The long-term impact of early HbA1c control on nephropathy, neuropathy, and retinopathy in type 2 diabetes: Findings from a large UK observational study.

There is conflicting evidence regarding optimal glycaemic targets to reflect the legacy effect of hyperglycaemia in people with type 2 diabetes (T2D). We examined the risks of microvascular complications and hospital admission with glycated haemoglobin (HbA1c) levels from the diagnosis of T2D. We identified individuals with incident T2D from 1998 to 2007 from the Clinical Practice Research Datalink and Hospital Episode Statistics. A composite microvascular outcome was defined as a new diagnosis of neuropathy, nephropathy or retinopathy. A multivariate time-varying Cox regression analysis was performed to assess the risk of microvascular disease associated with HbA1c at five different levels (1.0% (11 mmol/mol) intervals). HbA1c 6.5%-7.5% (48.0-58.9 mmol/mol) was defined as the reference. N = 172,869 (mean age 62.6 ± 14.0 years, 54.6% female) were analysed. Average follow-up was 11.2 years. The risk of microvascular disease increased with higher HbA1c levels, the highest risk in the ⩾9.6% (⩾81 mmol/mol; hazard ratio (HR): 1.29, 95% confidence interval (CI): 1.11-1.51) and the lowest in the <6.5% (<48.0 mmol/mol; HR: 0.94, 95% CI: 0.83-1.08). The risk of hospital admission suggested a U-shaped association with HbA1c, highest risk in the lowest (<6.5% (<48.0 mmol/mol); HR: 1.04, 95% CI: 1.01-1.07) followed by HbA1c groups (8.6%-9.6% (70.0-81.0 mmol/mol); HR: 1.02, 95% CI: 0.97-1.08) while the lowest risk for hospital admission was observed for targets with the reference group (target between 6.5% and 7.5%, (48.0-58.9 mmol/mol)). The risk of microvascular complications was lowest when HbA1c levels were within the non-diabetic range and increased with higher HbA1c levels. The risk of hospital admission was significantly elevated in individuals with HbA1c levels below 6.5%, suggesting a potential U-shaped association, although the increased risk at higher HbA1c levels did not reach statistical significance. This highlights the importance of maintaining individualised HbA1c targets in the management of T2D from diagnosis to prevent these complications.

Background and Aims Although the global prevalence of advanced diabetic kidney disease is increasing, the optimum glycemic target remains uncertain. Specifically, data pertaining to the association of hemoglobin A1c (HbA1c) level with micro- and macrovascular outcomes in patients with advanced diabetic kidney disease remain inconclusive. We examined the association between HbA1c levels and complications in patients with diabetes and chronic kidney disease (CKD) stage 4 and 5. Method In a Danish nationwide registry-based retrospective cohort study, we included persons ≥18 years of age with diabetes, an estimated glomerular filtration rate (eGFR) &amp;lt;30 mL/min/1.73m2 and a concurrent measured HbA1c between 2010 and 2022. Complications were categorized as 1) major adverse cardiovascular events (MACE) defined as a composite endpoint of acute myocardial infarction, stroke, and all-cause mortality; 2) microvascular complications defined as a composite endpoint of diabetic retinopathy, major lower extremity amputation, and start of dialysis; 3) hospitalization with hypoglycemia. Multiple outcome-specific Cox regressions stratified by HbA1c levels were performed to calculate the 1-year risk of complications standardized to the distribution of risk factors of all patients in the sample. The analyses regarding the risk of hypoglycemia were further stratified according to insulin treatment at baseline. Results In total, 34,046 patients were included. The median age was 76.2 (IQR 69.1-82.7) years and 54.6% were men. The median eGFR and HbA1c level was 26.4 (IQR 21.9-28.5) mL/min/1.73m2 and 53 (IQR 46-63) mmol/mol, respectively. Figure 1 depicts the 1-year risks of MACE and microvascular complications stratified by HbA1c level. We found a U-shaped association between HbA1c level and MACE where patients with an HbA1c level between 45-50 mmol/mol had the lowest risk. The risk increased significantly with an HbA1c level below 45 mmol/mol or above 65 mmol/mol compared with 45-50 mmol/mol (P&amp;lt;0.001). The risk of microvascular complications was lowest at an HbA1c level between 35-40 mmol/mol. The risk increased significantly with increasing levels of HbA1c above 50 mmol/mol compared with 35-40 mmol/mol (P&amp;lt;0.05). The 1-year risks of hospitalization with hypoglycemia stratified according to HbA1c level and insulin treatment are illustrated in Figure 2. For both groups, the risk was lowest at an HbA1c level between 30-40 mmol/mol and increased with increasing HbA1c levels. Conclusion In patients with diabetes and CKD stage 4 and 5, HbA1c levels &amp;gt;65 mmol/mol and &amp;lt;45 mmol/mol were associated with an increased risk of MACE, whereas HbA1c levels &amp;gt;50 mmol/mol were associated with a higher risk of microvascular complications. Our findings suggest that appropriate glycemic control can reduce adverse outcomes in patients with advanced CKD without increasing the risk of hypoglycemia, but also suggest that intensive glycemic control (HbA1c &amp;lt;45 mmol/mol) might be associated with an increased risk of MACE.

High preoperative hemoglobin A1c (HbA1c) levels have been suggested to increase complications after esophagectomy. Minimally invasive esophagectomy (MIE) is less invasive than open esophagectomy (OE) and may reduce postoperative complications. However, it has not been established whether MIE contributes to low morbidity in patients with high preoperative HbA1c levels. Thus, the current study aimed to elucidate the effect of preoperative HbA1c levels on the incidence of complications each after OE and MIE. A total of 280 patients who underwent OE and 304 patients who underwent MIE for esophageal cancer between April 2005 and April 2020 were retrospectively analyzed. The OE and MIE groups were further divided into two groups according to their preoperative HbA1c levels (< 6.9%, ≥ 6.9%). Patients with high HbA1c levels had a significantly higher incidence of surgical site infections (SSIs) after OE (P = 0.0048). Multivariate analysis demonstrated that a high HbA1c level was an independent risk factor for frequent SSIs after OE (hazard ratio 2.52; 95% confidence interval, 1.101- 5.739; P = 0.029). On the contrary, a high HbA1c level did not affect the incidence of SSI after MIE (P = 1.00). A high HbA1c level was not associated with the incidence of morbidities other than SSI after OE and MIE. A high preoperative HbA1c level significantly increased SSI risk after OE but not after MIE. It was suggested that lower invasiveness of MIE could contribute to a low incidence of SSI, even in patients with poor preoperative glycemic control.

To evaluate the new Clinical Practice Research Datalink (CPRD) Aurum database, we estimated 'correctness' (ie accuracy, validity) and 'completeness' (ie presence, missingness) of malignant breast cancer diagnoses recorded in CPRD Aurum compared to external linked data sources: Hospital Episode Statistics (HES) Admitted Patient Care (APC), HES Outpatient (OP), and Cancer Registry (CR), and to the previously validated CPRD GOLD. Linkage-eligible, female patients with incident malignant breast cancer diagnosis recorded in at least one study data source were selected. Correctness was the proportion of malignant breast cancer cases recorded in CPRD Aurum or GOLD who also had a diagnosis recorded in HES APC/OP (2004-2019) or CR (2004-2016). Completeness was estimated by identifying all malignant breast cancer diagnoses in HES APC/OP or CR and calculating the proportion with a concordant diagnosis in CPRD Aurum or GOLD. Compared to HES APC/OP, there were 85,659 and 31,452 eligible patients in CPRD Aurum and GOLD, respectively. Correctness estimates were high (CPRD Aurum 83.5%, GOLD 81.7%). Compared to CR, there were 70,190 and 29,597 eligible patients in CPRD Aurum and GOLD, respectively: correctness was 89.1% for CPRD Aurum and 88.2% for GOLD. Completeness estimates for CPRD Aurum and GOLD were high (>90%). Diagnoses were recorded in CPRD Aurum within -7 to 74 days of those in the linked sources. Reasons for discordant diagnostic coding included presence of treatment or other clinical codes only, diagnosis coded after end of follow-up, non-malignant breast cancer in linked data, and administrative codes in lieu of diagnostic codes. These results indicate that correctness and completeness of malignant breast cancer diagnoses in CPRD Aurum were high and similar to CPRD GOLD. This provides confidence in use of CPRD Aurum for research purposes. Where complete case capture is important, researchers should consider linkage to HES APC or CR.

Background: Diabetes where glycated Hemoglobin A1c (HbA1c) level is raised, a strong independent risk factor for the development of atherosclerosis which leads to acute coronary syndrome (ACS). This study is designed to compare the in-hospital outcomes in terms of developing arrhythmias, heart failure, cardiogenic shock, cardiac arrest and death among the normal HbA1c level (&lt;6.5%) and raised HbA1c level (≥6.5%) patients who presented with ACS.Objective: To compare the in-hospital outcomes of patients with raised HbA1c level (≥6.5%)and normal HbA1c level (&lt;6.5%) after first attack of acute coronary syndrome.Methods: A total of 104 patients admitted during the study period to coronary care unit (CCU) of Combined Military Hospital (CMH), Dhaka through emergency department or chest pain unit, who suffered from acute coronary syndrome were included in this study. Patients were divided into two groups, those having HbA1c ≥6.5% and &lt;6.5%. Patients were followed up till discharge to observe their outcome in the hospital.Results: A total of 104 patients were included in the study where 85(81.7%) were male and 19(18.3%) were female. Gender distribution were matched in both HbA1c level (p&gt;0.05). Risk factors including hypertension, smoking and dyslipidaemia were found significantly high among those who had HbA1c ≥6.5 (p&lt;0.05). There was no relation with family history of CAD with higher HbA1c level. Obesity was distributed evenly in both higher and lower HbA1c levels of the diagnosis of ACS 8(7.7%) were UA, 33(31.7%) were NSTEMI and 63(60.6%) were STEMI. There were less complications among the patients who had HbA1c &lt;6.5% (p&lt;0.05). Arrhythmias were found to be more common in HbA1c ≥6.5% group than HbA1c &lt;6.5% group was (p&lt;0.05), heart failure was more in HbA1c ≥6.5% group, 10(19.2%) and (p&lt;0.05), cardiogenic shock was found more commonly in HbA1c ≥6.5% group, 6(11.5%) (p&lt;0.05), cardiac arrest was more 10(19.2%) among HbA1c ≥6.5% group.Finally, death was more in HbA1c ≥6.5% group. 10(19.2%) than the HbA1c &lt;6.5% group and it was statistically significant (p&lt;0.05).Conclusion: Findings of the study suggest that higher HbA1c (≥6.5%) level is associated with more adverse in-hospital outcome among ACS patients. Bangladesh Med Res Counc Bull 2021; 47(3): 260-265

Diabetes Control and the Risks of ESRD and Mortality in Patients With CKD

ObjectiveTo evaluate if the lowest target level for glycated haemoglobin (HbA1c) of <6.5% is associated with lower risk for retinopathy and nephropathy than less tight control in children and adults...

Real-world data represents a valuable tool for pregnancy research. However, an algorithmic approach is needed to ascertain pregnancy timings from this complex data. The Clinical Practice Research Datalink (CPRD) GOLD Pregnancy Register, based on UK Primary care data, has therefore proven to be a valuable research tool. The same algorithmic approach was applied to the CPRD Aurum data to generate an equivalent register in the larger database. Records of female patients registered with a CPRD Aurum contributing practice between the 1st of January 1987 and the 30th of April 2021 were searched for evidence of pregnancy. The algorithm used to generate the CPRD GOLD Pregnancy Register was redeveloped and applied first to CPRD GOLD and then to CPRD Aurum. The resulting CPRD Aurum Pregnancy Register was validated against the CPRD GOLD register, linked Hospital Episode Statistics (HES) and the Office of National Statistics (ONS) live birth data. There are 16 833 427 pregnancy episodes in the CPRD Aurum Pregnancy Register from 6724 615 women, more than double the number in CPRD GOLD. The distribution of pregnancy outcome types was comparable between the registers. Across the whole register, there was good concordance between pregnancy episodes found in CPRD Aurum and linked HES. However, both CPRD registers saw a declining number of pregnancy episodes from 2007 onwards, steeper than in HES or the ONS birth data. A pregnancy register has been created in CPRD Aurum. Changes in antenatal care policies in the UK have led to declining numbers of pregnancies in EHR primary care data. However, the creation of this pregnancy register has tripled the number of patients in the CPRD Pregnancy Registers and will increase the capacity to study pregnancy in CPRD data, particularly rare or emerging exposures, and outcomes.

Glycated hemoglobin (HbA1c) reflects glycemic control over a period of a few months before examination, and thus is commonly used as an indicator and a goal for the treatment of diabetes. Several prospective studies have shown that good glycemic control evaluated by HbA1c could prevent the development and/or progression of diabetic microvascular complications, such as retinopathy and nephropathy1–3. Furthermore, good glycemic control might also prevent macrovascular complications, such as cardiovascular disease, when glycemic control was initiated in the early stages of the development of diabetes4,5. According to these data, the American Diabetes Society proposed that the goal for diabetic control be lower than a HbA1c level of 7.0%6. In contrast, several recent studies, such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study7 and Veterans Affairs Diabetes Trial (VADT)8 failed to prove the effect of good glycemic control on the reduction of mortality and macrovascular disease in subjects with type 2 diabetes. Recently, Craig Currie et al reported that there was a U-shaped association between HbA1c and the hazard ratio of all-cause mortality in subjects with type 2 diabetes, and the lowest hazard ratio was a HbA1c level of approximately 7.5%9. Briefly, the authors obtained data from routine general practice in the UK from a proprietary health data resource: the General Practice Research Database (GPRD)9 from November 1986 to November 2008, and identified all patients who had a diagnosis of type 2 diabetes and whose treatment history included evidence of a specific escalation of their diabetes treatment. Then, they classified the patients into two groups, one was defined as patients with a newly identified switch from oral monotherapy to a combination oral regimen with a sulfonylurea plus metformin (cohort 1; n = 27,965) and the other was defined as those who were initiated on insulin with or without concomitant oral hypoglycemic agents (cohort 2; n = 20,005). The cohorts were divided into deciles by the rank of the mean of all post-index HbA1c values or yearly values where appropriate. The post-index HbA1c was calculated as the mean of all observations recorded between the index date (first prescription of intensified diabetes therapy) and the respective outcome event (death or large-vessel event) or the censoring point (further switching of treatment or the last recorded database observation). The primary outcome measure was all-cause mortality, and the secondary outcome measure was occurrence of a major cardiovascular event. Mean follow-up was 4.5 and 5.2 years in cohort 1 and 2, respectively. As the results, unadjusted mortality rates were 16.2 deaths per 1000 person-years of follow-up in cohort 1 and 27.2 deaths in cohort 2. The hazard ratio for all-cause mortality in subjects of cohort 2 (2834 deaths) vs cohort 1 (2035) was 1.49, and there were more deaths in cohort 2. In cohort 1, a significant increase of all-cause mortality was found only in deciles 1 and 10, whereas for cohort 2, significant differences were observed for deciles 1, 2, 3, 9 and 10 (Figure 1). Therefore, increased unadjusted mortality was found both in the lowest and highest HbA1c deciles in both cohorts, and patients included in a decile whose median HbA1c of 7.5% had the lowest hazard of death. Similar to the results of all-cause mortality, insulin treatment (cohort 2 vs cohort 1) was associated with an increased risk of progression to first large-vessel disease with an adjusted hazard ratio of 1.36. Taking these results, the authors suggested the revision of the diabetes guidelines include a minimum HbA1c. Hazard ratios for all-cause mortality by HbA1c deciles in type 2 diabetes subjects given oral combination and insulin-based therapies. Hazard ratios for all-cause mortality by HbA1c deciles in type 2 diabetes subjects given (a) sulfonylurea plus metformin regimen and (b) insulin-based regimen are shown. Vertical bars show hazard ratios (HR), and horizontal bars show HbA1c range. Red circle indicates each reference decile. *Truncated value at lower quartile, †truncated value at upper quartile. This figure is reprinted from an article by Currie et al9. with permission from Elsevier (License number 2491840027075). From the results of many prospective studies1–3, it is clear that better glycemic control is beneficial for the prevention of the development and progression of diabetic microvascular complications. In contrast, the impact of strict glycemic control on cardiovascular disease and/or mortality has not yet been clarified. The UKPDS, in which glycemic control was initiated at the point of the first diagnosis of type 2 diabetes, proposed the beneficial effect of good glycemic control on cardiovascular events and mortality5. Similarly, although the subjects studied were type 1 diabetes, the DCCT/EDIC studies also found that better glycemic control at an early stage of diabetes has beneficial effects on a reduction in cardiovascular disease outcomes4. In contrast, the ACCORD study showed that type 2 diabetes subjects (with cardiovascular disease or at least two risk factors for cardiovascular disease or severe atherosclerosis) who underwent intensive glycemic control (target HbA1c < 6.0%) showed rather increased mortality (hazard ratio 1.22) compared with those who received standard glycemic control (target HbA1c 7.0–7.9%), and thus warned of the unexpected risk of strict glycemic control7. The results by Currie et al.9 supported the results of the ACCORD study, and were different from those of UKPDS and DCCT/EDIC. The reason might be explained by the difference in the subjects studied, because the subjects that they investigated were selected from routine general practice and already had high HbA1c levels at baseline (mean HbA1c levels were 7.73 and 8.31% in cohort 1 and 2, respectively), and were more similar to those in the ACCORD study (mean HbA1c was 8.3%), but were different from those in UKPDS (mean HbA1c was 7.1%). The prevalence of previous macrovascular disease was also high (22 and 30% in cohort 1 and 2, respectively) and again was similar to that of the ACCORD study (35.2%), but was different from that in UKPDS (2.1%). Therefore, although the proposal by Currie et al. to revise the diabetes guidelines to include a minimum HbA1c level might be used for subjects with type 2 diabetes who already have elevated HbA1c levels and/or have a high risk of macrovascular diseases, it might not be suitable in subjects in early stages of diabetes. Another observation by Currie et al. was that subjects receiving insulin treatment showed higher hazard ratios for all-causes of death and for progression to first large-vessel disease than those receiving sulfonylurea plus metformin regimen, implying the risk of insulin treatment itself. The U-shaped association was more abundant in cohort 2, and in that cohort, all three deciles lower than a mean HbA1c level of 7.5% showed a significant increase of all-cause mortality. Although the rates of hypoglycemic episodes were not investigated in this study, increased hypoglycemia under insulin treatment might be one reason. It has been suggested that hypoglycemia could increase cardiovascular events for several reasons, such as the enhancement of the adrenergic response and the destabilization of atherosclerotic plaques through the increase of oxidative stress and of other stress responses. However, as the authors discussed in their report, it should be taken in account that there are several differences in the subjects in cohort 1 and 2, such as higher frequency of previous cardiovascular events and of progressed nephropathy in cohort 2. Further investigation to clarify the impact of insulin treatment on mortality with detailed analysis, such as causes of death and frequencies of hypoglycemia, would be necessary. According to the results from the report by Currie et al. and from the ACCORD study, the proposal to revise the diabetes guidelines to include a minimum HbA1c seems reasonable, especially in subjects with poor glycemic control and a high risk of macrovascular complications who are treated by insulin, but this might not be applicable for subjects at an early stage of diabetes or those with few risks of macrovascular disease. In Japan, a new health check-up system that aimed to prevent and early diagnose lifestyle related diseases including diabetes started in 2008. The Japan Diabetes Society also encourages the early diagnosis of diabetes, and thus included the HbA1c level of 6.5% in the diagnostic criteria of diabetes in 2010 (Journal of the Japan Diabetes Society 2010; 53: 450–467, in Japanese). Because early diagnosis followed by early intervention of diabetes has now been encouraged and been proven to prevent most diabetic complications, careful discussion should be carried out to revise the goal of glycemic control.

Hemoglobin A1c (HbA1c) predicts future drug treatment for diabetes mellitus: a follow-up study using routine clinical data in a Japanese university hospital

ObjectivesWe aimed to evaluate recording of antibiotic prescribing from two primary care electronic health record systems.DesignCohort study.SettingUK general practices contributing to the Clinical Practice Research Datalink (CPRD) databases: CPRD GOLD...

Background: The study is to determine the relation between the high HbA1c and ESR as prognostic factors with the severity of the diabetic foot ulcer disease, particularly, in predicting the final outcome in the form of higher incidence of lower extremity amputation (LEA) and/or prolonged hospital stay. The study explored the importance of increased level of serum HbA1c and erythrocyte sedimentation rate (ESR) in determining the final outcome of the disease. It revealed that the severity of diabetic foot ulcer disease is more in patients who had concomitant high levels of baseline HbA1c and ESR on admission.Methods: This observational study was done in 89 patients who were admitted in the surgical wards of the two teaching hospitals in India. The cohort consisted of patients from the age of 26 to 83 years of age who presented with clinically infected foot ulcers. Routine blood tests were done which include HbA1C on the day of admission and fasting ESR (1st hour) on the next day morning. The standard X-ray plates were routinely taken on the first day for determination of the involvement of underlying bones and soft tissues. The outcome of the diabetic foot ulcer was assessed from the severity of the disease according to Meggit-Wagner classification, the incidence of lower extremity amputation and the duration of hospital stay.Results: The high levels of baseline HbA1C (more than 7.0%) in blood on the first day of admission was found in all of the 89 patients who were included in this study but the criteria for consideration of high risk was more than 9% which was found in 41 patients. The criteria for consideration of high ESR in this study was set to be 50 mm/h. High ESR of more than 50 mm was found in 63 patients. We had subdivided 31 patients into a High Risk Group whose baseline levels of HbA1C &gt; 9% and ESR &gt; 50 mm/h. The incidence of amputation was 79.31% and 44.44% with HbA1c of more than 9.0% and ESR of more than 50 mm respectively and was considerably increased (83.87%) when both HbA1c and ESR were more than the critical value as set in the study. Similarly, the incidence of prolonged hospital stay of more than 14 days was 58.54% in patients with HbA1C level of greater than 9 %, 51.85% in patients with baseline ESR &gt; 50 mm/h and 93.55% in presence of high levels of both HbA1C (&gt;9%) and ESR (&gt;50 mm/h)..Conclusions: The study observed that the patients who presented with baseline high levels of HbA1C, ESR or both on admission had unfavourable prognosis with increased incidence of lower extremity amputation and prolonged hospital stay than the other patients in the cohort.

The Effect of Prolonged Glucosamine Usage on HbA1c Levels and New-Onset Diabetes Mellitus in Overweight and Obese Middle-Aged Women

BackgroundTo evaluate the association of elevated blood glucose with the risk of acute exacerbations in patients with chronic obstructive pulmonary disease (COPD).MethodsTotally 526 consecutive patients with COPD recruited between Jan. 2018 and July 2019 were included in this study. Based on the American Diabetes Association’s Standards of Care, these patients were divided into three groups according to HbA1c level: low HbA1c level (HbA1c <5.7%, n=204), moderate HbA1c level (HbA1c 5.7–6.4%, n=165), and high HbA1c level (HbA1c ≥6.5%, n=157). All subjects were followed up for 18 months. Multivariate Cox regression analysis was used to evaluate the predicting value of HbA1c for the time of the next COPD severe exacerbation.ResultsTotally 141 (26.8%) patients in the study had at least 1 severe exacerbation. The proportion of patients suffering from at least 1 severe exacerbation was significantly higher (P<0.01) for patients with high (36.3%) and moderate HbA1c levels (25.5%) compared to those with low HbA1c levels (20.6%). Multivariate Cox regression analysis indicated that high (HR=2.74, 95% CI: 1.70–4.41; P<0.01) and moderate HbA1c levels (HR=2.19, 95% CI: 1.39–3.46; P<0.01) were significantly associated with a higher risk of the next severe exacerbation compared with low HbA1c level, after controlling for potential confounders including age, gender, body mass index (BMI), smoking status, disease duration of COPD, frequency of hospitalization due to acute exacerbation of COPD (AECOPD) in the past 12 months, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages, COPD assessment test (CAT) score, corticosteroids use, hypertension, and cardiovascular diseases. Subgroup analyses also indicated a significant association between HbA1c levels and risk of the next severe exacerbation in different GOLD stages and diabetes status.ConclusionElevated blood glucose, no matter with or without diabetes, is significantly associated with a higher risk of the next severe exacerbation for patients with COPD.

BackgroundPrevious research has supported the presence of an association between high glycated hemoglobin (HbA1c) levels and cardiovascular disease (CVD). The objective of the present study was to determine whether increased HbA1c levels are associated with high CVD prevalence among nondiabetics. Furthermore, we aimed to explore the possible interaction of HbA1c levels and age in regard to CVD.MethodsThis cross-sectional study analyzed data of 28,534 adult participants in the National Health and Nutrition Examination Survey 2005–2018. The association between HbA1c and CVD was assessed using univariate and multivariate logistic regression models. Propensity score matching was used to reduce selection bias. Subgroup analysis and restricted cubic spline (RCS) were used to further characterize the association between HbA1c levels and CVD. We modeled additive interactions to further assess the relationship between HbA1c levels and age.ResultsIn the multivariate logistic regression model, a positive association was found between CVD and increased HbA1c levels (highest quartile [Q4] vs. lowest quartile [Q1]: odds ratio [OR] = 1.277, 95% confidence interval [CI] = 1.111–1.469, P = 0.001). In the stratified analyses, the adjusted association between HbA1c and CVD was significant for those younger than 55 years (Q4 vs. Q1: OR = 1.437, 95% CI = 1.099–1.880, P = 0.008). RCS did not reveal a nonlinear relationship between HbA1c levels and CVD among nondiabetics (P for nonlinearity = 0.609). Additionally, a high HbA1c level was favorably connected with old age on CVD, with a synergistic impact.ConclusionsIncreased HbA1c levels were associated with high CVD prevalence among nondiabetics. However, we still need to carefully explain the effect of age on the relationship between HbA1c and CVD in nondiabetic population. Given the correlations of HbA1c with CVDs and CV events, HbA1c might be a useful indicator for predicting CVDs and CV events in the nondiabetic population.