Paul Ridker

Paul M. Ridker (born 1959) is a cardiovascular epidemiologist and biomedical researcher. He is currently the Eugene Braunwald Professor of Medicine at Harvard University and Brigham and Women's Hospital, where he directs the Center for Cardiovascular Disease Prevention. Ridker also holds an appointment as Professor in the Department of Epidemiology at the Harvard T.H. Chan School of Public Health.

Ridker's research has provided proof-of-principle for the inflammation hypothesis of atherosclerosis, the first FDA approved diagnostic test for vascular inflammation, and the first proven anti-inflammatory treatment for coronary artery disease. He is among the most cited researchers in cardiovascular medicine in the world and has an H-index above 220.

Early life Ridker was born in St. Louis, Missouri in 1959. He attended Brown University for his undergraduate studies, graduating with a Bachelor of Science in 1981. He attended Harvard Medical School, where he received his MD in 1986; Ridker completed his residency at Brigham and Women’s Hospital and West Roxbury VA Medical Center in Boston, Massachusetts. In 1992, Ridker earned a Master of Public Health degree at the Harvard T.H. Chan School of Public Health.

Ridker is best known for his work developing inflammatory biomarkers and his clinical trials defining 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.

Critical proof of the inflammation hypothesis of atherosclerosis came when Ridker and his international collaborators focused on the NLRP3 to Interleukin-1b to Interleukin-6 pathway of innate immunity and its role in coronary disease. 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. 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. In contrast, the federally funded CIRT (Cardiovascular Inflammation Reduction Trial) showed no benefit to low-dose Methotrexate but also no evidence of lowering Interleukin-1b, Interleukin-6 nor CRP. Thus, the positive CANTOS trial and the informative null CIRT trial defined the need to reduce signaling from the NLRP3 to Interleukin-1 to Interleukin-6 in order to lower vascular event rates. These findings were replicated with low-dose Colchicine in the 2019 COLCOT and 2020 LoDoCo2 trials. Ongoing work from Ridker’s group is testing whether direct targeting of Interleukin-6 itself can improve cardiovascular outcomes.

Ridker’s work has had wide biologic implications beyond atherosclerosis and heart disease. By reducing inflammation in the tumor microenvironment, CANTOS also demonstrated highly significant reductions in lung cancer and lung cancer fatality. These data have generated broad interest within the academic and pharmacologic communities resulting in multiple trials studying Interleukin-1 inhibition with or without adjunctive checkpoint inhibition as a novel therapy for non small cell lung cancers. Work from CANTOS has also demonstrated the potential human benefits of targeted Interleukin-1 therapy on anemia, renal failure, and large joint osteoarthritis.

In his work as a clinical trialist, Ridker has designed, conducted, and served as Trial Chair of the Steering Committee of PRINCE, VAL-MARC, PREVENT, LANCET, JUPITER, SPIRE-1, SPIRE-2, CANTOS and CIRT, as well as the ongoing PROMINENT, ACTIV-4B, and ZEUS trials.

Honors and awards

2020, Elected Member, National Academy of Medicine 2013, Distinguished Scientist Award, American Heart Association 2012, Elected Member, American Clinical and Climatological Association 2009, Doctorem Honoris Causa, Utrecht University, The Netherlands 2009, Doctorem Honoris Causa, Interamerican Open University 2007, Distinguished Fellow, International Atherosclerosis Society 2005, NIH Director’s Astute Clinician Award, National Institutes of Health 2004, TIME 100 Most Influential: Scientists & Thinkers 2001, TIME, America's Ten Best Researchers in Science and Medicine 2002, Elected Fellow, Association of American Physicians 2000, Elected Member, American Epidemiological Society 1999, Elected Member, American Society for Clinical Investigation 1993, Elected Fellow, American College of Cardiology