New insights into the mechanisms involved in B-type natriuretic peptide elevation and its prognostic value in septic patients

Introduction

Elevated plasma B-type natriuretic peptide (BNP) levels in patients with critical sepsis (severe sepsis and septic shock) may indicate septic cardiomyopathy. However, multiple heterogeneous conditions may also be involved in increased BNP level. In addition, the prognostic value of BNP in sepsis remains debatable. In this study, we sought to discover potential independent determinants of BNP elevation in critical sepsis. The prognostic value of BNP was also evaluated.

Methods

In this observational study, we enrolled mechanically ventilated, critically septic patients requiring hemodynamic monitoring through a pulmonary artery catheter. All clinical, laboratory and survival data were prospectively collected. Plasma BNP concentrations were measured daily for five consecutive days. Septic cardiomyopathy was assessed on day 1 on the basis of left and right ventricular ejection fractions (EF) derived from echocardiography and thermodilution, respectively. Mortality was recorded at day 28.

Results

A total of 42 patients with severe sepsis (N = 12) and septic shock (N = 30) were ultimately enrolled. Daily BNP levels were significantly elevated in septic shock patients compared with those with severe sepsis (P ≤0.002). Critical illness severity (assessed by Acute Physiology and Chronic Health Evaluation II and maximum Sequential Organ Failure Assessment scores), and peak noradrenaline dose on day 1 were independent determinants of BNP elevation (P <0.05). Biventricular EFs were inversely correlated with longitudinal BNP measurements (P <0.05), but not independently. Pulmonary capillary wedge pressures (PCWP) and volume expansion showed no correlation with BNP. In septic shock, increased central venous pressure (CVP) and CVP/PCWP ratio were independently associated with early BNP values (P <0.05).Twenty-eight-day mortality was 47.6% (20 of 42 patients). Daily BNP values poorly predicted outcome; BNP on day 1 > 800 pg/ml (the best cutoff point) fairly predicted mortality, with a sensitivity%, specificity% and area under the curve values of 65, 64 and 0.70, respectively (95% confidence interval = 0.54 to 0.86; P = 0.03). Plasma BNP levels declined faster in survivors than in nonsurvivors in both critical sepsis and septic shock (P ≤0.002). In septic shock, a BNP/CVP ratio >126 pg/mmHg/ml on day 2 and inability to reduce BNP <500 pg/ml implied increased mortality (P ≤0.036).

Conclusions

The severity of critical illness, rather than septic cardiomyopathy, is probably the major determinant of BNP elevation in patients with critical sepsis. Daily BNP values are of limited prognostic value in predicting 28-day mortality; however, fast BNP decline over time and a decrease in BNP <500 pg/ml may imply a favorable outcome.     

Inducible supraventricular tachycardias in patients referred for catheter ablation of atrial fibrillation.

AIMS: To investigate the prevalence of underlying, inducible supraventricular arrhythmias in patients referred for ablation of atrial fibrillation (AF). METHODS AND RESULTS: Electrophysiology study reports of 409 consecutive patients (18% female), aged 55 +/- 9 years, who were referred for catheter ablation of AF, were studied. At electrophysiology study, arrhythmias other than AF were induced in 31 patients (7.6%). Cavotricuspid-dependent atrial flutter was induced in 15 patients (3.7%), slow-fast atrioventricular nodal re-entrant tachycardia (AVNRT) in seven patients (1.7%), atrioventricular re-entrant tachycardia (AVRT) due to an accessory pathway in five patients (1.2%), and atrial tachycardia (AT) in four patients (0.98%). Specific ablation aimed at elimination of the underlying arrhythmia only was performed in 13 patients, isolation of the pulmonary veins without additional ablation in three patients, and a combined procedure was performed in the remaining 15 patients. No significant association was observed between type of induced arrhythmia and type of ablation performed (P = 0.338). Slow pathway ablation without pulmonary vein isolation was more common among patients with AVNRT (five patients, 71%). AF recurrence was higher among patients in whom atrial flutter was induced at electrophysiology study (eight patients, 53%) compared to those with AVRT (no patient), AT (no patient), or AVNRT (one patient) (P = 0.03). CONCLUSION: Patients referred for ablation of paroxysmal AF should be investigated for evidence of underlying supraventricular arrhytmias. In patients with AVNRT, slow pathway ablation may be the only procedure that is necessary for cure of AF. Inducibility of atrial flutter appears to carry an increased risk of AF recurrence regardless of whether the cavotricuspid isthmus is also ablated.     

An integrated assessment of family history on the risk of developing acute coronary syndromes (CARDIO2000 study)

OBJECTIVE: In this work we assessed a risk score for developing a first event of acute coronary syndrome (ACS) based on the family history of the cardiovascular risk factors. METHODS AND RESULTS: The studied population consisted of 848 randomly selected middle-aged patients with first event of ACS and 1078 sex-age-region matched controls admitted to the same hospitals for minor operations and without any clinical suspicion of cardiovascular disease in their life. A Family History Score (FHS) was developed based on the presence of coronary heart disease, hypertension, hypercholesterolaemia and diabetes mellitus, among first-degree relatives of the participants after adjusting for the family size. The evaluation of FHS was based on conditional logistic regression analysis, after controlling for demographic variables as well as for the mutual confounding effects of other risk factors. Family history of CHD, hypercholesterolaemia and diabetes was highly associated with the development of the disease. The introduced FHS was also highly associated with the development of ACS among participants who had no family history of CHD (odds ratio = 10.9, p < 0.001), whereas it was not associated with the development of the disease among participants who had a family history of CHD (odds ratio = 1.41, p = 0.543). CONCLUSIONS: The suggested FHS could be a useful tool in the primary prevention of ACS, as well as in detecting and understanding associations between genetic vulnerability and cardiovascular risk factors.     

The relationship between fish consumption and the risk of developing acute coronary syndromes among smokers: the CARDIO2000 case-control study

BACKGROUND AND AIM: We sought to investigate the relationship between fish consumption and the risk of developing non-fatal acute coronary syndromes (ACS) among current smokers. METHODS AND RESULTS: During 2000-2001, we conducted the CARDIO2000 case-control study that included patients hospitalized for a first event of ACS and matched (age, sex) individuals without clinical evidence of CHD (controls), from all the Greek regions. In the present analysis we studied data from 519 men (59+/-10 years old) and 45 women (62+/-9 years old) patients, as well as 444 men and 90 women controls, matched for age with the patients that reported current smoking. To evaluate the hypothesis tested we applied conditional logistic regression analysis after controlling for several potential confounders. Overall, 94% of controls and patients reported fish consumption at least once a week. Compared to low fish consumption (<60 g/week), moderate (60-180 g/week) intake was associated with 15% (p<0.05) lower risk of ACS, while increased (180-300 g/week, or >300 g/week) consumption was associated with 18% (p<0.05) and 19% (p = 0.53) higher risk, respectively. CONCLUSION: Moderate fish consumption seems to moderate the deleterious effect of smoking on the occurrence of ACS. However, increased intake does not seem to confer any benefit on coronary risk.     

Apolipoprotein E genotype in dyslipidemic patients and response of blood lipids and inflammatory markers to alpha-linolenic Acid

The objective of this study was to determine the effect of alpha-linolenic acid (ALA) supplementation on blood lipids and inflammatory markers, in relation to apolipoprotein (apo) E genotype. The diets of 50 dyslipidemic male patients were supplemented with 15 mL of flaxseed oil per day for 12 weeks. Retrospectively, 3 apo E genotype variants were found (epsilon2/epsilon3, n=7; epsilon3/epsilon3, n=33; epsilon3/epsilon4, n=10). No significant differences were found among apo E genotypes in any variables at baseline. ALA supplementation produced a small but significant decrease in high-density lipoprotein cholesterol (from 1.12 to 1.08 mmol/L, 43 to 42 mg/dL; p=0.008) and apo A-I levels (from 1.28 to 1.24 g/L, p=0.036) in the epsilon3/epsilon3 homozygotes. In addition, ALA supplementation resulted in a significant decrease in the serum concentration of serum amyloid A (SAA) (p=0.014), C-reactive protein (CRP) (p=0.013), macrophage colony-stimulating factor (MCSF) (p<0.001), and interleukin (IL)-6 (p=0.028). Serum SAA and MCSF were also significantly decreased in the epsilon3/epsilon4 group (p=0.005 and p=0.017, respectively). In contrast, ALA produced no effects on any of the inflammatory markers in the epsilon2/epsilon3 group. ALA may have beneficial effects on inflammation in dyslipidemic carriers of the apo epsilon3/epsilon3 and epsilon3/epsilon4 genotypes, but not in carriers of the epsilon2 allele.     

Abdominal obesity and inflammation predicts hypertension among prehypertensive men and women: the ATTICA Study

The aim of this work was to assess the 5-year incidence of hypertension and its predictors among prehypertensive adults. Under the context of the ATTICA Study, data from 1188 individuals, free of cardiovascular disease, but with defined high blood pressure levels (prehypertension) at baseline examination (during 2001–2002) were retrieved. In 2006, the 5-year follow-up of the study was performed, and 798 of the prehypertensive participants were allocated. In this work, incidence and determinants of developing hypertension were evaluated. The 5-year ageadjusted incidence of hypertension was 18.7% in men and 24.6% in women (P = 0.05); while almost one half of prehypertensive individuals at the age of 55–65 years developed hypertension, and approximately 6 out of 10 people over 65 years of age developed the disease. Multiple logistic regression analysis revealed that increased age (odds ratio [OR] per 1 year = 1.09, 95% confidence interval [CI] 1.07–1.12), male sex (OR = 0.40, 95% CI 0.21–0.68), high education status (OR per 1 year of school = 0.94, 95% CI 0.88–0.98), waist circumference (OR per 1 cm = 1.04, 95% CI 1.02-1.06) and C-reactive protein (OR per 1 mg/l = 1.12, 95% CI 1.05–1.20), were positively associated with the development of hypertension. Moreover, greater adherence to Mediterranean diet seems to protect only prehypertensive, with abdominal obesity patients prone to develop hypertension (OR = 0.94, 95% CI 0.90–0.98). Annual incidence of hypertension was roughly 4% in men and women. Older people, with low education, abdominal obesity, lower adherence to the Mediterranean diet, and increased inflammation, constitute a model of prehypertensive individuals that are prone to develop hypertension.     

Association between passive cigarette smoking and the risk of developing acute coronary syndromes: the CARDIO2000 study

Although the effect of smoking on human health has been established as a major risk factor, the effect of passive smoking is controversial. The purpose of this study was to investigate the association between passive smoking and the risk of acute coronary syndromes (ACS) among nonsmokers. Eight hundred and forty-eight patients with the first event of ACS and 1078 cardiovascular disease-free matched controls completed a detailed questionnaire regarding their exposure to environmental smoke. Two hundred and ninety-seven (35%) of the patients and 259 (24%) of the controls were defined as nonsmokers and passive smokers, respectively. After controlling for several potential confounders, the results showed that nonsmokers exposed to cigarette smoke increased the risk of ACS by 51% (odds ratio = 1.51, 95% confidence interval 1.21–2.99) compared with nonsmokers not exposed to smoke. It was estimated that 34 coronary events per 134 subjects would occur as a result of passive smoking during their lifetime. Consequently, this study supports the hypothesis that passive smoking increases the risk of developing acute coronary syndromes. Given the high prevalence of cigarette smoking in many developing societies, the public health consequences of passive smoking with regard to coronary heart disease may be important. Received: November 19, 2001 / Accepted: January 25, 2002