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. 2016 May;34(5):907-13.
doi: 10.1097/HJH.0000000000000864.

Synergistic association of combined glycemic and blood pressure level with risk of complications in US veterans with diabetes

Aidar R Gosmanov  1 , Jun L Lu, Keiichi Sumida, Praveen K Potukuchi, Connie M Rhee, Kamyar Kalantar-Zadeh, Miklos Z Molnar, Csaba P Kovesdy
Affiliations

Synergistic association of combined glycemic and blood pressure level with risk of complications in US veterans with diabetes

Aidar R Gosmanov et al. J Hypertens. 2016 May.

Abstract

Objectives: Hemoglobin A1c levels less than 7.0% and systolic blood pressure (SBP) less than 140 mmHg are each associated with lower risk of vascular complications in patients with diabetes mellitus. Associations between combined A1c level and SBP categories and risk of mortality and morbidity in diabetic patients are not well characterized.

Methods: We examined 891 670 US diabetic veterans with baseline estimated glomerular filtration rates more than 60 ml/min per 1.73 m (mean age 67 ± 11 years, 97% men, 17% African-Americans). The associations of mutually exclusive combined categories of A1c (<6.5, 6.5-6.9, 7.0-7.9, 8.0-8.9, 9.0-9.9, and ≥10%) and SBP (<100, 100-119, 120-139, 140-159, 160-179, and ≥180 mmHg) with the risk of all-cause mortality and incident chronic kidney disease (CKD), coronary heart disease, and stroke were examined in Cox models adjusted for baseline characteristics using patients with concomitant A1c 6.5-6.9% and SBP of 120-139 mmHg as the referent group.

Results: A total of 221 529 (25%) patients died, and 178 588 (20%), 43 373 (5%) and 36 935 (4%) developed CKD, coronary heart disease and stroke, respectively, during a median follow-up of 7.4 years. SBP displayed a J-shaped association with each outcome except CKD risk that was linearly associated with SBP across all A1c categories. A1c above 7.0% was associated with monotonically worse outcomes for all end points in all SBP categories. Patients with the combined highest A1c and SBP levels experienced the worst outcomes.

Conclusion: SBP greater than 120-139 mmHg and A1c greater than 7.0% are associated with higher mortality and vascular complications in diabetic patients, independent of each other. Combined efforts to improve both glycemic and blood pressure control may synergistically improve outcomes in patients with normal kidney function.

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Conflict of interest statement

Conflict of Interests.

ARG reports personal fees from AstraZeneca and Janssen Pharmaceutical and grant support from Sanofi and Novo Nordisk paid to the UTHSC, Memphis. MZM reports support from Czech Health Research Council, outside the submitted work. KK-Z reports personal fees from Abbott, AbbVie, Amgen, Fresenius, Genentech, Genzyme–Sanofi, Hospira, Keryx, Shire, and Vifor, non-financial support from DaVita, and grants from the US National Institutes of Health (NIH), outside the submitted work. CPK reports personal fees from Amgen, NPS, Relypsa, ZS Pharma, and Sanofi-Aventis, royalties from UpToDate for a review article about metabolic acidosis, and grants from the NIH, AbbVie, Amgen, OPKO, and Shire, outside the submitted work. CPK and KK-Z are employees of the US Department of Veterans Affairs and their opinions expressed in this paper are those of the authors’ and do not necessarily represent the opinion of the Department of Veterans Affairs. The other authors declare no competing interests.

Figures

Figure 1
Figure 1
Flow chart of patients’ selection
Figure 2
Figure 2
Associations of systolic blood pressure and A1c categories with the risk of death from any cause. The effects of the categories on the mortality risks were estimated from Cox proportional hazards models. Risk estimates were adjusted for the following factors at baseline: age, gender, race/ethnicity, baseline eGFR, various socio-economic parameters, service connection, adherence to medical interventions, comorbidities, body mass index and statin treatment. The adjusted hazard ratios are compared to the reference category of systolic blood pressure of 120–139mmHg and A1c of 6.5–7.0% taken as 1.0.
Figure 2
Figure 2
Associations of systolic blood pressure and A1c categories with the risk of death from any cause. The effects of the categories on the mortality risks were estimated from Cox proportional hazards models. Risk estimates were adjusted for the following factors at baseline: age, gender, race/ethnicity, baseline eGFR, various socio-economic parameters, service connection, adherence to medical interventions, comorbidities, body mass index and statin treatment. The adjusted hazard ratios are compared to the reference category of systolic blood pressure of 120–139mmHg and A1c of 6.5–7.0% taken as 1.0.
Figure 3
Figure 3
Associations of blood pressure and A1c categories with the risk of cardiovascular disease (panel A), stroke (panel B) and chronic kidney disease (panel C). The effects of the categories on the mortality risks were estimated from Cox proportional hazards models. Risk estimates were adjusted for the following factors at baseline: age, gender, race/ethnicity, baseline eGFR, various socio-economic parameters, service connection, adherence to medical interventions, comorbidities, body mass index and statin treatment. The adjusted hazard ratios are compared to the reference category of systolic blood pressure of 120–139mmHg and A1c of 6.5–7.0% taken as 1.0.
Figure 3
Figure 3
Associations of blood pressure and A1c categories with the risk of cardiovascular disease (panel A), stroke (panel B) and chronic kidney disease (panel C). The effects of the categories on the mortality risks were estimated from Cox proportional hazards models. Risk estimates were adjusted for the following factors at baseline: age, gender, race/ethnicity, baseline eGFR, various socio-economic parameters, service connection, adherence to medical interventions, comorbidities, body mass index and statin treatment. The adjusted hazard ratios are compared to the reference category of systolic blood pressure of 120–139mmHg and A1c of 6.5–7.0% taken as 1.0.
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