Pradeep Natarajan, M.D., M.M.Sc., FAHA, Amgen's vice president Global Research, head of Human Genetics, and head of Cardiometabolic Research, discusses what population studies can reveal about heart disease, why he joined Amgen, and how genetic clues can guide the search for medicines.
Summary
- Dr. Natarajan's work uses human genetics and large population studies to investigate cardiovascular disease.
- His research spans lipid disorders, coronary artery disease, clonal hematopoiesis, and approaches to risk prediction.
- At Amgen, he sees an opportunity to connect human genetics with the broader work of research and development.
Why do some people develop heart disease, while others don't?
Despite several important advances, heart disease has been the leading killer in the United States for over 100 years and has been the leading cause of death worldwide for the past 25 years. Breaking this cycle to unlock the important drivers of heart disease requires a new approach.
For Dr. Natarajan, questions like these led him to study human genetics and the patterns that emerge across large populations.
An internationally recognized cardiovascular geneticist and cardiologist by training, Dr. Natarajan has used these approaches to uncover genetic mechanisms linked to lipid disorders, coronary artery disease, and related conditions, while advancing cardiovascular risk prediction and precision medicine that may help identify people at elevated risk earlier in life.
In addition to his scientific discoveries, Dr. Natarajan has been a dedicated mentor to physician-scientists and trainees in clinical cardiac and vascular diseases, cardiovascular genetics research, and precision medicine. He has directed educational programs, mentored dozens of early-career investigators, and helped develop the next generation of leaders in cardiovascular genomics.
At the Presidential Session on Sunday, Nov. 8, the American Heart Association (AHA) presented Dr. Natarajan with its 2026 Population Research Prize during the Scientific Sessions in Chicago. The AHA recognized him for using human genetics and data from large, diverse populations to uncover genetic mechanisms linked to cardiovascular disease, yielding new insights in therapeutics, clinical biomarkers, and risk stratification.Below, Dr. Natarajan reflects on the clinical questions that drew him to human genetics, what population studies can reveal about cardiovascular disease, and how he hopes to contribute at Amgen
What does receiving the AHA's Population Research Prize mean to you?
I'm really honored. The AHA has been part of my professional life for a long time. I've served on its committees focused on data science and precision medicine, and on the Scientific Sessions Planning Committee. To receive this recognition from an organization I've worked with for years means a lot.
Cardiovascular disease remains the leading cause of death worldwide, so the need for better ways to prevent and treat it is still great. The AHA is one of the leading organizations working to change that, and that makes this recognition especially meaningful to me.
I also hope the prize draws attention to the value of population research. When you study health and genetic data across large groups, patterns can emerge that are hard to see in a smaller study. Those patterns give researchers better questions to investigate.
You trained as a cardiologist. What clinical questions led you to human genetics, and was there a moment that shaped your path?
I kept coming back to a basic question: Why does one person develop heart disease while another doesn't? The way that we identify high-risk people today doesn't give us the full picture. I wanted to understand the biological bases for risk to better prevent heart disease before it manifests in the first place. Population-scale human genetics, a research methodology that has emerged and evolved significantly over the last 20 years, gave me a way to study those biological questions in people.
Looking at the effects of naturally occurring genetic variants can offer clues about these predispositions directly in people. Those signals are a starting point for research, such as nominating a target that could be the basis for an important medicine. But the initial genetic signals are often between genes, so there is often a lot of additional work in better clarifying the right gene, tissue of interest, and why the genetic signal is linked to something like heart disease.
Beyond familiar risk factors such as high blood pressure and cholesterol, what can population genetics reveal about cardiovascular disease? And what heart-health lab tests should adults discuss with their clinician?
High blood pressure, diabetes, smoking, and cholesterol all matter. Improvements in these areas can meaningfully improve cardiovascular disease risk.
A standard cholesterol panel is an important part of assessing cardiovascular risk. The 2026 AHA/ACC guideline recommends that adults 19 years and older have a cholesterol panel that includes total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Lipoprotein(a), a genetic marker linked to cardiovascular disease risk, was recently recommended for screening among middle-aged adults in these recent guidelines. A clinician can advise whether other tests are appropriate based on a person's health and family history.
Genetic association studies have uncovered many regions of the genome linked to cardiovascular disease, both related and unrelated to these pathways. And we are using those studies to refine meaningful insights toward novel therapies. But the totality of that information can be synthesized for a patient into a “polygenic risk score.”
Polygenic risk scores combine information from many genetic variants to estimate inherited risk. They may help researchers study patterns of risk, and their use was recently incorporated in the 2026 ACC/AHA Dyslipidemia Guidelines to be considered for risk refinement among patients estimated to be at borderline risk by traditional risk factors. Their role in guiding prevention still needs careful evaluation.
What drew you to Amgen, and how does its research and development environment help move genetic discoveries toward potential medicines?
I wanted to work on both discovery and what comes after discovery. In an academic lab, you can pursue important questions about biology. Taking an idea through research and development calls for more teams and different kinds of expertise. Amgen offered the chance to work across that broader effort, in a way that fits with our mission to serve patients.
Repatha® stood out to me because its genesis is intimately linked to human genetics. Human genetic studies linked PCSK9 variants to low LDL cholesterol levels and lower likelihood of cardiovascular disease, thereby nominating PCSK9 as a drug target. Amgen then developed Repatha, which blocks PCSK9, showing that it recapitulates the genetic effects of lower LDL cholesterol and risk for cardiovascular disease. To me and to the world, it represents arguably one of the leading examples of how genetic findings can help guide the search for a medicine. Given my background and motivations, I felt strongly aligned with this empirically successful framework.
I was also familiar with Amgen deCODE Genetics through research collaborations and its population genetics work. The talent and infrastructure are world-class. Bringing that expertise together with Amgen's drug development capabilities and culture felt like an ideal fit.
One thing that continues to impress me is how many questions come after a genetic finding. You have to understand the biology, decide whether a target makes sense, and keep testing that idea as new evidence comes in. It takes rigor and teamwork, and sometimes it means changing course. I hope to bring my experience in human genetics to that work and learn from colleagues across the research organization.
What do you hope the AHA's recognition brings into focus about the future of population research?
I hope people see that population research is more than collecting a lot of data. It can help us spot important biological signals that are both consistent across and vary across communities and decide what questions to pursue. Then comes the hard work of understanding the biology and testing potential medicines carefully.
I'm grateful for the AHA's recognition, and I'm excited to join the Amgen team. I look forward to working with colleagues across the company to explore what human genetics can reveal about disease, how those findings might inform research and development, and ultimately improve lives.
Repatha® (evolocumab) is indicated:
- To reduce the risk of major adverse cardiovascular (CV) events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, coronary revascularization, or any ischemia-driven arterial revascularization) in adults at increased risk for these events.
- As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in:
Adults with hypercholesterolemia.
- Adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH).
- Adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH).
The safety and effectiveness of Repatha® have not been established in pediatric patients with HeFH or HoFH who are younger than 10 years old or in pediatric patients with other types of hypercholesterolemia.
IMPORTANT SAFETY INFORMATION
- Contraindication: Repatha® is contraindicated in patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in Repatha®. Serious hypersensitivity reactions including angioedema have occurred in patients treated with Repatha®.
- Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema, have been reported in patients treated with Repatha®. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with Repatha®, treat according to the standard of care, and monitor until signs and symptoms resolve.
- Adverse Reactions in Adults with Hypercholesterolemia: The most common adverse reactions (>5% of patients treated with Repatha® and more frequently than placebo) were: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions.
From a pool of the 52-week trial and seven 12-week trials: Local injection site reactions occurred in 3.2% and 3.0% of Repatha®-treated and placebo-treated patients, respectively. The most common injection site reactions were erythema, pain, and bruising. Hypersensitivity reactions occurred in 5.1% and 4.7% of Repatha®-treated and placebo-treated patients, respectively. The most common hypersensitivity reactions were rash (1.0% versus 0.5% for Repatha® and placebo, respectively), eczema (0.4% versus 0.2%), erythema (0.4% versus 0.2%), and urticaria (0.4% versus 0.1%).
- Adverse Reactions in the FOURIER Cardiovascular Outcomes Trial: The most common adverse reactions (>5% of patients treated with Repatha® and more frequently than placebo) were: diabetes mellitus (8.8% Repatha®, 8.2% placebo), nasopharyngitis (7.8% Repatha®, 7.4% placebo), and upper respiratory tract infection (5.1% Repatha®, 4.8% placebo).
Among the 16,676 patients without diabetes mellitus at baseline, the incidence of new-onset diabetes mellitus during the trial was 8.1% in patients treated with Repatha® compared with 7.7% in patients that received placebo.
- Adverse Reactions in the VESALIUS Cardiovascular Outcomes Trial: The safety profile of Repatha® in this trial was consistent with the known safety profile of Repatha®.
- Adverse Reactions in Pediatric Patients with HeFH: The most common adverse reactions (>5% of patients treated with Repatha® and more frequently than placebo) were: nasopharyngitis, headache, oropharyngeal pain, influenza, and upper respiratory tract infection.
- Adverse Reactions in Adults and Pediatric Patients with HoFH: In a 12-week study in 49 patients, the adverse reactions that occurred in at least two patients treated with Repatha® and more frequently than placebo were: upper respiratory tract infection, influenza, gastroenteritis, and nasopharyngitis. In an open-label extension study in 106 patients, including 14 pediatric patients, no new adverse reactions were observed.
- Immunogenicity: Repatha® is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity with Repatha®.
