Search

BackgroundTrimethylamine-N-oxide (TMAO), a diet-derived and gut microbiota-related metabolite, is associated with cardiovascular disease (CVD). However, major dietary determinants and specific gut bacterial taxa related to TMAO remain to be identified in humans.ObjectivesWe aimed to identify dietary and gut microbial factors associated with circulating TMAO.MethodsThis cross-sectional study included 3972 participants (57.3% women) aged 18-74 y from the Hispanic Community Health Study/Study of Latinos in the United States. Dietary information was collected by 24-h dietary recalls at baseline interview (2008-2011), and baseline serum TMAO and its precursors were measured by an untargeted approach. Gut microbiome was profiled by shotgun metagenomic sequencing in a subset of participants (n = 626) during a follow-up visit (2016-2018). Logistic and linear regression were used to examine associations of inverse-normalized metabolites with prevalent CVD, dietary intake, and bacterial species, respectively, after adjustment for sociodemographic, behavioral, and clinical factors.ResultsTMAO was positively associated with prevalent CVD (case number = 279; OR = 1.34; 95% CI: 1.17, 1.54, per 1-SD). Fish (P = 1.26 × 10-17), red meat (P = 3.33 × 10-16), and egg (P = 3.89 × 10-5) intakes were top dietary factors positively associated with TMAO. We identified 9 gut bacterial species significantly associated with TMAO (false discovery rate

BackgroundThe relationship between alcohol consumption and atherosclerosis has not been sufficiently examined among people living with HIV (PLWH).MethodsWe analyzed data from PLWH in the Women's Interagency HIV Study (WIHS; n = 1,164) and the Multicenter AIDS Cohort Study (MACS; n = 387) with no history of cardiovascular disease (CVD). Repeated measures of intima-media thickness of the right common carotid artery (CCA-IMT) were assessed using B-mode ultrasound from 2004 to 2013. Current alcohol consumption was collected at time of CCA-IMT measurement and was categorized according to gender-specific weekly limits. Group-based trajectory models categorized participants into past 10-year consumption patterns (1994 to 2004). Multivariate generalized estimating equations were conducted to assess the association of past and current alcohol use patterns on change in CCA-IMT by cohort, controlling for age, race, cigarette and illicit drug use, probable depression, HIV RNA viral load, antiretroviral therapy exposure, and hepatitis C coinfection.ResultsAmong the WIHS, past heavy alcohol consumption was associated with increased CCA-IMT level over time (β = 8.08, CI 0.35, 15.8, p = 0.04), compared to abstinence. Among the MACS, compared to abstinence, all past consumption patterns were associated with increased CCA-IMT over time (past low: β = 15.3, 95% CI 6.46, 24.2, p

ObjectivePeople living with HIV (PLWH) have chronic immune activation and increased cardiovascular disease (CVD) risk. Activation of monocytes and T lymphocytes causes upregulation of glucose transporter-1 (GLUT1) for efficient function. PLWH have an increased percentage of GLUT1-expressing monocytes and T lymphocytes, but it is unclear if these cells are associated with CVD. We evaluated the expression of GLUT1 and CD38 on monocyte and T lymphocyte populations from HIV-infected women with subclinical CVD.MethodsParticipants with more than 75th percentile (n = 15) and less than 25th percentile (n = 15) age-adjusted intima-media thickness (IMT) at the right common carotid artery and bifurcation were identified from the Women's Interagency HIV Study. Groups were matched by age, race/ethnicity, smoking status, and CD4 cell count. All women were receiving suppressive antiretroviral therapy except for one high and one low IMT participant. Monocyte and T lymphocyte populations were evaluated for GLUT1 and CD38 expression using flow cytometry.ResultsIntermediate monocytes from high IMT women had significantly increased expression of GLUT1 (310 MFI vs. 210 MFI, P = 0.024) (66.4% vs. 48.5%, P = 0.031) and CD38 (339 MFI vs. 211 MFI, P = 0.002) (10.5% vs. 3.8%, P = 0.0002) compared with women with low IMT. High and low IMT participants showed no differences in GLUT1 or CD38 expression on classical monocytes, nonclassical monocytes, CD4 and CD8 T lymphocytes.ConclusionGLUT1-expressing intermediate monocytes are elevated in HIV-infected women with subclinical CVD. These cells may contribute to development of CVD in PLWH and could be a novel target to limit inflammation.

Cardiovascular disease (CVD) is increasingly common among women with HIV, but literature on nonlipid CVD risk factor management is lacking. We examined semiannual trends from 2006 to 2014 in hypertension treatment and control (blood pressure

BackgroundIndividuals infected with human immunodeficiency virus (HIV) live longer as a result of effective treatment, but long-term consequences of infection, treatment, and immunological dysfunction are poorly understood.MethodsWe prospectively examined 1011 women (74% HIV-infected) in the Women's Interagency HIV Study and 811 men (65% HIV-infected) in the Multicenter AIDS Cohort Study who underwent repeated B-mode carotid artery ultrasound imaging in 2004-2013. Outcomes included changes in right common carotid artery intima-media thickness (CCA-IMT) and new focal carotid artery plaque formation (IMT >1.5 mm) over median 7 years. We assessed the association between HIV serostatus and progression of subclinical atherosclerosis, adjusting for demographic, behavioral, and cardiometabolic risk factors.ResultsUnadjusted mean CCA-IMT increased (725 to 752 µm in women, 757 to 790 µm in men), but CCA-IMT progression did not differ by HIV serostatus, either in combined or sex-specific analyses. Focal plaque prevalence increased from 8% to 15% in women and 25% to 34% in men over 7 years. HIV-infected individuals had 1.6-fold greater risk of new plaque formation compared with HIV-uninfected individuals (relative risk [RR] 1.61, 95% CI, 1.12-2.32), adjusting for cardiometabolic factors; the association was similar by sex. Increased plaque occurred even among persistently virologically suppressed HIV-infected individuals compared with uninfected individuals (RR 1.56, 95% CI, 1.07-2.27). HIV-infected individuals with baseline CD4+ ≥ 500 cells/µL had plaque risk not statistically different from uninfected individuals.ConclusionsHIV infection is associated with greater increases in focal plaque among women and men, potentially mediated by factors associated with immunodeficiency or HIV replication at levels below current limits of detection.

The menopausal transition is a pivotal time of cardiovascular risk, but knowledge is limited in HIV. We studied longitudinal carotid artery intima-media thickness (CIMT) in the Women's Interagency HIV Study (2004–2019; 979 women/3247 person-visits; 72% with HIV). Among women with HIV only, those who transitioned had greater age-related CIMT progression compared to those remaining premenopausal (difference in slope = 1.64 µm/year, P =.002); and CIMT increased over time in the pretransition (3.47 µm/year, P =.002) and during the menopausal transition (9.41 µm/year, P <.0001), but not posttransition (2.9 µm/year, P =.19). In women with HIV, menopause may accelerate subclinical atherosclerosis as measured by CIMT. [ABSTRACT FROM AUTHOR]

Background Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with human immunodeficiency virus (HIV), who have heightened immune activation and cardiovascular risks. Methods Among 609 postmenopausal women (1234 person-visits) in the Women's Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis: carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004–2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors. Results Women (mean age, 51 years; 80% HIV positive) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never-users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio, 0.57 [95% confidence interval {CI},.40–.80]; P <.01), 2.51 µm less progression of CIMT per year (95% CI, –4.60, to –.41; P =.02), and marginally lower incidence of plaque over approximately 7 years (risk ratio, 0.38 [95% CI,.14–1.03; P =.06), compared with never-users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment. Conclusions HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus (HIV) may affect the risk of death due to cardiovascular disease (CVD) differently in men versus women. Methods We examined CVD mortality rates between 2007 and 2017 among all New York City residents living with HIV and aged 13+ by sex, using data from city HIV surveillance and vital statistics and the National Death Index. Residents without HIV were enumerated using modified US intercensal estimates. We determined associations of HIV status with CVD mortality by sex and neighborhood poverty, defined as the percent of residents living below the federal poverty level, after accounting for age, race/ethnicity, and year. Results There were 3234 CVD deaths reported among 147 915 New Yorkers living with HIV, with the proportion of deaths due to CVD increasing from 11% in 2007 to 22% in 2017. The age-standardized CVD mortality rate was 2.7/1000 person-years among both men and women with HIV. The relative rate of CVD mortality associated with HIV status was significantly higher among women (adjusted rate ratio [aRR] 1.7, 95% confidence interval [CI] 1.6–1.8) than men (aRR 1.2, 95% CI 1.1–1.3) overall, and within strata defined by neighborhood poverty. Sex differences in CVD mortality rates were the greatest when comparing individuals living with HIV and having detectable HIV RNA and CD4+ T-cell counts <500 cells/uL with individuals living without HIV. Conclusions Among people with HIV, 1 in 5 deaths is now associated with CVD. HIV providers should recognize the CVD risk among women with HIV, and reinforce preventive measures (eg, smoking cessation, blood pressure control, lipid management) and viremic control among people living with HIV regardless of neighborhood poverty to reduce CVD mortality. Human immunodeficiency virus (HIV) increases cardiovascular disease mortality risks to a greater degree among women than men, even after accounting for neighborhood poverty. HIV providers should emphasize cardiovascular disease prevention (eg, smoking cessation, hypertension control, lipid management) and viremic control. [ABSTRACT FROM AUTHOR]

C1q/tumor necrosis factor (TNF)-related proteins (CTRPs) have been linked to energy homeostasis and vascular health. People with HIV are susceptible to cardiometabolic disease, but the contributions of different CTRPs are unknown. We investigated the associations of HIV and related factors with serum CTRPs, and CTRPs' relationships with cardiometabolic phenotypes. This involved a cross-sectional analysis of participants in the Women's Interagency HIV Study aged ≥35 with (n = 209) and without (n = 92) HIV who underwent carotid ultrasound in 2004–2005 and had stored serum available for measurement of total adiponectin and CTRPs 1, 3, 5, and 9. The Benjamini/Hochberg procedure was used to control the study-wide false-positive rate. HIV-positive women had significantly higher adiponectin than HIV-negative women after adjustment for sociodemographic, behavioral, and clinical variables [beta = 0.29 (95% confidence interval 0.11–0.47)]. Among HIV-positive women, lower CD4 count was associated with higher adiponectin and history of AIDS with higher CTRP9, but these were only nominally significant. There was no relationship between HIV status and CTRP 1, 3, or 5, nor was antiretroviral therapy or viral load associated with any CTRP. In the entire cohort, higher adiponectin was associated with significantly lower fasting glucose and insulin resistance, while higher CTRP5 [beta = -0.02 (−0.033 to −0.007)]—and, at a nominal level, CTRPs 1 and 3—was associated with significantly lower carotid intima-media thickness. In conclusion, in this sample of middle-aged women, HIV serostatus was positively associated with adiponectin, but not CTRPs. In turn, serum adiponectin was inversely associated with glucose dysregulation, whereas CTRP5 was inversely associated with carotid intima-media thickness. Further research is needed to determine CTRPs' role in atherosclerosis. [ABSTRACT FROM AUTHOR]

Reports on the associations between multiple clinical and behavioral health indicators and major health outcomes among older adults are scarce. We prospectively examined concordance with guidelines from the American Cancer Society and American Heart Association for disease prevention in relation to cancer, cardiovascular disease (CVD), and mortality among Cardiovascular Health Study enrollees aged 65-98 years who, at baseline assessment in 1989-1996 (n = 3,491), were free of CVD and cancer. Total and cause-specific mortality, as well as incidence of cancer and CVD, were lower with higher guideline concordance. Independent of body mass index, blood pressure, total cholesterol, and fasting plasma glucose, better health behaviors (diet, physical activity, and alcohol consumption) were associated with lower mortality (2-sided P < 0.0001). Among individuals with ideal levels for 3-4 of these 4 cardiometabolic biomarkers, those with poor concordance with health behavior recommendations had higher mortality compared with those who had the highest concordance with these behavioral recommendations (adjusted mortality hazard ratio = 1.82,95% confidence interval: 1.25,2.67). Older adults who are concordant with recommendations for cancer and CVD prevention have reduced rates of chronic disease and mortality. Interventions to achieve and maintain healthy lifestyle behaviors may offer benefits both in the presence and absence of adverse traditional clinical risk factors. [ABSTRACT FROM AUTHOR]

Background. Cardiovascular disease (CVD) has become more prominent among human immunodeficiency virus (HIV)-infected individuals. The extent to which CVD mortality rates are changing is unclear. Methods. We analyzed surveillance data for all persons aged ≥13 years with HIV infection between 2001 and 2012 reported to the New York City HIV Surveillance Registry. We examined age-specific and age-standardized mortality rates due to major CVDs. We compared mortality time trends among persons with HIV with the general population, and examined differences among HIV-infected persons by RNA level. Results. There were 29 588 deaths reported among 145 845 HIV-infected persons. Ten percent of deaths were attributed to CVD as the underlying cause, including chronic ischemic heart disease (42% of CVD deaths), hypertensive diseases (27%), and cerebrovascular diseases (10%). While proportionate mortality due to CVD among persons with HIV increased (6% in 2001 to 15% in 2012, P < .001), the CVD mortality rate decreased from 5.1 to 2.7 per 1000 person-years. After controlling for sex, race/ethnicity, borough of residence, and year, those with HIV had significantly higher CVD mortality than the general population in all age groups through age 65. The CVD mortality rate was highest among viremic persons (adjusted rate ratio [RR], 3.53 [95% confidence interval {CI}, 3.21-3.87]) but still elevated among virally suppressed (<400 copies/mL) persons (adjusted RR, 1.53 [95% CI, 1.41-1.66]) compared with the general population. Conclusions. Our findings support continued emphasis by HIV care providers on both viremic control and preventive measures including smoking cessation, blood pressure control, and lipid management. [ABSTRACT FROM AUTHOR]

Increased height is a known independent risk factor for atrial fibrillation (AF). However, whether genetic determinants of height influence risk is uncertain. In this candidate gene study, we examined the association of 209 height-associated single-nucleotide polymorphisms (SNPs) with incident AF in 3,309 persons of European descent from the Cardiovascular Health Study, a prospective cohort study of older adults (aged ≥65 years) enrolled in 1989–1990. After a median follow-up period of 13.2 years, 879 participants developed incident AF. The height-associated SNPs together explained approximately 10% of the variation in height (P = 6.0 × 10−8). Using an unweighted genetic height score, we found a nonsignificant association with risk of AF (per allele, hazard ratio = 1.01, 95% confidence interval: 1.00, 1.02; P = 0.06). In weighted analyses, we found that genetically predicted height was strongly associated with AF risk (per 10 cm, hazard ratio = 1.30, 95% confidence interval: 1.03, 1.64; P = 0.03). Importantly, for all models, the inclusion of actual height completely attenuated the genetic height effect. Finally, we identified 1 nonsynonymous SNP (rs1046934) that was independently associated with AF and may warrant future study. In conclusion, we found that genetic determinants of height appear to increase the risk of AF, primarily via height itself. This approach of examining SNPs associated with an intermediate phenotype should be considered as a method for identifying novel genetic targets. [ABSTRACT FROM PUBLISHER]

Abstract: Objectives: HIV disease is associated with increased arterial stiffness, which may be related to inflammation provoked by HIV-related immune perturbation. We assessed the association of T cell markers of immune activation and immunosenescence with carotid artery stiffness among HIV-infected women. Methods: Among 114 HIV-infected and 43 HIV-uninfected women, we measured CD4+ and CD8+ T cell populations expressing activation (CD38+HLA-DR+) and senescence (CD28-CD57+) markers. We then related these measures of immune status with parameters of carotid artery stiffness, including decreased distensibility, and increased Young''s elastic modulus, as assessed by B-mode ultrasound. Results: HIV infection was associated with increased CD4+ T cell activation, CD8+ T cell activation and CD8+ T cell senescence. Among HIV-infected women, adjusted for age, HIV medications, and vascular risk factors, higher CD4+CD38+HLA-DR+ T cell frequency was associated with decreased carotid artery distensibility (β =−2.00, 95% confidence interval [CI]=−3.86, −0.14, P =0.04) and increased Young''s modulus (β =1.00, 95% CI=0.03, 1.97, P =0.04). These associations were affected little by further adjustment for CD4+ T cell count and viral load. Among HIV-infected women, higher frequencies of immunosenescent T cells, including CD4+CD28-CD57+ and CD8+CD28-CD57+ T cells, were also associated with decreased arterial distensibility. Among HIV-uninfected women, frequencies of activated or senescent T cells were not significantly associated with measures of carotid stiffness. Discussion: T cell activation and senescence are associated with arterial stiffness, suggesting that pro-inflammatory populations of T cells may produce functional or structural vascular changes in HIV-infected women. [Copyright &y& Elsevier]

Background: Persistent inflammation in HIV infection is associated with elevated cardiovascular disease (CVD) risk, even with viral suppression. Identification of novel surrogate biomarkers can enhance CVD risk stratification and suggest novel therapies. We investigated the potential of interleukin 32 (IL-32), a proinflammatory multi-isoform cytokine, as a biomarker for subclinical carotid artery atherosclerosis in virologically suppressed women living with HIV (WLWH). Methods and Results: Nested within the Women's Interagency HIV Study, we conducted a cross-sectional comparison of IL-32 between 399 WLWH and 100 women without HIV, followed by a case-control study of 72 WLWH (36 carotid artery plaque cases vs. 36 age-matched controls without plaque). Plasma IL-32 protein was measured by ELISA, and mRNA of IL-32 isoforms (IL-32α, β, γ, D, ε, and θ) was quantified by reverse transcription polymerase chain reaction from peripheral blood mononuclear cells. Plasma IL-32 protein levels were higher in WLWH compared with women without HIV (P = 0.02). Among WLWH, although plasma IL-32 levels did not differ significantly between plaque cases and controls, expression of IL-32 isoforms α, β, and ε mRNA was significantly higher in peripheral blood mononuclear cells from cases (P = 0.01, P = 0.005, and P = 0.018, respectively). Upregulation of IL-32β and IL-32ε among WLWH with carotid artery plaque persisted after adjustment for age, race/ethnicity, smoking, systolic blood pressure, body mass index, and history of hepatitis C virus (P = 0.04 and P = 0.045); the adjusted association for IL-32α was marginally significant (P = 0.07). Conclusions: IL-32 isoforms should be studied further as potential CVD biomarkers. This is of particular interest in WLWH by virtue of altered IL-32 levels in this population. [ABSTRACT FROM AUTHOR]

Purpose: The Hispanic Community Health Study (HCHS)/Study of Latinos (SOL) is a comprehensive multicenter community based cohort study of Hispanics/Latinos in the United States. Methods: The Study rationale, objectives, design, and implementation are described in this report. Results: The HCHS/SOL will recruit 16,000 men and women who self-identify as Hispanic or Latino, 18 to 74 years of age, from a random sample of households in defined communities in the Bronx, Chicago, Miami, and San Diego. The sites were selected so that the overall sample would consist of at least 2000 persons in each of the following origin designations: Mexican, Puerto Rican and Dominican, Cuban, and Central and South American. The study includes research in the prevalence of and risk factors for heart, lung, blood and sleep disorders, kidney and liver function, diabetes, cognitive function, dental conditions, and hearing disorders. Conclusions: The HCHS/SOL will (1) characterize the health status and disease burden in the largest minority population in the United States; (2) describe the positive and negative consequences of immigration and acculturation of Hispanics/Latinos to the mainstream United States life-styles, environment and health care opportunities; and (3) identify likely causal factors of many diseases in a population with diverse environmental exposures, genetic backgrounds, and early life experiences. [Copyright &y& Elsevier]