This article explains atherosclerosis, a condition where fatty deposits build up in arteries, causing heart attacks, strokes, and other serious health problems. It affects over 37% of adults in the US and causes 31% of global deaths. Key factors include LDL ("bad") cholesterol, inflammation, and risk factors like high blood pressure and smoking. Treatments exist but face challenges in global access. Understanding how plaques form and progress helps patients manage risks.

Atherosclerosis: Causes, Risks, and Prevention

Table of Contents

• Key Points
• Background/Introduction
• Epidemiology
• How Atherosclerosis Starts
• Plaque Progression
• Diagnosis and Risk Assessment
• Management and Prevention
• Clinical Implications
• Limitations
• Patient Recommendations
• Frequently Asked Questions
• Source Information

Key Points

• Atherosclerosis involves fatty plaque buildup in arteries, leading to heart attacks and strokes.
• LDL cholesterol above 20-30 mg/dL enables plaque formation; inflammation and endothelial damage contribute.
• Statins reduce LDL by 30-60% and lower heart attack risk; PCSK9 inhibitors reduce LDL by 60%.
• Global treatment access is unequal, with 75% of CVD deaths in low/middle-income countries.
• Lifestyle changes like quitting smoking and reducing salt can lower risk.

Background/Introduction

Atherosclerosis develops when fatty material builds up in the inner layer of arteries (the intima). The term means "gruel" in Greek, describing the plaque's fatty core. These plaques can:

• Block blood flow, starving tissues of oxygen
• Rupture suddenly, causing life-threatening blood clots

This condition causes most heart attacks (myocardial infarctions), many strokes, and peripheral artery disease that can lead to limb amputations. Researchers emphasize that while treatments have improved outcomes, global access remains unequal. Understanding atherosclerosis is crucial because early intervention saves lives – most patients now survive acute events with proper care.

Epidemiology

Atherosclerotic cardiovascular disease (CVD) is the world's leading cause of death:

• 17 million+ deaths in 2015 (31% of global deaths)
• 7.4 million from coronary heart disease

6.7 million

• from strokes annually

In the US:

• 37.4% of men and 35.9% of women over 20 have CVD
• Higher prevalence in Black individuals (46.0% men, 47.7% women) vs. White individuals (37.7% men, 35.1% women)

Despite treatment advances:

• 75% of CVD deaths occur in low/middle-income countries
• Treatment access gaps exist globally, with only 33.2% of US patients achieving optimal LDL reduction in 2005-2008

Major risk factors include smoking, poor diet, physical inactivity, and obesity – with the obesity epidemic threatening progress.

How Atherosclerosis Starts

Atherosclerosis requires LDL cholesterol particles carrying cholesterol through blood. Key facts:

• Levels above 20-30 mg/dL (0.5-0.8 mmol/L) enable plaque formation
• Genetic evidence confirms LDL's causal role – people with familial hypercholesterolemia develop early CVD

How LDL causes damage:

1. LDL particles enter artery walls through damaged endothelium (blood vessel lining)
2. They oxidize (chemically change) in the artery wall
3. Oxidized LDL triggers inflammation and immune responses

Other key contributors:

• Inflammation: Immune cells respond to oxidized LDL, releasing chemicals that worsen plaque growth
• Endothelial dysfunction: Risk factors like high blood pressure damage blood vessel lining, allowing LDL entry
• Disturbed blood flow: Plaques form where blood flow is turbulent (e.g., artery branches)

Other risk factors include hypertension, diabetes, and smoking – all linked to inflammation. Biomarkers like hsCRP (high-sensitivity C-reactive protein) indicate inflammation levels and predict CVD risk.

Plaque Progression

Once initiated, plaques grow through:

• Foam cell formation: Immune cells (macrophages) engulf LDL, becoming fat-filled "foam cells"
• Smooth muscle migration: Muscle cells from artery walls move into plaques, producing collagen
• Extracellular matrix buildup: Collagen and other proteins form a fibrous cap over the fatty core

Advanced plaques contain:

1. Lipid core (cholesterol deposits)
2. Fibrous cap (collagen layer)
3. Calcium deposits

Plaques become dangerous when:

• Fibrous caps thin and rupture (Fig. 3)
• Blood clots form on ruptured plaques, blocking arteries
• Plaques grow large enough to restrict blood flow

T cells (immune cells) regulate this process – some types promote plaque growth while others protect against it.

Diagnosis and Risk Assessment

Doctors use multiple tools to assess atherosclerosis risk and severity:

Risk assessment considers both traditional factors (cholesterol, blood pressure) and emerging markers like inflammation levels.

Management and Prevention

Proven therapies include:

• Statins: Reduce LDL by 30-60%, lowering heart attack risk
• PCSK9 inhibitors: New drugs that reduce LDL by 60% in resistant cases
• Blood pressure control: Reduces strain on arteries

Between 1999-2008, US treatment rates for high LDL increased from 28.4% to 48.1%, with more patients achieving target levels. Global initiatives like WHO's Global Hearts aim to improve prevention through:

1. Tobacco control
2. Salt reduction in foods
3. Strengthened primary care

Despite progress, medication access remains unequal worldwide.

Clinical Implications

For patients, atherosclerosis can cause:

• Heart attacks when coronary arteries block
• Strokes from blocked brain arteries
• Peripheral artery disease causing leg pain or gangrene

Critical advances mean:

• Most patients survive acute events with timely treatment
• Early intervention reduces complications by 40%
• Heart failure remains a concern after major events

However, 18% of disability-adjusted life years are lost to CVD in wealthy nations, with higher burdens in developing countries.

Limitations

Important unanswered questions include:

• Oxidized LDL role: Strong in animals but unproven in humans
• Antioxidant therapies: Failed in clinical trials (e.g., succinobucol study)
• HDL cholesterol: High levels correlate with lower risk but raising it doesn't improve outcomes

Research gaps:

1. How exactly risk factors trigger plaque formation
2. Why plaques rupture unpredictably
3. How to reduce residual risk despite current treatments

Global challenges include unequal treatment access and rising obesity rates.

Patient Recommendations

Action steps to reduce risk:

1. Know your numbers:
   • Target LDL: Below 70 mg/dL if high risk
   • Blood pressure: Under 120/80 mmHg
2. Medication adherence:
   • Take prescribed statins consistently
   • Ask about PCSK9 inhibitors if LDL remains high
3. Lifestyle changes:
   • Quit smoking (doubles CVD risk)
   • Reduce dietary salt to <5g/day
   • Exercise 150+ minutes/week
4. Monitoring:
   • Get regular hsCRP tests if high risk
   • Discuss calcium scoring with your doctor

If diagnosed:

• Attend all cardiac rehabilitation sessions
• Report new chest pain or leg discomfort immediately
• Join support groups for medication adherence

Frequently Asked Questions

What is atherosclerosis and how does it cause heart attacks?

Atherosclerosis is a condition where fatty deposits, called plaques, build up in the inner layer of arteries. These plaques can block blood flow or rupture suddenly, causing blood clots that lead to heart attacks or strokes. The article explains that plaques form when LDL cholesterol enters artery walls, oxidizes, and triggers inflammation.

What are the main risk factors for atherosclerosis?

Major risk factors include high LDL cholesterol, high blood pressure, smoking, diabetes, poor diet, physical inactivity, and obesity. The article notes that inflammation, measured by hsCRP, also predicts risk. Genetic conditions like familial hypercholesterolemia cause early disease. These factors damage the endothelium and promote plaque formation.

How is atherosclerosis diagnosed and treated?

Doctors use blood tests for LDL and hsCRP, stress testing, CT scanning for calcium deposits, and coronary arteriography. Proven treatments include statins to lower LDL by 30-60% and PCSK9 inhibitors for resistant cases. Blood pressure control and lifestyle changes like quitting smoking and exercise are also recommended.

Why does atherosclerosis come back after treatment?

The article explains that despite treatments, plaques can still progress or rupture unpredictably. Residual risk remains due to factors like inflammation not fully addressed by LDL-lowering drugs. Research gaps include why plaques rupture and how to reduce this risk. Medication adherence and lifestyle changes are crucial to manage ongoing risk.

What does an LDL cholesterol level above 20-30 mg/dL mean for my risk of atherosclerosis?

LDL cholesterol levels above 20-30 mg/dL (0.5-0.8 mmol/L) enable plaque formation in arteries. This is based on genetic evidence showing that people with familial hypercholesterolemia, who have very high LDL, develop early cardiovascular disease. Keeping LDL as low as possible reduces the risk of atherosclerosis and its complications.

How does high blood pressure contribute to the development of atherosclerosis?

High blood pressure damages the endothelium, the lining of blood vessels. This damage allows LDL cholesterol particles to enter the artery wall, where they become oxidized and trigger inflammation. This process is a key step in the initiation of atherosclerosis, so controlling blood pressure is important for prevention.

What is a calcium score test and what does it detect?

A calcium score test is a type of CT scanning that detects calcium deposits in the arteries. These deposits are a sign of advanced atherosclerotic plaques. The test helps doctors assess the severity of atherosclerosis and predict cardiovascular risk, guiding decisions about treatment.

Source Information

Original Article: "Atherosclerosis"
Authors: Peter Libby, Julie E. Buring, Lina Badimon, Göran K. Hansson, John Deanfield, Márcio Sommer Bittencourt, Lale Tokgözoğlu, Eldrin F. Lewis
Published in: Nature Reviews Disease Primers (2019)
Note: This patient-friendly article is based on peer-reviewed research