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Drugs in Gestational Hypertension

Gestational Hypertension (GHTN) is defined as the new onset of systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg , on at least 2 occasions 4 hours apart , at or after 20 weeks of gestation in a previously normotensive woman . It is considered as one type of the major hypertensive disorders in pregnancy; which also includes Pre-eclampsia, eclampsia and chronic hypertension. [1]

Hypertensive disorders of pregnancy is one of the leading causes of maternal and perinatal mortality. It can complicate the pregnancy leading to multi-organ damage such as renal failure, liver failure, pulmonary edema, fetal growth retardation and cerebral symptoms. [1]

The main target in controlling the maternal BP readings is to reduce the risk of maternal stroke and heart failure. So we will talk briefly about the medications used during pregnancy that are considered safe to achieve this target.

* First-line Oral Drugs used to treat NON-severe HTN in pregnancy , the choice among these agents is based on adverse effects , contra-indications , availability and patient preference : [2]

1-Beta-blockers :

The preferred drug in this class is Labetalol [3]. Metoprolol and pindolol are acceptable alternatives, provided that they are less well-studied In pregnancy [4].

2-Calcium Channel Blockers :           

Nifedipine is the most widely used in pregnancy, preferred as intermediate- or extended-release formula [5]. Amlodipine can be used in early pregnancy, since it was not associated with increased risk of fetal malformations [6].

3-Methyldopa :

It is widely used in pregnancy due to its long term safety profile [7] .

4- Hydralazine :

The current available evidence does not support the use of Hydralazine as first line agent due to its adverse effects, reflex tachycardia and peripheral edema. So it’s preferred to be used as add-on therapy [8] .

Table 1 : summary of drugs used in NON-severe GHTN in pregnancy

** Here are some Common anti-hypertensive Drugs to be AVOIDED in pregnancy; due to increased risk of congenital malformations : [9],[10]

  • ACE inhibitors ( -pril , e.g : enalapril , lisinopril … etc )
  • ARBs ( -sartan, e.g : valsartan , candesartan … etc )
  • direct renin inhibitors ( e.g : Aliskiren )
  • Mineralocorticoid receptor antagonists ( such spironolactone , amiloride )

* First-line Drugs used ACUTELY to treat SEVERE blood pressure elevation in pregnancy ( BP ≥160/110 mmHg ) : [2],[11]

1- Labetalol, IV

2- Nifedipine , Immediate release capsules

3- Hydralazine , IV

Table 2 : summary of drugs used in SEVERE GHTN in pregnancy

A special thank you to my sister, Rawan Ya’acoub, a clinical pharmacist and assistant professor at the University of Jordan, who helped me write this blog.

References:

[1]- Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol. 2020 Jun;135(6):e237-e260. doi: 10.1097/AOG.0000000000003891. PMID: 32443079.

[2]- Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy:

Executive Summary . No. 307, May 2014 . Laura A. Magee, MD, Vancouver BC . Anouk Pels, MSc, Amsterdam, the Netherlands . Michael Helewa, MD, Winnipeg MB . Evelyne Rey, MD, Montreal QC . Peter von Dadelszen, MBChB, Vancouver BC.

[3]- Magee LA; CHIPS Study Group, von Dadelszen P, Singer J, Lee T, Rey E, Ross S, Asztalos E, Murphy KE, Menzies J, Sanchez J, Gafni A, Gruslin A, Helewa M, Hutton E, Koren G, Lee SK, Logan AG, Ganzevoort JW, Welch R, Thornton JG, Moutquin JM. Do labetalol and methyldopa have different effects on pregnancy outcome? Analysis of data from the Control of Hypertension In Pregnancy Study (CHIPS) trial. BJOG. 2016 Jun;123(7):1143-51. doi: 10.1111/1471-0528.13569. Epub 2015 Aug 11. PMID: 26265372.

[4]- Bateman BT, Heide-Jørgensen U, Einarsdóttir K, Engeland A, Furu K, Gissler M, Hernandez-Diaz S, Kieler H, Lahesmaa-Korpinen AM, Mogun H, Nørgaard M, Reutfors J, Selmer R, Huybrechts KF, Zoega H. β-Blocker Use in Pregnancy and the Risk for Congenital Malformations: An International Cohort Study. Ann Intern Med. 2018 Nov 20;169(10):665-673. doi: 10.7326/M18-0338. Epub 2018 Oct 16. PMID: 30326014; PMCID: PMC6854680.

[5]- Firoz T, Magee LA, MacDonell K, Payne BA, Gordon R, Vidler M, von Dadelszen P; Community Level Interventions for Pre-eclampsia (CLIP) Working Group. Oral antihypertensive therapy for severe hypertension in pregnancy and postpartum: a systematic review. BJOG. 2014 Sep;121(10):1210-8; discussion 1220. doi: 10.1111/1471-0528.12737. Epub 2014 May 16. PMID: 24832366; PMCID: PMC4282072.

[6]- Mito A, Murashima A, Wada Y, Miyasato-Isoda M, Kamiya CA, Waguri M, Yoshimatsu J, Yakuwa N, Watanabe O, Suzuki T, Arata N, Mikami M, Ito S. Safety of Amlodipine in Early Pregnancy. J Am Heart Assoc. 2019 Aug 6;8(15):e012093. doi: 10.1161/JAHA.119.012093. Epub 2019 Jul 26. PMID: 31345083; PMCID: PMC6761676.

[7]- Magee LA; CHIPS Study Group, von Dadelszen P, Singer J, Lee T, Rey E, Ross S, Asztalos E, Murphy KE, Menzies J, Sanchez J, Gafni A, Gruslin A, Helewa M, Hutton E, Koren G, Lee SK, Logan AG, Ganzevoort JW, Welch R, Thornton JG, Moutquin JM. Do labetalol and methyldopa have different effects on pregnancy outcome? Analysis of data from the Control of Hypertension In Pregnancy Study (CHIPS) trial. BJOG. 2016 Jun;123(7):1143-51. doi: 10.1111/1471-0528.13569. Epub 2015 Aug 11. PMID: 26265372.

[8]- Magee LA, Cham C, Waterman EJ, Ohlsson A, von Dadelszen P. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ. 2003 Oct 25;327(7421):955-60. doi: 10.1136/bmj.327.7421.955. PMID: 14576246; PMCID: PMC259162.

[9]- Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, Hall K, Ray WA. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006 Jun 8;354(23):2443-51. doi: 10.1056/NEJMoa055202. PMID: 16760444.

[10]- Hecker A, Hasan SH, Neumann F. Disturbances in sexual differentiation of rat foetuses following spironolactone treatment. Acta Endocrinol (Copenh). 1980 Dec;95(4):540-5. doi: 10.1530/acta.0.0950540. PMID: 7456979.

[11]- ACOG Committee Opinion No. 767: Emergent Therapy for Acute-Onset, Severe Hypertension During Pregnancy and the Postpartum Period. Obstet Gynecol. 2019 Feb;133(2):e174-e180. doi: 10.1097/AOG.0000000000003075. PMID: 30575639.

 

“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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Climate Change is a Biomedical and Healthcare Crisis

One thing that has been on my mind, and surely it must have crossed yours recently, is the fact that our planet’s climate, and the environment, are having an increasing impact on how healthcare and society functions. The frequency of extreme weather events is plain to see and often experience (heatwaves, fires, storms, floods, droughts, etc.). Important to note: these events, if isolated and thought of separately, have happened throughout history, stretching back decades and centuries. However, when seeing them collectively, the absolute increase in number of events, and the frequency of “extreme” weather, that’s the key to seeing our current problem more clearly.

 

Climate change, coupled with environmental degradation and pollution, have been thought of as issues for politicians to deal with, and for manufacturers and large-scale industry to rein in, and for energy generators and tech companies to innovate away from its abuse. And while all these points are very true and totally valid, I will rhetorically ask: which segment of the population do you think is at the forefront of dealing with climate change and the environment? I’d argue that healthcare systems are the first line of defense and most immediately impacted.

 

Our environments and the climate we live in are major factors in determining our individual health status. Our bodies, or organs, tissues, and down to our cells, are each tasked with doing whatever is needed to continue functioning in the environment and climate we exist in. humans and all species have developed, over many generations on the evolutionary timescale, a lot of impressive mechanisms that help them survive, and thrive, in the wide range of environments and climates that exist on this planet. Additionally, we’ve learned and advanced medical and societal innovations, which also assist us individually and collectively, in living and contributing to life on this planet. However, there are limits to what the body can handle, and currently limits to what biomedical advancements have been achieved in assisting life beyond certain conditions.

 

Our bodies and our knowledge cannot overcome prolonged extreme heat, or cold, or dehydration, or unrelenting chronic assault of pollution, or any of the many factors that our changing climate and degrading environment challenges those bodies at greater and more extreme frequency. Biomedical researchers and active healthcare professionals must continue to support actions designed to lower the negative impact of climate change and deterioration of our environments (local and global). Health impacts must be front and center in all discussions related to combating climate change. Some conversations about climate change can make it sound that the most affected people will be individuals living near coastal lines, or in faraway patches of land on earth that are not easily located or well known to most North Americans, Europeans, and people living in more developed nations. This is simply a false viewpoint. Climate change and the deterioration of the environment is already leading to more death and more debilitating lifestyles in every corner of the map.

 

These past few months, the Covid19 pandemic, has shown the world what a fast-expanding global health crisis can do to negatively impact how the world functions. Climate change and the constant deterioration of our living environments will be even more impactful than Covid19. Biomedical researchers and professional healthcare members have a major role to play in shaping the change narrative, and implementation of key actions to protect humanity from the worst outcomes of a hard climate, and a detrimental environment where we live. The world has been warned about climate change for decades, but maybe it needed a global healthcare crisis like the Covid19 pandemic to demonstrate a bit of, and stimulate our imagination to see, how bad things can get. Let’s hope the 2020’s is the decade that finally sets the world on the right direction to preserve what we have left. It might be our last chance.

“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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Let’s add Stress Reduction as the 8th step in the American Heart Association’s “Life’s Simple 7”

February is Heart Month!  An entire month dedicated to heart disease awareness in our community.  During this month, we also educate the community on why heart disease is a women’s biggest threat.  After all, heart disease takes more lives than all cancers combined.  Globally, that equates to one woman dying every 80 seconds.  More recently, research has revealed an emerging heart disease epidemic in young women resulting from uncontrolled risk factors such as obesity, blood pressure, elevated cholesterol and diabetes.

The good news is that 80% of heart disease can be prevented through risk factor management – this journey begins with a baseline assessment with a clinician.  Starting this journey early is critical – research has demonstrated that if a woman can reach 50 without developing a major risk factor for heart disease, her lifetime risk for heart disease is only 8%.  By contrast, women who have 2 or more risk factors for heart disease at 50 have a 50% risk of developing heart disease.

Heart month is a great time to start your journey to #knowyournumbers.  The three most important numbers to check are:

  • Blood Pressure
  • Cholesterol
  • Blood Sugar (A1C)

It’s also a great time to review your diet and exercise plan with your physician.

Furthermore, in women, an increasingly important aspect of cardiovascular health is the presence of psychological, psychosocial, and emotional stress.  Well-established epidemiological data has shown that psychological risk factors such as anxiety, depression, work-related exhaustion, or perceived home stress are significantly associated with heart attacks in women (1).  Another large study of young women presenting with heart attacks revealed that women reported higher amounts of perceived stress before their heart attacks symptoms compared with men. Overall, women reported worse baseline physical and mental health before heart attacks compared with men (2).  Therefore, an important assessment of a woman’s current emotional health status is imperative in my initial cardiac workup, particularly for women.

During the initial consultation and subsequent follow-up visits, I focus on learning details about my patients’ lifestyle habits including eating patterns, physical activity/exercise routine, sleep hygiene, and stress levels.  The key is to begin the discussion to open the door to awareness of how one’s lifestyle could be setting them up for the greater cardiovascular risk. The American Heart Association (AHA) has created a campaign for workplace health called “Life’s Simple 7” which defines ideal cardiovascular health in terms of seven risk factors (Life’s Simple 7) that people can improve through lifestyle changes: smoking status, physical activity, weight, diet, blood glucose, cholesterol, and blood pressure.  While I have leaned on AHAs “Life’s Simple 7”, I have added a very important 8th step to reduce cardiovascular risk in my patients: Reduce Stress.

When it comes to my women patients, I have found that they are usually suffering from a compounded impact of accumulated stress from both families, interpersonal relationships, and/or work.   To help improve mental health, I recommend practicing the 4-7-8 breathing technique, prioritizing self-compassion, and focusing on gratitude.  These simple steps help to create the mindfulness that helps mitigate stress and its potential impact on the heart.

The 4-7-8 breathing technique popularized by Dr. Andrew Weil in the West is based on the ancient Indian yogic breathing technique called Pranayama. This technique can slow down the nervous system that controls the “stress response” and in turn enhance the relaxation response in the body and the heart.   It is easily accessible for my “busy” women patients as it can be performed from any location without any equipment.  The goal is to ensure your exhalation is twice as long as your inhalation.

While there are officially 8 total steps to use this technique, I often ask my patients to simply inhale for the count of 4 in the nose, hold for a count of 7, and exhale for a count of 8 through the mouth.

Self-compassion is another effective way to enhance well-being and reduce burnout. Self-compassion is the act of directing compassion towards oneself when dealing with a failure, a personal struggle, or negative thoughts about oneself. Self-compassion leads with kindness and understanding instead of self-criticism and self-judgment in response to personal shortcomings.  Recent studies on self-compassion have revealed a direct relationship between self-compression and feelings of greater well-being.

Gratitude is another way to return kindness to one’s life.  It is the quality of being thankful. The creation of a gratitude practice in one’s life may take many different forms: journaling, meditation, active daily reminders or even prayer. The common theme is opening the emotional heart to recognize and appreciate the simple pleasures in life which may be overlooked during times of stress.  It is about cultivating a sense of thankfulness for what you have rather in your life no matter how small or simple.

Last year prior to a women’s heart disease awareness lecture series I delivered, I created a handout adapted from AHA’s “Life’s Simple 7” and added the additional 8th step: Reduce Stress. [See caption below] The details of how to actually begin that journey of self-awareness of perceived stress as well as important stress reduction techniques can now be found in this blog and hopefully will find their way to our patients.

Reference:

  1. Yusuf S, Hawken S, Ounpuu S et al. INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): a case-control study. Lancet. 2004; 364:937–952.
  2. Xu X, Bao H, Strait K et al. Sex differences in perceived stress and early recovery in young and middle-aged patients with acute myocardial infarction. Circulation. 2015; 131:614–623.
  3. Life’s Simple 7. https://heart.org/en/professional/workplace-health/lifes-simple-7. Accessed 2/14/2021

“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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Legacy

Dr. Elijah Saunders was born in Baltimore City in 1934. As a young student he received a BS degree from Morgan State College in 1956 and he received his MD degree from the University of Maryland School of Medicine in 1960. During his medical studies, he was one of only four African-Americans in his class of 140 students and was instrumental in helping to desegregate the medical wards. He then went on to become the first African-American resident in internal medicine at the University of Maryland School of medicine and the first African-American cardiologist in the state of Maryland in 1965. 

Following fellowship, Dr. Saunders led a successful private practice for the first 20 years of his career before he returned to the University of Maryland as a professor in Cardiology, where he pursued research on hypertension among African Americans. For many years, he led the Hypertension Division in the Department of Medicine. His critical research illuminated that ethnicity may influence the response to certain types of antihypertensive medications. As a result of his research and lobbying, it is now standard for trials to require African Americans to be included in research. Over his career, he published more than 50 peer-reviewed articles and eight books.

Beyond his many achievements, including increasing African American representation in cardiovascular drug trials, being a founding member of the Association of Black Cardiologists, and co-founder of Heart House of the American College of Cardiology; Dr. Saunders was known for his positive demeanor, caring disposition, and gentle spirit. As a young black man growing up in Maryland with an interest in cardiology, Dr. Saunders was someone who I always admired. During my fourth year of medical school I spent an away rotation at the University of Maryland in hopes of training under Dr. Saunders, but was saddened to hear of his untimely passing prior to my arrival. However, I eagerly listened to his patient’s detailed stories regarding his intellect, compassion, dedication to health equity, and desire to bring healthcare to non-traditional spaces to reach the most at-risk populations. This experience quickly reaffirmed that Dr. Saunders was the type of cardiologist I hoped to emulate: clinically skilled, empathetic, and a leader in healthcare innovation. 

Despite improvements in health distribution inequalities, African-American communities are continuously  plagued with cardiovascular disease at an alarming rate. Some of the main contributors to the high burden of disease are the persistent and increasing degrees of limited access to healthy food, low socioeconomic status, and poor nutritional awareness.  To address this, Dr. Saunders advocated for community screening and outreach in barbershops and churches in order to engage the black community in non-traditional spaces. In 2006, he developed the Hair, Heart and Health program, an innovative program that trained barbers and hairstylists to pre-screen customers for hypertension and then make referrals for medical care.  

I believe as medical professionals we have two profound responsibilities. The first is to be an effective clinician. It is our obligation to treat and heal patients to the best of our abilities, while cultivating and promoting prevention. The second, and perhaps more important, is to go beyond the hospital walls and become an innovator in healthcare. We must identify roadblocks that may impede healthy practices, and provide sustainable solutions for these challenges. I hope that we can all mimic Dr. Saunders’s spirit for innovation and love of patient care. 

“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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Start 2021 in a Good Night Sleep

Picture source: (Kuehn 2019)

Should you make new year’s resolutions? Many may think the new year’s resolutions are meaningless. Especially after a year of frustration and uncertainty, New year’s resolutions seem less encouraging. A few small and attainable goals could help to provide a sense of purpose and improve our well-being. The most popular goals for new year’s resolutions include exercise more, eat healthier, and get rid of bad habits.

[1]Sleep deprivation is one of the common bad habits in modern society. According to a study in the Centers for Disease Control and Prevention’s (CDC) Morbidity and Mortality Report, 1 in 3 Americans don’t get enough sleep on a regular basis. To promote optimal health and well-being, the American Academy of Sleep Medicine and the Sleep Research Society recommend at least 7 hours of sleep each night for adults aged 18-60 years old. The adverse effects of sleep deprivation (less than seven hours per day) include obesity(Beccuti and Pannain 2011), diabetes(Shan et al. 2015), high blood pressure(Gangwisch et al. 2006), cardiovascular disease(Nagai, Hoshide, and Kario 2010; Kuehn 2019), stroke, and mental distress(Baglioni et al. 2016). It’s undeniable that having sufficient sleep is essential to our optimal health and well-being. Here are some helpful tips to start your 2021 with a good night’s sleep.

Bedroom: light, noise, and temperature

Research shows artificial light at night can disrupt circadian rhythms and cause adverse effects on sleep(Aulsebrook et al. 2018). A dim bedroom environment can help the body to recognize the time to rest. Electronic devices emit blue lights, many studies show that blocking blue light is beneficial for patients to suffer from insomnia(Janků et al. 2020). Restricting electronic devices before sleep or using blue-light blocking approaches are helpful to maintain a good quality sleep.

Noise can also affect sleep(Basner and McGuire 2018). Try to reduce noise in the bedroom environment could fall asleep faster and minimize disruption during sleep. Both environmental and body temperature impact sleep duration and sleep quality(Troynikov, Watson, and Nawaz 2018). Increased bedroom and body temperature decrease sleep quality. Finding a comfortable temperature for yourself will improve sleep quality. For most people, the desirable bedroom temperature is around 70 ˚F (20 ˚C). Taking a good bath or shower before bed will prepare the body to adjust to a favorable temperature for sleep.

De-stress: mentally and physically

Most of us have experienced some form of insomnia when we have something in our minds. Integrative approaches to insomnia such as mind-body therapies (mindfulness mediation, yoga, tai chi) have been shown beneficial to de-stress the body as well the mind(Zhou, Gardiner, and Bertisch 2017). Exercise is beneficial for the overall well-being, can improve the quality of sleep(Kelley and Kelley 2017). Various approaches can help relax the body and mind, finding your favorite ones requires a little bit of exploration.

Routine: timing and time

We are creatures of habits. Especially when it comes to sleep. Disruption of the circadian clock adversely affects sleep, which causes cardiovascular diseases(Chellappa et al. 2019). Cultivating a wake-up and night-time routine will have profound impacts on the overall performance. When to go to bed is different for everyone. Anecdotally, it’s best to go to bed earlier and wake up early each day. This may not work for everyone’s schedule. Keeping the recommended amount of sleep is more important than strictly enforcing yourself against your circadian clock.

Food and drink

Investigation of the impact of food choice and consumption on sleep is an emerging field. Early clinical studies investigated the effects of certain macronutrients such as carbohydrate, protein or fat on daytime alertness and nighttime sleep. Some popular sleep–promoting foods, such as milk, fatty fish, cherries, and kiwifruit have been reported(St-Onge, Mikic, and Pietrolungo 2016). Avoid late caffeine consumption(Clark and Landolt 2017) and alcohol(Thakkar, Sharma, and Sahota 2015) are common practices to improve sleep quality.

All of the above are potential strategies for sleep improvement. Making small adjustments in your sleep hygiene routine could have a promising outcome. The key is to start small and stick to it until it incorporates into your day-to-day life.

Reference:

Aulsebrook, Anne E., Therésa M. Jones, Raoul A. Mulder, and John A. Lesku. 2018. “Impacts of Artificial Light at Night on Sleep: A Review and Prospectus.” Journal of Experimental Zoology Part A: Ecological and Integrative Physiology. https://doi.org/10.1002/jez.2189.

Baglioni, Chiara, Svetoslava Nanovska, Wolfram Regen, Kai Spiegelhalder, Bernd Feige, Christoph Nissen, Charles F. Reynolds, and Dieter Riemann. 2016. “Sleep and Mental Disorders: A Meta-Analysis of Polysomnographic Research.” Psychological Bulletin. https://doi.org/10.1037/bul0000053.

Basner, Mathias, and Sarah McGuire. 2018. “WHO Environmental Noise Guidelines for the European Region: A Systematic Review on Environmental Noise and Effects on Sleep.” International Journal of Environmental Research and Public Health. https://doi.org/10.3390/ijerph15030519.

Beccuti, Guglielmo, and Silvana Pannain. 2011. “Sleep and Obesity.” Current Opinion in Clinical Nutrition and Metabolic Care. https://doi.org/10.1097/MCO.0b013e3283479109.

Chellappa, Sarah L., Nina Vujovic, Jonathan S. Williams, and Frank A.J.L. Scheer. 2019. “Impact of Circadian Disruption on Cardiovascular Function and Disease.” Trends in Endocrinology and Metabolism. https://doi.org/10.1016/j.tem.2019.07.008.

Clark, Ian, and Hans Peter Landolt. 2017. “Coffee, Caffeine, and Sleep: A Systematic Review of Epidemiological Studies and Randomized Controlled Trials.” Sleep Medicine Reviews. https://doi.org/10.1016/j.smrv.2016.01.006.

Gangwisch, James E., Steven B. Heymsfield, Bernadette Boden-Albala, Ruud M. Buijs, Felix Kreier, Thomas G. Pickering, Andrew G. Rundle, Gary K. Zammit, and Dolores Malaspina. 2006. “Short Sleep Duration as a Risk Factor for Hypertension: Analyses of the First National Health and Nutrition Examination Survey.” Hypertension. https://doi.org/10.1161/01.HYP.0000217362.34748.e0.

Janků, Karolina, Michal Šmotek, Eva Fárková, and Jana Kopřivová. 2020. “Block the Light and Sleep Well: Evening Blue Light Filtration as a Part of Cognitive Behavioral Therapy for Insomnia.” Chronobiology International. https://doi.org/10.1080/07420528.2019.1692859.

Kelley, George A., and Kristi Sharpe Kelley. 2017. “Exercise and Sleep: A Systematic Review of Previous Meta-Analyses.” Journal of Evidence-Based Medicine. https://doi.org/10.1111/jebm.12236.

Kuehn, Bridget M. 2019. “Sleep Duration Linked to Cardiovascular Disease.” Circulation 139 (21): 2483–84. https://doi.org/10.1161/CIRCULATIONAHA.119.041278.

Nagai, Michiaki, Satoshi Hoshide, and Kazuomi Kario. 2010. “Sleep Duration as a Risk Factor for Cardiovascular Disease- a Review of the Recent Literature.” Current Cardiology Reviews. https://doi.org/10.2174/157340310790231635.

Shan, Zhilei, Hongfei Ma, Manling Xie, Peipei Yan, Yanjun Guo, Wei Bao, Ying Rong, Chandra L. Jackson, Frank B. Hu, and Liegang Liu. 2015. “Sleep Duration and Risk of Type 2 Diabetes: A Meta-Analysis of Prospective Studies.” Diabetes Care. https://doi.org/10.2337/dc14-2073.

St-Onge, Marie Pierre, Anja Mikic, and Cara E. Pietrolungo. 2016. “Effects of Diet on Sleep Quality.” Advances in Nutrition. https://doi.org/10.3945/an.116.012336.

Thakkar, Mahesh M., Rishi Sharma, and Pradeep Sahota. 2015. “Alcohol Disrupts Sleep Homeostasis.” Alcohol. https://doi.org/10.1016/j.alcohol.2014.07.019.

Troynikov, Olga, Christopher G. Watson, and Nazia Nawaz. 2018. “Sleep Environments and Sleep Physiology: A Review.” Journal of Thermal Biology. https://doi.org/10.1016/j.jtherbio.2018.09.012.

Zhou, Eric S., Paula Gardiner, and Suzanne M. Bertisch. 2017. “Integrative Medicine for Insomnia.” Medical Clinics of North America. https://doi.org/10.1016/j.mcna.2017.04.005.

[1] Picture source: (Kuehn 2019)

 

“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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Building Your Brand: Research Career Planning and Scientific Writing

AHA 20 had a fantastic session titled “Building Your Brand” and it provided excellent insights on how to be a successful researcher in academic medicine. Panel participants Dr. Erin Michos, Dr. Louise McCullough, Dr. Andrew Landstrom, and Dr. Pradeep Natarajan shared their stories on how they got involved in research and the lessons they learned along the way. While the session focused on fellows in training, I will present my viewpoint on how these general principles are applicable to early-career physicians (ECP). Based on this session, I have developed a step by step approach.

When is the right time to get involved in research?

No doubt, it is good to start as early as possible, but it is never too late. Residency is the ideal time to get involved in the research. This head start allows you to explore different areas of research, find what interests you, and at the same time allows ample time to acquire skills needed to conduct research. For ECP, this means if you already started research during your training you are on the right track. If you were not exposed to much research during training, you can always start now.

Step#1: Start now.

How to get started?

The significance of finding the right mentor cannot be over-emphasized. It is important to meet different potential mentors and get to know them. This allows you to assess overlapping areas of interest, learn how research shaped their careers and most importantly get inspiration from their journey. For an ECP, it is important to work with different mentors that can develop you in different areas of research. These mentors can be across different institutions in the country.

Step#2: Find your mentoring team.

What skills are needed and how to acquire them?

“Writing” and “Statistics” are the two most important skills needed for any type of research. There are multiple ways to acquire these skills depending on how much time you want to invest. Most of these skills can be acquired by taking online classes or a degree program. Most academic programs offer classes in scientific writing, epidemiology, biostatistics, clinical trial design, and grant writing. For an ECP, if you think you will be doing research throughout your career, consider getting additional training through a master’s degree in clinical and translational sciences or in some cases a PhD.

Step#3: Acquire scientific writing and statistical skills.

What are the effective strategies for manuscript writing?

Writing the first draft is challenging but it is important to write it quickly and not worry about perfection. Start by writing the methods, followed by results, and leave an introduction and discussion to the end. Feedback from your mentor and collaborators will improve the paper.

Step#4: Write the first draft quickly, following this order: methods, results, introduction, discussion.

Quality or Quantity?

While it is ideal to always conduct high-quality and novel research projects, in-reality all such projects need research funding. Therefore, early in your research career, it is important to be productive and complete some less extensive projects starting from case reports, review articles, and retrospective studies. This allows you to practice the skills you acquired and get some confidence that you carried an idea from start to finish. It will build your research profile and make you a competitive candidate for grant funding in the future.

Step#5: Publish something even if it is a case report or a retrospective study.

How to build a brand?

Once you have found your mentoring team, acquired writing and statistical skills, and published at least one manuscript, it is time to develop a focus. You cannot build a brand without a focus. The first step is to find an area of research that you truly find fascinating and it typically includes ideas that you cannot stop thinking about and questions that give you an epiphany. Often, the most important research questions arise from your clinical work. Second, see if these ideas are vital from a clinical, research, and public health standpoint (significance). Third, see if you have the right environment (research team, institutional support, skills) needed to turn this idea into reality (feasibility). Often, we have to spend many years exploring different research interests and acquiring more skills (grantsmanship) before we arrive at an idea that we see ourselves developing into a brand (niche). For ECP, if you are busy clinicians with an interest in research, try your best to align your clinical interests with your research interests. Once you have established your niche, it is extremely important to stay focused so that all your time and energy is spent on developing your brand.

Step#6: Develop your niche, advance your skills, align clinical work with research, stay focused, avoid distractions.

What personality traits are needed?

A key trait is showing persistence despite multiple failures as it is not uncommon to have your first manuscript rejected by a journal or multiple journals. Having the persistence to learn from this experience, improve your manuscript and resubmit, is necessary. For mentees, it is important to develop a “can-do attitude”, be authentic, honest and follow through on commitments.

Step#7: Develop persistence, learn from failure, be a good mentee.

I hope you found these steps useful for building your brand in research. “The game has its ups and downs, but you can never lose focus of your individual goals and you can’t let yourself be beat because of lack of effort.” (Michael Jordan)

 

This session will be available on-demand until January 4th, 2020, and AHA Partners have FREE access to Scientific Sessions 2020 OnDemand Extended Access through 2021. 

 

“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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DAPA-CKD: Is SGLT2i the ANSWER? Will the guidelines change?

Over the past years, series of clinical trials prove the beneficial effect of glucose cotransporter 2 (SGLT2) inhibitors in reducing the risk of cardiovascular events in people with type 2 diabetes mellitus. The results from these trials were consistent, significant, and demonstrated a considerable reduction in heart failure hospitalization among patients who used SGLT2 inhibitors, whereas the benefit on atherothrombotic events such as myocardial infarction and stroke was moderate.

Similar findings from The Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation trial (CREDENCE) were obtained for patients with type 2 diabetes mellitus and chronic kidney disease who are exceptionally at higher risk for cardiovascular disease. In CREDENCE trial, Canagliflozin reduced the risk of chronic kidney disease, cardiovascular death or hospitalization, myocardial infarction, and stroke. Although diabetes is not the only cause of chronic kidney disease, and people with chronic kidney disease are still at increased risk for cardiovascular disease, regardless if they had a preexisting history of cardiovascular disease or not. Therefore, its essential to implement guidelines that recommend the use of certain therapeutics as routine treatment for primary and secondary prevention of cardiovascular disease in patients with chronic kidney disease, regardless of their diabetes status.

During #AHA20, I enjoyed attending the online session by Dr. John McMurray, where he shared scientific breakthrough results from the Dapagliflozin And Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) Mega-Trial. The session reported the results of the effect of dapagliflozin on prespecified kidney and cardiovascular outcomes in patients with chronic kidney disease with and without diabetes. The DAPA-CKD trial was a randomized, double-blind, placebo-controlled, multicenter trial, where adults with or without type 2 diabetes, with estimated glomerular filtration rate (eGFR) between 25 and 75 ml/min/1.73 m2, and a urinary albumin-to-creatinine ratio (UACR) between 200 and 5000 mg/g were eligible for DAPA-CKD trial. In this trial, patients were randomized to dapagliflozin 10 mg once daily or placebo with follow up at 2 weeks, 2,4, and 8 months and at 4 months intervals thereafter. The primary composite outcome was the time to the first occurrence of any of the following: > 50% decline in eGFR, onset of end-stage renal disease, or death from kidney or cardiovascular disease. Moreover, secondary outcomes were: 1) kidney composite outcome identical to the primary endpoint with the exception of death from cardiovascular death 2)( a cardiovascular composite outcome consisting of hospitalization for heart failure or death from cardiovascular  causes; and 3) death from any cause.

 

Effects of dapagliflozin on prespecified clinical outcomes according to the baseline history of cardiovascular disease.

 The DAPA-CKD trial found that among patients with cardiovascular disease who received dapagliflozin, the primary composite outcome occurred in 11.2% participants, while the primary outcome occurred in 17.2% in participants who were in the placebo group, (HR 0.61; 95% CI, 0.47-0.79) and the corresponding numbers in people without cardiovascular disease were 7.9% and 12.9% respectively, (HR 0.61; 0.48-0.78).

The DAPA-CKD trial also found that for both the primary and secondary prevention patients, the event rates favored dapagliflozin for all components of the primary and secondary outcomes, although reduction in cardiovascular risk was not statistically significant.

DAPA-CKD Figure

Additionally, among patients with cardiovascular disease, cardiovascular death or hospitalization for heart failure occurred in 9.3% of participants in the dapagliflozin group and 12.8% of participants in the placebo group, (HR 0.7; 0.52-0.94) and the corresponding numbers for patients without cardiovascular disease were 1.8% and 2.7% respectively, (HR 0.67; 0.40-1.13). The observed reduction in cardiovascular risk for these two groups was driven by reduction in heart failure hospitalization which occurred in 4.1% of participants in the dapagliflozin group and 7.3% participants in the placebo group with cardiovascular disease and the corresponding numbers for patients without cardiovascular disease were 0.3% and 1.0% (HR, 0.31; 0.10-0.94) respectively. These results show that dapagliflozin reduced the risk of adverse kidney outcomes irrespective of baseline cardiovascular disease status. Moreover, the mortality benefit from dapagliflozin as demonstrated from the DAPA-CKD study supports the findings of the DAPA-HF trial. In summary, dapagliflozin reduced the risk of kidney failure, death from cardiac disease or hospitalization for heart failure, furthermore, it prolonged survival, in people with chronic kidney disease, irrespective of the presence of a concomitant cardiovascular disease.

 

What is next?

The data from DAPA-CKD trial for dapagliflozin effect on patients with cardiovascular disease and chronic kidney disease is clear, but we have so much work to do. Is Dapagliflozin the answer? How would this change the guideline directed medical therapy (GDMT) for the care of patients with an increased heart failure, cardiovascular or chronic kidney disease risk, regardless of their glycemic status?

 

References:

  1. Effect of Dapagliflozin on Clinical Outcomes in Patients with Chronic Kidney Disease, With and Without Cardiovascular Disease. John J.V. McMurray , David C. Wheeler , Bergur V. Stefánsson , Niels Jongs , Douwe Postmus , Ricardo Correa-Rotter , Glenn M. Chertow , Tom Greene , Claes Held , Fan Fan Hou , Johannes F.E. Mann , Peter Rossing , C. David Sjöström , Robert D. Toto , Anna Maria Langkilde , and Hiddo J.L. Heerspink for the DAPA-CKD Trial Committees and Investigators
  2. Presented by Dr. John J. V. McMurray at the American Heart Association Virtual Scientific Sessions, November 13, 2020.
  3. Heerspink HJ, Stefánsson BV, Correa-Rotter R, et al., on behalf of the DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients With Chronic Kidney Disease.N Engl J Med 2020;383:1436-46.
  4. Presented by Dr. Hiddo J.L. Heerspink at the European Society of Cardiology Virtual Congress, August 30, 2020.
  5. Rationale and protocol:Heerspink HJ, Stefansson BV, Chertow GM, et al., on behalf of the DAPA-CKD Investigators. Rationale and protocol of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial. Nephrol Dial Transplant 2020;35:274-82.

“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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Last Day of #AHA20: COVID-19 Galore!

The last day of the amazing #AHA20 featured a series of COVID-19-related research presentations.

First, data from the AHA COVID-19 Registry, a large database collecting data about COVID-19 patients and outcomes around the country, were shared. The registry includes data from 109 hospitals and over 22,500 records of patients who were hospitalized with COVID-19. Notably, large numbers of COVID-19 patients in this registry had cardiovascular risk factors such as hypertension and diabetes. Prior cardiovascular disease was also common. The disease was additionally noted to have a high morbidity and mortality rate, with more than 20% of hospitalized COVID-19 patients requiring mechanical ventilation.

One interesting study examined racial and ethnic differences in the AHA COVID-19 Registry of patients hospitalized with COVID-19, focusing primarily on the association of these factors with in-hospital death as the primary outcome and secondary outcomes such as major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, new onset heart failure or cardiogenic shock) or COVID-19 cardio-respiratory disease severity scale. Notably, Black and Hispanic patients accounted for >50% of hospitalizations in this Registry, suggesting significant over-representation of Black and Hispanic patients compared with the census demographics in their areas. Cardiovascular risk factors such as obesity and hypertension were also more common in Black and Hispanic patients. Mechanical ventilation and need for renal replacement therapy were more likely in Black patients. Overall in-hospital mortality was high at 18.4%, and particularly high for those older than 70 years old.

In fully adjusted models taking into account age, medical history and sociodemographic features, there was no statistically significant difference in mortality and MACE among different racial or ethnic groups, though Asian patients had a higher COVID-10 disease severity on presentation. These findings suggest that though race and ethnicity are not independently associated with worse in-hospital outcomes in COVID-19 patients, Black and Hispanic patients bear a greater burden of morbidity associated with COVID due to their disproportionate representation among patients hospitalized with CVOID-19. This study was simultaneously published online in Circulation.

One additional study examined the association between body mass index (BMI) with a composite of in-hospital death and/or mechanical ventilation (primary outcome), as well as with MACE (a composite of in-hospital all-cause death, stroke, heart failure, myocardial infarction), deep vein thrombosis and renal replacement therapy (secondary outcomes). Patients with a higher BMI were more likely to be admitted to the hospital with COVID-19. In analyses adjusting for age, sex, ethnicity, comorbidities, cardiovascular disease and chronic kidney disease, higher class obesity was associated with higher likelihood of in-hospital mortality or mechanical ventilation. MACE was not associated with obesity class. Deep venous thrombosis or pulmonary embolism were not associated with obesity class. Class I, II and III obesity, however, were noted to have a higher likelihood of need for mechanical ventilation, regardless of age. Moreover, when stratified by age, BMI >40 kg/m2 was associated with a higher risk of in-hospital death only in lower age groups (<50 years old). These findings suggest that better public health messaging may be required for younger obese individuals who may underestimate their own risk related to COVID-19. This study was also simultaneously published in Circulation.

 

“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.”