Association of glycated hemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium

Abstract

Background Biomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A1c (HbA1c) is used to monitor the quality of diabetes treatment. Its strength of association with cardiovascular outcomes in the general population remains uncertain. This study aims to assess the association of HbA1c with cardiovascular outcomes in the general population. Methods Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular disease (CVD) incidence, and overall mortality in subjects without diabetes (N = 32,496) and with diabetes (N = 3684). Results Kaplan–Meier curves showed higher event rates with increasing HbA1c levels (log-rank-test: p < 0.001). Cox regression analysis revealed significant associations between HbA1c (in mmol/mol) in the total study population and the examined outcomes. Thus, a hazard ratio (HR) of 1.16 (95% confidence interval (CI) 1.02–1.31, p = 0.02) for cardiovascular mortality, 1.13 (95% CI 1.03–1.24, p = 0.01) for CVD incidence, and 1.09 (95% CI 1.02–1.17, p = 0.01) for overall mortality was observed per 10 mmol/mol increase in HbA1c. The association with CVD incidence and overall mortality was also observed in study participants without diabetes with increased HbA1c levels (HR 1.12; 95% CI 1.01–1.25, p = 0.04) and HR 1.10; 95% CI 1.01–1.20, p = 0.02) respectively. HbA1c cut-off values of 39.9 mmol/mol (5.8%), 36.6 mmol/mol (5.5%), and 38.8 mmol/mol (5.7%) for cardiovascular mortality, CVD incidence, and overall mortality, showed also an increased risk. Conclusions HbA1c is independently associated with cardiovascular mortality, overall mortality and cardiovascular disease in the general European population. A mostly monotonically increasing relationship was observed between HbA1c levels and outcomes. Elevated HbA1c levels were associated with cardiovascular disease incidence and overall mortality in participants without diabetes underlining the importance of HbA1c levels in the overall population.

HbA1c, Coronary atheroma progression and cardiovascular outcomes

“…A wealth of evidence documents the association of greater HbA1c levels with adverse cardiovascular outcome in various cohorts [7] . In the setting of intensified diabetes mellitus therapies, poor glycemic control as reflected by high HbA1c levels was associated with increased all-cause mortality [3] .…”

“…Hemoglobin A1c (HbA1c) reflects long-term glycemic control and is central to the diagnosis and management of diabetes mellitus [ 1 , 2 ]. Elevated HbA1c is associated with an increased risk of cardiovascular events among diabetic and non-diabetic patients [2] , [3] , [4] , [5] , [6] , [7] ; with diabetic atherosclerosis manifesting within the arterial wall with accelerated disease progression and impaired arterial wall remodeling [8] . However, elevated HbA1c-levels are frequently concomitant with multiple other atherogenic risk factors, including dyslipidemia, hypertension, smoking and obesity which are all known drivers of plaque progression [9] , [10] , [11] .…”

Associations of the baseline level and change in glycosylated hemoglobin A1c with incident hypertension in non-diabetic individuals: a 3-year cohort study

“…Recently, the role of HbA1c outside of diabetes has received increasing attention. It has been shown that the HbA1c level is significantly associated with the risk of cardiovascular disease even in non-diabetic populations [ 7 , 8 ]. In addition, HbA1c is a reliable risk factor for all-cause and cardiovascular mortality in both diabetic and non-diabetic populations [ 8 , 9 ].…”

“…It has been shown that the HbA1c level is significantly associated with the risk of cardiovascular disease even in non-diabetic populations [ 7 , 8 ]. In addition, HbA1c is a reliable risk factor for all-cause and cardiovascular mortality in both diabetic and non-diabetic populations [ 8 , 9 ]. Recent studies have attempted to extend the role of HbA1c by including it as a useful component of the definition of metabolic syndrome [ 10 , 11 ].…”

Prospective Risk of Type 2 Diabetes in Normal Weight Women with Polycystic Ovary Syndrome

“…HbA1c compared to OGTT has low sensitivity for the diagnosis of prediabetes and T2D in PCOS [ 71 ], but HbA1c is a better predictor of cardiovascular disease and overall mortality than blood glucose during OGTT [ 71 , 72 ]. HbA1c could be used as an indicator for both increased metabolic and vascular risk [ 72 , 73 ], and prospective measurement of HbA1c is more feasible than measurement of fasting glucose or OGTT in a clinical setting. In some countries, the use of OGTT is preferable to HbA1c and fasting glucose, as other methods are unavailable or unreliable [ 70 ].…”