The association of clot lysis time with total obesity is partly independent from the association of PAI-1 with central obesity in African adults

Eksteen, Philna; Pieters, Marlien; Lange, Zelda de; Kruger, Herculina S.

doi:10.1016/j.thromres.2015.05.033

Cited by 13 publications

(8 citation statements)

References 41 publications

(59 reference statements)

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“…Plasma PAI-1 was found to be associated with several risk factors of hypertension, such as obesity [30,31], insulin resistance [31,32], and inflammation [33]. However, the observed association between plasma PAI-1 and hypertension in our study was unlikely to be confounded by these chronic conditions because these factors were adjusted in our statistical models.…”

Section: Discussionmentioning

confidence: 64%

Relationship between plasma plasminogen activator inhibitor-1 and hypertension in American Indians

Peng

Yeh

Simone

et al. 2017

Journal of Hypertension

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Objectives Deficient plasminogen activator inhibitor-1 (PAI-1) prevented hypertension in mice. Plasma PAI-1 was associated with hypertension in cross-sectional analyses, but the prospective association of PAI-1 with incident hypertension in large epidemiological studies is scarce. Methods Leveraging two longitudinal cohorts of American Indians in the Strong Heart Study (SHS, N = 1019) and the Strong Heart Family Study (SHFS, N = 1502), we examined the prospective association of plasma PAI-1 with incident hypertension by multivariate logistic regression, adjusting for age, sex, study site, smoking, drinking, dietary sodium, obesity, lipids, fasting glucose, kidney function, inflammation, and follow-up years. Family relatedness in the SHFS was accounted for using the GLIMMIX procedure. Plasma PAI-1 level at baseline was measured by immunoassay. All participants were free of hypertension, cardiovascular diseases, and chronic kidney disease at baseline. Results A total of 305 and 258 participants, respectively, from the SHS (57 ± 7 years) and the SHFS (33 ± 13 years) developed incident hypertension during follow-up. In the SHS, higher level of log-transformed PAI-1 was associated with 1.35-fold increased risk of hypertension [odds ratio (OR) (95% confidence interval): 1.35 (1.06–1.72)]. Analysis using categorical PAI-1 (in tertiles) showed that participants in the highest tertile (≥ 58 ng/ml) had 63% increased risk for hypertension [OR = 1.63 (1.12–2.37)] compared with those in the lowest tertile (<33 ng/ml). This association was confirmed in the SHFS with similar effect sizes [OR = 1.41 (1.11–1.81) for log-transformed PAI-1; OR = 1.64 (1.08–2.50) for categorical PAI-1: ≥ 58 vs. <33 ng/ml]. Conclusion A higher level of plasma PAI-1 is significantly associated with hypertension in American Indians, independent of established risk factors. The potential causality warrants further investigation.

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Section: Discussionmentioning

confidence: 64%

Relationship between plasma plasminogen activator inhibitor-1 and hypertension in American Indians

Peng

Yeh

Simone

et al. 2017

Journal of Hypertension

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“…30 Stolberg et al, 31 furthermore, reported improved fibrin clot properties in individuals who lost weight following gastric bypass surgery. More and consistent evidence is available for fibrinolytic resistance in obesity, in particular delayed CLTs, 32 although this may also be attributed to factors other than altered clot properties, such as increased PAI-1, thrombin activatable fibrinolysis inhibitor, α-2-antiplasmin, and prothrombin levels. 33,34 Regarding the procoagulant risk score, alcohol consumption emerged to have a protective effect.…”

Section: Discussionmentioning

confidence: 99%

Lifestyle Influences Changes in Fibrin Clot Properties Over a 10-Year Period on a Population Level

et al. 2021

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Case–control and observational studies have provided a plausible mechanistic link between clot structure and thrombosis. We aimed to identify lifestyle, demographic, biochemical, and genetic factors that influence changes in total fibrinogen concentration and clot properties over a 10-year period in 2,010 black South Africans. Clot properties were assessed with turbidimetry and included lag time, slope, maximum absorbance, and clot lysis time. Linear mixed models with restricted maximum likelihood were used to determine whether (1) outcome variables changed over the 10-year period; (2) demographic and lifestyle variables, biochemical variables, and fibrinogen single-nucleotide polymorphisms influenced the change in outcome variables over the 10-year period; and (3) there was an interaction between the exposures and time in predicting the outcomes. A procoagulant risk score was furthermore created, and multinomial logistic regression was used to determine the exposures that were associated with the different risk score categories. In this population setting, female gender, obesity, poor glycemic control, increased low-density lipoprotein cholesterol, and decreased high-density lipoprotein cholesterol contributed to the enhanced progression to prothrombotic clot properties with increasing age. Alcohol consumption on the other hand, offered a protective effect. The above evidence suggest that the appropriate lifestyle changes can improve fibrin clot properties on a population level, decreasing cardiovascular disease risk and thus alleviate the strain on the medical health care system.

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“…There is accumulating evidence implicating PAI-1 in the development of hypertension (167), and plasma PAI-1 is associated with several risk factors for hypertension, including obesity (168,169), insulin resistance (140,169), and inflammation (70) as discussed above. Genetic ablation of PAI-1 protects against hypertension and perivascular fibrosis induced by nitric oxide synthase (NOS) inhibition (170,171).…”

Section: Hypertensionmentioning

confidence: 99%

A Serpin With a Finger in Many PAIs: PAI-1's Central Function in Thromboinflammation and Cardiovascular Disease

Morrow

Whyte

Mutch

2021

Front. Cardiovasc. Med.

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Plasminogen activator inhibitor 1 (PAI-1) is a member of the serine protease inhibitor (serpin) superfamily. PAI-1 is the principal inhibitor of the plasminogen activators, tissue plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA). Turbulence in the levels of PAI-1 tilts the balance of the hemostatic system resulting in bleeding or thrombotic complications. Not surprisingly, there is strong evidence that documents the role of PAI-1 in cardiovascular disease. The more recent uncovering of the coalition between the hemostatic and inflammatory pathways has exposed a distinct role for PAI-1. The storm of proinflammatory cytokines liberated during inflammation, including IL-6 and TNF-α, directly influence PAI-1 synthesis and increase circulating levels of this serpin. Consequently, elevated levels of PAI-1 are commonplace during infection and are frequently associated with a hypofibrinolytic state and thrombotic complications. Elevated PAI-1 levels are also a feature of metabolic syndrome, which is defined by a cluster of abnormalities including obesity, type 2 diabetes, hypertension, and elevated triglyceride. Metabolic syndrome is in itself defined as a proinflammatory state associated with elevated levels of cytokines. In addition, insulin has a direct impact on PAI-1 synthesis bridging these pathways. This review describes the key physiological functions of PAI-1 and how these become perturbed during disease processes. We focus on the direct relationship between PAI-1 and inflammation and the repercussion in terms of an ensuing hypofibrinolytic state and thromboembolic complications. Collectively, these observations strengthen the utility of PAI-1 as a viable drug target for the treatment of various diseases.

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The association of clot lysis time with total obesity is partly independent from the association of PAI-1 with central obesity in African adults

Cited by 13 publications

References 41 publications

Relationship between plasma plasminogen activator inhibitor-1 and hypertension in American Indians

Relationship between plasma plasminogen activator inhibitor-1 and hypertension in American Indians

Lifestyle Influences Changes in Fibrin Clot Properties Over a 10-Year Period on a Population Level

A Serpin With a Finger in Many PAIs: PAI-1's Central Function in Thromboinflammation and Cardiovascular Disease

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