Relation between Tissue Factor Pathway Inhibitor Activity and Cardiovascular Risk Factors and Diseases in a Large Population Sample

Abstract Objective Tissue factor pathway inhibitor (TFPI) is a potent anticoagulant protein in the extrinsic coagulation pathway. In the present study, we aim to identify the cardiovascular determinants for total TFPI activity and its association with cardiovascular disease (CVD) and total mortality. Methods Total TFPI activity was assessed in a selection of the population-based Gutenberg Health Study (n = 5,000). Statistical analysis was performed to identify the determinants for total TFPI activity as well as the associations with CVD and mortality. Results Multivariable linear regression analysis identified smoking (β 0.095 [0.054–0.136]) as a positive determinant for total TFPI activity, while diabetes (β –0.072 [–0.134 to –0.009]), obesity (β –0.063 [–0.101 to –0.024]), and history of coronary artery disease (CAD) were negatively associated with total TFPI activity, independent of age, sex, and the remaining cardiovascular risk factors. After adjustment for lipoprotein levels, the association between total TFPI activity levels and obesity and CAD was lost. The analysis additionally revealed a strong positive association between total TFPI activity levels and low-density lipoprotein (β 0.221 [0.204–0.237]). The Cox regression models revealed that a higher total TFPI activity, above 97.5th percentile of the reference group, was associated with an increased mortality risk (hazard ratio = 2.58 [95% confidence interval: 1.49–4.47]), independent of age, sex, and cardiovascular risk profile. Conclusion In the Gutenberg Health Study population-based cohort, the highest percentage of total TFPI correlated with an increased mortality risk. While elevated TFPI may reflect endothelial cell activation, the associations between total TFPI activity and obesity and CAD, points to additional mechanistic interactions.

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Diastolic dysfunction in individuals with and without heart failure with preserved ejection fraction

Clinical Research in Cardiology ◽

10.1007/s00392-021-01907-x ◽

2021 ◽

Author(s):

Jan-Per Wenzel ◽

Ramona Bei der Kellen ◽

Christina Magnussen ◽

Stefan Blankenberg ◽

Benedikt Schrage ◽

...

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Cardiovascular Risk ◽

General Population ◽

Diastolic Dysfunction ◽

Cardiovascular Risk Factors ◽

Population Based ◽

Left Ventricular ◽

Health Study ◽

Common Finding

Abstract Aim Left ventricular diastolic dysfunction (DD), a common finding in the general population, is considered to be associated with heart failure with preserved ejection faction (HFpEF). Here we evaluate the prevalence and correlates of DD in subjects with and without HFpEF in a middle-aged sample of the general population. Methods and results From the first 10,000 participants of the population-based Hamburg City Health Study (HCHS), 5913 subjects (mean age 64.4 ± 8.3 years, 51.3% females), qualified for the current analysis. Diastolic dysfunction (DD) was identified in 753 (12.7%) participants. Of those, 11.2% showed DD without HFpEF (ALVDD) while 1.3% suffered from DD with HFpEF (DDwHFpEF). In multivariable regression analysis adjusted for major cardiovascular risk factors, ALVDD was associated with arterial hypertension (OR 2.0, p < 0.001) and HbA1c (OR 1.2, p = 0.007). Associations of both ALVDD and DDwHFpEF were: age (OR 1.7, p < 0.001; OR 2.7, p < 0.001), BMI (OR 1.2, p < 0.001; OR 1.6, p = 0.001), and left ventricular mass index (LVMI). In contrast, female sex (OR 2.5, p = 0.006), atrial fibrillation (OR 2.6, p = 0.024), CAD (OR 7.2, p < 0.001) COPD (OR 3.9, p < 0.001), and QRS duration (OR 1.4, p = 0.005) were strongly associated with DDwHFpEF but not with ALVDD. Conclusion The prevalence of DD in a sample from the first 10,000 participants of the population-based HCHS was 12.7% of whom 1.3% suffered from HFpEF. DD with and without HFpEF showed significant associations with different major cardiovascular risk factors and comorbidities warranting further research for their possible role in the formation of both ALVDD and DDwHFpEF.

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On the HUNT for cardiovascular risk factors and disease in patients with psoriatic arthritis: population-based data from the Nord-Trøndelag Health Study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2014-206824 ◽

2015 ◽

Vol 75 (5) ◽

pp. 819-824 ◽

Cited By ~ 38

Author(s):

Agnete Malm Gulati ◽

Anne Grete Semb ◽

Silvia Rollefstad ◽

Pål R Romundstad ◽

Arthur Kavanaugh ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Psoriatic Arthritis ◽

Cardiovascular Risk Factors ◽

Population Based ◽

Health Study

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Choroidal thickness is associated with cardiovascular risk factors and cardiac health: the Gutenberg Health Study

Clinical Research in Cardiology ◽

10.1007/s00392-019-01498-8 ◽

2019 ◽

Vol 109 (2) ◽

pp. 172-182 ◽

Cited By ~ 4

Author(s):

Alexander K. Schuster ◽

Anja Leuschner ◽

Constantin Feretos ◽

Philipp Blumenstein ◽

Sven-Oliver Troebs ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Choroidal Thickness ◽

Health Study ◽

Cardiac Health ◽

Gutenberg Health Study

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Lipid-Mediated Relation between Tissue Factor Pathway Inhibitor Activity and Cardiovascular Risk Factors and Diseases in a Large Population Sample

Blood ◽

10.1182/blood-2018-99-116932 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1169-1169

Author(s):

Pauline van Paridon ◽

Marina Panova-Noeva ◽

Rene van Oerle ◽

Andreas Schulz ◽

Jürgen Prochaska ◽

...

Keyword(s):

Risk Factors ◽

Tissue Factor ◽

Regression Models ◽

Tissue Factor Pathway Inhibitor ◽

Cox Regression ◽

Large Population ◽

Total Mortality ◽

Population Based ◽

Activity Levels ◽

Tissue Factor Pathway

Abstract Background: Tissue factor pathway inhibitor (TFPI), a Kunitz-type serine protease, is a potent anticoagulant protein in the extrinsic coagulation pathway and acts by inhibiting both the FXa and the Tissue Factor-FVIIa complex. In contrast to total and free TFPI antigen levels, the reference values and clinical determinants of total TFPI activity have not yet been studied in detail in the general population. In the present study, we aim to identify the cardiovascular determinants for total TFPI activity and investigate its association with cardiovascular disease (CVD) and total mortality, in a population at large. Methods: For this study, the first 4779 subjects of the population-based Gutenberg Health Study were examined in a highly standardized setting. Total TFPI activity was assessed in platelet poor plasma by the Actichrome TFPI activity assay (American Diagnostica, Stamford, CT, USA). Sex-specific nomograms were developed to demonstrate the relation of total TFPI activity with age. Multivariable regression analysis was performed to assess the determinants of total TFPI activity and to evaluate the association with CVD. Cox-regression models, adjusted for age, sex, cardiovascular risk factors (CVRFs) and CVD, were calculated to investigate the association between total TFPI activity and total mortality. Results: The multivariable linear regression analysis identified smoking (β, 0.0952 [0.0541 to 0.136],) as a positive determinant for total TFPI activity, while diabetes (β, -0.0716 [-0.134 to -0.00905],), obesity (β, -0.0627 [-0.101 to -0.024],) and history of coronary artery disease (CAD) were negatively associated with TFPI activity, independent of age, sex and the remaining CVRFs. After adjustment for high-density lipoprotein levels (HDL), low-density lipoproteins (LDL) and triglycerides, the association between TFPI activity levels and obesity and CAD was lost. The analysis additionally reveals a strong positive association between TFPI activity levels and LDL (β, 0.221 [0.204 to 0.237],). The Cox regression models revealed that a higher TFPI activity, above 97.5th percentile of the reference group, was associated with an increased mortality risk (HR = 2.58, [95% CI: 1.49/4.47], p=0.00074) independent of age, sex, CVRFs, CVD, oral contraceptives and hormonal replacement therapy. After additional adjustment for LDL levels, this relation became stronger. Conclusion: To the best of our knowledge, this is the first large, epidemiological study of the general population, revealing an increased mortality risk in individuals with higher TFPI activity, independent of CVRFs and CVD and emphasized by LDL-levels. Additionally, it demonstrates the negative association between total TFPI activity levels and CVD, particularly CAD. Furthermore, an association between TFPI activity and obesity, mediated through lipoprotein particles is explored. Lastly, it describes the age- and sex-related reference range of total TFPI activity levels in a large population-based data set. Disclosures No relevant conflicts of interest to declare.

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