Atherosclerosis Research

• ISCHEMIA study: The NHLBI-supported International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA)  was 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 to identify the best course of treatment for patients with coronary heart disease. Researchers followed patients over 5 years to determine whether an initial invasive strategy involving cardiac catheterization and coronary revascularization reduces mortality and non-fatal 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 anginal pain. Read more about the ISCHEMIA results.
• Comparing treatment strategies: The NHLBI-supported ISCHEMIA-Chronic Kidney Disease Trial, a companion trial to ISCHEMIA, examined whether an initial invasive strategy of cardiac catheterization and coronary revascularization reduces mortality and myocardial infarction more than an initial conservative strategy of guideline-directed medical treatment in patients with both coronary heart disease and advanced chronic kidney disease. During an average follow-up period of over 2 years, no benefit of the initial invasive strategy on these outcomes was observed. ISCHEMIA-EXTEND is a follow-up with the surviving ISCHEMIA participants that will compare the initial invasive strategy with the initial conservative strategy to see if the ISCHEMIA results change when follow up is longer. Additionally, it will examine the impact of nonfatal events on long-term heart disease and mortality. A more accurate heart disease risk score will be constructed to help doctors provide more precise care for their patients. The EXTEND results will be announced in 2025 or 2026.
• 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 its causes. Since then, the FHS has revealed major risk factors for atherosclerotic diseases, including smoking, high blood pressure, unhealthy blood cholesterol levels, obesity, physical inactivity, and diabetes. Through the FHS, scientists learned that many of those risks can be changed, leading to new ways to prevent or treat these conditions. The program is now identifying how genes, proteins, and other substances in the body influence the development of coronary heart disease and other conditions. Read Framingham at 70: Celebrating a Landmark Heart Study.

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 role of the immune system in atherosclerosis

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

• The role of immune cells: NHLBI-funded research is exploring how different types of immune cells interact with each other and change, causing plaque that is prone to breaking open and causing heart attacks.
• 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. For example, NHLBI support led to the discovery of genetic changes linked with familial hypercholesterolemia, an inherited condition that causes very high cholesterol levels, even in children. 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 FDA has approved medicines called PCSK9 inhibitors that bring down dangerously high cholesterol levels.

The focus of our research has widened to include studies of genes that may increase risk of atherosclerosis and its complications.

• 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 into human atherosclerosis to improve the diagnosis, treatment, and prevention of coronary heart disease. Learn more about NHLBI’s research on our genetic therapies page.
• Gene therapies: Other NHLBI-funded research is testing an atheroprotective gene therapy in rabbits with the goal of one day preventing and reversing atherosclerosis in humans.

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, for studying atherosclerotic plaques dynamics as they change in size, interact with immune cells, and become unstable.

• Cellular causes of inflammation: One project uses positron emission tomography combined with magnetic resonance imaging (PET/MRI) to track macrophages (a type of immune cell) as they interact with plaque and cause inflammation. The scientists aim to study changes in the cells and the plaque in mice exposed to stressors known to cause atherosclerosis in the animals. This line of research could lead to methods that could be used safely in future human studies.
• 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 will also look 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 (CPAP) therapy prevents plaque buildup. The study results may help identify people at high risk for atherosclerotic disease who could benefit from sleep apnea treatment.

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

Our Division of Intramural Research (DIR) includes some of the investigators at the NHLBI 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.

The Laboratory of Inflammation and Cardiometabolic Diseases focuses on understanding the link between inflammation, atherosclerosis, and metabolic diseases such as diabetes. The lab’s goal is to better define cardiovascular risk in people with inflammatory conditions like psoriasis 

Other DIR groups, such as the Systems Biology Center, also carry out 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 a heart-healthy lifestyle. 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 (JHS) is the largest investigation of causes of heart disease in African American people, involving more than 5,300 men and women in Jackson, Mississippi. The goal is to understand factors that raise this population’s risk for cardiovascular diseases, including those caused by atherosclerosis.  
• Atherosclerosis Risk in Communities Study (ARIC) study is investigating the causes of atherosclerosis, a disease 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 outcomes vary by race, sex, place, and time.
• Coronary Artery Risk Development in Young Adults (CARDIA) study examines the causes, risk factors, and natural history of cardiovascular disease that begin in young adulthood. For over 30 years, CARDIA has followed over 5,000 Black and white young adults who were recruited from four centers in 1985 to 1986. The study has helped researchers better understand the importance of early adulthood 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 men and women aged 65 and older. Annual exams included measures of possible and proven cardiovascular disease risk, including subclinical disease.
• Multi-Ethnic Study of Atherosclerosis (MESA) is an NHLBI-sponsored medical research study that looks at early, or subclinical, atherosclerosis. Atherosclerosis is a disease in which plaque builds up inside the arteries. Atherosclerosis can lead to serious problems, including heart attack, stroke, or even death. MESA participants are from six U.S. communities and include diverse racial and ethnic groups. MESA findings can help researchers understand how heart disease can have different symptoms based on a person’s sex or racial or ethnic group.
• The Strong Heart Study (SHS) is a study of cardiovascular disease and its risk factors among American Indian men and women. It is one of the largest epidemiological studies of American Indians ever undertaken.
• The Cardiothoracic Surgical Trials Network (CTSN) is an international network that studies coronary heart disease, heart valve disease, arrhythmias, heart failure, and complications of surgery. CTSN researchers have studied the success of treatments for atherosclerotic diseases. For example, they conducted a study in people who had atherosclerotic blockages in several coronary arteries. Network researchers compared multi-vessel percutaneous coronary intervention (PCI) and a hybrid procedure that uses PCI in some affected vessels and bypass surgery in others. The strategies were equally effective at preventing serious complications, including death, stroke, heart attack, and repeat surgeries in the year following the procedures. The results suggest that the hybrid procedure may be a treatment option for some patients, but further study with a longer follow-up period is needed.
• Scientists are using genetic information from the National Human Genome Research Institute (NHGRI) Centers for Common Disease Genomics (CCDG) program and NHLBI’s Trans-Omics for Precision Medicine (TOPMed) database. TOPMed contains data from more than 100,000 people of diverse ancestries. With this large body of data, researchers should be able to identify rare and complex gene patterns that affect the risk of plaque buildup.