Sublingual Microcirculation Characteristics and Determinants in Chinese and

Sublingual Microcirculation ——Characteristics and Determinants in Chinese and Flemish Populations Yan Li MD Ph. D Shanghai Institute of Hypertension http: //www. rjh. com. cn

Hypertension and Microcirculation Hypertension Impaired vasodilation … Structural rarefaction Functional rarefaction Apoptosis in endothelial cells

Vascular Glycocalyx 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.

Sublingual Capillary Microscopy and Glyco. Check Handheld Video Capillary Microscope (KK Research Technology, UK) interfaced with a computer running the Glyco. Check software (Glyco. Check BV, Maastricht, The Netherlands).

Glyco. Check Measurement 1 ― Capillary Density Total density (RBC filling >0%) no segments / mm 2 Perfused density (RBC filling ≥ 50%) Perfused-to-total density ratio Ø 0. 4 mm

Glyco. Check Measurements 2 ― Perfused Boundary Region (PBR) RBC column width at the 3000 capillary segments 10 um apart was determined and the median and the 5 th-95 th percentile interval of RBC width was used for the calculation of PBR.

Healthy and Impaired Glycocalyx as Measured by PBR

Previous Studies with Sublingual Glycocheck 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

Study Objective We investigated the characteristics and associations of the sublingual capillary density and glycocalyx with common CV risk factors in general Chinese and Flemish populations. 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. Jing. Ning County Villages in Jing. Ning She Minority

Measurements in the 3 Ethnic Groups Sublingual Glyco. Check Standardized questionnaires Anthropometric measurements Blood biochemical measurements

Characteristics of Participants (1) Han (n=252) She (n=220) Flemish (n=254) Age, y 51. 8 51. 7 49. 8 BMI, kg/m 2 23. 2‡ 23. 5† 26. 5 124/78*‡ 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 Characteristics SBP/DBP, mm. Hg Significance of the difference: * Han vs. She, † She vs. Flemish, ‡ Han vs. Flemish.

Characteristics of Participants (2) 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 29 (42) 36 (48) 38 (44) Previous CVD 3. 2 1. 8 5. 5 Diabetes 6. 4‡ 1. 8 0. 4 Characteristics, % HT (Anti-HT) Significance of the difference: * Han vs. She, † She vs. Flemish, ‡ Han vs. Flemish.

Glyco. Check Measurements Han (n=252) She (n=220) Flemish (n=254) PBR, nm 2019‡ 2000† 1876 Total Capillary density, NO/mm 2 580‡ 573† 546 Perfused Capillary density, NO/mm 2 342‡ 334 320 Perfused-to-total density ratio 0. 59 Significance of the difference : * Han vs. She, † She vs. Flemish, ‡ Han vs. Flemish.

PBR, Hemotocrit and Capillary Density Flemish 2700 2500 2300 2100 1900 1700 1500 30 35 40 ) (% rit 1 oc 0 at 00 m <0. P 500 50 600 55 1200 30 ae ) (% rit 1 oc 0 at 00 m <0. p 45 100 200 300 400 H 35 40 ae H ) (% rit oc 1 at 0 m. 00 ae <0 p H 100 200 300 40 400 45 500 50 600 55 rf us (n ed p< °/m d 0. m en 00 2 si ty 01 ) 1500 30 35 fu s (n ed p< °/m de 0. m 2 ns 00 ) it y 01 1900 Pe r 2100 45 50 100 200 300 400 Pe rf us (n ed P< °/m d 0. m en 00 2 si ty 01 ) She Pe PBR (nm) Han 500 600 55

Distribution of Standardized PBR

Standardized PBR P<0. 0001 StandardizedØ 2050 PBR (nm) P<0. 0001 Ø 2000 2024 1990 Ø 1950 Ø 1900 1875 Ø 1850 ØHan ØShe ØFlemish

Correlates 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/m 2) – 18. 4 – 17. 4 – 25. 3* MAP (+13. 1 mm. Hg) – 23. 3* DBP (+11. 2 mm. Hg) – 25. 4* 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 PBR by Ethnicities BMI MAP None of the between-ethnicity comparisons reached significance.

Correlates of Perfused Capillary Density Regression line (95% CI) in individual participants Mean (95%CI) per quintile Age Perfused density (n°/mm 2) 375 BMI p=0. 45 p=0. 0024 Framingham score Cholesterol p=0. 009 p=0. 14 350 325 300 30 40 50 60 year 70 80 15 20 25 30 35 kg/m 2 Perfused capillary density was standardised for ethnicity. 3 4 5 mmol/L 6 7 – 8 – 4 0 4 point 8 12

Correlates of Capillary Density Perfused Density Total density Correlates 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. 7 y) 9. 31† Framingham score (+6. 53 pts) … 7. 93† … The covariables considered were sex, age, BMI, smoking, cholesterol, glucose, g-GT, AH -drug, CVD. Model 1 additionally included MAP and PP, whereas Model 2 had Framingham risk score. Significance of effect size: * P≤ 0. 05.

Correlates of Perfused-to-Total Capillary Density Ratio 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/m 2) 0. 0085* Cholesterol (+1. 02 mm/L) 0. 0102* Smoking (0, 1) – 0. 0202* Framingham risk score (+6. 53 pts) 0. 0066 0. 0145†

Correlates of Perfused-to-Total Capillary Density Ratio by Ethnicities Age BMI TC FRS None of the between-ethnicity comparisons reached significance.

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 Leuven Shanghai Jan A. Staessen Jiguang Wang Yumei Gu Yan Li Yanping Liu Changsheng Sheng Lutgarde Thijs Tatiana Kuznetsova Peter Verhamme Thibault Petit Zhengyu Zhang Fangfei Wei Qifang Huang Shuai Wang Yuanyuan Kang Feika Li Jie Song Yibang Cheng Qianhui Guo

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