Carotid Artery Stiffness Accurately Predicts White Matter Hyperintensity Volume 20 Years Later: A Secondary Analysis of the Atherosclerosis Risk in the Community Study

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FIGURE.
Mean values of WMH and TBV in the quintiles of carotid sonography measurements. For strain, distensibility, and compliance, the higher quintiles reflect less carotid stiffness. For the Stiffness index and pressure-strain elastic modulus, the higher quintiles reflect more carotid stiffness.

Table 1:

Baseline demographics at visit 2 and P values for association with concurrent carotid distensibility measurement^a

Variable	Full Cohort (n = 1402)	P Value for Association with Carotid Distensibility
Age (mean)	55.6 ± 5.3	<.001^d
Male (No.) (%)	571, 40.7	.214
Caucasian (No.) (%)	1,023, 73.0	.007^d
Hypertension (No.) (%) (n = 1396)	280, 20.1	<.001^d
Diabetes (No.) (%) (n = 1398)	71, 5.1	.265
History of myocardial infarction (No.) (%)	26, 1.9	.898
History of stroke (No.) (%)	10, 0.7	.602
Prevalent coronary heart disease (No.) (%)	16, 1.2	.297
Current cigarette smoking (No.) (%) (n = 1400)	206, 14.7	<.001^d
Current alcohol consumption (No.) (%) (n = 1400)	846, 60.4	.009^d
Body mass index (mean)	27.1 ± 4.6	<.001^d
LDL cholesterol (mean) (mg/dL) (n = 1376)	131.2 ± 35.0	.493
HDL cholesterol (mean) (mg/dL) (n = 1328)	49.3 ± 16.7	.067
Fasting blood glucose (mean) (mmol/L)	5.9 ± 1.6	.077
Antihypertensive in last 2 weeks (No.) (%) (n = 1397)	248, 17.8	<.001^d
Aspirin in last 2 weeks (No.) (%) (n = 1400)	632, 45.1	.369
Statin in last 2 weeks (No.) (%) (n = 1400)	29, 2.1	.651
Plaque in either carotid on ultrasound (No.) (%) (n = 1392)	310, 22.3	.270
Voltage of left ventricular leads on ECG (mean) (n = 1391)	1174.2 ± 525.4	<.001^d
WMH volume (mean) (mL)	17.5 ± 17.4
Total brain volume (mean) (mL) (n = 1397)^b	1015.8 ± 109.4
Ratio of WMH/TBV (mean) (%) (n = 1397)^b	1.7 ± 1.7
Mean systolic blood pressure (mm Hg)^c	135.0 ± 12.4
Mean systolic SD (mm Hg)^c	15.8 ± 4.2
Mean number of blood pressure readings^c	23.3 ± 3.1
Years between carotid ultrasound and MRI (mean)	21.5 ± 0.9

Note:—ECG indicates electrocardiography; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
↵a Association tested with linear regression for continuous variables and Student t test for categoric variables.
↵b Derived from visit 5 MRI.
↵c Derived from all available blood pressure readings from visit 2 through visit 5.
↵d Significant.

Table 2:

Linear regression fit to WMHv and TBV on the visit 5 MRI

Ultrasound Variable	Model 1^a	Model 2^b	Model 3^c
WMHv (mL)
Strain
β	−1.2	−0.7	−0.9
95% CI	(−1.7 to −0.8)	(−1.2 to −0.2)	(−1.4 to −0.4)
P value	<.001	.007	.001
Distensibility
β	−1.9	−1.6	−1.7
95% CI	(−3.2 to −0.6)	(−2.9 to −0.3)	(−3.0 to −0.4)
P value	.003	.019	.009
Compliance
β	−0.1	−0.3	−0.2
95% CI	(−0.4–0.2)	(−0.6–0.1)	(−0.5–0.1)
P value	.355	.115	.127
Stiffness index
β	45.1	30.6	35.9
95% CI	(23.1–67.2)	(6.6–54.6)	(12.5–59.3)
P value	<.001	.012	.003
Pressure-strain elastic modulus
β	0.03	0.03	0.04
95% CI	(0.02–0.05)	(0.02–0.05)	(0.02–0.05)
P value	.001	<.001	<.001
TBV (mL)
Strain
β	0.1	0.7	0.3
95% CI	(−2.9–3.2)	(−1.7–3.1)	(−2.2–2.8)
P value	.940	.581	.820
Distensibility
β	4.1	4.4	2.8
95% CI	(−4.0–12.3)	(−1.7–10.4)	(−3.4–9.0)
P value	.319	.158	.382
Compliance
β	7.7	2.5	2.1
95% CI	(5.9–9.6)	(1.0–3.9)	(0.6–3.6)
P value	<.001	.001	.007
Stiffness index
β	−276.3	−72.7	−55.1
95% CI	(−417.7 to −135.9)	(−183.7–38.3)	(−170.6–60.3)
P value	<.001	.199	.349
Pressure-strain elastic modulus
β	−0.1	−0.1	−0.1
95% CI	(−0.2 to −0.01)	(−0.2–0.01)	(−0.1–0.03)
P value	.030	.070	.183

↵a Model 1: adjusted for systolic blood pressure mean between visit 2 and visit 5 (n = 1402 for WMH and n = 1397 for total brain volume).
↵b Model 2: WMH model adjusted for visit 2, patient age, sex, body mass index, HDL cholesterol, current smoking, history of hypertension (n = 1320). TBV model adjusted for patient age, sex, black race, fasting glucose, and current smoking (n = 1393).
↵c Model 3: WMH model adjusted for visit 3, patient age, current cigarette smoking, history of hypertension, and voltage of left ventricular leads on ECG (n = 1289). TBV model adjusted for patient age, sex, black race, diabetes, and HDL cholesterol level (n = 1296).