Version July 2025
INTRODUCTION —
Aortic valve thickening (sclerosis) without stenosis is common in older adults [1]. Aortic valve sclerosis is important clinically because it progresses to aortic stenosis in a minority of patients and is associated with increased cardiovascular risk, although this association does not appear to be causal.
This topic will discuss the pathogenesis of aortic sclerosis and calcific aortic stenosis and the diagnosis, prevalence, clinical significance, and management of aortic sclerosis.
The natural history, diagnosis, and management of aortic stenosis are discussed separately. (See "Natural history, epidemiology, and prognosis of aortic stenosis" and "Clinical manifestations and diagnosis of aortic stenosis in adults" and "Medical management of symptomatic aortic stenosis" and "Medical management of asymptomatic aortic stenosis in adults" and "High-gradient aortic stenosis in adults: Indications for valve replacement".)
DEFINITION —
Aortic sclerosis is defined as irregular thickening and/or calcification of the valve leaflets without stenosis (ie, antegrade transvalvular velocity is ≤2 m/s) [2]. Mild aortic regurgitation may be present.
PREVALENCE —
The prevalence of aortic valve sclerosis detected by echocardiography increases with age from <10 percent at mean age less than 60 years [3] to 35 percent between 75 and 84 years of age and approximately 50 percent of those over age 80 [4-6]. As an example, in the Cardiovascular Health Study of 5621 males and females aged 65 years or older, aortic valve sclerosis was present in around 25 percent of individuals [5], with similar prevalences in most large population studies of similarly aged individuals [1,3,7,8].
Valvular sclerosis is more common in certain populations, such as individuals with hypertension [9], those with end-stage kidney disease on maintenance dialysis, and individuals presenting to the emergency department with chest pain [10]. However, when adjusted for other cardiovascular risk factors, moderate chronic kidney disease is not significantly associated with aortic valve calcification, although it is associated with mitral annular calcification [11]. (See "Valvular heart disease in patients with end-stage kidney disease", section on 'Valvular thickening' and "Valvular heart disease in patients with end-stage kidney disease", section on 'Valvular and annular calcification'.)
PATHOGENESIS OF CALCIFIC AORTIC VALVE DISEASE —
The pathobiology of calcific aortic valve disease is an area of active research, and our understanding of the cellular and molecular mechanisms of disease is in flux [12-17].
The pathogenesis of aortic valve disease can be conceptualized in two stages: an early initiation phase associated with aortic sclerosis and a later propagation phase associated with progressive aortic stenosis [18].
Initiation phase
Primary processes — The early initiation phase of aortic sclerosis is characterized by three primary processes: lipid accumulation, inflammation, and calcification [1,19,20], thus demonstrating similarities to atherosclerosis. These processes were demonstrated in the following studies of aortic valves in individuals with aortic sclerosis or aortic stenosis.
●Focal areas of accumulation of apolipoproteins B, (a), and E, consistent with accumulation of low density lipoprotein (LDL) and lipoprotein(a), also referred to as Lp(a), with evidence of lipoprotein oxidation [19,21].
●Inflammation as evidenced by macrophage and T lymphocyte infiltration on histology [19,22,23], inflammatory mediators such as interleukin 1-beta and transforming growth factor beta-1 [24,25], and increased 18F-fluorodeoxyglucose uptake on positron emission tomography (PET) scanning [26,27].
●Local production of proteins that promote tissue calcification, suggesting that valve calcification is actively regulated rather than being an unregulated degenerative process [28-32]. Increased 18F-fluoride activity on PET is a marker of calcification activity [33].
●Production and activity of angiotensin converting enzyme [34,35].
●Upregulation of adhesion molecules and alterations in matrix metalloproteinase activity [36,37].
Role of mechanical stress and hypertension — Mechanical stress causing endothelial damage is thought to precipitate the development of aortic sclerosis with associated inflammatory cell infiltration and lipid deposition, analogous to early atherosclerosis [5]. This is perhaps best illustrated in the setting of a bicuspid aortic valve, which is associated with increased mechanical stresses in the valve leaflets and nearly invariable development of accelerated valve calcification and stenosis, although these patients may also have a genetic predisposition to tissue calcification [38]. It has been postulated that hypertension and the increased stiffness of the aortic root that occurs with ageing may also cause abnormally high mechanical stresses in the valve, which may contribute to the association of hypertension and aging with aortic stenosis [39].
The following studies suggest a possible causal relationship between hypertension and progression of calcific aortic valve disease:
●In a cohort study of 5.4 million patients with no known baseline cardiovascular disease, systolic blood pressure was continuously related to the risk of aortic stenosis, with each 20 mmHg increment in systolic blood pressure associated with a 41 percent higher risk of aortic stenosis (hazard ratio 1.41, 95% CI 1.38-1.45) [40].
●An association between blood pressure and incidence of aortic stenosis was further explored in a Mendelian randomization study of over 300,000 patients [41]. Each genetically associated 20 mmHg increment in systolic blood pressure was associated with an increased risk of aortic stenosis (odds ratio [OR] 3.26, 95% CI 1.50-7.10), supporting the causality of hypertension in development of calcific valve disease.
Relation to atherosclerosis — The incidence of aortic sclerosis and stenosis is associated with many of the traditional risk factors for atherosclerosis, supporting pathologic similarities between the early stages of these diseases. These include smoking, hypertension, hyperlipidemia, elevated Lp(a) levels, diabetes, and metabolic syndrome [4,5,9,17,42-49].
The following echocardiographic studies illustrate the range of associations between the incidence of aortic valve sclerosis, aortic stenosis, and atherosclerotic risk factors:
●A report from the Cardiovascular Health Study (CHS) evaluated 5176 patients ≥65 years of age: 26 percent had aortic valve sclerosis with visually apparent leaflet thickening and/or calcification, and 2 percent had aortic stenosis [5]. Multivariate analysis found significant correlations of aortic valve disease with age, male sex, Lp(a), LDL-cholesterol (LDL-C), hypertension, and smoking.
●In the Framingham Heart Study offspring cohort (n = 2683, mean age 61 years), 8 percent had at least one calcified valve, 5 percent had aortic sclerosis, and 1 percent had aortic stenosis [47]. The threshold for diagnosis of aortic sclerosis was higher in this study than in the CHS study, and the population was younger, which could at least partly explain the lower rate of reported aortic sclerosis. Valvular calcification was associated with age, hypertension, and diabetes.
Similar findings have been noted when aortic valve calcification was assessed by computed tomography (CT):
●In the Multi-Ethnic Study of Atherosclerosis (MESA) study (n = 6780, mean age 63 years), the prevalence of aortic valve calcification was higher among those with metabolic syndrome (12 percent in females, 22 percent in males) or diabetes (17 percent in females, 24 percent in males) compared with those with neither risk factor (8 percent in females, 14 percent in males) [48]. Metabolic syndrome and diabetes were also associated with higher frequency of new cases of aortic valve calcification (OR 1.67, 95% CI 1.21-2.31 for metabolic syndrome and OR 2.06, 95% CI 1.39-3.06 for diabetes) [50].
●In contrast to the above cited CHS study [5], in a MESA cohort of 5801 non-statin-using participants, LDL-C levels were associated with the presence of aortic valve calcification only in participants younger than 65 years, although the total cholesterol to high-density lipoprotein ratio was associated with a slight increase in risk for calcific disease across all ages [51]. There was a significant association between Lp(a) and the degree of aortic valve calcification across a sample of 4678 participants [52]. An Lp(a) >30 mg/dL was significantly associated with aortic valve calcification in White participants (relative risk [RR] 1.56, 95% CI 1.24-1.96) and was borderline significant in Black participants (RR 1.55, 95% CI 0.98-2.44; p = 0.059). In Hispanic and Chinese participants, no significant associations were observed.
Relation to mineral metabolism — While the majority of patients with aortic stenosis and aortic sclerosis have normal phosphate and calcium levels, disturbances of mineral metabolism may contribute to the development of aortic valve sclerosis and mitral annular calcification, as suggested by the following observations.
●In the CHS community-based cohort of older adults, each 0.5 mg/dL higher serum phosphate concentration was associated with 17, 12, and 12 percent higher adjusted prevalences of aortic sclerosis, mitral annular calcification, and aortic annular calcification, respectively [53]. Other markers of mineral metabolism, including serum calcium, parathyroid hormone (PTH), and 25 hydroxyvitamin D concentrations, were not associated with calcification.
●Similarly, among 439 participants with chronic kidney disease in MESA, each 1 mg/dL increase in serum phosphate within the normal range (2.5 to 4.5 mg/dL) was associated with 25 and 62 percent higher prevalences of aortic and mitral valve calcification, respectively, after adjustment for traditional risk factors for atherosclerosis, parathyroid hormone, and 1,25 dihydroxyvitamin D levels [54].
●Among 296,415 participants in the UK Biobank (mean age 56 years, 53 percent females), increased serum phosphate level, but not calcium or vitamin D serum levels, was associated with a higher risk of incident aortic stenosis; this association did not differ substantially between patients with and without decreased kidney function [55].
Considerations for calcium and vitamin D supplementation in patients with aortic sclerosis are discussed below. (See 'Management of calcium and vitamin D' below.)
Genetic factors — Genetic factors contribute to the risk of aortic sclerosis and aortic stenosis [17,56-67]. Genome-wide studies have identified multiple loci associated with calcific aortic valve disease [67]. Interestingly, these genes can be categorized into some of the various biological pathways implicated in the pathogenesis of aortic stenosis. These include genes related to lipid metabolism (PLA, LDL, APO, PCSK9, Lp-PLA2, PONS1), inflammation (IL-6, IL-10), calcification (PALMD, TEX41) and bone metabolism (PTH, VIT D, RUNX2, CACNA1C, ALPL), as well as additional pathways (NOTCH1, NAV1 and FADS1/2).
These associations are illustrated by the following studies:
●Genomic associations highlight the roles of lipid metabolism, inflammation, cellular senescence, and adiposity in the pathobiology of calcific aortic valve disease. A genome-wide study of 14,451 participants with calcific aortic valve disease and 398,544 controls in the Million Veteran Program identified five replicated genomic regions that were previously known risk loci for calcific aortic stenosis (PALMD, TEX41, IL6, LPA, FADS) and six novel regions (CEP85L, FTO, SLMAP, CELSR2, MECOM, CDAN1) [68].
●In a meta-analysis of 10 cohorts of European ancestry, 17 loci (including CELSR2-SORT1, NLRP6, and SMC2) were correlated with calcific aortic valve disease, with replication of these data in a large independent cohort [69]. These index variants provide a genetic risk score for aortic valve disease. Mendelian randomization analysis supported a causal role of apolipoprotein B LDL, Lp(a), and body mass index in risk of aortic valve stenosis.
Propagation phase — In the propagation phase of calcific aortic valve disease, clear differences from the initiation phase and the pathology of atherosclerosis emerge, most notably the predominance of calcification within the leaflets as the key driver to progressive valve stiffness and narrowing causing aortic stenosis [1,19].
The accumulation of valve calcification appears related to the action of osteoblast-like cells and a range of pro-calcific mediators commonly associated with skeletal bone formation. A histopathologic study of 256 end-stage excised calcified aortic valves demonstrated widespread evidence of active cartilage and bone formation, with 83 percent of valves showing regions of heterotopic ossification [31]. A PET imaging study in 121 adults with a range of calcific aortic valve severity demonstrated inflammation with early disease and calcification activity dominant with moderate and severe aortic stenosis [33,70]. Aortic valve calcification closely predicted aortic stenosis progression [71,72]. Similarly, assessments of valvular calcium burden provided by both echocardiography and CT predicted disease progression and clinical events in aortic stenosis [73].
Studies have demonstrated that Lp(a) levels are associated with aortic stenosis progression as well as its incidence. In a multimodality imaging study in 145 patients, Lp(a) levels >30 mg/dL were associated with increased calcification activity (18F-sodium fluoride on PET), faster disease progression on CT and echocardiography, and increased risk of aortic valve replacement [74]. A meta-analysis including data on 710 patients identified a consistent association between elevated Lp(a) level and faster aortic stenosis progression as assessed by echocardiography [75].
CLINICAL MANIFESTATIONS —
Aortic sclerosis is an asymptomatic condition that is generally detected either as a systolic ejection murmur on physical examination or as an incidental finding on echocardiography or CT.
Aortic sclerosis, in the absence of stenosis, may be associated with a midsystolic ejection murmur, which is usually best heard over the right second interspace. In general, the murmur is brief and not very loud. Many patients with aortic sclerosis have no murmur on physical examination.
A normal carotid pulse and normal S2 suggest the absence of aortic stenosis (figure 1). (See "Auscultation of cardiac murmurs in adults".)
However, the physical examination is neither sensitive nor specific for excluding aortic valve obstruction. Thus, echocardiography should be performed to distinguish aortic sclerosis from aortic stenosis and other cardiac abnormalities that might account for the murmur when present. (See "Echocardiographic evaluation of the aortic valve" and "Echocardiographic evaluation of the aortic valve", section on 'Obstruction to left ventricular outflow'.)
DIAGNOSIS
When to suspect aortic sclerosis — Aortic sclerosis should be suspected when a systolic murmur is heard on auscultation and is also frequently detected as an incidental finding on transthoracic echocardiography or as aortic valve calcification or thickening on CT.
Diagnostic features
●Key features – Aortic valve sclerosis is identified by the following features on echocardiography [1,5,7,76]:
•Irregular leaflet thickening and focal increased echogenicity (calcification) are the hallmarks of the condition. Focal areas of thickening are typically seen on the aortic side of the valve in the center of the valve cusp, rather than at the leaflet edges, often initially involving the noncoronary cusp.
•Leaflet excursion is not impaired and the commissures are not fused. Peak continuous-wave Doppler flow velocities across the valve are normal or only minimally elevated (<2 m/s).
●Common accompanying feature – Mitral annular calcification frequently accompanies aortic valve sclerosis [77,78]. (See "Echocardiographic evaluation of the mitral valve", section on 'Mitral annular calcification' and "Clinical manifestations and diagnosis of mitral annular calcification".)
Signs of progression — Reduction in leaflet mobility, increases in leaflet calcification, and increases in aortic transvalvular Doppler flow velocities are signs of progression from aortic sclerosis to aortic stenosis (table 1). (See 'Progression to aortic stenosis' below.)
DIFFERENTIAL DIAGNOSIS —
Aortic sclerosis should be differentiated from other causes of a systolic murmur, including the following conditions, based upon clinical signs (figure 1), electrocardiogram, and echocardiogram. As noted above, aortic sclerosis may or may not be associated with a midsystolic ejection murmur. (See 'Diagnostic features' above.)
Differentiation of murmurs of the following conditions on physical examination is challenging and even experts cannot reliably distinguish these conditions by examination alone. Echocardiography is performed when valve disease is suspected, including in asymptomatic adults with a grade 3 or louder murmur and in adults with potential cardiac symptoms and any cardiac murmur [2,79]. (See "Auscultation of cardiac murmurs in adults".)
●Aortic stenosis is associated with a midsystolic ejection murmur (table 2) that radiates into the neck and over both carotid arteries. Aortic stenosis is associated with evidence of flow obstruction in addition to valve thickening on echocardiography. (See "Clinical manifestations and diagnosis of aortic stenosis in adults".)
●Other causes of a midsystolic ejection murmur include:
•Supravalvular aortic stenosis is associated with a midsystolic ejection murmur. Echocardiography is helpful in identifying the location of obstruction above the aortic valve. (See "Valvar aortic stenosis in children".)
•Subvalvular aortic stenosis is associated with a midsystolic ejection murmur. Echocardiography is helpful in identifying the location and structure of the subaortic lesion. (See "Subvalvar aortic stenosis (subaortic stenosis)".)
•Hypertrophic cardiomyopathy with dynamic left ventricular outflow obstruction causes a midsystolic ejection murmur that increases upon standing from a squatting position. Echocardiographic findings include unexplained left ventricular hypertrophy, systolic anterior motion of the mitral valve, as well as Doppler evidence of left ventricular outflow obstruction. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'Echocardiography'.)
•An innocent midsystolic flow murmur is commonly thought to originate from vibrations in the pulmonary trunk. When an innocent murmur is present, an echocardiogram reveals no underlying cardiac lesion.
●The holosystolic murmurs of the following conditions should be distinguished from the midsystolic murmurs of aortic sclerosis and aortic stenosis:
•Mitral regurgitation (MR) is generally associated with a holosystolic murmur. Echocardiographic findings include mitral valve apparatus abnormalities consistent with primary or secondary MR as well as Doppler findings that aid in identifying and quantifying the MR jet. (See "Clinical manifestations and diagnosis of chronic mitral regurgitation".)
•Ventricular septal defects (VSDs) typically cause a holosystolic murmur if right ventricular pressure is lower than left ventricular pressure throughout systole. An echocardiogram is a sensitive means of detecting most VSDs. (See "Clinical manifestations and diagnosis of ventricular septal defect in adults".)
CLINICAL SIGNIFICANCE OF AORTIC SCLEROSIS —
Aortic valve sclerosis can progress to aortic stenosis and is a marker for increased cardiovascular risk.
Progression to aortic stenosis — As aortic valve leaflet thickening and calcification progress, increased valve stiffness results in obstruction at the valve level and transition from aortic sclerosis to stenosis [7].
Low rates of progression to aortic stenosis are illustrated by the following studies. Low conversion rates from aortic sclerosis to aortic stenosis present a challenge for strategies aimed at treating individuals with aortic sclerosis to prevent the development of aortic stenosis.
●Prospective clinical studies suggest that progression from aortic sclerosis to some degree of aortic stenosis occurs in approximately one of eight patients, with progression from sclerosis to severe stenosis occurring in 1 of 64 patients [78,80].
●The rate of progression from aortic sclerosis to aortic stenosis was 1.8 percent per year in an included echocardiographic study of 1610 patients with mean age 74 years [3,81] and 1.9 percent per year in an included CT study of 70 participants with mean age 70 years [3,82]. (See "Natural history, epidemiology, and prognosis of aortic stenosis".)
●A similar rate of progression was identified in a review of 2131 patients with aortic valve thickening detected on echocardiography: aortic stenosis developed in 338 (16 percent) after seven years [80]. The aortic stenosis was mild to moderate in 84 percent and severe in 16 percent.
The following factors are associated with progression from aortic sclerosis to significant aortic stenosis:
●Aortic valve gradient and valve area – A machine learning model found that echocardiographic features, including aortic valve mean gradient and valve area, identify patients with mild AS at increased risk of development of severe AS [83].
●Mitral annular calcification – In the above-cited study of 2131 patients with aortic sclerosis, mitral annular calcification, a pathologic process similar to aortic valve sclerosis, was significantly associated with progression to aortic stenosis in multivariable analysis [80].
●Aortic valve calcification – Factors associated with progressive aortic valve calcification were identified in 5880 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) [84]. The incidence rate of aortic valve calcium was 1.7 percent per year. Risk factors for incident aortic valve calcium included older age, male sex, a higher body mass index, current smoking, and the use of lipid-lowering and antihypertensive medications. The risk of aortic valve calcium progression was associated with male sex and, consistent with other studies, the severity of baseline calcification.
As described in the next section, both aortic valve sclerosis and mitral annular calcification may also be predictors of cardiovascular events and mortality.
Association with cardiovascular events — Studies have found a consistent association between presence of aortic sclerosis and risk of adverse cardiovascular events.
This relationship was illustrated by the above-cited meta-analysis of 22 studies, which found that participants with aortic sclerosis had a 68 percent increased risk of coronary events, 27 percent increased risk of stroke, 69 percent increased risk of cardiovascular mortality, and 36 percent increased risk of all-cause mortality compared with participants without this condition [3].
The mechanisms responsible for the association between aortic valve sclerosis and cardiovascular events and mortality are not fully understood [1,85]. The valve lesion itself is not likely to be causally related to cardiovascular events, since hemodynamics are normal or near normal and the time to increased risk is short compared with the rate of progression to aortic stenosis (see 'Pathogenesis of calcific aortic valve disease' above). A more probable explanation is that, given common risk factors for aortic valve sclerosis and atherosclerotic cardiovascular disease, aortic valve sclerosis is a marker for atherosclerosis [10,85]. (See 'Relation to atherosclerosis' above.)
An analysis of the SCOTHEART trial, in which CT was performed in outpatients with chest pain, found that patients with aortic or mitral valve calcification had higher coronary calcium scores and more obstructive coronary artery disease. It also confirmed the association between both aortic valve and mitral annular calcification and adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke). However, these associations were lost when coronary CT calcium scores or obstructive coronary artery disease were considered in the model. This implies that the association between aortic sclerosis and atherothrombotic events is noncausal and instead mediated by associated atheroma [86]. Thus, the finding of aortic sclerosis or mitral annular calcification on echocardiography likely represents a marker of increased risk of atherosclerotic cardiovascular disease, including coronary artery disease. However, data are lacking on whether presence of aortic sclerosis should prompt diagnostic evaluation or alterations in cardiovascular preventive therapies.
Embolic risk — No significant increase in stroke risk was found in studies comparing patients with aortic sclerosis with matched controls [7,87,88].
MANAGEMENT —
Patients with aortic sclerosis should receive follow-up for progression to aortic stenosis and full assessment of their cardiovascular risk profile with lifestyle and risk factor modification as appropriate [89].
Follow-up — Aortic valve sclerosis is a major type of Stage A (meaning "at risk of") valvular aortic stenosis (along with bicuspid aortic valve) (table 1) which requires follow-up as follows:
●At least annual clinical follow-up – Since aortic sclerosis often progresses to aortic stenosis, clinical follow-up by the primary care provider is recommended with periodic (at least annual) evaluation for changes in cardiac symptoms or signs.
●Echocardiography
•For change in symptoms or examination – Follow-up echocardiography is appropriate to evaluate any new cardiac symptoms, such as dyspnea on exertion, or changes in physical examination findings, such as an increase in the loudness of the murmur, a single second heart sound, or a decrease in carotid upstroke.
•Routine echocardiography – If there is no change in symptoms or examination findings, we favor repeating an echocardiogram every three to five years.
Risk factor modification — A prudent approach is to consider aortic valve sclerosis to be a marker of increased cardiovascular risk [1,43]. Thus, all patients with aortic sclerosis should undergo a careful history and physical examination with assessment of conventional cardiac risk factors (including hypertension, smoking, diabetes, and hyperlipidemia) and identification of any symptoms and signs of cardiovascular disease. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults" and "Cardiovascular disease risk assessment for primary prevention: Risk calculators".)
Risk factor reduction should be instituted based upon accepted guidelines. Aside from its beneficial effects with respect to atherosclerosis, there is no evidence that lipid-lowering therapy slows or prevents disease progression in patients with calcific valve disease [16,90]. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention)" and "Overview of primary prevention of cardiovascular disease in adults".)
In addition, further diagnostic evaluation and management may be needed in patients with clinical signs or symptoms of cardiovascular disease. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention)".)
Management of calcium and vitamin D — For adults with aortic sclerosis with an indication for calcium and vitamin D supplementation, guidance is the same as that for others at high cardiovascular risk (see "Calcium and vitamin D supplementation in osteoporosis", section on 'Cardiovascular disease'). This includes encouraging dietary intake of calcium rather than calcium supplements, and calcium doses of no more than 500 mg at a time. However, vitamin D supplementation can proceed at standard doses.
This approach is based on concern for possible risks of calcium supplementation in patients with aortic sclerosis, since these patients are at risk for atherosclerotic cardiovascular events (eg, myocardial infarction) and for progression to aortic stenosis. There are limited data suggesting that both of these risks may be exacerbated by calcium supplementation [91]:
●Atherosclerotic cardiovascular disease – The effects of calcium supplementation on cardiovascular risk (including myocardial infarction) are controversial, with some population studies (not focused on patients with aortic sclerosis) suggesting an association between calcium supplementation and increased cardiovascular risk, although an effect on cardiovascular mortality or overall mortality has not been established. These issues are discussed separately. (See "Calcium and vitamin D supplementation in osteoporosis", section on 'Cardiovascular disease'.)
●Progression to aortic stenosis – Data are lacking on the effects of dietary calcium intake or calcium supplementation in patients with aortic sclerosis.
While calcium supplementation in a general population is unlikely to significantly increase the incidence of aortic stenosis [92], two studies in patients with aortic stenosis suggested possible harm from calcium supplementation:
•In a retrospective study of 3257 patients (mean age of 71.7 years) with concomitant moderate aortic valve and mitral valve disease, among the 1045 patients with moderate aortic stenosis combined with mitral valve disease, calcium and vitamin D supplementation was associated an increased risk of all-cause mortality at a median of 22 months (hazard ratio [HR] 1.203, 95% CI 1.017-1.425) [93]. In contrast, among the 2212 patients with aortic regurgitation combined with mitral valve disease, calcium and vitamin D supplementation was not associated with all-cause mortality (HR 1.044, 95% CI 0.913-1.193).
•In the a retrospective study of 2657 patients with mild-moderate aortic stenosis followed for a median of 69 months, calcium (with or without vitamin D) supplementation was associated with a higher risk of all-cause mortality (absolute rate [AR] 43.0/1000 person-years; HR 1.31, 95% CI 1.07-1.62), cardiovascular mortality (AR 13.7/1000 person-years; HR 2.0, 95% CI 1.31-3.07), and aortic valve replacement (AR 88.2/1000 person-years; HR 1.48, 95% CI 1.24-1.78) [94]. However, vitamin D supplementation alone was not associated with adverse clinical outcomes.
Treatment of hyperphosphatemia — As noted above, there is some evidence suggesting that higher serum phosphate concentrations are associated with higher prevalences of calcific aortic sclerosis (see 'Relation to mineral metabolism' above). This may be an additional rationale for control of hyperphosphatemia, as in individuals with chronic kidney disease. (See "Overview of the causes and treatment of hyperphosphatemia" and "Management of hyperphosphatemia in adults with chronic kidney disease".)
Therapies that are not indicated
Antithrombotic therapy — Embolic events are not significantly associated with aortic valve sclerosis. No treatment has been established for prevention of calcific microemboli.
Patients with calcific aortic valve disease who have had an ischemic stroke or transient ischemic attack (TIA) with no other identifiable source are managed according to standard guidelines for secondary prevention of noncardioembolic stroke or TIA. (See "Long-term antithrombotic therapy for the secondary prevention of ischemic stroke", section on 'Summary and recommendations' and 'Embolic risk' above.)
Endocarditis prophylaxis — The presence of native aortic valve sclerosis is not an indication for endocarditis prophylaxis, as discussed separately [2]. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)
SUMMARY AND RECOMMENDATIONS
●Diagnosis – Aortic sclerosis is defined as irregular aortic leaflet thickening and focal increased echogenicity without impairment of leaflet excursion and with peak Doppler velocities across the valve <2 m/s. (See 'Diagnosis' above.)
●Prevalence – The prevalence of aortic sclerosis increases with age from less than 10 percent in middle-aged adults to ≥25 percent in adults ≥65 years old. (See 'Prevalence' above.)
●Clinical manifestations – Aortic sclerosis is an asymptomatic condition that is generally detected either as a systolic ejection murmur on physical examination or as an incidental finding on echocardiography or computed tomography (CT). (See 'Clinical manifestations' above.)
●Pathogenesis – The pathobiology of aortic sclerosis and early calcific aortic valve disease (the initiation phase) shares similarities with atherosclerosis involving lipid accumulation, inflammation, and calcification. The incidence of aortic sclerosis has been correlated with clinical risk factors for atherosclerosis, including smoking, hypertension, hyperlipidemia, and diabetes. The factors driving aortic stenosis progression in the propagation phase appear different, with calcification predominating. (See 'Pathogenesis of calcific aortic valve disease' above.)
●Genetic factors – Genetic factors related to lipid metabolism, inflammation, calcification, and bone metabolism have been associated with an increased risk of aortic valve calcification and the development of calcific aortic stenosis. (See 'Genetic factors' above.)
●Follow-up – Since aortic sclerosis can progress to aortic stenosis, clinical follow-up is recommended with periodic (eg, at yearly or greater intervals) evaluation for changes in cardiac symptoms or signs.
•Change in symptoms or signs – Follow-up echocardiography is appropriate to evaluate any new cardiac symptoms, such as dyspnea on exertion, or changes in physical examination findings, such as an increase in the loudness of the murmur, a single second heart sound, or a decrease in carotid upstroke.
•Routine echocardiography – In addition, we favor a routine follow-up echocardiogram every three to five years in adults with aortic sclerosis (even in the absence of any changes in signs or symptoms). (See 'Follow-up' above.)
●Prognostic significance – Patients with aortic valve sclerosis (including those with and without known cardiovascular disease) have an increased frequency of cardiovascular events and mortality. This may be explained by the association between aortic valve sclerosis and coronary and carotid atherosclerosis rather than representing a direct causal effect. (See 'Association with cardiovascular events' above.)
●Risk factor modification – All patients with aortic sclerosis should undergo a careful history and physical examination with assessment of conventional cardiac risk factors, including hypertension, smoking, diabetes, and hyperlipidemia. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults" and "Cardiovascular disease risk assessment for primary prevention: Risk calculators".)
Risk factor reduction should be instituted based upon accepted guidelines. In addition, further diagnostic evaluation may be needed in patients with clinical signs or symptoms of cardiovascular disease. (See 'Risk factor modification' above and "Prevention of cardiovascular disease events in those with established disease (secondary prevention)" and "Overview of primary prevention of cardiovascular disease in adults".)
There is no specific medical therapy to prevent disease progression in the valve leaflets in patients with aortic sclerosis. (See 'Risk factor modification' above.)
●Calcium and vitamin D – For adults with aortic sclerosis with an indication for calcium and vitamin D supplementation, guidance is the same as that for others at high cardiovascular risk (see "Calcium and vitamin D supplementation in osteoporosis", section on 'Cardiovascular disease'). This includes encouraging dietary intake of calcium rather than calcium supplements and calcium doses of no more than 500 mg at a time. However, vitamin D supplementation can proceed at standard doses. This approach is based on concern that calcium supplementation may increase the risk of cardiovascular disease and progression to aortic stenosis, although data are limited. (See 'Management of calcium and vitamin D' above.)
ACKNOWLEDGMENT —
The UpToDate editorial staff acknowledges David S Siscovick, MD, who contributed to earlier versions of this topic review.
