The inflammatory marker glycoprotein acetyls is associated with blood pressure and pulse wave velocity through childhood and adulthood: analysis of three population-based longitudinal cohorts

BackgroundChronic inflammation is associated with the development of atherosclerosis across the life course, but the effect of inflammation on preclinical cardiovascular measures is poorly characterized, particularly in children and younger adults. We investigated cross-sectional associations of inflammatory markers with preclinical cardiovascular measures in three population-based cohorts of children and adults. MethodsWe analyzed data from 9865 children and adolescents and 11,086 adults from: the Longitudinal Study of Australian Childrens Child Health CheckPoint (CheckPoint, Australia) (1325 parents, mean age 44.6 years; 1180 offspring, mean age 12.0 years), the Avon Longitudinal Study of Parents and Children (ALSPAC, UK) (6395 parents, mean age 49.2 years; 7371 offspring assessed at up to 3 time points, approximately 8, 18 and 24 years), and the Cardiovascular Risk in Young Finns Study (YFS, Finland) (2015, mean age 37.7 years). Inflammatory markers were glycoprotein acetyls (GlycA) and high sensitivity C-reactive protein (hsCRP). Cardiovascular measures included systolic (SBP) and diastolic blood pressure (DBP), carotid-femoral pulse wave velocity (PWV), and carotid intima-media thickness (cIMT). ResultsIn confounder-adjusted models, higher GlycA was cross-sectionally associated with higher blood pressure and PWV across CheckPoint and ALSPAC parents and offspring at each time point (e.g., for ALSPAC parents, difference in mean SBP 1.00 mmHg per 100 {micro}mol/L GlycA (95%CI: 0.69, 1.31), DBP 0.63 mmHg (0.43, 0.84); for CheckPoint parents, difference in mean PWV 0.16 m/s (0.09, 0.24)), and to a limited extent in YFS adults (difference in mean SBP 0.29 mmHg (0.02, 0.56), DBP 0.18 mmHg (-0.05, 0.40), PWV 0.01 m/s (-0.04, 0.05)). Higher hsCRP was also associated with higher blood pressure and PWV in some cohorts (e.g, in ALSPAC parents, difference in mean SBP 0.64 mmHg per 1 standard deviation increase in log-10 hsCRP (95%CI: 0.35, 0.92), DBP 0.93 mmHg (0.41, 1.45); in CheckPoint parents, PWV 0.7 m/s (0.0, 1.4)). Neither GlycA nor hsCRP were associated with consistent differences in cIMT, with evidence for an effect of higher GlycA and hsCRP on lower cIMT in some cohorts. ConclusionsHigher inflammation may contribute to higher blood pressure and arterial stiffness (PWV) from childhood onwards. GlycA is more evidently associated with these vascular measures in childhood than hsCRP. Clinical PerspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIThe association of inflammation with the development of cardiovascular disease risk-associated phenotypes across the life course is poorly understood at younger ages, despite adult data highlighting strong associations between inflammation and cardiovascular disease pathogenesis. C_LIO_LIHigh-sensitivity C-reactive protein (hsCRP) is the most widely investigated inflammation marker, but glycoprotein acetyls (GlycA) may be a more informative chronic subclinical inflammation marker for cardiovascular disease risk, including earlier in life. C_LIO_LIThis study investigated the effect of inflammation measured by hsCRP and GlycA on key preclinical cardiovascular measures across childhood and adulthood in large international cohorts. C_LI What are the clinical implications?O_LIIn cross-sectional analyses in different populations, higher GlycA is associated with higher blood pressure and pulse wave velocity, but not carotid intima-media thickness, from childhood to adulthood, after adjusting for traditional cardiovascular disease risk factors, with less consistent effects observed for hsCRP. C_LIO_LIReducing chronic inflammation in childhood may improve preclinical cardiovascular measures, with the potential to reduce cardiovascular disease across the life course. C_LIO_LIAdditional analyses with longitudinal repeat measures and causal analyses, such as Mendelian randomization at different ages, as well as biomarkers and functional measures of inflammation are needed to inform whether these findings reflect causal effects and provide targets for prevention. C_LI