Blood test: protein NT-proBNP

Blood test predicts cardiac events and death in heart patients

A simple blood test for the protein NT-proBNP accurately predicts the risk of heart attack, heart failure, stroke, and death in patients with known cardiovascular disease, according to a study led by a researcher at the San Francisco VA Medical Center.

The study of 987 men and women with stable coronary heart disease revealed that the higher a patient's level of NT-proBNP, the greater the chance the patient would die or have a cardiovascular event - heart attack, heart failure, or stroke.

"After adjusting for all other risk factors, it's clear that this marker is picking up something that we are otherwise unable to detect with standard tests such as echocardiography," says principal investigator Mary Whooley, MD, a staff physician at SFVAMC and an associate professor of medicine at the University of California, San Francisco.

NT-proBNP is a marker in the blood for BNP, a hormone that "goes up during times of cardiac stretch or stress," explains Whooley. "When the heart wall is over-expanded by too much blood volume, or damaged by lack of blood flow to the heart itself, BNP goes up, and NT-proBNP along with it."

Patients in the study were divided into four quartiles depending on their NT-proBNP blood levels, and followed for an average of 3.7 years each. Twenty-six percent died or had a cardiovascular event during the course of the study. The study reports that "each increasing quartile was associated with a greater risk of cardiovascular events or death." Patients in the quartile with the highest levels of the biomarker were 3.4 times more likely to die or have a cardiovascular event than patients in the group with the lowest levels.

Whooley cautions that the NT-proBNP test is "not something that we should order on every patient who comes in for a routine checkup," but would be most useful for patients with known coronary heart disease. "In the general population, the incidence of heart disease is so low relative to the incidence in heart disease patients that you get many more false positive results than true positives, which really lowers the value of the test," she says. "It's much better at predicting risk in a population with a high incidence of heart disease."

Whooley also notes that, even among heart patients, the value of the test is limited "because all of the therapies available to prevent cardiovascular events should already be used among these patients. The best it can do is help identify candidates for more aggressive therapy."

She says that one additional step for researchers is to see "whether there are therapeutic interventions that still remain to be developed that might prevent heart patients with elevated BNP from doing worse."

Patients in the current study were all enrolled in the Heart and Soul Study, a multi-year prospective study of one thousand heart patients directed by Whooley that is designed to investigate whether depression predicts heart disease. "Because the Heart and Soul Study measures heart disease so carefully, our data set has become extremely valuable for a wide range of cardiovascular studies, many of which have nothing to do with our original hypothesis," Whooley says. "This study is just one example."

University of California-San Francisco
http://www.brightsurf.com/news

Endothelial dysfunction and Pregnancy loss

A Link Among Preeclampsia, Recurrent Pregnancy Loss, and Future Cardiovascular Events?

Alfredo M. Germain; Mary Carmen Romanik; Irene Guerra; Sandra Solari; María Soledad Reyes; Richard J. Johnson; Karen Price; S. Ananth Karumanchi; Gloria Valdés
From the Departmentos de Obstetricia/Ginecología (A.M.G., M.C.R., M.S.R.), Nefrología (G.V.), and Laboratorio Clínico (I.G., S.S.), Escuela de Medicina Pontificia Universidad Católica, Santiago, Chile; the Section of Nephrology, Hypertension, and Transplantation (R.J.J., K.P.), University of Florida, Gainsville; the Departments of Medicine and Obstetrics and Gynecology (S.A.K.), and Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, Mass.

We tested the hypothesis that endothelial dysfunction could cause placentation-related defects, persist after the complicated pregnancy, and probably cause cardiovascular disease later in life. Brachial arterial reactivity and factors related to endothelial dysfunction, such as circulating cholesterol, uric acid, nitrites, L-arginine, asymmetrical dimethylarginine, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptor-1, in women with previous healthy pregnancies (n=22), patients with severe preeclampsia (n=25), or patients with recurrent pregnancy loss (n=29), at day 10 of the luteal phase of an ovulatory cycle an average of 11 to 27 months after pregnancy were evaluated. Both groups with placentation defects had a significant decrease in endothelium-dependent dilatation, a higher rate of endothelial dysfunction, lower serum nitrites, and higher cholesterol as compared with control subjects; subjects with previous preeclampsia additionally had higher normal blood pressures and a greater parental prevalence of cardiovascular disease. Patients with recurrent pregnancy loss also demonstrated a significantly lower endothelium-independent vasodilatation. A trend to an inverse correlation was found between serum cholesterol serum and endothelial-mediated vasodilatation in the whole study population. Uric acid, L-arginine, asymmetrical dimethylarginine, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptor-1 were similar in all of the groups. We postulate that endothelial dysfunction may represent a link between preeclampsia and increased cardiovascular disease latter in life and propose that women with unexplained recurrent miscarriages are also at increased cardiovascular risk. The identification and correction of endothelial dysfunction detected during the reproductive stage on obstetric outcome and on cardiovascular diseases needs to be elucidated.

Key Words: endothelial dysfunction • endothelium-mediated vasodilatation • pregnancy • preeclampsia • recurrent abortion • cardiovascular risk

http://hyper.ahajournals.org/cgi/content/abstract/49/1/90
Hypertension. 2007;49:90.

© 2007 American Heart Association, Inc.

Syncope: Heart-rate variability&Tilt test

Spectral and Time-Domain Analyses of Heart-Rate Variability During Head-Upright Tilt-Table Testing in Children with Neurally Mediated Syncope

Harun Evrengul (1, 4), Vedide Tavlı (2), Havva Evrengul (2), Talat Tavlı (3) and Dursun Dursunoglu (1)
1) Pamukkale University School of Medicine, Denizli, Turkey, 2) Division of Pediatric Cardiology, Dr. Behçet Uz Sick Children’s Hospital, Izmir, Turkey, 3) Celal Bayar University School of Medicine, Manisa, Turkey, 4) Yunus Emre Mh. 6402 sk., 12/7 Kınıklı, Denizli, Turkey

Neurocardiac syncope (NS) is a common cause of syncope in children. The mechanism, though related to abnormalities in autonomic function, has not been fully elucidated, particularly in pediatric patients. This study assessed the heart-rate variability (HRV) response to head-upright tilt-table test (HUT) in children with NS and normal volunteers. Spectral and time-domain analysis of HRV was used to assess changes in autonomic function in 27 children (9 male, mean age 12.3 ± 1.6 years) with a history of at least one episode of syncope and positive passive HUT and 27 age-matched normal volunteers with negative passive HUT before and during postural tilt and to attempt to relate such changes to specific types of hemodynamic response to tilt. Frequency-domain measurements of the high-(HF) and low-(LF) frequency bands and the ratio LF/HF were derived from Holter recordings and computed by fast Fourier analysis for 5-min intervals. Time-domain measurements of the SDNN, SDNNI, SDANN, RMSSD, and triangular index were derived from 24-h Holter recordings. There were no significant differences between clinical characteristics, time-domain, and basal frequency domain parameters of the groups. Mean values of LF and LF/HF ratio was increased and HF was decreased significantly in response to tilt in both patient and control groups. Mean values of LF and LF/HF ratio were higher and HF was lower compared to controls immediately after tilt. LF and LF/HF ratio showed a statistically significant decrease and a significant increase in HF during syncope in patients. The three subgroups of patients had similar patterns of changes in autonomic activity. The results of this study show that although the basal autonomic function was similar to that of the control group, patients with NS have a different pattern of response to the HUT. In our study, patients with NS demonstrated an exaggerated response to the HUT. This exaggerated response may be the factor that activates the pathological reflexes of NS. The pathological mechanism leading to NS appears to be independent of the specific type of hemodynamic response to HUT.

Key words: Neurocardiac syncope - Tilt test - Heart-rate variability

Pediatric Cardiology

Volume 27, Number 6 / December, 2006, p. 670-678

Preeclampsia: screening test

Inositol Phosphoglycan P-Type in Preeclampsia
A Novel Marker?

Philip J. Williams; Khalid Gumaa; Marco Scioscia; Christopher W. Redman; Thomas W. Rademacher
From the Department of Molecular Pathology (P.J.W., M.S., T.W.R.), Molecular Medicine Unit, Royal Free and University College Medical School, London, United Kingdom; the College of Medicine and Medical Sciences (K.G.), Arabian Gulf University, Manama, Kingdom of Bahrain; the Department of Obstetrics and Gynaecology (M.S.), University of Bari, Bari, Italy; and the Nuffield Department of Obstetrics and Gynaecology (C.W.R.), University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.

A state of insulin resistance has been demonstrated in active preeclampsia, and women with clinical evidence of insulin resistance are at higher risk to develop this syndrome during pregnancy. Recently, inositol phosphoglycan P-type, a putative second messenger of insulin action, has been implicated in the pathophysiology of preeclampsia and is increased in the placenta, amniotic fluid, and maternal urine of preeclamptic women compared with normal pregnant women. We report here a case–control study to assess the potential of urinary levels of inositol phosphoglycan P-type as a screening test for preeclampsia. Twenty-seven preeclamptic women and 47 healthy pregnant women were recruited. A polyclonal antibody-based ELISA was developed to detect levels of inositol phosphoglycan P-type in urine. Its content in urinary specimens was found to be 30-fold higher in preeclamptic subjects than control subjects (329.1±21.8 versus 9.2±1.5; P<0.001),>1 gestational date sample of urine was available, and retrospective analysis showed a significant time-related increase of the urinary level of inositol phosphoglycan P-type 7 weeks before clinical diagnosis of preeclampsia. Urinary level of inositol phosphoglycan P-type increased after diagnosis indicating a possible pathophysiological threshold level and steeply decreased after delivery.

Key Words: preeclampsia • screening test • inositol phosphoglycan • biological marker • insulin resistance

Hypertension. 2007;49:84.

© 2007 American Heart Association, Inc.

Blood Pressure: Control Outside

Effectiveness of Blood Pressure Control Outside the Medical Setting

J.R. Banegas, F. Rodríguez-Artalejo, J.J.de la Cruz (1); M.Gorostidi (5); Julián Segura (2); Javier Sobrino (3); A.de la Sierra (4); A. Sarría (6); L.M. Ruilope for the Spanish Society of Hypertension Ambulatory Blood Pressure Monitoring Registry Investigators
1) Department of Preventive Medicine and Public Health , Autonomous University of Madrid, Madrid, Spain; 2) Hypertension Unit, Doce de Octubre Hospital, Madrid, Spain; 3) Hypertension Unit, Esperit Sant Hospital, Santa Coloma de Gramenet, Barcelona, Spain; 4) Hypertension Unit, Clinic Hospital, Barcelona, Spain; 5) Nephrology Section, San Agustín Hospital, Avilés, Asturias, Spain; 6) Health Technology Assessment Agency, Carlos III Institute of Public Health, Madrid, Spain

We studied the effectiveness of blood pressure (BP) control outside the clinic by using ambulatory BP monitoring (ABPM) among a large number of hypertensive subjects treated in primary care centers across Spain. The sample consisted of 12 897 treated hypertensive subjects who had indications for ABPM. Office-based BP was calculated as the average of 2 readings. Twenty-four–hour ABPM was then performed using a SpaceLabs 90207 monitor under standardized conditions. A total of 3047 patients (23.6%) had their office BP controlled, and 6657 (51.6%) were controlled according to daytime ABPM. The proportion of office resistance or underestimation of patients’ BP control by physicians in the office (office BP 140/90 mm Hg and average daytime ambulatory BP <135/85 mm Hg) was 33.4%, and the proportion of isolated office control or overestimation of control (office BP <140/90 mm Hg and average daytime ambulatory BP 135/85 mm Hg) was 5.4%. BP control was more frequently underestimated in patients who were older, female, obese, or with morning BP determination than in their counterparts. BP control was more frequently overestimated in those who were younger, male, nonobese, smokers, or with evening BP determination. Ambulatory-based hypertension control was far better than office-based hypertension control. This conveys an encouraging message to clinicians, namely that they are actually doing better than is evidenced by office-based data. However, the burden of underestimation and overestimation of BP control at the office is still remarkable. Physicians should be aware that the likelihood of misestimating BP control is higher in some hypertensive subjects.


Key Words: office blood pressure • ambulatory blood pressure • treatment goals • guidelines • control

Hypertension. 2007;49:62.
© 2007 American Heart Association, Inc.
http://hyper.ahajournals.org/cgi/content/abstract/49/1/62