atherosclerosis background
Burden and significance of cardiovascular disease in the United States
Cardiovascular disease (CVD) imposes a profound burden on health, economy, and daily function. The CDC map of heart disease death rates from 2018 to 2020 shows geographic disparities, with darker regions indicating higher mortality and a notable concentration in the southern United States. Heart disease is the leading cause of death for men, women, and most racial and ethnic groups, and is the second leading cause of death for Pacific Islanders, Asian-Americans, American Indians, Alaska Natives, and Hispanic women. In 2022, people in the United States died from heart disease, which translates to roughly one in deaths. On average, someone dies from cardiovascular disease every seconds. Coronary artery disease (CAD), the most common form of heart disease, affects of adults and accounted for more than deaths in 2022. Notably, heart disease is not limited to older adults; about one in five CVD deaths occur in adults younger than 65. The economic burden is substantial, with costs exceeding annually in healthcare, medications, and lost productivity. From a physical therapy (PT) perspective, these statistics highlight an urgent need for action, as research indicates that over of outpatient PTs work with patients who have a diagnosed cardiovascular condition or are at significant risk for one, in at least a daily or twice-weekly caseload.
Atherosclerosis: pathophysiology and progression
The widespread burden of CVD is driven in large part by atherosclerosis, a progressive process in which fatty deposits (plaques) accumulate within arterial walls, narrowing and stiffening vessels and restricting blood flow to critical organs (heart, brain, kidneys, and limbs). The pathophysiology is commonly described by the response to injury hypothesis: endothelial damage initiates a cascade of changes. The endothelium, the innermost lining of arteries, normally acts as a selectively permeable barrier regulating macromolecule passage. When exposed to risk factors such as high cholesterol, hypertension, and smoking, endothelial integrity becomes compromised, allowing low-density lipoproteins (LDL) to accumulate in the tunica intima, the artery’s innermost layer. This triggers an inflammatory response with recruitment of immune cells, promoting plaque formation and arterial dysfunction. The earliest visible stage is the fatty streak, where lipid-laden macrophages and smooth muscle cells accumulate beneath the endothelium. Fatty streaks can be seen in individuals as young as age 12, underscoring how early atherosclerosis can begin. Over time, persistent inflammation drives progression to atheromatous plaques, which progressively narrow and stiffen the arterial lumen.
As endothelium over the plaque stretches and is disrupted, the plaque’s lipid core becomes exposed to circulating blood, creating a highly thrombogenic surface and increasing clot risk. Plaques mature, becoming more fibrous and calcified, further restricting blood flow. Calcification can be detected via imaging methods such as coronary artery calcium (CAC) scoring. At the most advanced stage, plaque rupture can trigger thrombosis that may fully occlude an artery, causing life-threatening events such as myocardial infarction (heart attack), ischemic stroke, or arterial dissection. In some cases, weakened arterial walls may form aneurysms with rupture risk. Atherosclerosis is not just a coronary disease; it affects multiple vascular beds and contributes to systemic ischemia.
Plaque evolution varies: some plaques remain stable while others slowly encroach on the lumen, and symptoms typically emerge when narrowing approaches ≈70 ag{%}, though this threshold varies between individuals. Ischemia manifests clinically as angina (cardiac ischemia in the heart) and claudication (leg pain due to reduced limb perfusion). A particularly dangerous event is plaque rupture, which exposes the plaque core to blood, triggering thrombus formation. The thrombus can rapidly grow, further narrowing or occluding the artery, causing organ infarction. Fragments may embolize to downstream vessels, causing acute events such as myocardial infarction, stroke, or critical limb ischemia. The systemic progression of atherosclerosis—narrowing arteries and ischemic damage to end organs—emphasizes the need for early detection and intervention.
Systemic distribution of atherosclerosis and clinical consequences
Atherosclerosis can target several key vascular regions:
In the heart: progressive narrowing of the coronary arteries reduces myocardial blood supply, causing angina; plaque rupture with thrombosis can lead to myocardial infarction with irreversible cardiac damage due to sustained ischemia.
In the brain: carotid or cerebral artery atherosclerosis is a leading cause of stroke. A transient ischemic attack (TIA) occurs when cerebral ischemia resolves before infarction; prolonged occlusion or embolic events can result in a cerebral vascular accident (ischemic stroke). Many ischemic strokes arise from emboli dislodging from carotid plaques, while some result from thrombosis at sites of severe atherosclerotic narrowing.
In the peripheral arteries: aortic atherosclerosis can elevate aneurysm risk, potentially rupturing and causing catastrophic hemorrhage. In the lower extremities, iliac or femoral artery narrowing leads to peripheral arterial disease (PID; commonly abbreviated as PAD in clinical practice) with exertional leg pain (claudication). Advanced stages may progress to critical limb ischemia, tissue necrosis, gangrene, and limb amputation.
The common thread across these outcomes is progressive arterial narrowing and ischemic injury to end organs, reinforcing the importance of screening, detection, and intervention.
Risk factors for cardiovascular disease: modifiable vs non-modifiable
The Framingham Heart Study—a landmark epidemiologic trial conducted in the 1950s—followed over participants for years. It demonstrated clear relationships between genetic predisposition, behavioral factors, and cardiovascular outcomes, establishing the central role of risk-factor assessment in preventing coronary heart disease. Risk factors identified fall into two categories:
Modifiable risk factors: behaviors and conditions that can be changed or managed through lifestyle or medical intervention. These include:
Smoking, which accelerates endothelial damage and promotes plaque formation.
Physical inactivity, associated with obesity.
Poor vascular health and hypertension.
Obesity and suboptimal diet, which raise cholesterol levels and contribute to inflammation and insulin resistance.
Hypertension, a major driver of endothelial injury and vascular remodeling.
Elevated LDL cholesterol, a primary contributor to atherosclerosis, and low HDL cholesterol, which normally exerts protective effects.
Diabetes, which exacerbates vascular damage and accelerates atherosclerotic changes.
Non-modifiable risk factors: inherent factors that cannot be changed, including:
Family history of cardiovascular disease, especially if a relative had an event before age 60.
Age: risk rises with advancing age.
Gender: men are at higher risk earlier in life; after menopause, women's risk increases to approach that of men.
Chronic stress, contributing to elevated blood pressure, inflammation, and stress-related behavioral risks.
These risk-factor concepts strongly influence clinical practice today. For instance, the American College of Sports Medicine (ACSM) risk-factor assessment uses many of these criteria to guide exercise testing and program design for individuals at risk. The Centers for Disease Control and Prevention (CDC) notes that nearly half of Americans have at least one of three key risk factors for heart disease: high blood pressure, high cholesterol, and smoking. For physical therapists, understanding these risk factors is essential for identifying patients at risk and incorporating preventative strategies into practice, as well as informing examination and clinical reasoning.
Implications for physical therapy practice: screening, examination, and referrals
In clinical reasoning, PTs may encounter patients with calf pain during walking and must consider cardiovascular risk factors as part of a differential diagnosis. The presence of risk factors such as smoking, hypertension, or elevated cholesterol increases the pretest probability that vascular insufficiency underlies symptoms rather than a musculoskeletal or neurologic cause. Objective examinations may include pedal pulse assessment, capillary refill, and the ankle-brachial index (ABI) to gather data on limb perfusion. If findings suggest vascular insufficiency, a timely referral for vascular evaluation is warranted, and exercise recommendations should be adjusted to account for ischemic limitations. This proactive approach enhances patient safety and functional outcomes, aligning with PTs’ role in screening and coordinating care within the broader health system.
Framingham study and its ongoing influence
The Framingham Heart Study’s long-term data continue to shape contemporary practice. It provided foundational knowledge about how genetic predisposition, lifestyle, and biological factors interact to drive cardiovascular risk. This work informed risk stratification approaches, influenced guidelines for screening and prevention, and helped establish the relationship between modifiable risk factors and coronary heart disease. Contemporary risk assessment tools used by clinicians and exercise professionals draw on the Framingham framework to estimate an individual’s baseline risk and tailor interventions accordingly.
Practical imaging and diagnostic references
The calcification of arterial plaques, detectable via imaging, is a key diagnostic marker. Coronary artery calcium scores are used to assess calcified plaque burden and inform risk stratification and management decisions. This calcification process reflects the cumulative exposure of arteries to risk factors and serves as a tangible marker of atherosclerotic disease progression.
Looking ahead: ischemic heart disease as a clinical focus
In the next session, the focus will shift to one of the most clinically significant manifestations of cardiovascular disease: ischemic heart disease. This will build on the pathophysiology, risk factors, and systemic implications outlined here, and it will connect to practical assessment and intervention strategies for PTs.