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Atherosclerosis

Last updated: September 16, 2021

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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 aneurysms, dissection, coronary heart disease (CHD), peripheral artery disease (PAD), intestinal ischemia, subcortical vascular dementia (Binswanger disease), thrombosis (e.g., acute coronary syndrome and stroke), and renovascular hypertension. 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 primary prevention strategies for ASCVD, such as lifestyle modifications or prophylactic statin therapy. Secondary prevention strategies for ASCVD should be recommended for individuals diagnosed with clinical ASCVD to minimize the risk of future cardiovascular events.

The terms “arteriosclerosis” and “atherosclerosis” are often used synonymously!


References:[1][2]

  • Leading cause of vascular disease worldwide
  • Sex: >

Epidemiological data refers to the US, unless otherwise specified.

The term metabolic syndrome refers to the presence of at least 3 of the following risk factors: obesity, elevated triglycerides, low high-density lipoprotein (HDL), diabetes mellitus, and arterial hypertension. [4]

Pathogenesis of atherosclerosis

  1. Chronic stress on the endothelium
  2. Endothelial dysfunction, which leads to
  3. Inflammation of the vessel wall
  4. Macrophages and SMCs ingest cholesterol from oxidized LDL and transform into foam cells.
  5. Foam cells accumulate to form fatty streaks (early atherosclerotic lesions).
  6. Lipid-laden macrophages and SMCs produce extracellular matrix (e.g., collagen) → development of a fibrous plaque (atheroma)
  7. 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
  8. Calcification of the intima (the amount and pattern of calcification affect the risk of complications) [7][8]
  9. 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.

Atherosclerotic diseases

References:[1][9][10][11][12]

Definition [13]

ASCVD or clinical ASCVD is an umbrella term for a group of conditions that affect the cardiovascular system and are most likely due to atherosclerosis. Examples include:

ASCVD risk assessment

Traditional ASCVD risk factors

Traditional ASCVD risk factors are a set of ASCVD risk factors included in the 2013 ACC/AHA pooled cohort equations (PCE) and used to estimate the risk of future clinical ASCVD.

Traditional ASCVD risk factors [14]
Demographics Patient history Clinical information
  • Age
  • Sex
  • Race

ASCVD risk-enhancing factors [15]

ASCVD risk-enhancing factors are factors associated with ASCVD that are not part of the PCE. They are used to guide primary prevention strategies for ASCVD. [16]

ASCVD risk-enhancing factors
Family history
  • Premature ASCVD in a first-degree relative < 55 years of age () or < 65 years of age ()
Medical history
Comorbidities
Abnormal laboratory findings
Other

2013 ACC/AHA pooled cohort equation (PCE) [14][17][18]

  • Overview
  • Important considerations
    • 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 nonhispanic 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”) [17][18][22][23]
    • 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

PCE should only be used in individuals with no history of ASCVD or familial hypercholesterolemia, who are not on statin therapy, and who have LDL cholesterol < 190 mg/dL. [17]

Indications for risk assessment and ASCVD risk categories

ASCVD risk assessment should be guided by clinical history, age-specific screening for traditional ASCVD risk factors, and identification of ASCVD risk-enhancing factors; see also screening for lipid disorders, screening for hypertension, and screening for diabetes mellitus.

ASCVD risk assessment

Individuals with no history of ASCVD Patients with a history of clinical ASCVD
Indications for risk assessment
  • All individuals aged 40–75 years (universal screening)
    • PCE calculates the 10-year ASCVD risk in this age group. [14]
    • Screening frequency should be individualized (not specifically defined).
  • Consider risk assessment in individuals aged 21–39 years. [19][20]
ASCVD risk categories [17]
  • Estimate the ACSVD risk using a risk-assessment calculator (e.g., PCE ). [19][20]
  • 10-year ASCVD risk categories (in individuals aged 40–75 years) [17]
    • Low risk: < 5%
    • Borderline risk: 5% to < 7.5%
    • Intermediate risk: 7.5% to < 20%
    • High risk: ≥ 20%
Further management

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. [17]

ASCVD prevention [17][21]

Overview of primary prevention strategies according to ASCVD risk categories [17]
All ages and risk categories
  • Reinforce adherence to healthy lifestyle practices.
  • Address any modifiable risk factors.
  • See “Primary prevention of ASCVD” for details (only the main interventions are detailed in this table).
Age < 40 years
Age 40–75 years with diabetes
or LDL ≥ 190 mg/dL
  • Initiate statin therapy regardless of risk category.
Age 40–75 years, no diabetes, and LDL < 190 mg/dL
  • Low risk: < 5%
    • Reinforce adherence to healthy lifestyle practices.
    • Address any modifiable risk factors.
  • Borderline risk: 5% to < 7.5%
  • Intermediate risk: 7.5% to < 20%
  • High risk: ≥ 20%
Age > 75 years
  • Discuss ASCVD preventive strategies based on life expectancy, comorbidities, and a risk-benefit assessment of preventive interventions.

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 [17][21][22][23]
Primary prevention of ASCVD Secondary prevention of ASCVD
Lifestyle modifications
  • Dietary modification with a heart-healthy diet
    • Replacement of saturated fat with monounsaturated and polyunsaturated fats
    • Reduced dietary cholesterol
    • Reduced dietary sodium intake (ideally < 1,500 mg/day) [17]
  • Exercise (ideally, the equivalent of one of the following per week) :
    • ≥ 150 minutes of moderate-intensity exercise
    • ≥ 75 minutes of high-intensity aerobic exercise
  • Smoking cessation (see “Counseling on smoking cessation”)
  • Limit alcohol use to ≤ 2 drinks/day () or ≤ 1 drink/day ()
Management of chronic medical conditions Blood pressure control
Cholesterol management
  • Consider high-intensity statin therapy for all patients.
  • Consider combination therapy for patients at very high risk for ASCVD and with LDL ≥ 70 mg/dL on the maximally tolerated statin dose.
Diabetes mellitus
  • Glycemic control: lifestyle modifications and medications as needed (see “Treatment” in “Diabetes mellitus”)
Overweight and obesity
Antiplatelet therapy
  • Consider low-dose aspirin for patients with all of the following : [17]

Remember the ABCDS of ASCVD primary and secondary prevention: Aspirin (if there are indications), Blood pressure control, Cholesterol management, Diabetes management, Smoking cessation. [21]

Smoking cessation is one of the most effective interventions to reduce all-cause mortality and prevent recurrent vascular events in patients with ASCVD! [28]

Interested in the newest medical research, distilled down to just one minute? Sign up for the One-Minute Telegram in “Tips and links” below.

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