Research method and findings<\b>
Using Mendelian randomization, the researchers analyzed genetic variants that predict HbA1c levels (as identified from genome wide association studies) and their associations with systolic and diastolic blood pressure, and hypertension (as defined according to ACC/AHA 2017 guidelines) in 376,644 men and women from the UK Biobank database. The researchers applied the usual selection criteria for participants in genetic studies, such as including only participants of genetically verified white British descent, exclusion of participants with sex chromosome aneuploidy etc. Blood pressure was measured using Omron HRM-7015IT digital BP monitor, whilst hypertension cases were identified from blood pressure readings, the use of antihypertensives, self-reports, hospital and death records.
The researchers found that the relation between HbA1c and hypertension was not clearly demonstrated using all genetic instruments for HbA1c. However, the positive association was clearer when invalid genetic instruments were excluded. The positive association between HbA1c and systolic blood pressure was not always clearly demonstrated albeit the direction of the estimates was similar across sensitivity analyses, whilst the association with diastolic blood pressure was not as clear.
Although the researchers used Mendelian randomization which is more robust to residual confounding compared to observational studies, there are some limitations such as potential violation of the Mendelian randomization assumption, potential selection bias in the UK Biobank, and the inability to assess the non-linearity between HbA1c and blood pressure phenotypes. Nevertheless, this study provides a potential mechanistic pathway in which HbA1c may increase heart disease risk.
Evaluation of the causal relation between hematocrit, hemoglobin, HbA1c, testosterone and cardiovascular outcomes in the UK Biobank using Mendelian randomization analysis
The aims of this study are to examine the causal effect of testosterone, HbA1c, hemoglobin and hematocrit on CVD risk factors, prevalent CVD and CVD deaths using Mendelian randomization analysis, with the relevant genetic variants as instruments in the UK Biobank. The proposed research will help investigate how these potential targets of intervention influence population health using Mendelian randomization design which is less susceptible to confounding than observational studies. The results will provide additional insights concerning the drivers of cardiovascular disease, with corresponding implications for public health policies and the development of interventions. We compare cardiovascular events and risk factors according to levels of genetically determined hematocrit, hemoglobin, HbA1c and testosterone. 500,000 participants (full cohort) for the analysis involving hematocrit, hemoglobin, HbA1c and genetic data. We will restrict the analysis involving testosterone and relevant genetic data among men.
|Lead investigator:||Shiu Lun Ryan Au Yeung|
|Lead institution:||University of Hong Kong|