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.


Lipopolysaccharide, TLR4 and Obesity: How They Relate

In my previous blog posts, I started to discuss the importance of toll-like receptor 4 (TLR4) and how it contributes to aortic aneurysms and how microbiota-derived lipopolysaccharide (LPS) can activate the whole signaling pathway. In today’s post, I thought to discuss the TLR4 pathway, in far more details and how it contributes to obesity and metabolic disturbances.

Production of LPS and secretion from intestinal epithelial cells results in LPS binding to cytokine receptors on hepatocytes/adipocytes and as a consequence, activation of a network of signaling pathways1. Upon binding of TRL4 to its co-receptor, myeloid differentiation factor 2 (MD2), a molecular complex is formed at surface level that becomes the binding site of LPS. LPS forms a complex with lipoprotein binding protein (LBP) that binds to cell surface CD142. Upon binding of LPS and its co-receptor CD14, the subsequent transfer of LPS to the TRL4-MD2 complex starts a cascade of events leading to the activation of transcription factors that enhances the expression of many proinflammatory cytokines. TLR4-MD2 complex signals through two major pathways: myeloid differentiation factor 88 (MyD88) and TIR domain containing adaptor-inducing IFNβ (TRIF; also known as TICAM1)2. Upon ligand recognition in the MyD88 dependent pathway, it is recruited to the cytoplasmic domain of TLR. Then, protein families of TNF-α receptor associated factor 6 (TRAF6), IL-1 receptor associated kinase 1 (IRAK1) and IRAK2 are recruited by MyD883. TRAF6 activates the transforming growth factor β-activated kinase 1 (TAK1) which promotes phosphorylation of kappa beta kinase (IKK) inhibitors α, β and γ. Phosphorylated IKK complex leads to the degradation of inhibitory kappa B (IκB) and as a consequence, translocation of NFκB to the nucleus resulting in the induction of proinflammatory cytokines4. Severe reactions to the LPS are attributed to the MyD88 activation pathway resulting in production of IL-12, IL-6 and TNF-α 2. Activation of TRIF (or MyD88 independent) pathway occurs after endocytosis of TLR4-MD2 complex and is characterized by the activation of mitogen activated protein kinases (MAPKs) such as p38, ERK1/2 and c-Jun N-terminal Kinases (JNK). In the independent pathway, the induction of IFNβ and IFN inducible proteins such as monocyte chemoattractant protein 1 (MCP-1 also known as CCL2), IFNγ-induced protein (IP10 also known as CXCL10) and RANTES (also known and CCL5) are triggered5. Cani group’s study in CD14 deficient mice showed that HFD or administration of LPS showed no effect on any parameters of metabolic syndrome symptoms, further suggesting a role for TLR4 in mediating metabolic endotoxemia, adiposity and insulinemia6. Another study confirmed the aforementioned suggestion by showing a less effect on adiposity of TLR4 deficient mice challenged with HFD7. The authors also reported a higher LPS content in the cecal samples in HFD mice compared to LFD, with a close link to TLR4 induction and NFκB activation. The latter induced the expression of iNOS and COX2 while HFD challenged TLR4 deficient mice did not show activation of NFκB and changes in the mRNA levels of proinflammatory cytokines. It is also worthy to mention that the metabolic endotoxemia induced by LPS is associated with insulin resistance by activation of JNK8. This activation has the potential to promote phosphorylation of insulin receptor substrate 1 (IRS-1) at serine sites which may inhibit the normal signal transduction through insulin receptor/IRS-1 axis resulting in insulin resistance9. In addition, activation of signaling cascade induced by LPS-TLR4 increases the expression of inducible nitric oxide synthase10. The latter reacts with cysteine residues to form adducts of S-nitrosothiols which inhibits insulin signal transduction via phosphorylation of IRS-1 in serine leading to insulin resistance in hepatic, muscle and adipose tissue10.

How LPS-derived metabolic endotoxemia results in obesity onset

How LPS-derived metabolic endotoxemia results in obesity onset. A high fat diet can result in a shift in gut microbiota composition which can contribute to increased gut permeability and metabolic endotoxemia. The gut microbiota-derived LPS activates TLRs which produce proinflammatory cytokines that can contribute to onset of obesity. Abbreviations: LPS, lipopolysaccharide; TLR, toll like receptor.

In a recent study on both Myd88-/- and Trif-/- mice by Fredrik Backhed group, authors investigated the effect of lard diet (rich in saturated lipids) on gut microbiota composition compared with fish oil fed (enriched in polyunsaturated fatty acids) mice11. Their result demonstrated that mice lacking MyD88 and TRIF are protected against lard-induced white adipose tissue (WAT) inflammation and metabolic perturbations and the saturated dietary lipids interact with gut microbiota to induce inflammation in WAT. Authors reported that lard fed mice showed an increase in the serum levels of LPS compared to fish oil fed group, indicating that microbial factors may be present in the periphery that may affect WAT inflammation. Moreover, they showed that fish oil diet had increased the levels of taxa from the genera Lactobacillus and Akkermansia. Also, studies on Akkermansia muciniphila have been shown a reduction in fat mass gain and WAT macrophage infiltration alongside improvement of gut barrier function when administered to mice with HFD-induced obesity12. Microbiota transplantation from fish oil fed mice into antibiotic treated mice also showed an increase in the levels of Akkermansia with partial protection against adiposity and inflammation after 3 weeks of lard diet11.

Additionally, Vijay-Kumar and his colleagues have shown that TLR5-deficinet C57Bl/6J mice exhibit hyperphagia and develop characteristics of metabolic syndrome such as increased adiposity, insulin resistance and hyperlipidemia13. They reported that loss of TLR5 and the observed metabolic changes correlated with microbiota compositional changes and induction of inflammatory signaling. TLR5 is a component of innate immune system that is expressed in the gut mucosa and flagellated bacteria can interact with TLR5 to induce activation of pro-inflammatory gene programs for host protection14.

Taken all together, current data suggest that intestinal inflammation could be the early consequence of HFD and may induce obesity via increased levels of LPS, suggesting a causative role for gut inflammation in the onset of obesity. In addition, TLR4 is the primary receptor mediating the proinflammatory effects of LPS, therefore regulating levels of LPS and/or ligand binding capacity of TLR4 may be a target to stop progression of obesity and metabolic syndrome.

Shayan Mohammad Moradi Headshot

Shayan is a caffeine-dependent Ph.D. Candidate at the Saha Cardiovascular Research Center, University of Kentucky. His research area is focused on vascular biology and lipid metabolism. He tweets @MoradiShayan, blogs at shayanmoradi.com and he is the Winner of World’s Best Husband Award (Category: nagging).


  1. Park DY, Ahn YT, Park SH, Huh CS, Yoo SR, Yu R, Sung MK, McGregor RA, Choi MS. Supplementation of lactobacillus curvatus hy7601 and lactobacillus plantarum ky1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity. PLoS One. 2013;8:e59470
  2. Needham BD, Trent MS. Fortifying the barrier: The impact of lipid a remodelling on bacterial pathogenesis. Nat Rev Micro. 2013;11:467-481
  3. Akashi-Takamura S, Miyake K. Tlr accessory molecules. Current Opinion in Immunology. 2008;20:420-425
  4. Kawai T, Akira S. Tlr signaling. Cell Death Differ. 2006;13:816-825
  5. Albiger B, Dahlberg S, Henriques-Normark B, Normark S. Role of the innate immune system in host defence against bacterial infections: Focus on the toll-like receptors. Journal of Internal Medicine. 2007;261:511-528
  6. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée E, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti J-F, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761-177
  7. Kim K-A, Gu W, Lee I-A, Joh E-H, Kim D-H. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the tlr4 signaling pathway. PLoS ONE. 2012;7:e47713
  8. Khan Muhammad T, Nieuwdorp M, Bäckhed F. Microbial modulation of insulin sensitivity. Cell Metabolism. 2014;20:753-760
  9. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. Journal of Clinical Investigation. 2006;116:1793-1801
  10. Sugita H, Kaneki M, Tokunaga E, Sugita M, Koike C, Yasuhara S, Tompkins RG, Martyn JAJ. Inducible nitric oxide synthase plays a role in lps-induced hyperglycemia and insulin resistance. American Journal of Physiology – Endocrinology and Metabolism. 2002;282:E386-E394
  11. Caesar R, Tremaroli V, Kovatcheva-Datchary P, Cani Patrice D, Bäckhed F. Crosstalk between gut microbiota and dietary lipids aggravates wat inflammation through tlr signaling. Cell Metabolism. 2015;22:658-668
  12. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM, de Vos WM, Cani PD. Cross-talk between akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proceedings of the National Academy of Sciences. 2013;110:9066-9071
  13. Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, Sitaraman SV, Knight R, Ley RE, Gewirtz AT. Metabolic syndrome and altered gut microbiota in mice lacking toll-like receptor 5. Science. 2010;328:228-231
  14. Vijay-Kumar M, Sanders CJ, Taylor RT, Kumar A, Aitken JD, Sitaraman SV, Neish AS, Uematsu S, Akira S, Williams IR. Deletion of tlr5 results in spontaneous colitis in mice. J Clin Invest. 2007;117

A Gateway To Better Health With Bariatric Surgery

This year’s AHA Scientific Sessions has already provided the medical community with a number of excellent studies. The “GATEWAY” trial addresses the role of bariatric surgery and its effect on hypertension.1 Patients with morbid obesity are well known to be at risk for a litany of cardiorespiratory complications such as hypertension, obstructive sleep apnea, atrial fibrillation, among others. For many, dietary and lifestyle changes are insufficient measures to lose weight. The past decade has seen the emergence of bariatric surgery as a valid therapeutic approach. In trained hands and with meticulous follow-up, the results can be life-changing.
There already exists published literature regarding the favorable effects on glycemic control and in some cases resolution of type II diabetes in patients followed after Roux-en-Y bypass.2
GATEWAY (Gastric Bypass to Treat Obese Patients With Steady Hypertension) was a randomized trial comparing the effects of surgery to standard medical therapy in patients with morbid obesity (defined as BMI 30-39.9 Kg/m2) with the purpose of achieving control of hypertension. The surgery technique employed is known as a Roux-en-Y gastric bypass; these patients also received medical treatment.
The primary endpoint was reduction of ≥30% of the total number of antihypertensive medications while maintaining systolic and diastolic blood pressure <140 mm/90 mm Hg, respectively, at 12 months. Although the study did not enroll patients with diabetes mellitus, and was limited to 100 patients, the results are intriguing. In fact, the surgical arm was six times more likely to require less antihypertensives with more than half achieving remission of hypertension using the above target value. Encouragingly, the surgical complication rate was low.

This is encouraging data which also leads to additional questions:

  • Are such results also obtainable with other surgical methods (Laparoscopic adjustable gastric banding; Sleeve gastrectomy;
  • Duodenal switch with biliopancreatic diversion etc)3?
  • Are the antihypertensive effects durable?

Larger studies will further validate these findings.


  1. Schiavon CA et al. Effects of Bariatric Surgery in Obese Patients With Hypertension The GATEWAY Randomized Trial (Gastric Bypass to Treat Obese Patients With Steady Hypertension). http://circ.ahajournals.org/content/early/2017/11/10/CIRCULATIONAHA.117.032130
  2. Schauer PR Burguera B, Ikramuddin S, Cottam D, Gourash W, Hamad G, Eid GM, Mattar S, Ramanathan R, Barinas-Mitchel E, Rao RH, Kuller L, Kelley D. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg. 2003 Oct;238(4):467-8
  3. Colquitt JL1, Pickett K, Loveman E, Frampton GK. Surgery for weight loss in adults. Cochrane Database Syst Rev. 2014 Aug 8;(8):CD00364

Christian Perzanowski Headshot

Christian Perzanowski is an electrophysiologist in Tampa, FL. His main interests are ablation techniques for atrial fibrillation and device therapy for congestive heart failure.