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Highlights of AHA18 – Bridging Lifestyle Medicine with Contemporary Medicine through Science

This year’s annual scientific meeting of the American Heart Association (AHA) held in Chicago, Illinois November 10-12, 2018 was excellent. The abbreviated 3-day meeting received positive feedback as this allowed practicing physicians to attend the meeting over the weekend and be able to return to their practice early in the work week rather than having to spend an extended time away from the office. It was great being a part of the AHA Early Career Blogger group as this allowed access to many of the embargoed sessions. At these sessions I was able to listen to the AHA 2018 updated Lipid Management Guidelines1 as well as The Physical Activity Guidelines for Americans, Second Edition2 prior to their release at the meeting. This gave me a chance to ask the guideline committee several questions related to patient management.

 

Opening Session:

The opening session by Dr. Ivor Benjamin, the President of the American Heart Association, delivered very powerful messages throughout his speech. He highlighted the track of his career and the important role of strong mentors throughout his career and the impact it had on his advancement throughout the field of cardiology. He also discussed both the importance of mentoring and diversity in the cardiology profession highlighting the fact that African American men account for only 3% of Cardiologists in the United States and the need to bridge this gap. I found this session very inspiring and encouraging especially with regards to mentoring and supporting junior colleagues and being grateful for the mentors I have had thus far in my career. I also welcomed the message of the importance of diversity and inclusion as this leads to a healthier work and training environment.

 

Bridging Lifestyle Medicine with Contemporary Medicine through Science:

This year’s meeting highlighted the value of integrating lifestyle medicine with contemporary medicine to achieve the best outcomes for patients with regards to the prevention of cardiovascular disease. This was supported by the release of the updated 2018 American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines on Lipid Management on the first day of this meeting1. This updated guideline emphasized the importance of the cholesterol management at all stages of adulthood along with the importance of therapeutic lifestyle changes1. The utility of coronary artery calcium (CAC) scoring with cardiac CT was also emphasized as a useful tool to further refine patients’ risk to determine the best management for patients who are at intermediate risk for atherosclerotic cardiovascular disease (ASCVD)1. This guideline also had included ezetimibe and PCSK9 inhibitors as having a complementary role when used with statin therapy in selected patients at high risk for ASCVD1. The release of this updated guidelines will be a useful in my management of patients with regards to primary and secondary prevention of ASCVD. I appreciated the role of CAC scoring which will be very helpful for the management of the intermediate risk patients.

The release of the U.S. Department of Health and Human Services’ second edition of the Physical Activity Guidelines for Americans on the last day of the meeting was also well received2. This second edition emphasized the importance of increasing physical activity for all age ranges throughout the population including women in pregnancy and the postpartum period, as well as adults with chronic diseases or disabilities2. This guideline update will assist me with counseling patients with regards to increasing their physical activity to improve their overall cardiovascular health.

 

Networking Opportunities:

There were many networking opportunities during the meeting. These included the Council on Clinical Cardiology dinner on the first night of the meeting which honored Dr. Judith Hochman the recipient of the James B. Herrick Award for Outstanding Achievement in Clinical Cardiology. Dr. Stacy Rosen was also the recipient of the Women in Cardiology Mentoring Award. This dinner was attended by many leaders in the field of Cardiology and was a great opportunity for me to meet these leaders. The Women in Cardiology Committee also hosted a networking luncheon on the first day of the meeting during which Dr. Sharonne Hayes from the Mayo Clinic was the keynote speaker. Dr. Hayes gave a very riveting interactive talk on leadership for women in cardiology, she was also the recipient of last year’s Women in Cardiology Mentoring Award. Her talk was useful with very powerful messages on navigating your professional and personal life to achieve overall job satisfaction, career success and personal happiness. I learned several tips that I will apply to my own career as well. Dr. Annabelle Volgman and the faculty at Rush University was gracious to host a wonderful networking dinner for Women in Cardiology (WIC) on the second night of the meeting. This dinner provided a great opportunity for me to meet fellow WIC colleagues and to discuss several relevant issues related to our practice in the Cardiology field.

Social Media Coverage:

There was also a broad social media coverage of the meeting on Twitter and this was assisted by the AHA Early Bloggers writing group. I was able to share live tweets during several sessions and this generated a lot of discussion amongst members on Twitter. This also allowed many colleagues who were unable to attend the meeting to be able to follow and comment on several meeting highlights.

 

Looking Forward to AHA 2019:

This year’s AHA Scientific Sessions embrace of lifestyle medicine and the value of preventive cardiology was refreshing and empowering. This meeting highlighted the importance of not only treating ASCVD but also the importance of preventing disease and empowering our patients to take responsibility for their health as well. In the words of Goethe as mentioned in Dr. Ivor Benjamin’s opening session “Choose well….your choice is brief, and yet endless.” We look forward to next year’s AHA 2019 meeting in the beautiful city of Philadelphia.

 

References:

1. Grundy SM, Stone NJ, Bailey AL, Beam LT, Birtcher KK, et al. 2018AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. JACC Nov 2018, 25709; DOI: 10.1016/j.jacc.2018.11.003

2. The Physical Activity Guidelines for Americans: THe HHS Roadmap for an Active Healthy Nation. Second Edition. ADM Brett P. Giroir, MD.

 

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The 2023 Cholesterol Guidelines

A few days ago, the long-anticipated 2018 AHA/ACC Cholesterol Clinical Practice Guidelines were released at the American Heart Association Scientific Sessions 2018 in Chicago.

The update from 2013 was viewed favorably in the cardiology community, as it reflected a large body of evidence that has accumulated since, specifically the recommendations for targeting LDL< 70 mg/dL in secondary prevention and using non-statin lipid-lowering medications (ezetimibe and PCSK9 inhibitors) with proven incremental reduction in cardiovascular events. In primary prevention, the recommendations for the use of coronary calcium score to decide on statin therapy in intermediate risk patients and the use of several ASCVD risk enhancers in borderline risk patients also reflected a decade of accumulating evidence.

In fact, many cardiologists feel that the new 2018 guidelines finally reflect what they already practice or would like to practice. I definitely feel this way, but are guidelines always meant to come that late after the evidence? Also, should guidelines be static documents at specific time intervals? When writing guidelines that will be used by millions around the globe, it is crucial to strike the right balance in being timely in providing guidance for clinicians but also cautious in not providing premature recommendations based on low levels of evidence, which could result in harm. This is not an easy job and the authors of the current guidelines successfully achieved this balance, in my opinion.

At Scientific Sessions 2018 where the new guidelines were released and made headlines in the morning, new science was being presented in the afternoon showing that these guidelines might already be outdated! The REDUCE-IT trial, which showed that icosapent ethyl 4g/day reduced major adverse cardiovascular events by 25%, was only one example.

I could not but reflect: What will be in the next cholesterol guidelines? How outdated will our current guidelines be if we wait another five years? And if new treatments will target triglycerides and inflammation, should we even change the name to “Atherosclerosis Management Guidelines”?

Here are my predictions for the next set of guidelines:

  • The LDL target cutoffs will be shifted downwards by 20-30mg/dL. In the highest risk patients we will be talking about LDL targets of <50mg/dL for secondary prevention and <70mg/dL for primary prevention. There is accumulating evidence that “lower is better” and that very low LDL (~20mg/dL) is safe, so as we become comfortable with targeting <70mg/dL in the coming few years, it would be reasonable to move the needle even lower.
  • Polygenic Risk Scores (PRS) will be used to risk-stratify patients <40 years of age and target a fraction of the population with high polygenic risk score who would benefit from statin therapy despite their LDL not being  >160mg/dL. The predictive ability of the polygenic risk score for CAD is already established and retrospective data show that statin therapy can attenuate the risk of CAD in those with highest polygenic risk score. Establishing the value of implementing PRS in clinical practice will require prospective randomized trials, and we are likely to see that in the near future.
  • New non-statin therapies to target ASCVD will emerge and have a major role in treatment. Icosapent Ethyl is leading the way, but other triglyceride lowering agents are also promising, specifically inhibitors of Angiopoietin-like 3 (ANGPTL3) and Apolipoprotein C-3 (APOC3). Antisense oligonucleotide inhibitors of  apolipoprotein(a) successfully reduced Lp(a) levels in a Phase 2 trial presented at this year’s scientific sessions. Future phase 3 trials will test whether lowering Lp(a) will reduce CV events. If proven, we might see more emphasis on Lp(a) screening and treatment cut-offs in the next guidelines. Finally and most importantly, the role of heightened inflammation in ASCVD risk is clear. While low-dose methotrexate did not reduce ASCVD outcomes in the CIRT trial, targeted anti-cytokine therapy with canakinumab did improve outcomes in the patients selected for high hsCRP in the CANTOS trial. The next guidelines will likely recommend routine hsCRP screening in secondary prevention to identify patients with residual inflammatory risk (high hsCRP, low LDL) who could benefit from anti-cytokine therapy.
  • And then there’s the atherosclerosis vaccine! A “Cutting Edge in Cardiovascular Science” presentation at Scientific Sessions 2018 by Dr. Klaus Ley highlighted that this is possible in mice. Will it be possible to safely manipulate the adaptive immune system in humans to  create an atherosclerosis vaccine? The answer is probably yes, but it would be wishful thinking to hope for it in the next guidelines.

 

Those are my predictions. What are yours?

 

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What to expect at Joint Hypertension 2018 Scientific Sessions – Treating Hypertension in 2018

Two AHA Councils, the Council on HAHA|ASH Hypertension Scientific Sessions 2018ypertension and the Council on Kidney in Cardiovascular Disease, have joined forces with the American Society of Hypertension to make Joint Hyptertension 2018 Scientific Sessions (#Hypertension18) among the most impactful. Dr. Karen Griffin, FAHA Vice Chair for the Council on Hypertension Scientific Sessions Planning Committee calls it the “premier scientific meeting on hypertension in the world”. Understandably so; it boast experts from areas of cardiorenal disease, cardiovascular disease, stroke, and genetics to make for a vast cross-disciplianry session with the up-to-date information on hypertension. This year’s meeting received 439 abstracts in 37 categories, over 125 expert peer reviewers, and more than 20 countries represented.

There will be several interactive sessions that will target the established researcher/clinician, early career, and everything in between. With the addition of the new concurrent session D-Track, Clinical Practice Clinical Science and Primary Care tracks, a dimension will be added for elucidate the research science/clinical practice as it relates to patient care. In light of all the sessions that are available one should not have a problem reaching the milestones set by the program coordinators (infra vide).

To point out a few conference highlights, there will be 24 oral sessions, 3 poster sessions, and travel award talks:

The Excellence Award for Hypertension Research (Saturday, September 8, 2018)

  • R. Clinton Webb, PhD, FAHA presents “A Study of the Innate Immune Response in Hypertension”
  • Paul K. Whelton, MB, MD, MSc, FAHA presents “Clinical Trials and Practice Guidelines: Evidence-Based Progress in Lowering Blood Pressure”

Conference Awards

  • 10 Council on Hypertension New Investigator Travel Awards
  • 10 Council on Kidney in Cardiovascular Disease New Investigator Awards
  • 4 New Investigator Travel Awards
  • 6 Hypertension Early Career Oral Award Finalists
  • 12 AFHRE Travel Award for Patient-Oriented or Clinical Research in Hypertension
  • 1 Clinical Science Investigator Award for Excellence in Translational or Clinical Hypertension Research
  • 3 New Investigator Awards for Japanese Fellows

25 Poster Presenters can potentially win the competition this year! Which has gone up significantly from the previous years.

I am excited to go to Chicago for #Hypertension18 this year. If there is anything you need to enhance your experience during your time at the conference contact the program officials (directions in the program book).

I look forward to meeting you all! If you see me around tweeting, introduce yourself. I love meeting new people and learning new things. After all, that is why we are all going, right? 🙂

#Hypertension18 Conference Learning Objectives:

  1. Discuss changes to the AHA/ACC guidelines for the management of hypertension and their clinical implications.
  2. Describe opportunities to improve blood pressure measurement in the clinical setting to provide more accurate results.
  3. Identify immune and inflammatory mechanisms that contribute to the development of hypertension and hypertension-related end-organ damage and discuss the research and clinical implications.
  4. Educate participants about medical approaches for the management of co-morbid obesity in patients with hypertension.
  5. Describe new and emerging strategies for treating resistant hypertension.
  6. Describe participants on the impact of value-based reimbursement on hypertension management and identify opportunities to improve its management.

 

Leave a comment or tweet @AnberithaT and @AHAMeetings if you have questions or are interested in something else specifically.

Follow me and @American_Heart @AHA_Research @AHAScience and @HyperAHA on twitter for more #HeartSmart information.

For meeting Tweets follow @AHAMeetings @HyperAHA @AHAScience #JAHAMeetingReports @JAHA_AHA for the latest on#Hypertension18!

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Of Mice And Men

I have run into zealous naysayers from both camps. From a clinical researcher: “Human trials are the ultimate, difficult to run, very different from animal studies which may have no clinical relevance.” From a bench scientist: “Epidemiologic studies are trash in, trash out. Well designed animal studies are real science that will advance health.”
 
There’s an element of truth to both sides. Patient trials are complex and costly, liable to inter-subject variation (diabetic nephropathy is notorious), lag-time bias, selection bias, and in the case of non-blinded trials there is potential treatment effect due to patient preference (see blog by #AHAEarlyCareerBlogger @LeonieKlompstra). Thus truly successful RCTs are uncommon. At #ISC18, it was remarkable to hear the findings from the DEFUSE 3 trial which showed that in select patients with suitable brain imaging profile, thrombectomy for ischemic stroke beyond the traditional 6-hour window (a 6-16 hour timeframe was specified) conferred improved functional and mortality outcomes compared to medical therapy alone. The trial was terminated early due to efficacy superiority, with a staggering number needed to treat (NNT) of two. The NNT declaration incited spontaneous cheering from the audience – uncommon at scientific meetings where we politely applaud at the end of talks – because it is rare to see such robust positive RCT outcomes.
 
For identifying at-risk cohorts or new targets for preventative healthcare, epidemiology is essential. The inherent limitation here is that correlation is not causality. With a large database (thousands of patients) sophisticated tools for multivariate and time-varying adjustments can result in a dizzying array of associations that have to be carefully interpreted. (Simple illustrative case: positive correlation between higher number of firemen in areas with more fires. The firemen didn’t cause the fires. I hope.)
 
Animal studies have their niche in that they allow for evaluation of disease or drug pathways in a living model when a human study is not feasible. Animal studies are fraught with their own set of flaws, the most prominent being translational failure due to the model not adequately replicating human disease. Dr. Jun Chen gave the Thomas Willis Lecture at #ISC18 and pointed out the importance of streamlining integrative methods in stroke models to make them clinically relevant. The majority of animal trials will not translate into approved clinical interventions, but still serve to advance our understanding of pathophysiology and drug effects. Some major discoveries (including insulin, erythropoietin, klotho, aspirin, and numerous anti-cancer therapies) would not have been possible without judicious animal research.
 
Advancements in patient care would not be possible without both basic science and patient trials (some impressive folks out there wear both hats!). Bench and clinical research each have their strengths and limitations and deserve to be critically interpreted, while prioritizing exchange of ideas and constructive feedback to collectively move medicine forward.
 
Wei Ling Lau Headshot
Wei Ling Lau, MD is Assistant Professor in Nephrology at University of California-Irvine, where she studies vascular calcification and brain microbleeds in chronic kidney disease. She is currently funded by an AHA Innovative Research Grant, and has been a speaker for CardioRenal University and the American Society of Nephrology.

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Making Epidemiology Make Sense For Clinicians

I discovered epidemiology through an interest in evidence-based practice and clinical research. Seeing patients brought up research questions, and I wanted to be able to answer those with numbers. What I learned is that our results differed from the few published studies that crafted the informal, “word on the street” guidelines we abided by, not because their research was flawed, but because our patient populations were different. Had the situation been two Table 1’s side by side, we would’ve seen the clear demographic differences.

Hannaford and Owen-Smith did a proof-of-concept literature search in 1998 to see how many population studies (epidemiologic studies) provided relevant data to answer their specific clinical question. There are a few points of comparison between epidemiology and clinical practice here:

Clinical vs Epidemiologic Research

So, this is where adjustment versus stratification comes in. Multivariable adjustment is a statistical method that attempts to isolate the effect of our exposure (oral contraceptives) on the outcome (cardiovascular risk). We often adjust for factors related to both, because we don’t want a relationship such as age (younger women more likely to be on oral contraceptives and are at decreased risk of cardiovascular events compared to older women) to secretly be explaining a statistical association. Specifically, Hannaford and Owen-Smith note that “in effect, these adjustments level the epidemiological playing field so that the real effects of combined oral contraceptives can be determined, but at a cost of losing information about the effects of the adjusting factor (in this case smoking) among contraceptive users.” There are many other ways to control for confounding, such as randomization, restriction, matching, stratification, and of course, adjustment. But more often than not in epidemiology, we use adjustment because it’s answering our question.

The clinical mind searches for subgroup analysis as the most efficient way to answer the question “What about my patient?” Such as – “What about men? Women? Comorbidities?” without having to calculate a beta coefficient (given the authors even provided it). In other words, instead of smoothing out the data over all possible groups (smokers, those with diabetes, etc.), we want to plot individual points on the graph.

Hannaford and Owen didn’t find many epidemiologic studies that answered their very specific clinical question in 1998 – hopefully the odds would be higher 20 years later. But, compromising epidemiologic methods or clinical methods isn’t the answer to meet in the middle. So, what can we do? Epidemiology provides methods to systematically think about patterns and causes of disease for the clinician. Many of my colleagues are physicians seeking additional research training. They compare anesthesia protocols for outcomes after colon cancer surgeries, while my academic colleagues look at cumulative environmental exposures and lifetime risk of colon cancer. The overarching topics are similar, but the questions and resulting methods are incredibly different.

How do we make population studies more relevant to clinicians? There are many ways, and I’d love to hear your thoughts, but some to get us started include: interdisciplinary teams of epidemiologist and clinicians when designing studies and analyses; utilizing different but valid methods such as stratification with or instead of adjustment (and powering our studies for subgroup analysis), and…what else?

Bailey DeBarmore Headshot
Bailey DeBarmore is a cardiovascular epidemiology PhD student at the University of North Carolina at Chapel Hill. Her research focuses on diabetes, stroke, and heart failure. She tweets @BaileyDeBarmore and blogs at baileydebarmore.com. Find her on LinkedIn and Facebook.

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Precision Medicine Through Big Data – A Game Changer

From clinical science supported by data to data science supported by clinicians

AHA Badge
We live in an era of a tremendous amount of information. Scientific research is particularly well suited by the possibilities offered by analyzing large sets of data. In the past, data has been locked up in individual data bases and were not openly shared or available. Over the last two decades access to data has been improved and more open sources for analyses are now available. With advancements in technology, including cloud computing, big data is now available to all researchers. Information gained from big data needs to be translated into knowledge.  Acute and chronic disease is a complex process and often displays itself in a variety of phenotypes with different outcomes. Consequently, data has to be complex in order to identify subgroups, to define disease phenotypes, and precise treatment strategies.

I recently attended the AHA Scientific Sessions meeting the “Early Career Day” to learn more about the AHA – Precision Medicine Platform (AHA-PMP) to access and also upload my own data and use the provided workspace, which is especially great for teams. Additionally, to AHA-PMP other data portals were presented and explored in small groups. These open portals included cardiovascular, cerebrovascular, and diabetes research such as the Cardiovascular Disease Knowledge Portal (CVDKP; broadcvdi.org), cerebrovascularportal.org (CDKP) and the type2diabetesgenetics.org (T2DKP) portal.

The goal of these platforms is to accelerate analyses of the genetics of cardiovascular and cerebrovascular disease as well as diabetes. For example, the CVDKP is an open-access resource that facilitates the translation of genomic data into actionable knowledge for better understanding and treatment of cardiovascular disease. For example data in the CVDKP are from 4 large Consortia namely the Atrial Fibrillation Consortium (AFGen), the Global Lipids Genetics Consortium (GLGC), the Myocardial Infarction Genetics Consortium (MIGen), and the CARDIoGRAMPlusC4D Consortium. The CVDKP was built on the Knowledge Portal platform originally designed for the Type 2 Diabetes Knowledge Portal (type2diabetesgenetics.org), which was produced by the Accelerating Medicines Partnership In Type 2 Diabetes.  It is part of the Knowledge Portal Network, which also includes the Cerebrovascular Disease Knowledge Portal (CDKP: cerebrovascularportal.org). Data in the CVDKP include GWAS data for CVD and other traits (anthropometric, glycemic, renal, and psychiatric traits), exome chip data, whole exome sequence data, disease-agnostic genomic resources and epigenomic data. Further, with evolving results from big data a paradigm shift in science has been recognized. While over the last few decades medicine has been mostly clinical science supported by data; now medicine is about to become data science supported by clinicians and artificial intelligence and machine learning (deep learning)  plays an important role. This new frontier of data science, provides a greater opportunity especially for younger investigators to develop and drive their own projects.

However, despite the widely endorsement of sharing data and the availability of open sources and platforms, the rate that these data are accessed and utilized are still low. This is one reason AHA wants to promote these valuable resources further to advance our understanding in medicine and facilitate new therapies.

The perception that open source data are underutilized is supported by recent studies.  A just published analysis showed that for example cardiometabolic study data from patient-level clinical trial data are less accessed than previously assumed. In this study by Vaduganathan et al. data were extracted from ClinicalStudyDataRequest.com, a large, multi-sponsor data-sharing platform hosting individual patient-level data from completed studies sponsored by 13 pharmaceutical companies. Over the last 4 years, the platform had data from 3374 clinical trials, of which 537 evaluated cardiometabolic therapeutics covering 74 therapies and 398 925 patients. Diabetes mellitus and hypertension were the most common study topics with a median follow up time of 79 months. As of May 2017, despite availability of data from more than 500 cardiometabolic trials in a multi-sponsor data-sharing platform, ClinicalStudyDataRequest.com, only 15% of these trials and 29% of phase 3 or 4 clinical trials have been accessed by investigators and almost all researchers were from academic centers in North America and Europe. Of note, only half of the proposals were funded, and most proposals were for secondary hypothesis-generating questions. To date, after a median of 19 months (9-32 months) only 3 peer-reviewed articles have been published.

Further, when analyzed if male and female researchers were requesting data access equally, the investigators found that only 15 % of female researchers accessed data while the majority, with 85%, were men.

In conclusion, during “Early Career Day” I learnt that available open sources for big data analysis are underutilized and researchers who access scientific data are predominately men.  Data platforms provide a huge opportunity for researchers, and especially women, to generate hypotheses which may then lead to (further) funding.

 Tanja Dudenbostel Headshot
Tanja Dudenbostel is an Internist, Hypertension Specialist within Cardiology at the University of Alabama at Birmingham where I divide my time as an Assistant Professor between clinical research and seeing patients in cardiology.