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Obesity, a driver of inflammation, is prevalent in patients with HFpEF. Ileana Pina asks Ambarish Pandey about GLP-1 inhibitors and SGLT2 inhibitors in HFpEF. Are these drugs anti-inflammatory? https://www.medscape.com/viewarticle/993980?src=soc_yt -TRANSCRIPT- Ileana L. Piña, MD, MPH: Hello, everyone. I'm Ileana Piña, professor of medicine at Jefferson University Hospital in Philadelphia. I'm the chief of quality. This is my blog. We have been hearing a lot of conversation about obesity. It's coming out of our endocrine division and our weight management division. And the patients are asking for things like bariatric surgery and maybe a holistic program of weight loss. A lot of the primary care doctors are starting to recommend glucagon-like peptide-1 (GLP-1) receptor agonists for those patients. But we deal with patients with heart failure with preserved ejection fraction (HFpEF), and a lot of our phenotypes are patients with obesity who happen to have hypertension and/or diabetes, and they are difficult to manage. Inflammation, Obesity, and HFpEF Piña: For today's conversation, there is nobody better than Dr Ambarish Pandey, who has a HFpEF program at the University of Texas Southwestern. Ambarish, welcome. Give me your thoughts overall about the link between obesity, inflammation, and HFpEF. Ambarish Pandey, MD: Thank you, Dr Piña. I'm excited to be on your blog and I'm glad that we are discussing such an important topic. The burden of heart failure, particularly HFpEF, has been increasing and is not just affecting older individuals. We see more younger folks with obesity in our HFpEF clinic coming in with symptoms of shortness of breath and fluid buildup. Our understanding of HFpEF has evolved quite a bit over the past two or three decades. Initially, it was thought to be a disease of largely impaired myocardial relaxation. And then Walter Paulus was one of the pioneers who proposed the concept of inflammation leading to HFpEF, and obesity being one of the important drivers of the inflammation that leads to the development of HFpEF. Now our understanding of HFpEF has evolved to it being a multisystem disorder that leads to dysfunction in different organ systems. One of the cardinal features that drives this dysfunction is upregulation of inflammatory pathways, increased inflammatory burden — and a lot of that is driven by obesity. Obesity is one of the most important modifiable risk factors for HFpEF. Piña: It is so common. In my clinic the other day, probably 3 out of 4 patients were obese. Pandey: Up to 75% of patients that we see in our program are over the 30 BMI cut-off, and a lot of the literature that has come from US HFpEF cohorts shows a very high average BMI in these patients. Piña: When we talk about inflammation, what are the chemical pathways of inflammation? For example, a long time ago, we tried to block TNF-alpha and it didn't quite work out. So, what pathways are we talking about? Pandey: I think a lot more work needs to be done to really understand the key drivers of inflammation and what pathways are being upregulated. As we know, inflammation is most commonly identified by elevation in levels of C-reactive protein (CRP), which serves as a marker of increased inflammation, but the upstream upregulation in IL-1– and IL-6–mediated pathways has been implicated in inflammation that drives development of diseases like HFpEF. There is an ongoing trial of ziltivekimab, which is an IL-1 inhibitor in patients with HFpEF. That's the HERMES trial led by Paul Ridker, one of the pioneers of inflammatory therapies in heart disease. We are starting to understand more about the key molecular pathways that are driving it. And now we're starting to target them, with the hope that we can actually halt the progression of HFpEF and improve the symptom burden as well as the risk for adverse outcomes in these patients. Are GLP-1 Inhibitors Anti-inflammatory? Piña: Do you think that the GLP-1s, or even now the SGLT2 inhibitors, are anti-inflammatory since we really don't know all the pathways? Pandey: I do think that GLP-1s, by virtue of causing weight loss and reduction in visceral adiposity and the bad fat depots that exist in our body, have a significant anti-inflammatory effect. And if you look at the data from the STEP trials that were done, looking at weight loss effects of semaglutide, a commonly used GLP-1 inhibitor, there was a good 30%-40% reduction in CRP levels, and that suggests that there is a significant anti-inflammatory effect. Now, whether it's a direct effect on anti-inflammatory pathways or is related to weight loss is a matter of debate. Piña: Are you using GLP-1 inhibitors in your HFpEF clinic? And what trials can we look forward to seeing concerning the use of these agents? https://www.medscape.com/viewarticle/993980?src=soc_yt

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For more Rapid Fat Loss tips: http://www.thebodyfirm.biz Fort Worth personal trainer Dave Fannin demonstrates how to measure your body parts as part of a fat loss and toning program. Tracking your progress in your weight(fat) loss program is essential to your success. Denial and vague ideas are of no use in the process of achieving results. You need to know exactly where you are when you begin. Then you need to set deadlines to measure again. This is how you measure progress. With clients I always get weight, Bodyfat percentage with calipers(the most important number of all), circumference measurements(like in the video) and photogaraphs. At home you can do all of these easily. But you'll need to buy some plastic Bodyfat calipers(search online) for an accurate measurement of bodyfat levels. What you do need to remember is as you dial in your eating and kick in the exercise you're going to lose inches. And the best way to track this is with a cloth or plastic tape measure. Take a piece of paper to record your measurements and put your starting date. Count out 4 weeks from today and that's when you'll measure again. Step on the scale and get your starting weight to go with these numbers. The key point to remember is consistency. 1. Get someone to help you. It's a lot easier. 2. Always measure the same side. If you start on the right. next month measure the right side. 3. Wear the same clothes for consistent numbers 4. Measure "cold". Don't measure immediately after you've worked out. 5. Set your deadlines to when you're going to measure again. And force yourself to stick to those deadlines. Get these numbers down and get to work. I guarantee you'll see smaller numbers next month. Dave For more Rapid Fat-Loss nutrition, workouts, meal plans, exercises, tips, secrets, and tactics go to http://www.thebodyfirm.biz For more info on getting the results you want fast go to http://www.thebodyfirm.biz More information on Rapid Results Fitness Bootcamps go to http://www.fortworthfitnesscamp.com

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Here is an ad for Diet Coke included on the VHS tape release of "Indiana Jones and the Last Crusade." A young lady goes to her adventurous kitchen with our favorite archeologist (not Miss Croft, the other one) to find her husband a soft drink. Why this wasn't made a dvd extra, I'll never know. Perhapse a future Blu-Ray release may have it.

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