Risk factors for incident heart failure with preserved or reduced ejection fraction, and valvular heart failure, in a community-based cohort

Abstract

Background: The lack of effective therapies for heart failure with preserved ejection fraction (HFpEF) reflects an incomplete understanding of its pathogenesis.

Design: We analysed baseline risk factors for incident HFpEF, heart failure with reduced ejection fraction (HFrEF) and valvular heart failure (VHF) in a community-based cohort.

Methods: We recruited 2101 men and 1746 women ≥60 years of age with hypertension, diabetes, ischaemic heart disease (IHD), abnormal heart rhythm, cerebrovascular disease or renal impairment. Exclusion criteria were known heart failure, left ventricular ejection fraction <50% or valve abnormality >mild in severity. Median follow-up was 5.6 (IQR 4.6-6.3) years.

Results: Median time to heart failure diagnosis in 162 participants was 4.5 (IQR 2.7-5.4) years, 73 with HFpEF, 53 with HFrEF and 36 with VHF. Baseline age and amino-terminal pro-B-type natriuretic peptide levels were associated with HFpEF, HFrEF and VHF. Pulse pressure, IHD, waist circumference, obstructive sleep apnoea and pacemaker were associated with HFpEF and HFrEF; atrial fibrillation (AF) and warfarin therapy were associated with HFpEF and VHF and peripheral vascular disease and low platelet count were associated with HFrEF and VHF. Additional risk factors for HFpEF were body mass index (BMI), hypertension, diabetes, renal dysfunction, low haemoglobin, white cell count and β-blocker, statin, loop diuretic, non-steroidal anti-inflammatory and clopidogrel therapies, for HFrEF were male gender and cigarette smoking and for VHF were low diastolic blood pressure and alcohol intake. BMI, diabetes, low haemoglobin, white cell count and warfarin therapy were more strongly associated with HFpEF than HFrEF, whereas male gender and low platelet count were more strongly associated with HFrEF than HFpEF.

Conclusions: Our data suggest a major role for BMI, hypertension, diabetes, renal dysfunction, and inflammation in HFpEF pathogenesis; strategies directed to prevention of these risk factors may prevent a sizeable proportion of HFpEF in the community.

Trial registration number: NCT00400257, NCT00604006 and NCT01581827.

Keywords: HFPEF; HFREF; incident heart failure; risk factors; valvular heart failure.

Conflict of interest statement

Competing interests: DJC has received payments from the Australasian Renin Academy for lectures. JMCa has received payments from Pfizer, Servier, Bayer and Alphpharm for lectures. DLP has received payment from Servier for sitting on their advisory board, and from Boehringer Ingelheim, CSL, Merck Sharp & Dohme and Sanofi Aventis for lectures. UB was an employee of Bupa Australia. DL has received honoraria from Pfizer, Sanofi, Astra-Zeneca, Abbott, Bayer, MSD, GSK, Novartis and Nycomed. SS has received unrestricted educational grants from Schering Plough and Boehringer Ingelheim, and was Principal Investigator of the Novartis sponsored Valsartan Intensified Primary Care Reduction of Blood Pressure (VIPER-BP) Study. HK received support from Novartis, Bristol-Myers Squibb and Ardian/Medtronic.

Figures

Figure 1

Consolidated Standards of Reporting Trials flow diagram describing participant recruitment and follow-up in the SCReening Evaluation of the Evolution of New HF (SCREEN-HF) study. Durations of follow-up for visits and phone review are shown as medians (IQR).

Figure 2

Cumulative incidence of total heart failure (total HF), heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) and valvular heart failure (VHF). Cumulative incidence curves were constructed with the use of the non-parametric cumulative incidence function of Fine and Gray, with non-HF-related death and other categories of HF as competing risks.

Figure 3

Forest plots showing univariate HRs and 95% CIs for risk factors for incident heart failure (HF) with preserved (HFpEF) and reduced ejection fraction (HFrEF) and valvular HF (VHF), where a risk factor was significantly associated with at least one category of HF; HRs significantly different from 1 (p2 drinks/day refers to consumption of more than two standard drinks on any day. HRs were calculated using a semiparametric proportional hazards model for the subdistribution of competing risk, with non-HF-related death and other categories of HF as competing risks.