Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125,222 participants. We also compared the frequency of Asp358Ala in 51,441 patients with coronary heart disease and in 136,226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele ≥0·04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34·3% (95% CI 30·4-38·2) and of interleukin 6 by 14·6% (10·7-18·4), and mean concentration of C-reactive protein was reduced by 7·5% (5·9-9·1) and of fibrinogen by 1·0% (0·7-1·3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3·4% (1·8-5·0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease. British Heart Foundation; UK Medical Research Council; UK National Institute of Health Research, Cambridge Biomedical Research Centre; BUPA Foundation.

Gestational diabetes mellitus (GDM) is associated with developing type 2 diabetes, but very few studies have examined its effect on developing cardiovascular disease. We conducted a retrospective cohort study utilizing a large primary care database in the United Kingdom. From 1 February 1990 to 15 May 2016, 9,118 women diagnosed with GDM were identified and randomly matched with 37,281 control women by age and timing of pregnancy (up to 3 months). Adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated for cardiovascular risk factors and cardiovascular disease. Women with GDM were more likely to develop type 2 diabetes (IRR = 21.96; 95% CI 18.31–26.34) and hypertension (IRR = 1.85; 95% CI 1.59–2.16) after adjusting for age, Townsend (deprivation) quintile, body mass index, and smoking. For ischemic heart disease (IHD), the IRR was 2.78 (95% CI 1.37–5.66), and for cerebrovascular disease 0.95 (95% CI 0.51–1.77; p-value = 0.87), after adjusting for the above covariates and lipid-lowering medication and hypertension at baseline. Follow-up screening for type 2 diabetes and cardiovascular risk factors was poor. Limitations include potential selective documentation of severe GDM for women in primary care, higher surveillance for outcomes in women diagnosed with GDM than control women, and a short median follow-up postpartum period, with a small number of outcomes for IHD and cerebrovascular disease. Women diagnosed with GDM were at very high risk of developing type 2 diabetes and had a significantly increased incidence of hypertension and IHD. Identifying this group of women in general practice and targeting cardiovascular risk factors could improve long-term outcomes.

Valid measurements of self-reported physical activity are very limited in Chinese populations, especially the elderly. Therefore, we examined the validity and reliability of the Chinese version of the International Physical Activity Questionnaire (IPAQ-C) in older Chinese people. Two hundred twenty-four older adults (66.1% women, 33.9% men, mean age 65.2 ± 5.7 yr) were randomly selected from the Guangzhou Biobank Cohort Study, a prospective cohort of older Chinese in Southern China. To examine the test-retest reliability, the participants completed the IPAQ-C twice during a 7-d interval. The criterion validity of the IPAQ-C was tested with pedometry. Good reliability was observed between the repeated IPAQ-C, with intraclass correlation coefficients (ICC) ranging from 0.81 to 0.89. Total activity measured by IPAQ-C correlated moderately with the pedometer-measured steps (partial r = 0.33 adjusted for sex, age, and education; P < 0.001). The walking domain of IPAQ-C was strongly associated with the number of steps (partial r = 0.58, P < 0.001), but there were no significant associations between other activity domains of the IPAQ-C and the pedometer data. This is the first reported validation study of an international standardized questionnaire (IPAQ-C) in older Chinese adults. Our study shows that the IPAQ-C is adequately valid and reliable for assessing total physical activity and that it may be a useful instrument for generating internationally comparable data on physical activity in this population.

The Guangzhou Biobank Cohort Study (GBCS), initiated by TH Lam (Hong Kong), CQ Jiang (Guangzhou), and KK Cheng (Birmingham), has been in part modelled on the Kadoorie Study of Chronic Disease in China (KSCDC)¹ and the UK Biobank.² Initial seed funding came from the Universities of Hong Kong and Birmingham, the Guangzhou No. 12 Hospital (Guangzhou Occupational Disease Prevention & Treatment Centre), the Guangzhou Public Health Bureau, and the Guangzhou Science and Technology Bureau. The Clinical Trials Service Unit at Oxford University has provided technical advice, especially in the planning and setting up of the project.