Soluble urokinase plasminogen activator receptor as a prognostic marker of all-cause and cardiovascular mortality in a black population

Botha, Shani; Fourie, C.M.T.; Schutte, Rudolph; Eugen‐Olsen, Jesper; Pretorius, Ronel; Schutte, Aletta E.

doi:10.1016/j.ijcard.2015.03.041

Cited by 46 publications

(36 citation statements)

References 48 publications

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“…Although this cohort is focused on the understudied African American population, associations between suPAR and outcomes, specifically both all-cause and cardiovascular mortality, have been described in multiple ethnic groups worldwide. [9][10][11][12][13][14][15][16][17] Nonetheless, the present findings warrant replication in a larger, multiethnic cohort before justifying risk stratification based on suPAR in the clinic.…”

Section: Strengths and Limitationsmentioning

confidence: 88%

“…Moreover, the multivariable models identifying determinants of suPAR levels that incorporate risk factors and clinical characteristics relevant to cardiovascular outcomes only explain a low percentage of the variance in suPAR levels. Thus, it appears likely that suPAR levels reflect cardiac and extracardiac pathophysiologic processes that are unaccounted for by known clinical characteristics, and therefore, may provide significant improvement to current risk stratification models . While we await additional studies to elucidate the pathogenic role of suPAR or the pathways its levels represent, we envision the potential for use of suPAR concentrations in risk stratification to personalize care and optimize resource allocation.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it appears likely that suPAR levels reflect cardiac and extracardiac pathophysiologic processes that are unaccounted for by known clinical characteristics, and therefore, may provide significant improvement to current risk stratification models. [9][10][11][12][13][14][15][16]41,44,45 While we await additional studies to elucidate the pathogenic role of suPAR or the pathways its levels represent, we envision the potential for use of suPAR concentrations in risk stratification to personalize care and optimize resource allocation.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8] Soluble urokinase plasminogen activator receptor (suPAR) is a marker of immune activation thought to be involved in the pathogenesis of kidney disease; suPAR concentrations have also been associated with mortality and cardiovascular disease in the general population (without comorbidities), in critically ill patients, patients with cerebrovascular disease, HIV infection, and kidney disease. [9][10][11][12][13][14][15][16][17][18][19][20][21] In contrast to hs-CRP, elevated suPAR is reportedly associated with the presence of CAC as well as peripheral arterial disease. 22,23 Whether suPAR levels provide further benefit in risk stratification in African Americans (AA) with T2D has not been studied.…”

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confidence: 99%

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Predicting Mortality in African Americans With Type 2 Diabetes Mellitus: Soluble Urokinase Plasminogen Activator Receptor, Coronary Artery Calcium, and High‐Sensitivity C‐Reactive Protein

Hayek

Divers

Raad

et al. 2018

JAHA

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BackgroundType 2 diabetes mellitus is a major risk factor for cardiovascular disease; however, outcomes in individual patients vary. Soluble urokinase plasminogen activator receptor (suPAR) is a bone marrow–derived signaling molecule associated with adverse cardiovascular and renal outcomes in many populations. We characterized the determinants of suPAR in African Americans with type 2 diabetes mellitus and assessed whether levels were useful for predicting mortality beyond clinical characteristics, coronary artery calcium (CAC), and high‐sensitivity C‐reactive protein (hs‐CRP).Methods and ResultsWe measured plasma suPAR levels in 500 African Americans with type 2 diabetes mellitus enrolled in the African American‐Diabetes Heart Study. We used Kaplan‐Meier curves and Cox proportional hazards models adjusting for clinical characteristics, CAC, and hs‐CRP to examine the association between suPAR and all‐cause mortality. Last, we report the change in C‐statistics comparing the additive values of suPAR, hs‐CRP, and CAC to clinical models for prediction of mortality. The suPAR levels were independently associated with female sex, smoking, insulin use, decreased kidney function, albuminuria, and CAC. After a median 6.8‐year follow‐up, a total of 68 deaths (13.6%) were recorded. In a model incorporating suPAR, CAC, and hs‐CRP, only suPAR was significantly associated with mortality (hazard ratio 2.66, 95% confidence interval 1.63‐4.34). Addition of suPAR to a baseline clinical model significantly improved the C‐statistic for all‐cause death (Δ0.05, 95% confidence interval 0.01‐0.10), whereas addition of CAC or hs‐CRP did not.ConclusionsIn African Americans with type 2 diabetes mellitus, suPAR was strongly associated with mortality and improved risk discrimination metrics beyond traditional risk factors, CAC and hs‐CRP. Studies addressing the clinical usefulness of measuring suPAR concentrations are warranted.

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Section: Strengths and Limitationsmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Predicting Mortality in African Americans With Type 2 Diabetes Mellitus: Soluble Urokinase Plasminogen Activator Receptor, Coronary Artery Calcium, and High‐Sensitivity C‐Reactive Protein

Hayek

Divers

Raad

et al. 2018

JAHA

View full text Add to dashboard Cite

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“…In addition to its associations to atherosclerosis, suPAR has also been shown to be a good prognostic marker of in-hospital mortality in patients suffering severe infection and septic shock (35), as well as being a prognostic marker in cardiovascular mortality in a black South African population (36) and various other settings (24,36). Interestingly, in a study of 60 patients undergoing coronary artery bypass surgery, perioperative levels of suPAR remained stable despite the extensive inflammatory reaction induced by such major surgery (37).…”

Section: Discussionmentioning

confidence: 99%

Soluble Urokinase-type Plasminogen Activator Receptor Predicts All-cause 5-Year Mortality in Ischemic Stroke and TIA

Onatsu

Taina

Mustonen

et al. 2017

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Racial Discrimination and Metabolic Syndrome in Young Black Adults

Heard-Garris,

Yu,

Brody

et al. 2024

JAMA Netw Open

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ImportanceMetabolic syndrome (MetS) is a common health condition that predisposes individuals to cardiovascular disease (CVD) and disproportionately affects Black and other racially and ethnically minoritized people. Concurrently, Black individuals also report more exposure to racial discrimination compared with White individuals; however, the role of discrimination in the development of MetS over time and associated mediators in these pathways remain underexplored.ObjectiveTo evaluate the association between racial discrimination and MetS in rural Black individuals transitioning from late adolescence into early adulthood and to identify potential mediating pathways.Design, Setting, and ParticipantsThis longitudinal cohort study included Black adolescents enrolled in the Strong African American Families Healthy Adults (SHAPE) Project between June 2009 and May 2021. Families resided in rural counties of Georgia, where poverty rates are among the highest in the nation. Analyses included 322 of the 500 participants who originally enrolled in SHAPE and who were eligible to participate. Guardians provided information about socioeconomic disadvantage. Analyses were conducted in April 2023.ExposuresYouths reported exposure to racial discrimination annually from ages 19 to 21 years.Main Outcomes and MeasuresMetS was the main health outcome and was measured at ages 25 and 31 years. MetS was diagnosed according to the International Diabetes Federation guidelines, which requires central adiposity (ie, waist circumference ≥94 cm for males and ≥80 cm for females) and at least 2 of the 4 additional components: signs of early hypertension (ie, systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥85 mm Hg); elevated triglyceride levels (ie, &gt;150 mg/dL); elevated fasting glucose level (ie, ≥100 mg/dL); or lowered high-density lipoprotein levels (ie, &lt;40 mg/dL in men and &lt;50 mg/dL in women). At age 25 years, markers of inflammatory activity (ie, soluble urokinase plasminogen activator receptor [suPAR]) and sleep problems were collected to consider as potential mediators.ResultsIn 322 participants (210 [65.2%] female) ages 19 to 21 years, more frequent exposure to racial discrimination was associated with higher suPAR levels (b = 0.006; 95% CI, 0.001-0.011; P = .01) and more sleep problems at age 25 years (b = 0.062; 95% CI, 0.028-0.097; P &lt; .001) as well as a 9.5% higher risk of MetS diagnosis at age 31 years (odds ratio [OR], 1.10; 95% CI, 1.01-1.20; P = .03). Both suPAR (b = 0.015; 95% CI, 0.002-0.037) and sleep problems (b = 0.020; 95% CI, 0.002-0.047) at age 25 years were significant indirect pathways. No significant interactions between sex and discrimination emerged.Conclusions and RelevanceThis study suggests that racial discrimination in late adolescence is associated with MetS among Black young adults through biobehavioral pathways. Thus, health interventions for MetS in Black adults will need to contend with sleep behaviors and inflammatory intermediaries as well as address and reduce exposure to racial discrimination to narrow disparities and promote health equity.

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Soluble urokinase plasminogen activator receptor as a prognostic marker of all-cause and cardiovascular mortality in a black population

Cited by 46 publications

References 48 publications

Predicting Mortality in African Americans With Type 2 Diabetes Mellitus: Soluble Urokinase Plasminogen Activator Receptor, Coronary Artery Calcium, and High‐Sensitivity C‐Reactive Protein

Predicting Mortality in African Americans With Type 2 Diabetes Mellitus: Soluble Urokinase Plasminogen Activator Receptor, Coronary Artery Calcium, and High‐Sensitivity C‐Reactive Protein

Soluble Urokinase-type Plasminogen Activator Receptor Predicts All-cause 5-Year Mortality in Ischemic Stroke and TIA

Racial Discrimination and Metabolic Syndrome in Young Black Adults

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