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AimsInsulin resistance (IR) adversely impacts memory and executive functioning in non-Hispanic whites without diabetes. Less is known in Hispanics/Latinos, despite the fact that Hispanics/Latinos have higher rates of insulin resistance than non-Hispanic whites. We investigated the association between IR and cognition and its variation by age.MethodsData from 5987 participants 45-74 years old without diabetes from the Hispanic Community Health Study/Study of Latinos. IR was considered continuously using homeostasis model assessment for insulin resistance (HOMA-IR) and also dichotomized based on clinically relevant thresholds for hyperinsulinemia (fasting insulin > 84.73 pmol/L or HOMA-IR > 2.6) and sample-based norms (75th percentile of fasting insulin or HOMA-IR). Cognitive testing included the Brief Spanish English Verbal Learning Test (B-SEVLT), Verbal Fluency, and Digit Symbol Substitution.ResultsThere was 90% overlap in participant categorization comparing clinically relevant and sample-based thresholds. In separate fully-adjusted linear regression models, age modified the association between HOMA-IR and Digit Symbol Substitution (p = 0.02); advancing age combined with higher HOMA-IR levels resulted in higher scores. Age also modified the association between clinically relevant hyperinsulinemia and B-SEVLT recall (p = 0.03); with increasing age came worse performance for individuals with hyperinsulinemia.ConclusionThe relationship of IR with cognition in Hispanics/Latinos without diabetes may reflect an age- and test-dependent state.

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

Five sequence variants in SLC16A11 (rs117767867, rs13342692, rs13342232, rs75418188, and rs75493593), which occur in two non-reference haplotypes, were recently shown to be associated with diabetes in Mexicans from the SIGMA consortium. We aimed to determine whether these previous findings would replicate in the HCHS/SOL Mexican origin group and whether genotypic effects were similar in other HCHS/SOL groups. We analyzed these five variants in 2492 diabetes cases and 5236 controls from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), which includes U.S. participants from six diverse background groups (Mainland groups: Mexican, Central American, and South American; and Caribbean groups: Puerto Rican, Cuban, and Dominican). We estimated the SNP-diabetes association in the six groups and in the combined sample. We found that the risk alleles occur in two non-reference haplotypes in HCHS/SOL, as in the SIGMA Mexicans. The haplotype frequencies were very similar between SIGMA Mexicans and the HCHS/SOL Mainland groups, but different in the Caribbean groups. The SLC16A11 sequence variants were significantly associated with risk for diabetes in the Mexican origin group (P = 0.025), replicating the SIGMA findings. However, these variants were not significantly associated with diabetes in a combined analysis of all groups, although the power to detect such effects was 85% (assuming homogeneity of effects among the groups). Additional analyses performed separately in each of the five non-Mexican origin groups were not significant. We also analyzed (1) exclusion of young controls and, (2) SNP by BMI interactions, but neither was significant in the HCHS/SOL data. The previously reported effects of SLC16A11 variants on diabetes in Mexican samples was replicated in a large Mexican-American sample, but these effects were not significant in five non-Mexican Hispanic/Latino groups sampled from U.S. populations. Lack of replication in the HCHS/SOL non-Mexicans, and in the entire HCHS/SOL sample combined may represent underlying genetic heterogeneity. These results indicate a need for future genetic research to consider heterogeneity of the Hispanic/Latino population in the assessment of disease risk, but add to the evidence suggesting SLC16A11 as a potential therapeutic target for type 2 diabetes.

BackgroundPeople living with HIV are at risk of increased myocardial infarction (MI). Cumulative HIV viral load (VL) has been proposed as a better measure of HIV inflammation than other measures of VL, like baseline VL, but its associations with MI are not known.MethodsThe multisite Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort includes clinical data and centrally adjudicated MI with distinction between atheroembolic MI (type 1) and MI related to supply-demand mismatch (type 2). We examined CNICS participants who were not on antiretroviral therapy (ART) at enrollment. Cumulative VL (copy-days of virus) from 6 months after enrollment was estimated with a time-weighted sum using the trapezoidal rule. We modeled associations of cumulative and baseline VL with MI by type using marginal structural Cox models. We contrasted the 75% percentile of the VL distribution with the 25% percentile.ResultsAmong 11,324 participants, 218 MIs occurred between 1996 and 2016. Higher cumulative VL was associated with risk of all MI (hazard ratio [HR] = 1.72; 95% confidence interval [CI] = 1.26, 2.36), type 1 MI (HR = 1.23; 95% CI = 0.78, 1.96), and type 2 MI (HR = 2.52; 95% CI = 1.74, 3.66). While off ART, cumulative VL had a stronger association with type 1 MI (HR = 2.13; 95% CI = 1.15, 3.94) than type 2 MI (HR = 1.25; 95% CI = 0.70, 2.25). Baseline VL was associated with all MI (HR = 1.60; 95% CI = 1.28, 2.01), type 1 MI (HR = 1.73; 95% CI = 1.26, 2.38), and type 2 MI (HR = 1.51; 95% CI = 1.10, 2.08).ConclusionsHigher cumulative and baseline VL is associated with all MI, with a particularly strong association between cumulative VL and type 2 MI.

BackgroundA goal of gerontology is discovering aging phenotypes that reflect biological aging distinct from disease pathogenesis. Biomarkers that strongly and independently associated with mortality and that statistically attenuated chronologic age could be used to define such a phenotype. We determined the association of a Biomarker Index (BI) with mortality and compared it with a validated Physiologic Index (PI) in older adults.MethodsThe indices were constructed in the Cardiovascular Health Study, mean (SD) age 74.5 (5.1) years. The BI incorporated circulating levels of new biomarkers, including insulin-like growth factor-1, insulin-like growth factor-binding protein 3, amino-terminal pro-B-type natriuretic peptide, dehydroepiandrosterone sulfate, and interleukin-6, and was built in test (N = 2,197) and validation (N = 1,124) samples. The PI included carotid intima-media thickness, pulmonary capacity, brain white matter grade, cystatin-C, and fasting glucose. Multivariable Cox proportional hazards models predicting death were calculated with 10 years of follow-up.ResultsIn separate age-adjusted models, the hazard ratio for mortality per point of the BI was 1.30 (95% confidence interval 1.25, 1.34) and the BI attenuated age by 25%. The hazard ratio for the PI was 1.28 (1.24, 1.33; 29% age attenuation). In the same model, the hazard ratio for the BI was 1.23 (1.18, 1.28) and for the PI was 1.22 (1.17, 1.26), and age was attenuated 42.5%. Associations persisted after further adjustment.ConclusionsThe BI and PI were significantly and independently associated with mortality. Both attenuated the age effect on mortality substantially. The indices may be feasible phenotypes for developing interventions hoping to alter the trajectory of aging.

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ObjectiveAmong people with HIV, there are few long-term studies of noninvasive ultrasound-based measurements of the carotid artery predicting major health events. We hypothesized that such measurements are associated with 10-year mortality in the Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS), and that associations differ by HIV serostatus.DesignNested cohort study.MethodsParticipants without coronary heart disease underwent B-mode carotid artery ultrasound, with measurement of common carotid artery intima-media thickness (IMT); carotid artery plaque (focal IMT > 1.5 mm) at six locations; and Young's modulus of elasticity, a measure of arterial stiffness. We examined all-cause mortality using Cox models, controlling for demographic, behavioral, cardiometabolic, and HIV-related factors.ResultsAmong 1722 women (median age 40 years, 90% nonwhite, 71% HIV-positive) and 1304 men (median age 50, 39% nonwhite, 62% HIV-positive), 11% died during follow-up. Mortality was higher among HIV-positive women [19.9 deaths/1000 person-years, 95% confidence interval (CI) 14.7-28.8] than HIV-positive men (15.1/1000, 95% CI 8.3-26.8). In adjusted analyses, plaque was associated with mortality (hazard ratio 1.44, 95% CI 1.10-1.88) regardless of HIV serostatus, and varied by sex (among women, hazard ratio 1.06, 95% CI 0.74-1.52; among men; hazard ratio 2.19, 95% CI 1.41-3.43). The association of plaque with mortality was more pronounced among HIV-negative (hazard ratio 3.87, 95% 1.95-7.66) than HIV-positive participants (hazard ratio 1.35, 95% CI 1.00-1.84). Arterial stiffness was also associated with mortality (hazard ratio 1.43 for highest versus lowest quartile, 95% CI 1.02-2.01). Greater common carotid artery-IMT was not associated with mortality.ConclusionCarotid artery plaque was predictive of mortality, with differences observed by sex and HIV serostatus.

BackgroundCD4+ T cells play an important role in atherosclerosis, but their antigen specificity is poorly understood. Immunization with apolipoprotein B (ApoB, core protein of low density lipoprotein) is known to be atheroprotective in animal models. Here, we report on a human APOB peptide, p18, that is sequence-identical in mouse ApoB and binds to both mouse and human major histocompatibility complex class II molecules.MethodsWe constructed p18 tetramers to detect human and mouse APOB-specific T cells and assayed their phenotype by flow cytometry including CD4 lineage transcription factors, intracellular cytokines, and T cell receptor activation. Apolipoprotein E-deficient ( Apoe-/-) mice were vaccinated with p18 peptide or adjuvants alone, and atherosclerotic burden in the aorta was determined.ResultsIn human peripheral blood mononuclear cells from donors without cardiovascular disease, p18 specific CD4+ T cells detected by a new human leukocyte antigen-antigen D related-p18 tetramers were mostly Foxp3+ regulatory T cells (Tregs). Donors with subclinical cardiovascular disease as detected by carotid artery ultrasound had Tregs coexpressing retinoic acid-related orphan receptor gamma t or T-bet, which were both almost absent in donors without cardiovascular disease. In Apoe-/- mice, immunization with p18 induced Tregs and reduced atherosclerotic lesions. After peptide restimulation, responding CD4+ T cells identified by Nur77-GFP (green fluorescent protein) were highly enriched in Tregs. A new mouse I-Ab-p18 tetramer identified the expansion of p18-specific CD4+ T cells on vaccination, which were enriched for interleukin-10-producing Tregs.ConclusionsThese findings show that APOB p18-specific CD4+ T cells are mainly Tregs in healthy donors, but coexpress other CD4 lineage transcription factors in donors with subclinical cardiovascular disease. This study identifies ApoB peptide 18 as the first Treg epitope in human and mouse atherosclerosis.

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

AimWe investigated the cross-sectional association between diet quality and severe periodontitis in a sample of diverse Hispanics from the Hispanic Community Health Study/Study of Latinos.Materials and methodsA total of 13,920 Hispanic/Latinos aged 18-74 years of different heritages underwent a full-mouth oral examination and completed two 24-hr dietary recalls during 2008-2011. Severe periodontitis was defined as having ≥30% tooth sites with clinical attachment loss ≥5 mm. Diet quality was assessed using the Alternative Healthy Eating Index (AHEI-2010). We evaluated the association of diet quality with severe periodontitis adjusting for age, sex, nativity status, income, education, last dental visit, current insurance, cigarette smoking, diabetes, and energy intake.ResultsRelative to those at the lowest quartile of diet quality, individuals at the highest quartile had significantly lower odds of severe periodontitis (adjusted OR = 0.57, 95% CI: 0.39-0.82), with evidence of a dose-response relationship across AHEI quartiles. Among AHEI-2010 components, higher consumption of whole grains and fruits, and lower consumption of red/processed meats were associated with lower odds of severe periodontitis.ConclusionBetter-quality diet was associated with lower prevalence of severe periodontitis although the causal pathways need to be clarified in future work.

ObjectiveHIV is a cardiovascular disease (CVD) risk factor. However, CVD risk is often underestimated in HIV-infected women. C-reactive protein (CRP) may improve CVD prediction in this population. We examined the association of baseline plasma CRP with subclinical CVD in women with and without HIV.DesignRetrospective cohort study.MethodsA total of 572 HIV-infected and 211 HIV-uninfected women enrolled in the Women's Interagency HIV Study underwent serial high-resolution B-mode carotid artery ultrasonography between 2004 and 2013 to assess carotid intima-media thickness (CIMT) and focal carotid artery plaques. We used multivariable linear and logistic regression models to assess the association of baseline high (≥3 mg/l) high-sensitivity (hs) CRP with baseline CIMT and focal plaques, and used multivariable linear and Poisson regression models for the associations of high hsCRP with CIMT change and focal plaque progression. We stratified our analyses by HIV status.ResultsMedian (interquartile range) hsCRP was 2.2 mg/l (0.8-5.3) in HIV-infected, and 3.2 mg/l (0.9-7.7) in HIV-uninfected, women (P = 0.005). There was no statistically significant association of hsCRP with baseline CIMT [adjusted mean difference -3.5 μm (95% confidence interval:-19.0 to 12.1)] or focal plaques [adjusted odds ratio: 1.31 (0.67-2.67)], and no statistically significant association of hsCRP with CIMT change [adjusted mean difference 11.4 μm (-2.3 to 25.1)]. However, hsCRP at least 3 mg/l was positively associated with focal plaque progression in HIV-uninfected [adjusted rate ratio: 5.97 (1.46-24.43)], but not in HIV-infected [adjusted rate ratio: 0.81 (0.47-1.42)] women (P = 0.042 for interaction).ConclusionIn our cohort of women with similar CVD risk factors, higher baseline hsCRP is positively associated with carotid plaque progression in HIV-uninfected, but not HIV-infected, women, suggesting that subclinical CVD pathogenesis may be different HIV-infected women.

Background and aimsThe Ankle-Brachial index (ABI) is a well-accepted measure of peripheral artery disease (arterial stenosis and stiffness) and has been shown to be associated with cognitive function and disorders; however, these associations have not been examined in Hispanics/Latinos. Therefore, we sought to examine relationships between ABI and cognitive function among diverse middle-age and older Hispanics/Latinos.MethodsWe used cross-sectional data on n = 7991 participants aged 45-74 years, without stroke or coronary heart disease, from the Hispanic Community Health Study/Study of Latinos. Our primary outcome, global cognition (GC), was a continuous composite score of four cognitive domains (verbal learning and memory, verbal fluency, executive function, and mental status). Secondary outcomes were the individual tests representing these domains. The ABI was analyzed continuously and categorically with standard clinical cut-points. We tested associations using generalized survey regression models incrementally adjusting for confounding factors. Age, sex, hypertension, diabetes, and dyslipidemia moderations were examined through interactions with the primary exposure.ResultsIn age, sex, and education adjusted models, continuous ABI had an inverse u-shape association with worse GC. We found similar associations with measures of verbal learning and memory, verbal fluency, executive function, but not with low mental status. The associations were attenuated, but not completely explained, by accounting for the confounders and not modified by age, sex, education, and vascular disease risks.ConclusionsIn addition to being a robust indicator of arterial compromise, our study suggests that abnormal ABI readings may also be useful for early signaling of subtle cognitive deficits.

ObjectiveThe purpose of this study is to examine the association between verbal learning, fluency, and processing speed with anxious depression symptomatology (ADS) among diverse Hispanics. We hypothesized an inverse association of anxious depression with neurocognition among Hispanics of different heritage.DesignData are from the Hispanic Community Health Study/Study of Latinos. The sample included 9,311participants aged 45-74 years (mean: 56.5 years). A latent class analysis of items from the Center for Epidemiological Studies for Depression scale and the Spielberger Trait Anxiety Inventory was used to derive an anxious depression construct. Neurocognitive measures included scores on the Brief Spanish English Verbal Learning Test (B-SEVLT, learning and recall trials), Word Fluency (WF), Digit Symbol Substitution (DSS) test, and a Global Cognitive Score (GCS). We fit survey linear regression models to test the associations between anxious depression symptomatology and cognitive function. We tested for effect modification by sex, Hispanic heritage, and age groups.ResultsAmong men, 71.6% reported low, 23.3% moderate, and 5.1% high ADS. Among women, 55.1% reported low, 33.2% moderate, and 11.8% high ADS. After controlling for age, sex, sociodemographic characteristics, cardiovascular risk factors and disease, and antidepressant use, we found significant inverse associations between moderate and high anxious depression (ref:low) with B-SEVLT learning and recall, DSS and GCS. Moderate, but not high, anxious depression was inversely associated with WF. Associations were not modified by sex, Hispanic heritage, or age.ConclusionsIncreased anxious depression symptomatology is associated with decreased neurocognitive function among Hispanics. Longitudinal studies are needed to establish temporality and infer if negative emotional symptoms precede cognitive deficits.

Higher urine albumin-to-creatinine ratio (UACR) has been associated with cardiac dysfunction in the general population. We assessed the association of UACR with cardiac structure and function in the Echocardiographic Study of Latinos (Echo-SOL), an ancillary study of the Hispanic Community Health Study/Study of Latinos across 4 US sites. Echo-SOL participants underwent standard 2-dimensional echocardiography, including speckle-tracking strain analysis. UACR was categorized as normal and high-normal (based on the midpoint of values below microalbuminuria), microalbuminuria (≥17 mg/g for men; ≥25 mg/g for women), and macroalbuminuria (≥250 mg/g; ≥355 mg/g). Simultaneous assessments were made of left ventricular (LV) mass index and hypertrophy and measures of LV systolic and diastolic dysfunction. We assessed the association of UACR with subclinical cardiac measures, adjusting for sociodemographic and cardiometabolic factors. Among 1,815 participants (median age 54, women 65%), 42% had normal UACR, 43% high-normal UACR, 13% microalbuminuria, and 2% macroalbuminuria. Prevalence of LV hypertrophy was 13%, LV systolic dysfunction (ejection fraction

Few genome-wide association studies (GWAS) of type 2 diabetes (T2D) have been conducted in U.S. Hispanics/Latinos of diverse backgrounds who are disproportionately affected by diabetes. We conducted a GWAS in 2,499 T2D case subjects and 5,247 control subjects from six Hispanic/Latino background groups in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Our GWAS identified two known loci (TCF7L2 and KCNQ1) reaching genome-wide significance levels. Conditional analysis on known index single nucleotide polymorphisms (SNPs) indicated an additional independent signal at KCNQ1, represented by an African ancestry-specific variant, rs1049549 (odds ratio 1.49 [95% CI 1.27-1.75]). This association was consistent across Hispanic/Latino background groups and replicated in the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium. Among 80 previously known index SNPs at T2D loci, 66 SNPs showed consistency with the reported direction of associations and 14 SNPs significantly generalized to the HCHS/SOL. A genetic risk score based on these 80 index SNPs was significantly associated with T2D (odds ratio 1.07 [1.06-1.09] per risk allele), with a stronger effect observed in nonobese than in obese individuals. Our study identified a novel independent signal suggesting an African ancestry-specific allele at KCNQ1 for T2D. Associations between previously identified loci and T2D were generally shown in a large cohort of U.S. Hispanics/Latinos.

BackgroundMonocytes and monocyte-derived macrophages promote atherosclerosis through increased inflammation and vascular remodeling. This may be especially true in chronic human immunodeficiency virus (HIV) infection.MethodsWe examined 778 women (74% HIV+) in the Women's Interagency HIV Study and 503 men (65% HIV+) in the Multicenter AIDS Cohort Study who underwent repeated B-mode carotid artery ultrasound imaging in 2004-2013. We assessed baseline associations of the serum macrophage inflammation markers soluble (s)CD163, sCD14, galectin-3 (Gal-3), and Gal-3 binding protein (Gal-3BP) with carotid plaque formation (focal intima-media thickness >1.5 mm) over 7 years.ResultsMarker levels were higher in HIV+ persons versus HIV- persons. Presence of focal plaque increased over time: from 8% to 15% in women, and 24% to 34% in men. After adjustment for demographic, behavioral, and cardiometabolic factors, and CRP and interleukin-6, each standard deviation increase in sCD14 was associated with increased plaque formation (risk ratio [RR] 1.24, 95% confidence interval [CI] 1.07-1.43). This pattern was consistentby sex. sCD163 was associated with plaque formation in virally suppressed HIV+ men (RR 1.52, 95% CI 1.04-2.22); Gal-3BP and Gal-3 were not associated with increased plaque.ConclusionssCD14 and sCD163 may play important roles in atherogenesis among HIV+ persons.

RationaleObesity-related asthma is associated with higher disease burden than normal-weight asthma among Hispanics. Adiposity, metabolic dysregulation, and inflammation are all implicated in pathogenesis of obesity-related asthma, but their independent contributions are poorly understood.ObjectiveTo examine the independent contributions of body fat distribution, metabolic abnormalities and inflammation on asthma symptoms and pulmonary function among Hispanics.MethodsParticipants of the Hispanic Community Health Study/Study of Latinos with doctor-diagnosed asthma who completed an asthma symptom questionnaire and performed a valid spirometry were included in the analysis (n = 1126). Multivariate analysis was used to examine the independent association of general adiposity (assessed using body mass index), truncal adiposity (assessed by waist circumference), metabolic dysregulation (presence of insulin resistance and low HDL) and inflammation (high-sensitivity C-Reactive Protein≥3 mg/L) with reported asthma symptoms or pulmonary function measures (FEV1, and FVC) while adjusting for demographic and clinical covariates.ResultsOf the 1126 participants, 334 (29.5%) were overweight, and 648 (57.8%) were obese. FEV1 and FVC were lower in obese compared to normal-weight asthmatics. In analyses controlling for metabolic and adiposity factors, high hs-CRP (>7 mg/L) was associated with more symptoms (prevalence-ratio 1.27 (95%CI 1.05, 1.54), and lower FVC (β -138 ml (95%CI -27 ml, -249 ml)) and FEV1 (β -155 ml (95% CI -38 ml, -272 ml). Low HDL was also associated with lower FVC (β -111 ml (-22 ml, -201 ml) and FEV1 (β -100 ml (-12 ml, -188 ml)). Results were similar in men and women.ConclusionsOur findings suggest that hs-CRP and low HDL, rather than general and truncal adiposity, are associated with asthma burden among overweight and obese Hispanic adults.

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.

Allostatic load (AL), an index of biological "wear and tear" on the body from cumulative exposure to stress, has been little studied in US Hispanics/Latinos. We investigated AL accumulation patterns by age, sex, and nativity in the Hispanic Community Health Study/Study of Latinos. We studied 15,830 Hispanic/Latinos of Mexican, Cuban, Dominican, Puerto Rican, Central and South American descent aged 18-74 years, 77% of whom were foreign-born. Consistent with the conceptualization of AL, we developed an index based upon 16 physiological markers that spanned the cardiometabolic, parasympathetic, and inflammatory systems. We computed mean adjusted AL scores using log-linear models across age-groups (18-44, 45-54, 55-74 years), by sex and nativity status. Among foreign-born individuals, differences in AL by duration of residence in the US (

ObjectiveType 2 diabetes mellitus (DM) has been associated with lung dysfunction, but this association has not been explored in Hispanics/Latinos. The relation between diabetic nephropathy and lung function and symptoms has not been explored.Research design and methodsThe Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a large, multicenter, observational study, recruited 16,415 participants aged 18-74 years (14,455 with complete data on variables of interest), between 2008 and 2011 from four U.S. communities through a two-stage area household probability design. Baseline measurements were used for analyses. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and dyspnea score were compared between individuals with and without DM, overall, and stratified by albuminuria. The analyses were performed separately for those with and without preexisting lung disease (chronic bronchitis, emphysema, asthma). Linear regression with sampling weights was used for all analyses.ResultsAmong Hispanics/Latinos without lung disease, those with DM had lower mean FEV1 and FVC values and a higher mean dyspnea score than those without DM (mean [95% CI] FEV1 3.00 [2.96-3.04] vs. 3.10 [3.09-3.11] L, P < 0.01; FVC 3.62 [3.59-3.66] vs. 3.81 [3.79-3.83] L, P < 0.001; dyspnea score 0.60 [0.49-0.71] vs. 0.41 [0.34-0.49], P < 0.001). Hispanics/Latinos with DM and macroalbuminuria showed 10% lower FVC (P < 0.001), 6% lower FEV1 (P < 0.001), and 2.5-fold higher dyspnea score (P = 0.04) than those without DM and with normoalbuminuria. Similar findings but with higher impairment in FVC were found in Hispanics/Latinos with lung disease.ConclusionsHispanics/Latinos with DM have functional and symptomatic pulmonary impairment that mirror kidney microangiopathy. The progression of pulmonary impairment in adults with DM needs to be investigated further.

The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype-phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90 years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci.

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

BackgroundWe examined the relationship between glucose homeostasis and comprehensive measures of cardiac structure and function among a representative sample of US Hispanics.Methods and resultsECHO-SOL (Echocardiographic Study of Latinos), an echocardiographic ancillary study of the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), enrolled 1818 Hispanic/Latino men (43%) and women (57%) aged ≥45 years (mean=56). Glucose intolerance was defined as follows: (1) prediabetes: hemoglobin (HbA1c) ≥5.7 and

Insulin-like growth factor 1 (IGF-I) has been associated with insulin resistance. Genome-wide association studies (GWASs) of fasting insulin (FI) identified single-nucleotide variants (SNVs) near the IGF1 gene, raising two hypotheses: (1) these associations are mediated by IGF-I levels and (2) these noncoding variants either tag other functional variants in the region or are directly functional. In our study, analyses including 5141 individuals from population-based cohorts suggest that FI associations near IGF1 are not mediated by IGF-I. Analyses of targeted sequencing data in 3539 individuals reveal a large number of novel rare variants at the IGF1 locus and show a FI association with a subset of rare nonsynonymous variants (PSKAT=5.7 × 10(-4)). Conditional analyses suggest that this association is partly explained by the GWAS signal and the presence of a residual independent rare variant effect (Pconditional=0.019). Annotation using ENCODE data suggests that the GWAS variants may have a direct functional role in insulin biology. In conclusion, our study provides insight into variation present at the IGF1 locus and into the genetic architecture underlying FI levels, suggesting that FI associations of SNVs near IGF1 are not mediated by IGF-I and suggesting a role for both rare nonsynonymous and common functional variants in insulin biology.

BackgroundFavorable levels of all readily measurable major cardiovascular disease risk factors (ie, low risk [LR]) are associated with lower risks of cardiovascular disease morbidity and mortality. Data are not available on LR prevalence among Hispanic/Latino adults of diverse ethnic backgrounds. This study aimed to describe the prevalence of a low cardiovascular disease risk profile among Hispanic/Latino adults in the United States and to examine cross-sectional associations of LR with measures of acculturation.Methods and resultsThe multicenter, prospective, population-based Hispanic Community Health Study/Study of Latinos examined 16 415 men and women aged 18 to 74 years at baseline (2008-2011) with diverse Hispanic/Latino backgrounds. Analyses involved 14 757 adults (mean age 41.3 years; 60.6% women). LR was defined using national guidelines for favorable levels of serum cholesterol, blood pressure, and body mass index and by not having diabetes mellitus and not currently smoking. Age-adjusted LR prevalence was low (8.4% overall; 5.1% for men, 11.2% for women) and varied by background (4.2% in men of Mexican heritage versus 15.0% in women of Cuban heritage). Lower acculturation (assessed using proxy measures) was significantly associated with higher odds of a LR profile among women only: Age-adjusted odds ratios of having LR were 1.64 (95% CI 1.24-2.17) for foreign-born versus US-born women and 1.96 (95% CI 1.49-2.58) for women residing in the United States

BackgroundAge and human immunodeficiency virus (HIV) treatment may affect the association of HIV infection with atherosclerosis.MethodsWe used identical carotid artery B-mode ultrasonographic methods in 5 cohorts participating in the National Heart, Lung, and Blood Institute HIV-CVD Collaborative to measure intima-media thickness of the right far wall of the common carotid artery (CCA-IMT) and carotid artery bifurcation (BIF-IMT) between 2010 and 2013. Participants aged 6-75 years were either HIV infected or uninfected. Linear regression assessed associations of CCA-IMT and BIF-IMT with HIV infection and cardiovascular disease risk factors, within age and HIV treatment groups. Adjustment variables included sex, race/ethnicity, smoking, height, weight, and use of antihypertensive and lipid-lowering drugs.ResultsWe studied 867 HIV-infected and 338 HIV-uninfected male and 696 HIV-infected and 246 HIV-uninfected female participants. Among both middle-aged (30-49 years) and older adults (50-75 years), HIV-infected participants had CCA-IMT and BIF-IMT values that were similar to or lower than those in HIV-uninfected participants. In contrast, among those aged 6-29 years, HIV infection was associated with higher CCA-IMT and BIF-IMT values. Among HIV-infected participants, associations of higher systolic blood pressure and lower high-density lipoprotein cholesterol with Carotid artery intima-media thickness strengthened with age.ConclusionsThe effects of HIV on carotid artery structure may differ across the lifespan, with traditional determinants of cardiovascular disease burden playing a larger role and HIV playing a lesser role in older adults than in young adults and children.

AimsTo examine among Hispanics in the U.S., a population with increased reliance on informal healthcare support structures, (1) the association between cognitive function and control of diabetes; and (2) whether this association is modified by family support.MethodsThe Digit Symbol Substitution Test (DSST), word fluency, and learning and delayed recall components of the Spanish English Verbal Learning Test were administered to 1794 Hispanic adults aged 45-76years with diagnosed diabetes. An executive function index and global cognitive function index (GCFI) were derived. Uncontrolled diabetes (HbA1c⩾7% [53mmol/mol]) was compared across quartiles of cognitive function using multivariable logit models with interaction terms for cognitive function and family support.ResultsAfter adjustment, lower DSST scores were associated with uncontrolled diabetes (P=0.03). Family support modified the relationship between other measures of cognition and diabetes control (Pinteraction: 0.002, 0.09). Among individuals with low family support, as cognitive function declined, the odds of uncontrolled diabetes increased (P-trend across quartiles of the GCFI, 0.015). Among those with low family support, persons in the lowest quartile of global cognitive function were more than twice as likely to have uncontrolled diabetes as those in the highest performing quartile (OR=2.31; 95% CI: 1.17, 4.55). There was no similar effect among those with high family support.ConclusionsFamily support may buffer the negative association between low cognitive functioning and diabetes control in US Hispanics/Latinos. Educational programs targeted at family members of middle-age and older persons with diabetes regardless of neurocognitive status may help improve population-level glycemic control.

ObjectivesTo ascertain whether older adults with extensive disease but relative vigor (adapters) shorten the period at the end of life in which they live with morbidity (compress morbidity).DesignProspective, community-based cohort study in four U.S. cities.SettingCardiovascular Health Study.ParticipantsIndividuals aged 65 and older.MeasurementsParticipants were categorized into three groups according to extent of disease (assessed noninvasively), vigor, and frailty (expected agers (n = 3,528, extent of disease similar to vigor and frailty-reference group), adapters (n = 882, higher disease but vigorous), and prematurely frail (n = 855, lower disease but frail)) and compared according to years of able life (YAL), years of self-reported healthy life (YHL), and mortality using multivariable regression and survival analysis.ResultsAfter adjustment, adapters had 0.97 (95% confidence interval (CI) = 0.60-1.33) more YAL and 0.54 (95% CI = 0.19-0.90) more YHL than expected agers, and those who were prematurely frail had -0.99 (95% CI = -1.36 to -0.62) fewer YAL and -0.53 (95% CI = -0.89 to -0.17) fewer YHL than expected agers. Adapters had 0.9 more and prematurely frail had 1.5 fewer years of total life than expected agers (P

ObjectivesTo investigate the association between diabetes mellitus and missing teeth in Hispanic/Latino adults from diverse heritage groups who reside in the USA.Research design and methodsThe Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a multicenter, population-based study of 18-74 years old who underwent a physical and oral examination (n=15 945). Glycemic status was categorized as diabetes, impaired, or normal, based on medication use, and American Diabetes Association criteria for fasting glucose and glycosylated hemoglobin (HbA1c). HbA1c7% indicated uncontrolled diabetes. We estimated ORs and 95% CIs for missing >9 teeth and being edentulous (missing all natural teeth), after adjustment for age, income, education, Hispanic background, study site/center, nativity, last dental visit, health insurance, diet quality, cigarette smoking, obesity, periodontitis, and C reactive protein.ResultsPersons with uncontrolled diabetes had a significant increased likelihood of missing >9 teeth and being edentulous as compared with persons with normal glycemic status (adjusted OR=1.92, 95% CI 1.44 to 2.55 and adjusted OR=1.73, 95% CI 1.22 to 2.46, respectively). The association appeared to be stronger at younger ages (18-44 years old; p for interaction

ObjectiveWe examined the associations of symptoms of sleep-disordered breathing (SDB), which was defined as loud snoring, stopping breathing for a while during sleep, and daytime sleepiness, and insomnia with glucose metabolism and incident type 2 diabetes in older adults.Research design and methodsBetween 1989 and 1993, the Cardiovascular Health Study recruited 5,888 participants ≥65 years of age from four U.S. communities. Participants reported SDB and insomnia symptoms yearly through 1989-1994. In 1989-1990, participants underwent an oral glucose tolerance test, from which insulin secretion and insulin sensitivity were estimated. Fasting glucose levels were measured in 1989-1990 and again in 1992-1993, 1994-1995, 1996-1997, and 1998-1999, and medication use was ascertained yearly. We determined the cross-sectional associations of sleep symptoms with fasting glucose levels, 2-h glucose levels, insulin sensitivity, and insulin secretion using generalized estimated equations and linear regression models. We determined the associations of updated and averaged sleep symptoms with incident diabetes in Cox proportional hazards models. We adjusted for sociodemographics, lifestyle factors, and medical history.ResultsObserved apnea, snoring, and daytime sleepiness were associated with higher fasting glucose levels, higher 2-h glucose levels, lower insulin sensitivity, and higher insulin secretion. The risk of the development of type 2 diabetes was positively associated with observed apnea (hazard ratio [HR] 1.84 [95% CI 1.19-2.86]), snoring (HR 1.27 [95% CI 0.95-1.71]), and daytime sleepiness (HR 1.54 [95% CI 1.13-2.12]). In contrast, we did not find consistent associations between insomnia symptoms and glucose metabolism or incident type 2 diabetes.ConclusionsEasily collected symptoms of SDB are strongly associated with insulin resistance and the incidence of type 2 diabetes in older adults. Monitoring glucose metabolism in such patients may prove useful in identifying candidates for lifestyle or pharmacological therapy. Further studies are needed to determine whether insomnia symptoms affect the risk of diabetes in younger adults.

ObjectivesTo identify genetic associations with hip osteoarthritis (HOA), we performed a meta-analysis of genome-wide association studies (GWAS) of HOA.MethodsThe GWAS meta-analysis included approximately 2.5 million imputed HapMap single nucleotide polymorphisms (SNPs). HOA cases and controls defined radiographically and by total hip replacement were selected from the Osteoporotic Fractures in Men (MrOS) Study and the Study of Osteoporotic Fractures (SOF) (654 cases and 4697 controls, combined). Replication of genome-wide significant SNP associations (p ≤5×10(-8)) was examined in five studies (3243 cases and 6891 controls, combined). Functional studies were performed using in vitro models of chondrogenesis and osteogenesis.ResultsThe A allele of rs788748, located 65 kb upstream of the IGFBP3 gene, was associated with lower HOA odds at the genome-wide significance level in the discovery stage (OR 0.71, p=2×10(-8)). The association replicated in five studies (OR 0.92, p=0.020), but the joint analysis of discovery and replication results was not genome-wide significant (p=1×10(-6)). In separate study populations, the rs788748 A allele was also associated with lower circulating IGFBP3 protein levels (p=4×10(-13)), suggesting that this SNP or a variant in linkage disequilibrium could be an IGFBP3 regulatory variant. Results from functional studies were consistent with association results. Chondrocyte hypertrophy, a deleterious event in OA pathogenesis, was largely prevented upon IGFBP3 knockdown in chondrocytes. Furthermore, IGFBP3 overexpression induced cartilage catabolism and osteogenic differentiation.ConclusionsResults from GWAS and functional studies provided suggestive links between IGFBP3 and HOA.

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.

ObjectiveSleep apnea (SA) has been linked with various forms of cardiovascular disease, but little is known about its association with peripheral artery disease (PAD) measured using the ankle-brachial index. This relationship was evaluated in the Hispanic Community Health Study/Study of Latinos.Approach and resultsWe studied 8367 Hispanic Community Health Study/Study of Latinos participants who were 45 to 74 years of age. Sleep symptoms were examined with the self-reported Sleep Health Questionnaire. SA was assessed using an in-home sleep study. Systolic blood pressure was measured in all extremities to compute the ankle-brachial index. PAD was defined as ankle-brachial index

BackgroundThe genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies.MethodsWe conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity.ResultsIn our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10(-10)).ConclusionsWe did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.

BackgroundHepatitis C virus (HCV) viremia is thought to have broad systemic effects on the cellular immune system that go beyond its impact on just those T cells that are HCV specific. However, previous studies of chronic HCV and circulating T-cell subsets (activation and differentiation phenotypes) in HIV negatives used general population controls, rather than a risk-appropriate comparison group. Studies in HIV positives did not address overall immune status (total CD4⁺ count).MethodsWe used fresh blood from HIV-positive and at-risk HIV-negative women, with and without chronic HCV, to measure percentages of activated CD4⁺ and CD8⁺ T cells, Tregs, and T-cell differentiation phenotypes (naive, central memory, effector memory (EM), and terminally differentiated effector). This included 158 HIV negatives and 464 HIV positives, of whom 18 and 63, respectively, were HCV viremic.ResultsIn multivariate models of HIV negatives, HCV viremia was associated with 25% fewer naive CD4⁺ (P = 0.03), 33% more EM CD4⁺ (P = 0.0002), and 37% fewer central memory CD8⁺ (P = 0.02) T cells. Among HIV positives, we observed only 1 of these 3 relationships: higher percentage of EM CD4⁺ among HCV viremic women. Furthermore, the association with EM CD4⁺ among HIV positives was limited to individuals with diminished immune status (total CD4⁺ count ≤500 cells/μL), as were associations of HCV viremia with higher percentages of activated CD4⁺ and Tregs. Among HIV positives with high CD4⁺ count, no significant associations were observed.ConclusionsThese data suggest that HCV viremia in HIV negatives is associated with accelerated T-cell differentiation, but among HIV positives, the impact of HCV viremia is less straightforward and varies by total CD4v count.

ObjectiveT-cell activation is a major pathway driving HIV disease progression. Little is known regarding the impact of T-cell activation on HIV-associated atherosclerosis and cardiovascular disease, a common comorbidity in HIV infection. We hypothesized that T-cell activation will predict vascular stiffness, a measure of subclinical atherosclerosis.DesignLinear regression models evaluated the covariate-adjusted association of T-cell activation with vascular stiffness.MethodsCD38 and HLA-DR expression on CD4⁺ and CD8⁺ T cells was assessed by flow cytometry among 59 HIV-negative and 376 HIV-infected (185 hepatitis C coinfected) women in the Women's Interagency HIV Study. T-cell activation was defined by CD8⁺CD38⁺DR+ and CD4⁺CD3⁺8DR+. Multiple activation assessments over 6.5 years were averaged. In 140 women, T-cell activation was measured before and after highly active antiretroviral therapy (HAART) initiation. Carotid artery ultrasounds were completed a median of 6.5 years after last measurement of T-cell activation and carotid artery stiffness including distensibility and elasticity were calculated.ResultsPercentages of CD4⁺ and CD8⁺ T-cell activation were significantly higher in HIV- infected compared with HIV-negative women. Among HIV-negative women, T-cell activation was not associated with carotid artery stiffness. Among HIV-infected women, higher CD4⁺ T-cell activation levels significantly predicted increased arterial stiffness independent of CD4⁺ cell count and HIV RNA. The association was stronger among HIV/hepatitis C-coinfected women compared with HIV-monoinfected women; however, the difference was not statistically significant (P for interaction >0.05). Pre- and post-HAART levels of CD4⁺ T-cell activation significantly predicted carotid artery stiffness.ConclusionsPersistent T-cell activation, even after HAART initiation, can contribute to structural and/or functional vascular damage accelerating atherogenesis in HIV infection. These results need to be confirmed in a longitudinal prospective study.

: In HIV negatives, markers of hemostasis, including D-dimer, factor VIII, plasminogen activator inhibitor-1 antigen (PAI-1), and total protein S are associated with all-cause and cardiovascular disease mortality. In HIV positives, studies of D-dimer and factor VIII with death were limited to short follow-up; associations of PAI-1 and total protein S with death have not been examined. In 674 HIV-infected women from the Women's Interagency HIV Study, markers from the first visit after enrollment were exposures of interest in multivariate analyses of death (AIDS and non-AIDS) in separate models at 5 and 16 years. There were 87 AIDS and 44 non-AIDS deaths at 5 years, and 159 AIDS and 113 non-AIDS deaths at 16 years. An inverse association of total protein S quartiles with non-AIDS deaths was observed at 5 (P trend = 0.002) and 16 years (P trend = 0.02); there was no association with AIDS deaths. The third quartile of PAI-1 was associated with AIDS deaths at 5 [hazard ratio (HR) = 4.0; 95% confidence interval (CI): 1.9 to 8.4] and 16 years (HR = 3.4; 95% CI: 1.9 to 5.9); and with non-AIDS deaths at 5 years (HR = 4.8; 95% CI: 1.6 to 13.9). D-dimer and factor VIII were not associated with AIDS or non-AIDS death at 5 or 16 years. Lower total Protein S was a consistent marker of non-AIDS death. We found no association between D-dimer with AIDS or non-AIDS death, in contrast to previous studies showing increased short-term (

ObjectiveInfection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) may be associated with atherosclerosis and vascular disease. Macrophages are a major component of atherosclerotic plaque, and classically activated (M1) macrophages contribute to plaque instability. Our goal was to identify plasma biomarkers that reflect macrophage inflammation and are associated with subclinical atherosclerosis.Approach and resultsWe tested whether M1 macrophages produce galectin-3-binding protein in vitro. Then, we measured galectin-3-binding protein and the soluble macrophage biomarkers soluble cluster of differentiation (CD) 163 and soluble CD14 in 264 participants in the Women's Interagency HIV Study. Women were positive for HIV, HCV, both, or neither (66 in each group, matched for age, race/ethnicity, and smoking status). Carotid artery disease was assessed by ultrasound measurement of right distal common carotid artery intima-media thickness, distensibility, and presence of atherosclerotic lesions (intima-media thickness >1.5 mm). Plasma galectin-3-binding protein was higher in HCV+ than HCV- women (P

BackgroundPrior national surveys capture smoking behaviors of the aggregated U.S. Hispanic/Latino population, possibly obscuring subgroup variation.PurposeTo describe cigarette use among Hispanic/Latino adults across subgroups of age, gender, national background, SES, birthplace, and degree of acculturation to the dominant U.S. culture.MethodsA cross-sectional survey of 16,322 participants in the Hispanic Community Health Study/Study of Latinos aged 18-74 years, recruited in Bronx NY, Chicago IL, Miami FL, and San Diego CA, was conducted during 2008-2011.ResultsPrevalence of current smoking was highest among Puerto Ricans (men, 35.0%; women, 32.6%) and Cubans (men, 31.3%; women, 21.9%), with particularly high smoking intensity noted among Cubans as measured by pack-years and cigarettes/day. Dominicans had the lowest smoking prevalence (men, 11.0%; women, 11.7%). Individuals of other national backgrounds had a smoking prevalence that was intermediate between these groups, and typically higher among men than women. Non-daily smoking was common, particularly although not exclusively among young men of Mexican background. Persons of low SES were more likely to smoke, less likely to have quit smoking, and less frequently used over-the-counter quit aids compared to those with higher income and education levels. Smoking was more common among individuals who were born in the U.S. and had a higher level of acculturation to the dominant U.S. culture, particularly among women.ConclusionsSmoking behaviors vary widely across Hispanic/Latino groups in the U.S., with a high prevalence of smoking among population subgroups with specific, readily identifiable characteristics.