Atherosclerosis Research

• ISCHEMIA study comparing treatment strategies: The NHLBI-supported International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) has been a game changer for the 18 million Americans living with coronary heart disease, which is caused by plaque buildup. More than 5,000 people in 37 countries participated in the study. Researchers monitored patients for 5 years to determine whether an initial invasive strategy involving cardiac catheterization and coronary revascularization reduces deaths and nonfatal coronary events more than an initial conservative strategy consisting of medicines and lifestyle changes. Although the initial invasive strategy did not reduce these outcomes, it was more effective in reducing angina pain.
• ISCHEMIA study comparing  chronic kidney disease  treatment strategies: The NHLBI-supported ISCHEMIA-Chronic Kidney Disease (CKD) Trial, a companion trial to ISCHEMIA, compared two different treatment approaches for people with both coronary heart disease and advanced chronic kidney disease. It examined whether an initial invasive strategy of guideline-directed medical treatment reduced the number of deaths and heart attacks more than an initial conservative strategy of medicine and lifestyle changes. During an average follow-up period of 3 years, ISCHEMIA-CKD scientists found that the initial invasive strategy did not result in fewer deaths compared to the conservative approach.
• ISCHEMIA study refining treatment strategies with a longer follow-up: ISCHEMIA-EXTEND is a follow-up study with surviving ISCHEMIA participants. It is comparing the initial invasive treatment strategy with the initial conservative strategy to see if the ISCHEMIA results change after a longer follow-up period. The aim is to develop a more accurate heart disease risk score to help healthcare providers deliver individualized care for their patients. By periodically following up with participants, ISCHEMIA-EXTEND researchers reported fewer cardiac deaths among those who had initial invasive treatment. However, the number of deaths due to any cause was similar in both groups. The final study results are expected in 2025, after an average of 10 years of follow-up for surviving participants.
• Framingham Heart Study: Launched in 1948, the NHLBI's landmark Framingham Heart Study (FHS) has followed atherosclerotic disease in three generations of families. By the mid-1940s, nearly half of American deaths were caused by cardiovascular disease, yet scientists knew very little about how or why the disease develops. Since then, FHS has revealed major risk factors for atherosclerotic diseases, including smoking, high blood pressure, unhealthy blood cholesterol levels, obesity, physical inactivity, diabetes, and even COVID-19. Through FHS, scientists learned that many of those risks can be lowered, leading to new ways to prevent or treat atherosclerosis. The program is now identifying how genes, proteins, and other substances in the body influence the development of coronary heart disease and other conditions.

Framingham Heart Study

Learn how the study follows multiple generations to help determine what factors lead to heart disease.

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Our Division of Cardiovascular Sciences and its Atherothrombosis and Coronary Artery Disease Branch support research to advance our understanding of atherosclerosis and find safe and effective ways to prevent and treat it. Our Center for Translation Research and Implementation Science supports research to identify the best strategies to help ensure that results of research are integrated into care to improve health.

Current research on the immune system in atherosclerosis

For decades, the NHLBI has supported research on the role of inflammation in atherosclerosis to spur the development of new therapies that prevent plaque buildup and treat atherosclerotic diseases.

• How immune responses to COVID-19 affect plaque buildup: NHLBI scientists showed that SARS-CoV-2 — the virus that causes COVID-19 — infects immune cells and the arteries  themselves and also stimulates greater production of atherosclerotic plaque. The plaque becomes highly inflamed, increasing the risk of heart attack and stroke. These findings may help explain why certain people who get COVID-19 have a greater chance of developing atherosclerotic heart disease or experiencing more heart-related complications if they already have it.
• Cellular links between atherosclerosis and other diseases: Other NHLBI-supported studies are focusing on macrophages (a type of immune cell) that may be a link between atherosclerosis and diabetes, a strong risk factor for plaque buildup.
• External influences on atherosclerosis: The NHLBI also supports research into factors such as psychosocial stress that may affect macrophages and worsen atherosclerosis.

Find more NHLBI-funded studies on atherosclerosis and inflammation at NIH RePORTER.

Current research on genes and atherosclerosis risk

Through its landmark studies, the NHLBI has identified key factors that affect atherosclerosis risk. The focus of our research has widened to include studies of genes that may increase risk of atherosclerosis and its complications.

• Genes for high cholesterol raise risk: NHLBI support led to the discovery of genetic changes linked to familial hypercholesterolemia, an inherited condition that causes very high cholesterol levels, even in children. About 1 in 250 people have this common genetic condition. Untreated, the disease can lead to heart attacks and other atherosclerosis complications at young ages. Based on successful research and results of  clinical trials , the U.S. Food and Drug Administration approved medicines called PCSK9 inhibitors. Use of PCSK9 inhibitors is outlined in clinical guidelines for reducing risk of atherosclerosis complications for people who have dangerously high cholesterol levels.
• Genetics and gene editing: The NHLBI funds research on genetic techniques to understand pathways that lead to plaque buildup. This knowledge could help in finding ways to reduce the risk of atherosclerosis. Scientists are using  genetic  techniques and  gene  editing in mice to investigate genes, inflammation, and immune cells involved in atherosclerosis. The results may yield new insights that improve the diagnosis, treatment, and prevention of coronary heart disease in humans. Learn more about the NHLBI's research on our gene therapies page.
• Protective factors: Some participants in the NHLBI-funded Hispanic Community Health Study/Study of Latinos (HCHS/SOL) are undergoing genetic testing and coronary artery calcium (CAC) scans to help researchers understand why Hispanic and Latino people tend to have lower CAC scores and a smaller risk of death from atherosclerotic disease compared to many other groups. Scientists hope to learn about factors that protect against atherosclerosis and develop tailored strategies to benefit all racial/ethnic groups.

Find more NHLBI-funded studies on atherosclerosis and genetic research at NIH RePORTER.

Current research on imaging in atherosclerosis

The NHLBI supports research to develop both noninvasive and invasive methods, such as imaging procedures, to study atherosclerotic plaques that change in size, interact with immune cells, and become unstable.

• An artificial intelligence (AI) screen for atherosclerosis risk: Each year, more than 20 million computed tomography scans are used to screen people in the United States for aortic aneurysms. A project is combining data from almost 50,000 existing scans with data from electronic health records to develop an AI tool that could analyze characteristics of abdominal tissues and help predict future risk of atherosclerotic disease.
• Sleep apnea and atherosclerosis: NHLBI-supported researchers are using state-of-the-art imaging techniques to study the function and stiffness of arteries in people with sleep apnea. The study is also looking at the amount and characteristics of atherosclerotic plaques and the extent of plaque-related inflammation in this group. Sleep apnea is common in people with cardiovascular disease. Observational studies suggest that atherosclerosis links the two conditions, but how this occurs is not known. Another question is whether continuous positive airway pressure therapy prevents plaque buildup. The study results may help identify people at high risk for atherosclerotic disease who could benefit from sleep apnea treatment.
• Improved risk assessment for atherosclerosis: Predicting risk of atherosclerosis-related complications and assessing effectiveness of cholesterol-lowering treatment are major challenges in people ages 75 and older. An NHLBI-supported project is looking into the usefulness of a combination of CAC scans and a high-sensitivity  troponin  blood test to learn whether the tests can improve atherosclerotic cardiovascular disease risk prediction and support individualized treatment strategies.

Find more NHLBI-funded studies on imaging and atherosclerosis at NIH RePORTER.

Current research on potential atherosclerosis treatments

Boosting natural processes to fight atherosclerosis: Higher levels of high-density lipoprotein (HDL) cholesterol, sometimes called "good cholesterol," can help prevent atherosclerosis and its complications. HDL works by helping the liver clear low-density lipoprotein (LDL) "bad" cholesterol in some groups of people. An NHLBI-supported project is testing a compound called trifluoroacetate in the lab and in animal models to assess its ability to enhance HDL activity and prevent atherosclerosis.

Testing an experimental device: Peripheral artery disease is the result of atherosclerotic plaque buildup in the legs and feet. It can cause severe pain and restrict a person's mobility. With funding from the NHLBI's Small Business Innovation Research program, a manufacturer prepared for clinical testing of a wearable device that delivers ultrasound therapy to affected limbs. The clinical trial started in 2023.

Stabilizingatheroscleroticplaques: When plaques become inflamed, they can cause  blood clots  to form and break off, leading to severe complications, including heart attack and stroke. With NHLBI support, a team of scientists is testing a medicine called senicapoc to assess its potential to strengthen and stabilize weak plaques and lower the risk of dangerous or fatal complications.

Find more NHLBI-funded studies on potential atherosclerosis treatments at NIH RePORTER.

Our Division of Intramural Research (DIR) includes investigators who are actively engaged in the study of atherosclerosis and its complications. The Division and its Cardiovascular Branch conduct research on diseases that affect the heart and blood vessels. Specific projects aim to improve prevention, diagnosis, and treatment of atherosclerosis and other cardiovascular conditions.

Other DIR groups, such as the Systems Biology Center, also conduct research on heart and vascular diseases.

• The Heart Truth® is a national education program that raises awareness about heart disease and encourages people to live heart-healthy lifestyles. The NHLBI offers Community Health Worker Tools — culturally appropriate resources to use in African American, Hispanic/Latino, American Indian, Alaska Native, and Asian American, Native Hawaiian, and other Pacific Islander communities.
• The Jackson Heart Study is the largest investigation of causes of heart disease in African American people, involving more than 5,300 participants in Jackson, Mississippi. The goal is to better understand factors that raise this population's risk for cardiovascular diseases, including those caused by atherosclerosis.
• The Atherosclerosis Risk in Communities Study (ARIC) study is investigating the causes of atherosclerosis, a process in which plaque builds up in the arteries, and the clinical outcomes from four U.S. communities. ARIC is also measuring how cardiovascular risk factors, medical care, and health outcomes vary, depending on a person's race, sex, location, and time.
• The Coronary Artery Risk Development in Young Adults (CARDIA) study examines the causes, risk factors, and natural history of cardiovascular disease that begins in young adulthood. For several decades, CARDIA researchers have monitored the health of more than 5,000 Black and White young adults who were recruited from four centers in 1985 and 1986. The study has helped researchers better understand the importance of early factors that increase the risk of cardiovascular disease later in life.
• The Cardiovascular Health Study (CHS) is a long-term, population-based study of risk factors for the development of coronary heart disease and stroke in people aged 65 and older. Annual exams conducted between 1989 and 1999 included measures of possible and proven cardiovascular disease risk, as well as subclinical disease. CHS researchers still regularly contact participants by phone.
• Multi-Ethnic Study of Atherosclerosis (MESA) is an NHLBI-sponsored medical research study that looks at early, or subclinical, atherosclerosis. MESA participants live in six U.S. communities and represent diverse racial and ethnic groups. MESA findings can help researchers understand how heart disease can present with different symptoms based on a person's sex or racial or ethnic group.
• The Strong Heart Study (SHS) is the largest and longest running epidemiologic study of cardiovascular disease and its risk factors among American Indians. In 2024, SHS scientists reported that more than half of the 1,400 American Indian teens and young adults in the study had unhealthy levels of cholesterol and fats in their blood, increasing their risk of developing atherosclerosis-related disease.
• The NHLBI's Trans-Omics for Precision Medicine (TOPMed) database in combination with the National Human Genome Research Institute Centers for Common Disease Genomics program, serve as key data sources researchers draw from to identify rare and complex gene patterns that affect the risk of plaque buildup. TOPMed contains data from more than 100,000 people of diverse ancestries.