Background
Methods
Literature search
Eligibility criteria
Data extraction
Statistical analysis and methodological quality appraisal
Classification | Criteria |
---|---|
Convincing evidence (Class I) | More than 1000 death events |
Significant summary associations (P < 10− 6) per random effects calculations | |
No evidence of small-study effects | |
No evidence of excess of significance | |
Prediction intervals not including the null | |
Not large heterogeneity (i.e., I2 < 50%) | |
Highly-suggestive evidence (Class II) | Significant summary associations (P < 10− 6) per random effects calculation |
More than 1000 death events | |
The largest study with 95% confidence intervals excluding the null | |
Suggestive evidence (Class III) | More than 1000 death events |
Significant summary associations (P < 10−3) per random effects calculations | |
Weak evidence | All other associations with P < 0.05 |
Non-significant associations | All associations with P > 0.05 |
Results
Evidence from qualitative systematic reviews
Summary effect sizes
Heterogeneity between studies
Small-study effects
Excess significance
Grading of the evidence
Author, year | Population | Mortality type | Sample size MDD/Deaths | k | Largest study ES (95% CI)a | Random effects summary RRb (95% CI) | Random effects P valuec | 95% prediction interval | I2 (%) | Excess significance O/Ed | Excess significance P- value |
---|---|---|---|---|---|---|---|---|---|---|---|
Associations supported by highly suggestive evidence | |||||||||||
Cuijpers, 2014 [51] Satin, 2009 [62] | Cancer | All-cause | 4034/4817 | 23 | 1.37 (1.26–1.50) | 1.55 (1.32–1.81) | < 10−6 | 0.80–2.50 | 69.6 | 11/4.53 | < 0.001 |
Cuijpers, 2014 [51] Sorensen, 2005 [64] Meijer, 2013 [67] van Melle, 2004 [58] | Post-AMI | All-cause | 4183/2358 | 20 | 1.48 (1.12–1.96) | 2.09 (1.66–2.63) | < 10−6 | 0.89–3.54 | 66.6 | 12/11.0 | 0.64 |
Cuijpers, 2014 [51] Fan, 2014 [28] Gathright 2017 [54] Sokoreli, 2016 [63] | HF | All-cause | 3418/4345 | 22 | 1.33 (1.19–1.42) | 1.46 (1.30–1.65) | < 10−6 | 0.89–1.92 | 81.0 | 14/6.5 | < 0.001 |
Baxter, 2011 [50] Cuijpers, 2002 [19] Cuijpers, 2014 [51] Walker, 2015 [16] | Mixed-samplee | All-cause | 87,633/242577 | 111 | 1.77 (1.41–2.17) | 1.48 (1.39–1.58) | < 10−6 | 0.84–2.23 | 89.3 | 55/17.8 | 0.00 |
Associations supported by suggestive evidence | |||||||||||
Barth, 2004 [26] Cuijpers, 2014 [51] Leung, 2012 [56] Meijer, 2013 [67] | CHD | All-cause | 2284/1533 | 10 | 1.21 (1.04–1.42) | 1.57 (1.27–1.94) | < 10−4 | 1.16–1.47 | 62.6 | 5/1.18 | < 0.001 |
Cuijpers, 2014 [51] Hofmann, 2013 [55] Park, 2013 [60] | DM | All-cause | 4373/7452 | 12 | 1.06 (0.96–1.18) | 1.60 (1.30–1.80) | < 10−6 | 0.90–3.21 | 83.6 | 8/5.72 | 0.18 |
Associations supported by weak evidence | |||||||||||
Cuijpers, 2014 [51] Stenman, 2016 [65] | CABG | All-cause | 503/347 | 4 | 2.40 (1.40–4.00) | 1.93 (1.43–2.60) | < 10−4 | 1.09–3.18 | 0 | 2/2.32 | 0.74 |
Cuijpers, 2014 [51] Meijer, 2013 [67] | ACS | All-cause | 324/163 | 3 | 2.80 (1.40–5.07) | 1.82 (1.02–3.26) | 0.04 | 0.06–48.2 | 86.4 | 2/0.54 | 0.02 |
Bartoli, 2013 [20] Cuijpers, 2014 [51] Pan, 2011 [59] | Stroke | All-cause | 3103/414 | 7 | 1.13 (1.06–1.21) | 1.46 (1.15–1.85) | 0.002 | 0.80–2.13 | 62.1 | 4/0.04 | 0.00 |
Pan, 2011 [59] | Stroke | Fatal Stroke | 1600/377 | 4 | 1.66 (1.16–2.39) | 1.58 (1.00–2.50) | 0.049 | 0.21–8.07 | 46.7 | 2/0.02 | 0.00 |
Cuijpers, 2014 [51] Dew, 2015 [52] | Post-transplant patientsf | All-cause | 405/433 | 6 | 1.66 (1.12–2.47) | 1.64 (1.37–1.95) | < 10−2 | 0.71–2.65 | 36.5 | 4/0.86 | < 10− 3 |
Cuijpers, 2014 [51] | HIV | All-cause | 1977/1580 | 4 | 1.60 (1.32–1.92) | 1.30 (1.05–1.61) | 0.017 | 0.61–2.70 | 55.1 | 1/1.79 | 0.42 |
Meijer, 2011 [57] | AMI | Cardiovascular Mortality | 995/114 | 5 | 5.51 (0.61–49.18) | 2.98 (1.65–5.38) | < 10−3 | 0.26–15.80 | 42.3 | 3/2.37 | 0.57 |
Cuijpers, 2014 [51] Palmer, 2013 [27] | CKD | All-cause | 922/930 | 12 | 0.98 (0.72–1.34) | 1.66 (1.20–2.30) | < 10−2 | 0.84–1.40 | 44.4 | 4/0.17 | 0.00 |
Cuijpers, 2014 [51] | COPD | All-cause | 338/261 | 5 | 1.93 (1.04–3.58) | 2.34 (1.69–3.24) | < 10−6 | 1.23–3.63 | 0.00 | 4/3.01 | 0.25 |
van Dooren, 2013 [53] | DM | Cardiovascular | 1255/536 | 4 | 1.25 (0.83–1.86) | 1.48 (1.08–2.03) | 0.014 | 0.61–3.00 | 52.5 | 2/0.38 | < 10−2 |
Correll, 2017 [66] | Mixed samplesg | Cardiovascular mortality | 175,726/14495 | 4 | 1.00 (0.85–1.17) | 1.56 (1.08–2.24) | 0.018 | 0.34–6.82 | 87.8 | 3/1.00 | 0.02 |
Sensitivity analyses
Subgroup | Sample size MDD/Deaths | k | Largest study ES (95% CI)a | Random effects summary ESb (95% CI) | Random effects P valuec | 95% prediction interval | I2 (%) | Excess significance | Classification | |
---|---|---|---|---|---|---|---|---|---|---|
O/Ed | P value | |||||||||
All-cause in cancer | ||||||||||
Structured interview | 145/462 | 5 | 2.85 (2.29–3.54) | 1.56 (0.87–2.8) | 0.133 | 0.28–8.56 | 71.9 | 1/1.02 | 0.979 | Weak |
Adjusted estimates only | 1066/2273 | 13 | 1.2 (0.9–1.4) | 1.6 (1.35–1.9) | < 10−6 | 1.02–2.51 | 42.3 | 8/5.16 | 0.097 | Class III |
Adjusted at least for age and sex | 691/1030 | 6 | 1.2 (0.9–1.4) | 1.69 (1.23–2.31) | 0.001 | 0.77–3.68 | 51.6 | 4/3.3 | 0.563 | Class III |
Adjusted comorbidities | 910/1951 | 9 | 1.2 (0.9–1.4) | 1.52 (1.27–1.83) | < 0.001 | 0.97–2.4 | 43.3 | 5/3.54 | 0.3 | Class III |
Inpatients | 764/618 | 10 | 1.66 (1.16–2.37) | 1.7 (1.35–2.13) | < 0.001 | 0.96–3 | 40.9 | 6/3.55 | 0.106 | Weak |
Outpatients | 453/1418 | 10 | 1.3 (0.98–1.73) | 1.56 (1.11–2.17) | 0.009 | 0.57–4.28 | 75.3 | 4/2.57 | 0.291 | Class III |
Prospective studies | 4034/4817 | 23 | 1.37 (1.26–1.5) | 1.55 (1.32–1.81) | < 10−6 | 0.86–2.78 | 69.6 | 11/6.21 | 0.023 | Class II |
Follow-up ≤ 5 years | 946/1580 | 15 | 1.2 (0.9–1.4) | 1.8 (1.42–2.28) | < 0.001 | 0.83–3.9 | 68.1 | 9/6.64 | 0.22 | Class III |
Follow-up > 5 years | 3088/3237 | 8 | 1.37 (1.26–1.5) | 1.29 (1.14–1.47) | < 0.001 | 1–1.68 | 22.5 | 2/1.52 | 0.658 | Class III |
All-cause in heart failure patientse | ||||||||||
Adjusted estimates only | 3383/4275 | 21 | 1.33 (1.19–1.42) | 1.46 (1.29–1.64) | < 10−6 | 0.93–2.27 | 79.1 | 14/9.83 | 0.068 | Class II |
Adjusted at least for age and sex | 2526/2935 | 13 | 1.33 (1.19–1.42) | 1.36 (1.22–1.52) | < 10−6 | 0.99–1.86 | 54.3 | 9/5.39 | 0.042 | Class II |
Adjusted for comorbidities | 2395/3371 | 12 | 1.33 (1.19–1.42) | 1.43 (1.26–1.62) | < 10−6 | 1–2.04 | 60.5 | 8/6.58 | 0.41 | Class II |
Inpatients | 1245/1500 | 7 | 2.02 (1.48–2.76) | 1.82 (1.28–2.6) | < 0.001 | 0.64–5.19 | 77.7 | 4/5.12 | 0.339 | Class III |
Outpatients | 639/583 | 6 | 1.31 (1.07–1.6) | 1.46 (1.08–1.96) | 0.013 | 0.67–3.16 | 75.2 | 4/1.8 | 0.049 | Weak |
Prospective studies | 3418/4345 | 22 | 1.33 (1.19–1.42) | 1.46 (1.3–1.65) | < 10−6 | 0.94–2.28 | 78.4 | 14/10.02 | 0.088 | Class II |
Follow-up ≤ 5 years | 2417/2358 | 16 | 1.33 (1.19–1.42) | 1.52 (1.3–1.77) | < 10−6 | 0.93–2.47 | 80.0 | 10/6.55 | 0.079 | Class II |
Follow-up > 5 years | 1001/1987 | 6 | 1.31 (1.07–1.6) | 1.4 (1.14–1.72) | 0.001 | 0.76–2.57 | 72.5 | 4/3.41 | 0.627 | Class III |
All-cause in mixed samplee | ||||||||||
Structured interview | 4746/29667 | 19 | 2.3 (2.1–2.5) | 1.64 (1.3–2.08) | < 0.001 | 0.62–4.38 | 88.7 | 11/13.06 | 0.277 | Class III |
Adjusted estimates only | 83,470/212385 | 81 | 1.77 (1.41–2.17) | 1.42 (1.33–1.5) | < 10−6 | 0.93–2.15 | 86.5 | 44/16.69 | 0 | Class II |
Adjusted at least for age and sex | 51,332/161660 | 42 | 1.1 (1.07–1.13) | 1.34 (1.25–1.43) | < 10−6 | 0.96–1.85 | 82.4 | 23/15.72 | 0.017 | Class II |
Adjusted for comorbidities | 34,122/41488 | 53 | 1.77 (1.41–2.17) | 1.38 (1.29–1.47) | < 10−6 | 0.97–1.96 | 71.6 | 31/3.66 | 0 | Class II |
Community | 32,269/69181 | 62 | 1.77 (1.41–2.17) | 1.48 (1.36–1.61) | < 10−6 | 0.83–2.63 | 88.2 | 31/8.76 | 0 | Class II |
Inpatients | 2209/2334 | 16 | 1.44 (1.1–1.88) | 1.58 (1.33–1.87) | < 10−6 | 0.93–2.68 | 56.0 | 10/5.69 | 0.019 | Class II |
Outpatients | 811/497 | 6 | 1.55 (1.06–2.26) | 1.47 (1.13–1.91) | 0.004 | 0.8–2.68 | 34.5 | 4/0.58 | 0 | Weak |
Primary care | 8730/4558 | 6 | 1.04 (0.93–1.15) | 1.44 (1.11–1.86) | 0.006 | 0.67–3.1 | 82.0 | 4/2.13 | 0.11 | Class III |
Prospective studies | 46,951/96860 | 95 | 1.77 (1.41–2.17) | 1.51 (1.4–1.62) | < 10−6 | 0.86–2.63 | 87.1 | 51/11.97 | 0 | Class II |
Follow-up ≤ 5 years | 24,944/26135 | 61 | 1.37 (1.19–1.48) | 1.62 (1.48–1.77) | < 10−6 | 0.96–2.71 | 75.7 | 34/17.79 | 0 | Class II |
Follow-up > 5 years | 62,689/216442 | 40 | 1.77 (1.41–2.17) | 1.36 (1.24–1.48) | < 10−6 | 0.81–2.26 | 93.8 | 21/8.41 | 0 | Class II |
All-cause in post-AMI | ||||||||||
Structured interview | 1688/638 | 5 | 1.48 (1.12–1.96) | 2.37 (1.36–4.14) | 0.002 | 0.41–13.76 | 86.3 | 4/4.12 | 0.886 | Weak |
Adjusted estimates only | 2381/1771 | 9 | 1.48 (1.12–1.96) | 2.2 (1.51–3.2) | < 0.001 | 0.71–6.81 | 80.7 | 7/7.88 | 0.374 | Class III |
Adjusted for comorbidities | 1507/579 | 3 | 1.48 (1.12–1.96) | 1.56 (1.18–2.06) | 0.001 | 0.79–3.1 | 5.1 | 2/2.15 | 0.843 | Weak |
Inpatients | 3998/2196 | 17 | 1.48 (1.12–1.96) | 2.09 (1.63–2.69) | < 10−6 | 0.9–4.85 | 70.3 | 10/12.89 | 0.102 | Class II |
Prospective studies | 4183/2358 | 20 | 1.48 (1.12–1.96) | 2.09 (1.66–2.63) | < 10−6 | 0.95–4.62 | 66.6 | 12/14.72 | 0.168 | Class II |
Follow-up ≤ 5 years | 3602/1789 | 16 | 1.67 (1.31–2.12) | 2.18 (1.66–2.86) | < 10−6 | 0.89–5.32 | 69.4 | 9/12.4 | 0.042 | Class II |
Follow-up > 5 years | 533/560 | 3 | 1.48 (1.12–1.96) | 1.57 (1.25–1.99) | < 0.001 | 0.94–2.63 | 0.0 | 2/1.31 | 0.42 | Weak |