Faculty Spotlight: Julio Lamprea Montealegre, MD, PhD, MPH

November 14, 2022

Two for One: Preventing Heart and Kidney Disease

Most people know that smoking, obesity and physical inactivity increase the likelihood of cardiovascular disease – but chronic kidney disease (CKD) is a stealth member of that infamous posse of risk factors. Cardiologist Julio Lamprea Montealegre, MD, PhD, MPH, is making it his life’s work to educate the community about how CKD portends poor outcomes in heart disease, and to develop effective public health interventions.

CKD usually develops slowly, and occurs when the kidneys are damaged and eventually become unable to filter waste products and extra fluid out of the blood as well as they should. It also impairs their ability to properly balance salts and minerals in the bloodstream and control blood pressure, among other important functions. It is estimated that more than 37 million Americans have CKD, but most go undiagnosed.

“When people think about CKD, they usually think about dialysis or kidney transplants,” said Dr. Lamprea Montealegre. “But the vast majority of CKD patients do not progress to those advanced stages of kidney disease. However, many of them will develop cardiovascular disease. At its early stages, CKD is really a marker of cardiovascular risk.”

It turns out that diabetes and hypertension are the main causes of CKD – and are also leading contributors to cardiovascular disease. If CKD and cardiovascular disease are canaries in the coal mine, CKD usually emits distress signals first. And that early warning is especially important for patients at highest risk of developing cardiovascular disease.

“It turns out that over 90 percent of all heart disease in people with diabetes is conferred on people with both diabetes and CKD,” said Dr. Lamprea Montealegre. “That fact is not well-known. We’re excellent at treating diseases when a patient already has symptoms, but we’re not so good at preventing people from ever getting heart disease. To do that, we have to tackle silent killers that don’t give you any symptoms until they’re very advanced.”

In other words, while diabetic patients with CKD may never develop advanced kidney disease, they are at very high risk of developing heart failure or another form of cardiovascular disease, or even having a heart attack or stroke. 

CKD: an Early Warning Sign

The biology underlying the shared vulnerabilities of the kidney and heart is still under investigation. We do know that problems such as inflammation of blood vessel walls, an abnormal accumulation of proteins in the blood vessels, and alteration of lipids – a phenomenon called dyslipidemia – contribute to atherosclerosis, or plaque buildup and narrowing of blood vessels. It takes a while for this damage to show up in coronary arteries and the body’s other large blood vessels, collectively known as the macrovasculature.

However, the microvasculature – the body’s network of tiny blood vessels – feels the impact earlier. This vast filigree is made up of capillaries and other small blood vessels. As those slender channels become damaged, they emit warning signs far earlier than the larger vessels that feed the heart. For example, CKD is usually diagnosed through a creatinine test, which tests the blood for kidney function, as well as an albuminuria test, which analyzes a patient’s urine for abnormally high levels of a protein called albumin, a marker of kidney damage.

“Many patients with CKD likely have microvascular disease of the heart, but we just can’t see it yet,” said Dr. Lamprea Montealegre. “We can only see the big blood vessels in the heart, not the microvasculature. But if a patient has high levels of albumin in the urine, it’s as if they’re telling you, ‘I have microvascular disease, and I’m at risk for developing accelerated atherosclerosis and heart disease in the bigger blood vessels that will put me at higher risk for heart attacks and heart failure in the next 10 years. You’d better do something to stop the progression of my microvascular disease before I develop full-blown cardiovascular disease.”

A Passion for Clinical Research

Dr. Lamprea Montealegre’s ambitious work to improve early detection and treatment of CKD to prevent cardiovascular disease weaves together the many threads of his background. He was born in Ibagué, Colombia. His father was an anesthesiologist at the local hospital and his mother, a microbiologist, ran the hospital’s lab. “Sometimes my dad was in the operating room overnight and my mom had to work the night shift, so they’d bring me to the hospital for the night,” he said. “The nurses would check on me to see how I was doing.”

He was inspired at an early age by his father, who spent several days each month going with a team of surgeons and anesthesiologists to remote areas of Colombia to provide free elective surgeries. “People waited for a whole year for the team to arrive, and they’d operate nonstop for three to four days,” said Dr. Lamprea Montealegre.

At the age of five, Dr. Lamprea Montealegre started playing tennis, and entered national competitions in Colombia. When he was 11, his parents sent him to Rocklin, a town near Sacramento, where he attended a tennis academy and traveled the U.S. playing competitive tennis. But after two years, he decided to return to Ibagué for high school.

In Colombia, medical school starts immediately after high school, so he moved to the capital city of Bogotá and earned his medical degree from Javeriana University School of Medicine. He did some of his clinical rotations back home in Ibagué, at the same hospital where his parents worked. “Many of the nurses who helped raise me were still there, and I got very special treatment from them,” he said with a laugh.

Many of his medical school mentors had trained at McMaster University in Ontario, Canada, with famed clinical epidemiologist David Sackett, MD, who is widely considered as one of the fathers of evidence-based medicine. “From early on, I was exposed to questions about how we interpret evidence, develop clinical guidelines, and communicate risk to patients” said Dr. Lamprea Montealegre. “I knew I wanted to base my career in clinical research.” 

He also was drawn to cardiology, both because of the breadth within the field – spanning imaging, coronary artery disease, cardiac arrhythmias, prevention, and much more – as well as its central importance to public health. “Heart disease is the number one killer in the world, so it was a very nice match with epidemiology and public health, and now my career as a clinical cardiologist,” said Dr. Lamprea Montealegre.

Falling in Love with Epidemiologic Methods

Eager to learn more about public health and evidence-based medicine, he decided to enroll in the Johns Hopkins Bloomberg School of Public Health in Baltimore. “Initially I was just going to get a master’s degree with an emphasis on epidemiology and biostatistics, but soon realized that if I really wanted to master the methods of public health, I had to do a little more,” said Dr. Lamprea Montealegre. After earning his MPH, he completed his PhD in cardiovascular epidemiology.

One of his mentors was Alvaro Muñoz, PhD, a fellow Colombian and statistician who helped lay the groundwork for the epidemiology of HIV. Among other projects, Dr. Muñoz was working with a cohort study of CKD in children. “My master’s project was trying to develop better methods to assess CKD in children,” said Dr. Lamprea Montealegre. “I really fell in love with statistics, and rigor of the methods used to design studies and analyze data.”

During his doctoral program, he worked closely with two other mentors. With internist L. Ebony Boulware, MD, MPH, he investigated ways to identify and address health care disparities in CKD care. He also worked closely with Moyses Szklo, MD, MPH, who created some of the largest cohort studies of cardiovascular disease in the U.S., and served as editor-in-chief of the American Journal of Epidemiology.

“Dr. Szklo was really involved in methods, biomarkers, and finding new ways to study the epidemiology of cardiovascular disease,” said Dr. Lamprea Montealegre. “But he always came back to the idea that we already know what causes the majority of cardiovascular disease – hypertension, diabetes, high cholesterol, smoking and lack of physical activity. The big question is, if we already know those are the big drivers, why don’t we do more? What is the gap between the evidence we already have, and the translation of that evidence into practice to try to reduce cardiovascular disease? That stayed in my mind for a long time.”

During his doctoral work, Dr. Lamprea Montealegre worked with the Multi-Ethnic Study of Atherosclerosis (MESA) Study, a large observational cohort study investigating which early warning signs are associated with the later development of cardiovascular disease. He also analyzed data from the Atherosclerosis Risk in Communities (ARIC) Study, which takes a similar approach to investigating atherosclerosis and its clinical outcomes. Dr. Szklo helped establish both of these important studies.

For his dissertation, Dr. Lamprea Montealegre studied the link between CKD and cardiovascular disease, focusing particularly on dyslipidemia – abnormal levels of lipids in the bloodstream. “I found that in people with CKD, having a high level of triglyceride-rich lipoproteins – which we do not generally treat – accounted for a large amount of cardiovascular disease in this population,” he said.

Bridging the Evidence-to-Practice Gap

After completing his PhD, Dr. Lamprea Montealegre completed his internal medicine residency at the University of Maryland Medical Center in Baltimore, his clinical cardiology fellowship at the University of Washington Medical Center, and a postdoctoral research fellowship at the University of Washington School of Medicine in Seattle.

In 2019, he was recruited to UCSF as postdoctoral research fellow through the Division of Cardiology and the Kidney Health Research Collaborative. “UCSF is a major driver of implementation science in the U.S., and I’m currently focused on bridging the evidence-to-practice gap to reduce cardiovascular disease through early detection and treatment of chronic kidney disease,” said Dr. Lamprea Montealegre.

The good news is that there have been significant recent advances in the prevention and treatment of CKD and heart disease. In 2013, the U.S. Food and Drug Administration (FDA) approved a new class of diabetes medications called SGLT2 inhibitors that were later shown to significantly reduce the risk of cardiovascular disease and the risk of CKD progression. “That was a major breakthrough in the diabetes field for the prevention of cardiovascular disease,” said Dr. Lamprea Montealegre.

In recent years the FDA also approved another class of medications called GLP-1 receptor agonists, which both lower cardiovascular disease risk in people with diabetes and also cause sustained weight loss. “Before the advent of GLP-1 receptor agonists, we had very few tools that were proven to be effective in lowering obesity,” said Dr. Lamprea Montealegre. “That marked a revolution in cardiovascular disease prevention.” 

Developing Holistic Approaches to Health

Now the challenge is to bring the revolution to the people who need it the most – those with both diabetes and CKD, who are at highest risk of developing cardiovascular disease. And with his training in cardiology, epidemiology and public health, Dr. Lamprea Montealegre is ideally positioned to help develop effective systems to bring these potentially life-saving interventions to patients who would reap the largest benefits.

“The entire field is shifting to a more holistic approach to care,” said Dr. Lamprea Montealegre. “Right now, what we call ‘cardio-renal-metabolic prevention programs’ are in their infancy. They combine expertise in diabetes, renal disease and cardiovascular prevention.” Rather than a siloed approach, this ideally involves primary care providers, endocrinologists, nephrologists and cardiologists working together in an integrated way to develop and implement screening and treatment plans for patients. “The advent of SGLT2 inhibitors and GLP-1 receptor agonists has been the driving force in making us think that our approach has to involve multidisciplinary teams of care,” he said. “How do we relay information to patients, communicate effectively about their risk, and develop better programs to prevent progression of diabetes, CKD and cardiovascular disease?”

Dr. Lamprea Montealegre recently received a K99/R00 Pathway to Independence grant from the National Heart, Lung, and Blood Institute to conduct research and develop interventions in this area. To better understand the problem, he is studying data about patients with both diabetes and CKD from the Veterans Affairs (VA) health care system, the largest integrated health care system in the U.S. He found that less than 15 percent of patients with both these conditions have been prescribed SGLT2 inhibitors. Surprisingly, he also found that patients with both diabetes and CKD were actually less likely to be prescribed SGLT2 inhibitors or GLP-1 receptor agonists than those who only had diabetes. “We want to find out why higher-risk patients were less likely to get these medications,” he said.

He is also very interested in discovering whether there are any racial disparities in how these medications are prescribed. “People tend to equate prescriptions with the ability to pay for them, but the VA minimizes that barrier because the copayments are very low, and a substantial proportion of veterans do not have to pay anything for their medications,” said Dr. Lamprea Montealegre. “We found that people of Black race or Hispanic or Latino ethnicity were less likely to be prescribed these medications compared with white patients.” The results of this research were recently published in the Journal of the American Medical Association.

Now he is discovering more about the underlying reasons for these trends. “For my quantitative findings, I’m using data sets that include millions of veterans,” said Dr. Lamprea Montealegre. “I want to contextualize these findings to really understand what’s going on.” As a next step, he will interview providers, showing them his data on race and ethnicity differences in prescribing practices as well as findings that the highest-risk patients are the least likely to be prescribed these medications – the opposite of what should be happening.

“I am going in with an open mind, trying to learn from providers what the major problems and gaps are,” said Dr. Lamprea Montealegre. “I will ask questions such as, ‘Could you help me understand why we’re seeing these differences?’ It’s fascinating, because the perspective of a primary care physician may be very different than that of an endocrinologist, nephrologist or cardiologist. There’s so much we can learn by exploring this in a standardized way through qualitative methods with different providers.”

Soon he also plans to interview patients with CKD, including Spanish-speaking patients. He wants to find out what they know about their condition, and what gaps in care they experience. “Ultimately, I’m trying to engage the community and learn as much as I can to develop responsive interventions that will address the barriers we find,” said Dr. Lamprea Montealegre. “I want patients to guide my research efforts, so we can develop effective tools.”

Improving Global Health

He plans to use his finding to pilot interventions to better detect, stage and manage CKD, which he hopes to eventually scale up. He is also passionate about applying his public health work internationally. “Low- and middle-income countries really have to prioritize their prevention efforts, because resources are limited,” said Dr. Lamprea Montealegre. “By improving detection and treatment of CKD at an early stage, they can identify people at highest risk and better help prevent cardiovascular disease at a population level.” He is already establishing partnerships in Colombia, and hopes this work could be applied throughout Latin America and elsewhere.

“In Latin America there is a large epidemic of diabetes, obesity and hypertension that’s not getting the attention it deserves,” said Dr. Lamprea Montealegre. “It’s already a big problem, and it will be a much bigger problem in the next decade. So this is the time to start asking questions about the best way to prevent the dire consequences of these diseases. Channeling prevention through CKD detection and treatment may be one of the best strategies.”

His dream study would be to start a large-scale clinical trial in Latin America which would screen participants for hypertension, diabetes and CKD, and use multidisciplinary teams to manage and treat these diseases holistically. “I’d want to compare this approach to the current standard of care, and to see if this indeed lowers the risk of cardiovascular disease,” said Dr. Lamprea Montealegre.

New Frontiers for Prevention

He has been developing some of the building blocks for this ambitious goal through his recent work at UCSF. After completing his postdoctoral research fellowship at UCSF, Dr. Lamprea Montealegre joined the UCSF Cardiology faculty at the beginning of 2022. “At UCSF, there’s a lot of help and mentorship, and a lot of excitement about my work and how to move it forward,” he said. “I get to work with a big team that brings together multiple specialties to tackle the problem of CKD.” His mentors have included the co-leaders of the Kidney Health Research Collaborative, nephrologist Michelle Estrella, MD, MHS and internist Michael Shlipak, MD, MPH, as well as internist Leah Karliner, MD.  

“Dr. Lamprea Montealegre’s research program is dedicated to improving the delivery of quality medical treatments for the high-risk population who have both diabetes and chronic kidney disease,” said Dr. Shlipak. “Furthermore, he brings highly creative approaches to improve ‘pharmacoequity’ – the elimination of racial or ethnic disparities in the utilization of novel, state-of-the-art therapeutics. We are grateful that he has joined and will enrich the UCSF faculty.” 

In addition to his research, Dr. Lamprea Montealegre has a weekly clinic and also cares for hospitalized patients about six weeks per year. “I try to help patients understand their condition, why it’s important, and work together with them to formulate a plan,” he said. “By empowering them with information and helping them understand why you are prescribing a medication, they do much better.” He also relishes working with trainees. “It’s been spectacular working with UCSF medical students, residents and fellows,” he said. “They really appreciate the time we spend together, learning from things we see on rounds, and that’s very fulfilling.”

In addition to medicine and research, Dr. Lamprea Montealegre enjoys playing tennis in Golden Gate Park, whiling away afternoons in City Lights Bookstore, and hiking with his wife, Nicole Errett, PhD, MSPH, an assistant professor in the Department of Environmental and Occupational Health Sciences at the University of Washington.

“The interest in cardio-metabolic-renal work is growing, but it’s still rare,” said Dr. Lamprea Montealegre. “So it’s a good time to get into this field. For those of us who are interested in prevention, it’s a really exciting time to advance holistic approaches to cardiovascular care.”

 

-       Elizabeth Chur