Background
Methods
Study design and participants
Procedures
Clinical outcomes
Statistical analysis
Sensitivity analyses
Results
Patient characteristics
No LTCs N = 172,593 (34.5%) | 1 LTC N = 163,705 (32.7%) | 2 LTCs N = 95,226 (19%) | 3 LTCs N = 43,120 (8.6%) | ≥ 4 LTCs N = 26,125 (5.2%) | Overall N = 500,769 | |
---|---|---|---|---|---|---|
Age; missing values n = 0 | ||||||
Age in years-mean (SD) | 54.0 (8.1) | 56.6 (8.0) | 58.5 (7.6) | 59.7 (7.2) | 60.3 (6.9) | 56.5 (8.1) |
Sex; missing values n = 0 | ||||||
Male | 79,947 (46.3%) | 75,240 (46.0%) | 43,448 (45.6%) | 19,170 (44.5%) | 10,695 (40.9%) | 228,500 (45.6%) |
Female | 92,646 (53.7%) | 88,465 (54.0%) | 51,778 (54.4%) | 23,950 (55.5%) | 15,430 (59.1%) | 272,269 (54.4%) |
Socioeconomic status based on Townsend Score; missing values n = 626 (0.13%) | ||||||
Townsend score-mean (SD) | − 1.5 (3.0) | − 1.4 (3.0) | − 1.2 (3.1) | − 0.9 (3.3) | − 0.4 (3.4) | − 1.3 (3.1) |
Smoking status; missing values n = 2794 (0.56%) | ||||||
Never | 102,365 (59.7%) | 90,168 (55.3%) | 48,593 (51.3%) | 20,443 (47.7%) | 11,220 (43.3%) | 272,779 (54.8%) |
Current or previous | 69,164 (40.3%) | 72,780 (44.7%) | 46,130 (48.7%) | 22.427 (52.3%) | 14,695 (56.7%) | 225,196 (45.2%) |
Alcohol status; missing values = 1345 (0.27%) | ||||||
Never or special occasions only | 26,451 (15.4%) | 29,356 (18.0%) | 20,995 (22.1%) | 11,750 (27.3%) | 9506 (36.5%) | 98,058 (19.6%) |
1–3 times/month | 18,797 (10.9%) | 17,898 (11.0%) | 10,760 (11.3%) | 5177 (12.0%) | 3075 (11.8%) | 55,707 (11.2%) |
1–4 times/week | 91,136 (53.0%) | 81,473 (49.8%) | 44,021 (46.3%) | 18,080 (42.0%) | 9423 (36.2%) | 244,133 (48.9%) |
Daily or almost daily | 35,541 (20.7%) | 34,670 (21.2%) | 19,260 (20.3%) | 8017 (18.7%) | 4038 (15.5%) | 101,526 (20.3%) |
Body mass index (BMI); missing values n = 3027 (0.6%) | ||||||
< 18.5 | 1033 (0.6%) | 833 (0.5%) | 438 (0.5%) | 177 (0.4%) | 128 (0.5%) | 2609 (0.5%) |
18.5–24.9 | 68,186 (39.8%) | 51,875 (31.8%) | 23,838 (25.2%) | 8733 (20.4%) | 4330 (16.8%) | 156,962 (31.5%) |
25–29.9 | 73,953 (43.2%) | 71,945 (44.1%) | 40,943 (43.2%) | 17,501 (40.9%) | 9241 (35.7%) | 213,583 (42.9%) |
30–34.9 | 22,261 (13%) | 28,672 (17.6%) | 20,535 (21.7%) | 10,699 (25.0%) | 7044 (27.2%) | 89,211 (17.9%) |
35–39.9 | 4555 (2.7%) | 7339 (4.5%) | 6434 (6.8%) | 3937 (9.2%) | 3255 (12.6%) | 25,520 (5.1%) |
≥ 40 | 1323 (0.7%) | 2359 (1.5%) | 2524 (2.6%) | 1780 (4.1%) | 1871 (7.2%) | 9857 (2.0%) |
Physical activity; missing values n = 6970 (1.39%) | ||||||
High | 24,815 (14.6%) | 16,443 (10.2%) | 6239 (6.7%) | 1837 (4.3%) | 679 (2.7%) | 50,013 (10.1%) |
Medium | 132,926 (78.3%) | 130,709 (80.7%) | 76,505 (81.3%) | 33,690 (79.2%) | 18,506 (72.7%) | 392,336 (79.5%) |
Low | 4655 (2.7%) | 5665 (3.5%) | 4173 (4.4%) | 2421 (5.7%) | 1931 (7.6%) | 18,845 (3.8%) |
None | 7463 (4.4%) | 9027 (5.6%) | 7185 (7.6%) | 4590 (10.8%) | 4340 (17%) | 32,605 (6.6%) |
Presence of at least 1 cardiometabolic condition | Not applicable | 52,592 (32.1%) | 52,807 (55.4%) | 29,833 (69.2%) | 20,957 (80.2%) | 156,189 (32.2%) |
Presence of previous cancer | Not applicable | 12,744 (7.8%) | 12,509 (13.1%) | 7574 (17.6%) | 5795 (22.2%) | 38,622 (7.7%) |
Multimorbidity and mortality
N = 500,769 | 7-year cumulative mortality | Unadjusted number of events = 14,348 | Adjusted* (missing values n = 12,045, 2.4%); number of events = 13,570 |
---|---|---|---|
Hazard ratios (95% confidence intervals) | |||
No LTC N = 172,593 | 2408 (1.4%) | 1 | 1 |
1 LTC N = 163,705 | 4147 (2.5%) | 1.52 (1.45–1.60) | 1.46 (1.38–1.54) |
2 LTC N = 95,226 | 3555 (3.7%) | 1.98 (1.88–2.08) | 1.77 (1.68–1.87) |
3 LTC N = 43,120 | 2213 (5.1%) | 2.53 (2.39–2.68) | 2.14 (2.01–2.28) |
≥ 4 LTC N = 26,125 | 2025 (7.8%) | 3.72 (3.50–3.95) | 2.79 (2.61–2.98) |
Cancer mortality | |||
N = 500,769 | 7-year cumulative cancer mortality | Unadjusted number of events = 8350 | Adjusted* (missing values n = 12,045; 2.4%); number of events = 8037 |
Hazard ratios (95% confidence intervals) | |||
No LTC N = 172,593 | 1524 (0.88%) | 1 | 1 |
1 LTC N = 163,705 | 2723 (1.66%) | 1.56 (1.46–1.66) | 1.50 (1.41–1.60) |
2 LTC N = 95,226 | 2086 (2.19%) | 1.80 (1.68–1.92) | 1.66 (1.55–1.78) |
3 LTC N = 43,120 | 1155 (2.67%) | 2.04 (1.89–2.21) | 1.79 (1.65–1.94) |
≥ 4 LTC N = 26,125 | 862 (3.29%) | 2.44 (2.25–2.66) | 2.01 (1.84–2.20) |
Vascular mortality | |||
7-year cumulative vascular mortality | Unadjusted number of events = 2985 | Adjusted* (missing values n = 12,045; 2.4%); number of events = 2799 | |
Hazard ratios (95% confidence intervals) for vascular mortality | |||
No LTC N = 172,593 | 429 (0.24%) | 1 | 1 |
1 LTC N = 163,705 | 691 (0.42%) | 1.41 (1.25–1.59) | 1.31 (1.15–1.48) |
2 LTC N = 95,226 | 729 (0.76%) | 2.25 (1.99–2.54) | 1.89 (1.67–2.14) |
3 LTC N = 43,120 | 565 (1.3%) | 3.58 (3.15–4.07) | 2.74 (2.39–3.13) |
≥ 4 LTC N = 26,125 | 571 (2.18%) | 5.80 (5.11–6.59) | 3.71 (3.23–4.27) |
Type of long-term conditions and clinical outcomes
Type of LTCs | N = 500,769. Adjusted analyses* (missing values n = 12,045; 2.4%) | ||
---|---|---|---|
Hazard ratios (95% confidence intervals) for All-cause mortality | Hazard ratios (95% confidence intervals) for cancer mortality | Hazard ratios (95% confidence intervals) for vascular mortality | |
No cardiometabolic conditions | 1 | 1 | 1 |
1 LTC-cardiometabolic | 1.19 (1.15–1.24) | 1.04 (0.99–1.10) | 1.79 (1.63–1.96) |
2 LTC-cardiometabolic | 1.67 (1.58–1.77) | 1.15 (1.06–1.24) | 3.42 (3.06–3.82) |
3 LTC-cardiometabolic | 2.52 (2.31–2.76) | 1.23 (1.05–1.44) | 7.31 (6.32–8.46) |
≥ 4 LTC-cardiometabolic | 3.20 (2.56–4.00) | 1.67 (1.12–2.51) | 8.20 (5.81–11.58) |
No previous cancer | 1 | 1 | 1 |
Presence history of Cancer | 2.83 (2.71–2.95) | 4.26 (4.06–4.47) | 0.99 (0.87–1.13) |
No non-cardiometabolic condition | 1 | 1 | 1 |
1 LTC (excluding cancer and cardiometabolic) | 1.08 (1.04–1.12) | 0.99 (0.95–1.04) | 1.02 (0.94–1.11) |
2 LTCs (excluding cancer and cardiometabolic) | 1.16 (1.10–1.22) | 0.98 (0.92–1.05) | 1.15 (1.03–1.29) |
3 LTCs (excluding cancer and cardiometabolic) | 1.25 (1.16–1.35) | 0.96 (0.86–1.07) | 1.29 (1.10–1.52) |
4 LTCs (excluding cancer and cardiometabolic) | 1.50 (1.36–1.67) | 0.89 (0.75–1.05) | 1.62 (1.31–1.99) |
Top 10 most impactful LTC combinations in each category of MM count | |||||
---|---|---|---|---|---|
Adjusted hazard ratios for all-cause mortality, when compared to reference group—no LTCs; number of deaths | |||||
Category LTC count = 2; N = 95,226; total number of deaths N = 3555 | Category 3: LTC count = 3, N = 43,120; total number of deaths N = 2213 | Category 4: LTC count = ≥ 4, N = 26,125; total number of deaths N = 2025 | |||
Cancer + bronchiectasis | 9.50 (3.56–25.36); N = 4 deaths | Cancer + HTN + CKD | 12.27 (5.50–27.39); N = 6 deaths | Cancer + HTN + CHD + epilepsy | 7.75 (2.48–24.21); N = 3 deaths |
Cancer + epilepsy | 9.06 (5.54–14.84); N = 16 deaths | HTN + CKD + diabetes | 11.46 (6.29–20.89); N = 13 deaths | HTN + CKD + CHD + diabetes | 7.16 (4.20–12.22); N = 17 deaths |
Alcohol problem + HTN | 7.49 (4.23–13.28); N = 12 deaths | Cancer + stroke/TIA + CHD | 8.16 (3.05–21.84); N = 4 deaths | Cancer + HTN + CHD + connective tissue disorders | 6.84 (3.40–13.76); N = 8 deaths |
Alcohol problem + depression | 5.71 (2.13–15.28); N = 4 deaths | HTN + CKD + CHD | 8.13 (3.37–19.61); N = 5 deaths | Cancer + HTN + depression + COPD | 6.60 (3.70–11.78); N = 12 deaths |
Epilepsy + diabetes | 5.60 (1.80–17.40); N = 3 deaths | Cancer + connective tissue disorders + osteoporosis | 8.07 (3.34–19.47); N = 5 deaths | Cancer + HTN + diabetes + COPD | 6.38 (3.81–10.70); N = 16 deaths |
Cancer + COPD | 5.54 (3.59–8.54); N = 22 deaths | Cancer + diabetes + CHD | 8.01 (3.78–16.93); N = 7 deaths | Cancer + HTN + depression + osteoporosis | 5.87 (2.19–15.69); N = 4 deaths |
Cancer + peripheral vascular disease | 5.14 (1.28–20.57); N = 2 deaths | CHD + COPD + diabetes | 7.84 (3.23–19.01); N = 5 deaths | Cancer + HTN + stroke/TIA + COPD | 5.38 (2.68–10.83); N = 8 deaths |
Cancer + IBD | 4.98 (2.58–9.59); N = 9 deaths | Cancer + HTN + IBD | 5.59 (1.80–17.35); N = 3 deaths | Cancer + HTN + diabetes + connective tissue disorders | 5.03 (1.61–15.68); N = 16 deaths |
IBD + osteoporosis | 4.88 (2.02–11.75); N = 5 deaths | Cancer + HTN + COPD | 5.55 (3.06–10.06); N = 11 deaths | HTN + diabetes + depression + stroke/TIA | 4.87 (2.90–8.18); N = 19 deaths |
Osteoporosis + epilepsy | 4.77 (1.53–14.80); N = 3 deaths | Cancer + HTN + stroke/TIA | 5.43 (3.62–8.14); N = 24 deaths | HTN + CHD + diabetes + stroke/TIA | 4.64 (3.50–6.14); N = 63 deaths |