Gender-specific differences of cardiac remodeling in subjects with left ventricular dysfunction: a population-based study

BACKGROUND: Recent studies suggest that female gender is associated with a lower prevalence and a more benign prognosis of heart failure. In the current population-based study, it was our objective to evaluate the implications of gender on the association between impaired left ventricular (LV) function and mass as well as neurohumoral activation. METHODS AND RESULTS: A total of 1883 subjects (992 female, 891 male) of two MONICA surveys in Augsburg, Germany, were analyzed. Participants of one of these surveys were additionally characterized with respect to neurohormonal activation. As compared to men, women were characterized by a slightly higher LV ejection fraction (EF, Teichholz-Method, 65.4 +/- 0.3% vs. 63.4 +/- 0.3, P<0.01) and a markedly lower LV mass index (LVMI 81 +/- 1 g/m(2) vs. 96 +/- 1, P<0.01). As compared to men with normal LV function, those with LV dysfunction (EF below mean minus two standard deviations, S.D.) were characterized by significantly increased LV mass (LVMI +48%, P<0.01), plasma BNP (+373%, P<0.01) and ANP (+57%, P<0.01), while no significant changes were observed in women (LVMI +3%, BNP +48%, ANP +27%, all P=n.s). Only a small subgroup of women with severe LVD (EF below mean - 3 S.D.) was characterized by significantly increased LV mass (LVMI +23%, P<0.05 vs. control and LVD), however, this increase was less pronounced as compared to men with severe LVD (LVMI +46%, P<0.01 vs. control). Gender-specific differences between LV function and structure were also confirmed by multivariate analysis. While LVMI was independently and significantly correlated with EF in male subjects in addition to systolic blood pressure, age, and body mass index (all P<0.01), these parameters displaced EF as a predictor of LVMI in female subjects. CONCLUSIONS: Men with moderate or severe LV dysfunction are characterized by an increase in both LV mass and cardiac natriuretic peptide plasma concentrations. In contrast, LV mass and natriuretic peptide concentrations increase to a lesser extent and only with severe LV dysfunction in women. These observational data suggest gender-specific control of myocardial adaptations to hemodynamic overload and a more rapid induction of LV hypertrophy during myocardial dysfunction in male subjects.     

Diastolic dysfunction without abnormalities in left atrial and left ventricular geometry does not affect quality of life in elderly women

BACKGROUND/AIMS:

Advanced age and female sex are associated with increased myocardial stiffness, even in the absence of cardiovascular disease. Left ventricular (LV) hypertrophy and left atrial (LA) enlargement are typical findings in patients with LV diastolic dysfunction (DD). Because DD has been described in asymptomatic subjects, its clinical impact remains controversial. It has previously been hypothesized that mild DD has no clinical impact when natriuretic peptide levels are normal. The present study aimed to determine the impact of LA volume and LV mass on DD in elderly women.

METHODS AND RESULTS:

A cross-sectional survey was used to investigate a cohort of 311 randomly selected, nonhospitalized elderly women (mean [± SD] age 74.3±2.9 years). Examination comprised quality of life, measurement of brain natriuretic peptide (BNP) levels and echocardiography. The prevalences of different degrees of DD were as follows: mild 47.9% (n=149), moderate 36.7% (n=114) and severe 4.8% (n=15). Compared with normal diastolic function, moderate and severe DD were associated with higher BNP levels (P=0.038 and P<0.001, respectively) and elevated indexes of LA volume (LAVI) (P=0.007 and P<0.001, respectively) and LV mass (LVMI) (P=0.074 and P=0.017, respectively). Participants with normal diastolic function and mild DD had no significant differences in quality of life, BNP levels, LAVI or LVMI.

CONCLUSION:

Mild DD is common in elderly women and is not associated with increased BNP levels or poor quality of life. Compared with individuals with moderate and severe DD, LAVI and LVMI are normal in patients with mild DD.     

The interplay between haemodynamic load, brain natriuretic peptide and left atrial size in the early stages of essential hypertension

OBJECTIVE: Left atrial (LA) enlargement is an index of adverse cardiovascular events. We sought to investigate any possible correlation between haemodynamic load, neurohumoral factors and LA size in the early stages of essential hypertension. METHODS: We studied 94 consecutive middle-aged subjects, with newly diagnosed stage I-II essential hypertension without left ventricular (LV) hypertrophy and 34 age and sex-matched normotensive individuals. Ambulatory blood pressure (BP) monitoring, plasma levels of brain natriuretic peptide (BNP), metabolic profile and left atrial volume index (LAVI), an echocardiographic measurement of LA volume indexed for the body surface area, constituted the work-up of all subjects. RESULTS: Hypertensive compared with normotensive subjects had significantly increased office and ambulatory systolic and diastolic BP (P < 0.0001 for all cases) as well as body mass index and waist-to-hip ratio (P < 0.05 for both cases). BNP levels were greater in hypertensive compared with normotensive subjects but were not statistically significant (20.4 versus 17.1 pg/ml, P = NS). Hypertensive compared with normotensive subjects also had significantly increased LV mass index (105 versus 84 g/m, P < 0.0001), LA diameter (39 versus 36 mm, P < 0.0001), and LAVI (22 versus 19 ml/m, P < 0.05). In the hypertensive population, LAVI exhibited significant positive relationships with office systolic BP, ambulatory pulse pressure, LV mass index and BNP. In multiple linear regression analysis only LV mass index and BNP were significantly associated with LAVI (beta = 0.298, P = 0.030 and beta = 0.322, P = 0.009, respectively). CONCLUSIONS: Increased LAVI, closely associated with LV mass index and BNP, was still found in the early stages of essential hypertension. However, the clinical significance of these findings remains to be elucidated in future studies.     

BNP as a marker of diastolic dysfunction in the general population: Importance of left ventricular hypertrophy

BNP is a marker of systolic left ventricular dysfunction (LVSD) and heart failure. To assess BNP for the detection of diastolic dysfunction in the general population, we examined 1678 subjects within an age- and sex-stratified survey (MONICA Augsburg). BNP was measured using a commercially available RIA (Shionogi). BNP increased in subjects with diastolic dysfunction (mean 20.3+/-4.7 pg/ml vs. control 9.6+/-0.5 pg/ml, p<0.001), but to a lesser extent than in subjects with LV hypertrophy (LVH, mean 37.3+/-49.1 pg/ml, p<0.001 vs. control) or LVSD (mean 76.2+/-23.2 pg/ml, p<0.001 vs. control). Individuals with sole diastolic abnormality displayed BNP concentrations at the control level (mean 9.7+/-1.7 pg/ml). In univariate analysis, age, BMI, systolic blood pressure, left atrial size, LV mass index, diastolic dysfunction and EF displayed a significant correlation with BNP (p<0.001). However, LV mass index displaced diastolic dysfunction as a significant predictor of BNP in multivariate analysis. Upon ROC analysis, sensitivity and specificity for the detection of diastolic dysfunction by BNP were only 61% and 55%, respectively. Nevertheless, a normal BNP test virtually excluded the presence of diastolic dysfunction and concomitant LVH (NPV 99.9%). Increased BNP concentrations in subjects with diastolic dysfunction are strongly related to LVH. Population-wide screening for diastolic dysfunction with BNP cannot be recommended although a normal BNP test usually excludes diastolic dysfunction and LV hypertrophy.     

Usefulness of B-type natriuretic peptide and C-reactive protein in predicting the presence or absence of left ventricular hypertrophy in patients with systemic hypertension

The diagnosis of left ventricular (LV) hypertrophy, an independent predictor of death and cardiovascular events, is difficult without using echocardiography. This study tested the hypothesis whether C-reactive protein (CRP) and B-type natriuretic peptide (BNP) would be useful to exclude echocardiographic LV hypertrophy. Consecutive hypertensive outpatients were asked to participate. Exclusion criteria were overt heart failure, severe renal insufficiency or any other severe concomitant illness. A venous blood sample was taken to measure plasma CRP and BNP concentrations. Echocardiographic LV hypertrophy was defined as LV mass > or =125 g/m2 for men and > or =110 g/m2 for women. In total, 320 patients were studied, and 37 patients (12%) had echocardiographic LV hypertrophy. Patients with LV hypertrophy were significantly older and had higher CRP and BNP concentrations and higher systolic blood pressure than those without LV hypertrophy. The optimal cut-off points for the diagnosis of LV hypertrophy were 35 pg/ml for BNP (sensitivity 73%, specificity 72%) and 2.5 mg/L for CRP (sensitivity 68%, specificity 59%). Only 1 of 123 patients with values of BNP and CRP less than the optimal cut-off point had echocardiographic LV hypertrophy, resulting in a high negative predictive value of 99% for the 2 blood tests combined to exclude LV hypertrophy. In conclusion, in hypertensive patients, echocardiographic LV hypertrophy can be excluded on the basis of a single blood sample for the determination of BNP and CRP.     

Left ventricular mass and systolic dysfunction in essential hypertension

A relation between left ventricular (LV) hypertrophy and depressed midwall systolic function has been described in hypertensive subjects. However, a strong confounding factor in this relation is concentric geometry, which is both a powerful determinant of depressed midwall systolic function and a correlate of LV mass in hypertension. To evaluate the independent contribution of LV mass to depressed systolic function, 1827 patients with never-treated essential hypertension (age 48 +/- 12 years, men 58%) underwent M-mode echocardiography under two-dimensional guidance. Relative wall thickness was the strongest determinant of low midwall fractional shortening (r = -0.63, P < 0.0001). The significant inverse relation observed between LV mass and midwall fractional shortening (r = -0.43, P < 0.0001) persisted after taking into account the effect of relative wall thickness (partial r = -0.27, P < 0.0001). Within each sex-specific quintile of relative wall thickness, prevalence of subnormal afterload-corrected midwall systolic function was greater in subjects with, than in subjects without, LV hypertrophy (P < 0.05 for the first, third, fourth and fifth quintile). In a multiple linear regression analysis, both LV mass (P < 0.0001) and relative wall thickness (P < 0.0001) were independent predictors of a reduced midwall fractional shortening. In conclusion, the inverse association between LV mass and midwall systolic function is partly independent from the effect of relative wall thickness. LV hypertrophy is a determinant of subclinical LV dysfunction independently of the concomitant changes in chamber geometry.     

Epidemiology of left ventricular systolic dysfunction in the general population of Germany: results of an echocardiographic study of a large population-based sample]

The prevalence of left ventricular systolic dysfunction (LVSD) in the general population is poorly defined. Specifically, the number of asymptomatic individuals with LVSD and, thus, the most appropriate strategy to identify and treat such subjects is still unknown. Therefore, the aim of this study was to document LV dysfunction in a middle-aged (25 to 75 years, mean 51.8+/-13.8) population - based sample in Germany (MONICA Augsburg, n=1678; echocardiography technically adequate n=1418) by M-mode and 2D-echocardiography and to analyze the importance of predisposing contributors. The overall prevalence of an ejection fraction (EF) less than 48% (mean minus 2 SD=LVSD) was 2.3% (n=33), with a slightly higher rate in men than in women (2.8% vs 1.9%, n.s.). LVSD rate increased with age: from 1.5% in individuals younger than 40 years to 4.0% among those older than 60 years of age (p<0.05). Of 33 participants with reduced left ventricular systolic function, 20 presented with at least one cardiovascular disease. The most frequent diagnoses were arterial hypertension, obesity and coronary heart disease. Only 13 subjects (0.9%) of the study population were asymptomatic without a history of cardiovascular disease. Furthermore, only 6 subjects (0.4%, 4 male) in this population presented with a moderate impairment of LV function (EF of 30 to 40%) and only 1 subject (0.07%, male) had severe LVSD (EF less than 30%). Almost all subjects with an EF less than 40% (6 of 7 individuals) had a known history of cardiovascular disease. In conclusion, LVSD is a relatively common finding in the general population. However, severe LVSD is rare in subjects without any concomitant cardiovascular disease. Thus, echocardiographic screening cannot be recommended in the unselected, middle-aged population to identify such patients.     

The BNP assay does not identify mild left ventricular diastolic dysfunction in asymptomatic diabetic patients

Aims We examined the usefulness of BNP for screening for leftventricular (LV) diastolic dysfunction in a sample of type 2diabetic patients, without structural heart disorder, who havenever presented symptoms or signs of heart failure (HF). Methods and results Seventy-six consecutive patients admittedto the Outpatient Diabetes Clinic were studied. Blood sampleswere analyzed using the Triage BNP fluorescence immunoassay(Biosite Diagnostics, La Jolla, CA, USA). Echocardiography examinationswere performed, with no knowledge of the BNP value. A totalof 39 patients out of 76 (51%) were diagnosed with LV diastolicdysfunction and 23 (30%) with LV hypertrophy. Of the patientswith LV diastolic dysfunction, impaired relaxation and pseudonormalpattern accounted for 97 and 3% of the cases, respectively.BNP levels among subjects with LV diastolic dysfunction (26±22pg/ml,n=39) were not significantly different from patients with normalLV function (24±23pg/ml, n=37pg/ml; Mann–WhitneyU-test, Z=–0.4, n.s.). Conclusions Our data confirm alarmingly high prevalence of LVdiastolic dysfunction in asymptomatic individuals with diabetes.Identification of patients with preclinical diabetic cardiomyopathyshould be a research and clinical priority. BNP levels cannotbe used to detect mild LV diastolic dysfunction in this subsetof patients, which requires Doppler echocardiography to be detected.     

Left ventricular hypertrophy in severe obesity: interactions among blood pressure, nocturnal hypoxemia, and body mass

Obese subjects have a high prevalence of left ventricular (LV) hypertrophy. It is unclear to what extent LV hypertrophy results directly from obesity or from associated conditions, such as hypertension, impaired glucose homeostasis, or obstructive sleep apnea. We tested the hypothesis that LV hypertrophy in severe obesity is associated with additive effects from each of the major comorbidities. Echocardiography and laboratory testing were performed in 455 severely obese subjects with body mass index 35 to 92 kg/m(2) and 59 nonobese reference subjects. LV hypertrophy, defined by allometrically corrected (LV mass/height(2.7)), gender-specific criteria, was present in 78% of the obese subjects. Multivariable regression analyses showed that average nocturnal oxygen saturation <85% was the strongest independent predictor of LV hypertrophy (P<0.001), followed by systolic blood pressure (P<0.015) and then body mass index (P<0.05). With regard to LV mass, there were synergistic effects between hypertension and body mass index (P interaction <0.001) and between hypertension and reduced nocturnal oxygen saturation. Severely obese subjects had normal LV endocardial fractional shortening (35+/-6% versus 35+/-6%) but mildly decreased midwall fractional shortening (15+/-2% versus 17+/-2%; P<0.001), indicating subtle myocardial dysfunction. In conclusion, more severe nocturnal hypoxemia, increasing systolic blood pressure, and body mass index are all independently associated with increased LV mass. The effects of increased blood pressure seem to amplify those of sleep apnea and more severe obesity.     

Why is the concentration of plasma brain natriuretic peptide in elderly inpatients greater than normal?

BACKGROUND: Higher than normal levels of plasma brain natriuretic peptide (BNP) are often found in elderly patients without overt heart failure. OBJECTIVE: To investigate the relationships between echocardiographic findings and levels of BNP in inpatients undergoing rehabilitation. METHODS: Ejection fraction, early-to-atrial peak transmitral velocity ratio (EAR) and left ventricular mass index were calculated. The patients were 34 men and 83 women, aged 83.4 +/- 0.8 years (mean +/- SEM). RESULTS: The average BNP was 3.5 times higher than the normal range. Age of and BNP level in patients with mild renal dysfunction were significantly greater than age of and BNP level in those with normal renal function. BNP level in patients with left ventricular hypertrophy (LVH) was higher than that in patients without LVH, and there was a positive correlation between left ventricular mass index and BNP level. However, there was no difference between BNP levels of patients with ejection fraction < 50% and > or = 50% (n = 27 versus 90, ejection fractions 40 versus 64%, BNP levels 22.6 +/- 4.0 versus 17.5 +/- 1.6 pmol/l). Moreover, even elderly inpatients without LVH, without cardiovascular diseases, with sinus rhythm, with normal renal function, and with normal left ventricle systolic function had BNP levels that were greater than normal (n = 21, BNP level 11.0 +/- 1.5 pmol/l). We measured EAR of 76 of 90 patients with normal left ventricle systolic function, and 72 of the 76 patients had EAR < 1. CONCLUSION: These results indicate that renal dysfunction and systolic dysfunction as well as cardiac hypertrophy and lower than normal diastolic function contribute to the elevation of BNP levels in elderly inpatients who do not have overt heart failure.     

Effect of left ventricular dyssynchrony on plasma B-type natriuretic peptide levels in patients with long-term right ventricular apical pacing

Right ventricular apical pacing (RAP) has been reported to have the potential to lead to left ventricular (LV) dyssynchrony and impaired LV function. The plasma level of B-type natriuretic peptide (BNP) is increased in the state of abnormal ventricular wall stretch. Therefore, the aim of the present study was to examine the effect of LV dyssynchrony on BNP levels in patients with chronic RAP. Thirty-four patients (17 women, age 69 +/- 11 years) with preserved LV systolic function on permanent RAP (duration, 7.0 +/- 4.7 years) underwent conventional echo-Doppler assessment and tissue Doppler imaging. Twenty-two normal subjects (8 women, age 66 +/- 9 years) served as controls. The standard deviation (SD) and dispersion of the time-to-peak systolic velocity (TPV) among the 6 basal LV segments were used as the indexes of LV dyssynchrony. Compared with control subjects, RAP patients had prolonged TPVs and heterogeneous LV contraction with greater values of TPV-SD (18 +/- 8 ms versus 39 +/- 15 ms, P < 0.001) and TPV-dispersion (42 +/- 20 ms versus 93 +/- 31 ms, P < 0.001). There were significant correlations between BNP levels and the indexes of LV dyssynchrony (r = 0.41, P = 0.017 for TPV-SD; r = 0.46, P = 0.006 for TPV-dispersion). RAP is associated with LV dyssynchrony, which may accelerate BNP secretion.     

Haemoglobin level influences plasma brain natriuretic peptide concentration

OBJECTIVE: It has been demonstrated that the haemoglobin (Hb) level is associated with the prognosis of congestive heart failure (CHF). Correction of anaemia has improved CHF outcomes even in patients without anaemia. Lower Hb level may play a more important role in left ventricular (LV) dysfunction than previously recognized. This study aimed to evaluate the association of Hb level with plasma brain natriuretic peptide (BNP) level as a marker of LV function adjusted for known determinants of BNP. METHODS AND RESULTS: Association of Hb level with plasma BNP level was studied in 279 outpatients of cardiology (mean age 61 +/- 16, 54% men) using multivariate regression analysis. Mean Hb level was 13.7 +/- 1.5 g/dl and 14% of patients had anaemia. Median BNP level was 28 pg/ml (range < 4 to 580 pg/ml). In total subjects, the multivariate model adjusted for age, sex, history of CHF, atrial fibrillation, serum creatinine level, LV wall motion abnormality, end-diastolic LV dimension, LV mass index, and cardiovascular risk factors showed that a lower Hb level was significantly associated with higher BNP level (p = 0.0243). In "normal" subjects who did not have a history of CHF, atrial fibrillation, LV wall motion abnormality, LV dilatation, valvular abnormality, or LV hypertrophy, a lower Hb level was significantly associated with a higher BNP level (p = 0.0012) after adjustment for age, sex, serum creatinine level, and cardiovascular risk factors. CONCLUSIONS: Lower Hb levels are associated with higher plasma BNP levels independent of age, sex, serum creatinine level, LV wall motion abnormality, LV hypertrophy, history of CHF, atrial fibrillation, and cardiovascular risk factors.     

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.     

Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction.

OBJECTIVES: This study sought to characterize factors influencing amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and to evaluate the ability of NT-proBNP to detect left ventricular (LV) dysfunction in a large community sample. BACKGROUND: Secretion of BNP increases in cardiac disease, making BNP an attractive biomarker. Amino-terminal proBNP, a fragment of the BNP prohormone, is a new biomarker. We evaluated factors influencing NT-proBNP in normal patients and compared the ability of NT-proBNP and BNP to detect LV dysfunction in a large community sample. METHODS: Amino-terminal pro-BNP was determined in plasma samples of a previously reported and clinically and echocardiographically characterized random sample (n = 1,869, age > or =45 years) of Olmsted County, Minnesota. RESULTS: In normal patients (n = 746), female gender and older age were the strongest independent predictors of higher NT-proBNP. Test characteristics for detecting an LV ejection fraction < or =40% or < or =50% were determined in the total sample with receiver operating characteristic curves. Amino-terminal pro-BNP had significantly higher areas under the curve for detecting an LV ejection fraction < or =40% or < or =50% than BNP in the total population and in several male and age subgroups, whereas areas were equivalent in female subgroups. Age- and gender-adjusted cutpoints improved test characteristics of NT-proBNP. Both assays detected patients with systolic and/or moderate to severe diastolic dysfunction to a similar degree, which was less robust than the detection of LV systolic dysfunction alone. CONCLUSIONS: Amino-terminal pro-BNP in normal patients is affected primarily by gender and age, which should be considered when interpreting values. Importantly, in the entire population sample NT-proBNP performed at least equivalently to BNP in detecting LV dysfunction and was superior in some subgroups in detecting LV systolic dysfunction.     

Elevated cardiac troponin T predicts adverse outcomes in hypertensive patients

Ongoing myocardial damage detected as elevated serum cardiac troponin T (cTnT) indicates increased risk for future cardiac events in patients with chronic heart failure. Whether elevated cTnT is associated with adverse outcomes in patients with hypertension (HT) without left ventricular (LV) systolic dysfunction is unknown.We measured cTnT levels in 176 patients with essential HT without LV systolic dysfunction (LV ejection fraction ≤ 55%), renal failure, and prior cardiovascular or cerebrovascular diseases and 39 normal controls. Levels of cTnT were elevated (≥ 0.02 ng/mL) in 15 (9%) of the 176 patients and in 0 (0%) of the 39 normal controls (P = 0.04). The rate of diabetes mellitus (DM), the cardiothoracic ratio, plasma B-type natriuretic peptide (BNP) value, and LV mass index were significantly higher in patients with than without elevated cTnT (DM, 8/15 versus 29/161, P = 0.004; cardiothoracic ratio, 54.5 ± 4.5 versus 51.6 ± 5.2%, P = 0.04; BNP, 103.3 ± 142.3 versus 36.9 ± 50.7 pg/mL, P = 0.04; LV mass index, 227 ± 87 versus 152 ± 57 g/m(2), P = 0.0001). Kaplan-Meier analysis demonstrated that significantly fewer (P < 0.000001) patients with, than without elevated cTnT remained free of events (hospitalization due to cardiovascular or cerebrovascular disease, n = 34). Stepwise Cox multivariate analysis revealed that elevated cTnT (hazard ratio, 6.58; P = 0.000001) and smoking (hazard ratio, 2.24; P = 0.04) were independent predictors of events.The present findings indicate that cTnT is a novel and useful predictor of future cardiovascular or cerebrovascular events in hypertensive patients.     

Ventricular production of natriuretic peptides and ventricular structural remodeling in hypertensive heart failure

OBJECTIVES: Brain natriuretic peptide (BNP) is a strong predictor of left ventricular (LV) hypertrophy (LVH) and dysfunction. However, our recent studies suggested that LVH is not necessarily associated with enhanced production of BNP in hypertension. This study aimed to clarify the relation of the characteristics of hypertrophy with the degree of gene expression of BNP in the developmental process of hypertensive heart failure. METHODS: Serial changes in LV geometry, histology and atrial natriuretic peptide (ANP) and BNP mRNA levels, were assessed in a hypertensive heart failure model using Dahl salt-sensitive rats (n = 24). We further studied effects of alpha1-receptor antagonist (doxazosin: 1 mg/kg per day, n = 5) and angiotensin II type 1 receptor (AT1R) antagonist (candesartan cilexetil: 1 mg/kg per day, n = 5). RESULTS: The BNP mRNA level was not elevated at the compensatory hypertrophic stage when ANP mRNA level was elevated. BNP mRNA level was increased with further progression of hypertrophy and development of fibrosis. AT1R blockade prevented such fibrosis and further progression of hypertrophy with normalization of BNP mRNA levels. Compensatory hypertrophy was not suppressed; therefore, ANP mRNA level, although decreased, was still beyond the normal level. The alpha1-receptor blockade slightly attenuated LV hypertrophy with a slight decrease in ANP mRNA levels. LV fibrosis was not prevented, and the BNP mRNA level was not decreased. CONCLUSIONS: BNP gene expression is not enhanced by initial compensatory hypertrophy, but is enhanced by LV fibrosis and late stage progression of hypertrophy dependent on AT1R-mediated signaling pathway.     

Elevation of plasma brain natriuretic peptide is a hallmark of diastolic heart failure independent of ventricular hypertrophy

OBJECTIVES: We tested a hypothesis that elevation of the plasma level of brain natriuretic peptide (BNP) is one of the characteristics of patients with diastolic heart failure (DHF) independent of left ventricular (LV) hypertrophy. BACKGROUND: The clinical characteristics of DHF are not well acknowledged, although DHF has become a great social burden. Such a lack of clinical information leads to inaccuracy in the diagnosis of DHF. We have demonstrated enhancement of ventricular production of BNP with progression of maladaptive ventricular hypertrophy, but not with development of compensatory hypertrophy in an animal DHF model. METHODS: Of 372 patients who presented to the emergency department because of acute pulmonary congestion without acute coronary syndrome between January 1996 and May 2002, those with an ejection fraction > or =45% upon admission, who were stably controlled at least for a year in our outpatient clinics, comprised the DHF group (n = 19). A control group consisted of 22 hypertensive patients with a LV mass index greater than or equal to its minimum value of the DHF group and an ejection fraction > or =45%, in whom cardiac symptoms had not occurred. RESULTS: Despite a similar distribution of LV mass index, the BNP level was higher in the DHF group than in the control group (149 +/- 38 vs. 31 +/- 5 pg/ml, p < 0.01). There was no difference in LV cavity size or parameters derived from pulsed Doppler transmitral flow velocity curves. CONCLUSIONS: An elevation of BNP may be a hallmark of patients with or at risk of DHF among subjects with preserved systolic function independent of LV hypertrophy.     

Effect of compensated renal dysfunction on approved heart failure markers: direct comparison of brain natriuretic peptide (BNP) and N-terminal pro-BNP

Brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are markers of heart failure. Although renal dysfunction may increase plasma concentrations, the magnitude of this effect has not been assessed in a head-to-head comparison between the clinically approved tests. We assessed the effect of compensated renal dysfunction on BNP (Triage BNP; Biosite) and NT-proBNP (elecsys proBNP; Roche) in 469 randomly selected stable outpatients after myocardial infarction (MI; Monitoring Trends and Determinants in Cardiovascular Diseases [MONICA] register Augsburg) who were characterized with respect to renal function (glomerular filtration rate [GFR]; Cockroft method) and left ventricular (LV) ejection fraction (EF) and mass (2D echocardiography). BNP and NT-proBNP were elevated in MI patients with LV dysfunction (LVD; EF <35%) compared with MI patients with preserved EF ( >45%; BNP 139+/-27 pg/mL versus 75+/-6; NT-proBNP 816+/-237 pg/mL versus 243+/-20; both P <0.03). Among all MI patients, the prevalence of renal dysfunction (GFR <85 mL/min) was 24%. BNP and NT-proBNP were significantly elevated in MI patients with renal dysfunction (BNP 132+/-17 pg/mL versus 68+/-4 without renal dysfunction; NT-proBNP 535+/-80 pg/mL versus 232+/-19; both P <0.05), and both markers were correlated with GFR in univariate and multivariate analyses (all P <0.01). When binary cut-off values were stratified according to the absence or presence of renal dysfunction (BNP 75 pg/mL and 125 pg/mL, respectively; NT-proBNP 100 pg/mL and 350 pg/mL, respectively), the predictive power of both markers for the detection of LVD increased substantially. BNP and NT-proBNP are almost similarly influenced by mild-to-moderate renal dysfunction. Renal dysfunction is a potential cause of elevated marker concentrations in the absence of LVD, and cut-off concentrations should be stratified according to renal function.     

Plasma levels of brain natriuretic peptide in various forms of obstruction to the left ventricular outflow tract

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the relationship between plasma concentrations of brain natriuretic peptide (BNP) and the type or degree of stenosis in the left ventricular outflow tract (LVOT). METHODS: The relationship between BNP plasma level and pressure gradient (PG) in the LVOT and LV wall thickness (LVWth) was analyzed in 25 patients with a PG > or = 30 mmHg in the LVOT from the mid-left ventricle to the aortic valve. Among patients, 14 had aortic valve stenosis (AS), five had subaortic type hypertrophic obstructive cardiomyopathy (HOCM), three had mid-ventricular type HOCM, and three had angled ventricular septum. Three patients with AS showed LV systolic dysfunction (ejection fraction (EF) < 50%). All patients were in sinus rhythm. LV peak-systolic pressure (LVPSP) was derived by adding maximum PG to cuff systolic arterial pressure. RESULTS: In AS patients without LV systolic dysfunction and HOCM patients, there was a significant positive correlation between BNP and LVPSP (r = 0.78, p = 0.001; r = 0.76, p = 0.007, respectively). In AS patients without LV systolic dysfunction, BNP was positively correlated with LVWth (r = 0.79, p = 0.001), but no correlation was found between BNP and LVWth in patients with HOCM. In AS patients including systolic LV dysfunction, BNP was negatively correlated with LVEF (r = -0.87, p < 0.0001), but no correlation was found between BNP and LVEF in patients with HOCM. CONCLUSION: These results suggest that BNP level is closely associated with severity of stenosis in patients with HOCM, but mainly with severity of stenosis and also degree of LV systolic dysfunction in patients with AS. The BNP-LVWth relationship appeared to differ between AS (a fixed stenosis with uniform myocardial hypertrophy) and HOCM (a dynamic stenosis with uneven myocardial hypertrophy).     

Left Ventricular Diastolic Function in a Population Sample of Elderly Men

BACKGROUND AND METHODS: Echocardiography with Doppler has been widely used to assess left ventricular (LV) diastolic function. Interpretation of the diastolic indices that are derived, however, is confounded by the effects of physiological aging on the LV diastolic function. In this study, the usefulness of different Doppler-derived indices of LV diastolic function was assessed in elderly subjects by using data from a health screening survey of 584 men aged 70 years. RESULTS: The index of early versus late transmitral blood flow, the E/A ratio, was found to be reduced in the apparently healthy subgroup (n = 195) of the population (0.96 +/- 0.25) compared with previous data from middle-aged subjects. However, E/A ratios similar to those in the apparently healthy subjects were found in subjects with coronary heart disease (CHD), hypertension, and diabetes mellitus. Only subjects with systolic dysfunction (ejection fraction < 40%) showed a significantly decreased E/A ratio (0.79 +/- 0.21, P < 0.05) compared with the apparently healthy subjects. Isovolumic relaxation time (IVRT) was, however, significantly prolonged in subjects with CHD or hypertension compared with the apparently healthy subjects (139 +/- 32, 127 +/- 25, and 118 +/- 21 milliseconds, respectively; P < 0.01), whereas the E wave deceleration times (DT) were alike in both apparently healthy and unhealthy subjects. The diastolic and systolic components of the pulmonary venous blood flow were alike in apparently healthy and unhealthy subjects. Left atrial size was increased in all patients with disease, possibly indicating increased preload. CONCLUSION: In this population sample of elderly men, the commonly used E/A ratio did not distinguish between apparently healthy subjects and those with cardiovascular diseases such as CHD or hypertension, which are known to be associated with LV diastolic dysfunction in the middle-aged population. IVRT appeared to be the most sensitive of the Doppler-derived indices of LV diastolic function used in the present study, but for this variable, the differences between apparently healthy subjects and unhealthy subjects were small. Thus, the age-associated changes in LV compliance appear to override the impact of these disorders on indices of LV diastolic function in elderly populations.