Logistic regression for the odds of higher blood pressure.

<p>OR: Odds ratio, 95% CI: 95% confidence intervals, LMr/H: Lean mass standardised residuals modelled on height; FMr/LM: Fat mass standardised residuals modelled on lean mass; CWV: Conditional weight velocity. Higher blood pressure (BP) for each component was defined using the cut-off criteria of ≥95^th centile, as recommended by the Working Group on High Blood Pressure in Children and Adolescents. However, clinical diagnosis of hypertension uses a different measurement protocol to our epidemiological approach, hence although derived using the same cut-off values, our higher BP sample does not represent a clinical hypertension sample. n = 5,719.</p>*<p>Birth weight and height are expressed in z-scores.</p

Testing a Capacity-Load Model for Hypertension: Disentangling Early and Late Growth Effects on Childhood Blood Pressure in a Prospective Birth Cohort

<div><h3>Background</h3><p>In 2005, it was estimated that hypertension affected 26.4% of the adult population worldwide. By 2025, it is predicted that it will affect about 60% of adults, a total of 1.56 billion. Both pre- and postnatal growth patterns have been associated with later blood pressure (BP), but in contrasting directions. These inconsistent associations of growth during different developmental periods merit elucidation. We tested a theoretical model treating birth weight as a marker of homeostatic metabolic capacity, and childhood height, lean mass and fat mass as independent indices of metabolic load. We predicted that decreased capacity and increased load would be independently associated with increased BP.</p> <h3>Methods and Findings</h3><p>Data from the ALSPAC cohort on growth from birth to 7 years, and body composition by dual-energy X-ray absorptiometry and BP at 9 years, were analysed (n = 6579). Data were expressed as standard deviation scores (SDS) or standardised regression residuals (SRR). BP was independently and positively associated with each of height, lean mass and fat mass. In a joint model systolic BP was positively associated with conditional weight velocity [males 0.40 (95%CI: 0.37–0.44) & females 0.44 (95%CI: 0.40–0.47) SDS/SRR], but not birth weight [0.00 (95%CI: −0.03–0.04) & 0.03 (95%CI: −0.01–0.07) SDS/SDS]. Adjusting for height, lean mass and fat mass, the association of systolic BP and conditional weight velocity attenuated [0.00(95%CI: −0.09–0.08) & −0.06(95%CI: −0.14–0.03) SDS/SRR], whereas that with birth weight became negative [−0.10 (95%CI: −0.14–0.06) & −0.09 (95%CI: −0.13–0.05) SDS/SDS]. Similar results were obtained for diastolic BP and pulse pressure.</p> <h3>Conclusions</h3><p>Consistent with our theoretical model, high metabolic load relative to metabolic capacity is associated with increased BP. Our data demonstrate the contribution of different growth and body composition components to BP variance, and clarify the developmental aetiology of hypertension.</p> </div

Correlations between pre- and postnatal growth indices and body composition at 9 years, for each sex (M = males; F = females).

<p>BLZ: Length at birth z-score; BWZ: Birth weight z-score; CHV Conditional height velocity; CWV: Conditional weight velocity; FMr/LM: Fat mass standardised residuals modelled on lean mass; LMr/H: Lean mass standardised residuals modelled on height.</p

Linear regression models for the prediction of blood pressure outcomes by height, weight, lean and fat mass, birth weight and conditional weight velocity.

<p>β: mean difference in outcome per 1 unit exposure, 95% CI: 95% confidence intervals, LMr/H: Lean mass standardised residuals modelled on height; FMr/LM: Fat mass standardised residuals modelled on lean mass; CWV: Conditional weight velocity.</p>*<p>Birth weight and height are expressed in z-scores.</p

Linear regression models for the prediction of blood pressure outcomes by height, weight, lean and fat mass.

<p>β: mean difference in outcome per 1 unit exposure, 95% CI: 95% confidence intervals, Wr/H: Weight standardised residuals modelled on height, LMr/H: Lean mass standardised residuals modelled on height, FMr/LM: Fat mass standardised residuals modelled on lean mass.</p>*<p>Height is expressed in z-scores.</p

Subject characteristics by sex.

<p>Subject characteristics by sex.</p

Diagram illustrating the concepts of metabolic capacity and metabolic load in relation to blood pressure.

<p>Metabolic capacity is indexed by nephron number, which scales positively with birth weight. Metabolic load is indexed by each of height, lean mass and fat mass, which are portrayed using a cylinder model, in which cylinder lengths are proportional to height, and the volumes are proportional to the masses of lean and fat mass. A high load and a low capacity are each predicted to increase blood pressure.</p

Observed and predicted live birth rates from updated IVFpredict and Templeton models stratified by characteristics of patients and treatment, in 130,960 IVF cycles.

<p>P-values are for differences between observed and predicted number of live births, and those smaller than the threshold for a family-wise error rate of 5% are highlighted.</p><p>* Not including 5 cycles where cervical cause of infertility only, for which meaningful confidence intervals cannot be calculated.</p><p>Observed and predicted live birth rates from updated IVFpredict and Templeton models stratified by characteristics of patients and treatment, in 130,960 IVF cycles.</p

Area under the receiver-operator curve for IVFpredict and Templeton models, and female age alone, for predicting live birth from 130,960 IVF cycles.

<p>* Based on 144,018 cycles occurring in the UK between 2003 and 2007 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121357#pone.0121357.ref012" target="_blank">12</a>].</p><p>** Model predicting decreasing probability of live birth with increasing female age.</p><p>*** Model predicting decreasing probability of live birth with increasing female age categories (18–34, 35–37, 38–39, 40–42, 43–44 and 45–50 years).</p><p>Area under the receiver-operator curve for IVFpredict and Templeton models, and female age alone, for predicting live birth from 130,960 IVF cycles.</p

Calibration plot for the IVFpredict and Templeton models.

<p>Based on 130,960 IVF cycles. Hosmer-Lemeshow test statistics: p<0.001. Solid line, IVFpredict model; dashed line, Templeton model; dotted, diagonal line, perfect prediction (reference).</p