CKD, Plasma Lipids, and Common Carotid Intima-Media Thickness: Results from the Multi-Ethnic Study of Atherosclerosis

Julio A. Lamprea-Montealegre; Brad C. Astor; Robin L. McClelland; Ian H. de Boer; Gregory L. Burke; Christopher T. Sibley; Daniel O’Leary; A. Richey Sharrett; Moyses Szklo

doi:10.2215/CJN.02090212

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Figure 1.
Crude and adjusted estimates of the association between LDL cholesterol and IMT (in micrometers). Restricted cubic spline model with knots at the 25th, 50th, and 75th percentiles for LDL cholesterol. The shaded area is the 95% confidence interval for the adjusted restricted cubic spline model. Adjusted for age (years), sex, race/ethnicity, lipid-lowering medication use, presence of diabetes mellitus, presence of hypertension, log-transformed body mass index, log-transformed urinary albumin/creatinine ratio, smoking status (current, former, never smoker), log-transformed triglycerides, log-transformed HDL cholesterol, log-transformed high-sensitivity C-reactive protein, and log-transformed IL-6. eGFR, estimated GFR; IMT, intima-media thickness.
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Figure 2.
Crude and adjusted estimates of the association between small-dense LDL and IMT (in micrometers). Restricted cubic spline model with knots at the 25th, 50th, and 75th percentiles for small-dense LDL. The shaded area is the 95% confidence interval for the adjusted restricted cubic spline model. Adjusted for age (years), sex, race/ethnicity, lipid-lowering medication use, presence of diabetes mellitus, presence of hypertension, log-transformed body mass index, log-transformed urinary albumin/creatinine ratio, smoking status (current, former, never smoker), log-transformed triglycerides, log-transformed HDL cholesterol, large LDL, log-transformed intermediate density lipoprotein, log-transformed high-sensitivity C-reactive protein, and log-transformed IL-6. eGFR, estimated GFR; IMT, intima-media thickness; Sd-LDL, small-dense LDL.
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Figure 3.
Adjusted estimates of the association between LDL cholesterol and IMT (in micrometers) according to level of kidney function and presence of inflammation. Restricted cubic spline model with knots at the 25th, 50th, and 75th percentiles for LDL cholesterol. The shaded area is the 95% confidence interval for the adjusted restricted cubic spline model. Adjusted for age (years), sex, race/ethnicity, lipid-lowering medication use, presence of diabetes mellitus, presence of hypertension, log-transformed body mass index, log-transformed urinary albumin/creatinine ratio, smoking status (current, former, never smoker), log-transformed triglycerides, and log-transformed HDL cholesterol. Inflammation is defined as the ≥90th percentile of either IL-6 (≥3 pg/ml) or high-sensitivity C-reactive protein (≥9 mg/L). eGFR, estimated GFR; IMT, intima-media thickness.

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Table 1.

Demographic and clinical characteristics of 6572 participants in the MESA cohort by levels of kidney function

Characteristic	eGFR ≥60 (n=5719)	eGFR 45–59 (n=709)	eGFR <45 (n=144)	P for Difference^a
Male sex	2721 (48)	311 (44)	66 (46)	0.17
Race				<0.001
Black	1600 (28)	168 (24)	45 (32)
Chinese	689 (12)	80 (11)	14 (10)
Hispanic	1294 (23)	111 (16)	30 (21)
White	2136 (37)	350 (49)	55 (38)
Age (yr)	60 (53–68)	71 (65–77)	75 (68–79)	<0.001
Body mass index (kg/m²)	27.5 (24.4–31.1)	27.6 (24.7–31.2)	28.3 (25.2–31.9)	0.14
Current smoker	782 (14)	45 (6)	10 (7)	<0.001
Diabetes	679 (12)	95 (13)	35 (24)	<0.001
Biguanide use	280 (5)	41 (6)	4 (3)
Sulfonylurea use	297 (5)	46 (6)	13 (9)
Hypertension	2353 (41)	453 (64)	123 (85)	<0.001
Angiotensin converting enzyme inhibitor use	168 (3)	41 (6)	15 (10)
β-blocker use	447 (8)	103 (15)	29 (20)
Use of any lipid-lowering medication	836 (15)	176 (25)	41 (29)	<0.001
Statin use	771 (13)	162 (23)	37 (26)	<0.001
Lipid levels (mg/dl)
Total cholesterol	192 (170–215)	192 (170–216)	191 (169–216)	0.95
LDL-C	116 (96–136)	113 (95–137)	113 (93–135)	0.30
HDL-C	48 (41–59)	50 (41–60)	44 (37–57)	<0.001
Triglycerides	109 (77–157)	116 (81–162)	122 (91–189)	<0.001
Lipoprotein particle concentration (nmol/L)
Small-dense LDL	518 (113–798)	489 (105–776)	563 (122–817)	0.06
Large LDL	601 (426–764)	596 (414–775)	518 (380–692)	0.03
IDL	102 (51–175)	112 (53–175)	117 (51–188)	0.14
High-sensitivity C-reactive protein (mg/L)	1.8 (0.8–4.2)	2.1 (1.0–4.5)	2.6 (1.3–5.7)	<0.001
IL-6 (pg/ml)	1.2 (0.7–1.8)	1.4 (1.0–2.1)	1.5 (1.1–2.2)	<0.001
Urinary albumin/creatinine ratio (mg/g)	5.1 (3.3–10.1)	6.2 (3.6–14.8)	16.4 (4.5–107.8)	<0.001
Intima-media thickness (μm)	830 (730–960)	910 (800–1040)	940 (830–1060)	<0.001

Data are n (%) or median (interquartile range). MESA, Multi-Ethnic Study of Atherosclerosis; eGFR, estimated GFR (ml/min per 1.73 m²); LDL-C, LDL cholesterol; HDL-C, HDL cholesterol; IDL, intermediate density lipoprotein.
↵a P values based on Fisher’s exact test and the Kruskal–Wallis test for categorical and continuous variables, respectively.

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Table 2.

Adjusted estimates and 95% confidence intervals of the difference in common carotid artery intima-media thickness (in micrometers) per specified differences in lipid particle concentrations, by level of kidney function

Lipid Particle	eGFR ≥60 (n=5719)	eGFR <60 (n=853)	P for Interaction^a
Total cholesterol per 10 mg/dl^b			0.01
<200 mg/dl	2.97 (0.71, 5.23)	−4.89 (−12.98, 3.20)
≥200 mg/dl	4.79 (2.40, 7.18)	13.13 (4.82, 21.42)
LDL-C per 10 mg/dl^c			0.01
<130 mg/dl	4.65 (2.27, 7.04)	−2.53 (−11.46, 6.09)
≥130 mg/dl	4.76 (2.05, 7.47)	15.91 (6.34, 25.49)
Log HDL-C	−21.41 (−41.00, −1.57)	−58.49 (−126.61, 9.63)	0.10
Log triglycerides	4.65 (−5.41, 14.72)	−2.58 (−38.97, 33.82)	0.42
NMR lipids
Small-dense LDL per 100 nmol/L	4.83 (3.16, 6.50)	7.48 (1.45, 13.50)	0.12
Large-dense LDL per 100 nmol/L	6.21 (4.08, 8.34)	12.18 (4.51, 19.86)	0.81
Log IDL	0.53 (−3.59, 4.65)	2.99 (−12.88, 18.86)	0.78

Adjusted for age (years), sex, race/ethnicity, lipid-lowering medication use, presence of diabetes mellitus, presence of hypertension, log-transformed body mass index, log-transformed urinary albumin/creatinine ratio, smoking status (current, former, never smoker), log-transformed high-sensitivity C-reactive protein, and log-transformed IL-6. eGFR, estimated GFR (ml/min per 1.73 m²); LDL-C, LDL cholesterol; HDL-C, HDL cholesterol; NMR, nuclear magnetic resonance; IDL, intermediate density lipoprotein.
↵a P values testing for the null hypothesis that all slopes across eGFR strata are identical in linear spline models.
↵b Continuous estimates presented before and after a linear spline knot at 200 mg/dl for eGFR ≥60 (<200, n=3397; ≥200, n=2322) and for eGFR <60 (<200, n=513; ≥200, n=340).
↵c Continuous estimates presented before and after a linear spline knot at 130 mg/dl for eGFR ≥60 (<130, n=3851; ≥130, n=1868) and for eGFR <60(<130, n=596; ≥130, n=257).

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Table 3.

Lipid Particle	eGFR ≥60 (n=5719)^a		P^b	eGFR<60 (n=853)^c		P^b
Lipid Particle	No Inflammation (n=4726)	Inflammation (n=993)	P^b	No Inflammation (n=670)	Inflammation (n=183)	P^b
Total cholesterol per 10 mg/dl			0.28			<0.01
<200 mg/dl	2.51 (0.02, 5.00)	5.71 (0.62, 10.81)		1.88 (−6.35, 10.13)	−25.90 (−45.53, −6.48)
≥200 mg/dl	5.65 (3.08, 8.23)	1.23 (−5.01, 7.48)		8.35 (1.07, 16.60)	38.18 (13.87, 62.49)
LDL-C per 10 mg/dl			0.65			<0.001
<130 mg/dl	4.41 (1.77, 7.05)	5.17 (−0.52, 10.87)		4.52 (-4.32, 13.37)	−26.02 (−48.70, −3.35)
≥130 mg/dl	5.44 (2.52, 8.37)	2.04 (−5.47, 9.56)		10.07 (0.63, 19.51)	42.04 (10.58, 73.50)
Log HDL-C	−14.15 (−35.90, 7.60)	−52.95 (−102.09, −3.81)	0.20	−45.39 (−115.92, 25.13)	−42.72 (−240.86, 155.4)	0.96
Log triglycerides	3.02 (−7.99, 14.03)	10.69 (−14.94, 36.31)	0.48	9.70 (−27.83, 47.22)	−16.90 (−128.97, 95.19)	0.30
NMR lipids
Small-dense LDL per 100 nmol/L	5.08 (3.25, 6.92)	3.28 (−0.01, 7.39)	0.89	7.62 (1.42, 13.82)	3.10 (−14.59, 20.77)	0.61
Large LDL per 100 nmol/l	5.85 (3.50, 8.19)	7.45 (2.26, 12.63)	0.89	16.45 (8.32, 24.58)	0.60 (−19.86, 21.04)	0.18
Log IDL cholesterol	0.27 (−4.13, 4.67)	2.15 (−9.63, 13.94)	0.66	−4.88 (−20.91, 11.14)	43.66 (−7.64, 94.96)	0.38

Adjusted for age (years), sex, race/ethnicity, lipid-lowering medication use, presence of diabetes mellitus, presence of hypertension, log-transformed body mass index, log-transformed urinary albumin/creatinine ratio, and smoking status (current, former, never smoker). Inflammation is defined as the ≥90th percentile of either IL-6 (≥3 pg/ml) or high-sensitivity C-reactive protein (≥9 mg/L). eGFR, estimated GFR; LDL-C, LDL cholesterol; HDL-C, HDL cholesterol; IDL, intermediate density lipoprotein.
↵a No inflammation (<200, n=2775; ≥200, n=1951) and inflammation (<200, n=622; ≥200, n=371) for total cholesterol; no inflammation (<130, n=3142; ≥130, n=1584) and inflammation (<130, n=709; ≥130, n=284) for LDL-C.
↵b P values are for interaction.
↵c No inflammation (<200, n=391; ≥200, n=279) and inflammation (<200, n=122; ≥200, n=61) for total cholesterol; no inflammation (<130, n=462; ≥130, n=208) and inflammation (<130, n=134; ≥130, n=49) for LDL-C.