Leukocyte telomere length and epigenetic-based mortality risk score: associations with all-cause mortality among older adults

Figures & data

Table 1. Characteristics of the ESTHER study participants at baseline according to quintiles of telomere length ^a.

Characteristics	All participants	Subsets based on the quintiles of telomere length
		Quintile 1	Quintile 2	Quintile 3	Quintile 4	Quintile 5	p-value
N	1517	303	304	305	301	304
Age (years)	62.1 (6.54)	64.1 (6.29)	62.2 (6.22)	62.1 (6.59)	61.6 (6.43)	60.5 (6.65)	<0.0001
Sex (male)	701 (46.2%)	150 (49.5%)	158 (52.0%)	144 (47.2%)	135 (44.9%)	114 (37.5%)	0.005
Smoking status ^b							0.892
Current smoker	272 (18.4%)	61 (20.5%)	57 (19.2%)	52 (17.6%)	52 (17.8%)	50 (16.8%)
Former smoker	502 (33.9%)	97 (32.7%)	104 (35.0%)	107 (36.3%)	99 (33.8%)	95 (32.0%)
Never smoker	705 (47.7%)	139 (46.8%)	136 (45.8%)	136 (46.1%)	142 (48.5%)	152 (51.2%)
Body mass index ^c							0.431
Underweight or normal weight (<25.0)	410 (27.1%)	77 (25.4%)	77 (25.4%)	83 (27.2%)	87 (28.9%)	86 (28.4%)
Overweight (25 to <30)	706 (46.6%)	151 (49.8%)	150 (49.5%)	139 (45.6%)	122 (40.5%)	144 (47.5%)
Obese (≥30.0)	399 (26.3%)	75 (24.8%)	76 (25.1%)	83 (27.2%)	92 (9.0%)	73 (24.1%)
Alcohol consumption ^d							0.515
Abstainer	474 (34.0%)	92 (33.6%)	96 (33.7%)	87 (31.5%)	95 (34.3%)	104 (36.8%)
Low	817 (58.6%)	159 (58.0%)	166 (58.3%)	171 (62.0%)	158 (57.0%)	163 (57.6%)
Intermediate	82 (5.9%)	19 (6.9%)	17 (6.0%)	12 (4.4%)	23 (8.3%)	11 (3.9%)
High	22 (1.6%)	4 (1.5%)	6 (2.1%)	6 (2.2%)	1 (0.4%)	5 (1.8%)
Physical activity ^e							0.367
Inactive	308 (20.3%)	65 (21.5%)	67 (22.0%)	55 (18.1%)	63 (20.9%)	58 (19.1%)
Low	692 (45.7%)	143 (47.4%)	127 (41.8%)	134 (44.1%)	134 (44.5%)	154 (50.8%)
Medium or high	514 (34.0%)	94 (31.1%)	110 (36.2%)	115 (37.8%)	104 (34.6%)	91 (30.0%)
Prevalence of major diseases
Cardiovascular disease	323 (21.3%)	80 (26.4%)	62 (20.4%)	61 (20.0%)	54 (17.9%)	66 (21.7%)	0.154
Diabetes ^f	240 (16.0%)	46 (15.2%)	58 (19.3%)	55 (18.2%)	36 (12.2%)	45 (15.1%)	0.143
Cancer	93 (6.1%)	21 (6.9%)	19 (6.3%)	15 (4.9%)	19 (6.3%)	19 (6.3%)	0.881
Mortality risk score (category)							<0.0001
0/None	284 (18.7%)	52 (17.2%)	50 (16.5%)	42 (13.8%)	67 (22.3%)	73 (24.0%)
1/Low	335 (22.1%)	53 (17.5%)	55 (18.1%)	71 (23.3%)	72 (23.9%)	84 (27.6%)
2–5/Moderate	691 (45.6%)	146 (48.2%)	150 (49.3%)	150 (49.2%)	122 (40.5%)	123 (40.5%)
> 5/High	207 (13.7%)	52 (17.2%)	49 (16.1%)	42 (13.8%)	40 (13.3%)	24 (7.9%)

a: Mean values (SD) for continuous variables and n (%) for categorical variables; Differences among subgroups of TL quintiles were tested for statistical significance by Kruskal-Wallis test (continuous variables) and Chi-square test (categorical variables);

b: Data missing for 38 participants;

c: Data missing for 2 participants;

d: Data missing for 122 participants. Categories defined as follows: abstainer, low (women: 0 to <20 g/d, men: 0 to <40 g/d), intermediate (20 to <40 g/d and 40 to <60 g/d, respectively), high (≥40 g/d and ≥60 g/d, respectively);

e: Data missing for 3 participants. Categories defined as follows: inactive (<1h of physical activity/week), medium or high (≥2 h of vigorous or ≥2 h of light physical activity/week), low (other);

f: Data missing for 17 participants;

Figure 1. Distributions of telomere length of the ESTHER study participants at baseline according to sex, age and mortality risk score.

Table 2. Association of mortality risk score with telomere length (z-score) at baseline.

	Model 1 ^a		Model 2 ^b		Model 3 ^c
Characteristic	Estimate (SE)	p-value	Estimate (SE)	p-value	Estimate (SE)	p-value
Mortality risk score (category)
0/None	Reference		Reference		Reference
1/Low	0.07 (0.08)	0.39	0.05 (0.08)	0.56	0.06 (0.08)	0.49
2–5/Moderate	-0.16 (0.07)	0.018	-0.23 (0.08)	0.003	-0.23 (0.08)	0.003
>5/High	-0.26 (0.09)	0.004	-0.32 (0.10)	0.002	-0.33 (0.11)	0.002
Mortality risk score (continuous)	-0.25 (0.06)	<0.0001	-0.31 (0.06)	<0.0001	-0.31 (0.07)	<0.0001

a: Adjusted for age, sex and population subgroups;

b: Additionally adjusted for alcohol consumption, smoking status, BMI class and physical activity;

c: Additionally adjusted for the leukocyte distribution (Houseman algorithm), the prevalence of CVD, diabetes and cancer;

Figure 2. Graphs of the best-fitting models for the associations of the continuous mortality risk score with telomere length (z-score, relative & absolute).

Table 3. Associations of baseline telomere length (z-score) and mortality risk score with all-cause mortality.

			Model 1 ^a		Model 2 ^b		Model 3 ^c		Model with both indicators ^d
Characteristics	N total	N death	HR (95% CI)	p-value	HR (95% CI)	p-value	HR (95% CI)	p-value	HR (95% CI)	p-value
Telomere length (quintile)
1	303	75	1.28 (0.88–1.86)	0.21	1.22 (0.83–1.82)	0.31	1.26 (0.84–1.88)	0.26	1.16 (0.78–1.73)	0.47
2	304	58	1.11 (0.75–1.65)	0.59	1.04 (0.69–1.57)	0.86	1.02 (0.67–1.55)	0.92	0.92 (0.60–1.40)	0.69
3	305	49	0.91 (0.60–1.36)	0.64	0.88 (0.57–1.36)	0.55	0.94 (0.61–1.46)	0.79	0.82 (0.53–1.28)	0.38
4	302	58	1.18 (0.80–1.75)	0.41	1.17 (0.78–1.76)	0.46	1.28 (0.85–1.94)	0.24	1.24 (0.82–1.88)	0.32
5	303	44	Reference		Reference		Reference		Reference
Telomere length (continuous)	1517	284	0.94 (0.83–1.07)	0.35	0.96 (0.84–1.10)	0.59	0.98 (0.86–1.12)	0.77	1.00 (0.87–1.14)	0.95
Mortality risk score (category)
0/None	284	14	Reference		Reference		Reference		Reference
1/Low	336	42	2.20 (1.20–4.03)	0.01	2.23 (1.13–4.40)	0.02	2.16 (1.10–4.26)	0.03	2.24 (1.13–4.41)	0.02
2–5/Moderate	690	141	3.68 (2.12–6.41)	<0.0001	3.49 (1.87–6.54)	<0.0001	3.22 (1.72–6.05)	0.0003	3.31 (1.76–6.22)	0.0002
> 5/High	207	87	7.97 (4.46– 14.23)	<0.0001	7.03 (3.60–13.74)	<0.0001	6.10 (3.12–11.95)	<0.0001	6.33 (3.22–12.41)	<0.0001
Mortality risk score (continuous)	1517	284	3.30 (2.59– 4.19)	<0.0001	2.82 (2.12–3.75)	<0.0001	2.56 (1.93–3.40)	<0.0001	2.64 (1.98–3.52)	<0.0001

a: Adjusted for age, sex and population subgroups;

b: Additionally adjusted for alcohol consumption, smoking status, BMI class and physical activity;

c: Additionally adjusted for the prevalence of CVD, diabetes and cancer; the models with mortality score were additionally adjusted for the leukocyte distribution (Houseman algorithm);

d: Adjusted for the same covariates in Model 3; In this model, telomere length and mortality risk score were included simultaneously.

Figure 3. Overview of the sampling procedures of participants for analysis.