Published Online
on June 8, 2009

A more recent version of this article appeared on June 23, 2009

This Article Full Text (PDF) CME: Take the course for this article: Circulation: June 23, 2009, Volume 119, Number 24 All Versions of this Article: 119/24/3070    most recent CIRCULATIONAHA.108.815944v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, D. S. Articles by Levy, D. Search for Related Content PubMed PubMed Citation Articles by Lee, D. S. Articles by Levy, D. Pubmed/NCBI databases Medline Plus Health Information Heart Failure Related Collections Congestive Epidemiology Related Articles

Submitted on August 19, 2008
Accepted on April 6, 2009

Relation of Disease Pathogenesis and Risk Factors to Heart Failure With Preserved or Reduced Ejection Fraction. Insights From the Framingham Heart Study of the National Heart, Lung, and Blood Institute

Douglas S. Lee MD, PhD, Philimon Gona PhD, Ramachandran S. Vasan MD, Martin G. Larson ScD, Emelia J. Benjamin MD, ScM, Thomas J. Wang MD, Jack V. Tu MD, PhD, and Daniel Levy MD^*

From the Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada (D.S.L., J.V.T.); University Health Network, University of Toronto, Toronto, Ontario, Canada (D.S.L.); Framingham Heart Study of the National Heart, Lung, and Blood Institute, Framingham, Mass (P.G., R.S.V., M.G.L., E.J.B., T.J.W., D.L.); Department of Mathematics and Statistics, Boston University, Boston, Mass (P.G., M.G.L.); Cardiology Section and Department of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Mass (E.J.B., R.S.V.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Mass (T.J.W.); Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada (J.V.T.); and Center for Population Studies of the National Heart, Lung, and Blood Institute, Bethesda, Md (D.L.).

^* To whom correspondence should be addressed. E-mail: levyd{at}nih.gov.

Background—The contributions of risk factors and disease pathogenesis to heart failure with preserved ejection fraction (HFPEF) versus heart failure with reduced ejection fraction (HFREF) have not been fully explored.

Methods and Results—We examined clinical characteristics and risk factors at time of heart failure onset and long-term survival in Framingham Heart Study participants according to left ventricular ejection fraction 45% (n=314; 59%) versus >45% (n=220; 41%) and hierarchical causal classification. Heart failure was attributed to coronary heart disease in 278 participants (52%), valvular heart disease in 42 (8%), hypertension in 140 (26%), or other/unknown causes in 74 (14%). Multivariable predictors of HFPEF (versus HFREF) included elevated systolic blood pressure (odds ratio [OR]=1.13 per 10 mm Hg; 95% confidence interval [CI], 1.04 to 1.22), atrial fibrillation (OR=4.23; 95% CI, 2.38 to 7.52), and female sex (OR=2.29; 95% CI, 1.35 to 3.90). Conversely, prior myocardial infarction (OR=0.32; 95% CI, 0.19 to 0.53) and left bundle-branch block QRS morphology (OR=0.21; 95% CI, 0.10 to 0.46) reduced the odds of HFPEF. Long-term prognosis was grim, with a median survival of 2.1 years (5-year mortality rate, 74%), and was equally poor in men and women with HFREF or HFPEF.

Conclusions—Among community patients with new-onset heart failure, there are differences in causes and time-of-onset clinical characteristics between those with HFPEF versus HFREF. In people with HFREF, mortality is increased when coronary heart disease is the underlying cause. These findings suggest that heart failure with reduced left ventricular systolic function and heart failure with preserved left ventricular systolic function are partially distinct entities, with potentially different approaches to early detection and prevention.

Key words: coronary disease • epidemiology • heart diseases • heart failure • hypertension • mortality • ventricles

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