1) Welcome to a new joint-accredited #tweetorial on the very foundation of the new “specialty” of #cardiometabolic medicine: organ crosstalk. I am @md_pollack. Follow this tweetorial to earn FREE 0.5h credit, #physicians #nurses #pharmacists! @MedTweetorials #FOAMed #medtwitter pic.twitter.com/HFvoOaWKF4
— cardio-met (@cardiomet_CE) August 31, 2021
3) The basis of the term “cardiometabolic medicine”–still a relatively new and inconsistently used term (even tho it provides a title of this educational initiative!)–is that there is “organ crosstalk” among the heart, kidneys, liver, endocrine system, CNS, and immune system. pic.twitter.com/Npa12XqlZC
— cardio-met (@cardiomet_CE) August 31, 2021
5) This close association and frequent co-existence among #CV, metabolic, & kidney diseases suggest a common pathological basis and significant interaction among these diseases. We know they share many common risk factors, and the “graying” of the population ⬆️their incidence.
— cardio-met (@cardiomet_CE) August 31, 2021
7) Close interactions among body systems are critical for protecting organs & promoting health (think of exercise-induced cardioprotection, likely through crosstalk between heart & skeletal muscle), they may also promote & expand pathology to other, multiple organs.
— cardio-met (@cardiomet_CE) August 31, 2021
9) The use of terms like “metabolic syndrome” & “cardiorenal syndrome” highlights strong clinical associations among disorders of the CV and metabolic systems.
— cardio-met (@cardiomet_CE) August 31, 2021
11) Patients diagnosed with cardiorenal syndrome have failure of either the 🫀 or kidney that leads to or accelerates failure of the other. We are now recognizing similar system crosstalk syndromes such as cardiohepatic, hepatorenal, & intestinal–renal (https://t.co/EnfOcxSJTs).
— cardio-met (@cardiomet_CE) August 31, 2021
13) Please answer the poll and return tomorrow for more on organ crosstalk in #cardiometabolic disease. Remember–you are earning CE/#CME while on Twitter! @TheEndoSociety @DrMarthaGulati @ShelleyZieroth @CMHC_CME @RajayNarain @IntMedAbel @atherometab @edgarvlermamd @aklfahed
— cardio-met (@cardiomet_CE) August 31, 2021
15) So that unexpected “discovery” referenced in yesterday’s poll was the recognition that treatment of #T2D with #SGLT2i had a beneficial impact on the development and progression of #heartfailure and diabetic kidney disease (#DKD) in those diabetics. This is system crosstalk!
— cardio-met (@cardiomet_CE) September 1, 2021
17) So let’s review the MOA of SGLT2i and see if that sheds light on their effects on multiple #cardiometabolic systems. SGLT2i’s act at the (shocker!) SGLT2 receptor in the renal tubules to ⬇️ glucose reabsorption, causing ⬇️in blood glucose but w/o stimulating insulin release. pic.twitter.com/RBaZ634bDu
— cardio-met (@cardiomet_CE) September 1, 2021
19) Blocking that receptor therefore has a direct impact on glucose homeostasis that is exaggerated in T2D. How effective at T2D tx is this class? In a 2014 meta-analysis, 24-week ⬇️of HbA1c with SGLT2i was greater in trials enrolling patients with a lower mean age, shorter . . .
— cardio-met (@cardiomet_CE) September 1, 2021
21) . . . with those pleiotropic effects listed above, like weight loss and ⬇️SBP (doi: 10.1097/MED.0000000000000311). So what are the “crosstalk pathways” that lead to improvement in diverse #CV and #renal outcomes with SGLT2i use–even in (wait for it!) PATIENTS W/O DIABETES?? pic.twitter.com/ffqws5W3c3
— cardio-met (@cardiomet_CE) September 1, 2021
23) This figure shows SGLT2i leading to 1) BP ⬇️, ⬆️diuresis/natriuresis, 3) improving cardiac energy metabolism, 4)⬇️inflammation, 5) weight loss, 6) improving glucose control, 7) inhibiting the sympathetic nervous system, 8) preventing adverse cardiac remodeling . . .
— cardio-met (@cardiomet_CE) September 1, 2021
25) . . . 16) ⬆️ circulating provascular progenitor cells, 17) ⬇️ oxidative stress, & 18) improving vascular function (from doi: 10.1016/j.jacbts.2020.02.004). WHEW! #Pleiotropic to the MAX!!
— cardio-met (@cardiomet_CE) September 1, 2021
27) . . . result in a 30% to 60% increase in urinary Na+ excretion, this has a cardioprotective effect. Next, as HF progresses, a continual ⬇️ in mitochondrial oxidative metabolism occurs. SGLT2i improve cardiac energetics and improving cardiac efficiency. pic.twitter.com/Nj3zxpueAZ
— cardio-met (@cardiomet_CE) September 1, 2021
29) Improved glucose control itself, + weight reduction, improve CV/HF outcomes. Remember we mentioned #CNS in the initial “crosstalk” discussion? Well, SGLT2i ⬇️ BP w/o ⬆️HR, suggesting a ⬇️ in sympathetic nervous system activity. But wait, there’s more! pic.twitter.com/pyTpHa43e8
— cardio-met (@cardiomet_CE) September 1, 2021
31) In a recent meta-analysis of 21 Ph 2b/3 dapagliflozin clinical trials, there was no suggestion of ⬆️risk for #MACE with dapa compared with control (doi: 10.1186/s12933-016-0356-y).
— cardio-met (@cardiomet_CE) September 1, 2021
33) But let’s not forget about the BEANS. Return tomorrow and we’ll talk about the #cardiorenal benefits of SGLT2i before taking you to your CE/#CME credit link. Don’t miss it! pic.twitter.com/j1WtSP0Hns
— cardio-met (@cardiomet_CE) September 1, 2021
35) I promised we'd talk kidneys today. The renal system is such a key component (and target!) of #cardiometabolic pathology. Recently McGuire et al gave us a meta-analysis to assess kidney outcomes of all 4 available SGLT2i in pts with #T2D (doi:10.1001/jamacardio.2020.4511).
— cardio-met (@cardiomet_CE) September 2, 2021
37) In the McGuire meta-analysis, SGLT2i were associated with ⬇️risk of MACE but significant heterogeneity for CV death. The largest benefit across the class was ⬇️ in risk for HHF & kidney outcomes, with benefits for HHF being the most consistent observation across the trials.
— cardio-met (@cardiomet_CE) September 2, 2021
39) In this analysis, outcomes of SGLT2i on hazard for progression of kidney disease overall and by ASCVD status showed a significant ⬇️ for kidney disease, but no interaction of outcome on progression of kidney disease observed for those with vs without ASCVD. Take a look: pic.twitter.com/gyVdQrtCJX
— cardio-met (@cardiomet_CE) September 2, 2021
41) . . . was lower by 34%, and the RR of ESRD alone was lower by 32%. The trial was stopped early for efficacy. pic.twitter.com/NJhxfhbxWo
— cardio-met (@cardiomet_CE) September 2, 2021
43) . . . disease in extended populations independent of DM status in pts with #CKD of diverse diabetic and nondiabetic kidney disease etiologies, was the DAPA-CKD trial of dapa vs placebo, which was also stopped early for efficacy (DOI: 10.1056/NEJMoa2024816).
— cardio-met (@cardiomet_CE) September 2, 2021
45) What about empa? The EMPA-KIDNEY trial is underway (NCT03594110), but existing data from EMPA-REG OUTCOME indicate that empagliflozin showed consistent risk reductions across @goKDIGO categories for kidney outcomes (doi: 10.2215/CJN.14901219).
— cardio-met (@cardiomet_CE) September 2, 2021
47) So #FLOZINATE to help heart and kidneys! In summary, the activity of the #SGLT2i class is a great example of how one therapy, through organ/system crosstalk, can impact more than one primary target in the #cardiometabolic axis. We picked a good name for this feed after all!
— cardio-met (@cardiomet_CE) September 2, 2021
48) And now your reward: 0.5h CE/#CME for #physicians #nurses #pharamcists #APPs. Just go to https://t.co/4mBRtE56I6. Also check out archived #cardiorenal programs, still available for credit, at https://t.co/XFPs2Ca0jj. #FOAMed @MedTweetorials #medtwitter #CardioTwitter
— cardio-met (@cardiomet_CE) September 2, 2021