Long-term cardiovascular outcomes of gestational diabetes mellitus: a prospective UK Biobank study

Abstract

Background: Previous studies showed that gestational diabetes mellitus (GDM) can be a risk factor for subsequent atherosclerotic cardiovascular disease. However, there is a paucity of information regarding diverse cardiovascular outcomes in elderly women after GDM. In the current study, we examined whether women with a history of GDM have an increased risk for long-term overall cardiovascular outcomes.

Methods: Among the UK participants, we included 219,330 women aged 40 to 69 years who reported at least one live birth. The new incidence of diverse cardiovascular outcomes was compared according to GDM history by multivariable Cox proportional hazard models. In addition, causal mediation analysis was performed to examine the contribution of well-known risk factors to observed risk.

Results: After enrollment, 13,094 women (6.0%) developed new overall cardiovascular outcomes. Women with GDM history had an increased risk for overall cardiovascular outcomes [adjusted HR (aHR) 1.36 (95% CI 1.18-1.55)], including coronary artery disease [aHR 1.31 (1.08-1.59)], myocardial infarction [aHR 1.65 (1.27-2.15)], ischemic stroke [aHR 1.68 (1.18-2.39)], peripheral artery disease [aHR 1.69 (1.14-2.51)], heart failure [aHR 1.41 (1.06-1.87)], mitral regurgitation [aHR 2.25 (1.51-3.34)], and atrial fibrillation/flutter [aHR 1.47 (1.18-1.84)], after adjustment for age, race, BMI, smoking, early menopause, hysterectomy, prevalent disease, and medication. In mediation analysis, overt diabetes explained 23%, hypertension explained 11%, and dyslipidemia explained 10% of the association between GDM and overall cardiovascular outcome.

Conclusions: GDM was associated with more diverse cardiovascular outcomes than previously considered, and conventional risk factors such as diabetes, hypertension, and dyslipidemia partially contributed to this relationship.

Keywords: Cardiovascular outcome; Gestational diabetes mellitus; Long-term outcomes; UK Biobank.

Fig. 1

Study population GDM gestational diabetes mellitus

Fig. 2

Frequency of prevalent diabetes, hypertension, and dyslipidemia by the age at enrollment (a) Diabetes (b) Hypertension (c) Dyslipidemia

Fig. 3

Occurrence of incident cardiovascular outcomes during follow up (a) Incidence of total cardiovascular outcome by the age at enrollment (b) Incidence of each cardiovascular outcomes p value: Adjusted for age at enrollment, race, BMI, smoking, alcohol consumption, early menopause, hysterectomy, prevalent comorbidities (hypertension, diabetes, dyslipidemia) and medication by Cox regression analysis CAD coronary artery disease, MI myocardial infarction, PAD peripheral artery disease, AS aortic stenosis, MR mitral regurgitation, Afib atrial fibrillation, Aflutter atrial flutter, VTE venous thromboembolism

Fig. 4

Hazard ratio of each cardiovascular outcomes

Fig. 5

Survival analysis of total cardiovascular outcomes (a) Total cardiovascular outcome (b) Atherosclerotic cardiovascular disease ^§ (c) Non-atherosclerotic cardiovascular disease. ^§ a composite of coronary artery disease, myocardial infarction (MI), ischemic stroke, and peripheral artery disease a composite of heart failure, aortic stenosis, mitral regurgitation, atrial fibrillation/ flutter, and venous thromboembolism aHR: adjusted hazard ratio [adjusted for age, race, BMI, smoking, alcohol consumption, early menopause, hysterectomy, prevalent diseases (hypertension, diabetes, or dyslipidemia), and medication (aspirin, anti-hypertensive, and cholesterol-lowering agent) by Cox proportional hazards regression analysis]