Gaganpreet Kaur is a postdoctoral research fellow at Brigham and Women’s Hospital. Her work focuses on stress signaling and its role in cardiovascular diseases.  In addition to bench work, she is passionate about science communication and enjoys every opportunity to improve her writing. Twitter: @Gaganpr39635338
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Lilly’s MounjaroTM (Tirzepatide): A New Sheriff in Town

Gaganpreet Kaur

The prevalence of diabetes is increasing at an alarming rate, with more than 34 million Americans suffering from diabetes1. Patients with type 2 diabetes make up 90% to 95% of total diabetes cases1. Type 2 diabetic patients either do not produce enough insulin or develop insulin resistance, resulting in elevation of their blood glucose levels2. The U.S. Food and Drug Administration (FDA) recently, as an adjunct to diet and exercise, approved Eli Lilly and Company’s MounjaroTM (tirzepatide) injection (under the skin, once a week) for Type 2 diabetic patients to control hyperglycemia.  Mounjaro will be offered in 6 different doses, 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg, in an auto-injected pen with a pre-attached hidden needle. However, Mounjaro has not been designated to use in Type 1 diabetic patients and is not yet tested for patients with pancreatitis or children under 18 years of age3.

Mechanism of Action of MounjaroTM (tirzepatide):

Eli Lilly and Company’s new drug is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor. GIP and GLP-1 are incretin hormones that are released from intestine upon ingestion of food. GLP-1 stimulates the release of insulin from beta cells of pancreas, increases the number and volume of beta cells, and decreases the levels of glucagon, a hormone also released by pancreas that instructs the liver to release stored glucose in the circulation2. Similarly, GIP also fuels insulin release, promotes beta cell production, and prevents destruction of beta cells2. In Type 2 diabetes, patients do not respond properly to incretin hormones. Mounjaro battles this issue by triggering the activation of GIP and GLP-1 receptor2.

Side Effects of MounjaroTM (tirzepatide):

The most common reported side effects, in at least 5% of patients, are nausea, diarrhea, reduced appetite, vomiting, constipation, indigestion, and abdominal pain. Mounjaro may cause severe side effects including hypoglycemia, pancreatitis, allergic reaction, kidney problems, gallbladder problems, and changes in vision. Further, a warning regarding thyroid cancer is issued; therefore, Mounjaro is not advised to use in patients with personal or family history of Medullary Thyroid carcinoma or Multiple Endocrine Neoplasia Syndrome Type 23.

SURPASS clinical trial program of MounjaroTM (tirzepatide):

The SURPASS trials evaluated the efficacy and safety of Mounjaro for Type 2 diabetes as a monotherapy and as an add-on to other standard care medications. Mounjaro was compared as other injectable medicines like semaglutide (GLP-1 mimic), insulin glargine and insulin degludec. Throughout the five global SURPASS studies, Mounjaro exhibited reduction in A1C among participants having Type 2 diabetes from an average of 5 to 13 years3.

  • SURPASS-1 (NCT03954834): A 40-week study tested the efficacy and safety of three different doses of Mounjaro (5 mg, 10 mg, and 15 mg) as monotherapy in comparison to placebo in Type 2 diabetic patients (naïve to injectable therapy and utilizing diet and exercise alone). Researchers reported that tirzepatide reduced A1C by 1.8% (with 5 mg) and 1.7% (with 10 mg and 15 mg) as compared to 0.1% with placebo. Further, participants lost weight on an average of 14 lb. (5 mg), 15 lb. (10 mg), and 17 lb. (15 mg) whereas participants in placebo group only lost 2 lb3,4.
  • SURPASS-2 (NCT03987919): In this 40-week study, participants were divided in 1:1:1:1 ratio to receive 5 mg, 10 mg, or 15 mg tirzepatide or 1 mg of semaglutide. Mounjaro reduced A1C by 2.0% (5 mg), 2.2% (10 mg) and 2.3% (15 mg) and semaglutide reduced A1C by 1.9%. In a key secondary endpoint, participants in Mounjaro group lost weight by a mean of 17 lb. (5 mg), 21 lb. (10 mg) and 25 lb. (15 mg) in comparison to 13 lb. reduced by semaglutide3,5.
  • SURPASS-3 (NCT03882970): A 52-week study compared the efficacy of previous doses of Mounjaro to insulin degludec (insulin analogue) as an add on to metformin with and without SGLT2 inhibitors. The trial reported 1.9% (5 mg), 2.0% (10 mg) and 2.1% (15 mg) reduction in A1C in patients receiving tirzepatide as compared to 1.3% reduction in patients receiving insulin degludec. Interestingly, participants on Mounjaro lost 15 lb. to 25 lb. depending on the dose, but participants taking insulin degludec gained an average of 4 lb3,6.
  • SURPASS-4 (NCT03730662): A 104-week study compared the efficacy of Mounjaro (5 mg, 10 mg, 15 mg) to insulin glargine in Type 2 diabetic patients with increased risk of cardiovascular disease. Researchers observed a 2.1% (5 mg), 2.3% (10 mg) and 2.4% (15 mg) reduction in A1C in patients receiving tirzepatide as compared to 1.4% reduction in patients receiving insulin glargine. Participants on Mounjaro lost weight (14 lb. with 5 mg, 20 lb. with 10 mg, and 23 lb with 15 mg), whereas insulin glargine group gained 4 lb3,7.
  • SURPASS-5 (NCT04039503): In this 40-week study, the efficacy and safety of Mounjaro as an add on drug to insulin glargine was compared to placebo. An average of 2.1% (5 mg), 2.4% (10 mg) and 2.3%* (15 mg) reduction was observed in Mounjaro group as compared to 0.9% in placebo group. Further, Mounjaro, as an add on drug, reduced body weight by 12 lb. to 19 lb. as compared to placebo group, where participants experienced 4 lb. weight gain3,8.

REFERENCE

  1. National Diabetes Statistics Report. Accessed January 14, 2022. https://www.cdc.gov/diabetes/data/statistics-report/index.html
  2. FDA approves trizepatide: A potent new drug for type 2 diabetes. Accessed May 20, 2022. https://www.medicalnewstoday.com/articles/fda-approves-tirzepatide-a-potent-new-drug-for-type-2-diabetes
  3. FDA arrpvoves Lilly’s MounjaroTM (tirzepatide) injection, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes. Accessed May 20, 2022. http://lilly.mediaroom.com/2022-05-13-FDA-approves-Lillys-Mounjaro-TM-tirzepatide-injection,-the-first-and-only-GIP-and-GLP-1-receptor-agonist-for-the-treatment-of-adults-with-type-2-diabetes
  4. Rosenstock J, Wysham C, Frías JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 07 10 2021;398(10295):143-155. doi:10.1016/S0140-6736(21)01324-6
  5. Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 08 05 2021;385(6):503-515. doi:10.1056/NEJMoa2107519
  6. Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 08 14 2021;398(10300):583-598. doi:10.1016/S0140-6736(21)01443-4
  7. Del Prato S, Kahn SE, Pavo I, et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 11 13 2021;398(10313):1811-1824. doi:10.1016/S0140-6736(21)02188-7
  8. Dahl D, Onishi Y, Norwood P, et al. Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 02 08 2022;327(6):534-545. doi:10.1001/jama.2022.0078

“The views, opinions, and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness, and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions, or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your health matters. If you think you are having a heart attack, stroke, or another emergency, please call 911 immediately.”
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COVID-19 and Endothelial Cell Dysfunction

Gaganpreet Kaur

Photo by CDC on Unsplash

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a global health crisis. Cough, fever, and shortness of breath are the most common reported symptoms; however, neurological and gastroenterological manifestations can also be present1. Angiotensin-converting enzyme 2 (ACE-2) has been shown to act as a co-receptor to facilitate coronavirus entry by efficiently binding to the S1 domain of spike protein, a surface glycoprotein of SARS-CoV2. The pathogenesis of COVID-19 depends on the localization of the coronavirus co-receptors. The epithelium of lungs and intestine is rich in ACE-2 expression, thereby providing a possible route of entry for SARS-CoV-2. Further, ACE-2 is also expressed on Type I and type II pneumocytes providing other entry sites for SARS-CoV-2. Virus entry can cause pathological changes at the alveoli-capillary interface. Additionally, copious expression of ACE-2 on the type II alveolar cells can promote rapid viral expansion resulting in further alveolar damage and hyperinflammation3,4.

ACE-2 is also present on endothelial cells, smooth muscle cells, and perivascular pericytes in all the organs, indicating that if SAR-COV-2 is transmitted to the blood circulation, the virus can quickly spread throughout the body3. The postmortem lung tissues of COVID-19 patients exhibited a higher number of ACE-2 positive endothelial cells and a higher prevalence of endothelial injury (disruption of cell membrane and presence of the intracellular virus) and microthrombi than lung tissues of patients who died from influenza-associated respiratory failure1,5. The most common comorbidities observed in COVID-19 patients are hypertension, diabetes, and obesity, all of which are associated with endothelial dysfunction. Further, COVID-19 patients are projected to be at a higher risk of deep vein thrombosis, systemic vasculitis, and acute pulmonary embolism6,7, possibly due to underlying endothelial cell injury and inflammation. Thrombi can directly affect gas exchange and cause and cause multisystem organ dysfunction in COVID-19 pneumonia8. Upon activation, platelets release polyphosphates, which accelerate the activation of factors V and XI, inhibit tissue factor pathway inhibitor and contribute to thicker fibrin strands synthesis. Further, the cytokine release can activate endothelial cells resulting in a prothrombotic environment1.

Acute respiratory distress syndrome is suggested to be caused by the dissociation between lung mechanics, loss of lung perfusion regulation and hypoxic vasoconstriction, and severe hypoxemia9. The loss of hypoxic vasoconstriction can be due to increased mitochondrial oxidative stress resulting in pulmonary endothelial cell dysfunction10. SARS-CoV-2 elements, accumulation of inflammatory cells, intracellular virus, and disrupted cell membranes are detected in the endothelial cells of COVID-19 patients5,11, further indicating endotheliitis /endothelial cell dysfunction during COVID-19 infection. Endothelial cell dysfunction can cause abnormalities in microcirculation in different vascular beds and contribute to life-threatening complications of COVID-19, including thromboembolism and multiple organ damage.

References:

  1. Huertas A, Montani D, Savale L, et al. Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)? Eur Respir J. 07 2020;56(1)doi:10.1183/13993003.01634-2020
  2. Ziegler CGK, Allon SJ, Nyquist SK, et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. 05 28 2020;181(5):1016-1035.e19. doi:10.1016/j.cell.2020.04.035
  3. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. Jun 2004;203(2):631-7. doi:10.1002/path.1570
  4. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 03 28 2020;395(10229):1033-1034. doi:10.1016/S0140-6736(20)30628-0
  5. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 07 09 2020;383(2):120-128. doi:10.1056/NEJMoa2015432
  6. Bompard F, Monnier H, Saab I, et al. Pulmonary embolism in patients with COVID-19 pneumonia. Eur Respir J. Jul 2020;56(1)doi:10.1183/13993003.01365-2020
  7. Criel M, Falter M, Jaeken J, et al. Venous thromboembolism in SARS-CoV-2 patients: only a problem in ventilated ICU patients, or is there more to it? Eur Respir J. Jul 2020;56(1)doi:10.1183/13993003.01201-2020
  8. Poor HD, Ventetuolo CE, Tolbert T, et al. COVID-19 critical illness pathophysiology driven by diffuse pulmonary thrombi and pulmonary endothelial dysfunction responsive to thrombolysis. Clin Transl Med. Jun 2020;10(2):e44. doi:10.1002/ctm2.44
  9. Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. COVID-19 Does Not Lead to a “Typical” Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 05 15 2020;201(10):1299-1300. doi:10.1164/rccm.202003-0817LE
  10. Guignabert C, Phan C, Seferian A, et al. Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension. J Clin Invest. 09 01 2016;126(9):3207-18. doi:10.1172/JCI86249
  11. Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 05 02 2020;395(10234):1417-1418. doi:10.1016/S0140-6736(20)30937-5

“The views, opinions, and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness, and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions, or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your health matters. If you think you are having a heart attack, stroke, or another emergency, please call 911 immediately.”
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How Poster Presentations Are Vital to the Conference

Gaganpreet Kaur

The poster presentation provides an excellent platform to communicate research findings and promote networking visually. Poster presentation helps make clever use of time and space for scientific discussion among conference attendees, thus are beneficially for both presenter and the conference organizer1,2. The outbreak of COVID-19 dramatically changed our lives, especially traveling and gatherings. With most scientific conferences online or hybrid, we now have an option of “e-posters”. Instead of printing your poster, you can submit a PDF version and insert a 2 to 5 minutes long video discussing your poster. In my opinion, e-posters are more beneficial as they allow you to share your work from the comfort of your home. Besides, speaking from personal experience, you can present your work at more conferences and across the borders without worrying about funding.

What are the benefits of poster/e-poster presentation, and why should you consider doing it?1

  1. Posters offer the opportunity to network and communicate with other attendees from your field, leading to collaborations and job offers. My own postdoctoral offer results from a conversation during a poster session.
  2. Due to time constraints and limited slot availability, not every trainee receives a chance for oral presentation. However, poster session allows a vast majority of trainees to share their work. Besides, question & answer session for oral presentation is typically 5 to 10 minutes and does not allow in-depth conversations. Conversely, poster sessions usually last a couple of hours, thus providing a platform for more extended discussion without time constraints.
  3. You can discuss specific aspects of your research receive detailed critiques, and impartial discussion/review by peers that can help you improve your work, ideas, or potential manuscripts. It can even provide you a new direction for your project.
  4. Poster presentations are an excellent platform to improve your presentation skills. One advantage is that those poster sessions allow you to explain your research differently. You can present as short as 3 minutes but can go up to 15-20 minutes. You also learn to communicate your work visually and verbally to a broader audience.
  5. In my opinion, abstracts and poster presentations are one of the ways to show your potential employees that you are active in the scientific community and participate in the meeting. Besides, almost all the conferences have poster awards thus, you have an opportunity to keep a feather in your cap or, should I say, resume.

What are some of the things to keep in mind for poster/e-poster presentation? 

Remember, the poster’s purpose is to visually communicate the latest research in a quick, efficient, and effective manner2. One should design your poster considering the readers and venue, especially doing an e-poster. Most people will view e-poster from their laptop screen; therefore, font size needs to be adjusted so that they don’t have trouble reading. Besides, a person might stop on your poster for less than a minute before deciding whether to engage in in-depth conversation or not. Therefore, I cannot emphasize enough the inclusion of graphical abstract, and your overall poster should synchronize as an illustrated abstract of your work. For more tips for designing a poster, please read a detailed article by Dr. Adam M. Persky2.

Two personal tips, something I learned over the year, are that:

  1. Don’t hesitate to invite people to your poster, especially when doing an e-poster. I have had valuable input to my projects from every person I invited to my e-poster. It helped me build my network too.
  2. Prepare your talk based on your audience. Suppose you attend a general regional conference, where people from all fields of science like engineering and biology are coming. In that case, you should be ready with a layman summary of your work so that people from other fields can understand your work. However, if you are going to conferences focused on your area of research, then you can include detailed results.

What are Vascular Discovery 2022 abstract submission categories?

  • Aortic Aneurysm Disease
  • Apolipoproteins and Lipid Metabolism
  • Blood Coagulation, Platelet Function and Antithrombotic Therapy
  • Cardiovascular Precision Medicine
  • COVID-19
  • Functional Genomics and Epigenetics in Vascular Disease
  • Immune Mechanisms of Atherosclerosis
  • Immunity and Inflammation in Vascular Biology
  • Metabolic Disorders and Atherosclerosis
  • Molecular and Cellular Mechanisms of Atherosclerosis
  • Molecular, Developmental and Cellular Biology of Vessel Wall
  • Peripheral Artery Disease, Carotid Artery Disease and Stroke
  • Population Science and Genetics in Vascular Discovery
  • Sex Differences in Cardiovascular Disease
  • Therapeutic Targets in Atherosclerosis
  • Venous Thromboembolism and Lymphatic Disease

What are the Vascular Discovery 2022 poster award categories?

  • Kenneth M. Brinkhous Young Investigator Prize in Thrombosis and the Irvine H. Page Young Investigator Research Award: Finalists will receive a chance to present oral abstracts during the meeting, and winners will be announced during council dinner. The Brinkhaus Prize recognizes outstanding endeavors in thrombosis, whereas the Page Award encourages investigators to continue careers in arteriosclerosis and vascular biology. Both awards are aimed to recognize new investigators.
  • ATVB Emerging Scientist Award for Women is sponsored by the ATVB Women’s Leadership Committee and recognizes excellent research conducted by women in the field of arteriosclerosis, thrombosis, and vascular biology. The finalists will present their abstracts during the poster session, give a 2-minute rapid-fire presentation during the Mentor of Women Award Luncheon, and the winner will be announced during the Council Dinner.
  • ATVB Investigators in Training Award recognizes pre-doctoral and postdoctoral in arteriosclerosis, thrombosis, and vascular biology who are members of the ATVB Council. The finalists will present their poster abstracts, and the winner will be announced at the Council Dinner.
  • ATVB Diversity Outreach Travel Grants encourages minority, early career investigators and students, to participate in the Vascular Discovery: From Genes to Medicine Scientific Sessions
  • 2 awards sponsored by the PVD Council (these are not competitions, and the winners will be recognized during the Council Dinner):
    • The Alan T. Hirsch, MD Mid-Career Award in Vascular Medicine supports mid-career level investigators studying the peripheral vascular disease. This award encourages participation in the PVD Council and AHA activities by providing travel funds to attend the Vascular Discovery: From Genes to Medicine Scientific Sessions, present research in oral or poster format, and engage in discussion with senior investigators.
    • The Robert W. Hobson, II, MD Early Career Investigator Award recognizes excellence in basic or clinical science in early career investigators in vascular and endovascular medicine, vascular surgery, or vascular biology.

Registration for the Vascular Discovery Conference is now open. Advance pricing opens on 4/1.  Register now for the best price!

REFERENCE

  1. Lab O. 7 reasons why you should present posters at a conference. Accessed March 20, 2022. https://people.clas.ufl.edu/oppenhe/2014/06/09/7-reasons-why-you-should-present-posters-at-a-conference/
  2. Persky AM. Scientific Posters: A Plea from a Conference Attendee. Am J Pharm Educ. Dec 25 2016;80(10):162. doi:10.5688/ajpe8010162

“The views, opinions, and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness, and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions, or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your health matters. If you think you are having a heart attack, stroke, or another emergency, please call 911 immediately.”
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Climate Change and Cardiovascular Diseases

Gaganpreet Kaur

Climate change is partly due to the increased atmospheric concentration of greenhouse gases emitted by burning fossil fuels like oil, natural gas, and methane produced by ruminant agricultural animals. The earth’s temperature has augmented by 0.85°C in the last century, and the rate of global warming has increased to 0.18°C/decade in the last three decades. The altering temperature, in particular increasing heat, is one of the critical features of climate change and can significantly affect cardiac health. In addition, extreme weather events, rising sea levels, and lack of food and water are expected outcomes of climate change1.

Cardiovascular Diseases (CVDs) are the leading cause of death globally, and climate change can worsen CVD incidence further. Heatwaves are expected to be more frequent and prolonged due to ongoing climate change. The intense heat can cause mortality and morbidity due to heatstroke, which is defined as hyperthermia associated with a systemic inflammatory response resulting in multiple organ failure and predominant encephalopathy. Heat stress is associated with acute cardiac events where heated blood circulates in peripheral circulation, and heat tolerance is impaired due to insufficient cardiac output to meet the body’s needs for sufficient heat loss1.

There is a U-shaped relationship between temperature and all-cause mortality where mortality increases with the shift from ‘optimum temperature’ at both cold and hot ends. In the Netherlands, the lowest mortality rate was observed with an average temperature of 16.5°C, and CVD mortalities accounted for 57% of cold-related death2. In 1976, daily deaths from coronary thrombosis increased two-fold during the London heatwave3. Additionally, daily mortality due to congestive heart failure is strongly associated with maximum daily temperature in Montreal, with an exponential increase starting at 25°C4. Similarly, during comparatively hotter summer, a U-shaped relationship between outer temperature and coronary artery disease deaths is reported in Taiwan5.

Lifestyle modifications on a large population scale are required to reduce the emission of greenhouse gases, thereby mitigating the extent of climate change. Reducing the use of motor vehicles for short-distance commuting can help reduce the emissions of greenhouse gases related to transportation and air pollution that can have adverse effects on health. Further, reducing the consumption of ruminant meat such as sheep and cows and increasing the use of renewable energy, including solar radiation or wind power, can help mitigate climate change, air pollution, and the risks of heart diseases1.

Another essential remedy to diminish climate change can be ‘active transport or self-transport that encompasses more physical activity and involves walking, cycling, and use of public transport as a mode of transportation. This will not only reduce the emanation of greenhouse gases but increased physical activity can confer several cardiac health benefits1. An extra kilometer walk is associated with a 4.8% reduction in risk of obesity which is a significant risk factor of CVD, whereas an extra hour spent in car/day is lined with a 6% increase in the likelihood of obesity6. Additionally, a study done in Finland reported a significant reduction in CVD risk and all-cause mortality in women who walked or cycled 15 minutes or more for work7.

In conclusion, we need to modify our lifestyle and make healthier choices to protect our hearts and earth. If you are further interested in the topic, you can get a detailed insight in the review article published in the Cardiology journal1 titled “The effects of climate change on cardiac health”.

 REFERENCE

  1. De Blois J, Kjellstrom T, Agewall S, Ezekowitz JA, Armstrong PW, Atar D. The Effects of Climate Change on Cardiac Health. Cardiology. 2015;131(4):209-17. doi:10.1159/000398787
  2. Kunst AE, Looman CW, Mackenbach JP. Outdoor air temperature and mortality in The Netherlands: a time-series analysis. Am J Epidemiol. Feb 01 1993;137(3):331-41. doi:10.1093/oxfordjournals.aje.a116680
  3. Keatinge WR, Coleshaw SR, Easton JC, Cotter F, Mattock MB, Chelliah R. Increased platelet and red cell counts, blood viscosity, and plasma cholesterol levels during heat stress, and mortality from coronary and cerebral thrombosis. Am J Med. Nov 1986;81(5):795-800. doi:10.1016/0002-9343(86)90348-7
  4. Kolb S, Radon K, Valois MF, Héguy L, Goldberg MS. The short-term influence of weather on daily mortality in congestive heart failure. Arch Environ Occup Health. 2007;62(4):169-76. doi:10.3200/AEOH.62.4.169-176
  5. Pan WH, Li LA, Tsai MJ. Temperature extremes and mortality from coronary heart disease and cerebral infarction in elderly Chinese. Lancet. Feb 11 1995;345(8946):353-5. doi:10.1016/s0140-6736(95)90341-0
  6. Frank LD, Andresen MA, Schmid TL. Obesity relationships with community design, physical activity, and time spent in cars. Am J Prev Med. Aug 2004;27(2):87-96. doi:10.1016/j.amepre.2004.04.011
  7. Barengo NC, Hu G, Lakka TA, Pekkarinen H, Nissinen A, Tuomilehto J. Low physical activity as a predictor for total and cardiovascular disease mortality in middle-aged men and women in Finland. Eur Heart J. Dec 2004;25(24):2204-11. doi:10.1016/j.ehj.2004.10.009

“The views, opinions, and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness, and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions, or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your health matters. If you think you are having a heart attack, stroke, or another emergency, please call 911 immediately.”
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A Scientific Statement from the American Heart Association on the Management of Cardiovascular Risk Factors for Adults with Type 2 Diabetes

Gaganpreet Kaur

The prevalence of diabetes is increasing at an alarming rate, with more than 34 million Americans suffering from diabetes1. Patients with type 2 diabetes make up 90% to 95% of total diabetes cases1. Cardiovascular diseases (CVD) are the principal cause of death and disability in type 1 and type 2 diabetes patients2. American Heart Association (AHA) recommends a comprehensive and patient-centered approach involving lifestyle management and pharmacological interventions to manage cardiovascular risk factors, such as smoking, obesity, glycemia, blood pressure (BP), and lipid abnormalities, in type 2 diabetes patients3.

A healthy lifestyle can substantially lower the risk of CVD events in type 2 diabetic patients. Lifestyle management involves physical activity, nutrition, psychological and emotional well-being, and smoking cessation3. The lifestyle interventions using meal replacement products and at least 175 minutes of moderate-intensity physical activity /week, with a calorie goal of 1200 to 1800 kcal per day (with <30% from fat and >15% from protein), resulted in weight loss and hemoglobin A1c. Individuals with either ≥10% reduction in their body weight or >2 metabolic equivalent increase in fitness experienced reductions in cardiovascular outcomes; however, the rate of a major adverse cardiovascular event (MACE) was not reduced4. Mediterranean, vegetarian, low-carbohydrate, and diets rich in protein and nuts can lower blood glucose and body weight in type 2 diabetes patients3. Mediterranean diet over 4.8 years exhibited the highest benefits in blood glucose regulation and 29% of CVD events3,5. Further, increased exercise and physical activity can improve blood glucose, blood pressure, insulin sensitivity, lipid profile, and inflammation in type 2 diabetes3. American Diabetes Association (ADA) has recommended more than recommends ≥150 minutes/week of moderate-to-vigorous intensity aerobic activity with no more than 2 days of inactivity in diabetes patients3,6. Including 2-3 sessions/week each of resistance and balance training is also recommended. Further, vigorous activity for a short duration (>75 minutes/week) or interval training is beneficial3,7. Patients with BMI ≥27 kg/m2 can use US Food and Drug Administration (FDA) approved weight loss medication. Orlistat, lorcaserin, liraglutide, naltrexone/bupropion are some of the weight management drugs approved by FDA have demonstrated ability to lower A1c3. Liraglutide at a lower dose can reduce cardiovascular risk in high-risk patients8. However, medicines should be immediately stopped if weight loss after 3 months is less than 5% or any safety concerns arise. Patients with BMI ≥40 kg/m2 or BMI 35.0 to 39.9 kg/m2 with no benefit with nonsurgical methods can consider metabolic surgery3. The long-term effects of weight-loss drugs and metabolic surgery on reducing cardiovascular events are yet to be studied.

Smoking is linked with abnormal lipid profile, worsening of glycemic measures, and increased pro-inflammatory marker in type 2 diabetes. Therefore, cessation of smoking is recommended3. Interestingly, light to moderate alcohol consumption compared to no drinking, particularly wine, has been associated with fewer heart attacks, whereas heavy alcohol consumption increases CVD risk3. Despite the benefits of moderate alcohol intake, non-drinks should not be advised to drink, and adults with diabetes should be mindful of the risk of hypoglycemia, weight gain, and hypertension. No more than 1 drink/day for women and 2 drinks/day for men are recommended3. In America, 12-ounce beer or 5-ounce wine, or 1.5 ounces of distilled spirits are considered as one drink.

In addition to lifestyle management, intensive glycemic control can be valuable to prevent cardiovascular disease events in diabetes patients. Randomized trials involving intensive glucose control using insulin reported a 17% reduction in myocardial infarction (MI), 15% reduction in coronary heart disease, 16% reduction in nonfatal MI, but no effect on stroke or all-cause mortality3. However, tight glucose control increases the two-fold risk of severe hypoglycemia and 47% risk of heart failure3. The research involving intensive glucose control using new anti-hyperglycemic agents is undergoing. Some newer agents are Dipeptidyl peptidase-4 (DPP4) inhibitors, GLP-1 receptor agonists, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. DPP4 inhibitors inhibit the DPP4 enzyme, thereby prolonging the action of incretin hormone GLP-1 and insulinotropic polypeptide, which ultimately results in increased insulin secretion and lower glucose. DPP4 inhibitors agents successfully lowered A1C but showed no reduction in MACE, and one of the agents was associated with an increased risk of heart failure3. GLP-1 receptor agonist stimulates insulin release and slows down gastric emptying to decrease glucose absorption. The intervention with GLP-1 receptor agonists resulted in a significant reduction in MACE, heart attack, stroke, and cardiovascular death; however, it had no beneficial effect on heart failure. The use of GLP-1 receptor agonists is associated with increased heart rate, pancreatitis, pancreatic cancer, thyroid cancer, and retinopathy. SGLT-2 inhibitors limit glucose reabsorption in the renal tubules3. SGLT-2 inhibitors lower the risk of hypertensive heart failure by 27-35%, MACE BY 11%, heart attacks by 11%, and cardiovascular death by 16%. SGLT-2 inhibitors are associated with genital and urinary infections, polyuria, acute kidney injury (with a higher dose), and reduction in bone mineral density3.

CVD risk increases with low and high blood pressure in patients with type 2 diabetes. When initiated at baseline (BP > 140/90 mmHg), Antihypertensive therapy resulted in CVD risk reduction but did not have a robust effect in type 2 diabetes patients compared to patients without diabetes3. ADA does not recommend a specific BP target but suggests risk classification to avoid overtreatment and polypharmacy3. In addition to BP abnormalities, an altered lipid profile is also a central risk factor for CVD in diabetes. The most common lipid abnormalities encountered in diabetes include:

  • Increased serum triglycerides.
  • Triglyceride-rich, very-low-density lipoprotein.
  • Mild increase in small dense low-density lipoprotein cholesterol (LDL-C).
  • Decreased HDL-C.

The lipid therapies include lowering LDL with statin/ non-statin, lowering triglycerides, and increasing HDL. Statin therapies reduce cardiovascular risk by 25%9, but HDL raising therapies had no effect3.

Lastly, clinical care only accounts for 10-20% of health outcomes; the rest 80-90% is contributed by social determinants, including socioeconomic factors, racism, environment, and individual behavior3. Therefore, we need a multifaced approach to address social determinants to eliminate disparities in CVD health. AHA recommends using a patient-centered approach and considering the patient’s family, community, and society while planning their cardiovascular risk management3. ADA and AHA have initiated a “Know Diabetes by Heart” program to improve CVD and outpatient care of type 2 diabetes patients. The program raises awareness about the link between diabetes and CVD, supports clinicians in patient engagement, and empowers patients3.

 Reference

  1. National Diabetes Statistics Report. Accessed January 14, 2022. https://www.cdc.gov/diabetes/data/statistics-report/index.html
  2. Cheng YJ, Imperatore G, Geiss LS, et al. Trends and Disparities in Cardiovascular Mortality Among U.S. Adults With and Without Self-Reported Diabetes, 1988-2015. Diabetes Care. 11 2018;41(11):2306-2315. doi:10.2337/dc18-0831
  3. Joseph JJ, Deedwania P, Acharya T, et al. Comprehensive Management of Cardiovascular Risk Factors for Adults With Type 2 Diabetes: A Scientific Statement From the American Heart Association. Circulation. Jan 10 2022:CIR0000000000001040. doi:10.1161/CIR.0000000000001040
  4. Fox CS, Golden SH, Anderson C, et al. Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence: A Scientific Statement From the American Heart Association and the American Diabetes Association. Circulation. Aug 25 2015;132(8):691-718. doi:10.1161/CIR.0000000000000230
  5. Esposito K, Maiorino MI, Bellastella G, Chiodini P, Panagiotakos D, Giugliano D. A journey into a Mediterranean diet and type 2 diabetes: a systematic review with meta-analyses. BMJ Open. Aug 10 2015;5(8):e008222. doi:10.1136/bmjopen-2015-008222
  6. Association AD. 5. Facilitating Behavior Change and Well-being to Improve Health Outcomes:. Diabetes Care. 01 2020;43(Suppl 1):S48-S65. doi:10.2337/dc20-S005
  7. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 09 10 2019;140(11):e596-e646. doi:10.1161/CIR.0000000000000678
  8. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 07 28 2016;375(4):311-22. doi:10.1056/NEJMoa1603827
  9. de Vries FM, Denig P, Pouwels KB, Postma MJ, Hak E. Primary prevention of major cardiovascular and cerebrovascular events with statins in diabetic patients: a meta-analysis. Drugs. Dec 24 2012;72(18):2365-73. doi:10.2165/11638240-000000000-00000

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”
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Fruits, Vegetables, Wholegrains, Plant proteins, and your Heart

Gaganpreet Kaur

Cardiovascular diseases (CVD) are the leading cause of death in Western countries and accounts for 17.3 million deaths/year globally1. In the United States, one in every three deaths are caused by CVD, and more than 130 million adults are projected to express CVD by 2035 clinically1. The unhealthy diet and physical inactivity, obesity, stress, smoking, and alcohol consumption are major risk factors for CVD development1. Nutrition has been reported to be the most preventable risk factor of CVD death1,2. Further, a healthy diet is crucial for managing body weight, diabetes, and hypertension1,3. Therefore, it is essential to identify foods and dietary patterns beneficial for cardiovascular health.

AHA 2021 Dietary Guidance to Improve Cardiovascular Health was presented for the first time by Dr. Alice Lichtenstein, a lead scientist at Tufts University, at #AHA21 scientific sessions and was recently published in Circulation4. AHA suggests that instead of emphasizing one food/nutrient, one should focus on dietary patterns that are the sum of all foods and beverages consumed4. The dietary habits can be adapted to personal preferences, ethical/religious practices, and life stages so that healthy patterns can be followed in the long run4. A heart-healthy diet promotes a healthy planet, meets essential nutrients and fiber requirements, and benefits stroke, type 2 diabetes, kidney disease, and cognitive function4. AHA 2021 Dietary Guidance is organized in following ten features:

 

  1. Adjust energy balance to achieve and maintain healthy body weight.
  2. Include plenty and a variety of fruits and vegetables.
  3. Pick food made with whole grains rather than refined grains.
  4. Choose healthy protein sources, mostly plants, fish, and seafood, and low-fat/fat-free dairy products. If meat or poultry is desired, replace red and processed meat with lean cuts and unprocessed form.
  5. Use liquid plant oils rather than tropical oils and trans-fat.
  6. Choose minimally processed foods.
  7. Minimize consumption of beverages and foods with added sugars.
  8. Consume food prepared with no or little salt.
  9. Limit intake of alcohol. If you do not drink alcohol, do not start.
  10. Adhere to this guidance regardless of where food is prepared or consumed,

 

However, is it easy for everyone to follow a heart-healthy diet? Our food environment is an essential element when we talk about diet quality and can make it difficult for people to adhere to heart health guidelines. Although diet quality improved from 1999 to 2012, disparities are evident based on race/ ethnicity, education, and income5. Dr. Maya Vadiveloo, assistant professor at the University of Rhode Island, explained that the food environment mainly consists of:

  1. Regulatory environment (federal, state, and local practices, and food marketing).
  2. Physical environment (places we eat, live, and acquire food).
  3. Social environment (family and peers).
  4. Individual choices.

She further explained that several state and federal policies, structural racism, neighborhood segregation, unhealthy built environments impede the adaption to a healthy diet. Furthermore, availability, price, and varied access make choosing unhealthy and processed food easier4. Federal food assistance programs, including Supplemental Nutrition Assistance Program (SNAP) and the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), are not universally effective and only cover a fraction of the monthly household supply4. Food companies tend to target low-income and racial minorities households. High processed food and beverages are telecasted more on TV, digital media, and print advertisements4. Dr. Vadiveloo concluded her talk by discussing the concept of precision nutrition which includes the evaluation of genetics, microbiome, dietary intake, and socioeconomic and physical environment to determine the most fruitful dietary plan to prevent and treat disease.  Increased access to affordable housing, enhancing access to supermarkets and green space, and increased access to online food delivery can help achieve dietary goals. She emphasized the power of artificial intelligence, which is unfortunately used for promoting unhealthy food. Still, it can help design personalized dietary interventions, population-level diet quality, and help people choose healthier and medical tailored diets when they buy groceries.

Following this, Dr. Lawrence J Appel, professor at John Hopkins University, explained how a multisector approach including government (regulatory and agriculture policy), health care sector, private sector, and health advocacy organizations is needed to change the default of food sector/eating. Dr. Appel focused on how policy changes can help individuals to eat healthily. In the US, processed and restaurant foods are significant sources (>70%) of sodium6. FDA generated guidance for food manufacturers and restaurants to reduce salt in their processed, packaged, and prepared foods to achieve a 12% reduction in sodium and slash rates of heart diseases7. WHO has generated public food procurement policies that require food and beverages served/sold in a public setting to promote a healthy diet8, indirectly influencing manufacturers to reformulate their products. Although not common in the US, several other countries have front-of-pack warning labels (nutrient specific labels, nurtiscore and guideline daily amount) and health taxes on sugary drinks and salty food. Currently, only New York City requires restaurants to post a warning label next to the menu that contains more than 2300 mg of sodium and applies to restaurants with more than 15 locations nationwide. He concluded his talk by the importance of advocating and supporting policies that improve the health of patients and the broader community.

The last talk of the session was by Dr. Anne N. Thorndike from Massachusetts General Hospital and Harvard Medical school. Dr. Thorndile explained how clinicians and the healthcare sector could help implement 2021 dietary guidelines. She suggested that clinicians emphasize overall nutritional patterns and ask patients about barriers to access and consuming a healthy diet. Further, a clinician can deliver simple patient-centered guidance consistently over time by encouraging fruits/vegetables, plant proteins and oils, whole grains and discouraging the use of added sugars, processed meat, and excess alcohol. Further, hospitals employ approximately 6 million people and treat 750 million people annually. Therefore, many patients are exposed to cafeteria food. Hospitals can opt for traffic-light labels to promote healthy eating where green light suggests choosing often, yellow light means choosing less often, and a red light indicates a better choice available.

There is plethora of scientific evidence present that have helped in building 2021 AHA dietary guidelines. However, we need a multisector approach which will help imply the dietary goals to a larger population.

Reference

  1. Casas R, Castro-Barquero S, Estruch R, Sacanella E. Nutrition and Cardiovascular Health. Int J Mol Sci. Dec 11 2018;19(12)doi:10.3390/ijms19123988
  2. Mozaffarian D, Ludwig DS. Dietary guidelines in the 21st century–a time for food. JAMA. Aug 11 2010;304(6):681-2. doi:10.1001/jama.2010.1116
  3. Lacroix S, Cantin J, Nigam A. Contemporary issues regarding nutrition in cardiovascular rehabilitation. Ann Phys Rehabil Med. Jan 2017;60(1):36-42. doi:10.1016/j.rehab.2016.07.262
  4. Lichtenstein AH, Appel LJ, Vadiveloo M, et al. 2021 Dietary Guidance to Improve Cardiovascular Health: A Scientific Statement From the American Heart Association. Circulation. Dec 07 2021;144(23):e472-e487. doi:10.1161/CIR.0000000000001031
  5. Rehm CD, Peñalvo JL, Afshin A, Mozaffarian D. Dietary Intake Among US Adults, 1999-2012. JAMA. Jun 21 2016;315(23):2542-53. doi:10.1001/jama.2016.7491
  6. Harnack LJ, Cogswell ME, Shikany JM, et al. Sources of Sodium in US Adults From 3 Geographic Regions. Circulation. May 09 2017;135(19):1775-1783. doi:10.1161/CIRCULATIONAHA.116.024446
  7. Edward E. New FDA guidance aims to drastically cut salt in food supply. NBC News. Accessed December 15, 2021. https://www.cnbc.com/2021/10/13/new-fda-guidance-aims-to-drastically-cut-salt-in-food-supply.html
  8. Public Food Procurement and Service Policies for Healthy Diet. WHO. Accessed December 15, 2021. https://apps.who.int/iris/bitstream/handle/10665/338525/9789240018341-eng.pdf

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”
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Cancer Warriors losing battle to heart disease?

Gaganpreet Kaur

Your cancer treatment may be over, but does it continue to cause side effects to your body? Chemotherapy and radiation have revolutionized the survival rates among cancer patients, but so is the development of cardiovascular diseases (CVD) in cancer survivors. The scientific session 2021 program committee organized an educational session on cardio-oncology, which included talks by experts on heart health after cancer treatment, feedback link between heart and cancer, racial disparities, and new clinical imaging technology. The session was moderated by Dr. Susan Gilchrist from Houston, TX, Dr. Daniel Addison from Columbus, OH, and Dr. Mary Branch from Oak Ridge, NC. However, my favorite part was a short talk by Ms. Kikkan Randall, the first American cross-country skier to win Olympic gold along with her teammate. The session walked through the science journey and a patient journey and provided us perspective on a healthy heart from both expert’s and patient’s point of view.

Cardiovascular diseases are the leading non-cancerous cause of death among cancer survivors. Cardiac dysfunction, atherosclerosis, arrhythmia, and valvular diseases are major complications observed among cancer survivors. The first speaker in the cardio-oncology session was Dr. Saro Armenian from the City of Hope Comprehensive Cancer Center. He started by discussing the nature of the problem using the “Multiple-Hit” hypothesis, where he discussed how the margin of safety declines following cancer diagnosis and treatment. He further addressed the effect of tumor and cancer therapies on cardiac output, pulmonary function, muscle integrity, and oxygen-carrying capacity, all events ultimately causing cardiovascular aging among patients. He further walks us through how clonal hematopoiesis (a condition where we accumulate somatic mutation in the blood) can be the underlying cause of cardiovascular aging and drive CVD development among cancer patients. You can further read about clonal hematopoiesis and premature aging in one of his publications:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192097/

After a fantastic talk on premature cardiovascular aging in cancer patients, Dr. Clyde Yancy provided an exciting perspective on racial disparities. Adverse differences in numerous cancer burdens exist among specific population groups in the United States. For example, African American men are 111% more like to develop prostate cancer, whereas American Indian/Alaska Natives are twice as likely to develop liver and bile duct cancer. Similarly, racial, and ethnic health care disparities are present in cardio-oncology due to structural racism, higher prevalence of CVD risk factors, and reduced access to specialty care. A multidisciplinary approach involving stakeholders, health care policymakers, clinicians, scientists, and patients is required to resolve these disparities. Lastly, Dr. Clyde Yancy highlighted the importance of diverse population-based study and, in addition to genetic factors, phenotyping the social determinants of CV health. Read one of his recent publications about how poverty can increase the risk of heart problems:

https://pubmed.ncbi.nlm.nih.gov/34240286/

The third talk was from Dr. Rudolf A. de Boer from University Medical Center Groningen about reverse cardio-oncology. When I think about cardio-oncology, I always think about how cancer patients end up developing heart problems. However, he explained how the reverse could be true. He shared preclinical findings on how heart failure promotes tumor growth. Both CVD and cancer share several risk factors. Further, angiogenesis and inflammation under CVD conditions can increase the risk of tumor development. To learn more about cardio-oncology, refer to his recent review: https://www.ahajournals.org/doi/pdf/10.1161/JAHA.119.013754

There were additional highlights on crosstalk on clinical imaging by Dr. Ana Barac from MedStar Heart. She listed the importance of cardiac imaging, echocardiography, and cardiac MRI.

Lastly, Olypoam Kikkan Randall, a cancer survivor, shared how she stayed committed to the 10-minute rule to keep her active despite adversity. Exercise training has been shown to confer beneficial effects in cancer patients at CVD risk. Here is an interesting article documenting a scientific statement from AHA for cancer survivors to manage cardiovascular outcomes. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000679

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”