Prediction of in-hospital mortality by brain natriuretic peptide levels and other independent variables in acutely ill patients with suspected heart disease

BACKGROUND: Brain natriuretic peptide (BNP) measurement can detect and assess heart failure. However, compared with traditional clinical parameters, its value for predicting the in-hospital mortality of patients with suspected heart disease has not been reported. STUDY DESIGN: Examination of the ability of 11 continuous and 22 categorical variables, including BNP levels measured at the time of admission, was conducted to predict in-hospital mortality. SETTING: A small, rural Irish hospital. SUBJECTS: Six hundred forty-two consecutive patients with suspected heart disease admitted as acute medical emergencies. RESULTS: Thirty-eight (5.9%) patients died while in hospital. They had significantly higher BNP levels on admission than did patients subsequently discharged alive (763+/-473 pg/mL versus 368+/-412 pg/mL, P<0.0001). Patients who died in hospital were older; had significantly higher white blood cell counts, blood urea, respiratory rates and modified early warning scores; and had significantly lower blood pressure and hemoglobin levels. Five variables were found to be independent predictors of mortality: a systolic blood pressure of 90 mmHg or less; a hemoglobin level of 100 g/L or less; a white blood cell count greater than 13.0 x 10(9)/L being unwell before the current illness; and a BNP level of 700 pg/mL or greater. The presence of three or more of these variables was associated with an in-hospital mortality rate of 39%. CONCLUSIONS: Five independent variables (hypotension, anemia, leukocytosis, prior illness and elevated BNP levels) are comparable predictors of in-hospital mortality in patients with suspected heart disease.     

Increased plasma 8-isoprostane levels in hypertensive subjects: the Tsurugaya Project.

To examine the relationship between 8-isoprostane and blood pressure, we measured plasma 8-isoprostane concentration and home blood pressure levels in an elderly Japanese population. Our study population comprised 569 subjects aged 70 years and over who were not receiving antihypertensive medication. On the basis of their blood pressure values, the participants were classified into three groups: normotensive (home blood pressure <135/85 mmHg), hypertensive (home blood pressure 135/85-160/90 mmHg), and severely hypertensive (home blood pressure > or =160/90 mmHg). The mean plasma 8-isoprostane level in the severely hypertensive group (21.1+/-5.2 pg/ml) was significantly higher than that in the normotensive (20.2+/-4.9 pg/ml) or hypertensive (19.7+/-5.1 pg/ml) group, and this result was unchanged when we adjusted for possible confounding factors such as age, sex, use of vitamin A, C or E supplements, smoking status, drinking status, body mass index, use of non-steroidal anti-inflammatory drugs, history of diabetes, hypercholesterolemia, home heart rate and serum creatinine level. Thus, the level of plasma 8-isoprostane appears to be elevated in older subjects with severe hypertension.     

Relationship between brain natriuretic peptide and coronary stenosis: influence of aging

OBJECTIVES: The relationship between brain natriuretic peptide (BNP) and coronary stenosis, and the utility of BNP for the prediction of coronary stenosis were investigated. METHODS: This study included 100 consecutive patients (48 men, 52 women, mean age 65.8 +/- 9.9 years) who underwent elective cardiac catheterization for the diagnosis of coronary stenosis without other heart diseases (heart failure, valvular heart disease, cardiomyopathy, sick sinus syndrome), and E/A was recorded by echocardiography. The relationship between coronary stenosis, left ventricular ejection fraction by left ventriculography, left ventricular end-diastolic pressure, E/A, left ventricular stroke volume index by echocardiography and BNP were investigated. RESULTS: Thirty-nine patients revealed coronary stenosis > or = 75% (CS), and 6 patients had chronic total occlusion. In the CS(+) group, BNP and left ventricular end-diastolic pressure were elevated significantly (50.7 +/- 48.5 vs 22.1 +/- 21.6 pg/ml, p < 0.05; 9.2 +/- 5.3 vs 6.4 +/- 3.4 mmHg, p < 0.05). In logistic regression analysis, BNP and left ventricular end-diastolic pressure had significant correlations with CS(+), independent of age, systolic blood pressure, E/A and left ventricular ejection fraction (p = 0.007, p = 0.05, respectively). Prognostic values of BNP (> 20 pg/ml) for the diagnosis of CS(+) were sensitivity of 79%, and specificity of 61% (p < 0.005). In the CS(-) group, the patients showing BNP > 20 pg/ml were older than the patients showing BNP < or = 20 pg/ml (68.4 +/- 8.5 vs 60.0 +/- 9.4, p < 0.05). Therefore, the prognostic values were reduced (sensitivity 78%, specificity 82%, p < 0.005) in the younger group (age < 65, n = 42). Even in patients with coronary stenosis but without chronic total occlusion, both BNP and left ventricular end-diastolic pressure were elevated significantly compared with the patients without coronary stenosis (22.1 +/- 21.6 vs 44.0 +/- 43.2 pg/ml, p < 0.01; 6.4 +/- 3.4 vs 9.1 +/- 5.2 mmHg, p < 0.01). CONCLUSIONS: Plasma BNP levels are useful markers for detecting coronary stenosis, especially in younger patients.     

Comparative effects of losartan and amlodipine on activities of sympathetic nerve,renin-angiotensin-aldosterone system and brain natriuretic peptide in the elderly hypertensive patients

This study investigated the comparative effects of losartan and amlodipine on the activation of the sympathetic nervous system, renin-angiotensin-aldosterone system (R-A-A system) and brain natriuretic peptide (BNP) in patients with essential hypertension. Twenty-four elderly patients who had received more than 12 months of antihypertensive treatment with amlodipine participated in this study. The treatment regimen of 5 mg/day amlodipine was changed to 50 mg/day losartan. Plasma catecholamines (norepinephrine, epinephrine and dopamine), active renin, aldosterone and BNP concentration were measured before and after an average of 5 months of losartan treatment. After losartan treatment, blood pressures were not changed, suggesting the comparable effect of 50 mg losartan and 5 mg amlodipine on elevated blood pressure. Losartan significantly reduced norepinephrine (799 +/- 277 pg/mL vs. 692 +/- 268 pg/mL, p < 0.05) and aldosterone concentration (81.2 +/- 35.3 pg/mL vs. 55.2 +/- 17.7 pg/mL, p < 0.01), whereas there were not any changes in BNP concentrations. These findings suggested that losartan might be superior to amlodipine in prevention of chronic or intermittent sympathetic hyperactivity and enhanced R-A-A system.     

Effects of calcium antagonist, benidipine, on the progression of chronic renal failure in the elderly: a 1-year follow-up

The number of patients who needs for dialysis therapy is increasing rapidly among the older population. Although control of hypertension can delay or arrest the progression of renal failure, there are lacking of studies about antihypertensive treatment of chronic renal failure in the elderly. We have studied the effects of treating hypertension with a calcium antagonist, benidipine, on renal function and blood pressure in 58 patients (mean age: 71 +/- 9) with hypertension and chronic renal insufficiency (the levels of creatinine ranging from 1.5 to 4.0 mg/dl). The underlying disease included glomerulopathies (in 33), diabetic nephropathy (in 15), and other causes (in 10). Forty two patients who had been treated with other antihypertensive drugs other than angiotensin converting enzyme (ACE) inhibitors, antihypertensive drugs were withdrawn 2 weeks before the entry. At the entry, patients should have sitting systolic blood pressure (SBP) of above 160 mmHg and diastolic blood pressure (DBP) of above 90 mmHg. In total, both SBP and DBP decreased from 169/95+/-12.5/8.9 to 148/81+/-16.1/8.0 mmHg (p<0.001) with remaining the serum creatinine levels from 2.2+/-0.8 vs 2.4+/-1.3 mg/dl (P>0.05). Retrospective analysis revealed that in 4 of 4 patients treated with benidipine and 2 of 3 patients with benidipine and ACE inhibitors with systolic blood pressure more than 160 mmHg at the end of the study, the levels of serum creatinine increased from 2.5+/-0.3 to 2.8+/-0.4 with significance (P<0.05). If systolic blood pressure was reduced less than 159 mmHg, 38 of 48 patients did not show any deterioration of renal function. Compared to the significance of SBP in preserving renal function, DBP did not associate with the changes in renal function. No patients died during the study. One patient had transient ischemic attack and one patient had stroke in benidipine treated group. One patient had angina pectoris in benidipine-ACE inhibitors treated group. The results of our trial seem to give some support for the idea that long-acting calcium antagonists such as benidipine are renoprotective through reduction of SBP in the elderly people with hypertension and chronic renal insufficiency. However, if systolic blood pressure was not reduced below 160 mmHg throughout a year, the substantial declines in renal function would be expected.     

Plasma brain natriuretic peptide levels in normotensive noninsulin-dependent diabetic patients with microalbuminuria.

Brain natriuretic peptide (BNP), a member of the natriuretic peptide family, is produced and released from cardiac ventricles. BNP regulates the body fluid volume, blood pressure, and vascular tones through the A-type guanylate cyclase-coupled receptor. The presence of renal dysfunction in patients with diabetes affects the plasma levels of atrial natriuretic peptide (ANP). In the present study, we investigated the plasma levels of BNP and ANP and their relationship in normotensive diabetic patients with normoalbuminuria and microalbuminuria. Forty-seven normotensive lean noninsulin-dependent diabetic patients (31 with normoalbuminuria, 16 with microalbuminuria), with normal cardiac function, and 30 age-matched control subjects were enrolled in this study. The plasma levels of BNP in diabetic patients with microalbuminuria were significantly higher than those in diabetic patients with normoalbuminuria (16.7+/-2.4 vs. 9.6+/-1.3 pg/mL, P<0.01) or normal subjects (16.7+/-2.4 vs. 7.0+/-0.6 pg/mL, P<0.01). There was a significant positive correlation between plasma BNP levels and urinary albumin excretion rate in all diabetic patients (r = 0.58, P<0.0001). There was also a significantly positive correlation between plasma BNP and ANP levels in diabetic patients (r = 0.62, P<0.0001). The increased plasma level of BNP in patients with microalbuminuria and its significant correlation with urinary albumin excretion rate suggest that the elevated circulating levels of BNP are caused by the presence of diabetic nephropathy. Down-regulation of A-type guanylate cyclase-coupled receptor of renal tubules may explain the increased plasma levels of both BNP and ANP in normotensive diabetic patients with microalbuminuria.     

Value of plasma BNP levels as a prognostic marker in lung and heart disorders

In this study we included 155 subjects, 35 patients with left heart failure, 49 chronic obstructive pulmonary disease (COPD)-cor pulmonale, 26 COPD, 20 pulmonary embolism and 25 healthy subjects. Plasma BNP level in patient with left heart failure was significantly higher than COPD-cor pulmonale, COPD and control subject in respect 1167 +/- 746, 434 +/- 55, 32 +/- 36 and 32 +/- 12 pg/mL. Plasma BNP in group of cor pulmonale was higher than COPD and control subject 434 +/- 55 vs. 32 +/- 12 pg/mL. There were no difference between COPD and control subject 32 +/- 36 vs. 32 +/- 12 pg/mL. In pulmonary embolism BNP was higher than controls 357 +/- 391 vs. 32 +/- 12 pg/mL and BNP levels of massive pulmonary embolism was higher non-massive embolism 699 +/- 394 vs 166 +/- 213 pg/mL. In this study BNP levels negative correlated with EF and positive correlated with pulmonary artery pressure. We suggest that increased BNP levels are correlated with ventricular failure and BNP is diagnostic and prognostic marker of heart failure and increased right ventricular pressure contributes to elevated BNP in patients with PE.     

A rapid test for B-type natriuretic peptide correlates with falling wedge pressures in patients treated for decompensated heart failure: a pilot study

OBJECTIVES: To determine if changes in B-type natriuretic peptide (BNP) levels can accurately reflect acute changes in pulmonary capillary wedge pressure during treatment of decompensated heart failure. BACKGROUND: Tailored therapy of decompensated congestive heart failure with hemodynamic monitoring is controversial. Other than the expense and complications of Swan-Ganz catheters, its use in titration of drug therapy has no conclusive end point. Because BNP reflects both elevated left ventricular pressure and neurohormonal modulation and has a short half-life, we hypothesized that levels of BNP would decline in association with falling wedge pressures. Final BNP levels would perhaps signify a new set point of neuromodulation. METHODS AND RESULTS: Twenty patients with decompensated New York Heart Association (NYHA) class III-IV congestive heart failure (CHF) undergoing tailored therapy were studied. BNP levels were drawn every 2 to 4 hours for the first 24 hours (active treatment phase) and then every 4 hours for the next 24 to 48 hours (stabilization period). Hemodynamic data was recorded simultaneously. In 15 patients whose wedge pressure responded to treatment in the first 24 hours, there was a significant drop in BNP levels (55%) versus nonresponders (8%). There was a significant correlation between percent change in wedge pressure from baseline per hour and the percent change of BNP from baseline per hour (r = 0.79, P <.05). When the wedge pressure was kept at a stable, low level during the stabilization phase, BNP levels continued to fall another 37% (937 +/- 140 pg/mL at 24 hours to 605 +/- 128 pg/mL). Patients who died (n = 4) had higher final BNP levels (1,078 +/- 123 pg/mL v 701 +/- 107 pg/mL). CONCLUSIONS: The data suggest that rapid testing of BNP may be an effective way to improve the in-hospital management of patients admitted with decompensated CHF. Although BNP levels will not obviate the need for invasive hemodynamic monitoring, it may be a useful adjunct in tailoring therapy to these patients.     

Effects of percutaneous balloon mitral valvuloplasty on plasma B-type natriuretic peptide in rheumatic mitral stenosis with and without atrial fibrillation

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the effect of percutaneous balloon mitral valvuloplasty (PBMV) on plasma B-type natriuretic peptide (BNP) levels in patients in sinus rhythm (SR) and with atrial fibrillation (AF). METHODS: Thirty patients with rheumatic mitral stenosis who underwent successful PBMV were included in the study. Of these patents, 21 were in SR (SR group) and nine had AF (AF group). Plasma BNP levels were measured using the Triage BNP Test in all patients before, and at 20 min and 24 h after, PBMV. Control levels were measured in eight healthy volunteers. RESULTS: Basal plasma BNP levels in patients were significantly higher than those in controls (123.5 +/- 69.5 versus 16.4 +/- 7.6 pg/ml, p < 0.01), and correlated with mean left atrial pressure (mLAP; r = 0.441, p < 0.05) and pulmonary artery pressure (PAP; r = 0.488, p < 0.01). No significant difference was observed in BNP levels between the SR and AF groups. In the SR group, BNP levels decreased after PBMV (pre-PBMV 128.7 +/- 75.9 pg/ml; at 20 min, 88.6 +/- 62.0 pg/ml; at 24 h, 43.4 +/- 26.7 pg/ml; respectively, p < 0.05). Changes in plasma BNP (deltaBNP) correlated positively with those in mLAP (deltamLAP) (r = 0.696, p < 0.01) and PAP (deltaPAP) (r = 0.456, p < 0.05). Left ventricular end-diastolic volume (LVEDV) (96.1 +/- 21.6 versus 111.5 +/- 25.2 ml, p < 0.01) and stroke volume (SV) (59.2 +/- 15.8 versus 69.0 +/- 17.9 ml, p < 0.05) augmented accordingly without any changes in left ventricular end-diastolic pressure (LVEDP) (p = NS). In contrast, in group AF, BNP levels remained unchanged (pre-PBMV 111.6 +/- 53.4 pg/ml; at 20 min, 122.0 +/- 68.7 pg/ml; at 24 h, 106.1 +/- 56.2 pg/ml; respectively, p = NS), while LVEDP increased (6.4 +/- 3.6 versus 8.6 +/- 3.2 mmHg, p < 0.01), without any changes in LVEDV and SV (p = NS). CONCLUSION: The study results indicate that, in mitral stenosis patients, a high BNP level is associated with high mLAP and PAP. Cardiac rhythm may play an important role in changes of BNP level after PBMV. BNP may be a valid marker to reflect changes in mLAP and PAP after PBMV in patients with SR, but not in those with AF.     

Snake skin pattern gastropathy in cirrhotic patients

Gastric mucosal lesions are common in patients with cirrhosis. Among them, snake skin pattern gastropathy (SSPG) is the most distinguishing one. A prospective study was conducted to investigate the incidence of SSPG in cirrhotic patients, the relationship between the degree of portal pressure and SSPG, and the possible association of SSPG with serum levels of gastrin and pepsinogen I. SSPG was found to be significantly more common in 100 cirrhotic patients than in 100 age- and sex-matched healthy controls (41% vs 0%, P less than 0.0001). Hepatic venous pressure gradient and serum gastrin and pepsinogen I levels were measured in 21 cirrhotic patients with SSPG and 25 cirrhotics without SSPG. There was no significant difference in hepatic venous pressure gradient (16.1 +/- 4.4 mmHg vs 16.1 +/- 4.9 mmHg, P greater than 0.05), serum gastrin level (78.0 +/- 26.7 pg/mL vs 80.1 +/- 32.5 pg/mL, P greater than 0.05) and serum pepsinogen I level (69.5 +/- 26.6 ng/mL vs 65.2 +/- 26.1 ng/mL, P greater than 0.05) in cirrhotic patients with or without SSPG. In conclusion, SSPG is common in cirrhotic patients. Portal pressure per se may not be the only factor causing SSPG--other aggressive factors may be needed together to cause the gastropathy. There is no evidence of correlation between serum gastrin or pepsinogen I level and SSPG.     

Effect of telmisartan on blood pressure control and kidney function in hypertensive, proteinuric patients with chronic kidney disease

OBJECTIVES: To assess the antihypertensive and antiproteinuric efficacy and safety of the angiotensin II type 1 receptor blocker telmisartan in patients with hypertension and chronic kidney disease. METHODS: A multicenter, prospective trial was performed in adults with hypertension [systolic blood pressure (SBP)/diastolic blood pressure (DBP) >130/85 mmHg), chronic renal insufficiency (serum creatinine <4.0 mg/dl), and proteinuria (>1 g/24 h). In addition to existing antihypertensive therapy, the nature and doses of which remained unchanged throughout the study, patients received once-daily telmisartan 40 mg for the first 3 months followed by forced titration to telmisartan 80 mg for the subsequent 3 months to achieve a target SBP/DBP of <130/85 mmHg. The rationale for using telmisartan was its long half-life efficacy, greater antihypertensive effect compared with valsartan or losartan, and newly discovered potential antidiabetic effect. RESULTS: The study was conducted in 92 patients (45 men, 47 women), of whom 60 had diabetes mellitus (54 patients with type 2 disease). Five patients discontinued prematurely: two because of hyperkalemia, two because of protocol violation, and one because of lack of efficacy. After 6 months' telmisartan treatment, office trough seated SBP was reduced by 19.6 mmHg (P<0.001) from 154.9+/-14.6 mmHg and DBP by 11.8 mmHg (P<0.001) from 91.7+/-8.1 mmHg. Seated trough SBP/DBP of <130/85 mmHg was achieved at 6 months in 34.8% of patients. Ambulatory blood pressure monitoring also demonstrated significant reductions in mean daytime SBP of 10.9 mmHg (P=0.01), night-time SBP of 12.1 mmHg (P=0.05), daytime DBP of 3.1 mmHg (P=0.05), and night-time DBP of 6.5 mmHg (P=0.05). Proteinuria decreased significantly from 3.6+/-3.4 to 2.8+/-2.8 g/24 h (P=0.01). A decrease in proteinuria depended significantly on a decrease in SBP at the end of the study (P=0.044). Each decrease in SBP of about 10 mmHg led to a decrease in proteinuria of about 0.79 g/24 h (95% CI 0.02-1.56 g/24 h). Serum creatinine increased from 1.96+/-0.79 to 2.08+/-0.89 mg/dl (P=0.01), whereas creatinine clearance did not change significantly. CONCLUSIONS: Telmisartan effectively and safely reduced blood pressure and brought about regression of proteinuria in diabetic and nondiabetic, hypertensive, proteinuric patients with chronic kidney disease, even in those with mild-to-moderate chronic renal failure.     

Association of arginine vasopressin and arterial blood pressure in a population-based sample

BACKGROUND: The role of arginine vasopressin (AVP) in the development and maintenance of arterial hypertension is controversial. Furthermore, it remains unclear whether chronic treatment with antihypertensive agents modulates levels of AVP, with potential secondary effects on vascular tone and fluid homeostasis. OBJECTIVE: To investigate the relation between plasma AVP and arterial blood pressure in a population-based sample of 534 middle-aged subjects. RESULTS: Overall, levels of AVP were higher in hypertensive subjects (2.15 +/- 0.26 pg/ml; n = 289) than in normotensive subjects (1.45 +/- 0.15 pg/ml; n = 245; P < 0.05). (Hypertension was defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg, or receiving antihypertensive medication.) In untreated individuals, plasma levels of AVP were found to be correlated with both systolic (r = 0.15, P = 0.002) and diastolic (r = 0.14, P = 0.005) blood pressure. The differences between the lowest and highest quartile of AVP levels were 5.1 mmHg (P = 0.03) and 2.6 mmHg (NS) for systolic and diastolic blood pressure, respectively, after adjustment for age and sex. Moreover, it appeared that the relation between AVP and blood pressure was particularly strong in subjects with low levels of renin (< 10 mU/l; n = 118; systolic blood pressure r = 0.24, P = 0.007; diastolic blood pressure r = 0.19, P = 0.03). Specifically, patients receiving monotherapy with diuretics (n = 39) or beta-blockers (n = 54) displayed elevated plasma levels of AVP (2.93 +/- 0.98 pg/ml and 2.74 +/- 0.74 pg/ml respectively); however, only in patients taking diuretics was this finding apparently independent of confounding variables. Other monotherapies with angiotensin-converting enzyme inhibitors (n = 9) or Ca(2+)-antagonists (n = 19) were not associated with levels of AVP. CONCLUSION: The data suggest that plasma levels of AVP display a discernible relationship with arterial blood pressure and hypertension, particularly when renin levels are low. In addition, with the exception of diuretics, no modulation of AVP levels is attributable to the intake of antihypertensive agents as it occurs in a population-based sample.     

Efficacy of and tolerance to prolonged release prazosin in patients with hypertension and non-insulin dependent diabetes

The treatment of hypertension represents one of the major elements of the cardiovascular prognosis in type II diabetes. Among antihypertensive drugs, alpha blockers may be interesting because of the absence of unfavourable effects on plasma glucose and lipid levels. OBJECTIVE: The aim of this study was to evaluate the effectiveness and the safety of prazosin osmotic tablet treatment in non-insulin-dependent diabetic patients with mild to moderate arterial hypertension. METHODS: After an initial 4-week-single-blind placebo period, 81 hypertensive subjects (162 +/- 11/96 +/- 5 mmHg) with type II diabetes were included in the study to receive prazosin osmotic tablet (o.t) open-label therapy at the dose of 2.5 mg/day for 12 weeks. After 4 weeks of treatment the dosage of prazosin o.t was increased to 5 mg/day if the diastolic blood pressure remained > or = 90 mmHg. RESULTS: Both supine and standing systolic and diastolic blood pressures were significantly decreased (P < 0.001) with prazosin therapy from 162 +/- 10/96 +/- 5 mmHg in supine and 160 +/- 12/95 +/- 6 mmHg in the upright position, to 149 +/- 15/86 +/- 9 mmHg and 148 +/- 16/86 +/- 9 mmHg respectively at the end of the 12-week-treatment period. There were no significant changes in the glycemic parameters (glycemia, haemoglobin A1c) during the prazosin therapy compared with baseline values. A significant decrease of triglycerides (P = 0.005), total cholesterol (P < 0.001) and LDL cholesterol (P = 0.03) levels was observed during prazosin therapy compared with the baseline measurements, whereas HDL cholesterol remained stable. Only 6% of the patients reported adverse events in relation with the study drug during the active treatment period. CONCLUSION: This study showed a significant decrease of the blood pressure in hypertensive subjects with type II diabetes after prazosin o.t treatment, without any change of glycemic parameters. Moreover, there was a favourable evolution of the lipidic parameters during the study characterised by a significant decrease of triglycerides and total and LDL cholesterol.     

Brain natriuretic peptide predicts successful cardioversion in patients with atrial fibrillation and maintenance of sinus rhythm

BACKGROUND: Brain natriuretic peptide (BNP) is released from the heart by hemodynamically induced muscle stretch. Patients with atrial fibrillation have higher levels of BNP than those in sinus rhythm. OBJECTIVE: To assess the usefulness of BNP as a predictor of successful cardioversion in patients with persistent atrial fibrillation and subsequent maintenance of sinus rhythm. SUBJECTS AND METHODS: Twenty patients undergoing cardioversion for persistent atrial fibrillation were enrolled. BNP levels were measured before electric cardioversion, and 30 min and two weeks after cardioversion. Baseline echocardiograms and 12-lead electrocardiograms were obtained from all patients. Patients with valvular disease, previous mitral valve surgery or significant left ventricular dysfunction were excluded. RESULTS: The mean BNP level and the mean heart rate were significantly higher before cardioversion than 30 min after (197+/-132 pg/mL versus 164+/-143 pg/mL, P=0.02, and 77+/-17 beats/min versus 57+/-12 beats/min, P=0.0007, respectively). Patients who reverted back to atrial fibrillation after two weeks had a baseline BNP of 293+/-106 pg/mL, while those who remained in sinus rhythm for two weeks had a lower baseline BNP of 163+/-122 pg/mL (P=0.02). CONCLUSION: In patients with persistent atrial fibrillation, BNP levels are associated with successful cardioversion and maintenance of sinus rhythm two weeks after cardioversion.     

Relationship between B-type natriuretic peptide levels and ventilatory response during cardiopulmonary exercise test in patients with chronic heart failure

AIM: Aim of the study was to evaluate if brain natriuretic peptide (BNP) levels, a cardiac neurohormone well correlated with prognosis in chronic heart failure (CHF), are associated with enhanced ventilatory response to exercise, in ambulatory patients with intermediate peak oxygen uptake (PVO2). METHODS: Resting BNP was measured in 129 consecutive stable CHF patients with mild to moderate heart failure (90% New York Heart Association (NYHA) class II or III) and intermediate (10-18 mL/kg/min) PVO2, assessed during cardiopulmonary exercise test. Mean (SD) left ventricular ejection fraction (EF) and pulmonary systolic pressure (PAP) were 41 +/- 3% and 47 +/- 14 mmHg, respectively. The enhanced ventilatory response to exercise (EVR) was assessed as a slope of the relation between minute ventilation and carbon dioxide production (VE/VCO2 slope) > 35. RESULTS: Thirty-three over 129 patients (26%) had EVR. Mean BNP plasma level was 394 +/- 347 pg/mL. A significant correlation between BNP and EVR (r = 0.310; p < 0.01), was observed. In the logistic multivariate model, a BNP plasma level > 100 pg/mL had an independent predictive value for EVR (95% IC 1.68 to 10.5, Odds Ratio 4.23, p = 0.02). We found a significant correlation between BNP and PAP (r = 0.390; p < 0.001), and between PAP and EVR (r = 0.511; p < 0.01). CONCLUSIONS: In CHF patients with intermediate PVO2, plasma BNP is clearly related to the enhanced ventilatory response to exercise. In this subset, BNP levels could represent an effective alternative tool for the clinical assessment in patients with unreliable cardiopulmonary exercise test.     

The limited value of plasma B-type natriuretic peptide for screening for left ventricular hypertrophy among hypertensive patients

BACKGROUND: Several reports have suggested that plasma B-type natriuretic peptide (BNP) levels are elevated in hypertensive patients especially with left ventricular (LV) hypertrophy. However, few data have been available concerning the utility of plasma BNP measurement to identify LV hypertrophy in hypertensive patients in a general population screening context. METHODS: We measured plasma BNP concentrations in 1112 volunteers in a health screening program (mean age, 57 years). All subjects underwent electrocardiography, chest X-ray, and echocardiography. Among the sample, 284 subjects were designated as hypertensive because they were on antihypertensive drugs or showed elevated systemic blood pressure. By echocardiography, 36 of the hypertensive patients showed significant LV hypertrophy. RESULTS: There were no significant differences in age and sex between the LV hypertrophy and non-LV hypertrophy groups. Plasma BNP levels in the LV hypertrophy group were significantly higher than in the non-LV hypertrophy group (19.4 +/- 18.9 v 28.2 +/- 28.2 pg/mL; P <.05). However, the ability of plasma BNP levels to discriminate between LV hypertrophy and non-LV hypertrophy patients was not sufficient as the area under the receiver operating characteristic curve was 0.588 (95% CI: 0.528-0.646) with sensitivity of 50.0% and specificity of 69.0%. Positive and negative predictive values for detecting LV hypertrophy among hypertensive patients were 18.9% and 90.5%, respectively. This ability did not improve significantly when the screening was limited to patients with untreated LV hypertrophy or concentric LV hypertrophy. CONCLUSIONS: Plasma BNP testing in a mass screening setting is of limited use for the identification of LV hypertrophy patients among hypertensive patients with heterogeneous etiology.     

Control of blood pressure and prevention of end-organ damage in patients with accelerated hypertension by combination with arotinolol and extended release nifedipine.

In patients with accelerated (malignant) hypertension, end-organ damage is the determinant factor for prognosis. Although recent advances in antihypertensive therapy have improved the outcome of patients with accelerated hypertension, the effectiveness of antihypertensive therapy still remains less convinced. In this study, we followed 13 patients clinically diagnosed with accelerated hypertension (defined as diastolic blood pressure > 130 mmHg, retinopathy with K-W IV and accelerated renal impairment) for 3 yr. One patient died due to acute myocardial infarction arising from poor compliance with antihypertensive therapy. One patient was maintained on hemodialysis for 3 yr. One patient was introduced for continuous ambulatory peritoneal dialysis (CAPD) for a year and then lived without dialysis therapy. The remaining 10 patients were followed for 3 yr. All patients were initially treated with intravenous administration of calcium antagonist for reduction of blood pressure, followed by hemodialysis therapy if needed. After stabilization of blood pressure, combination therapy with extended release nifedipine (40 to 80 mg daily) and arotinolol (20 mg daily) was started. The targets for blood pressure control were a systolic pressure of 135 mmHg and a diastolic pressure of 80 mmHg. If blood pressure control was unsatisfactory, guanabenz (2 to 4 mg before bedtime), a central acting drug, was added. At presentation, the mean diastolic blood pressure (mDBP) among the 10 remaining patients was 134 +/- 2 mmHg, the mean serum creatinine (mScr) was 4.5 +/- 0.7 mg/dl and the left ventricular mass index (LVMi) as measured by echocardiography was 150 +/- 9 g/m2. At 1 yr, the mDBP was reduced to 90 +/- 3 mmHg, the mScr to 2.9 +/- 0.9 mg/dl and the LVMi to 140 +/- 9 g/m2. At 3 yr, the mDBP was stabilized at 79 +/- 3 mmHg, the mScr maintained at 2.2 +/- 0.4 mg/dl, and the LVMi reduced to 128 +/- 9 g/m2. These results indicate that appropriate blood pressure control is important for improvement of renal impairment and cardiac damage in patients with accelerated hypertension. Moreover, combination therapy with arotinolol and extended release nifedipine may be beneficial for this purpose.     

Elevation of serum soluble E- and P-selectin in patients with hypertension is reversed by benidipine, a long-acting calcium channel blocker.

Hypertension is a major risk factor for atherosclerotic cardiovascular disease. Selectins, cell-surface adhesion molecules involved in leukocyte rolling and attachment to the vascular endothelium, play a role in the initiation of atherosclerosis. We investigated whether or not serum levels of soluble adhesion molecules are elevated in patients with essential hypertension (EH) and examined whether antihypertensive therapy lowers such levels. Twenty-one patients who had untreated mild to moderate EH without diabetes mellitus, hyperlipidemia, or obesity were recruited at a clinic for hypertensive patients. Blood pressure was measured, and the serum levels of soluble E-selectin, P-selectin, L-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular-cell adhesion molecule 1 (VCAM-1) were determined by enzyme-linked immunosorbent assays before and after 12, 24, and 53 weeks of antihypertensive treatment with benidipine, a long-acting calcium channel blocker, given at a dose of 6 mg/day for 53 weeks. As a control, 21 age- and sex-matched patients without hypertension were studied. Serum E- and P-selectin levels were significantly higher in the subjects with EH than in the controls (p < 0.01). There were no differences in serum levels of soluble L-selectin, VCAM-1, or ICAM-1 levels between the patients with EH and the controls. Treatment with benidipine decreased the elevated blood pressure over a 53-week study period (mean blood pressure: 119.8 +/- 6.5 mmHg at baseline, 101.0 +/- 5.9 mmHg at 12 weeks, 98.6 +/- 7.3 mmHg at 24 weeks, and 93.9 +/- 5.5 mmHg at 53 weeks). Serum levels of soluble E- and P-selectin decreased after the initiation of benidipine treatment and correlated with diastolic blood pressure. Serum levels of soluble L-selectin, VCAM-1, and ICAM-1 did not change significantly during the period of benidipine treatment. Benidipine treatment reduced the content of P-selectin in the platelets from patients with EH, as determined by Western blot analysis. In conclusion, decreased blood pressure may reduce the rate of progression of atherosclerosis by affecting the expression of E- and P-selectin in the endothelium, the platelets, or both. Benidipine may be protective against vascular damage in people with hypertension, not only by lowering blood pressure, but also by inhibiting the expression of selectins.     

Clinical significance of B-type natriuretic Peptide in the assessment of untreated hypertension.

BACKGROUND: Recent studies suggest that B-type natriuretic peptide (BNP) is an important predictor of cardiac events in hypertensive patients. METHODS AND RESULTS: The relationship between the plasma BNP level and various clinical parameters was examined in 154 untreated hypertensive patients without heart failure or atrial fibrillation (mean age: 58.0+/-10.7; mean blood pressure: 164.5+/-15.2/99.1+/-9.7 mmHg; mean BNP: 32.7+/-36.7 pg/ml). First, the patients were divided into 2 groups based on BNP: normal (<18.5 pg/ml, mean 9.7+/-5.7, n=69); or elevated (>18.5 pg/ml, mean 51.4+/-40.4, n=85). The elevated BNP group had a significantly greater electrocardiographic voltage index (SV1+RV5; 3.7+/-1.2 vs 3.2+/-0.8 mV, p=0.0029), cardiothoracic ratio/chest radiography (CTR; 49.1 vs 46.9%, p=0.0037), left ventricular mass index (LVMI; 122.2+/-31.7 vs 103.1+/-26.4 g/m2, p=0.0005) and deceleration time (DT; 241+/-39 vs 208+/-30 ms, p=0.0001), as well as a smaller E-wave to A-wave (E/A ratio) (0.80+/-0.22 vs 0.96+/-0.28, p=0.0003), compared with the normal BNP group. There were no significant differences in casual blood pressure, body mass index, serum creatinine and ejection fraction between the 2 groups. Next, the patients were divided into 3 groups based on BNP: normal (<18.5, n=69), moderate (18.5 to 40, mean 27.0+/-5.7, n=43) and high (40<, mean 76.3+/-45.3, n=42). In the high BNP group, most clinical parameters indicated the most severe organ damage compared with other groups, including SV1+RV5, DT and LVMI. In all patients, logarithmic BNP was positively correlated with the age, pulse pressure, SV1+RV5, CTR, ventricular wall thickness, DT, LVMI and negatively correlated with hemoglobin, renin and E/A ratio. Using multiple regression analysis, renin and DT were significantly associated with BNP. No gender differences in the relationship between BNP and clinical parameters were found. CONCLUSIONS: Results suggest that BNP is a useful indicator for the initial assessment of the severity of essential hypertension, detecting both cardiac hypertrophy and diastolic dysfunction, and may also be valuable for risk stratification.