Table 2.
Association Between Hypoglycemia and Incident CAD With Time Interaction in the Entire Cohort and Subgroups of Different Vascular Risk
| Hypoglycemia, n (%) | Entire Cohort (n = 9173) |
Low Vascular Risk (n = 7350) |
High Vascular Risk (n = 1823) |
Age ≥65 Years and High Risk (n = 996) |
||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 285 (3.11) |
230 (3.13) |
55 (3.02) |
38 (3.82) |
|||||||||
| HR | 95%CI | P Value | HR | 95%CI | P Value | HR | 95%CI | P Value | HR | 95%CI | P Value | |
| Hypoglycemia (univariable model) | ||||||||||||
| Main effect | 1.90 | (1.09–3.31) | .023 | 1.61 | (0.82–3.18) | .168 | 2.86 | (1.09–7.50) | .033 | 4.27 | (1.53–11.86) | .003 |
| TVC | 0.83 | (0.69–0.99) | .044 | 0.85 | (0.68–1.05) | .133 | 0.81 | (0.58–1.13) | .210 | 0.73 | (0.48–1.11) | .140 |
| 1 year | 1.58 | (1.03–2.42) | .034 | 1.37 | (0.81–2.31) | .235 | 2.31 | (1.11–4.79) | .024 | 3.13 | (1.48–6.61) | .003 |
| 2 years | 1.31 | (0.94–1.85) | .115 | 1.17 | (0.77–1.77) | .469 | 1.87 | (1.04–3.38) | .037 | 2.29 | (1.20–4.37) | .012 |
| 3 years | 1.09 | (0.78–1.54) | .609 | 0.99 | (0.66–1.49) | .970 | 1.52 | (0.82–2.82) | .186 | 1.68 | (0.77–3.68) | .197 |
| Hypoglycemia (CAD risk factor adjusted multivariable model) | ||||||||||||
| Main effect | 2.15 | (1.24–3.74) | .007 | 1.90 | (0.97–3.75) | .063 | 3.01 | (1.15–7.91) | .025 | 4.62 | (1.65–12.90) | .004 |
| TVC | 0.84 | (0.71–1.01) | .061 | 0.86 | (0.69–1.06) | .159 | 0.81 | (0.57–1.13) | .136 | 0.75 | (0.50–1.13) | .173 |
| 1 year | 1.82 | (1.19–2.78) | .006 | 1.63 | (0.97–2.75) | .066 | 2.46 | (1.18–5.10) | .016 | 3.46 | (1.63–7.37) | .001 |
| 2 years | 1.53 | (1.09–2.16) | .014 | 1.40 | (0.92–2.13) | .115 | 2.00 | (1.11–3.62) | .022 | 2.60 | (1.35–4.99) | .004 |
| 3 years | 1.29 | (0.92–1.82) | .142 | 1.20 | (0.80–1.81) | .384 | 1.63 | (0.88–3.03) | .122 | 1.95 | (0.88–4.30) | .099 |
| Hypoglycemia (fully adjusted multivariable model) | ||||||||||||
| Main effect | 1.65 | (0.95–2.87) | .078 | 1.37 | (0.69–2.72) | .365 | 2.32 | (0.88–6.09) | .089 | 3.37 | (1.19–9.57) | .022 |
| TVC | 0.84 | (0.70–1.01) | .057 | 0.85 | (0.69–1.06) | .143 | 0.83 | (0.60–1.15) | .268 | 0.79 | (0.53–1.19) | .255 |
| 1 year | 1.39 | (0.90–2.13) | .134 | 1.17 | (0.69–1.99) | .562 | 1.93 | (0.92–4.04) | .082 | 2.67 | (1.22–5.82) | .014 |
| 2 years | 1.17 | (0.82–1.65) | .382 | 0.97 | (0.65–1.53) | .989 | 1.60 | (0.88–2.94) | .126 | 2.10 | (1.07–4.15) | .032 |
| 3 years | 0.98 | (0.69–1.39) | .922 | 0.85 | (0.56–1.30) | .450 | 1.34 | (0.71–2.51) | .369 | 1.80 | (0.80–4.01) | .153 |
TVC, time varying covariate, time interaction with hypoglycemia. Main effect: effect estimate of hypoglycemia after accounting for time interaction; 1, 2, and 3 years: we calculated the hypoglycemia effect estimates for the first year, the first 2 years, and the first 3 years using linear combinations of coefficients postestimation; CAD risk factor adjusted model: model adjusted for age, sex, race/ethnicity, education attainment, BMI, HbA1c, dyslipidemia, and hypertension; fully adjusted model: model included covariates in CAD risk factor adjusted model and additionally adjusted for insulin use, sulfonylurea use, microvascular complications, total chronic medication count, exposure to 3 or more classes of antidiabetic agents, HDL, LDL, eGFR, and 2 or more HbA1c measurements per year; high vascular risk: age 55 years or older and HbA1c 7.5% and greater and 2 or more CAD risk factors: BMI 30 kg/m2 or greater, hypertension, or dyslipidemia. Age 65 years or older and high risk: subset of high vascular risk patients aged 65 years or older; low vascular risk: patients who did not meet criteria for high vascular risk.