Association Between Lipid Profile and Risk of Incident Systemic Sclerosis: A Nationwide Population-Based Study

Figures & data

Figure 1 Flow diagram of the study population.

Abbreviations: NHIS, National Health Insurance Service; SSc, systemic sclerosis.

Table 1 Comparison of Baseline Characteristics According to the Development of Systemic Sclerosis During Follow Up Stratified by Sex

	Male		P value	Female		P value
	SSc Not Developed (N = 5,398,644)	SSc Developed (N = 237)		SSc Not Developed (N = 4,494,997)	SSc Developed (N = 1118)
Age, years	46.0±13.6	52.4±12.0	<0.001	48.8±14.5	51.9±10.4	<0.001
Age groups, years, n (%)			<0.001			<0.001
20–39	1,966,904 (36.4)	34 (14.4)		1,091,948 (24.3)	95 (8.5)
40–64	2,827,552 (52.4)	161 (67.9)		2,702,784 (60.1)	888 (79.4)
≥65	604,188 (11.2)	42 (17.7)		700,265 (15.6)	135 (12.1)
BMI, kg/m^2	24.1±3.1	24.2±3.2	0.550	23.2±3.3	23.3±3.1	0.468
BMI groups, kg/m^2, n (%)			0.773			0.133
<18.5	121,964 (2.3)	3 (1.3)		245,247 (5.5)	46 (4.1)
<23	1,818,978 (33.7)	81 (34.2)		2,043,654 (45.5)	511 (45.7)
<25	1,454,168 (26.9)	68 (28.7)		981,644 (21.8)	267 (23.9)
<30	1,808,069 (33.5)	75 (31.7)		1,068,896 (23.8)	262 (23.4)
≥30	195,465 (3.6)	10 (4.2)		155,556 (3.5)	32 (2.9)
Region, urban, n (%)	2,439,313 (45.2)	92 (38.8)	0.049	2,079,215 (46.3)	526 (47.1)	0.595
Income, n (%)			0.009			0.583
Q1	811,491 (15.0)	50 (21.1)		1,117,976 (24.9)	286 (25.6)
Q2	1,183,173 (21.9)	43 (18.1)		1,084,827 (24.1)	251 (22.5)
Q3	1,631,664 (30.2)	60 (25.3)		1,077,183 (24.0)	253 (22.6)
Q4	1,882,316 (23.8)	84 (35.4)		1,215,011 (27.0)	328 (29.3)
Smoking, n (%)			0.043			0.220
Non-smoker	1,641,784 (30.4)	62 (26.2)		4,257,643 (94.7)	1,070 (95.7)
Ex-smoker	1,336,898 (24.8)	75 (31.7)		82,192 (1.8)	20 (1.8)
Current smoker	2,419,962 (44.8)	100 (42.2)		155,162 (3.5)	28 (2.5)
Drinking, n (%)			0.142			<0.001
Non-drinker	1,754,296 (32.5)	85 (35.9)		3,364,902 (74.9)	912 (81.6)
Mild drinker	2,908,676 (53.9)	113 (47.7)		1,080,529 (24.0)	197 (17.6)
Heavy drinker	735,672 (13.6)	39 (16.5)		49,566 (1.1)	9 (0.8)
Regular exercise, n (%)	1,075,428 (19.9)	61 (25.7)	0.025	701,803 (15.6)	163 (14.6)	0.341
Hypertension, n (%)	1,506,642 (27.9)	88 (37.1)	0.002	1,184,248 (26.4)	316 (28.3)	0.145
Type 2 diabetes, n (%)	535,638 (9.9)	32 (13.5)	0.065	335,017 (7.5)	87 (7.8)	0.676
Dyslipidaemia, n (%)	900,085 (16.7)	54 (22.8)	0.012	903,262 (20.1)	212 (19.0)	0.345
Lipid-lowering agents, n (%)	437,888 (8.1)	37 (15.6)	<0.001	521,220 (11.6)	142 (12.7)	0.248
CKD, n (%)	331,633 (6.1)	16 (6.8)	0.697	356,275 (7.9)	95 (8.5)	0.480
Height, cm	170.0±6.4	168.2±6.5	<0.001	156.5±6.2	156.1±5.8	0.055
Weight, kg	69.8±10.5	68.7±10.6	0.099	56.7±8.4	56.7±8.2	0.990
Waist Circumference, cm	83.6±7.8	84.5±8.1	0.062	76.3±8.9	76.3±8.1	0.748
Systolic BP, mmHg	124.7±14.1	124.5±14.0	0.861	119.8±15.7	118.3±15.7	0.001
Diastolic BP, mmHg	78.0±9.7	77.8±9.9	0.747	74.3±10.1	73.6±10.0	0.016
Fasting glucose, mg/dL	99.2±25.8	101.9±31.7	0.098	95.1±21.2	94.4±19.1	0.225
Estimated GFR, mL/min/1.73m^2	87.9±51.5	86.7±25.1	0.729	87.2±36.5	84.0±28.2	0.004
TC, mg/dL	194.2±36.1	187.7±35.2	0.005	195.9±37.6	193.7±37.9	0.051
HDL-C, mg/dL	53.1±25.3	51.7±17.5	0.381	59.7±30.5	56.4±30.6	<0.001
LDL-C, mg/dL	112.0±38.8	104.7±34.9	0.004	115.5±38.3	114.8±34.3	0.550
Triglyceride^a, mg/dL	128.6 (128.6–128.7)	133.8 (124.3–144.1)	0.286	95.9 (95.9–96.0)	102.4 (99.2–105.6)	<0.001

Note: ^aGeometric mean (95% confidence interval).

Abbreviations: BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; GFR, glomerular filtration rate; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; SSc, systemic sclerosis; TC, total cholesterol.

Table 2 Incidence of Systemic Sclerosis According to Lipid Profile in Continuous Variable

	N	SSc	Duration (pyrs)	IR/100,000 pyrs	Model 1	P value	Model 2	P value	Model 3	P value	Model 4	P value
TC, per 10 mg/dL	9,894,996	1,335	90,710,452.37	1.47	0.982 (0.967–0.996)	0.016	0.959 (0.945–0.974)	<0.001	0.959 (0.945–0.974)	<0.001	0.959 (0.945–0.974)	<0.001
HDL-C, per 10 mg/dL					0.992 (0.968–1.014)	0.497	0.942 (0.908–0.978)	0.001	0.936 (0.900–0.974)	0.001	0.936 (0.900–0.974)	0.001
LDL-C, per 10 mg/dL					0.995 (0.981–1.010)	0.500	0.968 (0.953–0.984)	<0.001	0.968 (0.952–0.983)	<0.001	0.968 (0.952–0.983)	<0.001
Triglyceride, per 10 mg/dL					0.989 (0.982–0.995)	0.001	1.002 (0.996–1.009)	0.546	1.004 (0.998–1.011)	0.227	1.004 (0.998–1.011)	0.227

Notes: Model 1: Crude model. Model 2: Adjusted for age and sex. Model 3: Adjusted for age, sex, BMI, residence, income, smoking status, alcohol consumption, physical activity, hypertension, type 2 diabetes, and CKD. Model 4: Adjusted for age, sex, BMI, residence, income, smoking status, alcohol consumption, physical activity, hypertension, type 2 diabetes, CKD, and lipid-lowering agents.

Abbreviations: BMI, body mass index; CKD, chronic kidney disease; HDL-C, high-density lipoprotein cholesterol; IR, incidence rate; LDL-C, low-density lipoprotein cholesterol; pyrs, person-years; SSc, systemic sclerosis; TC, total cholesterol.

Figure 2 Cumulative incidence of SSc over time.

Abbreviation: SSc, systemic sclerosis.

Figure 3 Spline curves showing the relationship between (A) TC, (B) HDL-C, (C) LDL-C, (D) triglyceride and risk of incident SSc.

Abbreviations: TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; HR, hazard ratio; CI, confidence interval; SSc, systemic sclerosis.

Table 3 Subgroup Analysis of the Association Between Levels of HDL-C and Incidence of Systemic Sclerosis

	Subgroup	HDL-C	N	SSc	Duration (pyrs)	IR /100,000 pyrs	HR^a (95% CI)	p for interaction
Age groups, years
	<40	Q1	712,748	32	6,627,853.72	0.48	1 (Ref.)	0.298
		Q2-4	2,346,233	97	21,799,687.03	0.45	0.567 (0.379–0.848)
	40–64	Q1	1,471,779	277	13,591,301.46	2.04	1 (Ref.)
		Q2-4	4,059,606	772	37,571,670.57	2.05	0.759 (0.661–0.873)
	≥65	Q1	415,308	58	3,484,831.92	1.66	1 (Ref.)
		Q2-4	889,322	119	7,635,107.68	1.56	0.843 (0.615–1.155)
Sex
	Male	Q1	1,789,377	80	16,273,744.73	0.49	1 (Ref.)	0.024
		Q2-4	3,609,504	157	32,931,033.66	0.48	0.989 (0.755–1.297)
	Female	Q1	810,458	287	7,430,242.36	3.86	1 (Ref.)
		Q2-4	3,685,657	831	34,075,431.62	2.44	0.699 (0.611–0.802)
Obesity
	No	Q1	1,452,497	248	13,180,804.70	1.88	1 (Ref.)	0.032
		Q2-4	5,214,134	728	47,862,090.39	1.52	0.675 (0.583–0.782)
	Yes	Q1	1,147,338	119	10,523,182.40	1.13	1 (Ref.)
		Q2-4	2,081,027	260	19,144,374.89	1.36	0.899 (0.723–1.119)
Abdominal obesity
	No	Q1	1,874,232	270	17,113,551.75	1.58	1 (Ref.)	0.613
		Q2-4	6,069,804	835	55,825,679.67	1.50	0.757 (0.658–0.871)
	Yes	Q1	725,603	97	6,590,435.35	1.47	1 (Ref.)
		Q2-4	1,225,357	153	11,180,785.61	1.37	0.703 (0.544–0.907)
Hypertension
	No	Q1	1,753,573	241	16,164,971.59	1.49	1 (Ref.)	0.171
		Q2-4	5,450,129	710	50,388,785.88	1.41	0.708 (0.611–0.822)
	Yes	Q1	846,262	126	7,539,015.51	1.67	1 (Ref.)
		Q2-4	1,845,032	278	16,617,679.40	1.67	0.847 (0.686–1.047)
Type 2 diabetes
	No	Q1	2,274,635	330	20,852,214.90	1.58	1 (Ref.)	0.042
		Q2-4	6,749,587	906	62,167,331.47	1.46	0.720 (0.633–0.820)
	Yes	Q1	325,200	37	2,851,772.20	1.30	1 (Ref.)
		Q2-4	545,574	82	4,839,133.81	1.69	1.100 (0.746–1.621)

Notes: ^aAdjusted for age, sex, BMI, residence, income, smoking status, alcohol consumption, physical activity, hypertension, type 2 diabetes, CKD, and lipid-lowering agents.

Abbreviations: BMI, body mass index; CI, confidence interval; CKD, chronic kidney disease; HDL-C, high-density lipoprotein cholesterol; HR, hazard ratio; IR, incidence rate; pyrs, person-years; SSc, systemic sclerosis.

Figure 4 Summary of the present study.

Abbreviations: TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; HR, hazard ratio; CI, confidence interval.