http://www.rjh.com.cnhttp://www.rjh.com.cn

Yan Li MD PhD

Shanghai Institute of Hypertension

Sublingual Microcirculation

——Characteristics and Determinants in

Chinese and Flemish Populations

Hypertension and Microcirculation

Apoptosis in endothelial cells

Hypertension

Impaired

vasodilation

…

Functional rarefaction

Structural rarefaction

The glycocalyx is a gel-like layer about 0.5 μm thick covering the endothelium. It serves as a physical

barrier and plays an important role in vascular hemeostasis.

Vascular Glycocalyx

Handheld Video Capillary Microscope (KK Research Technology, UK) interfaced with a computer running the

GlycoCheck software (GlycoCheck BV, Maastricht, The Netherlands).

Sublingual Capillary Microscopy

and GlycoCheck

GlycoCheck Measurement 1

― Capillary Density

GlycoCheck Measurement 1

― Capillary Density

Total density (RBC filling >0%)

no segments / mm2

Perfused density (RBC filling ≥50%)

Perfused-to-total density ratio

0

.4

m

m

GlycoCheck Measurements 2

― Perfused Boundary Region (PBR)

GlycoCheck Measurements 2

― Perfused Boundary Region (PBR)

RBC column width at the 3000 capillary segments 10 um apart was determined and the median and

the 5th-95th percentile interval of RBC width was used for the calculation of PBR.

Healthy and Impaired Glycocalyx as Measured by PBRHealthy and Impaired Glycocalyx as Measured by PBR

The sublingual glycocalyx estimated by the PBR is decreased in patients with

DM, CKD, CVD, and critically ill patients.

Limitations: case-control studies; small sample size; no population data

Previous Studies with

Sublingual Glycocheck

We investigated the characteristics and associations of the sublingual capillary

density and glycocalyx with common CV risk factors in general Chinese and

Flemish populations.

Study Objective

Gu YM, et al. Hypertension. 2015;65:993-1001.

Study Populations ― Flemish

From April 2013 to June 2014, 487 participants were invited, 320 signed informed

consent(65.7%). The number of participants analyzed totaled 254.

Eksel, Belgium Coordinating Center in Leuven, Beglium

Study Populations ― Han and She Chinese

In May 2013, 931 Chinese were invited, 663 (71.2%) gave informed consent. The number

of participants analyzed totaled 472, including 252 Han and 220 She people.

JingNing County Villages in JingNing She Minority

Measurements in the 3 Ethnic GroupsMeasurements in the 3 Ethnic Groups

Sublingual GlycoCheck

Standardized questionnaires

Anthropometric measurements

Blood biochemical measurements

Characteristics of Participants (1)

Characteristics Han (n=252)

She (n=220)

Flemish (n=254)

Age, y 51.8 51.7 49.8

BMI, kg/m2 23.2‡ 23.5† 26.5

SBP/DBP, mmHg 124/78*‡ 129/81 129/83

PP, mm Hg 46.8 47.6 46.5

Pulse rate, beats/min 72.1‡ 73.2† 63.3

Hematocrit, % 43.3‡ 42.7† 41.1

Total cholesterol, mmol/L 5.40‡ 5.57† 4.82

Blood glucose, mmol/L 4.99‡ 4.79† 4.57

Significance of the difference: * Han vs. She, † She vs. Flemish, ‡ Han vs. Flemish.

Characteristics of Participants (2)

Characteristics,% Han (n=252)

She (n=220)

Flemish (n=254)

Women 55.6 62.7† 46.9

Smokers 21.8 17.3 14.2

Drinking alcohol 34.1‡ 31.4† 76.4

HT (Anti-HT) 29 (42) 36 (48) 38 (44)

Previous CVD 3.2 1.8 5.5

Diabetes 6.4‡ 1.8 0.4

Significance of the difference: * Han vs. She, † She vs. Flemish, ‡ Han vs. Flemish.

GlycoCheck Measurements

Han (n=252)

She (n=220)

Flemish (n=254)

PBR, nm 2019‡ 2000† 1876

Total Capillary density, NO/mm2 580‡ 573† 546

Perfused Capillary density, NO/mm2 342‡ 334 320

Perfused-to-total density ratio 0.59 0.59 0.59

Significance of the difference : * Han vs. She, † She vs. Flemish, ‡ Han vs. Flemish.

PBR, Hemotocrit and Capillary DensityPBR, Hemotocrit and Capillary Density

She

Perfu

sed d

ensi

ty

(n°/m

m2)

2700

2500

2300

2100

1900

1700

1500

30

35

40

45

55

50600

500

400

300

200

100

Haematocrit (%

)

p<0.0001p<0.

0001

Flemish

2500

2300

2100

1900

1700

1500

1200

30

35

40

45

55

50600

500

400

300

200

100

Perfu

sed d

ensi

ty

(n°/m

m2)

Haematocrit (%

)

P<0.0001P<0.

0001

Han

2700

2500

2300

2100

1900

1700

150030

35

40

45

55

50600

500

400

300

200

100

Perfu

sed d

ensi

ty

(n°/m

m2)

Haematocrit (%

)

PB

R (

nm

)

p<0.0001 p<0.00

01

Distribution of Standardized PBRDistribution of Standardized PBR

Standardized PBR (nm)

P<0.0001

Standardized PBRStandardized PBR

Han She Flemish1800

1850

1900

1950

2000

2050

2024

1990

1875

P<0.0001

The covariables considered were sex, age, BMI, smoking, cholesterol, glucose, g-GT, AH-drug, CVD, and MAP and PP in Model 1, or SBP and DBP in Model 2. or

Framingham risk score in Model 3. Significance of effect size: * P≤0.05.

Correlates of Standardized PBRCorrelates of Standardized PBR

Model 1 Model 2 Model 3

Han (vs. average) 50.4* 49.3* 53.6*

She (vs. average) 24.3 24.6 20.8

Flemish (vs. average) –74.7* –73.9* –74.5*

BMI (+3.9 kg/m2) –18.4 –17.4 –25.3*

MAP (+13.1 mmHg) –23.3*

DBP (+11.2 mmHg) –25.4*

Correlates of Standardized PBR

by Ethnicities

Correlates of Standardized PBR

by Ethnicities

None of the between-ethnicity comparisons reached significance.

BMI MAP

Perfused capillary density was standardised for ethnicity.

Correlates of Perfused Capillary DensityCorrelates of Perfused Capillary Density

80

Regression line (95% CI) in individual participants

Mean (95%CI) per quintile

Pe

rfu

sed

den

sit

y (n

°/m

m2)

30 40 50 60 70

p=0.0024

year

375

350

325

300

Age

p=0.009

–8 –4 0 4 8

point

12

Framingham score

p=0.45 p=0.14

15 20 25 30 35

kg/m2

3 4 5 6 7

mmol/L

BMI Cholesterol

CorrelatesPerfused Density Total density

Model 1 Model 2 Model 1 Model 2

Han (vs. average) 10.0* 9.29* 15.2* 13.5*

She (vs. average) 1.58 1.49 6.65 6.59

Flemish (vs. average) –11.6* –10.8* –21.8* –20.1*

Age (+13.7y) 9.31† …

Framingham score

(+6.53 pts) 7.93† …

The covariables considered were sex, age, BMI, smoking, cholesterol, glucose, g-GT, AH-drug, CVD. Model1 additionally included MAP and PP,

whereas Model 2 had Framingham risk score. Significance of effect size: * P≤0.05.

Correlates of Capillary Density

Model 1 Model 2

Han (vs. average) 0.0060 0.0050

She (vs. average) –0.0051 –0.0027

Flemish (vs. average) –0.0009 –0.0023

Age (+14.4 y) 0.0092*

BMI (+3.90 kg/m2) 0.0085* 0.0066

Cholesterol (+1.02mm/L) 0.0102*

Smoking (0,1) –0.0202*

Framingham risk score (+6.53pts) 0.0145†

Correlates of Perfused-to-Total

Capillary Density Ratio

Correlates of Perfused-to-Total

Capillary Density Ratio

Correlates of Perfused-to-Total

Capillary Density Ratio by Ethnicities

Correlates of Perfused-to-Total

Capillary Density Ratio by Ethnicities

None of the between-ethnicity comparisons reached significance.

Age BMI TC FRS

Summary

Higher age, body mass index, total cholesterol and Framingham risk score were associated with functional capillary recruitment.

In capillaries that remain perfused, glycocalyx width increased with higher BMI, MAP and DBP.

There were no ethnic differences in these associations.

Conclusion

A higher cardiovascular risk profile is associated with recruitment of

capillaries with preserved glycocalyx that protects the endothelium.

Further research on microcirculation with the use of this novel technique

is warranted.

Acknowledgements

Shanghai

Jiguang Wang

Yan Li

Changsheng Sheng

Qifang Huang

Shuai Wang

Yuanyuan Kang

Feika Li

Jie Song

Yibang Cheng

Qianhui Guo

Leuven

Jan A. Staessen

Yumei Gu

Yanping Liu

Lutgarde Thijs

Tatiana Kuznetsova

Peter Verhamme

Thibault Petit

Zhengyu Zhang

Fangfei Wei

Thank You

谢

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