What are the causes of blocked coronary arteries in adults, particularly those with high cholesterol, hypertension, diabetes, and a family history of heart disease?

Causes of Blocked Coronary Arteries

Blocked coronary arteries result primarily from atherosclerosis—a chronic inflammatory process driven by lipid accumulation in the arterial wall, accelerated by traditional cardiovascular risk factors including hypercholesterolemia, hypertension, diabetes mellitus, smoking, and family history of premature coronary disease. 1

Primary Pathophysiological Mechanism

Atherosclerosis represents the core pathological process underlying coronary artery blockage 1. The disease progresses through distinct stages:

• Initial endothelial dysfunction precedes visible atherosclerotic changes and represents the earliest manifestation of coronary disease 1
• Extracellular lipid accumulation in the subintima progresses to the fibrofatty stage 1
• Fibrous cap formation with underlying lipid core develops, which may subsequently weaken 1
• Plaque disruption triggers thrombogenesis, leading to acute coronary syndromes when the fibrous cap ruptures 1

The process is now recognized as an inflammatory/immunomodulatory reaction to oxidized low-density lipoproteins within the arterial wall, with macrophages, T lymphocytes, and mast cells playing central roles in both development and progression to high-risk phenotypes 2.

Major Modifiable Risk Factors

Hypercholesterolemia

• Elevated LDL cholesterol is a major contributor to atherosclerotic plaque accumulation 1
• The extent of atherosclerotic lesions rises exponentially with increasing number of risk factors present 1
• Aggressive treatment of lipid abnormalities may prevent or slow atherosclerosis progression when initiated early 1

Hypertension

• Hypertension accelerates endothelial injury and plaque formation 1
• Systolic blood pressure >160 mm Hg or diastolic >100 mm Hg requires lifestyle advice and drug treatment if sustained 3
• Left ventricular hypertrophy resulting from hypertension confers additional risk, with a hazard ratio of 1.45 for each 50 g/m² increment in LV mass 3
• The combination of hyperglycemia with high systemic blood pressure independently predicts worse outcomes beyond plaque progression 4

Diabetes Mellitus

• Diabetes significantly increases CAD risk and is considered a coronary heart disease risk equivalent 1
• Patients with diabetes are at particularly high risk and should be treated as coronary disease equivalents 3, 1
• High fasting plasma glucose (diabetes or fasting plasma glucose >100 mg/dL) is independently associated with rapid plaque progression 4
• The combination of hyperglycemia with low HDL-C (high-density lipoprotein cholesterol <40 mg/dL in males and <50 mg/dL in females) is associated with rapid plaque progression independently of other risk factors 4
• Accelerated atherosclerosis in diabetes occurs through mechanisms unique to diabetes including non-enzymatic glycation of proteins, oxidative modification of lipoproteins, and propensity to thrombosis 5

Cigarette Smoking

• Smoking causes direct vascular injury and oxidative stress 1
• Smoking is among the characteristics that most improve predictive accuracy in CAD risk models 6
• Active or recent smoking substantially increases the probability of ischemic heart disease 3

Low HDL Cholesterol

• Low HDL cholesterol independently predicts cardiovascular disease incidence 1
• When combined with hyperglycemia, low HDL-C is independently associated with rapid plaque progression 4

Family History as a Non-Modifiable Risk Factor

Family history of premature CAD represents the net effect of shared genetic, biochemical, and environmental components 3:

• A positive family history (heart attack, treated angina, or coronary procedures in a male first-degree relative before age 55 or female before age 65) is an important independent risk factor 3
• The risk associated with positive family history persists even after adjusting for coexistent risk factors, with a 1.5- to 2.0-fold relative risk 3
• Sibling history of premature CAD has a stronger relationship than parental history 3
• The strength of risk increases with younger age of onset, increasing numbers of relatives affected, and the relative's genealogical proximity 3
• Almost 75% of those with premature CHD have a positive family history 3
• At least 60 independent genetic loci contribute to CAD susceptibility, with each individual locus contributing a small effect 1

Additional Contributing Factors

Obesity and Physical Inactivity

• Obesity affects blood pressure, lipid metabolism, and glucose tolerance through multiple mechanisms 1
• Physical inactivity represents a significant modifiable risk factor 1

Dietary Factors

• Atherogenic diet high in saturated fats and low in fruits/vegetables contributes to disease development 1

Socioeconomic Stress

• Socioeconomic and psychosocial stress independently contribute to disease development 1

Expanded Pathophysiological Mechanisms Beyond Simple Blockage

Macrovascular Level

• Fixed flow-limiting stenoses in large or medium coronary arteries contribute to disease 1
• Diffuse atherosclerotic lesions without identifiable luminal narrowing cause ischemia under stress 1
• Dynamic epicardial vasospasm causes transient ischemia 1

Microvascular Level

• Coronary microvascular dysfunction (CMD) is increasingly recognized as prevalent across the entire chronic coronary syndrome spectrum 1
• Functional and structural microcirculatory abnormalities can cause angina and ischemia even without obstructive epicardial disease 1

Critical Integration

• Risk factors that promote epicardial atherosclerosis simultaneously cause endothelial dysfunction and abnormal vasomotion throughout the entire coronary tree, including the arterioles regulating coronary flow and resistance 1
• Multiple mechanisms of ischemia act concomitantly in individual patients 1

Early Development and Progression

• Fatty streaks are present in coronary arteries in 50% of children and 85% of young adults 1
• Fibrous plaques increase from 8% prevalence in childhood to 69% in young adulthood 1
• Cardiovascular risk factors measured in childhood significantly correlate with extent of coronary atherosclerotic lesions 1
• Autopsy studies show atherosclerotic lesion prevalence ranging from 17% at age 20 to 85% at age 50 1

Common Pitfalls to Avoid

Do not assume that traditional risk factors in isolation determine atherosclerosis severity—the relationship between CHD events and atherosclerosis is imprecise, and multivariate analyses struggle to adequately differentiate between the mutual inter-relationships, genetic influence, and age dependence of hypercholesterolemia, hypertension, diabetes, and obesity 7. Instead, recognize that multiple risk factors cluster together and confer substantially increased cardiovascular risk compared to single risk factors 6, 1.

Do not overlook the importance of tight control of all modifiable risk factors simultaneously—therapeutic strategies must achieve tight control of hyperglycemia, hypertension, and hyperlipidemia in addition to smoking cessation and weight management 5.