Plasma lipids and cerebral small vessel disease

Supplemental material

Contents:

  1. Supplemental tables
  2. Table e-1: Associations between lipid levels (TG, LDL-C, HDL-C) and vascular risk factors, circulating CRP and IL-6 levels, and APOEε4 or APOEε2 carrier status, 3C-Dijon Study and EVA Study
  3. Table e-2: Association between lipid levels and MRI-markers of small vessel disease, stratified by gender-specific median age or gender, 3C-Dijon Study, EVA Study
  4. Table e-3: Comparison between participants with MRI and without MRI, 3C-Dijon Study and EVA Study
  5. Supplemental references

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  1. Supplemental tables
  1. Table e-1: Associations between lipid levels (TG, LDL-C, HDL-C) and vascular risk factors, circulating CRP and IL-6 levels, and APOEε4 or APOEε2 carrier status, 3C-Dijon Study

Triglycerides / LDL-cholesterol / HDL-cholesterol
N / β±SE / p* / β±SE / p* / β±SE / p*
3C-Dijon Study / Age, years / 1842 / -0.0010±0.0023 / 0.66 / -0.0030±0.0046 / 0.51 / 0.0015±0.0023 / 0.50
Gender (women) / 1842 / -0.0726±0.0194 / 0.0002 / 0.1480±0.0390 / 0.0002 / 0.2785±0.0179 / <0.0001
TG, mmol/L / 1841 / 0.4719±0.0461 / <0.0001 / -0.4328±0.0190 / <0.0001
LDL-C, mmol/L / 1839 / 0.1147±0.0112 / <0.0001 / -0.0155±0.0107 / 0.15
HDL-C, mmol/L / 1842 / -0.5090±0.0223 / <0.0001 / -0.0735±0.0508 / 0.15
Systolic blood pressure, mmHg / 1842 / 0.0012±0.0004 / 0.0064 / -0.0004±0.0009 / 0.67 / -0.0007±0.0004 / 0.086
Blood-pressure lowering medication / 1842 / 0.0745±0.0194 / 0.0001 / -0.2123±0.0387 / <0.0001 / -0.0963±0.0178 / <0.0001
Smoking status / 1842 / 0.0779±0.0178 / <0.0001 / -0.0370±0.0359 / 0.30 / 0.0001±0.0165 / 0.99
Diabetes / 1837 / 0.1501±0.0339 / <0.0001 / -0.3896±0.0680 / <0.0001 / -0.1839±0.0311 / <0.0001
BMI, kg/m² / 1841 / 0.0293±0.0024 / <0.0001 / -0.0072±0.0050 / 0.15 / -0.0336±0.0021 / <0.0001
Lipid-lowering drug intake / 1842 / -0.0623±0.0201 / 0.0020 / -0.4129±0.0393 / <0.0001 / -0.0342±0.0186 / 0.065
APOEε4 carrier status (ε24 excluded) / 1808 / -0.0126±0.0236 / 0.59 / 0.1267±0.0472 / 0.0073 / -0.0100±0.0217 / 0.64
APOEε2 carrier status (ε24 excluded) / 1808 / 0.0772±0.0294 / 0.0087 / -0.4416±0.0579 / <0.0001 / 0.0533±0.0269 / 0.048
IL-6 (tertiles) / 1691 / 0.0309±0.0112 / 0.0059 / -0.0739±0.0225 / 0.0011 / -0.0415±0.0102 / <0.0001
CRP (tertiles) / 1691 / 0.0797±0.0129 / <0.0001 / 0.0260±0.0263 / 0.32 / -0.1160±0.0116 / <0.0001
EVA Study / Age, years / 766 / 0.0061± 0.0051 / 0.23 / -0.0197±0.0109 / 0.072 / 0.0024±0.0056 / 0.67
Gender (women) / 766 / -0.1172±0.0304 / 0.0001 / 0.2007±0.0654 / 0.0022 / 0.3082±0.0316 / 0.0001
TG, mmol/L / 765 / 0.3325±0.0767 / 0.0001 / -0.5148±0.0348 / 0.0001
LDL-C, mmol/L / 765 / 0.0723±0.0167 / 0.0001 / -0.0641±0.0183 / 0.0001
HDL-C, mmol/L / 765 / -0.4323±0.0292 / 0.0001 / -0.2477±0.0706 / 0.0001
Systolic blood pressure, mmHg / 766 / 0.0051±0.0008 / 0.0001 / 0.0005±0.0018 / 0.18 / -0.0047±0.0009 / 0.0009
Blood-pressure lowering medication / 766 / 0.1825±0.0319 / 0.0001 / -0.1768±0.0697 / 0.023 / -0.2024±0.0348 / 0.0001
Smoking status / 766 / -0.0127±0.0039 / 0.22 / 0.0221±0.0084 / 0.34 / 0.0205±0.0042 / 0.66
Diabetes / 766 / -0.0177±0.1331 / 0.96 / -0.3659±0.2851 / 0.15 / 0.0321±0.1454 / 0.79
BMI, kg/m² / 755 / 0.0377±0.0038 / 0.0001 / 0.0090±0.0088 / 0.14 / -0.0436±0.0042 / 0.0001
Lipid-lowering drug intake / 766 / -0.0260±0.0322 / 0.58 / -0.2997±0.0683 / 0.0001 / 0.0339±0.0351 / 0.63

APOE: apolipoprotein E; β: regression coefficient; BMI: body mass index; CRP: C-reactive protein; IL-6: Interleukin 6; lipid-lowering drug: statin and/or fibrate intake; SE: standard error; * age and gender-adjusted results, except for age and gender

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  1. Table e-2. Association between lipid levels and MRI-markers of small vessel disease, stratified by gender-specific median age or gender, 3C-Dijon Study, EVA Study

Triglycerides / LDL-cholesterol
N / β±SE/OR (95% CI) / p / β±SE/OR (95% CI) / p / β±SE/OR(95%CI) / p / β±SE/OR (95% CI) / p
<median age / >median age / <median age / >median age
3C, model adjusted for age and gender
WMHV* / 900 - 880 / 0.0746±0.0392 / 0.057 / 0.0974±0.0459 / 0.034 / -0.0285±0.0189 / 0.13 / -0.0120±0.0233 / 0.61
EXT-WMHV / 211/900 - 235/880 / 1.13 (0.77, 1.66) / 0.52 / 1.70 (1.18, 2.45) / 0.0040 / 0.82 (0.68, 0.999) / 0.049 / 0.97 (0.80, 1.16) / 0.71
Lacunes / 52/927 - 96/915 / 1.43 (0.72, 2.83) / 0.30 / 1.81 (1.09, 3.00) / 0.021 / 0.90 (0.63, 1.27) / 0.54 / 0.91 (0.69, 1.21) / 0.53
EVA, model adjusted for age and gender
WMHV* / 390 - 375 / 0.0553±0.0639 / 0.39 / 0.1487±0.0668 / 0.026 / -0.0088± 0.0286 / 0.76 / -0.0580± 0.0322 / 0.07
EXT-WMHV / 97/390 – 97/375 / 1.32 (0.74, 2.34) / 0.35 / 1.66 (0.97, 2.86) / 0.067 / 0.89 (0.68, 1.15) / 0.36 / 0.83 (0.63, 1.08) / 0.16
Lacunes / 40/386 – 45/376 / 1.54 (0.70, 3.39) / 0.28 / 1.60 (0.78, 3.29) / 0.20 / 0.91 (0.62, 1.33) / 0.62 / 1.09 (0.76, 1.56) / 0.63
men / women / men / women
3C, model adjusted for age
WMHV * / 703 - 1077 / 0.0624±0.0458 / 0.17 / 0.1063±0.0400 / 0.0079 / -0.0404±0.0250 / 0.11 / -0.0127±0.0186 / 0.49
EXT-WMHV / 200/703 – 246/1077 / 1.30 (0.89, 1.91) / 0.18 / 1.51 (1.06, 2.17) / 0.024 / 0.93 (0.75, 1.15) / 0.50 / 0.87 (0.73, 1.03) / 0.12
Lacunes / 91/731 – 57/1111 / 1.96 (1.17, 3.26) / 0.0099 / 1.25 (0.64, 2.44) / 0.52 / 0.81 (0.60, 1.08) / 0.15 / 1.05 (0.76, 1.44) / 0.77
EVA, model adjusted for age
WMHV * / 317 - 448 / 0.0744±0.0642 / 0.25 / 0.1370±0.0655 / 0.037 / 0.0566± 0.0368 / 0.12 / -0.0741± 0.0263 / 0.0051
EXT-WMHV / 80/317 – 114/448 / 1.19 (0.67, 2.11) / 0.55 / 1.82 (1.06, 3.12) / 0.031 / 1.20 (0.86, 1.66) / 0.28 / 0.73 (0.58, 0.92) / 0.0088
Lacunes / 49/313 – 36/449 / 2.10 (1.05, 4.17) / 0.035 / 1.03 (0.43, 2.44) / 0.95 / 1.03 (0.70, 1.52) / 0.89 / 0.99 (0.69, 1.41) / 0.94

β: regression coefficient; CI: confidence interval; EXT-WMHV: large WMHV (age-specific top quartile); OR: odds ratio;SE: standard error; Triglycerides: log-transformed triglycerides; WMHV: white matter hyperintensity volume at baseline, log transformed; * additionally adjusted for white matter mask volume

  1. Table e-3: Comparison between participants with and without MRI, 3C-Dijon Study and EVA Study

3C-Dijon Study, with MRI
N=1,842 / 3C-Dijon Study, without MRI
N=3.067 / p / EVA Study, with MRI
N=766 / EVA Study without MRI
N=602 / p
Age, years, mean ± standard error / 72.8±4.1 / 76.0±6.2 / <0.0001 / 68.8±3.0 / 69.1±3.0 / 0.20
Women, N (%) / 1111 (60.3) / 1919 (62.6) / 0.11 / 448 (58.5) / 355 (59.0) / 0.86
Triglycerides, mmol/L / 1.2±0.6 / 1.3±0.6† / 0.0017 / 1.3±0.6 / 1.3±0.6† / 0.30
Total cholesterol level, mmol/L / 5.7±0.9 / 5.8±1.0† / 0.0006 / 6.1±1.0 / 6.2±1.0† / 0.47
HDL-cholesterol level, mmol/L / 1.6±0.4 / 1.6±0.4† / 0.029 / 1.7±0.5 / 1.8±0.5† / 0.059
LDL-cholesterol level, mmol/L / 3.6±0.8 / 3.7±0.9† / <0.0001 / 3.8±0.9 / 3.8±0.8† / 0.57
Hypercholesterolemia / 1045 (56.7) / 1711 (60.2) / 0.018 / 510 (66.6) / 258 (65.1)† / 0.63
Lipid-loweringdrugintake / 618 (33.5) / 935 (30.5) / 0.026 / 251 (32.8) / 109 (27.1)† / 0.047
Systolicblood pressure / 148.6±22.4 / 150.9±23.5 / 0.0007 / 135.1±18.2 / 137.8±21.0† / 0.03
Diastolicblood pressure. / 84.8±11.5 / 83.6±11.9 / 0.0002 / 77.1±10.6 / 78.7±11.0† / 0.015
Hypertension / 1416 (76.9) / 2503 (81.8) / <0.0001 / 419 (54.7) / 234 (58.2)† / 0.25
Smoker / 719 (39.0) / 1159 (37.8) / 0.41 / 29 (10.2)* / 23 (15.6)* / 0.098
Diabetes / 158 (8.6) / 298 (10.7) / 0.018 / 10 (1.3) / 8 (2.0)† / 0.37
Prevalent stroke / 66 (3.6) / 193 (6.4) / <0.0001 / 10 (1.3) / 4 (1.0)† / 0.78‡
Prevalentdementia / 7 (0.4) / 61 (2.0) / <0.0001 / n.a / n.a / NA
WMHV, cm3 / 5.50±4.99 / NA / NA / 4.54±4.11 / NA / NA
WMHV, median (IQR) / 4.02 (2.76, 6.33) / NA / NA / 3.35 (2.19, 5.42) / NA / NA
Lacunes / 148 (8.0) / NA / NA / 82 (10.7) / NA / NA

Values are mean±standard error or N (%). n.a.: not available; WMHV: white matter hyperintensity volume; Diabetes: fasting blood glucose ≥ 7mmol/L or use of andiabetic drugs or medical history of diabetes; Hypercholesterolemia: total cholesterol >=6.2mmol/L or lipid-lowering drug intake; Hypertension: systolic blood pressure ≥140mmHg, or diastolic blood pressure ≥90mmHg, or use of antihypertensive drugs; IQR: interquartile range; NA: not applicable; Smoker: ever smoker for the 3C-Dijon study and current smoker for the EVA study; * >62% undetermined; † >10% missing data; ‡ Fisher’s exact test;

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  1. Supplemental references

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e8.Smith EE, Nandigam KR, Chen YW, et al. MRI markers of small vessel disease in lobar and deep hemispheric intracerebral hemorrhage. Stroke 2010;41:1933-1938.

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