Of the 1583 men and women who agreed to participate, 57 were excluded (24 were pregnant, 2 left after recruitment and 31 were unreliably linked to earlier data) leaving 1526 (59% of those traced and 19% of the original cohort). Fibrinogen values were available for 1492, hsCRP for 1472 and PAI-1 for 1469. Compared with the original birth cohort, 7% more of the participants in this study were male, maternal literacy was 6% higher, and mean birthweight was 32 g heavier. BMI and height in infancy, childhood and adolescence were approximately 0.1 SD lower. Mean concentrations of the pro-inflammatory/pro-thrombotic variables are shown in . HsCRP concentrations were positively correlated with fibrinogen and PAI-1 (r=0.21 and r=0.14, p<0.001 for all, adjusted for age and sex).
Body measurements at birth, 2, 11 and 26-32 years, adult pro-inflammatory and pro-thrombotic parameters and other cardiovascular risk factors
Associations of outcomes with current (adult) factors
All the pro-inflammatory/pro-thrombotic outcomes, especially hsCRP, were positively related to adult adiposity. Correlations coefficients (r) for BMI with fibrinogen, hsCRP and PAI-1 were 0.09, 0.26 and 0.20 in men and 0.13, 0.44, 0.09 in women respectively (p<0.05 for all), and there were similar correlations with sum of skinfolds and waist circumference. All outcomes were higher in participants with metabolic syndrome (N=435, 29%) than in the rest of the cohort: fibrinogen (2.94 g/L v 2.72 g/L; p=0.001) in women; PAI-1 in men (100.1 ng/ml v 83.3 ng/ml; p<0.001); and hsCRP in both sexes (2.25 mg/l v 1.86 mg/l; p=0.003 in men and 3.45 mg/l v 1.64 mg/l; p<0.001 in women).
In men, fibrinogen and PAI-1 rose with increasing socio-economic status (p=0.05 and 0.01) and PAI-1 rose with increasing alcohol intake (p=0.005). In women, hsCRP rose with increasing parity (p=0.008), PAI-1 was lower in those reporting more physical activity (p=0.05). HsCRP and PAI-1 were higher in men, and hsCRP was higher in women with a positive family history of CVD or diabetes (p<0.01 for all). None of the outcomes was related to tobacco use.
Associations of outcomes with BMI in early life
In women, BMI at birth and 2 years was inversely related to adult fibrinogen and hsCRP concentrations ( and ). Similar associations to those with BMI at birth were present with birthweight (fibrinogen p=0.01; hsCRP [after adjustment for adult BMI] p=0.003). There were no associations between size at birth and adult outcomes in men. None of the findings were changed after adjusting for gestational age at birth.
Mean plasma fibrinogen, serum CRP and plasma TPAI-1 concentrations according to body mass index (BMI) at birth, at age 2 years, 11 years and in adulthood
Age-adjusted correlations between BMI in earlier life and adult fibrinogen, hsCRP and PAI-1
In men, BMI at 2 years was inversely related to hsCRP and PAI-1 concentrations and BMI at 11 years was positively related to adult hsCRP concentration in both sexes after adjusting for adult BMI ( and ). Adult BMI was positively related to all outcomes in both sexes.
Conditional regression analyses showed that greater BMI gain from 2-11 years and/or 11 years to adulthood was associated with higher adult hsCRP concentrations (both sexes), higher PAI-1 in men, and higher fibrinogen in women (). These positive associations were attenuated after adjusting for adult adiposity (BMI or sum of skinfolds and waist circumference).
Multiple linear regression analyses using conditional BMI SD-scores in earlier life to predict adult outcomes
We analysed the outcomes in relation to combinations of BMI at birth or during infancy with adult BMI or conditional adult BMI, to determine whether the adverse effects of adult BMI were greater in individuals with lower early BMI. The highest fibrinogen, hsCRP and PAI-1 values tended to be in participants who were small at birth (women) or two years (both sexes) and adipose as adults (Supplementary Table 1
). However, for fibrinogen and hsCRP, there were no interactions of either BMI at birth or 2-years with adult BMI or conditional BMI gain (11 years-adult). For PAI-1, there was a greater increase in concentrations with conditional adult BMI in men of lower 2 year BMI.
Associations of outcomes with height in early life
In comparison with BMI, there were only weak associations of height in early life with the adult pro-inflammatory markers (Online Supplementary Tables 2
). Height at birth, 2 and 11 years, was inversely related to hsCRP in women, and height at 11 years was inversely related to hsCRP in men, after adjusting for adult BMI. Height at 2 years and 11 years was positively related to PAI-1 in men, but these associations were attenuated after BMI adjustment. Shorter adult height was associated with higher fibrinogen concentrations in women and higher CRP concentrations in men after BMI adjustment. Less height gain between 11 years and adulthood was associated with higher PAI-1 concentrations in women.
All analyses were repeated after excluding participants on medication that could alter inflammatory markers (corticosteroids N=1, oral contraceptives N=23, aspirin and other antiplatelet medications N=4, non-steroidal anti-inflammatory drugs N=33) and antibiotics (indicating current infection, N=12). The findings were unchanged.