Predictors of dying suddenly versus surviving heart attack identified

ScienceDaily (July 26, 2011) — Is it possible to predict whether someone is likely to survive or die suddenly from a heart attack? A new study by researchers at Wake Forest Baptist Medical Center has answered just that.

"For some people, the first heart attack is more likely to be their last," said Elsayed Z. Soliman, M.D., M.Sc., M.S., director of the Epidemiological Cardiology Research Center (EPICARE) at Wake Forest Baptist and lead author of the study. "For these people especially, it is important that we find ways to prevent that first heart attack from ever happening because their chances of living through it are not as good."

While there are many traits that are common among heart attack patients -- both those who survive the event and those who die suddenly -- researchers found that some traits, such as hypertension, race/ethnicity, body mass index (BMI), heart rate, and additional markers that can be identified by an electrocardiogram (ECG) can differentiate between dying suddenly versus living through a heart attack, Soliman said.

The study, published by the journal Heart, is now available online.

Somewhere between 230,000 and 325,000 people in the U.S. succumb to sudden cardiac death every year, Soliman said. Most of these sudden deaths are caused by coronary heart disease.

"Since sudden cardiac death usually occurs before patients ever make it to the hospital, there is very little that can be done to save them," Soliman said. "Identifying specific predictors that separate the risk of sudden cardiac death from that of non-fatal or not immediately fatal heart attacks would be the first step to address this problem, which was the basis for our study."

Researchers analyzed data from two of the largest U.S. cardiovascular studies -- the ARIC (Atherosclerosis Risk in Communities) and the CHS (Cardiovascular Health Study) -- containing records for more than 18,000 participants. After taking into account common risk factors for coronary heart disease and the competing risk of sudden cardiac death with coronary heart disease, they found that:

Black race/ethnicity (compared to non-black) was predictive of high sudden cardiac death risk, but less risk of coronary heart disease.Hypertension and increased heart rate were stronger predictors of high risk of sudden cardiac death compared to coronary heart disease.Extreme high or low body mass index was predictive of increased risk of sudden cardiac death but not of coronary heart disease.Additional, more technical traits that a doctor evaluating an ECG report could use to evaluate risk of sudden cardiac death in their patients. (Prolongation of QTc and abnormally inverted T wave were stronger predictors of high risk of sudden cardiac death. On the other hand, elevated electrocardiographic ST height in V2 was not predictive of sudden cardiac death but predictive of coronary heart disease.)

If the results are validated and confirmed in other studies, Soliman predicts that doctors will have a way to identify patients who are at greater risk of dying suddenly if they experience a heart attack and, therefore, a group of patients for whom early intervention, including risk factor modification, may be a life-saving option.

"Our next step in this path of research is to see if we can come up with a risk stratification score that can be applied to the general population, as well as to look at interventions that reverse the effect that these traits are having on susceptibility to sudden cardiac death," Soliman said. "We need to know if lowering hypertension, BMI or resting heart rate would reduce the risk of dying suddenly."

The study was funded by the Donald W. Reynolds Cardiovascular Clinical Research Center at the Johns Hopkins University School of Medicine. The ARIC and CHS studies are supported by the National Heart, Lung, and Blood Institute.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Wake Forest Baptist Medical Center, via EurekAlert!, a service of AAAS.

Journal Reference:

E. Z. Soliman, R. J. Prineas, L. D. Case, G. Russell, W. Rosamond, T. Rea, N. Sotoodehnia, W. S. Post, D. Siscovick, B. M. Psaty, G. L. Burke. Electrocardiographic and clinical predictors separating atherosclerotic sudden cardiac death from incident coronary heart disease. Heart, 2011; DOI: 10.1136/hrt.2010.215871

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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Epigenetic 'memory' key to nature versus nurture

ScienceDaily (July 25, 2011) — Researchers at the John Innes Centre have made a discovery, reported this evening (24 July) in Nature, that explains how an organism can create a biological memory of some variable condition, such as quality of nutrition or temperature. The discovery explains the mechanism of this memory -- a sort of biological switch -- and how it can also be inherited by offspring.

The work was led by Professor Martin Howard and Professor Caroline Dean at the John Innes Centre.

Professor Dean said "There are quite a few examples that we now know of where the activity of genes can be affected in the long term by environmental factors. And in some cases the environment of an individual can actually affect the biology or physiology of their offspring but there is no change to the genome sequence."

For example, some studies have shown that in families where there was a severe food shortage in the grandparents' generation, the children and grandchildren have a greater risk of cardiovascular disease and diabetes, which could be explained by epigenetic memory. But until now there hasn't been a clear mechanism to explain how individuals could develop a "memory" of a variable factor, such as nutrition.

The team used the example of how plants "remember" the length of the cold winter period in order to exquisitely time flowering so that pollination, development, seed dispersal and germination can all happen at the appropriate time.

Professor Howard said "We already knew quite a lot about the genes involved in flowering and it was clear that something goes on in winter that affects the timing of flowering, according to the length of the cold period."

Using a combination of mathematical modelling and experimental analysis the team has uncovered the system by which a key gene called FLC is either completely off or completely on in any one cell and also later in its progeny. They found that the longer the cold period, the higher the proportion of cells that have FLC stably flipped to the off position. This delays flowering and is down to a phenomenon known as epigenetic memory.

Epigenetic memory comes in various guises, but one important form involves histones -- the proteins around which DNA is wrapped. Particular chemical modifications can be attached to histones and these modifications can then affect the expression of nearby genes, turning them on or off. These modifications can be inherited by daughter cells, when the cells divide, and if they occur in the cells that form gametes (e.g. sperm in mammals or pollen in plants) then they can also pass on to offspring.

Together with Dr Andrew Angel (also at the John Innes Centre), Professor Howard produced a mathematical model of the FLC system. The model predicted that inside each individual cell, the FLC gene should be either completely activated or completely silenced, with the fraction of cells switching to the silenced state increasing with longer periods of cold.

To provide experimental evidence to back up the model, Dr Jie Song in Prof. Dean's group used a technique where any cell that had the FLC gene switched on, showed up blue under a microscope. From her observations, it was clear that cells were either completely switched or not switched at all, in agreement with the theory.

Dr Song also showed that the histone proteins near the FLC gene were modified during the cold period, in such a way that would account for the switching off of the gene.

Funding for the project came from BBSRC, the European Research Council, and The Royal Society.

Professor Douglas Kell, Chief Executive, BBSRC said "This work not only gives us insight into a phenomenon that is crucial for future food security -- the timing of flowering according to climate variation -- but it uncovers an important mechanism that is at play right across biology. This is a great example of where the research that BBSRC funds can provide not only a focus on real life problems, but also a grounding in the fundamental tenets of biology that will underpin the future of the field. It also demonstrates the value of multidisciplinary working at the interface between biology, physics and mathematics."

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Biotechnology and Biological Sciences Research Council, via EurekAlert!, a service of AAAS.

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here