Showing papers by "Barry E. Hurwitz published in 2022"
TL;DR: The study shows that hepatic FoxO transcription factors are regulators of the ApoM/S1P pathway, and shows that insulin resistance in humans and mice is associated with decreased HDL-associated S1P.
Abstract: Multiple beneficial cardiovascular effects of HDL depend on sphingosine-1-phosphate (S1P). S1P associates with HDL by binding to apolipoprotein M (ApoM). Insulin resistance is a major driver of dyslipidemia and cardiovascular risk. However, the mechanisms linking alterations in insulin signaling with plasma lipoprotein metabolism are incompletely understood. The insulin-repressible FoxO transcription factors mediate key effects of hepatic insulin action on glucose and lipoprotein metabolism. This work tested whether hepatic insulin signaling regulates HDL-S1P and aimed to identify the underlying molecular mechanisms. We report that insulin-resistant, nondiabetic individuals had decreased HDL-S1P levels, but no change in total plasma S1P. This also occurred in insulin-resistant db/db mice, which had low ApoM and a specific reduction of S1P in the HDL fraction, with no change in total plasma S1P levels. Using mice lacking hepatic FoxOs (L-FoxO1,3,4), we found that hepatic FoxOs were required for ApoM expression. Total plasma S1P levels were similar to those in controls, but S1P was nearly absent from HDL and was instead increased in the lipoprotein-depleted plasma fraction. This phenotype was restored to normal by rescuing ApoM in L-FoxO1,3,4 mice. Our findings show that insulin resistance in humans and mice is associated with decreased HDL-associated S1P. Our study shows that hepatic FoxO transcription factors are regulators of the ApoM/S1P pathway.
2 citations
1 citations
TL;DR: In this paper , the authors examined whether sex differences in associations of vitality exhaustion with CVD risk markers are accounted for by unique associations of VE with regional adiposity and found that VE is more strongly associated with cardiovascular disease (CVD) risk for women than men.
1 citations
TL;DR: Findings indicate that ABC treatment of 30–50 year-old PWH on stable ART is not likely to contribute in a robust way to higher CVD risk.
Abstract: Objective Indices of cardiovascular disease (CVD) risk, vascular endothelial dilation, arterial stiffness and endothelial repair were examined in persons with HIV (PWH) on an antiretroviral therapy (ART) that included abacavir (ABC+) in comparison with PWH on ART without abacavir (ABC-), and with HIV seronegative (HIV-) individuals. Approach The 115 participants (63% men), aged 30–50 years, did not have CVD, metabolic, endocrine, or chronic renal conditions. PWH were on stable ART for six-months or more. Vascular assessments included flow-mediated dilation (FMD), aortic, radial and femoral arterial stiffness (cAIx, crPWV, cfPWV), and thigh and calf arterial compliance (Vmax50). Endothelial repair was indexed by endothelial progenitor cell colony forming units (EPC-CFU). Traditional CVD risk measures included blood pressure, central adiposity, lipids, insulin resistance (HOMA-IR), CRP and ASCVD score. Analyses controlled for demographics (age, sex, education), medications (antihypertensive, statin/fibrate, antipsychotic), and substance abuse (ASSIST). Results No group differences were observed in central adiposity, HOMA-IR, CRP, or ASCVD risk score. However, the ABC- group displayed greater dyslipidemia. The ABC+ group displayed no difference on FMD, cAIx, cfPWV or calf Vmax50 compared with other groups. When CD4 count and viral load were controlled, no additional differences between the ABC+ and ABC- groups emerged. Analyses of crPWV and thigh Vmax50 suggested supported by a trend toward lower EPC-CFU in the HIV+ groups than the HIV- group. Conclusions Findings indicate that ABC treatment of 30–50 year-old PWH on stable ART is not likely to contribute in a robust way to higher CVD risk.
1 citations
TL;DR: Patients with an inverted CD4:CD8 ratio had higher total Chol/HDL levels, which has been associated with a higher risk of CV disease, and statin use in this high-risk population was lower despite having more CV risk factors and atrial fibrillation/flutter.
Abstract:
Background:
In People with HIV (PWH) with virologic suppression, the CD4:CD8 ratio inversely correlates with immune senescence response. The association between CD4:CD8 ratio and cardiovascular (CV) risk in PWH remains unclear.
Methods:
A retrospective chart review was performed of patients who received HIV care at the University of Miami/Jackson Memorial Hospital between 2017-2019 with available CD4: CD8 ratio (n=1,137). We stratified patients according to the CD4:CD8 ratio ≥1 or <1, and compared available data.
Results:
The prevalence of CD4:CD8 ratio <1 was 69.5%. A ratio <1 was associated with male gender (57.1% vs 45.8%, p<0.001), lower body mass index (28.29 vs 29.80 kg/m2, p=0.001), lower HDL cholesterol (Chol) (47.57 vs. 53.25 mg/dL, p<0.001), higher total Chol/HDL (4.22 vs. 3.8, p=0.001), higher CRP levels (4.94 vs. 2.61 mg/L, and less statin use (25% vs 35.3%, p<0.001), p=0.02) compared to those with a ratio ≥1. Those with a CD4:CD8 ratio <1 were more likely to have a detectable viral load (35.9% vs. 14.6%. p<0.001), have been on antiretroviral therapy for <6 months (4% vs 1.5%, p=0.27), to be current smokers (27.6% vs. 16.5%, p<0.001), current drug users (9.7% vs 5.5%, p=0.025), and had higher rates of atrial fibrillation/flutter (1.9% vs 0%, p=0.008) than those with a ratio ≥1.
Conclusion:
Patients with an inverted CD4:CD8 ratio had higher total Chol/HDL levels, which has been associated with a higher risk of CV disease. Statin use in this high-risk population was lower despite having more CV risk factors and atrial fibrillation/flutter. Further studies are needed to determine the usefulness of the CD4:CD8 ratio as a marker of immune activation and predictor of CV risk in PWH.
TL;DR: In this paper , the relationship between air pollution exposure and incident heart failure has been investiagted; less is known about effects of AP on subclinical cardiac structure and function preceding clinical diagnosis.
Abstract: Background and Aim The relationship between air pollution (AP) exposure and incident heart failure has been investiagted; less is known about effects of AP on subclinical cardiac structure and function preceding clinical diagnosis. Cross-sectional associations between fine particulate matter (PM2.5) and nitrogen dioxide (NO2) and echocardiographic were assessed among 1,660 participants aged 45-74 years of the Echocardiographic Study of Latinos, an ancillary study to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods Measures including left ventricular (LV) mass index, relative wall thickness, average global longitudinal strain (GLS), LV ejection fraction, e’, left atrial volume index, E/e’ ratio, and diastolic function grades were assessed by echocardiogram. AP concentrations were estimated from spatio-temporal models at participant building residence. Primary exposures were interquartile range (IQR) increases in annual average PM2.5 and NO2 prior to clinical visit 1 (2008-2011). Survey linear regression estimated the effect of AP on measures of cardiac structure and function adjusting for age, sex, study site, alcohol use, physical activity, and education. Strain measurements are expressed as negative percentages (more positive numbers indicating worse myocardial strain). Results 42.3% were male and 35.4% had no high school diploma. Average concentrations for PM2.5 and NO2 were 10.30 µg/m3 (standard deviation (SD) 1.9) and 17.4 ppb (SD 6.3), respectively. PM2.5 was associated with increased (worse) GLS (2.40%; 95% CI 1.03, 3.76) and decreased LV ejection fraction (-2.36; 95% CI -4.34, -0.38) per IQR increase. NO2 was associated with increased GLS (1.57; 95% CI 0.69, 2.46) and decreased LV ejection fraction (-2.07; 95% CI -3.77, -0.37) per IQR increase. Associations with other measures of cardiac structure and function were not found. Conclusion These results provide evidence that in this Hispanic/Latino cohort, AP adversely affects GLS and EF, both known precursors to clinical heart failure.
TL;DR: In this article , the authors assessed longitudinal associations between fine particulate matter (PM), nitrogen dioxide (NO), and cardiac structure and function among 1,660 participants in the Echocardiographic Study of Latinos, in the Hispanic Community Health Study/Study of Latinos.
Abstract:
Background:
Air pollutants may affect cardiac function; effects preceding clinical diagnosis of heart failure are not understood. We assessed longitudinal associations between fine particulate matter (PM
2.5
), nitrogen dioxide (NO
2
) and cardiac structure and function among 1,660 participants in the Echocardiographic Study of Latinos, in the Hispanic Community Health Study/Study of Latinos.
Hypothesis:
Air pollution is associated with longitudinal changes in subclinical structure/function.
Methods:
Left ventricular (LV) mass index, relative wall thickness, average global longitudinal strain (GLS), LV ejection fraction, e’, left atrial (LA) volume index, E/e’ ratio, and diastolic function grades were assessed by echocardiogram. Air pollution concentrations were estimated from validated spatio-temporal models at home locations, as mean concentrations of PM
2.5
and NO
2
for the year
prior to clinical visit 1 (V1, 2008-2011) and 2 (V2, 2015-2018). A mixed effects model was used to jointly model cross-sectional and longitudinal relationships between time-varying air pollution and continuous measures of CF, adjusted for baseline physical activity, gender, education, age, BMI, SBP, DBP, statin use, diabetes, and hypertension status and time-varying smoking and alcohol use, with random intercepts for clinical center and primary sampling unit.
Results:
Participants’ mean age was 56.4 years at V1; mean follow-up was 6.52 years. Mean PM
2.5
was 10.3 μg/m
3
at V1 and 8.8 μg/m
3
at V2. Mean NO
2
was 17.4 ppb at V1 and 14.3 at V2. Per interquartile range of pollutant, higher PM
2.5
and NO
2
were associated with a 0.52% (95% CI -0.16, 1.11) and 0.98% (95% CI 0.13, 1.23) increase in GLS, respectively. NO
2
was associated with -1.07% (95% CI -2.24, 0.10) decrease in LV ejection fraction. PM
2.5
was associated with a 0.75 (95% CI 0.39, 1.12) increase in e’ and a 1.25 (95% -1.95, -0.56) decrease in E/e’ ratio. No other associations with air pollution and echo measures were found.
Conclusion:
These findings suggest that air pollution is associated with longitudinal changes in GLS, LV ejection fraction, e’, and E/e’ ratio in a US Hispanic/Latino cohort, an important understudied population. Air pollution may represent a modifiable risk factor in the development of clinical heart failure.
TL;DR: The elevated presence of CV risk factors in this Haitian PWH cohort highlights the urgent need to better understand the patho-etiological basis for these differences and to develop effective and specific primary and secondary prevention strategies among this group.
Abstract:
Introduction:
Cardiovascular disease (CVD) has increased in prevalence among people with HIV (PWH) in the last decade, with the non-Hispanic Black population being disproportionately affected. There is paucity of data addressing disparities among underserved minority groups regarding CVD and its determinants. The purpose of this study was to evaluate the natural history of CVD and cardiovascular (CV) risk factors in PWH of Haitian ethnicity.
Methods:
A retrospective chart review (n=1,202) of PWH seen at the University of Miami/Jackson Memorial Hospital Special Immunology clinic between 2017-2019 was performed. Data regarding demographic, clinical, and laboratory results were obtained from medical records. Prevalence of different traditional CV risk factors and CVD among PWH who per system records, self-identified as Haitians vs non-Haitians (including Black, White, and Hispanic population) was examined. Between-group statistical comparisons were performed for continuous data using the T-test and Mann-Whitney U test was used for nonparametric variables. Categorical variables were compared using Chi-squared test. Significant p-values were α<0.05.
Results:
A total of 156 subjects (12.9%) self-identified as Haitians, with 88 (56.4%) being females. Haitians compared with non-Haitians were significantly older (54.7 ± 11.6 vs 51.8 ± 11.8 years, p=0.004), and had increased prevalence of diabetes mellitus (28.8% vs 16.7%), hypertension (48.7% vs 40.9%), heart failure with reduced ejection fraction (14.9% vs 11.0%). Haitians also had significantly lower prevalence of smoking (14.1% vs 28.2%), alcohol consumption (5.1% vs 19.6%), and drug use (0.6% vs 9.3%). In addition, Haitians had lower triglycerides (122 ± 64.0 vs 153 ± 107.2 mg/dL, p<0.001), and more elevated systolic blood pressure (139 ± 22.3 mmHg vs 132 ± 20.4 mmHg, p<0.001), with a trend for a difference in diastolic blood pressure (77 ± 10.3 mmHg vs 75 ± 12.1 mmHg, p=0.060). No statistical differences were found in terms of coronary and peripheral artery disease, myocardial infarction, angina, atrial fibrillation, and valvulopathies. Body mass index, HDL, LDL, and total cholesterol were also not significantly different between groups.
Conclusions:
The elevated presence of CV risk factors in this Haitian PWH cohort highlights the urgent need to better understand the patho-etiological basis for these differences and to develop effective and specific primary and secondary prevention strategies among this group. Further large-scale studies are needed in order to better characterize this population and respond to the emerging epidemic of CVD in underserved minority ethnic groups as Haitians in the US.
TL;DR: In this article , a retrospective chart review was performed of patients who received HIV care at the University of Miami/Jackson Memorial Hospital between 2017-2019 with an available echocardiogram (n=396).
Abstract:
Introduction:
Pericardial effusion was previously described as one of the most common forms of cardiovascular involvement in People with HIV (PWH). The presence of pericardial effusion was considered a marker of advanced HIV infection and associated with a low CD4 cell count. This study describes the incidence and association of pericardial disease with HIV-related factors in an era of wider availability of antiretroviral therapy (ART).
Methods:
A retrospective chart review was performed of patients who received HIV care at the University of Miami/Jackson Memorial Hospital between 2017-2019 with an available echocardiogram (n=396). We stratified patients according to the presence (n=51) or absence of pericardial effusion (n=345) and compared demographic, clinical, imaging, and laboratory data. A p-value <0.05 was considered statistically significant.
Results:
We found a prevalence of pericardial effusion in PWH of 4.5%. There was no statistically significant difference in age, gender, or race between groups. PWH with pericardial effusion had higher creatinine (2.1 mg/dL vs. 1.6 mg/dL, p=0.025) and pro-BNP (12,088 pg/mL vs. 6364 pg/mL, p=0.021) levels, were more likely to have chronic kidney disease (43.1% vs. 18%, p<0.001), tricuspid regurgitation (64.6% vs. 44.2%, p=0.009), and mitral regurgitation (60.8% vs. 35.9%, p<0.001) compared to PWH without pericardial effusion. There was no difference in CD4 count, CD8 count, viral load, length on ART, or history of tuberculosis between groups.
Conclusions:
We report a lower prevalence of pericardial effusion in PWH than previous results before the wide availability of ART (around 11%). In PWH with pericardial effusion, we found no association with HIV-related factors or length on ART. In this population, pericardial effusion was associated with comorbidities like chronic kidney disease and valvular abnormalities.