Atherosclerosis is the most common type of arteriosclerosis, or thickening and stiffening of the arterial wall. Major risk factors include smoking, diabetes mellitus, arterial hypertension, dyslipidemia, family history of early heart disease, and advanced age. The pathogenesis is a complicated process precipitated by endothelial damage, which leads to an invasion of inflammatory cells into the tunica intima and adhesion of platelets to the disrupted endothelium. Invading smooth muscle cells (SMCs) and macrophages take up cholesterol from oxidized low-density lipoprotein (LDL) in the vessel wall. They then become foam cells, which accumulate in early atherosclerotic lesions (fatty streaks), triggering the production of extracellular matrix (e.g., collagen). This leads to the formation of fibrous plaques (foam cells, extracellular matrix, free cholesterol, and cellular debris), which may rupture and lead to thrombosis. Common sites of atherosclerosis include the abdominal aorta, coronary arteries, popliteal arteries, and carotid arteries. Depending on the location, atherosclerosis may lead to a variety of conditions, collectively known as atherosclerotic cardiovascular disease (ASCVD), which include arterial , , (CHD), (PAD), , subcortical (Binswanger disease), thrombosis (e.g., and ), and . The risk of ASCVD should be estimated in all individuals aged 40–75 years using ASCVD risk calculators (e.g., the 2013 ACC/AHA pooled cohort equations) to guide timely , such as lifestyle modifications or prophylactic statin therapy. should be recommended for individuals diagnosed with to minimize the risk of future cardiovascular events.
Arteriosclerosis: arterial wall thickening (hardening) and elasticity loss with variable pathogenesis
- Atherosclerosis (most common type of arteriosclerosis)
- (less common)
Arteriolosclerosis: hardening of the small arteries and arterioles
- Hyaline arteriolosclerosis
- Hyperplastic arteriolosclerosis
The terms “arteriosclerosis” and “atherosclerosis” are often used synonymously!
- Modifiable risk factors
- Nonmodifiable risk factors
Pathogenesis of atherosclerosis
- Chronic stress on the endothelium
Endothelial dysfunction, which leads to
- Invasion of inflammatory cells (mainly monocytes and lymphocytes) through the disrupted endothelial barrier
- Adhesion of platelets to the damaged vessel wall → platelets release inflammatory mediators (e.g., cytokines) and platelet-derived growth factor (PDGF)
- PDGF stimulates migration and proliferation of smooth muscle cells (SMC) in the tunica intima and mediates differentiation of fibroblasts into myofibroblasts
- Inflammation of the vessel wall
- Macrophages; and SMCs ingest cholesterol from oxidized LDL; and transform into foam cells.
- Foam cells accumulate to form fatty streaks (early atherosclerotic lesions).
- Lipid-laden macrophages and SMCs produce extracellular matrix (e.g., collagen) → development of a fibrous plaque (atheroma)
- Inflammatory cells in the atheroma (e.g., macrophages) secrete matrix metalloproteinases → weakening of the fibrous cap of the plaque due to the breakdown of extracellular matrix → minor stress ruptures the fibrous cap
- Calcification of the intima (the amount and pattern of calcification affect the risk of complications) 
- Plaque rupture; → exposure of thrombogenic material; (e.g., collagen) → thrombus formation with vascular occlusion or spreading of thrombogenic material
Common sites (in order of increasing frequency)
To remember the order of vessels affected by atherosclerosis (in increasing order of frequency), think of the “Die hard” plot: Bruce Willis CAtches a Perceptive Criminal named HAns.
- Weakening of vessel wall: arterial or
- Demand-supply mismatch: ; (CHD), ; (PAD), , and subcortical (Binswanger disease)
- Thrombosis and thromboembolism: ,
- : atherosclerosis of the renal artery → activation of the renin-angiotensin-aldosterone system
- Ischemic heart disease
- (including )
|Traditional ASCVD risk factors |
|Demographics||Patient history||Clinical information|
|ASCVD risk-enhancing factors|
|Abnormal laboratory findings|
2013 ACC/AHA pooled cohort equation (PCE) 
- Risk assessment calculators can be used to estimate the ASCVD risk in individuals with no history of ASCVD (see the table below for specific indications).
- PCE, which is based on , is appropriate in most instances. 
- PCE estimates the following risk categories:
- ASCVD risk categories should be used to guide patient counseling and risk reduction management : See “ASCVD prevention.” 
- Individuals with LDL ≥ 190 mg/dL or familial hypercholesterolemia are at high risk of ASCVD; PCE should not be used to assess risk in this group of individuals.
- PCE is currently only validated for African American and non-Hispanic white individuals aged 40–79 years.
- There is insufficient data to accurately estimate ASCVD risk in individuals from other races and ethnicities using PCE.
- PCE has not been validated for use in individuals older than 79 years of age.
Impact of treatment on ASCVD risk: not accounted for in the original 2013 ACC/AHA ASCVD risk calculator
- Included in the ASCVD Risk Estimator Plus (see “Tips and Links”) 
- Includes additional factors for risk estimation such as LDL cholesterol and current statin and/or aspirin therapy
- Can be used to assess ASCVD risk and to estimate the impact of therapeutic interventions during follow-up visits
Indications for risk assessment and ASCVD risk categories
ASCVD risk assessment
|Individuals with no history of ASCVD||Patients with a history of clinical ASCVD|
|Indications for risk assessment|| || |
|ASCVD risk categories || |
ASCVD risk assessment is not recommended in individuals with familial hypercholesterolemia or LDL ≥ 190 mg/dL, as these individuals are considered high risk for ASCVD regardless of the risk assessment score. 
ASCVD prevention 
- The aim of ASCVD prevention is to reduce the estimated ASCVD risk to the optimal ASCVD risk.
- Primary prevention is aimed at individuals with no prior history of ASCVD.
- Secondary prevention is aimed at patients with a previous history of ASCVD.
- Common components of primary and secondary prevention include :
- Additionally, should include management of the underlying condition. See the following for further details:
|Overview of primary prevention strategies according to ASCVD risk categories |
|All ages and risk categories|
|Age < 40 years|
|Age 40–75 years with diabetes |
or LDL ≥ 190 mg/dL
|Age 40–75 years, no diabetes, and LDL < 190 mg/dL|| |
|Age > 75 years|
Although ASCVD risk calculators are important tools for guiding primary prevention strategies in individuals with no history of ASCVD, results should always be considered in conjunction with other factors, e.g., ASCVD risk-enhancing factors, coronary artery calcium scoring, and patient preferences.
|Strategies for primary and secondary prevention of ASCVD |
|Primary prevention of ASCVD||Secondary prevention of ASCVD|
|Lifestyle modifications|| |
|Management of chronic medical conditions||Management of hypertension|
|40–75 years) (in adults aged|| |
|Management of obesity|
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