tomography, X-Ray Computed

B-type natriuretric peptide (BNP) is a marker of cardiac dysfunction that is released from myocytes in response to ventricular wall stress. Previous studies suggested that BNP predicts stroke events in addition to classical risk factors. It was suggested that the BNP-associated risk results from coronary atherosclerosis or atrial fibrillation.. Three thousand six hundred and seventy five subjects from the population-based Heinz Nixdorf Recall study (45-75 years; 47.6% men) without previous stroke, coronary heart disease, myocardial infarcts, open cardiac valve surgery, pacemakers and defibrillators were followed up over 110.1 ± 23.1 months. Cox proportional hazards regressions were used to examine BNP as a stroke predictor in addition to vascular risk factors (age, gender, systolic blood pressure, low-density lipoprotein, high-density lipoprotein, diabetes, smoking), renal insufficiency, atrial fibrillation/known heart failure and coronary artery calcification.. Eighty-nine incident strokes occurred (80 ischaemic, 9 hemorrhagic). Subjects suffering stroke had significantly higher BNP values at baseline than the remaining subjects [26.3 (Q1; Q3 = 12.9; 51.0) vs. 17.4 (9.4; 31.4); P < 0.001]. In a multivariable regression, log10 BNP was an independent stroke predictor [hazard ratio 1.96, 95% confidence interval (CI) 1.13-3.41; P = 0.017] in addition to age (1.24 per 5 years, CI 1.04-1.49; P = 0.016), systolic blood pressure (1.25 per 10 mmHg, CI 1.14-1.38; P < 0.001), smoking (2.05, CI 1.24-3.39; P = 0.005), atrial fibrillation/heart failure (2.25, CI 1.05-4.83; P = 0.037) and computed-tomography-based log10 (coronary artery calcification + 1) (1.47, CI 1.15-1.88; P = 0.002). Log10 BNP predicted stroke in men but not women, both in subjects ≤65 and >65 years. In subsequent analyses, BNP discriminated the incidence of cardioembolic stroke (P for trend = 0.001), but not stroke of macroangiopathic (P = 0.555), microangiopathic (P = 0.809) or unknown (P = 0.367) origin.. BNP predicts presumable cardioembolic stroke independent of coronary calcification.

Topics: Age Factors; Aged; Biomarkers; Calcinosis; Coronary Artery Disease; Female; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Factors; Sex Factors; Stroke

Aortic valve sclerosis (AVSc), the early asymptomatic stage of calcific aortic valve disease (CAVD), is characterized by a progressive thickening of the aortic cusps without obstruction of the left ventricular outflow. In spite of its high prevalence, there are no molecular markers to characterize the early stages of CAVD before it progresses to a severe, symptomatic stage of aortic valve stenosis (AVS). The study aim was to identify any correlation between circulating biomarkers and transesophageal echocardiography (TEE) evaluation.. A total of 330 patients with various degrees of CAVD was enrolled into the study. Blood was collected from each patient prior to surgery, and analyzed using ELISA kits following the manufacturers' instructions.. Significantly higher plasma osteopontin (OPN) levels were observed in AVSc patients (72.7 +/- 1.8 ng/ml; p < 0.001) and AVS patients (64.3 +/- 5.1 ng/ml; p < 0.001) when compared to controls (30.3 +/- 1.8 ng/ml). Parathyroid hormone (PTH) levels in AVSc and AVS patients (164.1 +/- 16.5 and 134.3 +/- 14.6 pg/ml; p < 0.001 and p = 0.04, respectively) were also significantly higher than in controls (61.8 +/- 4.92 pg/ml). Upon further analysis, plasma levels of OPN (p < 0.001) and PTH (p < 0.001) were found to be significantly higher in asymptomatic AVSc patients, even before calcium deposition was detected on TEE evaluation. Fetuin-A levels were lower at all stages of CAVD when compared to controls (p < 0.001 and p < or = 0.05, respectively), but were comparable among the patient groups. NT-proBNP levels were significantly higher in AVS patients than in controls (p < or = 0.01).. Serum levels of OPN, PTH, and fetuin-A showed a significant association with different stages of CAVD, with variations in their levels occurring before calcium nodules are visualized during TEE evaluation. The study results may help not only to provide a better understanding of the progression of CAVD but also to develop new tools that can be used to stage these patients.

Topics: Aged; Aged, 80 and over; alpha-2-HS-Glycoprotein; Aortic Valve; Aortic Valve Stenosis; Arginine; Biomarkers; Calcinosis; Case-Control Studies; Echocardiography, Transesophageal; Female; Humans; Male; Natriuretic Peptide, Brain; Osteopontin; Parathyroid Hormone; Peptide Fragments; Sclerosis; Severity of Illness Index

Coronary artery disease (CAD) is the major cause of morbidity and mortality in type 2 diabetic patients. Severe vitamin D deficiency has been shown to predict cardiovascular mortality in type 2 diabetic patients.. We investigated the association among severe vitamin D deficiency, coronary calcium score (CCS), and asymptomatic CAD in type 2 diabetic patients with elevated urinary albumin excretion rate (UAER) >30 mg/24 h. This was a cross-sectional study including 200 type 2 diabetic patients without a history of CAD. Severe vitamin D deficiency was defined as plasma 25-hydroxyvitamin D (p-25[OH]D3) <12.5 nmol/L. Patients with plasma N-terminal pro-brain natriuretic peptide >45.2 ng/L or CCS ≥400 were stratified as being high risk for CAD (n= 133). High-risk patients were examined by myocardial perfusion imaging (MPI; n = 109), computed tomography angiography (n = 20), or coronary angiography (CAG; n = 86). Patients' p-25(OH)D3 levels were determined by high-performance liquid chromatography/tandem mass spectrometry.. The median (range) vitamin D level was 36.9 (3.8-118.6) nmol/L. The prevalence of severe vitamin D deficiency was 9.5% (19/200). MPI or CAG demonstrated significant CAD in 70 patients (35%). The prevalence of CCS ≥400 was 34% (68/200). Severe vitamin D deficiency was associated with CCS ≥400 (odds ratio [OR] 4.3, 95% CI [1.5-12.1], P = 0.005). This association persisted after adjusting for risk factors (4.6, 1.5-13.9, P = 0.007). Furthermore, severe vitamin D deficiency was associated with asymptomatic CAD (adjusted OR 2.9, 1.02-7.66, P = 0.047).. In high-risk type 2 diabetic patients with elevated UAER, low levels of vitamin D are associated with asymptomatic CAD.

Topics: Adult; Aged; Albuminuria; Calcifediol; Calcinosis; Coronary Artery Disease; Cross-Sectional Studies; Denmark; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Vitamin D Deficiency

The N-terminal prohormone B-type natriuretic peptide (NT-proBNP) is a reliable marker of cardiac strain. In hypertensive heart disease, NT-proBNP levels increase and may lose its protective function. Simultaneously, the vasculature is also subject to hemodynamic stress, resulting in vascular matrix remodeling and stiffening which contribute to further cardiac alterations. Alkaline phosphatase (ALP) is a marker of osteoblast activity and is involved in vascular calcification. We explored the link between NT-proBNP and ALP in Black and Caucasian African men.. This study included 128 Black (mean age, 41.1 years) and 118 Caucasian (mean age, 36.4 years) men. Conventional measurements were acquired along with serum NT-proBNP and ALP.. NT-proBNP correlated positively with ALP (r=0.29; p<0.001) in Black Africans, but inversely in Caucasians (r=-0.20; p=0.024). After minimal adjustment (age, body mass index, systolic blood pressure and arterial compliance), the positive significant correlation of NT-proBNP with ALP remained in Black men (r=0.225; p=0.014), whereas significance was lost in Caucasian men. Multiple regression analyses confirmed the independent association of NT-proBNP with ALP in Black men (R2=0.37; beta=0.248; p=0.005), as well as in younger Black men (R2=0.26; beta=0.375; p<0.001; n=96), with no significance in Caucasians.. NT-proBNP is independently and positively associated with ALP in Black African men. This was however not evident in Caucasian men. These results suggest that African men are susceptible to potential early vascular calcification and may develop increased cardiac afterload prematurely.

Topics: Adult; Alkaline Phosphatase; Biomarkers; Black People; Blood Vessels; Calcinosis; Cross-Sectional Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; South Africa; Vascular Stiffness; White People

To determine whether serum levels of N-terminal (NT) pro-B-type natriuretic peptide (pro-BNP) are higher in patients with poorly compressible arteries (PCA) than in patients with peripheral artery disease (PAD) and control subjects without PCA or PAD.. Medial arterial calcification in the lower extremities results in PCA and may be associated with increased arterial stiffness and hemodynamic/myocardial stress. PCA was defined as having an ankle-brachial index >1.4 or an ankle blood pressure >255 mm Hg, whereas PAD was defined as having an ankle-brachial index ≤0.9. Study participants with PCA (n=100; aged 71±10 years; 70% men) and age- and sex-matched patients with PAD (n=300) were recruited from the noninvasive vascular laboratory. Age- and sex-matched controls (n=300) were identified from a community-based cohort and had no history of PAD. NT pro-BNP levels were approximately 2.5-fold higher in patients with PCA than in patients with PAD and approximately 4-fold higher than in age- and sex-matched controls. In multivariable regression analyses that adjusted for age, sex, smoking, hypertension, history of coronary heart disease/stroke, systolic blood pressure, and serum creatinine, NT pro-BNP levels remained significantly higher in patients with PCA than in patients with PAD and controls (P<0.001).. Patients with medial arterial calcification and PCA have higher serum levels of NT pro-BNP than patients with PAD and controls, which is suggestive of an adverse hemodynamic milieu and increased risk for adverse cardiovascular outcomes.

Topics: Aged; Aged, 80 and over; Ankle Brachial Index; Arteries; Biomarkers; Blood Pressure; Calcinosis; Case-Control Studies; Cross-Sectional Studies; Elasticity; Female; Humans; Linear Models; Lower Extremity; Male; Middle Aged; Minnesota; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Risk Assessment; Risk Factors; Ultrasonography, Doppler, Duplex; Up-Regulation

The main causes of congestive heart failure (CHF) are coronary artery disease (CAD) and arterial hypertension. Coronary artery calcification (CAC) evidencing coronary atherosclerosis may occur prior to clinical CAD. The aim of our study was to assess the association between CAC as a sign of subclinical CAD and CHF in a general unselected population.. Participants of the Heinz Nixdorf Recall Study without known CAD but with known CHF as defined by a physicians' diagnosis of CHF and dyspnea were identified. B-natriuretic peptide was measured and an exercise stress test was performed as possible. Cardiovascular risk factors and the EBCT-based CAC Agatston score were determined.. Those 105/4,230 subjects (2.5%) with CHF (age 65 +/- 7 years, 44% males), had higher brain natriuretic peptide (BNP) levels (median BNP 36.8 [16.5-70.1] vs. 17.6 [9.5-31.7] pg/ml, p<0.01) and lower exercise capacity (108.7 +/- 39.4 vs. 130.0 +/- 40.7 W, p<0.01) than those without. CAC in subjects with CHF was significantly higher than in those without (median CAC 64.7 [8.5-312.3] vs. 11.6 [0-109.8], p<0.01). In univariate analysis, CAC-burden after logarithmic transformation according to log(2)(CAC + 1) showed a significant association with the presence of CHF (odds ratio (OR) (95% CI): 1.16 (1.1-1.23), p<0.0001). Adjustment for age and sex (OR 1.11 (1.04-1.18), p<0.001), additional Framingham risk score (OR 1.09 (1.02-1.16), p = 0.015), and additional cardiovascular medication (OR 1.07 (0.998-1.14), p = 0.058) attenuated this association. Age, systolic blood pressure, antihypertensive medication and increased body mass index also remained significantly associated with presence of CHF in the full multivariate model.. The observed association between CAC and CHF in persons without clinically overt CAD is partly determined by risk factors that are involved in the natural history of both CAC and CHF. Whether CAC has a role to identify subjects at risk of future CHF remains to be determined using follow-up analyses.

Topics: Aged; Calcinosis; Calcium; Cohort Studies; Coronary Artery Disease; Coronary Vessels; Exercise Test; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prospective Studies; Risk Factors

Arterial calcification is a risk factor for atherosclerosis. Calumenin (CALU), a protein regulating proteins involved in coagulation and arterial calcification also has extracellular functions related to atherosclerosis. We recently described that CALU polymorphism A29809G was related to acenocoumarol requirements, and we wanted to evaluate its role in arterial calcification and prognosis.. A total of 374 consecutive patients with non-ST-elevation acute coronary syndrome (nSTACS). In 175 of them, who underwent percutaneous coronary intervention, we assessed calcification in each main coronary artery. Follow-up at 1 and 6 months was performed for adverse end-points.. CALU 29809G carriers were more frequent in the low calcium group (P = 0.037). The presence of >or=3 cardiovascular risk factors and CALU polymorphism were associated with arterial calcification (OR 2.34, P = 0.049; and OR 0.34, P = 0.019, respectively). CALU 29809G allele was the only variable associated with events at 1 month (HR 0.42; P = 0.042). Multivariate analysis showed that, at 6 months, age and severe anginal symptoms were associated with worse prognosis (HR 2.13, P = 0.023; and HR 2.01, P = 0.011, respectively), whereas CALU 29809G allele associated with good prognosis (HR 0.59, P = 0.044). Our results suggest that CALU A29809G is associated with arterial calcification and short-term prognosis of the outcome of patients with nSTACS.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Biomarkers; Calcinosis; Calcium-Binding Proteins; Coronary Artery Disease; Female; Genotype; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Polymorphism, Single Nucleotide; Prognosis; Prospective Studies

Decreased vitamin D serum levels have been recently related to arterial stiffening and vascular calcifications in haemodialysis (HD) patients, but the pathophysiology of this association is not yet clear. The aim of this study was to evaluate the relationship between vascular calcifications, cardiovascular risk factors [including brain natriuretic peptide (BNP), pulse pressure (PP) and left ventricular mass index] and 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D3] serum levels.. We performed a cross-sectional study with 223 prevalent HD patients, 48% females, 27% diabetics, with the mean age of 62.7 +/- 15.3 years and the mean HD time of 42.9 +/- 39.3 months. Forty-seven percent of the patients were taking active forms of vitamin D.. Serum levels of [25(OH)D3] were low (21.6 +/- 12.2 ng/mL) and negatively correlated with age (r = -0.31, P < 0.001), diabetes mellitus (DM) (r = -0.20, P = 0.004), C-reactive protein (r = -0.25, P < 0.001), log(10) BNP (r = -0.22, P = 0.002), PP > 65 mmHg (r = -0.21, P = 0.003) and vascular calcifications (r = -0.26, P < 0.001). Levels of [25(OH)D3] were positively correlated with [1,25(OH)(2)D3] (r = 0.25, P < 0.001) and albumin (r = 0.23, P = 0.001). On multivariate analysis, levels of [25(OH)D3] were independently associated with DM (P < 0.001), lower albumin levels (P = 0.003), higher BNP values (P = 0.005), PP > 65 mmHg (P = 0.006) and a higher vascular calcification score (>or= 3) (P = 0.002).. These results suggest that lower levels of [25(OH)D3] are a cardiovascular risk marker in HD patients, since they are strongly associated with higher BNP levels, increased PP and with the presence of vascular calcifications. The exact role of [25(OH)D3] deficiency on cardiovascular morbi-mortality needs to be clarified in large randomized controlled trials.

Topics: Aged; Calcifediol; Calcinosis; Calcitriol; Cardiovascular Diseases; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; Risk Factors; Vascular Diseases; Vitamin D Deficiency

Fibroblast growth factor 23 (FGF-23) is a phosphorus-regulating hormone. In chronic kidney disease (CKD), circulating FGF-23 levels are markedly elevated and independently associated with mortality. Left ventricular hypertrophy and coronary artery calcification are potent risk factors for mortality in CKD, and FGFs have been implicated in the pathogenesis of both myocardial hypertrophy and atherosclerosis. We conducted a cross-sectional study to test the hypothesis that elevated FGF-23 concentrations are associated with left ventricular hypertrophy and coronary artery calcification in patients with CKD.. In this study, 162 subjects with CKD underwent echocardiograms and computed tomography scans to assess left ventricular mass index and coronary artery calcification; echocardiograms also were obtained in 58 subjects without CKD. In multivariable-adjusted regression analyses in the overall sample, increased log FGF-23 concentrations were independently associated with increased left ventricular mass index (5% increase per 1-SD increase in log FGF-23; P=0.01) and risk of left ventricular hypertrophy (odds ratio per 1-SD increase in log FGF-23, 2.1; 95% confidence interval, 1.03 to 4.2). These associations strengthened in analyses restricted to the CKD subjects (11% increase in left ventricular mass index per 1-SD increase in log FGF-23; P=0.01; odds ratio of left ventricular hypertrophy per 1-SD increase in log FGF-23, 2.3; 95% confidence interval, 1.2 to 4.2). Although the highest tertile of FGF-23 was associated with a 2.4-fold increased risk of coronary artery calcification > or =100 versus <100 U compared with the lowest tertile (95% confidence interval, 1.1 to 5.5), the association was no longer significant after multivariable adjustment.. FGF-23 is independently associated with left ventricular mass index and left ventricular hypertrophy in patients with CKD. Whether increased FGF-23 is a marker or a potential mechanism of myocardial hypertrophy in CKD requires further study.

Topics: Aged; C-Reactive Protein; Calcinosis; Chronic Disease; Comorbidity; Coronary Occlusion; Cross-Sectional Studies; Diabetes Mellitus; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glomerular Filtration Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Phosphates; Radiography; Single-Blind Method; Ultrasonography; Vitamin D

The N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a sensitive indicator of hemodynamic stress and its increased level is associated with higher mortality in acute coronary syndrome (ACS) patients. Virtual histology-intravascular ultrasound (VH-IVUS) can provide quantitative information on plaque components.. We measured preprocedural serum NT-pro-BNP levels in 156 ACS patients with preserved left ventricular systolic function and normal serum creatinine. VH-IVUS classified the color-coded tissue into four major components: fibrotic, fibro-fatty, dense calcium, and necrotic core (NC). Thin-cap fibroatheroma (TCFA) was defined as focal, NC-rich (>or=10% of the cross-sectional area) plaques being in contact with the lumen in a plaque burden of at least 40%. We divided the patients into two groups according to the NT-pro-BNP levels [group I: >or=200 pg/ml (n = 58) vs. group II: <200 pg/ml (n = 98)].. The percent areas of NC at the minimum lumen site (19.8+/-13.1% vs. 15.2+/-11.1%, P = 0.027) and at the largest NC site (24.7+/-10.3% vs. 19.2+/-11.4%, P = 0.015) were significantly greater in group I than in group II. Percent NC volume was significantly greater in group I than in group II (15.8+/-8.1% vs. 10.1+/-9.1%, P = 0.008). The total number of TCFAs was 38 in group I and 56 in group II. The presence of at least one TCFA (58 vs. 38%, P = 0.009) and multiple TCFAs (25 vs. 10%, P = 0.005) within culprit lesions were observed more frequently in group I than in group II. The TCFAs were located more in proximal in group I than in group II [the length from coronary ostium to TCFA: 10.8+/-7.6 mm in group I vs. 25.7+/-16.3 mm in group II (P<0.001)]: 85% of TCFAs was located within 20 mm from coronary ostium in group I; conversely only 36% of TCFAs was located within 20 mm from coronary ostium in group II (P<0.001).. VH-IVUS analysis shows that ACS patients with high NT-pro-BNP levels had more vulnerable plaque component (more NC-containing lesions and higher frequency of culprit lesion TCFAs) and had more proximally located TCFAs.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Biomarkers; Calcinosis; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Creatinine; Female; Fibrosis; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Necrosis; Peptide Fragments; Predictive Value of Tests; Retrospective Studies; Ultrasonography, Interventional; Up-Regulation; Ventricular Function, Left

B-type natriuretic peptide (BNP) has prognostic implications in patients with acute and chronic cardiac symptoms. Its prognostic role in asymptomatic patients with evidence of subclinical disease remains unclear. The population of this study included 2,458 asymptomatic adults (47% women) with an average Framingham risk score of 8.8 +/- 7% who underwent computed tomographic evaluation of coronary artery calcium (CAC). BNP levels were measured using the Triage CardioProfilER panel method. Cox proportional-hazards models were used to estimate time to a cardiovascular (CV) event (n = 84; 16 deaths, 12 myocardial infarctions, 8 cerebrovascular accidents or transient ischemic attacks, and 48 diagnoses of incident symptomatic coronary disease). Relative risk was calculated. The median follow-up time was 3.9 years (25th and 75th percentiles 2.9 and 4.0). The relative hazard for a CV event ranged from 2.2 to 7.5 for BNP values of 40 to 99.9 and > or =100 pg/ml (p <0.0001) compared to BNP <40 pg/ml. Similarly, CAC score was also highly predictive of CV events, with elevated hazard ratios of 2.8- to 48.7-fold for scores of 11 to 100 to > or =1,000 (p <0.0001) compared to no CAC. In a stepwise model, BNP was the second greatest estimator of CV outcomes (p = 0.016) after CAC (p <0.0001), even in models that included blood pressure and age. Hypertension, age > or =65 years, and CAC contained 28.4%, 40.7%, and 56.8%, respectively, of BNP risk. The combination of BNP > or =100 pg/ml and CAC score > or =400 identified 52.4% and 35.7% of CV events in patients with hypertension and in elderly patients beyond the Framingham risk score. In conclusion, BNP and CAC are independently predictive of CV events.

Topics: Age Factors; Aged; Biomarkers; C-Reactive Protein; Calcinosis; Coronary Angiography; Coronary Artery Disease; Coronary Disease; Female; Follow-Up Studies; Humans; Hyperlipidemias; Hypertension; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Prospective Studies; Registries; Risk Assessment; Stroke; Tomography, X-Ray Computed

Cardiovascular mortality is increased in systemic lupus erythematosus (SLE). Increased plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with cardiovascular morbidity and mortality in the general population. We examined the hypothesis that NT-proBNP concentrations are higher in patients with SLE, and are related to inflammation, augmentation index, coronary atherosclerosis, and cardiovascular risk factors.. Serum concentrations of NT-proBNP were measured in 113 patients with SLE and in 80 control subjects. Coronary calcification and augmentation index were measured by electron beam computed tomography and noninvasive pulse wave analysis, respectively.. Patients with SLE had higher concentrations of NT-proBNP [median 38.6 (interquartile range 2.5-126.9) pg/ml] than controls [11.7 (1.6-47.9) pg/ml] (p = 0.002). Augmentation index was higher in patients with SLE [25.0% (20.5%-31.5%)] than controls [20.5% (12.0%-29.0%)] (p = 0.04). In patients with SLE, NT-proBNP concentrations were associated with disease damage (rho = 0.31, p < 0.001) and duration (rho = 0.21, p = 0.02) but not with disease activity, C-reactive protein, erythrocyte sedimentation rate, tumor necrosis factor-alpha, interleukin 6, coronary calcium score, or augmentation index (all p > or = 0.18).. Patients with SLE have increased concentrations of NT-proBNP, but this is not explained by atherosclerotic burden, augmentation index, or inflammatory state.

Topics: Calcinosis; Case-Control Studies; Colonography, Computed Tomographic; Coronary Artery Disease; Elasticity; Female; Humans; Lupus Erythematosus, Systemic; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pulsatile Flow

Increased concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with cardiovascular morbidity and mortality, but little is known about their relationship to chronic inflammation. Patients with rheumatoid arthritis (RA) have chronic inflammation, increased arterial stiffness, and accelerated coronary atherosclerosis. This study was undertaken to test the hypothesis that NT-proBNP concentrations are elevated in patients with RA and are associated with coronary artery calcification and markers of inflammation.. In 159 patients with RA (90 with early RA and 69 with longstanding RA) without heart failure and 88 control subjects, serum concentrations of NT-proBNP, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFalpha) were measured and coronary calcification was assessed. Associations between NT-proBNP levels and the other parameters were investigated.. NT-proBNP concentrations were elevated in patients with longstanding RA (median 142.8 pg/ml [interquartile range 54.8-270.5]) and those with early RA (median 58.1 pg/ml [interquartile range 19.4-157.6]) compared with controls (18.1 [3.2-46.0]) (P < 0.001). In patients with RA, NT-proBNP concentrations were associated with age (rho = 0.35, P < 0.001), levels of IL-6 (rho = 0.33, P < 0.001), TNFalpha (rho = 0.23, P = 0.003), and C-reactive protein (CRP) (rho = 0.21, P = 0.01), coronary calcium score (rho = 0.30, P < 0.001), systolic blood pressure (rho = 0.30, P < 0.001), and disease activity (rho = 0.29, P < 0.001). After adjustment for age, race, and sex, the associations between NT-proBNP concentrations and disease activity, TNFalpha, IL-6, and CRP remained significant, but those with systolic blood pressure and coronary calcium score were attenuated.. NT-proBNP concentrations are increased in patients with RA without clinical heart failure and may indicate subclinical cardiovascular disease and a chronic inflammatory state.

Topics: Adult; Age Factors; Aged; Arthritis, Rheumatoid; Biomarkers; Blood Pressure; C-Reactive Protein; Calcinosis; Coronary Artery Disease; Female; Humans; Inflammation; Interleukin-1; Lipids; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Regression Analysis; Severity of Illness Index; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

Topics: Animals; Aortic Valve; Aortic Valve Stenosis; Calcinosis; Clinical Trials as Topic; Disease Models, Animal; Echocardiography; Female; Follow-Up Studies; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Time Factors; Tomography, X-Ray Computed

While there is generell agreement that patients with aortic stenosis (AS) who have already developed symptoms, such as exertional dyspnea, angina or dizziness and syncope, require urgent surgery because of their otherwise very poor outcome, the management of asymptomatic severe AS remains controversial. Although prevention of sudden death, prevention of irreversible myocardial damage, lower operative risk and a possible short duration of the asymptomatic phase of the disease have been proposed as arguments for early elective surgery, currently available data do not support that the risk of surgery and prosthesis-related long-term complications can generally be outweighed by a potential benefit. Thus, surgery cannot be recommended for all asymptomatic patients. Since patients often do not report their symptoms immediately and waiting lists for surgery exist in some countries, risk stratification with selection of those patients who are likely to develop symptoms and require surgery within a short time period seems to be the ideal approach. The most important predictors of outcome are the degree of valvular calcification, the hemodynamic progression rate, the development of symptoms during exercise testing, and plasma levels of cardiac neurohomones.

Topics: Age Factors; Aged; Aortic Valve Stenosis; Calcinosis; Clinical Trials as Topic; Death, Sudden, Cardiac; Disease Progression; Echocardiography; Exercise; Exercise Test; Follow-Up Studies; Humans; Natriuretic Peptide, Brain; Patient Selection; Prognosis; Risk Assessment; Risk Factors; Time Factors