Author + information
- Jay N. Cohn, MD* ()
- ↵*Reprint requests and correspondence:
Dr. Jay N. Cohn, Cardiovascular Division, Mayo Mail Code 508, University of Minnesota Medical School, 420 Delaware Street SE, Minneapolis, Minnesota 55455
Heart failure is a clinical syndrome that is a consequence of a wide array of left ventricular functional and structural disorders. As opposed to other morbid cardiovascular events, such as acute myocardial infarction and stroke, which are predominantly a consequence of atherosclerosis and thrombosis, heart failure may also be a complication of pressure overload, volume overload, aging, and nonischemic diseases of the myocardium. Therefore, seeking a single factor or factors predictive of this clinical syndrome seems likely doomed to failure, and a prominent role of any predictive factor would be highly dependent on the specific population being evaluated. Furthermore, any biomarker correlated with incident heart failure in this population would be expected to relate to only a subset of the population, not all incidences of the clinical syndrome.
Despite these admonitions, Kalogeropoulos et al. (1) explored the Health ABC (Aging and Body Composition) Study population to determine whether inflammatory markers might be useful in predicting incident heart failure. When added to the previously identified risk factor model described by Butler et al. (2) in this population, they demonstrated that these biomarkers, especially interleukin-6, improve the model for predicting heart failure.
It is important to appreciate the uniqueness of this population. They were apparently healthy people in their eighth decade living in the Pittsburgh and Memphis metropolitan areas when they were recruited in 1997 to 1998. They had obviously survived without significant disability the cardiovascular diseases that lead to most premature morbidity and mortality. Heart failure developing in the ensuing 10 years in this population would be expected to reflect the aging process, and a high percentage apparently exhibited the clinical syndrome with maintenance of a normal ejection fraction and therefore a nondilated left ventricle. That inflammatory biomarkers added to the predictive value of age, blood pressure, a history of coronary disease, and routine blood chemistries is not surprising given the known association of inflammatory markers with atherosclerosis and vascular aging (3). Whether such biomarkers would be comparably predictive in a younger population with a different pattern of heart failure episodes is unknown.
The more important issue is whether such examination of statistical associations in population risk can be clinically useful. Characterization of stage A heart failure by the American College of Cardiology/American Heart Association guidelines (4) has invited efforts to seek markers in asymptomatic individuals that place them at increased risk of progression to stage B, with structural cardiac abnormalities, and stage C with symptomatic heart failure. Can identification of such markers be useful clinically to reduce the incidence of heart failure?
Public health policy has been aimed at risk factor reduction in the community. This approach has been advocated especially for atherosclerotic disease with an emphasis on blood pressure, cholesterol, smoking, and obesity. A reduction in atherosclerosis should also reduce the incidence of heart failure, especially in a somewhat younger population than that examined in the Health ABC Study population. So risk factor models can be used to inform public health policy that can be applied in an effort to reduce population risk. How could inflammatory biomarkers be used in this community approach? Inflammation has been demonstrated to exhibit a modest association with cardiovascular disease (5), but there is little evidence that the inflammation associated with these biomarkers is causative and needs to be treated (6). In the absence of persuasive therapeutic outcome studies, there is no justification for routine assessment of interleukin-6 to help steer community-wide preventive efforts.
Could measurement of interleukin-6 be used as a screening tool to identify higher risk patients for inclusion in a large-scale outcome trial aimed at preventing heart failure? These data raise this future possibility, but there is certainly no current enthusiasm for such a study and no attractive therapy to use in asymptomatic individuals without demonstrable structural cardiac abnormalities.
Can a risk model for heart failure developed in an elderly population serve a useful purpose in individualized patient care? The hazard ratio of any risk marker for a future morbid event would need to be quite formidable to justify using that marker to guide individualized therapy. This issue also remains a concern with the future prospects of genome-associated personalized medicine. Is even a doubling of risk associated with a marker adequate to introduce therapy in a patient with the marker and withhold it in one without the marker? Individualized patient care would seem to demand more precision than these statistical associations can provide.
Even if one chose to use the data from the Health ABC Study population to identify individuals in whom heart failure is more likely to develop in the future, how would one intervene? There is no evidence to support anti-inflammatory therapy and no rationale to initiate preventive therapy in individuals without structural heart disease or without demonstrable risk factors that mandate treatment.
Rather than risk factors and biomarkers, which seem unlikely to ever achieve the diagnostic precision to be useful in individualized patient management, emphasis probably should be placed on more precise early diagnosis of the functional and structural disease likely to progress. Clinical heart failure is always preceded by functional and structural abnormalities of the heart and/or vasculature that can be detected by simple noninvasive testing (7,8). Therapy aimed at these demonstrable abnormalities is known to slow the progression of the disease (9,10).
It is therefore time to initiate and document the effectiveness of efforts to identify early stages of cardiovascular disease with a goal of reducing the occurrence of symptomatic disease. Screening, much like that currently used routinely to identify early cancer, is a strategy that should be adopted by the cardiovascular community. For heart failure, it would be a focus on early identification of stage B with innovative interventions to prevent progression to stage C.
Dr. Cohn is the Director of Cohn Prevention Centers, LLC, and the Director of Hypertension Diagnostics, Inc.
↵* Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of the JACCor the American College of Cardiology.
- American College of Cardiology Foundation
- Kalogeropoulos A.,
- Georgiopoulou V.,
- Psaty B.M.,
- et al.,
- Health ABC Study Investigators
- Butler J.,
- Kalogeropoulos A.,
- Georgiopoulou V.,
- et al.
- Hunt S.A.,
- Abraham W.T.,
- Chin M.H.,
- et al.
- Ridker P.M.
- Duprez D.A.,
- Cohn J.N.
- Duprez D.A.,
- Florea N.D.,
- Jones K.,
- Cohn J.N.