Aortic Sclerosis

Aortic Sclerosis 

• Aortic sclerosis is thickening or calcification of the aortic valve in absence of valve obstruction
• Aortic sclerosis is the precursor to aortic stenosis, in which progressive valve thickening causes obstruction of blood flow through the valve and out the heart

Epidemiology

• Common in elderly people
• Observed in a quarter of patients older than 65 years
• Observed in half of patients older than 80 years
• Progressive aortic valve leaflet thickening can lead to increased stiffness, valve obstruction, and transition to aortic stenosis
• Prospective studies suggest disease progresses from aortic sclerosis to aortic stenosis in 1 of 8 patients

Etiology

• Etiology of aortic sclerosis and early stage of aortic stenosis (initiation phase) includes:
  • Lipid deposition
  • Inflammatory processes involving endothelial damage
  • Profibrotic pathways
  • Genetic factors
• Mechanical stress causes endothelial damage and infiltration of inflammatory cells and lipids—such as LDL and lipoprotein (a)—in the valve
• Resident valve interstitial cells develop a fibroblast then an osteoblast phenotype; these cells coordinate fibrosis, calcification, and thickening of the valve
• Later stages of aortic stenosis (propagation phase) are characterized by a vicious cycle of calcification, mechanical leaflet injury, inflammation, fibrosis, and further calcification

Risk Factors

• Clinical risk factors for aortic sclerosis are similar to atherosclerosis and include:
  • Smoking
  • Hypertension
  • Hyperlipidemia
  • Elevated lipoprotein (a) levels
  • Diabetes
  • Metabolic syndrome
• Disturbances in bone metabolism also are associated with aortic sclerosis, notably serum phosphate concentrations
• No data suggest that appropriate calcium supplementation in patients with osteoporosis increases risk of valve calcification or aortic sclerosis
• Risk factors for later disease progression and the propagation phase of disease relate more closely to markers of mineral metabolism and the baseline calcium burden in the valve
• Individuals with bicuspid aortic valves have a higher incidence of aortic sclerosis
• Genetic risk factors
  • Although not classically an inherited condition, several genes have been associated with increased risk of valve leaflet calcification, including:
    • A single-nucleotide polymorphism located in an intron of the lipoprotein (a) gene (rs10455872) has been associated with incident aortic valve calcification
    • PALMD (palmdelphin) on chromosome 1p21.2 has been associated with calcific aortic valve stenosis
    • A weighted genetic risk score for LDL cholesterol demonstrated an association with aortic valve calcium and incident aortic stenosis in a Mendelian randomization study
    • The NOTCH1 receptor has been associated with a variety of aortic valve problems (eg, bicuspid aortic valve) and with aortic valve calcification

Approach to Diagnosis

• Aortic sclerosis is an asymptomatic condition
• Diagnosis is made as an incidental finding during any of the following:
  • Physical examination: murmur detection
  • Echocardiography: thickened valve leaflets in absence of valve obstruction
  • CT: calcific deposits observed in the valve leaflets
• Echocardiography is used to differentiate between aortic sclerosis and aortic stenosis and to identify other causes of a systolic murmur
• Both aortic stenosis and aortic sclerosis are characterized by valve thickening, but in aortic stenosis, evidence of valve obstruction is also present

Diagnostic Criteria

• Echocardiography: aortic valve thickening visible
• CT: evidence of calcific leaflet deposits visible
• Doppler echocardiography: peak aortic valve jet velocity of less than 2 m/second

Workup

History

• Aortic sclerosis is an asymptomatic condition

Physical Examination

• May be associated with a midsystolic murmur best heard over the right second intercostal space
  • Murmur generally is brief and often is not loud
  • Murmur does not radiate and is associated with a normal carotid pulse and second heart sound
• Many patients with aortic sclerosis do not have a murmur

Imaging Studies

Echocardiography

• Diagnosis is based on 2 findings:
  • Irregular leaflet thickening and focal increased echogenicity (calcification)
  • No obstruction to aortic valve flow. Peak continuous wave Doppler flow velocities across the valve are normal (less than 2 m/second)

Ct

• Calcification of the aortic valve leaflets can be seen on both contrast and non–contrast media-enhanced CT scans of the heart
• Sometimes, valve leaflet calcification can be appreciated on non–ECG-gated CT scans performed for noncardiac indications, although cardiac motion can make interpretation challenging
• Occasionally, irregular noncalcific leaflet thickening may be seen
• All of these observations suggest either aortic sclerosis or aortic stenosis; diagnosis is differentiated based on Doppler echocardiographic findings

Other Diagnostic Tools

• Increased valve thickening can sometimes be appreciated on cardiovascular MRI

Differential Diagnosis

Condition	Description	Differentiated by
Aortic stenosis	Aortic valve thickening and stiffening associated with obstruction to flow	Ejection systolic murmurIncreased Doppler jet velocities are present across aortic valve in aortic stenosis but not in aortic sclerosis
Supravalvular aortic stenosis	Stenosis originating in aorta above aortic valve	Midsystolic murmurEchocardiography or cardiovascular MRI identifies obstruction above level of aortic valve
Subvalvular aortic stenosis	Stenosis originating below aortic valve in left ventricular outflow tract	Midsystolic murmurEchocardiography or cardiovascular MRI identifies obstruction below levels of aortic valve
Mitral regurgitation	Leaking of mitral valve	Pansystolic murmurDifferentiated from aortic sclerosis on echocardiography
Hypertrophic cardiomyopathy	Dynamic outflow obstruction related to systolic anterior motion of the mitral valve	Midsystolic ejection murmurEchocardiography demonstrates regional wall thickening, systolic anterior motion of mitral valve, and left ventricular outflow tract obstruction
Ventricular septal defect	Defect in septumMurmur is present if left ventricular pressure is higher than right ventricular pressure	Holosystolic murmurEchocardiography reveals defect in septum and left-to-right flow
Flow murmur	Innocent flow murmur, thought to be due to turbulent flow in the pulmonary trunk	Midsystolic murmurNo structural or valvular abnormalities detected on echocardiography or other imaging modalities

Treatment

Approach to Treatment

• There is no treatment proven to prevent or slow progression of aortic stenosis, nor is there one to prevent or slow transition from aortic sclerosis to stenosis
• Patients with aortic sclerosis are at increased risk for cardiovascular events (eg, stroke, myocardial infarction)
• Pay close attention to cardiovascular risk factors (eg, hypertension, hypercholesterolemia); advise patients to avoid smoking, exercise regularly, and eat a balanced Mediterranean diet low in sugar and processed food

Follow-up

Monitoring

• Repeat echocardiography every 5 years to check for transition to aortic stenosis
• Consider assessing patients who have bicuspid aortic valve for aortic dilation

Prognosis

• Patients with aortic sclerosis are at increased risk for cardiovascular events (including stroke and myocardial infarction) and cardiovascular mortality
  • This increased risk is unlikely to be related to the valve lesion itself because hemodynamics are normal and time to cardiovascular events is short compared with the period over which advanced aortic stenosis might develop
  • It is more likely that aortic valve sclerosis serves as a marker for underlying atherosclerosis, given the common risk factors and similar underlying pathology
• In the recent SCOT-HEART (Scottish Computed Tomography of the Heart) Trial, patients with aortic calcification evident on CT had higher coronary calcium scores and more obstructive coronary artery disease; they also had a near 3-fold increased risk of myocardial infarction, stroke, or cardiovascular death. This association was lost when the coronary calcium score or obstructive coronary artery disease were added to the analysis of data
  • This finding suggests the association between aortic sclerosis and atherothrombotic events is not causal but instead mediated by associated atheroma

Screening

• Aortic sclerosis is usually picked up as an incidental finding on auscultation, echocardiography, or CT
• Reporting aortic valve thickening or calcification when clearly observed on echocardiography or CT helps ensure appropriate patient assessment and follow-up

Summary

• Aortic sclerosis is defined by presence of aortic valve leaflet thickening or calcification in absence of obstruction to valve opening (peak velocity less than 2 m/second on Doppler echocardiography)
• Aortic sclerosis is frequently detected as an incidental finding:
  • As a systolic murmur on auscultation
  • As valve thickening or calcification on echocardiography or CT
• Echocardiography is used to differentiate aortic sclerosis from other causes of a systolic murmur, including aortic stenosis in which aortic valve thickening is accompanied by valve obstruction
• There is no treatment proven to prevent or slow the transition from aortic sclerosis to stenosis
• Patients with aortic sclerosis are at increased risk for myocardial infarction, stroke, and cardiovascular death, although this risk is not causal but instead mediated by associated atherosclerosis

References

Otto CM et al. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med. 1999;341(3):142-147.