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Trends among platelet function, arterial calcium, and vascular function measures

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posted on 2023-08-23, 11:00 authored by Jason Cunha, Melissa V. Chan, Bongani B. Nkambule, Florian Thibord, Amber Lachapelle, Robin E. Pashek, Ramachandran S. Vasan, Jian Rong, Emelia J. Benjamin, Naomi M. Hamburg, Ming-Huei Chen, Gary F. Mitchell, Andrew D. Johnson

Arterial tonometry and vascular calcification measures are useful in cardiovascular disease (CVD) risk assessment. Prior studies found associations between tonometry measures, arterial calcium, and CVD risk. Activated platelets release angiopoietin-1 and other factors, which may connect vascular structure and platelet function. We analyzed arterial tonometry, platelet function, aortic, thoracic and coronary calcium, and thoracic and abdominal aorta diameters measured in the Framingham Heart Study Gen3/NOS/OMNI-2 cohorts (n = 3,429, 53.7% women, mean age 54.4 years ±9.3). Platelet reactivity in whole blood or platelet-rich plasma was assessed using 5 assays and 7 agonists. We analyzed linear mixed effects models with platelet reactivity phenotypes as outcomes, adjusting for CVD risk factors and family structure. Higher arterial calcium trended with higher platelet reactivity, whereas larger aortic diameters trended with lower platelet reactivity. Characteristic impedance (Zc) and central pulse pressure positively trended with various platelet traits, while pulse wave velocity and Zc negatively trended with collagen, ADP, and epinephrine traits. All results did not pass a stringent multiple test correction threshold (p < 2.22e-04). The diameter trends were consistent with lower shear environments invoking less platelet reactivity. The vessel calcium trends were consistent with subclinical atherosclerosis and platelet activation being inter-related.

What is the context?

Prior research has reported that measures of vascular system-influencing proteins such as angiopoietin-2, arterial calcium plaque formation, and arterial stiffness assessed by tonometry are associated with CVD risk.

Since activated platelets produce and release vascular proteins like angiopoietin when activated, and microparticles that interact with endothelium, release of the foregoing mediators could provide one way in which vascular structure and platelet function influence each other.

To our knowledge, no prior studies have directly investigated associations between these measures in a large sample. This investigation relates platelet function to arterial tonometry, aortic and arterial diameter, and arterial calcium measures in the Framingham Heart Study (FHS) Gen3/NOS/OMNI-2 cohorts (n = 3,429).

Prior research has reported that measures of vascular system-influencing proteins such as angiopoietin-2, arterial calcium plaque formation, and arterial stiffness assessed by tonometry are associated with CVD risk.

Since activated platelets produce and release vascular proteins like angiopoietin when activated, and microparticles that interact with endothelium, release of the foregoing mediators could provide one way in which vascular structure and platelet function influence each other.

To our knowledge, no prior studies have directly investigated associations between these measures in a large sample. This investigation relates platelet function to arterial tonometry, aortic and arterial diameter, and arterial calcium measures in the Framingham Heart Study (FHS) Gen3/NOS/OMNI-2 cohorts (n = 3,429).

What’s new?

Generally, higher arterial calcium measures trended with higher platelet reactivity, whereas larger aortic diameters trended with lower platelet reactivity.

Arterial tonometry measures had positive and negative trends with platelet functions, including platelet measures with opposite relations to negative-inverse carotid-femoral pulse wave velocity (niCFPWV) and characteristic impedance (Zc). All tonometry, calcium, and diameter results did not reach a more stringent multiple testing threshold (p < 2.22e-04).

Generally, higher arterial calcium measures trended with higher platelet reactivity, whereas larger aortic diameters trended with lower platelet reactivity.

Arterial tonometry measures had positive and negative trends with platelet functions, including platelet measures with opposite relations to negative-inverse carotid-femoral pulse wave velocity (niCFPWV) and characteristic impedance (Zc). All tonometry, calcium, and diameter results did not reach a more stringent multiple testing threshold (p < 2.22e-04).

What’s the impact?

The aortic diameter trends are consistent with lower shear stress invoking less platelet reactivity.

The vessel calcium trends are consistent with increased vascular calcium buildup that could provoke platelet activation, thereby contributing to increased blood clot risk. Conversely, increased platelet activation could contribute to increased inflammation and thrombosis, leading to calcification in the arterial wall.

The aortic diameter trends are consistent with lower shear stress invoking less platelet reactivity.

The vessel calcium trends are consistent with increased vascular calcium buildup that could provoke platelet activation, thereby contributing to increased blood clot risk. Conversely, increased platelet activation could contribute to increased inflammation and thrombosis, leading to calcification in the arterial wall.

Funding

This research was primarily supported by a special Population Sciences funding award to A.D.J. from the National Heart, Lung, and Blood Institute (NHLBI) Intramural Research program. The Framingham Heart Study (FHS) acknowledges the support of Contracts [NO1‐HC‐25195, HHSN268201500001I, and 75N92019D00031] from the NHLBI and grants [HL107385, HL126136, HL93328, HL142983, HL143227, and HL131532] for this research. Dr. Benjamin was supported in part by R01HL092577. A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center.

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