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ABSTRACT: Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus.
We identified 11 223 patients referred for coronary angiography (CAG) in 1998-2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD (P< 0.001). In Cox's models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27-1.83) for patients with normal coronary arteries and 1.85 (1.51-2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07-1.56) and 1.52 (1.24-1.88), respectively.
Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.
European Heart Journal 09/2011; 33(6):734-44. · 10.48 Impact Factor
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Clinical Chemistry 12/2005; 51(11):2173-6. · 7.91 Impact Factor
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ABSTRACT: N-terminal pro-brain natriuretic peptide (NT-proBNP) provides important prognostic information in patients with chronic heart failure and in the general population. The aim of this study was to evaluate NT-proBNP as a prognostic marker of cardiovascular morbidity and death in a sample of subjects with hypertension and preserved left ventricular systolic function from the general population.
The study population was recruited from 4 general practitioners. The study participants (n = 569 subjects; ages, 50-89 years) completed a heart failure questionnaire and were submitted to blood pressure measurement, electrocardiography, echocardiography, and blood sampling. After exclusion of subjects with left ventricular ejection fraction of <50%, 270 subjects fulfilled the following criteria for hypertension: history of hypertension or blood pressure >150/90 mmHg. During 3 years of follow-up, 28 subjects (10.4%) reached the composite end point of death, stroke/transient ischemic attack, or myocardial infarction. After adjustment for cardiovascular risk factors, NT-proBNP (logarithmically transformed) independently predicted the risk of experiencing a composite end point (hazard ratio, 1.94; P < .0001), and death (hazard ratio, 2.28; P < .0001). The risk of having a composite end point (21 vs 7; P = .005) was significantly higher for subjects with NT-proBNP above the study median than for subjects with NT-proBNP below the study median.
In this sample of subjects with hypertension and preserved left ventricular systolic function from the general population, plasma NT-proBNP was found to be a valuable cardiovascular risk marker, independently of traditional risk factors and prevalent cardiovascular disease.
Journal of Cardiac Failure 06/2005; 11(5 Suppl):S70-5. · 3.66 Impact Factor
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ABSTRACT: B-type natriuretic peptides have been shown to predict cardiovascular disease in apparently healthy individuals but their predictive ability for mortality and future cardiovascular events compared with C-reactive protein (CRP) and urinary albumin/creatinine ratio is unknown.
To assess the prognostic value of the N-amino terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) vs CRP and urinary albumin/creatinine ratio in an older adult population.
A population-based prospective study of 764 participants aged 50 to 89 years from a community in Copenhagen, Denmark, in which 658 participants provided blood and urinary samples and were examined between September 1, 1998, and January 24, 2000. Of these participants, 626 without heart or renal failure were enrolled. A subgroup of 537 had no history of cardiovascular disease at baseline. During 5 years of follow-up (to December 31, 2003), 94 participants died and 65 developed a first major cardiovascular event.
Risk of mortality and first major cardiovascular event by baseline levels of NT-proBNP, CRP, and urinary albumin/creatinine ratio levels.
After adjustment for the cardiovascular risk factors of age, sex, smoking, diabetes mellitus, hypertension or ischemic heart disease, total cholesterol, and serum creatinine, the hazard ratio (HR) of mortality for values above the 80th percentile of NT-proBNP was 1.96 (95% confidence interval [CI], 1.21-3.19); for CRP, 1.46 (95% CI, 0.89-2.24); and for urinary albumin/creatinine ratio, 1.88 (95% CI, 1.18-2.98). Additional adjustment for left ventricular systolic dysfunction did not markedly attenuate the predictive value of NT-proBNP (HR, 1.82; 95% CI, 1.11-2.98). The absolute unadjusted increase in mortality risk for participants with values above the 80th percentile vs equal to or below the 80th percentile was 24.5% for NT-proBNP, 7.8% for CRP, and 19.5% for urinary albumin/creatinine ratio. The NT-proBNP levels were associated with first major cardiovascular events (nonfatal myocardial infarction, fatal coronary heart disease, unstable angina, heart failure, stroke, and transient ischemic attack) with an adjusted HR of 3.24 (95% CI, 1.80-5.79) vs 1.02 (95% CI, 0.56-1.85) for CRP and 2.32 (95% CI, 1.33-4.05) for urinary albumin/creatinine ratio when comparing participants with values above the 80th percentile with those with values equal to or below the 80th percentile.
Measurements of NT-proBNP provide prognostic information of mortality and first major cardiovascular events beyond traditional risk factors. NT-proBNP was a stronger risk biomarker for cardiovascular disease and death than CRP was in nonhospitalized individuals aged 50 to 89 years.
JAMA The Journal of the American Medical Association 05/2005; 293(13):1609-16. · 30.03 Impact Factor
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ABSTRACT: Symptoms in patients with heart failure and preserved left ventricular ejection fraction may be caused by isolated diastolic dysfunction. The purpose of this study was to assess the prevalence of diastolic dysfunction as a potential cause of dyspnea in a sample of elderly subjects, as well as of isolated diastolic dysfunction as a potential cause of dyspnea in a subgroup with a preserved left ventricular ejection fraction and normal lung function.
A total of 152 subjects with dyspnea underwent echocardiography, electrocardiography, and lung function testing. Subjects with normal lung function test results (n = 60) underwent cardiac magnetic resonance imaging, chest radiography, bicycle exercise tests, and blood tests. Left ventricular diastolic function was assessed by a variety of echocardiographic/Doppler techniques.
Of 129 subjects with dyspnea, 81 (63%) had signs of lung disease or 'obvious' cardiac disease. In the remaining 48 subjects, 32 (67%) had a potential cardiac/noncardiac cause of dyspnea. In all subjects with dyspnea, 1% to 11% had diastolic dysfunction, and in the 48 remaining subjects, 0% to 10% had isolated diastolic dysfunction, depending on the definition used.
The frequency of diastolic dysfunction was low in the sample of elderly subjects with dyspnea as well as in the subgroup of persons with no signs of lung disease, left ventricular systolic dysfunction, atrial fibrillation, or valvular heart disease. Diastolic dysfunction was infrequent as a possible cause of dyspnea, and coexisting potential causes of dyspnea were often present.
The American Journal of Medicine 02/2005; 118(1):25-31. · 5.43 Impact Factor
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ABSTRACT: Recently there has been a growing interest in risk assessment of individuals, using biochemical markers of cardiac risk, with an increasing focus on a multi-marker strategy. Natriuretic peptides (BNP and NT-proBNP) are well-established markers of increased risk in the general population and in high-risk groups with hypertension, and coronary heart disease. However, there is at present no indication for routine measurements of natriuretic peptides in the risk assessment of individuals or patients, as there is no evidence for subsequent therapeutic initiatives. Natriuretic peptides are useful when screening for heart failure in symptomatic individuals. However, the use of NT-proBNP screening for risk or left ventricular systolic dysfunction in the general population is still a matter of debate.
Scandinavian journal of clinical and laboratory investigation. Supplementum 02/2005; 240:138-42.
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ABSTRACT: To determine the prognosis, total mortality and cardiac morbidity, of patients with left ventricular systolic dysfunction and heart failure (HF) in a general population sample.
A total of 764 subjects, 432 females and 332 males, median age (range) 66 years (50-89), participated in this cross sectional survey. The study population was recruited from randomly selected general practitioners and stratified to include a minimum of 150 persons in each age decade stratum. Each participant filled in a heart failure questionnaire and ECG, blood tests and echocardiography were performed. Median (range) follow-up was 1145 (51-1197) days. Subjects with LVEF < or = 0.40 had a significantly higher all-cause mortality (27.8% vs. 5.6%, P<0.0001), admission rate for HF (25.0% vs. 1.9%, P<0.0001) and for other cardiac causes (25.0% vs. 6.3%, P<0.0001) than in subjects with LVEF>0.40. The age and gender adjusted 2-year relative risk of death was 4.6 (95% C.I.=1.6-13.2). No significant difference in mortality was found between subjects with or without heart failure symptoms.
Significantly higher mortality as well as cardiac morbidity was found in subjects with symptomatic and asymptomatic LV systolic dysfunction compared to those with normal systolic function. These conditions were among the strongest predictors of all-cause mortality and cardiac morbidity.
European Journal of Heart Failure 08/2004; 6(5):653-61. · 4.90 Impact Factor
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ABSTRACT: Knowledge about the occurrence of isolated diastolic dysfunction (DD) in the general population is limited.
This population study was performed to assess the frequency and distribution pattern of echocardiographic indices of left ventricular (LV) DD in an elderly population aged 50-89 years in which LV systolic function is preserved.
The study population (n=764) recruited from the background population answered a heart failure questionnaire and underwent echocardiography. Excluding subjects with a LV ejection fraction <50% or atrial fibrillation, diastolic function was evaluated in 647 subjects. The frequency of impaired relaxation according to earlier guidelines was 0.5%, vs. 2.5% using age- and gender-specific normal values of 'E/A-ratio' and 'deceleration time'. In a subpopulation of 167 participants, 6.6% had 'pseudonormalisation'. No difference was found in the frequency of dyspnea in subjects with impaired relaxation or 'pseudonormalisation' compared to subjects with normal filling pattern.
The prevalence of LV impaired relaxation was highly dependent on the choice of normal (cut-off) values for Doppler indices. Furthermore, our findings suggest that either isolated DD is often asymptomatic, or that Doppler flow derived parameters as a diagnostic method for assessing DD have a low specificity when used as a screening tool in the general population.
European Journal of Heart Failure 06/2004; 6(4):439-47. · 4.90 Impact Factor
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ABSTRACT: N-terminal B-type natriuretic peptide (NT-pro-BNP) is secreted from the cardiac ventricles in response to volume expansion and pressure overload, and serum levels are elevated in systolic heart failure. The aim of this study was to evaluate the influence of thyroid function on NT-pro-BNP.
Patients with overt or subclinical thyroid disease were evaluated before and after treatment for their dysthyroid state.
Seventeen overt and 21 subclinical hypothyroid patients together with six subclinical and 13 overt hyperthyroid patients without cardiac disease were included. Subclinical states had, by definition, free T4 and free T3 estimates within reference ranges.
Serum levels of NT-pro-BNP and thyroid hormones were measured, and in 31 patients resting cardiac output was measured by impedance cardiography in the untreated state.
NT-pro-BNP levels were more than four times higher in hyperthyroid than hypothyroid patients, with mean values of 30 and 7 pmol/l, respectively (P < 0.001). Serum NT-pro-BNP levels correlated to the thyroid function (vs. free T4 estimate: r = 0.52, P < 0.0001, n = 57). Treatment resulted in significant increases in NT-pro-BNP in both hypothyroid groups, and decreases in both hyperthyroid groups. A multiple linear regression analysis demonstrated that free T4 and free T3 (P < 0.001) estimates were independently associated with a high serum NT-pro-BNP, whereas cardiac output and resting pulse rate were not.
Serum NT-pro-BNP levels are affected by thyroid function. This seems due to a direct stimulatory effect of thyroid hormones.
Clinical Endocrinology 01/2004; 60(1):54-9. · 3.17 Impact Factor
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ABSTRACT: Previously, electrical injuries have been suggested caused only by the concomitant heat developed during the passage of an electrical current. Recent experimental studies on fully anesthetized pigs and the study of one human case have, however, shown typical electrical alterations. The purpose of the present study was further to evaluate the histology of electrically induced changes in the skin in humans. In addition, supplementary in vivo methods for evaluation of skin changes as high-frequency ultrasound and Raman spectroscopy were used. The skin of 11 patients treated with a defibrillation of the heart was examined for macroscopic changes, the skin of eight of them also for histologic changes and for changes observable via supplementary methods. Immediately and 7 days after the defibrillation, fractions of a narrow red ring were observed along the periphery of the tin-foil electrode. Epidermis showed signs previously observed following electrical influence: segmental alterations often related to the openings of sweat ducts, darkstaining or "empty" nuclei and homogeneous cytoplasm, eosinophilic or pale. Dermis did not show the specific sign of electrical influence: deposits of calcium salts on dermal fibres, neither via histologic examination nor via high-frequency ultrasonography and Raman spectroscopy. Fractions of a narrow red ring along the periphery of the electrode showing histological signs of electric influence in epidermis thus appear to be characteristic of high voltage electrical injury.
Forensic Science International 08/2003; 134(2-3):134-41. · 2.30 Impact Factor
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ABSTRACT: Measurement of cardiac natriuretic peptides or their precursors in plasma appears promising in the diagnosis of heart failure. However, the currently available assays to measure pro-B-type natriuretic peptide (proBNP)-derived peptides have produced grossly discrepant results.
We treated plasma with trypsin before assay and used in the assay an antibody specific for a processing-independent epitope of human proBNP. We then determined the total concentration of proBNP and its products in healthy volunteers and heart-failure patients.
The antiserum produced (no. 98192) required an intact proBNP NH2 terminus for binding and displayed a high titer, index of heterogeneity, and binding affinity, implying that the RIA was monospecific and highly sensitive. Preanalytical tryptic treatment of plasma cleaved proBNP forms to release the N-terminal 1-21 fragment. Furthermore, enzymatic treatment of plasma also was efficient in avoiding nonspecific interference from plasma proteins, making it an expedient alternative to extraction. In healthy individuals, the total proBNP concentrations increased with age from 2.0 pmol/L (range, 0-15 pmol/L; ages 51-65 years) to 22 pmol/L (range, 3-40 pmol/L; ages 66-88 years; P <0.0001). The increase in plasma proBNP in the elderly, however, also seems to reflect the prevalence of cardiac disease. Plasma concentrations in patients with heart failure were all markedly increased [median, 89 pmol/L (range, 29-659) vs 1.0 pmol/L (range, 0-16) in age-matched controls; P <0.0001].
The processing-independent analysis measures the total proBNP product irrespective of the degree of proBNP processing. The results show that proBNP and its products circulate in low picomolar concentrations in healthy individuals.
Clinical Chemistry 08/2002; 48(7):1035-42. · 7.91 Impact Factor
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ABSTRACT: Brain- and N-terminal pro brain natriuretic peptide (NT-proBNP) have been identified as promising markers for heart failure. However, previous studies have revealed that they may hold insufficient diagnostic power for implementation into clinical practice because of a significant overlap in the range of plasma levels between healthy subjects and subjects with heart failure. We hypothesized that imprecision of the reference method (ie, the echocardiographic evaluation of left ventricular [LV] function) may have affected results from those earlier studies. We therefore wanted to investigate the diagnostic potential of NT-proBNP with magnetic resonance imaging as the reference method for the cardiac measurements.
Forty-eight patients with stable symptomatic heart failure in New York Heart Association functional classifications II to IV were examined once with blood samples and magnetic resonance imaging along with 20 age-matched and gender-matched healthy control subjects.
NT-proBNP was associated with LV end-diastolic (r = 0.69; P <.0001) and end-systolic (r = 0.73; P <.0001) volume indices, LV mass index (r = 0.69; P <.0001), and LV ejection fraction (r = -0.75; P <.0001). Receiver operating characteristic curves were calculated for the ability of NT-proBNP to detect LV end-diastolic volume index (>105 mL. m(-2)[cut-off]; sensitivity/specificity, 82%/87%), LV end-systolic volume index (>35 mL. m(-2); sensitivity/specificity, 86%/86%), LV mass index (>152 g. m(-2); sensitivity/specificity, 85%/86%), and LV ejection fraction (<58%; sensitivity/specificity, 84%/85%) deviating more than 2 standard deviations from control values.
NT-proBNP is a powerful marker for LV dimensions and systolic function in patients with heart failure and discriminates well between healthy subjects and subjects with impaired LV systolic function or increased LV dimensions.
American heart journal 06/2002; 143(5):923-9. · 4.65 Impact Factor
