@article {1476, title = {Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {29}, year = {1997}, month = {1997 Mar 01}, pages = {630-4}, abstract = {

OBJECTIVES: The aim of this study was to determine the prevalence of aortic sclerosis and stenosis in the elderly and to identify clinical factors associated with degenerative aortic valve disease.

BACKGROUND: Several lines of evidence suggest that degenerative aortic valve disease is not an inevitable consequence of aging and may be associated with specific clinical factors.

METHODS: In 5,201 subjects > or = 65 years of age enrolled in the Cardiovascular Health Study, the relation between aortic sclerosis or stenosis identified on echocardiography and clinical risk factors for atherosclerosis was evaluated by using stepwise logistic regression analysis.

RESULTS: Aortic valve sclerosis was present in 26\% and aortic valve stenosis in 2\% of the entire study cohort; in subjects > or = 75 years of age, sclerosis was present in 37\% and stenosis in 2.6\%. Independent clinical factors associated with degenerative aortic valve disease included age (twofold increased risk for each 10-year increase in age), male gender (twofold excess risk), present smoking (35\% increase in risk) and a history of hypertension (20\% increase in risk). Other significant factors included height and high lipoprotein(a) and low density lipoprotein cholesterol levels.

CONCLUSIONS: Clinical factors associated with aortic sclerosis and stenosis can be identified and are similar to risk factors for atherosclerosis.

}, keywords = {Aged, Aged, 80 and over, Aortic Valve, Aortic Valve Stenosis, Calcinosis, Female, Heart Valve Diseases, Humans, Male, Prospective Studies, Risk Factors, Sclerosis}, issn = {0735-1097}, author = {Stewart, B F and Siscovick, D and Lind, B K and Gardin, J M and Gottdiener, J S and Smith, V E and Kitzman, D W and Otto, C M} } @article {997, title = {Clinical factors, but not C-reactive protein, predict progression of calcific aortic-valve disease: the Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {50}, year = {2007}, month = {2007 Nov 13}, pages = {1992-8}, abstract = {

OBJECTIVES: The purpose of this study was to examine the relationship between C-reactive protein (CRP) and calcific aortic valve disease in a large, randomly selected, population-based cohort.

BACKGROUND: The pathobiology of calcific aortic stenosis involves an active inflammatory, atheromatous, osteogenic process. Elevations in CRP, a measure of systemic inflammation, have been associated with aortic stenosis.

METHODS: Two-dimensional and Doppler echocardiography and CRP measurement were performed at baseline in 5,621 participants in the Cardiovascular Health Study. Multivariable analysis was used to identify CRP as a predictor of baseline and incident aortic stenosis.

RESULTS: At a mean echocardiographic follow-up of 5 years, 9\% of subjects with aortic sclerosis progressed to some degree of aortic stenosis. Increasing age (odds ratio [OR] 1.13, 95\% confidence interval [CI] 1.09 to 1.16; p < 0.001) and male gender (OR 3.05, 95\% CI 1.76 to 5.27; p < 0.001) were related to risk of incident aortic stenosis, whereas increasing height (OR 0.96, 95\% CI 0.94 to 0.99; p = 0.013) and African-American ethnicity conveyed a lower risk (OR 0.49, 95\% CI 0.25 to 0.95; p = 0.035). C-reactive protein, treated as a continuous variable, was not associated with baseline aortic stenosis, progression to aortic sclerosis (adjusted OR 0.93, 95\% CI 0.85 to 1.02; p = 0.107), or progression to aortic stenosis (adjusted OR 0.85, 95\% CI 0.70 to 1.03; p = 0.092).

CONCLUSIONS: In this large population-based cohort, approximately 9\% of subjects with aortic sclerosis progressed to aortic stenosis over a 5-year follow-up period. There was no association between CRP levels and the presence of calcific aortic-valve disease or incident aortic stenosis. C-reactive protein appears to be a poor predictor of subclinical calcific aortic-valve disease.

}, keywords = {Aged, Aged, 80 and over, Aortic Valve, Aortic Valve Stenosis, C-Reactive Protein, Calcinosis, Cardiovascular Diseases, Cohort Studies, Disease Progression, Female, Follow-Up Studies, Heart Valve Diseases, Humans, Male, Risk Factors}, issn = {1558-3597}, doi = {10.1016/j.jacc.2007.07.064}, author = {Novaro, Gian M and Katz, Ronit and Aviles, Ronnier J and Gottdiener, John S and Cushman, Mary and Psaty, Bruce M and Otto, Catherine M and Griffin, Brian P} } @article {1292, title = {Association of annular calcification and aortic valve sclerosis with brain findings on magnetic resonance imaging in community dwelling older adults: the cardiovascular health study.}, journal = {J Am Coll Cardiol}, volume = {57}, year = {2011}, month = {2011 May 24}, pages = {2172-80}, abstract = {

OBJECTIVES: The objective of this study was to investigate the associations of mitral annular calcification, aortic annular calcification, and aortic valve sclerosis with covert magnetic resonance imaging (MRI)-defined brain infarcts.

BACKGROUND: Clinically silent brain infarcts defined by MRI are associated with increased risk for cognitive decline, dementia, and future overt stroke. Left-sided cardiac valvular and annular calcifications are suspected as risk factors for clinical ischemic stroke.

METHODS: A total of 2,680 CHS (Cardiovascular Health Study) participants without clinical histories of stroke or transient ischemic attack underwent brain MRI in 1992 and 1993, 1 to 2 years before echocardiographic exams (1994 to 1995).

RESULTS: The mean age of the participants was 74.5 {\textpm} 4.8 years, and 39.3\% were men. The presence of any annular or valvular calcification (mitral annular calcification, aortic annular calcification, or aortic valve sclerosis), mitral annular calcification alone, or aortic annular calcification alone was significantly associated with a higher prevalence of covert brain infarcts in unadjusted analyses (p < 0.01 for all). In models adjusted for age, sex, race, body mass index, physical activity, creatinine, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, diabetes, coronary heart disease, and congestive heart failure, the presence of any annular or valve calcification remained associated with covert brain infarcts (risk ratio: 1.24; 95\% confidence interval: 1.05 to 1.47). The degree of annular or valvular calcification severity showed a direct relation with the presence of covert MRI findings.

CONCLUSIONS: Left-sided cardiac annular and valvular calcifications are associated with covert MRI-defined brain infarcts. Further study is warranted to identify mechanisms and determine whether intervening in the progression of annular and valvular calcification could reduce the incidence of covert brain infarcts as well as the associated risk for cognitive impairment and future stroke.

}, keywords = {Aged, Aortic Valve Stenosis, Brain, Brain Infarction, Calcinosis, Cohort Studies, Female, Humans, Magnetic Resonance Imaging, Male, Mitral Valve Stenosis, Retrospective Studies}, issn = {1558-3597}, doi = {10.1016/j.jacc.2011.01.034}, author = {Rodriguez, Carlos J and Bartz, Traci M and Longstreth, W T and Kizer, Jorge R and Barasch, Eddy and Lloyd-Jones, Donald M and Gottdiener, John S} } @article {9649, title = {Large-Scale Proteomics Identifies Novel Biomarkers and Circulating Risk Factors for Aortic Stenosis.}, journal = {J Am Coll Cardiol}, volume = {83}, year = {2024}, month = {2024 Feb 06}, pages = {577-591}, abstract = {

BACKGROUND: Limited data exist regarding risk factors for aortic stenosis (AS). The plasma proteome is a promising phenotype for discovery of novel biomarkers and potentially causative mechanisms.

OBJECTIVES: The aim of this study was to discover novel biomarkers with potentially causal associations with AS.

METHODS: We measured 4,877 plasma proteins (SomaScan aptamer-affinity assay) among ARIC (Atherosclerosis Risk In Communities) study participants in mid-life (visit 3 [V3]; n~=~11,430; age 60 {\textpm} 6 years) and in late-life (V5; n~=~4,899; age 76 {\textpm} 5 years). We identified proteins cross-sectionally associated with aortic valve (AV) peak velocity (AVmax) and dimensionless index by echocardiography at V5 and with incident AV-related hospitalization after V3 with the use of multivariable linear and Cox proportional hazard regression. We assessed associations of candidate proteins with changes in AVmax over 6 years and with AV calcification with the use of cardiac computed tomography, replicated analysis in an independent sample, performed Mendelian randomization, and evaluated gene expression in explanted human AV tissue.

RESULTS: Fifty-two proteins cross-sectionally were associated with AVmax and dimensionless index at V5 and with risk of incident AV-related hospitalization after V3. Among 3,413 participants in the Cardiovascular Health Study, 6 of those proteins were significantly associated with adjudicated moderate or severe AS, including matrix metalloproteinase 12 (MMP12), complement C1q tumor necrosis factor-related protein 1 (C1QTNF1), and growth differentiation factor-15. MMP12 was also associated with greater increase in AVmax over 6 years, greater degree of AV calcification, and greater expression in calcific compared with normal or fibrotic AV tissue. C1QTNF1 had consistent potential causal effects on both AS and AVmax according to Mendelian randomization analysis.

CONCLUSIONS: These findings identify MMP12 as a potential novel circulating biomarker of AS risk and C1QTNF1 as a new putative target to prevent AS progression.

}, keywords = {Aged, Aged, 80 and over, Aortic Valve, Aortic Valve Stenosis, Biomarkers, Calcinosis, Humans, Matrix Metalloproteinase 12, Middle Aged, Proteomics, Risk Factors}, issn = {1558-3597}, doi = {10.1016/j.jacc.2023.11.021}, author = {Shelbaya, Khaled and Arthur, Victoria and Yang, Yimin and Dorbala, Pranav and Buckley, Leo and Claggett, Brian and Skali, Hicham and Dufresne, Line and Yang, Ta-Yu and Engert, James C and Thanassoulis, George and Floyd, James and Austin, Thomas R and Bortnick, Anna and Kizer, Jorge and Freitas, Renata C C and Singh, Sasha A and Aikawa, Elena and Hoogeveen, Ron C and Ballantyne, Christie and Yu, Bing and Coresh, Josef and Blaha, Michael J and Matsushita, Kunihiro and Shah, Amil M} }