Senior Staff Writer

Survival rates higher in

obese heart failure patients

Patients who were obese before developing heart failure lived longer than normal weight patients with the same condition according to a new study in the Journal of the American College of Cardiology that examined the "obesity paradox" by following obese and non-obese heart failure patients for more than a decade. Using data from the Atherosclerosis Risk in Communities Study, researchers looked at body mass index before the initial diagnosis of heart failure in 1,487 patients and followed them for 10 years, comparing the survival rates of obese, overweight and normal weight patients after the development of heart failure. The majority of patients included in the study were overweight (35%) or obese (47%) prior to their initial diagnosis of heart failure.

During the 10 year follow-up period, 43% of the patients in the study group died, but the overweight and obese patients had better survival rates compared to the normal weight patients. Over the decade of follow-up, 38% of obese and 45% of overweight patients died compared to 51% of normal weight patients. Obese and overweight patients were more likely at the outset to have other health issues, including hypertension and diabetes.

This is the first study to demonstrate that higher BMI before heart failure diagnosis is independently associated with better survival outcomes after the development of heart failure, over a long follow-up period. Previous studies have shown that although obesity is an independent risk factor for the development of heart failure, higher body mass index, as measured in patients with established heart failure, is associated with improved survival.

The study's findings could suggest that obese patients have a higher metabolic reserve than the normal BMI patients, perhaps providing a survival advantage when spontaneous weight loss due to heart failure occurs, or that obese heart failure patients manifest symptoms of heart failure earlier in the disease process, the authors said.

"Most patients with heart failure have pre-existing overweight or obesity, yet they have lower mortality compared to normal body mass index heart failure patients," said the study's senior author, Anita Deswal, of the Michael E. DeBakey V.A. Medical Center and Baylor College of Medicine (Houston). "Our findings suggest that a major component of the so-called obesity paradox is premorbid obesity and it's unlikely that spontaneous weight loss due to advanced heart failure is the only contributing factor to the obesity paradox."

In an accompanying editorial, Thomas Wang, a physician at Vanderbilt University Medical Center (Nashville, Tennessee), said the study demonstrates the best evidence to date that the obesity paradox is not simply due to extreme weight loss in late-stage heart failure and drives home the need for a better understanding of what causes the obesity paradox.

Scientists focus on delivery

problem associated with NO

A group of scientists led by researchers at the Université de Versailles' Institut Lavoisier (France) has worked out how to stably gift-wrap a chemical gas known as nitric oxide within metal-organic frameworks. Such an encapsulated chemical may allow doctors to administer nitric oxide in a more highly controlled way to patients, suggesting new approaches for treating dangerous infections and heart conditions with the biologically-active substance.

Not to be confused with the chemically-distinct anesthetic dentists use, its cousin nitrous oxide (NO2), also known as laughing gas - nitric oxide (NO) is one of very few gas molecules known to be involved in biological signaling pathways, the physiological gears that make the body tick at the microscopic level. It is very active biologically and can be found in bacteria, plant, animal and fungi cells.

In humans, NO is a powerful vasodilator, increasing blood flow and lowering vascular pressure. For this reason, gaseous NO is sometimes used to treat respiratory failure in premature infants. It also has strong antibacterial potency, owing to its molecular action as a biologically disruptive free radical, and cells in the human immune system naturally produce NO as a way of killing pathogenic invaders. Additionally, nitric oxide is believed to be the main vasoactive neurotransmitter regulating male erection, as aging nerves with reduced stimulation can inhibit the release of the molecule, thus causing erectile dysfunction. This, of course, can be mediated by taking nitric oxide supplements to achieve an erection.

While such activity would seem to make NO a prime candidate for drug design, the problem is delivery because it is a gas. In recent years, the gas storage capacity and biocompatibility of metal-organic-frameworks – dissolvable compounds consisting of metal ions and rigid organic chemicals that can stably trap gas molecules – have gained significant attention as candidates for delivering gas-based drugs. The new work extends this further than ever before, showing that these metal-organic frameworks can store and slowly deliver NO over an unprecedented amount of time, which is key for the drug's anti-thrombogenic action.

"This is an elegant and efficient method to store and deliver large amounts of NO for antibacterial purposes," said Christian Serre, a CNRS research director at the institute. "Or it can release controlled amounts of nitric oxide at the very low biological level for a prolonged period of time, in order to use it as a way to inhibit platelet aggregation."

Serre and his group worked in collaboration with Russell Morris's team at the University of St Andrews (Scotland) and researchers from Université de Basse-Normandie (France). The groups analyzed the NO adsorption and release properties of several porous biodegradable and biocompatible iron carboxylate metal-organic frameworks by use of infrared spectroscopy analysis, adsorption & desorption isotherms and water-triggered release tests.

In doing so, they confirmed the large nitric oxide absorption capacity of the iron frameworks, and that the NO was strongly bonding to the acidic metal sites on the molecules. Serre's group and coauthors also found that partially reducing the iron (III) into iron (II) enhances the affinity of the NO molecules for the framework. This strong interaction allows for a controlled release for a prolonged state of time - days, at the biological level. This time scale depends on both the metal-organic framework structure and the oxidation state of iron, which can be carefully calibrated as needed for drug treatment.

These performances, associated with the biodegradable and low toxicity character of these metal-organic frameworks, might pave the way for their use in medical therapies or cosmetics formulation, which is one of the objectives of Serre's consortium in the near future. Current and forthcoming work includes using further spectroscopic experiments to understand the complex behavior of the iron frameworks once loaded with nitric oxide.

Stroke looses rank as cause of death

Stroke has dropped from the nation's fourth-leading cause of death to No. 5, according to new federal statistics. It is the second time since 2011 that stroke has dropped a spot in the mortality rankings. According to the Centers for Disease Control and Prevention report released recently, stroke swapped positions with unintentional injuries, which killed 1,579 more people than stroke in 2013.

The stroke death rate dropped slightly, from 36.9% in 2012 to 36.2% in 2013. While the death rate from heart disease dropped somewhat between 2012 and 2013, it remains the No. 1 cause of death in the nation. Cancer is the second-leading cause of death, followed by chronic lower respiratory diseases.

The decline in stroke deaths may be due in part to improvements in treatment and prevention, said Ralph Sacco, past president of the American Heart Association (AHA; Dallas) and chairman of neurology at the University of Miami Miller School of Medicine.

"There are more stroke centers now operating in the U.S., and the acute care of stroke is improving," said Sacco, who in 2010 became the first neurologist to be named AHA president. "However, although mortality from stroke is dropping, we know that the number of people having strokes in the U.S. is rising each year due to the aging of our population and other signs that strokes have increased in younger groups."

Indeed, despite the lower death rate, 432 more people died from stroke in 2013 than in 2012, the report found.

AHA features 10 advances in research in 2014

The American Heart Association (AHA; Dallas) has highlighted what it considers the top advances in heart disease and stroke research in 2014. The organization has compiled an annual list of the major advances in heart disease and stroke research each year since 1996.

• No clear winner in comparison of two Marfan syndrome drugs: Put to the test, two types of drugs are generally equally matched for treating Marfan syndrome, giving doctors new information for treating the genetic disorder.

• Blood test finds early heart damage: A new, highly sensitive blood test shows that people with diabetes may have increasing heart damage, according to a study published in the American Heart Association journal Circulation.

• Anti-clotting med, aspirin reduce heart attacks: Extended use of aspirin plus a second anti-clotting medication reduced the likelihood of blood clots and heart attacks, although it raised the risk of bleeding.

• HBP procedure doesn't live up to early promise: Despite showing early promise, renal denervation was no better than a sham procedure at reducing high blood pressure, according to a trial published this year.

• Bariatric surgery helped, study said: Bariatric surgery improved blood sugar control, reduced the need for medications and improved the quality of life for obese patients with Type II diabetes, according to a three-year follow-up study.

• Promising drug for heart failure reduces deaths: A new experimental drug could help many people with a certain kind of heart failure live longer, better lives, according to a large research trial.

• Future treatment could lower cholesterol for life: A single injection could eliminate a lifetime of high cholesterol, if humans respond to it as dramatically as mice did.

• Study finds aspirin doesn't lower risk: Aspirin is known to help reduce heart attacks in people who have already had one, but a large-scale study in Japan points out the lack of benefits and the risks of daily aspirin for people without heart disease.

• Systems speed treatment, benefit stroke patients: Two studies used forward-thinking emergency medical systems and hospitals to shave treatment times and benefit stroke patients. Fast treatment after a stroke can save lives and help survivors avoid long-term disabilities.

• New methods lead to new treatments: Two innovative models to study and test how specific genes affect the heart and blood vessels are leading to successful experimental treatments, opening a new frontier in medicine.

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