Global health & Local efforts: Strengthening the heart

Asked to name the leading cause of death worldwide, many people automatically would respond with cancer. New treatments and ongoing research often are in the news and most people know someone who has suffered from it. But while cancer certainly is responsible for many deaths globally, it is actually the world’s second leading cause of death, and the number one killer is cardiovascular diseases (CVD), responsible for 20.5 million deaths in 2021. About 75 percent of those deaths are in low- and middle-income nations, according to the World Health Organization (WHO), due in part to the lack of access to primary healthcare and screening for risk factors.

CVDs include a range of ailments affecting blood vessels and the heart. Among the most common are coronary heart disease, congestive heart failure and atherosclerosis, which progress over time and could lead to a stroke or heart attack.

Lifestyle interventions

The fact that people often don’t know that they have a CVD until it is too late likely accounts for the high mortality rate. Ironically, unlike many other potentially fatal diseases, CVDs are for the most part preventable. As many as 80 percent of cases could be prevented, according to the World Heart Federation.

Eating a low-fat diet, exercising, avoiding tobacco, and not drinking alcohol excessively can significantly reduce the likelihood of getting a CVD. Global efforts to reduce the number of cases have focused on prevention, including education about what constitutes a heart-healthy diet, the importance of regular exercise, and improving access to screening and healthcare. According to the WHO, within the European Union, about 10,000 people a day die from CVDs, with men dying at a higher rate than women,. Large amounts of salt in people’s diets in many European countries contribute to a high rate of hypertension, or high blood pressure, a contributing factor for heart attacks and strokes. 

In Finland, the North Karelia Project, which began 50 years ago, has has a revolutionary impact.

Widespread prevention efforts and improved treatments have resulted in a steady decline in deaths from CVDs in the Nordic countries, and the rate is lower here than in most European countries. In Finland, the North Karelia Project, which began 50 years ago, has has a revolutionary impact. When launched, coronary heart disease mortality among men was the highest in the world. The goal was to lower cholesterol and blood pressure through dietary changes, including a reduction in the use of butter and salt. As a result of the lifestyle interventions, that continued beyond the initial five years of the project and then expanded to all of Finland, there were significant reductions in serum cholesterol levels, hypertension, smoking prevalence, and CVD mortality. The project demonstrates that successful population-based lifestyle interventions serve as a sustainable public health solution to the growing chronic disease burden (Puska et al., Sage Journals, 2020).

Identifying higher-risk patients

All Nordic countries worked to reduce the incidences of chronic ischemic heart disease (IHD), the most prevalent CVD condition in the Nordic countries, affecting about 700,000 people, with many cases in Sweden. One study funded in part by NordForsk and completed in 2022 involved using data analysis to diagnose and predict an individual’s risk of IHD and applying the information to develop targeted treatments to improve effectiveness and avoid over- or under-medicating patients. Among those involved were cardiologists from Rigshospitalet, researchers from the University of Copenhagen and specialists from Norway and Iceland. 

Researchers found that by using sophisticated diagnostic methods and predictive models, they were able to effectively pinpoint subgroups of patients with IHD who were at lower risk and possibly being over-treated. This meant that their treatment could be more targeted and personalized, potentially eliminating redundant treatments and lowering costs. Higher-risk patents, once identified, could benefit from more aggressive treatment and monitoring.

Inotropes

Nordic companies also are pursuing new solutions for CVDs. Sweden’s clinical stage biopharmaceutical company AnaCardio is focused on perfecting a better treatment for heart failure, which affects almost 100 million people globally. While drugs are available to slow progression and ease the symptoms, currently none effectively address the underlying cause, which is a decrease in the heart’s ability to contract and pump blood, called contractility. Drugs called inotropes do improve contractility, but the ones currently in use can cause life-threatening side effects.

Our agents work by increasing the sensitivity of the heart muscle to this calcium, so that the contraction becomes stronger.

AnaCardio is developing an inotropic drug that strengthens the heart without creating new symptoms.

“Each heart contraction is caused by an influx of calcium into the heart cell,” explains AnaCardio CEO Patrik Strömberg. “Our agents work by increasing the sensitivity of the heart muscle to this calcium, so that the contraction becomes stronger.” 

Inotropes usually only are used in hospitals, and Strömberg’s goal is to make them safer, more effective, and more accessible. “I think this addresses one of the largest unmet needs in heart failure,” he says.

“Heart failure often is caused by hypertension and/or a myocardial infarction, but there also are a range of less common causes, such as valve disease and autoimmune or infectious causes, and there could be a genetic pre-disposition,” he notes.

“Heart failure often is caused by hypertension and/or a myocardial infarction, but there also are a range of less common causes, such as valve disease and autoimmune or infectious causes, and there could be a genetic pre-disposition,” he notes.

Better treatments would give patients more freedom. Heart failure is a chronic and taxing disease that often requires hospitalization. The symptoms include shortness of breath, irregular heart rate, and fatigue which reduce people’s quality of life. “The biggest burden is on patients and healthcare providers,” Strömberg says.

Personalized strategies

High cholesterol is an important risk factor of CVDs. It can lead to the formation of atherosclerotic plaques, which are fat deposits in arterial walls that can block the blood flow and lead to heart attack and stroke. Currently, a significant proportion of high-risk patients do not achieve optimal blood cholesterol levels and remain at elevated risk for CVD. In Finland, diagnostic company Moncyte Health has developed a technology that quantifies individual differences in cellular lipid uptake and storage which link to high blood cholesterol and the effectiveness of common lipid-lowering drugs. The readouts are derived from white blood cells, including monocytes, which play key roles in atherosclerotic plaque formation and inflammation.

“Precisely quantifying these individual differences enables personalized treatment strategies in combination with risk assessment which can help patients achieve optimal blood cholesterol levels faster and thereby reduce the risk for CVDs,” explains Tamara Alagirova, co-founder and CEO of Moncyte Health. “Instead of quantifying a biomarker in blood, our diagnostic test provides insight into why the biomarker is altered by looking at the cellular processes which influence it.”

The company has recently joined a 4-year Horizon funded project, FH_EARLY, a consortium of 15 international institutions working together to enable new strategies for earlier diagnosis and co-management of familial hypercholesterolemia (FH). FH is the world’s most common inherited metabolic disorder, affecting around 2.5 million Europeans. The project will develop three interrelated solutions for FH: and array for earlier diagnosis, an assay for risk stratification, and co-management strategies. “People with FH presente a high cardiovascular risk, but these individuals are often not being clinically identified. Our technology provides valuable insights on how cholesterol is transported and stored in cells. In addition our technology can help to identify novel factors which contribute to the progression of FH and CVD in general,” says Alagirova.

There is significant variability of biological disease processes in individuals, which calls for personalized strategies in lipid-lowering treatment.

There are many factors that contribute to high cholesterol and CVDs, such as genetic, diet, and environment. Regardless all efforts to lower blood cholesterol and prevent CVDs, up to 80% of high-risk patients fail to reach cholesterol target levels (Ray et al., DA VINCI study, 2021, Eur. J Prev. Cardiol.) and are therefore at increased risk, emphasizes Tamara Alagirova.

“Currently, it is challenging to identify patients with high residual risk that could be prone for developing a life threatening event. Cellular mechanisms differ in individuals, even if they carry the same genetic mutation which predisposes to increased blood cholesterol,” she says. “Consequently, there is significant variability of biological disease processes in individuals, which calls for personalized strategies in lipid-lowering treatment,” she concludes.