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The Protective Role of Anti-Hypertension Medication Among Patients with Comorbidities for COVID-19 Outcomes

Millions of people around the world take Angiotensin-converting enzyme inhibitors (ACEi) and Angiotensin II receptor blockers (ARB) to manage hypertension, heart failure, and coronary artery disease. Concerns of ACEi and ARB potentially increasing the risk of COVID-19 illness severity and mortality among vulnerable populations heightened once scientists reported that risk factors for developing complications included being older, male, and having cardiovascular comorbidities1. One comprehensive study using over 17,000 primary care records found that chronic heart disease has a hazard ratio of 1.57 for COVID-19 related death and the hazard ratio remained high at 1.17 even when accounting for confounding variables, suggesting that people with heart disease are at increased risk of mortality2. In the same study, high blood pressure or hypertension diagnoses were associated with hazard ratio of 0.89, a lower risk of COVID-19 mortality compared to people with normal blood pressure, but insight into how age, sex, comorbidities, and medications influence outcomes were not directly addressed. Such findings fueled a debate about whether ACEI/ARB should be maintained or withdrawn in patients with COVID-19.

The role of ACEi and ARBS drugs in COVID-19 outcomes among cardiovascular patients also became a point of interest due to their mechanism of action in the human body. ACEi and ARB act on the renin-angiotensin-aldosterone system (RAAS), a hormone system important for regulating blood pressure, fluid balance, and inflammation processes that affect cardiovascular health outcomes. While ACEi and ARB drugs are used as the first line of treatment to manage vasoconstriction, there is a question as to how these medications can alter the RAAS balance. In a previous blog, we discussed how the SARS-CoV-2 virus uses the  of angiotensin-converting enzyme 2 (ACE2) receptor to enter host target cells3. This receptor not only acts as the entry point for the virus, but normally acts as a crucial element for regulating RAAS biochemical processes. The inflammatory, tissue damaging, and vasoconstriction effects of Angiotensin II (Ang II) in the body are mitigated by ACE2 activity, and ARB and ACEi drugs also target the Ang II protein4. COVID-19 related research has provided a new understanding of how underlying disease states, behavioral habits like smoking, or genetics could influence ACE2 activity in the body. The unique collaboration between clinicians and scientists during the COVID-19 pandemic has provided new mechanistic insight about how the complex RAAS pathway and the factors that influence disease progression.

Ongoing population studies such as The International Study of Inflammation in COVID-19 (ISIC) and The Michigan Medicine COVID-19 Cohort (M2C2) make use of detailed medical records bio-banked human samples, and advanced statistical modeling to evaluate the potential benefits and harms of ACEi and ARB medications. Using stored blood samples and electronic medical records from patients hospitalized specifically for COVID-19, researchers were able to assess for an association between ACEi or ARB use and in-hospital patient outcomes, such as requiring mechanical ventilation or admission into intensive care. The research team overseeing the ISIC and M2C2 studies analyzed the health outcomes of about 1,600 people hospitalized for COVID-19 and reported that patients taking ACEi or ARB had about 10% mortality compared to 14% who were not on those medications5. Among those taking medications, 24% of patients required ventilation during hospitalization, compared to 20% of those not any treatment. These results were surprising as people taking medication also had significantly more comorbidities such as diabetes compared with the non-ACEi/ARB group. Knowing that people who use ACE inhibitors or ARB are not more susceptible to severe COVID-19 illness or increased risk of mortality during hospitalization has now led to the widely accepted practice of not discontinuing these drugs in people who are infected with SARS-CoV-2. In fact, people on anti-hypertensive medication had lower levels of inflammation biomarkers during hospital admission compared to those who don’t take ACEi and ARB drugs. This insight suggests that ACEi/ARB drugs could counter the inflammatory effects of COVID-19, which could be an interesting future direction of this research. Large scale studies have been valuable for providing evidence on how to mitigate detrimental outcomes during the COVID-19 pandemic and future findings will continue to influence guidelines for monitoring cardiovascular homeostasis, targeting treatments for vulnerable populations, and managing chronic illnesses.

References:

  1. Patel AB, & Verma A. (2020). COVID-19 and Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: What Is the Evidence? JAMA. https://doi.org/10.1001/jama.2020.4812
  2. Williamson EJ, Walker AJ, Bhaskaran K, et al. (2020). Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020;584(7821):430-436. doi:1038/s41586-020-2521-4
  3. Raizada MK, & Ferreira AJ, (2007). ACE2: A New Target for Cardiovascular Disease Therapeutics. Journal of Cardiovascular Pharmacology, 50(2), 112–119. https://doi.org/10.1097/FJC.0b013e3180986219
  4. Monterrosa Mena, J. ACE-2 and Immune System Changes in Smokers May Underlie COVID-19 Vulnerability. https://earlycareervoice.professional.heart.org/ace-2-and-immune-system-changes-in-smokers-may-underlie-covid-19-vulnerability/
  5. Pan N, Hayek S, the ISIC Group, et al. (2021). Angiotensin‐Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Outcomes in Patients Hospitalized for COVID‐ Journal of the American Heart Association, 10(24), e023535. https://doi.org/10.1161/JAHA.121.023535

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

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Blood Pressure and Hypertension Control Matter for Young Adults

Many young adults (18-39 year-olds) view themselves as physically healthy and may wonder why their doctor is concerned about their blood pressure. However, being young does not prevent you from developing elevated or high blood pressure. Uncontrolled blood pressure in young adults is a significant public health concern. In the U.S., 1 in 5 young men and 1 in 6 young women have hypertension. Hypertension control also varies by age group, with only 39% of U.S. young adults with hypertension having achieved control (blood pressure < 140/90 mmHg) compared with 58% of middle-aged adults (40-59 year-olds) and 54% of older adults (≥60 year-olds). Importantly, given that young adults with hypertension have more prolonged exposure to high blood pressure, they ultimately have a higher lifetime risk for cardiovascular disease. Early monitoring, diagnosis, and managed treatment are important to reduce the risk of serious medical conditions associated with uncontrolled hypertension.

Here’s a quick primer on blood pressure values and meanings and the effect of elevated blood pressure on cardiac structure and functioning:

Blood pressure is the force that blood applies to the walls of arteries as it’s pumped throughout the body.

Generally, your arteries can withstand some pressure, but there are limits to what the arteries can handle. For this reason, blood pressure is measured and monitored, and the values are categorized based on how the level of pressure affects our health. The four blood pressure categories are:

  • Normal: systolic less than 120, and diastolic less than 80
  • Elevated: 120 – 129, and less than 80
  • Hypertension (stage 1): 130 – 139, or 80 – 89
  • Hypertension (stage 2): 140 or higher, or 90 or higher
  • Hypertensive crisis: higher than 180, and/or higher than 120

Only normal blood pressure is considered healthy, while elevated or high blood pressure is associated with damaging the heart and arteries by forcing the heart to pump harder. When the heart works harder to pump blood, this can cause the heart muscles to thicken (altering the structure of the heart) and make it harder for the heart to fill with and pump blood (altering the functioning of the heart). The body’s arteries will also begin to narrow and harden, limiting the normal flow of blood.

Fortunately, high blood pressure is treatable and preventable. But uncontrolled hypertension affects nearly half of adults in the U.S., with many people unaware they even have the condition. The CDC recommends that knowing key facts about hypertension, getting your blood pressure checked regularly, and taking action to control your blood pressure if it is high is key to lowering your risk.

Source: “6 Facts About High Blood Pressure.” Venngage. https://venngage.net/pl/bVswgLzcpM

Since hypertension does not cause noticeable symptoms, it mustn’t be ignored. Over time, high blood pressure quietly damages the circulatory system and increases one’s risk of developing adverse health conditions – thus, hypertension is known as a silent killer. Additionally, high blood pressure is associated with poorer outcomes with COVID.

Steps to lower your blood pressure are often considered manageable and include common lifestyle modifications:

  • Smoking cessation
  • Maintaining a healthy weight
  • Consuming low levels of salt
  • Getting plenty of exercise
  • Limiting alcohol
  • Eating healthy

However, the patient experience among young adults with hypertension suggests significant barriers to receiving adequate blood pressure control management exist for this population. In a multi-center qualitative study, Johnson et al. (2016) identified unique emergent themes among young adults with hypertension that differed from prior hypertension qualitative studies in older age groups. Young adults voiced that the chronic disease diagnosis and the recommended lifestyle modifications made them feel older than their biological age. The participants also mentioned ongoing adverse psychological effects associated with their diagnosis and feeling a sense of self-blame and shame. This may be a critical point of intervention for healthcare teams to understand and address the negative emotional and mental health effects that a hypertension diagnosis has on young adults. Other emergent themes identified in the focus groups included the cost-benefit analysis performed by young adults when determining the necessity of recommended blood pressure treatment plan (e.g., lifestyle modifications, medication) and concern about experiencing negative social stigma based on their behavior choices reflecting new lifestyle modifications. Finally, most participants reported discarding hypertension education materials after leaving the clinic, citing that the materials were not tailored to young adults and their lifestyles.

These themes identified important barriers to young adult patients’ education on hypertension awareness and risks and opportunities for hypertension treatment non-adherence related to both medication and lifestyle modifications. Young adults with hypertension represent a unique population that could benefit from targeted interventions to improve hypertension control and cardiovascular disease prevention.

References:

  1. Centers for Disease Control and Prevention. Hypertension Cascade: Hypertension Prevalence, Treatment and Control Estimates Among US Adults Aged 18 Years and Older Applying the Criteria From the American College of Cardiology and American Heart Association’s 2017 Hypertension Guideline—NHANES 2013–2016. Atlanta, GA: US Department of Health and Human Services; 2019.
  2. Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics-2020 update: a report from the American Heart Association. Circulation 2020;141:e139-596.
  3. Wall HK, Hannan JA, Wright JS. Patients with undiagnosed hypertension: Hiding in plain sight. JAMA2014;312(19):1973–1974.
  4. Parcha V, Patel N, Kalra R, Arora G, Arora P. Prevalence, Awareness, Treatment, and Poor Control of Hypertension Among Young American Adults: Race-Stratified Analysis of the National Health and Nutrition Examination Survey. Mayo Clin Proc. 2020 Jul;95(7):1390-1403. doi: 10.1016/j.mayocp.2020.01.041. PMID: 32622447.
  5. Johnson HM, Warner RC, LaMantia JN, Bowers BJ. “I have to live like I’m old.” Young adults’ perspectives on managing hypertension: a multi-center qualitative study. BMC Family Practice. 2016 Dec;17(1):1-9.
  6. https://www.houstonmethodist.org/blog/articles/2020/jan/why-your-blood-pressure-matters-even-in-your-20s-and-30s/
  7. https://www.cdc.gov/bloodpressure/5_surprising_facts.htm
  8. “6 Facts About High Blood Pressure.” Venngage. https://venngage.net/pl/bVswgLzcpM

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

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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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Hypertension and Stroke: Current State of Evidence

Stroke is the fifth leading cause of death in the country and the top reason for adult disability (1). Each year about 795,000 people experience a stroke in the United States with nearly 25% of these strokes being recurrent events in people with a prior history of a stroke (2).  Hypertension is the considered to be the most important modifiable risk factor for stroke. Therefore, treatment of hypertension is one of the most effective strategies for primary and secondary prevention of stroke (3). In a large meta-analysis from 2002, which included 1 million patients, a direct association was seen between blood pressure measurements and risk of vascular mortality including stroke and ischemic heart disease (4). There is a continuous relationship with risk throughout the normal range of blood pressure, down at least as far as 115/75 mm Hg according to this meta-analysis of 61 prospective clinical studies. However, there has been a lack of consensus among experts about the most appropriate blood pressure targets for cardiovascular disease and stroke prevention.

In the Secondary Prevention of Small Subcortical Strokes (SPS-3) trial, investigators compared systolic blood pressure targets of 130-149 mm Hg and less than 130 mm Hg (5). About 3000 patients with a recent history of an MRI confirmed lacunar stroke were randomized to one of the two treatment groups and followed for a mean of 3.7 years. Primary outcome of recurrent stroke was seen at a lower rate in the lower target group with an annualized stroke rate of 2.25% as compared to 2.77% in the higher target group. Despite a signal toward benefit of a lower BP target, these results did not reach statistical significance. The rates of intracerebral hemorrhage were noted to be significantly lower with a lower BP target.

In a clinical trial enrolling patients with diabetes and a high cardiovascular risk, blood pressure target of less than 120 mm Hg was not superior to a target of less than 140 mm Hg for reducing risk of cardiovascular events with the exception of stroke (6). In this study, the intensive blood pressure target lead to a significant risk reduction for stroke but not for myocardial infarction or all-cause mortality.

To further ascertain an ideal blood pressure target, investigators in the SPRINT trial enrolled over 9000 persons with SBP of more than 129 mm Hg without a history of diabetes (7). The participants were randomized to intensive treatment (target <120 mm Hg) or standard treatment groups (target <140 mm Hg). Primary outcome was a composite of myocardial infarction, heart failure, stroke or vascular death. After a median follow up of 3.3 years, the trial was stopped early due to a significantly lower rate of primary composite outcome in the intensive blood pressure group as compared to the standard treatment. Interestingly, even though there was a signal of benefit for stroke risk reduction, this was not statistically significant. The investigators of the study make note of this finding and hypothesize that this could be due to the fact that this trial excluded patients with a prior history of stroke and TIA. This has also raised questions about the limited applicability of these results to patients with a history of stroke.

The investigators also looked at cognitive outcomes for the two groups of patients in this trial (8). The composite outcome of mild cognitive impairment and dementia was seen in a significantly lower number of patients in the intensive BP treatment group as compared to the standard treatment group. Due to the early termination of SPRINT, the study was underpowered to show a significant difference in the risk of dementia.

The current guidelines (9) from the American Heart Association/ American College of Cardiology recommend initiating treatment at SBP>130 mm Hg for patients with a high cardiovascular risk. Using the current definition of hypertension, it is estimated that 46% of adults in the US have hypertension and about 36% should be prescribed antihypertensive medications (10). Applying these new guidelines, only about half of all US adults on medications for hypertension are currently below the target BP numbers.

With hypertension playing such an important role in the development of the two most common neurological illnesses (Stroke and cognitive disorders), authors of a recent paper in JAMA Neurology (11) urge neurologists to play a greater role in treatment of hypertension as a preventive strategy for their patients. Traditionally stroke neurologists and neurointensivists have been involved in treatment of the cardiovascular risk factors including hypertension but most of that is done after the patient has had a major event such as an ischemic stroke or intracerebral hemorrhage. The authors argue that neurologists should participate in treatment of hypertension for their patients as a primary preventive strategy as it would lead to an overall improved brain health of our ageing population.

To learn more about the latest advancements in the field of hypertension research, I encourage the readers to attend Hypertension 2019 Scientific Sessions being held in New Orleans September 5-8, 2019.

 

References:

  1. Vital Signs: Recent trends in stroke death rates – United States, 2000-2015. MMWR 2017;66.
  2. Benjamin EJ, Blaha MJ, Chiuve SE, et al. on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2017 update: a report from the American Heart Association. Circulation. 2017;135:e229-e445.
  3. Katsanos AH, Filippatou A, Manios E, et al. Blood pressure reduction and secondary stroke prevention: a systematic review and metaregression analysis of randomized clinical trials. Hypertension. 2017;69(1):171-179.
  4. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies Lancet. 2002;360(9349):1903-1913.
  5. Benavente OR, Coffey CS, Conwit R, et al; SPS3 Study Group. Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial. Lancet. 2013;382(9891):507-515.
  6. Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-1585
  7. Wright JT  Jr, Williamson  JD, Whelton  PK,  et al; SPRINT Research Group.  A randomized trial of intensive versus standard blood-pressure control  [published correction appears in N Engl J Med. 2017;377(25):2506].  N Engl J Med. 2015;373(22):2103-2116.
  8. Williamson JD, Pajewski NM, Auchus AP, et al; SPRINT MIND Investigators for the SPRINT Research Group. Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial.JAMA. 2019;321(6):553- 561
  9. Whelton PK, Carey RM, Aronow WS, et al.
  10. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018;71:e127-e248.
  11. Muntner P, Carey RM, Gidding S, et al. Potential US population impact of the 2017 ACC/AHA high blood pressure guideline. Circulation. 2018;137(2): 109-118.
  12. Betjemann J, Hemphill JC, Sarkar U. Time for Neurologists to Drop the Reflex Hammer on Hypertension. JAMA Neurol.Published online August 19, 2019. doi:10.1001/jamaneurol.2019.2588
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Managing High Blood Pressure by Managing Stress

manage stressWe are faced with a number of changes in our lives. The old saying, “life happens” generally means take the changes as they come and keep it moving. The human body is not equipped to distinguish between distress and eustress. Amazing life changes happens such as getting acknowledged for an accomplishment, passing the preliminary exams for a PhD program, getting the job of your dreams, or even getting the funding you have worked so hard to apply for consideration. Contrarily, changes that can be viewed as less than optimal such as being passed over for a promotion, losing the sole source of your family’s income, death of dreams, and rejection are all sources of stress. Good or bad, these events affect hypertensive rates potentially leading to a more serious chronic illness such as heart attacks, strokes, or even metabolic disease.

Often people, especially scientist and clinicians think their stress is just a way of life and there is nothing that can be done about that constant state. Scientist are always on the hunt for research funding and publishing; while clinicians holds the consequences of a person’s life in each of their decisions. These are significant burdens for a person to hold. It is imperative to manage stress as a means of preventing and treating high blood pressure. It is definitely easier said than done, but attempting these steps to control stress could lead to a better life:

  • Sleep quality and quantity can make a huge difference in managing mental alertness and energy but sleep allows the body time to relax and heal. Quality sleep can aid in the reduction of blood pressure leading to vascular repair.
  • Reiki principles that include meditation enhances muscle and mental relaxation. This include activities such as guided imagery, deep breathing, and massage therapy to act as stress-relievers.
  • Strengthen your social network. Connect with others by taking a class, joining an organization, or participating in a support group.
  • Try to resolve negative situations quickly so they do not fester. It is best to let go of adverse events and interactions; whether it is something that is in or out of your control
  • Don’t be afraid to ask for help from a counselor. Although there is a negative stigma surrounding seeing a therapist they are the best resource for dealing with stressful situations because your spouse, friends, and neighbors generally have as much going on as you and their opinions can be clouded by their own experiences.

I recently started working with a mentor to help with stress and how to interact with individuals to manage stress. As the young adults say, “I like to keep it 100” but often being brutally honest is not received well by the masses. I also made the determination that whether working or interacting on a personal level, I will not extend myself beyond my comfort zone nor will I compromise my values or ethics to fit into anyone’s idea of what I should be doing. Staying true to oneself is among the first steps to happiness and managing blood pressure. I have found that when I over extend myself, my stress level increases and my performance decrease in some areas (namely self care). My life, your life, is not worth negativity. Being that stress is inevitable, I choose the eustress. It is my opinion that this type of stress leads to self happiness and the contribution of the happiness of others.

Thank you for reading this blog. If you would like to share some of your methods for dealing with stress or how you keep your life stress limited, let me know comment or tweet @AnberithaT so we can share ideas.

 

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Let’s Talk About Race and Stroke Recurrence

There has been a growing body of evidence pointing to potential differences in outcomes of stroke based on race/ethnicity. Recent investigations by Hao et al1, presented at the ISC 19, examined ethnic variation in stroke recurrence, from the angle of intracranial atherosclerotic stenosis [ICAS]. ICAS is estimated to be the underlying pathology in about 15% of ischemic stroke patients2, and is associated with high risk of stroke recurrence even with utmost medical treatment1. The investigators of this study included patients with ICAS in major vessels with >50% stenosis identified on Magnetic resonance angiography or computed tomography angiography. The authors observed higher rate of 3-months as well as long-term recurrence among non-White compared to White patients, although this did not reach statistical significance, possibly due to insufficient power.

Going from ischemic stroke [IS] to intracerebral hemorrhage [ICH], King et al3 assessed recurrence of ICH based on race/ethnicity. They used comprehensive claims data that included hospital discharges in California between 2005-2011. The authors included patients who survived to discharge. Similar to what has been observed in IS, King et al found higher rates of ICH recurrence among Black and Asian compared to White patients.

There are some suggestions on potential explanations on those differences based on the burden of specific clinical conditions by race/ethnicity, such as hypertension4 and chronic kidney disease as reported by Hao et al1. However, this is an area that needs further investigations in representative samples of patients.

 

REFERENCES:

[1] Hao, Qing, et al. “Abstract TP157: Ethnic Difference in Stroke Recurrence for Patients With Intracranial Atherosclerotic Stenosis.” Stroke 50.Suppl_1 (2019): ATP157-ATP157.

[2] Bose, Arani, et al. “A novel, self-expanding, nitinol stent in medically refractory intracranial atherosclerotic stenoses: the Wingspan study.” Stroke 38.5 (2007): 1531-1537.

[3] King, Zachary A., et al. “Abstract WMP97: Racial/Ethnic Disparities in the Risk of Intracerebral Hemorrhage Recurrence.” Stroke 50.Suppl_1 (2019): AWMP97-AWMP97.

[4] Rodriguez-Torres, Axana, et al. “Hypertension and intracerebral hemorrhage recurrence among white, black, and Hispanic individuals.” Neurology 91.1 (2018): e37-e44.

 

 

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Under Pressure: What Does Retina Say About Hypertension?

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, in fact, 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 hypertension.

 

Hypertension or high blood pressure is predominantly caused due to increased resistance to the walls of the blood vessels. What this leads to is increased chances of developing diseases of the cerebral, cardiovascular or even peripheral arteries. Risk factors can range from dietary habits to genetics and ethnicity, and less than half of those with hypertension are unaware of their condition. Interestingly, the eye offers a very useful set-up to get a closer look at blood vessels – without even having to inject or cut open anything. This non-invasiveness of the eye has been widely used by clinicians and researchers to diagnose diseases of the blood vessels – hypertension being one of them. This article highlights some interesting findings that researchers derived simply by examining the retinal blood vessels.

A fundoscopic photograph of the back of the eye (like seen in the image below), allows to capture the retinal blood vessels. These blood vessels share many physiological and anatomical similarities with vessels in other systems, like the brain and the heart. Naturally, any changes in the structure or integrity of these vessels have been documented and researchers have found many links and associations with the pathology of hypertension5. I previously discussed how the retinal vessels gave a sneak peek into the brain and heart, where dimensions like the diameter or tortuosity were able to indicate early signs of stroke or cardiovascular diseases.

Source: Cheung et al., Hypertension. 2012;60:1094–1103

 

As early as the 1960s, scientists learned that narrowing of retinal arteries were important signs of hypertension. The population-based Rotterdam study published in 2005 looked at individuals in over 55 years of age and were “pre-hypertensive.” Their findings suggested that the narrowing of both retinal arterioles and venules were associated with increased risk of hypertension and preceded development of high blood pressure2. Similarly, the Blue Mountains Eye study in Sydney found that these abnormalities in the retinal vessels predicted a 5-year incidence of severe hypertension in a patient population of older cohort3.

Source: M. Kamran Ikram et al., Hypertension. 2005;47:189–194 

This image of an eye fundus shows a semi-automated system used to measure the diameters of arterioles and venules in the retina.

 

Making use of this unique retinal fundoscopic tool, another group explored measurement of blood flow to the retina, in response to light-flicker in patients with high blood pressure3. They found that hypertensive patients had impaired blood flow in the retina, possibly caused due to prolonged constricted vessels. This approach is among the first to test blood flow to the retinal, instead of measuring the vessel itself – adding another asset to retinal fundus images.

Retinal images have also been used in genetic linkage studies. Large population data sets are analyzed for tracing genes and variations of the genes associated with diseases among different individuals. It is clear that changes in the diameter of retinal vessels can precede hypertension, but are there genetic predeterminants to an individual’s retinal diameters? In 2006, the Beaver Dam Study found that apart from genetic linkages found between retinal diameters and hypertension and other associated diseases, there are genetic factors that predetermine the retinal diameters – independent of hypertension4.

This simply means that there are other factors present in our systems that are genetically related to the structure and size of one’s retinal vessels. Interestingly, another research group looked retinal vessels of 6-year-old students with hypertensive parents6. They found that only the girls (not boys) had narrowing retinal vessels and were predisposed to developing hypertension later in life. This also suggests a genetic link between retinal vessels and blood pressure.

Researchers around the world have used retinal parameters as indicators of hypertension. Evidently, retinal imaging provides for a powerful tool in identifying markers of cardiovascular complications. However, this still remains a tool widely used only among researchers, and validation of retinal imaging for clinical use still remains to be seen. With emerging advanced technology, clinicians should consider a non-invasive method like this one as a diagnostic tool.

 

References:

  1. M. Kamran Ikram et al., Retinal Vessel Diameters and Risk of Hypertension. Hypertension. 2005;47:189–194
  2. Smith et al., Retinal Arteriolar Narrowing Is Associated With 5-Year Incident Severe Hypertension. Hypertension. 2004;44:442–447
  3. Ritt et al., Impaired Increase of Retinal Capillary Blood Flow to Flicker Light Exposure in Arterial Hypertension. Hypertension. 2012;60:871–876.
  4. Xing et al., Genome-Wide Linkage Study of Retinal Vessel Diameters in the Beaver Dam Eye Study. Hypertension. 2006;47:797–802
  5. Cheung et al., Retinal Microvasculature as a Model to Study the Manifestations of Hypertension. Hypertension. 2012;60:1094–1103.
  6. Gopinath et al., Parental History of Hypertension Is Associated With Narrower Retinal Arteriolar Caliber in Young Girls. Hypertension. 2011;58:425–430.
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What’s Happening Here At The International Stroke Conference in Hawaii?

Getting to Hawaii was quite the event! I underestimated the flight and how I would feel with such time zone changes. However, the International Stroke Conference 2019 (#ISC19) was worth all the efforts. The meeting objectives were sufficiently described in the program book and my previous blog. As promised, there were sessions to equip scientists and clinicians with tools in diagnosis, treatment, prevention, management, and rehabilitation of cerebrovascular disease as well as nursing. The sessions that I was able to partake in were the following:

  1. Clinical Rehabilitation and Recovery Oral – I spent the first part of the morning here learning about the biomarkers to improve stroke rehabilitation covered in the clinical trial data and predictors of post stroke depression using qualitative data in patient after ischemic stroke. Although these presentations were informative, I had my eye set on other topics as well, so I had to leave the session a tad early.
  2. Medical therapy for Symptomatic Carotid Stenosis: Time for Modern Data – Seemant Chaturvedi, MD shared his research on ‘Genetic Guidance for Antiplatelet Therapy’ followed by Brian Hoh, MD discussing the answers he found to the question ‘Do HTN Targets Matter?’ Studies presented here show there is a link between hypertension and changes in white matter in the brain that affect cognitive functions. Dr. Bath expounded on his recent article in Stroke (2018) sharing mechanisms of how this damage could potentially occur.
  3. Looking into the Brain Through the Eye: Re-examining the Retina as a Surrogate Marker for Cognitive Disorders – There is growing evidence that the dental and optical examinations can be a window into health. I previously blogged about the bacteria found in the mouth is also identified in atherosclerotic plaques. In this session, clinicians/scientist looked at the retina as a window to the brain and subsequently health. These sessions suggested the retina can assist in the post-mortem prediction of Alzheimer’s disease and stroke based on the linear relationship between number of plaques in the retina and the brain. Current research tools are extremely invasive thus predictions are not feasible in living patients. The tools described here included Optical Coherence Tomography (OCT, not to be confused with over-the-counter) as a diagnostic tool, adding to repertoire of skills to increase the ability to interpret cognitive impairment.

I am looking forward to the information presented on tomorrow. I will give more insights into what I think is the highlights of the meet in my next blog. Keep following me on Twitter @AnberithaT and be sure to ask any question that may be answered during the ISC19 or after.

 

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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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What to expect at Joint Hypertension 2018 Scientific Sessions – Treating Hypertension in 2018

Two AHA Councils, the Council on HAHA|ASH Hypertension Scientific Sessions 2018ypertension and the Council on Kidney in Cardiovascular Disease, have joined forces with the American Society of Hypertension to make Joint Hyptertension 2018 Scientific Sessions (#Hypertension18) among the most impactful. Dr. Karen Griffin, FAHA Vice Chair for the Council on Hypertension Scientific Sessions Planning Committee calls it the “premier scientific meeting on hypertension in the world”. Understandably so; it boast experts from areas of cardiorenal disease, cardiovascular disease, stroke, and genetics to make for a vast cross-disciplianry session with the up-to-date information on hypertension. This year’s meeting received 439 abstracts in 37 categories, over 125 expert peer reviewers, and more than 20 countries represented.

There will be several interactive sessions that will target the established researcher/clinician, early career, and everything in between. With the addition of the new concurrent session D-Track, Clinical Practice Clinical Science and Primary Care tracks, a dimension will be added for elucidate the research science/clinical practice as it relates to patient care. In light of all the sessions that are available one should not have a problem reaching the milestones set by the program coordinators (infra vide).

To point out a few conference highlights, there will be 24 oral sessions, 3 poster sessions, and travel award talks:

The Excellence Award for Hypertension Research (Saturday, September 8, 2018)

  • R. Clinton Webb, PhD, FAHA presents “A Study of the Innate Immune Response in Hypertension”
  • Paul K. Whelton, MB, MD, MSc, FAHA presents “Clinical Trials and Practice Guidelines: Evidence-Based Progress in Lowering Blood Pressure”

Conference Awards

  • 10 Council on Hypertension New Investigator Travel Awards
  • 10 Council on Kidney in Cardiovascular Disease New Investigator Awards
  • 4 New Investigator Travel Awards
  • 6 Hypertension Early Career Oral Award Finalists
  • 12 AFHRE Travel Award for Patient-Oriented or Clinical Research in Hypertension
  • 1 Clinical Science Investigator Award for Excellence in Translational or Clinical Hypertension Research
  • 3 New Investigator Awards for Japanese Fellows

25 Poster Presenters can potentially win the competition this year! Which has gone up significantly from the previous years.

I am excited to go to Chicago for #Hypertension18 this year. If there is anything you need to enhance your experience during your time at the conference contact the program officials (directions in the program book).

I look forward to meeting you all! If you see me around tweeting, introduce yourself. I love meeting new people and learning new things. After all, that is why we are all going, right? 🙂

#Hypertension18 Conference Learning Objectives:

  1. Discuss changes to the AHA/ACC guidelines for the management of hypertension and their clinical implications.
  2. Describe opportunities to improve blood pressure measurement in the clinical setting to provide more accurate results.
  3. 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.
  4. Educate participants about medical approaches for the management of co-morbid obesity in patients with hypertension.
  5. Describe new and emerging strategies for treating resistant hypertension.
  6. Describe participants on the impact of value-based reimbursement on hypertension management and identify opportunities to improve its management.

 

Leave a comment or tweet @AnberithaT and @AHAMeetings if you have questions or are interested in something else specifically.

Follow me and @American_Heart @AHA_Research @AHAScience and @HyperAHA on twitter for more #HeartSmart information.

For meeting Tweets follow @AHAMeetings @HyperAHA @AHAScience #JAHAMeetingReports @JAHA_AHA for the latest on#Hypertension18!