Bhaskaran and colleagues analysed data on 84,010 patients admitted to hospital with a heart attack between 2003 and 2006 and compared this with daily temperatures in England and Wales. The results were adjusted to take into account factors such as air pollution, influenza activity, seasonality and long term trends. 

He found that a 1°C reduction in average daily temperature was associated with a cumulative 2% increase in risk of heart attack for 28 days. The highest risk was within two weeks of exposure. The heightened risk may seem small but in the UK there are an estimated 146,000 heart attacks every year, so even a small increase in risk translates to around 200 extra heart attacks for each 1°C reduction in temperature on a single day.

“Older people between the ages of 75 and 84 and those with previous coronary heart disease seemed to be more vulnerable to the effects of temperature reductions,” comments Krishnan Bhaskaran, “while people who had been taking aspirin long-term were less vulnerable.” He continues, “We found no increased risk of heart attacks during higher temperatures, possibly because the temperature in the UK is rarely very high in global terms. Our results suggest that even in the summer, the risk is increased by temperature reductions.” In conclusion, he says “our study shows a convincing short term increase in the risk of myocardial infarction (heart attacks) associated with lower ambient temperature, predominantly in the two weeks after exposure.” 

He says that further studies need to be conducted to see what measures could be used to avoid the increased risk, such as advising patients, particularly the elderly, to wear suitable clothing and to heat their homes sufficiently.

The stamps feature six areas of medical specialism including cardiovascular medicine, drug therapy, transplant surgery, ophthalmology, medical imaging and parasitology.

From Sir Ronald Ross’s 1897 evidence that mosquitoes carry malaria, which features on the 88p stamp, to Sir Godfrey Hounsfield’s 1971 invention of the computed tomography scanner – which appears on the 97p stamp, Medical Breakthroughs marks the huge contribution UK scientists have made to the health of people worldwide. Two of these achievements are particularly relevant to Arrhythmia Watch.

1^st Class stamp – commemorating Heart-regulating beta-blockers synthesised by Sir James Black, 1962

Beta blockers are widely used in the treatment of cardiac arrhythmias. Propranolol was the first clinically useful beta adrenergic receptor antagonist. Introduced by Sir James W. Black, (who died in March 2010) it revolutionised the medical management of angina pectoris and is considered to be one of the most important contributions to clinical medicine and pharmacology of the 20th century.

97p stamp commemorating – CT scanner invented by Sir Godfrey Hounsfield, 1971

While on an outing in the country, Hounsfield came up with the idea that one could determine what was inside a box by taking X-ray readings at all angles around the object. Hounsfield built a prototype head scanner and tested it first on a preserved human brain, then on a fresh cow brain from a butcher shop, and later on himself.

In September 1971, CT scanning was introduced into medical practice with a successful scan on a cerebral cyst patient at Atkinson Morley Hospital in Wimbledon, London

Philip Parker, Head of Stamp Strategy for Royal Mail, said: “Since William Harvey first described the circulation of the blood in 1628, British physicians and scientists can rightly take credit for the discovery and application of a tremendous number of medical breakthroughs from beta-blockers to hip replacement surgery.

“This striking set of stamps highlights six excellent examples of how science – and scientists – have risen to the challenges of mass health care, and in doing so transformed the lives of people around the globe.”

Daughters (XX) do not inherit the Y chromosome and therefore should not share the phenotype of CSS fathers. However results from this study found that although daughters were genetically identical to females from the host strain, their phenotype is attributed to this transgenerational genetic effect. In this first test for the generality of heritable epigenetic changes, the authors found that the frequency and strength of phenotypic effects resulting from transgenerational and conventional inheritance were comparable in frequency and strength, suggesting that this unconventional mode of inheritance rivals conventional genetics in its impact on biological variation and disease risk.

‘‘We found striking evidence for frequent and strong phenotypic changes in daughters that are attributable in a transgenerational genetic manner to the parental Y chromosome’’

In addition to phenotype screening, a carefully designed behavioural test strongly suggested that transgenerational rather than social and environmental factors lead to altered behaviour in the daughters from CSS males.

‘‘These results are especially surprising given the relatively small number of genes on the Y chromosome’’ Nadeau and his team found themselves asking ‘‘Do other chromosomes lead to transgenerational effects? Do transgenerational effects occur in humans? What is the molecular basis for these effects?’’

If genetic variants act across generations, then traits have a genetic basis, however this study found that certain ‘disease genes’ can occur in previous generations and not necessarily in the affected individuals. Undeniably these transgenerational effects depend on the interaction between the background and epigenetic factors relating to the Y chromosome. Nadeau and his colleagues state these transgenerational genetic effects contribute to ‘missing heritability’ which could persist for generations and that these epigenetic effects can most probably be applied to humans. Thus the attributes of an individual today could depend as much on ancestral parental genetics as on the genetic variants that they inherited.

The next major step in the study of transgenerational effects is to unfold the sequence of molecular events that initiate these epigenetic changes which occur in one generation yet subsequently lead to phenotypic changes is following generations.

The full article is available at http://www.futuremedicine.com/toc/epi/2/4

Notes

About Epigenomics

Epigenomics promises to elucidate the inner workings of the genome. The power of this new discipline lies in its promise to provide us with novel insights into the inner workings of our genomes through its potential to detect quantitative changes, multiple modifications and the regulatory sequences outside that of our gene sequences. The advent of numerous epigenomics strategies has emerged to detect large numbers of DNA methylation variations and chromatin modifications – two mechanisms that are at the core of epigenomic research.

With the creation of the Human Epigenome Project, many research groups have joined forces to further elucidate and exploit new technologies to better understand the basis of normal development and human disease.

Epigenomics provides the forum to address the rapidly progressing research developments in this ever-expanding field; to report on the major challenges ahead and critical advances that are propelling the science forward. The journal delivers this information in concise, at-a-glance article formats – invaluable to a time constrained community.

Substantial developments in our current knowledge and understanding of genomics and epigenetics are constantly being made, yet this field is still in its infancy. Epigenomics provides a critical overview of the latest and most significant advances as they unfold and explores their potential application in the clinical setting.

The results show that if a normal, healthy individual has their level of low density lipoprotein (LDL), substantially lowered with a potent statin, then the level of HDL in that person no longer bears any relation to the remaining cardiovascular risk.

The original JUPITER trial (2) was designed to answer the critical question of whether rosuvastatin prevents cardiovascular disease among healthy people with normal LDL cholesterol (LDL-C) levels, but increased levels of high-sensitivity C-reactive protein, a marker of chronic low level inflammation, considered a new risk factor for cardiovascular events.

The current Lancet study showed that when 17,802 subjects were divided into quartiles of HDL cholesterol concentrations (HDL-C) , HDL cholesterol concentrations were inversely related to vascular risk at the end of study for individuals randomised to placebo, with the top quartile having a 46% reduced risk compared to the bottom quartile (p=0.0039).

In contrast, however, among those subjects given active treatment with rosuvastatin, vascular risk was calculated to be similar for subjects in both the top and bottom HDL quartiles (p=0.82)

 “Although measurement of HDL–cholesterol concentration is useful as part of initial cardiovascular risk assessment, HDL-cholesterol concentrations are not predictive of residual vascular risk among patients treated with potent statin therapy who attain very low concentrations of LDL cholesterol,” the authors of the study conclude. 

ESC spokesperson Professor Dan Atar, from Oslo University Hospital, Norway, believes there are dangers in interpreting the study as showing that raising HDL levels produces no beneficial cardiovascular effects.

“It’s a matter of statistics.  If you’re looking at populations with a very low incidence of cardiovascular events, and then with an intervention of any kind you reduce the risk of events even further, it’s logical that you’ll washout the influence of any other effect. These patients already have achieved such low levels of LDL that no other marker will prevail as a predictor of the few remaining events.”

He added that he had concerns that readers of the paper might not appreciate that more data was needed before the scientific community could make a qualified decision about whether raising HDL levels was beneficial or not. “With subgroup analyses, such as the one presented here, you just can’t make such judgements,” he said.

In fact, previous studies, such as the Helsinki Heart Study (3) and the VA-HIT Study (4), have been successful in raising HDL and reducing cardiovascular events, using gemfibrozil, however this agent also concomitantly lowers LDL.

Additionally, the drug nicacin has been shown to be effective at elevating HDL and reducing cardiovascular morbidity in the Coronary Drug Project Study (5), but this strategy could not easily be implemented into clinical practice due to unpleasant side effects, notably flushing.  It is hoped that laropiprant, a novel flushing pathway inhibitor, will overcome this limitation.

A clearer indication of the benefit of raising HDL, Atar added, will come from the ongoing phase III Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), which has enrolled 25,000 patients to investigate whether the combination of niacin/laropiprant can further reduce the risk for myocardial infarction, stroke and the need for revascularisation in patients already treated to lower LDL.

References:

1. Ridker PM, Genest J, Boekholdt SM et al. HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial.  Lancet. Published online July 22, 2010.

2. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359: 2195-207.

3. Frick MH, Elo O, Haapa K, et al.  Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987; 317:1237-45.

4. Robins SJ, Collins D, Wittes JT, et al. VA-HIT Study Group. Veterans Affairs High-Density Lipoprotein Intervention Trial. Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA. 2001;285:1585-91.

5. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W.: Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Col Cardiol. 1986 6:1245-55.

“This study shows that as a country, we do a good job in treating patients with heart attack,” said John S. Rumsfeld, M.D., Ph.D., chief science officer and chair of the NCDR and acting national director of cardiology for the Veterans Affairs Health Administration. “More patients with heart attacks qualify for urgent angioplasty and stenting, and they are getting it quicker. There have also been improvements in giving recommended medications to heart attack patients—many of which reduce the risk of death and long-term complications.”

Equally impressive are the results for coronary angioplasty and stenting. These procedures, which fall under the umbrella term percutaneous coronary intervention (PCI), involve threading a slender tube into the arteries of the heart, expanding a tiny balloon to widen the artery and, usually, leaving an expandable metal stent in place to hold the artery open.

“We’re seeing lower complication rates with PCI, despite greater complexity in both the types of patients and the lesions,” said Matthew T. Roe, M.D., M.H.S., associate professor of medicine at Duke University Medical Center and the Duke Clinical Research Institute, Durham, NC. “In fact, the very nature of PCI is changing, with new medications and new stents used during procedures.”

For the study, researchers drew from two large NCDR registry programs. To characterize recent trends in treatment and outcomes of heart attack, they analyzed data from the ACTION Registry^®–GWTG™. The NCDR ACTION Registry-GWTG is a partnership between the ACC and the American Heart Association and includes data on the hospital care of patients with two types of heart attack known as STEMI and NSTEMI. The resulting study group consisted of all 131,980 patients treated for a heart attack at approximately 250 participating hospitals from January 2007 through June 2009.

The data analysis showed significant improvements in several key aspects of heart attack care, including:

• Increase from 90.8 percent to 93.8 percent in the use of treatments to restore blood flow to the heart in patients with STEMI heart attacks.
• Increase from 64.5 percent to 88 percent in the number of patients with STEMI heart attacks treated with PCI within 90 minutes of arriving at the hospital—a key quality benchmark.
• Improvement from 89.6 percent to 92.3 percent in overall performance scores that measure timeliness and appropriateness of therapy for STEMI heart attacks.
• Improvement in achieving correct dosing of several types of “blood thinners” among NSTEMI patients.
• Reduction from 6.2 percent to 5.5 percent in risk-adjusted hospital death rates among STEMI patients and from 4.3 percent to 3.9 percent among NSTEMI patients.

Improvement in prescribing guidelines-recommended medications, including aspirin, clopidogrel, statins, beta blockers and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, as well as in counseling patients to stop smoking and referring patients to cardiac rehabilitation.

Patients are also taking important steps toward improving heart attack care by heeding the warning signs of heart attack, the data reveal. The time from the beginning of heart attack symptoms to the patient’s arrival at the hospital dropped significantly during the study period, from 1.7 hours to 1.5 hours, on average.

“Patients are coming to the hospital sooner,” Dr. Rumsfeld said. “That shows a greater awareness by the public that if you have unexplained chest pain or shortness of breath, you need to get to the hospital quickly. The sooner you get treatment for a heart attack, the better your chances of survival and the less likely you are to experience long-term complications like heart failure.”

To evaluate PCI trends, investigators analyzed data from the NCDR CathPCI Registry^® database, which contains hospital data on diagnostic cardiac catheterization and PCI. It is a partnership between the ACC and the Society for Cardiovascular Angiography and Interventions. The resulting PCI study group consisted of all 1,708,247 patients who had PCI from January 2005 through June 2009. During that time, participating hospitals grew from 436 to 959.

The data analysis revealed several notable trends, including:

Increase in procedural complexity, including treatment of significantly more patients with challenging “type C” lesions.

Reduction in complications related to bleeding or injury to the arteries used for passing tubes to the heart.

Changes in the use of medications designed to prevent unwanted blood clots, reflecting the results of recent clinical trials and recommendations from new clinical practice guidelines.

Reduction in the overall use of drug-eluting stents, partially balanced by increased use of new types of drug-eluting stents.

In addition to its encouraging findings, the analysis also highlights specific areas in need of improvement and identifies targets for future research, particularly those aimed at reducing the bleeding risk associated with even the best therapies.

Moreover, the analysis highlights the value of clinical registries themselves and the unique information they provide. Insurance databases document how many patients had a particular diagnosis or procedure, while randomized clinical trials test therapies under tightly controlled circumstances and in narrowly defined groups of patients. But the information from the NCDR documents the cardiovascular treatments average patients receive every day, and how those treatments affect their health. In short, it helps doctors give better cardiovascular care in daily practice.

“This is direct clinical data from doctors and hospitals themselves on which patients got which treatments and how they did,” Dr. Rumsfeld said. “If you want to actually understand the risk of a given patient and match the best treatment to their situation, you need real clinical data.”

The NCDR also helps hospitals and cardiologists to achieve the highest quality of care, by allowing them to compare their treatments and clinical outcomes against those of similar volume and size across the nation. Patients who understand the value of clinical registries can be advocates for improving healthcare quality in their communities.

“Educated consumers can stimulate improvements in their community,” Dr. Roe said. “If your hospital is not participating in the NCDR and other clinical registries, you should ask, ‘Why not? What are you doing to respond to and collect data that will allow you to take better care of your patients?’”

Notes

CDR is an initiative of the American College of Cardiology Foundation^®, with partnering support from the following organizations: CARE Registry—The Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, American Academy of Neurology, American Association of Neurological Surgeons/Congress of Neurological Surgeons, and Society for Vascular Medicine; CathPCI Registry—The Society for Cardiovascular Angiography and Interventions; ICD Registry—Heart Rhythm Society; IMPACT Registry—The Society for Cardiovascular Angiography and Interventions and American Academy of Pediatrics; IC³ Program—MedAxiom and Spirit of Women; ACTION Registry–GWTG— An initiative of the American College of Cardiology Foundation and the American Heart Association, with partnering support from Society of Chest Pain Centers.

This prospective, multi-center, randomized (2:1), controlled, two-arm clinical study will enroll up to 350 patients at up to 15 sites throughout Europe. Patients in this study will be followed for one year after ablation.

The study is intended to test the hypothesis that the NAVISTAR(R) THERMOCOOL(R) catheter using the CARTO(R) 3 System is superior to fluoroscopy-guided PVAC(R) for efficacy and safety and will demonstrate non-inferiority for efficiency comparing the NAVISTAR(R) THERMOCOOL(R) catheter used with the CARTO(R) 3 System to the PVAC(R) catheter. Interim results from the study will be disclosed after completion of the enrollment phase and the final results will be available at the end of the 1-year follow up period.

“The CLARITY-AF trial is the first multi-center randomized trial comparing atrial fibrillation ablation devices. This trial will compare the Medtronic PVAC(R) catheter to the Biosense Webster NAVISTAR(R) THERMOCOOL(R) catheter. Primary endpoints are freedom from any atrial fibrillation, atrial tachycardia, pulmonary vein stenosis and procedure time. Given the growing epidemic of atrial fibrillation, the results of this trial will guide optimal treatment in a large patient population” said Prof. Mattias Duytschaever from AZ St Jan Hospital in Bruges, Belgium, and principal investigator of the CLARITY-AF study.

CARTO(R) 3 is the third generation of the CARTO(R) electro-anatomical mapping system. The system is built on the core magnetic based CARTO(R) proprietary technology, with a special focus on increased performance, ease of use and Electrophysiology-lab efficiency.

Dr Ian Starke, RCP Medical Director for Revalidation, said that the detailed investigation and report would be crucial in improving the appraisal and revalidation processes and in meeting the concerns of UK doctors:

“In ensuring we covered every aspect of appraisal, we were able to collect and fully represent the views of the pilot appraisers and appraisees from many specialties, gathering vital information about the positive and negative aspects, and perceptions of the proposed system.  This means that the rumours and media speculation about the way in which the appraisal process may or may not work are now replaced with firm conclusions and recommendations.

The medical royal colleges, UK Programme Board,  Revalidation Support Team, GMC and BMA can now work together to implement those recommendations.  The findings of this study have already been shared with those developing the next series of revalidation pilot studies, and this process will continue. I am optimistic that the work carried out by the RCP will lead to improvements all round for any future pilots and the final roll-out of revalidation, and we will be able to use effectively the extra year before implementation suggested by the Secretary of State for Health, Andrew Lansley.”

Notes

The full report is available on the Revalidation Support Team website, the Executive Summary begins at page 6 of the pdf:

http://www.revalidationsupport.nhs.uk/files/RCPMerseyFinalReport17.06.10.pdf

The project was led by a Steering Group including representatives from those directly involved in revalidation and appraisal programmes and medical education, the Revalidation Support Team, GMC, BMA, and also included a patient representative.  The pilot project was managed by the Revalidation Programme Manager at the Royal College of Physicians in London. Most of the day-to-day on-site project management was carried out by a local Project Co-ordinator who was appointed in February 2009 and was based within the Liverpool Medical Institution (LMI). The Project Co-ordinator provided day-to-day project management, co-ordination of electronic linkage of appraiser/appraisee pairs, regular site visits to individual Trusts and participants, a general help-line in relation to the practicalities of the pilot process and administrative support for the Project Steering Group. The steering group met every two months throughout the project.

Nonetheless the task of putting into place measures that are genuinely useful to patients and clinicians should not be underestimated. It is essential that commissioning groups work collaboratively with specialists to develop integrated care pathways and that any shift in clinical priorities is carefully considered to ensure that the desired outcome is not overshadowed by unintended consequences.

Delivering public health should be the responsibility of all health professionals and the drive to address the wider determinants of health to enable positive behaviour change are encouraging.

The vision for the NHS outlined today offers a real opportunity for forging positive clinical engagement but this can only be fully achieved by ensuring that policy is underpinned by clear, practical and evidence-based systems” Sir Ian concluded.

He presented data during the 20^th European Meeting  on Hypertension, in Oslo, recently, from 2014 apparently healthy men aged 45-59 years who were included in the Oslo Ischemia Study, between 1972-75 and who were followed for 35 years. By this time some 272 men (14% of total) had a diagnosis of AF.

The adjusted risk of developing AF was increased by 63% for study participants with baseline BP>128 mmHg (p=0.0003) compared to participants with SBP <128 mmHg. This therefore represented a “strong, independent long-term predictor of AF” according to these investigators.

“Within the ESC we accept NICE as one of the main sources of reference for clinical decision making in cardiology,” says ESC spokesman Joep Perk, from Linnaeus University (Sweden). “Currently even if individuals try to eat healthy diets there are issues out of their control, such as the salt content in bread, that have an adverse effect on their cardiovascular health. This document details the legislative changes that could be introduced to protect them.”

The NICE guidance, which focuses mainly on food production and its influence on the nation’s diet, aims to change the cardiovascular risk factors faced by the UK population through regulation, legislation, subsidy and taxation or by rearranging the physical layout of communities. Previously the UK has focused on individual interventions, an approach which identifies and treats people at higher risk. Physical inactivity, smoking and excessive alcohol consumption are also covered to a lesser extent in the NICE document.

Simon Capewell, an ESC spokesperson from the University of Liverpool (UK), who is also Vice Chair of the NICE Guidance Development Group, says, “There was a feeling that dietary interventions have been largely neglected, yet have a big potential to deliver CVD benefits. The guidance shows how by introducing simple changes at the population level huge gains could be made in reducing the death toll from cardiovascular disease. This is no longer an optional discussion, but an issue that governments and the rest of society have to confront.”

The intention of the document, says Capewell, is to get the evidence for change firmly into the public arena “The idea is to kick start a debate, and persuade politicians to set both short term and long term goals for change,” he says.

Key evidence outlined in the NICE document includes:

Reducing mean salt intakes by 3 g per day for adults (to achieve a target of 6 g daily) would in the UK lead to around 14–20,000 fewer annual deaths from CVD each year. Reducing salt added during the manufacturing process is considered especially important since this is estimated to represent 70 to 90% of the population’s total salt intake.

Evidence suggests that reducing saturated fat intakes from 14% to 7 % of energy intake (to reach the levels seen in Japan) might prevent up to 30,000 CVD deaths annually.

If industrially-produced trans fats were banned (as successfully done in Denmark) would 4,500 and 7000 lives might be saved annually.

The guidance also considers the evidence for wider policy actions, such as extending restrictions on TV advertising for foods high in saturated fats, salt and sugar, making healthy food alternatives cheaper than junk food, establishing traffic light food labelling systems and giving local authorities powers to limit fast food outlets. The document places particular emphasis on the importance of taking action to prevent the elevation of CVD risk factors among children. “It’s well known that CVD commences in child-hood, making this aspect of the report of vital importance for future generations,” says Perk.

The NICE document indicates how introducing such changes would rapidly become self financing. Reducing population cardiovascular risk by even 1% would generate discounted savings of approximately £260 million per year. The good news, adds Capewell, is that introducing such changes can deliver rapid results. 
“In Eastern Europe when food subsidies for animal fats were abolished in the 1990s death rates from CVD dropped by one quarter within five years,” he says.

“You have only to look at the recent tobacco battles – where banning smoking in public places rapidly decreased the amount of acute coronary syndromes by 17% – to take inspiration and see how enormously effective political action can be,” says Rydén.

For maximum impact, adds Rydén, CVD needs to be tackled at both the European wide level and on an individual country basis. “Ideally each European country needs to bespoke the NICE evidence to their own situation, but the fact that few other European countries have NICE type organisations may make the process problematic,” he says.