Is It a Coincidence that Death Rhymes with Breath?

Abstract & Commentary

By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips is a consultant for Cephalon, and serves on the speakers bureaus for Resmed and Respironics.

Synopsis: Pulmonary function can help predict cardiovascular death risk in individuals in the intermediate-risk group of Framingham Risk Scores.

Source: Lee HM, et al. Forced vital capacity paired with Framingham Risk Score for prediction of all-cause mortality. Eur Respir J 2010;36:1002-1006.

These authors set out to discover whether simple spirometric pulmonary function measures can improve on the prediction of all-cause mortality provided by Framingham Risk Score (FRS).1 To do this, they undertook a secondary analysis of 5485 never-smoking American adults from the Third National Health and Nutrition Examination Survey (NHANES).2 Participants had baseline pulmonary function measured, and follow-up data were available for a mean of about 9 years. Never-smoking status was based on self-report and cotinine levels, and cardiovascular disease was defined by self-report for stroke, congestive heart failure, and myocardial infarction.

The investigators stratified the two primary spirometric measures, the Forced Vital Capacity (FVC) and the Forced Expiratory Volume in one second (FEV1) into three categories: low (≤ 85% predicted), borderline (86%-94% predicted), and normal (≥ 95% predicted). They then applied these stratifications of low, medium, and high pulmonary function to the three Framingham Risk group classifications of 10-year cardiovascular mortality risk groups of low (< 10%), intermediate (10%-20%), and high (> 20%). The aim was to determine if pulmonary function could enhance the accuracy of cardiovascular mortality risk predicted by the Framingham Risk Score.

The low, intermediate, and high Framingham Risk Score groups included 79.5% (n = 4361), 10.1% (n = 555), and 10.4% (n = 569) of the people in this cohort, respectively. Men had a 4% greater 10-year risk of coronary heart disease estimated by the Framingham than women did. Caucasians had the highest 10-year risk of heart disease at 5.5% compared to African-Americans at 3.1% and Mexican-Americans at 3.5%. There were no significant differences in the predicted FVC across sex, but African-Americans had lowest predicted FVCs and Mexican-Americans had the highest.

Both the FVC and the FEV1 increased the accuracy of the FRS in predicting cardiac death in those who were in the intermediate FRS group; in this group, mortality was 10.7%, 18.2%, and 42.8% per 1000 person-years from highest to lowest FVC categories, respectively. Those with low FVC had an almost three-fold greater risk of death than those with normal FVC. The authors concluded that evaluation of lung function may be useful to improve risk stratification in persons with intermediate cardiovascular disease risk.

Commentary

Heart disease remains the leading cause of death in the developed world.1,3 The Framingham Risk Score (FRS) is a widely used tool to estimate 10-year coronary heart disease; it includes multiple risk factors such as age, sex, smoking history, systolic blood pressure, and total cholesterol and high-density lipoprotein cholesterol risk, and is generally applied to those who have not been already diagnosed with heart disease. The Framingham is an imperfect predictor, however, and efforts to tweak its accuracy are ongoing.1 In that regard, pulmonary function testing, which is safe, simple, and inexpensive, is an ideal candidate to incorporate into the Framingham predictive model. Reduced pulmonary function predicts cardiovascular disease and death,4-7 as well as all-cause mortality even in never-smokers.8-10

This application of pulmonary function to the FRS is a logical approach to improving its predictive value. This investigation has indeed demonstrated that spirometric measures can improve risk stratification for mortality, particularly for people in the intermediate Framingham group. This is not an inconsequential finding, as people in this risk group are often quite heterogenous. In their discussion, the authors note that people with low FVC in the intermediate risk group might be "bumped up" into the next-highest risk category, and might be considered for more aggressive clinical management, as has been suggested for other measures of subclinical disease.

A caveat or two is in order here. As a pulmonologist, I am used to considering all spirometric predicted values above 80% as "normal." In this study, those whose FVC or FEV1 were below 85% were classified in the "low" group. This report will change the way I think about these predicted percentiles.

As to the mechanism by which pulmonary function could influence cardiovascular disease, the authors note that inflammation is the causal pathway of both pulmonary and cardiac disease,11,12 and is a likely culprit.

What does this mean to us as clinicians? In this era of increasing demand for high-tech, inexpensive risk assessment tools such as spiral CT scans and coronary artery calcification scores, we still have a an expensive, radiation-free, highly predictive tool: good old pulmonary function testing.

References

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2. Centers for Disease Control and Prevention, National Center for Health Statistics. Third National Health and Nutrition Examination Survey laboratory/medical technologists procedures and manual. Hyattsville, MD; 1994.

3. Gluckman TJ, et al. A practical and evidence-based approach to cardiovascular risk reduction. Arch Intern Med 2004;164:1490-1500.

4. Thompson J, et al. Primary prevention for patients with intermediate Framingham risk scores. Curr Cardiol Rep 2006;8:261-266.

5. Kannel WB, et al. Vital capacity as a predictor of cardiovascular disease: The Framingham study. Am Heart J 1983;105:311-315.

6. Marcus EB, et al. Pulmonary function as a predictor of coronary heart disease. Am J Epidemiol 1989;129: 97-104.

7. Enstrom G, et al. Lung function and cardiovascular risk: Relation with inflammation-sensitive plasma proteins. Circulation 2002;106:2555-2560.

8. Sin DD, et al. The relationship between reduced lung function and cardiovascular mortality: A population-based study and a systematic review of the literature. Chest 2005;127:1952-1959.

9. Hole DJ, et al. Impaired lung function and mortality risks in men and women: Findings from the Renfrew and Paisley prospective population study. BMJ 1996;313:711-715.

10. Lange P, et al. Spirometric findings and mortality in never-smokers. J Clin Epidemiol 1990;43:867-873.

11. Shaaban R, et al. Change in C-reactive protein levels and FEV1 decline: A longitudinal population-based study. Respir Med 2006;100:2112-2120.

12. Fogarty AW, et al. Systemic inflammation and decline in lung function in a general population: A prospective study. Thorax 2007;62:515-520.