Paul Ridker

Paul M. Ridker is a medical researcher and the Eugene Braunwald Professor of Medicine at Harvard University. He is also on staff at Brigham and Women's Hospital in Boston, Massachusetts, known for his work on inflammation and its role in heart disease. He also directs the Center for Cardiovascular Disease Prevention at the Brigham and Women’s Hospital and is on faculty at the Harvard Medical School and the Harvard T.C. Chan School of Public Health.[1]

Paul Ridker

Early life

Ridker is a graduate of Brown University (1981), the Harvard Medical School (1986), and the Harvard T.C.Chan School of Public Health (1992). He completed his medical internship, residency, and cardiology fellowship all at the Brigham and Women’s Hospital, Harvard Medical School.[2]

Career

Ridker’s translational research combines the tools of epidemiology and vascular biology to determine the root causes of heart disease, stroke, and diabetes.[3][4][5] He is responsible for the clinical development of high sensitivity C-reactive protein (hsCRP), a marker of inflammation, that is used to evaluate the risk of heart attack and stroke, and coined the term “residual inflammatory risk” to describe patients who are at risk due to vascular inflammation rather than high cholesterol levels. Early in his career, Ridker recognized that elevated cholesterol levels were absent in almost half of all heart attack victims and that the pro-inflammatory response detected by hsCRP was responsible for a large proportion of “unexplained risk”.[6][7][8]

Ridker is best known for his work developing inflammatory biomarkers and anti-inflammatory treatments for cardiovascular disease. In 1997, Ridker showed that elevated levels of hsCRP and interleukin-6 in healthy individuals were a major risk marker for future heart attack, stroke, diabetes, and cardiovascular death, independent of traditional risk factors.[9] Further, between 1998 and 2005, Ridker showed that individuals with elevated hsCRP but low levels of cholesterol were at substantial risk and that statin drugs used to lower cholesterol also lowered hsCRP and thus had important anti-inflammatory properties.[10] This work, largely funded by the National Institutes of Health, eventually led to the design and conduct of the multi-national JUPITER trial which in 2008 demonstrated that individuals with elevated hsCRP levels could reduce by half their risk of future heart attack or stroke by taking statin therapy.[11]

Much of Ridker’s current work is addressing whether reducing the upstream drivers of inflammation such as interleukin-6 and interleukin-1 can reduce rates of heart attack and stroke. Toward this end, in 2010, Ridker obtained parallel funding from the National Heart Lung and Blood Institute and from the pharmaceutical industry to design and conduct two multi-national cardiovascular inflammation reduction trials known as CANTOS and CIRT. The CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) reported in late 2017 that inflammation inhibition with Canakinumab, a monoclonal antibody targeting interleukin-1-beta, can significantly reduce future risks of heart attack, need for expensive coronary revascularization procedures, and cardiovascular deaths among high-risk heart disease patients with residual inflammatory risk.[12] Canakinumab had no effects on either cholesterol or blood pressure, and thus these data provided the fundamental first proof-of-concept for the inflammation hypothesis of Atherosclerosis.[13][14] CANTOS also demonstrated that the magnitude of inflammation reduction, as measured by on-treatment hsCRP, drives the cardiovascular benefit with 30% decreases in cardiovascular death and all-cause mortality among robust Canakinumab responders.[15] By reducing inflammation in the tumor microenvironment, CANTOS also demonstrated highly significant reductions in lung cancer and lung cancer fatality.[16] The federally funded CIRT (Cardiovascular Inflammation Reduction Trial) is still ongoing and expected to report out in late 2018.

In 2013, Ridker and Nancy Cook noted that the calculator used in the US guidelines for heart disease prevention and treatment over-estimated risk, an important issue since this risk calculator is the primary tool used to determine which patients will get treated with statin therapy and aspirin.[17][18] While Ridker is an advocate of statin therapy for heart disease prevention, his group was also demonstrated that statin therapy is associated with a small increase in the risk of developing diabetes. Ridker and Cook have thus advocated for the risk calculator to be re-calibrated to better reflect the concepts of “personalized medicine” so that the right treatments can be given to the right patients and so that the benefits as well as hazards of treatment can be better reflected for patient care.[19]

Recognition

Dr. Ridker was included in TIME magazine's list of 100 most influential people of 2004. Previously, TIME and CNN named Dr. Ridker as one of "America’s Best in Science and Medicine". Ridker has received all three career development awards given by the American Heart Association (Dallas, TX) for research, a Clinician Scientist Award (1992-1997), an Established Investigator Award (1997-2002), and a Distinguished Scientist Award (2013). Between 2000 and 2005, he was the recipient of a Distinguished Scientist Award from the Doris Duke Charitable Foundation and has had philanthropic research support from the Leducq Foundation of Paris and the Donald W. Reynolds Foundation (Las Vegas, USA). In 2005, he received the Harvard School of Public Health Alumni Award of Merit. He is the recipient of multiple honorary degrees.[2]

See also

References
  1. "Researchers find apparent trigger of heart attack and strokes"". New York Times. April 3, 1997.
  2. "Paul M. Ridker, MD - Department of Medicine".
  3. "TINSAL-CVD: Salsalate fails to reduce progression of noncalcified coronary plaque volume". Cardiology Today. July 29, 2016.
  4. "Citing cost, top doctors back limits on PCSK9 cholesterol fighters - FiercePharma".
  5. MD, Gregory Curfman (22 September 2015). "Join us for a special webcast: "Rethinking Cholesterol" - Harvard Health Blog".
  6. "Researchers find apparent trigger of heart attack and strokes". New York Times. April 3, 1997.
  7. "Artery inflammation is linked to heart attacks and strokes". Wall Street Journal. April 3, 1997.
  8. "Predicting heart attacks". New York Times. November 17, 2002.
  9. Ridker PM et al, Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336:973-9.
  10. Ridker PM et al, C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342:836-843.
  11. Ridker PM et al, Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359:2195-207.
  12. Ridker PM; et al. (2017-09-21). "Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease". New England Journal of Medicine. 377 (12): 1119–1131. doi:10.1056/NEJMoa1707914. PMID 28845751.
  13. Baylis RA; et al. (November 2017). "The CANTOS Trial. One Important Step for Clinical Cardiology but a Giant Leap for Vascular Biology". Arteriosclerosis, Thrombosis, and Vascular Biology. 37 (11): e174–e177. doi:10.1161/ATVBAHA.117.310097. PMC 5685554. PMID 28970294.
  14. Ibanez B, Fuster V (2017-12-08). "CANTOS. A Gigantic Proof-of-Concept Trial". Circulation Research. 121 (12): 1320–1322. doi:10.1161/CIRCRESAHA.117.312200. PMID 29217712.
  15. Ridker PM; et al. (2017-11-13). "Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial". The Lancet.
  16. Ridker PM; et al. (2017-08-27). "Effect of interleukin-1beta inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial". The Lancet.
  17. "Risk calculator for cholesterol appears flawed"". New York Times. November 17, 2013.
  18. "Doctors at odds on heart-disease risk calculator". Boston Globe. November 19, 2013.
  19. Ridker PM et al, Cardiovascular benefits and diabetes risks of statin therapy in primary prevention. Lancet 2012; 380:565-571.
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