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Multicenter Study
. 2009 Jun 23;119(24):3070-7.
doi: 10.1161/CIRCULATIONAHA.108.815944. Epub 2009 Jun 8.

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  1 , Philimon Gona, Ramachandran S Vasan, Martin G Larson, Emelia J Benjamin, Thomas J Wang, Jack V Tu, Daniel Levy
Affiliations
Multicenter Study

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 et al. Circulation. .

Abstract

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 < or =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.

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Conflict of interest statement

DISCLOSURES

No conflicts of interest to disclose.

Figures

Figure 1
Figure 1. Association of pre-onset clinical factors with HFREF vs. HFPEF
Age/sex-adjusted ORs of HFPEF using pre-onset factors (OR>1: greater odds of HFPEF). ORs for age are sex-adjusted, and ORs for sex are age-adjusted. ORs for continuous measures are: age (per 10 years), body mass index (per 2 kg/m2), systolic blood pressure (per 10 mmHg), diastolic blood pressure (per 5 mmHg), total cholesterol (per 10 mg/dL), HDL cholesterol (per 5 mg/dL). Reference groups for categorical variables are those without the characteristic.
Figure 2
Figure 2. Association of clinical factors at time of onset with HFREF vs. HFPEF
Age/sex-adjusted ORs of HFPEF using characteristics at time of HF onset (OR>1: greater odds of HFPEF). ORs for continuous measures are: heart rate (per 10 beats/minute), respiratory rate (per 10 breaths/minute), Na+ (per 5 mEq/L), K+ (per 1 mEq/L), creatinine (per 1 mg/dL), and blood urea nitrogen (BUN, per 10 mg/dL). Units for systolic and diastolic blood pressure as per Figure 1. Reference groups for LBBB and RBBB was those without BBB. For all other categorical variables, reference groups were those without the characteristic.
Figure 3
Figure 3. Time to death after HF onset: HFREF vs HFPEF
Survival in participants with HFPEF or HFREF compared to controls without HF.
Figure 4
Figure 4. Survival after HF onset in HFPEF
Survival of participants with HFPEF by etiology.
Figure 5
Figure 5. Survival after HF onset in HFREF
Survival for participants with HFREF by etiology.
See this image and copyright information in PMC

Comment in

References

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