Beta-blockers heal the heart via the brain

Heart failure treated 'in the brain'

Beta-blockers heal the heart via the brain when administered during heart failure, according to a new study by UCL (University College London). Up to now, it was thought that beta-blockers work directly on the heart, but the new study shows that the drugs may also act via the brain, suggesting that future therapies to treat cardiovascular disease could be targeting the central nervous system.

Heart failure patients are routinely given beta-blockers, although doctors do not know exactly how these drugs boost cardiac performance and reduce the risk of death. The UCL study, based on the rat model of postmyocardial infarction-induced heart failure and published in the journal Circulation Research, has discovered that the beta-adrenoceptor blocker metoprolol acts directly in the brain to slow the progression of heart failure. The action seems to be localised to a group of brain cells that UCL researchers have identified previously as being crucial in the control of blood pressure and heart rate.

Professor Mike Spyer, UCL Vice-Provost and co-author of the study, says: "Our study shows the importance of the brain in regulating the cardiovascular system. This is often ignored by cardiologists who concentrate on the dynamics of cardiac contraction and the receptors on the heart that influence this, rather than how the nervous innervation of the heart is regulated."

Millions of heart failure patients worldwide are routinely treated with beta-blockers, which were pioneered in the 1970s for the treatment of arterial hypertension and are one of the most important advances in heart failure therapy. However, it has not entirely been clear how long-term treatment with beta-blockers slows the development of heart failure, improves heart function and exercise capacity and reduces the risk of sudden cardiac death.

Dr Alexander Gourine, UCL Department of Neuroscience, Physiology and Pharmacology, says: "Many people have assumed that beta-blockers have a direct salutary influence on the heart, but our findings challenge this view, suggesting that beta-blockers may act directly in the brain and this action could underlie their beneficial effect on the failing heart. This study suggests that novel ways might be found to treat cardiovascular disease aimed at sites within the brain."

University College London, March 26, 2008 
http://www.brightsurf.com/news/

AHA dietary guidelines - Metabolic syndrome

Burgers, fries, diet soda: Metabolic syndrome blue-plate special

January 23, 2008 - American Heart Association rapid access journal report
Otherwise-healthy adults who eat two or more servings of meat a day - the equivalent of two burger patties - increase their risk of developing metabolic syndrome by 25 percent compared with those who eat meat twice a week, according to research published in Circulation: Journal of the American Heart Association.

Metabolic syndrome is a cluster of cardiovascular disease and diabetes risk factors including elevated waist circumference, high blood pressure, elevated triglycerides, low levels of high-density lipoprotein (HDL or "good") cholesterol and high fasting glucose levels. The presence of three or more of the factors increases a person's risk of developing diabetes and cardiovascular disease.

But it's not just meat that adds inches to the waist, increases blood pressure and lowers HDL - "it's fried foods as well," said Lyn M. Steffen, Ph.D., M.P.H., R.D., co-author of the study and an associate professor of epidemiology at the University of Minnesota.

Dairy products, by contrast, appeared to offer some protection against metabolic syndrome.

Steffen said that, "Fried foods are typically synonymous with commonly eaten fast foods, so I think it is safe to say that these findings support a link between fast-food consumption and an increase in metabolic risk factors."

The findings emerged from an analysis of dietary intake by 9,514 participants in the Atherosclerosis Risk In Communities (ARIC) study. ARIC is a collaborative study funded by the National Heart, Lung, and Blood Institute.

Unlike other researchers who have investigated relationships between nutrients and cardiovascular risk, "we specifically studied food intake. When making recommendations about dietary intake it is easier to do so using the framework of real foods eaten by real people," Steffen said.

Researchers assessed food intake using a 66-item food frequency questionnaire. From those responses, they categorized people by their dietary preferences into a Western-pattern diet or a prudent-pattern diet.

In general, the Western-pattern diet was heavy on refined grains, processed meat, fried foods, red meat, eggs and soda, and light on fish, fruit, vegetables and whole grain products.

Prudent diet eating patterns, by contrast, favored cruciferous vegetables (e.g., cabbage, radish and broccoli), carotenoid vegetables (e.g., carrots, pumpkins, red pepper, cabbage, broccoli and spinach), fruit, fish and seafood, poultry and whole grains, along with low-fat dairy.

Researchers also assessed associations with individual food items: fried foods, sweetened beverages (regular soda and fruit drinks), diet soda, nuts and coffee.

After nine years of follow-up, 3,782 (nearly 40 percent) of the participants had three or more of the risk factors for metabolic syndrome.

At baseline, participants were 45 to 64 years old - ages at which many people gain weight.

Steffen said that weight gain over the years of follow-up might explain some of the cases of metabolic syndrome. But "after adjusting for demographic factors, smoking, physical activity and energy intake, consumption of a 'Western' dietary pattern was adversely associated with metabolic syndrome," she said.

"One surprising finding was while it didn't increase the risk of metabolic syndrome, there was no evidence of a beneficial effect of consuming a prudent diet either. I had expected to find a beneficial effect because we have seen that in other studies."

When Steffen and colleagues analyzed the results by specific foods, they found that meat, fried foods and diet soda were all significantly associated with increased risk of metabolic syndrome, but consumption of dairy products was beneficial.

The study did not address the mechanisms involved in the increased risk of metabolic syndrome seen with certain foods, but Steffen speculated that "it may be a fatty acid mechanism since saturated fats are a common link and certainly overweight and obesity are contributing to the development of metabolic syndrome." She also said more research on the relationship between diet soda and its association to metabolic syndrome is needed.

The fact that 60.5 percent of the ARIC population had metabolic syndrome at the start of the study or developed it during nine years of follow-up is troubling, researchers said.

Steffen said the study's results are clear: Too much meat, fried foods and diet soda, do not add up to a healthy life.

American Heart Association dietary guidelines for healthy Americans age 2 and older include:

* Limit saturated fat, trans fat, cholesterol and sodium in the diet.
* Minimize the intake of food and beverages with added sugars.
* Eat a diet rich in vegetables, fruits and whole-grain foods.
* Select fat-free and low-fat dairy.
* Eat fish at least twice per week.
* Emphasize physical activity and weight control.
* Avoid use of and exposure to tobacco products.
* Achieve and maintain healthy cholesterol, blood pressure and blood glucose levels.

American Heart Association
http://www.brightsurf.com/news/

Seasonal changes in weight

Seasonal weight changes linked to metabolic syndrome

January 23, 2008 - Seasonal changes in weight increase the risk for metabolic syndrome, a group of scientists from National Public Health Institute, Helsinki, Finland, reports in a study published in the January 23 issue of the online, open-access journal PLoS ONE.

This finding was based on analysis of 8,028 individuals, representative of the general population aged over 30, who attended a nationwide health examination survey.

According to the current study, individuals with metabolic syndrome have more seasonal changes in their mood and behavior. The study concludes that the seasonal changes in weight in particular are linked to metabolic syndrome.

People having winter blues the risk of metabolic syndrome is heightened by 56 per cent. The negative effect of the seasonal changes equals to the protective effect against metabolic syndrome gained with regular physical exercise.

Because of easy assessment the scoring of seasonal changes in weight might be taken as a routine part of health status examination in persons being at risk of or currently having metabolic syndrome. If there were these changes, treatment options including scheduled exposures to light and regular physical exercise need to be considered.

"Disruption of circadian rhythms has been implicated in the pathogenesis of metabolic disorders. Our results give support to the hypothesized links between the metabolic and circadian cycles generated and guided by the circadian clock", says Timo Partonen, MD, academy research fellow of the group. "Our findings herein now extend these links to include relationships between the metabolic and seasonal fluctuations."

The current findings now suggest that abnormalities in the circadian clockwork predispose to seasonal changes in weight and to metabolic syndrome. This means that the circadian clockwork may well be a key to public health.

Obesity is an increasing problem concerning public health. High caloric intake or low physical exercise for example may lead not only to obesity but also to hypertension, insulin resistance and abnormal circulating lipid levels. These abnormalities tend to coincide and contribute to the term metabolic syndrome.

Public Library of Science
http://www.brightsurf.com/news/

Metabolic syndrome in US teens

Metabolic syndrome affects nearly 1 in 10 US teens

Lack of standard definition of risk factors makes measuring problem difficult

About nine percent of teenagers may have metabolic syndrome, a clustering of risk factors that put them on the path toward heart disease and diabetes in adulthood. This shocking statistic represents some of the first concentrated efforts to define and measure metabolic syndrome in children and adolescents - a necessary starting point for combating the problem, but one that has proven even trickier in youth than it has been in adults.

With the number of obese children in the United States rising at an alarming rate, pediatricians, family practitioners and researchers are concerned about what it means to for children's future health. The U.S. cholesterol guidelines have defined the metabolic syndrome for adults who have a cluster of risk factors, including increased waist circumference (central adiposity), hypertension (or elevated blood pressure), low HDL cholesterol, elevated triglycerides and an elevated fasting glucose. Even though these same components can be found in children, they have not been developed into a universal definition or diagnosis. In fact, they have only recently gained attention with the first publication on the syndrome by Stephen Cook, M.D., M.P.H., assistant professor of Pediatrics at the University of Rochester Medical Center, in 2003, which was based on national data from 1988 to 1994.

In the summer of 2006, a handful of national experts were convened by the National Institutes of Health with a task to define the metabolic syndrome for children and adolescents. The Pediatric Metabolic Syndrome Working Group (PMSWG) chose to tackle this problem affecting overweight and obese youth, tapping Cook to participate. The National Institute of Child Health and Human Development, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases and the National Institutes of Health Office of Rare Diseases sponsored the conference.

As part of the committee, Cook performed a study, published with a collection of reports from the working group in February's Journal of Pediatrics, which analyzes how many teens in the U.S. could be considered to have the metabolic syndrome based on four different definitions of it.

Based on the most recently available data from the National Health and Nutrition Examination Survey from 1999 to 2002, the study shows that the definition Cook developed in Rochester (a waist circumference at or above the 90th percentile for age and sex; blood pressure at or above the 90th percentile; a high triglyceride level at or above 10 mg/dL; a low HDL cholesterol level at or above 40 mg/dL; and an impaired glucose metabolism at or above 100 mg/dL), reveals that 2.9 million teens - 9.4 percent of teens overall, and over a third of obese teens - meet the definition of the metabolic syndrome.

The original work by Cook and colleagues published in 2003 showed only 4 percent of teens meet this definition and that the increased prevalence is driven by the rise in obesity.

Using two other well-reported definitions with more stringent cut points, the study also reports rates as low as 2 percent (or 600,000 teens); using analyses that apply the U.S. adult definitions, it reported rates of 1.8 million teens -5.8 percent of all teens, and 25 percent of obese teens.

"Even if there is no consensus on a pediatric-specific definition, the fact that 1 in 4 obese teens meet the adult definition for this clustering of cardiovascular disease risk factors is enough of a concern," said Cook, who is a pediatrician and adult-internist at Golisano Children's Hospital at Strong. "Many longitudinal studies have shown that adults with this definition are at increased risk for developing type 2 diabetes, heart disease and dying prematurely from heart disease."

While one goal of the committee was to define the metabolic syndrome in pediatric populations, the bigger picture was to recognize the importance of obesity on cardiovascular risk for pediatric populations.

"We are not saying that adolescents who meet a definition for metabolic syndrome are going to develop diabetes or have a heart attack in the next few years, but some of the longitudinal studies presented at this meeting showed they were at very high risk for developing diabetes or heart disease in their 30s," Cook said. "When you consider all the success we've had with lowering the death rate from heart disease for middle aged and older adults, it's really disheartening to see actual data showing heart disease going up in young adults."

Cook said there have been advances in technology, pharmaceuticals and tremendous public health victories seen with reductions in tobacco use and exposure, so the increased rates in cardiovascular risk factors in young adults must be considered "the first wave of severe consequences of the modern obesity epidemic."

January 25, 2008
University of Rochester Medical Center
http://www.brightsurf.com/news/headlines/35557/Metabolic_syndrome_affects_nearly_1_in_10_US_teens.html

Christmas Blessings for all!

Christmas Blessings for all!

Dietary: Cerebral and Myocardial Infarctions

Association of Dietary Intake of Soy, Beans, and Isoflavones With Risk of Cerebral and Myocardial Infarctions in Japanese Populations

 
Yoshihiro Kokubo, MD; Hiroyasu Iso, MD; Junko Ishihara, PhD; Katsutoshi Okada, MD; Manami Inoue, MD; Shoichiro Tsugane, MD, for the JPHC Study Group

Soy and isoflavones have been proposed to reduce the risk of cardiovascular risk factors, but their potential as preventatives for cardiovascular disease remains uncertain. We investigated the association of soy and isoflavone intake with risk of cerebral and myocardial infarctions (CI and MI).

To examine the association of soy and isoflavone intake with the risk of CI and MI, we studied 40 462 Japanese (40 to 59 years old, without cardiovascular disease or cancer at baseline). They completed a food-frequency questionnaire (1990–1992) and received follow-up to 2002. After 503 998 person-years of follow-up, we documented incidence of CI (n=587) and MI (n=308) and of mortality for CI and MI combined (n=232). For women, the multivariable hazard ratios and 95% confidence limits for soy intake 5 times per week versus 0 to 2 times per week were 0.64 (0.43 to 0.95) for risk of CI, 0.55 (0.26 to 1.09) for risk of MI, and 0.31 (0.13 to 0.74) for cardiovascular disease mortality. Similar but weaker inverse associations were observed between intake of miso soup and beans and risk of cardiovascular disease mortality. The multivariable hazard ratios for the highest versus the lowest quintiles of isoflavones in women were 0.35 (0.21 to 0.59) for CI, 0.37 (0.14 to 0.98) for MI, and 0.87 (0.29 to 2.52) for cardiovascular disease mortality. An inverse association between isoflavone intake and risk of CI and MI was observed primarily among postmenopausal women. No significant association of dietary intake of soy, miso soup, and beans and isoflavones with CI or MI was present in men.

High isoflavone intake was associated with reduced risk of CI and MI in Japanese women. The risk reduction was pronounced for postmenopausal women.

Circulation. 2007;116:2553-2562.
© 2007 American Heart Association, Inc.

Exertion and Acute Aortic Dissection

Role of Exertion or Emotion as Inciting Events for Acute Aortic Dissection

Ioannis S. Hatzaras MD, Jesse E. Bible MD, George J. Koullias MD, Maryann Tranquilli RN, Mansher Singh MD and John A. Elefteriades MD
Section of Cardiothoracic Surgery, Yale University School of Medicine, New Haven, Connecticut.

It is well known that hypertension, aortic dilatation, and collagen disorders predispose to acute aortic dissection (AAD). The inciting events that precede the instant of AAD are incompletely understood.
One hundred seventy-five consecutive patients having AAD, treated at our institution during a 10-year period, were reviewed; 65 were women and 110 were men (mean age 61 years). The ascending aorta was affected in 110 patients, and the descending in 65. Information was collected using patients’ charts supplemented with direct telephone interviews. Ninety patients were contacted; 65 (24 women, 41 men, mean age 61 years, average aortic size 5.56 cm) could recall specific inciting events for their dissection. In 34 patients, the ascending aorta was involved and in 31 the descending. Eighteen patients (28%) had a positive family history of aortic disease, defined as having ≥1 first-degree relative with aortic disease (aneurysm or dissection). In 24 of the 90 patients contacted (27%), strenuous activity was identified as a clear precipitating factor before the acute onset of thoracic pain; in 36 of 90 (40%) severe emotional stress preceded the onset of dissection pain. Three dissections were iatrogenic. Two additional patients reported a severe exacerbation of chronic obstructive pulmonary disease before their acute onset of chest pain.
In conclusion, severe physical and emotional stress may precipitate AAD, presumably on the basis of a transient, severe hypertensive reaction.

The American Journal of Cardiology
Volume 100, Issue 9, 1 November 2007, Pages 1470-1472

Losartan decreased myocardial ischemia

Effect of Losartan in Treatment of Exercise-Induced Myocardial Ischemia

Giancarlo Longobardi MD (a), Graziamaria Corbi MD, PhD (a, b), Francesco Cacciatore MD (a), Pasquale Abete MD (c), Giuseppe Furgi MD (a), Dino Franco Vitale MD (a), Franco Rengo MD (a, c) and Nicola Ferrara MD (a,b)

a) Cardiology Division, Fondazione “Salvatore Maugeri,” IRCCS, Scientific Institute of Telese Terme, Telese Terme, Italy; b) Department of Health Sciences, School of Medicine, University of Molise, Molise, Italy; c) Department of Clinical Medicine, Cardiovascular and Immunological Sciences, “Federico II” University of Naples, Naples, Italy.

Because no controlled clinical studies are available about the possible role of angiotensin II receptor blockers in preventing effort myocardial ischemia, we evaluated the effect of angiotensin II receptor blocker/losartan in preventing exercise-induced myocardial ischemia in patients with coronary artery disease.
Twenty-four sedentary patients with chronic stable ischemia were prospectively randomized to 28 days (double blind) of losartan 100 mg or losartan placebo in 2 divided doses. In each patient the treatment was crossed over to the alternative regimen (28 days, double blind) after a 1-week placebo period (single blind). At the end of each phase a new exercise stress test was performed. At baseline, systolic blood pressure was significantly decreased after losartan 100 mg compared with losartan placebo. At submaximal exercise, systolic blood pressure and rate–pressure product were lower after losartan 100 mg administration compared with losartan placebo, and these findings remained significant at 1-mm ST depression and at peak exercise. Losartan 100 mg administration versus losartan placebo significantly delayed the time to 1-mm ST-depression onset and decreased ST-segment depression at peak exercise and time to recovery of ST-segment depression. Losartan 100 mg administration compared with losartan placebo was able to significantly increase exercise duration and maximal workload during exercise stress testing.
In conclusion, in our study, losartan decreased electrocardiographic parameters of myocardial ischemia in patients with coronary artery disease, suggesting a possible role of this drug in treatment of patients with effort myocardial ischemia.

The American Journal of Cardiology
Volume 100, Issue 10, 15 November 2007, Pages 1517-1521

Coronary syndromes: Treating depression

Treating depression may improve recovery of heart rate variability following coronary syndromes

Patients with depression appear to have an impaired ability to recover their heart rate variability following acute coronary syndromes such as heart attack, a factor that could increase their risk of coronary death, according to a report in the September issue of Archives of General Psychiatry, one of the JAMA/Archives journals. However, patients who are treated with antidepressants or whose mood lifts may experience more of an improvement in heart rate variability than those who are untreated or remain depressed.
Heart rate variability refers to the degree to which the heart rate changes from beat to beat in response to normal impulses. "Low heart rate variability predicts death after myocardial infarction [heart attack]," the authors write as background information in the article. "It is reduced in depressed compared with non-depressed patients after myocardial infarction and has been proposed to be a mediator of the increased mortality associated with depression." In non-depressed patients who have an acute coronary episode, heart rate variability drops and then recovers substantially but not completely during the next few months.
Alexander H. Glassman, M.D., of the Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, and colleagues measured heart rate variability in 290 depressed patients an average of three weeks after they were hospitalized for acute coronary syndrome, a term encompassing heart events such as heart attack. The patients were then randomly assigned to take either the antidepressant sertraline or placebo for 24 weeks. After 16 weeks, 258 patients returned for a second heart rate variability reading. The severity of each participants' depression and their clinical response to depression treatment also were measured on previously established scales.
At the beginning of the study, previous episodes of depression were associated with lower heart rate variability. At the 16-week follow-up visit, the depressed patients had recovered their heart rate variability more slowly than expected and some even experienced a decrease. Patients who took sertraline had a 9 percent increase in heart rate variability and patients who took placebo had a 10 percent decrease, compared with the 28 to 33 percent increase in recovery of heart rate variability observed in previous studies of non-depressed patients.
"Both sertraline treatment and symptomatic recovery from depression were associated with increased heart rate variability compared with placebo-treated and non-recovered post-acute coronary syndrome control groups, respectively, but this results primarily from decreased heart rate variability in the comparison groups," the authors write.
The mechanisms behind the relationship between heart rate variability, depression and cardiac death remain unclear, the authors note. "What is clear is that depression is associated with biological changes involving increased heart rate, inflammatory response, plasma norepinephrine, platelet reactivity, decreased heart rate variability and now absent post-acute coronary syndrome heart rate variability recovery, all of which is associated with life-threatening consequences. Understanding why these characteristics so strongly associate with depression is crucial to understanding the nature of depression itself," they conclude.
"From a clinician's point of view, patients with depression after myocardial infarction, especially those with prior episodes, should be both carefully watched and aggressively treated, because they are at an elevated cardiac risk and less likely to get better spontaneously."

September 04, 2007
JAMA and Archives Journals

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Dark chocolate induces coronary vasodilation

Dark Chocolate Improves Coronary Vasomotion and Reduces Platelet Reactivity

Andreas J. Flammer MD, Frank Hermann MD, Isabella Sudano MD, PhD, Lukas Spieker MD, Matthias Hermann MD, Karen A. Cooper MSc, PhD, Mauro Serafini PhD, Thomas F. Lüscher MD, Frank Ruschitzka MD, Georg Noll MD, and Roberto Corti MD
From Cardiovascular Center (A.J.F., F.H., I.S., L.S., M.H., T.F.L., F.R., G.N., R.C.), Cardiology, University Hospital Zurich, Zurich, Switzerland; Nestlé Research Center (K.A.C.), Lausanne, Switzerland; and Antioxidant Research Laboratory (M.S.), Unit of Human Nutrition INRAN, Rome, Italy

Dark chocolate has potent antioxidant properties. Coronary atherosclerosis is promoted by impaired endothelial function and increased platelet activation. Traditional risk factors, high oxidative stress, and reduced antioxidant defenses play a crucial role in the pathogenesis of atherosclerosis, particularly in transplanted hearts. Thus, flavonoid-rich dark chocolate holds the potential to have a beneficial impact on graft atherosclerosis.

We assessed the effect of flavonoid-rich dark chocolate compared with cocoa-free control chocolate on coronary vascular and platelet function in 22 heart transplant recipients in a double-blind, randomized study. Coronary vasomotion was assessed with quantitative coronary angiography and cold pressor testing before and 2 hours after ingestion of 40 g of dark (70% cocoa) chocolate or control chocolate, respectively. Two hours after ingestion of flavonoid-rich dark chocolate, coronary artery diameter was increased significantly (from 2.36±0.51 to 2.51±0.59 mm, P<0.01), p="0.01)." p="0.04)">

Dark chocolate induces coronary vasodilation, improves coronary vascular function, and decreases platelet adhesion 2 hours after consumption. These immediate beneficial effects were paralleled by a significant reduction of serum oxidative stress and were positively correlated with changes in serum epicatechin concentration.

November 5, 2007

http://circ.ahajournals.org/cgi/content/abstract/CIRCULATIONAHA.107.713867v1

Vegetarian diet - Diminishes the risk for heart disease

Vegetarian Basics
Melissa Stevens, MS, RD, LD, Nutrition Program Coordinator, Preventive Cardiology and Rehabilitative Services

Following a vegetarian dietary pattern is one of the best ways to minimize your risk for coronary heart disease.

Benefits of a Vegetarian Diet
Rich in grains, fruits, vegetables, legumes, nuts and seeds, a vegetarian diet provides a host of phytonutrients, dietary fiber, vitamins and minerals found to help fend off disease.

In addition to reducing heart disease risk, people who follow a vegetarian or plant-based diet enjoy the following health benefits:

• Reduced risk of hypertension (high blood pressure).
  
• Lower total and LDL cholesterol levels.
  
• Lower body weight and reduced risk for obesity.
  
• Reduced risk of certain cancers (like colon and breast).
  
• Less risk of diverticular disease and digestive disorders.
  
• Increased longevity.
  

Types of Vegetarian Diets
There are many types of vegetarian diets. Some are followed for personal, religious, humanitarian or environmental reasons. The following are just some types of vegetarianism:

Semi-Vegetarian: Will usually eat everything but red meat. Poultry is often excluded, but fish and dairy products are almost always included.

Lacto-ovo-vegetarian: Will eat all dairy products, including butter, cheese and eggs but no meat, poultry or fish.

Lacto-vegetarian: Will eat dairy products but no eggs, meat, poultry or fish.

Vegan: Eats only plant foods like cereals, grains, fruits, vegetables, nuts and seeds. Excludes all foods of animal origin, including foods that contain any ingredients derived from an animal.

http://www.clevelandclinic.org/

Detecting deadly aortic aneurysms

A new key to detecting deadly aortic aneurysms

October 25, 2007 - New Haven, Conn.-Yale scientists have discovered a way to use a simple blood test that may accurately detect thoracic aneurysm disease (TAA), which gives little warning and is almost always fatal if untreated.

The study, published this month in Public Library of Science (PLoS), represents the collaborative work of Yale School of Medicine, Applied Biosystems, and Celera Diagnostics.

TAAs occur in the part of the aorta that passes through the chest. They can become huge without causing symptoms. In fact, only one in 20 patients has symptoms before internal rupture occurs-making advance detection key to treatment. Once the aneurysm ruptures, a person can go into shock and die from internal bleeding. Currently detection of these aneurysms is made by relatively expensive tests such as a chest X-ray or CT scan-typically when a patient is being evaluated for other conditions.

"A standardized blood-based test capable of detecting individuals at risk for aneurysm disease would represent a major advance in clinical care," said John Elefteriades, M.D., section chief of cardiothoracic surgery. "This study indicates we may be able to develop such a test."

In this study Elefteriades and his colleagues took blood samples from 58 persons diagnosed with TAA disease and 36 spouses who did not have the disease. Using a gene expression profiling technology, they identified a 41-gene signature in blood cells that distinguishes TAA patients from those without the disease. The gene expression signature and the prediction model were identified using a complete workflow of instruments, reagents, and software from Applied Biosystems. These signature genes were further validated using TaqMan® real-time PCR assays. The accuracy rate in various analyses is 78 percent to 85 percent.

"It has become increasingly evident that the immune system plays a pivotal role in the development of aortic aneurysms," Elefteriades said. "We thus hypothesized that gene expression patterns in peripheral blood cells may reflect TAA disease status."

The next step, which the researchers say is underway, is validation in real-time clinical studies. The investigative team is also interested in determining if abdominal aneurysms share a similar RNA signature, and if the RNA can predict rupture or dissection of an aneurysm.

Yale University
http://www.brightsurf.com/news/headlines/33844/A_new_key_to_detecting_deadly_aortic_aneurysms.html

Early signs of heart disease

Obese children show early signs of heart disease

Children who are obese or who are at risk for obesity show early signs of heart disease similar to obese adults with heart disease, a study by researchers at Washington University School of Medicine in St. Louis has found.

"Based on this study, these subtle markers can help us predict who could be at risk for heart disease and heart attacks," said Angela Sharkey, M.D., associate professor of pediatrics at Washington University School of Medicine and a pediatric cardiologist at St. Louis Children's Hospital.

The study was published in the Winter 2007 issue of the Journal of Cardiometabolic Syndrome.

Childhood obesity in the United States is an epidemic - nationwide, 19 percent of children ages 6 to 11 and 17 percent of those 12 to 19 are overweight, according to the Centers for Disease Control and Prevention (CDC). Those who are overweight during childhood also have an increased risk of obesity in adulthood and are at greater risk for complications such as diabetes, high blood pressure and heart disease, because obesity increases total blood volume, which leads to extra stress on the heart.

Sharkey and Steven M. Lorch, M.D., a former fellow at the School of Medicine now at University of Texas Health Science Center at Houston, analyzed data from 168 children ages 10 to 18 who had been referred to them for cardiac ultrasound with symptoms including heart murmur, chest pain, acid reflux or high blood cholesterol. Based on CDC guidelines for body mass index for age (BMIA), 33 patients were found to have a BMIA as obese, or the 95th percentile or above for their age; 20 had a BMIA that classified them as at risk for obesity, or between the 85th and 94th percentile; and 115 were considered normal, or below the 85th percentile.

To analyze the hearts of the obese children and those at risk, Sharkey and Lorch used a new tissue Doppler imaging technique called vector velocity imaging which tracks the movement of the heart's muscular wall. Any changes in the rate of motion of heart muscle were averaged within each group and compared to the normal rate of motion.

"In the patients who are obese, the rate of motion of heart muscle changed," Sharkey said. "As a child's BMIA increases, we see alterations in both the relaxation and contraction phase of the heartbeat. Many of these changes that have been seen in adults were assumed to be from long-standing obesity, but it may be that these changes start much earlier in life than we thought."

As vector velocity imaging becomes more broadly available, Sharkey said, it could potentially help pediatric cardiologists follow these children more closely over time to see if changes in the heart progress.

"We may be able to determine whether we could intervene in the process, such as focusing the families on understanding the importance of regular exercise and dietary modifications for weight loss and prescribing statin drugs for high-blood cholesterol," she said.

Sharkey said the results of the study give more ammunition to physicians to use in counseling pediatric patients and their parents about the risks of obesity and the need to attain a healthy weight.
"Even in teenagers, obesity leads to decreased myocardial performance and abnormal diastolic function," she said.
Further study is needed to determine how soon the changes in the heart set in after a child becomes obese and whether those changes are reversible with weight loss.

Washington University School of Medicine
http://www.brightsurf.com/news/

Sudden Cardiac Death - Genetic investigations

Contribution of Inherited Heart Disease to Sudden Cardiac Death in Childhood

Nynke Hofman, MS (a), Hanno L. Tan, MD, PhD (b), Sally-Ann Clur, MD (c), Mariel Alders, PhD (d), Irene M. van Langen, MD, PhD (a) and Arthur A. M. Wilde, MD, PhD (b)
a ) Departments of Clinical Genetics; b)  Cardiology; c) Pediatric Cardiology; d)  Molecular Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

BACKGROUND. In children aged 1 to 18 years, the causes of sudden cardiac death may remain unresolved when autopsy results are negative. Because inherited cardiac diseases are likely, cardiologic and genetic investigations of relatives may still yield the diagnosis in these cases. Moreover, these investigations provide timely identification of relatives who are also at risk of sudden cardiac death. We aimed to establish the cause of sudden cardiac death in the children of whom the family was referred to our cardiogenetics department and the diagnostic yield of these investigations.

METHODS AND RESULTS. We genetically counseled 25 consecutive, unrelated families after sudden cardiac death of a child (aged 1 to 18 years) who was disease-free during lifetime and in whose family there was no known inherited heart disease. We performed cardiac investigation (electrocardiography, exercise testing, and echocardiography) of first-degree and second-degree relatives and performed diagnosis-directed DNA analysis. Autopsy was performed in 20 case subjects. A diagnosis was identified in 14 of 25 families. In addition, we studied 10 children after aborted sudden cardiac death; in 6 of them, a diagnosis was made. Overall, in 17 of the 19 families in whom an inherited disease was diagnosed, a disease-causing mutation in either a first-degree relative or the index patient confirmed the diagnosis.

CONCLUSIONS. Sudden cardiac death in children seems to be caused often by inherited cardiac diseases. Cardiac and genetic examination of relatives combined, if possible, with postmortem analysis after sudden cardiac death of a child has a high diagnostic yield (14 of 25), comparable to analysis in surviving victims of sudden cardiac death (6 of 10). Because sudden cardiac death can be prevented by timely treatment, these results warrant active family screening after unexplained sudden cardiac death of a child.

Key Words: sudden cardiac death • children • molecular genetics • arrhythmia • genetic counseling

http://pediatrics.aappublications.org/cgi/content/abstract/120/4/e967
PEDIATRICS Vol. 120 No. 4 October 2007, pp. e967-e973
© 2007 American Academy of Pediatrics.

Myocardial infarction occurs in children

Myocardial Infarction in Healthy Adolescents

John R. Lane, MD and Giora Ben-Shachar, MD
The Heart Center, Akron Children's Hospital, Akron, Ohio

OBJECTIVE. Chest pain in children and adolescents is a frequent cause for office or emergency department visits. However, it is unclear whether myocardial infarction occurs in children with no anatomic abnormality presenting with chest pain.

METHODS. Clinical history, electrocardiography, echocardiography, and cardiac enzyme levels were evaluated in patients presenting to the emergency department over a period of 11 years (June 1995 to May 2006). Patients in whom findings were suggestive of acute myocardial infarction, in addition, underwent drug screening, serum lipid profile, and hypercoagulability workup and, when myocardial infarction was diagnosed, heart catheterization with coronary angiography.

RESULTS. Nine patients (8 boys; age range: 12–20 years; mean: 15.5 years) met established criteria for myocardial infarction. Abnormal electrocardiograms were found in 8 patients (6 with ST elevation and 2 with nonspecific ST-T abnormalities), abnormal cardiac enzyme levels in all, and echocardiographic abnormalities in 3. Cardiac dysrhythmias were found in 4 patients, 3 with nonsustained ventricular tachycardia. Drug abuse, lipid profile, and hypercoagulability studies were negative in all. Left ventricular focal hypokinesia was seen by echocardiogram or angiography in 5 patients and abnormal coronary anatomy in none. Cardiac function normalized in 8 patients. One patient had a persistent focal inferior hypokinesis. Calcium channel blocker therapy was initiated in all of the patients with no recurrence of anginal chest pain on follow-up. One patient complained of chest pain distinct from anginal pain.

CONCLUSIONS. Myocardial infarction can occur in adolescents with normal coronary arterial anatomy. Adolescents who present for emergency care with typical chest pain need electrocardiographic and cardiac enzyme workups. Those with results that are suggestive of acute infarction require additional workup. Coronary vasodilation therapy seems helpful, but given the lack of coronary thrombosis in these patients, thrombolytic therapy seems unwarranted. Long-term follow-up is necessary, and adjustments in therapy may be required with time.

PEDIATRICS Vol. 120 No. 4 October 2007, pp. e938-e943
http://pediatrics.aappublications.org/cgi/content/abstract/120/4/e938

High blood pressure in the Children

We usually think of high blood pressure, or hypertension, as a problem that affects adults. But, in fact, this condition can be present at any age, even in infancy. About five of every hundred children have higher than normal blood pressure, although fewer than one in a hundred has medically significant hypertension.

How blood pressure is measured

The term blood pressure actually refers to two separate measurements:

• systolic blood pressure is the highest pressure reached in the arteries as the heart pumps blood out for circulation through the body
  

• diastolic blood pressure is the much lower pressure that occurs in the arteries when the heart relaxes to take blood in between beats
  

If either or both of these measurements are above the range found in healthy individuals of similar age and sex, it’s called hypertension.

Who gets high blood pressure

• Hypertension is more common among individuals of color than whites. It also seems to be more prevalent in some parts of the world; for example, it’s very rare among Alaskan Inuit, but affects as many as forty of every hundred adults in northern Japan.
  

• In many cases hypertension seems to develop with age. As a result, your child may show no signs of high blood pressure as an infant, but may develop the condition as she grows.
  

• Youngsters who are overweight are also more prone to have hypertension (and other chronic diseases). Thus good eating habits (without overeating and without emphasizing high-fat foods) and plenty of physical activity are important throughout the early years of childhood (and for the rest of her life).
  

http://www.aap.org

Light cigarette smoking and Cardiovascular diseases

Light cigarette smoking impairs coronary microvascular functions as severely as smoking regular cigarettes

Hakan Gullu, Mustafa Caliskan, Ozgur Ciftci, Dogan Erdogan, Semra Topcu, Erkan Yildirim, Aylin Yildirir, Haldun Muderrisoglu
1 ) Baskent University, Faculty of Medicine, Cardiology Department, Ankara, Turkey; 
2) Baskent University, Faculty of Medicine, Radiology Department, Ankara, Turkey

Background: Smoking is the most prevalent and most preventable risk factor for cardiovascular diseases. Smoking low-tar, low-nicotine cigarettes (light cigarettes) would be expected to be less hazardous than smoking regular cigarettes owing to the lower nicotine and tar yield.

Objective: To compare the chronic and acute effects of light cigarette and regular cigarette smoking on coronary flow velocity reserve (CFVR).

Methods: 20 regular cigarette smokers (mean (SD) age 24.8 (5.0)), 20 light cigarette smokers (mean age 25.6 (6.4)), and 22 non-smoker healthy volunteers (mean age 25.1 (4.2)) were included. First, each subject underwent echocardiographic examination, including CFVR measurement, after a 12 hour fasting and smokeless period. Two days later, each subject smoked two of their normal cigarettes in a closed room within 15 minutes. Finally, within 20–30 minutes, each subject underwent an echocardiographic examination, including CFVR measurement.

Results: Mean (SD) CFVR values were similar in light cigarette and regular cigarette smokers and significantly lower than in the controls (2.68 (0.50), 2.65 (0.61), 3.11 (0.53), p = 0.013). Before and after smoking a paired t test showed that smoking two light cigarettes acutely decreased the CFVR from 2.68 (0.50) to 2.05 (0.43) (p = 0.001), and smoking of two regular cigarettes acutely decreased CFVR from 2.65 (0.61) to 2.18 (0.48) (p = 0.001).

Conclusion: Our study suggest that reducing the nicotine and tar yield is not sufficient for a cigarette to be called less hazardous, and other noxious compounds in cigarettes continue to compromise human health. Smoking low-tar, low-nicotine cigarettes seems to have the same unfavourable effect on the coronary microvascular functions as smoking regular cigarettes. Action should be taken to prohibit misleading terminology such as "light".

Heart 2007;93:1274-1277
http://heart.bmj.com/cgi/content/abstract/93/10/1274
© 2007 BMJ Publishing Group Ltd & British Cardiovascular Society

Septic myocardial dysfunction

Sepsis and the Heart

M.W. Merx, MD; C. Weber, MD
From the Department of Medicine (M.W.M.), Division of Cardiology, Pulmonary Diseases and Vascular Medicine and the Institute of Molecular Cardiovascular Research (IMCAR) at the University Hospital (C.W.), RWTH Aachen University, Aachen, Germany.

Sepsis is generally viewed as a disease aggravated by an inappropriate immune response encountered in the afflicted individual.
As an important organ system frequently compromised by sepsis and always affected by septic shock, the cardiovascular system and its dysfunction during sepsis have been studied in clinical and basic research for more than 5 decades.
Although a number of mediators and pathways have been shown to be associated with myocardial depression in sepsis, the precise cause remains unclear to date.
There is currently no evidence supporting global ischemia as an underlying cause of myocardial dysfunction in sepsis; however, in septic patients with coexistent and possibly undiagnosed coronary artery disease, regional myocardial ischemia or infarction secondary to coronary artery disease may certainly occur.
A circulating myocardial depressant factor in septic shock has long been proposed, and potential candidates for a myocardial depressant factor include cytokines, prostanoids, and nitric oxide, among others.
Endothelial activation and induction of the coagulatory system also contribute to the pathophysiology in sepsis. Prompt and adequate antibiotic therapy accompanied by surgical removal of the infectious focus, if indicated and feasible, is the mainstay and also the only strictly causal line of therapy. In the presence of severe sepsis and septic shock, supportive treatment in addition to causal therapy is mandatory.
The purpose of this review is to delineate some characteristics of septic myocardial dysfunction, to assess the most commonly cited and reported underlying mechanisms of cardiac dysfunction in sepsis, and to briefly outline current therapeutic strategies and possible future approaches.

Key Words: immune system • infection • inflammation • shock • sepsis

Circulation. 2007;116:793-802.
© 2007 American Heart Association, Inc.

Body Mass Index in Patients with Chronic Heart Failure

Body Mass Index and Prognosis in Patients With Chronic Heart Failure: Insights From the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Program

Satish Kenchaiah, MD, MPH; Stuart J. Pocock, PhD; Duolao Wang, PhD at al.

Background. In individuals without known cardiovascular disease, elevated body mass index (BMI) (weight/height2) is associated with an increased risk of death. However, in patients with certain specific chronic diseases, including heart failure, low BMI has been associated with increased mortality.

Methods and Results. We examined the influence of BMI on prognosis using Cox proportional hazards models in 7599 patients (mean age, 65 years; 35% women) with symptomatic heart failure (New York Heart Association class II to IV) and a broad spectrum of left ventricular ejection fractions (mean, 39%) in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. During a median follow-up of 37.7 months, 1831 patients died. After adjustment for potential confounders, compared with patients with BMI between 30 and 34.9, patients in lower BMI categories had a graded increase in the risk of death. The hazard ratios (95% confidence intervals) were 1.22 (1.06 to 1.41), 1.46 (1.24 to 1.71), and 1.69 (1.43 to 2.01) among those with BMI of 25 to 29.9, 22.5 to 24.9, and <22.5,>0.20). However, lower BMI was associated with a greater risk of all-cause death in patients without edema but not in patients with edema (P for interaction <0.0001). Lower BMI was associated with a greater risk of cardiovascular death and noncardiovascular death. Baseline BMI did not influence the risk of hospitalization for worsening heart failure or due to all causes.

Conclusions. In patients with symptomatic heart failure and either reduced or preserved left ventricular systolic function, underweight or low BMI was associated with increased mortality, primarily in patients without evidence of fluid overload (edema).

Circulation. 2007;116:627-636.
© 2007 American Heart Association, Inc.

HRQL in cardiac patients

Poor Health-Related Quality of Life Is a Predictor of Early, But Not Late, Cardiac Events After Percutaneous Coronary Intervention

Susanne S. Pedersen, Ph.D., Elisabeth J. Martens, Ph.D., Johan Denollet, Ph.D., and Ad Appels, Ph.D.
From CoRPS–Center of Research on Psychology in Somatic diseases, Tilburg Univ., The Netherlands; Dept. of Medical Psychology, Maastricht Univ., The Netherlands. Send correspondence and reprint requests to Susanne S. Pedersen, Ph.D., CoRPS, Dept. of Medical Psychology, Room P503a, Tilburg Univ., Warandelaan 2, PO Box 90153, 5000 LE Tilburg, The Netherlands.

Poor health-related quality of life (HRQL) is associated with mortality in cardiac patients.

Patients (N=667) with poor HRQL after percutaneous coronary intervention had a higher incidence of early ( 6 months) major adverse cardiac events (MACE) than did patients with good HRQL, whereas there was no difference for late (>6 months) MACE over a 2-year follow-up period.

Poor HRQL remained an independent predictor of early, but not late MACE, adjusting for other risk factors. The same pattern was found for early and late death/non-fatal myocardial infarction.

However, further research is warranted before recommending the use of HRQL measures as screening tools in clinical practice. Full Text

Psychosomatics 48:331-337, August 2007

© 2007 Academy of Psychosomatic Medicine