High-Density Lipoprotein Cholesterol and the Risk of First Ischemic Stroke in a Chinese Hypertensive Population

Figures & data

Table 1 Baseline Characteristics of Study Participants with First Ischemic Stroke and Age- and Sex-Matched Controls

	Control Subjects (n= 2463)	First Ischemic Stroke (n= 2463)	P value
Age, yrs	67.6 ± 9.4	67.6 ± 9.4	0.998
Male, no. (%)	1110 (45.1)	1110 (45.1)	1.000
SBP, mmHg	147.7 ± 20.8	153.1 ± 21.9	<0.001
DBP, mmHg	86.7 ± 13.1	90.0 ± 13.7	<0.001
BMI, kg/m^2	25.5 ± 3.7	26.0 ± 4.0	<0.001
Fasting glucose, mg/dL	6.0 ± 2.0	6.5 ± 2.5	<0.001
History of diabetes, yes, no. (%)	222 (9.0)	363 (14.7)	<0.001
TC, mg/dL	212.8 ± 46.5	213.2 ± 47.4	0.751
TG, mg/dL	129.0 ± 86.2	143.7 ± 96.0	<0.001
HDL-C, mg/dL	62.0 ± 15.6	59.6 ± 15.1	<0.001
LDL-C, mg/dL	126.1 ± 32.4	128.7 ± 32.7	0.004
Total homocysteine, μmol/L	13.5 ± 8.8	14.1 ± 7.8	0.009
≥15μmol/L, no. (%)	558 (22.7)	675 (27.4)	<0.001
Smoking status, no. (%)			0.051
Never	1786 (72.5)	1754 (71.2)
Former	196 (8.0)	168 (6.8)
Current	481 (19.5)	541 (22.0)
Alcohol consumption, no. (%)			0.001
Never	1785 (72.5)	1849 (75.1)
Former	89 (3.6)	120 (4.9)
Current	589 (23.9)	492 (20.0)
Antihypertensive drugs, yes, no. (%)	906 (36.8)	1193 (48.4)	<0.001
Glucose lowering drugs, yes, no. (%)	105 (4.3)	198 (8.0)	<0.001
eGFR, mL/min per 1.73 m^2	95.0 ± 13.8	93.9 ± 14.6	0.007

Table 2 Association of Fasting Serum Lipid Levels with Incident Risk of First Ischemic Stroke

	N	Cases (%)	Crude Model OR (95% CI)	P value	Adjusted Model* OR (95% CI)	P value
HDL-C^#, mg/dL
Continuous, Per SD	4926	2463 (50.0)	0.84 (0.79,0.89)	<0.001	0.91 (0.85,0.98)	0.014
Tertiles
T1 (<53.0)	1600	873 (54.6)	Ref		Ref
T2 (53.0–65.4)	1685	846 (50.2)	0.83 (0.72,0.95)	0.007	0.92 (0.79,1.08)	0.328
T3 (≥65.4)	1641	744 (45.3)	0.67 (0.58,0.77)	<0.001	0.82 (0.69,0.98)	0.030
P for trend				<0.001		0.029
Clinical cut-off
Males<40/Females<50	763	417 (54.7)	Ref		Ref
Males≥40/Females≥50	4163	2046 (49.1)	0.79 (0.67,0.92)	0.004	0.93 (0.77,1.13)	0.454
TG^†, mg/dL
Continuous, Per SD	4926	2463 (50.0)	1.20 (1.13,1.28)	<0.001	1.10 (1.02,1.17)	0.007
Tertiles
T1 (<89.5)	1628	738 (45.3)	Ref		Ref
T2 (89.5–140.8)	1647	810 (49.2)	1.18 (1.03,1.36)	0.017	1.06 (0.92,1.23)	0.405
T3 (≥140.8)	1651	915 (55.4)	1.55 (1.34,1.79)	<0.001	1.27 (1.09,1.49)	0.003
P for trend				<0.001		0.003
Clinical cut-off
<150	3480	1666 (47.9)	Ref		Ref
≥150	1446	797 (55.1)	1.36 (1.19,1.54)	<0.001	1.17 (1.02,1.34)	0.025
LDL-C^║, mg/dL
Continuous, Per SD	4926	2463 (50.0)	1.10 (1.04,1.17)	0.002	1.04 (0.97,1.12)	0.239
Tertiles
T1 (<111.4)	1647	769 (46.7)	Ref		Ref
T2 (111.4–138.1)	1653	827 (50.0)	1.17 (1.02,1.35)	0.027	1.10 (0.95,1.28)	0.203
T3 (≥138.1)	1626	867 (53.3)	1.36 (1.17,1.57)	<0.001	1.20 (1.02,1.42)	0.027
P for trend				<0.001		0.027
Clinical cut-off
<130	2825	1365 (48.3)	Ref		Ref
≥130	2101	1098 (52.3)	1.20 (1.06,1.35)	0.004	1.11 (0.97,1.27)	0.116
TC^‡, mg/dL
Continuous, Per SD	4926	2463 (50.0)	1.01 (0.95,1.08)	0.723	0.98 (0.91,1.05)	0.512
Tertiles
T1 (<190.6)	1648	817 (49.6)	Ref		Ref
T2 (190.6–229.3)	1637	824 (50.3)	1.03 (0.90,1.19)	0.648	1.06 (0.91,1.23)	0.441
T3 (≥229.3)	1641	822 (50.1)	1.03 (0.88,1.19)	0.742	0.96 (0.81,1.13)	0.606
P for trend				0.743		0.603
Clinical cut-off
<200	2077	1034 (49.8)	Ref		Ref
≥200	2849	1429 (50.2)	1.02 (0.90,1.15)	0.781	0.98 (0.86,1.12)	0.769

Notes: Adjusted model*: adjusted for body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, smoking status, alcohol consumption, use of antihypertensive drugs, and glucose-lowering drugs, total homocysteine (tHcy), and estimated glomerular filtration rate (eGFR). ^#For HDL, adjusted for all the above variables plus TG and LDL-C. ^†For TG, adjusted for all the above variables plus TC. ^‡For TC, adjusted for all the above variables plus TG. ^||For LDL, adjusted for all the above variables plus HDL-C and TG.

Figure 1 Smoothing curves for the association of first IS with HDL-C, TG, LDL-C and TC. All the panels adjusted for body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, smoking status, alcohol consumption, use of antihypertensive drugs, and glucose-lowering drugs, total homocysteine (tHcy), and estimated glomerular filtration rate (eGFR). HDL-C (A): adjusted for all the above variables plus TG and LDL-C.TG (B): adjusted for all the above variables plus TC.LDL-C (C): adjusted for all the above variables plus HDL-C and TG.TC (D): adjusted for all the above variables plus TG.

Table 3 Combined Association of HDL-C and LDL-C Tertiles with First IS

HDL-C Tertiles mg/dL	LDL-C Tertiles mg/dL	N (%)	Crude OR (95% CI)	Adjusted OR* (95% CI)	P-value
T1 (≥65.4)	<111.4	180 (40.8)	Ref	Ref
	111.4 −138.1	236 (45.8)	1.22 (0.94,1.58)	1.10 (0.84,1.45)	0.483
	≥138.1	328 (47.9)	1.32 (1.03,1.69)	1.10 (0.85,1.43)	0.479
T2 (53.0–65.4)	<111.4	228 (46.5)	1.26 (0.97,1.64)	1.12 (0.85,1.47)	0.425
	111.4 −138.1	302 (49.7)	1.45 (1.13,1.86)	1.21 (0.92,1.57)	0.169
	≥138.1	316 (53.8)	1.69 (1.31,2.17)	1.27 (0.97,1.67)	0.088
T3 (<53.0)	<111.4	361 (50.4)	1.45 (1.14,1.85)	1.16 (0.89,1.51)	0.278
	111.4 −138.1	289 (54.5)	1.75 (1.35,2.27)	1.25 (0.94,1.67)	0.123
	≥138.1	223 (63.0)	2.47 (1.85,3.30)	1.66 (1.19,2.31)	0.003

Notes: *Adjusted for body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, smoking status, alcohol consumption, use of antihypertensive drugs, and glucose-lowering drugs, total homocysteine (tHcy), and estimated glomerular filtration rate (eGFR), and TG (continuous).

Figure 2 Association of LDL-C or TG with first IS stratified by HDL-C levels. (A) Adjusted for body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, smoking status, alcohol consumption, use of antihypertensive drugs, and glucose-lowering drugs, total homocysteine (tHcy), and estimated glomerular filtration rate (eGFR) and TG (continuous). (B) Adjusted for body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, smoking status, alcohol consumption, use of antihypertensive drugs, and glucose-lowering drugs, total homocysteine (tHcy), and estimated glomerular filtration rate (eGFR) and LDL-C (continuous).

Table 4 Combined Association of HDL-C and TG Tertiles with First IS

HDL-C Tertiles mg/dL	TG Tertiles mg/dL	N (%)	Crude OR (95% CI)	Adjusted OR^# (95% CI)	P-value
T1 (≥65.4)	<89.5	346 (42.5)	Ref	Ref
	89.5 −140.8	266 (46.1)	1.16 (0.93,1.44)	1.00 (0.79,1.26)	0.992
	≥140.8	132 (53.0)	1.53 (1.14,2.04)	1.23 (0.89,1.69)	0.205
T2 (53.0–65.4)	<89.5	255 (47.0)	1.22 (0.98,1.51)	1.10 (0.87,1.40)	0.410
	89.5 −140.8	314 (51.0)	1.43 (1.16,1.77)	1.23 (0.98,1.53)	0.074
	≥140.8	277 (52.6)	1.53 (1.23,1.92)	1.21 (0.95,1.54)	0.122
T3 (<53.0)	<89.5	137 (50.6)	1.38 (1.05,1.83)	1.18 (0.86,1.60)	0.302
	89.5 −140.8	230 (50.7)	1.39 (1.10,1.75)	1.13 (0.87,1.46)	0.356
	≥140.8	506 (57.8)	1.94 (1.59,2.37)	1.47 (1.17,1.84)	<0.001

Notes: ^#Adjusted for body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, smoking status, alcohol consumption, use of antihypertensive drugs, and glucose-lowering drugs, total homocysteine (tHcy), and estimated glomerular filtration rate (eGFR), and LDL-C (continuous).

Data Availability

The study protocol and statistical analysis plan of this article are available from the corresponding author upon reasonable request. All data requests should first be submitted to Gang Li for consideration. Access to available fully anonymized data may be granted 12 months after publication. Requesters will be asked to complete an application form detailing specific requirements, rationale, and proposed use. A data-sharing agreement must be signed. Requested data will be made available, along with supporting documentation (eg, data dictionary) on a secure server.