Background
Gender minorities and cisgender women face barriers to healthcare access. Prior work suggests cost may represent a particular barrier to accessing care for transgender and gender diverse ...(TGD) individuals.
Objective
To examine odds of delaying care for any reason and, secondarily, for 7 specific reasons among TGD individuals and cisgender women compared with cisgender men in the All of Us Research Program.
Design
We calculated the odds of delayed care by gender identity relative to cisgender men using multivariable-adjusted logistic regression, with adjustment for age, race, income, education, and Charlson comorbidity index.
Participants
We examined 117,806 All of Us participants who completed the healthcare access and utilization survey.
Main Measures
The primary outcome was self-reported delayed care in the past 12 months for any of 7 potential reasons: cost (out-of-pocket cost, co-payment costs, and/or high deductible), lack of childcare, lack of eldercare, nervousness associated with visiting the healthcare provider, rurality, inability to take time off work, and lack of transportation.
Key Results
Compared with cisgender men, the multivariable-adjusted odds ratio (OR) for delaying care for any reason was 1.48 (95% CI, 1.44–1.53;
P
< 0.001) among cisgender women, 1.65 (95% CI, 1.24–2.21;
P
< 0.001) among TGD individuals assigned male at birth, and 2.76 (95% CI, 2.26–3.39;
P
< 0.001) among TGD individuals assigned female at birth. Results were consistent across multiple sensitivity analyses. TGD individuals were substantially more likely to cite nervousness with visiting a healthcare provider as a barrier, whereas cisgender women were more likely to delay care due to lack of childcare coverage.
Conclusions
Cisgender women and TGD individuals were more likely to delay seeking heath care compared with cisgender men, and for partially different reasons. These findings highlight the need to address common and distinct barriers to care access among marginalized groups.
Hematopoietic stem cells (HSCs) are polyfunctional, regenerating all blood cells via hematopoiesis throughout life. Clonal hematopoiesis (CH) is said to occur when a substantial proportion of mature ...blood cells is derived from a single dominant HSC lineage, usually because these HSCs have somatic mutations that confer a fitness and expansion advantage. CH strongly associates with aging and enrichment in some diseases irrespective of age, emerging as an independent causal risk factor for hematologic malignancies, cardiovascular disease, adverse disease outcomes, and all-cause mortality. Defining the molecular mechanisms underlying CH will thus provide a framework to develop interventions for healthy aging and disease treatment. Here, we review the most recent advances in understanding the molecular basis of CH in health and disease.
Genome sequencing and genotyping/karyotyping studies have established that clonal hematopoiesis (CH) is characterized by mosaic postzygotic genomic alterations that include single-nucleotide variants/indels and mosaic chromosomal alterations that confer a fitness and expansion advantage in hematopoietic stem cells (HSCs).Emerging data suggest that DNA damage and inflammatory signaling (which are reciprocally related) resulting from aging processes, infection, lifestyle, inherited genetic variation, environmental exposures, or disease, are major selective pressures and drivers of epigenetic drift and lead to the emergence and expansion of CH-associated mutations in HSCs.CH is an emerging public health challenge that is prevalent in the aging population, independently increasing the risk of hematologic malignancy, cardiovascular disease, and worse disease outcomes.
Women with HIV (WWH) face heightened risks of heart failure; however, insights on immune/inflammatory pathways potentially contributing to left ventricular (LV) systolic dysfunction among WWH remain ...limited.
Massachusetts General Hospital, Boston, Massachusetts.
Global longitudinal strain (GLS) is a sensitive measure of LV systolic function, with lower cardiac strain predicting incident heart failure and adverse heart failure outcomes. We analyzed relationships between GLS (cardiovascular magnetic resonance imaging) and monocyte activation (flow cytometry) among 20 WWH and 14 women without HIV.
WWH had lower GLS compared to women without HIV (WWH vs. women without HIV: 19.4±3.0 vs. 23.1±1.9%, P<0.0001). Among the whole group, HIV status was an independent predictor of lower GLS. Among WWH (but not among women without HIV), lower GLS related to a higher density of expression of HLA-DR on the surface of CD14+CD16+ monocytes (ρ = -0.45, P = 0.0475). Further, among WWH, inflammatory monocyte activation predicted lower GLS, even after controlling for CD4+ T-cell count and HIV viral load.
Additional studies among WWH are needed to examine the role of inflammatory monocyte activation in the pathogenesis of lower GLS and to determine whether targeting this immune pathway may mitigate risks of heart failure and/or adverse heart failure outcomes.
Clinical trials.gov registration: NCT02874703.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVE:Women with HIV (WHIV) on antiretroviral therapy (ART) face an increased risk of cardiovascular disease (CVD) in the context of heightened systemic immune activation. Aortic stiffness, a ...measure of vascular dysfunction and a robust predictor of CVD outcomes, is highly influenced by immune activation. We compared aortic stiffness among women with and without HIV and examined interrelationships between aortic stiffness and key indices of systemic immune activation.
METHODS:Twenty WHIV on ART and 14 women without HIV group-matched on age and body mass index (BMI) were prospectively recruited and underwent cardiovascular magnetic resonance imaging, as well as metabolic and immune phenotyping.
RESULTS:Age and BMI did not differ significantly across groups (age52 ± 4 vs. 53 ± 6 years; BMI32 ± 7 vs. 32 ± 7 kg/m). Aortic pulse wave velocity (aPWV) was higher among WHIV (8.6 ± 1.3 vs. 6.5 ± 1.3 m/s, P < 0.0001), reflecting increased aortic stiffness. Among the whole group and among WHIV, aPWV related to sCD163 levels (whole groupR = 0.65, P < 0.0001; WHIVR = 0.73, P = 0.0003) and to myocardial fibrosis (extracellular volume; whole groupR = 0.54, P = 0.001; WHIVR = 0.47, P = 0.04). Both HIV status and sCD163 levels independently predicted aPWV, controlling for age, BMI, cigarette smoking status, and systolic blood pressure (HIV statusβ-estimate = 0.69, 95% CI 0.1 to 1.3, P = 0.02; sCD163β-estimate = 0.002, 95% CI 0.0006 to 0.004, P = 0.01). Among WHIV, sCD163 levels independently predicted aPWV, controlling for duration of HIV, CD4 count, and HIV viral load (sCD163β-estimate = 0.004, 95% CI 0.002 to 0.005, P = 0.0005).
CONCLUSIONS:Asymptomatic WHIV on ART have increased aortic stiffness as compared to matched control subjects. Among WHIV, aPWV related to heightened monocyte activation (sCD163) and to downstream CVD pathology (myocardial fibrosis).
CLINICALTRIALS.GOV REGISTRATION:NCT02874703.
Purpose of Review
Transgender individuals are at disproportionate risk for HIV infection, with prevalence rates highest among transgender women of color. Antiretroviral therapy (ART)-treated people ...with HIV (PWH) are at increased risk for cardiovascular disease (CVD), in relation to persistent systemic immune activation and metabolic dysregulation. The purpose of this review is to examine parameters which may affect CVD risk among transgender PWH.
Recent Findings
Among transgender women and men, prospective longitudinal studies have shown that gender-affirming hormonal therapy (GAHT) is associated with select deleterious cardiometabolic effects such as increases in visceral adipose tissue. Retrospective studies among transgender women and men suggest an increase in CVD risk, such as venous thromboembolism, cerebrovascular accidents, and myocardial infarction. Studies among transgender PWH adhering to GAHT and ART suggest heightened systemic immune activation/inflammation.
Summary
Prospective longitudinal studies assessing factors associated with increased CVD events among transgender PWH are needed to guide the development of CVD prevention strategies in this at-risk population.
People with HIV (PWH) on antiretroviral therapy (ART) globally are disproportionately affected by obesity, with prevalence rates highest among women with HIV. The purpose of this review is to discuss ...rates of obesity, factors associated with obesity, and adverse consequences of obesity among PWH.
Among PWH on ART, rates of obesity have increased over the last several decades and tend to be higher than the general population. Weight gain with the initiation of new ART regimens such as integrase strand transfer inhibitor (INSTI)-based regimens are thought to contribute to higher rates of obesity among PWH on ART. Other factors, such as sex and ethnicity, also are associated with obesity among PWH on ART. Higher obesity rates among PWH may contribute to heightened cardiometabolic disease risk and lower health-related quality of life.
Prospective studies which identify factors associated with increased obesity prevalence and weight gain among PWH are necessary for the development and implementation of obesity prevention and treatment strategies among PWH on ART and, in turn, reduce the prevalence of obesity in this population.
Purpose
People with HIV (PHIV) with access to modern antiretroviral therapy (ART) face a two-fold increased risk of heart failure as compared with non-HIV-infected individuals. The purpose of this ...review is to consider evolving risks, mechanisms, and preventive considerations pertaining to heart failure among PHIV.
Recent Findings
While unchecked HIV/AIDS has been documented to precipitate heart failure characterized by overtly reduced cardiac contractile function, ART-treated HIV may be associated with either heart failure with reduced ejection fraction (HFrEF) or with heart failure with preserved ejection fraction (HFpEF). In HFpEF, a “stiff” left ventricle cannot adequately relax in diastole—a condition known as diastolic dysfunction. Diastolic dysfunction, in turn, may result from processes including myocardial fibrosis (triggered by hypertension and/or immune activation/inflammation) and/or myocardial steatosis (triggered by metabolic dysregulation). Notably, hypertension, systemic immune activation, and metabolic dysregulation are all common conditions among even those PHIV who are well-treated with ART. Of clinical consequence, HFpEF is uniquely intransigent to conventional medical therapies and portends high morbidity and mortality. However, diastolic dysfunction is reversible—as are contributing processes of myocardial fibrosis and myocardial steatosis.
Summary
Our challenges in preserving myocardial health among PHIV are two-fold. First, we must continue working to realize UNAIDS 90-90-90 goals. This achievement will reduce AIDS-related mortality, including cardiovascular deaths from AIDS-associated heart failure. Second, we must work to elucidate the detailed mechanisms continuing to predispose ART-treated PHIV to heart failure and particularly HFpEF. Such efforts will enable the development and implementation of targeted preventive strategies.
Abstract
Background
People with human immunodeficiency virus (HIV) have heightened incidence/risk of diastolic dysfunction and heart failure. Women with HIV have elevated cardiac fibrosis, and plasma ...osteopontin (Opn) is correlated to cardiac pathology. Therefore, this study provides mechanistic insight into the relationship between osteopontin and cardiac fibrosis during HIV infection.
Methods
Mouse embryonic fibroblasts (MEFs) modeled cardiac fibroblasts in vitro. Simian immunodeficiency virus (SIV)-infected macaques with or without antiretroviral therapy and HIV-infected humanized mice modeled HIV-associated cardiac fibrosis.
Results
Lipopolysaccharide-stimulated MEFs were myofibroblast-like, secreted cytokines, and produced Opn transcripts. SIV-infected animals had elevated plasma Opn at necropsy, full-length Opn in the ventricle, and ventricular interstitial fibrosis. Regression modeling identified growth differentiation factor 15, CD14+CD16+ monocytes, and CD163 expression on CD14+CD16+ monocytes as independent predictors of plasma Opn during SIV infection. HIV-infected humanized mice showed increased interstitial fibrosis compared to uninfected/untreated animals, and systemic inhibition of osteopontin by RNA aptamer reduced left ventricle fibrosis in HIV-infected humanized mice.
Conclusions
Since Opn is elevated in the plasma and left ventricle during SIV infection and systemic inhibition of Opn reduced cardiac fibrosis in HIV-infected mice, Opn may be a potential target for adjunctive therapies to reduce cardiac fibrosis in people with HIV.
Osteopontin (Opn) was identified as a potential driver of cardiac fibrosis in 2 animal models of HIV infection. Systemically inhibiting Opn reduced cardiac fibrosis, leveraging Opn as a potential therapeutic target for reducing cardiac fibrosis in people with HIV.
Persistent immune activation is thought to contribute to increased cardiovascular disease risk in HIV and statins may help modulate systemic immune activation. We aimed to compare the effects of two ...key statins on markers of systemic immune activation and arterial inflammation in the HIV population.
Double-blind, active-controlled, parallel-group comparative trial performed in 45 sites.
Two hundred and fifty-two antiretroviral therapy-treated HIV-infected participants with dyslipidemia were randomized (1 : 1) to pitavastatin 4 mg daily vs. pravastatin 40 mg daily in the HIV-infected patieNts and TREatment with PItavastatin vs. pravastatin for Dyslipidemia (INTREPID) trial. In this analysis of the INTREPID trial, we assessed markers of immune activation and arterial inflammation using a modified intent-to-treat population. This trial is registered with ClinicalTrials.gov (NCT01301066).
One hundred and twenty-six participants were randomized to receive pitavastatin and 126 to pravastatin. Ninety-nine participants in the pitavastatin group and 91 participants in the pravastatin group completed the study. Median age was 50 (45, 56) years median (interquartile range). Baseline, low-density lipoprotein-cholestrol (LDL-C) was 153 (135, 171) mg/dl, log HIV-1 viral load was 1.1 ± 0.2 copies/ml, and CD4 cell count was 580 (439, 794) cells/μl. At week 52, the pitavastatin group had a significantly greater reduction (% change) compared with pravastatin in soluble CD14 (sCD14), (-10.0 vs. 0.6%, P = 0.02), oxidized LDL (oxLDL) (-26.9 vs. -17.5%, P = 0.02), and lipoprotein-associated phospholipase 2 (Lp-PLA2) (-26.6 vs. -15.5%, P = 0.005) (pitavastatin vs. pravastatin).
Fifty-two weeks of pitavastatin 4 mg daily (vs. pravastatin 40 mg daily) led to a greater reduction in select markers of immune activation and arterial inflammation (sCD14, oxLDL, and LpPLA2) among HIV-infected participants. Further work is needed to assess whether immune-modulatory effects of pitavastatin reduce cardiovascular disease risk in HIV.
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