Correspondence
Aortic-Valve Sclerosis
N Engl J Med 1999; 341:1856-1857December 9, 1999
- Article
To the Editor:
Otto et al. (July 15 issue)1 reported that the presence of aortic-valve disease without stenosis was associated with an increased risk of death from any cause and death from cardiovascular causes among the participants in the Cardiovascular Health Study and its supplemental cohort. One plausible explanation for this finding is inadequate adjustment for confounding variables. In fact, the authors did not adjust for the presence of renal insufficiency or impaired functional capacity — two variables that differed significantly between subjects with and those without aortic sclerosis.
Furthermore, a multivariate analysis from the same study group2 (which excluded the 687 supplemental subjects but included the 92 subjects with aortic stenosis) defined predictors of death from any cause in the Cardiovascular Health Study population. In addition to the factors adjusted for by Otto et al., annual income less than $50,000 per year, low weight, lack of moderate or vigorous physical activity, high brachial and low tibial systolic blood pressure, use of diuretics by those without hypertension or congestive heart failure, low serum albumin level, elevated serum creatinine level, congestive heart failure, low forced vital capacity, abnormal ejection fraction, major electrocardiographic abnormalities, and impaired function as measured by three assessment variables were all independently associated with mortality.
Why did the authors not adjust for all the variables included in the prior analysis? Is the disparity due to the slight differences in populations? Were all those other variables nonsignificant predictors of outcome in the analysis of aortic sclerosis? Is the disparity due to the additional end points tested (i.e., death from cardiovascular causes and myocardial infarction)? Could the absence of adjustment for renal insufficiency and functional impairment account for their findings?
2 ReferencesWilliam S. Getchell, M.D., M.P.H.
Portland Veterans Affairs Medical Center, Portland, OR 972071
Otto CM ,Lind BK ,Kitzman DW ,Gersh BJ ,Siscovick DS . Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med 1999;341:142-147
Full Text | Web of Science | Medline2
Fried LP ,Kronmal RA ,Newman AB , et al. Risk factors for 5-year mortality in older adults: the Cardiovascular Health Study. JAMA 1998;279:585-592
CrossRef | Web of Science | Medline
To the Editor:
The article by Otto et al. reveals a correlation between aortic sclerosis and an increase in deaths from any cause and from cardiovascular causes. It would have been interesting to know how many of the subjects with aortic sclerosis had mitral annular calcification. A study by Boon et al.1 showed that mitral annular calcification and aortic sclerosis, stenotic or nonstenotic, were associated with a higher incidence of atherosclerotic risk factors, suggesting that these characteristics might be expressions of generalized atherosclerosis. Patients with mitral annular calcification also had a high prevalence of aortic-valve sclerosis (43 percent) and calcific aortic-valve stenosis (17 percent), though a significant association could not be proved. If aortic sclerosis is a novel risk factor for increased morbidity and mortality, we need further information to demonstrate any relation between mitral annular calcification and aortic sclerosis as risk factors for cardiovascular morbidity and mortality. In addition, Honda et al.2 state that hypertension may be a strong contributing factor promoting aortic sclerosis, suggesting that aortic sclerosis is part of a multifactorial process rather than a single marker for cardiovascular events.
2 ReferencesDaryl K. Kim, M.D.
Vijay Rajput, M.D.
University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, Camden, NJ 081031
Boon A ,Cheriex E ,Lodder J ,Kessels F . Cardiac valve calcification: characteristics of patients with calcification of the mitral annulus or aortic valve. Heart 1997;78:472-474
Web of Science | Medline2
Honda T ,Yano K ,Matsuoka H ,Hamada M ,Hiwada K . Evaluation of aortic distensibility in patients with essential hypertension by using cine magnetic resonance imaging. Angiology 1994;45:207-212
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To the Editor:
Otto et al. make an important contribution to our understanding of aortic-valve sclerosis, and we agree with their conclusions. Since the Cardiovascular Health Study apparently has follow-up echocardiograms for their large cohort of elderly subjects, we wonder how many of the 1610 subjects who had aortic sclerosis at base line went on to have aortic stenosis during the course of the study. We suspect that this number is more than trivial, since in our experience, severe obstruction can develop well within the five years of follow-up included in the study.
One important practical issue is what to do with a 70-year-old patient with aortic sclerosis who is otherwise healthy (no gradient on echocardiography) and who requires coronary-artery bypass grafting. Should the aortic valve be replaced prophylactically, or should one wait until stenosis develops and then do a second open-heart operation? We would be interested in whatever data the authors can provide that would be relevant to this vexing clinical question, as well as in learning their own approach to the problem.
Stephen C. Achuff, M.D.
William A. Baumgartner, M.D.
Johns Hopkins Hospital, Baltimore, MD 21287Author/Editor Response
The authors reply:
To the Editor: We examined the relation between aortic-valve sclerosis and clinical outcome in the Cardiovascular Health Study population. Getchell is concerned that the observed associations may have been due to inadequate adjustment for other variables — specifically, those identified in an earlier Cardiovascular Health Study report on risk factors for five-year mortality.1 Although aortic stenosis was identified as an independent risk factor for mortality in this earlier study, subjects with aortic stenosis were excluded from the analysis of the relative risk associated with aortic sclerosis in our more recent study. As the earlier report noted, “the presence of subclinical disease provides unique information in predicting mortality.” Our recent evaluation provides a detailed evaluation of a specific subclinical factor (e.g., aortic sclerosis) that was not examined previously. We did correct for age, sex, and clinical factors associated with aortic sclerosis in the Cox regression analysis, and it is unlikely that the other factors mentioned by Getchell differed substantially between subjects with and those without aortic sclerosis.2 Still, we share the concern that unevaluated factors may have contributed to the observed associations. The relation between aortic-valve sclerosis and adverse cardiovascular outcomes needs to be confirmed in other independent studies.
Kim and Rajput note that a relation between mitral annular calcification and atherosclerotic risk factors has been reported. In our study, we did not evaluate whether there was an association between mitral annular calcification and cardiovascular outcome, but we agree that a study of this possible association would be of interest. It can be hypothesized that factors leading to cardiac-valve and annular calcification may be associated and that both types of cardiac calcification are likely to represent the same underlying disease process.
Achuff and Baumgartner raise the issue of progression of aortic-valve obstruction. In our study, aortic sclerosis was defined as focal leaflet thickening without restriction of leaflet motion. Prospective natural-history studies suggest that the rate of hemodynamic progression is low in this subgroup of patients with mild disease.3 However, differences in techniques and reporting of data between the first and subsequent echocardiographic studies in the Cardiovascular Health Study preclude a direct assessment of the rate of progression in the study group.
3 ReferencesCatherine M. Otto, M.D.
David S. Siscovick, M.D., M.P.H.
University of Washington School of Medicine, Seattle, WA 981951
Fried LP ,Kronmal RA ,Newman AB , et al. Risk factors for 5-year mortality in older adults: the Cardiovascular Health Study. JAMA 1998;279:585-592
CrossRef | Web of Science | Medline2
Stewart BF ,Siscovick D ,Lind BK , et al. Clinical factors associated with calcific aortic valve disease: Cardiovascular Health Study. J Am Coll Cardiol 1997;29:630-634
CrossRef | Web of Science | Medline3
Otto CM ,Burwash IG ,Legget ME , et al. Prospective study of asymptomatic valvular aortic stenosis: clinical, echocardiographic, and exercise predictors of outcome. Circulation 1997;95:2262-2270
Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Pasquale Palmiero, Maria Maiello, Andrea Passantino, Sanjeev Wasson, Hanumanth K. Reddy. (2007) Aortic Valve Sclerosis: Is It a Cardiovascular Risk Factor or a Cardiac Disease Marker?. Echocardiography 24:3, 217-221
CrossRef
