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

http://www.brightsurf.com/news/

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

Circadian rhythm and Coronary death

When Throughout the Year Is Coronary Death Most Likely to Occur?
A 12-Year Population-Based Analysis of More Than 220 000 Cases

Robert A. Kloner, MD, PhD; W. Kenneth Poole, PhD; Rebecca L. Perritt, MS
From the Heart Institute Research Laboratory, Good Samaritan Hospital and Section of Cardiology, University of Southern California (R.A.K.), Los Angeles, Calif, and Research Triangle Institute, Research Triangle, NC (W.K.P., R.L.P.).

Background. Previous studies have suggested that there is an increase in cardiac events in the morning. Fewer data relate cardiac events to months of the year and season.

Methods and Results. We analyzed all monthly death certificate data from Los Angeles County, California, for death caused by coronary artery disease from 1985 through 1996 (n=222 265). The mean number of deaths was highest in December at 1808 and January at 1925; the lowest rates were in June, July, August, and September at 1402, 1424, 1418, and 1371, respectively. December and January had significantly higher rates than would be expected from a uniform distribution of monthly deaths (P=0.00001). The percent of yearly coronary deaths was defined by the quadratic U-shaped equation [percent=13.1198-1.5238(month)+0.0952(month2), where January=1, February=2, etc]. When monthly deaths were plotted by year, there was a decrease from 1985 through 1996. Monthly mortality correlated inversely with temperature. During the months with the highest frequency of death (December, January), however, there was an increase in deaths that peaked around the holiday season and then fell, which could not be explained solely on the basis of the daily temperature change.

Conclusions. Even in the mild climate of Los Angeles County, there are seasonal variations in the development of coronary artery death, with 33% more deaths occurring in December and January than in June through September. Although cooler temperatures may play a role, other factors such as overindulgence or the stress of the holidays might also contribute to excess deaths during these peak times.

Key Words: cardiovascular diseases • circadian rhythm • coronary disease • death, sudden • heart diseases

Circulation. 1999;100:1630-1634.
© 1999 American Heart Association, Inc.

Cocoa may lower blood pressure

Cocoa, but not tea, may lower blood pressure

Current guidelines advise individuals with hypertension (high blood pressure) to eat more fruits and vegetables, according to background information in the article. Compounds known as polyphenols or flavonoids in fruits and vegetables are thought to contribute to their beneficial effects on blood pressure and cardiovascular risk. "Tea and cocoa products account for the major proportion of total polyphenol intake in Western countries," the authors write. "However, cocoa and tea are currently not implemented in cardioprotective or anti-hypertensive dietary advice, although both have been associated with lower incidences of cardiovascular events."

Dirk Taubert, M.D., Ph.D., and colleagues at the University Hospital of Cologne, Germany, conducted a meta-analysis of 10 previously published trials, five of cocoa's effects on blood pressure and five involving tea. All results were published between 1966 and 2006, involved at least 10 adults and lasted a minimum of seven days. The studies were either randomized trials, in which some participants were randomly assigned to cocoa or tea groups and some to control groups, or used a crossover design, in which participants' blood pressure was assessed before and after consuming cocoa products or tea.

The five cocoa studies involved 173 participants, including 87 assigned to consume cocoa and 86 controls, 34 percent of whom had hypertension (high blood pressure). They were followed for a median (middle) duration of two weeks. Four of the five trials reported a reduction in both systolic (the top number, when the heart contracts) and diastolic (the bottom number, when the heart relaxes) blood pressure. Compared with those who were not consuming cocoa, systolic blood pressure was an average of 4.7 millimeters of mercury lower and diastolic blood pressure was an average of 2.8 millimeters of mercury lower.

The effects are comparable to those achieved with blood pressure-lowering medications, the authors note. "At the population level, a reduction of 4 to 5 millimeters of mercury in systolic blood pressure and 2 to 3 millimeters of mercury in diastolic blood pressure would be expected to substantially reduce the risk of stroke (by about 20 percent), coronary heart disease (by 10 percent) and all-cause mortality (by 8 percent)," they write.

Of the 343 individuals in the five tea studies, 171 drank tea and 172 served as controls, for a median duration of four weeks. Drinking tea was not associated with a reduction in blood pressure in any of the trials.

Tea and cocoa are both rich in polyphenols, but while black and green tea contain more compounds known as flavan-3-ols, cocoa contains more of another type of polyphenol, procyanids. "This suggests that the different plant phenols must be differentiated with respect to their blood pressure-lowering potential and thus cardiovascular disease prevention, supposing that the tea phenols are less active than cocoa phenols," the authors write.

The findings do not indicate a widespread recommendation for higher cocoa intake to decrease blood pressure, but it appears reasonable to substitute phenol-rich cocoa products such as dark chocolate for other high-calorie or high-fat desserts or dairy products, they continue. "We believe that any dietary advice must account for the high sugar, fat and calorie intake with most cocoa products," the authors conclude. "Rationally applied, cocoa products might be considered part of dietary approaches to lower hypertension risk."

JAMA and Archives Journals, April 10, 2007
http://www.brightsurf.com/news/

Genetic determinants of hemodynamic and chronotropic responses

Heritability, Linkage, and Genetic Associations of Exercise Treadmill Test Responses

Erik Ingelsson, MD, PhD; Martin G. Larson, ScD; Ramachandran S. Vasan, MD*; Christopher J. O’Donnell, MD, MPH; Xiaoyan Yin, MS; Joel N. Hirschhorn, MD, PhD; Christopher Newton-Cheh, MD, MPH; Jared A. Drake, BA; Stacey L. Musone, BA; Nancy L. Heard-Costa, PhD; Emelia J. Benjamin, MD, ScM; Daniel Levy, MD; Larry D. Atwood, PhD; Thomas J. Wang, MD; Sekar Kathiresan, MD

Background. The blood pressure (BP) and heart rate responses to exercise treadmill testing predict incidence of cardiovascular disease, but the genetic determinants of hemodynamic and chronotropic responses to exercise are largely unknown.

Methods and Results. We assessed systolic BP, diastolic BP, and heart rate during the second stage of the Bruce protocol and at the third minute of recovery in 2982 Framingham Offspring participants (mean age 43 years; 53% women). With use of residuals from multivariable models adjusted for clinical correlates of exercise treadmill testing responses, we estimated the heritability (variance-components methods), genetic linkage (multipoint quantitative trait analyses), and association with 235 single-nucleotide polymorphisms in 14 candidate genes selected a priori from neurohormonal pathways for their potential role in exercise treadmill testing responses. Heritability estimates for heart rate during exercise and during recovery were 0.32 and 0.34, respectively. Heritability estimates for BP variables during exercise were 0.25 and 0.26 (systolic and diastolic BP) and during recovery, 0.16 and 0.13 (systolic and diastolic BP), respectively. Suggestive linkage was found for systolic BP during recovery from exercise (locus 1q43–44, log-of-the-odds score 2.59) and diastolic BP during recovery from exercise (locus 4p15.3, log-of-the-odds score 2.37). Among 235 single-nucleotide polymorphisms tested for association with exercise treadmill testing responses, the minimum nominal probability value was 0.003, which was nonsignificant after adjustment for multiple testing.

Conclusions. Hemodynamic and chronotropic responses to exercise are heritable and demonstrate suggestive linkage to select loci. Genetic mapping with newer approaches such as genome-wide association may yield novel insights into the physiological responses to exercise.

Circulation. 2007;115:2917-2924.
© 2007 American Heart Association, Inc.
http://circ.ahajournals.org/cgi/content/abstract/115/23/2917

Depression in Patients With Heart Failure

Recognition of Depression in Medical Patients With Heart Failure

Harold G. Koenig, M.D.
From the Duke University Medical Center and GRECC VA Medical Center. Send correspondence and reprint requests to Dr. Koenig, Box 3400, Duke University Medical Center, Durham, NC 27710.

The author examined physician and patient factors related to recognition of depression in depressed medical patients. Medical inpatients over age 50 were systematically identified with depressive disorder (N=1,000). Medical physicians (N=422) treating these patients were asked whether they believed patients had depression warranting specific treatment. Frequency of seeing and treating older depressed patients and attitudes toward treatment effectiveness were key factors related to physicians’ recognition of depression. Patient factors were younger age, white race, female gender, and persistence of depression after discharge. Although physicians’ intuition about depression course was often correct, persistent depression was not recognized in nearly 40% of patients.

For patients with congestive heart failure (CHF), depression accounts for nearly $5 billion of the $20 billion total treatment costs, and severely depressed CHF patients show a fourfold increase in mortality. Approximately 14 to 20 million Americans have chronic pulmonary disease (CPD), which is the fourth leading cause of death in the United States, and death rates are likewise increased by over threefold among depressed patients. Studies using structured psychiatric interviews have reported that depressive disorder is present in 36%–59% of medical inpatients with CHF (16%–22% with minor and 20%–37% with major depression). Depression rates in patients with CPD are also high (7%–57%). This is particularly true for hospitalized CPD patients, where the rate of depressive disorder is close to 60% (unpublished data). Thus, a significant proportion of hospitalized patients with CHF/CPD (CHF and/or CPD) have depressive disorders that interfere with functioning, quality of life, and medical outcomes. Underrecognition of depression is widespread among older medical patients in general and CHF/CPD patients in particular (over 90% in one study).

When told that their patient met criteria for a depressive disorder, only two-thirds of physicians agreed with the diagnosis and need for treatment. Although physicians were often quite accurate in assessment (based on remission of depression after hospitalization), nearly 40% of the time they were wrong, and these patients continued to suffer from depression for months after discharge (most without treatment). For physicians managing patients in the hospital, there are patient characteristics (age, gender, race) and physicians’ attitudes toward treatment that influence whether or not they believe that patients have depressive disorder warranting treatment, and these factors are independent of the type of depressive disorder, severity of depression, or the course of depression after discharge. This may be partially the result of bias or stereotyping. Medical training programs should emphasize the recognition and treatment of depression in older patients with CHF/CPD and the necessity for referral if patients are not responding to treatment.

Full Text

Psychosomatics 48:338-347, August 2007

© 2007 Academy of Psychosomatic Medicine

Association Between Birth Weight and Hypertension

Genetic and Shared Environmental Factors Do Not Confound the Association Between Birth Weight and Hypertension
A Study Among Swedish Twins

Niklas Bergvall, MSc; Anastasia Iliadou, PhD; Stefan Johansson, MD; Ulf de Faire, MD, PhD; Michael S. Kramer, MD; Yudi Pawitan, PhD; Nancy L. Pedersen, PhD; Paul Lichtenstein, PhD; Sven Cnattingius, MD, PhD

From the Department of Medical Epidemiology and Biostatistics (N.B., A.I., S.J., Y.P., N.L.P., P.L., S.C.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine and Department of Cardiology, Karolinska University Hospital (U.d.F.), Karolinska Institutet, Stockholm, Sweden, and Departments of Pediatrics and of Epidemiology and Biostatistics, McGill University Faculty of Medicine, Montreal, Canada (M.S.K.).

Background. Studies have found associations between low birth weight and increased risks of cardiovascular diseases in adulthood. However, these associations could be due to confounding by genetic or socioeconomic factors.

Methods and Results. We performed a study on Swedish like-sexed twins with known zygosity who were born from 1926 to 1958. First, to obtain an overall effect of birth weight on risk of hypertension, we performed cohort analyses on all twins (n=16 265). Second, to address genetic and shared environmental confounding, we performed a nested co-twin control analysis within 594 dizygotic and 250 monozygotic twin pairs discordant for hypertension. Birth characteristics, including birth weight, were obtained from original birth records. Information from adulthood was collected from a postal questionnaire in 1973 (body mass index, height, smoking, and alcohol use) and from a telephone interview conducted from 1998 to 2002 (hypertension and socioeconomic status). Hypertension was defined as reporting both high blood pressure and treatment with antihypertensive medication. In the cohort analysis, the adjusted odds ratio for hypertension in relation to a 500-g decrease in birth weight was 1.42 (95% confidence interval, 1.25 to 1.61). In the co-twin control analyses, the corresponding odds ratios were 1.34 (95% confidence interval, 1.07 to 1.69) for dizygotic and 1.74 (95% confidence interval, 1.13 to 2.70) for monozygotic twins.

Conclusions. In the largest twin study on the fetal origins of hypertension, we found that decreased birth weight is associated with increased risk of hypertension independently of genetic factors, shared familial environment, and risk factors for hypertension in adulthood, including body mass index.

Circulation. 2007;115:2931-2938.
© 2007 American Heart Association, Inc.
http://circ.ahajournals.org/cgi/content/abstract/115/23/2931

Hibiscus flower: Control cholesterol levels

Hibiscus Flowers to Prevent Heart Attacks

Hibiscus flower extract may have the same health benefits as red wine and tea according to new research by scientists in Taiwan. Hibiscus contains antioxidants that help control cholesterol levels and reduce heart disease, says the research in Journal of the Science of Food and Agriculture.

Chau-Jong Wang and his team at Chung Shan Medical University in the Republic of China found that the antioxidant properties of flavonoids, polyphenolic compounds and anthocyanins contained in the flower can prevent the oxidation of Low-Density Lipoproteins (LDL), which is associated with the disease.

Healthy properties
Hibiscus sabdariffa is used in folk medicine to treat hypertension and liver disorder, and is used to make popular soft drinks in various countries across the world. Some health benefits of taking Hibiscus have now been verified: "Experiments have shown that compounds extracted from red wine and tea reduces cholesterol and lipid build-up in the arteries of rats. This is the first study to show that Hibiscus extract has the same effect", says Wang.

Diet testing
In the study, rats were divided in to four groups and given different diets; one control, one high cholesterol control, and two high cholesterol diets supplemented with different amounts of Hibiscus extract. After 12 weeks, the rats were given blood tests to assess their health. Results showed that the extract significantly reduced cholesterol content in blood serum and successfully prevented oxidation of Low-density Lipoproteins.

These data strongly suggest that the extract has potential to prevent cholesterol deposition and may therefore be useful in the prevention and even treatment of a number of cardiovascular diseases in which cholesterol plays a major role.

Society of Chemical Industry
http://www.brightsurf.com/news/

Tobacco smoke: Influencing on the Healthy Children

Tobacco Smoke Exposure Is Associated With Attenuated Endothelial Function in 11-Year-Old Healthy Children

Katariina Kallio, MD; Eero Jokinen, MD, PhD; Olli T. Raitakari, MD, PhD; Mauri Hämäläinen, PhD; Marja Siltala; Iina Volanen, MD; Tuuli Kaitosaari, MD; Jorma Viikari, MD, PhD; Tapani Rönnemaa, MD, PhD; Olli Simell, MD, PhD
From the Research Centre of Applied and Preventive Cardiovascular Medicine (K.K., M.S., I.V., T.K.), and the Departments of Clinical Physiology (O.T.R.), Medicine (J.V., T.R.), and Pediatrics (O.S.), University of Turku, Turku, Finland; Department of Pediatrics (E.J.), University of Helsinki, Helsinki, Finland; and Joint Clinical Biochemistry Laboratory of University of Turku, Turku University Central Hospital and Wallac Oy (M.H.), Turku, Finland.

Background. Passive smoking is associated with early arterial damage in adults, but its effect on endothelial function in children is unknown.

Methods and Results. Serum cotinine concentration was measured annually in children between 8 and 11 years of age who had participated since infancy in a randomized, prospective atherosclerosis prevention trial (Special Turku Coronary Risk Factor Intervention Project for children [STRIP]). At age 11, endothelium-dependent flow-mediated vasodilatory responses of the brachial artery were examined with high-resolution ultrasound in 402 children. These children were divided into 3 groups according to serum cotinine concentrations: the noncotinine group (nondetectable cotinine, n=229), the low cotinine group (cotinine between 0.2 and 1.6 ng/mL, n=134), and the top decile cotinine group (cotinine 1.7 ng/mL, n=39). Longitudinal cotinine data in children aged 8 to 11 years and ultrasound studies were available in 327 children. At age 11, the increase in cotinine concentration was associated with attenuated peak flow-mediated dilation response (mean±SD: the noncotinine group 9.10±3.88%, the low-cotinine group 8.57±3.78%, and the top-decile cotinine group 7.73±3.85%; P=0.03 for trend). Similarly, total dilation response (the area under the dilation response versus time curve between 40 and 180 seconds after hyperemia) was affected by the cotinine level (P=0.02 for trend). These trends were not explained by traditional atherosclerosis risk factors. Arterial measures and passive smoking showed even stronger associations when longitudinal cotinine data were used (peak flow-mediated dilation, P=0.01 for trend; total dilation response, P=0.008 for trend).

Conclusions. Exposure to environmental tobacco smoke confirmed by serum cotinine concentrations impairs endothelial function in a dose-dependent manner in 11-year-old children.

Circulation. 2007;115:3205-3212.
© 2007 American Heart Association, Inc.
http://circ.ahajournals.org/cgi/content/abstract/115/25/3205

Cold periods and Coronary events

Cold periods and coronary events: an analysis of populations worldwide

Adrian G Barnett (1), Annette J Dobson (1), Patrick McElduff (2), Veikko Salomaa (3), Kari Kuulasmaa (3), Susana Sans (4) for the WHO MONICA project

1) School of Population Health, University of Queensland, Herston, Australia; 2) The Medical School, University of Manchester, Manchester, UK; 3) KTL-NPHI, Department of Epidemiology, Helsinki, Finland; 4) Institute of Health Studies, Department of Health, Barcelona, Spain

Study objective: To investigate the association between cold periods and coronary events, and the extent to which climate, sex, age, and previous cardiac history increase risk during cold weather.

Design: A hierarchical analyses of populations from the World Health Organisation’s MONICA project.

Setting: Twenty four populations from the WHO’s MONICA project, a 21 country register made between 1980 and 1995.

Patients: People aged 35–64 years who had a coronary event.

Main results: Daily rates of coronary events were correlated with the average temperature over the current and previous three days. In cold periods, coronary event rates increased more in populations living in warm climates than in populations living in cold climates, where the increases were slight. The increase was greater in women than in men, especially in warm climates. On average, the odds for women having an event in the cold periods were 1.07 higher than the odds for men (95% posterior interval: 1.03 to 1.11). The effects of cold periods were similar in those with and without a history of a previous myocardial infarction.

Conclusions: Rates of coronary events increased during comparatively cold periods, especially in warm climates. The smaller increases in colder climates suggest that some events in warmer climates are preventable. It is suggested that people living in warm climates, particularly women, should keep warm on cold days.

Keywords: coronary disease; myocardial infarction; risk factors; MONICA project

Journal of Epidemiology and Community Health 2005;59:551-557
© 2005 BMJ Publishing Group Ltd
http://jech.bmj.com/cgi/content/abstract/59/7/551

Cardiopulmonary arrest: Seasonal variations

Seasonal variations in out of hospital cardiopulmonary arrest

J P Pell (a), J Sirel (b), A K Marsden (c), S M Cobbe (b)

a) Department of Public Health Medicine, Greater Glasgow Health Board, Dalian House, 350 St Vincents Street, Glasgow G3 8YU, UK; b) Department of Medical Cardiology, Glasgow Royal Infirmary, Glasgow, UK; c) Scottish Ambulance Service, Edinburgh, UK

OBJECTIVE. To determine whether there are seasonal variations in survival following out of hospital cardiopulmonary arrest.

DESIGN. Prospective cohort study using the Heartstart (Scotland) database.

SETTING. All of Scotland.

PATIENTS. 10 890 people who suffered out of hospital cardiopulmonary arrest in the summer or winter between December 1988 and August 1997 inclusive.

INTERVENTION. Univariate comparisons of 5406 arrests occurring in summer with 5484 in winter, in terms of patient characteristics, management, and survival using 2 and Mann-Whitney U tests. Multivariate analysis of the association between season and survival following adjustment for case mix.

MAIN OUTCOMES MEASURES. Survival to discharge from hospital, survival pre-admission, in-hospital survival.

RESULTS. Only 6% of people who arrested in winter survived to discharge, compared to 8% of those who arrested in summer (odds ratio 0.77, p < 0.001). People who arrested in winter had a poorer risk profile in that they were older, more likely to arrest at home, less likely to have a witness, and less likely to receive defibrillation. However, after adjustment for case mix, people who arrested in winter were still 19% less likely to survive compared to those who arrested in summer. Deaths pre-admission were significantly higher in winter (odds ratio 1.18, p < 0.05) but in-hospital deaths were not.

CONCLUSIONS. People who suffer cardiopulmonary arrest in winter have a significantly lower likelihood of surviving. This is, in part, caused by the higher frequency of a number of recognised risk factors. However, their prognosis remains poorer even after adjustment for these factors.

Keywords: cardiopulmonary arrest; cardiopulmonary resuscitation; seasonal variations; ischaemic heart disease

Heart 1999;82:680-683 ( December )
http://heart.bmj.com/cgi/content/abstract/82/6/680

Grapefruit - Help at heart disease

Red grapefruit appears to lower cholesterol, fight heart disease

A grapefruit a day - particularly the red variety - can help keep heart disease at bay, according to a new study by Israeli researchers. In a controlled study group of patients with heart disease, the scientists found that feeding some patients the equivalent of one grapefruit daily significantly reduced levels of cholesterol in comparison to patients that did not eat grapefruit. Chronic high blood cholesterol is a major risk factor for heart disease.

The study, which strengthens a growing body of evidence supporting the heart-healthy benefits of eating citrus fruit, was published Feb. 3 on the website of the American Chemical Society's Journal of Agricultural and Food Chemistry . The findings come at an appropriate time: The month of February has been designated as American Heart Month and heart disease is the number one killer of women in the United States. The study will appear in the journal's March 22 print issue.

The study included 57 patients, both men and women, with hyperlipidemia (high blood cholesterol) who recently had coronary bypass surgery and whose high lipid levels failed to respond significantly to statin drugs. Statins are commonly prescribed to lower cholesterol, according to study leader Shela Gorinstein, Ph.D., a chief scientist at the Hebrew University of Jerusalem.

The patients, equally divided into three treatment groups, were given either a single serving of fresh red grapefruit, white (blond) grapefruit or no grapefruit, along with regular, balanced meals for 30 consecutive days. Israeli Jaffa red and white grapefruit varieties, which are available in the U.S., were used in this study.

The patients who received either red or white grapefruit showed significant decreases in blood lipid levels, whereas the patients that did not eat grapefruit showed no changes in lipid levels, according to the researchers. Red grapefruit was more effective than white in lowering lipids, particularly blood triglycerides, a type of cholesterol whose elevated levels are often associated with heart problems, the researchers say.

It is likely that antioxidants in the grapefruits are responsible for their health benefits, says Gorinstein, adding that the red variety generally has higher antioxidants than the white. But it's also possible that red grapefruit may contain unknown chemicals that are responsible for the observed triglyceride-lowering effect, she says. Additional studies are planned.

Both the fresh fruit and the juice are believed to be equally beneficial, Gorinstein and her associates say. One cup of fresh grapefruit is roughly equivalent to half a cup of juice.

Grapefruit is known to interact with certain medications -sometimes adversely - so the researchers caution people on prescription medication to consult with their doctor or pharmacist to determine whether their medicine will interact before consuming grapefruit products. Appropriate exercise, well-balanced nutrition and avoidance of tobacco also are important factors in reducing the risk of heart disease, health experts say.

American Chemical Society

http://www.brightsurf.com/news/

Heart Failure Therapy: men and women

Clinical Investigations Does Heart Failure Therapy Differ According to Patient Sex?

Josep Lupón M.D., Agustín Urrutia, M.D., Beatriz González C.N., Crisanto Díez, M.D., Salvador Altimir, M.D., Carlos Albaladejo, M.D., Teresa Pascual, M.D., Celestino Rey-Joly, M.D., Vicente Valle, M.D.
Unitat d'Insuficiència Cardíaca, Hospital Universitari Germans Trias i Pujol, Badalona, Spain

Objectives. To assess differences in clinical characteristics, treatment and outcome between men and women with heart failure (HF) treated at a multidisciplinary HF unit. All patients had their first unit visit between August 2001 and April 2004.

Patients. We studied 350 patients, 256 men, with a mean age of 65 ± 10.6 years. In order to assess the pharmacological intervention more homogeneously, the analysis was made at one year of follow-up.

Results. Women were significantly older than men (69 ± 8.8 years vs. 63.6 ± 10.9 years, p < 0.001). Significant differences were found in the HF etiology and in co-morbidities. A higher proportion of men were treated with ACEI (83% vs. 68%, p < 0.001) while more women received ARB (18% vs. 8%, p = 0.006), resulting in a similar percentage of patients receiving either of these two drugs (men 91% vs. women 87%). No significant differences were observed in the percentage of patients receiving beta-blockers, loop diuretics, spironolactone, anticoagulants, amiodarone, nitrates or statins. More women received digoxin (39% vs. 22%, p = 0.001) and more men aspirin (41% vs. 31%, p = 0.004). Carvedilol doses were higher in men (29.4 ± 18.6 vs. 23.8 ± 16.4, p = 0.03), ACEI doses were similar between sexes, and furosemide doses were higher in women (66 mg ± 26.2 vs. 56 mg ± 26.2, p < 0.05). Mortality at 1 year after treatment analysis was similar between sexes (10.4% men vs. 10.5% women).

Conclusions. Despite significant differences in age, etiology and co-morbidities, differences in treatment between men and women treated at a multidisciplinary HF unit were small. Mortality at 1 year after treatment analysis was similar for both sexes.

Keywords: heart failure • treatment • sex

Clinical Cardiology Volume 30, Issue 6 , Pages 301 – 305 (June 2007)
Copyright © 2007 Wiley Periodicals, Inc.

http://www3.interscience.wiley.com/cgi-bin/abstract/114276980/ABSTRACT

Cocaine and Myocardial infarction

Clinical Investigations Traditional Risk Factors and Acute Myocardial Infarction in Patients Hospitalized with Cocaine-Associated Chest Pain

Darpan Bansal, M.D. (1), Marsha Eigenbrodt, M.D., MPH. (2), Ekta Gupta, M.D. 1, J. L. Mehta, M.D., Ph.D. (3)
1) Division of Cardiovascular Medicine, Department of Internal Medicine, Little Rock, Arkansas, USA; 2) Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA; 3) Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA

Background. Cocaine causes coronary artery constriction and may cause acute myocardial infarction (AMI). The role of traditional coronary risk factors in cocaine-associated myocardial infarction is unclear.

Hypothesis. We hypothesized that traditional risk factors play a major role in predicting AMI in patients admitted with cocaine-associated chest pain

Methods. After reviewing 165 admissions for chest pain in patients with a history of recent cocaine use and/or a positive drug screen from January 2001 to December 2004, we identified 151 patients with information available on at least 6 of the following 7 risk factors: gender, hypertension, hyperlipidemia, diabetes, smoking, family history of coronary artery disease (CAD) and known CAD. AMI was diagnosed using WHO criteria. A risk score was calculated on the basis of the number of risk factors, gender and age. Association of AMI was evaluated with the individual risk factors and with the risk score.

Results. AMI was identified in 21 patients (14%). All patients diagnosed with AMI were smokers. Continuous risk score (p < 0.0001), highest vs. lowest quartile of risk score (p = 0.007), known CAD, age, hyperlipidemia and family history of CAD were individually associated with the diagnosis of AMI (p0.05). Each quartile of risk score was associated with increased odds of the diagnosis of AMI and score of 8 or higher was statistically significant.

Conclusion. Several traditional risk factors are associated with the diagnosis of AMI among patients hospitalized with cocaine-associated chest pain and increasing risk factor score was associated with increasing odds of AMI diagnosis. Copyright © 2007 Wiley Periodicals, Inc.

Keywords: cocaine • chest pain • myocardial infarction

Clinical Cardiology - Volume 30, Issue 6 , Pages 290 – 294 (June 2007)
Copyright © 2007 Wiley Periodicals, Inc.

Lead to heart attack treatments

System to analyze beating heart stem cells could lead to heart attack treatments

New research at the University of Nottingham, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), is paving the way for techniques that use stem cells to repair the damage caused by heart attacks.

The research, highlighted in the new issue of BBSRC Business, is looking at the process that turns a stem cell into a cardiomyocyte - the beating cell that makes up the heart. The Nottingham researchers are developing a new system to monitor cardiomyocytes in real time as they differentiate from stem cells into beating heart cells. The system uses electrophysiology to record the electrical properties in a cell and will be the first time it has been used to study cardiomyocyte cells in the UK.

The researchers hope that their research could provide more detailed information on the electrical activity of stem cell derived cardiomyocytes. In the longer term, this could facilitate their use in regenerating the damaged hearts of heart attack victims.

"Human embryonic stem cells promise unrivalled opportunities. However, they are difficult, time-consuming and expensive to grow in the lab", Dr Denning explains. "Our understanding of how to convert them into cardiomyocytes is poor. At the moment we only know how to produce a few million cardiomyocytes, but to treat just one heart attack patient, we may need one billion that all function in the correct way."

To help overcome the many challenges that stem cells bring, Dr Denning and his team plan to engineer a novel system for real-time analysis of cardiomyocytes during early development so their properties are better understood.

The team have already demonstrated that sufficient numbers of stem cell-derived cardiomyocytes can be produced for detailed analysis and they plan to use new 'electrophysiology' systems to record changes in the cells when cultured. Electrophysiology is the study of cells' electrical properties and this is the first time that the method has been used in the UK to study stem cell-cardiomyocyte biology.

"This research will enable rapid development of stem cell-derived cardiomyocytes as a tool for understanding the heart and its diseases," says Dr Denning. However, he cautions: "Before we can consider using stem cells to treat heart-attack patients there are many problems which will take many years to solve. We don't yet know how to deliver the cells to a patient's heart and prevent them being washed away so that they actually stay in the heart and both survive and function. It will take many years to overcome these challenges and put stem cell-derived cardiomyocytes into medical usage."

The researchers will also be monitoring how the cells respond to different pharmacological agents in order to improve drug-screening processes and reduce the need for animal testing.

"A key part of the project is to monitor the effects of different drugs on the cells. At present, only limited information is available on how they respond to pharmacological or gene modulating agents.

"Between 1990 and 2001, 8 different drugs were withdrawn from the market in the USA at an estimated cost of $8billion because they caused unexpected deaths in several hundred patients. Our aim is to reduce such occurrences by having better test methods to test the drugs before they reach the clinic.

"By studying the drugs' effects on the heart cells in the lab, this could reduce the need for animals in clinical trials."

Biotechnology and Biological Sciences Research Council
http://www.brightsurf.com/news/

Blood Pressure and Stroke Recurrence

Relationship Between Blood Pressure and Stroke Recurrence in Patients With Intracranial Arterial Stenosis

Tanya N. Turan, MD; George Cotsonis, MA; Michael J. Lynn, MS; Seemant Chaturvedi, MD; Marc Chimowitz, MB, ChB, for the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) Trial Investigators

From Emory University, Atlanta, Ga (T.N.T., G.C., M.J.L., M.C.), and Wayne State University, Detroit, Mich (S.C.).

Background. Many clinicians allow blood pressure to run high in patients with intracranial stenosis to protect against hypoperfusion. We sought to determine whether higher blood pressure decreases the risk of stroke in these patients.

Methods and Results. Data on 567 patients in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial were analyzed. Time to ischemic stroke and stroke in the same territory of the stenotic vessel was compared in patients grouped by mean systolic blood pressure (SBP) and mean diastolic blood pressure (DBP) during the study. Additional analyses were based on severity and location of stenosis. Ischemic stroke risk increased with increasing mean SBP and DBP on univariate analysis (P<0.0001, P<0.0001) and after adjustment for risk factors (P=0.0008, P<0.0001). Elevated mean SBP and DBP also resulted in increased risk of stroke in the territory in univariate (P=0.0065, P<0.0001) and adjusted (P=0.0002, P=0.0005) analyses. The increased risk of stroke with increasing SBP was driven largely by patients in the highest SBP group. Patients with moderate (<70%) stenosis had increased risk of stroke (P<0.0001, P=0.003) and stroke in the territory (P=0.0002, P=0.010) with increased SBP and DBP. Patients with severe (70%) stenosis had increased risk of stroke and stroke in the territory with elevated DBP (P=0.004, P=0.004).

Conclusions. In patients with intracranial stenosis, higher blood pressure is associated with increased (not decreased) risk of ischemic stroke and stroke in the territory of the stenotic vessel. These findings argue strongly against the common clinical practice of maintaining high blood pressure in patients with intracranial stenosis.

Circulation. 2007;115:2969-2975.
© 2007 American Heart Association, Inc.
http://circ.ahajournals.org/

Neopterin - Prognostic Value

Long-Term Prognostic Value of Neopterin
A Novel Marker of Monocyte Activation in Patients With Acute Coronary Syndrome

Kausik K. Ray, MRCP, MD; David A. Morrow, MD, MPH; Marc S. Sabatine, MD, MPH; Amy Shui, MA; Nader Rifai, PhD; Christopher P. Cannon, MD; Eugene Braunwald, MD

From the Department of Public Health and Primary Care (K.K.R.), University of Cambridge, Cambridge, United Kingdom; TIMI Study Group (D.A.M., M.S.S., A.S., C.P.C., E.B.), Cardiovascular Division and the Department of Medicine, Brigham and Women’s Hospital/Harvard Medical School, Boston, Mass; and Children’s Hospital (N.R.), Boston, Mass.

Background. Monocyte activation is believed to play an important role in the pathogenesis of acute coronary syndromes (ACS). Neopterin is a soluble marker of monocyte activation, and elevated levels are of prognostic value in patients with stable coronary artery disease.

Methods and Results. Neopterin levels were measured on average at 7 days (in 3946 patients) and at 4 months (in 3369 patients) after ACS in the PRavastatin Or atorVastatin Evaluation Infection Therapy–Thrombolysis In Myocardial Infarction (PROVE IT–TIMI 22) trial. We assessed the relationship between plasma neopterin levels and the risk of death and death or acute coronary events (nonfatal myocardial infarction or unstable angina) over 2 years. Seven days after an ACS event, neopterin levels 12.11 nmol/L (upper quartile, derived from a post hoc analysis) were associated with an increased risk of death and an increased risk of death or acute coronary events after adjustment for age, gender, history of diabetes mellitus, history of hypertension, history of smoking, type of ACS presentation, use of percutaneous coronary intervention for the index event, statin regimen, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein (hazard ratio, 1.86 [95% CI, 1.24 to 2.77], P=0.003; and hazard ratio, 1.33 [95% CI, 1.09 to 1.63] P=0.006, respectively). Neopterin levels 12.11 nmol/L at 4 months remained a predictor of death alone and of death or acute coronary events after multivariable adjustment that included adjustment for month 4 low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and statin regimen (hazard ratio, 2.39 [95% CI, 1.43 to 3.99], P=0.001; and hazard ratio, 1.60 [95% CI, 1.21 to 2.11], P=0.001). High-dose atorvastatin significantly attenuated the risk among subjects with neopterin levels 12.11 nmol/L at baseline (interaction P for death or acute coronary event, 0.018).
Conclusions. Increased monocyte activation detected by an elevated plasma neopterin level identifies patients at long-term risk of death or recurrent acute coronary events after ACS. Intensive statin therapy significantly attenuates the risk of recurrent events among patients with an elevated neopterin level.

Circulation. 2007;115:3071-3078.
© 2007 American Heart Association, Inc.
http://circ.ahajournals.org/cgi/content/abstract/115/24/3071

Coronary artery calcification

Coronary Artery Calcification Progression Is Heritable

Andrea E. Cassidy-Bushrow, PhD, MPH; Lawrence F. Bielak, DDS, MPH; Patrick F. Sheedy, II, MD; Stephen T. Turner, MD; Iftikhar J. Kullo, MD; Xihong Lin, PhD; Patricia A. Peyser, PhD
From the Department of Epidemiology, University of Michigan, Ann Arbor (A.E.C.-B., L.F.B., P.A.P.); Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, Mich (A.E.C.-B.); Department of Diagnostic Radiology (P.F.S.), Division of Hypertension, Department of Internal Medicine (S.T.T.), and Division of Cardiovascular Diseases (I.J.K.), Mayo Clinic and Foundation, Rochester, Minn; and Department of Biostatistics, Harvard University, Boston, Mass (X.L.).

Background. Coronary artery calcification (CAC), a marker of coronary artery atherosclerosis, can be measured accurately and noninvasively with the use of electron beam computed tomography. Serial measures of CAC quantify progression of calcified coronary artery plaque. Little is known about the role of genetic factors in progression of CAC quantity.

Methods and Results. We quantified the relative contributions of measured risk factors and unmeasured genes to CAC progression measured by 2 electron beam computed tomography examinations an average of 7.3 years apart in 877 asymptomatic white adults (46% men) from 625 families in a community-based sample. After adjustment for baseline risk factors and CAC quantity, the estimated heritability of CAC progression was 0.40 (P<0.001). Baseline risk factors and CAC quantity explained 64% of the variation in CAC progression. Thus, genetic factors explained 14% of the variation [(100–64)x(0.40)] in CAC progression. After adjustment for risk factors, the estimated genetic correlation (pleiotropy) between baseline CAC quantity and CAC progression was 0.80 and was significantly different than 0 (P<0.001) and 1 (P=0.037). The environmental correlation between baseline CAC quantity and CAC progression was 0.42 and was significantly different than 0 (P=0.006).

Conclusions. Evidence was found that many but not all genetic factors influencing baseline CAC quantity also influence CAC progression. The identification of common and unique genetic influences on these traits will provide important insights into the genetic architecture of coronary artery atherosclerosis.

Circulation. 2007;116:25-31.
© 2007 American Heart Association, Inc.
http://circ.ahajournals.org/