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;
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.).
Correspondence to Daniel Levy, MD, Director, Framingham Heart Study, 73 Mt Wayte Ave, Suite 2, Framingham, MA 01702-5827. E-mail levyd@nih.gov
Received August 19, 2008; accepted April 6, 2009.
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.