Cardiovascular diseases, characterized as a group of disorders of the heart and blood vessels, are the leading cause of death worldwide. In fact, in the U.S. alone, it is thought that one person dies every 33 seconds from cardiovascular disease.
Although clearly a huge health problem throughout the world, developing cures for cardiovascular diseases is a tricky business. As of yet, no one has managed to come up with a successful solution for reversing or curing these types of disorders, despite the vast amount of research that has been conducted over the years increasing our understanding of different types of cardiovascular diseases and their causes.
What are the challenges in developing cures for cardiovascular diseases?
One of the main challenges here lies in reversing the effects of cardiovascular diseases. For example, in coronary heart disease, the arteries that supply the heart muscle with oxygen-rich blood, called coronary arteries, become narrowed by a build-up of fatty plaque, reducing the blood flow to the heart. This process is known as atherosclerosis, and, although it can be slowed down by medication and lifestyle changes, there is no way to reverse it.
Another example is a form of heart disease called heart valve disease, in which one or more of your heart valves do not open or close properly, disrupting the blood flow; in severe cases, if the heart valve becomes stiff and calcified, there is no way to restore its flexibility, except for having an operation to repair it, or replace it.
Equally, if a heart attack occurs, and heart muscle becomes damaged or dies, the cells cannot be regenerated.
Consequently, current treatment regimens largely rely on making lifestyle changes and taking medications such as statins and antihypertensive drugs to reduce risk factors like high cholesterol and high blood pressure respectively, which is generally a lifelong burden for people living with these types of disorders.
Toll on people living with cardiovascular diseases
Currently approved medications generally involve taking a pill every single day for the rest of your life. This means that, coupled with lifestyle changes, people living with cardiovascular diseases need to stick to a strict routine.
However, this can be difficult for many people, and both forgetfulness and a sense of burden can play a key role in people not following the correct treatment regimen. This can be seen in the fact that only around 39% of patients report sticking with their statin regimen in the year following a heart attack.
It is thought that cardiovascular diseases create a greater toll on people’s health than most other conditions. According to a study, the sense of burden that people feel is mainly related to the acceptance of long-term medicine use, medication-related concerns or dissatisfaction, the interference of medicines with social and daily lives, and the interaction and communication with health care providers.
Additionally, loss of income and medical care expenditures are major causes for concern that impact people across a wide variety of racial and ethnic backgrounds.
At the minute, a lot of research is focused on developing cardiovascular drugs that address some of the limitations of existing medications, with new drugs being more targeted so that they can reduce side effects and improve patient adherence. These are mainly to be used in combination with addressing lifestyle habits to prevent risk factors like high cholesterol.
But, given that the total system-wide costs of dealing with cardiovascular diseases in the U.S. are expected to reach $1.1 trillion per year by 2035, the real question is: where are we in terms of finding a cure for cardiovascular diseases?
Can gene therapy offer a potential cure for cardiovascular diseases?
Gene therapy is currently being explored as a potential method of curing certain types of cardiovascular diseases, with a particular focus on genetic conditions. These occur due to different abnormalities in the heart that can cause progressive heart failure or even sudden death, which can happen at any age.
Inherited heart muscle disease, known as genetic cardiomyopathy, is one such group of genetic conditions being explored as an indication for gene therapy treatment. People with genetic cardiomyopathies have a 50/50 risk of passing faulty genes onto their child, and current treatment options are lifelong, expensive, and do not change the underlying disease.
The CureHeart project, which brings together researchers across the U.K., U.S., and Asia, as well as commercial and patient advocacy partners, is focused on the development of effective gene therapies in an attempt to create a cure for genetic cardiomyopathy.
The project aims to develop gene therapies that correct the faulty genes in the hearts of patients with the disease. By developing ways to ‘switch off’ the faulty copy, researchers will address cardiomyopathy that happens because a fault in one of the two gene copies stops the other from working. Furthermore, they will also develop genetic tools to fix a faulty gene by editing it to correct the sequence of its genes.
With this work, the project is building on advances made in gene editing to treat Duchenne muscular dystrophy (DMD) and their approaches have already been shown to work in animal models.
Last year, the project was awarded a £30 million grant from the British Heart Foundation after winning the Big Beat Challenge, which is a global competition that challenges researchers to form international, multidisciplinary teams to identify and propose transformative solutions to heart and circulatory diseases.
Another way that gene therapy is being used to prevent cardiovascular diseases is through the disruption of the PCSK9 gene, which inhibits the removal of cholesterol from the blood, in turn raising the risk factors for developing cardiovascular problems. It has been found that individuals who have mutations that disrupt this gene have lower cholesterol levels, which also means they have an 80% lower risk of having a heart attack.
There are already drugs available that inhibit the PCSK9 protein, such as Praluent and Repatha, but Verve Therapeutics are aiming to develop a one-shot gene therapy that will directly disrupt PCSK9 – as well as other high-risk genes – and permanently lower cholesterol levels.
The benefit of this compared to other PCSK9-inhibiting drugs is that it is a one-time therapy, meaning it will eliminate the burden on people with cardiovascular diseases to take medication for the rest of their lives.
mRNA vaccines as promising therapies for cardiovascular diseases
As well as gene therapies, mRNA vaccines could also be an answer in finding a cure for cardiovascular diseases; Moderna is currently evaluating the use of an mRNA therapeutic that encodes for vascular endothelial growth factor-A (VEGF-A) in patients undergoing coronary artery bypass grafting (CABG).
“In addition, we are evaluating the use of our mRNA relaxin candidate, which is designed to produce the naturally occurring cardioprotective hormone relaxin. We continue to explore the application of mRNA in the potential treatment of cardiovascular and other ischemic vascular diseases with the goal of addressing serious unmet needs to improve patients’ lives,” said Cesar Sanz Rodriguez, vice president, Medical Affairs, Europe & Switzerland, at Moderna.
In fact, in a report by The Guardian last month, Moderna stated that vaccines for cardiovascular diseases – among others – could be ready by the end of the decade, giving patients with cardiovascular diseases reason to be hopeful.
Lifestyle changes as a preventive measure
Until a cure is possible, however, lifestyle changes, in combination with medication, do still help people living with cardiovascular diseases. According to the World Health Organization (WHO), most cardiovascular diseases can actually be prevented by addressing behavioral risk factors.
“For those diagnosed with CVD and recovering from any sort of cardiovascular event, it is crucial that they learn how to trust their heart and bodies again, but also how to live with their diagnosis.”
The most crucial risk factors are as follows: an unhealthy diet, physical inactivity, tobacco use and harmful use of alcohol. All of these factors can lead to high blood pressure, high blood glucose, raised blood lipids, and obesity, which indicates an increased risk of suffering from a heart attack, stroke, heart failure, and other complications.
For some people, taking the steps towards maintaining healthy habits, particularly after suffering from a heart attack, can be a challenge, and they might not have the necessary information to fully understand how they need to adapt their lifestyle in order to lower their risk.
The benefits of cardiac rehabilitation
This is where cardiac rehabilitation, which involves supervised exercise by a clinical exercise psychologist, education surrounding nutrition, medication, mental health, and heart health, could be useful for people with cardiovascular diseases.
“For those diagnosed with cardiovascular disease and recovering from any sort of cardiovascular event, it is crucial that they learn how to trust their heart and bodies again, but also how to live with their diagnosis. Experiencing any sort of heart event or surgery is a scary situation and can oftentimes lead to increased anxiety & fear around pushing yourself too hard physically. Cardiac rehab is intended to help patients regain their trust in their bodies while also getting them back to doing the activities they love most,” said Gina Iovenitti, who oversees growth operations at Carda Health, a virtual cardiac and pulmonary rehab company.
“The understanding around how important physical therapy is to those who receive a new joint or have any sort of orthopedic surgery is strong. You wouldn’t not go to PT after a knee replacement; the same goes for your heart & cardiac rehabilitation. It is the most important muscle in your body and deserves the same, if not more, recovery and rehabilitation as any other injury would receive.”
Furthermore, the results are positive, as cardiac rehabilitation has been shown to reduce hospital admissions, lower deaths from cardiovascular diseases, reduce the risk of further cardiovascular complications, and improve overall quality of life.
Barriers to cardiac rehabilitation
However, there is an issue with attendance. In the U.K., for example, it is estimated that only around 43% of eligible people actually attend cardiac rehabilitation. And a recent study in the U.S. found that only around 24% of people attended, with most of those who did attend, not completing enough sessions to gain maximum benefit.
Iovenitti believes that convenience is a big factor in this, as well as the lack of education on the benefits of cardiac rehabilitation. “We talk to a lot of patients who say their doctor told them they didn’t need it and ‘to just go for a walk around your neighborhood a few times a week’. This is a disservice to the patient because they likely will not do this, and need the accountability and support from a Clinical Exercise Physiologist. I talk to a lot of other patients who are put on waiting lists that are 2 months or longer to start their programs. When people are in a vulnerable state right after a heart event or new diagnosis, it’s the most crucial time to make a change and they are being forced to wait to do so and lose the urgency.”
“In that same thought, commute times, scheduling and, for some patients, transportation in general, are big barriers to being able to participate in a center based rehab program. Increased stress around finding a ride or driving themselves, maybe a 30 plus-minute commute, plus having to schedule it in the middle of your day, three times a week…are all factors in why compliance and commitment to center based programs is low. Most center based cardiac rehab centers are only open during normal business hours, which for people who still work, just isn’t realistic.”
With this in mind, Carda Health offers virtual programs, which Iovenitti believes can help to increase attendance due to the fact it eliminates the need for commuting and patients can do it on their own schedule.
Although many cardiovascular diseases can be effectively treated with lifestyle changes, with cardiac rehabilitation providing many benefits, serious forms of certain conditions can be difficult to control and clearly it can be difficult for people living with them to stick to a good routine, whether that’s taking medication on time or putting in the necessary effort to address behavioral risk factors.
Finding a cure would certainly alleviate the concerns for people living with cardiovascular diseases. Given the ongoing research on gene therapy, GLP-1 agonists, and Moderna’s possible mRNA vaccine as potential approaches to tackling cardiovascular diseases, a cure for certain cardiovascular conditions might just be on the horizon.
New technologies related to cardiovascular disease
- Therapy for Wound Healing and Cardiovascular Disease – University of Sussex
- Machine Learning Algorithm for Cardiovascular Disease Stratification and Drug Discovery – Heidelberg University
- Noninvasive Detection of Preclinical Cardiovascular Disease – Lawrence Berkeley National Laboratory