Associations of Glycemic Control With Cardiovascular Outcomes Among US Hemodialysis Patients With Diabetes Mellitus

Abstract

Background: There is a lack of data on the relationship between glycemic control and cardiovascular end points in hemodialysis patients with diabetes mellitus.

Methods and results: We included adult Medicare-insured patients with diabetes mellitus who initiated in-center hemodialysis treatment from 2006 to 2008 and survived for >90 days. Quarterly mean time-averaged glycated hemoglobin (HbA_1c) values were categorized into <48 mmol/mol (<6.5%) (reference), 48 to <58 mmol/mol (6.5% to <7.5%), 58 to <69 mmol/mol (7.5% to <8.5%), and ≥69 mmol/mol (≥8.5%). Medicare claims were used to identify outcomes of cardiovascular mortality, nonfatal myocardial infarction (MI), fatal or nonfatal MI, stroke, and peripheral arterial disease. We used Cox models as a function of time-varying exposure to estimate multivariable adjusted hazard ratios and 95%CI for the associations between HbA_1c and time to study outcomes in a cohort of 16 387 eligible patients. Patients with HbA_1c 58 to <69 mmol/mol (7.5% to <8.5%) and ≥69 mmol/mol (≥8.5%) had 16% (CI, 2%, 32%) and 18% (CI, 1%, 37%) higher rates of cardiovascular mortality (P-trend=0.01) and 16% (CI, 1%, 33%) and 15% (CI, 1%, 32%) higher rates of nonfatal MI (P-trend=0.05), respectively, compared with those in the reference group. Patients with HbA_1c ≥69 mmol/mol (≥8.5%) had a 20% (CI, 2%, 41%) higher rate of fatal or nonfatal MI (P-trend=0.02), compared with those in the reference group. HbA_1c was not associated with stroke, peripheral arterial disease, or all-cause mortality.

Conclusions: Higher HbA_1c levels were significantly associated with higher rates of cardiovascular mortality and MI but not with stroke, peripheral arterial disease, or all-cause mortality in this large cohort of hemodialysis patients with diabetes mellitus.

Keywords: cardiovascular outcomes; diabetes mellitus; glycemic control; hemodialysis.

Figure 1

Study population derived from the US Renal Data System and electronic health records of DaVita, Inc.

Figure 2

Hazard ratios, 95% CI, and P‐trends for the associations between time‐averaged glycated hemoglobin (HbA_1c) and 3 different cardiovascular outcomes (cardiovascular mortality, nonfatal MI, and fatal or nonfatal MI) from model 4. This model adjusted for end‐stage renal disease incidence; census division (a marker for location); demographic variables such as age, sex, race/ethnicity; Medicare/Medicaid dual eligibility; area‐level geocoded socioeconomic standards variables such as median rent, median household income, percentage living below poverty, percentage unemployed, and percentage with less than high school education; baseline body mass index and estimated glomerular filtration rate; preexisting comorbidities including heart failure, arrhythmias, coronary artery disease, other cardiac disease, peripheral arterial disease, hypertension, chronic obstructive pulmonary disease, current tobacco use, cancer, and alcohol dependence; and laboratory variables such as albumin, normalized protein catabolic rate, hemoglobin, platelet count, white blood cell count, ferritin, mean arterial pressure, pulse pressure, serum calcium, serum phosphorus, parathyroid hormone level, and predialysis weight. For each outcome, HbA_1c categories are represented as the following: ᴏ, <6.5% (reference group); +, 6.5% to <7.5%; ×, 7.5% to <8.5%; and Δ, ≥8.5%. CV indicates cardiovascular; MI, myocardial infarction.