Using cardio-metabolic analysis to combat the cardiovascular disease epidemic

The problem with cardiovascular disease: We can’t detect it early enough

Cardiovascular disease is the leading cause of death in the United States, costing approximately $550 billion to the US economy every year [1]. Cardiovascular disease comprises various conditions, including common and low-risk ailments such as hypertension and more severe and potentially deadly ones such as heart failure and ischemic heart disease. 

• Hypertension: The condition where a person’s blood pressure rises at dangerously high levels for prolonged durations during the day. It impacts approximately 100 million individuals in the US [1]. 

• Ischemic heart disease (AKA Coronary Artery Disease): The condition where a person’s heart arteries get clogged, restricting blood flow to the heart. Arteries affected are those supplying the blood your heart needs to beat, not the blood pumped to the rest of the body. It impacts approximately 20 million individuals in the US [1].  

• Heart failure: The condition where a person’s heart weakens and pushes less blood to the body. It impacts approximately 10 million individuals in the US [1]. 

• Valvular disease: The condition where one or more of the four valves of the heart get clogged or damaged thus preventing blood from flowing through the heart. This restriction impacts the blood pumped from the heart to the body. It impacts approximately 8 million individuals in the US [2].  

Ischemic heart disease is the number one cause of death in the United States, whereas heart failure is the most costly condition for the US healthcare system [1]. It is estimated however that 80-90% of these conditions are entirely preventable if diagnosed early. Our inability to detect these conditions early enough is due to the absence of precise but at the same time cost-effective diagnostic methods, that everyone can have easy access to without going to a hospital or sophisticated medical facility. Here are some of the diagnostic methods typically used for detecting along with their drawbacks:

• ECG stress testing: This assessment includes the measurement of your heart’s electrical signal during exercise conditions. It is typically used for the detection of ischemic heart disease but due to its low sensitivity and specificity of ~50% the U.S. Preventive Services Task Force has argued against its application [3]. 

• Stress echocardiography:  This assessment includes viewing a person’s heart using ultrasound during exercise conditions. Although it has a high specificity and sensitivity (~80-90%), it requires experienced medical personnel who analyze the heart's ultrasound video feed in real-time and its efficacy also depends on the skill level of the tester [4]. 

• Nuclear stress testing: This is a highly invasive procedure that includes the injection of radioactive material into the bloodstream which reveals blockages in your heart arteries. Although it is highly sensitive and specific (~90%) it requires very expensive equipment and experienced personnel found only in sophisticated medical centers [5]. Moreover, its extensive usage has been linked to an increase in cancer cases caused by the deleterious effects of the radioactive material [6]. 

• Coronary Artery Calcium Scoring (CACS): This assessment provides a highly sensitive and specific procedure without the usage of radioactive material. It still requires sophisticated and expensive medical equipment as well as experienced medical personnel. [7]  

Given the drawbacks of these diagnostic methods, doctors have been largely unable to early detect IHD and heart failure. 

Why breath analysis offers a solution

Breath analysis holds the promise of a precise enough, non-invasive, and easy to conduct assessment capable of early detecting IHD and heart failure. A breath analysis test (AKA VO2max test, metabolic test, cardiopulmonary exercise testing) measures the amount of oxygen consumed and carbon dioxide produced by the human body. By measuring oxygen consumption, during a graded exercise test (i.e. an assessment conducted on a treadmill or stationary bike where exercise intensity rises gradually) one is able to detect the presence of these conditions:

IHD can be identified by looking for flattenings in the amount of oxygen your heart pumps per heartbeat, a metric referred to as 02pulse. Your heart is a muscle and just like any muscle, it needs blood to work and pump oxygen-rich blood into the body. In case one of the arteries supplying blood to the heart to work is clogged, it can’t work effectively enough and consequently, the amount of oxygen-rich blood it pumps to the body will gradually diminish as the intensity rises during a graded exercise test. As a result, O2pulse has been shown as a reliable and accurate indicator of IHD showing sensitivity and specificity that is nearly double that of ECG stress testing and nearly as high as nuclear stress testing [5]. 

Heart failure can be identified by looking at the peak oxygen consumption you achieve during a graded exercise test. Heart failure causes your heart to beat less forcefully and ultimately pump less oxygen-rich blood into your body thus reducing the maximum amount of oxygen your body absorbs. Consequently, VO2peak constitutes the gold standard metric for assessing overall cardiovascular health and determining improvement or deterioration among individuals suffering from heart failure [8]. 

Examples from PNOĒ

As a clinical-grade cardiopulmonary exercise testing device, PNOE can measure the variables necessary to derive VO2peak and O2pulse during a graded exercise test. The examples below provide a clear overview of the differences in O2pulse between a healthy individual and one who is suffering from cardiovascular disease. 

Figure 1 shows how 02pulse (yellow line) evolves in an individual suffering from IHD. The flattening and subsequent reduction become apparent from the early stages of the test. On the contrary, Figure 2 shows how O2pulse evolves in the case of a healthy individual. In this case, 02pulse continues to increase linearly as exercise intensity increased.

Figure 1 O2pulse (yellow line), VO2 (blue line), VCO2 (red line) of an individual suffering from ischemic heart disease.

 Figure 2 O2pulse (yellow line), VO2 (blue line), VCO2 (red line) of a healthy individual.