Endothelial Dysfunction and Cardiometabolic Risk Factors in Mexican American Adults: The Cameron County Hispanic Cohort.

Endothelial dysfunction assessed by impaired brachial flow-mediated dilation (FMD) predicts incident cardiovascular disease (CVD). We have previously shown that clustering of diabetes mellitus, obesity, and metabolic syndrome in young Hispanic patients was associated with subclinical atherosclerosis. This study aimed to assess determinants of impaired FMD response (%FMD), an earlier marker of atherosclerosis, in a population-based sample of asymptomatic Mexican Americans. Cardiometabolic biomarkers and FMD were obtained from 960 Cameron County Hispanic Cohort participants. Gender-specific median values of %FMD were used to categorize participants into those with %FMD below or above the median. The sample was further stratified into those younger and older than 55 years. Survey-weighted logistic regression analyses were conducted to evaluate the effects of cardiometabolic biomarkers on the %FMD groups. The low %FMD group was significantly older, had higher visceral adipose tissue, systolic blood pressure, or plasma glucose, and had metabolic syndrome compared with those in the high %FMD group. Multivariable-adjusted age-stratified logistic regression analyses showed that in older participants, male gender (odds ratio [OR] = 2.4 [1.4 to 4.2]) and having hypertension (OR = 2.3 [1.3 to 4.3]) or prediabetes mellitus (OR = 3.4 [1.5 to 7.5]) remained significantly associated with odds of low %FMD. In younger participants, high low-density lipoprotein (OR = 2.8 [1.6 to 4.9]) or having the metabolic syndrome (OR = 1.9 [1.1 to 3.6]) were significantly associated with odds of low %FMD. In conclusion, we found age-dependent associations between cardiometabolic biomarkers and an FMD response below the gender-specific median in a sample composed of Mexican Americans without previous CVD. Targeting specific risk factors by age may mitigate progression to incident CVD in this high-risk racial disparity group.

Sex-specific associations between adipokine profiles and carotid-intima media thickness in the Cameron County Hispanic Cohort (CCHC).

BACKGROUND: Adipokines are hormones secreted from adipose tissue and are associated with cardiometabolic diseases (CMD). Functional differences between adipokines (leptin, adiponectin, and resistin) are known, but inconsistently reported associations with CMD and lack of studies in Hispanic populations are research gaps. We investigated the relationship between subclinical atherosclerosis and multiple adipokine measures. METHODS: Cross-sectional data from the Cameron County Hispanic Cohort (N = 624; mean age = 50; Female = 70.8%) were utilized to assess associations between adipokines [continuous measures of adiponectin, leptin, resistin, leptin-to-adiponectin ratio (LAR), and adiponectin-resistin index (ARI)] and early atherosclerosis [carotid-intima media thickness (cIMT)]. We adjusted for sex, age, body mass index (BMI), smoking status, cytokines, fasting blood glucose levels, blood pressure, lipid levels, and medication usage in the fully adjusted linear regression model. We conducted sexes-combined and sex-stratified analyses to account for sex-specificity and additionally tested whether stratification of participants by their metabolic status (metabolically elevated risk for CMD as defined by having two or more of the following conditions: hypertension, dyslipidemia, insulin resistance, and inflammation vs. not) influenced the relationship between adipokines and cIMT. RESULTS: In the fully adjusted analyses, adiponectin, leptin, and LAR displayed significant interaction by sex (p < 0.1). Male-specific associations were between cIMT and LAR [ß(SE) = 0.060 (0.016), p = 2.52 × 10-4], and female-specific associations were between cIMT and adiponectin [ß(SE) = 0.010 (0.005), p = 0.043] and ARI [ß(SE) = - 0.011 (0.005), p = 0.036]. When stratified by metabolic health status, the male-specific positive association between LAR and cIMT was more evident among the metabolically healthy group [ß(SE) = 0.127 (0.015), p = 4.70 × 10-10] (p for interaction by metabolic health < 0.1). However, the female-specific associations between adiponectin and cIMT and ARI and cIMT were observed only among the metabolically elevated risk group [ß(SE) = 0.014 (0.005), p = 0.012 for adiponectin; ß(SE) = - 0.015 (0.006), p = 0.013 for ARI; p for interaction by metabolic health < 0.1]. CONCLUSION: Associations between adipokines and cIMT were sex-specific, and metabolic health status influenced the relationships between adipokines and cIMT. These heterogeneities by sex and metabolic health affirm the complex relationships between adipokines and atherosclerosis.

Demonstration of ultrasound-mediated therapeutic delivery of fibrin-targeted pioglitazone-loaded echogenic liposomes into the arterial bed for attenuation of peri-stent restenosis.

Peri-stent restenosis following stent implantation is a major clinical problem. We have previously demonstrated that ultrasound-facilitated liposomal delivery of pioglitazone (PGN) to the arterial wall attenuated in-stent restenosis. To evaluate ultrasound mediated arterial delivery, in Yucatan miniswine, balloon inflations were performed in the carotid and subclavian arteries to simulate stent implantation and induce fibrin formation. The fibrin-binding peptide, GPRPPGGGC, was conjugated to echogenic liposomes (ELIP) containing dinitrophenyl-L-alanine-labelled pioglitazone (DNP-PGN) for targeting purposes. After pre-treating the arteries with nitroglycerine, fibrin-binding peptide-conjugated PGN-loaded ELIP (PAFb-DNP-PGN-ELIP also termed atheroglitatide) were delivered to the injured arteries via an endovascular catheter with an ultrasound core, either with or without ultrasound application (EKOSTM Endovascular System, Boston Scientific). In arteries treated with atheroglitatide, there was substantial delivery of PGN into the superficial layers (5 µm from the lumen) of the arteries with and without ultrasound, [(1951.17 relative fluorescence units (RFU) vs. 1901.17 RFU; P-value = 0.939)]. With ultrasound activation there was increased penetration of PGN into the deeper arterial layers (up to 35 µm from the lumen) [(13195.25 RFU vs. 7681.00 RFU; P-value = 0.005)]. These pre-clinical data demonstrate ultrasound mediated therapeutic vascular delivery to deeper layers of the injured arterial wall. This model has the potential to reduce peri- stent restenosis.

Association of Visceral Adipose Tissue and Subclinical Atherosclerosis in US-Born Mexican Americans but not First Generation Immigrants.

Background Excess visceral adipose tissue (VAT) is a primary driver for the cardiometabolic complications of obesity; VAT-associated cardiovascular disease risk varies by race, but most studies have been done on Non-Hispanics. This study aimed to evaluate the clinical and metabolic correlates of VAT, its association with subclinical atherosclerosis, and the factors affecting this association in Mexican Americans. Methods and Results Participants (n=527) were drawn from the Cameron County Hispanic Cohort (CCHC), on whom a carotid ultrasound to assess carotid intima media thickness and a dual-energy X-ray absorptiometry scan to assess for VAT were obtained. Those in the highest quartiles of VAT were more likely to have hypertension, hypertriglyceridemia, low high-density lipoprotein, diabetes mellitus, and metabolic syndrome. Increased carotid intima media thickness was more prevalent in those in the highest quartile for VAT (57.4% versus 15.4% for the lowest quartile; P<0.001). There was a graded increase in mean carotid intima media thickness with increasing VAT, after adjusting for covariates; for every 10 cm2 increase in VAT, there was an increase of 0.004 mm (SE=0.002; P=0.0299) in mean carotid intima media thickness. However, this association was only seen among second or higher generation US-born Mexican Americans but not among first generation immigrants (P=0.024). Conclusions Excess VAT is associated with indicators of metabolic disorders and subclinical atherosclerosis in Mexican Americans regardless of body mass index. However, acculturation appears to be an important modulator of this association. Longitudinal follow-up with targeted interventions among second or higher generation Hispanics to lower VAT and improve cardiometabolic risk may help prevent premature cardiovascular disease in this cohort.

Stabilizing Peri-Stent Restenosis Using a Novel Therapeutic Carrier.

Late in-stent restenosis remains a significant problem. Bare-metal stents were implanted into peripheral arteries in miniature swine, followed by direct intra-arterial infusion of nitric oxide-loaded echogenic liposomes (ELIPs) and anti-intercellular adhesion molecule-1 conjugated ELIPs loaded with pioglitazone exposed to an endovascular catheter with an ultrasonic core. Ultrasound-facilitated delivery of ELIP formulations into stented peripheral arteries attenuated neointimal growth. Local atheroma-targeted, ultrasound-triggered delivery of nitric oxide and pioglitazone, an anti-inflammatory peroxisome proliferator-activated receptor-γ agonist, into stented arteries has the potential to stabilize stent-induced neointimal growth and obviate the need for long-term antiplatelet therapy.

Statin Prescription for Patients With Atherosclerotic Cardiovascular Disease from National Survey Data.

Despite strong evidence for the use of statins for patients with atherosclerotic cardiovascular disease (ASCVD), statin prescription is still suboptimal. We aimed to determine the rates and factors that influence statin prescription using national survey data. This is a cross-sectional retrospective study on 8,468 patients with clinical ASCVD who were drawn from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from years 2011 to 2015. Survey-weighted analysis was conducted to estimate weighted prevalence and odds ratios for statin prescription. There was a significant increase in statin prescription from the years 2011 to 2015. Nevertheless, only 52% of ASCVD patients (55.4% in coronary heart disease and 37.7% in noncoronary heart disease) were prescribed a statin. Based on multivariable regression analysis, after adjusting for covariates, males had 1.28 (1.06, 1.55) higher odds of statin prescription, in coronary heart disease patients only. In the overall study population, Black n on-Hispanics had 31% lower odds of statin prescription compared with White non-Hispanics, and patients seen only by a healthcare provider other than a physician were 80% less likely to have a statin prescribed to them. In conclusion, the disparity in statin prescription in patients with ASCVD exists across minority groups, and our findings underscore existing variations in healthcare delivery.

The combined effect of physical activity and sedentary behavior on subclinical atherosclerosis: a cross-sectional study among Mexican Americans.

BACKGROUND: Physical activity and sedentary behavior are considered independent risk factors for chronic disease. However, we do not fully understand their interrelation with key health outcomes such as subclinical atherosclerosis. This study examines the combined effects of sedentary behavior and physical activity on carotid intima-media thickness (cIMT) and presence of carotid plaque in a Mexican American population on the Texas-Mexico border. METHODS: This cross-sectional study was conducted using retrospective data from a sample (n = 612) of participants from the Cameron County Hispanic Cohort. Carotid ultrasound was used to measure cIMT and presence of carotid plaque. Self-reported questionnaires were used to assess leisure time physical activity and sedentary behavior (TV/movie sitting and total sitting). A series of multivariable regression models were used to assess study aims. An interaction term between physical activity and sedentary behavior was included in models for each respective outcome. Models were controlled for demographic and health-related variables. RESULTS: There were no significant associations found between physical activity, sedentary behavior and mean cIMT, or cIMT thickness ≥ 75th percentile for age and gender. However, there was a significant interaction between physical activity and TV/movie sitting with presence of carotid plaque. Participants who reported moderate levels of physical activity had significantly lower odds for presence of plaque compared to participants with no activity when TV/movie sitting time was ≤3 h per day. However, there was no significant difference in odds for presence of plaque between physical activity groups when TV/movie sitting exceeded 3 h/day. These results were consistent with models examining total sitting time. CONCLUSIONS: Our results indicate that for Mexican Americans, there is a combined effect of sedentary behavior and physical activity on presence of carotid plaque. Participating in moderate physical activity is optimal for having lower levels of carotid plaque in addition to avoiding excessive levels of TV/movie sitting (≥3 h/day) and/or total sitting (≥8.5 h/day).

Frequency of Nonalcoholic Fatty Liver Disease and Subclinical Atherosclerosis Among Young Mexican Americans.

Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of the metabolic syndrome, whose criteria are risk factors for atherosclerotic cardiovascular disease. We aimed to evaluate the prevalence of NAFLD, its association with subclinical atherosclerosis, and factors that may account for this association in Mexican Americans. In a population-based cross-sectional sample drawn from the Cameron County Hispanic Cohort in Texas, carotid intima media thickness (cIMT), an indicator of subclinical atherosclerosis, was measured. Abnormal carotid ultrasound study was defined as mean cIMT >75th percentile for age and gender and/or plaque presence. NAFLD was defined as steatosis by ultrasound in the absence of other causes of liver disease. Multivariable weighted regression analyses were performed to evaluate associations between NAFLD and cIMT. Mean age was 50.4 ± 1.2 years with 58.3% women. Mean body mass index was 31.0 ± 0.4 kg/m2, and 54.0% had the metabolic syndrome. NAFLD was highly prevalent (48.80%); subjects with NAFLD had greater body mass index, central obesity, fasting glucose levels, and dyslipidemia and were more likely to have the metabolic syndrome. Nearly 1/3 of subjects with NAFLD also had evidence of subclinical atherosclerosis (31.2%). After adjusting for covariates, there was an independent association between NAFLD and increased cIMT only in younger subjects <45 years (p = 0.0328). Subjects with both abnormal liver and carotid ultrasound studies tended to be obese, diabetic and have the metabolic syndrome. In conclusion, NAFLD is highly prevalent in this Mexican American cohort, with an independent association between NAFLD and subclinical atherosclerosis among younger subjects; clustering of diabetes, obesity, and metabolic syndrome in this health disparity cohort increases the risk of both liver disease and early atherosclerosis in young adults.

One Health Interactions of Chagas Disease Vectors, Canid Hosts, and Human Residents along the Texas-Mexico Border.

BACKGROUND: Chagas disease (Trypanosoma cruzi infection) is the leading cause of non-ischemic dilated cardiomyopathy in Latin America. Texas, particularly the southern region, has compounding factors that could contribute to T. cruzi transmission; however, epidemiologic studies are lacking. The aim of this study was to ascertain the prevalence of T. cruzi in three different mammalian species (coyotes, stray domestic dogs, and humans) and vectors (Triatoma species) to understand the burden of Chagas disease among sylvatic, peridomestic, and domestic cycles. METHODOLOGY/PRINCIPAL FINDINGS: To determine prevalence of infection, we tested sera from coyotes, stray domestic dogs housed in public shelters, and residents participating in related research studies and found 8%, 3.8%, and 0.36% positive for T. cruzi, respectively. PCR was used to determine the prevalence of T. cruzi DNA in vectors collected in peridomestic locations in the region, with 56.5% testing positive for the parasite, further confirming risk of transmission in the region. CONCLUSIONS/SIGNIFICANCE: Our findings contribute to the growing body of evidence for autochthonous Chagas disease transmission in south Texas. Considering this region has a population of 1.3 million, and up to 30% of T. cruzi infected individuals developing severe cardiac disease, it is imperative that we identify high risk groups for surveillance and treatment purposes.

Nitric Oxide-Enhanced Molecular Imaging of Atheroma using Vascular Cellular Adhesion Molecule 1-Targeted Echogenic Immunoliposomes.

The aim of this study was to determine whether pre-treatment with nitric oxide-loaded echogenic liposomes (NO-ELIP) plus ultrasound can improve highlighting by molecularly targeted (anti-vascular cell adhesion molecule 1 [VCAM-1]) ELIP of atheroma components. Atherosclerotic animals were treated with anti-VCAM-1-ELIP or immunoglobulin (IgG)-ELIP. Each group was selected at random to receive pre-treatment with standard ELIP plus ultrasound, NO-ELIP without ultrasound and NO-ELIP plus ultrasound. Intravascular ultrasound highlighting data for the same arterial segments were collected before and after treatment. Pre-treatment with NO-ELIP plus ultrasound resulted in a significant increase in acoustic enhancement by anti-VCAM-1-ELIP (21.3 ± 1.5% for gray-scale value, 53.9 ± 3.1% for radiofrequency data; p < 0.001 vs. IgG-ELIP, p < 0.05 vs. pre-treatment with standard ELIP plus ultrasound or NO-ELIP without ultrasound). NO-ELIP plus ultrasound can improve highlighting of atheroma by anti-VCAM-1 ELIP. This NO pre-treatment strategy may be useful in optimizing contrast agent delivery to the vascular wall for both diagnostic and therapeutic applications.

Subclinical atherosclerosis and obesity phenotypes among Mexican Americans.

BACKGROUND: Data on the influence of obesity on atherosclerosis in Hispanics are inconsistent, possibly related to varying cardiometabolic risk among obese individuals. We aimed to determine the association of obesity and cardiometabolic risk with subclinical atherosclerosis in Mexican-Americans. METHODS AND RESULTS: Participants (n=503) were drawn from the Cameron County Hispanic Cohort. Metabolic health was defined as <2 of the following: blood pressure ≥130/85; triglyceride ≥150 mg/dL; high-density lipoprotein cholesterol <40 mg/dL (men) or <50 mg/dL (women); fasting glucose ≥100 mg/dL; homeostasis model assessment of insulin resistance value >5.13; or high-sensitivity C-reactive protein >3 mg/L. Carotid intima media thickness (cIMT) was measured. A high proportion of participants (77.8%) were metabolically unhealthy; they were more likely to be male, older, with fewer years of education, and less likely to meet daily recommendations regarding fruit and vegetable servings. One-third (31.8%) had abnormal carotid ultrasound findings. After adjusting for covariates, mean cIMT varied across the obesity phenotypes (P=0.0001); there was no difference among the metabolically unhealthy regardless of whether they were obese or not. In multivariable analysis, after adjusting for covariates, cardiometabolic risk (P=0.0159), but not obesity (P=0.1446), was significantly associated with subclinical atherosclerosis. CONCLUSIONS: In Mexican-Americans, cardiometabolic risk has a greater effect on early atherosclerosis development than body mass index. Non-obese but metabolically unhealthy participants had similar development of subclinical atherosclerosis as their obese counterparts. Interventions to maintain metabolic health among obese and non-obese patients may be a more important goal than weight loss alone.

Left atrial thrombus after complete left atrial appendage exclusion with LARIAT device.

A 74-year-old woman with paroxysmal atrial fibrillation underwent left atrial appendage (LAA) exclusion with a LARIAT snare device. Transesophageal echocardiogram one month later demonstrated a left atrial thrombus at orifice of the completely occluded LAA that subsequently resolved with two months of anticoagulation. This case highlights that LAA ligation with LARIAT device continues to pose a risk for left atrial thrombosis in the immediate post-operative period. It also emphasizes the need for further evidence regarding antiplatelet and anticoagulation therapy in these patients. © 2014 Wiley Periodicals, Inc.

Alternative splicing impairs soluble guanylyl cyclase function in aortic aneurysm.

Nitric oxide (NO) receptor soluble guanylyl cyclase (sGC) is a key regulator of several important vascular functions and is important for maintaining cardiovascular homeostasis and vascular plasticity. Diminished sGC expression and function contributes to pathogenesis of several cardiovascular diseases. However, the processes that control sGC expression in vascular tissue remain poorly understood. Previous work in animal and cell models revealed the complexity of alternative splicing of sGC genes and demonstrated its importance in modulation of sGC function. The aim of this study was to examine the role of alternative splicing of α1 and ß1 sGC in healthy and diseased human vascular tissue. Our study found a variety of α1 and ß1 sGC splice forms expressed in human aorta. Their composition and abundance were different between samples of aortic tissue removed during surgical repair of aortic aneurysm and samples of aortas without aneurysm. Aortas with aneurysm demonstrated decreased sGC activity, which correlated with increased expression of dysfunctional sGC splice variants. In addition, the expression of 55-kDa oxidation-resistant α1 isoform B sGC (α1-IsoB) was significantly lower in aortic samples with aneurysm. The α1-IsoB splice variant was demonstrated to support sGC activity in aortic lysates. Together, our results suggest that alternative splicing contributes to diminished sGC function in vascular dysfunction. Precise understanding of sGC splicing regulation could help to design new therapeutic interventions and to personalize sGC-targeting therapies in treatments of vascular disease.

Three-dimensional echocardiography-based prediction of posterior leaflet resection.

Clinical long-term outcomes have shown that partial leaflet resection followed by ring annuloplasty is a reliable and reproducible surgical repair technique for treatment of mitral valve (MV) leaflet prolapse. We report a 61-year-old male for three-dimensional transesophageal echocardiography (3DTEE)-based virtual posterior leaflet resection and ring annuloplasty. Severe mitral regurgitation was found and computational evaluation demonstrated substantial leaflet malcoaptation and high stress concentration. Following virtual resection and ring annuloplasty, posterior leaflet prolapse markedly decreased, sufficient leaflet coaptation was restored, and high stress concentration disappeared. Virtual MV repair strategies using 3DTEE have the potential to help optimize MV repair.

Nitric oxide pretreatment enhances atheroma component highlighting in vivo with intercellular adhesion molecule-1-targeted echogenic liposomes.

We present an ultrasound technique for the detection of inflammatory changes in developing atheromas. We used contrast-enhanced ultrasound imaging with (i) microbubbles targeted to intercellular adhesion molecule-1 (ICAM-1), a molecule of adhesion involved in inflammatory processes in lesions of atheromas in New Zealand White rabbits, and (ii) pretreatment with nitric oxide-loaded microbubbles and ultrasound activation at the site of the endothelium to enhance the permeability of the arterial wall and the penetration of ICAM-1-targeted microbubbles. This procedure increases acoustic enhancement 1.2-fold. Pretreatment with nitric oxide-loaded echogenic liposomes and ultrasound activation can potentially facilitate the subsequent penetration of targeted echogenic liposomes into the arterial wall, thus allowing improved detection of inflammatory changes in developing atheromas.

Mitral valve repair using ePTFE sutures for ruptured mitral chordae tendineae: a computational simulation study.

Mitral valve (MV) repair using expanded polytetrafluoroethylene sutures is an established and preferred interventional method to resolve the complex pathophysiologic problems associated with chordal rupture. We developed a novel computational evaluation protocol to determine the effect of the artificial sutures on restoring MV function following valve repair. A virtual MV was created using three-dimensional echocardiographic data in a patient with ruptured mitral chordae tendineae (RMCT). Virtual repairs were designed by adding artificial sutures between the papillary muscles and the posterior leaflet where the native chordae were ruptured. Dynamic finite element simulations were performed to evaluate pre- and post-repair MV function. Abnormal posterior leaflet prolapse and mitral regurgitation was clearly demonstrated in the MV with ruptured chordae. Following virtual repair to reconstruct ruptured chordae, the severity of the posterior leaflet prolapse decreased and stress concentration was markedly reduced both in the leaflet tissue and the intact native chordae. Complete leaflet coaptation was restored when four or six sutures were utilized. Computational simulations provided quantitative information of functional improvement following MV repair. This novel simulation strategy may provide a powerful tool for evaluation and prediction of interventional treatment for RMCT.