Paul M. Ridker (born 1959) is a
cardiovascular
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
epidemiologist
Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population.
It is a cornerstone of public health, and shapes policy decisions and evidenc ...
and
biomedical research
Research is " creative and systematic work undertaken to increase the stock of knowledge". It involves the collection, organization and analysis of evidence to increase understanding of a topic, characterized by a particular attentiveness ...
er. He is currently the
Eugene Braunwald
Eugene Braunwald (born August 15, 1929 in Vienna, Austria) is an Austrian-born American cardiologist.
Early life
Braunwald was born to Jewish parents Wilhelm Braunwald and Clara Wallach in Vienna. He obtained his A.B. and M.D. at New York Univer ...
Professor of Medicine at
Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of high ...
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
The Harvard T.H. Chan School of Public Health is the public health school of Harvard University, located in the Longwood Medical Area of Boston, Massachusetts. The school grew out of the Harvard-MIT School for Health Officers, the nation's first ...
.
Ridker's research has provided proof-of-principle for the
inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
hypothesis of
atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...
, 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
The ''h''-index is an author-level metric that measures both the productivity and citation impact of the publications, initially used for an individual scientist or scholar. The ''h''-index correlates with obvious success indicators such as ...
above 220.
Early life
Ridker was born in
St. Louis, Missouri
St. Louis () is the second-largest city in Missouri, United States. It sits near the confluence of the Mississippi and the Missouri Rivers. In 2020, the city proper had a population of 301,578, while the bi-state metropolitan area, which e ...
in 1959. He attended
Brown University for his undergraduate studies, graduating with a Bachelor of Science in 1981. He attended
Harvard Medical School
Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...
, 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
The Harvard T.H. Chan School of Public Health is the public health school of Harvard University, located in the Longwood Medical Area of Boston, Massachusetts. The school grew out of the Harvard-MIT School for Health Officers, the nation's first ...
.
Career
Ridker’s translational research combines the tools of
epidemiology
Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population.
It is a cornerstone of public health, and shapes policy decisions and evide ...
,
vascular biology, and
randomized clinical trials
A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
to determine the root causes of
heart disease,
stroke, and
diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
. 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
Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia (high levels of lipids in the blood), hyperlipoproteinemia (high levels of lipoproteins in the blood), ...
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 and the central signaling cytokine
Interleukin 6
Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene.
In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth ...
were responsible for a large proportion of “unexplained risk”.
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.
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. This work, largely funded by the
National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
, eventually led to the design and conduct of the multi-national
JUPITER primary prevention 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, even if cholesterol levels were already low.
Critical proof of the inflammation hypothesis of atherosclerosis came when Ridker and his international collaborators focused on the
NLRP3
NLR family pyrin domain containing 3 (NLRP3) (previously known as NACHT, LRR and PYD domains-containing protein 3 ALP3and cryopyrin), is a protein that in humans is encoded by the ''NLRP3'' gene located on the long arm of chromosome 1.
NLRP3 is ...
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
The National Heart, Lung, and Blood Institute (NHLBI) is the third largest Institute of the National Institutes of Health, located in Bethesda, Maryland, United States. It is tasked with allocating about $3.6 billion in FY 2020 in tax revenue to ...
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
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.
Monoclonal antibodies ...
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.
CANTOS also demonstrated that the magnitude of inflammation reduction, as measured by on-treatment levels of Interleukin-6, drives the cardiovascular benefit with 36% decreases in cardiovascular death and all-cause mortality among robust Canakinumab responders. 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 the inexpensive generic oral agent
Colchicine
Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever. Colchicine is taken b ...
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
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
,
renal failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
, and large joint
osteoarthritis
Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...
.
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
The National Academy of Medicine (NAM), formerly called the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, Eng ...
* 2013, Distinguished Scientist Award,
American Heart Association
* 2012, Elected Member,
American Clinical and Climatological Association
* 2009, Doctorem Honoris Causa,
Utrecht University
Utrecht University (UU; nl, Universiteit Utrecht, formerly ''Rijksuniversiteit Utrecht'') is a public research university in Utrecht, Netherlands. Established , it is one of the oldest universities in the Netherlands. In 2018, it had an enrollme ...
, The Netherlands
* 2009, Doctorem Honoris Causa,
Interamerican Open University
* 2007, Distinguished Fellow, International Atherosclerosis Societ
* 2005, NIH Director’s Astute Clinician Award,
National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
* 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
The Association of American Physicians (AAP) is an honorary medical society founded in 1885 by the Canadian physician Sir William Osler and six other distinguished physicians of his era for "the advancement of scientific and practical medicine." ...
* 2000, Elected Member,
American Epidemiological Society The American Epidemiological Society is an American honorary society dedicated to epidemiology. It was established in 1927, and has held annual meetings since 1968. It is the oldest epidemiology organization in the United States. Past members of the ...
* 1999, Elected Member,
American Society for Clinical Investigation
The American Society for Clinical Investigation (ASCI), established in 1908, is one of the oldest and most respected medical honor societies in the United States.
Organization and purpose
The ASCI is an honorary society to which more than 2,800 ph ...
* 1993, Elected Fellow,
American College of Cardiology
The American College of Cardiology (ACC), based in Washington, D.C., is a nonprofit medical association established in 1949. It bestows credentials upon cardiovascular specialists who meet its qualifications. Education is a core component of the ...
See also
*
JUPITER trial The JUPITER trial (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin trial) was a clinical trial aimed at evaluating whether statins reduce heart attacks and strokes in people with normal chole ...
References
External links
*
*
{{DEFAULTSORT:Ridker, Paul
Living people
1959 births
People from St. Louis
Brown University alumni
Harvard Medical School alumni
Harvard School of Public Health alumni
Harvard Medical School faculty
American medical researchers