Can Better Diagnostics Lead to Improved Treatment for Cardiovascular Diseases?

Coronary artery disease (CAD) is the biggest contributor to cardiovascular diseases, accounting for about half of the 18 million global deaths attributable to cardiovascular disease every year. 

Its underlying cause is atherosclerosis, a gradual pathological furring up of critical coronary vessels, strangling blood supply to the vital heart muscle they serve. This malign process is propagated by the complex interplay of numerous contributory biochemical, mechanical, genetic, and lifestyle factors. 

The nature and rate of progression toward a clinical event, e.g., a heart attack, is unpredictable and greatly varied between individuals.

Tackling coronary artery disease 

Since the 1990s, unequivocal progress has been made in the fight against CAD, with notable big hitting contributions like the widespread adoption of statins to lower LDL-cholesterol. 

With progress plateauing in recent years, significant residual risk persists—for example, about 800,000 people have a heart attack every year in the US alone. 

Current treatments take a largely population approach, squeezing out benefit via the optimization of factors like cholesterol, blood pressure, and diet. A patient and disease-specific appreciation of each person’s disease is lacking. 

A critical question therefore is how can we better characterize, risk stratify, and treat each individual patient?

Are we using all the available technology?

Electrocardiograms

Electrocardiograms, or ECGs or EKGs, have been in regular use to map the electrical activity of the heart for over a century and remain the gold standard for the diagnosis of acute coronary events or cardiac rhythm abnormalities. 

Troponin T

A Troponin T blood test will confirm the presence of cardiac muscle damage in the instance of an acute event, but in terms of assessing a patient’s disease status blood tests are of little value. 

Lipoproteins

Measuring cholesterol-carrying lipoproteins (e.g., LDL) informs the level of aggression needed in terms of lipid-lowering therapy, but the overall aim is to get these cholesterol levels as low as possible. 

C-reactive protein

More recently, the role of inflammation in disease has been proven, thus, measuring systemic markers of inflammation like high-sensitivity C-reactive protein (CRP) will also help estimate risk. However, neither are specific to the patient’s disease and many patients with unremarkable levels of lipids and inflammatory markers still progress to coronary events. 

CT scans

Coronary computerized tomography angiography (CCTA), a CT scan focused on coronary arteries, is now considered a first line assessment in patients with chest pain to evaluate the presence of atherosclerotic plaque in coronary arteries. This enables the visualization of disease ahead of any potential interventional procedure. 

However, CCTA often identifies many patients with non-obstructive disease who do not meet the criteria for intervention (balloon angioplasty or stenting), even though this group accounts  for a large proportion of subsequent coronary events. 

Being able to accurately identify which of these areas of moderate disease go on to cause events is critical to enhance patient care and prevent events.

New ways to detect coronary inflammation

AI-enabled methods

New AI-enabled techniques that measure coronary inflammation have generated impressive data to support this need, however, the next challenge is how to treat this apparent inflammation and which inflammatory processes and signaling proteins should be targeted—and in whom. 

Site-of-disease blood sampling for precision profiling

Site-of-disease intracoronary blood sampling could help identify which biomolecules are contributing to disease in which individuals to help stratify patients and support the use of precision medicines to target each patient’s specific biochemical disease profile. 

This sampling technique is being developed using coronary catheters designed to mix biomolecules localizing close to the diseased endothelial wall into the central flow, then extract simultaneous samples downstream and upstream of disease. This enables assessment and quantification of plaque-associated biomolecules that may be implicated in the patient’s CAD progression. 

Toward precision medicine in coronary artery disease 

The residual risk of coronary events is significant despite best current standard of care. Good progress has been made establishing the role of inflammation in disease and identifying apparently mild to moderate disease that is more likely to progress to a life-threatening event. 

Combining state-of-the are art diagnostic technologies holds huge potential to better stratify patients, inform the development programs of anti-inflammatory medicines, and ultimately help herald a new and much needed era of precision medicine in coronary artery disease.