Relation between cardiovascular risk factors and nonrheumatic severe calcific aortic stenosis among patients with a three-cuspid aortic valve
2003; Elsevier BV; Volume: 91; Issue: 1 Linguagem: Inglês
10.1016/s0002-9149(02)03010-2
ISSN1879-1913
AutoresMarcel Peltier, Faouzi Trojette, Maurice Enriquez‐Sarano, Francesco Grigioni, Michel Slama, Christophe Tribouilloy,
Tópico(s)Aortic Disease and Treatment Approaches
ResumoValvular aortic stenosis (AS) caused by degenerative calcification of the valvar structures has become the most common valvar disease requiring cardiac surgery in industrialized countries. Roberts1Roberts W.C. The senile cardiac calcification syndrome.Am J Cardiol. 1986; 58: 572-574Abstract Full Text PDF PubMed Scopus (179) Google Scholar suggested as early as 1986 that factors predisposing to atherosclerosis in the coronary arteries also predispose the aortic valve to calcification in the elderly. Previous clinical studies reported that atherosclerotic risk factors associated with AS could vary with the etiology.2Chan K.L. Ghani M. Woodend K. Burwash I.G. Case-controlled study to assess risk factors for aortic stenosis in congenitally bicuspid aortic valve.Am J Cardiol. 2001; 88: 690-693Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar, 3Mohler E.R. Sheridan M.J. Nichols R. Harvey W.P. Waller B.F. Development and progression of aortic valve stenosis atherosclerosis risk factors—a causal relationship? A clinical morphologic study.Clin Cardiol. 1991; 14: 995-999Crossref PubMed Scopus (199) Google Scholar To our knowledge, no data are available in patients with exclusively severe calcific degenerative AS. This prospective study, controlled for age and sex, was designed to examine the specific relation between the presence of severe calcific degenerative AS and cardiovascular risk factors.Between September 1996 and February 2000, 220 consecutive patients with severe calcific degenerative AS (mean age of 68 ± 9 years, range 52 to 82; 135 men, 85 women) considered for surgery prospectively underwent coronary angiography and transthoracic echocardiography. Severe AS was defined as the presence of an aortic valve area ≤0.75 cm2 computed with the continuity equation, using standard methods in transthoracic echocardiography. All patients gave informed consent to participate in the study. These patients were compared with 220 age- and gender-matched patients (mean age of 68 ± 8 years, range 50 to 86; 135 men, 85 women) with valvular regurgitation, but without AS, referred for surgery during the same period. The diagnosis of calcific degenerative AS was performed on the basis of clinical criteria (no history of rheumatic disease and/or no history of murmur at a younger age) and on the echocardiographic findings of thickening and increased echogenicity of the cusps, excluding the free edges with reduced systolic opening. The morphologic confirmation of diagnosis of calcific degenerative AS at surgery was an additional diagnostic criterion defined as a stenotic 3-cuspid aortic valve excised as 3 individual cusps (i.e., no commissural fusion) in patients in whom the mitral valve was normal. Patients with surgical evidence of probable rheumatic aortic valve disease or congenital bicuspid valve were excluded.Significant coronary artery disease (CAD) was defined as a ≥50% reduction of the internal diameter of ≥1 of the coronary arteries. The cardiovascular risk factors recorded were total cholesterol and triglycerides concentrations, systemic hypertension, history of smoking, diabetes mellitus, body mass index (BMI), and family history of CAD. Patients on lipid-lowering medications were excluded. Blood was drawn after a 14-hour overnight fast for determination of serum total cholesterol and triglycerides with standard methods. Hypercholesterolemia was considered present if the fasting total cholesterol was >200 mg/dl, diabetes mellitus if the fasting glucose in the hospital was >140 mg/dl, or if the patient required previous or ongoing therapy. Systemic hypertension was defined as either systolic pressure ≥140 mm Hg and/or diastolic pressure ≥90 mm Hg or elevation of diastolic or systolic pressure requiring pharmacologic therapy for blood pressure control. A history of smoking was defined as ≥10 pack-years of cigarette smoking. BMI was computed as weight divided by height squared. Obesity was defined as BMI ≥30 kg/m2. A positive family history of CAD was defined as myocardial infarction or known CAD in a parent or sibling noted at ≤65 years.Results are expressed as mean ± SD. Student's t test was used to compare continuous variables, and chi-square was used to compare categorical variables. A p 200 mg/dl, BMI >30 kg/m2, history of smoking, and systemic hypertension as independent markers of AS. After adjustment for conventional risk factors and presence of CAD (model 2), systemic hypertension, history of smoking, total cholesterol >200 mg/dl, and BMI >30 kg/m2 remained strongly associated with AS (Table 2). TABLE 1Prevalences and Characteristics of Cardiovascular Risk Factors in Patients With and Without Nonrheumatic Severe Calcific Aortic StenosisVariableNonrheumatic Aortic Stenosis GroupControl Groupp Value(n = 220)(n = 220)Age (yrs)68 ± 968 ± 80.678Men/women135/85 (61%/49%)135/85 (61%/49%)1.000Systemic hypertension122 (55%)72 (32%)<0.001Smoker101 (46%)68 (31%)0.001Diabetes mellitus41 (19%)33 (15%)0.307Family history of CAD53 (24%)41 (19%)0.169BMI (kg/m2)28.02 ± 4.8425.44 ± 3.86<0.001Total cholesterol (mg/dl)211 ± 43193 ± 48<0.001Triglycerides (mg/dl)111 ± 61100 ± 520.054CAD104 (47%)82 (37%)0.033 Open table in a new tab TABLE 2Multivariate Logistic Analysis of Risk Factors Related to the Presence of Nonrheumatic Severe Calcific Aortic StenosisVariableModel 1Model 2Odds Ratio95% Confidence Intervalsp ValueOdds Ratio95% Confidence Intervalsp ValueSystemic hypertension2.211.48–3.32<0.0012.171.44–3.27 30 kg/m22.031.24–3.340.0052.031.24–3.340.005Total serum cholesterol >200 mg/dl2.141.44–3.20<0.0012.111.41–3.16<0.001CAD———1.160.77–1.760.470 Open table in a new tab Roberts1Roberts W.C. The senile cardiac calcification syndrome.Am J Cardiol. 1986; 58: 572-574Abstract Full Text PDF PubMed Scopus (179) Google Scholar claimed that because calcified deposits in the aortic valve cusps are observed in a population that develops coronary atherosclerosis, it seems reasonable to assume that calcific valves in the elderly have similar predisposing factors. The results of the present large and prospective case-control study show a strong association of hypertension, obesity, hypercholesterolemia, and smoking with the presence of calcific degenerative AS, independently of the presence of CAD. An association between hypertension, smoking, and hypercholesterolemia with mild AS or aortic sclerosis has been reported in previous studies.2Chan K.L. Ghani M. Woodend K. Burwash I.G. Case-controlled study to assess risk factors for aortic stenosis in congenitally bicuspid aortic valve.Am J Cardiol. 2001; 88: 690-693Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar, 3Mohler E.R. Sheridan M.J. Nichols R. Harvey W.P. Waller B.F. Development and progression of aortic valve stenosis atherosclerosis risk factors—a causal relationship? A clinical morphologic study.Clin Cardiol. 1991; 14: 995-999Crossref PubMed Scopus (199) Google Scholar, 4Nassimiha D. Aronow W.S. Ahn C. Goldman M.E. Association of cororonary risk factors with progression of valvular aortic stenosis in older persons.Am J Cardiol. 2001; 87: 1313-1314Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Hoagland P.M. Cook F. Flatley M. Walker C. Goldman L. Case-control analysis of risk factors for presence of aortic stenosis in adults (age 50 years or older).Am J Cardiol. 1985; 55: 744-747Abstract Full Text PDF PubMed Scopus (67) Google Scholar, 6Stewart B.F. Siscovick D. Lind B.K. Gardin J.M. Gottdiener J.S. Smmith V.E. Kitzman D.W. Otto C.M. Cardiovascular Heart StudyClinical factors associated with calcific aortic valve disease.J Am Coll Cardiol. 1997; 29: 630-634Abstract Full Text Full Text PDF PubMed Scopus (1567) Google Scholar, 7Boon A. Cheriex E. Lodder J. Kessels F. Cardiac valve calcification characteristics of patients with calcification of the mitral annulus or calcific aortic valve disease.Heart. 1997; 78: 472-474PubMed Google Scholar However, these studies are retrospective,3Mohler E.R. Sheridan M.J. Nichols R. Harvey W.P. Waller B.F. Development and progression of aortic valve stenosis atherosclerosis risk factors—a causal relationship? A clinical morphologic study.Clin Cardiol. 1991; 14: 995-999Crossref PubMed Scopus (199) Google Scholar, 4Nassimiha D. Aronow W.S. Ahn C. Goldman M.E. Association of cororonary risk factors with progression of valvular aortic stenosis in older persons.Am J Cardiol. 2001; 87: 1313-1314Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Hoagland P.M. Cook F. Flatley M. Walker C. Goldman L. Case-control analysis of risk factors for presence of aortic stenosis in adults (age 50 years or older).Am J Cardiol. 1985; 55: 744-747Abstract Full Text PDF PubMed Scopus (67) Google Scholar based only on transthoracic echocardiographic examinations,6Stewart B.F. Siscovick D. Lind B.K. Gardin J.M. Gottdiener J.S. Smmith V.E. Kitzman D.W. Otto C.M. Cardiovascular Heart StudyClinical factors associated with calcific aortic valve disease.J Am Coll Cardiol. 1997; 29: 630-634Abstract Full Text Full Text PDF PubMed Scopus (1567) Google Scholar, 7Boon A. Cheriex E. Lodder J. Kessels F. Cardiac valve calcification characteristics of patients with calcification of the mitral annulus or calcific aortic valve disease.Heart. 1997; 78: 472-474PubMed Google Scholar with no specific analysis of morphologic etiology6Stewart B.F. Siscovick D. Lind B.K. Gardin J.M. Gottdiener J.S. Smmith V.E. Kitzman D.W. Otto C.M. Cardiovascular Heart StudyClinical factors associated with calcific aortic valve disease.J Am Coll Cardiol. 1997; 29: 630-634Abstract Full Text Full Text PDF PubMed Scopus (1567) Google Scholar, 7Boon A. Cheriex E. Lodder J. Kessels F. Cardiac valve calcification characteristics of patients with calcification of the mitral annulus or calcific aortic valve disease.Heart. 1997; 78: 472-474PubMed Google Scholar and limited by referral bias and narrow age range.2Chan K.L. Ghani M. Woodend K. Burwash I.G. Case-controlled study to assess risk factors for aortic stenosis in congenitally bicuspid aortic valve.Am J Cardiol. 2001; 88: 690-693Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar, 4Nassimiha D. Aronow W.S. Ahn C. Goldman M.E. Association of cororonary risk factors with progression of valvular aortic stenosis in older persons.Am J Cardiol. 2001; 87: 1313-1314Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Hoagland P.M. Cook F. Flatley M. Walker C. Goldman L. Case-control analysis of risk factors for presence of aortic stenosis in adults (age 50 years or older).Am J Cardiol. 1985; 55: 744-747Abstract Full Text PDF PubMed Scopus (67) Google Scholar, 6Stewart B.F. Siscovick D. Lind B.K. Gardin J.M. Gottdiener J.S. Smmith V.E. Kitzman D.W. Otto C.M. Cardiovascular Heart StudyClinical factors associated with calcific aortic valve disease.J Am Coll Cardiol. 1997; 29: 630-634Abstract Full Text Full Text PDF PubMed Scopus (1567) Google Scholar, 7Boon A. Cheriex E. Lodder J. Kessels F. Cardiac valve calcification characteristics of patients with calcification of the mitral annulus or calcific aortic valve disease.Heart. 1997; 78: 472-474PubMed Google Scholar To our knowledge, the present study is the first to demonstrate a specific association of multiple cardiovascular risk factors with severe AS due to calcific degeneration. This study enabled us to assess both the morphologic valve with operative macroscopic data and functional status of calcific degenerative AS with echocardiographic findings. Morphology of the aortic valve was based on echocardiography or electron beam tomography in previous studies.2Chan K.L. Ghani M. Woodend K. Burwash I.G. Case-controlled study to assess risk factors for aortic stenosis in congenitally bicuspid aortic valve.Am J Cardiol. 2001; 88: 690-693Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar, 3Mohler E.R. Sheridan M.J. Nichols R. Harvey W.P. Waller B.F. Development and progression of aortic valve stenosis atherosclerosis risk factors—a causal relationship? A clinical morphologic study.Clin Cardiol. 1991; 14: 995-999Crossref PubMed Scopus (199) Google Scholar, 4Nassimiha D. Aronow W.S. Ahn C. Goldman M.E. Association of cororonary risk factors with progression of valvular aortic stenosis in older persons.Am J Cardiol. 2001; 87: 1313-1314Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Hoagland P.M. Cook F. Flatley M. Walker C. Goldman L. Case-control analysis of risk factors for presence of aortic stenosis in adults (age 50 years or older).Am J Cardiol. 1985; 55: 744-747Abstract Full Text PDF PubMed Scopus (67) Google Scholar, 6Stewart B.F. Siscovick D. Lind B.K. Gardin J.M. Gottdiener J.S. Smmith V.E. Kitzman D.W. Otto C.M. Cardiovascular Heart StudyClinical factors associated with calcific aortic valve disease.J Am Coll Cardiol. 1997; 29: 630-634Abstract Full Text Full Text PDF PubMed Scopus (1567) Google Scholar, 7Boon A. Cheriex E. Lodder J. Kessels F. Cardiac valve calcification characteristics of patients with calcification of the mitral annulus or calcific aortic valve disease.Heart. 1997; 78: 472-474PubMed Google Scholar, 8Pohle K. Mäffert R. Ropers D. Moshage W. Stilinakis N. Daniel W.G. Achenbach S. Progression of aortic valve calcification. Association with coronary atherosclerosis and cardiovascular risk factors.Circulation. 2001; 104: 1927-1932Crossref PubMed Scopus (362) Google Scholar We also found a strong association with increased BMI and calcific degenerative AS, whereas previous studies produced conflicting results.6Stewart B.F. Siscovick D. Lind B.K. Gardin J.M. Gottdiener J.S. Smmith V.E. Kitzman D.W. Otto C.M. Cardiovascular Heart StudyClinical factors associated with calcific aortic valve disease.J Am Coll Cardiol. 1997; 29: 630-634Abstract Full Text Full Text PDF PubMed Scopus (1567) Google Scholar, 9Lindroos M. Kupari M. Valvanne J. Strandberg T Heikkila J. Tilvis R. Factors associated with calcific valve degeneration in the elderly.Eur Heart J. 1994; 15: 865-870PubMed Google Scholar Recently, Agmon et al10Agmon Y. Khandheria B.K. Meissner I. Sicks J.D. O'Fallon W.M. Wiebers D.O. Whisnant J.P. Sewart J.B. Tajik A.J. Aortic valve sclerosis and aortic atherosclerosis different manifestations of the same disease? Insights from a population-based study.J Am Coll Cardiol. 2001; 38: 827-834Abstract Full Text Full Text PDF PubMed Scopus (197) Google Scholar found a positive relation betweeen increased BMI and aortic valve sclerosis. They postulated that the relation might be mediated through associated metabolic abnormalities or increased mechanical stress upon the aortic valve due to hemodynamic changes. In the present study, we did not measure physical activity level or low-density lipoprotein cholesterol and high-density lipoprotein cholesterol concentrations. It would be interesting to know the effects of these factors on severe calcific AS.In summary, this large case-control study shows that the development of severe AS caused by the calcific degenerative process is not simply a consequence of aging. Thus, systemic hypertension (odds ratio 2.17, 95% confidence intervals 1.44 to 3.27, p 200 mg/dl (odds ratio 2.11, 95% confidence intervals 1.41 to 3.16, p 30 kg/m2 (odds ratio 2.03, 95% confidence intervals 1.24 to 3.34, p = 0.005) are strongly associated with nonrheumatic severe calcific AS. Valvular aortic stenosis (AS) caused by degenerative calcification of the valvar structures has become the most common valvar disease requiring cardiac surgery in industrialized countries. Roberts1Roberts W.C. The senile cardiac calcification syndrome.Am J Cardiol. 1986; 58: 572-574Abstract Full Text PDF PubMed Scopus (179) Google Scholar suggested as early as 1986 that factors predisposing to atherosclerosis in the coronary arteries also predispose the aortic valve to calcification in the elderly. Previous clinical studies reported that atherosclerotic risk factors associated with AS could vary with the etiology.2Chan K.L. Ghani M. Woodend K. Burwash I.G. Case-controlled study to assess risk factors for aortic stenosis in congenitally bicuspid aortic valve.Am J Cardiol. 2001; 88: 690-693Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar, 3Mohler E.R. Sheridan M.J. Nichols R. Harvey W.P. Waller B.F. Development and progression of aortic valve stenosis atherosclerosis risk factors—a causal relationship? A clinical morphologic study.Clin Cardiol. 1991; 14: 995-999Crossref PubMed Scopus (199) Google Scholar To our knowledge, no data are available in patients with exclusively severe calcific degenerative AS. This prospective study, controlled for age and sex, was designed to examine the specific relation between the presence of severe calcific degenerative AS and cardiovascular risk factors. Between September 1996 and February 2000, 220 consecutive patients with severe calcific degenerative AS (mean age of 68 ± 9 years, range 52 to 82; 135 men, 85 women) considered for surgery prospectively underwent coronary angiography and transthoracic echocardiography. Severe AS was defined as the presence of an aortic valve area ≤0.75 cm2 computed with the continuity equation, using standard methods in transthoracic echocardiography. All patients gave informed consent to participate in the study. These patients were compared with 220 age- and gender-matched patients (mean age of 68 ± 8 years, range 50 to 86; 135 men, 85 women) with valvular regurgitation, but without AS, referred for surgery during the same period. The diagnosis of calcific degenerative AS was performed on the basis of clinical criteria (no history of rheumatic disease and/or no history of murmur at a younger age) and on the echocardiographic findings of thickening and increased echogenicity of the cusps, excluding the free edges with reduced systolic opening. The morphologic confirmation of diagnosis of calcific degenerative AS at surgery was an additional diagnostic criterion defined as a stenotic 3-cuspid aortic valve excised as 3 individual cusps (i.e., no commissural fusion) in patients in whom the mitral valve was normal. Patients with surgical evidence of probable rheumatic aortic valve disease or congenital bicuspid valve were excluded. Significant coronary artery disease (CAD) was defined as a ≥50% reduction of the internal diameter of ≥1 of the coronary arteries. The cardiovascular risk factors recorded were total cholesterol and triglycerides concentrations, systemic hypertension, history of smoking, diabetes mellitus, body mass index (BMI), and family history of CAD. Patients on lipid-lowering medications were excluded. Blood was drawn after a 14-hour overnight fast for determination of serum total cholesterol and triglycerides with standard methods. Hypercholesterolemia was considered present if the fasting total cholesterol was >200 mg/dl, diabetes mellitus if the fasting glucose in the hospital was >140 mg/dl, or if the patient required previous or ongoing therapy. Systemic hypertension was defined as either systolic pressure ≥140 mm Hg and/or diastolic pressure ≥90 mm Hg or elevation of diastolic or systolic pressure requiring pharmacologic therapy for blood pressure control. A history of smoking was defined as ≥10 pack-years of cigarette smoking. BMI was computed as weight divided by height squared. Obesity was defined as BMI ≥30 kg/m2. A positive family history of CAD was defined as myocardial infarction or known CAD in a parent or sibling noted at ≤65 years. Results are expressed as mean ± SD. Student's t test was used to compare continuous variables, and chi-square was used to compare categorical variables. A p 200 mg/dl, BMI >30 kg/m2, history of smoking, and systemic hypertension as independent markers of AS. After adjustment for conventional risk factors and presence of CAD (model 2), systemic hypertension, history of smoking, total cholesterol >200 mg/dl, and BMI >30 kg/m2 remained strongly associated with AS (Table 2). Roberts1Roberts W.C. The senile cardiac calcification syndrome.Am J Cardiol. 1986; 58: 572-574Abstract Full Text PDF PubMed Scopus (179) Google Scholar claimed that because calcified deposits in the aortic valve cusps are observed in a population that develops coronary atherosclerosis, it seems reasonable to assume that calcific valves in the elderly have similar predisposing factors. The results of the present large and prospective case-control study show a strong association of hypertension, obesity, hypercholesterolemia, and smoking with the presence of calcific degenerative AS, independently of the presence of CAD. An association between hypertension, smoking, and hypercholesterolemia with mild AS or aortic sclerosis has been reported in previous studies.2Chan K.L. Ghani M. Woodend K. Burwash I.G. Case-controlled study to assess risk factors for aortic stenosis in congenitally bicuspid aortic valve.Am J Cardiol. 2001; 88: 690-693Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar, 3Mohler E.R. Sheridan M.J. Nichols R. Harvey W.P. Waller B.F. Development and progression of aortic valve stenosis atherosclerosis risk factors—a causal relationship? A clinical morphologic study.Clin Cardiol. 1991; 14: 995-999Crossref PubMed Scopus (199) Google Scholar, 4Nassimiha D. Aronow W.S. Ahn C. Goldman M.E. Association of cororonary risk factors with progression of valvular aortic stenosis in older persons.Am J Cardiol. 2001; 87: 1313-1314Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Hoagland P.M. Cook F. Flatley M. Walker C. Goldman L. Case-control analysis of risk factors for presence of aortic stenosis in adults (age 50 years or older).Am J Cardiol. 1985; 55: 744-747Abstract Full Text PDF PubMed Scopus (67) Google Scholar, 6Stewart B.F. Siscovick D. Lind B.K. Gardin J.M. Gottdiener J.S. Smmith V.E. Kitzman D.W. Otto C.M. Cardiovascular Heart StudyClinical factors associated with calcific aortic valve disease.J Am Coll Cardiol. 1997; 29: 630-634Abstract Full Text Full Text PDF PubMed Scopus (1567) Google Scholar, 7Boon A. Cheriex E. Lodder J. Kessels F. Cardiac valve calcification characteristics of patients with calcification of the mitral annulus or calcific aortic valve disease.Heart. 1997; 78: 472-474PubMed Google Scholar However, these studies are retrospective,3Mohler E.R. Sheridan M.J. Nichols R. Harvey W.P. Waller B.F. Development and progression of aortic valve stenosis atherosclerosis risk factors—a causal relationship? A clinical morphologic study.Clin Cardiol. 1991; 14: 995-999Crossref PubMed Scopus (199) Google Scholar, 4Nassimiha D. Aronow W.S. Ahn C. Goldman M.E. Association of cororonary risk factors with progression of valvular aortic stenosis in older persons.Am J Cardiol. 2001; 87: 1313-1314Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Hoagland P.M. Cook F. Flatley M. Walker C. Goldman L. Case-control analysis of risk factors for presence of aortic stenosis in adults (age 50 years or older).Am J Cardiol. 1985; 55: 744-747Abstract Full Text PDF PubMed Scopus (67) Google Scholar based only on transthoracic echocardiographic examinations,6Stewart B.F. Siscovick D. Lind B.K. Gardin J.M. Gottdiener J.S. Smmith V.E. Kitzman D.W. Otto C.M. Cardiovascular Heart StudyClinical factors associated with calcific aortic valve disease.J Am Coll Cardiol. 1997; 29: 630-634Abstract Full Text Full Text PDF PubMed Scopus (1567) Google Scholar, 7Boon A. Cheriex E. Lodder J. Kessels F. Cardiac valve calcification characteristics of patients with calcification of the mitral annulus or calcific aortic valve disease.Heart. 1997; 78: 472-474PubMed Google Scholar with no specific analysis of morphologic etiology6Stewart B.F. Siscovick D. Lind B.K. Gardin J.M. Gottdiener J.S. Smmith V.E. Kitzman D.W. Otto C.M. Cardiovascular Heart StudyClinical factors associated with calcific aortic valve disease.J Am Coll Cardiol. 1997; 29: 630-634Abstract Full Text Full Text PDF PubMed Scopus (1567) Google Scholar, 7Boon A. Cheriex E. Lodder J. Kessels F. Cardiac valve calcification characteristics of patients with calcification of the mitral annulus or calcific aortic valve disease.Heart. 1997; 78: 472-474PubMed Google Scholar and limited by referral bias and narrow age range.2Chan K.L. Ghani M. Woodend K. Burwash I.G. Case-controlled study to assess risk factors for aortic stenosis in congenitally bicuspid aortic valve.Am J Cardiol. 2001; 88: 690-693Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar, 4Nassimiha D. Aronow W.S. Ahn C. Goldman M.E. Association of cororonary risk factors with progression of valvular aortic stenosis in older persons.Am J Cardiol. 2001; 87: 1313-1314Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Hoagland P.M. Cook F. Flatley M. Walker C. Goldman L. Case-control analysis of risk factors for presence of aortic stenosis in adults (age 50 years or older).Am J Cardiol. 1985; 55: 744-747Abstract Full Text PDF PubMed Scopus (67) Google Scholar, 6Stewart B.F. Siscovick D. Lind B.K. Gardin J.M. Gottdiener J.S. Smmith V.E. Kitzman D.W. Otto C.M. Cardiovascular Heart StudyClinical factors associated with calcific aortic valve disease.J Am Coll Cardiol. 1997; 29: 630-634Abstract Full Text Full Text PDF PubMed Scopus (1567) Google Scholar, 7Boon A. Cheriex E. Lodder J. Kessels F. Cardiac valve calcification characteristics of patients with calcification of the mitral annulus or calcific aortic valve disease.Heart. 1997; 78: 472-474PubMed Google Scholar To our knowledge, the present study is the first to demonstrate a specific association of multiple cardiovascular risk factors with severe AS due to calcific degeneration. This study enabled us to assess both the morphologic valve with operative macroscopic data and functional status of calcific degenerative AS with echocardiographic findings. Morphology of the aortic valve was based on echocardiography or electron beam tomography in previous studies.2Chan K.L. Ghani M. Woodend K. Burwash I.G. Case-controlled study to assess risk factors for aortic stenosis in congenitally bicuspid aortic valve.Am J Cardiol. 2001; 88: 690-693Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar, 3Mohler E.R. Sheridan M.J. Nichols R. Harvey W.P. Waller B.F. Development and progression of aortic valve stenosis atherosclerosis risk factors—a causal relationship? A clinical morphologic study.Clin Cardiol. 1991; 14: 995-999Crossref PubMed Scopus (199) Google Scholar, 4Nassimiha D. Aronow W.S. Ahn C. Goldman M.E. Association of cororonary risk factors with progression of valvular aortic stenosis in older persons.Am J Cardiol. 2001; 87: 1313-1314Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Hoagland P.M. Cook F. Flatley M. Walker C. Goldman L. Case-control analysis of risk factors for presence of aortic stenosis in adults (age 50 years or older).Am J Cardiol. 1985; 55: 744-747Abstract Full Text PDF PubMed Scopus (67) Google Scholar, 6Stewart B.F. Siscovick D. Lind B.K. Gardin J.M. Gottdiener J.S. Smmith V.E. Kitzman D.W. Otto C.M. Cardiovascular Heart StudyClinical factors associated with calcific aortic valve disease.J Am Coll Cardiol. 1997; 29: 630-634Abstract Full Text Full Text PDF PubMed Scopus (1567) Google Scholar, 7Boon A. Cheriex E. Lodder J. Kessels F. Cardiac valve calcification characteristics of patients with calcification of the mitral annulus or calcific aortic valve disease.Heart. 1997; 78: 472-474PubMed Google Scholar, 8Pohle K. Mäffert R. Ropers D. Moshage W. Stilinakis N. Daniel W.G. Achenbach S. Progression of aortic valve calcification. Association with coronary atherosclerosis and cardiovascular risk factors.Circulation. 2001; 104: 1927-1932Crossref PubMed Scopus (362) Google Scholar We also found a strong association with increased BMI and calcific degenerative AS, whereas previous studies produced conflicting results.6Stewart B.F. Siscovick D. Lind B.K. Gardin J.M. Gottdiener J.S. Smmith V.E. Kitzman D.W. Otto C.M. Cardiovascular Heart StudyClinical factors associated with calcific aortic valve disease.J Am Coll Cardiol. 1997; 29: 630-634Abstract Full Text Full Text PDF PubMed Scopus (1567) Google Scholar, 9Lindroos M. Kupari M. Valvanne J. Strandberg T Heikkila J. Tilvis R. Factors associated with calcific valve degeneration in the elderly.Eur Heart J. 1994; 15: 865-870PubMed Google Scholar Recently, Agmon et al10Agmon Y. Khandheria B.K. Meissner I. Sicks J.D. O'Fallon W.M. Wiebers D.O. Whisnant J.P. Sewart J.B. Tajik A.J. Aortic valve sclerosis and aortic atherosclerosis different manifestations of the same disease? Insights from a population-based study.J Am Coll Cardiol. 2001; 38: 827-834Abstract Full Text Full Text PDF PubMed Scopus (197) Google Scholar found a positive relation betweeen increased BMI and aortic valve sclerosis. They postulated that the relation might be mediated through associated metabolic abnormalities or increased mechanical stress upon the aortic valve due to hemodynamic changes. In the present study, we did not measure physical activity level or low-density lipoprotein cholesterol and high-density lipoprotein cholesterol concentrations. It would be interesting to know the effects of these factors on severe calcific AS. In summary, this large case-control study shows that the development of severe AS caused by the calcific degenerative process is not simply a consequence of aging. Thus, systemic hypertension (odds ratio 2.17, 95% confidence intervals 1.44 to 3.27, p 200 mg/dl (odds ratio 2.11, 95% confidence intervals 1.41 to 3.16, p 30 kg/m2 (odds ratio 2.03, 95% confidence intervals 1.24 to 3.34, p = 0.005) are strongly associated with nonrheumatic severe calcific AS. Thanks to Edward Frohlich, MD, who revised this manuscript.
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