Heart Attack and LVD

What Is a Heart Attack?
According to the American Heart Association, someone dies from heart and blood vessel disease every 34 seconds in the US.
It is America’s number-one killer. A "coronary" or heart attack occurs when the blood flow to a part of the heart is blocked. This blockage often results from a clot because the arteries that supply the heart with blood are affected by fat, cholesterol, and other substances called plaque.
If the plaque breaks open and a blood clot forms, it can block the flow of blood to the heart. Without blood to nourish the muscle in the heart, it begins to die. The longer the artery remains blocked, the more damage is done until the muscle supplied by that artery is completely dead.

What is LVD?
The left lower chamber (ventricle) of the heart receives blood from the left atrium and pumps it out to the body under high pressure through the aorta.
When the heart muscle tissue has been scarred from a heart attack to the point it is not as effective as it should be, it does not pump enough blood to the rest of the body. This is known as left ventricular dysfunction or LVD.
LVD is often diagnosed after a heart attack. In some cases, it develops over time and is not diagnosed right away. There may be no symptoms with LVD, but they could develop if the heart muscle continues to weaken. This will lead to symptoms of heart failure.


Major Causes and Risk Factors
The plaque that builds up in the arteries can eventually rupture and cause a blood clot in a coronary artery.
This is a major, underlying cause of heart attacks. Factors that increase your risk for narrowed coronary arteries - and thus a heart attack - include family history of heart disease, a high level of LDL cholesterol (the "bad" cholesterol), high blood pressure, smoking, obesity, and physical inactivity.

These risk factors are described in detail below:

• High blood pressure is usually defined as 140/90 mmHg or more. Slight fluctuations are normal. However, if the pressure remains high for a long period of time, there is increased danger that it will speed up atherosclerosis or the buildup of fatty deposits in the blood vessels.
• High cholesterol is one of the main reasons that blood vessels become clogged and narrower than they should be. If you have too much cholesterol, you increase the risk of narrowing your arteries and thus the risk of having a heart attack. Some cholesterol, called high density lipoprotein (HDL) cholesterol, is good; but the low density type (LDL) is bad. This comes mainly from foods that are high in fats and cholesterol.
• Cigarette smoking and exposure to second-hand smoke can do more damage than just cause lung cancer. It is also responsible for depositing cholesterol on the walls of the blood vessels.
• Not enough exercise can be a risk factor for heart attacks. Physical activity and regular exercise help to keep your blood pressure in control and also help to reduce your cholesterol.
• Being overweight is a risk factor for heart attacks because it can indicate that you do not get enough exercise and do not eat properly. People who also have diabetes may be at increased risk for heart disease. Diabetes refers to the inability of the body to produce enough of a hormone called insulin or the inability of your body’s insulin to process blood sugar properly. Having diabetes can result in increased cholesterol levels.
• Too much stress and tension in your life can increase your blood pressure, which can put you at risk for a heart attack.
• Drinking too much alcohol can raise your blood pressure and triglyceride levels, and that can increase your risk for a heart attack.
• Of course, some people are more prone to heart attack because of family history. If you have close relatives who have had heart attacks, you might be at risk as well.
  

http://www.coreg.com/ncmp/heartattack/causes_of_heart_attack.htm

Transthoracic Doppler echocardiography

Noninvasive Visualization and Measurement of Middle Cardiac Vein Flow by Transthoracic Doppler Echocardiography

Kenji Harada, Masamichi Tamura and Manatoma Toyono
Department of Pediatrics, Akita University School of Medicine, 010-8543 Akita, Japan

Transthoracic Doppler echocardiography offers a noninvasive approach for imaging posterior descending coronary artery (PD) running in the posterior longitudinal sulcus along the middle cardiac vein (MCV).

To evaluate whether the MCV flow velocity reserve can reflect the PD flow reserve, 22 children with various heart diseases were examined using transthoracic Doppler echocardiography.

Introduction of a modified transthoracic two chamber view with the transducer rotated counterclockwise and angulated posteriorly allows visualization of the MCV and PD. Peak systolic flow velocity and average peak systolic flow velocity in the MCV and peak diastolic flow velocity and average peak diastolic flow velocity in the PD were measured at rest and hyperemic conditions (intravenous administration of adenosine of 0.16 mg/kg/min).

Coronary flow reserve was defined as the ratio of peak hyperemic to basal average peak flow velocity. ATP infusion induced significant increases in the peak systolic flow velocity and average peak systolic flow velocity in the MCV. The mean MCV flow velocity reserve in the patients was 1.94 ± 0.44. Significant increases in the peak diastolic flow velocity and the average peak diastolic flow velocity in the PD were also observed during ATP infusion, and the mean PD flow velocity reserve (2.19 ± 0.62) was significantly higher than the GCV flow velocity reserve (p < 0.0001).

There was a good correlation between the MCV flow velocity reserve and PD flow velocity reserve (r = 0.86, p <>

However, the degree of the MCV flow during hyperemia was less than that of the PD flow. This underestimation should be considered when the reactive hyperemic response is evaluated from the MCV flow velocity.

Keywords. Transthoracic Doppler echocardiography - Coronary flow reserve - Posterior descending coronary artery - Middle cardiac vein

Pediatric Cardiology

Volume 27, Number 6 / December, 2006, p. 679-684

Familial atrial fibrillation

Atrial Fibrillation with Hyperthyroidism in a 14-Year-Old Male

Hisashi Takasugi, Kota Ao, Tetsuya Sato, Akihiko Maeda, Taisuke Okada and Hiroshi Wakiguchi
Department of Pediatrics, Program of Baio-signaling and Infection Control, Kochi Medical School, Kochi University, Kohasu, Oko, Nankoku Kochi, 783-8505, Japan

Atrial fibrillation is an uncommon feature of hyperthyroidism in childhood. We report a 14-year-old male who was referred to our hospital with hyperthyroidism and atrial fibrillation. He had a family history of atrial fibrillation. Spontaneous conversion of atrial fibrillation to sinus rhythm occurred 20 weeks after achieving euthyroid state by an antithyroid agent and a β-blocker. Atrial fibrillation reoccurred after reduction of antithyroid medication and persisted for 19 weeks. Successful electrical cardioversion was performed resulting in conversion of heart rhythm to sinus. Usually, hyperthyroidism associated atrial fibrillation spontaneously reverts to sinus rhythm several weeks after achieving a euthyroid state. Control of thyroid function and heart rate is the goal of therapy for this type of atrial fibrillation.

Keywords: Hyperthyroidism - Arrhythmia - Atrial fibrillation - Familial atrial fibrillation - Cardioversion

Pediatric Cardiology
Volume 27, Number 6 / December, 2006, p. 772-774

Aortic stenosis: Standard of care

Aortic Stenosis: The Spectrum of Practice

O. Khalid1, D.M. Luxenberg1, C. Sable2, O. Benavidez3, T. Geva3, B. Hanna4 and R. Abdulla1
1) The University of Chicago, MC 4051, Chicago, IL 60637-1470, USA,

2) Children’s National Medical Center, Washington, DC, USA,

3) Children’s Hospital Boston, Boston, MA, USA, 4) Children Hospital of Philadelphia, Philadelphia, PA, USA

There is significant variation in practice patterns in managing congenital aortic valve stenosis. Review of medical literature reveals no significant information regarding the current practice methods in the treatment of a simple lesion such as aortic stenosis (AS). Therefore, this survey-based study was conducted in an attempt to better understand the uniformity or heterogeneity of practice in treating AS. A questionnaire was prepared to evaluate the style of management of AS. This survey was designed to assess the practice of follow-up visitations, type and frequency of investigative studies, pharmacological therapy, and exercise recommendations. Questions about therapeutic intervention included those of timing and type of intervention. Questionnaires were sent to all academic pediatric cardiology programs in the United States (48 program) and selected international programs from Europe, Asia, and Australasia (19 program). The total number of surveys sent out was 67, and the total number of respondents was 25 (37%), 15 (31%) from the United States and 9 (53%) from outside the United States. The definition of moderate AS varied among respondents. The range provided for mild AS was identified as that with a peak-to-peak pressure gradient of <> 50–60 mmHg, peak instantaneous Doppler gradient of > 64–80 mmHg, or mean Doppler gradient of > 45–64 mmHg. In assessing follow-up patterns, 84% of respondents recommended seeing patients with mild AS annually, the longest time of follow-up listed in the questionnaire, whereas 20% suggested follow-up every 6 months. There was no consensus among survey centers regarding follow-up of patients with moderate AS. For severe AS, 16% recommend immediate intervention, 16% arrange follow-up every 6 months, and 56 and 28% recommend follow-up in 3 and 1 month(s), respectively. In making the decision to proceed with biventricular versus univentricular repair in patients with AS in the neonatal period, many factors were considered. Ninety-two percent of respondents rely on mitral valve z score, 84% on aortic valve z score, 52% on left ventricle length, 48% on the presence of antegrade ascending aorta flow, and only 32% considered significant endocardial fibroelastosis as a factor. Rhodes score was used by 20% of respondents in decision making regarding the approach to management of this subset of AS. This study shows that there is consensus in the management of mild and severe forms of AS. As expected, disagreement is present in the definition, evaluation, and therapy of moderate aortic valve stenosis. There is a tendency for catheter intervention except in the presence of dysplastic aortic valve or moderate to severe aortic regurgitation. There is also disagreement regarding methods used to determine biventricular versus univentricular repair of a borderline hypoplastic left heart.

Key words: Aortic stenosis - Congenital heart disease - Standard of care - Survey

Pediatric Cardiology

Volume 27, Number 6 / December, 2006, p.661-669

Congestive Heart Failure: Depression

Depression Outcome in Inpatients With Congestive Heart Failure

Harold G. Koenig, MD

Background. High rates of depression are found among hospitalized patients with congestive heart failure. Little is known about the outcome of depression in these patients or factors that influence that outcome.

Methods. To assess baseline patient characteristics as predictors of time to remission in depressed inpatients with congestive heart failure, consecutive patients older than 50 years admitted with congestive heart failure were screened for major and minor depression using a structured clinical interview. Patients with minor depression were reevaluated at 6 and 12 weeks, and those with major depression at 6, 12, 18, and 24 weeks using the Longitudinal Interview Follow-up Evaluation.

Results. Of a total of 473 depressed patients, 404 (247 with minor depression and 157 with major depression) were identified and followed up. Patients with minor depression were followed up for an average of 11.3 weeks, during which 64.0% went into remission; those with major depression were followed up for 20.2 weeks, during which 47.8% went into remission. Baseline predictors of shorter time to remission for minor depression were less severe depression (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.92-0.98) and fewer comorbid illnesses (HR, 0.92; 95% CI, 0.87-0.98); patients who were younger and had better physical functioning and those not treated with antidepressants also tended to go into remission faster. For major depression, less severe depression was the primary predictor (HR, 0.92; 95% CI, 0.88-0.96), although patients who were younger, male, without a history of depression, and with fewer comorbid medical disorders also tended to go into remission faster. Fewer than 50% of patients with major depression received treatment, and only 12% had psychiatric consultations.

Conclusions. The outcome of minor depression may be more dependent on physical stressors, whereas major depression seems more affected by intrinsic vulnerability. Many patients with major depression were not treated, and few had psychiatric consultations.

http://archinte.ama-assn.org/cgi/content/abstract/166/9/991

Archives of Internal Medicine 2006; Vol. 166 No. 9, p.991-996
© 2006 American Medical Association.

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

Blood Pressure and Kidney Disease in Type 1 Diabetes

Relationship Between Low-Normal Blood Pressure and Kidney Disease in Type 1 Diabetes

Anoop Shankar; Ronald Klein; Barbara E.K. Klein; F. Javier Nieto; Scot E. Moss
From the Department of Community, Occupational, and Family Medicine (A.S.), National University of Singapore, Singapore; and the Departments of Ophthalmology and Visual Sciences (R.K., B.E.K.K., S.E.M.) and Population Health Sciences (F.J.N.), University of Wisconsin, School of Medicine and Public Health, Madison.

Current recommendations, largely based on studies in type 2 diabetes, suggest lower target blood pressures (BPs) for individuals with diabetes than for the general population. However, the effect of lower BP on renal outcomes in type 1 diabetes is uncertain. In a population-based cohort of type 1 diabetes adults (mean age: 33.1 years) based in Wisconsin, of which the distribution of baseline BP was in the low-normal range, we examined the relationship between decreasing categories of systolic and diastolic BP and the 16-year incidence of proteinuria (n=232 of 604) and estimated glomerular filtration rate of <60 mL/min/1.73 m2 (n=158 of 547). Decreasing BP categories had lower relative risk (RR) of developing incident proteinuria (RR comparing decreasing quartiles of systolic BP: 1.00, 0.76, 0.58, 0.73; P for trend=0.03; RR comparing decreasing quartiles of diastolic BP: 1.00, 0.81, 0.66, 0.42; P for trend <0.0001) and incident estimated glomerular filtration rate <60 mL/min/1.73 m2 (RR comparing decreasing quartiles of systolic BP: 1.00, 0.83, 0.61, 0.65; P for trend=0.03; RR comparing decreasing quartiles of diastolic BP: 1.00, 0.84, 0.82, 0.43; P for trend=0.001). These associations were independent of glycemic control and several putative confounding factors. Subjects with either systolic BP <120 mm Hg or diastolic BP <70 mm Hg had significantly lower RR (95% confidence interval) of incident proteinuria (0.63 [0.48 to 0.82]) and incident estimated glomerular filtration rate <60 mL/min/1.73 m2 (0.60 [0.43 to 0.82]); corresponding population-attributable risks for these outcomes were 26.7% and 29.5%, respectively. Our study suggests that lower BP levels, even below the accepted normal range, are protective against kidney disease in adults with type 1 diabetes. Interventional trials are desirable to clarify the clinical significance of this association.

Key Words: type 1 diabetes • blood pressure • chronic kidney disease • GFR • proteinuria • WESDR

Hypertension. 2007;49:48.

© 2007 American Heart Association, Inc.

Obesity: Autonomic Contribution to Blood Pressure

Autonomic Contribution to Blood Pressure and Metabolism in Obesity

Cyndya Shibao; Alfredo Gamboa; Andre Diedrich; Andrew C. Ertl; Kong Y. Chen; Daniel W. Byrne; Ginnie Farley; Sachin Y. Paranjape; Stephen N. Davis; Italo Biaggioni
From the Division of Clinical Pharmacology and the Autonomic Dysfunction Center (C.S., A.G., A.D., G.F., S.Y.P., I.B.) and Divisions of Gastroenterology (K.Y.C.) and Diabetes, Endocrinology, and Metabolism (A.C.E., S.N.D.), Department of Medicine, and the Department of Biostatistics and the General Clinical Research Center (D.W.B.), Vanderbilt University School of Medicine, Nashville, Tenn.

Obesity is associated with alterations in the autonomic nervous system that may contribute to the increase in blood pressure and resting energy expenditure present in this condition. To test this hypothesis, we induced autonomic withdrawal with the ganglionic blocker trimethaphan in 10 lean (32±3 years) and 10 obese (35±3 years) subjects. Systolic blood pressure fell more in obese compared with lean subjects (–17±3 versus –11±1 mm Hg; P=0.019) because of a greater decrease in total peripheral resistance (–310±41 versus 33±78 dynes/sec/cm–5; P=0.002). In contrast, resting energy expenditure decreased less in obese than in lean subjects, (–26±21 versus –86±15 kcal per day adjusted by fat-free mass; P=0.035). We confirmed that the autonomic contribution to blood pressure was greater in obesity after including additional subjects with a wider range of blood pressures. Systolic blood pressure decreased –28±4 mm Hg (95% CI: –38 to –18.0; n=8) in obese hypertensive subjects compared with lean (–9±1 mm Hg; 95% CI: –11 to –6; n=22) or obese normotensive subjects (–14±2 mm Hg; 95% CI: –18 to –10; n=20). After removal of autonomic influences, systolic blood pressure remained higher in obese hypertensive subjects (109±3 versus 98±2 mm Hg in lean and 103±2 mm Hg in obese normotensive subjects; P=0.004) suggesting a role for additional factors in obesity-associated hypertension. In conclusion, sympathetic activation induced by obesity is an important determinant to the blood pressure elevation associated with this condition but is not effective in increasing resting energy expenditure. These results suggest that the sympathetic nervous system could be targeted in the treatment of obesity-associated hypertension.

Key Words: obesity • hypertension • autonomic nervous system • sympathetic nervous system • vascular resistance • metabolism

http://hyper.ahajournals.org/cgi/content/abstract/49/1/27
Hypertension. 2007;49:27.

© 2007 American Heart Association, Inc.

Myogenic tone: basal coronary resistance

Beating myocardium counteracts myogenic tone of coronary microvessels: involvement of ATP-sensitive potassium channels

Satoru Takeda, Tatsuya Komaru, Katsuaki Takahashi, Kouichi Sato, Hiroshi Kanatsuka, Yasunori Kokusho, Kunio Shirato, and Hiroaki Shimokawa
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

Myogenic tone is intrinsic to vascular tissue and plays an important role in determining basal coronary resistance. However, the effect of the beating heart on myogenic tone is unknown. We investigated the effects of myocardium-derived vasoactive factors on the myogenic tone of coronary microvessels in the resting condition and during increased metabolism. Pressurized isolated coronary vessels (detector vessel, DV) of rabbits (n = 33, maximal inner diameter 201 ± 8 µm) were gently placed on beating hearts of anesthetized dogs and observed with an intravital microscope equipped with a floating objective. To shut off the myocardium-derived vasoactive signals, we placed plastic film between DV and the heart. The intravascular pressure was changed from 120 to 60 cmH2O, and pressure-diameter curves were obtained with and without the contact of DV and the myocardium. The direct contact shifted the pressure-diameter curve upward (P <>

coronary microcirculation; vasomotor signals; vasodilation; myocardial metabolism; endothelium

Am J Physiol Heart Circ Physiol 291: H3050-H3057, 2006.

Copyright © 2006 by the American Physiological Society.

Hypercholesterolemia: microvascular levels

Hypercholesterolemia Impairs Transduction of Vasodilator Signals Derived From Ischemic Myocardium
Myocardium-Microvessel Cross-Talk

Kouichi Sato; Tatsuya Komaru; Hiroki Shioiri; Satoru Takeda; Katsuaki Takahashi; Hiroshi Kanatsuka; Masaharu Nakayama; Kunio Shirato
From the Department of Cardiovascular Medicine (K. Sato, T.K., H.S., S.T., K.T., M.N., K. Shirato), Tohoku University Graduate School of Medicine, Sendai, Japan; and the Department of Comprehensive Medicine (H.K.), Tohoku University Hospital, Sendai, Japan.

Objective. Coronary microvessels are functionally coupled to the myocardial metabolic state. In hypercholesterolemia, the coronary vascular dysfunction extends to microvascular levels. We hypothesized that the vasodilator signal transduction from ischemic heart is impaired in the coronary microvascular wall of hypercholesterolemia.

Methods and Results. Rabbits were fed with normal chow (control group) or 2% high-cholesterol diet (hypercholesterolemia group) for 8 weeks. Coronary microvessels isolated from rabbit hearts were pressurized and gently placed on a beating canine heart. Myocardial ischemia was produced in the beating heart and the diameter of the isolated microvessel was observed using an intravital microscope with a floating objective. In control group, the isolated microvessels significantly dilated 2 minutes after the onset of ischemia, and a plateau was observed at 10 minutes. In contrast, the microvessels from hypercholesterolemia group did not dilate during ischemia. Dihydroethidium fluorescence microscopy revealed an elevated superoxide level in the microvessels of hypercholesterolemia group. The application of tiron (free radical scavenger) significantly dilated the isolated microvessels only from hypercholesterolemic animals.

Conclusions. We conclude that the transduction of vasodilator signals derived from ischemic myocardium is impaired in the coronary microvascular wall of hypercholesterolemia. Enhanced oxidative stress in hypercholesterolemia may alter the microvascular function.
We evaluated the cross-talk between the coronary microvessels and the ischemic myocardium by using a novel bioassay method. We elucidated that hypercholesterolemia impairs the transduction of vasodilator signals derived from the ischemic myocardium in the coronary microvascular wall. The impaired cross-talk may underlie the susceptibility to ischemic insults.

Key Words: coronary circulation • hyperlipoproteinemia • ischemia • reactive oxygen species • vasodilation

Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2034.
© 2004 American Heart Association, Inc.

Myocardial infarction: Climate study

Climate Impacts on Myocardial infarction deaths in the Athens Territory: the CLIMATE study

P Dilaveris, A Synetos, G Giannopoulos, E Gialafos, A Pantazis and C Stefanadis

The 1-st Department of Cardiology, University of Athens Medical School, Hippokration Hospital, Athens, Greece

Objective: To evaluate the impact of meteorological variables on daily and monthly deaths caused by acute myocardial infarction (AMI).

Methods: All death certificate data from the Athens territory were analysed for AMI deaths in 2001. Daily atmospheric temperature, pressure and relative humidity data were obtained from the National Meteorological Society for Athens for the same year.

Results: The total annual number of deaths caused by AMI was 3126 (1953 men) from a population of 2 664 776 (0.117%). Seasonal variation in deaths was significant, with the average daily AMI deaths in winter being 31.8% higher than in summer (9.89 v 7.35, p < r2 =" 0.109," r2 =" 0.541," p =" 0.004).

Conclusion: Ambient temperature is an important predictor of AMI mortality even in the mild climate of a Mediterranean city like Athens, its effects being predominantly evident in the elderly. Mean monthly humidity is another meteorological factor that appears to affect monthly numbers of AMI deaths. These findings may be useful for healthcare and civil protection planning.

Abbreviations: AMI, acute myocardial infarction; MONICA, MONitoring trends and determinants In CArdiovascular disease; PM, particulate matter

Heart 2006;92:1747-1751

© 2006 by BMJ Publishing Group Ltd & British Cardiovascular Society