Effect of Body Weight and Other Metabolic Factors on Risk of Non-Small Cell Lung Cancer among Veterans with HIV and a History of Smoking
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Risk Factors for NSCLC among Veterans with HIV
Univariate Analyses
2.2. Multivariable Analyses
3. Discussion
4. Materials and Methods
4.1. Methods
4.1.1. Study Population and Design
4.1.2. HIV-Positive Cohort
4.1.3. Smoking Cohort
4.1.4. Variable Specification
Outcomes
Covariates
Baseline Covariates
Time-Updated Covariates
Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variable | Levels | Well-Controlled HIV | Total (n = 33,351) | |
---|---|---|---|---|
Yes | No | |||
(n = 13,301) | (n = 20,050) | |||
n (%) | n (%) | n (%) | ||
Age at Index date, years | <50 | 7010 (52.7%) | 12,453 (62.1%) | 19,463 (58.4%) |
50–59 | 4418 (33.2%) | 5626 (28.1%) | 10,044 (30.1%) | |
60+ | 1873 (14.1%) | 1971 (9.8%) | 3844 (11.5%) | |
Gender | Female | 332 (2.5%) | 536 (2.7%) | 868 (2.6%) |
Male | 12,969 (97.5%) | 19,514 (97.3%) | 32,483 (97.4%) | |
Race/Ethnicity | Black | 6204 (46.6%) | 11,552 (57.6%) | 17,756 (53.2%) |
Hispanic | 803 (6.0%) | 1002 (5.0%) | 1805 (5.4%) | |
Other | 127 (1.0%) | 176 (0.9%) | 303 (0.9%) | |
Unreported | 347 (2.6%) | 550 (2.7%) | 897 (2.7%) | |
White | 5820 (43.8%) | 6770 (33.8%) | 12,590 (37.7%) | |
BMI at Index date, kg/m2 | <18.5 | 219 (1.6%) | 366 (1.8%) | 585 (1.8%) |
18.5–25 | 4723 (35.5%) | 5418 (27.0%) | 10,141 (30.4%) | |
25–30 | 3991 (30.0%) | 3855 (19.2%) | 7846 (23.5%) | |
30+ | 1798 (13.5%) | 1688 (8.4%) | 3486 (10.5%) | |
unmeasured | 2570 (19.3%) | 8723 (43.5%) | 11,293 (33.9%) | |
LDL-C at Index date, mg/dL | <100 | 3573 (26.9%) | 4487 (22.4%) | 8060 (24.2%) |
100–129 | 2129 (16.0%) | 2383 (11.9%) | 4512 (13.5%) | |
130–159 | 1088 (8.2%) | 1141 (5.7%) | 2229 (6.7%) | |
160+ | 502 (3.8%) | 527 (2.6%) | 1029 (3.1%) | |
unmeasured | 6009 (45.2%) | 11,512 (57.4%) | 17,521 (52.5%) | |
HDL-C at Index date, mg/dL | <40 | 4106 (30.9%) | 4622 (23.1%) | 8728 (26.2%) |
40–60 | 2712 (20.4%) | 3309 (16.5%) | 6021 (18.1%) | |
>60 | 725 (5.5%) | 899 (4.5%) | 1624 (4.9%) | |
unmeasured | 5758 (43.3%) | 11,220 (56.0%) | 16,978 (50.9%) | |
Triglycerides at Index date, mg/dL | <150 | 4220 (31.7%) | 5590 (27.9%) | 9810 (29.4%) |
150+ | 3709 (27.9%) | 3801 (19.0%) | 7510 (22.5%) | |
unmeasured | 5372 (40.4%) | 10,659 (53.2%) | 16,031 (48.1%) | |
History of statin use at Index date | Yes | 999 (7.5%) | 988 (4.9%) | 1987 (6.0%) |
History of diabetes at Index date | Yes | 780 (5.9%) | 1017 (5.1%) | 1797 (5.4%) |
History of COPD at Index date | Yes | 938 (7.1%) | 1178 (5.9%) | 2116 (6.3%) |
HIV diagnosis date, years | <2001 | 5117 (38.5%) | 9428 (47.0%) | 14,545 (43.6%) |
2001–2009 | 5399 (40.6%) | 6263 (31.2%) | 11,662 (35.0%) | |
2010+ | 2785 (20.9%) | 4359 (21.7%) | 7144 (21.4%) | |
Statin exposure * | Yes | 6736 (50.6%) | 6299 (31.4%) | 13,035 (39.1%) |
Nadir CD4 * | <200 | 5095 (38.3%) | 8729 (43.5%) | 13,824 (41.5%) |
200–500 | 5175 (38.9%) | 5170 (25.8%) | 10,345 (31.0%) | |
>500 | 1782 (13.4%) | 1400 (7.0%) | 3182 (9.5%) | |
unmeasured | 1249 (9.4%) | 4751 (23.7%) | 6000 (18.0%) | |
ART (% time) * | <50% | 2558 (19.2%) | 9480 (47.3%) | 12,038 (36.1%) |
50–80% | 4327 (32.5%) | 5241 (26.1%) | 9568 (28.7%) | |
80%+ | 6416 (48.2%) | 2421 (12.1%) | 8837 (26.5%) | |
Non-cannabis substance abuse * | Yes | 5389 (40.5%) | 9878 (49.3%) | 15,267 (45.8%) |
Alcohol abuse * | Yes | 6418 (48.3%) | 10,547 (52.6%) | 16,965 (50.9%) |
Variable | Levels | All | Well-Controlled HIV | ||||
---|---|---|---|---|---|---|---|
Yes | No | ||||||
HR and 95% CI | p-Value | HR and 95% CI | p-Value | HR and 95% CI | p-Value | ||
Age at Index date, years | <50 | 1.0 (reference) | 1.0 (reference) | 1.0 (reference) | |||
50–59 | 3.25 (2.75–3.84) | <0.0001 | 2.85 (2.12–3.83) | <0.0001 | 3.65 (2.97–4.48) | <0.0001 | |
60+ | 4.36 (3.49–5.45) | <0.0001 | 4.28 (2.97–6.16) | <0.0001 | 5.11 (3.82–6.85) | <0.0001 | |
Gender | F vs. M | 0.82 (0.492–1.369) | 0.45 | 0.72 (0.27–1.94) | 0.52 | 0.84 (0.45–1.58) | 0.59 |
Race/ethnicity | White | 1.0 (reference) | 1.0 (reference) | 1.0 (reference) | |||
Black | 0.96 (0.82–1.12) | 0.58 | 0.95 (0.73–1.23) | 0.67 | 0.93 (0.76–1.13) | 0.43 | |
Hispanic | 0.34 (0.19–0.58) | 0.0001 | 0.32 (0.13–0.79) | 0.01 | 0.33 (0.16–0.67) | 0.002 | |
Other | 0.20 (0.03–1.45) | 0.11 | 0.57 (0.08–4.09) | 0.578 | 0.000 (0.000–Infty) | 0.96 | |
Unreported | 0.48 (0.22–1.08) | 0.07 | 0.44 (0.11–1.79) | 0.25 | 0.55 (0.20–1.49) | 0.24 | |
HIV diagnosis date, years | pre 2001 | 1.0 (reference) | 1.0 (reference) | 1.0 (reference) | |||
2001–2009 | 1.19 (1.01–1.39) | 0.04 | 1.15 (0.87–1.51) | 0.33 | 1.27 (1.03–1.56) | 0.02 | |
2010+ | 1.11 (0.82–1.51) | 0.50 | 0.73 (0.37–1.43) | 0.35 | 1.34 (0.94–1.91) | 0.11 | |
Cachexia * | none | 1.0 (reference) | 1.0 (reference) | 1.0 (reference) | |||
current cachexia | 6.01 (4.91–7.35) | <0.0001 | 7.18 (5.15–9.99) | <0.0001 | 5.27 (4.06–6.84) | <0.0001 | |
recent cachexia | 1.36 (0.89–2.08) | 0.16 | 1.49 (0.72–3.06) | 0.28 | 1.20 (0.69–2.08) | 0.51 | |
distant past or rebounded | 1.28 (1.05–1.57) | 0.01 | 1.44 (1.04–1.98) | 0.02 | 1.14 (0.87–1.49) | 0.35 | |
undefined/first year after index | 1.08 (0.77–1.50) | 0.67 | 0.81 (0.32–2.04) | 0.65 | 0.96 (0.65–1.40) | 0.82 | |
BMI at Index date, kg/m2 | <18.5 | 2.06 (1.36–3.13) | 0.0007 | 2.29 (1.16–4.53) | 0.02 | 1.84 (1.06–3.17) | 0.03 |
18.5–25 | 1.0 (reference) | 1.0 (reference) | 1.0 (reference) | ||||
25–30 | 0.63 (0.51–0.78) | <0.0001 | 0.71 (0.51–0.97) | 0.03 | 0.58 (0.44–0.76) | 0.0002 | |
30+ | 0.47 (0.34–0.66) | <0.0001 | 0.53 (0.32–0.88) | 0.01 | 0.45 (0.29–0.70) | 0.0004 | |
missing | 0.85 (0.71–1.01) | 0.07 | 0.77 (0.54–1.09) | 0.15 | 0.79 (0.64–0.98) | 0.03 | |
Nadir CD4 cell count, cells/mm3 * | <200 | 1.0 (reference) | 1.0 (reference) | 1.0 (reference) | |||
200–500 | 0.88 (0.73–1.05) | 0.15 | 0.85 (0.64–1.14) | 0.27 | 0.91 (0.72–1.15) | 0.42 | |
>500 | 0.81 (0.62–1.06) | 0.13 | 0.64 (0.41–1.01) | 0.05 | 0.94 (0.66–1.35) | 0.75 | |
missing | 1.02 (0.80–1.29) | 0.88 | 0.92 (0.58–1.45) | 0.71 | 0.95 (0.71–1.28) | 0.73 | |
% Time with undetectable VL * | <50% | 1.0 (reference) | |||||
50–80% | 0.94 (0.76–1.16) | 0.54 | --- | --- | --- | --- | |
80%+ | 1.01 (0.85–1.20) | 0.91 | --- | --- | --- | --- | |
H/O COPD at Index date | Y/N | 2.19 (1.69–2.85) | <0.0001 | 2.21 (1.41–3.48) | 0.0006 | 2.19 (1.55–3.10) | <0.0001 |
Current HDL-C, mg/dL * | <40 | 1.0 (reference) | 1.0 (reference) | 1.0 (reference) | |||
40–60 | 0.84 (0.69–1.01) | 0.06 | 0.85 (0.63–1.15) | 0.30 | 0.86 (0.67–1.09) | 0.21 | |
>60 | 0.98 (0.75–1.27) | 0.85 | 0.99 (0.66–1.50) | 0.97 | 0.99 (0.70–1.42) | 0.99 | |
missing | 0.64 (0.52–0.79) | <0.0001 | 0.61 (0.40–0.91) | 0.01 | 0.57 (0.44–0.73) | <0.0001 | |
Current LDL-C, mg/dL * | <100 | 1.0 (reference) | 1.0 (reference) | 1.0 (reference) | |||
100–129 | 0.90 (0.74–1.09) | 0.29 | 0.89 (0.64–1.22) | 0.46 | 0.89 (0.69–1.15) | 0.38 | |
130–159 | 0.77 (0.58–1.02) | 0.06 | 0.92 (0.60–1.41) | 0.71 | 0.68 (0.46–1.01) | 0.05 | |
160+ | 0.69 (0.45–1.08) | 0.10 | 0.49 (0.22–1.13) | 0.09 | 0.83 (0.48–1.43) | 0.50 | |
missing | 0.65 (0.53–0.79) | <0.0001 | 0.67 (0.46–0.99) | 0.04 | 0.54 (0.43–0.69) | <0.0001 | |
Current Triglycerides, mg/dL * | <150 | 1.0 (reference) | 1.0 (reference) | 1.0 (reference) | |||
150+ | 0.67 (0.56–0.79) | <0.0001 | 0.77 (0.58–1.01) | 0.06 | 0.63 (0.49–0.79) | <0.0001 | |
missing | 0.55 (0.45–0.68) | <0.0001 | 0.56 (0.37–0.84) | 0.005 | 0.48 (0.38–0.61) | <0.0001 | |
% Time on statins* | none | 1.0 (reference) | 1.0 (reference) | 1.0 (reference) | |||
<50% | 1.28 (1.05–1.55) | 0.01 | 1.04 (0.75–1.44) | 0.81 | 1.49 (1.16–1.92) | 0.001 | |
50–80% | 1.31 (0.97–1.77) | 0.07 | 1.39 (0.93–2.08) | 0.11 | 1.51 (0.95–2.42) | 0.08 | |
80%+ | 1.75 (1.25–2.44) | 0.001 | 1.64 (1.03–2.61) | 0.03 | 2.46 (1.48–4.07) | 0.0005 | |
Current diabetes* | Y/N | 1.07 (0.87–1.32) | 0.52 | 1.17 (0.85–1.62) | 0.33 | 1.07 (0.81–1.41) | 0.64 |
COPD history (so far) * | Y/N | 2.57 (2.19–3.00) | <0.0001 | 2.43 (1.87–3.17) | <0.0001 | 2.72 (2.22–3.32) | <0.0001 |
Pneumonia episodes (so far) * | 0 | 1.0 (reference) | 1.0 (reference) | 1.0 (reference) | |||
1 | 1.80 (1.49–2.17) | <0.0001 | 1.83 (1.34–2.49) | 0.0001 | 1.77 (1.40–2.24) | <0.0001 | |
2+ | 2.18 (1.66–2.84) | <0.0001 | 2.56 (1.68–3.99) | <0.0001 | 2.01 (1.43–2.83) | <0.0001 | |
% Time on metformin (from diabetes) * | no metformin | 1.0 (reference) | 1.0 (reference) | 1.0 (reference) | |||
<50% | 0.88 (0.57–1.38) | 0.58 | 0.99 (0.50–1.98) | 0.99 | 0.82 (0.45–1.49) | 0.51 | |
50–80% | 1.32 (0.76–2.27) | 0.32 | 1.45 (0.66–3.18) | 0.35 | 1.12 (0.49–2.56) | 0.79 | |
80%+ | 0.68 (0.32–1.43) | 0.30 | 0.49 (0.14–1.68) | 0.26 | 0.78 (0.27–2.22) | 0.64 | |
no DM | 0.88 (0.66–1.19) | 0.41 | 0.82 (0.49–1.35) | 0.43 | 0.87 (0.59–1.27) | 0.46 | |
Alcohol abuse (so far) * | Y/N | 1.29 (1.11–1.51) | 0.0010 | 1.28 (0.99–1.66) | 0.06 | 1.28 (1.05–1.56) | 0.01 |
Non-cannabis substance use (so far) * | Y/N | 1.14 (0.98–1.33) | 0.09 | 1.04 (0.79–1.36) | 0.76 | 1.17 (0.96–1.42) | 0.12 |
Variable | Levels | Well-Controlled HIV | |||
---|---|---|---|---|---|
Yes | No | ||||
HR and 95% CI | p-Value | HR and 95% CI | p-Value | ||
Age at Index date, years | <50 | 1.0 (reference) | 1.0 (reference) | ||
50–59 | 2.55 (1.88–3.46) | <0.0001 | 3.29 (2.66–4.06) | <0.0001 | |
60+ | 3.79 (2.56–5.62) | <0.0001 | 4.44 (3.25–6.08) | <0.0001 | |
Race | White | 1.0 (reference) | 1.0 (reference) | ||
Black | 0.98 (0.74–1.30) | 0.89 | 0.94 (0.76–1.16) | 0.53 | |
Hispanic | 0.35 (0.14–0.86) | 0.02 | 0.37 (0.18–0.75) | 0.006 | |
Other | 0.83 (0.12–5.98) | 0.85 | 0.00 (0.00–Infty) | 0.96 | |
Unreported | 0.49 (0.12–2.01) | 0.32 | 0.56 (0.21–1.51) | 0.24 | |
Gender | F vs. M | 0.89 (0.33–2.43) | 0.82 | 0.99 (0.53–1.88) | 0.98 |
COPD history (so far) * | Y/N | 1.87 (1.42–2.47) | <0.0001 | 2.07 (1.68–2.56) | <0.0001 |
HIV diagnosis date, years | pre 2001 | 1.0 (reference) | 1.0 (reference) | ||
2001–2009 | 0.98 (0.73–1.31) | 0.89 | 1.07 (0.86–1.32) | 0.56 | |
2010+ | 0.54 (0.27–1.08) | 0.08 | 0.93 (0.64–1.37) | 0.72 | |
Nadir CD4 cell count, cell/mm3 * | <200 | 1.0 (reference) | 1.0 (reference) | ||
200–500 | 0.99 (0.74–1.33) | 0.95 | 1.02 (0.80–1.29) | 0.88 | |
>500 | 0.89 (0.56–1.42) | 0.61 | 1.17 (0.81–1.69) | 0.39 | |
BMI at Index date, kg/m2 | <18.5 | 1.73 (0.87–3.44) | 0.11 | 1.25 (0.72–2.16) | 0.43 |
18.5–25 | 1.0 (reference) | 1.0 (reference) | |||
25–30 | 0.75 (0.54–1.04) | 0.08 | 0.61 (0.46–0.81) | 0.0006 | |
30+ | 0.52 (0.31–0.86) | 0.01 | 0.40 (0.26–0.63) | <0.0001 | |
Cachexia * | none | 1.0 (reference) | 1.0 (reference) | ||
current cachexia | 6.34 (4.52–8.88) | <0.0001 | 4.42 (3.39–5.77) | <0.0001 | |
recent cachexia | 1.37 (0.66–2.83) | 0.39 | 1.06 (0.61–1.83) | 0.84 | |
distant past or rebounded | 1.39 (1.01–1.93) | 0.04 | 1.07 (0.81–1.40) | 0.64 | |
undefined/first year after index | 1.04 (0.39–2.78) | 0.93 | 1.23 (0.80–1.88) | 0.34 | |
Current LDL-C, mg/dL * | <100 | 1.0 (reference) | 1.0 (reference) | ||
100–129 | 1.05 (0.76–1.45) | 0.78 | 1.01 (0.78–1.31) | 0.93 | |
130–159 | 1.18 (0.77–1.82) | 0.44 | 0.83 (0.56–1.24) | 0.36 | |
160+ | 0.67 (0.29–1.53) | 0.33 | 1.08 (0.62–1.88) | 0.79 | |
Current HDL-C, mg/dL * | <40 | 1.0 (reference) | 1.0 (reference) | ||
40–60 | 0.79 (0.56–1.08) | 0.13 | 0.77 (0.59–0.99) | 0.03 | |
> 60 | 0.77 (0.49–1.19) | 0.24 | 0.76 (0.53–1.09) | 0.13 | |
Current Triglycerides, mg/dL * | <150 | 1.0 (reference) | 1.0 (reference) | ||
150+ | 0.80 (0.60–1.08) | 0.14 | 0.65 (0.51–0.84) | 0.0007 | |
Pneumonia episodes (so far) * | 0 | 1.0 (reference) | 1.0 (reference) | ||
1 | 1.41 (1.02–1.95) | 0.03 | 1.34 (1.05–1.71) | 0.02 | |
2+ | 1.64 (1.05–2.58) | 0.03 | 1.23 (0.86–1.75) | 0.25 | |
Alcohol (so far) * | Y/N | 1.22 (0.90–1.64) | 0.19 | 1.11 (0.88–1.40) | 0.36 |
% Time on statins * | none | 1.0 (reference) | 1.0 (reference) | ||
<50% | 0.91 (0.65–1.28) | 0.58 | 1.23 (0.95–1.59) | 0.12 | |
50–80% | 1.14 (0.75–1.75) | 0.53 | 1.04 (0.64–1.69) | 0.86 | |
80%+ | 1.27 (0.77–2.09) | 0.34 | 1.59 (0.94–2.69) | 0.08 | |
Non-cannabis substance use (so far) * | Y/N | 0.91 (0.66–1.25) | 0.56 | 1.01 (0.80–1.28) | 0.92 |
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Garcia, J.M.; Kramer, J.R.; Richardson, P.A.; Ahmed, S.; Royse, K.E.; White, D.L.; Raychaudhury, S.; Chang, E.; Hartman, C.M.; Silverberg, M.J.; et al. Effect of Body Weight and Other Metabolic Factors on Risk of Non-Small Cell Lung Cancer among Veterans with HIV and a History of Smoking. Cancers 2020, 12, 3809. https://doi.org/10.3390/cancers12123809
Garcia JM, Kramer JR, Richardson PA, Ahmed S, Royse KE, White DL, Raychaudhury S, Chang E, Hartman CM, Silverberg MJ, et al. Effect of Body Weight and Other Metabolic Factors on Risk of Non-Small Cell Lung Cancer among Veterans with HIV and a History of Smoking. Cancers. 2020; 12(12):3809. https://doi.org/10.3390/cancers12123809
Chicago/Turabian StyleGarcia, Jose M., Jennifer R. Kramer, Peter A. Richardson, Sarah Ahmed, Kathryn E. Royse, Donna L. White, Suchismita Raychaudhury, Elaine Chang, Christine M. Hartman, Michael J. Silverberg, and et al. 2020. "Effect of Body Weight and Other Metabolic Factors on Risk of Non-Small Cell Lung Cancer among Veterans with HIV and a History of Smoking" Cancers 12, no. 12: 3809. https://doi.org/10.3390/cancers12123809