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Reducing Disparities in Access to Cardiovascular Disease Prevention with the Polypill

This year’s AHA 2020 Scientific Session is taking place using combined modalities, including live, simulive, and on-demand sessions. Despite the change from the traditional in-person modality to the virtual approach, listening to the opening session and findings from emerging science reminded me of the mission of the American Heart Association to be a relentless force for a world of longer, healthier lives. This year’s scientific sessions also align with a wide range of events we all have experienced this year, ranging from the COVID-19 pandemic, to racial/ethnic, gender, and income disparities leading to health inequity in our society. These further present a call to action in order to address these very same societal issues that are likely to impact on health equity for the most vulnerable groups.

The cardiovascular polypill, or combined aspirin, cholesterol, and blood-pressure-lowering agents into a single pill has been proposed for nearly a decade as a complementary option in the prevention of cardiovascular diseases in intermediate- and high-risk patient populations.1 Yet there have been previous limitations in understanding its efficacy and relative safety in developing countries.2  The findings of the International Polycap Study (TIPS)-3 presented by Dr. Salim Yusuf during the late-breaking science session bring a ray of hope to the global disparities in cardiovascular disease prevention.3 The study resulted in a 30% reduction in cardiovascular risk with a combined regimen composed of Aspirin and a polypill (atenolol, ramipril, hydrochlorothiazide, and a statin).3  Based on the TIPS-3 study, the polypill approach presents a safe and cost-effective strategy with the potential for satisfactory medication adherence.

While these findings are promising for developing countries, the polypill may present a viable solution to underserved, low-income minority groups in developed countries.4  Another important takeaway from this study was the inclusion of women, who represented 53% of the sample.  Their inclusion in global studies such as this one also highlights the move into health equity and awareness of women’s health globally at a time when cardiovascular disease continue to present women’s greatest health threat. Traditionally, the enrollment of women in clinical trials has been limited. This has resulted in a limited understanding of risk factors and benefits from treatment regimens for cardiovascular disease-specific to women.5

As we observe the benefits related to polypill, it is also important to keep in mind that it may not align with the medical trend in developed countries for precision medicine, leading to individualized, targeted therapy.6  With cardiovascular disease remaining the leading cause of mortality and morbidity in developed and developing countries, and low-income, ethnic minorities affected by it, the question remains on long-term, best preventive strategies in the reduction of cardiovascular risk factors for all. It will also be important to measure long-term outcomes related to polypill strategies in future studies.

 

References:

  1. Lafeber M, Spiering W, Singh K, Guggilla RK, Patil V, Webster R; SPACE collaboration. The cardiovascular polypill in high-risk patients. Eur J Prev Cardiol. 2012 Dec;19(6):1234-42. doi: 10.1177/1741826711428066. Epub 2011 Oct 21. PMID: 22019908.
  2. Nguyen C, Cheng-Lai A. The polypill: a potential global solution to cardiovascular disease. Cardiol Rev. 2013 Jan-Feb;21(1):49-54. doi: 10.1097/CRD.0b013e3182755429. PMID: 23018668.
  3. Joseph P, Pais P, Dans AL, Bosch J, Xavier D, Lopez-Jaramillo P, Yusoff K, Santoso A, Talukder S, Gamra H, Yeates K, Lopez PC, Tyrwhitt J, Gao P, Teo K, Yusuf S; TIPS-3 Investigators. The International Polycap Study-3 (TIPS-3): Design, baseline characteristics and challenges in conduct. Am Heart J. 2018 Dec;206:72-79. doi: 10.1016/j.ahj.2018.07.012. Epub 2018 Aug 2. PMID: 30342297; PMCID: PMC6299262.
  4. Muñoz D, Uzoije P, Reynolds C, Miller R, Walkley D, Pappalardo S, Tousey P, Munro H, Gonzales H, Song W, White C, Blot WJ, Wang TJ. Polypill for Cardiovascular Disease Prevention in an Underserved Population. N Engl J Med. 2019 Sep 19;381(12):1114-1123. doi: 10.1056/NEJMoa1815359. PMID: 31532959; PMCID: PMC6938029.
  5. Saeed A, Kampangkaew J, Nambi V. Prevention of Cardiovascular Disease in Women. Methodist Debakey Cardiovasc J. 2017 Oct-Dec;13(4):185-192. doi: 10.14797/mdcj-13-4-185. PMID: 29744010; PMCID: PMC5935277.
  6. Psaty BM, Dekkers OM, Cooper RS. Comparison of 2 Treatment Models: Precision Medicine and Preventive Medicine. JAMA. 2018 Aug 28;320(8):751-752. doi: 10.1001/jama.2018.8377. PMID: 30054607.

 

“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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Modifiable Factors Influence Non-modifiable Factors for Cardiovascular Health?

The scientific community continues its full force swing at reducing cardiovascular disease risk. In the Scientific Session titled “Microbiome in Cardiovascular Disease,” the complexity of accounting for human variation was the theme. The important difference and interactions between non-modifiable (genetics) and modifiable (diet, exercise, smoking, etc..) factors were presented. Dr. Katherine Tucker opened up the session by highlighting work from Thanassoulis et. al., 2012, which identified 13 single nucleotide polymorphisms (SNPs) to generate a genetic risk score (GRS) to predict cardiovascular events and coronary artery calcium (CAC). Single nucleotide polymorphisms are the most common type of genetic variation among people and are used to help quantify the variation in individuals (1). The CAC score comes from a test that quantifies the amount of calcium accumulation in the walls of the coronary arteries. A lower score represents a greater risk and a lower score relates to a lower risk of heart disease. Dr. Tucker went on to explain the genetic risk is influenced by individual environmental factors (i.e. smoking, exercise, and diet) (2). Recent data from the CARDIA study supports this in reporting that, “low-carbohydrate diets at a younger age is associated with an increased risk of subsequent CAC progression, particularly when animal protein or fat are chosen to replace carbohydrates. (3).”

Figure 1 source: https://doi.org/10.1093/nutrit/nux001

The changes in macronutrient content in a diet is related to what happens in the gut. Within the gut, there are trillions of bacteria that make up a microbiome. An individual microbiome modulates the immune system and metabolic processes. The microbiome influence on human health is so pronounced in that it actively reprograms the genome in response to the environment, changing the bacteria phyla ratios that lead to down-stream effects that could influence cardiovascular health (Figure 1) (2). Dietary fiber and prebiotic consumption are two components that modulate the composition of the gut microbiome (Figure 2) (4). Also, there is some great news for you Kombucha fans out there! Fermented foods have some benefits for the gut.

Figure 2. Source: https://doi.org/10.1093/nutrit/nux062

Bhat and Kapila 2017 further highlight diet in a review stating “The composition of the gut microbiota has a tremendous influence on host metabolism.” Perhaps specific dietary interventions can reduce the risk of cardiovascular disease with the focus on obtaining an optimal microbiota composition. Zhang et. al., 2020, showed how detrimental diets with contain highly processed foods can be the bacteria in our gut (Figure 3) (5).

Figure 3. Source: https://doi.org/10.1093/ajcn/nqaa276

To further highlight how much people differ from one another, Dr. Tang from the Cleveland Clinic explained only 37% of the gut is actually shared between twins. In addition, there are significant diurnal variations in response to meals consumed among people. The work presented the relationship between microbiota and trimethylamine (TMA)/trimethylamine–N-oxide(TMAO) generation. Elevated TMAO levels predict major adverse cardiac events like death, myocardial infarction (MI), and stroke (Figure 4) (6). Dr. Tang explained that risk is highest with people who displayed the highest baseline levels of two TMAO precursors choline or L-carnitine, while some may show no risk with higher levels. Dr. Tang emphasized the variation again among individuals.

Figure 4. Source: Tang, W. W., & Hazen, S. L. (2014)

We are only scratching the surface with the modifiable risk factors for heart disease. Specifically, the gut shows an area rich for investigation. The gut microbiota contributes to human physiology and diseases and it is something to be excited about for biomedical researchers.

 

References:

  1. Thanassoulis G, Peloso GM, Pencina MJ, Hoffmann U, Fox CS, Cupples LA, Levy D, D’Agostino RB, Hwang SJ, O’Donnell CJ. A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study. Circ Cardiovasc Genet. 2012 Feb 1;5(1):113-21. doi: 10.1161/CIRCGENETICS.111.961342. Epub 2012 Jan 10.
  2. Mohd Iqbal Bhat, Rajeev Kapila, Dietary metabolites derived from gut microbiota: critical modulators of epigenetic changes in mammals, Nutrition Reviews, Volume 75, Issue 5, May 2017, Pages 374–389, https://doi.org/10.1093/nutrit/nux001
  3. Gao, J. W., Hao, Q. Y., Zhang, H. F., Li, X. Z., Yuan, Z. M., Guo, Y., … & Liu, P. M. (2020). Low-Carbohydrate Diet Score and Coronary Artery Calcium Progression: Results From the CARDIA Study. Arteriosclerosis, Thrombosis, and Vascular Biology, ATVBAHA-120.
  4. Genelle R Healey, Rinki Murphy, Louise Brough, Christine A Butts, Jane Coad, Interindividual variability in gut microbiota and host response to dietary interventions, Nutrition Reviews, Volume 75, Issue 12, December 2017, Pages 1059–1080, https://doi.org/10.1093/nutrit/nux062
  5. Zefeng Zhang, Sandra L Jackson, Euridice Martinez, Cathleen Gillespie, Quanhe Yang, Association between ultraprocessed food intake and cardiovascular health in US adults: a cross-sectional analysis of the NHANES 2011–2016, The American Journal of Clinical Nutrition, https://doi.org/10.1093/ajcn/nqaa276
  6. Tang, W. W., & Hazen, S. L. (2014). The contributory role of gut microbiota in cardiovascular disease. The Journal of clinical investigation, 124(10), 4204-4211.

 

“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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Bending the Curve for CV Disease- Precision or PolyPill?

Source: https://www.phri.ca/

Drs. Yusuf and Pais from the Population Health Research Institute in Ontario, Canada presented data from the International Polycap Study (TIPS)-3 study[1] as part of the Late-Breaking Science Session: Bending the Curve for CV Disease-Precision or PolyPill? at the AHA20 Scientific Sessions. The aim of this study was to try to simplify primary prevention via a ‘polypill’ (Polycap) for not only cardiovascular disease (CVD) but also conditions with similar risk profiles, such as breast cancer and osteoporosis. The polypill contains 3 blood pressure medications (hydrochlorothiazide (25mg), atenolol (100 mg), ramipril (10mg)) and a statin (simvastatin (40 mg). They are searching for a ‘magic bullet’ if you will, to reduce these chronic diseases with a high burden in the U.S and around the world. Precision medicine can be effective but is costly. The use of a polypill can help to reduce the curve of disease burden or at least shift it towards reducing the number of high cardiovascular risk people worldwide.

Source: Joseph et al. The International Polycap Study-3 (TIPS-3): Design, baseline characteristics and challenges in conduct. Am Heart J. 2018 206:72-79

This study enrolled 5,713 middle aged participants from 10 different countries (Including India, Tanzania, and Tunisia). With a 2x2x2 factorial design, randomized controlled trial investigators aimed to assess the effectiveness of PolyCap the ‘Polypill’.  Participants were eligible for the study if they did not have prior heart disease or stroke. Participants were excluded if they had any contraindications to the study medications, low and symptomatic  hypotension, history of malignancy, and inability to attend follow-up. There were three treatment arms. The participants were randomized to the polypill vs placebo. In addition, participants were also randomized to receive aspirin (75 mg) and vitamin D (60,000 IU monthly) each vs. placebo. The primary outcome was major cardiovascular disease (CVD) (CV death, non-fatal stroke, non-fatal MI), plus heart failure, resuscitated and cardiac arrest, or revascularization with evidence of ischemia in participants taking Polycap versus placebo. For the aspirin arm, the primary outcome was composite CV events ( CV death, MI or stroke) and cancer. For vitamin D arm, the primary outcome was risk of fractures in participants taking Vitamin D. The data presented at AHA2020 Scientific Sessions was for the Polypill with and without aspirin alone vs. placebo. This was an intention to treat analysis. Investigators also conducted a sensitivity analysis for those who were not able to adhere to medications and identified outcomes at 30 days in the active and placebo groups.

Source: Joseph et al. The International Polycap Study-3 (TIPS-3): Design, baseline characteristics and challenges in conduct. Am Heart J. 2018 206:72-79

After a follow-up time up to 5 years, the investigators enrolled a cohort of 53% women with intermediate CVD risk based on the IH (INTERHEART) risk score (1.5 % per year risk of CVD). For participants taking the Polypill vs. placebo, there was a significant mean reduction in systolic blood pressure by approximately 5 mm Hg and LDL-C by approximately 19 mg/dL. There was a 21% reduction in the primary outcome; however, overall mortality was not significantly different. The greatest reduction was seen with revascularization with a 60% reduction compared to the placebo. There was a reduction in cancer outcomes as well, but not significantly; this is likely related to low events. The bleeding risk profile was low. With the combination of aspirin and the Polypill, there was a 31 % risk reduction compared to placebo, aspirin alone, and the Polypill alone ( compared to 14% with aspirin vs. placebo alone)  in the composite primary outcome but no overall mortality benefit. This was mainly driven by a reduction in stroke. CVD death and cancer were significantly reduced by 30% compared to placebo. There was also a reduction with systolic blood pressure and LDL-C as seen with the Polypill alone. Aspirin alone did not show any difference with major/minor bleeding or GI bleeding likely related to having a run-in period and a lower dose of asa (75 mg). In both cases, the heart failure rate was higher in both groups but this was not significant with a wide confidence interval with low event. It is important to note that lifestyle modification teaching was also instituted and the reduction in outcomes is therefore contributed to both the medication and education.  One main issue was adherence to the medications (just two pills) up to 43%! This was in part due to COVID19 by the end of the study.  Per the sensitivity analysis, the outcomes of those with some adherence (<30 days) were still significantly lower than the placebo. Taking something for even a short period of time is better than nothing.

The authors highlight the significant limitation of non-adherence which can create a selection bias in the data. However,  if only half eligible people adhere to this regimen, 3-5 million CVD events can be avoided each year globally. They note that the challenge of adherence lies in social determinants of health, which have a great impact on CVD outcomes. More needs to be done to understand cost-effective ways to ‘bend the CVD curve’ by identifying effective implementation programs (including telehealth) to distribute this combination of medications.

References:

Joseph et al. The International Polycap Study-3 (TIPS-3): Design, baseline characteristics and challenges in conduct. Am Heart J. 2018 206:72-79

 

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The Role of Intestinal Microbiota and Cardiovascular Disease

In recent years, the role of intestinal microbiome and host health has gained wide interest due to many findings suggesting gut microbiota may play a role in the development and maintenance of cardiovascular disease (CVD) and metabolic disorders, such as hypertension, obesity, diabetes mellitus, and metabolic syndromes. Hypertension, one of the important risk factors for CVD, plays a significant role in intestinal dysbiosis. Dysbiosis is a change in the gut microbiota that imbalance the ratio of Firmicutes (F) to Bacteroidetes (B) (F/B) and is considered as a biomarker for gut dysbiosis. When environmental factors, dietary habits, medications such as antibiotics, intestinal infections or other factors alter the species and balance of the intestinal microorganism ecosystem in the adult gut, dysbiosis can take place, causing inflammation and metabolic disorders, thus promoting the development of CVD.

The recently discovered contribution of intestinal microbiota and its contribution to the development of CVDs and its risk factors has significantly increased attention to the important connection between the heart and the gut. The intestinal microbiota function as a filter of our largest environmental exposure, that is what we eat. What we eat provides nutrients for intestinal microbial metabolism. Several intestinal microbial metabolites are biologically active and could possibly affect the host phenotype and health outcomes.

The gut microbiota resembles a large virtual endocrine organ that is capable of responding and reacting to circulating signaling molecules within the host. Intestinal microbiota- host interaction occurs through many pathways, including trimethylamine-N-oxide (TMAO) and short chain fatty acids (SCFA). This interaction has been shown to affect the host phenotypes relevant to cardiovascular disease, ranging from inflammation, obesity, and insulin resistance, to more direct process like atherosclerosis and susceptibility to hypercoagulability. Furthermore, multiple animal and human clinical studies revealed striking association between either gut microbiota composition, or their derived metabolites, and both the presence and incident development of CVD.

The healthy gut microbiome

 The composition of the healthy gut microbiome can vary significantly across individuals. However, this composition is relatively stable over time. The gut microbiome is primarily composed of species within the Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria and Cerrucomicrobia phylae. The precise composition of species varies among individuals due to variety of genetic and environmental factors, including diet and medications used such as antibiotics. It is not surprising that microbial metabolite profiles are strongly associated with enterotypes. For instance, Bacteroidetes bacteria predominantly metabolize proteins, whereas, Prevotella species are saccharolytic bacteria that primarily metabolize carbohydrates. The gut microbiota has evolved to play a symbiotic role in extracting calories from indigestible macromolecules. Indigestible carbs and proteins are fermented by the colonic bacteria to form short chain fatty acid (SCFA) such as acetate, propionate and butyrate which play a significant role in weight loss and provide various health benefits. Microorganisms that are incapable of catabolism of indigestible macromolecules, use the SCFA produced by other microbiota as fuel in a process called cross-feeding. In addition to its role as an important energy source for both host and microbiota, the SCFA is important in regulation of the inflammatory response. Furthermore, commensal gut bacteria are necessary for dampening the immune response to non-pathogenic bacteria, hence they protect the host from the harms of sterile inflammation and they are also responsible for establishing an intact gut epithelial barrier, thus preserving the digestive and absorptive functions of the intestine and protecting from the invasion of pathogens and toxic metabolites into the circulation.

 The Intestinal Microbiota and CVD:

 The unique link between the gut microbiota and cardiovascular diseases has been described recently with the discovery of the link of Trimethylamine-N-Oxide (TMAO) to atherosclerosis. TMAO is produced by the breakdown of Phosphatidylcholine and other trimethylamine containing compounds by the intestinal bacteria. In a recent human experiment that consisted of ingestion of two hard boiled eggs (high in phosphatidylcholine) and deuterium [d9]-labeled phosphatidylcholine before and after suppression of intestinal microbiota with oral broad-spectrum antibiotics, it was found that circulating TMAO and its d9 isotopologue (both molecules are derived from the metabolism of phosphatidylcholine) was remarkably elevated after the phosphatidylcholine challenge.  However, plasma levels of TMAO were markedly suppressed after the administration of antibiotics and then reappeared after withdrawal of antibiotics. In a large independent clinical cohort (n=4,007), patients in the highest quartile of plasma TMAO levels had a 2.5-folds higher risk of major adverse cardiovascular event than patients in the lowest quartile. Furthermore, higher fasting plasma levels were found to correlate with the risk of incident major adverse cardiovascular events independent of the classic cardiovascular risk factors. In mouse models, studies confirmed that dietary supplementation of Choline or TMAO increased TMAO levels, macrophage foam cell formation and inflammation, and atherosclerosis development. Moreover, TMAO has also been shown to enhance platelet hyperactivity and thrombosis risk. In a human cohort study, there was a dose-dependent association between plasma TMAO levels and platelets aggregation. This association explains the increased risk of cardiovascular events with high TMAO levels.

Ahmadmehrabi S, Tang WHW. Gut microbiome and its role in cardiovascular diseases. Curr Opin Cardiol. 2017;32(6):761-766. doi:10.1097/HCO.0000000000000445

Dysbiosis has been linked to increased CVD risk. A lower ratio of Bacteroidetes to Firmicutes has been associated with significantly increased risk to hypertension, diabetes mellitus, obesity and atherosclerosis. When there is decreased intestinal microbiota diversity (decreased Bacteroidetes to Firmicutes ratio) there will be an increase in the plasma TMAO levels and reduced SCFA level which is important for increasing insulin sensitivity, secretion of the satiety hormone GLP1, lower BMI and increase HDL levels. Higher levels of TMAO and lower levels of SCFA has been associated with increased risk for Type 2 Diabetes (T2DM) and metabolic syndrome. Hypertension has also shown to be associated with gut dysbiosis; however, the exact mechanism is still unknown.

 

Therapeutic Interventions:

The recent discovery of the TMAO and SCFA pathways and evidence for links between gut dysbiosis and several risk factors for cardiovascular disease now provides new opportunities for therapeutic interventions. Now knowing that alteration in the gut microbiota community is associated with much pathology, therapeutic interventions aimed at restoring microbial composition balance present an auspicious therapeutic approach. A fiber rich diet has been reported to increase SCFA- producing microbiota and lower blood pressure in patients with end-stage-renal disease. Dietary supplements of prebiotics, which are typically food indigestible molecules have a favorable impact on intestinal microbiota composition and can be beneficial. Similarly, probiotics, which are compilation of live bacteria administered to promote gut microbiome health have shown to have beneficial effects on the gut microbial environment and to be associated with cardioprotective effects. While prebiotics and probiotics focus on eliciting the growth of healthy gut bacteria, antibiotics treatment is focused on reducing the harmful bacteria content. However, the lack of specificity of broad-spectrum antibiotics makes them a less favorable approach.

With the recent discovery of the unique pathways between the gut microbiome and the heart and their association with CVD, we are presented with a new and a promising opportunity for CVD treatment and prevention. The most up-to-date discoveries and use of a structural analog of choline,3,3-dimethyl-1-butanol (DMB), was shown to inhibit TMA production and reduce circulating plasma TMAO levels and to reduce macrophage foam cell formation and risk of atherosclerosis, more importantly, this small-molecule inhibitor shown not be lethal to the gut microbiota ecosystem.

References:

  1. Ahmadmehrabi S, Tang WHW. Gut microbiome and its role in cardiovascular diseases. Curr Opin Cardiol. 2017;32(6):761-766. doi:10.1097/HCO.0000000000000445
  2. Yang T, Richards EM, Pepine CJ, Raizada MK. The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease. Nat Rev Nephrol. 2018;14(7):442-456. doi:10.1038/s41581-018-0018-2
  3. Jin M, Qian Z, Yin J, Xu W, Zhou X. The role of intestinal microbiota in cardiovascular disease. J Cell Mol Med. 2019;23(4):2343-2350. doi:10.1111/jcmm.14195
  4. Tang WHW, Bäckhed F, Landmesser U, Hazen SL. Intestinal Microbiota in Cardiovascular Health and Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(16):2089-2105. doi:10.1016/j.jacc.2019.03.024
  5. Yoshida N, Yamashita T, Hirata KI. Gut Microbiome and Cardiovascular Diseases. Diseases. 2018;6(3):56. Published 2018 Jun 29. doi:10.3390/diseases6030056

“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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Cardiovascular diseases in women: the heart of the matter

It was 4 am one winter night on call when I got paged:

“Youngish diabetic female, mid-thirties, chest pain for a few hours. Unremarkable ECG. Let me send troponins and see. Doesn’t seem cardiac.”

“Doesn’t seem cardiac”

Dismissed, just like that, because she was young, and because she was a woman.

A proper listen to her symptoms revealed that this could indeed, be cardiac. She was admitted, her troponins were raised, a coronary angiography done a few hours later showed an occluded principal obtuse marginal branch which was stented. She was symptom-free the same day.

Fortunately for her, a definitive culprit lesion in her coronaries could be identified, that was amenable to stenting and thus treated. For the majority of women with non-obstructive coronaries, presenting with myocardial infarction with non-obstructive coronary arteries (MINOCA)1 or ischemia with no obstructive coronary arteries (INOCA), investigations would very likely have stopped right there, with that normal coronary angiography. Dismissed.

CVD in women

Cardiovascular disease (CVD) is the number one cause of mortality among women across the globe.2 Despite improved treatment algorithms and the enormous strides made in cardiovascular care, women continue to have worse clinical outcomes than men, partly owing to them being underdiagnosed, understudied and undertreated.

One size does not fit all: A spectrum of differences

The inherent biological differences between men and women, in addition to the socio-cultural attributes of gender, mean that women have very different characteristics of ischemia in terms of symptoms, triggers, and aetiologies.3

Symptoms: While chest pain is the predominant presenting symptom in both men and women in acute coronary syndrome (ACS), historically, women have been known to present with more “atypical” symptoms such as neck pain, fatigue, dyspnea or nausea, often triggered by emotional stress but even this time-honored notion has been challenged by a recent study that found that typical symptoms were more common among women and have greater predictive value in women than in men with myocardial infarction.4

Co-morbidities: Women with ACS are known to be older, with a clustering of risk factors and greater prevalence of co-morbidities.3  Particularly, diabetes, smoking and a family history of ischaemic heart disease have been shown to have a stronger impact on event rates among women.3 Younger women with ACS have been found to have a worse pre-event health status (both physical and mental) in comparison to men.5

The age paradox: Premenopausal women are thought to be relatively protected against CVD compared to similar-aged men, owing to favorable effects of estrogen on cardiovascular function and metabolism. Intriguingly though, recent studies report an increase in hospitalization rates of ACS among young women, despite a decline among younger men. The mechanisms behind these differences remain a fairly understudied area.

Delayed presentation: Women are also known to present later, frequently attributing their symptoms to a non-cardiac-related condition such as acid reflux, stress, or anxiety.2,3 This inaccurate symptom attribution, in addition to a lack of awareness of risk, and barriers to self-care in general, lead to a delay in seeking treatment, contributing to poorer outcomes.

Different etiologies: By virtue of an obstructed coronary artery, my patient got lucky in terms of prompt diagnosis and treatment. In about 10% of all patients, and in about a third of women, such a culprit coronary lesion cannot be identified on angiography.2,3 Furthermore, microvascular angina affects close to a half of patients with non-obstructive coronary arteries.7 This coronary microvascular dysfunction (CMD) is defined as the presence of symptoms and objective evidence of ischemia in absence of obstructive coronary artery disease, with blood flow reserve and/or inducible microvascular spasmAngina with no obstructive coronary arteries is twice as prevalent in women as in men, 7 and might also contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF), which is also more commonly observed in women.9

Women are still under-studied in clinical trials

In the face of such a formidable gender disparity in CVD, women continue to be under-represented in some areas of cardiovascular clinical trials, particularly in ischaemic heart disease and heart failure drug trials, the most common cardiovascular conditions affecting women. In fact, a number of pivotal cardiovascular drug trials of 2019 had less than a quarter of women enroll.12-15 Interestingly, the PARAGON-HF trial, where 51.7% of patients were women, found a heterogeneity in treatment response: women with HFpEF responded better to valsartan-sacubitril, with a 28% reduction (rate ratio 0.73) in the primary endpoint.

In a compelling 2018 editorial, doctors Pilote and Raparelli explore the practical reasons for under-enrollment of women in cardiovascular drug trials, notably male-patterned inclusion criteria and gender-related barriers to screening and participation in trials, such as caretaking roles and low socioeconomic status. While proposing interventions to mitigate this issue (childcare and such support for women during time spent as a research participant, inclusion criteria that consider sex differences in pathophysiology, prespecified subgroup analyses, etc.), they warn that such under-representation of women could lead to sex-biased outcome measurements and missed opportunities to transfer results in clinical practice.

The issue, in essence, is not just about researching CVD in women: even within this large cohort, differences in symptoms, presentation and outcomes, heterogeneity related to age, ethnicity and geographic locations exist. Why younger women with ACS tend to have unfavorable prognoses is an as-yet unanswered question, with huge scope for research, as is microvascular dysfunction, known to be more prevalent among women.

What can be done?

With February being national heart month, and the American Heart Association’s #GoRedForWomen campaign soaring at its highest, it seems like a good time to reflect on what can (and should) be done for women with CVD. Because there is plenty left to do.

Raise awareness: It’s vital that both women and men are aware that heart disease is as big a killer in women as in men. The AHA’s signature women’s initiative Go Red for Women (https://www.goredforwomen.org/) and the sub-initiatives of Wear Red Day are great platforms dedicated to increase women’s heart health awareness. The Women’s Heart Alliance (https://www.womensheartalliance.org/) is another organization working to promote gender equity in research, prevention, awareness and treatment.

Enroll more women in clinical trials: it’s important to identify barriers accounting for the low inclusion of women in clinical trials, and actively intervene to overcome them.

Women’s Heart Health Clinic: a number of programs have successfully initiated women’s heart health clinics, exclusively catering to the diagnosis and treatment of this often-underestimated patient group.

Get more women involved: at every level, be it as clinical trialists, advocates, physicians, nurses or other health-care providers.

As physicians, perhaps the best thing we can do for our female patients is to pay more attention. Don’t dismiss a symptom, because nothing should “not seem cardiac” until proven otherwise.

So, yes:

Listen to her.

Diagnose her.

Investigate her.

Study her.

Treat her.

And don’t just #GoRedForWomen in February. #GoRedForWomen throughout the year.

 

References

  1. Pasupathy S, Tavella R, Beltrame JF. Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): The Past, Present, and Future Management. Circulation. 2017;135(16):1490-1493.
  2. Mehta LS, Beckie TM, DeVon HA, Grines CL, Krumholz HM, Johnson Mnet al; American Heart Association Cardiovascular Disease in Women and Special Populations Committee of the Council on Clinical Cardiology, Council on Epidemiology and Prevention, Council on Cardiovascular and Stroke Nursing, and Council on Quality of Care and Outcomes Research. Acute Myocardial Infarction in Women: A Scientific Statement From the American Heart Association. Circulation. 2016;133(9):916-47.
  3. Haider A, Bengs S, Luu J, Osto E, Siller-Matula JM, Muka T, et al. Sex and gender in cardiovascular medicine: presentation and outcomes of acute coronary syndrome. European Heart Journal (2019) 0, 1–14.
  4. Ferry AV, Anand A, Strachan FE, Mooney L, Stewart SD, Marshall L, et al. Presenting Symptoms in Men and Women Diagnosed With Myocardial Infarction Using Sex-Specific Criteria. J Am Heart Assoc. 2019 Sep 3;8(17):e012307.
  5. Dreyer RP, Smolderen KG, Strait KM, Beltrame JF, Lichtman JH, Lorenze NP, et al. Gender differences in prevent health status of young patients with acute myocardial infarction: a VIRGO study analysis. Eur Heart J Acute Cardiovasc Care 2016;5:43–54.
  6. Arora S, Stouffer GA, Kucharska-Newton AM, Qamar A, Vaduganathan M, Pandey A, et al. Twenty year trends and sex differences in young adults hospitalized acute myocardial infarction: the ARIC Community Surveillance Study. Circulation. 2019;139:1047–1056.
  7. 037137Jespersen L, Hvelplund A, Abildstrom SZ, Pedersen F, Galatius S, Madsen JK, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J 2012;33:734–744.
  8. Ong P, Camici PG, Beltrame JF, Crea F, Shimokawa H, Sechtem U,et al. International standardization of diagnostic criteria for microvascular angina. Int J Cardiol 2018;250:16–20.
  9. Srivaratharajah K1 Coutinho T, deKemp R, Liu P, Haddad H, Stadnick E, et al. Reduced Myocardial Flow in Heart Failure Patients With Preserved Ejection Fraction. Circ Heart Fail. 2016;9(7).
  10. Scott PE, Unger EF, Jenkins MR, Southworth MR, McDowell TY, Geller RJ, et al. Participation of Women in Clinical Trials Supporting FDA Approval of Cardiovascular Drugs. J Am Coll Cardiol. 2018;71(18):1960-1969.
  11. Pilote L, Raparelli V. Participation of Women in Clinical Trials: Not Yet Time to Rest Our Laurels. J Am Coll Cardiol. 2018;71(18):1970-1972.
  12. Mehran R, Baber U, Sharma SK, Cohen DJ, Angiolillo DJ, Briguori C, et al. Ticagrelor with or without Aspirin in High-Risk Patients after PCI. N Engl J Med. 2019;381(21):2032-2042.
  13. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008.
  14. Schüpke S, Neumann FJ, Menichelli M, Mayer K, Bernlochner I, Wöhrle J, et al; ISAR-REACT 5 Trial Investigators. Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes. N Engl J Med. 2019 ;381(16):1524-1534.
  15. Presented by Dr Judith S. Hochman at the American Heart Association Scientific Sessions (AHA 2019), Philadelphia, PA, November 2019. https://www.ischemiatrial.org/system/files/attachments/ISCHEMIA%20MAIN%2012.03.19%20MASTER.pdf

 

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

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Follow Your Heart But Take Your Mind With You: Insights on Vascular Dementia

Cardiovascular diseases such as diabetes and hypertension are established risk factors for mild cognitive impairment (MCI) and vascular dementia (VD). Vascular pathology occurs alongside neurodegenerative disease pathology, and both are associated with interactive effects on the clinical presentation of VD1. Several cardiovascular risk factors of VD could be modified during the preclinical course of the disease during midlife rather than later in life or closer to VD onset2,3.

In this year at ISC19, Angela L. Jefferson reported results supporting that age-related aortic stiffness contributes to transmission of damaging pulsatility and reduction in blood flow. This contributes to blood brain barrier compromise, resulting in reduced cerebral perfusion and subsequent tissue damage4. Brain MRI results suggest that vascular dysregulation may drive neurodegeneration over time, possibly due to neurofibrillary tangle formation or synaptic degradation4.

Looking from another angle, Lawrence J. Fine presented on the interplay between CVD and VD in epidemiological studies. According to data from the American Heart Association, loss of a perfect cardiovascular health during midlife is concurrently associated with steep increase in risk of MCI and vascular dementia. A recent report from the Women Health Initiative Memory Study (WHIMS) assessed MCI and Parkinson’s disease (PD) in women with myocardial infarction (MI). The data suggests modest absolute numbers, but higher rates of MCI and Parkinson’s disease (PD) cases in women with myocardial infarction (MI) (adjusted HR for PD or MCI was 2.23, 95% CI 1.51 to 3.30)5.

Investigators of the SprintMind trial examined the effect of one or more intensive high blood pressure treatment than is currently recommended. SprintMind was a randomized controlled trial that compared intensive treatment (goal SBP < 120 mm hg) to standard treatment (goal SBP < 140 mm Hg). Patients with major CVD as strokes, diabetes and congestive heart failure were excluded. The results suggest that intensive blood pressure control causes no harm on cognition with actual reduction in MCI risk compared to standard treatment6.

Overall, these observations add novel insights on the association between CVD and VD. More data is needed to assess the extent to which CVD contributes to the occurrence of MCI and dementia in more diverse populations and over longer follow-up periods.

 

REFERENCES

  1. Yaffe, Kristine. “Prevention of cognitive impairment with intensive systolic blood pressure control.” Jama (2019).
  2. Gottesman, Rebecca F., et al. “Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) cohort.” Jama neurology 74.10 (2017): 1246-1254.
  3. Gottesman, Rebecca F., et al. “Association between midlife vascular risk factors and estimated brain amyloid deposition.” Jama 317.14 (2017): 1443-1450.
  4. Jefferson, Angela L., et al. “Higher Aortic Stiffness Is Related to Lower Cerebral Blood Flow and Preserved Cerebrovascular Reactivity in Older Adults.” Circulation 138.18 (2018): 1951-1962.
  5. Haring, Bernhard, et al. “Cardiovascular Disease and Cognitive Decline in Postmenopausal Women: Results from the Women’s Health Initiative Memory Study.” Journal of the American Heart Association 2.6 (2013): e000369.
  6. Williamson, Jeff D. “A randomized trial of intensive versus standard systolic blood pressure control and the risk of mild cognitive impairment and dementia: results from SPRINT MIND.” Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association 14.7 (2018): P1665-P1666.

 

 

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Heart Health and HIV: An Opportunity for Global Health Partnership

Slightly over five years ago, I immersed myself in a growing literature that documented the increase in heart disease in people living with HIV (PLHIV). While almost of all of these studies were in well-developed “high income” countries, the conclusion was always the same. The HIV medications worked, and those who had access to them were aging and developing conditions associated with aging including, prominently, cardiovascular disease (CVD). People living with HIV seemed to be developing these conditions more frequently than those who were not living with HIV, and no one was able to tease apart the myriad reasons why this was happening.

 

Global Burden of Atherosclerotic Cardiovascular Disease in People Living With HIV                                          
DOI: (10.1161/CIRCULATIONAHA.117.033369

Others had the same realization and earlier this year. Anoop Shah, MD, from the University of Edinburgh, conducted the first meta-analysis examining the global burden of CVD in PLHIV. Pooling data from almost 800,000 PLHIV with 3.5 million person years of follow up, they found that the global burden of HIV-Associated CVD has tripled in the past 20 years, especially in low and middle-income nations.

Specifically, Dr. Shah and his team measured the population attributable fraction of CVD in PLHIV. This metric combines the risk associated with CVD with the prevalence of HIV- an approach that can quantify the actual impact of risk on a population. This is important because in low and middle-income countries where the HIV prevalence is high and resources are scarce, interventions to reduce the risk of CVD will likely have a bigger impact. Dr. Shah’s work revealed that those in sub-Saharan Africa experience a “double hit” of both HIV and CVD, with higher rates of traditional risk factors such as high blood pressure, and context-specific risk factors including air pollution.

To address these risk factors, Dr. Shah suggests that while there are studies leveraging cutting edge science to help us identify those living with or at risk for CVD (e.g. biomarkers), we need more research testing evidence-based strategies to improve cardiovascular outcomes in PLHIV in low and middle-income countries. This includes testing traditional pharmacological (e.g., antihypertensive and dyslipidemia) and non-pharmacological (e.g., diet, exercise and smoking cessation) strategies tailored to the setting and the population. Critically, this research must also account for the pivotal role health systems have in delivering these interventions.

This year the theme of World AIDS Day is “Building Partnerships through Leadership” and Dr. Shah captured this promise when discussing how to improve health systems to reduce CVD.  “Based on my experience, in Sub-Saharan Africa HIV clinics are incredibly well run and effective, but they only do one thing- treat HIV; but what if we could partner with this HIV clinics across Africa [and other low and middle income settings] to start to provide better CVD prevention and treatment? By building on the existing systems, and expanding to other populations, we could deliver the change that is needed to improve cardiovascular health to PLHIV and beyond”.

Today is World AIDS Day and I am part of the first generation where AIDS has always existed.  I was born a week after the MMRW report  documented the first case of what would become known as AIDS. Since then we have made so much progress, and continue to make strides in preventing, treating, and eventually curing HIV. I look forward to the day when HIV will no longer be a part of anyone’s life. But until that happens, my work, and the work of many scientists, clinicians, advocates and allies will continue to build a better understanding of how to help all PLHIV enjoy the healthiest life possible, with less risk for cardiovascular diseases and stroke.  By working with HIV organizations there are incredible opportunities for innovative and exciting partnerships to improve cardiovascular health in PLHIV, and millions of others around the globe. The American Heart Association can and should have an important role in this quest for longer, healthier lives.

Over the next year, I will explore what is known about the various causes of cardiovascular disease in this population in this series on Heart Health and HIV. I will work to incorporate high quality science with the perspectives of the both clinicians caring for PLHIV and the voices of the patients themselves. I look forward to engaging with all of you and, together, trying to solve these important issues.

 

 

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The Evolution of Cardiac Care- “Moving the Needle from Predominantly Treatment to Additional Prevention of Cardiovascular Disease”

Cardiovascular disease (CVD) remains the number one cause of mortality for both men and women in the United States1. Although CVD related mortality is decreasing with advanced diagnostic testing and therapies of CVD, the prevalence of this disease remains high including in the younger aged population younger than 55 years of age1. This suggests that as providers we have done a successful job at treating CVD however there remains a lot of work to be done with regards to preventing this disease.

 

Moving the Needle

The prevention of CVD disease requires effort not just at the individual provider- patient level, but requires effort at the professional organization/societal and legislative level. The focus of the recent 2018 American Heart Association Scientific Meeting on several areas of Preventive Cardiology  such as the recently released 2018 Cholesterol Practice Guidelines as well as the recently released Department of Health and Human Services Physical Activity Guidelines for Americans indicates that there is some momentum and interest in moving the focus of health care from solely treating CVD to also preventing CVD in addition to treatment. The 2018 Cholesterol management guideline document has indicated that assessment of CVD risk begins as early as 20-39 years of age and this provides an opportunity to counsel these patients on heart healthy lifestyle modification to improve their cholesterol profile and therefore decrease their CVD risk2. The cholesterol guidelines also focus on the fact that the lower the cholesterol level the lower the CVD risk2.

It has been shown that most individuals in the United States do not report enough physical activity to meet the American Heart Association physical activity guidelines1. The recently released Department of Health and Human Services Physical Activity Guidelines for Americans also indicates that there is also legislative support for increasing physical activity in an effort to improve the cardiovascular health of Americans3.

The Million Hearts 2022  national initiative that is co-led by the Centers for Disease Control and Prevention and the Centers for Medicare & Medicaid Services is also another effort in the prevention of CVD. The goal of this initiative is to prevent 1 million heart attacks and strokes in 5 years through focused partner actions on several priorities selected for their impact on heart disease, stroke, and related conditions.

These initiatives indicate that there is an effort to move the needle of healthcare to preventative medicine. This plays an important role in decreasing CVD prevalence and will therefore lead to improved CVD outcomes for the United States population.

 

Impact on our Patients

A heart healthy diet and a physically active lifestyle has been shown to decrease the risk of developing CVD disease1. Counselling patients on a heart healthy lifestyle positively impacts our patients as it raises their awareness of the impact of lifestyle on overall cardiovascular health and also encourages them to adopt a heart healthy lifestyle.

 

More Work to be Done

Adequate training in Preventive Cardiology for fellows has been lacking as many of our trainees are not being taught the required amount of preventive cardiology during their General Cardiology fellowship training4. A survey in 2012 indicated that only a quarter of the surveyed General Cardiology fellowship training programs met the Core Cardiology Training Symposium (COCATS) guidelines recommendation of a dedicated 1 month rotation in preventive cardiology. In view of this, many Cardiologists in practice do not include nutritional and physical activity assessment as a part of their clinical evaluation. As a result, counselling on a heart healthy lifestyle as a part of preventive cardiology is not practiced by many Cardiologists. This void in training and experience in preventive cardiology provides an opportunity for us to assess and improve our own practice in this area as Cardiologists and also provides an opportunity to develop formal training in Preventive Cardiology for our cardiology fellows.

 

Despite the fact that CVD disease related mortality is decreasing in the United States, the prevalence remains high1. This indicates that providers within the Cardiovascular community have done a great job in treating CVD disease but there is still a need to improve our practice with regards to preventing CVD. The movement by the American Heart Association,  Centers for Disease Control and Prevention and the Centers for Medicare & Medicaid Services in focusing on areas of lifestyle medicine and preventive cardiology indicates that there is an effort to shift the needle from not just treating CVD disease but also preventing this disease. This movement therefore provides an opportunity for the Cardiovascular community to improve our practice in this area and to equip our cardiology fellows with adequate training in Preventive Cardiology to become better practitioners in this area in their future role as Cardiologists.

 

References:

  1. Benjamin EJ, Virani SS, Callaway CW, sChamberlain AM, Chang AR, et al. Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association
  2. Grundy SM, Stone NJ, Bailey AL, Beam LT, Birtcher KK, et al. 2018AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. JACC Nov 2018, 25709; DOI: 10.1016/j.jacc.2018.11.003
  3. The Physical Activity Guidelines for Americans: THe HHS Roadmap for an Active Healthy Nation. Second Edition. ADM Brett P. Giroir, MD
  4. Pack QR,Keteyian SJ, McBride PE, Weaver WD, Kim HE. Current status of preventive cardiology training among United States cardiology fellowships and comparison to training guidelines. Am J Cardiol 2012;110:124-8.

 

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Joint Hypertension 2018 Scientific Sessions – You Should Have Been There

hypertension 2018

Just as promised, the Joint Hypertension 2018 Scientific Sessions (Hypertension18) was indeed among the most impactful meetings one could have attended. Council on Hypertension Scientific Sessions Planning Committee Vice Chair Dr. Karen Griffin, FAHA was accurate in her statement that it would be “the premier scientific meeting.” There were experts from all parts of the world covering more cardiovascular topics that I think my fingers could not keep up with in note taking, and each session was more informative than the next with up-to-date information on hypertension.

During the President’s Welcome Address, Dr. Ivor Benjamin, FAHA foreshadowed what was to be expected during the meeting. He gave general overviews of the hypertension guidelines, what the changes mean to clinicians and researchers, as well as the role AHA will play in helping drive those changes forward. His welcome was a great introduction to the ‘Recent Advances in Hypertension’ Session chaired by Drs. Joey Granger from the University of Mississippi Medical Center and John Bisognano from University of Rochester Medical Center. This session covered the new guidelines, implementation, and basic research advances of clinical hypertension moving forward by Drs Basile, Egan, Oparil, and Ellison. The whirlwind of information was just the icebreaker! During the refreshment break and exhibits, I met a number of “Rockstars” including clinicians and researchers from University of Alabama Birmingham, Drs. David and Jennifer Pollock and AHA Early Career blogger Tanja Dudenbostel. Additionally, this was the only time I spent visiting with vendors. Among them, Hulu explained the importance of calibrating automatic blood pressure machines. Historically blood pressure was taken with a manual sphygmomanometer and a technician listening for ausculatory sounds via a stethoscope, but now it is all automated. Generally one machine is used for all patients. This technology forces us to question the accuracy of the readings of the machines. Are they calibrated? Should the BP be taken radially or at the wrist? Should the machine be changed throughout the day? There was Aegis representatives sharing information about products to assist medical professionals determine patient compliance to therapy and toxicology testing equipment. During these conversations, it was surprising to discover some of the rationales behind why people would opt to not take medicine as prescribed.

With my research being focused on oxidative stress-induced vascular injury and since I have become increasingly more interested in health and wellness, I took particular interest in the session focused on “Lifestyle Modifications and Impact on BP” chaired by the Associate Editor of Hypertension, David Harrison, MD, FACC, FAHA, “Recent Advances Obesity and Cardiovascular Disease” chaired by the consulting Editor of Hypertension Suzann Oparil, MD, FAHA, and “Obesity, Diabetes, and Metabolic Syndrome” chaired by Drs. Kamal Rahmouni and Carmen De Miguel. During these sessions, it was not surprising that regular exercise reduced vascular stiffness, but what was noteworthy was that weight training contributes to atherosclerosis. Additionally, the sympathetic nervous system seems to be important in glomerular filtration. Dr. Elizabeth Lambert delivered an intriguing talk about how diet and exercise can significantly decrease metabolic syndrome in middle aged obese individuals, which is consistent with a recent study (Hypertension18 Meeting Report P388) that suggests lifestyle changes can reduce hypertension in both men and women. Further, the study suggests that following the DASH diet, exercising, and weight management over a course of 16 weeks were contributing factors in reducing BP in test subjects. We all know anti-hypertensives work in reducing BP. Lifestyle changes should be the first line of defense in evading hypertension and getting it under control at the onset, according to the American Heart Association/American College of Cardiology  Hypertension Guidelines. We have all heard that we have to get out there and get moving. Choosing the right exercise is just as important as exercising, according to Dr. Tanaka.

I recently wrote a blog discussing metabolic syndrome and therein indicated there is not a direct correlation between obesity and diet. During this conference, Dr. John Hall lectured on the recent advances in CVD and obesity. He suggested that epigenetic transmission of obesity in humans (and others) is associated with increased adiposity and insulin resistance, depletion of nuclear protein, influence chromatin conformation, and altered germ cell methylation and gamete micro RNA.

The new concurrent session Clinical Practice Clinical Science and Primary Care tracks did not go unnoticed. Although I did not get to attend many of these sessions, I did pass them to see that they were well attended. I did attend some of the lunch meetings and they were very insightful. Please refer to my Twitter to see my detailed notes. As mentioned in my pre-conference blog, with all the sessions that were available one should not have had an issue meeting the goals outlined in the program by coordinators (infra vide). Several sessions that met the interest of all researchers/clinicians, early career, and everyone in between. Not a person that attended Hypertension18 could say they could not find a learning opportunity at the Joint Hypertension 2018 Scientific Sessions! Even if one was merely a passerby, there was a session relevant to them. For example, I was on my way to get coffee when I encountered Drs. Yagna Jarajapu from North Dakota State University and Daniel Batlle from University of Chicago discussing research concerning STZ diabetic Foxn1 mice that were ischemic for several days. Subsequently, Eric Metterhausen shared his mission of services (MOS, for you military people) with me as we conversed about field medicine with the United States Public Health Services (USPHS). I did know our US Armed Forces had research officers and divisions of research, but the amount of detail that Major Metterhausen described was a beast that I had not known. Conversations such as these lead to increased mentoring relationship, as well as potential collaborations in research and grant proposals. We all go to conferences to learn, to purchase new research equipment, and to present our data, but we also should not forget to network and build relationships.

Conference Learning Objectives:

  • Discuss changes to the AHA/ACC guidelines for the management of hypertension and their clinical implications.
  • Describe opportunities to improve blood pressure measurement in the clinical setting to provide more accurate results.
  • Identify immune and inflammatory mechanisms that contribute to the development of hypertension and hypertension-related end-organ damage and discuss the research and clinical implications.
  • Educate participants about medical approaches for the management of comorbid obesity in patients with hypertension.

 

  • Describe participants on the impact of value-based reimbursement on hypertension management and identify opportunities to improve its management.

 

See you all in Chicago at Scientific Sessions 2018!!!

  • Leave a comment and follow me on Twitter @AnberithaT and @AHAMeetings if you have questions or are interested in something else specifically.

 

Anberitha Matthews, PhD is a Postdoctoral Fellow at the University of Tennessee Health Science Center in Memphis TN. She is living a dream by researching vascular injury as it pertains to oxidative stress, volunteers with the Mississippi State University Alumni Association, serves as Chapter President and does consulting work with regard to scientific editing.

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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