Risk of heart attack may be increased in periods of high car pollution
Increases in air pollutants found to be linked to increased numbers of myocardial infarctions for up to 6 h
Research published online in the British Medicine Journal has reported that transient increases in the amount of air pollution in an area can increase the numbers of myocardial infarctions (MIs) for as long as 6 h. As the effect was only true for 72 h following an increase in pollution, the London-based researchers have concluded that pollutant molecules may simply increase the chance of an attack, however they went on to agree with calls for air pollution to be reduced for health protection.
Although it is known that air pollution is bad for your overall cardiovascular health, the study from the London School of Hygiene and Tropical Medicine, UK, is the first study to analyze how transient changes in the levels of air pollutants can be linked to specific increases in MIs in a population. Comparing the levels of common pollutants such as ozone, CO2 and NO2 from the National Air Quality Archive to the time of MI from the Myocardial Ischemia National Audit Project (MINAP), the researchers were able to assess the link between the two on an hourly basis.
The risk of MI was found to be increased per 10 µg/m3 rise in pollutants particles and NO2 – markers of traffic-related pollution – for a very short time frame (1–6 h). This was followed by a later reduction in risk levels after 72 h, indicating to the researchers that the pollution may hasten the incidence of MIs, not directly cause an attack.
The mechanisms that are thought to cause this temporary rise in MI incidence are currently unknown, however it is known that pollutants can thicken the blood, making it more likely to clot and cause cardiovascular events.
As it seems that high pollution only brought forward an attack, the authors, led by Krishnan Bhaskaran (London School of Hygiene and Tropical Medicine, UK), saw only “limited potential” in using the link to reduce the number of MIs. However, when speaking to Future Cardiology, Bhaskaran went on to recommend that “The elderly and those with existing cardiovascular or respiratory problems might be well advised to avoid prolonged exposure to congested roads when pollution levels are high, and also to avoid vigorous exercise at such times.” He also encouraged the need to “set and enforce ambitious targets” to reduce the amount of pollution people come into contact with.
The need for future research into what drives the link was also mentioned by Bhaskaran. “We also need more experimental evidence to clarify the biological mechanisms through which pollution affects cardiovascular health.”
Sources: Bhaskaran K, Hajat S, Armstrong B et al. The effects of hourly differences in air pollution on the risk of myocardial infarction: case crossover analysis of the MINAP database. BMJ 2343, d5531 (2011); Eurek Alert Press Release: www.eurekalert.org/pub_releases/2011–09/bmj-hpl091911.php
Research team engineer human cardiac cells that can be paced using light
A research team from Stanford University (CA, USA) has recently described the engineering of human cardiac cells that can be paced with light using optogenetics, the combining of genetic and optical techniques to control living cells. The team were able to produce cardiac cells that contracted when stimulated with blue light. The Stanford team are optimistic that in the long term this research could lead to new light-based pacemakers and the introduction of patches of tissue that are genetically matched to a patient and can be used to replace cardiac muscle damaged by a heart attack.
In their article, published in Biophysical Journal, the researchers describe how they induced optogenetic control in cardiac cells experimentally by expressing the protein channelrhodopsin-2 (ChR2), a light-gated cation channel, in human embryonic stem cells that were then differentiated into cardiomyocytes; the cardiac cells were subsequently photostimulated, which resulted in ChR2 opening and allowing sodium ions to enter the cardiac cells; this resulted in the generation of an action potential. Following these experimental results, the team used a computational model to investigate the potential effects of introducing the photostimulated cells into different locations in a human heart. The computational modeling has allowed the researchers to examine and predict the activation sequences that would occur in a human heart caused by different light-activated pacing sites.
The research team are hopeful that the results generated in the study will be useful in developing new pacemakers that are free from some of the problems that can occur with existing pacemakers. In their article, the team highlight the potential advantage of light-based pacing over conventional direct electrical stimulation, “Unlike pacing leads for electrical stimulation, which are known to have a high failure rate due to mechanical fatigue, the light source for optical stimulation does not have to sit directly on the continuously moving heart muscle. Light pacing might therefore be an attractive remote, less invasive and more durable alternative to current electrical pacing leads”. Christopher Zarins, professor emeritus of surgery and one of the study‘s authors, elaborated, “Instead of surgically implanting a device that has electrodes poking into the heart, we would inject these engineered light-sensitive cells into the faulty heart and pace them remotely with light, possibly even from outside of the heart”.
The study also brings immediate benefits for researchers studying the heart; Oscar Abilez, the lead author of the paper, commented, “Heart researchers are often seeking to measure electric response in the heart … but it takes quite a lot of electricity to stimulate the heart and the resulting electrical signal is relatively weak. This makes it hard to distinguish stimulus from response. It‘s like trying to hear a whisper in a crowded room”. The use of light-activated cardiac tissue could potentially remove this problem.
It is also hoped that eventually, if successfully implemented in the heart, the techniques could provide significant benefits for a wide range of therapeutic areas; in their article the researchers conclude, “We believe that this concept will be widely applicable to systematically manipulate electrically active cells and, ultimately, support the design of novel therapies for various types of neuronal, musculoskeletal, pancreatic and cardiac disorders such as depression, schizophrenia, cerebral palsy, paralysis, diabetes, pain syndromes and cardiac arrhythmias”.
Source: Abilez OJ, Wong J, Prakash R, Deisseroth K, Zarins CK, Kuhl E. Multiscale computational models for optogenetic control of cardiac function. Biophysical J. 101, 1326–1334 (2011).
Phase III trial shows apixaban significantly reduces the risk of stroke or systemic embolism compared with warfarin
Results of a Phase III clinical trial has demonstrated apixaban to be superior to warfarin in reducing stroke or systemic embolism risk in patients with atrial fibrillation. The trial, known as ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation), included a total of 18,201 patients with atrial fibrillation and at least one risk factor for stroke with the aim of comparing apixaban to warfarin for the prevention of systemic embolism or stroke. The results of the study, recently published in the New England Journal of Medicine, demonstrated that apixaban reduced mortality by 11%, reduced major bleeding risk by 31% and reduced stoke or systemic embolism risk by 21%. Adverse events were shown to be similar for those taking apixaban (81.5%) and warfarin (83.1%). In addition, the rate of serious adverse events (35 and 36.5%, respectively) were also similar. However, discontinuation of the drug during the study was lower among those taking apixaban (25.3%, and 3.6% due to death) compared with warfarin (27.5%, and 3.8% due to death).
“The risk for stroke in patients with atrial fibrillation is a major public health concern in an aging population. We are therefore encouraged by the outcome of the ARISTOTLE trial, which showed that apixaban, as compared with warfarin, significantly reduced the risk of stroke or systemic embolism, major bleeding and mortality” concluded the lead investigator of the study, Christopher B Granger, Duke University Medical Center, NC, USA.
Source: Granger CB, Alexander JH, McMurray JJ et al. Apixaban versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 365(11), 981–992 (2011).
High residual platelet reactivity may be associated with increased risk of ischemic events following percutaneous coronary intervention
A large observational cohort study has found that high residual platelet reactivity (HRPR) following a loading dose of the antiplatelet agent clopidogrel may be associated with a high risk of ischemic cardiovascular events following percutaneous coronary intervention (PCI). The findings, published in the Journal of the American Medical Association, suggest that HPRP may become an important consideration in developing future antiplatelet therapy.
Dilating the coronary arteries with PCI is an established treatment in the treatment of acute coronary syndromes such as a myocardial infarction (MI) and unstable angina. Residual platelet reactivity following antithrombotic medical intervention has been associated with the occurrence of cardiovascular side effects in this patient group, however the critical details required to make it predictive of CV events has not been elucidated.
Using the ADP test for platelet aggregation, the authors of the Italian-based study found that HRPR (≥70% aggregation) following a 600-mg loading dose of clopidogrel was significantly associated with increased risk of an ischemic event, such as cardiac death, MI and stroke, at 2-year follow-up (14.6% in HRPR patients vs 8.7% in those with low platelet reactivity). Among the 1789 patients investigated, stent thrombosis was also found to be twofold higher in the HRPR group than the low reactivity group.
Although the results suggest that HRPR would be an attractive target in the hunt for prognostic markers, the authors were cautious, recommending that the results only be used as “hypothesis generating for future studies of tailored therapy using new antithrombotic agents”.
Sources: Parodi G, Marcucci R, Valenti R et al. High residual platelet reactivity after clopidogrel loading and long-term cardiovascular events among patients with acute coronary syndromes undergoing PCI. JAMA 306(11), 1215–1223 (2011); Eurek Alert Press release: www.eurekalert.org/pub_releases/2011–09/jaaj-sep091511.php; Trial Registration: www.clinicaltrials.govIdentifier:NCT01231035