Hemoglobin A1c levels and the risk of cardiovascular disease in people without known diabetes

Atsushi Goto, Mitsuhiko Noda, Yumi Matsushita, Maki Goto, Masayuki Kato, Akihiro Isogawa, Yoshihiko Takahashi, Kayo Kurotani, Shino Oba, Akiko Nanri, Tetsuya Mizoue, Kazumasa Yamagishi, Hiroshi Yatsuya, Isao Saito, Yoshihiro Kokubo, Norie Sawada, Manami Inoue, Hiroyasu Iso, Takashi Kadowaki, Shoichiro Tsugane

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Abstract

High hemoglobin A1c (HbA1c) levels are strongly associated with an increased risk of cardiovascular disease (CVD) in people with and without diabetes. However, information regarding the relationship between low HbA1c levels and the risk of CVD among people without known diabetes is limited. The aim of this large-scale, prospective, population-based cohort study was to clarify the association between HbA1c levels and CVD risk among people without known diabetes. We followed-up 10,980 men and 18,079 women (46-80 years old and free of CVD and cancer at baseline) in the Japan Public Health Center-based Prospective Study. Using Cox models, we estimated the hazard ratios for CVD risk with adjustments for age, sex, geographic areas, body mass index, smoking status, sports and physical exercise, alcohol intake, systolic blood pressure, non-high-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. During the median follow-up of 9.4 years, 935 CVD events (770 strokes and 165 coronary heart diseases) occurred. We observed a nonlinear association between HbA1c levels and CVD risk in participants without known diabetes. Compared with HbA1c levels of 5.0 to 5.4% (31-36 mmol/mol), the hazard ratios for CVD in participants without known diabetes were 1.50 (95% confidence interval: 1.15- 1.95), 1.01 (0.85-1.20), 1.04 (0.82-1.32), and 1.77 (1.32-2.38) for HbA1c levels of <5.0% (<31 mmol/mol), 5.5 to 5.9% (37-41 mmol/ mol), 6.0 to 6.4% (42-47 mmol/mol), and ≥6.5% (≥48 mmol/mol), respectively (P value for nonlinear trend: <0.001). In addition, the hazard ratio for CVD was 1.81 (1.43-2.29) in patients with known diabetes compared with participants with HbA1c levels of 5.0 to 5.4% and without known diabetes. This nonlinear relation persisted after excluding people with kidney dysfunction, liver dysfunction, anemia, body mass index <18.5 kg/m2, or early events within 3 years of followup (P value for nonlinear trend: <0.01 for all tests). In conclusion, both low and high levels of HbA1c were associated with a higher risk of CVD in a Japanese general population without known diabetes.

Original languageEnglish
Pages (from-to)e785
JournalMedicine (United States)
Volume94
Issue number17
DOIs
Publication statusPublished - 01-05-2015

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Hemoglobins
Cardiovascular Diseases
Body Mass Index
Blood Pressure
Risk Adjustment
Proportional Hazards Models
HDL Cholesterol
Population
Sports
Coronary Disease
Liver Diseases
Anemia
Japan
Cohort Studies
Public Health
Smoking
Stroke
Alcohols
Prospective Studies
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Goto, A., Noda, M., Matsushita, Y., Goto, M., Kato, M., Isogawa, A., ... Tsugane, S. (2015). Hemoglobin A1c levels and the risk of cardiovascular disease in people without known diabetes. Medicine (United States), 94(17), e785. https://doi.org/10.1097/MD.0000000000000785
Goto, Atsushi ; Noda, Mitsuhiko ; Matsushita, Yumi ; Goto, Maki ; Kato, Masayuki ; Isogawa, Akihiro ; Takahashi, Yoshihiko ; Kurotani, Kayo ; Oba, Shino ; Nanri, Akiko ; Mizoue, Tetsuya ; Yamagishi, Kazumasa ; Yatsuya, Hiroshi ; Saito, Isao ; Kokubo, Yoshihiro ; Sawada, Norie ; Inoue, Manami ; Iso, Hiroyasu ; Kadowaki, Takashi ; Tsugane, Shoichiro. / Hemoglobin A1c levels and the risk of cardiovascular disease in people without known diabetes. In: Medicine (United States). 2015 ; Vol. 94, No. 17. pp. e785.
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Goto, A, Noda, M, Matsushita, Y, Goto, M, Kato, M, Isogawa, A, Takahashi, Y, Kurotani, K, Oba, S, Nanri, A, Mizoue, T, Yamagishi, K, Yatsuya, H, Saito, I, Kokubo, Y, Sawada, N, Inoue, M, Iso, H, Kadowaki, T & Tsugane, S 2015, 'Hemoglobin A1c levels and the risk of cardiovascular disease in people without known diabetes', Medicine (United States), vol. 94, no. 17, pp. e785. https://doi.org/10.1097/MD.0000000000000785

Hemoglobin A1c levels and the risk of cardiovascular disease in people without known diabetes. / Goto, Atsushi; Noda, Mitsuhiko; Matsushita, Yumi; Goto, Maki; Kato, Masayuki; Isogawa, Akihiro; Takahashi, Yoshihiko; Kurotani, Kayo; Oba, Shino; Nanri, Akiko; Mizoue, Tetsuya; Yamagishi, Kazumasa; Yatsuya, Hiroshi; Saito, Isao; Kokubo, Yoshihiro; Sawada, Norie; Inoue, Manami; Iso, Hiroyasu; Kadowaki, Takashi; Tsugane, Shoichiro.

In: Medicine (United States), Vol. 94, No. 17, 01.05.2015, p. e785.

Research output: Contribution to journalArticle

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T1 - Hemoglobin A1c levels and the risk of cardiovascular disease in people without known diabetes

AU - Goto, Atsushi

AU - Noda, Mitsuhiko

AU - Matsushita, Yumi

AU - Goto, Maki

AU - Kato, Masayuki

AU - Isogawa, Akihiro

AU - Takahashi, Yoshihiko

AU - Kurotani, Kayo

AU - Oba, Shino

AU - Nanri, Akiko

AU - Mizoue, Tetsuya

AU - Yamagishi, Kazumasa

AU - Yatsuya, Hiroshi

AU - Saito, Isao

AU - Kokubo, Yoshihiro

AU - Sawada, Norie

AU - Inoue, Manami

AU - Iso, Hiroyasu

AU - Kadowaki, Takashi

AU - Tsugane, Shoichiro

PY - 2015/5/1

Y1 - 2015/5/1

N2 - High hemoglobin A1c (HbA1c) levels are strongly associated with an increased risk of cardiovascular disease (CVD) in people with and without diabetes. However, information regarding the relationship between low HbA1c levels and the risk of CVD among people without known diabetes is limited. The aim of this large-scale, prospective, population-based cohort study was to clarify the association between HbA1c levels and CVD risk among people without known diabetes. We followed-up 10,980 men and 18,079 women (46-80 years old and free of CVD and cancer at baseline) in the Japan Public Health Center-based Prospective Study. Using Cox models, we estimated the hazard ratios for CVD risk with adjustments for age, sex, geographic areas, body mass index, smoking status, sports and physical exercise, alcohol intake, systolic blood pressure, non-high-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. During the median follow-up of 9.4 years, 935 CVD events (770 strokes and 165 coronary heart diseases) occurred. We observed a nonlinear association between HbA1c levels and CVD risk in participants without known diabetes. Compared with HbA1c levels of 5.0 to 5.4% (31-36 mmol/mol), the hazard ratios for CVD in participants without known diabetes were 1.50 (95% confidence interval: 1.15- 1.95), 1.01 (0.85-1.20), 1.04 (0.82-1.32), and 1.77 (1.32-2.38) for HbA1c levels of <5.0% (<31 mmol/mol), 5.5 to 5.9% (37-41 mmol/ mol), 6.0 to 6.4% (42-47 mmol/mol), and ≥6.5% (≥48 mmol/mol), respectively (P value for nonlinear trend: <0.001). In addition, the hazard ratio for CVD was 1.81 (1.43-2.29) in patients with known diabetes compared with participants with HbA1c levels of 5.0 to 5.4% and without known diabetes. This nonlinear relation persisted after excluding people with kidney dysfunction, liver dysfunction, anemia, body mass index <18.5 kg/m2, or early events within 3 years of followup (P value for nonlinear trend: <0.01 for all tests). In conclusion, both low and high levels of HbA1c were associated with a higher risk of CVD in a Japanese general population without known diabetes.

AB - High hemoglobin A1c (HbA1c) levels are strongly associated with an increased risk of cardiovascular disease (CVD) in people with and without diabetes. However, information regarding the relationship between low HbA1c levels and the risk of CVD among people without known diabetes is limited. The aim of this large-scale, prospective, population-based cohort study was to clarify the association between HbA1c levels and CVD risk among people without known diabetes. We followed-up 10,980 men and 18,079 women (46-80 years old and free of CVD and cancer at baseline) in the Japan Public Health Center-based Prospective Study. Using Cox models, we estimated the hazard ratios for CVD risk with adjustments for age, sex, geographic areas, body mass index, smoking status, sports and physical exercise, alcohol intake, systolic blood pressure, non-high-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. During the median follow-up of 9.4 years, 935 CVD events (770 strokes and 165 coronary heart diseases) occurred. We observed a nonlinear association between HbA1c levels and CVD risk in participants without known diabetes. Compared with HbA1c levels of 5.0 to 5.4% (31-36 mmol/mol), the hazard ratios for CVD in participants without known diabetes were 1.50 (95% confidence interval: 1.15- 1.95), 1.01 (0.85-1.20), 1.04 (0.82-1.32), and 1.77 (1.32-2.38) for HbA1c levels of <5.0% (<31 mmol/mol), 5.5 to 5.9% (37-41 mmol/ mol), 6.0 to 6.4% (42-47 mmol/mol), and ≥6.5% (≥48 mmol/mol), respectively (P value for nonlinear trend: <0.001). In addition, the hazard ratio for CVD was 1.81 (1.43-2.29) in patients with known diabetes compared with participants with HbA1c levels of 5.0 to 5.4% and without known diabetes. This nonlinear relation persisted after excluding people with kidney dysfunction, liver dysfunction, anemia, body mass index <18.5 kg/m2, or early events within 3 years of followup (P value for nonlinear trend: <0.01 for all tests). In conclusion, both low and high levels of HbA1c were associated with a higher risk of CVD in a Japanese general population without known diabetes.

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