Atrial fibrillation (AF) is the most common chronic arrhythmia in adults. An estimated 2.3 million adults in the U.S. have AF, and the prevalence of AF increases with age, with a substantial overall lifetime risk of about one in four for both men and women. The increase in AF incidence with age coincides with a rapid age-related increase in aortic stiffness, which is associated with increased pulse pressure, which increases cardiac load and may increase AF risk.

Increased pulse pressure (the difference between systolic and diastolic blood pressure) appears to be an important predictor of the risk for new onset AF, according to a new study.

Gary Mitchell, MD, of Cardiovascular Engineering (Waltham, Massachusetts) and colleagues examined the association between pulse pressure and the development of AF.

The study, appearing in the February issue of Nature Clinical Practice Cardiovascular Medicine, included 5,331 participants of the Framingham Heart Study who were age 35 years and older and initially free from AF (median [midpoint] age, 57 years; 55% women). During an average of 16 years of follow-up, 363 men and 335 women developed AF with a median time-to-event of 12 years after pulse pressure assessment.

The researchers found that after adjusting for age and sex, a 20 mm Hg increase in pulse pressure was associated with a 34% increase in the risk for developing AF. The association between pulse pressure and AF remained significant after further adjusting for average arterial pressure and clinical risk factors for AF; each 20 mm Hg increase in pulse pressure was associated with a 24% increase in the risk for developing AF. In contrast, average arterial pressure was not associated with increased risk for developing AF.

Cumulative 20-year AF incidence rates were 5.6% for pulse pressure of 40 mm Hg or less (25th percentile) and 23.3% for pulse pressure greater than 61 mm Hg (75th percentile).

“In summary, we have shown that increased pulse pressure, a simple and readily accessible if somewhat indirect measure of arterial stiffness, is likely an important risk factor for development of AF in a community-based sample. Arterial stiffness increases with advancing age, even in a relatively healthy sample. However, increased arterial stiffness with advancing age is not inevitable and appears to be modifiable [such as by reducing various cardiovascular disease risk factors]. As a result, increased arterial stiffness may represent a major modifiable risk factor for development of AF.”

The researchers ssaid that, given aging demographics, additional research should be undertaken to determine if interventions aimed at reducing pulse pressure or preventing the increase in pulse pressure with advancing age, would effectively reduce the incidence of AF.

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Off-pump CABG nobetter for cognitive function

The negative downstream effects of coronary artery bypass surgery (CABG) are well known and often cited, but until angioplasty came along, patients with severe blockage had few options. But many patients are not viable candidates for stents, and so they must undergo a thoracic procedure that involves significant trauma.

The use of a heart-lung machine to maintain cardiopulmonary function is as old as the CABG, but has some drawbacks. The tubing may carry infectious agents or foreign matter, and blood cells are prone to damage. Another notorious side effect of bypass surgery is a decline in cognitive function, and researchers have wondered if avoiding the pump offered a drop in the impairment of cognitive function.

The procedure, which requires the use of pharmaceuticals to slow the heart rate, is already known to be less expensive, and because it requires a smaller opening, allows patients to head home sooner. However, it was not known whether the lower rate of dislodged aortic accumulations would translate to better cognitive outcomes.

In 1998, a team of researchers at the University Medical Center Utrecht (Utrecht, the Netherlands) drew up and started a study to examine whether the off-pump procedure was less stress on cognitive function. The resulting article, which appeared in the Feb. 21 edition of the Journal of the American Medical Association, notes that not only can the intervention in the ascending aorta dislodge accumulations in the aorta, “leading to stroke,” but it also can increase the permeability of the blood-brain barrier and trigger the accumulation of atherosclerotic tissues in blood vessels, “which may adversely affect cognitive function.”

The authors state that the cognitive decline in CABG on-pump patients is often measured at 5%-30%, depending on the measure, and that about 3% of CABG patients experience a stroke.

These factors have led to “a renewed interest in bypass surgery on the beating heart,” but the off-pump procedure “is technically more demanding,” the article points out. However, the trial of more than 280 patients, dubbed the Octopus Study, presented researchers with more questions than answers.

“In the Octopus Study, we found a trend toward better cognitive outcomes after three months after surgery, but the difference disappeared at 12 months and now appears to remain absent at five years.” The team opined that “this is remarkable because several studies have demonstrated that off-pump CABG surgery is associated with less cerebral embolization” than surgeries using the heart-lung machine. And the authors hypothesize that “factors other than cardiopulmonary bypass may be responsible for cognitive decline, such as anesthesia and the general inflammatory response that is associated with major surgical procedures.”

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The heart-shape of the heart explained

Why is the heart shaped the way it is? The heart first develops as a simple tube; later, the tube walls bulge outward to form the cardiac chambers, giving it its characteristic shape.

In a study published online in the open access journal PLoS Biology, Heidi Auman, Deborah Yelon, and colleagues found, by using transgenic zebrafish in which they can watch individual cardiac cells, that cells change size and shape, enlarging and elongating to form the bulges in the heart tube and eventually the chambers. Since the heart is beating as it develops, they asked whether cardiac function influences cell shape.

Using zebrafish mutants with functional defects, they found that both blood flow and cardiac contractility influence cardiac cell shape. The researchers propose that a balance of the cell’s internal forces (through contractility) with external forces (such as blood flow) is necessary to create the cell shapes that generate chamber curvatures. Disruption of this balance may underlie the aberrations observed in some types of heart disease. In almost all forms of heart failure, the heart begins to express genes that are normally only expressed in the fetal heart. Researchers have known for years that this fetal-gene reactivation happens, yet not what regulates it.

Now, investigators at the University of Pennsylvania School of Medicine (Philadelphia) have discovered that an enzyme important in fetal heart-cell development regulates the enlargement of heart cells, known as cardiac hypertrophy, which is a precursor to many forms of congestive heart failure (CHF).

The study, which paves the way for new targets for treating cardiac hypertrophy and heart failure, appears in an advanced online publication of Nature Medicine.

“It’s as if old programs are being reactivated in a sick heart,” said senior author Jonathan Epstein, MD, the W.W. Smith Endowed Chair for Cardiovascular Research at Penn. “In an adult heart, stresses such as high blood pressure induce the reexpression of a fetal gene program.”

The investigators found that by inhibiting the enzyme HDAC in adult mice the fetal-gene program can be prevented from restarting. “We found that in various mouse models of cardiac hypertrophy and heart failure, treatment with chemical HDAC inhibitors or genetic deletion of HDAC2 prevented the beginning of the downward slide to progressive heart failure,” says Epstein.

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Molecular ‘clock,’ morningheart attack linkprobed

Heart attacks and strokes occur most often in the early morning. Now, researchers at the University of Pennsylvania School of Medicine (Philadelphia) provide the evidence for the role of the body’s internal molecular clock in this circumstance. Published online in the Proceedings of the National Academy of Sciences, the report points to the possibility of modifying blood pressure to prevent early-morning heart attack.

The upswing in heart attacks tracks with rising blood pressure, which undergoes a circadian — 24-hour — rhythm. This rise is amplified in patients with high blood pressure. However, scientists have debated as to whether this event signifies a role for the molecular clock, or merely reflects the relationship of clock time to stresses in our environment -- such as waking, hurried dressing, the rush to work.

The molecular clock consists of genes in an area of the brain that tightly regulate circadian rhythms in behavior, temperature, and metabolism. Researchers now appreciate that this “master clock” also interacts with clocks in almost all types of tissues.

Using mice in which the function of major clock genes have been disrupted, the investigators found distinct and complementary effects on blood pressure and its circadian variation. Using a mouse model in which catecholamines and blood pressure were made to surge, the researchers found that the rise in both blood pressure and catecholamines depended on the time of the stress.

The greatest response occurred at a time that would correspond to the early morning hours.

“These results integrate for the first time the two leading explanations for the diurnal variation in blood pressure and reveal an unexpected role for a clock gene in regulating the stress response” said senior author Garret FitzGerald, MD, director of the Institute for Translational Medicine and Therapeutics at Penn FitzGerald. “They raise the novel possibility of modifying blood pressure and consequently the early-morning risk of heart attack and stroke by using drugs to ‘reset’ the molecular clock.”

Since blood pressure response (via rising catecholamines) to stress in the early morning is tied to one’s internal clock, tamping down the clock using drugs could be a treatment for high blood pressure, whose upswing in pressure is amplified in the morning anyway.