10.3 The Four Horsemen of Chronic Disease

In his bestselling book Outlive: The Science & Art of Longevity, Dr. Peter Attia highlights four chronic conditions, referred to as the “Four Horsemen of Chronic Disease,” that contribute significantly to mortality and declining lifespan and healthspan worldwide (Attia & Gifford, 2023).

Over time, these conditions slowly cause irreversible damage to the body, often without the person even knowing it. Damage often takes the form of reduced energy levels, making everyday activities, like sports or simply staying active, far more challenging. Treatments for these conditions may bring unintended side effects, which can further diminish healthspan.

Preventing or effectively managing these conditions is essential not just for extending lifespan but also for maintaining healthspan.

1. Metabolic Disease

This is an umbrella term for a handful of related illnesses that impact our metabolic processes, such as maintaining stable blood sugar and insulin levels, healthy blood pressure, and favourable cholesterol and triglyceride levels.

The main drivers of metabolic disease are poor diet, lack of exercise, excessive weight, stress, poor sleep, and hormone imbalances.

Deaths per year: Exact numbers vary because metabolic disease often contributes to other conditions (heart disease, stroke, etc.). According to the Institute for Health Metrics and Evaluation (2024), diabetes alone was the direct cause of 1.6 million deaths worldwide. Considering complications and related metabolic disorders, the total number of deaths influenced by metabolic disease may reach several million each year.

2. Heart Disease

Also known as cardiovascular disease, this includes a variety of conditions affecting the heart and blood vessels (arteries and veins). Heart disease develops over many years without noticeable symptoms, which is the reason why it is a leading cause of death globally.

The main drivers of heart disease are high LDL (bad) cholesterol, high blood pressure, smoking, diabetes, and a sedentary lifestyle.

Deaths per year: According to WHO (2021), heart disease accounted for nearly 17.9 million deaths globally.

3. Cancer

Cancer is marked by abnormal cells growing uncontrollably, sometimes spreading (metastasizing) to other parts of the body. It can begin in almost any part of the body, leading to a diverse range of types and outcomes. Early detection and getting the right treatment can make an enormous difference in survival.

The main drivers for cancer are genetics, smoking, exposure to chemicals, obesity, poor diet, physical inactivity, radiation, air pollution, and excessive sun exposure.

Deaths per year: According to WHO (2025), cancer accounted for nearly 10 million deaths in 2020.

4. Neurodegenerative Disease

This is a term used to describe a decline in cognitive ability (i.e., memory, thinking, and decision making) severe enough to affect everyday life. This leads to confusion, mood swings, and difficulty with basic tasks like speaking or recognizing faces, even including close loved ones. Over time, conditions progressively worsen, eventually leading to complete dependence on others for care.

Main drivers: genetics, poor heart health, high blood pressure, diabetes, smoking, a lack of physical activity, insulin resistance, and poor blood flow to the brain.

Deaths per year: Often, neurogenerative disease itself is not the direct cause of death but contributes to fatal complications (e.g., infections, injuries from falls, or inability to manage other illnesses); however, according to the Global Burden of Disease Study (2019) the number of deaths attributed to neurodegnerative conditions approached 2 million globally (Institute for Health Metrics and Evaluation, 2024).

“The Four Horsemen” image: OpenAI. (2025). ChatGPT. [Large language model]. https://chat.openai.com/chat  Prompt: Create an image of four men riding horses. They are in the distance and a silhouette.