Introduction

Different blood vessel (vascular) conditions often present with similar symptoms but have diverse underlying causes. The features of such conditions are crucial for ensuring an accurate diagnosis and effective management. This is true for fibromuscular dysplasia (FMD) and atherosclerosis, two distinct vascular diseases with some common characteristics. 

FMD is a rare, idiopathic condition, which causes abnormal cell growth within the arterial walls of any artery, but most commonly the renal and carotid arteries. This condition causes narrowing of the arteries (stenosis), bulging, or a string-of-beads appearance, restricting blood flow to specific areas. Depending on the affected site, it can result in hypertension, stroke, and other vascular complications.¹ 

On the other hand, atherosclerosis is a common, progressive condition characterised by plaque build-up inside the arteries, which also restricts blood flow and causes hardening of the arteries. This condition manifests with various signs and symptoms and can lead to numerous cardiovascular diseases (CVDs).²

The epidemiological data greatly diverges between the two conditions. FMD is much less common, with the median onset of the disease being 48 years and uncertainty about its exact prevalence in the general population. However, a large study on healthy candidates for renal transplant documented a 3-4% prevalence.³ 

Furthermore, FDI is predominantly found in people assigned female at birth (AFAB) compared to those assigned male at birth (AMAB), with a 3:1 ratio.¹ Contrarily, atherosclerosis is a common and major cause of multiple CVDs, affecting hundreds of thousands of people worldwide.⁴ More details help to form a clearer picture of these two diseases and distinguish them for more accurate treatment.

Causes, risk factors and pathophysiology

Fibromuscular dysplasia

The exact aetiology of FMD remains unknown, however, several factors have been associated with the disease including:

• Genetics: An inheritance pattern is speculated as a potential contributor to FMD. However, the rarity and multitype profile of FMD make it difficult to accumulate evidence for a clear genetic contribution^1,5
• Hormonal influences: The disparity of FMD noticed between people AFAB and those AMAB could propose that sex hormones play a significant role in the disease onset and physiology. Nonetheless, a clear connection has not been stated as very limited data is available on hormones and hormonal supplementation and pathogenesis of FMD⁶
• Environmental factors: Cigarette smoking seems to potentially increase the risk of FMD although further studies are needed to certify this relationship⁵
• Other disorders: Numerous other disorders have been associated with FMD, including Marfan syndrome, Williams syndrome, tuberous sclerosis, pheochromocytoma and more¹

As mentioned above FMD can involve any small and medium arteries, but is most commonly found in renal arteries, at 58% of all cases, and craniocervical arteries at 32% of cases. Different types of FMD have been identified which can coexist, leading to a classification system based on the appearance of the arterial beds upon angiography:⁵

• Multifocal FMD: The vessels have the characteristic string-of-beads appearance
• Focal FMD: Arterial stenosis or lesions occurring at any arterial segment

Atherosclerosis

Atherosclerosis involves plaque formation in the inner arterial wall, a long process that occurs through specific stages:⁴

1. Some arterial areas are predisposed to atherosclerosis, where fatty streaks are formed. These flat, yellow lesions composed of foam cells, deposit on the inner arterial lining (endothelium), where they ingest low-density lipoproteins (LDL) cholesterol. As lipid accumulation continues, inflammation also occurs
2. Smooth muscle cells migrate to the endothelium, forming a protective layer, known as a fibrous cap, over the lipid-rich core, creating a stable plaque
3. As the disease progresses the plaque grows, narrowing the artery and limiting blood flow, while the fibrous cap thins and becomes prone to rupture
4. Eventually, the plaque either ruptures or erodes, triggering blood clot (thrombus) formation and leading to complete or partial blockage of blood flow, causing acute cardiovascular events like stroke

Many risk factors have been identified for atherosclerosis, some of which are modifiable while others are not. These include:^7,8

• Age: Atherosclerosis may start early and progresses with ageing. Most cardiovascular events are predominantly seen in the elderly, with heart attacks and strokes mostly occurring in individuals above the age of 55
• Genetics and family history: Hundreds of genetic traits and gene variations have been identified to play a significant role in the development of atherosclerosis. Inheritance of common or rare atherosclerotic-contributing genes increases the susceptibility of individuals to developing CVDs
• Sex hormones: Studies have shown that oestrogens have a protective mechanism against CVDs. Data suggests that people AMAB have a higher risk of developing atherosclerosis at a younger age compared to those AFAB, but the risk reverses after menopause, due to the drastic decrease in oestrogen levels
• Diabetes: Type II diabetes and metabolic syndrome dysregulated blood sugar levels and contribute to atherosclerosis by modifying LDL levels and increasing inflammation 
• Overweight/obesity: Just like other infectious conditions and autoimmune disorders, these states exacerbate atherosclerotic risk because of the presence of chronic inflammation
• High cholesterol and high lipid levels: High LDL levels as seen in familial hypercholesterolaemia, low levels of specific protective high-density lipoproteins types, and triglyceride-rich lipoproteins have all been associated with an elevated risk for atherosclerosis
• Hypertension
• Smoking
• Unhealthy diet
• Lack of exercise

Signs and symptoms

FIbromuscular dysplasia

The clinical symptoms of FMD depend on the affected site and the severity of the lesions. Some patients may be completely asymptomatic, while others may not. Below are some of the documented symptoms for the two most common FMD locations.

In FMD of the renal arteries, the most common symptoms are:^5,6

• Resistant hypertension
• Abdominal or flank bruit
• Flank pain
• Renal aneurysm
• Renal infarction
• Renal artery dissection
• Chronic kidney disease
• Headaches

FMD in craniocervical arteries manifests with symptoms such as:^5,6

• Cervical bruit
• Headache (often migraine headache)
• Pulsatile tinnitus and other types of tinnitus
• Neck pain
• Dizziness
• Transient ischemic attack (TIA)
• Stroke
• Subarachnoid haemorrhage 
• Carotid and intracerebral aneurysms
• Cervical artery dissection
• Horner syndrome

Atherosclerosis

Atherosclerotic symptoms may not be noticeable at first, as plaque build-up and inadequate blood supply progressively happen with ageing. Symptoms vary and depend on the affected arteries but generally include discomfort, cold sweats, dizziness, tiredness, and erectile dysfunction.⁹

In coronary arteries symptoms and other resulting conditions include:⁹ 

• Heart-related symptoms like palpitations, chest pain or discomfort during exercise
• Coronary artery disease
• Angina Pectoris
• Heart attack

In cerebral and carotid arteries:⁹

• Neurological deficits like weakness, difficulty in speech, problems with vision and cognitive impairment like dementia, and brain damage
• Ischemic stroke
• TIA

In renal arteries, atherosclerosis can lead to resistant hypertension and kidney damage.⁹

In peripheral arteries, affecting the limbs:⁹

• Claudication
• Skin sores and tissue death

Diagnostic evaluation

FIbromuscular dysplasia

The disease’s rarity has provided only a little evidence of the accuracy of the various diagnostic approaches for FMD, but currently, the standard methods used include non-invasive imaging techniques like:⁵

• Catheter-based angiography: This minimally invasive procedure is the gold standard for diagnosing and treating renal FMD. It detects the typical string-of-beads appearance or stenosis in renal arteries and can also be used for cerebrovascular FMD
• Duplex ultrasound: This tool provides a valuable, non-invasive approach to diagnosing renal and carotid artery FMD but has some limitations in imaging branch arteries and aneurysms
• Computed tomographic angiography (CTA): CTA is another reliable method for assessing renal FMD, though with lower sensitivity for mild lesions, and arterial branches. It can also be used for carotid and vertebral arteries, particularly for detecting cerebral aneurysms but with limitations in subtler lesions
• Magnetic resonance angiography (MRA): MRA is a radion-free screening tool, suitable for younger patients and those who cannot receive intravenous contrast for CTA. It offers high sensitivity for the feature of FMD but also has limitations

Atherosclerosis

An effective evaluation method for atherosclerotic CVDs is done by measuring the associated risk factors, i.e., by checking LDL and plasma glucose levels. Further screening tests are available for the diagnosis of atherosclerosis and other related diseases and include:⁴

• Abdominal and carotid ultrasound
• Doppler measurements for peripheral artery disease
• Electrocardiogram
• Electron beam computed tomography
• Angiography
• CTA
• Cardiac magnetic resonance imaging

Treatment options

FIbromuscular dysplasia

The current management for FMD relies on relieving symptoms and controlling risk factors such as smoking. The medical management of hypertension with pharmacological agents such as ACE inhibitors, angiotensin II receptor blockers, diuretics, calcium channel blockers, or beta-blockers is recommended, with continuous monitoring of kidney function. Antiplatelet and anticoagulation therapies are provided in some cases to prevent ischemic results. Finally, revascularisation and angioplasty may be performed in more severe cases of stenosis, aneurysm, or dissection.¹

Atherosclerosis

Atherosclerosis management begins with holistic lifestyle modifications to address modifiable risk factors, such as reducing dietary fat intake to lower blood cholesterol, quitting smoking, and increasing physical activity. Medications like statins are commonly prescribed to reduce cholesterol, along with other agents that address any underlying conditions like hypertension or high blood sugar.⁸

Summary

FMD and atherosclerosis are two distinct vascular diseases with overlapping characteristics. FMD is a rare condition that involves abnormal cell growth on arterial walls, leading to narrowing, bulging, or the typical string-of-beads appearance, predominantly affecting renal and craniocervical arteries. In contrast, atherosclerosis is a common, progressive disease caused by plaque build-up in various arteries, including renal and carotid arteries. 

Both conditions lead to arterial narrowing and reduced blood flow and can result in more severe vascular complications. Depending on the affected arteries, both conditions can manifest with similar symptoms including headache, hypertension, and potential kidney damage. Only an effective diagnosis using the appropriate imaging techniques can identify the exact arterial abnormalities and differentiate between FMD and atherosclerosis. The best treatment options for either condition can then be selected, depending on the arterial site and severity of the disease and can include lifestyle modifications, pharmacotherapy, and in some cases, other invasive procedures.