Associations between remnant cholesterol levels and mortality in patients with diabetes

Table 1 Baseline characteristics

	Male	Female	All participants	P value
Sample size	2447	2293	4740
Age [mean (SD)]	61.8 (13.7)	61.3 (14.3)	61.6 (14.0)	0.09
Body mass index, median (IQR)	29.7 (26.2-33.7)	31.4 (27.4-37.0)	30.5 (26.7-35.4)	< 0.01
Ethnicity, n (%)
Mexican American	466 (19.0)	471 (20.5)	937 (19.8)	< 0.01
Other Hispanic	228 (9.3)	230 (10.0)	458 (9.7)
Non-Hispanic white	986 (40.3)	790 (34.5)	1776 (37.5)
Non-Hispanic black	539 (22.0)	611 (26.7)	1150 (24.3)
Others	228 (9.3)	191 (8.3)	419 (8.8)
Education, n (%)
Less than 9th grade	547 (22.4)	559 (24.4)	1106 (23.3)	< 0.01
9-11th grade	422 (17.3)	426 (18.6)	848 (17.9)
High school graduate	631 (25.8)	573 (25.0)	1204 (25.4)
College	471 (19.3)	491 (21.4)	962 (20.3)
College graduate or above	365 (14.9)	232 (10.1)	597 (12.6)
Unknown	11 (0.45)	12 (0.52)	23 (0.48)
Poverty-income ratio, n (%)
< 1	439 (17.9)	536 (23.4)	975 (20.6)	< 0.01
1-3	1265 (51.7)	1242 (54.2)	2507 (52.9)
> 3	743 (30.7)	515 (22.5)	1258 (26.6)
Smoke, n (%)
Every day	299 (12.2)	196 (8.6)	495 (10.4)	< 0.01
Some days	46 (1.9)	43 (1.9)	89 (1.9)
Not at all	76 (31.7)	414 (18.1)	1190 (25.1)
Unknown	1326 (54.2)	1640 (71.3)	2966 (62.6)
Alcohol consumption, n (%)
Non-drinker	358 (14.7)	437 (19.7)	795 (16.8)	< 0.01
1-3 drinks per day	969 (39.6)	745 (32.5)	1714 (36.2)
≥ 4 drinks per day	378 (15.5)	12 (5.3)	499 (10.1)
Unknown	742 (30.3)	990 (43.2)	1732 (36.6)
Hypertension, n (%)	1490 (60.9)	1519 (66.3)	3009 (63.5)	< 0.01
Hypercholesterolemia, n (%)	1324 (54.1)	1300 (56.7)	2624 (55.4)	0.3
Plasma fasting glucose (mmol/L), median (IQR)	9.8 ± 3.5	8.5 ± 3.5	8.6 ± 3.5	< 0.01
HbA1c, %, median (IQR)	7.2 ± 1.8	7.1 ± 1.7	7.2 ± 1.8	0.21
Remnant cholesterol, median (IQR)	0.68 (0.45-1.07)	0.68 (0.46-1.03)	0.68 (0.46-1.04)	0.53
TC, median (IQR)	4.53 (3.80-5.38)	4.86 (4.11-5.69)	4.68 (3.93-5.53)	< 0.01
HDL-C, median (IQR)	1.09 (0.93-1.32)	1.29 (1.06-1.58)	1.19 (0.98-1.45)	< 0.01
LDL-C, median (IQR)	2.43 (1.71-3.18)	2.59 (1.81-3.34)	2.51 (1.76-3.23)	< 0.01
Triglyceride, median (IQR)	1.48 (1.02-2.21)	1.58 (1.05-2.11)	1.48 (1.04-2.16)	0.97

IQR: Interquartile range; TC: Total cholesterol; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol.

Table 2 Association of remnant cholesterol and all-cause and cardiovascular mortality in patients with diabetes

	Hazard ratio (95%CI)
	Q1	Q2	Q3	Q4	Per SD	P value
All-cause mortality
Model 1	Reference	0.88 (0.68-1.15)	0.65 (0.50-0.84)	0.87 (0.68-1.10)	1.04 (0.97-1.11)	0.01
Model 2	Reference	0.80 (0.62-1.03)	0.67 (0.52-0.86)	0.93 (0.73-1.17)	1.13 (1.04-1.22)	< 0.01
Model 3	Reference	0.80 (0.62-1.02)	0.66 (0.52-0.85)	0.92 (0.72-1.17)	1.13 (1.04-1.22)	< 0.01
Model 4	Reference	0.81 (0.62-1.03)	0.66 (0.52-0.85)	0.92 (0.73-1.17)	1.12 (1.02-1.21)	< 0.01
Cardiovascular mortality
Model 1	Reference	1.13 (0.72-1.77)	0.60 (0.38-0.96)	0.92 (0.61-1.39)	1.07 (0.95-1.21)	< 0.01
Model 2	Reference	1.01 (0.65-1.55)	0.63 (0.40-0.99)	0.99 (0.66-1.50)	1.19 (1.04-1.37)	< 0.01
Model 3	Reference	1.02 (0.66-1.57)	0.64 (0.41-1.01)	0.98 (0.65-1.48)	1.18 (1.03-1.35)	< 0.01
Model 4	Reference	1.05 (0.68-1.63)	0.67 (0.42-1.07)	1.01 (0.67-1.52)	1.16 (1.01-1.32)	< 0.01

Model 1: No adjustment; Model 2: Adjusted for age, gender, ethnicity, body mass index (BMI), poverty-income ratio, education, survey period; Model 3: Adjusted for age, gender, ethnicity, BMI, poverty-income ratio, education, smoking status, alcohol consumption, survey period; Model 4: Adjusted for age, gender, ethnicity, BMI, poverty-income ratio, education, smoking status, alcohol consumption, survey period, hypercholesterolemia, hypertension, heart failure, coronary heart disease, and cancer.

Table 3 Subgroup analyses on remnant cholesterol and all-cause and cardiovascular mortality

	Hazard ratio (95%CI)
	Q1	Q2	Q3	Q4	P for interaction
All-cause mortality
Gender
Male	Reference	0.84 (0.61-1.16)	0.67 (0.48-0.94)	0.96 (0.71-1.32)	0.36
Female	Reference	0.83 (0.57-1.19)	0.64 (0.44-0.93)	0.85 (0.59-1.23)
Age
> 60	Reference	0.93 (0.65-1.07)	0.72 (0.55-0.95)	0.89 (0.68-1.17)	0.45
< 60	Reference	0.76 (0.39-1.51)	0.44 (0.24-0.81)	0.91 (0.55-1.51)
BMI
> 30	Reference	1.13 (0.78-1.63)	0.77 (0.52-1.12)	1.09 (0.75-1.57)	0.57
< 30	Reference	0.70 (0.51-0.96)	0.66 (0.47-0.93)	0.89 (0.64-1.22)
Duration of diabetes
> 10 yr	Reference	0.97 (0.68-1.38)	0.69 (0.47-1.02)	0.78 (0.54-1.12)	0.53
< 10 yr	Reference	0.80 (0.57-1.11)	0.68 (0.49-0.94)	1.02 (0.73-1.41)
Ethnicities
Mexican American	Reference	0.59 (0.29-1.20)	0.55 (0.28-1.05)	0.73 (0.39-1.37)	0.85
Non-Hispanic white	Reference	0.85 (0.61-1.19)	0.62 (0.45-0.86)	0.86 (0.63-1.18)
Non-Hispanic black	Reference	0.91 (0.62-1.33)	0.97 (0.60-1.59)	1.02 (0.62-1.70)
Others	Reference	0.54 (0.27-1.07)	0.57 (0.28-1.15)	1.37 (0.71-2.63)
Cardiovascular mortality
Gender
Male	Reference	1.40 (0.75-2.61)	1.06 (0.58-1.95)	1.31 (0.76-2.26)	0.17
Female	Reference	0.75 (0.41-1.34)	0.39 (0.19-0.81)	0.76 (0.42-1.37)
Age
> 60	Reference	1.09 (0.70-1.71)	0.60 (0.36-1.01)	0.91 (0.58-1.44)	0.3
< 60	Reference	0.78 (0.22-2.81)	1.11 (0.35-3.49)	1.43 (0.46-4.49)
BMI
> 30	Reference	1.20 (0.65-2.19)	0.96 (0.50-1.85)	0.87 (0.48-1.58)	0.16
< 30	Reference	1.1 (0.60-2.07)	0.30 (0.15-0.60)	1.55 (0.90-2.66)
Duration of diabetes
> 10 yr	Reference	1.03 (0.54-2.00)	0.88 (0.44-1.77)	0.93 (0.47-1.80)	0.4
< 10 yr	Reference	1.14 (0.62-2.03)	0.53 (0.29-0.97)	1.07 (0.62-1.86)
Ethnicities
Mexican American	Reference	5.3 (1.44-19.01)	0.72 (0.18-2.91)	4.21 (1.20-14.7)	0.16
Non-Hispanic white	Reference	1.15 (0.65-2.04)	0.70 (0.39-1.26)	0.96 (0.56-1.67)
Non-Hispanic black	Reference	1.28 (0.69-2.38)	1.17 (0.49-2.81)	1.46 (0.73-2.91)
Others	Reference	0.35 (0.12-1.06)	0.12 (0.03-0.45)	0.57 (0.18-1.84)

Model 1: No adjustment; Model 2: Adjusted for age, gender, ethnicity, body mass index (BMI), poverty-income ratio, education, survey period; Model 3: Adjusted for age, gender, ethnicity, BMI, poverty-income ratio, education, smoking status, alcohol consumption, survey period; Model 4: Adjusted for age, gender, ethnicity, BMI, poverty-income ratio, education, smoking status, alcohol consumption, survey period, hypercholesterolemia, hypertension, heart failure, coronary heart disease, and cancer. BMI: Body mass index.

Table 4 Sensitivity analysis of remnant cholesterol and all-cause and cardiovascular mortality after excluding patients who died within 1 year of follow-up

	Hazard ratio (95%CI)
	Q1	Q2	Q3	Q4	Per SD	P value
All-cause mortality
Model 1	Reference	0.95 (0.72-1.24)	0.70 (0.54-0.92)	0.95 (0.74-1.21)	1.04 (0.97-1.12)	0.04
Model 2	Reference	0.89 (0.69-1.14)	0.72 (0.56-0.93)	0.98 (0.76-1.25)	1.11 (1.02-1.20)	< 0.01
Model 3	Reference	0.88 (0.69-1.13)	0.72 (0.56-0.92)	0.99 (0.77-1.26)	1.11 (1.02-1.21)	< 0.01
Model 4	Reference	0.88 (0.69-1.12)	0.70 (0.54-0.91)	0.97 (0.76-1.25)	1.10 (1.01-1.20)	< 0.01
Cardiovascular mortality
Model 1	Reference	1.30 (0.81-2.09)	0.65 (0.39-1.07)	0.96 (0.62-1.49)	1.04 (0.91-1.19)	0.05
Model 2	Reference	1.19 (0.76-1.87)	0.66 (0.41-1.07)	0.98 (0.64-1.51)	1.12 (0.97-1.29)	< 0.01
Model 3	Reference	1.20 (0.77-1.88)	0.67 (0.42-1.08)	0.98 (0.64-1.50)	1.11 (0.97-1.28)	< 0.01
Model 4	Reference	1.21 (0.77-1.90)	0.69 (0.43-1.13)	0.98 (0.64-1.52)	1.10 (0.96-1.26)	< 0.01

Model 1: No adjustment; Model 2: Adjusted for age, gender, ethnicity, body mass index (BMI), poverty-income ratio, education, survey period; Model 3: Adjusted for age, gender, ethnicity, BMI, poverty-income ratio, education, smoking status, alcohol consumption, survey period; Model 4: Adjusted for age, gender, ethnicity, BMI, poverty-income ratio, education, smoking status, alcohol consumption, survey period, hypercholesterolemia, hypertension, heart failure, coronary heart disease, and cancer.

Table 5 Sensitivity analysis of remnant cholesterol and all-cause and cardiovascular mortality after further adjusting serum triglycerides

	Hazard ratio (95%CI)
	Q1	Q2	Q3	Q4	Per SD	P value
All-cause mortality
Model 4	Reference	1.30 (0.81-2.09)	0.65 (0.39-1.07)	0.96 (0.62-1.49)	1.04 (0.91-1.19)	< 0.01

Model 4: Adjusted for age, gender, ethnicity, body mass index, poverty-income ratio, education, smoking status, alcohol consumption, survey period, hypercholesterolemia, hypertension, heart failure, coronary heart disease, and cancer.

Table 6 Sensitivity analysis of remnant cholesterol and all-cause and cardiovascular mortality after adjusting for lipid-lowering drug and anti-hypertensive drug

	Hazard ratio (95%CI)
	Q1	Q2	Q3	Q4	Per SD	P value
All-cause mortality
Model 6	Reference	1.08 (0.70-1.65)	0.65 (0.41-1.03)	0.98 (0.66-1.47)	1.37 (1.13-1.65)	0.05

Model 6: Adjusted for age, gender, ethnicity, body mass index, poverty-income ratio, education, smoking status, alcohol consumption, survey period, hypercholesterolemia, hypertension, heart failure, coronary heart disease, cancer, lipid-lowering drug and anti-hypertensive drug.

Table 7 Sensitivity analysis of remnant cholesterol and cardiovascular mortality after accounting for all-cause death as a competing event by Fine and Gray competing risks model

	Hazard ratio (95%CI)
	Q1	Q2	Q3	Q4	Per SD	P value
Cardiovascular mortality
Model 4	Reference	1.14 (0.74-1.77)	0.73 (0.46-1.16)	1.03 (0.69-1.55)	1.12 (0.99-1.28)	< 0.01

Model 4: Adjusted for age, gender, ethnicity, body mass index, poverty-income ratio, education, smoking status, alcohol consumption, survey period, hypercholesterolemia, hypertension, heart failure, coronary heart disease, and cancer.