The impact of glycated hemoglobin on risk of hypertension: a Mendelian randomization study using UK Biobank.

BACKGROUND: Observational studies suggest higher glycated hemoglobin (HbA1c) associated with higher hypertension risk although these associations could be confounded. We examined the relation using a Mendelian randomization design in a large Biobank, the UK Biobank. METHODS: We identified 38 single nucleotide polymorphisms (SNPs) strongly and independently related to HbA1c from a large genome wide association study (n = 123 665) and applied them to the UK Biobank (n = 376 644). We used inverse variance weighting (IVW) to assess the relation of HbA1c with risk of hypertension (defined using the American College of Cardiology/American Heart Association 2017 guidelines), and SBP and DBP. Sensitivity analyses included Mendelian randomization-Egger, weighted median, Mendelian randomization pleiotropy residual sum and outlier and exclusion of pleiotropic SNPs. RESULTS: HbA1c was not clearly associated with hypertension risk using IVW (odds ratio 1.11, 95% confidence interval 0.76-1.62) in the main analysis. However, Mendelian randomization pleiotropy residual sum and outlier suggested potential horizontal pleiotropy. After excluding potentially invalid SNPs, HbA1c was associated with hypertension risk (IVW odds ratio 1.22 per %, 95% confidence interval 1.01-1.46), with consistent estimates from sensitivity analyses. HbA1c was positively associated with SBP in some, but not all analyses, albeit with directionally consistent estimates. The relation with DBP was unclear. CONCLUSION: Our study suggests HbA1c may increase hypertension risk and could be one underlying mechanistic pathway between HbA1c and coronary artery disease risk.

Late prematurity and adiposity in adolescents: Evidence from "Children of 1997" birth cohort.

OBJECTIVE: The association of late prematurity with later adiposity is unclear, and the mediating role of infant growth is seldom studied. We assessed the association of late prematurity with markers of adiposity in adolescence and tested whether accelerated infant weight gain mediated the association. METHODS: In the Chinese birth cohort "Children of 1997," we used multivariable linear regression to assess the adjusted association of late premature (n = 295), compared to term (n = 6874), births with markers of adiposity at 14 years. We tested whether any association was mediated by accelerated weight gain from birth to 12 months, i.e., a change in weight z-score ≥0.67. RESULTS: Late premature births had greater body mass index (BMI) z-score (0.21, 95% confidence interval (CI) 0.07, 0.35), waist-hip ratio z-score (0.16, 95% CI 0.03, 0.29), and waist-height ratio z-score (0.27, 95% CI 0.14, 0.40) than term births in adolescence. The association of late prematurity with higher adolescent BMI, but not waist ratios, was mediated by accelerated infant weight gain. CONCLUSIONS: Late prematurity was associated with higher BMI and waist ratios in adolescence, but only the association with BMI was mediated by infant weight gain, suggesting vulnerability to metabolic risk in late premature births may arise through multiple pathways.

Simulated growth trajectories and blood pressure in adolescence: Hong Kong's Chinese Birth Cohort.

BACKGROUND: Patterns and amounts of growth may determine adult blood pressure. Growth at different phases is correlated and affects current size, making effects on blood pressure difficult to distinguish. We decomposed growth to 13 years into independent associations with blood pressure and estimated how reaching the same size by different routes could affect adolescent blood pressure. METHODS: Using estimates from partial least squares for the associations of birth weight, height, and BMI at 3 months, growth at 3-9 months, 9-36 months, 3-8 years and 8-13 years and size at 13 years with SBP and DBP in 5247 term births (67% follow-up) from Hong Kong's 'Children of 1997' Birth Cohort, we estimated SBP and DBP at 13 years for 99 simulated growth trajectories resulting in the same size using nonparametric bootstrapping. RESULTS: High birth weight followed by slower growth was associated with lower SBP in both sexes and DBP in boys. Greater height to 3 years followed by slower height growth was associated with lower SBP in boys. Higher BMI until 9 months followed by slower BMI growth was associated with lower blood pressure in boys. CONCLUSION: High birth weight or larger early size was associated with lower blood pressure if followed by slower later growth, consistent with the fetal origin hypothesis. However, whether these patterns are due to fetal and infant metabolic programming or to allowing slower growth at periods when rapid growth is harmful is unknown.