Primary Aldosteronism and Ischemic Heart Disease

Young Men Who Take Steroids Have Impaired Coronary Flow, Even After Quitting

Young men who use anabolic-androgenic steroids, or those who've used them in the past, are more likely to have reduced myocardial flow reserve than those who've never taken the drugs, according to Danish data.

The findings, researchers say, suggest that "supraphysiologic doses of testosterone and synthetic steroids could have adverse impacts in coronary microcirculation." Led by Yeliz Bulut, MD (Copenhagen University Hospital-Rigshospitalet, Denmark), the study was published Monday in JAMA Network Open.

Senior investigator Caroline Kistorp, MD, PhD (Copenhagen University Hospital-Rigshospitalet), told TCTMD that her interest in the topic was borne out of her own clinical experience as an endocrinologist seeing men present with steroid side effects, as well as growing awareness of the adverse effects these performance-enhancing drugs have on the cardiovascular system.

"Every time we looked into the heart, we found something new," Kistorp said, citing LV dysfunction and hypertrophy as well as increased LV mass.

With the latest study, what's especially worrisome is that participants were, on average, in their mid-30s but already had signs of damage after steroid use, she noted. Most of the patients she sees have heard anecdotally about "friends who might have some problems with their heart, but they're all young men: they think, 'This is never going to happen to me.'"

Also concerning, it's possible "that some of the changes in the cardiac structure and function may be irreversible, since we found them years after they stopped," said Kistorp. "We can't find any pattern that after 3 years or something like that, then you're [in the] clear."

Aaron L. Baggish, MD (Université de Lausanne/Centre Hospitalier Universitaire Vaudois, Switzerland), whose 2017 Circulation paper linked use of anabolic-androgenic steroids among male weightlifters to myocardial dysfunction and accelerated coronary atherosclerosis, commented on the new findings for TCTMD.

The Danish study "offers yet another part of the cardiovascular system—in this case it's the microvasculature—which seemed to be responsive in a negative way to anabolic steroid use," Baggish said, adding that the method they used to look at coronary microcirculation is the gold standard. One limitation, he added, is that steroid use is quantified by duration of use and abstinence, not dose. Another approach would be to estimate testosterone equivalents, thereby capturing how much drug is actually used.

That said, it's interesting that "use over longer periods of time, which probably means more exposure to more drug, seems to have a more lasting effect on the coronary microvasculature," said Baggish. Whether the damage is permanent is not yet known, he specified, though it's possible that the impact is twofold, with steroids causing both acute toxicity and longer-term pathology.

Baggish described anabolic-androgenic steroids as a "huge public health issue, and that is despite the fact that we continue to learn more and more scientifically about the evils of these drugs.

"To be clear, this is no longer a story of elite athletes," he continued. "This is a story of . . . Typically community-dwelling men in their 30s, 40s, and 50s who simply want to or need to get bigger and feel bigger. Globally, there are millions of men that are subjecting themselves to this, because it's so easy to get steroids and the sad truth is that they work. [Plus,] it's really difficult for some men, once they get started, to stop."

Every time we looked into the heart, we found something new. Caroline Kistorp

The study included 90 men (mean age 35.1 years) recruited via gyms, social media, word of mouth, and endocrine outpatient clinics in the Copenhagen area: 33 with current use of anabolic-androgenic steroids, 31 with former use, and 27 controls. For those who had quit, the time since steroid cessation was a geometric mean of 1.5 years, with 58.1% quitting more than a year earlier.

Systolic blood pressure and LDL levels were higher, and body fat was lower, in current steroid users than in former users or controls. Participants who formerly used anabolic-androgenic steroids were more likely to have previously used other illicit drugs than were current users or controls.

Bulut and colleagues used 82Rb positron emission tomography/computed tomography (PET/CT) to measure myocardial flow reserve, with levels below 2.0 mL/g/min considered clinically relevant.

Among current steroid users, 18.8% had clinically impaired myocardial flow reserve, as did 3.2% of former users. None of the controls showed impairment (P= 0.02). Subclinically impaired myocardial flow reserve—levels below 2.5 mL/g/min—was seen in 28.1% of individuals currently on steroids, 25.8% of those who had quit, and 3.7% of controls (P = 0.02).

In multivariable logistic regression analysis, accumulated exposure was linked to higher risk of impaired flow reserve. With every doubling of weekly duration in anabolic-androgenic steroid use, the risk of having myocardial flow reserve below 2.5 mL/g/min also doubled (OR 2.1; 95% CI 1.03-4.35).

"Early and persistent impaired myocardial microcirculation could be of clinical importance and a potential underlying mechanism of frequent and early cardiac disease among individuals with anabolic-androgenic steroid use and a future potential target for intervention," the researchers conclude.

Next up, said Kistorp, the investigators plan to do a similar study: this time on women, who make up a minority of steroid users.

As for how clinicians should apply these findings, Kistorp said it makes most sense to check into steroid use when patients have high cholesterol or other risk factors without an obvious cause. At her center, she said, cardiologists first "do the more classical workup, and if they can't find anything, then they start asking if you have been using steroids."

If [clinicians] don't ask about steroid use either prior or active, they will never be told, and they will be surprised how often they'll learn about it if they ask. Aaron L. Baggish

Baggish said it's too soon to draw firm conclusions from this one study but generally speaking, he agreed that when a young male patient presents with an unexplained cardiovascular condition, physicians should bring up the topic. "If they don't ask about steroid use either prior or active, they will never be told, and they will be surprised how often they'll learn about it if they ask," he said.

This knowledge might not only guide treatment but also encourage patients to quit steroids, said Baggish. "I find in my practice that many anabolic steroid users have no idea that these drugs can cause heart disease. When they're confronted with a new diagnosis and they reconcile with the fact that they may have done this to themselves, there can be a pretty strong motivation to stop using steroids. If you don't ask and don't help the patient make that link, you don't give them the opportunity to make the wise choice, which is to drop the drugs."

Coronary Artery Disease

Coronary artery disease (CAD; also atherosclerotic heart disease) is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the myocardium (the muscle of the heart) with oxygen and nutrients. It is sometimes also called coronary heart disease (CHD). Although CAD is the most common cause of CHD, it is not the only one.

CAD is the leading cause of death worldwide. While the symptoms and signs of coronary artery disease are noted in the advanced state of disease, most individuals with coronary artery disease show no evidence of disease for decades as the disease progresses before the first onset of symptoms, often a "sudden" heart attack, finally arises. After decades of progression, some of these atheromatous plaques may rupture and (along with the activation of the blood clotting system) start limiting blood flow to the heart muscle. The disease is the most common cause of sudden death, and is also the most common reason for death of men and women over 20 years of age. According to present trends in the United States, half of healthy 40-year-old males will develop CAD in the future, and one in three healthy 40-year-old women. According to the Guinness Book of Records, Northern Ireland is the country with the most occurrences of CAD. By contrast, the Maasai of Africa have almost no heart disease.

As the degree of coronary artery disease progresses, there may be near-complete obstruction of the lumen of the coronary artery, severely restricting the flow of oxygen-carrying blood to the myocardium. Individuals with this degree of coronary artery disease typically have suffered from one or more myocardial infarctions (heart attacks), and may have signs and symptoms of chronic coronary ischemia, including symptoms of angina at rest and flash pulmonary edema.

A distinction should be made between myocardial ischemia and myocardial infarction. Ischemia means that the amount of blood supplied to the tissue is inadequate to supply the needs of the tissue. When the myocardium becomes ischemic, it does not function optimally. When large areas of the myocardium becomes ischemic, there can be impairment in the relaxation and contraction of the myocardium. If the blood flow to the tissue is improved, myocardial ischemia can be reversed. Infarction means that the tissue has undergone irreversible death due to lack of sufficient oxygen-rich blood.

An individual may develop a rupture of an atheromatous plaque at any stage of the spectrum of coronary artery disease. The acute rupture of a plaque may lead to an acute myocardial infarction (heart attack).

Coronary Artery Disease: Blood Flow Measurement Refines Clinical Decision-making

Myocardial blood flow measurement tools can reveal real-time insights into a person's cardiovascular health.Credit: Magicmine/ Getty

A patient with a prolonged history of shoulder pain attributed to arthritis, sought medical attention. Because this pain could also be a sign of cardiovascular issues, the physician recommended an electrocardiogram (ECG) to keep tabs on the patient's heart health. Despite inconclusive ECG results, one test eventually revealed concerning cardiac changes, even though the patient's symptoms remained unchanged, unmasking the correct diagnosis and overturning the misattribution to arthritis.

Upon referral, interventional cardiologist Dr. Nils Johnson, a professor of medicine at McGovern Medical School at UTHealth in Houston, ordered a positron emission tomography (PET) scan with objective blood flow measurements. These measurements provide insights into total blood flow through the heart tissue. Understanding myocardial blood flow (MBF) has become increasingly crucial in managing coronary artery disease (CAD). Software packages now allow clinicians to monitor MBF routinely during cardiac PET scans. This real-time data enables accurate CAD detection, reducing the reliance on older surrogate markers and invasive tests like heart catheterization.

In Dr. Johnson's case, MBF data from a heart PET scan played a pivotal role. It guided the treatment journey — from resolving an ambiguous clinical scenario to guiding initial noninvasive management and monitoring the success of later bypass surgery following disease progression. "Blood flow data helped us treat this patient across his entire spectrum of care," he says.

Importantly, many patients may not need invasive diagnostic tests or treatment for their CAD. MBF measurement by cardiac PET helps physicians accurately identify those who should advance to an invasive evaluation, and those who shouldn't.

Making the right choice

For decades, doctors have used cardiac PET scans to identify the presence or absence of CAD in people who have symptoms and/or risk factors. The results can help clinicians with treatment planning and monitoring outcomes over time.

"Based on commonly used tests, patients often go on to the cath lab for an angiogram. But those who go to the trouble of getting one are frequently told they need no further interventions," says Dr. Johnson. "Ideally, cardiac PET could have told the patient upfront that an invasive angiogram was not needed."

Dr. Robert Bober, at Sutter Health East Bay Medical Group in Oakland, California, agrees that MBF data can improve patient selection for these treatments: "We can now measure blood flow all over the heart muscle and do it before the patient even enters the cath lab, meaning we can select the right people for procedures."

Dr. Bober suggests that the angiogram is not the gold standard cardiologists are taught to believe. The appearance of arteries during an angiogram can be deceiving, looking severely blocked or diseased. But MBF data often show that blood flow is acceptable. "The angiogram is actually the surrogate for flow. But it's become too easy for us to resort to angiography to find a blocked vessel that appears to decrease flow," he says. "We see a blockage on angiography and make assumptions. However, our cardiac PET data1 show that many times the flow is adequate even with a blockage."

It's like checking the plumbing of a house. If the pipes are clogged, they will get fixed. But if the water flow is already good, no action needs to be taken. Similarly, PET with MBF data showing flow capacity helps doctors decide when to fix heart blood flow using stents or surgery.

Go with the flow

One such cardiology practice that took on the mantra of angiogram-as-surrogate is Memorial Katy Cardiology Associates in Cypress, Texas, which has used an MBF software package called HeartSee for the past two years. "At first, my partners at the practice weren't sold on the significance of the software," says Dr. James Feldman, a cardiologist at the practice. "As time has passed, they really can't see themselves reading nuclear imaging studies without it. We get so much extra data. It's helpful for all of us."

Dr. Feldman says that cardiologists can measure absolute flow per gram of heart tissue across different heart regions, and that the software allows them to directly see a patient's flow capacity, which clarifies their prognosis. "Most patients who have known or suspected CAD could benefit from MBF diagnostic tools because we can now quantitate flows, which is useful for determining medical management."

Drs. Johnson and Bober believe that this software helps interventional cardiologists avoid superfluous steps, so that their procedures can be more focused. "I've gotten the most exciting feedback when showing the interventionalists PET pictures with blood flow data," says Dr. Johnson. "We've designed them in such a way that it really focuses their attention when they get into the cath lab."

Breaking barriers

For Dr. Johnson, using MBF software is an important part of making top-notch, PET-focused cardiac care more widely available. He highlights that when health systems and practices invest in PET, it's a considerable upfront cost, with ongoing investment in infrastructure and training. Part of deciding whether to make that investment includes how they're going to approach patients with suspected CAD.

"Are they going to perform low-value invasive procedures, or do they want to screen first to see who actually needs to be there?" asks Dr. Johnson, adding that the time and money saved can be better focused on the subset of patients who actually need stent procedures or bypass surgery.

Though various MBF technologies are available, Drs. Johnson, Bober, and Feldman use HeartSee. In 2023, Dr. Bober's team investigated the accuracy of several software systems in measuring resting blood flow in regions with damaged heart tissue from a previous heart attack. They found that HeartSee provided precise and consistent measurements in these scarred regions, compared to similar software2.

Drs. Johnson and Bober have been working with Bracco, the healthcare company that markets HeartSee, to reduce barriers to this technology. "We are developing a Windows-based version of the software that allows for easy integration in hospitals and clinics," Dr. Johnson says, emphasizing that better technology means better patient selection and subsequently, better care. "This technology should be user-friendly and available for everyone."

HeartSee™

INDICATIONS FOR USE

HeartSee™ Software for cardiac positron emission tomography (PET) is indicated for determining regional and global absolute rest and stress myocardial perfusion in cc/min/g, Coronary Flow Reserve and their combination into the Coronary Flow Capacity (CFC) Map in patients with suspected or known coronary artery disease (CAD) in order to assist clinicalinterpretation of PET perfusion images by quantification of their severity.

HeartSee™ is intended for use by trained professionals such as nuclear technicians, nuclear medicine or nuclear cardiology physicians, or cardiologists with appropriate training andcertification. The clinician remains ultimately responsible for the final assessment and diagnosis based on standard practices, clinical judgment and interpretation of PET images or quantitative data.

HEARTSEE is a trademark of The University of Texas Health Science Center at Houston on behalf of the Board of Regents of The University of Texas System, and used under a license by Bracco Diagnostics Inc.

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