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Aims: This study aims to develop the first race‐specific and sex‐specific risk prediction models for heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF). Methods and results: We created a cohort of 1.8 million individuals who had an outpatient clinic visit between 2002 and 2007 within the Veterans Affairs (VA) Healthcare System and obtained information on HFpEF, HFrEF, and several risk factors from electronic health records (EHR). Variables were selected for the risk prediction models in a ‘derivation cohort’ that consisted of individuals with baseline date in 2002, 2003, or 2004 using a forward stepwise selection based on a change in C‐index threshold. Discrimination and calibration were assessed in the remaining participants (internal ‘validation cohort’). A total of 66 831 individuals developed HFpEF, and 92 233 developed HFrEF (52 679 and 71 463 in the derivation cohort) over a median of 11.1 years of follow‐up. The HFpEF risk prediction model included age, diabetes, BMI, COPD, previous MI, antihypertensive treatment, SBP, smoking status, atrial fibrillation, and estimated glomerular filtration rate (eGFR), while the HFrEF model additionally included previous CAD. For the HFpEF model, C‐indices were 0.74 (SE = 0.002) for white men, 0.76 (0.005) for black men, 0.79 (0.015) for white women, and 0.77 (0.026) for black women, compared with 0.72 (0.002), 0.72 (0.004), 0.77 (0.017), and 0.75 (0.028), respectively, for the HFrEF model. These risk prediction models were generally well calibrated in each race‐specific and sex‐specific stratum of the validation cohort. Conclusions: Our race‐specific and sex‐specific risk prediction models, which used easily obtainable clinical variables, can be a useful tool to implement preventive strategies or subtype‐specific prevention trials in the nine million users of the VA healthcare system and the general population after external validation.

SUMMARYObjectiveTo compare four haemoglobin measurement methods in whole blood donors.BackgroundTo safeguard donors, blood services measure haemoglobin concentration in advance of each donation. NHS Blood and Transplant’s (NHSBT) usual method has been capillary gravimetry (copper sulphate), followed by venous HemoCue® (spectrophotometry) for donors failing gravimetry. However, gravimetry/venous HemoCue® results in 10% of donors being inappropriately bled (i.e., with haemoglobin values below the regulatory threshold).MethodsThe following were compared in 21,840 blood donors (aged ≥18 years) recruited from 10 mobile centres of NHSBT in England, with each method compared with the Sysmex XN-2000 haematology analyser, the reference standard: 1) gravimetry/venous HemoCue®; 2) “post donation” approach, i.e., estimating current haemoglobin concentration from that measured by a haematology analyser at a donor’s most recent prior donation; 3) capillary HemoCue®; and 4) non-invasive spectrometry (MBR Haemospect® or Orsense NMB200®). We assessed each method for sensitivity; specificity; proportion of donors who would have been inappropriately bled, or rejected from donation (“deferred”) incorrectly; and test preference.ResultsCompared with the reference standard, the methods ranged in test sensitivity from 17.0% (MBR Haemospect®) to 79.0% (HemoCue®) in men, and from 19.0% (MBR Haemospect®) to 82.8% (HemoCue®) in women. For specificity, the methods ranged from 87.2% (MBR Haemospect®) to 99.9% (gravimetry/venous HemoCue®) in men, and from 74.1% (Orsense NMB200®) to 99.8% (gravimetry/venous HemoCue®) in women. The proportion of donors who would have been inappropriately bled ranged from 2.2% in men for HemoCue® to 18.9% in women for MBR Haemospect®. The proportion of donors who would have been deferred incorrectly with haemoglobin concentration above the minimum threshold ranged from 0.1% in men for gravimetry/venous HemoCue® to 20.3% in women for OrSense®. Most donors preferred non-invasive spectrometry.ConclusionIn the largest study reporting head-to-head comparisons of four methods to measure haemoglobin prior to blood donation, our results support replacement of venous HemoCue® with the capillary HemoCue® when donors fail gravimetry. These results have had direct translational implications for NHS Blood and Transplant in England.

Many measures have been proposed to summarize the prognostic ability of the Cox proportional hazards (CPH) survival model, although none is universally accepted for general use. By contrast, little work has been done to summarize the prognostic ability of the stratified CPH model; such measures would be useful in analyses of individual participant data from multiple studies, data from multi-centre studies, and in single study analysis where stratification is used to avoid making assumptions of proportional hazards. We have chosen three measures developed for the unstratified CPH model (Schemper and Henderson's V , Harrell's C-index and Royston and Sauerbrei's D), adapted them for use with the stratified CPH model and demonstrated how their values can be represented over time. Although each of these measures is promising in principle, we found the measure of explained variation V very difficult to apply when data are combined from several studies with differing durations of participant follow-up. The two other measures considered, D and the C-index, were more applicable under such circumstances. We illustrate the methods using individual participant data from several prospective epidemiological studies of chronic disease outcomes.

Objectives. To assess associations of circulating levels of apolipoprotein (apo) AI, apoB and the apoB/AI ratio (apoB/A) with risk of incident coronary heart disease (CHD). Design. Literature-based meta-analysis of prospective studies. Data sources. Prospective studies in essentially general populations that reported on associations between apoAI, apoB or apoB/A and first incident CHD outcomes. Studies were identified by computer-based searches and by manual searches of the relevant literature. Results. Data from 23 relevant studies were identified. For apoAI, with 6333 CHD cases in 21 studies, comparison of individuals in the bottom third with those in the top third of baseline values yielded a combined relative risk of 1.62 (95% confidence interval: 1.43–1.83), i.e. an inverse association. For apoB, a combined analysis of 6320 CHD cases from 19 studies gave a relative risk of 1.99 (1.65–2.39) for a comparison of individuals in the top third versus those in the bottom third of baseline values. For apoB/A, with 3730 CHD cases from seven studies, a comparison of individuals in the top third versus the bottom third of baseline values gave a combined relative risk of 1.86 (1.55–2.22). These associations were somewhat stronger following correction for within-person variations in apolipoprotein levels. There was evidence of heterogeneity amongst the published studies, but it was only partly explained by available study-level characteristics. Conclusions. The present quantitative review suggests the existence of moderately strong associations between baseline levels of each of apoAI, apoB, and apoB/A and risk of CHD. More detailed analysis, perhaps based on individual participant data from prospective studies, could help to overcome several limitations in the present review and to clarify any relevance of these apolipoproteins to disease prediction and aetiology.