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Steven Grinspoon

Steven Grinspoon is an American physician who is a Professor of Medicine at Harvard Medical School, Chief of the Massachusetts General Hospital (MGH) Metabolism Unit and Director of the Nutrition Obesity Research Center at Harvard. In addition, he is the MGH Endowed Chair in Neuroendocrinology and Metabolism. His work investigates the neuroendocrine regulation of body composition, and physiologic consequences of fat distribution on cardiovascular disease and inflammation.[1] In 2015, he became the Principal Investigator of the NIH-funded Nutrition Obesity Research Center at Harvard.[2]

Education

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Grinspoon graduated from Cornell University in 1983.[3] He attended the University of Rochester School of Medicine, graduating in 1988.[4] He did his medical residency and Chief Residency at Columbia Presbyterian from 1988 to 1992 and his Endocrinology Fellowship at Massachusetts General Hospital from 1992 to 1995.[5]

Research and awards

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Grinspoon’s primary research focus has been to investigate the effects of augmenting endogenous GH pulsatility on visceral fat in lipodystrophic patients with abdominal fat accumulation and nonalcoholic fatty liver disease. This work was initiated by an observation of reduced GH secretion in HIV patients with lipodystrophy. Subsequent studies examined the mechanisms and demonstrated reduced area under the curve per peak, but maintenance of the GH pulse generator in such patients. Reasoning that augmentation of GH pulsatility might reduce visceral fat, because of its potent effects to oxidize adipose tissue, Grinspoon led a series of studies culminating in a NEJM paper demonstrating that Tesamorelin, a GHRH1-44 secretagogue, reduced visceral fat by 20% and reduced triglyceride, while improving adiponectin.[6] This work led to FDA approval of Tesamorelin as the only such approved drug for HIV lipodystrophy and first in class molecule. Subsequent studies, published in JAMA and Lancet HIV, demonstrated that Tesamorelin reduced hepatic steatosis as well, the first drug to demonstrate a significant effect among patients with HIV lipodystrophy.[7][8][9] Subsequent work demonstrated significant effects to stimulate hepatic oxidative pathways and reduce inflammatory pathways in gene set enrichment studies.[10] Grinspoon was granted a US Patent entitled “GHRH or Analogues thereof for the Use in Treatment of Hepatic Disease” for this work.[11] Tesamorelin was also investigated in generalized obesity and showed significant effects to reduce cIMT, inflammatory markers, lipids and visceral adiposity.[12]

A second and related focus of Grinspoon’s work has been to investigate the mechanisms and strategies for CVD in HIV.  In this regard, he led an AHA sponsored State of the Science Symposium on CVD in HIV. The conclusions from this conference called for a better understanding and treatment strategies of CVD in HIV. This work began with epidemiologic studies demonstrating increased myocardial infarction rates in HIV patients in the JCEM.[2] This data was followed by a series of mechanistic studies demonstrating increased prevalence of plaque, particularly noncalcified, lipid rich, plaque. Grinspoon used FDG PET to demonstrate for the first time significant arterial inflammation in asymptomatic low traditional risk HIV patients, compared to Framingham risk matched control subjects, as well as non HIV patients with known CVD, published in JAMA.[13] Of note, increased arterial inflammation was most significantly associated with increased markers of immune activation. He also recently proposed the first use of tilmanocept as a CD206 specific imaging agent for arterial inflammation, with success in HIV published in JID.[14] This work was followed by studies in HIV patients in which he phenotyped the morphological characteristics of coronary plaque in HIV patients, demonstrating an increased prevalence of high risk plaque with low attenuation and positive remodeling, more vulnerable to rupture.[15] His studies suggested that treatment with a statin might uniquely target both traditional risk factors including low-density lipoprotein (LDL) but also increased immune activation indices driving atypical noncalcified high risk plaque in this population. This work culminated in a recent paper in Lancet HIV, in which he showed for the first time that a statin can significantly reduce high risk plaque volume as well as improve the high-risk morphological features in coronary lesions in HIV.[16] In recognition of this work, he has led the REPRIEVE trial, a global primary prevention study performed in 12 countries, since 2013 and gave the plenary lecture at CROI 2015 on this topic.[17][18] The REPRIEVE trial was recently closed early by its Data Safety Monitoring Board for a robust efficacy signal, demonstrating that a statin strategy reduced major adverse cardiovascular event (primary heart attacks, strokes, and cardiovascular death) by 35% over 5 years, compared to placebo. This trial was recently published in the New England Journal of Medicine and the data presented by Grinspoon at the International AIDS Society 2023 meeting in Brisbane and featured in news articles and podcasts.[19][20][21][22][23]

Grinspoon has worked to understand the mechanism, and treatment strategies for metabolic dysregulation in HIV, and was among the first to assess metformin and rosiglitazone to reverse insulin resistance and increase adipogenesis in this population. He also recognized reduced DICER as a factor that may contribute to dysfunctional adipose tissue in HIV.[6][7][8]

Awards

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Grinspoon was elected to the American Society for Clinical Investigation in 2003.[24]

In 2016, he received the Gerald D. Aurbach Laureate Award for Outstanding Translational Research from the Endocrine Society.[25]

Selected works

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  • Grinspoon, Steven K. (April 2003). "Weight loss and wasting in patients infected with human immunodeficiency virus.” Clinical Infectious Diseases 36 (69-78).[26]
  • Grinspoon, Steven K. (19 June 2008). “Initiative to Decrease Cardiovascular Risk and Increase Quality of Care for Patients Living With HIV/AIDS”.Circulation (journal) 18[27]
  • Grinspoon, Steven K. ;Lake, Jordan, Stanley, Takara; Apovian, Caroline; Brown, Todd. (15 May 2017). “Practical Review of Recognition and Management of Obesity and Lipohypertrophy in Human Immunodeficiency Virus Infection”. Clinical Infectious Diseases 64 (1422–1429).[28]
  • Grinspoon, Steven K; Brown, Todd T. (2020) Williams Textbook of Endocrinology:”Endocrinology of HIV/AIDS”. Elsevier.[29]
  • Grinspoon, Steven K; Stlanley, Takara L. (January 2022) Oxford Textbook of Endocrinology and Diabetes: “Abnormalities in HIV Infection”. Oxford University Press.[30]
  • Grinspoon, Steven K; Zanni, Markella V.; Fitchenbaum, Carl J. (July 23, 2023) New England Journal of Medicine: “Pitavastatin to Prevent Cardiovascular Disease in HIV Infection”. Massachusetts Medical Society.[31]

References

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  1. ^ Achermann, John C.; et al. (2016-01-01). "Contributors". Williams Textbook of Endocrinology: v–xiv. doi:10.1016/B978-0-323-29738-7.00047-2. ISBN 9780323297387.
  2. ^ a b Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007 Jul;92(7):2506-12. doi:10.1210/jc.2006-2190 Epub 2007 Apr 24. PMID 17456578; PMCID: PMC2763385.
  3. ^ "Steven Kyle Grinspoon, M.D." Harvard.edu. Retrieved 1 July 2024.
  4. ^ "Miss Sandler Married To Dr. S. K. Grinspoon". New York Times. 5 June 1988. Retrieved 1 July 2024.
  5. ^ "Steven Grinspoon, MD - Neuroendocrinology". Massachusetts General Hospital. Retrieved 2021-04-07.
  6. ^ a b Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, Grinspoon SK. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. 2014 Jul 23-30;312(4):380-9. doi:10.1001/jama.2014.8334 PMID 25038357; PMCID: PMC4363137.
  7. ^ a b Hadigan, Colleen; Yawetz, Sigal; Thomas, Abraham; Havers, Fiona; Sax, Paul E.; Grinspoon, Steven (2004-05-18). "Metabolic Effects of Rosiglitazone in HIV Lipodystrophy". Annals of Internal Medicine. 140 (10): 786–794. doi:10.7326/0003-4819-140-10-200405180-00008. ISSN 0003-4819. PMID 15148065. S2CID 53089714.
  8. ^ a b Torriani M, Srinivasa S, Fitch KV, Thomou T, Wong K, Petrow E, Kahn CR, Cypess AM, Grinspoon SK. Dysfunctional Subcutaneous Fat With Reduced Dicer and Brown Adipose Tissue Gene Expression in HIV-Infected Patients. J Clin Endocrinol Metab. 2016 Mar;101(3):1225-34. doi:10.1210/jc.2015-3993 Epub 2016 Jan 12. PMID 26756119; PMCID: PMC4803164.
  9. ^ Newman, Mark (2016-01-22). "Meet the 2016 Laureate Award Winners: Steven Grinspoon, MD". Endocrine News. Retrieved 2022-10-17.
  10. ^ Fourman LT, Billingsley JM, Agyapong G, Ho Sui SJ, Feldpausch MN, Purdy J, Zheng I, Pan CS, Corey KE, Torriani M, Kleiner DE, Hadigan CM, Stanley TL, Chung RT, Grinspoon SK. Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD. JCI Insight. 2020 Aug 20;5(16):e140134. doi:10.1172/jci.insight.140134 PMID 32701508; PMCID: PMC7455119.
  11. ^ US 10946073, Grinspoon, Steven K., "GHRH or analogues thereof for use in treatment of hepatic disease", published 2021-03-16, assigned to Massachusetts General Hospital 
  12. ^ Makimura H, Feldpausch MN, Rope AM, Hemphill LC, Torriani M, Lee H, Grinspoon SK. Metabolic effects of a growth hormone-releasing factor in obese subjects with reduced growth hormone secretion: a randomized controlled trial. J Clin Endocrinol Metab. 2012 Dec;97(12):4769-79. doi:10.1210/jc.2012-2794 Epub 2012 Sep 26. PMID 23015655; PMCID: PMC3513535.
  13. ^ Subramanian, Sharath; Tawakol, Ahmed; Burdo, Tricia H.; Abbara, Suhny; Wei, Jeffrey; Vijayakumar, Jayanthi; Corsini, Erin; Abdelbaky, Amr; Zanni, Markella V.; Hoffmann, Udo; Williams, Kenneth C. (2012-07-25). "Arterial Inflammation in Patients With HIV". JAMA. 308 (4): 379–386. doi:10.1001/jama.2012.6698. ISSN 0098-7484. PMC 3724172. PMID 22820791.
  14. ^ Zanni MV, Toribio M, Wilks MQ, Lu MT, Burdo TH, Walker J, Autissier P, Foldyna B, Stone L, Martin A, Cope F, Abbruzzese B, Brady T, Hoffmann U, Williams KC, El-Fakhri G, Grinspoon SK. Application of a Novel CD206+ Macrophage-Specific Arterial Imaging Strategy in HIV-Infected Individuals. J Infect Dis. 2017 Apr 15;215(8):1264-1269. doi:10.1093/infdis/jix095 PMID 28204544; PMCID: PMC5853590.
  15. ^ Zanni MV, Abbara S, Lo J, Wai B, Hark D, Marmarelis E, Grinspoon SK. Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography angiography in HIV-infected men. AIDS. 2013 May 15;27(8):1263-72. doi:10.1097/QAD.0b013e32835eca9b PMID 23324657; PMCID: PMC3740057.
  16. ^ Lo J, Lu MT, Ihenachor EJ, Wei J, Looby SE, Fitch KV, Oh J, Zimmerman CO, Hwang J, Abbara S, Plutzky J, Robbins G, Tawakol A, Hoffmann U, Grinspoon SK. Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial. Lancet HIV. 2015 Feb;2(2):e52-63. doi:10.1016/S2352-3018(14)00032-0 Epub 2015 Jan 9. PMID 26424461; PMCID: PMC4820828.
  17. ^ "Steven K. Grinspoon, MD". REPRIEVE Trial. Retrieved 2021-04-07.
  18. ^ "Cardiovascular Disease in HIV Patients: An Emerging Paradigm and Call to Action". CROI Conference. 24 February 2015. Retrieved 2021-04-07.
  19. ^ "Daily Statin Medication Reduces Risk of Major Cardiovascular Events by More Than One-Third in People Living with HIV". Massachusetts General Hospital. Retrieved 2023-11-22.
  20. ^ "Daily statin reduces heart disease risk among adults living with HIV". National Institutes of Health (NIH). 2023-07-24. Retrieved 2023-11-22.
  21. ^ "Preventing HIV's Collateral Cardiovascular Damage: ITT Episode 15". New England Journal of Medicine. 389 (7): e11. 2023-08-17. doi:10.1056/NEJMp2307347. ISSN 0028-4793.
  22. ^ Ryan, Benjamin (2023-09-10). "For 'Silver Tsunami' With H.I.V., New Hope for Healthy Aging". The New York Times. ISSN 0362-4331. Retrieved 2023-11-22.
  23. ^ "For people with HIV, statins show 35 percent drop in heart attack risk". Washington Post. 2023-09-29. ISSN 0190-8286. Retrieved 2023-11-22.
  24. ^ "The American Society for Clinical Investigation". the-asci.org. Retrieved 1 July 2024.
  25. ^ Newman, Mark (2016-01-22). "Meet the 2016 Laureate Award Winners: Steven Grinspoon, MD". Endocrine News. Retrieved 2022-10-17.
  26. ^ Grinspoon, Steven K.; Mulligan, Kathleen (April 2003). "Department of Health and Human Services Working Group on the Prevention and Treatment of Wasting and Weight Loss. Weight loss and wasting in patients infected with human immunodeficiency virus". Clinical Infectious Diseases. doi:10.1086/367561. PMID 12652374. Retrieved 1 July 2024.
  27. ^ Grinspoon, Steven K.; et, al (19 June 2008). "State of the Science Conference: Initiative to Decrease Cardiovascular Risk and Increase Quality of Care for Patients Living With HIV/AIDS: Executive Summary". Circulation. 18. doi:10.1161/CIRCULATIONAHA.107.18962. Retrieved 25 July 2024.
  28. ^ Lake, Jordan; Stanley, Takara; Apovian, Caroline; Brown, Todd; Grinspoon, Steven (15 May 2017). "Practical Review of Recognition and Management of Obesity and Lipohypertrophy in Human Immunodeficiency Virus Infection". Clinical Infectious Diseases. 64 (10): 1422–1429. doi:10.1093/cid/cix178. PMC 5411395. Retrieved 24 July 2024.
  29. ^ Grinspoon, Steven K.; Brown, Todd T. (2020). Williams Textbook of Endocrinology:”Endocrinology of HIV/AIDS”. Elsevier. ISBN 978-0-323-55596-8.
  30. ^ Grinspoon, Steven K.; Stanley, Takara L. (January 2022). Oxford Textbook of Endocrinology and Diabetes (3 ed.). Oxford University Press. p. 1715–1724. ISBN 9780191840739.
  31. ^ Grinspoon, Steven K.; Fitch, Kathleen D.; Zanni, Markella V.; Fitchenbaum, Carl J. (23 July 2023). "Pitavastatin to Prevent Cardiovascular Disease in HIV Infection". New England Journal of Medicine. 389. doi:10.1056/NEJMoa2304146. PMC 10564556. Retrieved 1 August 2024.
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