scholarly journals Association of Circulating Hepatocyte Growth Factor and Risk of Incident Peripheral Artery Disease: The Multi-Ethnic Study of Atherosclerosis

Angiology ◽  
2020 ◽  
Vol 71 (6) ◽  
pp. 544-551
Author(s):  
Parveen K. Garg ◽  
Petra Buzkova ◽  
Christina L. Wassell ◽  
Matthew Allison ◽  
Michael Criqui ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Ankle Brachial Index ◽  
Arterial Disease ◽  
Ethnic Study ◽  
Increased Risk ◽  
Artery Disease ◽  
Peripheral Arterial ◽  
Hepatocyte Growth

Higher levels of hepatocyte growth factor (HGF) have been associated with the presence of peripheral arterial disease (PAD), but prospective associations are unknown. We examined the association of circulating HGF levels with incident PAD. Between 2000 and 2002, HGF was measured in 6742 Multi-Ethnic Study of Atherosclerosis participants without PAD. Incident clinical PAD, adjudicated on the basis of a positive history for the presence of disease-related symptoms or treatment, was ascertained through 2015. Incident low ankle-brachial index (ABI), defined as an ABI < 0.9 and a decline of ≥ 0.15, was assessed among 5736 individuals who had an ABI > 0.9 at baseline and ≥1 follow-up ABI measurement 3 to 10 years later. There were 116 clinical PAD and 197 low ABI events that occurred over a median follow-up of 14 and 9 years, respectively. After adjustment for demographic and clinical variables, a standard deviation increment of HGF (303 ng/L) was associated with an increased risk of clinical PAD (hazard ratio: 1.21; 95% confidence interval [CI]: 1.05-1.39) but not a low ABI (rate ratio: 1.03; 95% CI: 0.85-1.25). In conclusion, higher HGF levels were modestly associated with an increased risk of developing clinical PAD.

scholarly journals Safety Evaluation of Clinical Gene Therapy Using Hepatocyte Growth Factor to Treat Peripheral Arterial Disease

Hypertension ◽  
2004 ◽  
Vol 44 (2) ◽  
pp. 203-209 ◽  
Author(s):  
Ryuichi Morishita ◽  
Motokuni Aoki ◽  
Naotaka Hashiya ◽  
Hirofumi Makino ◽  
Keita Yamasaki ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Growth Factor ◽  
Peripheral Arterial Disease ◽  
Hepatocyte Growth Factor ◽  
Safety Evaluation ◽  
Arterial Disease ◽  
Clinical Gene Therapy ◽  
Peripheral Arterial ◽  
Hepatocyte Growth

Potential Role of Hepatocyte Growth Factor, a Novel Angiogenic Growth Factor, in Peripheral Arterial Disease

Circulation ◽  
1999 ◽  
Vol 100 (suppl_2) ◽  
Author(s):  
Shin-ichiro Hayashi ◽  
Ryuichi Morishita ◽  
Shigefumi Nakamura ◽  
Kei Yamamoto ◽  
Atsushi Moriguchi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Peripheral Arterial Disease ◽  
Hepatocyte Growth Factor ◽  
Hind Limb ◽  
Arterial Disease ◽  
Angiogenic Growth Factor ◽  
Peripheral Arterial ◽  
Hepatocyte Growth ◽  
Hypoxic Treatment

Background —Although hepatocyte growth factor (HGF), a novel angiogenic growth factor, plays an important role in angiogenesis, regulation of local HGF production under hypoxia has not yet been clarified in vascular smooth muscle cells (VSMC) and endothelial cells (EC). Thus, we have studied the role of HGF in hypoxia-induced endothelial injury and the regulation of local vascular HGF expression in response to hypoxia. Methods and Results —HGF attenuated hypoxia-induced endothelial cell death. Importantly, hypoxic treatment of EC resulted in a significant decrease in local HGF production according to the severity of hypoxia and increased VEGF. Similarly, hypoxia significantly decreased in mRNA and protein of HGF and increased VEGF production in VSMC. In organ culture system, local HGF production was also significantly decreased by hypoxia ( P <0.01). Downregulation of HGF by hypoxia is due to a significant decrease in cAMP, as hypoxic treatment decreased cAMP, a stimulator of HGF. Although active TGF-β, a suppressor of HGF, was increased at 72 hours after hypoxic treatment, treatment of anti-TGF-β antibody did not attenuate decreased HGF production. Finally, rHGF was intra-arterially administered into unilateral hind limb ischemia rabbits, to evaluate in vivo angiogenic activity. Of importance, a single intra-arterial administration of rHGF reduced severe necrosis due to ischemia in rabbit muscle, accompanied by a significant increase in angiographic score ( P <0.01). Conclusions —Overall, these data demonstrated that hypoxic treatment of vascular cells significantly downregulated HGF production due to decreased cAMP, suggesting their potential roles in the pathophysiology of ischemic diseases. Moreover, administration of rHGF induced therapeutic angiogenesis, accompanied by improvement of necrotic changes in the ischemic hind limb model, as cytokine supplement therapy for peripheral arterial disease.

Abstract 16346: Soluble P-Selectin Predicts Lower Extremity Peripheral Artery Disease Incidence and Change in the Ankle Brachial Index: The Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Christina L Wassel ◽  
Cecilia Berardi ◽  
James S Pankow ◽  
Nicholas B Larson ◽  
Paul A Decker ◽  
...  
Keyword(s):  
Disease Incidence ◽  
Ankle Brachial Index ◽  
Arterial Disease ◽  
Population Based ◽  
Ethnic Study ◽  
Growth Curve Models ◽  
C Statistic ◽  
Artery Disease ◽  
Peripheral Arterial ◽  
D Dimer

Background: Given the global burden of peripheral arterial disease (PAD) and the associated morbidity, continuing investigation of potential biomarkers as therapeutic targets for preventing PAD is warranted. The association of P-selectin, an endothelial cell adhesion molecule, with the ankle brachial index (ABI) and PAD is not well established. Thus, we examined the association of circulating P-selectin with prevalent and incident PAD, the ABI, and change in the ABI. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective population-based cohort including 6814 non-Hispanic white, African American, Hispanic and Chinese men and women aged 45-84 at baseline (2000-02). For this analysis, 5700 participants with both P-selectin at Exam 2 (2002-04) and the ABI at Exam 3 (2004-05) were available, with change in ABI from Exam 3 to Exam 5 (2010-12) available on 4276 participants. P-selectin was modeled per standard deviation (SD), while prevalent and incident PAD were defined as ABI ≤ 0.90 after excluding those with ABI>1.4. Linear regression was used for ABI, growth curve models for change in ABI, and logistic regression for prevalent and incident PAD. Results: In models adjusted for demographics, lifestyle factors, comorbidities, blood pressure, lipids, fasting glucose, c-reactive protein (CRP), interleukin-6 (IL-6), D-dimer, and fibrinogen, each SD (13 ng/mL) higher P-selectin was significantly associated with 0.007 lower ABI (95% CI ((-0.011, -0.004)), p<0.001), and an average change in the ABI of -0.006 ((-0.010, -0.003, p<0.001). P-selectin was also significantly associated with a 1.14-fold greater odds of prevalent PAD ((1.00, 1.28), p=0.04), and a 1.30-fold greater odds of incident PAD ((1.10, 1.55), p<0.001). There were no significant interactions of p-selectin by race/ethnicity or gender. Addition of P-selectin to models containing traditional PAD risk factors as well as CRP, IL-6, D-dimer and fibrinogen did not improve the c-statistic or net reclassification for incident PAD. Conclusions: P-selectin appears to be strongly associated with the development of PAD. However, further research is needed in population-based studies to confirm prospective associations of p-selectin with incident PAD and change in the ABI.

scholarly journals GlycA, a Novel Inflammatory Marker and Its Association With Peripheral Arterial Disease and Carotid Plaque: The Multi-Ethnic Study of Atherosclerosis

Angiology ◽  
2019 ◽  
Vol 70 (8) ◽  
pp. 737-746 ◽  
Author(s):  
Oluwaseun E. Fashanu ◽  
Abayomi O. Oyenuga ◽  
Di Zhao ◽  
Martin Tibuakuu ◽  
Samia Mora ◽  
...  
Keyword(s):  
Carotid Plaque ◽  
Inflammatory Marker ◽  
Ankle Brachial Index ◽  
Arterial Disease ◽  
Prevalence Odds Ratio ◽  
Ethnic Study ◽  
Mixed Regression ◽  
Artery Disease ◽  
Peripheral Arterial ◽  
Incident Cases

GlycA, a composite biomarker of systemic inflammation, is associated with cardiovascular disease (CVD) and mortality, but its relationship with peripheral artery disease (PAD) is unknown. We assessed whether plasma GlycA is associated with ankle–brachial index (ABI), carotid plaque (CP), and incident clinical PAD among 6466 Multi-Ethnic Study of Atherosclerosis participants without CVD at baseline. GlycA, ABI, and CP were measured at baseline. Both ABI and CP were remeasured at 10 years. Incident clinical PAD was ascertained from hospital records. We used logistic, Cox, and linear mixed regression models adjusted for demographic and lifestyle factors. Mean (standard deviation, SD) was 62 (10) years for age and 381 (61) µmol/L for GlycA; 53% were women. GlycA was associated with both prevalent low ABI ≤0.8 (prevalence odds ratio [95% confidence interval, CI] per SD increment in GlycA, 1.65 [1.39-1.97]) and CP (1.19 [1.11-1.27]) at baseline. There were no significant associations of GlycA with incident low ABI, incident CP, or 10-year change in ABI or CP score. We identified 110 incident cases of PAD after 79 590 person-years. The hazard ratio (95% CI) of incident PAD per SD increment in GlycA was 1.38 (1.14-1.66). In conclusion, GlycA was associated with prevalent low ABI, prevalent CP, and incident PAD after a median of 14 years.

Abstract 11471: Peripheral Arterial Disease and Risk of Atrial Fibrillation and Stroke: The Multi-Ethnic Study of Atherosclerosis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Wesley T O’Neal ◽  
Jimmy T Efird ◽  
Saman Nazarian ◽  
Alvaro Alonso ◽  
Susan R Heckbert ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Peripheral Arterial Disease ◽  
Cox Regression ◽  
Ankle Brachial Index ◽  
Arterial Disease ◽  
Ethnic Study ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Peripheral Arterial

Introduction: Peripheral arterial disease (PAD) shares several risk factors with atrial fibrillation (AF) and persons with PAD have an increased risk of stroke. It is unclear if PAD is associated with an increased risk for AF and whether such an association explains the increased risk of stroke associated with PAD. Methods: We examined the association between PAD, as measured by the ankle-brachial index (ABI), and incident AF and incident stroke, separately, in 6,568 participants (mean age 62 ± 10; 53% women; 62% non-white) from the Multi-Ethnic Study of Atherosclerosis (MESA). ABI values <1.0 or >1.4 defined PAD in this analysis. Participants were free of baseline clinical cardiovascular disease and AF. AF was ascertained by review of hospital discharge records and from Medicare claims data until December 31, 2010. An independent adjudication committee ascertained stroke events. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95%CI) for the association between PAD and AF and stroke. Results: A total of 774 (12%) participants had baseline PAD. Over a median follow-up of 8.5 years, 301 (4.6%) participants developed AF and 140 (2.1%) developed stroke. In a model adjusted for socio-demographics, cardiovascular risk factors, and potential confounders, PAD was associated with an increased risk of AF (HR=1.5, 95%CI=1.1, 2.0). In a similar model, PAD was associated with incident stroke (HR=1.7, 95%CI=1.1, 2.5) and the magnitude of risk was not different after inclusion of AF as a time-dependent covariate (HR=1.7, 95%CI=1.1, 2.5). Similar results were obtained in subgroup analyses stratified by age, sex, and race/ethnicity. Conclusions: PAD is independently associated with an increased risk of AF and stroke in the MESA study. The relationship between PAD and stroke is not mediated by AF.

scholarly journals Valvular calcification and risk of peripheral artery disease: the Multi-Ethnic Study of Atherosclerosis (MESA)

2019 ◽  
Vol 21 (10) ◽  
pp. 1152-1159 ◽  
Author(s):  
Parveen K Garg ◽  
Petra Buzkova ◽  
Zahra Meyghani ◽  
Matthew J Budoff ◽  
Joao Lima ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Cardiac Computed Tomography ◽  
Ankle Brachial Index ◽  
Cox Proportional Hazards ◽  
Peripheral Artery ◽  
Ethnic Study ◽  
Valvular Calcification ◽  
Increased Risk ◽  
Artery Disease

Abstract Aims The detection of cardiac valvular calcification on routine imaging may provide an opportunity to identify individuals at increased risk for peripheral artery disease (PAD). We investigated the associations of aortic valvular calcification (AVC) and mitral annular calcification (MAC) with risk of developing clinical PAD or a low ankle–brachial index (ABI). Methods and results AVC and MAC were measured on cardiac computed tomography in 6778 Multi-Ethnic Study of Atherosclerosis participants without baseline PAD between 2000 and 2002. Clinical PAD was ascertained through 2015. Incident low ABI, defined as ABI &lt;0.9 and decline of ≥0.15, was assessed among 5762 individuals who had an ABI &gt;0.9 at baseline and at least one follow-up ABI measurement 3–10 years later. Adjusted Cox proportional hazards and Poisson regression modelling were used to determine the association of valvular calcification with clinical PAD and low ABI, respectively. There were 117 clinical PAD and 198 low ABI events that occurred over a median follow-up of 14 years and 9.2 years, respectively. The presence of MAC was associated with an increased risk of clinical PAD [hazard ratio 1.79; 95% confidence interval (CI) 1.04–3.05] but not a low ABI (rate ratio 1.28; 95% CI 0.75–2.19). No significant associations were noted for the presence of AVC and risk of either clinical PAD. Conclusion MAC is associated with an increased risk of developing clinical PAD. Future studies are needed to corroborate our findings and better understand whether MAC holds any predictive value as a risk marker for PAD.

scholarly journals Lipoprotein-associated phospholipase A2 and risk of incident peripheral arterial disease in a multi-ethnic cohort: The Multi-Ethnic Study of Atherosclerosis

2016 ◽  
Vol 22 (1) ◽  
pp. 5-12 ◽  
Author(s):  
Parveen K Garg ◽  
Neal W Jorgensen ◽  
Robyn L McClelland ◽  
Nancy S Jenny ◽  
Michael H Criqui ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Significant Interaction ◽  
Regression Models ◽  
Ankle Brachial Index ◽  
Arterial Disease ◽  
Logistic Regression Models ◽  
Increased Risk ◽  
Adjusted Logistic Regression ◽  
Peripheral Arterial

Prospective studies supporting a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident peripheral arterial disease (PAD) are limited. We evaluated the association of Lp-PLA2 with incident PAD in a multi-ethnic cohort without clinical cardiovascular disease. A total of 4622 participants with measurement of Lp-PLA2 mass and Lp-PLA2 activity and an ankle–brachial index (ABI) between 0.9 and 1.4 were followed for the development of PAD (median follow-up = 9.3 years), defined as an ABI ⩽0.9 and decline from baseline ⩾0.15. There were 158 incident PAD events during follow-up. In adjusted logistic regression models, each higher standard deviation of both Lp-PLA2 activity and mass did not confer an increased risk of developing PAD [odds ratios, (95% confidence intervals)]: 0.92 (0.66–1.27) for Lp-PLA2 activity and 1.06 (0.85–1.34) for mass. Additionally, no significant interaction was found according to ethnicity: p=0.43 for Lp-PLA2 activity and p=0.55 for Lp-PLA2 mass. We found no evidence of an association between Lp-PLA2 and incident PAD.

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