‘Smoldering’ cardiovascular crisis

Photo illustration by Liz Zonarich/Harvard Staff

Jacob Sweet

Harvard Staff Writer

May 15, 2025 9 min read

Downward trend in deaths appears stalled due to lack of urgency among doctors, patients, along with healthcare barriers

Starting in the late 1960s, cardiovascular disease deaths fell and fell. Mortality decreased by 70 percent — from 206 deaths per 100,000 in 1968 to 62 deaths in 2017. The share of all premature deaths attributable to heart disease fell, too.

The trends no longer look so promising. Around 2010, the long decline in cardiovascular deaths began to level off and appear stalled. Some studies find that they’re increasing year over year for the first time since the 1950s.

Scientific innovation hasn’t stopped. Fundamental research has led to new drugs, treatments, and interventions. Public health campaigns warn against smoking, and some of the most powerful drugs to treat high blood pressure and high cholesterol — two major, common risk factors —are widely available and cheaper than ever. Those who actually suffer a heart attack survive more than 90 percent of the time.

But, health professionals say, greater awareness of the urgency of the problem is needed. Too many ignore lifestyle practices like healthy diets and regular exercise, and medical professionals need to be more aggressive about preventive care. In addition, there are deficiencies in the healthcare system itself. Working on all of this, along with continued innovation, is viewed as key to getting the nation back on track.

Heart disease is a lifelong struggle. For Rishi Wadhera, a cardiologist at the Beth Israel Deaconess Medical Center and associate professor of medicine at Harvard Medical School, the problems start with young people. “I call it a smoldering crisis,” he says.

Wadhera researches heart health in younger adult populations and finds that they’re putting more stress on their hearts. In a paper published in the journal JAMA, Wadhera and his colleagues found that between 2009 and 2020, people between 20 and 44 saw increases in diabetes (3 percent to 4.1 percent), obesity (32.7 percent to 40.9 percent), and hypertension (9.3 to 11.5 percent).

These risk factors lead to earlier heart attacks. In the European Heart Journal, Wadhera and colleagues reported that heart attacks for people between 25 and 64 rose from 155 per 100,000 people to 161. This cohort of adults also suffered more instances of heart failure (from 165.3 to 225.3 per 100,000) and ischemic strokes (76.3 to 108.1 per 100,000).

Wadhera called the report “alarming.” In lower-income communities, cardiovascular hospitalization rates among younger adults were two to three times larger than in their high-income counterparts. Black Americans fared particularly poorly; about 40 percent of hospitalized younger adults from low-income communities were Black. These disparities did not narrow over time.

Plenty of progress has been made over the last few decades. Of the total number of premature deaths in the U.S., nearly 39 percent of them were heart-disease related in 1980. Today, that number is 20 percent. Overall rates of premature deaths related to cardiovascular disease is down about 70 percent since its 1968 peak.

Still, heart disease remains the leading cause of death for Americans.

Cardiologists believe public-health campaigns will be critical to lowering heart disease — from increasing awareness of new treatments, to focusing on prevention, to simply raising awareness of the risk of heart disease in the U.S.

The last factor, says Michelle O’Donoghue, McGillycuddy-Logue Endowed Chair in Cardiology at Brigham and Women’s Hospital, is still not common knowledge. “There’s this misconception that cancer — in particular, breast cancer — is what women need to hear about the most when it comes to conditions that may affect them in their lifetime,” she said. “But in fact, cardiovascular disease remains, unfortunately, the No. 1 killer of both women and men.”

This lack of awareness has downstream effects. O’Donoghue has found that women are likely to be undertreated when it comes to heart disease compared to men. They’re also less likely than men to correctly identify symptoms of a heart attack, which can sometimes vary by sex.

Rishi Wadhera. — *Stephanie Mitchell/Harvard Staff Photographer*

The most common symptom in both men and women is chest tightness or heaviness, with women more likely to experience accompanying dizziness, nausea, and fatigue. But even presenting the same symptoms, O’Donoghue says, women are likelier to be ignored.

This lack of attention paid to heart disease in both men and women, O’Donoghue argues, makes it easier for patients — and doctors — to perpetually delay treatment. “Your primary care doctor may say, ‘Your blood pressure is a little high. Let’s check it again next time,’” said O’Donoghue. “And, you know, that inevitably keeps happening.”

That’s if people have access to a doctor at all. Wadhera says there are still significant barriers for preventative screenings. “If you look at Boston right now, it’s very hard to get an appointment to see a primary care doctor,” Wadhera said. “And if you don’t have access to a primary care provider, how are you supposed to receive important preventive screenings and care?”

The barriers continue from there. “Even if you have coverage, copay or deductibles may be high, creating barriers to obtaining testing and treatments that mitigate the risk of developing heart disease, heart attacks, or stroke.” For those who need more powerful drugs than statins, the cost can be insurmountable.

Due to the slow-burn nature of heart disease, the barriers to screenings, and the limited attention paid to preventative care, patients don’t always follow medical advice or use their prescriptions. According to a 2023 paper in the Annals of Internal Medicine, the use of statins jumped from 11.6 percent in 1999-2000 to 33.6 percent in 2013-2014 by guideline-eligible patients, and have since stagnated.

Today, only about one-third of patients eligible to take statins actually do so. “If we could get that number up closer to 100 percent,” said Wadhera, “we could probably make a huge dent in reducing cardiovascular risk and improving cardiovascular outcomes at the population level.”

“Cardiovascular disease remains, unfortunately, the No. 1 killer of both women and men.”
Michelle O’Donoghue

Most doctors argue that even with new treatments, implementation remains an issue.

“In a large healthcare system, there is just inertia,” says Marc Sabatine, the Lewis Dexter M.D. Endowed Chair in Cardiovascular Medicine at Brigham and Women’s Hospital.

For Type 2 diabetes, for example, Sabatine notes that many patients remain on older drugs that may control blood-glucose levels but would be better off taking drugs that also have been proven to reduce the risk of adverse heart outcomes.

It can be difficult for a doctor to say, “Even though you feel OK, we have data to suggest that we should change your medical regimen,” says Sabatine — especially because the first time a patient may feel the effects of dealing with risk factors could be sudden cardiac death.

But these sorts of proactive shifts could be crucial to improving heart health. Sabatine points to LDL cholesterol — also known as “bad” cholesterol — as a risk factor that doctors could target more aggressively. While doctors generally consider 100 mg/dL a healthy level of LDL cholesterol in the blood, Sabatine argues the standard should be lowered to about 70 mg/dL, the point at which arterial plaque begins to actually decline.

In all, Sabatine thinks the way the U.S. deals with heart disease is inadequate.

“Periodic visits with a primary care physician is a relatively inefficient way to do it,” he said. Instead of cramming preventative care into a few minutes a year with a physician, argues Sabatine, it has been shown that medical systems can train nurse practitioners and pharmacists to measure patients’ risk factors more frequently and adjust medications as needed under the supervision of physicians.

But while doctors see plenty of room to improve with the current, accessible medications, they see promise in the state of drug development.

“It used to be that we had a very small arsenal of drugs available to us,” O’Donoghue said. But the possibilities are growing. GLP-1 receptor agonists — originally developed to treat diabetes — can help people lose weight and improve heart health.

Verve Therapeutics, founded by former Harvard Medical School Professor Sekar Kathiresan, is running Phase 1b trials on gene-editing therapies that could lower cholesterol by rewriting DNA instructions in liver cells that control cholesterol production. New scientific developments carry not only the potential to treat symptoms, but also to address some of the logistical limitations of existing heart-disease treatment.

New scientific developments carry not only the potential to treat symptoms, but also to address some of the logistical limitations of existing heart-disease treatment.

O’Donoghue herself is working on a drug with the pharmaceutical company Amgen that significantly lowers lipoprotein(a) concentration in the blood. Though this form of cholesterol is about 90 percent genetically predetermined — especially high for people of African and South Asian descent, as well as for women after menopause — there is no current treatment.

As a graduate student in Andrew Kruse’s lab, Sarah Erlandson figured out the structure and function of RXFP-1 receptor, which interacts with the hormone relaxin to dilate blood vessels, boost blood flow, break down collagen in the heart, and reduce inflammation — effects that could make it a powerful target for treating heart failure.

After mapping how the receptor functioned, Erlandson teamed up with Kruse, the Springer Professor of Biological Chemistry and Molecular Pharmacology, to design a new therapeutic that mimics the hormone’s beneficial effects but lasts much longer in the body.

With help from Harvard’s Office of Technology Development (OTD), the University patented the new molecule and out-licensed it to Tectonic Pharmaceuticals, a company Kruse founded. Fewer than five years after the original prototype, Tectonic is now testing an updated version of Erlandson’s molecule in Phase 2 clinical trials.

Other technologies aim to treat other advanced stages of heart disease. Backed by Harvard’s Blavatnik Biomedical Accelerator, stem cell and regenerative biology professor Richard T. Lee and engineering professor Jia Liu co-developed a flexible, tissue-like device designed to both detect and stop atrial fibrillation — an irregular heart rhythm that can lead to stroke and heart failure. “If you could stop it before it gets going, then you really have something,” Lee said.

“We’ve made good progress,” Sabatine said, “and we should celebrate the progress we’ve made.” But with rates remaining as stubborn as they have been in half a century, Sabatine and his colleagues are committed to searching for novel ways to get better treatment for more people. “We need to continue to drive rates ever downward,” he said.

Harvard Gazette

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