What are the primary causes of ST-Elevation Myocardial Infarction (STEMI) in patients with a history of cardiovascular disease, including conditions like hypertension, hyperlipidemia, and diabetes mellitus?

Causes of STEMI

The overwhelming majority of STEMI cases result from complete thrombotic occlusion of a major coronary artery, triggered by physical disruption (rupture or erosion) of an atherosclerotic plaque with subsequent formation of an occluding thrombus. 1, 2

Primary Pathophysiologic Mechanism

Atherosclerotic plaque disruption with thrombotic occlusion is the causative mechanism in most STEMI cases, accounting for the vast majority of presentations 1:

• Plaque rupture exposes thrombogenic material (lipid core, collagen) to circulating blood, triggering platelet adhesion and aggregation followed by fibrin stabilization of the thrombus 1
• Plaque erosion represents a less common mechanism where thrombus forms on superficial endothelial erosion without frank rupture 1
• Concomitant coronary vasoconstriction and microembolization contribute to the reduction in coronary blood flow 1

Critical Plaque Characteristics

The vulnerability of atherosclerotic plaques depends on specific features that increase rupture risk 1:

• Thin fibrous caps with large lipid pools are particularly prone to disruption, even without significant luminal stenosis 1
• Three-quarters of infarct-related thrombi develop over plaques causing only mild to moderate stenosis 1
• Outward remodeling ("compensatory enlargement") allows substantial plaque burden without angiographic evidence of stenosis 1
• Inflammation plays a central role in plaque instability, with elevated C-reactive protein and interleukin-6 correlating with acute coronary syndrome outcomes 1

Underlying Risk Factors in Cardiovascular Disease Patients

In patients with established cardiovascular disease and traditional risk factors (hypertension, hyperlipidemia, diabetes), the pathophysiology remains atherosclerotic plaque disruption, but these conditions accelerate disease progression 1:

• Diabetes mellitus promotes endothelial dysfunction, accelerated atherosclerosis, and hypercoagulability 1
• Hypertension increases mechanical stress on vulnerable plaques and contributes to plaque instability 1
• Hyperlipidemia (particularly oxidized lipids) drives arterial inflammation, plaque expansion, and destabilization through macrophage and T-lymphocyte activation 1
• Activated macrophages and T lymphocytes at the plaque shoulder increase metalloproteinase expression, causing fibrous cap thinning and rupture 1

Less Common Causes of STEMI

While atherothrombotic occlusion dominates, clinicians must recognize alternative mechanisms 1:

• Dynamic coronary obstruction from intense focal spasm (Prinzmetal's angina) can occur on top of atherosclerotic plaques or in relatively normal vessels 1
• Coronary artery dissection should be considered, particularly in peripartum women presenting with STEMI 1
• Cocaine-induced coronary spasm represents a specific cause of dynamic obstruction leading to STEMI 1
• Secondary causes where conditions extrinsic to coronary arteries create supply-demand mismatch (fever, tachycardia, thyrotoxicosis, hypotension, anemia, hypoxemia) can precipitate STEMI in patients with underlying stenosis 1

Temporal and Triggering Factors

Understanding triggers helps identify high-risk periods 1:

• Circadian variation shows higher STEMI incidence in early morning hours due to β-adrenergic stimulation (increased vascular tone and blood pressure), blood hypercoagulability, and platelet hyper-reactivity 1
• Physical or emotional stress associated with sympathetic stimulation and vasoconstriction can trigger plaque disruption and coronary thrombosis 1
• Delay between plaque rupture and clinical consequences can extend up to 2 weeks, during which dynamic thrombosis and clot lysis occur simultaneously 1

Critical Pitfall: Patent Infarct-Related Arteries

In 25-30% of patients undergoing primary PCI, initial angiography shows a patent infarct-related artery 1, indicating:

• Dynamic thrombosis with spontaneous lysis may have occurred
• Intermittent flow obstruction and distal embolization can cause STEMI even without persistent occlusion
• This finding does not exclude the diagnosis or change the need for intervention

Prognostic Implications of Thrombus Burden

The size and composition of intracoronary thrombus directly impacts outcomes 3:

• Large thrombus burden impairs both epicardial blood flow and myocardial perfusion through major vessel occlusion and distal embolization 3
• High monocyte count on admission independently predicts high thrombus burden in STEMI patients (OR = 1.318,95% CI = 1.140-1.524) 4
• Elevated creatinine/albumin ratio predicts higher in-hospital mortality in STEMI patients without standard modifiable risk factors 5