Regenerates after stroke: New insight

Cellular cues identified for stroke recovery

New insight into how the brain regenerates after stroke.

When a stroke strikes, the supply of blood to the part of the brain affected is interrupted, starving it of oxygen. Brain cells can be seriously damaged or die, impairing local brain function.

But the brain is a battler. Within weeks of a stroke, new blood vessels begin to form, and, like marching ants, newly born neurons migrate long distances to the damaged area to aid the regeneration process. What’s not known is what the right cellular environment is, and what the cellular cues are for this process of regeneration and migration to take place.

Now, in the Journal of Neuroscience, currently online, S. Thomas Carmichael, M.D., Ph.D., an assistant professor in the Department of Neurology at the UCLA Geffen School of Medicine, and colleagues report that in the mouse model, this neuron march is the direct result of signaling from the newly blooming blood vessels, thus casually linking angiogenesis the development of new blood vessels and neurogenesis, the birth of new neurons. Further, they have identified what these molecular signals are. The results hold promise for eventual clinical applications that may spur brain repair after stroke.Stroke is the leading cause of adult disability, said Carmichael. And while much is known about the mechanisms of cell death in stroke, little is known about the mechanisms of neurological recovery after a stroke. His lab studies the mechanisms of brain repair and the recovery of function after a stroke.

Recent research has revealed that in the adult brain, new neurons form in a region of the forebrain known as the subventricular zone (SVZ). In mice, after a stroke was initiated in a part of the brain located far from the SVZ, the researchers, using a combination of mitotic, genetic, and viral labeling, tracked newly formed neuroblasts (immature brain cells from which mature adult neurons form) as they traveled through healthy brain tissue to the stroke area. Once there, these immature neurons wrapped themselves around the immature vascular cells that were in the process of forming new blood vessels in the damaged area. The neurons were found to arrive at the site within the first two to four weeks after the stroke.

Further, the researchers found that two proteins, stromal-derived factor 1 (SDF1) and angiopoietin 1 (Ang1), that are given off by these newly-forming blood vessels, are what trigger the thousands of immature neurons to the site of damage.

“The SDF1 and Ang1 proteins are what link the two processes of neurogenesis and angiogenesis together by promoting post-stroke neuroblast migration,” said Carmichael. They also appear to effect behavioral recovery as well, he noted. The researchers produced the stroke in an area of the brain that controls the mouse’s facial whiskers. When the mouse was infused by the researchers with Ang1 and SDF1, improvement in the function of the whisker’s was seen to the same levels as the control (non-stroke) mice.

If harnessed properly, said Carmichael, the molecular mechanisms for neuronal regeneration hold the promise of regenerating and reconnecting brain cells near the area where stroke occurs. While the process may vary between mice and humans, he said, it’s known that neurogenesis occurs in humans. “We’re hopeful that we can take advantage of the brain’s plasticity,” said Carmichael. “This work could lead to the development of new therapies that will promote brain repair after stroke.”

University of California–Los Angeles
http://brightsurf.com/news

Concordant ventriculoarterial connections

Hearts with concordant ventriculoarterial connections but parallel arterial trunks

T Cavalle-Garrido1, A Bernasconi1, D Perrin2 and R H Anderson3
1) Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada

2) Division of Pathology, Department of Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada

3) Cardiac Unit, Institute of Child Health, University College, London, UK

Objectives: To determine the characteristic morphological features of hearts with concordant ventriculoarterial connections and parallel arterial trunks, and to provide unequivocally a method to describe their anatomy.

Design, methods and patients: The entire cardiac database and cardiac pathological archive at the Hospital for Sick Children, Toronto, Ontario, Canada, was interrogated to identify all patients with concordant ventriculoarterial connections and parallel arterial trunks. The clinical records, autopsy reports and actual cardiac specimens of those who underwent autopsy, were reviewed.

Results: 8 cases meeting our criteria were identified. The infundibular anatomy was variable, including four hearts with bilateral infundibulums, three with subpulmonary infundibulums and one with bilaterally absent infundibulums. Considerable variability was also found in the type of atrial arrangement, along with the morphology of the atrioventricular junctions. The most common findings were the usual atrial arrangement (n = 5), left juxtaposition of the right atrial appendages (n = 3), an atrial septal defect (n = 6), univentricular atrioventricular connection (n = 5), ventricular septal defect (n = 8) and pulmonary obstruction (n = 4). In addition, five specimens had either a single coronary artery or two coronary arteries arising from the anticipated right coronary aortic sinus.

Conclusions: Concordant ventriculoarterial connections with parallel arterial trunks can be found in a variety of segmental combinations. An accurate diagnosis of these rare hearts can be achieved by detailed analysis of not only the ventriculoarterial connections but also the infundibular anatomy and the spatial relationship of the arterial trunks. Particular attention to the coronary arteries is warranted.

Heart 2007;93:100-106

© 2007 by BMJ Publishing Group Ltd & British Cardiovascular Society

Small-vessel vasculitis: association with subclinical atherosclerosis

Increased prevalence of subclinical atherosclerosis in patients with small-vessel vasculitis

G Chironi1, C Pagnoux2, A Simon1, M Pasquinelli-Balice1, M Del-Pino1, J Gariepy1 and L Guillevin2
1) Centre de Médecine Préventive Cardiovasculaire, Groupe Hospitalier Broussais-HEGP, Université Paris V, Paris, France
2) Service de Médecine Interne, Hôpital Cochin, Université Paris V, Paris, France

Background and objective: Although changes in smaller vessels is the hallmark of medium-sized and small-vessel vasculitis, it has been suggested that large arteries of such patients may also be affected by the early atherosclerotic process because of coexisting risk factors or systemic inflammation. This study aimed to bring additional arguments supporting this hypothesis.

Design, setting and patients: 50 consecutive patients with primary systemic necrotising vasculitis and 100 controls matched for age and sex underwent ultrasonic detection of plaque in three peripheral vessels (carotid and femoral arteries and abdominal aorta). Cardiovascular risk factors and inflammation (C reactive protein (CRP)) were concomitantly measured in all participants, and diagnosis of high-risk status was defined by the presence of known history of cardiovascular disease, type 2 diabetes or 10-year-Framingham Risk Score >20%.

Results: Patients had higher frequency of plaque than controls in the carotid arteries (p<0.05), in the aorta (p<0.01) and in the three vessels examined (p<0.001), and adjustment for high-risk status did not confound such difference in the aorta and in the three vessels. In the overall population of patients and controls, vasculitis was associated with a higher frequency of three-vessel plaques (p<0.05), independently of high-risk status and CRP. In patients, the higher frequency of three-vessel plaques was associated with high-risk status (p<0.05) but not with CRP, or disease and treatment characteristics.

Conclusions: Small-vessel vasculitis is associated with more frequent subclinical atherosclerosis, especially extended to multiple peripheral vessels, and such association is not entirely explained by cardiovascular risk factors and systemic inflammation.

Abbreviations: CRP, C reactive protein; IMT, intima–media thickness

Heart 2007;93:96-99
© 2007 by BMJ Publishing Group Ltd & British Cardiovascular Society

Birthday anxiety: Vascular events

Birthday blues
Milton Alter, MD, PhD

Is it possible that happy occasions such as birthdays have negative effects on some people? I recall a 74-year-old woman, in apparent good health, who dreaded her upcoming 75th birthday. As the day approached, she became more and more anxious. She kept her fears to herself because they did not make sense. The "happy day" arrived and was celebrated as planned. Only some 7 months after the event was she willing to confide her worries to her doctor. She had vague complaints like a headache, dizzy spells, and fatigue but three different doctors found nothing more unusual than a rapid heartbeat. What caused her 75th birthday anxiety? She finally admitted that her mother had died at age 75 and she was convinced that she too was doomed to die at this age.

How was the study done? The researchers counted all visits to a hospital emergency room (ER) in their region to determine the expected number of vascular events that occur on a daily basis. Vascular events included major strokes, transient ischemic attacks (TIAs or mini strokes that last less than a day), and acute heart attacks. This expected number was compared with a control group, which included an expected number of nonvascular conditions. Asthma, appendicitis, and head trauma were chosen as the control conditions because people tend to go to the ER with these problems as quickly as they would for the vascular events.

What did the study find? The chance of having a stroke, TIA, or heart attack on a birthday was 27% higher than the expected daily average. However, the number of vascular events that occurred during the birthday week (3 days before and 3 days after the birthday) was no different than the expected number of ER visits. There was no increase in the number of visits to the ER for any of the control conditions on the birthday. Also, there were more vascular events on birthdays than on other special calendar events like Christmas, New Year, or other holidays. Interestingly, milestone birthdays (40, 50, 60) were no different from ones that occurred at other ages.

What did these findings mean? The researchers looked for a reason why vascular events were more common on the birthday than any other day. They discovered that the group with the vascular events was more likely to have had a history of high blood pressure. When the subgroup with high blood pressure was looked at more closely, the association between vascular events and birthdays was even higher. This was actually not surprising because it is well known that high blood pressure is a big risk factor for strokes and heart attacks.
The risk of having a vascular event increases rapidly after age 45 years, earlier in men than in women. But even if age is a risk factor that cannot be controlled, why should the risk be increased on the birthday? The article mentions other studies that have shown an increase in stroke, heart attack, and even sudden cardiac death associated with stressful events. Natural disasters (e.g., earthquakes), terrorist attacks, and even major exciting sporting events such as the World Cup Football (soccer) are associated with increased vascular events. These events have in common a tendency to provoke anxiety.

How can anxiety cause a vascular event? Anxiety can certainly increase blood pressure and speed up the heart rate, which are vascular risk factors. Normally the arteries of the heart dilate (expand) during mental stress. However, in people with atherosclerotic arteries (clogged by fatty deposits), these vessels may actually constrict (narrow) with mental stress. When the vessel becomes too narrow a heart attack results. Studies have shown that the risk of a heart attack doubles in the hour after strong negative emotions like frustration or sadness. Mental stress may also cause certain areas of the brain to trigger irregular heartbeats and increase blood pressure.

What can be done to prevent birthday risk? Saposnik and coworkers suggest that people with known vascular risk factors should be a little more cautious. They should avoid too much fatty or salty food and alcoholic drinks on the "happy day." Alcohol can decrease the heart’s ability to contract and increase irregular heartbeats. Too much physical activity and exposure to cold weather should also be avoided. If a big party is planned extra help may be hired to reduce stress. Surprise birthday parties should probably be avoided. A mild tranquilizer might be prescribed if the birthday is stressful. Planning should be done well in advance of the party to avoid last minute running about. These common sense plans, discussed with the patient and family before the birthday, may help assure "many happy returns!" of the day.

What makes the brain so special? The brain, like all organs in the body, depends on a steady blood supply to function, but it receives way more than its share for its size. However, this is not surprising given all the work the brain does with its own thinking and planning functions as well as masterminding and controlling the body as a whole. The brain has two hemispheres (the right and the left) and, although they are connected, each half controls mostly the opposite side of the body. Specialized areas in the brain control movement of the arms and legs, feeling, speech, hearing, and vision, as well as many other functions. If the blood supply to the brain fails, loss of one or more of these specialized functions occurs in minutes. This rapid onset of deficit allows one to suspect that a vascular event has occurred and what part of the brain is damaged. Unlike Alzheimer dementia or Parkinson disease, which evolve over years, a vascular event comes on suddenly, though may progress over minutes to hours. This event is an emergency; it is a brain attack: call 911! Quick treatment is needed if the brain tissue that has lost its blood supply is to be saved from permanent damage. Usually, special treatment can be given only within 3 hours of onset of loss of function so a vascular event is an emergency. It is taught that time is brain tissue. It makes sense that this event is called a stroke.

Different types of stroke? The most common type of vascular event in the brain results from blockage of an already narrowed and rigid brain blood vessel. This is most often due to atherosclerosis (clogging of the arteries with fatty materials). Although this is more common in older people, the process begins many years earlier and can happen even to young adults. This blockage of the blood supply causes an ischemic stroke. Sometimes, a thickened and rigid vessel wall forms a blood clot which can block blood flow at the original site. This leads to a massive stroke with lots of damage. However, in other cases, the clot can break loose, float downstream, and block a smaller vessel in the brain. Depending on the size of this smaller vessel and the area it supplies, the damage may be less. Such a stroke is called an embolic stroke. Yet another type of stroke is caused when a weakened blood vessel ruptures and blood jets out into the brain itself with each heartbeat. This causes a hemorrhagic stroke. One of the major causes of this blood vessel weakening is high blood pressure. Sometimes deficits like weakness and numbness on one side of the body or loss of speech come on suddenly and disappear after a few hours. This could be a transient ischemic attack (TIA for short). Although the patient may rapidly improve, this type of stroke cannot be ignored. It is a warning that a big stroke may be about to happen and medical help must be sought immediately.

Different types of stroke treatment? Each type of stroke may produce similar signs because the loss of function depends more on the part of the brain that is damaged than the type of stroke. However, different types of stoke need different types of treatment. A person with an ischemic stroke may benefit from a treatment to try to dissolve the blood clot. This type of treatment would be avoided if a person had a brain hemorrhage. The type of stroke can now be determined with studies like a computerized tomogram (CT) and a computerized magnetic image (MRI). The blood vessels themselves can be seen with an angiogram. These sensitive tools help confirm the suspicion of a vascular event in the brain and what area is affected. The best treatment for the particular vascular event can then be started.

What are risk factors for stroke? The chances of having a vascular event increases rapidly after age 45 years. Men have a higher risk than women until old age when women catch up and even surpass the risk in surviving men. One of the biggest risk factors for stroke is high blood pressure. This can and should be treated and watched very closely. Diet also seems to play a key role in stroke risk. Obesity, diabetes, and too much cholesterol all can be at least partially, if not entirely, improved by what you choose to eat and avoiding overeating. Lack of regular exercise often goes along with poor fitness and is another risk factor. New risks are being found regularly by researchers. In the present issue of this journal, a new one has been identified that is somehow associated with a birthday. Because we do not yet know what, specifically, about a birthday increases risk, more research is needed. Many of the risk factors for vascular events are controllable and we certainly do not want to stop celebrating birthdays.

What can be done to avoid a stroke? Have your blood pressure checked regularly and, if it is high, take the medications you are given and follow the advice of your doctor. Change your diet so you have five to seven servings of fruits and vegetables per day, avoid fatty foods (especially deep fried foods and fatty meats), and do not eat too much (only eat when you are hungry, not because you are bored or anxious). Enjoy getting regular exercise by walking, gardening, swimming, or even dancing. If you smoke, stop or get help to stop. Try to reduce stress by taking time for activities you enjoy and people you like to be with. Many of the risk factors for stroke can be controlled: put yourself in charge of doing all you can to avoid this unhappy event.

NEUROLOGY 2006;67:E3-E4
© 2006 American Academy of Neurology

Alcohol septal ablation

Pathological effects of alcohol septal ablation for hypertrophic obstructive cardiomyopathy
A L Baggish1, R N Smith2, I Palacios1, G J Vlahakes3, D M Yoerger1, M H Picard1, P A Lowry1, I-k Jang1 and M A Fifer1
1) Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
2) Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
3) Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA

Background: The pathological effects and the mechanisms of action of intracoronary administration of ethanol for alcohol septal ablation (ASA) for the management of hypertrophic obstructive cardiomyopathy (HOCM) are unknown.

Methods: We examined surgical specimens and, in one case, autopsy specimens from four patients who underwent surgical septal myectomy 2 days to 14 months after unsuccessful ASA.

Results: Pathological examination early after ASA showed coagulative necrosis of both the myocardium and the septal perforator arteries. Affected arteries were distended and occluded by necrotic intraluminal debris, without platelet–fibrin thrombi. Late after unsuccessful ASA, excised septal tissue was heterogeneous, containing a region of dense scar, and adjacent tissue containing viable myocytes and interspersed scar.

Conclusions: Intracoronary administration of ethanol in patients with HOCM causes acute myocardial infarction with vascular necrosis. The coagulative necrosis of the arteries, their distension by necrotic debris and the absence of platelet–fibrin thrombi distinguish ethanol-induced infarction from that caused by atherosclerotic coronary artery disease. The direct vascular toxicity of ethanol may be an important aspect of the mechanism of successful ASA.

Abbreviations: ASA, alcohol septal ablation; CCS, Canadian Cardiovascular Society; HOCM, hypertrophic obstructive cardiomyopathy; LVOT, left ventricular outflow tract; MVR, mitral valve replacement; NYHA, New York Heart Association; SAM, systolic anterior motion

Heart 2006;92:1773-1778

© 2006 by BMJ Publishing Group Ltd & British Cardiovascular Society

Christmas Blessings for all!

Holidays: Risk Factor for Death

Cardiac Mortality Is Higher Around Christmas and New Year’s Than at Any Other Time
The Holidays as a Risk Factor for Death
David P. Phillips, PhD; Jason R. Jarvinen, BA; Ian S. Abramson, PhD; Rosalie R. Phillips, MPH
From the Departments of Sociology (D.P.P., J.R.J.) and Mathematics (I.S.A.), University of California–San Diego, La Jolla, the San Diego Center for Patient Safety (D.P.P.), and the Tufts Health Care Institute, Tufts University School of Medicine (R.R.P.), Boston, Mass.

Background— Research published in Circulation has shown that cardiac mortality is highest during December and January. We investigated whether some of this spike could be ascribed to the Christmas/New Year’s holidays rather than to climatic factors.

Methods and Results— We fitted a locally weighted polynomial regression line to daily mortality to estimate the number of deaths expected during the holiday period, using the null hypothesis that natural-cause mortality is unaffected by the Christmas/New Year’s holidays. We then compared the number of deaths expected during the holiday period, given the null hypothesis, with the number of deaths observed. For cardiac and noncardiac diseases, a spike in daily mortality occurs during the Christmas/New Year’s holiday period. This spike persists after adjusting for trends and seasons and is particularly large for individuals who are dead on arrival at a hospital, die in the emergency department, or die as outpatients. For this group during the holiday period, 4.65% (±0.30%; 95% CI, 4.06% to 5.24%) more cardiac and 4.99% (±0.42%; 95% CI, 4.17% to 5.81%) more noncardiac deaths occur than would be expected if the holidays did not affect mortality. Cardiac mortality for individuals who are dead on arrival, die in the emergency department, or die as outpatients peaks at Christmas and again at New Year’s. These twin holiday spikes also are conspicuous for noncardiac mortality. The excess in holiday mortality is growing proportionately larger over time, both for cardiac and noncardiac mortality.

Conclusions— Our findings suggest that the Christmas/New Year’s holidays are a risk factor for cardiac and noncardiac mortality. There are multiple explanations for this association, including the possibility that holiday-induced delays in seeking treatment play a role in producing the twin holiday spikes.

Key Words: epidemiology • mortality • heart diseases • patients • holidays Full Text

http://circ.ahajournals.org/cgi/content/abstract/110/25/3781
Circulation. 2004;110:3781-3788.

© 2004 American Heart Association, Inc.

New-onset hypertension in acute ischemic stroke

New-onset hypertension and inflammatory response/poor outcome in acute ischemic stroke

M. Rodríguez-Yáñez, MD, PhD, M. Castellanos, MD, PhD, M. Blanco, MD, PhD, M. M. García, PhD, F. Nombela, MD, PhD, J. Serena, MD, PhD, R. Leira, MD, PhD, I. Lizasoain, MD, PhD, A. Dávalos, MD, PhD and J. Castillo, MD, PhD
From the Department of Neurology, Stroke Unit, Hospital Clínico Universitario, University of Santiago de Compostela, Santiago de Compostela, Spain (M.R.-Y., M.B., R.L., J.C.); Department of Neurology, Stroke Unit (M.C., J.S.), and Unit of Biostatistics, Hospital Doctor Josep Trueta, Girona, Spain (M.M.G.); Department of Neurology, Stroke Unit (F.N.), Hospital de la Princesa, Madrid, Spain; Department of Pharmacology, School of Medicine, University Complutense, Madrid, Spain (I.L.); and Department of Neurology, Stroke Unit, Hospital Trias i Pujol, Barcelona, Spain (A.D.).

Objective: To study the association of previously unknown high blood pressure (HBP) during the acute phase of stroke (new-onset hypertension) with the inflammatory response and clinical outcome.

Methods: We classified 844 patients with hemispheric ischemic stroke into three groups according to history of hypertension and presence of HBP within the first 24 hours after symptom onset: Group I (n = 412), normotensive patients; Group II (n = 265), chronic hypertensive patients; and Group III (n = 167), new-onset hypertensive patients. Interleukin 6 (IL-6), tumor necrosis factor (TNF- ), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and metalloproteinase 9 (MMP-9) were measured in blood samples obtained on admission. The influence of new-onset HBP and markers of inflammation on poor neurologic outcome at 3 months was evaluated by logistic regression analysis.

Results: New-onset HBP was found in 19.9% of patients. Patients in this group had higher plasma concentrations of IL-6, TNF- , ICAM-1, VCAM-1, and MMP-9 than the other two groups. New-onset HBP was associated with poor outcome at 3 months (odds ratio [OR] 2.10; 95% CI 1.54 to 3.52; p < 0.0001) after adjustment for other prognostic factors. However, when markers of inflammation were included in the model, IL-6 (OR 1.01; 95% CI 1.00 to 1.03; p = 0.020) and MMP-9 (OR 1.01; 95% CI 1.00 to 1.01; p < 0.0001), but not new-onset HBP, were independently associated with poor neurologic outcome.

Conclusions: New-onset high blood pressure in acute ischemic stroke, but not chronic hypertension, is associated with an inflammatory response and poor neurologic outcome. Full Text

http://www.neurology.org/cgi/content/abstract/67/11/1973

NEUROLOGY 2006;67:1973-1978

© 2006 American Academy of Neurology

Hypothermia and microvascular thrombus

Sustained hypothermia accelerates microvascular thrombus formation in mice

Nicole Lindenblatt,1,2 Michael D. Menger,3 Ernst Klar,2 and Brigitte Vollmar1
1) Department of Experimental Surgery and
2) Department of General Surgery, University of Rostock, Rostock; and 3Department of Clinical and Experimental Surgery, University of Saarland, Homburg-Saar, Germany

Cold is supposed to be associated with alterations in blood coagulation and a pronounced risk for thrombosis. We studied the effect of clinically encountered systemic hypothermia on microvascular thrombosis in vivo and in vitro. Ferric chloride-induced microvascular thrombus formation was analyzed in cremaster muscle preparations from hypothermic mice. Additionally, flow cytometry and Western blot analysis was used to evaluate the effect of hypothermia on platelet activation. To test whether preceding hypothermia predisposes for enhanced thrombosis, experiments were repeated after hypothermia and rewarming to 37°C. Control animals revealed complete occlusion of arterioles and venules after 742 ± 150 and 824 ± 172 s, respectively. Systemic hypothermia of 34°C accelerated thrombus formation in arterioles and venules (279 ± 120 and 376 ± 121 s; P <>

Keywords: hemodynamics; glycoproteins; microcirculation; platelets

Am J Physiol Heart Circ Physiol 289: H2680-H2687, 2005.
© 2005 by the American Physiological Society.

Socioeconomic Status and Mortality

Socioeconomic Status and Mortality after Acute Myocardial Infarction

David A. Alter, MD, PhD; Alice Chong, BS; Peter C. Austin, PhD; Cameron Mustard, MD, PhD; Karey Iron, MHSc; Jack I. Williams, PhD; Christopher D. Morgan, MD; Jack V. Tu, MD, PhD; Jane Irvine, PhD; C. David Naylor, MD, DPhil, for the SESAMI Study Group

Background: Gradients that link socioeconomic status and cardiovascular mortality have been observed in many populations, including those of countries that provide publicly funded comprehensive medical coverage. The intermediary causes of such gradients remain poorly elucidated.
Objective: To examine the relationships among socioeconomic status, other health factors, and 2-year mortality rates after acute myocardial infarction (MI).
Design: Prospective cohort study.
Setting: Ontario, Canada.
Patients: 3407 patients who were hospitalized for acute MI in 53 large-volume hospitals in Canada from December 1999 to February 2003.
Measurements: The authors obtained self-reported measures of income and education and developed profiles of the patients' prehospitalization cardiac risks and comorbid conditions. To create these profiles, the authors used the patients' self-reports and retrospectively linked no less than 12 years' worth of previous hospitalization data. Mortality rates 2 years after acute MI were examined with and without sequential risk adjustment for age, sex, ethnicity, social support, cardiovascular history and risk, comorbid conditions, and selected in-hospital process factors.
Results: Income was strongly and inversely correlated with 2-year mortality rate (crude hazard ratio for high-income vs. low-income tertile, 0.45 [95% CI, 0.35 to 0.57]; P < 0.001). However, after adjustment for age and preexisting cardiovascular events or conventional vascular risk factors, the effect of income was greatly attenuated (adjusted hazard ratio for high-income vs. low-income tertile, 0.77 [CI, 0.54 to 1.10]; P = 0.150). Noncardiovascular comorbid conditions and in-hospital process factors had negligible explanatory effect.
Limitations: Previous cardiovascular risks were ascertained through self-report or retrospectively through the longitudinal tracking of the hospitals' administrative databases. The study began with a cohort of patients who had an index cardiac event rather than with asymptomatic individuals.
Conclusions: Age, past cardiovascular events, and current vascular risk factors accounted for most of the income–mortality gradient after acute MI. This observation suggests that the "wealth–health gradient" in cardiovascular mortality may be partially ameliorated by more rigorous management of known risk factors among less affluent persons.

Ann Intern Med 2006, Volume 144 Issue 2, Pages 82-93
Copyright © 2006 by the American College of Physicians.

Overweight, Obesity, and Mortality

Overweight, Obesity, and Mortality in a Large Prospective Cohort of Persons 50 to 71 Years Old

Kenneth F. Adams, Ph.D., Arthur Schatzkin, M.D., Tamara B. Harris, M.D., Victor Kipnis, Ph.D., Traci Mouw, M.P.H., Rachel Ballard-Barbash, M.D., Albert Hollenbeck, Ph.D., and Michael F. Leitzmann, M.D.
From the Nutritional Epidemiology Branch (K.F.A., A.S., T.M., M.F.L.), Division of Cancer Epidemiology and Genetics and the Biometry Research Group (V.K.), Division of Cancer Prevention, and the Division of Cancer Control and Population Sciences (R.B.-B.), National Cancer Institute, and the Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging (T.B.H.), the National Institutes of Health, Bethesda, Md.; and the AARP, Washington, D.C. (A.H.).

Background: Obesity, defined by a body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) of 30.0 or more, is associated with an increased risk of death, but the relation between overweight (a BMI of 25.0 to 29.9) and the risk of death has been questioned.

Methods: We prospectively examined BMI in relation to the risk of death from any cause in 527,265 U.S. men and women in the National Institutes of Health–AARP cohort who were 50 to 71 years old at enrollment in 1995–1996. BMI was calculated from self-reported weight and height. Relative risks and 95 percent confidence intervals were adjusted for age, race or ethnic group, level of education, smoking status, physical activity, and alcohol intake. We also conducted alternative analyses to address potential biases related to preexisting chronic disease and smoking status.

Results: During a maximum follow-up of 10 years through 2005, 61,317 participants (42,173 men and 19,144 women) died. Initial analyses showed an increased risk of death for the highest and lowest categories of BMI among both men and women, in all racial or ethnic groups, and at all ages. When the analysis was restricted to healthy people who had never smoked, the risk of death was associated with both overweight and obesity among men and women. In analyses of BMI during midlife (age of 50 years) among those who had never smoked, the associations became stronger, with the risk of death increasing by 20 to 40 percent among overweight persons and by two to at least three times among obese persons; the risk of death among underweight persons was attenuated.

Conclusions: Excess body weight during midlife, including overweight, is associated with an increased risk of death.

© 2006 Massachusetts Medical Society.

Rose angina: Population study

A population study of the long-term consequences of Rose angina: 20-year follow-up of the Renfrew–Paisley study

N F Murphy 1, S Stewart 2, C L Hart 3, K MacIntyre 3, D Hole 3 and J J V McMurray 1
1)Department of Cardiology, Western Infirmary, Glasgow, UK
2)Baker Heart Research Institute, Melbourne, Australia
3)Department of Public Health and Health Policy, University of Glasgow, Glasgow, UK

Objective: To examine the long-term cardiovascular consequences of angina in a large epidemiological study.
Design: Prospective cohort study conducted between 1972 and 1976 with 20 years of follow-up (the Renfrew–Paisley Study).
Participants: 7048 men and 8354 women aged 45–64 years who underwent comprehensive cardiovascular screening at baseline, including the Rose Angina Questionnaire and electrocardiography (ECG).
Main outcome measures: All deaths and hospitalisations for cardiovascular reasons occurring over the subsequent 20 years, according to the baseline Rose angina score and baseline ECG.
Results: At baseline, 669 (9.5%) men and 799 (9.6%) women had angina on Rose Angina Questionnaire. All-cause mortality for those with Rose angina was 67.7% in men and 43.3% in women at 20 years compared with 45.4% and 30.4%, respectively, in those without angina (p<0.001). Values are expressed as hazards ratio (HR) (95% confidence interval (CI). In a multivariate analysis, men with Rose angina had an increased risk of cardiovascular death or hospitalisation (1.49 (1.33 to 1.66), myocardial infarction (1.63 (1.41 to 1.85)) or heart failure (1.54 (1.13 to 2.10)) compared with men without angina. The corresponding HR (95% CI) for women were 1.38 (1.23 to 1.55), 1.56 (1.31 to 1.85) and 1.92 (1.44 to 2.56). An abnormality on the electrocardiogram (ECG) increased risk further, and both angina and an abnormality on the ECG increased risk most of all compared with those with neither angina nor ischaemic changes on the ECG. Compared with men, women with Rose angina were less likely to have a cardiovascular event (0.54 (0.46 to 0.64)) or myocardial infarction (0.44 (0.35 to 0.56)), although there was no sex difference in the risk of stroke (1.11 (0.75 to 1.65)), atrial fibrillation (0.84 (0.38 to 1.87)) or heart failure (0.79 (0.51 to 1.21)).
Conclusions: Angina in middle age substantially increases the risk of death, myocardial infarction, heart failure and other cardiovascular events.
Abbreviations: ECG, electrocardiography; ICD9, International classification of diseases, 9th revision

Heart 2006;92:1739-1746
© 2006 by BMJ Publishing Group Ltd & British Cardiovascular Society

Arrhythmogenic right ventricular dysplasia

Arrhythmogenic right ventricular dysplasia, a cell adhesion cardiomyopathy: insights into disease pathogenesis from preliminary genotype—phenotype assessment

A A Tsatsopoulou1, N I Protonotarios1 and W J McKenna2
1) Yannis Protonotarios Medical Center, Hora Naxos, Naxos, Greece
2) Department of Medicine, University College London and University College London Hospitals Trust, London, UK

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is a genetically determined heart muscle disorder presenting clinically with even lethal ventricular arrhythmias, particularly in the young and athletes. It is reported familial with recessive and most commonly dominant inheritance. Disease-causing genes are increasingly recognised among desmosomal proteins plakoglobin, desmoplakin, plakophilin2, and desmoglein2 displaying phenotypic heterogeneity. Mutations in the plakoglobin and desmoplakin genes have been identified to underlie recessive ARVC associated with woolly hair and palmoplantar keratoderma (Naxos disease), while mutations in plakophilin2, desmoglein2 as well as desmoplakin have been identified to underlie the dominant non-syndromic form. Preliminary genotype–phenotype assessment indicates that mutations affecting the outer dense plaque of desmosome (desmoglein2, plakoglobin, plakophilin2 and the N-terminal of desmoplakin) result in ARVC with the ordinary described phenotype. However, mutations at the inner dense plaque, particularly affecting the desmin-binding site of desmoplakin, may result in ARVC with predominantly left ventricular involvement and clinical overlapping with dilated cardiomyopathy. The interesting finding of abnormal distribution of plakoglobin, independently of the primarily affected protein, might suggest a common pathway for plakoglobin in ARVC pathogenesis.

Abbreviations: ARVC, arrhythmogenic right ventricular dysplasia/cardiomyopathy; DCM, dilated cardiomyopathy
Keywords: arrhythmogenic right ventricular dysplasia/cardiomyopathy; Naxos disease; cell-adhesions; desmosomal proteins; sudden death

Heart 2006;92:1720-1723

© 2006 by BMJ Publishing Group Ltd & British Cardiovascular Society

Validation of a new index for estimating arterial stiffness: Measurement of the QPV interval by doppler ultrasound
Min-Yi Lee, M.D. 1, Chih-Sheng Chu, M.D. 2, Kun-Tai Lee, M.D. 2, Chan-Ming Wu, M.D. 1, Ho-Min Su, M.D. 2, Shin-Jing Lin, M.D. 2, Sheng-Hsuing Sheu, M.D. 2, Wen-Ter Lai, M.D. 2 *
1)Division of Cardiology, Department of Internal Medicine, Kaohsiung Municipal United Hospital, Kaohsiung, Taiwan
2)Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Background: Pulse wave velocity (PWV), a relevant indicator of arterial stiffness, can be measured noninvasively with a variety of automatic devices, but most are complexly equipped. We developed a novel index for estimating arterial stiffness as QPV interval, which was determined by means of surface electrocardiogram and Doppler ultrasound of the brachial artery simultaneously.
Hypothesis: This study aimed to validate the QPV interval as an exact and convenient index for estimation of arterial stiffness.
Methods: Forty-seven patients with untreated essential hypertension and 19 normotensive subjects were enrolled. Brachial-ankle PWV (baPWV) was measured using an automatic volume-plethysmographic apparatus, and Doppler ultrasound was implemented sequentially to measure the QPV interval in each subject. Clinical biochemistry and echocardiography were performed on the same day.
Results: Mean baPWV was significantly higher in hypertensive patients than in normotensive subjects (p = 0.002), whereas mean QPV interval was significantly shorter in hypertensive patients than in the normotensive group (p = 0.019). A simple regression analysis demonstrated an inverse correlation between the QPV interval and baPWV (r = -0.671, p < 0.001) in all enrolled subjects. In a stepwise regression model that adjusted for age, systolic blood pressure, and other determinants of baPWV, the negative association remained between the QPV interval and baPWV (p < 0.001).
Conclusion: The QPV interval correlates inversely with baPWV, independent of age and other determinants of baPWV; hence, the QPV interval can serve as a simple and convenient index for assessing arterial stiffness in clinical practice.

Keywords: arterial stiffness • pulse wave velocity • QPV interval • Doppler ultrasound

Volume 29, Issue 8 , Pages 345 - 351
© 2006 Verlag Chemie, GmbH

Vascular events: Stress associated with birthdays

Does a birthday predispose to vascular events?

Gustavo Saposnik, MD, MSc, Akerke Baibergenova, MD, PhD, Jason Dang and Vladimir Hachinski, MD, DSc, FRCP(C)
From the Stroke Team (G.S., V.H.), Department of Clinical Neurological Sciences, London Health Sciences Center, University of Western Ontario; Stroke Research Program (G.S.), Department of Medicine, Division of Neurology, University of Toronto; Department of Clinical Epidemiology and Biostatistics (A.B.), McMaster University, Hamilton; and Department of Applied Health Sciences (J.D.), University of Waterloo, Ontario, Canada.

Objective: To examine the influence of birthdays on the onset and course of vascular events such as stroke, TIA, and acute myocardial infarction (AMI).
Methods: This population-based study included all emergency department (ED) admissions due to ischemic stroke, TIA, or AMI from April 2002 to March 2004 in Ontario, Canada. All cases were identified through the National Ambulatory Care Reporting System. Calculations of daily and weekly numbers of events were centered on the patient’s birthday and the week of the birthday. Statistical analyses include binomial tests and logistic regression.
Results: During the study period, there were 24,315 ED admissions with acute stroke, 16,088 with TIAs, and 29,090 with AMI. The observed number of vascular events during the birthday was higher than the expected daily number of visits for stroke (87 vs 67; p = 0.009), TIA (58 vs 44; p = 0.02), and AMI (97 vs 80; p = 0.027) but not for selected control conditions (asthma, appendicitis, head trauma). Vascular events were more likely to occur on birthday (242 vs 191; odds ratio [OR] = 1.27). No significant differences were observed during the birthday week for any of the conditions. Multivariate logistic regression showed that birthday vascular events were more likely to occur in patients with a history of hypertension (OR = 1.88; 95% CI 1.09 to 3.24). Sensitivity analyses with alternative definitions of birthday week did not alter the results.
Conclusions: Stress associated with birthdays may trigger vascular events in patients with predisposing conditions. Full Text

http://www.neurology.org/cgi/content/abstract/67/2/300
NEUROLOGY 2006;67:300-304
© 2006 American Academy of Neurology

Blood pressure: Acute effects of cold

Acute effects of cold exposure on central aortic wave reflection

David G. Edwards,1 Amie L. Gauthier,2 Melissa A. Hayman,2 Jesse T. Lang,2 and Robert W. Kenefick2
1)Department of Health, Nutrition, and Exercise Sciences, University of Delaware, Newark, Delaware; and
2)Department of Kinesiology, University of New Hampshire, Durham, New Hampshire

The purpose of this study was to determine the effects of acute cold exposure on the timing and amplitude of central aortic wave reflection and central pressure. We hypothesized that cold exposure would result in an early return of reflected pressure waves from the periphery and an increase in central aortic systolic pressure as a result of cold-induced vasoconstriction. Twelve apparently healthy men (age 27.8 ± 2.0 yr) were studied at random, in either temperate (24°C) or cold (4°C) conditions. Measurements of brachial artery blood pressure and the synthesis of a central aortic pressure waveform (by noninvasive radial artery applanation tonometry and use of a generalized transfer) were conducted at baseline and after 30 min in each condition. Central aortic augmentation index (AI), an index of wave reflection, was calculated from the aortic pressure waveform. Cold induced an increase (P <>

These results demonstrate that cold exposure and the resulting peripheral vasoconstriction increase wave reflection and central systolic pressure. Additionally, alterations in central pressure during cold exposure were not evident from measures of brachial blood pressure.
arterial stiffness; blood pressure

J Appl Physiol 100: 1210-1214, 2006.
Copyright © 2006 by the American Physiological Society.

Cardiovascular Risk Scoring

The value of risk scores

J S Jürgensen
Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany

Efforts to improve cardiovascular risk scoring should not be limited to broadening the biomarkers but should also include the individual’s personal circumstances and socioeconomic status.

POTENTIAL VALUE OF RISK SCORES

Coronary heart disease follows a very variable course. More than a quarter of patients with myocardial infarction or sudden death have been asymptomatic. This highlights the need to identify individuals at-risk before an initial event for appropriate risk-modifying primary and secondary prevention. From a societal perspective the quantification of risk could inform clinical decision making and would allow a more efficient allocation of scarce resources to those at highest risk. Likewise over-treatment in low-risk populations could be reduced.

On an individual level communication of accurate prognostic information offers the patient an opportunity to make fully informed choices about the medical care. Often these decisions mean a trade-off between quality of life and quantity of life. Inaccurate predictions may alter the patient’s choice of treatment. Both the level of risk based upon a single patient’s characteristics and her or his value-laden views and preferences on the initiation of treatment are necessary to tailor advice and individualise treatment. Consequently, the development of tools that enable us to predict as accurately as possible could further improve cardiovascular disease prevention by medical means.

CURRENT LIMITATIONS OF RISK SCORES

Risk scores are only of broad clinical value if they work when applied in a population other than the one from which they were derived. However, the portability of the currently recommended risk scoring methods derived from the Framingham study is limited. The overall absolute coronary risk assigned to individuals in the United Kingdom and most other European populations has been systematically and significantly overestimated. Furthermore, the accuracy of the Framingham risk score is better than any single risk factor or clinical acumen alone, but the predictive power leaves room for improvement. Ideally, a suitable risk score should consider the most relevant causal factors to quantify accurately the risk of disease.

WHAT CAUSES DISEASE?

Robert Koch (1843–1910) postulated a mono-causal origin of communicable diseases. His concept was soon to be extended and the perception prevailed that the interaction of inherited and environmental factors causes disease. Epigenetics and complex concepts like socioeconomic status, job control and social hierarchy further added to a more comprehensive understanding of causes of disease well beyond classical behavioural, chemicophysical, or infectious risk factors.

HOW CAN SCORES BE REFINED?

First, to increase the external validity of the prediction, data from populations with different absolute cardiovascular risk level should be pooled to derive common risk functions. This approach is being pursued by the SCORE study group. Further, regional recalibration methods seem attractive. Second, methodological improvement of prediction rules—for example, neural network techniques instead of conventional logistic regression—seems promising. Third, in spite of rather disappointing previous efforts, improvement of the accuracy by inclusion of additional risk factors should be investigated. Currently, several major risk factors are not considered in the Framingham or European risk calculations. These include independent risk factors for coronary heart disease like family history of premature myocardial infarction and ethnicity. Obesity, the metabolic syndrome, insulin resistance, lack of exercise, markers of inflammation, and psychological stress, which emerged as another major factor, are missing.

Another very important risk factor complex comprises renal diseases. Of note, renovascular disease and microalbuminuria add to the risk prediction independent of traditional cardiovascular risk factors. In addition, a reverse correlation of glomerular filtration rate and incidence of cardiovascular disease has been shown even for mildly reduced renal function. In turn, the devastating cardiovascular effect of end-stage renal disease can be stopped by restoration of renal function through transplantation.

LOW SOCIOECONOMIC STATUS

Finally, there is ample evidence to support the idea that lower socioeconomic status—usually expressed as education, occupation, income or combinations of these—increasingly confers heightened cardiovascular risk and mortality. In accord with this concept, impaired functional capacity and abnormal heart rate recovery is strongly associated with low socioeconomic status and explains a major proportion of the correlation between socioeconomic status and mortality. In the United States less educated individuals were found to have 9.2 less potential life-years than those who were better educated, and ischaemic heart disease was the major contributor (0.84 years per person) to this striking educational disparity.16 The mediating pathways remain poorly elucidated and to prove causality is further complicated by the fact that individual health is both an outcome of socioeconomic status and also a determinant. It is unlikely that access to high quality medical treatment is a key factor that explains the excess mortality and morbidity rates among the less affluent; this is because even countries with publicly funded comprehensive medical coverage and strong emphasis on egalitarian healthcare policies face this gradient.
Some authors suggest that the "wealth–health gradient" in cardiovascular mortality may be partially mediated by known risk factor pathways—but the causes of the uneven distribution of these risk factors by socioeconomic status remain vague.
The most widely used risk scores do not consider socioeconomic status or any surrogate marker. Thus, in sharp contrast to the overall overestimation of risk in many populations a serious underestimation of cardiovascular risk for less affluent or deprived groups within these populations is no surprise. Recent examples include the Scottish heart health extended cohort (SHHEC) study and another prospective study by Brindle from the West of Scotland. The authors of these studies warn that the systematic underestimation of risk in socially deprived individuals could be misleading and may exacerbate the social gradients of disease via relative undertreatment of the most needy.

CONCLUSION

Efforts to improve risk scores should not be limited to methodological issues and calibration. Further causal factors of diseases need to be considered. These are not limited to biomarkers and behavioural points but include socioeconomic status. The recognition that an individual’s circumstances and status interact with biological risk factors offers opportunities for refined risk prediction and prevention.
In tune with Rudolf Virchow’s remark that medicine was "a social science, and politics nothing but medicine on a grand scale", the measures required are not confined to the health care systems and allocation of preventive medical treatment—concerted political action is also needed. At a societal level measures should tackle risk factors with high population attributable risk percentage (smoking and obesity) and seek more equitable distribution of public and private resources. In the best case, refined risk scores will gain acceptance and help to individually target resources for rigorous management of known risk factors supported by public health measures that address the social gradient of health.

Heart 2006;92:1720-1723

© 2006 by BMJ Publishing Group Ltd & British Cardiovascular Society

Cardiovascular Disease: Assessment in the Primary Prevention

Accuracy and impact of risk assessment in the primary prevention of cardiovascular disease: a systematic review

P Brindle(1), A Beswick(1), T Fahey (2) and S Ebrahim (3)
1) Department of Social Medicine, University of Bristol, Bristol, UK
2) Tayside Centre for General Practice, University of Dundee, Dundee, UK

3) London School of Hygiene & Tropical Medicine, London, UK

Objective: To determine the accuracy of assessing cardiovascular disease (CVD) risk in the primary prevention of CVD and its impact on clinical outcomes.

Selection of studies: Any study that compared the predicted risk of coronary heart disease (CHD) or CVD, with observed 10-year risk based on the widely recommended Framingham methods (review A). Randomised controlled trials examining the effect on clinical outcomes of a healthcare professional assigning a cardiovascular risk score to people predominantly without CVD (review B).

Review methods: Data were extracted on the ratio of the predicted to the observed 10-year risk of CVD and CHD (review A), and on cardiovascular or coronary fatal or non-fatal events, risk factor levels, absolute cardiovascular or coronary risk, prescription of risk-reducing drugs and changes in health-related behaviour (review B).

Results: 27 studies with data from 71 727 participants on predicted and observed risk for either CHD or CVD were identified. For CHD, the predicted to observed ratios ranged from an underprediction of 0.43 (95% CI 0.27 to 0.67) in a high-risk population to an overprediction of 2.87 (95% CI 1.91 to 4.31) in a lower-risk population. In review B, four randomised controlled trials confined to people with hypertension or diabetes found no strong evidence that a cardiovascular risk assessment performed by a clinician improves health outcomes.

Conclusion: The performance of the Framingham risk scores varies considerably between populations and evidence supporting the use of cardiovascular risk scores for primary prevention is scarce.

Abbreviations: CHD, coronary heart disease; CVD, cardiovascular disease; INSIGHT, Intervention as a Goal in Hypertension Treatment

Heart 2006;92:1752-1759

http://heart.bmj.com/cgi/content/abstract/92/12/1752

© 2006 by BMJ Publishing Group Ltd & British Cardiovascular Society

Sudden Cardiac Death: Winter Peak

Seasonality and Daily Weather Conditions in Relation to Myocardial Infarction and Sudden Cardiac Death in Olmsted County, Minnesota, 1979 to 2002

Yariv Gerber, PhD (a,b), Steven J. Jacobsen, MD, PhD (b), Jill M. Killian, BS (b), Susan A. Weston, MS (b) and Véronique L. Roger, MD, MPH (a,b)

a) Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota.

b) Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.

OBJECTIVES: We assessed the relationship of season and weather types with myocardial infarction (MI) and sudden cardiac death (SCD) in a geographically defined population, and tested the hypothesis that the increased risk in winter was related to weather.

BACKGROUND: Winter peaks in coronary heart disease (CHD) have been documented. Yet, it is uncertain if seasonality exists for both incident events and deaths, and the role of weather conditions is not clear.

METHODS: The daily occurrence of incident MI and SCD in Olmsted County was examined with data from the National Weather Service. Poisson regression models were used to assess the relative risks (RRs) associated with season and climatic variables. Subsequent analysis stratified SCD into those with and without antecedent CHD (unexpected SCD).

RESULTS: Between 1979 and 2002, 2,676 MI and 2,066 SCD occurred. The age-, gender-, and year-adjusted RR of SCD, but not of MI, was increased in winter versus summer (1.17, 95% confidence interval [CI] 1.03 to 1.32) and in low temperatures (1.20, 95% CI 1.07 to 1.35, for temperatures below 0°C vs. 18°C to 30°C). These associations were stronger for unexpected SCD than for SCD with prior CHD (p < rr =" 1.38," rr =" 1.06,">

CONCLUSIONS: These data suggest that the winter peak in SCD can be accounted for by daily weather.

Abbreviations and Acronyms: CHD - coronary heart disease, CI - confidence interval, ICD - International Classification of Diseases, MI - myocardial infarction, RR - relative risk, SCD - sudden cardiac death

J Am Coll Cardiol, 2006; 48:287-292,

© 2006 by the American College of Cardiology Foundation

Climate:Myocardial infarction deaths

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

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

Department of Cardiology, University of Athens Medical School, Hippokration Hospital, Athens, Greece

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

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

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

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

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

Heart 2006;92:1747-1751

© 2006 by BMJ Publishing Group Ltd & British Cardiovascular Society

Obesity cardiomyopathy

How does obesity cardiomyopathy occur?

Obesity is a well-established risk factor for congestive heart failure, but the pathogenic mechanisms leading to the underlying myocardial alterations remain unclear. Di Bello’s group in Pisa, Italy, used ultrasonic backscatter analysis (IBS) (an expression of increased myocardial collagen content) to look at subclinical alterations of left ventricular (LV) structure and function in severe obesity. Sixty severely obese patients (mean age 31.8 years) with no other medical problems were enrolled, while 48 age- and sex-matched controls were recruited as control patients. All underwent conventional two-dimensional colour Doppler echocardiography, pulsed wave Doppler tissue imaging at mitral annulus level, and IBS. Furthermore an insulin resistance index was used to assess insulin resistance in the two groups. Obese patients had a greater LV mass index by height (58.5 (14) g/m2.7) than did the control subjects (37 (8) g/m2.7; p < 0.0001) because of a compensatory response to volume overload caused by a greater cardiac output (p < 0.02). There were also significant increases in left atrial dimension (p < 0.0001) and LV ejection fraction (p < 0.03) in obese patients. Pulsed wave Doppler tissue imaging also showed an impairment of diastolic LV longitudinal function and increased LV diastolic filling pressure in obese patients. The IBS values at septum level were significantly higher for the septum in the obese group (57.8 (8)%) than in the control group (42.3 (9)%; p < 0.0001), and a significant association was found between the insulin resistance index and both the IBS index of myocardial reflectivity at septum level or LV mass. Therefore obese patients exhibit myocardial structural and functional alterations related to insulin resistance and to LV volume overload, which could be considered to be the beginning of incipient obesity cardiomyopathy.

Di Bello V, Santini F, Di Cori A, et al. Obesity cardiomyopathy: is it a reality? An ultrasonic tissue characterization study.

J Am Soc Echocardiogr 2006;19:1063–71.[CrossRef][Medline]

Obesity: predicts mortality

Body mass index predicts mortality

Some doubt has been cast on whether body mass index (BMI) is an adequate measure of obesity. Waits measurement alone is suggested as an alternative. Obesity, defined by a BMI (weight in kilograms divided by the square of the height in metres) of 30.0 or more, is associated with an increased risk of death, but the relation between overweight (a BMI of 25.0 to 29.9) and the risk of death has been questioned. The authors prospectively examined BMI in relation to the risk of death from any cause in 527 265 US men and women in the National Institutes of Health–AARP cohort who were 50–71 years old at enrolment in 1995–96. BMI was calculated from self-reported weight and height. Relative risks and 95% CIs were adjusted for age, race or ethnic group, level of education, smoking status, physical activity, and alcohol intake. During a maximum follow-up of 10 years through 2005, 61 317 participants (42 173 men and 19 144 women) died. Initial analyses showed an increased risk of death for the highest and lowest categories of BMI among both men and women, in all racial or ethnic groups, and at all ages. When the analysis was restricted to healthy people who had never smoked, the risk of death was associated with both overweight and obesity among men and women. In analyses of BMI during midlife (age of 50 years) among those who had never smoked, the associations became stronger, with the risk of death increasing by 20–40% among overweight persons and by two to at least three times among obese persons; the risk of death among underweight persons was attenuated.

Adams KF, Schatzkin A, Harris TB, et al.

Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old. N Engl J Med 2006;355:763–78.[Abstract/Free Full Text]

Heart 2006;92:1886-1888

© 2006 by BMJ Publishing Group Ltd & British Cardiovascular Society

Long Term Hypertension: Hyperinsulinemia

HYPERINSULINEMIA AND LEFT VENTRICULAR HYPERTROPHY IN PATIENTS WITH LONG TERM HYPERTENSION

O.Yarynkina, O.Kupchinska, L.Zelenenka, M.Mospan, N.Tchyrulneva
Department of Hypertension, Institute of Cardiology, Kiev, Ukraine

Objective: The hyperinsulinemia has been associated with higher risk of target organ-damage. We evaluate relationship between the left ventricular function characteristics and insulinemia in the essential hypertension (EH) under 10 years observation.

Design and methods: We examined 57 patients with moderate EH at the primary appeal to the hospital and in 10 years after. Immunoreactive insulin (IRI) concentration was measured under standard oral glucose tolerance test (OGTT) at fasting and 60 and 120 min by radioimmunoassay. Left ventricular values were measured by echocardiography. Blood samples were drawn for the determination plasma creatinine and lipid concentration.

Results: Systolic blood pressure did not changed (162+7,2 and 165+5,3 mmHg accordingly) but DBP was significantly lower (103+3,3 and 97+4,5 mmHg, p<0,001)>

We found correlation of high IRI level under OGTT with LVMI2 (r=0,39,p<0,05) r="0,34,p<0,05).">

Conclusions: There are hyperinsulinemia in more than 50 % patients with longitudinal arterial hypertension that associated with LVMI increasing. This information indicates that hyperinsulinemia plays significant role in LV hypertrophy.

Heart Attacks: Treatment

Statin users risk heart attacks by dropping treatment or taking low doses

Thousands of statin users worldwide are suffering preventable heart attacks, simply because they are not complying with their treatment or are taking too low a dose.

These life-saving drugs, used to lower cholesterol levels in people at risk of coronary heart disease (CHD), can only be optimally effective if patients use them properly – and many are not.

That is the conclusion by the research team, who followed the prescription records of nearly 60,000 patients in the Netherlands for up to 14 years.

Dr Fernie Penning-van Beest and colleagues from the PHARMO Institute2, the Utrecht Institute of Pharmaceutical Sciences and the Academic Hospital in Amsterdam, analysed 548,084 prescriptions of statin treatment issued over the first two years of treatment3 in 59,094 new users in the period January 1991-December 2004, and followed the patients until their first hospital admission for heart attack, death, or the end of the study in December 2004.

The aim was to see how effective robust statin treatment was for primary and secondary CHD in the ‘real world’ – as opposed to in clinical trials. Their results enabled them to calculate the absolute number of avoidable heart attacks that occurred because patients had stopped taking their drugs or were not taking them consistently. They were also able to compare the preventive effects of different doses and types of statins.Patients were divided into two groups – those at high risk of heart attack and those at intermediate or low risk, with over a fifth of patients (12,762) considered high risk.

They found more than half of all patients (31,557) stopped taking statins within two years and only just over a third (20,883) were persistent users on a high or intermediate dose.

Among persistent users, hospital admission for heart attacks fell by nearly a third (30%) compared to non-persistent users, in both primary and secondary prevention groups. In the primary prevention group, admission was down from 0.52 per 100 patient years among non-persistent users to 0.42 per 100 patient years in persistent users. In the secondary prevention group it was down from 0.86 to 0.62.

Among patients using the high or intermediate doses the risk reduction was as high as 40%, while a low dose reduced the risk by only 20%.The researchers calculated that, every year, around 300 to 400 statin users in the Netherlands have an avoidable heart attack because of sub-optimal doses or discontinuing treatment. They believe the results are likely to be typical of Europe as a whole and of the USA, which means 7,000 to 9,000 Europeans and 5,000 to 7,000 Americans a year are suffering unnecessary heart attacks.

“What this clearly tells us,” said lead researcher Dr Penning-van Beest, a research associate at the PHARMO Institute, “is that our observational study supports robust cholesterol lowering, as recommended on the basis of clinical trials. But, drugs are only really effective if they are used properly and persistently.

Unfortunately, statins are not being used optimally, so thousands of people are having unnecessary heart attacks. Getting users to stay on statins and to use them persistently saves lives, and doctors must get over to patients the message that complying with treatment is essential.

”Different types of statins are used in different doses, so the researchers dealt with these differences by grading the five statins they assessed for equipotency (the dose of one type of statin needed to achieve the same effect as another type).

They found that as well as the largest reduction in heart attacks needing hospital admission being among patients consistently taking the drugs over the whole two-year period at persistently high or intermediate equipotent doses, these patients were also relatively more likely to be using second generation statins i.e. atorvastatin or rosuvastatin, rather than the first generation types, pravastatin, fulvastatin or simvastatin. Higher doses of first generation statins were being prescribed, but increasing the dose of these older statins is limited by the maximum safe dose.

Co-author Dr Ron Herings, scientific director of the PHARMO Institute and associate professor of pharmacoepidemiology at Utrecht University, said: “It is preferable to achieve a high equipotent dose by using the new, highly potent statins. But, the new statins have considerable economic impact on pharmaceutical budgets and the opposite trend is being encouraged in the Netherlands and Germany, where reimbursement measures promote the use of relatively inexpensive generic older types.”

He said: “This is fine, as long as guidelines for higher doses of these older statins are implemented, and bearing in mind that there may be limitations to giving the highest doses. But, restricting the use of older generic statins to standard low doses will make the problems worse.”Ideally, to improve the population effectiveness of statin treatment, persistent drug use and the use of new, potent statins, should be encouraged.

European Society of Cardiology
http://brightsurf.com/news

Metabolic Syndrome: Statistics

Adolescents

The prevalence of metabolic syndrome (MetS) among 12–19-year-old US adolescents was estimated in an analysis of NHANES III data, by applying a modification of the ATP III definition (Third Report of the National Cholesterol Education Program [NCEP] Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [ATP III, NHLBI]) for adults. MetS during adolescence was defined as 3 or more of the following abnormalities:
—Serum triglyceride level of 110 mg/dL or higher.
—High-density lipoprotein (HDL) cholesterol level of 40 mg/dL or lower.
—Elevated fasting glucose of 110 mg/dL or higher.
—Blood pressure at or above the 90th percentile for age, sex and height.
—Waist circumference at or above the 90th percentile for age and sex (NHANES III data set)

An estimated 1 million 12–19-year-old adolescents in the United States have MetS, or 4.2% overall (6.1% of males and 2.1% of females).

–Of adolescents with MetS, 73.9% were overweight and 25.2% were at risk of overweight.
–The mean BMI of adolescents with the MetS (30.1%) was just above the 95th percentile of the CDC Growth Chart; thus they are likely to represent a fairly common clinical problem in pediatrics.
–MetS was present in 28.7% of overweight adolescents (BMI 95th percentile of CDC Growth Chart) compared with 6.8% of at-risk-of-overweight adolescents, and 0.1% of those with BMI below the 85th percentile (P<0.001).
–Among adolescents with MetS, 40.9% had 1 criterion; 14.2% had 2 criteria; 4.2% had 3 criteria and 0.9% had 4 criteria for MetS. For overweight adolescents, 88.5% had 1 criterion; 54.4% had 2 criteria; 28.7% had 3 criteria and 5.8% had 4 criteria for MetS.

• Among more than 3400 children examined in 1 study, 1 in 10 had MetS.
• Using a sample of adolescents from NHANES III, the overall prevalence of MetS was 38.7% in moderately obese subjects and 49.7% in severely obese subjects. The prevalence of MetS in severely obese black subjects was 39%.
  

Adults

People with MetS are at increased risk for developing diabetes and cardiovascular disease as well as increased mortality from CVD and all causes. Unless otherwise stated, the following data are based on the definition of the metabolic syndrome as determined in the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III, NHLBI).

• An estimated 47 million US residents have MetS.
• The age-adjusted prevalence of MetS for adults is 23.7%.
  –The prevalence ranges from 6.7% among people ages 20–29 to 43.5% for ages 60–69 and 42.0% for those age 70 and older.
  –The age-adjusted prevalence is similar for men (24.0%) and women (23.4%).
  –Mexican Americans have the highest age-adjusted prevalence of MetS (31.9%). The lowest prevalence is among whites (23.8%), African Americans (21.6%) and people reporting an "other" race or ethnicity (20.3%).
  –Among African Americans, women had about a 57% higher prevalence than men. Among Mexican Americans, women had a 26% higher prevalence than men did.
• The prevalences of people with MetS are 24.3%, 13.9% and 20.8 % for white, black and Mexican-American men, respectively. For women the percentages are 22.9, 20.9 and 27.2, respectively.
• In a study of over 15 000 men and women, ages 45–64, in the ARIC study, MetS prevalence was 30% and 27% using ATP III and modified WHO definitions with substantial variation across race and gender subgroups. CHD prevalence was greater in those with than without MetS (ATP III 7.4% versus 3.6%; WHO 7.8% versus 3.6%, both P<0.0001).>

Circulation. 2006;113:e85-e151. © 2006 American Heart Association, Inc.

Blood Pressure:Psychological Stress

Delayed Blood Pressure Recovery After Psychological Stress Is Associated With Carotid Intima-Media Thickness

Andrew Steptoe; Ann E. Donald; Katie O’Donnell; Michael Marmot; John E. Deanfield
From the Department of Epidemiology and Public Health (A.S., K.O., M.M.), and the Vascular Physiology Unit (A.E.D., J.E.D.) Institute of Child Health, UCL, London.

Objective. Delayed blood pressure (BP) recovery after psychological stress is associated with low socioeconomic status (SES) and prospectively with increases in clinic BP. We tested whether poststress BP recovery was related to carotid atherosclerosis.

Methods and Results. Psychophysiological stress testing was performed with a healthy subgroup of the Whitehall II epidemiological cohort, and recovery systolic BP was monitored 40 to 45 minutes after stressful behavioral tasks. Carotid ultrasound scanning was conducted on 136 men and women (aged 55.3±2.7 years) 3 years after stress testing. Participants were divided into those whose systolic BP had returned to baseline in the recovery period (adequate recovery, n=37), and those whose BP remained elevated (delayed recovery, n=99). Systolic BP stress responses did not differ in the 2 groups. Carotid intima-media thickness (IMT) was associated with delayed recovery in lower SES (means 0.78 versus 0.65 mm) but not higher SES participants (means 0.75 versus 0.74 mm) after adjustment for age, gender, baseline systolic BP, and resting BP, smoking, body mass and fasting cholesterol at the time of ultrasound scanning (P=0.010).

Conclusions. Variations in poststress recovery reflect dysfunction of biological regulatory processes, and may partly mediate psychosocial influences on cardiovascular disease.

Delayed blood pressure recovery after psychological stress was associated with carotid intima-media thickness (IMT) in men and women of low but not high socioeconomic status independently of conventional risk factors. Variations in poststress recovery reflect dysfunction of biological regulatory processes, and may partly mediate psychosocial influences on cardiovascular disease.

Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2547.
© 2006 American Heart Association, Inc.