This population-based survey demonstrated that the higher HbA1c levels would dramatically aggravate the risk of hypertension as well as ISH in subjects without diabetes, which further emphasized the role of abnormal glucose metabolism in the pathogenesis of hypertension. Owing to the specific merits, HbA1c generally serves as an effective indicator in the management of diabetes, rather than FPG and postload plasma glucose. Firstly, HbA1c has less biological variability and higher stability . Secondly, HbA1c could be less affected by relevant factors such as acute infection, short-term lifestyle alterations and recent eating behavior. Thirdly, FPG only reflected the immediate glycemia level at that time in a single measurement, in contrast, HbA1c could stably indicate the chronic glycemia levels which reflect the average glycemia levels within nearly 2-3 months. A cohort study consisting of 31,148 adults revealed that HbA1c was closely correlated to all -cause mortality and coronary heart disease in contrast to the fasting glucose . Arbel et al  has an investigation on the relationship between the glucometabolic markers (including admission glucose, FPG and HbA1c) and the severity of coronary artery disease in non-diabetic patients, which indicated that only HbA1c was associated with the severity of coronary artery disease.
The relationship between glycemic control and hypertension can be explained by several possible mechanisms. Firstly, the function deficits of pancreatic beta cells as well as insulin resistance could be indicated by the expressions of HbA1c[9,10]. It was well recognized that insulin resistance was the common pathophysiological basis for the developments of type 2 diabetes and hypertension . When the homeostasis model assessment of insulin resistance (HOMA-IR) was applied to estimate insulin resistance, it revealed that HOMA-IR dramatically up-regulated across the quartile levels of HbA1c in Korean males without diabetes. Additionally, HbA1c was also reported to be one of the best indices in identifying insulin resistance in the obese non-diabetic individuals . Secondly, numerous researches have implied that HbA1c may play a role in arterial stiffness via pro-inflammatory cell signaling and oxidative stress [30,31]. It was demonstrated in a cross-sectional survey containing 11,014 Chinese participants that brachial-ankle pulse wave velocity and central systolic blood pressure markedly elevated across the quartiles of HbA1c. Thirdly, increased levels of HbAlc can contribute to the endothelial damage that would further promote the release of endothelin from endothelial cells, and inhibit the production of nitric oxide and prostacyclin, which would result in vasomotor dysfunction and further the blood pressure[24,33]. Moreover, it has been reported that there was a direct association between HbAlc and the activation of the renin-angiotensin - aldosterone-system, and a liner relationship between HbAlc and renin activity and direct renin concentration . Also, it has been indicated in clinical researches that blood lipids could be positively regulated by the high level of HbAlc, which contributed to the increase of blood viscosity and further the incidence of cardiovascular diseases. With the increase of HbA1c level, the number of cardiovascular risk factors clustering including fasting blood glucose, high total cholesterol, high triglyceride, high and low density lipoprotein cholesterol, and low high density lipoprotein cholesterol were also dramatically up-regulated .
To our knowledge, only a few studies have investigated the relationship between the HbA1c levels and the risk of hypertension, but the conclusions were inconsistent. A cohort study in American with 9,603 participants demonstrated that the higher baseline HbA1c concentrations were predominantly associated with the incidence of hypertension independently of obesity indices and other factors in diabetes as well as in non-diabetic individuals. Similarly, in a Women’s Health Study, 19,858 American women initially without diabetes were followed up with a median of 11.6 years. The subjects were grouped based on HbA1c by clinical cutpoints quintiles, and the Hazard Ratios (HR) for the highest group of HbA1c in comparison with that of the lowest was statistically significant in both the unvariable analysis and multivariable analysis. However, when grouped HbA1c by quintiles, the above significant association eliminated after normalizing for BMI, which showed the crucial role of obesity in the correlation between glucose metabolism and hypertension. Moreover, elevated HbA1c dramatically aggravated the risk of hypertension in an independent manner even after normalizing traditional risk factors in general middle-aged and elderly Chinese subjects . Besides that, the Framingham Heart Study also demonstrated that the high HbA1c expression was associated with the prevalence of hypertension, which was only based on an unvariate analysis . Yeung et al `conducted a survey based on a Mendelian randomization design and identified related Single Nucleotide Polymorphisms (SNPs) that was strongly correlated to HbA1c in an independent manner, suggesting that there may be a correlation between HbA1c and the risk of hypertension. However, in a Japanese cohort study with 5-year follow-up, 9,584 individuals were investigated, implying that the elevated expressions of HbA1c were not associated with increasing risk of developing hypertension in the multivariable analysis . An increment in the HbA1c level was reported not to be independently involved in the future development of hypertension among Israel populations . Kroke et al revealed that there was a non-significant relationship between HbA1c and arterial hypertension in non-diabetic participants, nevertheless, arterial hypertension was defined as blood pressure ≥ 160/95 mmHg. The inconsistencies may be explained by the diversity of HbA1c in age, gender and ethnicity.
The present study further demonstrated that HbAlc has played a significantly interactive role in abdominal obesity rather than general obesity on the risk of hypertension. Several studies have suggested that abdominal fat distribution may be more strongly related to adverse outcomes such as cardiovascular disease than BMI. It is well acknowledged that obesity was a predominant risk factor of hypertension. When evaluating the predicted performances of different obesity indices on hypertension, WC was superior to BMI based on the ROC curve analysis . It was illustrated that obesity was dramatically associated with the elevated HbA1c levels in diabetes as well as in non-diabetic subjects. Obesity can lead to insulin resistance, and result in the poor glycemic control . In addition, adipocytokines secreted from the adipose tissue were also involved in the insulin resistance and the dysfunction of beta cells. Furthermore, the occurrence of hypertension was the combinative consequence of genetic and environmental effects. Family history of hypertension was a simple and alternative genetic indicator. Moreover, a case-control study among Chinese individuals have also proven that family history of hypertension and BMI were positively interacted on hypertension. Our results also illustrated that HbAlc had a remarkable interaction with family history of hypertension on the risk of hypertension.
However, there were several limitations in our study. Firstly, the causality of the results were failed to be inferred for it was a cross-sectional study. Secondly, the effects of different antihypertensive drugs varied on glucose metabolism, which were not investigated. Thirdly, the blood pressure was measured in a single session, which may influenced by various external factors.