‘Smoldering’ cardiovascular emergency

Beginning in the late 1960s, fatalities from cardiovascular diseases significantly decreased. Death rates fell by 70 percent — from 206 deaths per 100,000 in 1968 to 62 fatalities in 2017. The proportion of all untimely deaths due to heart disease also declined.

However, the situation no longer appears as optimistic. Around 2010, the steady drop in cardiovascular mortality started to plateau and seems to be stagnating. Some research indicate that they are increasing annually for the first time since the 1950s.

Scientific advancements continue. Core research has resulted in new medications, therapies, and interventions. Public health initiatives caution against smoking, and some of the most effective drugs for treating high blood pressure and cholesterol — two prevalent risk factors — are now widely accessible and more affordable than ever. Those who do experience a heart attack survive over 90 percent of the time.

Nevertheless, health experts assert that there is a pressing need for heightened awareness regarding the seriousness of the issue. Many overlook healthy lifestyle choices like nutritious diets and regular physical activity, and healthcare providers must adopt a more proactive approach to preventive healthcare. Additionally, there are gaps within the healthcare system itself. Addressing these issues, coupled with ongoing innovation, is seen as crucial to getting the nation back on track.

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Heart disease is an ongoing challenge. For Rishi Wadhera, a cardiologist at the Beth Israel Deaconess Medical Center and associate professor of medicine at Harvard Medical School, the concerns begin with younger demographics. “I refer to it as a smoldering crisis,” he states.

Wadhera investigates heart health in younger adult groups and observes that they are placing more strain on their cardiovascular systems. In a study published in the journal JAMA, Wadhera and his collaborators discovered that between 2009 and 2020, individuals aged 20 to 44 experienced increases in diabetes (from 3 percent to 4.1 percent), obesity (from 32.7 percent to 40.9 percent), and hypertension (from 9.3 to 11.5 percent).

These risk factors contribute to earlier heart attacks. In the European Heart Journal, Wadhera and associates indicated that heart attacks among individuals aged 25 to 64 increased from 155 to 161 per 100,000 people. This group also faced a rise in heart failure cases (from 165.3 to 225.3 per 100,000) and ischemic strokes (from 76.3 to 108.1 per 100,000).

Wadhera described the report as “alarming.” In lower-income neighborhoods, hospitalization rates for cardiovascular issues among younger adults were two to three times higher than those in affluent areas. Black Americans particularly struggled; approximately 40 percent of hospitalized young adults from low-income backgrounds identified as Black. These disparities did not lessen over time.

Numerous advancements have occurred in recent decades. In 1980, nearly 39 percent of all premature deaths in the U.S. were linked to heart disease. Today, this figure stands at 20 percent. The overall incidence of premature deaths due to cardiovascular disease has decreased by about 70 percent since its peak in 1968.

Despite this progress, heart disease remains the foremost cause of death for individuals in the United States.

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Cardiologists believe that public health initiatives will be vital in reducing heart disease — from enhancing awareness of new treatments to emphasizing prevention, to simply informing the public about the risks of heart disease in the U.S.

The latter aspect, according to Michelle O’Donoghue, McGillycuddy-Logue Endowed Chair in Cardiology at Brigham and Women’s Hospital, is still not widely recognized. “There’s this notion that cancer — particularly breast cancer — is what women need to be informed about the most regarding health conditions that may affect them throughout their lives,” she mentioned. “However, cardiovascular disease continues to be, unfortunately, the primary cause of death for both men and women.”

This lack of understanding has subsequent consequences. O’Donoghue has found that women are often undertreated for heart disease compared to men. They are also less likely than men to accurately recognize the symptoms of a heart attack, which can sometimes differ by gender.

The predominant indication for both genders is a feeling of pressure or heaviness in the chest, with females being more susceptible to experiencing additional symptoms like dizziness, nausea, and exhaustion. However, even when the symptoms manifest similarly, O’Donoghue notes that women are more likely to be overlooked.

This oversight surrounding heart conditions in both genders, O’Donoghue contends, facilitates continuous delays in treatment for patients — and practitioners alike. “Your primary care provider might remark, ‘Your blood pressure is somewhat elevated. Let’s revisit it at the next appointment,’” commented O’Donoghue. “And, you know, this pattern tends to persist.”

This is provided individuals even have access to a healthcare professional. Wadhera points out that considerable obstacles remain for preventive screenings. “If you observe the current situation in Boston, securing an appointment with a primary care physician is quite challenging,” Wadhera remarked. “If you don’t have a primary care provider, how can you obtain crucial preventive assessments and care?”

The obstacles persist beyond this point. “Even with insurance, copays or deductibles may be steep, posing hurdles to securing tests and treatments that lessen the risk of heart disease, myocardial infarction, or cerebrovascular accident.” For those requiring more potent medications than statins, the financial burden can be overwhelming.

Due to the gradual progression of heart disease, the limitations to screenings, and the scant emphasis on preventive care, patients may not consistently adhere to medical recommendations or utilize their prescriptions. A 2023 publication in the Annals of Internal Medicine revealed that statin usage among guideline-eligible patients surged from 11.6 percent in 1999-2000 to 33.6 percent in 2013-2014, but has since plateaued.

Currently, only about one-third of those eligible for statins actually take them. “If we could elevate that figure closer to 100 percent,” mentioned Wadhera, “we could likely create a substantial impact on decreasing cardiovascular risk and enhancing cardiovascular outcomes at the population level.”

“Cardiovascular ailments remain, regrettably, the primary cause of death for both women and men.”

Michelle O’Donoghue

Many physicians assert that despite the arrival of new therapies, implementation continues to pose a challenge.

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

For instance, regarding Type 2 diabetes, Sabatine observes that numerous patients stick with older medications that may manage blood sugar levels but would benefit more from drugs that also lower the risk of detrimental heart outcomes.

It can be challenging for a healthcare provider to convey, “Even if you feel fine, we have evidence suggesting the need to modify your treatment plan,” says Sabatine — particularly because the initial indication patients might have risk factors could manifest as sudden cardiac arrest.

However, such proactive modifications could be vital to enhancing heart health. Sabatine highlights LDL cholesterol — often referred to as “bad” cholesterol — as a risk factor that could be targeted more vigorously. While practitioners generally classify 100 mg/dL as a healthy LDL cholesterol level in the bloodstream, Sabatine argues that the benchmark should be decreased to around 70 mg/dL, the threshold at which arterial plaque starts to actually diminish.

In general, Sabatine believes that the approach the U.S. employs regarding heart disease is insufficient.

“Frequent visits with a primary care physician are a relatively ineffective method,” he stated. Rather than cramming preventive measures into a few minutes per year with a doctor, argues Sabatine, it has been demonstrated that healthcare systems can train nurse practitioners and pharmacists to assess patients’ risk factors more regularly and adjust treatments as necessary under the oversight of physicians.

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Yet, while healthcare professionals identify ample opportunities for enhancement with the current, available medications, they remain optimistic about advancements in drug development.

“Previously, we had a very limited selection of drugs at our disposal,” O’Donoghue mentioned. Yet, the future appears promising. GLP-1 receptor agonists — initially created for diabetes management — are capable of aiding individuals in losing weight and improving cardiovascular health.

Verve Therapeutics, established by former Harvard Medical School Professor Sekar Kathiresan, is conducting Phase 1b trials on gene-editing treatments that could reduce cholesterol by reprogramming DNA instructions in liver cells responsible for cholesterol production. New scientific advancements offer not just the potential to alleviate symptoms but also to tackle some of the logistical constraints tied to existing heart disease therapies.

New scientific advancements offer not just the potential to alleviate symptoms but also to tackle some of the logistical constraints tied to existing heart disease therapies.

O’Donoghue is personally collaborating with the pharmaceutical firm Amgen to develop a medication that significantly decreases lipoprotein(a) levels in the blood. Although this variant of cholesterol is largely determined by genetics — particularly elevated among individuals of African and South Asian heritage as well as women post-menopause — no effective treatment is currently available.

During her time as a graduate student in Andrew Kruse’s laboratory, Sarah Erlandson elucidated the structure and mechanism of the RXFP-1 receptor, which interacts with the hormone relaxin to dilate blood vessels, enhance blood flow, degrade collagen in the heart, and lessen inflammation — effects that could make it an impactful target for heart failure treatment.

After delineating how the receptor operated, Erlandson partnered with Kruse, the Springer Professor of Biological Chemistry and Molecular Pharmacology, to create a novel therapy that emulates the hormone’s advantageous effects but remains effective in the body for a prolonged period.

With assistance from Harvard’s Office of Technology Development (OTD), the University patented the innovative molecule and licensed it to Tectonic Pharmaceuticals, a company founded by Kruse. Less than five years after the initial prototype, Tectonic is now evaluating an upgraded version of Erlandson’s molecule in Phase 2 clinical trials.

Other innovations aim to address various advanced stages of heart disease. Supported by Harvard’s Blavatnik Biomedical Accelerator, Richard T. Lee, a professor of stem cell and regenerative biology, and Jia Liu, a professor of engineering, collaboratively developed a flexible, tissue-like device designed to both identify and halt atrial fibrillation — an abnormal heart rhythm that can result in strokes and heart failure. “If you could prevent it before it escalates, then you truly have a breakthrough,” Lee noted.

“We’ve made commendable strides,” Sabatine commented, “and we should celebrate the progress we’ve achieved.” However, with rates remaining as persistent as they have over the past fifty years, Sabatine and his colleagues are dedicated to exploring innovative methods to enhance treatment access for more individuals. “We must continue to drive these rates downward,” he asserted.