@article {690, title = {No association of plasma prothrombin concentration or the G20210A mutation with incident cardiovascular disease: results from the Cardiovascular Health Study.}, journal = {Thromb Haemost}, volume = {87}, year = {2002}, month = {2002 Apr}, pages = {614-21}, abstract = {

Prothrombin is a key factor in blood clotting, a process intimately involved in thrombotic disease. We assessed prothrombin levels and G20210A genotype in a case-control study within the Cardiovascular Health Study. Cases included angina, myocardial infarction, stroke, and the presence of MRI-detectable infarcts (n approximately 250 each). Population-based controls free of clinical cardiovascular disease (CVD) (n approximately 500) and a subset free of clinical and subclinical CVD (n approximately 250) were used for comparison. The 20210 A allele, frequency 2.9\%, was associated with higher mean prothrombin levels: 166.3 vs. 139.5 microg/ml (P <0.001). Significant correlates of prothrombin included gender, plasma lipids, other vitamin K-dependent proteins, and inflammatory markers, but not race, smoking, hypertension, diabetes, measures of subclinical CVD, or markers of procoagulant activity. Compared to controls, neither genotype nor prothrombin level was associated with any CVD case group. We conclude that, in the elderly, neither prothrombin level nor 20210 genotype were associated with either CVD risk factors or events. This is consistent with the lack of association of prothrombin levels with measures of underlying CVD or procoagulant markers.

}, keywords = {3{\textquoteright} Untranslated Regions, Aged, Aged, 80 and over, Alleles, Angina Pectoris, Blood Proteins, Cardiovascular Diseases, Case-Control Studies, Comorbidity, Diabetes Mellitus, Female, Genetic Predisposition to Disease, Humans, Hyperlipidemias, Hypertension, Male, Mutation, Myocardial Infarction, Obesity, Promoter Regions, Genetic, Prothrombin, Risk Factors, Smoking, Stroke, Vermont}, issn = {0340-6245}, author = {Smiles, Adam M and Jenny, Nancy S and Tang, Zhonghua and Arnold, Alice and Cushman, Mary and Tracy, Russell P} } @article {9906, title = {Plasma Proteomic Assessment of Calcific Aortic Valve Disease in Older Adults.}, journal = {J Am Heart Assoc}, volume = {14}, year = {2025}, month = {2025 Mar 04}, pages = {e036336}, abstract = {

BACKGROUND: Calcific aortic valve disease (CAVD), and ensuing severe aortic stenosis (AS), is the foremost valvular disorder of aging, yet preventive therapies are lacking. A better understanding of the molecular underpinnings of aortic valve calcification (AVC) is necessary to develop pharmacologic interventions.

METHODS AND RESULTS: We undertook large-scale plasma proteomics in a cohort study of adults >=65 years old, the CHS (Cardiovascular Health Study), to identify individual proteins associated with echocardiographic AVC and incident moderate/severe AS. Proteomics measurements were performed with the aptamer-based SomaLogic platform of ~5000 proteins. Significant proteins were validated in a second cohort, the AGES-RS (Age, Gene/Environment Susceptibility-Reykjavik Study), which assessed AVC and AS by computed tomography. The potential causal associations of replicated proteins were tested in 2-sample Mendelian randomization using identified cis protein quantitative trait loci in consortia having computed tomography-quantified AVC or AS as outcomes. Six proteins showed Bonferroni-corrected significant relationships with AVC in CHS. Three of these, CXCL-12 (C-X-C chemokine ligand 12), KLKB1 (kallikrein), and leptin, replicated in AGES-RS, of which the former 2 are novel. Only 1 protein, CXCL6, which showed a near-significant association with AS in the replication cohort, was significantly (positively) associated with incident AS. Mendelian randomization analysis was conducted for KLKB1, CXCL12, and CXCL6, which supported a causal relationship for higher KLKB1 with lower AVC (beta=-0.25, =0.009).

CONCLUSIONS: This study of older adults newly identified and largely replicated associations of 3 circulating proteins with calcific aortic valve disease, of which the relationship of plasma KLKB1 may have a causal basis. Additional investigation is necessary to determine if KLKB1 could be harnessed for calcific aortic valve disease therapeutics.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aortic Valve, Aortic Valve Stenosis, Biomarkers, Blood Proteins, Calcinosis, Chemokine CXCL12, Echocardiography, Female, Humans, Male, Mendelian Randomization Analysis, Proteomics, Severity of Illness Index}, issn = {2047-9980}, doi = {10.1161/JAHA.124.036336}, author = {Bortnick, Anna E and Austin, Thomas R and Hamerton, Emily and Gudmundsdottir, Valborg and Emilsson, Valur and Jennings, Lori L and Gudnason, Vilmundur and Owens, David S and Massera, Daniele and Dufresne, Line and Yang, Ta-Yu and Engert, James C and Thanassoulis, George and Tracy, Russell P and Gerszten, Robert E and Psaty, Bruce M and Kizer, Jorge R} }