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The American Heart and Go Red for Women Month!

It is February: The American Heart and Go Red for Women Month!

February has just started with all its excitement and optimistic thoughts!! I would like to talk about some of the amazing initiatives, including American Heart Month and Go Red for Women initiatives, that are in place to inspire and encourage more of my colleagues, women and men equally, to step up and be proactive about women’s health and education!

  • When was the first American Heart Month?

It was in February 1964, proclaimed by President Lyndon B. Johnson, and Congress subsequently requested the President to issue a proclamation designating February as American Heart Month annually.

  • What is the Go Red for Women Initiative?

It is an initiative, launched in 2004, to end heart disease and stroke in women; by increasing awareness of these diseases in women and removing barriers women face to achieve a healthy life. Here is what GO RED means:

  • G: GET YOUR NUMBERS

Ask your doctor to check your blood pressure and cholesterol.

  • O: OWN YOUR LIFESTYLE

Stop smoking, lose weight, exercise, and eat healthy.

  • R: REALIZE YOUR RISK

Know your risk; heart disease is responsible for 1 in every 5 female deaths [1].

  • E: EDUCATE YOUR FAMILY

Make healthy food choices for you and your family.

  • D: DON’T BE SILENT

Tell every woman you know that heart disease is our No. 1 killer [1].

  • How about “Research Goes Red” initiative?

It is an initiative to increase women’s participation in scientific research. Both healthy women and those with acute or chronic diseases are encouraged to participate.

  • What impact have these initiatives achieved?

The impact of these initiatives has been remarkable and quite impressive!! Here are some of their achievements:

  • More than 25,000 women registered for the Research Goes Red initiative!
  • Around 19 million women interact with Go Red through digital platforms annually.
  • $600 million raised to support research, education, advocacy, prevention and awareness programs.

Seeing the impact of these initiatives, I am hopeful not only that these initiatives continue to include and support more women, but also I am optimistic that more initiatives are launched to: (1) increase awareness of different heart diseases in women, (2) empower women to know the differences in the clinical presentations of different diseases, (3) implement strategies to avoid health care disparities based on gender and race, and (4) help more women and minorities access health care, not only across the nation but also across the globe.

 

Reference

 

“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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Seeing and Serving Invisible Populations

Like many of you, I chose to be a nurse because I wanted to serve people during their most vulnerable times, knowing that this work would make a difference. Working with people at their most vulnerable has taught me a lot, including that my patients can be braver, kinder, more frightened, angrier, disappointed, lovelier, and in general more surprising than I expect when I walk in the door.

A growing and perhaps surprising population at disproportionally high risk for heart attacks are individuals who identify as transgender. Transgender individuals are those whose gender identity is different from the sex they were assigned at birth. People identifying as transgender can be any age or race, from any background, and reside in all 50 states. In 2016 there were approximately 1.4 million people in the United States who identified as transgender.  Given the increase in the transgender population, new initiatives are attempting to understand the unique health needs of this population in order to provide high-quality health care. Little is known about the cardiovascular health of this population, which prompted a recent study by Dr. Alzahrani from George Washington University who found that the transgender population had a higher reported history of heart attacks compared with the cisgender (those whose gender corresponds with their birth sex) population.

This first-of-its-kind study examined approximately 720,000 U.S. adults who completed the telephone-based Behavioral Risk Factor Surveillance System survey, conducted by the Centers for Disease Control and Prevention between the years of 2014-2017. Of these, 3,055 adults identified as transgender. In gender stratified analyses, Dr. Alzahrani and colleagues found that after adjusting for known cardiovascular risk factors transgender men had (i.e. they were told by a doctor, nurse or health care professional that they had a heart attack) compared to cisgender men and women. And transgender women had a 2-fold increase in the rate of heart attacks compared with cisgender women. Importantly, the investigators also found that transgender men and women were more likely to smoke and be sedentary, and that these and other traditional risk factors were associated with increased odds of experiencing a heart attack. This suggests that while there are about the long-term cardiovascular risk of gender affirming-hormones, mitigating these traditional risk factors are important first line targets for this and all populations.

In an accompanying editorial Dr. Paul Chan evoked Ralph Ellison’s Invisible Man, citing the narrator “I am invisible, understand, simply because people refuse to see me.” Dr. Chan states that today transgender individuals are invisible. But they don’t have to be. We have to actively reject any implicit or explicit expectations we have about this population and simply see them and treat them as they present. This sentiment is echoed by Dr. Billy Carceres, Nurse and Post-Doctoral Fellow at Columbia University Program for Study of LGBT health, “There’s this perception that we can spot transgender people; but if we don’t ask the question about gender identity we might be missing out on people who are at risk. Patients want to have conversations with health care providers about things that influence their health.”

Table 1 lists several steps that can help us start to have these conversations. Adopting such steps in our clinical practice and research are critical against the backdrop of the increased social stress, poor socioeconomic status, health disparities, violence, and a perpetuating fear of mistreatment by healthcare professionals experienced by transgender populations. These steps will help us to see this invisible population, gain their trust, and ultimately help engage them in activities to improve their cardiovascular health.

Table 1. Steps to Reducing Cardiovascular Risk in Transgender Populations

  1. Assess the gender of all your patients or research participants on multiple levels
  2. Ask which pronouns they would like you to use
  3. Understand the terminology used by the trans community
  4. Recognize that transgender people may avoid seeking out health care because of fear of discrimination and create a safe and welcoming environment
  5. Assess all potential cardiovascular risk factors for transgender patients and work with them to collaboratively develop a plan to reduce their risk factors
  6. Learn more about the unique health care needs of your transgender patients. Your health care institution may have good local resources and the Center of Excellence for Transgender Health at UCSF and the World Professional Association for Transgender Health have up-to-date resources.

While Dr. Alzahrani’s new article highlights a significant disparity in an often overlooked and vulnerable population, ultimately we need a lot more data before we can develop and tailor cardiovascular treatment guidelines for transgender populations. As Dr. Sangyoon Shin, Medical Director of Co-Management Service for Gender Affirmation Surgery of Mount Sinai stated, “Its important to realize that the transgender population has specialized needs because they are more marginalized and face high rates of discrimination; But the health care practices the guidelines geared towards them need to be just as evidence-based as with any other population.“ Anything less would be a disservice.

People who seek out a health care provider – a nurse, physician, physical therapist, or pharmacist – do so because they need our help. Our job is to serve them, all of them, as they are, with high quality evidence-based health care. How we treat invisible populations, no matter how different or perplexing they are to us, is the true mark of our professionalism.

 

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Five Lessons From My Heart Attack Patients

In only few months, I leave my clinic where I have been seeing patients with heart disease for the past three years. It was not until I started discussing with them the transition to a new cardiologist that I appreciated the unique relationship we have built.  It has only been few years since we first met in in the Emergency Department in the middle of the night as they were having a heart attack, but somehow this journey feels longer.  I witnessed their heart attacks change their lives in many different ways, as they learned to cope, recover and carry on in life with a story to tell. Being one of the characters in their stories, I learned five lessons about life that will stay with me.

 

1- You can make any terrible event a wake up call or the beginning of the end.

A big heart attack or sudden cardiac arrest is arguably the most terrible event one could experience. As my patients recovered from such an event and came to see me in clinic, I could tell that the event changed them, either to the better or to the worse. While some lost weight, started training regularly, left their high stress jobs, or decided to travel the world, others became even more sedentary, gained weight, and started lamenting their bad luck and “missed opportunity” for good health.  It was striking to observe those two trajectories of opposite directions. Like my heart attack patients, when you are faced with a terrible event in life, you can either use it as a wake up call to do better afterwards or fall off a ledge and spiral down. You decide your own fate.

 

2- A supporting family is worth all the medicine of the world.

One patient after another, it became clear to me that the presence of a supporting family member that cares for you during difficult times is worth the most state-of-the-art medicine. It is that person that ensures that your food is low in salt and has no butter, that you do your daily exercise and not miss your medication, that you come to your appointments and ask all the right questions, or that simply hold your hand and tell you it’s going to be okay when things turn sour.

 

3- You’re as old as you think you are.

I met a 90 year-old woman who had a big heart attack and went for the most aggressive therapies. A year later she still shows to my clinic fully groomed and cheerful telling me she picked up dancing and life could not be any better.  I also met a 50 year-old man who after a small heart attack gave up on enjoying life or hoping for better future and couldn’t be convinced otherwise.

 

4- Faith, hope, and courage are your best friends when you’re not in control.

When patients are waiting for a high risk surgery or intervention, they simply are not in control of their fate. I found that those that fared well had three unique characteristics. First, they had faith in themselves, their doctors, or God. Second, they always hoped for the best. Third, they had the courage to face a difficult reality when things don’t go as well.  Whenever you’re not in control, let faith, hope, and courage always be your best friends.

 

5- Write your best story today because you never know when it ends.

While I learned so much from the stories of those patients who made it to my clinic, many did not, and their stories ended in the hospital. As you go through life, live every day to the fullest and write your best story page by page, because you really never know when it ends.

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Precision Medicine: Is It The Future For Heart Diseases?

Cardiovascular disease is famously known as a disease that “rose from relative oblivion to the uno numero killer worldwide.” Globally, there were an estimated 422.7 million cases of cardiovascular diseases (CVD) and 17.92 million deaths in 2015. Over the past 50 years, significant efforts have been made to suppress or even eradicate cardiovascular diseases. The figure1 to the left is adopted from Havlik and Feinleib illustrates the various strategies applied to reduce the deaths associated with coronary heart disease, which are also relevant for CVD more broadly.

While discussions are aimed towards who or what deserves the credit for this decline, the prevention and cure still remain obscure, highlighting that we need a shift in management of these patients. Currently, the approach to CVD treatment is evidence-based medicine. This supposes “one size fits all,” that individuals with common symptoms share the same disease and will respond to similar management strategies, and ignores that patients are unique at large. Moreover, current healthcare is expensive and inefficient at most part.

 

Precision Medicine

Precision medicine represents a new approach where patient care is targeted towards prevention and cure considering individual differences of patients. The goal is to identify what’s best for a particular patient than what benefits the average population. As figure to the left shows, it is aimed to achieve through the accumulation of personalised data (clinical, biological, environmental & genetic) and computed predictive models that will inform logical therapy for each patient2.

The success of precision medicine relies on extensive clinical testing, electronic health records, genetic profiling, big data sets, and novel analytical and implementation methods to create a person-specific information that can then be used to identify an optimal intervention with minimal risk.

The benefits of precision medicine included better medical management, safer dosing options, reduced adverse events, reduce inappropriate procedures and medical interventions, and improved patient management.

 

Precision Medicine in Cardiology and Challenges

Cardiology has been slower than other disciplines in pursuing precision medicine. This is now changing as several attempts are beginning to take shape. Efforts are in place to define distinctive patient groups, identify molecular targets, develop risk models and evaluate the effects of drugs through genome scale metabolic models.  But there are several barriers in precision medicine that also limits the widespread application and advancement of it in modern medicine. First of all, the multidisciplinary approach requires synchronisation between several departments, calls for advances in technology, regulatory oversights, big data storage, and ethical concerns with the use of genetic information storage.

There is also a large concern that precision medicine is just like stem cell revolution, where the promise to become what it is may not be achievable but will have incremental gains on a case by case basis. But by comprehensive understanding, united efforts, clinical application, evidence-based practices and technological advancements, precision medicine could change the entire landscape of cardiovascular health care system in the near future.

 

References:

  1. Jones DS and Greene JA. The decline and rise of coronary heart disease: understanding public health catastrophism. American journal of public health. 2013;103:1207-1218.
  2. Duffy DJ. Problems, challenges and promises: perspectives on precision medicine. Briefings in Bioinformatics. 2015;17:494-504.

 

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Thiamine: An Important Nutrient to Consider in Treatment of Congestive Heart Failure

Thiamine deficiency is an uncommon nutritional deficiency in the developed world. The population most at risk in North America and Europe has been noted to be alcoholics with poor diets. This nutrient deficiency can manifest as several different syndromes, one of which is “beriberi.” Beriberi was first described by Dr. Wenckebach in the early 1900s who observed the presence of dependent edema, elevated venous pressures, and an enlarged heart in patients who had three or more months of a thiamine deficient diet, with recovery after thiamine administration. What followed years after were several case reports of alcoholics with signs of congestive heart failure who improved drastically with administration of thiamine.

Although today beriberi heart disease is a rare diagnosis, what it does show is that thiamine is an important micronutrient for the heart, and lack of thiamine can cause symptoms of heart failure.

Given that thiamine is excreted through the urine, another population that has been deemed to be at risk for thiamine deficiency is those on high doses of diuretics such as furosemide1. Interestingly, this population includes the difficult-to-control heart failure patients that we see on the wards every day. Biochemically, one study has shown that thiamine uptake in cardiac cells can be inhibited by furosemide2.

Yet, treatment of patients with congestive heart failure on diuretics with thiamine is not currently standard of practice.

Looking at the literature, there have been only two randomized double blind placebo controlled trials on thiamine use in patients with congestive heart failure: Shimon et al 19953 and Schoenenberger et al 20124. Both of these trials showed a statistically significant increase in left ventricular ejection fraction with the use of thiamine in patients presenting with symptomatic congestive heart failure. Granted, the ejection fraction only improved by 3-4% which we could say was due to echocardiography interpretation variability. However, being that thiamine is cheap and there is evidence that points towards its use as a medication in heart failure, should we institute it into our daily practice?

What do you think?

 

References:

  1. Katta N, Balla S, Alpert MA. Does Long-Term Furosemide Therapy Cause Thiamine Deficiency in Patients with Heart Failure? A Focused Review. Am J Med. 2016;129(7):753.e7-753.e11.
  2. Zangen A, Botzer D, Zangen R, Shainberg A. Furosemide and digoxin inhibit thiamine uptake in cardiac cells. Eur J Pharmacol. 1998;361(1):151-5.
  3. Shimon I, Almog S, Vered Z, et al. Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Am J Med. 1995;98(5):485-90.
  4. Schoenenberger AW, Schoenenberger-berzins R, Der maur CA, Suter PM, Vergopoulos A, Erne P. Thiamine supplementation in symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled, cross-over pilot study. Clin Res Cardiol. 2012;101(3):159-64.

 

 

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Red Dresses & Red Ribbons: What Every Health Care Provider Needs to Know about Cardiovascular Disease and HIV in Women

Lead Image (created by Cynthia Rentrope):

Lead Image (created by Cynthia Rentrope):

Each February, we celebrate Go Red for Women – a time for healthcare providers to reacquaint ourselves with the shocking fact that on average one woman dies from cardiovascular disease (CVD) every minute – and recommit to doing better. In the United States and the around the globe, women living with HIV are at higher risk for developing cardiovascular disease, yet not all women are affected equally. There are disparities in the quality of cardiovascular care in women, especially younger women, compared to men. Simultaneously, women living with HIV are at increased risk for cardiovascular disease than HIV uninfected women and receive less guideline-based cardiovascular care. In order to provide better preventative, diagnostic, and curative care we have to understand why women living with HIV are at higher risk for cardiovascular disease and stroke and what we can do about it.

Women living with HIV are at higher risk for CVD and stroke

The reasons why women living with HIV are at higher risk for CVD and stroke are not entirely understood. However, scientists have described several likely reasons. HIV is an inflammatory disease and women infected with HIV have higher levels of inflammatory cytokines and markers of immune activation. In turn, this inflammation may increase the risk of CVD by accelerating development of atherosclerotic plaques and making these plaques more ‘vulnerable’ to rupture, causing more heart attacks and strokes. Additionally, we recently reported that inflammation was also associated with reduced cardiorespiratory fitness in adults living with HIV, which may help explain this increased risk. Women living with HIV have elevated rates of depression, obesity, stigma, and homelessness, also associated with increased CVD.

However, there are also unique biological factors that increase the risk for CVD in women living with HIV, particularly with aging. According to Dr. Sara Looby RN, PhD, Assistant Professor of Medicine at Harvard Medical School and Massachusetts General Hospital, hormone changes experienced during menopause such as estrogen loss and reduced ovarian reserve may negatively influence immune activation and the development of subclinical CVD in women living with HIV.  Her current study funded by the National Institute of Allergy and Infectious Disease is exploring this and the results are expected in the next 4 years.

Strategies to Reduce the risk of CVD in Women Living with HIV

Yet it is not enough to know there is a risk and even to partially understand why; health care providers- cardiologists, nurses, primary care providers, and HIV and emergency room physicians -chose their profession because they wanted to improve health. And all of us have an important role in helping women living with HIV accomplish this goal. There are several evidence-based strategies we can use to improve cardiovascular health in this population.

  • Take HIV medications. This strategy is well known among HIV nurses and physicians but those not trained in HIV may not realize the significance of HIV medications to reducing CVD in this population. Having a suppressed HIV viral load, obtained through adherence to effective HIV medicines, is consistently associated with reduced CVD.
  • Recognize and treat the cluster of traditional cardiovascular risk factors in HIV. Increased traditional cardiovascular risk factors in women living with HIV, including hypertension, dyslipidemia, diabetes, and obesity, need to be effectively addressed using guideline-based care. For a good resource on how to do this, check out the American Heart Association’s Life Simple 7
  • Assess sex-specific risk factors in women including menopause history. This may not be routine for HIV, cardiovascular or family health providers but it is important for understanding cardiovascular risk. Increasing evidence indicates we should use a woman’s menopause history to improve understanding of her risk of CVD and provide good cardiovascular treatment. Other health conditions unique to women, such as a history of pre-eclampsia, can also influence risk and are recommended as “risk enhancers” in the most recent AHA Cholesterol Practice Guidelines.
  • Engage women in their cardiovascular health. While this may be the hardest strategy to implement, it is the most important because for so long, women living with HIV have focused on surviving HIV that they do not perceive they are at elevated CVD risk. Dr. Looby acknowledges, “It can be difficult to find time to do this given the competing demands of clinical care, but education is essential to empowering women living with HIV to become active participants in their care. Delivering education in plain language that is easily understood by patients. Asking patients basic questions like, “Do you know what heart disease is?” or “Do you know your cholesterol levels and what they mean?” can provide simple snap shots of important information that can be built upon at subsequent visits, or followed up by providing supplemental educational materials.” Through this patient-focused engagement women living with HIV will be able to take charge and reduce their blood pressure, cholesterol, weight, and smoking resulting in improved cardiovascular health.

Almost every minute a woman dies from heart disease. But they don’t have to. We are privileged to serve in a profession dedicated to improving the health of our fellow humans. But human health is complex and, for women living with HIV, we cannot just treat their HIV or their CVD or their depression or their symptoms of menopause- we have to treat these intertwining conditions together. There are countless barriers to doing this well, and as new models of delivering cardiovascular care in HIV are under investigation, I am confident we will learn how to do this better. In the meantime, we have start today and commit to implementing strategies in our own practice to improve the heart health of women living with HIV.

 

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Eye: A Window To The Heart

An eye oftentimes feels like the most underappreciated systems in the field of vascular biology. An eye is a highly vascular organ then it gets credit for and here’s why – ranging from high blood pressure or diabetes to early signs of stroke, an eye exam can tell a physician a lot about one’s health.

In a series of blog posts, I decided to highlight these key connections between the eye and the human body. This article will focus on the current knowledge linking eye and the heart.

There are quite a few similarities between the vasculature (or simply put, blood vessels) of the eye and heart. Not only are there functional and structural similarities, but the eye and heart also share many of the common risk factors. For example, risk factors like high cholesterol, high glucose, hypertension that contribute to atherosclerosis, can also lead to eye diseases like macular degeneration and retinal vein occlusions. Photo taken of the back of the eye, that clinicians refer to as a fundus image, lets ophthalmologists look at blood vessels directly (as shown in the picture) – an eye is possibly the only organ that gives one an all-access backstage pass to its performances. Researchers and clinicians, rightfully call the eye as the window to one’s heart (this could probably apply beyond just biomedical sciences!).

Changes in the small micro-vessels of the eye can be directly correlated to underlying cardiovascular disorders. In the late 1970’s, clinical researchers learned that atherosclerotic lesions in the retinal vessels were indications of coronary artery disease and this was found by simple observation of fundoscopic images of patients. It is also possible to measure vessel dynamics like tortuosity (twists and turns) and caliber (diameter) with retinal exams coupled with flicker-light. With advanced imaging techniques, researchers are also able to calculate small changes in the microcirculation by simply imaging the retinal vessels. An interesting study performed in twin children, measuring the retinal arteriole, was able to predict signs of myocardial infarction as well.

The non-invasiveness of imaging the retinal vessels can certainly be an appeal to clinicians who otherwise rely on angiography to diagnose coronary complications. The retinal vessels can be quite information rich, but one only needs to look closely.

 

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Diabetes Makes Heart Disease Worse

Global awareness has made us cognizant that people with diabetes are susceptible to various disorders involving eye, kidney or nervous system and blood circulation affecting the limbs in the long run. Along these lines, type 2 diabetic patients are more likely to develop heart disease and have a greater incidence of heart attack. According to American Heart Association (AHA), diabetes is one of the major contributing factors for cardiovascular disease and accounts for at least 68 percent of diabetic population of age 65 or older to die from some form of heart disease.

Diabetic heart disease (DHD) is a broader term used to explain heart problems in patients who have diabetes. DHD may include conditions like coronary heart disease, where plaque accumulating in your arteries reduces the blood flow to the heart eventually leading to heart failure, a condition where your heart cannot pump enough blood to meet your body’s requirements. Another consequence of diabetes can be diabetic cardiomyopathy where the damage is extended to the structure and function of the heart. Patients with diabetic cardiomyopathy are more predisposed to develop irregular heartbeat disorders called arrhythmias.

Arrhythmias are conditions in which there is a problem with the rate or rhythm of your heartbeat. It is observed when the electrical signals to the heart that coordinate heartbeats do not function properly. This leads to increase in heart rate (basal rate of more than 100bpm), a condition called trachycardia or decrease in heart rate (basal rate less than 60bpm), called bradycardia. The detailed illustration of these conditions can be found at AHA website. While these conditions can have serious complications in patients, the condition becomes far worse in patients with DHD.

Under normal conditions, mitochondrias which are the energy sources of the cell, give rise to dangerous chemicals known as reactive oxygen species (ROS), byproducts of aerobic metabolism. Oxidative stress occurs when there is excessive production of ROS and if these chemicals are not removed, they possess damage to proteins, tissues and genetic material of the heart cells. However, mitochondria have antioxidant defense systems which decrease ROS production. Under pathological conditions such as diabetes, glucose fluctuations far exceed the ROS production than the oxidative defense systems are capable of cleaning and thus the problem becomes far more intense.

At this year’s Scientific Sessions, one of my colleagues presented his work establishing an interesting link between oxidative stress and arrhythmias. His project focused on protein which is a key enabler of ROS- mediated cardiac arrhythmias, known as mitochondrial translator protein (TSPO). TSPO is an outer mitochondrial membrane protein, previously described as peripheral benzodiazepine receptor, a secondary binding site for diazepam. It’s primarily associated with cholesterol transport to inside the cell, while the group explains its potential role in mitochondrial instability during arrhythmias by mechanism, where excess ROS generated in diabetic patient positively up-regulates its own levels – a process called ROS induced ROS-release (RIRR). Thus, TSPO can be a potential therapeutic target against arrhythmias in diabetic patients. Preliminary data by the group confirmed the increased levels of TPSO in hearts of diabetic rats, which might be responsible for increased propensity of diabetic hearts to arrhythmic events. While TPSO is probably upregulated as compensatory mechanism during type 2 diabetes, its global gene silencing may interfere with essential homeostatic function including cholesterol import and mitochondrial biogenesis. In relation to that, the group is further looking into avenues for targeted and specific TSPO inhibition in the areas affected after heart attack.

Personally, I am not only proud of his work but also hopeful that research studies like his help us to identify potential targets for curing serious conditions like DHD.

 

References:

Ilkan ZAkar FG. The Mitochondrial Translocator Protein and the Emerging Link Between Oxidative Stress and Arrhythmias in the Diabetic Heart.Front Physiol. 2018;26;9:1518

Ilkan Z, Strauss B, Akar FG. Reversal of TSPO Upregulation in the Diabetic Heart by Chronic TSPO Gene Silencing Causes Metabolic Sink via an Increase in ROMK Expression. Circulation. 2018;138:A16826.

 

 

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How the Immune System Favors Females in Pulmonary Artery Hypertension? Another Regulatory T Cell Story.

While it is commonly thought that cardiovascular disease is a man’s disease, CVD is the number one killer of women with the same number of deaths per year as cancer, diabetes and respiratory disease combined (according to 2015 statistical data from AHA). In addition, women exhibit different and more silent symptoms of heart attacks. There is a lot of interest in the difference between how males and females respond to CVD. A lot of emphasis is put on hormonal differences, but the immune system also seems to play an important role in this disparity. Females have a more robust immune system and therefore respond faster to infections providing more protection than in males. However, a more responsive immune system also means a more reactive immune system that can result in increased incidence of autoimmune diseases, such as rheumatoid arthritis and lupus.

Part of the difference in the immune system response in females can be attributed to the fact that multiple immune-related genes are expressed on the X chromosome. Since females have two alleles of the X chromosomes and males have only one, it is evident that females express more genes that regulate immune system functions. One of these genes is Foxp3, the key transcription factor for regulatory T cells, an adaptive immune cell which I have discussed before in a previous post. Regulatory T cells play an important protective role in CVD, especially in atherosclerosis and hypertension.

Pulmonary artery hypertension (PAH) is a fatal cardio-pulmonary disorder where the pulmonary arterioles narrow leading to a right ventricular fibrosis, heart failure and death. Regulatory T cells play an important role in this disease as animal models that lack regulatory T cells are more susceptible to PAH. Adding regulatory T cells back prevents the development of PAH showing the protective power of these cells. A recent study published in the journal Circulation Research, shows that in the absence of regulatory T cells, females rats are more prone to PAH than male animals due to a lower levels of PGI2, a pulmonary vasodilator, and the lack of the enzyme COX-2 that regulated PGI2. The researchers conducting the study show that by transferring regulatory T cells into these rats, these immune cells were sufficient to restore the levels of COX-2 and PGI2, as well as other immune inhibitory molecules PDL1 and IL-10. The authors suggest that regulatory T cells have both a direct and indirect effects on the arteries. The direct effects are exerted on the endothelial cells directly via COX-2 and PGI2, and the indirect effect is through the release of inhibitory molecules such as IL-10 and TGF, both of which would result in immune suppression and preventing inflammation. The results from this report suggested that females are more reliant on regulatory T cells for protection against PAH.

These new findings highlight the subtlety of immune regulation between females and males and further proves that in addition to hormonal differences, immune regulation disparities between genders that can alter the outcome of cardiovascular diseases. By understanding more about gender differences in CVD and the immune system, and figuring out ways to manipulate these subtle differences, scientists hope to achieve a more personalized and effective therapies to women versus men to combat CVD.

 

Dalia Gaddis Headshot

Dalia Gaddis is a postdoctoral fellow at the La Jolla Institute for Allergy and Immunology. She has a Ph.D. in microbiology and immunology. She is currently working on understanding the interactions between the immune system and atherosclerosis development

 

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A Shift in Focus: From a Multi to Single Modality Approach

Since the first A-mode echocardiogram, there have been great revolutional changes and the use of noninvasive cardiac imaging has grown substantially during the past decade. Echocardiography and nuclear modality have been the primary imaging modalities for management in patients with different cardiovascular diseases. The introduction of cardiac magnetic resonance (CMR), computer tomography (CT), and three-dimensional (3D) printing, makes things quite different. Multi-modality imaging plays a role in all cardiovascular diseases that includes ventricular function, coronary artery disease, valvular disease, congenital heart disease, guidance for interventions, and vascular diseases. However, the use of each modality requires knowledge, expertise and forethought about cardiac diagnoses to avoid excess coast, inappropriate testing and to improve outcomes. Unnecessary duplication of investigations must be avoided for cost effective healthcare delivery.

For more than a decade, organizations such as the American College of Radiology and the American College of Cardiology Foundation have published criteria delineating the appropriate use of cardiac imaging. These specialty society guidance documents are designed to provide clinicians with recommendations regarding the use of imaging and are focused on reducing unnecessary and inappropriate testing. In response to rapid and unsustainable growth in the use of cardiac imaging procedures, various professional medical organizations have developed appropriate use criteria (AUC) to guide physicians and payers on effective use of these procedures. The AUC serves as a guide for physicians to incorporate symptoms, risk factors, and clinical history in selecting the patients for whom testing is most appropriate, based on the best available evidence or expert consensus; Furthermore, the AUC can help physicians steer other patients to alternative tests or no testing at all.

The AUC classify the appropriateness of testing across a range of clinical scenarios in 3 categories: “appropriate” (established value), “may be appropriate” (uncertain value), and “rarely appropriate” (no clear value). The AUC are intended to be used as part of a comprehensive disease management plan to maximize the value of care by minimizing unnecessary imaging and resultant downstream invasive procedures. (1). Appropriate use helps to avoid excess costs; enhances the value of imaging in risk stratification and decision making; and reduces radiation risk, particularly in women (2). Moreover, the principle of applying expert consensus criteria to choose the best testing strategy for each patient is widely accepted by payers, physicians, and patient groups.

  • The goal of this statement is not to showcase CMR as the exclusive modality for cardiac diagnosis but to highlight this tool as the corner stone of noninvasive cardiac imaging. By using a static and a gradient magnetic field in combination with a radiofrequency field, CMR imaging has evolved from a less commonly used technique into a tool with the potential to find an important clinical role in the near future for the noninvasive assessment of morphological and functional aspects of the heart. Consequently, CMR belongs to the fastest growing new fields of broad MR application. At the same time, CMR uses some of the strongest and fastest switching electromagnetic gradients available in MR imaging. CMR has become the primary imaging tool in many centers in characterizing disease severity and planning of patient management.
  • Volumes and Function: CMR measures ventricular volumes and mass using a simple acquisition of a 3D stack of contiguous short-axis cines with full biventricular coverage. CMR is significantly more accurate and reproducible than other techniques which makes it the technique of choice for longitudinal study of patients over time and for reducing sample size for drug studies.
  • Great Vessels: Three-dimensional angiography with gadolinium enhancement may show the lesion more clearly in high resolution, but it also shows any associated pathology (collaterals). CMR is fast and accurate for the diagnosis of aortic dissection although local issues relative to availability will determine whether CMR, CT, or echocardiography is used.
  • Valvular Heart Disease: CMR has a significant role in valve disease, but it usually acts as a second-line technique to assist when echocardiography with Doppler has proved problematic because of limited acoustic access, highly eccentric jets, or the need for quantification. The quantification of valve regurgitation is a strength of CMR because of its capability of measuring accurate ventricular stroke volumes from multislice ventricular planimetry and comparing this with the measurement of great vessel flow from velocity mapping.
  • Congenital Heart Disease: CMR is widely used to assess congenital heart disease, and when used in concert with echocardiography, the need for invasive assessment has been significantly reduced. CMR is particularly useful for the safe, accurate, and reproducible quantification of the left-to-right shunting of blood that occurs frequently in congenital heart defects such as atrial or ventricular septal defects, patent ductus arteriosus, aortopulmonary window, and partial or total anomalous pulmonary venous return.
  • Myocardial Ischemia: CMR is a safe and proven modality for detecting ischemic heart disease. Within a single study, CMR is able to assess rest and stress regional contraction, and localize and evaluate regions of myocardial ischemia and viability, of importance given the prognostic impact for the patient. With performance that is comparable to PET/SPECT and at times favorable compared to stress echocardiography, it is now an essential tool for diagnosing ischemia and for determining the likelihood of success following myocardial revascularization.
  • Non ischemic cardiomyopathy: CMR with its higher spatial resolution is considered the gold standard for evaluating ventricular mass, volumes, and ejection fraction. CMR can be used for accurate diagnosis of several conditions, especially cardiomyopathies. CMR is an invaluable tool, not only in differentiating nonischemic from ischemic cardiomyopathy, but also in aiding the accurate diagnosis of the subtype of nonischemic cardiomyopathy. CMR should routinely be integrated in the diagnostic workup of various cardiomyopathies.

CMR is a valuable tool for the evaluation of patients with, or at risk for, heart failure and has a growing impact on diagnosis, clinical management, and decision making. Through its ability to characterize the myocardium by using multiple different imaging parameters, it provides insight into the etiology of the underlying heart failure and its prognosis. CMR continues to develop across a broad range of clinical applications, and much can be expected of this technology in the future.

Fawaz Alenezi Headshot

Dr. Fawaz Abdulaziz M Alenezi is a Clinical Imaging Fellow at the Duke University Health Systems. He conducts medical research on the derivation and validation of novel echocardiographic approaches to myocardial deformation and a new echocardiographic technique which assists patients with heart ventricular function.