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Study Highlights: , Feb 17, 2012 (GlobeNewswire via COMTEX) — Women who developed pregnancy-related hypertension (preeclampsia) or diabetes were at increased risk of cardiovascular disease (CVD) later in life.

– Preeclampsia was associated with a wider range of CVD risk factors and may be a better predictor of CVD in middle age than other pregnancy-related complications.

– Pregnancy may provide an opportunity to identify women at increased risk of CVD when they’re relatively young — allowing them to make lifestyle changes and get medical intervention earlier in life.

DALLAS, Feb. 17, 2012 (GLOBE NEWSWIRE) — If you develop pregnancy-related hypertensive disorders or diabetes, you may have an increased risk of cardiovascular disease later in life, according to research in Circulation: Journal of the American Heart Association.

“We wanted to learn about possible explanations as to why women with pregnancy complications tend to have more heart disease later in life,” said Abigail Fraser, M.P.H., Ph.D., School of Social and Community Medicine at the University of Bristol, United Kingdom.

Researchers studied 3,416 pregnant women enrolled in the Avon Longitudinal Study of Parents and Children in the early 1990s. Among them, 1,002 (29.8 percent) had one pregnancy complication, 175 (5.2 percent) had two and 26 (0.8 percent) had three.

The complications included gestational or pregnancy diabetes, hypertensive (or high blood pressure-related) disorders of pregnancy (also known as preeclampsia), preterm delivery, and size of babies at birth (top and bottom 10 percent in weight). Researchers correlated these with cardiovascular (CVD) risk factors measured 18 years later when the women were an average of 48 years old.

Researchers then calculated the women’s odds of experiencing a cardiovascular event in the next decade using the 10-year CVD Framingham risk score, which includes such factors as age, total and HDL (“good”) cholesterol, systolic blood pressure, diabetes and smoking status.

They found:

– Preeclampsia, gestational diabetes and giving birth to babies small for
gestational age were associated with an increased risk of heart disease.
Each complication was associated with different CVD risk factors.

– Gestational diabetes was associated with a 26 percent and preeclampsia
31 percent greater risk of developing heart disease in middle age.

– Among women who experienced these pregnancy complications, gestational
diabetes was associated with higher levels of fasting glucose and
insulin.

– Preeclampsia was associated with higher body mass index and larger waist
circumference, as well as higher blood pressure, lipids and insulin.

– Women who gave birth to babies large for gestational age had larger
waist circumference and higher concentrations of blood glucose. Those
who had preterm babies had higher blood pressure.

“Pregnancy may provide an opportunity to identify women at increased risk of heart disease while they are relatively young; thus, it would be useful for medical professionals to have information on pregnancy complications so they can recommend lifestyle changes and any necessary medical intervention sooner,”
Fraser said. “A woman who experiences complications during pregnancy should be proactive and ask her doctor about future CVD risk and steps she should take to modify her risk.”

The women in the study had not experienced a CVD event, so the researchers couldn’t determine whether preeclampsia and/or pregnancy diabetes have separate, independent effects on future CVD risk.

A larger study with longer follow-up could help determine whether pregnancy complications could affect how the 10-year CVD Framingham risk score is calculated for these women, Fraser said.

Furthermore, because the study population was predominantly white, replicating the research with other racial groups will provide additional data on the association between pregnancy complications and CVD risk, she said.

Co-authors are Scott M. Nelson, M.B.Ch.B., Ph.D.; Corrie Macdonald-Wallis, M.Sc.; Lynne Cherry, Ph.D.; Elaine Butler; Naveed Sattar, M.B.Ch.B., Ph.D.; and Debbie A Lawlor, M.B.Ch.B., Ph.D. Author disclosures are on the manuscript.

The British Heart Association, Wellcome Trust and United States National Institute of Diabetes and Digestive and Kidney Diseases funded the research.

SOURCE: American Heart Association

Every cell in the body has chromosomes with so-called telomeres, which are shortened over time and also through lifestyle choices such as smoking and obesity. Researchers have long speculated that the shortening of telomeres increases the risk of heart attack and early death. Now a large-scale population study in Denmark involving nearly 20,000 people shows that there is in fact a direct link, and has also given physicians a future way to test the actual cellular health of a person.

In an ongoing study of almost 20,000 Danes, a team of researchers from the University of Copenhagen have isolated each individual’s DNA to analyse their specific telomere length – a measurement of cellular aging.

“The risk of heart attack or early death is present whether your telomeres are shortened due to lifestyle or due to high age,” says Clinical Professor of Genetic Epidemiology Borge Nordestgaard from the Faculty of Health and Medical Sciences at the University of Copenhagen. Professor Nordestgaard is also a chief physician at Copenhagen University Hospital, where he and colleagues conduct large scale studies of groups of tens of thousands of Danes over several decades.

Lifestyle can affect cellular aging

The recent “Copenhagen General Population Study” involved almost 20,000 people, some of which were followed during almost 19 years, and the conclusion was clear: If the telomere length was short, the risk of heart attack and early death was increased by 50 and 25 per cent, respectively.

“That smoking and obesity increases the risk of heart disease has been known for a while. We have now shown, as has been speculated, that the increased risk is directly related to the shortening of the protective telomeres – so you can say that smoking and obesity ages the body on a cellular level, just as surely as the passing of time,” says Borge Nordestgaard.

The study also revealed that one in four Danes has telomeres with such short length that not only will they statistically die before their time, but their risk of heart attack is also increased by almost 50 per cent.

“Future studies will have to reveal the actual molecular mechanism by which the short telomere length causes heart attacks,” says Borge Nordestgaard, and asks, “Does one cause the other or is the telomere length and the coronary event both indicative of a third – yet unknown – mechanism?”

Another possible prospect of the study is that general practitioners could conduct simple blood tests to reveal a person’s telomere length and thereby the cellular wear and age.

The study “Short Telomere Length, Myocardial Infarction, Ischemic Heart Disease, and Early Death ” is scheduled for the March issue of the journal Arteriosclerosis, Thrombosis and Vascular Biology published by the American Heart Association. The March issue will mail on 16 February 2012, and the journal article is also available online.

BOSTON, MA (February 15, 2012) — For decades, researchers have sought a genetic explanation for idiopathic dilated cardiomyopathy (DCM), a weakening and enlargement of the heart that puts an estimated 1.6 million Americans at risk of heart failure each year. Because idiopathic DCM occurs as a familial disorder, researchers have long searched for genetic causes, but for most patients the etiology for their heart disease remained unknown.

Now, new work from the lab of Christine Seidman, a Howard Hughes Investigator and the Thomas W. Smith Professor of Medicine and Genetics at Harvard Medical School and Brigham and Women’s Hospital, and Jonathan Seidman, the Henrietta B. and Frederick H. Bugher Foundation Professor of Genetics at Harvard Medical School, has found that mutations in the gene TTN account for 18 percent of sporadic and 25 percent of familial DCM.

Source: Eurekalert Feb 15 2012

“Until the development of modern DNA sequencing platforms, the enourmous size of the TTN gene prevented a comprehensive analyses – but now we know TTN is a major cause of DCM,” said Christine Seidman, who reported the findings February 16 in the New England Journal of Medicine.

Idiopathic DCM is one of three different types of cardiomyopathy (the term “idiopathic” indicates that acquired causes for DCM such as atherosclerosis, excess drinking or viral infections have been excluded). It affects only about 4 in 10,000 Americans, but may be under-diagnosed because symptoms often appear late in the course of disease. DCM may cause shortness of breath, chest pain, and limited exercise capacity. DCM increases the risk of developing heart failure, for which no cure is available, and the risk of stroke and sudden cardiac death.

These findings will not only help patients understand the cause of their DCM symptoms, but also help to screen family members who might be at risk of developing the condition. Early identification of those at risk allows early intervention with medications that reduce workload on the heart and help prevent the changes in heart muscle, called remodeling, that lead to heart failure.

As DCM progresses, remodeling of the heart tissue makes the heart more prone to disturbances in the normal heart rhythm that can lead to stroke, heart attack and sudden death. “One of the added values to knowing that you are at risk for developing DCM is that we can do prophylactic screening so that silent arrhythmias are picked up before they become harmful,” said Christine Seidman. “The discovery is immediately translatable into clinical practice to provide patients with gene-based diagnosis.” The Partner’s Laboratory for Molecular Medicine, an HMS affiliate, has incorporated TTN analyses.

The Seidmans and others had previously linked other gene mutations to about 20 to 30 percent of idiopathic DCM cases — and, with more success, to a related disease, hypertrophic cardiomyopathy. They had examined almost all of the genes linked to muscle units known as sarcomeres, but saved the biggest for last: TTN, which encodes the protein titin. At approximately 33,000 amino acids, titin is the largest human protein.

“Titin was a missing link,” said Christine Seidman. “A very large missing link.”

The Seidmans’ collaborated with researchers from the Imperial College (London) and the University of Washington. Traditional sequencing methods had previously found only a few TTN variants in patients with DCM because complete, accurate sequencing was too expensive.

Using next generation sequencing tools that substantially reduce the cost per base (the TTN sequence contains 100,000 bases) by orders of magnitude over earlier standards, the Seidmans were able to perform comprehensive screening for TTN mutations for the first time. They analyzed TTN in 312 DCM patients, 231 HCM patients, and 249 individuals with no disease. Of the many mutations identified, 72 make the titin protein shorter.

Called TTN truncating variants, these specific mutations appeared almost exclusively in patients with DCM. “Our hypothesis is that any variant that shortens titin is going to cause DCM, which will lead to heart failure by the same mechanism,” said Jonathan Seidman.

To identify the pathological mechanism, the Seidmans plan to model a handful of TTN truncating mutations in mice.

One concern in the search for disease causing genes is that, while there will be many gene variants discovered, only a few will cause disease. This is particularly true for missense mutations that cause single nucleotide changes — changes that substitute a single amino acid within the protein.

“We often don’t know if a missense mutation significantly impacts a protein’s function, until we model it and study its effects,” said Jonathan Seidman.

However, in the case of truncating mutations, “it’s the converse,” he continued. “We don’t have to model all of those different mutations that truncate titin, becuase they all foreshorten the protein. We can pick a few representative ones and expect that they will reveal a common mechanism.”

A better understanding of the mechanism may lead to better and more direct therapies for treatment and prevention of DCM.

UCSF study identifies possible way to minimize heart damage

A UCSF stem cell study conducted in mice suggests a novel strategy for treating damaged cardiac tissue in patients following a heart attack. The approach potentially could improve cardiac function, minimize scar size, lead to the development of new blood vessels – and avoid the risk of tissue rejection.

In the investigation, reported online in the journal PLoS ONE, (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030329) the researchers isolated and characterized a novel type of cardiac stem cell from the heart tissue of middle-aged mice following a heart attack.

Then, in one experiment, they placed the cells in the culture dish and showed they had the ability to differentiate into cardiomyocytes, or “beating heart cells,” as well as endothelial cells and smooth muscle cells, all of which make up the heart.

In another, they made copies, or “clones,” of the cells and engrafted them in the tissue of other mice of the same genetic background who also had experienced heart attacks. The cells induced angiogenesis, or blood vessel growth, or differentiated, or specialized, into endothelial and smooth muscle cells, improving cardiac function.

“These findings are very exciting,” said first author Jianqin Ye, PhD, MD, senior scientist at UCSF’s Translational Cardiac Stem Cell Program. First, “we showed that we can isolate these cells from the heart of middle-aged animals, even after a heart attack.” Second, he said, “we determined that we can return these cells to the animals to induce repair.”

Importantly, the stem cells were identified and isolated in all four chambers of the heart, potentially making it possible to isolate them from patients’ hearts by doing right ventricular biopsies, said Ye. This procedure is “the safest way of obtaining cells from the heart of live patients, and is relatively easy to perform,” he said.

“The finding extends the current knowledge in the field of native cardiac progenitor cell therapy,” said senior author Yerem Yeghiazarians, MD, director of UCSF’s Translational Cardiac Stem Cell Program and an associate professor at the UCSF Division of Cardiology. “Most of the previous research has focused on a different subset of cardiac progenitor cells. These novel cardiac precursor cells appear to have great therapeutic potential.”

The hope, he said, is that patients who have severe heart failure after a heart attack or have cardiomyopathy would be able to be treated with their own cardiac stem cells to improve the overall health and function of the heart. Because the cells would have come from the patients, themselves, there would be no concern of cell rejection after therapy.

The cells, known as Sca-1+ stem enriched in Islet (Isl-1) expressing cardiac precursors, play a major role in cardiac development. Until now, most of the research has focused on a different subset of cardiac progenitor, or early stage, cells known as, c-kit cells.

The Sca-1+ cells, like the c-kit cells, are located within a larger clump of cells called cardiospheres.

The UCSF researchers used special culture techniques and isolated Sca-1+ cells enriched in the Isl-1expressing cells, which are believed to be instrumental in the heart’s development. Since Isl-1 is expressed in the cell nucleus, it has been difficult to isolate them but the new technique enriches for this cell population.

The findings suggest a potential treatment strategy, said Yeghiazarians. “Heart disease, including heart attack and heart failure, is the number one killer in advanced countries. It would be a huge advance if we could decrease repeat hospitalizations, improve the quality of life and increase survival.” More studies are being planned to address these issues in the future.

An estimated 785,000 Americans will have a new heart attack this year, and 470,000 who will have a recurrent attack. Heart disease remains the number one killer in the United States, accounting for one out of every three deaths, according to the American Heart Association.

Medical costs of cardiovascular disease are projected to triple from $272.5 billion to $818.1 billion between now and 2030, according to a report published in the journal Circulation.

UC Davis Department of Design students today unveiled eight red dresses they created to raise awareness that heart disease is the leading cause of death among women.

The distinct, youthful designs were modeled at the UC Davis Women’s Heart Care Education and Awareness Forum for Community Leaders, an event held in Sacramento each year on National Wear Red Day to empower women to take charge of their heart health.

ORLANDO, Fla., February 6, 2012 – It’s well known that exercising reduces body weight because it draws on fat stores that muscle can burn as fuel. But a new study at Sanford-Burnham Medical Research Institute (Sanford-Burnham) suggests that the heart also plays a role in breaking down fat. In their study, published February 6 in the Journal of Clinical Investigation, Sheila Collins, Ph.D. and colleagues detail how hormones released by the heart stimulate fat cell metabolism. These hormones turn on a molecular mechanism similar to what’s activated when the body is exposed to cold and burns fat to generate heat. This study adds another dimension to our understanding of how the body regulates fat tissue and may someday lead to new ways to manipulate the process with drugs to reduce weight in obese patients or maintain it in individuals who experience pathological weight loss during chronic heart failure.

“Exercise is always going to raise your blood pressure some, so there’s the potential that these heart hormones—called cardiac natriuretic peptides—are being released and contributing to the breakdown of fats,” said Collins, professor in the Diabetes and Obesity Research Center at Sanford-Burnham’s Lake Nona campus in Orlando and senior author of the study. “Over a period of time, natriuretic peptides could also be leading to an increase in the numbers of brown fat cells, which we know are very important for protection against diet-induced obesity, at least in laboratory experiments.”

Brown fat cells, unlike white fat cells typically associated with body fat, not only store fat but also readily convert calories into energy—a process that malfunctions in obesity.

Calorie-burning brown fat (shown here) gets a boost from natriuretic peptides produced by the heart. (Collins lab, Sanford-Burnham Medical Research Institute)

In their study, Collins and her team found that the metabolic effects caused by natriuretic peptides depend largely on the ratio of two different kinds of receptors—message-receiving proteins—on the surface of fat cells. One, called NPRA, is a “signaling” receptor and its presence helps boost brown fat cells and burn white fat. The other, called NPRC, is a “clearance” receptor and seems to prevent natriuretic peptides from activating NPRA, resulting in a greater accumulation of white fat cells.

When exposed to cold in this study, mice had elevated amounts of natriuretic peptides in their circulatory system. They also showed increased levels of the NPRA signaling receptor, relative to the NPRC clearance receptor, on fat cells. As a result, fatty acids were mobilized and the calorie-burning brown fat machinery was turned on in these mice. Exactly what alters the levels of the different types of receptors is still unknown.

“In the next phases of our work, we hope to not only more tightly link the physiology and genetics, but also understand how these receptors are regulated,” Collins said.

A progressive understanding of what regulates NPRA and NPRC receptors, and therefore how natriuretic peptides control white fat cell mass, could lead to new therapeutic targets to manage obesity and metabolic disease. For example, blocking the NRPC clearance receptor, or creating agents that favor binding NPRA, could help obese patients lose weight.

More information about how this system works could also give hope to patients suffering from cardiac cachexia, a severe body wasting that can occur in chronic heart failure. High levels of natriuretic peptides are characteristic of heart failure and are used as diagnostic markers of the severity of the disease. One hypothesis is that the high levels of circulating natriuretic peptides seen in cardiac cachexia patients may be leading to abnormally high levels of brown fat production, energy expenditure, and therefore weight loss. In these patients, suppressing the production of the peptides might slow or halt this process. The Collins lab is now gearing up to test this hypothesis in the lab.

This research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and The Italian Society of Hypertension. Co-authors include Marica Bordicchia, Sanford-Burnham and University Politecnica delle Marche; Dianxin Liu, Sanford-Burnham, Ez-Zoubir Amri, Université de Nice Sophia-Antipolis; Gerard Ailhaud, Université de Nice Sophia-Antipolis; Paolo Dessi-Fulgheri, University Politecnica delle Marche; Chaoying Zhang, Sanford-Burnham; Nobuyuki Takahashi, Tohoku University Graduate School of Pharmaceutical Sciences and Medicine; Riccardo Sarzani, University Politecnica delle Marche; and Sheila Collins, Sanford-Burnham.

For atrial fibrillation patients at risk for stroke

MAYWOOD, Ill. — Within a few years, a new generation of easy-to-use blood-thinning drugs will likely replace Coumadin for patients with irregular heartbeats who are at risk for stroke, according to a journal article by Loyola University Medical Center physicians.

Unlike Coumadin, the new drugs do not require patients to come in to the clinic on a regular basis to check the dose. Nor do the drugs require extensive dietary restrictions.

First author Sarkis Morales-Vidal, MD, and colleagues describe the new drugs in a review article in the February issue of the journal Expert Reviews. Co-authors are Michael J. Schneck, MD, Murray Flaster, MD, and José Biller, MD. All are in the Department of Neurology, Stroke Program, of Loyola University Chicago Stritch School of Medicine. Biller is department chair.

The new drugs include rivaroxaban (Xarelto®), dabigatran etexilate (Pradaxa®) and apixaban (Eliquis®). They do not share the disadvantages of Coumadin, and may provide equal or superior prevention against clots, Morales and colleagues write.

Atrial fibrillation is the most common form of irregular heartbeat, and a major cause of stroke in the elderly. Electrical signals, which regulate the heartbeat, become erratic. Instead of beating regularly, the upper chambers of the heart quiver. Not all the blood gets pumped out, so clots can form. The clots can migrate to the brain and cause strokes.

More than 3 million Americans have atrial fibrillation, and the number is increasing, due in part to the aging population.

Coumadin’s generic name is warfarin. For more than 30 years, the drug had been the only anticoagulant for primary and secondary stroke prevention in patients with atrial fibrillation. But the Food and Drug Administration recently approved dabigatran and rivaroxaban to reduce the risk of stroke and blood clots in patients with atrial fibrillation that is not caused by a heart valve problem. The FDA is considering an application to approve apixaban for the same use.

Coumadin must be carefully monitored. If the dose is too high, a patient could experience excessive bruising and be at higher risk for brain hemorrhages. If the dose is too low, the drug would be ineffective in preventing blood clots. Patients typically must come in at least once a month for a blood test to determine whether the dose needs to be adjusted. Some patients have to come in as often as twice a week.

Coumadin patients also must restrict their diets. For example, they should consume only small amounts of cranberry juice and alcohol and not eat large amounts of foods that are rich in vitamin K, such as spinach, brussels sprouts and green tea.

Disadvantages of the new medications include the limited clinical experience and lack of antidotes, the researchers wrote. The newer drugs are more expensive than Coumadin, but reduce the cost of patient monitoring and blood testing, Morales said.

Dabigatran is an effective alternative to Coumadin for stroke prevention in patients with non-valvular atrial fibrillation. Rivaroxaban is another promising alternative for those patients. Apixaban appears to be better than aspirin for stroke prevention in atrial fibrillation patients who are not candidates for Coumadin therapy, Morales and colleagues wrote.

The authors predict that within the next few years, the new drugs will likely replace Coumadin for long-term anticoagulation in selective patients with non-valvular atrial fibrillation.

A short spinning session can trigger the same biochemical indications as a heart attack – a reaction that is probably both natural and harmless, but should be borne in mind when people seek emergency treatment for chest pain, reveals a study from the Sahlgrenska Academy.

Heart attacks increase the secretion of enzymes known as cardiac biomarkers, which can be measured using a simple blood test. This is important for rapid diagnosis and initiation of treatment. However, levels of these biomarkers also increase in situations that have nothing to do with heart disease, such as long periods of strenuous physical exertion like marathons, triathlons or long skiing races.

Important for accurate assessment

Researchers at the University of Gothenburg’s Sahlgrenska Academy have now investigated whether shorter and less intensive forms of exercise have the same effect on cardiac biomarkers. This information is important for the accurate assessment of patients seeking emergency medical treatment after exercise.

Heart attack levels

The study included ten healthy people, with an average age of 30, who took part in an hour-long spinning session where researchers measured cardiac biomarkers in the blood immediately before the session as well as one hour after and again 24 hours after. The study showed that levels of a commonly used cardiac biomarker, the heart enzyme troponin T, doubled an hour after the session. In two of the individuals the enzyme rose to levels that are routinely used as the threshold for heart attacks.

More awareness needed

The exercise-induced increase in cardiac biomarkers in healthy people is probably not dangerous but is, instead, a normal bodily reaction to exercise. However, Duttaroy feels that the similarities with heart attacks mean that emergency treatment teams must be more aware.

“When somebody with chest pains comes for emergency treatment, and a blood test shows that the cardiac biomarkers are rising, it’s important to recognise that this kind of increase can also occur in healthy people after a normal exercise session.”

Passing the knowledge

“Levels returned to normal in everyone in the study 24 hours after the spinning session,” says Smita Duttaroy, researcher at the Sahlgrenska Academy. “This is an important difference to patients who’ve had a heart attack, where levels of the markers can remain raised for several days afterwards.”

Duttaroy and her research colleague Mats Börjesson, who were responsible for the study, now hope to be able to pass this knowledge on to colleagues who work with patients with chest pains.

The study “A single-bout of one-hour spinning exercise increases troponin T in healthy subjects” has been published in the Scandinavian Cardiovascular Journal.

Source: Eurekalert February 6 2012

Though pacemakers require only small amounts of energy (about 1 millionth of a Watt), their batteries have to be replaced periodically, which means multiple surgeries for patients. Researchers have searched for ways to prolong battery life – trying to generate energy to power a pacemaker using blood sugar, or the motion of the hands and legs – but these methods either interfere with metabolism or require a more drastic surgery, such as passing a wire from the limbs to the chest area. Aerospace engineers from the University of Michigan in Ann Arbor have developed a prototype device that could power a pacemaker using a source that is surprisingly close to the heart of the matter: vibrations in the chest cavity that are due mainly to heartbeats.

The authors describe the technique and their progress developing it in a paper recently published in the AIP’s Applied Physics Letters. In their method, vibrations in the chest cavity deform a layer of piezoelectric material, which is able to convert mechanical stress into electrical current. Tests indicate that the device could perform at heart rates from 7 to 700 beats per minute (well below and above the normal range), and that it could deliver eight times the energy required for a pacemaker. Furthermore, the authors write, the amount of energy generated is always larger than the amount required to run a pacemaker, regardless of heart rate. Though the team has yet to develop a prototype that is biocompatible, they say that the potential to package this energy harvester with pacemakers gives it an advantage over competing methods.

Article: “Powering Pacemakers from Heartbeat Vibrations Using Linear and Nonlinear Energy Harvesters” is published in Applied Physics Letters.

Authors: M. Amin Karami (1) and Daniel J. Inman (1).
(1) Department of Aerospace Engineering, University of Michigan

Source: Eurekalert

American Heart Association Abstract #152, press release

For patients with a type of irregular heart beat called atrial fibrillation (AF), a new anti-clotting drug might be better at preventing clot-related strokes while minimizing the risk of causing a bleeding stroke. The research was presented at the American Stroke Association’s International Stroke Conference 2012.

The finding stems from a sub-analysis of data in a large, randomized clinical trial called ROCKET AF, conducted in 45 countries at 1,178 sites. ROCKET AF tested the new drug rivaroxaban against warfarin — a medicine long used to thin the blood and prevent strokes from blockages, called ischemic strokes — in patients with atrial fibrillation. People with the condition face about five times the risk of stroke compared with the general public.

Among patients with the most common type of atrial fibrillation, without any history of heart valve damage, those who received rivaroxaban were 34 percent less likely to experience an intracranial hemorrhage, compared with those on warfarin, the study found.

“We have to be very careful about giving anticoagulants to patients at risk of bleeding into the brain, and therefore need to be able to identify who these patients are,” said Graeme J. Hankey, lead author and neurologist at the Royal Perth Hospital and University of Western Australia. “Anticoagulant drugs can prevent ischemic strokes, but paradoxically, they can cause intracranial bleeding, including hemorrhagic strokes.”

The new study also identified five risk factors, independent of the treatment used, that increased the likelihood that AF patients would suffer intracranial bleeding:

• Blacks had a 4.2-fold increased risk compared to whites; Asians’ increased risk was two-fold. Other races did not have a meaningful higher risk.
• In older people, risk increased by one third for every 10 years of age.
• A prior stroke or transient ischemic attack (TIA), also called a “mini-stroke,” boosted the risk 51 percent.
• Decreased levels of serum albumin, a protein that helps keep fluid from leaking out of blood vessels, increased the risk 42 percent for every decrease in albumin by 0.5 g/l.
• A low platelet count also increased the risk of intracranial bleeding.

Stroke ranks fourth among the leading causes of death in the United States. New or recurrent strokes strike about 795,000 Americans annually. Ischemic strokes account for 87 percent of all strokes, and 10 percent are from an intracranial hemorrhage. The remaining 3 percent result from bleeding in the subarachnoid space between the brain and the tissues covering it.

ROCKET AF’s primary finding, reported last year at the American Heart Association’s Scientific Sessions 2010, showed rivaroxaban equal to warfarin in preventing stroke or systemic blood clots in the AF patients. However, rivaroxaban patients had less intracranial bleeding and fatal bleeding. The new research aimed to determine the rate and locations of intracranial bleeding that occurred in ROCKET AF. None of the study participants had experienced intracranial bleeding at enrollment, but 53 percent had suffered a prior ischemic stroke.

After a median follow-up of about two years, researchers found 136 of the 14,264 participants had experienced an intracranial bleed – a low rate overall of about 0.5% per year according to Hankey.

Use of aspirin or a thienopyridine drug was associated with an increased risk of intracranial bleeding during the trial. However, taking rivaroxaban during the trial was associated with a lower risk of intracranial hemorrhage than taking warfarin.

The findings apply only to nonvalvular AF patients at moderate or high risk of stroke, such as those enrolled in the ROCKET AF trial, Hankey said. The validity of these findings in other populations of patients with AF awaits further study.

Co-authors and disclosures are on the abstract. Johnson & Johnson and Bayer HealthCare funded the study.

Statements and conclusions of study authors that are presented at American Stroke Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position. The association makes no representation or warranty as to their accuracy or reliability.

Angina.com Editor’s note Xarelto® is the brand name for the drug  rivaroxaban.