While it’s no surprise that sexual activity tends to decline slightly for both men and women during the year following a heart attack, or acute myocardial infarction (AMI), researchers found that many patients who said they did not get medical counsel prior to hospital discharge either unnecessarily delayed or refrained from sex.

In a survey of 1,879 heart attack patients, less than a half of men and roughly a third of women recall receiving instructions about when to safely return to sexual activity before leaving the hospital. After a year of follow-up, only 41 percent of men and 24 percent of women reported having a discussion with their doctor about sex since their heart attack.

Results from the study published today in The American Journal of Cardiology are in line with early findings presented at an American Heart Association conference in 2010. Lead author, Stacy Tessler Lindau, MD, associate professor of obstetrics and gynecology at the University of Chicago Medicine, said the study underscores the need for more doctors to address sex as an important part of overall physical function, even after a life-threatening event such as a heart attack.

“Doctors need to understand the significant role they play in helping AMI patients avoid needless fear and worry about the risk of relapse or even death with return to sexual activity,” said Lindau, a renowned expert on helping women with complex illnesses maintain sexual function. “Receiving instructions, prior to hospital discharge, about resuming sex was a major predictor of whether patients resumed sexual activity in the year following AMI. For women, this was the only significant predictor. The discharging cardiologist has detailed knowledge of the patient’s condition, has provided life-saving care and is best positioned to advise on the safety of engaging in physical activity, including sex.”

Without counseling, patients are left to make their own, often flawed, assumptions about risk associated with sexual activity. Multiple studies have shown that sex puts less of a strain on the heart than people might think. Images from overly dramatic movie scenes and sensational news stories reinforce common misconceptions. In reality, only about 1 percent of all heart attacks occur during sex. Far less than 1 percent of heart attack survivors die due to a sexual encounter, according to other research.

“This study may help doctors address issues that they’re traditionally reluctant to discuss,” said study author, Harlan Krumholz, MD, professor of medicine and epidemiology and public health at Yale University School of Medicine. “We’re showing that addressing sexual health may make a difference to long-term outcomes.”

Current guidelines developed by groups of leading cardiologists, including Krumholz, state that stable heart patients without complications can resume sexual activity with their usual partner within one week to 10 days. In January, the American Heart Association (AHA) put more weight behind those recommendations with its most comprehensive review to date of research on sexual activity among heart patients. The report substantiated a longstanding rule of thumb: If patients can engage in moderate exercise – such as walking up a couple of flights of stairs – they are generally healthy enough for sex. The AHA also points to respected guidelines for care after AMI, which include patient counseling on resuming sexual activity.

“The goal is to restore a patent’s whole health,” said John Spertus, MD, of the University of Missouri in Kansas City, who designed the study. “That means not only minimizing further progression of coronary disease, but also maximizing quality of life.”

The researchers said doctors should resist making assumptions about which patients value their sexual lives. “The study shows that most male and nearly half of female heart attack patients are sexually active,” Lindau added, “and previous work has shown that even sexually inactive patients still view sexuality as relevant for health and overall quality of life.”

Lindau, Krumholz, Spertus and their colleagues are now honing in on the female patients in this study to understand how to improve sexual outcomes after an AMI.

Additional authors of the study include Paul S. Chan, MD, from the University of Missouri, Kansas City; Erica S. Spatz from Yale University; and Emily Abramsohn, MPH and Kristen Wroblewski, MS, from the University of Chicago Medicine.

This study was supported by grants from the National Heart, Lung and Blood Institute; Cardiovascular Outcomes Inc.; and the National Institute on Aging.

The study focused on the most serious form of heart attack, ST-elevation myocardial infarction (STEMI). A STEMI typically involves complete blockage of the blood flow to the heart. Opening the blocked artery as quickly as possible is crucial to improving survival.

Physicians often use PCI, also known as angioplasty, to open blocked coronary arteries. A tiny balloon is inserted through a catheter, or tube, into the affected area. The balloon is inflated to widen the blocked areas. Physicians often combine the procedure with the insertion of a stent to help prop the artery open and decrease the chance of another blockage.

Opening the blockage with clot-busting drugs is used when timely access to PCI is not an option.

Many emergency medical services (EMS) guidelines for transporting STEMI patients recommend bypassing hospitals that can’t provide PCI and going to one that can.

“Until now, no well designed study had examined this recommendation,” said Emil L. Fosbol, M.D., Ph.D., the study’s first author and a research fellow at Duke University in Durham, N.C. “The only rationale we had was the sooner you get there, the better.”

The researchers reviewed North Carolina’s EMS records from June 2008 to September 2010 and linked these to a clinical registry of patients with STEMI. Of the 1,224 STEMI patients who met the study’s specifications, 765 (63 percent) went directly to a PCI-capable hospital (bypass group), and 479 (37 percent) stopped first at a non-PCI hospital (non-bypass group) before being transferred for a PCI procedure.

Researchers found:

• The time from first medical contact (FMC) to artery-opening treatment — PCI or clot-busting drug — averaged 93 minutes for the bypass group and 124 minutes for the non-bypass group, a substantial time difference that could improve a STEMI patient’s chances of surviving.
• For patients who received only PCI, the time from FMC to PCI averaged 93 minutes for the bypass group and 161 minutes for the non-bypass arm.
• Patients in the bypass group were almost three times as likely to get treatment within guideline recommendations compared to the non-bypass group.

“PCI is contingent on getting the patient very quickly to a hospital with a catheter lab,” Fosbol said. “Our results suggest that when logistically feasible, EMS should transfer STEMI patients directly to the nearest PCI-capable hospital.”

Co-authors are Christopher Granger, M.D.; James Jollis, M.D.; Lisa Monk, M.D.; Li Lin, M.D.; Barbara Lytle, M.D.; Ying Xian, M.D.; Lee Garvey, M.D.; Greg Mears, M.D.; Claire M Corbett, M.D.; Eric D Peterson, M.D.; and Seth Glickman, M.D.

The American Heart Association-Pharmaceutical Roundtable and David and Stevie Spina funded the study. Additional disclosures are on the abstract.

The American Heart Association’s Mission: Lifeline®-STEMI program supports systems of care to improve emergency response and treatment by quickly getting patients to the facilities with the most appropriate care. Additionally, the American Heart Association’s Mission: Lifeline® Heart Attack Referring/Receiving Center Accreditation program recognizes hospitals for their ability to quickly and appropriately treat heart attack patients. Learn more at www.heart.org/myhospital.

Statements and conclusions of study authors presented at American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect the association’s policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies)

Wayne A. Ray, Ph.D., professor of Preventive Medicine, and C. Michael Stein, M.B.Ch.B., the Dan May Chair in Medicine and professor of Pharmacology, collaborated on the research published in the May 17 edition of the New England Journal of Medicine.

Azithromycin, commonly called a “Z-pack” is one of the most popular treatments for bacterial sinus infections and bronchitis. Although it was previously considered to carry little to no cardiac risk, the researchers noted well-documented reports in the published literature as FDA database reports linking azithromycin with serious arrhythmias. Based on this evidence, the Vanderbilt researchers sought to examine cardiovascular deaths in patients who were taking the antibiotic.

Tennessee Medicaid (TennCare) patient records were examined from 1992 to 2006.

The researchers took many steps in this large, observational, population-based study to rule out other reasons for the increase in cardiovascular deaths in patients taking azithromycin. About 348,000 recorded prescriptions of azithromycin were compared with millions of similar records from people who were not treated with antibiotics or were treated with other antibiotics. The primary comparison was with amoxicillin, an antibiotic that is considered to be heart safe and is used in similar clinical circumstances as azithromycin.

While the absolute number of deaths was quite low, relative to amoxicillin, there were about 47 more deaths per million courses of therapy in those taking the azithromycin. That risk increased to 245 additional cardiovascular deaths per million in patients already known to have a high risk for heart problems.

The researchers emphasized that the decision to prescribe any antibiotic requires careful balancing of both potential benefits and risks. This calculation must consider the severity of the infection, the susceptibility of the organism, the availability of alternative antibiotics and adverse effects.

“We believe this study adds important information on the risk profile for azithromycin,” said Ray. “For patients with elevated cardiovascular risk and infections for which there are alternative antibiotics, the cardiovascular effects of azithromycin may be an important clinical consideration.”

Other authors of this study include Kathy Murray, M.D., associate professor of Cardiology, Kathi Hall, systems analyst, and Patrick Arbogast Ph.D., associate professor of Preventive Medicine and Biostatistics.

Source:  Eurekalert

The benefits for heart failure patients are similar to those for anyone who exercises: there’s less muscle-wasting, and their bodies become conditioned to handle more exercise. Age of the patients didn’t matter, either, researchers found.

“Many physicians – and insurance companies – still believe that cardiac rehabilitation does not really help in old age. This study clearly falsifies this belief,” said Stephan Gielen, M.D., lead co-author and Deputy Director of Cardiology at the University Hospital, Martin-Luther-University of Halle, Germany.

Between 2005 and 2008, researchers recruited 60 heart-failure patients and 60 healthy volunteers. Half of each group was 55 years and younger and the other half, 65 years and older, resulting in an average age difference of 20 years between the groups. Half the participants in each age group were randomly assigned to four weeks of supervised aerobic training or no exercise. Researchers took muscle biopsies of all participants before and after the intervention.

In both age groups, four training sessions of 20 minutes of aerobic exercise per day, five days a week plus one 60 minute group exercise session was associated with increased muscle force endurance and oxygen uptake. Heart failure patients 55 and under increased their peak oxygen uptake by 25 percent, while those 65 and over increased it by 27 percent.

Using biopsy results, researchers found that levels of a muscle protein indicating muscle breakdown, known as MuRF1, were higher in participants with heart failure than in their healthier counterparts. However, exercise reduced MuRF1 and reduced muscle inflammation, measured by levels of a protein called TNF-alpha.

The strength of participants’ leg muscles was measured before and after the exercise. Younger and older heart failure patients increased muscle strength after the four-week exercise regimen. Muscle size was unaffected.

These findings offer a possible treatment to the muscle breakdown and wasting associated with heart failure and suggest that exercise is therapeutic even in elderly heart failure patients. The findings also suggest an avenue for drug development to slow muscle breakdown in heart failure patients.

“Exercise switches off the muscle-wasting pathways and switches on pathways involved in muscle growth, counteracting muscle loss and exercise intolerance in heart failure patients,” Gielen said.

According to the American Heart Association, about 5,700,000 Americans age 20 and older have heart failure.

“Over the last three decades, hospital admissions for heart failure have increased fourfold and will continue to do so, due chiefly to the aging of the population,” Gielen said. Estimates of costs vary, but are in the tens of billions of dollars per year in the United States alone, researchers said.

The lead co-author is Marcus Sandri, M.D. and other co-authors are Irina Kozarez, M.D.; Jurgen Kratzsch, M.D.; Daniel Teupser, M.D.; Joachim Thiery, M.D.; Sandra Erbs, M.D.; Norman Mangner, M.D.; Karsten Lenk, M.D.; Rainer Hambrecht, M.D.; Gerhard Schuler, M.D. and Volker Adams, M.D.

Sildenafil, also known as the erectile dysfunction drug Viagra, may give a boost to underdeveloped hearts in children and young adults with congenital heart defects. Researchers from The Children’s Hospital of Philadelphia report that sildenafil significantly improved echocardiographic measures of heart function in children and young adult survivors of single ventricle heart disease palliation.

“Although researchers will need to evaluate clinical benefits over a longer period with a larger number of patients, this finding offers a potential advance in the management of patients with these types of heart defects,” said study leader David J. Goldberg, M.D., a pediatric cardiologist at The Children’s Hospital of Philadelphia.

The study appeared online recently in the journal Pediatric Cardiology.

The researchers randomly assigned 27 children and young adults at Children’s Hospital to receive either sildenafil or a placebo for six weeks. After a six-week break in treatment, the subjects were switched to the opposite treatment course. The study team used echocardiograms to measure myocardial performance index (MPI), an indicator of the heart’s overall ability to pump blood.

The patients in this double-blind, short-term study, who had a mean age of 14.9 years, had undergone a Fontan operation in early childhood, a mean of 11.3 years previously. The Fontan surgery redirects blood circulation in patients born with a severely underdeveloped ventricle, one of the heart’s two pumping chambers. The operation is the third in a staged series of surgeries for life-threatening single-ventricle defects.

Although surgical advances over the past 20 years have dramatically improved survival for single-ventricle defects, patients with the condition continue to have long-term illness and risk of early death. The staged surgeries do not recreate normal heart circulation, but instead redirect blood flowing from the veins directly to the lungs, bypassing the heart. However, blood vessels in the lungs develop resistance to this blood, often reducing a patient’s ability to tolerate exercise.

Sildenafil, which reduces blood vessel resistance to the flow of blood, is already used to treat pulmonary hypertension (high blood press in lung vessels), as well as erectile dysfunction. Because sildenafil has also shown promise as a treatment for adults with heart failure, the Children’s Hospital researchers are exploring whether it may benefit younger patients with certain types of congenital heart disease.

The current study is part of a broader phase 2 clinical trial at The Children’s Hospital of Philadelphia, the Sildenafil After the Fontan Operation (SAFO) trial. A previous study from the same research team, published in March 2011, found improvements in exercise performance, as measured by ventilator efficiency, in children and young adults with single-ventricle disease who took sildenafil compared to those who took placebo.

The current study was the first to show that sildenafil improved echocardiographic measures of ventricular performance in children and young adults with single-ventricle physiology. The biological mechanisms that affect ventricular performance are not fully understood, said Goldberg, but he noted that studies in other patients with heart disease suggest that inhibiting the abnormally high levels of the enzyme phosphodiesterase E5 (PDE5) may produce the physiological benefits seen in the single-ventricle patients.

Goldberg cautioned that further research should be pursued to determine if the observed improvements in ventricular performance persist beyond the short term and if they provide clear quality-of-life benefits. “If sildenafil is safe over the medium and long-term, and if it produces durable functional improvements, patients with single-ventricle heart disease could have their first effective long-term treatment,” he added.

Goldberg’s co-authors were Anita L. Szwast, M.D., Michael G. McBride, Ph.D., Nicole Mirarchi, M.A., Brian D. Hanna, M.D., Ph.D., Gil Wernovsky, M.D., and Jack Rychik, M.D., all from Children’s Hospital; Benjamin French, Ph.D., from the Perelman School of Medicine of the University of Pennsylvania; and Bradley S. Marino, M.D., MSCE, of Cincinnati Children’s Hospital Medical Center.

Although rare, SCD often receives widespread attention because it is unexpected and can occur during childhood. Those factors have prompted many parents and policy makers to support screening programs. To help decision makers and the public understand whether more SCD screening is warranted, the authors, including collaborating clinical researchers from Children’s Hospital Boston, compared the potential life saving benefits (measured in terms of life years saved) to program costs. They considered two groups thought to be at elevated risk: school-aged children taking stimulants, which are often used to treat Attention Deficit Hyperactivity Disorder (ADHD), and adolescents playing organized sports. The research team determined that each year of life saved would cost from $90,000 (to screen adolescents before they participate in sports) to $200,000 (to screen children before they take ADHD medications).

Although there is no hard and fast line separating worthwhile and expensive public health interventions, programs can be compared to get an idea of their value. For example, interventions that cost $90,000 to $200,000 per life year saved are considered expensive, compared to other interventions, which often save life years at $50,000 to $100,000, or even less. The results of this study suggest that finite public health resources might be better spent elsewhere.

The “human cost” of screening suggests its true price may be even higher. Because conditions causing SCD are so rare, even an occasional “false positive” means that for every previously undiagnosed child accurately identified, many children who would never have died from SCD may be labeled as being at-risk.

The research team stressed that the cardiac conditions causing SCD in children are incredibly rare. Many are cardiac conditions are genetic and there may be a family history of early (< 50 years of age) or unexplained SCD in a family member. Dr. Leslie advises that “the most concerning family history in a child is when a parent or sibling is diagnosed with a likely familial cardiac disease; those children should certainly be evaluated.” Since some disorders that cause SCD may not be identifiable on an ECG until late adolescence or early adulthood, an ECG in a parent with a positive family history may provide more information than an ECG in a child. Another indication to consult with a doctor is if a child reports any experiences of fainting or shortness of breath with strong emotions or during exertion (not related to a medical condition like asthma).

UCSF researchers, however, question the way the previous study was conducted, and their new analysis, scheduled to be published May 4 in BMJ, reaches a very different conclusion.

“We found no clinically or statistically significant increase in serious adverse cardiovascular events associated with using varenicline,” said lead author Judith J. Prochaska, PhD, MPH, an associate professor in UCSF’s Department of Psychiatry and researcher with the Center for Tobacco Control Research and Education. “The findings from 22 trials with more than 9,200 participants indicate a difference in risk of only 0.27 percent between those on varenicline versus placebo, or about a quarter of one percent.”

Prochaska identified the need for the re-analysis after reading the CMAJ publication and finding the conclusion inconsistent with the small differences within trials. Prochaska had received an “investigator-initiated research award” from Pfizer, the maker of Chantix, that spring for a separate study of varenicline in hospitalized smokers, many with heart disease. Prochaska says she was compelled to more closely examine the data to quantify the level of risk before using the medication on UCSF patients.

DIFFERENCES IN META-ANALYTIC METHODS

Prochaska and Joan F. Hilton, ScD, MPH, a professor in UCSF’s Department of Epidemiology & Biostatistics, conducted the new study, which, like the prior one, used meta-analytic statistical techniques to combine results from different trials of varenicline with tobacco users. The UCSF and prior analysis, however, differed in several fundamental ways.

The previous study, led by Sonal Singh, MD, MPH, assistant professor of medicine at Johns Hopkins University, looked at a sample size of 8,216 patients in 14 trials and ¬¬¬reported a 72 percent (relative) increase in risk of heart attack or other serious heart problems.

The UCSF analysis included 22 double-blind, randomized controlled trials with 9,232 participants. More than half of the studies included participants with active or past history of cardiovascular disease. Eight trials had no events. The UCSF study found a 0.27 percent (absolute) risk difference, which it determined was neither clinically nor statistically significant.

“We identified eight separate trials with nearly 1,600 tobacco users randomized to varenicline or placebo that did not have a single serious cardiovascular event,” Prochaska said. “This information is meaningful and the Singh analysis excluded these trials.”

UCSF researchers say varenicline lasts in the body about seven days after a person stops using the medication. The new analysis examined events occurring during the drug treatment window or within 30 days after a patient stopped using the drug, rather than the entire trial period, which in many cases was a year in Singh’s study.

“The longer you follow heavy, long-term tobacco users – and in these studies, the average participant smoked a pack a day for 25 years – the more likely you will see serious cardiovascular events related to their compromised health,” Prochaska said. “In addition, 13 of the 14 studies in the Singh analysis experienced greater attrition in the placebo group than in the test group, which could inflate the treatment effect.”

ABSOLUTE DIFFERENCE VS. RELATIVE DIFFERENCE

Singh’s study found that 1.06 percent of those who took varenicline had serious heart-related complications, compared to 0.82 percent of the placebo group. Although the simple absolute difference was only 0.24 percent – similar to the UCSF study finding based on meta-analytic methods – Singh’s paper reported the weighted, relative difference, which was 72 percent.

“What made the headlines is this claim of a huge increase, but it’s a relative measure; it’s a unit-less measure,” Prochaska said. “And so if you increase something small by a little bit, you can claim that it’s a 72 percent increase, but that obscures the fact that it’s still a very small risk.”

“For someone not accustomed to these measures, it might not be obvious that the 72 percent increase was relative to a very small base – interpretations the Singh study didn’t stress,” Hilton said.

The new meta-analysis provides a more comprehensive examination of varenicline by presenting and comparing the four most relevant summary measures for this type of analysis.

“Among these, we found that the methods used by Singh and colleagues produced the most extreme estimates of treatment effect,” said Hilton. “We identified the specific conditions under which this statistic is inflated. We recommended the summary based on the (absolute) risk difference because it is methodologically appropriate in our setting and gives a clear quantitative sense of the excess risk.”

SMOKING AND CARDIOVASCULAR RISK

Cardiovascular disease is the leading cause of death among smokers. Tobacco use also increases a person’s risk of stroke, cancer and lung disease.

“One of the most important things you can do for your heart is to quit smoking,” Prochaska said. “Clinical practice guidelines recommend the use of FDA medications to quit smoking. All medications carry some risk; however, we hope the FDA and other experts compare the Singh analysis to ours to determine what action, if any, should be taken with regard to varenicline and cardiovascular risk. Tobacco is a deadly addiction, and patients need effective treatments.”

Funding for this meta-analysis was provided by grants to Prochaska from the State of California Tobacco-Related Disease Research Program (TRDRP) and the National Institute on Drug Abuse.

It has been almost eight years since Vioxx® was withdrawn by Merck from the market, provoking an intense controversy about the role inhibitors of the enzyme COX-2 play in causing heart attacks and strokes. Since then, other drugs in the class from Pfizer, Novartis, and Merck have been withdrawn (Bextra®); have failed to be approved (Arcoxia®, Prexige®); or have been retained on the market in the US with a “black box” warning on the label (Celebrex®).

COX-2 is one of two similar enzymes that churn out short-lived fats called prostaglandins. The other, COX-1, works in platelets — cells in the blood that stick together in the first stages of clotting. COX-2 is active in the cells that line blood vessels. These enzymes have diverse, potent, and often contrasting effects in the body. For example, low-dose aspirin protects against heart attacks and strokes by blocking COX-1 from forming a prostaglandin called thromboxane A2 in platelets. On the other hand, COX-2 is the more important source of prostaglandins, particularly one called prostocyclin, which causes pain and inflammation.

COX-2 inhibitors are a subclass of nonsteroidal anti-inflammatory drugs (NSAIDs), among the most common drugs consumed on the planet. Older NSAIDs include drugs like Naprosyn, which inhibits mostly COX-1; Advil®, which inhibits COX-1 and COX-2; and Voltaren® and Mobic®, which mostly inhibit COX-2. The newer drugs were developed because targeting COX-2 reduced serious gastrointestinal side effects like bleeding ulcers. However, aggressive direct-to-consumer advertising meant that drugs like Vioxx and Celebrex were taken mostly by patients who had never had the GI problems with the older, cheaper NSAIDs.

Just before Celebrex and Vioxx were approved and launched, a group led by Garret FitzGerald, MD, chair of the department of Pharmacology, and director of the Institute for Translational Medicine and Therapeutics at Penn, observed that both drugs suppressed prostacyclin in humans, as reflected by its major metabolite in urine, PGI-M. Based on the potentially cardioprotective properties of prostacyclin, which relaxes blood vessels and unglues platelets in test tube experiments, the team predicted that shutting down this protection with inhibitors would cause heart attacks and strokes.

More than 10 years later, it is now clear what the COX inhibitors do in the body. Eight placebo-controlled, randomized trials, performed to find new uses of these drugs, showed that they posed a cardiovascular hazard, similar in magnitude to that resulting from being a smoker or a diabetic, notes FitzGerald. “Despite this, controversy has continued about how all this came about, until now.”

Arguments against the proposed mechanism were threefold. First, it was proposed that COX-2 didn’t exist under normal circumstances in the blood-vessel lining and PGI-M came from some other source. The kidneys were suggested as the source by some researchers. Second, even if blood-vessel prostacyclin was blocked, other protective mechanisms, especially formation of nitric oxide (NO) would take over. And third, although NSAIDs elevate blood pressure, it was proposed that this observation was unrelated to COX-2 and treating high blood pressure would deal with the problem.

FitzGerald’s group has now “closed the loop” with its earlier clinical studies and answered these questions in a paper just published in Science Translational Medicine. In it, they confirm that COX-2 is expressed in cells lining blood vessels and that selectively removing it predisposes mice to blood clotting and high blood pressure. These mice, just like humans taking COX-2 inhibitors, also see a fall in PGI-M. What’s more, the Penn group discovered that COX-2 in lining cells controls the expression of eNOS, the enzyme that makes NO in the body. “So, rather than replacing the missing prostacyclin, as others have proposed, NO is lost and amplifies the effects of COX-2 inhibition on the cardiovascular system,” says FitzGerald.

Indeed, the lost NO may not be the only step that magnifies the effects of losing prostacyclin. In a second paper, published in April 2012, in the Proceedings of the National Academy of Sciences, FitzGerald’s group shows that arachidonic acid, the fat broken down by COX-2 to make prostacyclin, can be shunted down another pathway to make a new series of dangerous fats called leukotrienes when COX-2 is disrupted.

Clinical studies have shown that those most at risk from COX-2 inhibitors are patients who already have heart disease. However, the Penn group now suggests broader implications. Here, the group resolves one aspect of the controversy, showing that COX-2 disruption causes hardening of the arteries in mice. This result is provocative because randomized trials of Vioxx and Celebrex in patients at low risk of heart disease detected an increase in heart attacks after patients had been taking the drugs for more than a year. These current Penn studies raise the disturbing prospect that heart-healthy patients taking NSAIDs for prolonged periods might be gradually increasing their risk of heart attacks and strokes by progressively hardening their arteries.

“However, it’s not all bad news,” says FitzGerald. This risk of hardening of the arteries was diminished in mice by reducing leukotriene formation, via blocking a critical protein called the 5-lipoxygenase activating protein, or FLAP. Inhibitors of FLAP are already in trials in humans to see if they work in asthma. Perhaps, FitzGerald concludes, they can now find an additional use — protecting the heart from NSAIDs.

The study, carried out over 9.3 years, evaluated the risk of different blood pressure categories among 6,273 participants aged 30 years old and above. The results showed that the risk of developing incident CVD and CHD was significantly higher in people with high normal blood pressure during middle-age (between 30 and 60 years of age) than for people with the same high normal blood pressure aged 60 years and older. Incident CVD and CHD risk was, however, similarly high in people with diagnosed high blood pressure across all age-groups.

“These results reinforce the fact that high blood pressure is a serious risk for CVD in all age groups,” said Dr. F. Hadaegh, Prevention of Metabolic Disorders Research Center, Tehran, Iran. “However, the results also suggest that when looking to manage high normal blood pressure resources should be focused on those individuals that are in middle age.”

High blood pressure is defined as a repeatedly elevated systolic pressure of 140 mmHg or higher OR a diastolic pressure of 90 mmHg or higher. This study was carried out over 9.3 years and the study protocol established before new guidelines around high normal blood pressure were adapted. In 2003, the Joint National Committee 7(JNC7) from the United States introduced the concept of prehypertension into guidelines categorizing the individuals with systolic blood pressure between 120-139 mmHg or diastolic blood pressure between 80-89 as prehypertension groups.

Hypertension and CVD

Hypertension (high blood pressure) is one of the major preventable risk factors for premature death from CVD worldwide. High blood pressure contributes to around half of all CVD and the risk of developing CVD doubles for every 10-point increase in diastolic blood pressure.

High blood pressure that is left untreated can greatly increase a person’s risk of developing CVD. Treating raised blood pressure has been associated with a 35 per cent reduction in the risk of stroke and at least a 16 per cent reduction in the risk of myocardial infarction

These findings, being presented at the American Heart Association’s Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) 2012 Scientific Sessions in Chicago April 20, 2012, may help in identifying the molecular culprit, with the goal of creating targeted therapies for atherosclerosis before the disease forms.

Coronary artery disease is a narrowing of the small blood vessels that supply blood and oxygen to the heart.

Tapan Chatterjee, PhD, and researchers in the division of cardiovascular diseases at UC found through global gene expression analysis (measurement of the activity of thousands of genes at once) that this outer fat tissue—known as perivascular fat tissue—is different from subcutaneous (beneath the skin) fat tissues in other parts of the body.

Research has previously shown that perivascular fat tissue in humans with coronary artery diseases is highly inflamed, leading to the belief that dysfunctional perivascular fat is the real culprit in the formation of coronary artery diseases.

Chatterjee’s team was able to replicate this inflammation in animal models.

“The proximity of the perivascular fat to the artery easily influences the function of the coronary blood vessel wall,” Chatterjee says. “The perivascular fat is very sensitive to high-fat diet induced inflammatory changes in mice. We found that by transplanting perivascular fat from high-fat diet fed obese mice to the carotid artery of lean mice, the tissue was detrimental to the blood vessel wall and promptly caused disease to form there.

“Our next steps will be to identify various secreted factors, or signals, from perivascular fat tissue of obese mice that could negatively influence the functions of the blood vessel wall,” he continues. “We believe this cross-talk between perivascular fat and the coronary artery is very important in triggering coronary artery diseases. We hope this knowledge helps in targeting the molecules before the onset of coronary artery diseases and treating patients before they ever experience the disease.”

This study was funded by the National Heart Lung and Blood Institute.

Source: Eurekalert: 4/21/2012