A1C and Cardiovascular Outcomes in Type 2 Diabetes
A nested case-control study
Article Figures & Tables
Figures
- Figure 1
Selection of study population.
Tables
- Table 1
Patient characteristics
Variable Case subjects Control subjects P n 11,157 44,628 Mean age (years) 65.5 ± 10.5 65.5 ± 10.5 Matching variable Male sex 6,359 (57) 25,436 (57) Matching variable Mean A1C level (%) ≤6 1,580 (14.2) 5,801 (13.0) 0.001 >6–8 6,818 (61.1) 29,564 (66.3) <0.001 >8 2,759 (24.7) 9,263 (20.8) <0.001 Measured ≥6 A1Cs over 3-year follow-up 6,055 (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 only 2,102 (18.8) 3,386 (7.6) <0.001 Metformin only 681 (6.1) 5,908 (13.2) <0.001 Sulfonylurea only 2,230 (20.0) 10,142 (22.7) <0.001 Insulin and oral medications 2,579 (23.1) 5,747 (12.9) <0.001 Other oral medications/oral combination 2,444 (21.9) 14,413 (32.3) <0.001 No diabetes medications 1,121 (10.1) 5,032 (11.3) <0.001 Mean proportion of days covered of diabetes medications 0.69 ± 0.35 0.71 ± 0.35 <0.001 Other medications Statins 7,787 (69.8) 33,602 (75.3) <0.001 ACE inhibitors/ARBs 8,624 (77.3) 35,731 (80.1) <0.001 Other antihypertensives/antiplatelets 4,241 (38.0) 11,195 (25.1) <0.001 Antipsychotics 1,822 (16.3) 1,102 (2.5) <0.001 Antiarrhythmics 423 (3.8) 510 (1.1) <0.001 Tricyclic antidepressant 505 (4.5) 468 (1.1) <0.001 ESAs 1,385 (12.4) 911 (2.0) <0.001 β-Agonists 2,292 (20.5) 4,905 (11.0) <0.001 Prior cardiovascular event 2,604 (23.3) 2,601 (5.8) <0.001 MI only 293 (11.3) 428 (16.5) Stroke only 224 (8.6) 289 (11.1) Heart failure only 1,436 (55.1) 899 (34.6) Arrhythmia only 491 (18.9) 911 (35.0) MI and stroke 7 (0.3) 5 (0.2) MI and heart failure 60 (2.3) 24 (0.9) MI and arrhythmia 15 (0.6) 22 (0.8) Stroke and heart failure 6 (0.2) 2 (0.1) Stroke and arrhythmia 6 (0.2) 2 (0.1) Heart failure and arrhythmia 66 (2.5) 19 (0.7) Cardiovascular diagnosis 10,297 (92.3) 38,761 (86.9) <0.001 Hypertension only 5,342 (51.9) 30,495 (78.7) Peripheral vascular disease only 88 (0.8) 235 (0.6) Heart failure only 123 (1.3) 144 (0.3) Peripheral vascular disease and heart failure 34 (0.3) 26 (0.1) Hypertension and heart failure 1,861 (18.1) 3,025 (7.8) Hypertension and peripheral vascular disease 1,423 (13.8) 3,590 (9.3) Hypertension, peripheral vascular disease, and heart failure 1,426 (13.8) 1,246 (3.2) LDL >100 mg/dl 3,499 (31.4) 15,465 (34.7) <0.001 LDL ≤100 mg/dl 6,478 (58.0) 25,768 (57.7) Missing LDL 1,180 (10.6) 3,395 (7.6) HDL >40 mg/dl 5,278 (47.3) 27,409 (61.4) <0.001 HDL ≤40 mg/dl 4,669 (41.8) 13,760 (30.8) Missing HDL 1,210 (10.8) 3,459 (7.8) Retinopathy 3,886 (34.8) 10,062 (22.6) <0.001 Nephropathy 8,005 (71.8) 23,194 (52.0) <0.001 Neuropathy 4,487(40.2) 12,016 (26.9) <0.001 Prior amputations 466 (4.2) 274 (0.6) <0.001 Prior severe hypoglycemia 447 (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
Covariate Odds ratio (95% CI) P Mean A1C level (%) ≤6.0 1.20* (1.10–1.31) <0.001 >6.0–8.0 Reference — >8.0 1.16* (1.09–1.25) <0.001 ≥6 A1C tests over prior 3 years 0.84 (0.80–0.89) <0.001 A1C range >1.0% 1.29 (1.21–1.38) <0.001 Diabetes medications Insulin only 2.65 (2.31–3.05) <0.001 Metformin only 1.06 (0.92–1.23) 0.41 Sulfonylurea only 1.55 (1.36–1.76) <0.001 Insulin and oral medications 2.56 (2.19–3.00) <0.001 Other oral medications/oral combination 1.55 (1.33–1.80) <0.001 No diabetes medications Reference — Mean proportion of days covered of diabetes medications 0.56 (0.49–0.63) <0.001 Statins 0.75 (0.70–0.80) <0.001 ACE inhibitors/ARBs 0.80 (0.74–0.86) <0.001 Other antihypertensives/antiplatelets 1.34 (1.25–1.43) <0.001 Antipsychotics 7.10 (6.24–8.09) <0.001 Antiarrhythmics 1.54 (1.30–1.83) <0.001 Tricyclic antidepressant 2.91 (2.44–3.46) <0.001 ESAs 2.75 (2.46–3.08) <0.001 β-Agonists 1.63 (1.52–1.75) <0.001 Prior cardiovascular event 3.10 (2.87–3.36) <0.0001 Cardiovascular diagnosis 1.41 (1.28–1.56) <0.0001 LDL >100 mg/dl 1.14 (1.06–1.22) 0.0033 HDL > 40 mg/dl 0.67 (0.63–0.71) <0.0001 Retinopathy 1.13 (1.07–1.21) <0.0001 Nephropathy 1.68 (1.58–1.79) <0.0001 Neuropathy 1.19 (1.12–1.26) <0.0001 Prior amputations 3.28 (2.52–4.26) <0.0001 Prior severe hypoglycemia 1.67 (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
Subgroup n A1C (%) Odds ratio (95% CI)* P LDL <100, no other CV drug† 20,871 ≤6 1.39 (1.15–1.67) 0.0006 >8 1.20 (1.03–1.40) 0.02 LDL >100, no other CV drug† 13,983 ≤6 1.05 (0.79–1.39) 0.74 >8 1.41 (1.18–1.69) 0.0002 On other cardiovascular drug, LDL <100† 9,555 ≤6 1.10 (0.85–1.43) 0.45 >8 1.25 (0.95–1.63) 0.11 On other cardiovascular drug, LDL >100† 4,038 ≤6 0.89 (0.39–2.01) 0.78 >8 1.32 (0.70–2.49) 0.39 Patients using antipsychotics‡ 2,539 ≤6 1.05 (0.53–2.07) 0.90 >8 3.15 (1.18- 8.44) 0.02 Patients not using antipsychotics† 53,246 ≤6 1.26 (1.15–1.38) <0.0001 >8 1.17 (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.
