Figure 1
A. Study design. B. Mediator screening process.
HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TDI, Townsend deprivation index; TV, television.
Table 1
The characteristics of included participants.
| TOTAL | NON-CVD (n = 8577, 88.93%) | CVD (n = 1068, 11.07%) | P-VALUE | |
|---|---|---|---|---|
| Age, years, mean (SD) | 50.6 (17.3) | 48.7 (16.9) | 66.10 (12.2) | <0.001 |
| Gender, Male n (%) | 4718 (48.9%) | 4104 (47.9%) | 614 (57.5%) | <0.001 |
| Race, n (%) | <0.001 | |||
| Mexican American | 1286 (13.3%) | 1195 (13.9%) | 91 (8.5%) | |
| Other Hispanic | 968 (10.0%) | 889 (10.4%) | 79 (7.4%) | |
| Non-Hispanic White | 4329 (44.9%) | 3719 (43.4%) | 610 (57.1%) | |
| Non-Hispanic Black | 1916 (19.9%) | 1690 (19.7%) | 226 (21.2%) | |
| Other Race – Including Multi-Racial | 1146 (11.9%) | 1084 (12.6%) | 62 (5.8%) | |
| Education level, n (%) | <0.001 | |||
| High school and below | 4151 (43.0%) | 3567 (41.6%) | 584 (54.7%) | |
| Above high school | 5494 (57.0%) | 5010 (58.4%) | 484 (45.3%) | |
| Ratio of family income to poverty, ratio, mean (SD) | 2.6 (1.6) | 2.6 (1.7) | 2.3 (1.5) | <0.001 |
| PHQ-9, points, n (%) | 809 (8.4%) | 640 (7.5%) | 169 (15.8%) | <0.001 |
| Smoking, n (%) | 4291 (44.5%) | 3643 (42.5%) | 648 (60.7%) | <0.001 |
| Drinking, n (%) | 7325 (76.0%) | 6524 (76.1%) | 801 (75.0%) | 0.443 |
| History of dyslipidemia, n (%) | 3542 (36.7%) | 2851 (33.2%) | 691 (64.7%) | <0.001 |
| History of hypertension, n (%) | 3675 (38.1%) | 2888 (33.7%) | 787 (73.7%) | <0.001 |
| History of diabetes, n (%) | 1359 (14.1%) | 993 (11.6%) | 366 (34.3%) | <0.001 |
| SBP, mmHg, mean (SD) | 124.2 (18.5) | 123.3 (18.0) | 131.3 (21.1) | <0.001 |
| DBP, mmHg, mean (SD) | 70.3 (11.7) | 70.5 (11.5) | 68.0 (13.1) | <0.001 |
| BMI, kg/m2, mean (SD) | 29.2 (6.9) | 29.1 (6.8) | 30.5 (7.3) | <0.001 |
| TG, mmol/L, mean (SD) | 1.3 (0.7) | 1.3 (0.7) | 1.5 (0.8) | <0.001 |
| TC, mmol/L, mean (SD) | 4.9 (1.1) | 5.0 (1.0) | 4.6 (1.1) | <0.001 |
| HDL, mmol/L, mean (SD) | 1.4 (0.4) | 1.4 (0.4) | 1.3 (0.4) | <0.001 |
| LDL, mmol/L, mean (SD) | 2.9 (0.9) | 3.0 (0.9) | 2.6 (1.0) | <0.001 |
[i] CVD, cardiovascular disease; PHQ-9, 9-item Patient Health Questionnaire; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure.
Table 2
Logistic regression associations of depression with CVD in adults.
| VARIABLE | MODEL 1 | MODEL 2 | MODEL 3 | |||
|---|---|---|---|---|---|---|
| OR (95% CI) | P VALUE | OR (95% CI) | P VALUE | OR (95% CI) | P VALUE | |
| Cardiovascular disease | 2.36(1.83–3.05) | <0.001 | 2.60(1.95–3.46) | <0.001 | 2.07(1.55–2.76) | <0.001 |
| Coronary heart disease | 1.71(1.14–2.56) | 0.011 | 2.14(1.44–3.18) | <0.001 | 1.73(1.12–2.69) | 0.016 |
| Heart attack | 2.13(1.52–3.00) | <0.001 | 2.21(1.52–3.21) | <0.001 | 1.77(1.22–2.56) | 0.004 |
| Angina pectoris | 2.82(1.95–4.08) | <0.001 | 2.90(1.97–4.28) | <0.001 | 2.17(1.37–3.43) | 0.001 |
| Heart failure | 3.43(2.26–5.20) | <0.001 | 3.10(1.91–5.03) | <0.001 | 2.45(1.51–3.98) | <0.001 |
| Stroke | 2.75(1.72–4.40) | <0.001 | 2.44(1.41–4.21) | 0.002 | 2.06(1.21–3.53) | 0.010 |
[i] Model 1 was univariate logistic regression model; Model 2 was adjusted as age, race, gender, education, and ratio of family income to poverty; Model 3 was adjusted as age, race, gender, education, ratio of family income to poverty, smoking, drinking, dyslipidemia, hypertension, diabetes, diastolic pressure, systolic pressure, TG, TC, HDL-C, LDL-C and BMI based on stepwise regression model. OR, odds ratio; 95% CI, 95% confidence interval; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.
Table 3
The association of depression and CVD risk factors in adults.
| VARIABLE | DEPRESSION AND CVD RISK FACTORS | CVD RISK FACTORS AND CVD | ||||
|---|---|---|---|---|---|---|
| β (95% CI) | OR (95% CI) | P VALUE | β (95% CI) | OR (95% CI) | P VALUE | |
| Smoking | 0.95(0.73,1.17) | 2.60(2.08–3.23) | <0.001 | 0.52(0.33,0.71) | 1.68(1.39,2.03) | <0.001 |
| Drinking | 0.19(–0.02,0.4) | 1.21(0.98–1.49) | 0.081 | 0.06(–0.15,0.27) | 1.06(0.86,1.31) | 0.582 |
| Hypertension | 0.61(0.38,0.84) | 1.84(1.46–2.32) | <0.001 | 0.94(0.74,1.15) | 2.16(1.75,2.65) | <0.001 |
| Diabetes | 0.77(0.49,1.05) | 2.15(1.62–2.85) | <0.001 | 0.90(0.66,1.14) | 2.57(2.10,3.15) | <0.001 |
| Dyslipidemia | 0.43(0.20,0.66) | 1.54(1.22–1.93) | <0.001 | 0.77(0.56,0.98) | 2.45(1.93,3.12) | <0.001 |
| Education | –0.74(–0.96,–0.52) | 0.48(0.38–0.59) | <0.001 | –0.35(–0.53,–0.16) | 0.71(0.59,0.85) | <0.001 |
| Income | –0.95(–1.10,–0.81) | <0.001 | –0.19(–0.25,–0.13) | 0.83(0.78,0.88) | <0.001 | |
| BMI | 1.97(1.39,2.55) | <0.001 | 0.05(0.03,0.06) | 1.05(1.03,1.06) | <0.001 | |
[i] Logistic regression model was adjusted as age, race, gender. OR, odds ratio; 95% CI, 95% confidence interval; CVD, cardiovascular disease; BMI, body mass index.
Figure 2
A. Mendelian randomization (MR) estimates of the causal associations of depression on cardiovascular diseases. B. MR estimates of proportions mediated by mediators in the causal association between depression on cardiovascular diseases.
OR, odds ratio; CI, confidence interval; HTN, hypertension; HPL, hyperlipidemia; DM2, type 2 diabetes; POU, prescription opioid use; CHD, coronary heart disease; MI, myocardial infarction; TS, total stroke, AF, atrial fibrillation.
Table 4
The mediation analysis results of depression on various CVD via mediators.
| NUMBER OF SNPS | β (95%CI)) | OR (95%CI) | P | |
|---|---|---|---|---|
| Depression on mediators | ||||
| Type 2 diabetes | 48 | 0.147(0.024,0.270) | 1.158(1.024,1.309) | 0.019 |
| Hypertension | 48 | 0.217(0.094,0.340) | 1.242(1.098,1.405) | 5.62E–04 |
| Hyperlipidemia | 48 | 0.217(0.094,0.339) | 1.242(1.099,1.404) | 5.33E–04 |
| Prescription opioid use | 48 | 0.318(0.224,0.412) | 1.375(1.252,1.510) | 2.99E–11 |
| Type 2 diabetes on CVD | ||||
| Coronary heart disease | 153 | 0.131(0.091,0.171) | 1.140(1.095,1.187) | 1.37E–10 |
| Myocardial infarction | 153 | 0.118(0.076,0.16) | 1.125(1.079,1.173) | 2.72E–08 |
| Stroke | 152 | 0.095(0.067,0.122) | 1.099(1.069,1.130) | 2.13E–11 |
| Hypertension on CVD | ||||
| Coronary heart disease | 138 | 0.26(0.194,0.325) | 1.296(1.214,1.384) | 7.36E–15 |
| Myocardial infarction | 137 | 0.24(0.171,0.308) | 1.271(1.187,1.361) | 7.17E–12 |
| Atrial fibrillation | 138 | 0.184(0.138,0.229) | 1.201(1.148,1.258) | 3.42E–15 |
| Hyperlipidemia on CVD | ||||
| Coronary heart disease | 32 | 0.515(0.371,0.659) | 1.673(1.449,1.932) | 2.34E–12 |
| Myocardial infarction | 32 | 0.519(0.358,0.680) | 1.680(1.430,1.973) | 2.69E–10 |
| Stroke | 34 | 0.124(0.063,0.186) | 1.133(1.065,1.204) | 7.30E–05 |
| Prescription opioid use on CVD | ||||
| Stroke | 8 | 0.211(0.039,0.384) | 1.236(1.040,1.468) | 0.016 |
[i] Summary MR analysis of the IVW methods for the effect of depression on mediators and the effect of mediators CVD. SNP, Single nucleotide polymorphism; OR, odds ratio; CI, confidence interval; CVD, cardiovascular disease.
Table 5
The mediation effect of depression on various CVD via mediators.
| EXPOSURE | MEDIATOR | OUTCOME | MEDIATION EFFECT | PROPORTION MEDIATED % |
|---|---|---|---|---|
| Depression | HPL | CHD | 0.111 (0.041, 0.183) | 87.06% |
| Depression | HTN | CHD | 0.056 (0.021, 0.091) | 43.92% |
| Depression | DM2 | CHD | 0.019 (0.002, 0.036) | 14.90% |
| Depression | HPL | MI | 0.113 (0.040, 0.186) | 64.91% |
| Depression | HTN | MI | 0.052 (0.019, 0.085) | 29.87% |
| Depression | DM2 | MI | 0.017 (0.002, 0.033) | 9.77% |
| Depression | POU | TS | 0.067 (0.009, 0.125) | 54.33% |
| Depression | HPL | TS | 0.027 (0.007, 0.047) | 21.89% |
| Depression | DM2 | TS | 0.014 (0.002, 0.026) | 11.35% |
| Depression | HTN | AF | 0.040 (0.015, 0.065) | 31.51% |
[i] CVD, cardiovascular disease; HTN, hypertension; HPL, hyperlipidemia; DM2, type 2 diabetes; POU, prescription opioid use; CHD, coronary heart disease; MI, myocardial infarction; TS, total stroke, AF, atrial fibrillation.