Serial Measurements of N-Terminal Pro-Brain Natriuretic Peptide in Patients with Coronary Heart Disease

Objective

To assess the prognostic value of 12-months N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) levels on adverse cardiovascular events in patients with stable coronary heart disease.

Methods

NT-proBNP concentrations were measured at baseline and at 12-months follow-up in participants of cardiac rehabilitation (median follow-up 8.96 years). Cox-proportional hazards models evaluated the prognostic value of log-transformed NT-proBNP levels, and of 12-months NT-proBNP relative changes on adverse cardiovascular events adjusting for established risk factors measured at baseline.

Results

Among 798 participants (84.7% men, mean age 59 years) there were 114 adverse cardiovascular events. 12-months NT-proBNP levels were higher than baseline levels in 60 patients (7.5%) and numerically more strongly associated with the outcome in multivariable analysis (HR 1.65 [95% CI 1.33–2.05] vs. HR 1.41 [95% CI 1.12–1.78], with a net reclassification improvement (NRI) of 0.098 [95% CI 0.002–0.194] compared to NRI of 0.047 [95% CI −0.0004–0.133] for baseline NT-proBNP levels. A 12-month 10% increment of NT-proBNP was associated with a HR of 1.35 [95% CI 1.12–1.63] for the onset of an adverse cardiovascular event. Subjects with a 12-month increment of NT-proBNP had a HR of 2.56 [95% CI 1.10–5.95] compared to those with the highest 12-months reduction.

Conclusions

Twelve-months NT-proBNP levels after an acute cardiovascular event are strongly associated with a subsequent event and may provide numerically better reclassification of patients at risk for an adverse cardiovascular event compared to NT-proBNP baseline levels after adjustment for established risk factors.     

N-Terminal Pro-Brain Natriuretic Peptide Is a Useful Prognostic Marker in Patients with Pre-Capillary Pulmonary Hypertension and Renal Insufficiency

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a routinely used prognostic parameter in patients with pre-capillary pulmonary hypertension (PH). As it accumulates in the presence of impaired renal function, the clinical utility of NT-proBNP in PH patients with concomitant renal insufficiency remains unclear. In a retrospective approach, patients with pre-capillary PH (group I or IV) and concomitant renal insufficiency at time of right heart catheterization (glomerular filtration rate (GFR) ≤60 ml/min/1.73 m²) were identified out of all prevalent pre-capillary PH patients treated at a single center. Forty patients with renal insufficiency (25.8%) were identified and matched regarding hemodynamic parameters with a control group of 56 PH patients with normal renal function (GFR >60 ml/min/1.73 m²). Correlations of NT-proBNP levels with hemodynamic and prognostic parameters (time to clinical worsening and overall survival) were assessed. Overall, GFR correlated inversely with NT-proBNP and had the strongest influence on NT-proBNP levels in a stepwise multiple linear regression model including hemodynamic parameters and age (r² = 0.167). PH patients with renal insufficiency had significant higher levels of NT-proBNP (median: 1935 ng/l vs. 573 ng/l, p = 0.001). Nevertheless, NT-proBNP correlated with invasive hemodynamic parameters in these patients. Using higher cut-off values than in patients with preserved renal function, NT-proBNP levels were significantly associated with time to clinical worsening (>1660 ng/l, p = 0.001) and survival (>2212 ng/l, p = 0.047) in patients with renal insufficiency. Multivariate Cox’s proportional hazards analysis including established prognostic parameters, age and GFR confirmed NT-proBNP as an independent risk factor for clinical worsening in PH patients with renal insufficiency (hazard ratio 4.8, p = 0.007). Thus, in a retrospective analysis we showed that NT-proBNP levels correlated with hemodynamic parameters and outcome regardless of renal function. By using higher cut-off values, NT-proBNP seems to represent a valid clinical marker even in PH patients with renal insufficiency.     

Association of N-Terminal Pro-Brain Natriuretic Peptide with Cognitive Function and Depression in Elderly People with Type 2 Diabetes

Background

Type 2 diabetes mellitus is associated with risk of congestive heart failure (CHF), cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS).

Methodology and Principal Findings

Cross-sectional analysis of 1066 men and women aged 60–75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, ‘g’. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS) assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower ‘g’ and higher depression scores (ß −0.09, 95% CI −0.13 to −0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p<0.001, respectively). Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of ‘g’) and ‘possible’ depression (HADS depression ≥8) (OR 1.80; 95% CI: 1.20, 2.70; p = 0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (β −0.02, 95% CI −0.07 to 0.03, p>0.05 for ‘g’; β 0.03, 95% CI −0.02 to 0.07, p>0.05 for depression scores).

Conclusion

Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.     

Pericardial Fat Is Associated with Coronary Artery Calcification in Non-Dialysis Dependent Chronic Kidney Disease Patients

Pericardial fat (PF) a component of visceral adipose tissue has been consistently related to coronary atherosclerosis in the general population. This study evaluated the association between PF and coronary artery calcification (CAC) in non-dialysis dependent chronic kidney disease (CKD) patients. This is a post-hoc cross sectional analysis of the baseline of a prospective cohort of 117 outward CKD patients without manifest coronary artery disease (age, 56.9±11.0 years, 64.1% males, 95.1% hypertensives, 25.2% diabetics, 15.5% ever smokers, CKD stage 2 to 5 with estimated glomerular filtration rate 36.8±18.1 ml/min). CAC scores, PF volume and abdominal visceral fat (AVF) areas were measured by computed tomography. The association of PF as a continuous variable with the presence of CAC was analyzed by multivariate logistic regression. CAC (calcium score >0) was present in 59.2% patients. Those presenting CAC were on average 10 years older, had a higher proportion of male gender (78.7% vs. 42.9%, p<0.001), and had higher values of waist circumference (95.9±10.7 vs. 90.2±13.2 cm, p = 0.02), PF volumes (224.8±107.6 vs. 139.1±85.0 cm³, p<0.01) and AVF areas (109.2±81.5 vs. 70.2±62.9 cm², p = 0.01). In the multivariate analysis, adjusting for age, gender, diabetes, smoking and, left ventricular concentric hypertrophy, PF was significantly associated with the presence of CAC (OR: 1.88 95% CI: 1.03–3.43 per standard deviation). PF remained associated with CAC even with additional adjustments for estimated glomerular filtration rate or serum phosphorus (OR: 1.85 95% CI: 1.00–3.42, p = 0.05). PF is independently associated with CAC in non-dialysis dependent CKD patients.     

血清网膜素-1 与绝经后女性冠心病的相关性

目的：网膜素是最近发现的脂肪因子,肥胖或2 型糖尿病（diabetes mellitus, DM）患者血清网膜素-1 较正常者明显降低。本 次研究主要为观察绝经后女性血清网膜素-1 水平与冠心病的相关性。方法：选取我院心内科住院有心绞痛症状,并行冠脉造影的 105 例绝经后女性患者。依据冠脉造影结果分为冠心病组(67 例)和对照组例（3）,常规收集临床资料,包括年龄、体重指数（body mass index, BMI）、吸烟史、高血压病史、糖尿病史及血液生化和血脂指标;酶联免疫吸附剂测定(enzyme linked immunosorbent assay, ELISA)法检测血清网膜素-1 浓度。结果：冠心病组血清网膜素-1 水平显著低于对照组（205.62± 73.31 vs 401.64± 146.79, P<0.001）。单因素logistic回归分析示吸烟、高血压病史、糖尿病史、高脂血症史、网膜素-1 水平降低是冠心病组的独立危险因素 (P<0.05)。多因素logistic 回归分析示血清网膜素-1 水平降低是冠心病组的独立危险因素(P<0.001)。结论：绝经后女性血清网膜素 -1 水平下降是冠心病的独立危险因素,可能可成为绝经后女性冠心病的预测指标。     

Neutrophil/Lymphocyte Ratio Is Associated with Non-Calcified Plaque Burden in Patients with Coronary Artery Disease

Background

Elevations in soluble markers of inflammation and changes in leukocyte subset distribution are frequently reported in patients with coronary artery disease (CAD). Lately, the neutrophil/lymphocyte ratio has emerged as a potential marker of both CAD severity and cardiovascular prognosis.

Objectives

The aim of the study was to investigate whether neutrophil/lymphocyte ratio and other immune-inflammatory markers were related to plaque burden, as assessed by coronary computed tomography angiography (CCTA), in patients with CAD.

Methods

Twenty patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and 30 patients with stable angina (SA) underwent CCTA at two occasions, immediately prior to coronary angiography and after three months. Atherosclerotic plaques were classified as calcified, mixed and non-calcified. Blood samples were drawn at both occasions. Leukocyte subsets were analyzed by white blood cell differential counts and flow cytometry. Levels of C-reactive protein (CRP) and interleukin(IL)-6 were measured in plasma. Blood analyses were also performed in 37 healthy controls.

Results

Plaque variables did not change over 3 months, total plaque burden being similar in NSTE-ACS and SA. However, non-calcified/total plaque ratio was higher in NSTE-ACS, 0.25(0.09–0.44) vs 0.11(0.00–0.25), p<0.05. At admission, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios, CD4+ T cells, CRP and IL-6 were significantly elevated, while levels of NK cells were reduced, in both patient groups as compared to controls. After 3 months, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios and CD4+ T cells remained elevated in patients. Neutrophil/lymphocyte ratios and neutrophil counts correlated significantly with numbers of non-calcified plaques and also with non-calcified/total plaque ratio (r = 0.403, p = 0.010 and r = 0.382, p = 0.024, respectively), but not with total plaque burden.

Conclusions

Among immune-inflammatory markers in NSTE-ACS and SA patients, neutrophil counts and neutrophil/lymphocyte ratios were significantly correlated with non-calcified plaques. Data suggest that these easily measured biomarkers reflect the burden of vulnerable plaques in CAD.     

Fractional Flow Reserve Is Not Associated with Inflammatory Markers in Patients with Stable Coronary Artery Disease

Background

Atherosclerosis is an inflammatory condition and increased blood levels of inflammatory biomarkers have been observed in acute coronary syndromes. In addition, high expression of inflammatory markers is associated with worse prognosis of coronary artery disease. The presence and extent of inducible ischemia in patients with stable angina has previously been shown to have strong prognostic value. We hypothesized that evidence of inducible myocardial ischemia by local lesions, as measured by fractional flow reserve (FFR), is associated with increased levels of blood based inflammatory biomarkers.

Methods

Whole blood samples of 89 patients with stable angina pectoris and 16 healthy controls were analyzed. The patients with stable angina pectoris underwent coronary angiography and FFR of all coronary lesions.We analyzed plasma levels of cytokines IL-6, IL-8 and TNF-α and membrane expression of Toll-like receptor 2 and 4, CD11b, CD62L and CD14 on monocytes and granulocytes as markers of inflammation.Furthermore, we quantified the severity of hemodynamically significant coronary artery disease by calculating Functional Syntax Score (FSS), an extension of the Syntax Score.

Results

For the majority of biomarkers, we observed lower levels in the healthy control group compared with patients with stable angina who underwent coronary catheterization.We found no difference for any of the selected biomarkers between patients with a positive FFR (≤0.75) and negative FFR (>0.80). We observed no relationship between the investigated biomarkers and FSS.

Conclusion

The presence of local atherosclerotic lesions that result in inducible myocardial ischemia as measured by FFR in patients with stable coronary artery disease is not associated with increased plasma levels of IL-6, IL-8 and TNF-α or increased expression of TLR2 and TLR4, CD11b, CD62L and CD14 on circulating leukocytes.     

血清网膜素-1与绝经后女性冠心病的相关性

目的：网膜素是最近发现的脂肪因子,肥胖或2型糖尿病（diabetesmellitus,DM）患者血清网膜素-1较正常者明显降低。本次研究主要为观察绝经后女性血清网膜素-1水平与冠心病的相关性。方法：选取我院心内科住院有心绞痛症状,并行冠脉造影的105例绝经后女性患者。依据冠脉造影结果分为冠心病组（67例）和对照组例（3）,常规收集临床资料,包括年龄、体重指数（bodvmassindex,BMI）、吸烟史、高血压病史、糖尿病史及血液生化和血脂指标;酶联免疫吸附剂测定（enzymelinkedimmunosorbentassay,ELISA）法检测血清网膜素-1浓度。结果：冠心痛组血清网膜素-1水平显著低于对照组（205．62±73．31vs401．64±146．79．P〈0．001）。单因素logistic回归分析示吸烟、高血压痛史、糖尿病史、高脂血症史、网膜素-1水平降低是冠心病组的独立危险因素（P〈0．05）。多因素logistic回归分析示血清网膜素-1水平降低是冠心病组的独立危险因素（P〈0．001）。结论：绝经后女性血清网膜素-1水平下降是冠心痛的独立危险因素,可能可成为绝经后女性冠心病的预测指标。     

The Biological Variation of N-Terminal Pro-Brain Natriuretic Peptide in Postmenopausal Women with Type 2 Diabetes: A Case Control Study

Background

The incidence of heart failure in type 2 diabetes is high and it has poorer prognosis when compared with patients without diabetes. Access to echocardiography is limited and alternative methods to identify early heart failure such as the measurement of natriuretic peptides levels have been proposed. However, their wide biological variation could limit their clinical utility. Our aim was to determine if the intrinsic biological variation of one of these peptides, N-terminal proBNP, is as wide in type 2 diabetes as it is in health and to calculate the critical difference values that could be utilised in clinical practice to ensure changes observed between two samples are due to intervention rather than to its biological variability.

Methodology/Principal Findings

12 postmenopausal women with diet controlled type 2 diabetes and without heart failure were compared with 11 control postmenopausal women without diabetes. N-terminal proBNP levels were measured on 10 occasions. The biological variation was calculated according to Fraser''s methods. The mean NT-proBNP level was similar in both groups (mean ± standard deviation; type 2 diabetes, 10.7 pmol/L± 8.5 versus 8.49±6.0 pmol/L, p = 0.42). The biological variation was also similarly wide. The critical difference in patients with type 2 diabetes was between −70% and ±236%.

Conclusions

Type 2 diabetes does not appear to significantly influence the marked biological variation of N-terminal proBNP in postmenopausal women. The critical difference values reported in this study could be used to titrate therapy or monitor response to interventions although the change required in between samples is wide and this might limit its utility.     

冠心病相关循环miRNA

冠心病诊断中最主要的挑战就是从常规的血液样本中鉴定出可靠的临床生物标志物.循环miRNA是一种可以稳定存在于体液中的小分子RNA,具有较高的组织、疾病特异性及敏感性,具有作为新的冠心病非侵入性生物标志物的潜力.通过综述血液样本（全血、血浆、血清、外周血单核细胞（PBMC）、内皮祖细胞（EPC）及血小板）中冠心病相关循环miRNA,及探讨循环miRNA研究中存在的一些问题,为未来筛选出真正具有临床应用价值的循环miRNA生物标志物奠定基础.     

Inverse Association of N-Terminal Pro-B-Type Natriuretic Peptide with Metabolic Syndrome in Patients with Congestive Heart Failure

Background

Metabolic syndrome has been shown to be associated with lower levels of plasma N-terminal pro-B-type natriuretic peptide (Nt-proBNP) in the general population. We sought to elucidate the relationship between Nt-proBNP and components of metabolic syndrome in patients with congestive heart failure (CHF).

Methods

Fasting blood samples were obtained from 93 patients in our institution. Plasma levels of Nt-proBNP and other biochemical data were measured. The New York Heart Association (NYHA) classification system (I-IV) was used to define the functional capacity of CHF. Metabolic syndrome and its components were defined using diagnostic criteria from the International Diabetes Federation.

Results

Forty-nine patients (52.7%) had CHF. There was a positive correlation between plasma Nt-proBNP levels and NYHA functional capacity in CHF patients. Plasma Nt-proBNP levels increased significantly with each increasing NYHA class of the disease. The prevalence of metabolic syndrome in CHF patients was higher than that in patients without CHF. Most importantly, we found that plasma Nt-proBNP levels were lower in CHF patients with metabolic syndrome attributable to inverse relationships between plasma Nt-proBNP and body mass index (β = −0.297), plasma triglyceride (β = −0.286) and homeostasis model assessment of insulin resistance (HOMA-IR; β = −0.346). Fasting glucose to insulin ratio (FGIR, an insulin sensitivity index) was positively associated with plasma Nt-proBNP levels (β = 0.491), and was the independent predictor of plasma Nt-proBNP levels in CHF patients.

Conclusions

Plasma Nt-proBNP levels are inversely associated with metabolic syndrome in CHF patients. Reduced plasma Nt-proBNP levels in CHF patients may lead to impaired lipolysis and metabolic function, and may contribute to the development of metabolic syndrome in CHF patients.     

High N-Terminal Pro-B-Type Natriuretic Peptide Levels Are Associated with Reduced Heart Rate Variability in Acute Myocardial Infarction

Aim

We investigated the relationships between the autonomic nervous system, as assessed by heart rate variability (HRV) and levels of N-terminal Pro-B-type Natriuretic Peptide (Nt-proBNP) in patients with acute myocardial infarction (MI).

Methods and Results

The mean of standard deviation of RR intervals (SDNN), the percentage of RR intervals with >50 ms variation (pNN50), square root of mean squared differences of successive RR intervals (rMSSD), and frequency domain parameters (total power (TP), high frequency and low frequency power ratio (LF/HF)) were assessed by 24 h Holter ECG monitoring. 1018 consecutive patients admitted <24 h for an acute MI were included. Plasma Nt-proBNP (Elecsys, Roche) was measured from blood samples taken on admission. The median (IQR) Nt-proBNP level was 681(159–2432) pmol/L. Patients with the highest quartile of Nt-proBNP were older, with higher rate of risk factors and lower ejection fraction. The highest Nt-proBNP quartile group had the lowest SDNN, LF/HF and total power but similar pNN50 and rMSSD levels. Nt-proBNP levels correlated negatively with SDNN (r = −0.19, p<0.001), LF/HF (r = −0.37, p<0.001), and LF (r = −0.29, p<0.001) but not HF (r = −0.043, p = 0.172). Multiple regression analysis showed that plasma propeptide levels remained predictive of LF/HF (B(SE) = −0.065(0.015), p<0.001)), even after adjustment for confounders.

Conclusions

In conclusion, our population-based study highlights the importance of Nt-proBNP levels to predict decreased HRV after acute MI.     

Anti-Cyclic Citrullinated Peptide Antibody Is Associated with Interstitial Lung Disease in Patients with Rheumatoid Arthritis

Objective

Patients with rheumatoid arthritis (RA) are at risk to develop RA-associated interstitial lung disease (RA-ILD). This retrospective study aimed to investigate the potential association of the positivity of serum anti-cyclic citrullinated peptide antibody (anti-CCP2) and rheumatoid factor (RF) with RA-ILD in RA patients.

Methods

A total of 285 RA patients were recruited at the inpatient service of Peking Union Medical College Hospital in China between 2004 and 2013. Individual patients were evaluated for the evidence of ILD. The concentrations of serum anti-CCP2 and RF in individual patients were measured. The potential risk factors for ILD in RA patients were assessed by univariate and multivariate models.

Results

There were 71 RA patients with RA-ILD, accounting for 24.9% in this population. The positive rates of anti-CCP2 and RF in the patients with RA-ILD were significantly higher than that in the patients with RA-only (88.7% vs. 67.3%, p<0.001; 84.5% vs. 70.6%, p = 0.02, respectively). Univariate and multivariate logistic regression analysis revealed that RA patients with positive serum anti-CCP2, but not RF, were associated with an increased risk of ILD (crude odds ratio [cOR] 3.83, 95% confidence interval [CI] 1.74–8.43, p<0.001; adjusted odds ratio [aOR] 3.50, 95% CI 1.52–8.04, p<0.001).

Conclusion

Our findings suggest that positive serum anti-CCP2, but not RF, may be associated with RA-ILD in RA patients.     

The IL-33-ST2L Pathway Is Associated with Coronary Artery Disease in a Chinese Han Population

The effects of interleukin-33 (IL-33) on the immune system have been clearly demonstrated; however, in cardiovascular diseases, especially in coronary artery disease (CAD), these effects have not yet been clarified. In this study, we investigate the genetic role of the IL-33-ST2L pathway in CAD. We performed three-stage case-control association analyses on a total of 4,521 individuals with CAD and 4,809 controls via tag SNPs in the genes encoding IL-33 and ST2L-IL-1RL1. One tag SNP in each gene was significantly associated with CAD (rs7025417^T in IL33, p_adj = 1.19 × 10⁻²⁸, OR = 1.39, 95% CI: 1.31–1.47; rs11685424^G in IL1RL1, p_adj = 6.93 × 10⁻³⁰, OR = 1.40, 95% CI: 1.32–1.48). Combining significant variants in two genes, the risk for CAD increased nearly 5-fold (p_adj = 8.90 × 10⁻²¹, OR = 4.98, 95% CI: 3.56–6.97). Traditional risk factors for CAD were adjusted for the association studies by SPSS with logistic regression analysis. With the two variants above, both located within the gene promoter regions, reporter gene analysis indicated that the rs7025417 C>T and rs11685424 A>G changes resulted in altered regulation of IL33 and IL1RL1 gene expression, respectively (p < 0.005). Further studies revealed that the rs7025417 genotype was significantly associated with plasma IL-33 levels in the detectable subjects (n = 227, R² = 0.276, p = 1.77 × 10⁻¹⁷): the level of IL-33 protein increased with the number of rs7025417 risk (T) alleles. Based on genetic evidence in humans, the IL-33-ST2L pathway appears to have a causal role in the development of CAD, highlighting this pathway as a valuable target for the prevention and treatment of CAD.     

Renal Artery Stenosis Predicts Coronary Artery Disease in Patients with Hypertension

In hypertensive patients with indication of renal arteriography to investigate renal artery stenosis (RAS) there are no recommendations regarding when to investigate coronary artery disease (CAD). Moreover, the predictors of CAD in patients with RAS are not clear. We aimed to evaluate the frequency and the determinants of CAD in hypertensive patients referred to renal angiography. Eighty-two consecutive patients with high clinical risk suggesting the presence of RAS systematically underwent renal angiography and coronary angiography during the same procedure. Significant arterial stenosis was defined by an obstruction≥70% to both renal and coronary territories. Significant CAD was present in 32/82 (39%) and significant RAS in 32/82 (39%) patients. Both CAD and RAS were present in 25.6% from the 82 patients. Patients with severe CAD were older (63±12 vs. 56±13 years; p = 0.03) and had more angina (41 vs. 16%; p = 0.013) compared to patients without severe CAD. Significant RAS was associated with an increased frequency of severe CAD compared to patients without significant RAS (66% vs. 22%, respectively; p<0.001). Myocardial scintigraphy showed ischemia in 21.8% of the patients with CAD. Binary logistic regression analysis showed that RAS≥70% was independently associated with CAD≥70% (OR: 11.48; 95% CI 3.2–40.2; p<0.001), even in patients without angina (OR: 13.48; 95%CI 2.6–12.1; p<0.001). Even considering a small number of patients with significant RAS, we conclude that in hypertensive patients referred to renal angiography, RAS≥70% may be a strong predictor of severe CAD, independently of angina, and dual investigation should be considered.     

Cautious Application of Pleural N-Terminal Pro-B-Type Natriuretic Peptide in Diagnosis of Congestive Heart Failure Pleural Effusions among Critically Ill Patients

Background and Objective

Several studies on diagnostic accuracy of pleural N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) for effusions from congestive heart failure (CHF) conclude that pleural NT-pro-BNP is a useful biomarker with high diagnostic accuracy for distinguishing CHF effusions. However, its applicability in critical care settings remains uncertain and requires further investigations.

Methods

NT-proBNP was measured in pleural fluid samples of a prospective cohort of intensive care unit patients with pleural effusions. Receiver operating characteristic curve analysis was performed to determine diagnostic accuracy of pleural NT-proBNP for prediction of CHF effusions.

Results

One hundred forty-seven critically ill patients were evaluated, 38 (26%) with CHF effusions and 109 (74%) with non-CHF effusions of various causes. Pleural NT-proBNP levels were significantly elevated in patients with CHF effusions. Pleural NT-pro-BNP demonstrated the area under the curve of 0.87 for diagnosing effusions due to CHF. With a cutoff of 2200 pg/mL, pleural NT-proBNP displayed high sensitivity (89%) but moderate specificity (73%). Notably, 29 (27%) of 109 patients with non-CHF effusions had pleural NT-proBNP levels >2200 pg/mL and these patients were more likely to experience septic shock (18/29 vs. 10/80, P<0.001) or acute kidney injury (19/29 vs. 9/80, P<0.001).

Conclusions

Among critically ill patients, pleural NT-proBNP measurements remain a useful diagnostic aid in evaluation of pleural effusions. However, patients with non-CHF effusions may exhibit high pleural NT-proBNP concentrations if they suffer from septic shock or acute kidney injury. Accordingly, it is suggested that clinical context should be taken into account when interpreting pleural NT-proBNP values in critical care settings.     

Coronary Collateral Circulation in Patients of Coronary Ectasia with Significant Coronary Artery Disease

Objectives

Patients with coronary ectasia (CE) usually have coexisting coronary stenosis resulting in myoischemia. Coronary collateral plays an important role in protecting myocardium from ischemia and reducing cardiovascular events. However, limited studies investigate the role of CE in coronary collaterals development.

Methods

We evaluated 1020 consecutive patients undergoing coronary angiography and 552 patients with significant coronary artery disease (SCAD), defined as diameter stenosis more than 70%, were finally analyzed. CE is defined as the ectatic diameter 1.5 times larger than adjacent reference segment. Rentrop collateral score was used to classify patients into poor (grades 0 and 1) or good (grades 2 and 3) collateral group.

Results

73 patients (13.2%) had CE lesions which were most located in the right coronary artery (53.4%). Patients with CE had a lower incidence of diabetes (43.8% vs 30.1%, p = 0.03), higher body mass index (25.4±3.5 vs 26.7±4.6, p = 0.027) and poorer coronary collateral (58.2% vs 71.2%, p = 0.040). Patients with poor collateral (n = 331) had a higher incidence of CE (15.7% vs 9.5%, p = 0.040) and fewer diseased vessels numbers (1.96±0.84 vs 2.48±0.69, p<0.001). Multivariate analysis showed diabetes (odd ratio (OR) 0.630, p = 0.026), CE (OR = 0.544, p = 0.048), and number of diseased vessels (OR = 2.488, p<0.001) were significant predictors of coronary collaterals development.

Conclusion

The presence of CE was associated with poorer coronary collateral development in patients with SCAD.