Personalized medicine coming to cardiovascular, stroke care

Several late-breaking clinical science presentations suggest that personalized medicine could bring the kind of improvement to cardiovascular and stroke outcomes that oncologists have been reporting for more than a decade. The combination of improved biomarkers and highly targeted therapeutic agents can help clinicians identify which patients are more likely to show robust response to specific treatments.

A new sensitivity analysis of the CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) data found that a subset of patients who show a high initial response to treatment also had a significant reduction in cardiovascular mortality and all-cause mortality. Patients with high initial response to canakinumab, which targets the interleukin-1β innate immunity pathway, also showed reduced risk for incident lung cancer and lung cancer mortality. Inflammation is an important element in the pathogenesis of both atherosclerosis and lung cancer.

“There has been growing evidence that reducing inflammation might reduce the risk of cardiovascular disease,” said Paul M. Ridker, MD. “But there has never been proof that atherosclerosis is an inflammatory disease. Now we have seen that reducing inflammation using canakinumab reduces cardiovascular events out to five years. And we have a tool that allows us to predict who is most likely to respond to biologic treatment.”

That tool is an individual patient’s response to an initial dose of canakinumab.

Patients who showed a robust response as measured by hsCRP levels of 2.0 mg/L or lower had a 25 percent reduction in MACE, a 31 percent reduction in cardiovascular mortality, and a 31 percent reduction in all-cause mortality at five years. The primary outcome of CANTOS, presented earlier this year, showed a 15-17 percent reduction in cardiovascular event rates with no change in lipid levels.

“The lipid reduction world has been very successful and showed us that lower is better,” said Ridker, the Eugene Braunwald Professor of Medicine at Harvard Medical School. “CANTOS showed that lower is better in inflammation as well.”

Patients with the most robust anti-inflammatory response — hsCRP levels below 1.2 mg/L — had the most robust reduction in cardiovascular events, a 29-percent drop. Those in the middle tertile with hsCRP between 1.2 and 2.0 mg/L had a 17-percent reduction, while those whose hsCRP remained above 2.0 mg/L had only a 1-percent drop in cardiovascular events. The relationship between elevated anti-inflammatory response and reduced cardiovascular events was consistent at all doses of canakinumab used in the trial.

“This is what our oncology colleagues have been doing for 15 years, using individual biology to target disease,” Ridker said. “It is time for cardiology to follow their lead.”

Data from the Biomarker for Cardiovascular Risk Assessment in Europe consortium suggest that serum metabolites could become the next generation of prognosticators and predictors for coronary heart disease.

Serum Metabolomic Profiles Predict Coronary Heart Disease in the General Population  (BiomarCaRE) is the largest population-based study evaluating the value of metabolites in coronary heart disease. BiomarCaRE combined six European population studies to create a cohort of 10,741 individuals that included 2,166 individuals with coronary heart disease. The full BiomarCaRE population includes more than 300,000 individuals from over 30 cohorts with up to 28 years of follow-up.

“Metabolites are good candidates for biomarkers because they reflect genomic changes in individuals and indicate changes in phenotypes,” said Tanja Zeller, PhD, professor of genomics and systems biology at the University of Hamburg in Germany. “In our cohort of middle-aged, largely healthy individuals, we found four metabolites that are significantly associated with coronary heart disease.”

The four metabolites are phosphatidylcholines, lipoproteins that play important roles in membrane function and signaling. All four metabolites have an inverse relationship with coronary heart disease. Lower metabolite levels increase risk while higher metabolite levels are protective. The predictive strength of metabolite biomarkers is similar to classical risk factors such as lipid levels, hypertension, smoking, obesity and diabetes.

More research and validation is needed before serum metabolites are ready for clinical use, she said. But the BiomarCaRE results demonstrate the value of metabolomics to develop novel biomarkers and improve risk stratification.

A third late-breaking science presentation found that clinicians do not routinely use the one biomarker that is available to predict clinical response to antiplatelet therapy in stroke and cardiovascular care.

An update to the P2Y12 Inhibitor Switching in Response to Routine Notification of CYP2C19 Clopidogrel Metabolizer Status Following Acute Coronary Syndromes (GEMINI-ACS-1) trial found that switching between P2Y12 inhibitors based on the result of pharmacogenomics testing for reduced or enhanced function alleles of CYP2C19 is not common.

Clopidogrel currently carries a black box warning that recommends CYP2C19 testing because patients with reduced function alleles have higher platelet reactivity and a potentially higher risk of ischemic events, especially following PCI. Only 6.5 percent of patients in the trial switched P2Y12 inhibitors, and most of the switches were unrelated to CYP2C19 metabolizer status.

“GEMINI looked at clinical outcomes for rivaroxaban versus aspirin with either clopidogrel or ticagrelor,” said E. Magnus Ohman, MD, professor medicine and member of the Duke Clinical Research Institute in Durham, North Carolina. “This update looks at the impact of mandatory CYP2C19 metabolizer status testing and reporting on switching, especially from clopidogrel to ticagrelor.”

A central lab reported CYP2C19 status for 99 percent of the 3,037 patients in the trial. About 1,700 patients were on ticagrelor and 1,300 were on clopidogrel. The study protocol made no recommendations to investigators with regard to which anti-platelet agent to use or about switching between agents based on CYP2C19 metabolizer status or other factors.

In the total study population, 34.4 percent were ultra metabolizers of clopidogrel, 37.8 percent were extreme metabolizers, 25.5 percent were intermediate metabolizers and 3.2 percent were reduced metabolizers.

Before randomization and CYP2C19 status testing, about half of investigators said they would switch reduced metabolizers from clopidogrel to ticagrelor. But after test results were reported, only 4 percent of clopidogrel patients switched to ticagrelor, Ohman reported. The majority of the switches — 57 percent — were related to bleeding and other adverse events or recurrent ischemic events, not to metabolizer status.

“Our findings do not support the utility of mandatory pharmacogenomics testing for P2Y12 inhibitor use because clinicians do not act on it,” Ohman said.

New blood pressure guidelines released

The American Heart Association, along with the American College of Cardiology and nine other associations, released the 2017 Hypertension Clinical Practice Guidelines on Monday, Nov. 13, during Scientific Sessions 2017. This marks the first time the guidelines have been updated since 2003 and the first reclassification of blood pressure since 1993.

The key takeaways from these guidelines focus on how blood pressure is evaluated and measured. The 2017 standards are now defined as:

  • Normal: Less than 120 systolic mm HG; less than 80 diastolic mm HG
  • Elevated: Systolic between 120-129 mm Hg; diastolic less than 80 mm Hg
  • Stage 1 Hypertension: Systolic between 130-139 mm HG; diastolic between 80-89 mm HG
  • Stage 2 Hypertension: Systolic at least 140 mm Hg or diastolic at least 90 Hg
  • Hypertensive crisis: Systolic over 180 mm Hg and/or diastolic over 120 mmHg

Previously, high blood pressure was defined as readings greater than 140 for the systolic measurement and greater than 90 for the diastolic measurement.

“It’s a new system,” says Paul Whelton, MB, MD, MSc, lead author of the guidelines, which were published in the American Heart Association journal Hypertension and in the Journal of the American College of Cardiology.

“It will take a while to get used to it, but I think it’s the right system. It will capture those at risk better than our former system,” he says, in the AHA video “Understanding the 2017 Hypertension Guidelines.”

The category of prehypertension has been eliminated. Individuals who were previously classified with prehypertension will now be categorized as having either elevated blood pressure or Stage 1 hypertension. Individuals previously diagnosed with hypertension will now fall into the Stage 2 hypertension category.

Why the change in nomenclature? “We didn’t like the previous term (prehypertension) because it suggests that you’re still OK. You’re ‘pre’ hypertension. You don’t have it yet,” explains Whelton. “It’s clear from the information that’s available now that you’re not normal. You’re in that Stage 1 category at about twice the risk for a heart attack as somebody with a normal blood pressure. That’s why we changed it.”

The change in categories is expected to triple the number of men under 45 who have high blood pressure and double the number of women under 45. However, this change isn’t expected to lead to a large increase in the number of individuals prescribed blood pressure medications. Instead, individuals affected at the lower end of the scale will be encouraged to make lifestyle changes to lower their numbers.

The guidelines introduce new methods to evaluate blood pressure. An individual’s blood pressure measurement needs to be based on an average of two or three readings on at least two different occasions. Individuals are strongly encouraged to take their own blood pressure at home using a validated device. This monitoring can reveal “masked hypertension,” where blood pressure registers as normal in a clinical setting but higher at home.

The guidelines will work best with an implemented team approach between clinicians and patients. According to Whelton, “The patient is really important in all aspects of diagnosis, understanding the true exposure of the body to blood pressure and, then of course, in the therapy of those who have high blood pressure.”

Other guideline changes include:

  • Only prescribing medication for Stage 1 hypertension if a patient has already had a cardiovascular event or is at risk of heart attack or stroke based on age or the presence of certain diseases
  • As many individuals will need multiple medications to manage their blood pressure, medications will need to be combined into a single pill so as to encourage individuals to take the pill consistently
  • Identifying socioeconomic status and psychosocial stress as risk factors for high blood pressure

The 2017 Hypertension Clinical Practice Guidelines are based on a study involving 21 multidisciplinary groups that evaluated more than 900 studies. Click here to watch the complete video of Whelton discussing the guidelines with John Warner, MD, president of the American Heart Association. The complete guidelines manuscript is available online, as well.

Fogarty celebrates 50 years

On July 1, 1968, President Lyndon Johnson signed an Executive Order that established the John E. Fogarty International Center for the Advanced Study in the Health Sciences at the National Institutes of Health. Since then, the Fogarty Center has grown to involve 5,000 scientists and impacts more than 100 countries.

To celebrate the center’s 50 years, a special half-day symposium was held on Tuesday, Nov. 14, during AHA Scientific Sessions 2017. Titled “Fogarty, NHLBI, NIH and the Future of Global Cardiovascular Health Research,” the symposium showcased both the ongoing and future programs at the center that promote the global health agenda and encouraged young academics to pursue global health research in their own specialties.

Dorairaj Prabhakaran, MD, DM, MSc, FRCP, FNASc, from New Delhi, India, presented the keynote address. Prabhakaran spoke about global cardiovascular research and training to achieve global heart health goals.

The symposium was divided into two additional sessions. One session explored priority research and research methods for global cardiovascular health, including healthcare funding and policy; heart failure in sub-Saharan Africa; and big data in global health. The second session examined topics related to early career global cardiovascular research, with examples provided from Kenya, India and Malawi.

HealthTech competition showcases innovations

The popular HealthTech competition returned to AHA Scientific Sessions 2017 on Monday, Nov. 13. Eight medical start-up companies demonstrated their products and services as they competed for the Judge’s Award and the Audience Choice Award. Each company presented to a panel of judges representing distinguished cardiologists, venture capitalists and industry thought leaders, as well as attendees in the Science & Technology Hall.

Admetsys, the Judge’s Choice winner, uses high-tech connected health care to real-time measure, model and treat patients. Its product is an artificial pancreas for hospital and surgical care, leveraging adaptive learning algorithms and counterbalancing treatment of insulin and glucose.

The Audience Choice award went to Procyrion. Its product, Aortix, is a minimally invasive cathether-deployed heart pump for heart failure patients who are too sick for medication alone.

The other finalists and their demonstrations were:

  • AMICOMED — a fully digital platform for blood pressure management
  • Bodyport — comprehensive cardiovascular data in one simple step
  • MobioSense — a product to prevent and detect heart attacks with portable HERO in 10 minutes
  • Play-it Health — personalized software and services for sustainable adherence to health regimens
  • Tasso Inc. — HemoLink, a user-friendly way to self collect blood
  • TupeloLife — connected health solutions for home including hardware, software and services

Simulation Zone offers hands-on learning

During AHA Scientific Sessions 2017, attendees were able to sharpen their skills via four hands-on demonstration areas in the Simulation Zone. Each of the areas focused on a different area of cardiac knowledge, skills and critical thinking.

The simulations offered were:

  • Body Interact. This screen-based 3-D immersive training platform virtualized acute and chronic medical conditions with a lifelike virtual patient. The simulation included dynamic monitoring, dialoguing, diagnostic tests, medications, imaging, intervention options and performance debriefing.
  • Cardiovascular Interventional Simulation. Multiple sessions focused on basic through advanced skills in the areas of coronary interventional, electrophysiology, valvular heart disease and peripheral artery disease. Attendees had the opportunity to practice a wide range of procedures under the guidance of expert clinicians, plus have hands-on experience using various interventional equipment such as guidewires, diagnostic catheters, transcatheter heart valves, pacing electrodes, balloons and stents.
  • Hemodynamic Simulation. This session (formerly the Mechanical Circulatory Support Simulation) featured a total artificial heart mock circulatory loop that provided a hands-on opportunity to model critical scenarios and observe hemodynamic consequences. Both adult and pediatric sessions were offered and included scenarios such as inadequate preload/afterload conditions, chronic heart failure and shock and device obstruction.
  • SimMan Vascular. New to the Simulation Zone for 2017, this activity incorporated a full team training environment from the onset of acute event through recovery. During this immersive simulation, attendees witnessed a variety of invasive skills while focusing on critical time management, decision-making and communication.

Let the learning continue

Whether you missed a session, want to share a session with a colleague or if you simply want to listen to a presentation for a second time, Sessions OnDemand™ Premium is for you. This digital video library contains approximately 400 hours of presentations given at AHA Scientific Sessions 2017.

Available online or via a USB drive, Sessions OnDemand™ delivers slides with synchronized audio, PDFs of presentations and MP3 audio files. You can even earn CME credits for watching a session then clicking on the CME Test button. Additionally, access is available from any computer, tablet or smartphone.

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Opportunities abound in 2018

Stethoscope on chartLearn the latest in cardiovascular and cerebrovascular science. Network with your peers. Explore related products and services. You can do this — and more — when you attend these American Heart Association/American Stroke Association conferences in 2018. Mark your calendar now. We’ll see you there!

International Stroke Conference 2018
Pre-conference and nursing symposium: Jan. 23
Jan. 24-26
Los Angeles

March 20-23
New Orleans

April 6-7
Arlington, Virginia

May 10-12
San Francisco

July 30-Aug. 2
San Antonio, Texas

Sept. 6-9

Scientific Sessions
Nov. 10-14