Abstract P007: Circulating Levels of Soluble P-selectin and Subclinical and Clinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Bielinski Suzette J , Pankow James S , Tsai Michael , Sale Michele , de Andrade Mariza , Sicotte Hugues , Tang Weihong , Hanson Naomi , Decker Paul , Kirsch Phillip , Polak Joseph 
Published: July 2021

P-selectin is a cellular adhesion molecule that enhances procoagulant activity and activation of leukocyte integrins. P-selectin has been shown to be crucial in the development of atherosclerosis. Using a stratified random sample of 2406 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) at Exam 2, we investigated the association of soluble P-selectin and cardiovascular disease. The Tobit model was used to investigate the association of P-selectin levels and coronary artery calcium (CAC) and Cox proportional hazards regression was used to assess the association between protein level and incident cardiovascular disease (CVD) events (myocardial infarction, stroke, angina, or other atherosclerotic death). Mean levels of soluble P-selectin differed significantly by ethnicity; 46±18 ng/mL African Americans, 58±20 ng/mL Caucasians, 43±15 ng/mL Chinese, and 61±20 ng/mL Hispanics (p<0.0001). CAC was present in 46% of African Americans, 61% of Caucasians, 52% of Chinese, and 53% of Hispanics. P-selectin levels were significantly associated with CAC in Caucasians (p < 0.001) and African Americans (p = 0.025), see Table. This association was robust to adjustment for traditional risk factors and a significant interaction of P-selectin and ethnicity was observed (p= 0.02). Over an average of 6.5 years of follow-up there were 111 incident CVD events after MESA exam 2, 26 in African Americans, 33 in Caucasians, 16 in Chinese, and 36 in Hispanics. The risk of CVD events increased 34% per standard deviation increase in P-selectin levels only in Caucasians (p = 0.007) and this finding was consistent after adjustment for CVD risk factors (HR = 1.30, p = 0.017). We have shown in this large cohort that mean circulating P-selectin levels differed by ethnicity. Despite similar percentages of subjects with CAC in each ethnic group, P-selectin levels were significantly associated with CAC only in African Americans and Caucasians. Furthermore, in Caucasians only, P-selectin levels were associated with incident CVD events.

Association of P-selectin, per SD (20 ng/mL) for the population and cardiovascular disease

Outcome
African Americans n = 579
Caucasians n = 620
Chinese n = 602
Hispanics n = 605

CAC, Agatston Score
Beta (S.E.)
P-value
Beta (S.E.)
P-value
Beta (S.E.)
P-value
Beta (S.E.)
P-value

Model 1
85.9 (38.4)
0.025
99.4 (28.7)
<0.001
8.2 (33.3)
0.81
32.1 (27.3)
0.24

Model 2
79.3 (39.8)
0.046
94.7 (29.1)
0.001
−19.5 (33.6)
0.56
27.8 (27.6)
0.31

CVD Events
HR (CI)

HR (CI)

HR (CI)

HR (CI)

Model 1
1.08 (0.75, 1.57)
0.67
1.34 (1.08, 1.65)
0.007
1.09 (0.57, 2.08)
0.80
0.99 (0.71, 1.39)
0.97

Model 2
1.10 (0.76, 1.58)
0.61
1.30 (1.05, 1.62)
0.017
0.82 (0.38, 1.78)
0.62
1.00 (0.71, 1.43)
0.98

Model 1 = age and sex ; Model 2 = age, sex, BMI, smoking status, LDL, HDL, triglycerides, hypertension, diabetes