Proteomic Analysis of Longitudinal Changes in Blood Pressure

Abstract

Hypertension is the leading risk factor for premature death worldwide. The identification of modifiable causes of hypertension remains an imperative task. We aimed to investigate associations between 79 proteins implicated in cardiovascular disease and longitudinal blood pressure (BP) changes in three Swedish prospective cohorts. In a discovery phase, we investigated associations between baseline circulating protein levels assessed with a proximity extension assay and BP stage progression at follow-up 5 years later among persons without BP-lowering drugs at baseline in two independent community-based cohorts from the Prospective Investigation of the Vasculature in Uppsala Seniors study (PIVUS) and the Uppsala Longitudinal Study of Adult Men (ULSAM). We used an independent cohort, the Malmö Diet and Cancer Study (MDC), for replication. The primary outcome of BP stage progression was defined as per the 2017 AHA/ACC (American Heart Association/ American College of Cardiology) Guideline BP categories. We also investigated associations of protein levels with changes in BP on a continuous scale, and meta-analyzed all three cohorts. Levels of renin were associated with BP stage progression with a 5% false discovery rate (FDR) in the ULSAM (n = 238) and PIVUS (n = 566) cohorts, but we could not replicate this association in the MDC cohort (n = 2659). The association in the discovery cohorts was modest, with an odds ratio for BP stage progression over 5 years of 1.33 (95% confidence interval 1.14 to 1.56) per standard deviation of baseline renin. In conclusion, we could not find any novel robust associations with longitudinal BP increase in a proximity extension assay-based proteomics investigation in three cohorts.

Associations of Proteomics With Hypertension and Systolic Blood Pressure: KORA S4/F4/FF4 and KORA Age1/Age2 Cohort Studies

“…We only found 3 cross-sectional studies with small sample sizes 6 – 8 and 1 longitudinal study. 10 A few previously reported proteins in the 3 cross-sectional studies were replicated in our discovery analysis, including latency-associated peptide TGF-β1 (transforming growth factor beta-1), 7 TNFRSF14 (tumor necrosis factor receptor superfamily member 14), and PLC (perlecan). 8 Using the same protein measurement technology as in the present study, Lin et al 10 identified REN from 79 plasma CVD I–based proteins, showing a positive association with BP progression in the discovery cohort only.…”

“…To date, there is only 1 longitudinal proteomic study on primary hypertension. Lin et al 10 investigated the associations of 79 plasma CVD-related proteins with BP progression over 5 years and found that REN was positively associated with BP progression in the discovery cohort (n=804) but not in the validation cohort (n=2659). Only 2 repeated measurements of BP were included in their longitudinal analysis, with a relatively short follow-up duration.…”

Comparing biomarkers for COVID-19 disease with commonly associated preexisting conditions and complications

“…Modules or clusters of proteins were identified by weighted correlation network analysis (WGCNA) using a Pearson-based weighted adjacency matrix (signed, β=14) and average linkage hierarchical clustering 23 . Modules were evaluated for enriched biological processes 24 and used to compare study associations with the differential protein profiles of other diseases including myocardial infarction (MI) [25][26][27] , cardiovascular-related death (CVD) / heart failure (HF) 27 , stroke 27,28 , hypertension 29 , atherosclerosis 30 , diabetes 31 , smoking 32 , kidney function 33 , and chronic kidney disease (CKD) 33 . Findings were not significantly affected after correcting for sample handling, although there was a minor improvement in the variability ( Supplementary Table S2, S3).…”

Focus on blood pressure levels and variability in the early phase of acute ischemic stroke with hypertension and carotid stenosis

“…19 After discharge, the treatments were consistent with 2013 AHA/ASA guidelines for the prevention of stroke in patients with stroke and transient ischemic attack. 19 Supine BP was measured by trained nurses with a standard mercury sphygmomanometer 20 , 21 , 22 , 23 , 24 (YUTU‐XJ11E; Medical Instrument Co, Shanghai, China) on the non‐paralyzed arm every 4 h for 3 days after stroke onset. Blood pressure was measured two consecutive readings between each measurement.…”

“…19 After discharge, the treatments were consistent with 2013 AHA/ASA guidelines for the prevention of stroke in patients with stroke and transient ischemic attack. 19 Supine BP was measured by trained nurses with a standard mercury sphygmomanometer [20][21][22][23][24]…”