Heart attacks have long been associated with cholesterol and blocked arteries, but emerging evidence reveals that inflammation plays a central, and often underappreciated, role in precipitating these life-threatening events.
Rather than cholesterol alone, it is the body's inflammatory response to arterial injury that can destabilize plaques and trigger the cascade leading to myocardial infarction.
The Dual Nature of Inflammation: Friend and Foe
Inflammation is a natural and vital process that helps the body repair injuries and fight infections. For example, when you sprain an ankle, immune cells rush to the site, causing redness and swelling to promote healing. However, when inflammation occurs chronically within the arteries, it becomes harmful.
Dr. Peter Libby has explained, "Chronic inflammation within the arterial wall—from factors like hypertension or metabolic stress—can injure the endothelium, promote plaque development, and trigger plaque disruption leading to acute events."
How Inflammation Initiates and Propagates Arterial Damage
The inner lining of arteries (endothelium) can be injured by toxins, mechanical stress, or metabolic imbalances. This injury activates immune cells and releases inflammatory mediators such as cytokines and chemokines. These substances attract white blood cells to the artery walls, where they engulf cholesterol and other debris, forming fatty plaques.
Over time, this inflammatory environment weakens the fibrous cap of plaques. The immune cells secrete enzymes that degrade the cap, making plaques prone to rupture. When a plaque ruptures, it exposes thrombogenic material to the bloodstream, triggering clot formation that can abruptly block blood flow, causing a heart attack.
The Immune Players Behind Myocardial Injury
Following a heart attack, the body mounts a robust inflammatory response to clear dead cells and initiate repair. This involves neutrophils, monocytes, macrophages, and lymphocytes releasing pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α). While necessary for healing, excessive or prolonged inflammation can enlarge the infarct size and impair cardiac function.
Research led by Dr. Matthew J. Feinstein highlights "Dysregulated systemic inflammation plays a central role in the development of HFpEF, linking metabolic stress with myocardial dysfunction and structural remodeling."
Targeting Inflammation: A New Frontier in Heart Attack Prevention
Traditional therapies focus on lowering cholesterol and controlling blood pressure, but anti-inflammatory treatments are gaining ground. A recent trial led by Dr. Joseph Cheriyan demonstrated that low doses of aldesleukin, an immune-modulating drug, reduced arterial inflammation and lowered the risk of subsequent heart attacks.
Professor Ziad Mallat, a cardiovascular medicine expert, remarks, "Harnessing the body’s anti-inflammatory pathways, such as boosting regulatory T cells, could revolutionize post-heart attack care and improve long-term outcomes."
Lifestyle Factors That Influence Arterial Inflammation
Chronic inflammation is exacerbated by lifestyle choices. Obesity—especially visceral fatty accumulation—sedentary behavior, and poor diet contribute to systemic inflammation and arterial injury. Managing these factors is crucial in reducing the inflammatory burden on the cardiovascular system.
Dr. Paul M. Ridker emphasizes, "Half of all heart attacks occur in people with normal cholesterol, underscoring the importance of inflammation as an independent risk factor."
Inflammation is not merely a bystander but a central driver in the development and acute rupture of atherosclerotic plaques leading to heart attacks. As research advances, targeting inflammation offers promising new strategies to prevent and treat cardiovascular disease.
