Table 3. Cox proportional hazards regression models for the effect of interaction between psychological stress and quartiles of coronary artery disease (CAD) genetic risk score (GRS) on incident CAD, fatal myocardial infarction (MI), non-fatal MI, and cardiovascular death.
| GRS Quartiles | |||||
|---|---|---|---|---|---|
| End point | Q1 | Q2 | Q3 | Q4 | P for interaction† |
| CAD | |||||
| No. (Events) | 4640 (370) | 4640 (462) | 4641 (507) | 4039 (599) | |
| HR (95% CI) |
HR (95% CI) |
HR (95% CI) |
HR (95% CI) |
||
| Minimal model‡ | |||||
| Low stress | Reference |
1.35*** (1.09–1.67) |
1.53*** (1.24–1.89) |
1.92*** (1.56–2.35) |
|
| Intermediate stress | 1.15 (0.92–1.44) |
1.58*** (1.28–1.95) |
1.59*** (1.29–1.96) |
1.94*** (1.58–2.38) |
|
| High stress |
1.38* (1.02–1.88) |
1.13 (0.82–1.57) |
1.93*** (1.46–2.57) |
2.01*** (1.53–2.65) |
|
| Multivariable model§ | |||||
| Low stress | Reference |
1.33* (1.07–1.64) |
1.53*** (1.24–1.89) |
1.87*** (1.53–2.30) |
|
| Intermediate stress | 1.05 (0.84–1.31) |
1.41** (1.14–1.75) |
1.44*** (1.17–1.77) |
1.77*** (1.44–2.18) |
|
| High stress | 1.26 (0.92–1.71) |
0.94 (0.68–1.31) |
1.75*** (1.32–2.33) |
1.77*** (1.34–2.33) |
n.s. |
| Fatal MI | |||||
| No. (Events) | 4640 (81) | 4640 (113) | 4641 (116) | 4039 (126) | |
| HR (95% CI) |
HR (95% CI) |
HR (95% CI) |
HR (95% CI) |
||
| Minimal model‡ | |||||
| Low stress | Reference | 1.59 (0.97–2.62) |
2.27*** (1.41–3.65) |
2.22** (1.38–3.56) |
|
| Intermediate stress |
1.65* (1.00–2.72) |
2.53*** (1.59–4.04) |
1.94** (1.19–3.15) |
2.60*** (1.62–4.17) |
|
| High stress |
2.41** (1.27–4.58) |
2.04* (1.04–3.99) |
2.94*** (1.56–5.52) |
2.74** (1.46–5.15) |
|
| Multivariable model§ | |||||
| Low stress | Reference | 1.55 (0.94–2.56) |
2.24*** (1.39–3.61) |
2.15** (1.33–3.46) |
|
| Intermediate stress | 1.48 (0.90–2.44) |
2.16** (1.35–3.46) |
1.66* (1.02–2.71) |
2.19** (1.36–3.52) |
|
| High stress |
2.06* (1.08–3.92) |
1.57 (1.80–3.09) |
2.59** (1.37–4.88) |
2.30* (1.22–4.32) |
n.s. |
| Non-fatal MI | |||||
| No. (Events) | 4640 (227) | 4640 (253) | 4641 (291) | 4638 (337) | |
| HR (95% CI) |
HR (95% CI) |
HR (95% CI) |
HR (95% CI) |
||
| Minimal model‡ | |||||
| Low stress | Reference | 1.16 (0.88–1.52) |
1.24 (0.94–1.62) |
1.54** (1.19–1.99) |
|
| Intermediate stress | 0.99 (0.75–1.31) |
1.23 (0.94–1.61) |
1.35* (1.04–1.76) |
1.58*** (1.22–2.05) |
|
| High stress | 1.11 (0.74–1.66) |
0.78 (0.49–1.23) |
1.72** (1.20–2.45) |
1.74** (1.23–2.46) |
|
| Multivariable model§ | |||||
| Low stress | Reference | 1.14 (0.87–1.49) |
1.23 (0.93–1.61) |
1.50** (1.16–1.94) |
|
| Intermediate stress | 0.90 (0.68–1.19) |
1.09 (0.83–1.43) |
1.24 (0.95–1.62) |
1.45** (1.12–1.89) |
|
| High stress | 1.01 (0.68–1.52) |
0.65 (0.41–1.04) |
1.58* (1.10–2.26) |
1.54* (1.09–2.19) |
n.s. |
| Cardiovascular death | |||||
| No. (Events) | 4640 (239) | 4640 (246) | 4641 (290) | 4039 (296) | |
| HR (95% CI) |
HR (95% CI) |
HR (95% CI) |
HR (95% CI) |
||
| Minimal model‡ | |||||
| Low stress | Reference | 0.83 (0.62–1.11) |
1.45** (1.11–1.88) |
1.33* (1.02–1.72) |
|
| Intermediate stress | 1.11 (0.85–1.46) |
1.33* (1.02–1.73) |
1.24 (0.95–1.62) |
1.47** (1.13–1.92) |
|
| High stress | 1.18 (0.78–1.78) |
1.34 (0.90–1.99) |
1.53* (1.03–2.28) |
1.52* (1.03–2.23) |
|
| Multivariable model§ | |||||
| Low stress | Reference | 0.82 (0.61–1.09) |
1.43** (1.10–1.85) |
1.28 (0.98–1.66) |
|
| Intermediate stress | 1.01 (0.77–1.32) |
1.15 (0.88–1.50) |
1.11 (0.85–1.45) |
1.31* (1.01–1.71) |
|
| High stress | 1.03 (0.68–1.56) |
1.10 (0.74–1.63) |
1.35 (0.90–2.02) |
1.29 (0.88–1.91) |
n.s. |
*p<0.05
**p<0.01
***p<0.001
CAD = Coronary artery disease; CI = Confidence Interval; GRS = Genetic risk score; HR = Hazard Ratio; MI = Myocardial infarction; n.s. = non-significant.
†Likelihood ratio test for overall interaction term
‡Minimal models are adjusted for gender and age
§Multivariable models are adjusted for gender, age, education, socioeconomic index, smoking, drinking, prevalent diabetes mellitus, Body Mass Index, hypertension, and use of lipid lowering medication