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Original Research

A1C and Cardiovascular Outcomes in Type 2 Diabetes

A nested case-control study

  1. Danielle C. Colayco, PHARMD, MS1,
  2. Fang Niu, MS2,
  3. Jeffrey S. McCombs, PHD1 and
  4. T. Craig Cheetham, PHARMD, MS2
  1. 1University of Southern California School of Pharmacy, Department of Pharmaceutical Economics & Policy, Los Angeles, California;
  2. 2Kaiser Permanente, Pharmacy Analytical Services, Downey, California.
  1. Corresponding author: Danielle C. Colayco, colayco{at}usc.edu.
Diabetes Care 2011 Jan; 34(1): 77-83. https://doi.org/10.2337/dc10-1318
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    Figure 1

    Selection of study population.

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  • Table 1

    Patient characteristics

    VariableCase subjectsControl subjectsP
    n11,15744,628
    Mean age (years)65.5 ± 10.565.5 ± 10.5Matching variable
    Male sex6,359 (57)25,436 (57)Matching variable
    Mean A1C level (%)
        ≤61,580 (14.2)5,801 (13.0)0.001
        >6–86,818 (61.1)29,564 (66.3)<0.001
        >82,759 (24.7)9,263 (20.8)<0.001
    Measured ≥6 A1Cs over 3-year follow-up6,055 (54.3)22,150 (49.6)<0.001
    A1C range >1.0%8,186 (73.4)29,251 (65.5)<0.001
    Diabetes medications
        Insulin only2,102 (18.8)3,386 (7.6)<0.001
        Metformin only681 (6.1)5,908 (13.2)<0.001
        Sulfonylurea only2,230 (20.0)10,142 (22.7)<0.001
        Insulin and oral medications2,579 (23.1)5,747 (12.9)<0.001
        Other oral medications/oral combination2,444 (21.9)14,413 (32.3)<0.001
        No diabetes medications1,121 (10.1)5,032 (11.3)<0.001
        Mean proportion of days covered of diabetes medications0.69 ± 0.350.71 ± 0.35<0.001
    Other medications
        Statins7,787 (69.8)33,602 (75.3)<0.001
        ACE inhibitors/ARBs8,624 (77.3)35,731 (80.1)<0.001
        Other antihypertensives/antiplatelets4,241 (38.0)11,195 (25.1)<0.001
        Antipsychotics1,822 (16.3)1,102 (2.5)<0.001
        Antiarrhythmics423 (3.8)510 (1.1)<0.001
        Tricyclic antidepressant505 (4.5)468 (1.1)<0.001
        ESAs1,385 (12.4)911 (2.0)<0.001
        β-Agonists2,292 (20.5)4,905 (11.0)<0.001
    Prior cardiovascular event2,604 (23.3)2,601 (5.8)<0.001
        MI only293 (11.3)428 (16.5)
        Stroke only224 (8.6)289 (11.1)
        Heart failure only1,436 (55.1)899 (34.6)
        Arrhythmia only491 (18.9)911 (35.0)
        MI and stroke7 (0.3)5 (0.2)
        MI and heart failure60 (2.3)24 (0.9)
        MI and arrhythmia15 (0.6)22 (0.8)
        Stroke and heart failure6 (0.2)2 (0.1)
        Stroke and arrhythmia6 (0.2)2 (0.1)
        Heart failure and arrhythmia66 (2.5)19 (0.7)
    Cardiovascular diagnosis10,297 (92.3)38,761 (86.9)<0.001
        Hypertension only5,342 (51.9)30,495 (78.7)
        Peripheral vascular disease only88 (0.8)235 (0.6)
        Heart failure only123 (1.3)144 (0.3)
        Peripheral vascular disease and heart failure34 (0.3)26 (0.1)
        Hypertension and heart failure1,861 (18.1)3,025 (7.8)
        Hypertension and peripheral vascular disease1,423 (13.8)3,590 (9.3)
        Hypertension, peripheral vascular disease, and heart failure1,426 (13.8)1,246 (3.2)
    LDL >100 mg/dl3,499 (31.4)15,465 (34.7)<0.001
    LDL ≤100 mg/dl6,478 (58.0)25,768 (57.7)
    Missing LDL1,180 (10.6)3,395 (7.6)
    HDL >40 mg/dl5,278 (47.3)27,409 (61.4)<0.001
    HDL ≤40 mg/dl4,669 (41.8)13,760 (30.8)
    Missing HDL1,210 (10.8)3,459 (7.8)
    Retinopathy3,886 (34.8)10,062 (22.6)<0.001
    Nephropathy8,005 (71.8)23,194 (52.0)<0.001
    Neuropathy4,487(40.2)12,016 (26.9)<0.001
    Prior amputations466 (4.2)274 (0.6)<0.001
    Prior severe hypoglycemia447 (4.0)520 (1.2)<0.001
    • Data are n (%) or means ± SD. Prior cardiovascular event = hospitalization for MI, stroke, heart failure, or arrhythmia in the 3-year preindex period. Cardiovascular diagnosis = hypertension, heart failure, and/or peripheral vascular disease. Prior severe hypoglycemia = emergency-room visit or hospitalization with a primary diagnosis of hypoglycemia.

  • Table 2

    Conditional logistic regression model of cardiovascular events

    CovariateOdds ratio (95% CI)P
    Mean A1C level (%)
        ≤6.01.20* (1.10–1.31)<0.001
        >6.0–8.0Reference—
        >8.01.16* (1.09–1.25)<0.001
    ≥6 A1C tests over prior 3 years0.84 (0.80–0.89)<0.001
    A1C range >1.0%1.29 (1.21–1.38)<0.001
    Diabetes medications
        Insulin only2.65 (2.31–3.05)<0.001
        Metformin only1.06 (0.92–1.23)0.41
        Sulfonylurea only1.55 (1.36–1.76)<0.001
        Insulin and oral medications2.56 (2.19–3.00)<0.001
        Other oral medications/oral combination1.55 (1.33–1.80)<0.001
        No diabetes medicationsReference—
    Mean proportion of days covered of diabetes medications0.56 (0.49–0.63)<0.001
    Statins0.75 (0.70–0.80)<0.001
    ACE inhibitors/ARBs0.80 (0.74–0.86)<0.001
    Other antihypertensives/antiplatelets1.34 (1.25–1.43)<0.001
    Antipsychotics7.10 (6.24–8.09)<0.001
    Antiarrhythmics1.54 (1.30–1.83)<0.001
    Tricyclic antidepressant2.91 (2.44–3.46)<0.001
    ESAs2.75 (2.46–3.08)<0.001
    β-Agonists1.63 (1.52–1.75)<0.001
    Prior cardiovascular event3.10 (2.87–3.36)<0.0001
    Cardiovascular diagnosis1.41 (1.28–1.56)<0.0001
    LDL >100 mg/dl1.14 (1.06–1.22)0.0033
    HDL > 40 mg/dl0.67 (0.63–0.71)<0.0001
    Retinopathy1.13 (1.07–1.21)<0.0001
    Nephropathy1.68 (1.58–1.79)<0.0001
    Neuropathy1.19 (1.12–1.26)<0.0001
    Prior amputations3.28 (2.52–4.26)<0.0001
    Prior severe hypoglycemia1.67 (1.40–1.99)<0.0001
    • ↵*Odds ratio estimated using multivariate analysis controlling for all covariates listed in table. Prior cardiovascular event = hospitalization for MI, stroke, heart failure, arrhythmia in the 3-year preindex period. Cardiovascular diagnosis = hypertension, heart failure, and/or peripheral vascular disease. Prior severe hypoglycemia = emergency-room visit or hospitalization with primary diagnosis of hypoglycemia.

  • Table 3

    Conditional logistic regression model of cardiovascular events, stratified by subgroup

    SubgroupnA1C (%)Odds ratio (95% CI)*P
    LDL <100, no other CV drug†20,871≤61.39 (1.15–1.67)0.0006
    >81.20 (1.03–1.40)0.02
    LDL >100, no other CV drug†13,983≤61.05 (0.79–1.39)0.74
    >81.41 (1.18–1.69)0.0002
    On other cardiovascular drug, LDL <100†9,555≤61.10 (0.85–1.43)0.45
    >81.25 (0.95–1.63)0.11
    On other cardiovascular drug, LDL >100†4,038≤60.89 (0.39–2.01)0.78
    >81.32 (0.70–2.49)0.39
    Patients using antipsychotics‡2,539≤61.05 (0.53–2.07)0.90
    >83.15 (1.18- 8.44)0.02
    Patients not using antipsychotics†53,246≤61.26 (1.15–1.38)<0.0001
    >81.17 (1.09–1.26)<0.0001
    • LDL units are in mg/dl. Other cardiovascular drugs include antiplatelets and antihypertensives other than ACE inhibitors and ARBs.

    • ↵*Odds ratio for A1C category compared with A1C 6–8% (reference).

    • ↵†Not on antipsychotics. Model controlled for number of A1C tests in the 3-year index period, A1C range, diabetes medications, proportion of days covered of diabetes medications, use of statins, ACE inhibitors, ARBs, antiarrhythmics, tricyclic antidepressants, ESAs, β-agonists, diagnosis of hypertension, heart failure or peripheral vascular disease, retinopathy, nephropathy, neuropathy, prior cardiovascular events in 3-year preindex period, and severe hypoglycemia.

    • ↵‡Model controlled for prior cardiovascular events, HDL level, use of β-agonists, and ESAs.

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A1C and Cardiovascular Outcomes in Type 2 Diabetes
Danielle C. Colayco, Fang Niu, Jeffrey S. McCombs, T. Craig Cheetham
Diabetes Care Jan 2011, 34 (1) 77-83; DOI: 10.2337/dc10-1318

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A1C and Cardiovascular Outcomes in Type 2 Diabetes
Danielle C. Colayco, Fang Niu, Jeffrey S. McCombs, T. Craig Cheetham
Diabetes Care Jan 2011, 34 (1) 77-83; DOI: 10.2337/dc10-1318
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