Dataset Information

Platelet Activity and Cardiovascular Risk in CKD and Peripheral Artery Disease.

ABSTRACT:

Introduction

Platelet dysfunction and cardiovascular risk are well-recognized features of chronic kidney disease (CKD). Platelets drive the development and progression of cardiovascular disease (CVD). The relationships between kidney function, platelet activity, and cardiovascular risk are poorly defined.

Methods

We compared platelet activity and incident cardiovascular events by CKD status (estimated glomerular filtration rate [eGFR] < 60 ml/min per 1.73 m²) using data from the Platelet Activity and Cardiovascular Events study, a prospective cohort study that enrolled adults with peripheral artery disease (PAD) undergoing lower extremity revascularization. Platelet activity was measured using light transmission aggregometry (LTA) in response to submaximal dose agonist stimulation, and the subjects were followed for incident adverse cardiovascular events for a median of 18 months.

Results

Overall, 113 of 285 (40%) subjects had CKD. Subjects with, versus without, CKD had higher platelet aggregation in response to stimulation with adenosine diphosphate (ADP), serotonin, epinephrine, and arachidonic acid (AA) + ex vivo aspirin (P < 0.05 for each). Following multivariable adjustment, subjects with CKD had elevated risk for myocardial infarction (MI) (adjusted hazard ratio 2.2, 95% confidence interval [1.02-4.9]) and major adverse cardiovascular events (MACE) (1.9 [1.2-3.3]) compared to those without CKD. Platelet aggregation in response to submaximal dose agonist stimulation mediated 7% to 26% of the excess risk for cardiovascular events associated with CKD.

Conclusion

Among subjects with PAD undergoing lower extremity revascularization, CKD is associated with increased platelet activity that mediates, in part, elevated cardiovascular risk.

SUBMITTER: Cofer LB

PROVIDER: S-EPMC9546761 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Platelet Activity and Cardiovascular Risk in CKD and Peripheral Artery Disease.

Cofer Lucas B LB Soomro Qandeel H QH Xia Yuhe Y Luttrell-Williams Elliot E Myndzar Khrystyna K Charytan David M DM Berger Jeffrey S JS

Kidney international reports 20220804 10

<h4>Introduction</h4>Platelet dysfunction and cardiovascular risk are well-recognized features of chronic kidney disease (CKD). Platelets drive the development and progression of cardiovascular disease (CVD). The relationships between kidney function, platelet activity, and cardiovascular risk are poorly defined.<h4>Methods</h4>We compared platelet activity and incident cardiovascular events by CKD status (estimated glomerular filtration rate [eGFR] < 60 ml/min per 1.73 m<sup>2</sup>) using data ...[more]

PMID: 36217517

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Project description:Background We investigated the causal associations between the genetic liability to cardiovascular and lifestyle risk factors and peripheral artery disease (PAD), using a Mendelian randomization approach. Methods and Results We performed a 2-sample inverse-variance weighted Mendelian randomization analysis, multiple sensitivity analyses to assess pleiotropy and multivariate Mendelian randomization analyses to assess mediating/confounding factors. European-ancestry genomic summary data (P<5×10-8) for type 2 diabetes, lipid-fractions, smoking, alcohol and coffee consumption, physical activity, sleep, and education level were selected. Genetic associations with PAD were extracted from the Million-Veteran-Program genome-wide association studies (cases=31 307, controls=211 753, 72% European-ancestry) and the GoLEAD-SUMMIT genome-wide association studies (11 independent genome-wide association studies, European-ancestry, cases=12 086, controls=449 548). Associations were categorized as robust (Bonferroni-significant (P<0.00294), consistent over PAD-cohorts/sensitivity analyses), suggestive (P value: 0.00294-0.05, associations in 1 PAD-cohort/inconsistent sensitivity analyses) or not present. Robust evidence for genetic liability to type 2 diabetes, smoking, insomnia, and inverse associations for higher education level with PAD were found. Suggestive evidence for the genetic liability to higher low-density lipoprotein cholesterol, triglyceride-levels, alcohol consumption, and inverse associations for high-density lipoprotein cholesterol, and increased sleep duration were found. No associations were found for physical activity and coffee consumption. However, effects fully attenuated for low-density lipoprotein cholesterol and triglycerides after correcting for apoB, and for insomnia after correcting for body mass index and lipid-fractions. Nonsignificant attenuation by potential mediators was observed for education level and type 2 diabetes. Conclusions Detrimental effects of smoking and type 2 diabetes, but not of low-density lipoprotein cholesterol and triglycerides, on PAD were confirmed. Lower education level and insomnia were identified as novel risk factors for PAD; however, complete mediation for insomnia and incomplete mediation for education level by downstream risk factors was observed.

Dataset Information

Platelet Activity and Cardiovascular Risk in CKD and Peripheral Artery Disease.

Introduction

Methods

Results

Conclusion

Publications

Platelet Activity and Cardiovascular Risk in CKD and Peripheral Artery Disease.

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