Polak, Joseph F.

Introduction: Accreditation of vascular laboratories has been shown to lead to overall improvements in quality patient care. However, there are still factors that needlessly delay the granting of full accreditation. We performed a retrospective analysis looking at factors associated with delays in accreditation in extracranial carotid artery ultrasound examinations by the Intersocietal Accreditation Commission - Vascular Testing (IAC-VT) division. Materials and Methods: We accessed an active database from the IAC-VT division between 2014 and 2020 and extracted data linked to vascular laboratory accreditation in extracranial carotid ultrasound studies. We used the ‘Delay” versus the “Grant” status as outcome and looked at the association with 18 metrics that are part of the application evaluation. We further used a modified Delphi method to determine the relative role played by either the technologist/sonographer or the interpreting physician for each metric. Statistical significance was evaluated by Chi-square. Results: A “Delay” status was assigned in 1638 (58.6%) out of 2794. Ten factors were noted to be significant univariate predictors of a “Delay” status. The three major factors were solely associated with the interpreting physician while adherence to technical factors showed mostly shared responsibility. Conclusion: This retrospective study indicated that the accreditation process is strongly dependent on interpreting physician performance. Targeted interventions may help decrease time and effort associated with the costs of the accreditation process.

Introduction: Hepatocyte growth factor (HGF) is released in response to endothelial injury, and higher levels of circulating HGF are associated with atherosclerosis. However, the association of HGF with atherosclerosis progression is unknown. Hypothesis: Circulating HGF is positively associated with atherosclerosis progression, measured as progression of 1) carotid artery plaque and 2) coronary artery calcium (CAC). Methods: The Multi-Ethnic Study of Atherosclerosis is a large, population-based cohort study of adults aged 45-84 and free of clinical cardiovascular disease. Participants had HGF measured in serum at baseline (2000-02), and were followed for progression of carotid plaque and CAC through 2012. We defined CAC and carotid plaque progression as dichotomous variables (progression, no progression). Carotid plaque progression is an increase in the number of carotid plaques. We used the Hokanson method to define CAC progression as an increase of ≥ 2.5 mm 3 in the square root-transformed calcium volume score. Relative risk regression quantified the association between HGF and carotid plaque progression. Cox regression models using inverse-probability-of-attrition weights estimated the association of HGF with progression of CAC. All effect estimates are adjusted for potential confounding variables. Results: The cohort included 6714 Americans with HGF measurements: 2593 non-Hispanic white, 797 Chinese, 1848 black, and 1476 Hispanic Americans. In 3363 participants with measurements for both carotid plaque and HGF, each standard deviation (259 pg/ml) increase in HGF was associated with a 4% greater risk (95% CI: 1.01-1.07) of carotid plaque progression (n=1875), which did not differ by race/ethnicity (interaction p = 0.3). Out of 6714 participants with measurements for both CAC and HGF, 2994 had CAC progression during follow-up. The association of HGF with CAC progression differed by race/ethnicity (interaction p = 0.01). Each standard deviation increase of HGF was associated with a 10% greater risk of CAC progression in non-Hispanic white (95% CI: 1.05-1.16) and black Americans (95% CI: 1.03-1.17), while HGF was not associated with CAC progression in Chinese (p = 0.5) nor Hispanic (p = 0.7) American participants. Conclusions: Circulating HGF was associated with a modestly increased risk of atherosclerosis progression in this large and diverse population, with the strongest associations between HGF and CAC progression in non-Hispanic white and black Americans. Our results suggest that HGF may have utility as a marker of atherosclerosis progression in some populations.

L-selectin is an adhesion molecule constitutively expressed on leukocytes and mediating their interaction with the endothelium. As a member of the selectin family, it plays a crucial role in leukocyte adhesion to and migration through the endothelial wall during inflammation. A protective role of L-selectin in early atherosclerosis was demonstrated in animal models. Previous studies assessing the relationship of this protein with cardiovascular disease were inconsistent. Lower serum L-selectin levels were found in patients with coronary artery disease (CHD) and peripheral artery disease (PAD) compared to controls. In contrast, plasma levels of L-selectin were increased in patients with CHD and PAD. These inconsistencies might be due to an interaction of soluble L-selectin with clotting factors or anticoagulants present in plasma but not in serum. Also, the small number and Caucasian predominance of patients included in previous studies represent limitations that need to be addressed using a rigorous, population-based approach. Herein, we seek to investigate the association of serum L-selectin with subclinical outcomes in a large, ethnically heterogeneous population. In a randomly selected subset of 720 subjects for each of the four ethnicities included in the Multi-Ethnic Study of Atherosclerosis (MESA), serum samples were available for 2403 individuals (579 African Americans, 620 Caucasians, 600 Chinese and 604 Hispanics). Serum L-selectin levels and intima-media thickness (IMT) were measured at exam 2 and CAC was measured at exam 2 or 3 during the cohort follow up. Regression analysis and the Tobit model were used to assess the association of L-selectin levels with IMT and CAC respectively. The mean age was 63±10 years and 47% were men. The mean±SD protein levels were significantly different across ethnicities (867±192 ng/mL in African Americans, 956±215 ng/mL in Caucasians, 834±174 ng/mL in Chinese and 904±195 ng/mL in Hispanics; p<0.0001). In the univariate analysis, age was inversely correlated to the protein levels; in addition, levels were lower in males, regardless of ethnicity and in smokers, except among Hispanics. L-selectin was associated with modestly lower CAC only among Chinese (p=0.030), the association persisted after adjustment for traditional risk factors (p=0.046). No significant association was demontrated between the protein levels and IMT. In conclusion, in this large diverse population, we found that serum L-selectin was modestly associated to measures of subclinical atherosclerosis in Chinese but not in African, European or Hispanic Americans.

Objective To determine if hepatocyte growth factor (HGF), a promising biomarker of coronary heart disease (CHD) given its release into circulation in response to endothelial damage, is associated with subclinical and clinical CHD in a racial/ethnic diverse population. Methods HGF was measured in 6738 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Highest mean HGF values (pg/mL) were observed in Hispanic, followed by African, non-Hispanic white, then Chinese Americans. Results In all races/ethnicities, HGF levels were associated with older age, higher systolic blood pressure (SBP) and body mass index, lower high-density lipoprotein, diabetes and current smoking. In fully adjusted models, each SD higher HGF was associated with an average increase in coronary artery calcium (CAC) of 55 Agatston units for non-Hispanic whites (p<0.001) and 51 Agatston units for African-Americans (p=0.007) but was not in the other race/ethnic groups (interaction p=0.02). There were 529 incident CHD events, and CHD risk was 41% higher in African (p<0.001), 17% in non-Hispanic white (p=0.026) and Chinese (p=0.36), and 6% in Hispanic Americans (p=0.56) per SD increase in HGF. Conclusion In a large and diverse population-based cohort, we report that HGF is associated with subclinical and incident CHD. We demonstrate evidence of racial/ethnic heterogeneity within these associations, as the results are most compelling in African-Americans and non-Hispanic white Americans. We provide evidence that HGF is a biomarker of atherosclerotic disease that is independent of traditional risk factors.