MedicalResearch.com Interview with:
Christopher Labos MD CM, MSc FRCPC
Division of Epidemiology, Biostatistics and Occupational Health
McGill University
Montreal, Quebec
Canada
Medical Research: What is the background for this study? What are the main findings?
Response: There have been great advances in the field of genetics in recent years. Especially in cardiology, a number of genetic variants have been identified that are associated with cardiovascular disease. But it is not clear how useful these variants are in terms of predicting future evens in patients that have already suffered a myocardial infarction. What we found in our study is that a genetic risk score composed of the 30 most common genetic variants associated with cardiovascular diseases was not useful in predicting recurrent events in the first year after a patient suffered a myocardial infarction.
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MedicalResearch.com Interview with:
Venkatesh L. Murthy, MD, PhD, FACC, FASNC
University of Michigan
and Dr. Ravi Shah MD
Beth Israel Deaconess Medical Center
MedicalResearch: What is the background for this study? Response: Recent changes recommend statin therapy for cardiovascular risk reduction in an increasingly large number of Americans. Conversely, a number of studies have identified an increased risk of diabetes with statin treatment. Thus, there is increasing need for tools to target statin therapy to those with a favorable risk-benefit profile.
MedicalResearch: What are the main findings?Response: In our study, we analyzed data from 3,153 individuals from the Multi-Ethnic Study of Atherosclerosis who underwent CT scanning at baseline for assessment of calcium score. The CT scans were analyzed to assess liver attenuation as a measure of the amount of liver fat. We demonstrated that high liver fat doubled the risk of diabetes over a median of 9 years of follow-up. Importantly, statin therapy also doubled the risk of diabetes. The two together had an additive effect, even after adjusting for BMI, age, gender, family history of diabetes, waist circumference, lipids, hsCRP and exercise habits. As in prior studies, the risk of cardiovascular disease (CVD) events increased with increasing calcium score, as has previously been shown in MESA and in other studies.
We then divided the cohort into six groups based on calcium score (0, 1-100 and >100) and liver fat (low/high). Using published data from meta-analyses of statin trials, we computed the number needed to treat to prevent one hard CVD event for statin therapy. Using data from our study, we computed the number needed to harm to cause one additional case of diabetes from statin therapy. The numbers needed to treat with ranged from 29-40 for calcium score of >100 to 218-252 for calcium score of 0. Conversely, the numbers needed to harm were approximately 63-68 for those with low liver fat versus 22-24 for those with high liver fat. Thus the combination of calcium score and liver fat assessment, from a single standard calcium score scan, allows for physicians to provide better assessment of risk and benefit of statins in discussion with their patients. (more…)
Medical Research Interview with:
Prof. Johan Bosmans
Interventional cardiologist
University Hospital Antwerp, Wilrijkstraat 10, 2650,
Edegem, Belgium
MedicalResearch: What is the background for this study? What are the main findings?Prof. Bosmans : Transcatheter aortic valve replacement (TAVR) has become standard of care for patients who cannot undergo surgery. With this, it is important to ensure that the risks associated with TAVR be fully understood, and if possible prevented. Even at this stage of the adoption of TAVR, large trials continue to provide information to the clinician about how to select the right patients to ensure the best possible outcomes. The ADVANCE Study is a prospective, multicenter study that evaluated the use of TAVR in 1015 patients at 44 experienced TAVR centers, which was designed to reflect routine clinical practice.
We know that the risk of serious adverse events, such as stroke or transient ischemic attack (TIA), in post-TAVR patients can vary based on the timing before and after the procedure. A patient’s baseline demographics and medical history can affect their risk of procedure-related events as well as long-term outcomes. The manipulations required crossing the aortic valve and appropriately positioning any type of TAV has been thought to be related to procedural stroke events. Therefore, we performed a multivariable analysis looking for predictors of stroke – or stroke and TIA at 3 unique time periods (periprocedural, early and late) following TAVR.
The most striking result from our analyses was that we were not able to identify any predictors of periprocedural (either during the procedure or on the day after) stroke, illustrating this very multifactorial etiology. We were able to show that being female, experiencing acute kidney injury or a major vascular complication positively predicted stroke during the early (2-30 days post procedure) time period. When we combined the outcome of stroke or TIA, we found that a history of prior atrial fibrillation (AF) was also a predictor. The only late predictor (day 31-730 post-procedure) of stroke was a history of coronary artery bypass grafting, which could reflect the patients’ risk of vascular disease.
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MedicalResearch.com Interview with: Carl "Chip" Lavie MD, FACC FACP, FCCP
Medical Director, Cardiac Rehabilitation and Prevention
Director, Exercise Laboratories
John Ochsner Heart and Vascular Institute
Professor of Medicine
Ochsner Clinical School-UQ School of Medicine
Editor-in-Chief, Progress in Cardiovascular Diseases
Medical Research: What is the background for this study? What are the main findings?
Dr. Lavie: This was a review of the literature on this topic.The main findings are that various lifestyle choices, including obesity, hypertension, metabolic syndrome/diabetes, obstructive sleep apnea , moderate and high alcohol intakes, and sedentary lifestyle but also very high exercise doses are all associated with increased risk of atrial fibrillation (AF).
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MedicalResearch.com Interview with:
Dr. Ankur Pandya Ph.D.
Assistant Professor of Health Decision Science
Department of Health Policy and Management
Harvard T.H. Chan School of Public Health
Boston, MAMedical Research: What is the background for this study? What are the main findings?
Dr. Pandya: The American College of Cardiology and the American Heart Association (ACC-AHA) cholesterol treatment guidelines were controversial when first released in November 2013, with some concerns that healthy adults would be over-treated with statins.
We found that the current 10-year ASCVD risk threshold (≥7.5%) used in the ACC-AHA cholesterol treatment guidelines has an acceptable cost-effectiveness profile (incremental cost-effectiveness ratio of $37,000/QALY), but more lenient ASCVD thresholds would be optimal using cost-effectiveness thresholds of $100,000/QALY (≥4.0%) or $150,000/QALY (≥3.0%). (more…)
MedicalResearch.com Interview with:
Azfar B. Sheikh, M.D.
Internal Medicine Resident Physician
Staten Island University Hospital
New York
Medical Research: What is the background for this study?Dr. Sheikh: The background of this review article circles around the impact of
atrial fibrillation on epidemiology, trends in hospitalizations, costs
associated with hospitalization and outpatient care, in the United
States. This article also describes the benefits of newer treatment
modalities compared to the standard of care with regards to
symptomatic improvement and prevention of thromboembolism. These
findings are supported by several cost-utility analyses.
Medical Research: What are the main findings?Dr. Sheikh: The main findings of the study are:
The cost of hospitalization is three times higher for patients with
atrial fibrillation than those without atrial fibrillation.
5 million new cases are being reported annually.
The incidence of atrial fibrillation is projected to increase from
1.2 million cases in 2010 to 2.6 million cases by 2030. Due to this
increase in incidence, the prevalence of atrial fibrillation is
projected to increase from 5.2 million cases to 12.1 million cases by
2030.
The most common co-moribidites associated with atrial fibrillation
were hypertension, diabetes mellitus, and chronic obstructive lung
disease.
According to the NIS database, the atrial fibrillation.
hospitalization rate has increased from 1552 to 1812 per one million
US residents per year from 2000 to 2010 (relative increase 14.4%).
According to the NIS database, the mortality associated with atrial
fibrillation hospitalizations has decreased significantly from 1.2% in
2000 to 0.9% in 2010 (relative decrease 29.2%).
The median length of stay in the hospital is 3 days and increases
proportionally with a rise in CHADS2 score.
The largest source of direct healthcare costs associated with
atrial fibrillation is hospitalization. According to the NIS database,
the mean cost of inpatient atrial fibrillation hospitalization
increased significantly from $6401 in 2001 to $8439 in 2010 (relative
increase 24.0%). The mean cost of atrial fibrillation hospitalization
also increases proportionally with a rise in CHADS2 score.
In the outpatient setting, the highest costs were associated with
physician office visits in comparison to emergency room and urgent
care visits.
With regards to prevention of thromboembolism, the new oral
anticoagulant agents (dabigatran, rivaroxaban, and apixaban) have been
found to be more cost-effective compared to warfarin.
Left atrial catheter ablation is more effective than rate control
and rhythm control. It is more cost-effective in younger patients who
are moderate risk for stroke.
MedicalResearch.com Interview with:
Amelia Stanton, Graduate Student
Department of Psychology
The University of Texas at Austin
Austin, TX
Medical Research: What is the background for this study? What are the main findings?
Response: Heart rate variability (HRV) has emerged as a valuable non-invasive test to assess autonomic nervous system (ANS) activity. Several studies have linked low resting Heart rate variability to mental health conditions including depression, anxiety, and alcohol dependence, indicating these disorders may be related to an imbalance in autonomic activity. As Heart rate variability is an index of the balance of sympathetic nervous system (SNS) and parasympathetic nervous system activity (PNS), it has proven a useful tool for examining the relative role of SNS activity in female sexual arousal. Moderate SNS dominance (relative to PNS activity) has been shown to predict women’s genital arousal in the laboratory, while high levels of SNS activation have been shown to inhibit genital arousal. Based on this background evidence and on a growing clinical literature indicating that low HRV (generally indicative of high SNS) is associated with negative health outcomes, we predicted a positive linear relationship between Heart rate variability and sexual arousal function. That is, we predicted that women with autonomic balance indicating moderate or low resting SNS activity (relative to PNS activity) would be less likely than women with autonomic balance indicating high resting SNS to report clinically relevant sexual arousal dysfunction. We also predicted that this relationship would hold for overall sexual function.
To test this hypothesis, sexual arousal function, overall sexual function, and resting HRV were assessed in 72 women, aged 18-39. The main finding of the study is that women with below average Heart rate variability were significantly more likely to report sexual arousal dysfunction (p < .001) and overall sexual dysfunction (p < .001) than both women with average HRV and women with above average HRV. Based on these results, we concluded that low HRV may be a risk factor for female sexual arousal dysfunction and overall sexual dysfunction.
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MedicalResearch.com Interview with:
Dr Emanuele Di Angelantonio FESC FAHA
University Lecturer | University of Cambridge
Director | MPhil in Public Health, University of Cambridge
Deputy Director | NIHR Biomedical Research Unit in Donor Health and Genomics
Honorary Consultant | NHS Blood and Transplant
Department of Public Health and Primary Care
Strangeways Research Laboratory
Cambridge, UK
Medical Research: What is the background for this study? What are the main findings?
Response: Previous research as mainly focused on individual with one cardiometabolic condition alone and, despite it could be expected that having more than one condition poses a greater risk, this is the first study that is able to precisely quantify how much is worst. Furthermore, given that the conditions we study (diabetes, heart attack, and stroke) share several risk factors, it could be expected that the combination of these will not be multiplicative. We were somewhat surprised to find that participants who had 1 condition had about twice the rate of death; 2 conditions, about 4 times the rate of death; and all 3 conditions, about 8 times the rate of death. We estimated that at the age of 60 years, men with any two of the cardiometabolic conditions studied would on average have 12 years of reduced life expectancy, and men with all three conditions would have 14 years of reduced life expectancy. For women at the age of 60 years, the corresponding estimates were 13 years and 16 years. The figures were even more dramatic for patients at a younger age. At the age of 40 years, men with all three cardiometabolic conditions would on average have 23 years of reduced life expectancy; for women at the same age, the corresponding estimate was 20 years.
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MedicalResearch.com Interview with:
Mohamed Boutjdir, PhD, FAHA
Director of the Cardiovascular Research Program
VA New York Harbor Healthcare System
Professor, Depts of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Medical Center and
NYU School of Medicine, New York, NY
Medical Research: What is the background for this study? What are the main findings?
Dr. Boutjdir: Patients with autoimmune diseases including Sjogren’s syndrome, systemic lupus erythematosus and other connective tissue diseases who are seropositive for anti-SSA/Ro antibodies may present with corrected QTc prolongation on the surface ECG. This QTc prolongation can be arrhythmogenic and lead to Torsades de Pointes fatal arrhythmia.
In our study, we established for the first time an animal model for this autoimmune associated QTc prolongation that is reminiscent of the clinical long QT2 syndrome. We also demonstrated the functional and molecular mechanisms by which the presence of the anti-SSA/Ro antibodies causes QTc prolongation by a direct cross-reactivity and then block of the hERG channel (Human ether-a-go-go-related gene). This hERG channel is responsible for cardiac repolarization and its inhibition causes QTc prolongation. We were able to pinpoint to the target epitope at the extracellular pore forming loop between segment 5 and segment 6 of the hERG channel.
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MedicalResearch.com Interview with:
Liana C. Del Gobbo, PhD
Postdoctoral Research Fellow
Friedman School of Nutrition Science & Policy
Tufts University Boston MA
Medical Research: What is the background for this study? What are the main findings?
Dr. Del Gobbo: Heart failure most commonly develops in adults over 65 years old- the most rapidly growing portion of the US population. The condition greatly reduces the quality of life of older adults. Heart failure is the leading cause of hospitalizations in the US among those on Medicare, and is associated with large health care costs. Prevention is key for reducing the burden of this disease.
A detailed analysis of factors that might help prevent heart failure, such as a person's pattern of eating (as well as individual foods), in addition to other lifestyle factors (eg. smoking, physical activity, etc), had not been previously examined all together, in the same study.
To get a fuller picture of how to prevent this condition, this study examined the relative importance of dietary habits and other lifestyle factors for development of heart failure.
Our paper shows that older adults can cut their risk in half by adhering to a few healthy lifestyle factors, including moderate physical activity, modest alcohol consumption (eg. more than one drink/week, but not more than 1-2 drinks/day), not smoking, and maintaining a healthy weight.
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MedicalResearch.com Interview with:
Dr. Gary K Owens Ph.D
Robert M. Berne Cardiovascular Research Center
University of Virginia, Charlottesville, Virginia
Medical Research: What is the background for this study?
Dr. Owens: The leading cause of death in the USA and worldwide is cardiovascular disease with many of the clinical consequences including heart attacks (myocardial infarctions) and strokes being secondary consequences of atherosclerosis, commonly referred to as hardening of the arteries. Importantly, a heart attack is not caused by gradual narrowing of a large coronary artery by the atherosclerotic plaque, but rather is caused by acute rupture of a plaque that results in a catastrophic thrombotic event that can completely occlude a major coronary artery shutting off blood supply to a major heart region. Similarly, rupture of a plaque can result in formation of a thrombus that breaks off and circulates to a cerebral vessel where it can occlude blood flow to a brain region leading to a stroke. As such, it is critical to understand the mechanisms that regulate the stability of plaques, and the likelihood of plaque rupture.
The general dogma among clinicians and cardiovascular researchers has been that atherosclerotic plaques that have an abundance of macrophages and macrophage-derived foam cells relative to smooth muscle cells (SMC), the cells that normally line all of your blood vessels, are less stable and more prone to rupture with subsequent clinical consequences. However, the evidence for this is based on use of methods that are unreliable in identifying which cells within the plaque are truly derived from macrophages versus SMC, and even more importantly, what mechanisms regulate phenotypic transitions of these cells that are critical in the pathogenesis of this disease. Indeed, results of studies in cultured smooth muscle cells and macrophages have shown that each cell can express markers of the other cell type in response to stimuli likely to be present within advanced atherosclerotic lesions while down-regulating expression of their typical cell selective markers. As such, previous studies in the field have likely mis-identified which cell is which in many cases.
The goals of our studies were to clearly identify which cells within advanced atherosclerotic lesions are derived from SMC, to determine the various phenotypes exhibited by these cells and their functional role in lesion pathogenesis, and to determine what regulates these phenotypic transitions.
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MedicalResearch.com Interview with:
Anita P. Courcoulas M.D., M.P.H., F.A.C.S
Professor of Surgery
Director, Minimally Invasive Bariatric & General Surgery
University of Pittsburgh Medical Center
Medical Research: What is the background for this study?
Dr. Courcoulas: This study is a randomized clinical trial that was originally funded through the American Recovery and Reinvestment Act of 2009 (ARRA) as a high priority comparative effectiveness topic; the goal of which was to better understand the role of surgical versus non-surgical treatments for Type 2 diabetes mellitus (T2DM) in people with lower Body Mass Index (BMI) between 30 and 40 kg/m2. This report highlights longer-term outcomes at 3 years following random assignment to either an intensive lifestyle weight loss intervention for 1 year followed by a low-level lifestyle intervention for 2 years or surgical treatments (Roux-en-Y gastric bypass [RYGB] or laparoscopic adjustable gastric banding [LAGB]) followed by low-level lifestyle intervention in years 2 and 3.
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MedicalResearch.com Interview with:
Duk-Woo Park, MD, PhD.
Professor, Division of Cardiology
Asan Medical Center, University of Ulsan College of Medicine
Seoul, Korea
Medical Research: What is the background for this study? What are the main findings?
Response: The applicability and potential clinical effects of the 2013 ACC/AHA cholesterol guidelines on major cardiovascular outcomes in the “real-world” population remains uncertain and also should also be evaluated in multiple groups of various ethnic backgrounds. We determined the proportions of adult persons eligible for statin therapy by changes of 2013 ACC/AHA cholesterol guidelines using a nationally representative sample from an Asian country (South Korea) and also we evaluated the potential clinical effects of this cholesterol guideline on future cardiovascular outcomes using an external validation cohort from the Korean National Health Examination.
Similar to findings from the United States and the European cohort, our study showed that the 2013 ACC/AHA guidelines would substantially increase the number of adults who would be potentially eligible for statin therapy in Korean population. In addition, the 2013 ACC/AHA guidelines would have identified more cases with higher events of cardiovascular disease (CVD) for statin treatment than the ATP-III guidelines. (more…)
MedicalResearch.com Interview with:Jennifer A. Sumner, Ph.D.
Columbia University Mailman School of Public Health
New York, NY 10032
Medical Research: What is the background for this study? What are the main findings?
Dr. Sumner: Cardiovascular disease, which includes conditions like heart attack and stroke, is the leading cause of death worldwide. Stress has long been thought to increase risk of cardiovascular disease, and posttraumatic stress disorder (PTSD) is the quintessential stress-related mental disorder. Some individuals who are exposed to traumatic events, such as unwanted sexual contact, the sudden unexpected death of a loved one, and physical assault, develop PTSD, which is characterized by symptoms of re-experiencing the trauma (e.g., nightmares), avoidance of trauma reminders (e.g., avoiding thinking about the trauma), changes in how one thinks and feels (e.g., feeling emotionally numb), and increased physiological arousal and reactivity (e.g., being easily startled). PTSD is twice as common in women as in men; approximately 1 in 10 women will develop PTSD in their lifetime. Research has begun to suggest that rates of cardiovascular disease are higher in people with PTSD. However, almost all research has been done in men.
My colleagues and I wanted to see whether PTSD was associated with the development of cardiovascular disease in a large sample of women from the general public. We looked at associations between PTSD symptoms and new onsets of heart attack and stroke among nearly 50,000 women in the Nurses’ Health Study II over 20 years, beginning in 1989. Women with the highest number of PTSD symptoms (those reporting 4+ symptoms on a 7-item screening questionnaire) had 60% higher rates of developing cardiovascular disease (both heart attack and stroke) compared to women who were not exposed to traumatic events. Unhealthy behaviors, including lack of exercise and obesity, and medical risk factors, including hypertension and hormone replacement use, accounted for almost 50% of the association between elevated PTSD symptoms and cardiovascular disease. We also found that trauma exposure alone (reporting no PTSD symptoms on the screening questionnaire) was associated with elevated cardiovascular disease risk compared to no trauma exposure.
Our study is the first to look at trauma exposure and PTSD symptoms and new cases of cardiovascular disease in a general population sample of women. These results add to a growing body of evidence suggesting that trauma and PTSD have profound effects on physical health as well as mental health.
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MedicalResearch.com Interview with:
Dr. Carsten Lennerz
Deutsches Herzzentrum
München
Medical Research: What is the background for this study? What are the main findings?Response: The number of cardiovascular implantable electronic devices (CIEDs) is increasing. Worldwide more than 4 million people rely on an implanted pacemaker (PM) or implantable cardioverter defibrillator ICD. Sensing intrinsic cardiac electrical activity is the core principle of all CIED devices, however in case of electromagnetic interference (EMI) exogenous electric and magnetic fields can be picked up by the sensing circuit and mistakenly interpreted as a cardiac signal by the CIED. PM can respond to EMI with pacing-inhibition, leading to bradycardia or asystole and resulting in syncope. In ICDs EMI may be detected as a life threatening ventricular arrhythmia with the subsequent delivery of inappropriate shocks.
Early studies on EMI, run more than 10 years ago, have identified mobile phones as a source of EMI with pacemakers. Based on these pacemaker studies the CIED manufacturer and the regulatory authorities (e.g. Food and Drug Administration [FDA]) currently recommend a safety distance, i.e. hold the phone to the contra-lateral ear and avoid placing a turned-on phone next to the generator pocket.
In the meantime telecommunication and the CIED techniques have dramatically evolved. The classic mobile phone has been replaced by modern smartphones, furthermore the network standards have changed from GSM to UMTS (3G) and LTE (4G). New cardiac devices are now in use including more devices for cardiac resynchronisation therapy (CRT) or for the protection from sudden cardiac death (ICD); some of them are even compatible for MRI diagnostics.
With the use of a hemertic titanium shell, new filtering properties of the feed-throughs, sense amplifiers and noise protection algorhythms as well as the predominant use of bipolar leads the CIED may be better shielded against external influences and adverse effects of EMI.
In light of the above, the purpose of our study was to evaluate if previous precautions recommended to cardiovascular implantable electronic devices recipients are still up-to-date or if they can be abandoned. By today there are neither studies focusing on EMI between modern smartphones and modern CIEDs nor on newer mobile network standards (UMTS or LTE).
In a cross-sectional study we enrolled 308 patients and exposed them to the electromagnetic field of three smartphones (Samsung Galaxy 3, Nokia Lumia, HTC One XL) by placing the handhelds directly over the pulse generator. Installing an own base mobile network station we ensured that each smartphone went through a standardized protocol that included the entire calling process (connecting, ringing, talking), the handovers between all current network standards (GSM, UMTS, LTE where applicable) and operation at maximal transmission power.
More than 3.400 tests on electromagnetic interference were performed. One out of 308 patients (0.3%) was repeatedly affected by EMI caused by smartphones. The patient’s MRI compatible CRT-defibrillator malfunctioned with short-term ventricular and atrial oversensing when exposed to Nokia or HTC smartphones operating at GSM and UMTS. (more…)
MedicalResearch.com Interview with:
Jessica Parsh MD
Hitinder Gurm MBBS
Department of Internal Medicineb
University of Michigan Health System
Medical Research: What is the background for this study? What are the main findings?
Response: Chronic kidney disease (CKD) is associated with adverse events after percutaneous coronary interventions (PCI). Estimated glomerular filtration rate (eGFR) is used for CKD stage classification and there are several widely used eGFR equations, including the Cockcroft-Gault, CKD-EPI, and MDRD. Others have shown that the CKD-EPI equation is more accurate, more precise and less bias. The current Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend the use of CKD-EPI. Even so, there remains wide variability among equation choice between different institutions as well as between different health care providers (physicians, pharmacists, etc). In addition, in a recent survey, up to 12% of providers were "unsure" of which equation they used. Furthermore, the FDA has no clear guidelines regarding equation selection for pharmacokinetic studies of novel medications and the equation used for development of a particular drug is not always clearly labeled on package inserts.
Using data from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium for almost 130,000 patients who underwent PCI, we investigated whether use of different eGFR equations would lead to discrepant eGFR output, how this would lead to CKD stage reclassification and whether CKD stage reclassification by a certain equation led to improved risk prognostication for adverse events. We also studied how calculation of eGFR by various equations would affect drug dosing recommendations for common renally-dosed antiplatelet and antithrombotic medications. We found that there was wide discrepancy among the eGFR output of the various equations and this led to significant CKD stage reclassification (with agreement on stage classification as low as 56% for CKD-EPI and Cockcroft-Gault). Further, our data from receiver operating characteristic analysis and net reclassification index analysis support CKD-EPI as superior for risk prognostication for renal adverse outcomes of acute kidney injury and new requirement for dialysis. In regards to drug dosing, agreement between all three equations on dosing adjustment was as low as 34% (bivalirudin with eGFR cutoff < 30 ml/min/1.732).
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MedicalResearch.com Interview with:
Sean D. Pokorney, MD, MBA
Division of Cardiology, Duke University Medical Center
Duke Clinical Research Institute, Durham, North Carolina
Medical Research: What is the background for this study?
Dr. Pokorney: About 350,000 people die of sudden cardiac death in the US each year. Patients who have weakened heart function, particularly those with heart muscle damage as a result of a heart attack, are more likely to experience sudden cardiac death. Defibrillators have been around since the 1980s, and have prolonged countless lives. A previous study showed that 87% of patients who had a cardiac arrest were eligible for an implantable-cardioverter defibrillator (ICD) beforehand but did not get an ICD implanted prior to their arrest. The timing of ICD implantation is critical, as studies have not found a benefit to ICD implantation early after myocardial infarction (MI). Guidelines recommend primary prevention ICD implantation in patients with an EF ≤ 35% despite being treated with optimal medical therapy for at least 40 days after an MI. Given the need to wait for at least 40 days after an MI, ICD consideration is susceptible to errors of omission during the transition of post-MI care between inpatient and outpatient care teams. Also, the benefit of ICDs remains controversial among older patients, as these patients were underrepresented in clinical trials.
Medical Research: What are the main findings?Dr. Pokorney: We looked at Medicare patients discharged from US hospitals after a heart attack between 2007 and 2010. We focused on those patients who had weak heart function, and this left us with a little over 10,300 patients from 441 hospitals for our study. This was an older patient population with a median age of 78 years. We looked to see how many of these patients got an ICD within the first year after MI, and how many patients survived to 2 years after their heart attack. Only 8% of patients received an ICD within 1 year of their heart attack. ICD implantation was associated with a third lower risk of death within 2 years after a heart attack, and this was consistent with the benefit that were seen in the randomized clinical trials. Importantly, 44% of the patients in our study were over 80 years old, and we found that the relationship between ICD use and mortality was the same for patients over and under age 80 years. Increased patient contact with the health care system through early cardiology follow-up or re-hospitalization for heart failure or MI was associated with higher likelihood of ICD implantation. Rates of ICD implantation remained around 1 in 10 patients within 1 year of MI even among patients with the largest heart attacks and the weakest hearts (lowest ejection fractions), who were least likely to have improvement in their heart function over time. Similarly, even after excluding patients at highest risk for non-arrhythmic death (prior cancer, prior stroke, and end stage renal disease), ICD implantation rates remained around 1 in 10 patients.
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MedicalResearch.com Interview with:Satoru Kishi, MD
Division of Cardiology
Johns Hopkins University
Baltimore, Maryland
MedicalResearch: What is the background for this study? What are the main findings?Dr. Kishi: Blood pressure (BP) at the higher end of the population distribution may represent a chronic exposure that produces chronic injury to the cardiovascular system. Cumulative BP exposure from young adulthood to middle age may adversely influence myocardial function and predispose individuals to heart failure (HF) and other cardiovascular disease (CVD) later in life. The 2005 guidelines for the diagnosis and treatment of HF from the American College of Cardiology and American Heart Association highlight the importance of early recognition of subclinical cardiac disease and the importance of non-invasive tests in the clinical evaluation of heart failure.
Our main objective was to investigate how cumulative exposure to high blood pressure from young to middle adulthood influence LV function. In the Coronary Artery Risk Development in Young Adults (CARDIA) study, multiple repeated measures of BP and other cardiovascular risk factors was recorded over a 25 year time span, starting during early adulthood (ages 18-30). (more…)
MedicalResearch.com Interview with:
Prof. Wilhelm Krek
Institute of Molecular Health Sciences
Zürich, Switzerland
MedicalResearch: What is the background for this study? What are the main findings?
Prof. Krek: Fructose and glucose are major components of dietary sugars consumed in the western world. A current prevailing view holds that glucose is used directly by various tissues as an energy source while fructose is first and foremost metabolized to fat by the liver arguing that these dietary sugars are metabolized differently despite having identical caloric values. Accordingly, overconsumption of fructose causes fatty liver disease and through dissemination of fat to peripheral organs such that adipose tissue contributes to obesity.
The key enzyme in fructose metabolism is ketohexokinase (KHK). KHK-A and KHK-C are two isoforms of KHK that are produced through mutually exclusive alternative splicing of the KHK pre-mRNA. KHK-C displays a much higher affinity for fructose than KHK-A. Unlike other tissues that normally express KHK-A, the liver produces predominantly KHK-C providing a possible explanation of the above-noted pathologies upon overconsumption of fructose. Whether fructose metabolism is subject to signal-induced changes in alternative splicing of KHK isoform expression as a mechanism to mediate context-dependent changes in cell metabolism is not known. In this work, we identify the splicing factor SF3B1 as a key mediator of ketohexokinase alternative splicing and thus activator of fructose metabolism and further show that the SF3B1-KHK system is a direct target of regulation by hypoxia and promoter of heart disease. From the analysis of a series of genetic mouse models of pathologic cardiac hypertrophy and human samples of heart disease, we conclude that activation of the newly identified HIF1α-SF3B1-KHK-C axis and the ensuing promotion of fructose metabolism is essential for pathologic stress-induced anabolic growth and the development of heart disease.
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MedicalResearch.com Interview with:
Dr. Mary Vaughan SarrazinPh.D.
Associate Professor
University of Iowa Roy and Lucille Carver College of Medicine, and
Iowa City VA Medical Center, Center for Comprehensive Access & Delivery
Research and Evaluation (CADRE)
Iowa City, IA
Dr. Rajesh Kabra MD
Division of Cardiology, Department of Internal Medicine
University of Tennessee Health Science Center, Memphis, Tennessee
MedicalResearch: What is the background for this study? What are the main findings?
Response: Atrial fibrillation is associated with high risk of stroke and death. It is not known if these outcomes are different in whites, blacks and Hispanics.
In our study of over 500,000 Medicare patients over the age of 65 years with newly diagnosed atrial fibrillation, we noted that compared to whites, blacks and Hispanics had a higher risk of mortality (46% and 11% higher respectively) and stroke (66% and 21% respectively). However after correcting for other co-morbidities and illnesses, the risk of mortality was the same in all the races; the higher risk of stroke was decreased in blacks and eliminated in Hispanics. This suggests that in blacks and Hispanics, atrial fibrillation is a marker for higher mortality and identifies patients at higher risk of death.
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MedicalResearch.com Interview with:
José C. Nicolau, MD, PhD, FACC
Professor -University of São Paulo Medical School
Director - Acute Coronary Disease Unit, Heart Institute
MedicalResearch: What is the background for this study?
Dr. Nicolau: Previous studies, mainly performed in patients undergoing percutaneous coronary intervention (PCI), have shown that concomitant use of proton-pump inhibitors (PPIs) diminishes the antiplatelet effect of the drug clopidogrel. This diminished response to clopidogrel has in turn been associated with an increased risk of stent thrombosis and ischemic events. Our paper presented results from a secondary analysis performed in patients enrolled in the TRILOGY ACS randomized clinical trial. Our study is the first to examine the influence of interactions between PPIs and clopidogrel or the newer, more potent antiplatelet drug prasugrel, as well as correlations with platelet reactivity and clinical outcomes in high-risk patients who were receiving medical management without revascularization following acute coronary syndrome (ACS).
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MedicalResearch.com Interview with:Jaana Halonen Ph.D
Finnish Institute of Occupational Health
Kuopio, FinlandMedicalResearch: What is the background for this study? What are the main findings?Dr. Halonen: Research on predictors of cardiovascular disease has increasingly focused on exposures to risk factors other than the conventional behavioral and biological ones, such as smoking, hypertension, dyslipidaemia, or diabetes. One of the potential predictors beyond the conventional risks is exposure to childhood psychosocial adversities. Previous studies have found that people who had experienced financial difficulties, serious conflicts and long-term disease in the family in childhood have a higher level of cardiovascular risk factors and increased cardiovascular morbidity in adulthood, but the underlying mechanisms linking childhood exposure to adult disease remain unclear. It is possible that childhood adversity sets an individual on a risk pathway leading to adverse future exposures. An important source of adversity experienced in adulthood is residence in a socioeconomically disadvantaged neighborhood. However, no previous study had examined the combined effect of childhood psychosocial adversity and adult neighborhood disadvantage on cardiovascular disease risk.
We found that exposure to childhood psychosocial adversity and adult neighborhood disadvantage in combination was associated with a doubling of the risk of incident cardiovascular disease in adulthood when compared to the absence of such exposures. This association was not explained by conventional cardiovascular risk factors. Neither childhood psychosocial adversity nor adult neighborhood disadvantage alone were significantly associated with incident CVD, although they were associated with CVD risk factors.
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MedicalResearch.com Interview with:
Professor Phyo Kyaw Myint MBBS MD FRCP(Edin) FRCP(Lond)
Clinical Chair in Medicine of Old Age
Epidemiology Group, Division of Applied Health Sciences
University of Aberdeen
Scotland
Medical Research: What is the background for this study? What are the main findings?
Response: The research was carried out by academics from the Universities of Aberdeen, Manchester, Cambridge and East Anglia, as well as the Lancashire Teaching Hospital, the Medical Research Council Epidemiology Unit, Cambridge and the Academic Medical Centre, Amsterdam. It has been published online in the journal Heart. The team base their findings on almost 21,000 adults taking part in the EPIC-Norfolk study, which is tracking the impact of diet on the long term health of 25,000 men and women in Norfolk, England, using food frequency and lifestyle questionnaires. The researchers also carried out a systematic review of the available international published evidence on the links between chocolate and cardiovascular disease, involving almost 158,000 people—including the EPIC study participants.
The EPIC-Norfolk participants (9214 men and 11 737 women) were monitored for an average of almost 12 years, during which time 3013 (14%) people experienced either an episode of fatal or non-fatal coronary heart disease or stroke. Around one in five (20%) participants said they did not eat any chocolate, but among the others, daily consumption averaged 7 g, with some eating up to 100 g.
Higher levels of consumption were associated with younger age and lower weight (BMI), waist: hip ratio, systolic blood pressure, inflammatory proteins, diabetes and more regular physical activity —all of which add up to a favourable cardiovascular disease risk profile. Eating more chocolate was also associated with higher energy intake and a diet containing more fat and carbs and less protein and alcohol.
The calculations showed that compared with those who ate no chocolate higher intake was linked to an 11% lower risk of cardiovascular disease and a 25% lower risk of associated death. It was also associated with a 9% lower risk of hospital admission or death as a result of coronary heart disease, after taking account of dietary factors. And among the 16,000 people whose inflammatory protein (CRP) level had been measured, those eating the most chocolate seemed to have an 18% lower risk than those who ate the least. The highest chocolate intake was similarly associated with a 23% lower risk of stroke, even after taking account of other potential risk factors.
Of nine relevant studies included in the systematic review, five studies each assessed coronary heart disease and stroke outcome, and they found a significantly lower risk of both conditions associated with regular chocolate consumption. And it was linked to a 25% lower risk of any episode of cardiovascular disease and a 45% lower risk of associated death.
The study concluded that cumulative evidence suggests higher chocolate intake is associated with a lower risk of future cardiovascular events.
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MedicalResearch.com Interview with:
Ms. Rikke Elmose Mols
Department of Cardiology, Lillebaelt Hospital-Vejle, Vejle, Denmark.
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Current ESC guidelines for patients with chest pain and low to intermediate pre-test probability of coronary artery disease (CAD) recommend control and modification of risk factors. However, patients with an elevated cardiovascular risk profile are frequently inadequately motivated for lifestyle changes and medicine adherence from knowledge about risk factors and information about risk reduction alone. Coronary artery calcification (CAC) is a marker of coronary atherosclerosis. The degree of coronary artery calcification may be assessed by the Agatston score (AS) derived by non-enhanced cardiac computed tomography, whereas non-invasive CT imaging of the coronary arteries require contrast-enhancement (coronary computed tomography angiography [CTA]). The presence of CAC is associated with an elevated probability of obstructive coronary artery disease (CAD) and an unfavorable clinical outcome. In symptomatic patients, demonstration of non-obstructive CAD identified by coronary CTA is associated with risk modifying behavior and intensified prophylactic medical treatment in observational studies. Among asymptomatic individuals, those with the highest Agatston score levels seem to be motivated for the adoption of risk modifying behaviour and visualization of CAC may stimulate adherence to lipid-lowering therapy and aspirin and a healthier lifestyle. The aim of the present prospective, randomized controlled study was to test the effect of adding visualization of coronary artery calcification to the standard information about risk and lifestyle modification on cholesterol levels and other risk markers in patients with a new diagnosis of non-obstructive CAD.
Visualization of coronary artery calcification and brief recommendations about risk modification (ESC guidelines) after coronary CTA in symptomatic patients with hyperlipidemia and non-obstructive CAD may have a favorable influence on plasma total-cholesterol concentration, adherence to statin therapy and risk behavior. Further investigations are needed.
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MedicalResearch.com Interview with:
Mariusz Kowalewski, MD
Department of Cardiac Surgery, Dr Antoni Jurasz Memorial University Hospital
Bydgoszcz,
Systematic Investigation and Research on Interventions and Outcomes
Medicine Research Network, Poland
Medical Research: What is the background for this study? What are the main findings?
Dr. Kowalewski: Sternal wound infections occurring after heart surgery performed via median sternotomy, and in particular, after coronary artery bypass grafting (CABG), although rare, still pose serious postoperative complications that increase the length of hospital stay and healthcare costs. One of many ways to prevent them from happening, except from optimal glucose control, tight-fixed closure of the sternum at the end of surgery and perioperative iv. antibiotics, is to insert a gentamicin collagen sponge between two sternal edges, just before wiring them together. High local concentrations of gentamicin were shown to eliminate any microbial growth in the area, in the same time, not affecting the kidneys, as would be the case with systemic administration. Gentamicin sponges are widely used in orthopadic, gastro-intestinal and vascular surgery and were shown to reduce postoperative infection rates. Although extensively tested in the field of heart surgery, findings of one recent multicenter study have questioned their true benefit. We aimed to perform a comprehensive meta-analysis of studies assessing the efficacy of implantable gentamicin-collagen sponges in sternal wound infection prevention.
After screening multiple databases, a total of 14 studies (N = 22,135 patients, among them 4 randomized controlled trials [N = 4,672 pts]) were included in the analysis. Implantable gentamicin-collagen sponges significantly reduced the risk of sternal wound infection by approximately 40% when compared with control (risk ratio [RR], 0.61; 95% confidence interval [CI], 0.39-0.98; P = .04 for randomized controlled trials and RR, 0.61; 95% CI, 0.42-0.89; P = .01 for observational studies). A similar, significant benefit was demonstrated for deep sternal wound infection (RR, 0.60; 95% CI, 0.42-0.88; P = .008) and superficial sternal wound infection (RR, 0.60; 95% CI, 0.43-0.83; P = .002). The overall analysis revealed a reduced risk of mediastinitis (RR, 0.64; 95% CI, 0.45-0.91; P = .01). The risk of death was unchanged.
In addition, we investigated, by means of meta-regression, the correlation between sternal wound infections and extent to which the bilateral internal thoracic artery (BITA) was harvested. We found that the benefit provided by the gentamicin sponge was attenuated when BITA was harvested; these results suggest that another potentially preventive measure must be taken in such patients, as with severely reduced blood supply to the sternum (as is the case with BITA), sponge itself might not be enough to prevent wound infection.
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MedicalResearch.com Interview with:
Louise Sun, MD SM FRCPC
Assistant Professor Department of Anesthesiology,
University of Ottawa Staff | Division of Cardiac Anesthesiology
University of Ottawa Heart Institute
Medical Research: What is the background for this study? What are the main findings?Dr. Sun: Preoperative testing provides important information for perioperative
planning and decision-making. However, given the rapid increase in health
care costs, there has been growing emphasis on the more rational use of
resources and thus the need to better understand the utilization patterns
of specific tests. Preoperative pulmonary function tests (PFTs) are
important in helping perioperative physicians identify patients at risk
for postoperative pulmonary complications, but few appropriate use
guidelines exist for this test. We conducted a population-based study
using linked administrative databases in Ontario, Canada to describe
temporal trends in preoperative pulmonary function tests
and assess whether the recent 2006 American College of Physicians (ACP) guidelines on risk assessment and prevention of postoperative pulmonary complications for non-cardiothoracic surgery influenced these trends.
We examined 511,625 individuals undergoing non-cardiothoracic surgery, amongst whom
3.6% underwent preoperative pulmonary function tests while 3.3% had non-operative PFTs.
Preoperative pulmonary function tests rates decreased over the study period and following the 2006 ACP guidelines while non-operative rates remained stable. By 2013,
preoperative pulmonary function tests were performed in fewer than 8% of Ontario patients with risk factors for pulmonary complications, while preoperative testing
rates among individuals without known respiratory disease had approached
rates seen in the non-operative setting. The decreasing preoperative pulmonary function tests rates contrast starkly against concurrent increases in rates of other
perioperative interventions such as preoperative anesthesia consultations
and stress testing.
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MedicalResearch.com Interview with:
Nicholas Tatonetti, PhD
Department of Biomedical Informatics
Department of Systems Biology, Department of Medicine
Columbia University
New York, NY
Medical Research: What is the background for this study? What are the main findings?
Dr. Tatonetti: For decades, researchers have studied the link between disease incidence and the seasons. We’ve known, for example, that those born when the dust mite population is highest (summer) will have an increased chance of developing asthma. Traditionally, diseases have been studied one at a time to identify these seasonal trends. Because of the rapid adoption of electronic health records, it is now possible to study thousands of diseases, simultaneously. That is what we did in this study. We evaluated over 1,600 diseases and discovered 55 that showed this seasonal trend. Many of these had been studied previously, but several are new discoveries — most prominently, we found that the lifetime risk of developing cardiovascular disease is highest for those born in the spring.
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MedicalResearch.com Interview with:
Jacob Hollenberg M.D., Ph.D.
Assistant Professor, Cardiologist
Head of Research, Centre for Resuscitation Science
Karolinska Institutet, Stockholm, Sweden
Editor’s note: Dr. Hollenberg and colleagues published two articles in the NEJM this week discussing CPR performed by bystanders in out-of-hospital cardiac arrests.MedicalResearch: What is the background for the first study?Dr. Hollenberg: There are 10,000 cases of cardiac arrest annually in Sweden. Cardiopulmonary Resuscitation (CPR) has been taught to almost a third of Sweden’s population of 9.7 million. In recent years the value of bystander CPR has been debated, largely due to a lack of a randomized trial demonstrating that bystander CPR is lifesaving.
In this study, which included all cases of emergency medical services (EMS) treated and bystander-witnessed out-of-hospital cardiac arrests recorded in the Swedish Cardiac Arrest Registry from January 1, 1990, through December 31, 2011, our primary aim was to assess whether CPR initiated before the arrival of EMS was associated with an increase in the 30-day survival rate.
MedicalResearch: What were the main findings?Dr. Hollenberg: Early CPR prior to arrival of an ambulance more than doubled the chance of survival. (30-day survival rate was 10.5% among patients who underwent CPR before EMS arrival, as compared with 4.0% among those who did not (P<0.001).)
This association held up in all subgroups regardless of sex, age, cause of cardiac arrest, place of arrest, EKG findings or time period (year analyzed).
MedicalResearch: How did the patients who survived cardiac arrest do from a disability standpoint?Dr. Hollenberg: We had cerebral performance scores from 474 patients who survived for 30 days after cardiac arrest. (higher scores indicate greater disability).
At the time of discharge from the hospital, 81% of these patients had a score of category of 1. Less than 2% had category scores of 4 or 5.
MedicalResearch: What should patients and providers take away from this report?Dr. Hollenberg:
For patients with an out-of-hospital cardiac arrest, CPR performed by bystanders before the arrival of emergency medical personnel, saves lives. This has been validated by both the size of this study and the consistency of the results over three decades.
CPR education needs to continue and to increase. In Sweden about one-third of the population has been taught CPR. Legislation has recently been passed that mandates CPR be taught to all teenagers in school which should allow an entire generation to become familiar with this lifesaving technique.
The willingness of the public to become involved also needs to increase. We need new ways of educating lay people to recognize cardiac arrest and to motivate them to perform it. The knowledge that bystander CPR saves lives may enhance that motivation.
MedicalResearch.com Interview with:
James V. Freeman MD, MPH, MS
Yale University School of Medicine
New Haven, CT
Medical Research: What is the background for this study? What are the main findings?
Dr. Freeman: Atrial fibrillation (AF) substantially increases the risk of major adverse clinical outcomes such as stroke and death, but it can also cause frequent symptoms, affect patient’s functional status, and impair their quality of life. While prior studies have reported the range of AF-related symptoms in patient populations, these studies were generally from highly selected patients and referral based practices, and may not reflect results in community practice or results with contemporary AF management. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), a large, contemporary, prospective, community-based outpatient cohort, we evaluated the type and frequency of symptoms in patients with Atrial fibrillation. In addition, we measured the degree to which physician assessed symptom severity (using the European Heart Rhythm Association [EHRA] classification system) was correlated with patient reported quality of life (assessed by the Atrial Fibrillation Effect on QualiTy-of-life [AFEQT] questionnaire). Finally, we association between symptoms or quality of life with clinical outcomes, including death, hospitalization, stroke and major bleeding.
In our community-based study, the majority of AF patients (61.8%) were symptomatic (EHRA >2) and 16.5% had severe or disabling symptoms (EHRA 3-4). EHRA symptom class was well correlated with the AFEQT quality of life score (Spearman correlation coefficient -0.39). Over 1.8 years of follow-up, Atrial fibrillation symptoms were associated with a higher risk of hospitalization (adjusted HR for EHRA ≥2 vs EHRA 1 1.23, 95% CI 1.15-1.31) and a borderline higher risk of major bleeding. Lower quality of life was associated with a higher risk of hospitalization (adjusted HR for lowest quartile of AFEQT vs highest 1.49, 95% CI 1.2-1.84), but not other major adverse events including death. (more…)
MedicalResearch.com Interview with
Dr. Karin Rådholm MD Ph.D. student
Division of Community Medicine, Primary Care, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University
Department of Local Care West, County Council of Östergötland,
Linköping, Sweden
MedicalResearch: What is the background for this study? Dr. Rådholm: Psychosocial risk factors and depressive disorders often co-occur with general medical comorbidities, such as myocardial infarction. Depression is more common in patients with diabetes than in patients without diabetes. About 10-30% of patients with diabetes have a comorbid depressive disorder, which is double the estimated prevalence of depression in individuals without diabetes. There is an association between comorbid depressive symptoms and diabetes complications. This is believed to be mainly due to poor adherence to treatment recommendations and diabetes self-management activities, but could also possibly be due to biological and behavioural causes that could predispose for both metabolic and affective disorders. The general risk of myocardial infarction is strongly dependent on age and sex, where men have an earlier disease onset compared to women. In the general population women are at much lower risk for ischemic heart disease mortality than men are. However, women with diabetes are at especially high risk for coronary heart disease, relatively more so than men with type 2 diabetes, meaning that the impact of diabetes on the risk of coronary death is significantly greater for women than men. The age- and gender-specific risk for myocardial infarction due to diabetes with coexistent depression has not previously been described. Data on all dispensed drug prescriptions in Sweden are available in the Swedish Prescribed Drug Register and all myocardial infarctions are registered in the Myocardial Infarction Statistics. These registers are population-based and have a total national coverage and high validity, which has been previously shown. Prescribed and dispensed antidiabetics and antidepressants were used as markers of disease.
Our objective was to prospectively explore the gender- and age-specific risk of first myocardial infarction in people treated with antidiabetic and/or antidepressant drugs compared to participants with no pharmaceutical treatment for diabetes or depression in a nationwide register study.
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MedicalResearch.com Interview with:
Christopher Labos MD CM, MSc FRCPC
Division of Epidemiology, Biostatistics and Occupational Health
McGill University
Montreal, Quebec
Canada
Medical Research: What is the background for this study? What are the main findings?
Response: There have been great advances in the field of genetics in recent years. Especially in cardiology, a number of genetic variants have been identified that are associated with cardiovascular disease. But it is not clear how useful these variants are in terms of predicting future evens in patients that have already suffered a myocardial infarction. What we found in our study is that a genetic risk score composed of the 30 most common genetic variants associated with cardiovascular diseases was not useful in predicting recurrent events in the first year after a patient suffered a myocardial infarction.
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