Risk for Incident Heart Failure: A Subject‐Level Meta‐Analysis From the Heart “OMics” in AGEing (HOMAGE) Study

Abstract

BackgroundTo address the need for personalized prevention, we conducted a subject‐level meta‐analysis within the framework of the Heart “OMics” in AGEing (HOMAGE) study to develop a risk prediction model for heart failure (HF) based on routinely available clinical measurements.Methods and ResultsThree studies with elderly persons (Health Aging and Body Composition [Health ABC], Valutazione della PREvalenza di DIsfunzione Cardiaca asinTOmatica e di scompenso cardiaco [PREDICTOR], and Prospective Study of Pravastatin in the Elderly at Risk [PROSPER]) were included to develop the HF risk function, while a fourth study (Anglo‐Scandinavian Cardiac Outcomes Trial [ASCOT]) was used as a validation cohort. Time‐to‐event analysis was conducted using the Cox proportional hazard model. Incident HF was defined as HF hospitalization. The Cox regression model was evaluated for its discriminatory performance (area under the receiver operating characteristic curve) and calibration (Grønnesby‐Borgan χ2 statistic). During a follow‐up of 3.5 years, 470 of 10 236 elderly persons (mean age, 74.5 years; 51.3% women) developed HF. Higher age, BMI, systolic blood pressure, heart rate, serum creatinine, smoking, diabetes mellitus, history of coronary artery disease, and use of antihypertensive medication were associated with increased HF risk. The area under the receiver operating characteristic curve of the model was 0.71, with a good calibration (χ2 7.9, P=0.54). A web‐based calculator was developed to allow easy calculations of the HF risk.ConclusionsSimple measurements allow reliable estimation of the short‐term HF risk in populations and patients. The risk model may aid in risk stratification and future HF prevention strategies.

Proteomic Bioprofiles and Mechanistic Pathways of Progression to Heart Failure

“…In both phases we corrected for multiple testing using a false discovery rate (FDR) of 1% 23 . Additional adjustment for the pre-specified clinical risk factors previously found to represent the best clinical prognostic model for incident HF in the HOMAGE population 24 (smoking, diabetes, history of coronary artery disease, serum creatinine, body mass index, systolic blood pressure, use of antihypertensive medication, and heart rate) was also performed, providing similar results (Supplemental Table 3). Since proteins were measured using NPX (Normalized Protein eXpression) values on a log2 scale, the odds ratio for each protein estimates the increase in the odds of HF associated with a doubling in the protein concentration.…”

“…Cases had higher BMI, creatinine, were more often hypertensive (with anti-hypertensive medications), diabetic, and had more often coronary artery disease. All these variables were included in the HOMAGE prognostic model 24 and were used for further adjustment in the models (please see below).…”

“…All 38 proteins were positively associated with incident HF, except for TWEAK (tumor necrosis factor ligand superfamily member 12) and PON3 (paraoxonase), where patients with higher concentrations of these proteins were less likely to develop HF. Further adjusting for the clinical risk factors (smoking, diabetes, history of coronary artery disease, serum creatinine, body mass index, systolic blood pressure, use of antihypertensive medication, and heart rate) previously determined in the well calibrated HOMAGE clinical risk model 24 , provides similar associations to those presented in Table 2, suggesting that these associations were independent of the patients` clinical risk (also supported by the weak correlation between the study proteins and the clinical risk factors). Supplemental Table 3 & 4.…”

Potential spironolactone effects on collagen metabolism biomarkers in patients with uncontrolled blood pressure

“…Heart failure (HF) is a serious and growing problem that impairs quality of life, causes recurrent hospitalisations and shortens life expectancy1 and thus greater efforts to delay or prevent its onset are justified 2. For patients with hypertension, effective blood pressure (BP) control reduces the incidence of cardiovascular (CV) events,3 4 especially HF 5…”

The year in cardiology 2018: heart failure

“…There is a growing interest in prevention of heart failure. Cohort studies show that the common risk factors are, predictably, the presence of cardiovascular disease and risk-factors, including age (19).…”