Celebrating 25 years of lifesaving cardiovascular research

Throughout his life, John Crisp rarely missed a day of work or school. He experienced good health throughout adulthood. However, in 2001, he had a shocking moment that he credits with changing his health and probably saving his life.

That moment was prompted by what appeared to be an abnormal EKG, which assesses the electrical activity of the heart. After having been previously diagnosed with high cholesterol, Crisp, who lives in Pennsylvania, traveled to Johns Hopkins Medicine to seek additional cardiovascular disease risk assessments. “I didn’t want to have a heart attack or bypass surgery,” Crisp recalls telling his primary care doctor at the time.

After consulting with Lou and Nancy Grasmick Professor of Cardiology Wendy Post, M.D., M.S., a preventive cardiologist and the director of cardiovascular research at Johns Hopkins, Crisp was relieved to hear that his EKG results were fine. However, due to his concerns and underlying risks, Post scheduled an additional test, a computed tomography or CT scan, to assess the levels of calcium in his coronary (heart) arteries.

This test revealed dangerously elevated levels of calcium deposits, which are a component of underlying atherosclerotic plaque. Eventually, plaque can continue to accumulate and block blood flow or rupture, leading to a blood clot — which can lead to events like having a heart attack or a need for bypass surgery. Ideal levels are zero; Crisp’s score was around 700, well above the average level for an 80-year-old man. He was 58.

“I could see from her body language that she was somewhat startled,” says Crisp.

“We were both alarmed,” says Post, who has worked with Crisp ever since. “His coronary artery calcium score was very high, especially for his age.” Crisp’s stress test, which was used as an extra precautionary measure at the time due to his concerns, was completely normal, she recalls. “He didn’t have any symptoms.”

While Crisp’s coronary artery calcium test results were surprising, they came at an opportune time. Crisp’s father died suddenly from a ruptured aortic aneurysm when he was 59. Like Crisp, he didn’t have any symptoms. Crisp doesn’t know if he has genetic risks for experiencing the same fate. Outside of his father’s death, he doesn’t recall having a family history of heart disease. He never had signs of heart problems, such as feeling short of breath or chest discomfort.

After seeing Crisp’s results, Post treated Crisp’s heart disease risk factors aggressively. This included increasing his blood pressure medications, adding additional cholesterol-lowering therapies and low-dose aspirin, and spending a lot of time talking about lifestyle modification, including diet and exercise.

“He followed every recommendation and has done extraordinarily well over the past two-and-a-half decades,” says Post. This has translated into ideal blood pressure, cholesterol and body weight. “He exercised daily and never had any symptoms.”

The preventive care and insights that Crisp viewed as leading edge at the time are now part of mainstream medicine. In March 2026, clinical guidelines for assessing risks and treating elevated cholesterol and other lipid levels were updated for the first time in eight years.

The new guidelines, which are designed to help clinicians work with patients to assess 10-year risks for atherosclerosis, a hardening or narrowing of the arteries due to plaque, incorporate key themes. One is starting risk assessments earlier in life. Another is using additional factors, like assessing levels of coronary artery calcium, to help inform risk assessments for some people with borderline or intermediate risks when treatment decisions are uncertain.

These updates have been informed by clinical trials and supported by large bodies of research, including the Multi-Ethnic Study of Atherosclerosis (MESA), a National Institutes of Health (NIH)-funded study that started in 2000. The study’s investigators, including Post, enrolled 6,814 adults without heart disease, who were between ages 45 and 84 at the time, from six metropolitan regions throughout the country, including Baltimore, to better understand factors that may not immediately present as physical symptoms, but that can increase risks for cardiovascular disease.

For example, a recent MESA study published in Circulation found that adults with severely elevated coronary artery calcium levels, like Crisp, were at least five times as likely as those with zero detectable calcium to develop coronary artery disease about 10 years later. These findings were based on research from study participants who had chest CT scans taken for other reasons, such as screening for lung cancer, breast cancer or an infection like pneumonia.

“Coronary artery calcium predicts risk above and beyond anything that we can measure other than age,” says Post. “It’s the strongest risk factor for heart disease that we have.”

Post explains that it’s also an early indicator that frequently goes unnoticed. “Coronary calcium often isn’t causing significant blockages or causing any symptoms,” says Post, “but can signal risk for having a heart attack in the future.”

In addition to identifying coronary artery calcium as a risk predictor for coronary heart disease, the decades-long study has also helped researchers better understand how genetics, different lipids, like lipoprotein(a), and even sleep patterns and air pollution are connected to cardiovascular health.

MESA has also helped investigators assess the role that indicators of cardiovascular health and other factors may have in influencing risks for other conditions. This includes heart valve disease, lung disease, cognitive decline and dementia — among others.

The strength of these ancillary studies is to be able to use longitudinal data collected over time — including blood tests, imaging exams, genetic insights, and information about lifestyle and environmental factors — to pair with follow-up assessments. Similar to identifying early signs of heart disease, the goal is to support earlier detection, prevention and care for conditions that may directly relate to or correlate with the health of the heart and blood vessels.

“I didn’t want to be a ticking time bomb,” Crisp explains about his decision to seek personalized cardiovascular disease risk screenings 25 years ago. He didn’t participate in MESA, but has benefitted from learning about the results of the study and others like it. “With Dr. Post’s help, I’m still doing everything I can to prevent a major cardiac event,” he says. “I believe she saved my life.”

About MESA:

MESA recently celebrated its 25^th anniversary. More than 6,800 adults, who were between ages 45 and 84 at the time of enrollment, have supported this longstanding NIH-funded cardiovascular health study. The participants, all of whom were free of heart disease, live in one of six metropolitan regions throughout the country. This includes Baltimore, Chicago, New York, Los Angeles, St. Paul, Minn., and Forsyth County, North Carolina.

One of the strengths of the study has been its diverse representation — including a sample that consists of about half men and half women. MESA includes people who self describe their race and ethnicity as white, Black, Chinese or Hispanic. Through regular study assessments, investigators have studied how numerous factors are associated with increased risks for cardiovascular disease, including heart attacks, heart failure, atrial fibrillation and stroke.

One of MESA’s most important contributions has been understanding the role that underlying factors, like coronary artery calcium, can have with improving cardiovascular disease risk predictions. The study has also generated insights into the roles that genetics, lifestyle factors (such as diet, exercise, and sleep), stress, and the environment, including air pollution, can have with influencing cardiovascular health. Additionally, the research has shown how closely social determinants of health, such as having access to healthcare or healthful foods, are connected to increased risks for cardiovascular disease.

With the support of study participants, most of whom are now in their 70s to 90s, the investigators continue to study how markers of cardiovascular health and other factors may influence or relate to other conditions, including other types of heart disease as well as Alzheimer’s disease and dementia.

Active heart disease research

The MESA amyloidosis study, which is led by Joao Lima, M.D., a cardiologist at Johns Hopkins, is studying how protein deposits (amyloid) in the heart, detected through cardiovascular imaging, may lead to heart failure.

Through other research, MESA investigators are studying the role that different factors, like increased levels of lipoprotein(a), can have in contributing to increased calcium in the aortic heart valve — a leading risk factor for aortic stenosis. The condition, which is caused by a narrowing of the opening of the aortic valve, often requires a valve replacement for severe cases.

This study, led by Johns Hopkins cardiologists Michael Blaha, M.D., M.P.H., and Seamus Whelton, M.D. M.P.H., are investigating how these insights can help support earlier risk predictions, improve screenings and inform clinical trials to study new therapies for prevention.

MESA MIND

The MESA-MIND study aims to better understand the role that cardiovascular health has and plays in influencing risks for cognitive decline and for dementia, including Alzheimer’s disease. Findings from this study may inform long-term prevention strategies, support earlier risk monitoring and provide new insights to support the development of targeted therapies.

Resources

Learn more about MESA by watching a Clinical Connections video with study investigators from the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease.