Parental history: a stronger predictor of myocardial infarction than genetic and INTERHEART risk factors
An analysis of 12,000 subjects from the global INTERHEART study has demonstrated that individuals who have a parent or both parents who have experienced myocardial infarction (MI), is a strong predictor of future MI, independent of behavioral, biological, psychosocial and genetic factors. This association with parental history continues across socioeconomic, age and gender groups and even persists across world regions.
The INTERHEART study raised attention, owing to the report that 90% of the global risk for acute MI could be predicted by the presence of nine traditional and modifiable risk factors. This latest research by Clara Chow and colleagues from George Institute for Global Health (Sydney, Australia) not only demonstrated that parental history of MI was higher among INTERHEART participants who went on to experience a MI than control participants, it was only slightly attenuated when behavioral, biological and psychosocial factors were taken into account. This association persisted after adjustments were made for sex, age and region, independent of whether the mother or father experience MI and socioeconomic factors.
Chow explained that “Having one parent with a history of MI nearly doubles your risk of future MI even after accounting for a list of other established risk factors and some genetic risk factors. In addition, the risk more than doubles if two parents are affected or the history of MI is premature”.
Chow continued “A number of researchers have raised questions regarding the validity of self-reported health history and a concern that in certain population groups self-reported health history is less reliable. This study puts to rest these concerns”.
In a subset analysis of INTERHEART subjects, MI risk was investigated in accordance with genetic data. After adjustment for genotype score, the odds ratio associated with a parental history of MI remained. The genotype score was higher amongst MI subjects than those who did not experience MI and it was not any higher in those with a parental history of MI than those who did not. Chow explained “This indicates that measurement of current genetic variants does not add much above clinical risk factors to patient assessment at this stage. In addition, this also indicates to me that we don‘t really know what family history is a marker of. It probably is a marker of multiple exposures that include, but are not limited to genetics that cluster in families – for example, common early life exposures or environmental factors”.
Dr Rongling Li from the National Human Genome Research institute (Berthesda, MD, USA), commented on the study and confirmed that “Parental history of MI accounts for a significant portion of disease risk that is due to family aggregation of unknown genetic, cultural and environmental factors. Thus, it is important to include parental history of MI in clinical practice guidelines and clinical decision-support systems to help clinicians to identify high-risk patients for early diagnosis and treatment”.
Li noted that the study genotyped 1536 SNPs from 103 genes that have been linked to MI and selected the top 20 most significant SNPs from univariable analyses, finally selecting nine SNPs that remained significant in logistic regression models. Li added that “The relatively small sample size of this genetic subanalysis may have precluded the discovery of already-genotyped SNPs that may have a weak association with MI or of relevant gene–gene and gene–environment interactions”.
In the future, Chow would like to see that individuals with a family history of MI should undergo a cardiovascular risk assessment and concluded that “The presence of a family history should trigger clinicians to think about other tests for these individuals, for example, a computed tomography calcium score, as traditional risk calculators underestimate the risk in this group. In low-income countries, family history is a very simple-to-measure risk factor and should be considered for inclusion in ‘low-information‘ tools advocated by the WHO and other groups for risk assessment in these regions. While you may not be able to change your family history, certainly there are a lot of other things that you can modify to lower your risk”.
Sources: Chow CK, Islam S, Bautista L et al.: Parental history and myocardial infarction risk across the world: the INTERHEART study. J. Am. Coll. Cardiol. 57, 619–627 (2011); www.theheart.org/article/1176241.do
hERG channel study unlocks clues to heartbeat control and sudden cardiac death
A recent study by researchers at the Victor Chang Research Institute (Sydney, Australia), have come a step closer to understanding how the rhythm of the heartbeat is controlled and the reason why some common drugs can cause an abnormal and potentially fatal heart rhythm. It is currently estimated that 40–50% of drugs in development will block one of the main channels in the heart important for the conduction of electrical impulses, causing arrhythmia and potentially sudden cardiac death.
The researchers, led by Jamie Vandenburg, studied the hERG potassium channel, which plays a key role in determining the length of each heartbeat and is a channel most likely to be blocked by the action of drugs. Vandenburg explained “Our body has a series of channels that carry ions, into and out of cells, to trigger a heartbeat. Depending on the position of these ‘gates‘, many common drugs bind or attach themselves to these channels, blocking the ions from passing through, causing Long QT syndrome, where the length of the heartbeat is longer than usual, which greatly increases the risk of arrhythmia”.
Antipsychotic drugs are most commonly associated with this side effect and patients prescribed these drugs are three-times more likely to die of sudden cardiac death owing to an abnormal heart rhythm. Most drugs will bind to the hERG channel when it is closed and it was the aim of this study to determine how these channels operate, in the hope that in the future drugs can be designed more effectively to minimize the unwanted side effects.
Vandenburg added that “The gates to this channel operate in a much more complex way than was previously thought. They require a series of complicated, interrelated movements to open them. It is not simply a matter of lifting and shutting a lid as was commonly believed”.
Vandenburg concluded “The biggest benefit of this research is that it should allow the better design of drugs, so they no longer block these important electrical channels in the heart. In time, this should allow patients the freedom and peace of mind to take their medication without the fear of their heart suddenly stopping”.
Sources: Wang DT, Hill AP, Mann SA, Tan PS, Vandenberg JI: Mapping the sequence of conformational changes underlying selectivity filter gating in the Kv11.1 potassium channel. Nat. Struct. Mol. Biol. 18(1), 35 (2010); www.sciencedaily.com/releases/2011/01/110128095049.htm
US FDA concludes the benefits of stenting outweigh the risks among standard-risk surgical patients
The US FDA Circulatory System Devices Panel has voted in favor of expanding the indication for the RX Acculink™ Carotid Stent System (Abbott, Abbott Park, IL, USA), concluding that the benefits of carotid stenting in patients at standard risk for adverse events from endarterectomy outweigh the risks.
The RX Acculink Stent is approved for use in patients requiring carotid revascularization who are at high risk for adverse events from carotid endarterectomy. These patients must meet a certain criteria, which includes having a reference vessel diameter ranging from 4.0–9.0 mm at the target lesion and be symptomatic with a stenosis of the internal or carotid artery of 50% or more. The stent has also been approved for use in high-risk patients without neurological symptoms, but who have a stenosis of the common or internal carotid artery of 80% or greater.
Carotid stenting would be an option in standard-risk patients with neurological symptoms and 70% or stenosis of the common or internal carotid artery by ultrasound or 50% or more stenosis based on this new indication. Stenting would also be an option in patients without neurological symptoms who have 70% or more stenosis of the common or internal carotid artery by ultrasound or 60% or more stenosis measured by angiogram; however, the patient must meet the same criteria for reference vessel diameter.
Richard Page (University of Wisconsin, WI, USA) a panel member commented “I was satisfied that it met the safety threshold. I felt the sponsor succeeded in completing a tough trial and demonstrated efficacy. With a balance of safety and efficacy I wanted to vote in the affirmative. I have to say that I think the panel got it right, because if this were 100% in favor I don‘t think that would reflect my own angst about this. I think follow-up is important and the training is critically important. This is a high-risk procedure, but I feel like we‘re in the right place”.
The advisory panel heard presentations from Abbott Vascular and the FDA, both of whom analyzed the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) for the premarket approval application, a noninferiority per-protocol analysis of 2307 symptomatic and asymptomatic patients at standard risk for carotid endarterectomy. The per-protocol analysis demonstrated that both treatments were equivalent in the combined primary end point but the rates of stroke were higher among patients treated with stenting, while rates of MI were higher among those who underwent surgery. Data from CREST demonstrated that minor stroke drove the increased stroke rate and that stroke was not associated with a long-term increased risk of death, whereas MI was associated with an increased risk of mortality. Panel members were concerned about the increased risks, particularly for a therapy designed to reduce the long-term risk of stroke, but agreed approval on the benefit of treatment and it was noted that stroke rates markedly declined after 2005 in CREST, the second half of the 10-year trial, evidence that the risk will decrease with operator experience.
Christopher White from the Ochsner Medical Center (LA, USA), said that the stroke rate is concerning but pointed out that these minor strokes did not result in debilitation. “The surgeons tend to minimize the MI-issue, but it‘s been proven that vascular-surgery patients who have enzyme leaks after surgery have an increased risk of mortality over a 5-year period. It‘s pretty well documented that a perioperative MI has a mortality consequence. That‘s not true for minor stroke”. However, White stressed that this is not a choice between two adverse events and physicians are looking to avoid both consequences.
Study indicates the use of heart stem cells for rebuilding a child‘s heart
A study led by Sunjay Kaushal, from the Division of Cardiovascular Thoracic Surgery at Children‘s Memorial Hospital and the Northwestern University Feinberg School of Medicine (Chicago, IL, USA) has demonstrated that heart stem cells from children with congenital heart disease were able to rebuild the damaged heart in the laboratory.
Commenting on the study, Kaushal said “Due to the advances in surgical and medical therapies, many children born with cardiomyopathy or other congenital heart defects are living longer but may eventually succumb to heart failure. This project has generated important preclinical laboratory data showing that we may be able to use the patient‘s own heart stem cells to rebuild their hearts, allowing these children to potentially live longer and have more productive lives”.
In the study, cells were obtained from patients aged from a few days after birth to 13 years who were undergoing routine congenital cardiac surgery. The findings demonstrate that the number of heart stem cells was greatest in neonates and rapidly decreased with age. The highest numbers of stem cells were found to be located in the right atrium. In addition, the study demonstrated that the cardiac stem cells are functional and have the potential for use in repairing the damaged heart, it is also the first and largest systematic study to focus on children.
Kaushel added “Heart disease in children is different to heart disease in adults. Whereas adults might suffer heart failure from coronary artery disease or atherosclerosis, heart failure in children primarily occurs because they acquire cardiomyopathy or have a congenital condition in which the heart chambers are small or in the wrong position causing the heart to pump inefficiently. The potential of cardiac stem cell therapy for children is truly exciting”.
A clinical trial is pending FDA approval, and if successful could start as early as this autumn.
Source: www.sciencedaily.com/releases/2011/01/110127141755.htm
Review questions the prescription of statins in patients at low risk of cardiovascular disease
Cardiovascular disease (CVD) is the most common cause of death wordwide, and statins are the first-line treatment for heart failure patients owing to the well established benefits of this treatment. However, the evidence supporting the use of statins in patients with no previous history of CVD to prevent heart problems is limited. Low cholesterol has been demonstrated to increase the risk of death from other causes, so it is conceivable that statin prescription may do more harm than good.
Researchers from the Cochrane Heart Group at the London School of Hygiene and Tropical Medicine, (London, UK) led by Fiona Taylor reviewed data from 14 trials involving 34,272 patients. Patient outcome was compared between those prescribed statins and placebos or usual care. Data combined from eight trials involving 28,161 patients that provided data on death from all causes, demonstrated that statins reduced the risk of dying from nine to eight deaths for every 100 people treated with statins each year. In addition, statins reduced both fatal and nonfatal events such as heart attack and stroke.
However, researchers exercised caution and believe that the results are limited by unclear, selective and potentially biased reporting and consideration should be given to patient‘s risk profiles before prescribing statins.
Taylor explained “It is not as simple as just extrapolating the effects from studies in people who have a history of heart disease. This review highlights important shortcomings in our knowledge about the effects of statins in people who have no previous history of CVD. The decision to prescribe statins in this group should not be taken lightly”.
In response to the fact that most trials were industry-sponsored Taylor said “We know that industry-sponsored, trials are more likely to report favorable results for drugs versus placebos, so we have to be cautious about interpreting these results. The numbers eligible for treatment with statins are potentially great, so there might be motivations, for instance, to stop trials earlier if interim results support their use”.
Source: www.sciencedaily.com/releases/2011/01/110118200808.htm