BackgroundThe lack of effective therapies for heart failure with preserved ejection fraction (HFpEF) reflects an incomplete understanding of its pathogenesis.DesignWe analysed baseline risk factors for incident HFpEF, heart failure with reduced ejection fraction (HFrEF) and valvular heart failure (VHF) in a community-based cohort.MethodsWe 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.ResultsMedian 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.ConclusionsOur 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 numberNCT00400257, NCT00604006 and NCT01581827.

Aims We investigated which serum amino‐terminal pro‐B‐type‐natriuretic peptide (NT‐proBNP) levels inform heart failure (HF) risk in a community‐based population at increased cardiovascular disease (CVD) risk. Methods and results Inclusion criteria were age ≥ 60 years with one or more of self‐reported hypertension, diabetes, heart disease, abnormal heart rhythm, cerebrovascular disease, or renal impairment. Exclusion criteria were known HF, ejection fraction (EF) < 50%, or more than mild valve abnormality. NT‐proBNP levels were measured in 3842 participants on enrolment. HF was diagnosed in 162 participants at a median of 4.5 (interquartile range 2.7–5.4) years after enrolment, 73 with HF with preserved EF (HFpEF), 53 with HF with reduced EF (HFrEF), and 36 with valvular HF (VHF). Areas under the receiver operating characteristic curve (AUC) for 5‐year prediction of total HF were similar for NT‐proBNP alone (0.79, 95% confidence interval 0.74–0.83) and a 7‐parameter multivariable model (0.82, 0.77–0.86, P = 0.035). NT‐proBNP cut‐points of 11, 16, and 25 pmol/L for individuals aged 60–69, 70–79, and ≥ 80 years, respectively, achieved sensitivities > 76% and specificities of 47–69% for 5‐year prediction of total HF in men and women in all three age groups. Sensitivities were ≥ 75% in most subgroups according to body mass index, estimated glomerular filtration rate, and the presence or absence of atrial fibrillation, pacemaker, or CVD, and for the prediction of HFpEF, HFrEF and VHF. Conclusion Age‐specific serum NT‐proBNP levels inform prognosis, and hence therapeutic decisions, regarding HF risk in individuals at increased CVD risk.

Aims We investigated whether addition of diastolic dysfunction (DD) and longitudinal strain (LS) to Stage B heart failure (SBHF) criteria (structural or systolic abnormality) improves prediction of symptomatic HF in participants of the SCReening Evaluation of the Evolution of New Heart Failure study, a self‐selected population at increased cardiovascular disease risk recruited from members of a health insurance fund in Melbourne and Shepparton, Australia. Both American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) criteria and age‐specific Atherosclerosis Risk in Communities (ARIC) study criteria, for SBHF and DD, and ARIC criteria for abnormal LS, were examined. Methods and results Inclusion criteria were age ≥60 years with one or more of self‐reported ischaemic or other heart disease, irregular or rapid heart rhythm, cerebrovascular disease, renal impairment, or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known HF, or ejection fraction <50% or >mild valve abnormality detected on previous echocardiography or other imaging. Echocardiography was performed in 3190 participants who were followed for a median of 3.9 (interquartile range: 3.4, 4.5) years after echocardiography. Symptomatic HF was diagnosed in 139 participants at a median of 3.1 (interquartile range: 2.1, 3.9) years after echocardiography. ARIC structural, systolic, and diastolic abnormalities predicted HF in univariate and multivariable proportional hazards analyses, whereas ASE/EACVI structural and systolic, but not diastolic, abnormalities predicted HF. ARIC and ASE/EACVI SBHF criteria predicted HF with sensitivities of 81% and 55%, specificities of 39% and 76%, and C statistics of 0.60 (95% confidence interval: 0.57, 0.64) and 0.66 (0.61, 0.71), respectively. Adding ARIC DD to SBHF increased sensitivity to 94% with specificity of 24% and C statistic of 0.59 (0.57, 0.61), whereas addition of ASE/EACVI DD to SBHF increased sensitivity to 97% but reduced specificity to 9% and the C statistic to 0.52 (0.50, 0.54, P < 0.0001). Addition of LS to ARIC or ASE/EACVI SBHF criteria had minimal impact on prediction of HF. Conclusions Age‐specific ARIC DD criteria, but not ASE/EACVI DD criteria, predicted symptomatic HF, and addition of age‐specific ARIC DD criteria to ARIC SBHF criteria improved prediction of symptomatic HF in asymptomatic individuals with cardiovascular disease risk factors. Addition of LS to ASE/EACVI or ARIC SBHF criteria did not improve prediction of symptomatic HF.

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Background Body mass index †Deceased. (BMI) is a risk factor for heart failure with preserved ejection fraction (HFpEF). Design We investigated the threshold BMI and sex-specific waist circumference associated with increased HFpEF incidence in the SCReening Evaluation of the Evolution of New Heart Failure (SCREEN-HF) study, a cohort study of a community-based population at increased cardiovascular disease risk. Methods Inclusion criteria were age ≥60 years with one or more of self-reported hypertension, diabetes, heart disease, abnormal heart rhythm, cerebrovascular disease or renal impairment. Exclusion criteria were known heart failure, ejection fraction <50% or more than mild valve abnormality. Among 3847 SCREEN-HF participants, 73 were diagnosed with HFpEF at a median of 4.5 (interquartile range: 2.9–5.5) years after enrolment. Results HFpEF incidence rates were higher for BMI ≥27.5 kg/m2 than for BMI < 25 kg/m2, and for waist circumference >100 cm (men) or > 90 cm (women) than for waist circumference ≤94 cm (men) or ≤ 83 cm (women) in Poisson regression analysis. Semiparametric proportional hazards analyses confirmed these BMI and waist circumference thresholds, and exceeding these thresholds was associated with an attributable risk of HFpEF of 44–49%. Conclusions Both central obesity and overweight were associated with increased HFpEF incidence. Although a randomised trial of weight control would be necessary to establish a causal relationship between obesity/overweight and HFpEF incidence, these data suggest that maintenance of BMI and waist circumference below these thresholds in a community similar to that of the SCREEN-HF cohort may reduce the HFpEF incidence rate by as much as 50%.

This population demonstrated substantial potential to reduce cardiovascular and renal morbidity and mortality and healthcare costs through more effective management of modifiable risk factors.

Background Given the age-related decline in glomerular filtration rate (GFR) in healthy individuals, we examined the association of all-cause death or cardiovascular event with the Kidney age - Chronological age Difference (KCD) score, whereby an individual’s kidney age is estimated from their estimated GFR (eGFR) and the age-dependent eGFR decline reported for healthy living potential kidney donors. Methods We examined the association between death or cardiovascular event and KCD score, age-dependent stepped eGFR criteria (eGFRstep), and eGFR < 60 ml/min/1.73 m2 (eGFR60) in a community-based high cardiovascular risk cohort of 3837 individuals aged ≥60 (median 70, interquartile range 65, 75) years, followed for a median of 5.6 years. Results In proportional hazards analysis, KCD score ≥ 20 years (KCD20) was associated with increased risk of death or cardiovascular event in unadjusted analysis and after adjustment for age, sex and cardiovascular risk factors. Addition of KCD20, eGFRstep or eGFR60 to a cardiovascular risk factor model did not improve area under the curve for identification of individuals who experienced death or cardiovascular event in receiver operating characteristic curve analysis. However, addition of KCD20 or eGFR60, but not eGFRstep, to a cardiovascular risk factor model improved net reclassification and integrated discrimination. KCD20 identified individuals who experienced death or cardiovascular event with greater sensitivity than eGFRstep for all participants, and with greater sensitivity than eGFR60 for participants aged 60–69 years, with similar sensitivities for men and women. Conclusions In this high cardiovascular risk cohort aged ≥60 years, the KCD score provided an age-adapted measure of kidney function that may assist patient education, and KCD20 provided an age-adapted criterion of eGFR-related increased risk of death or cardiovascular event. Further studies that include the full age spectrum are required to examine the optimal KCD score cut point that identifies increased risk of death or cardiovascular event, and kidney events, associated with impaired kidney function, and whether the optimal KCD score cut point is similar for men and women. Trial registration ClinicalTrials.gov NCT00400257, NCT00604006, and NCT01581827.

Most individuals with treated blood pressures above target receive only one or two antihypertensive drug classes. Prescribing additional antihypertensive drug classes and lifestyle modification may improve blood pressure control in this population of individuals at increased cardiovascular risk.