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ImportanceLipoprotein(a) (Lp[a]) is a genetically determined risk-enhancing factor for atherosclerotic cardiovascular disease (ASCVD). The Lp(a) distribution among the diverse Hispanic or Latino community residing in the US has not been previously described, to the authors’ knowledge.ObjectiveTo determine the distribution of Lp(a) levels across a large cohort of diverse Hispanic or Latino adults living in the US and by key demographic groups.Design, Setting, and ParticipantsThe Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a prospective, population-based, cohort study of diverse Hispanic or Latino adults living in the US. At screening, participants aged 18 to 74 years were recruited between 2008 and 2011 from 4 US metropolitan areas (Bronx, New York; Chicago, Illinois; Miami, Florida; San Diego, California). HCHS/SOL included 16 415 noninstitutionalized adults recruited through probability sampling of randomly selected households. The study population represents Hispanic or Latino participants from diverse self-identified geographic and cultural backgrounds: Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American. This study evaluated a subset of HCHS/SOL participants who underwent Lp(a) measurement. Sampling weights and surveys methods were used to account for HCHS/SOL sampling design. Data for this study were analyzed from April 2021 to April 2023.ExposureLp(a) molar concentration was measured by a particle-enhanced turbidimetric assay with minimized sensitivity to apolipoprotein(a) size variation.Main Outcome and MeasureLp(a) quintiles were compared using analysis of variance among key demographic groups, including self-identified Hispanic or Latino background. Median percentage genetic ancestry (Amerindian, European, West African) were compared across Lp(a) quintiles.ResultsLp(a) molar concentration was measured in 16 117 participants (mean [SD] age, 41 [14.8] years; 9680 female [52%]; 1704 Central American [7.7%], 2313 Cuban [21.1%], 1436 Dominican [10.3%], 6395 Mexican [39.1%], 2652 Puerto Rican [16.6%], 1051 South American [5.1%]). Median (IQR) Lp(a) level was 19.7 (7.4-59.7) nmol/L. Across Hispanic or Latino background groups, there was significant heterogeneity in median Lp(a) levels ranging from 12 to 41 nmol/L in those reporting a Mexican vs Dominican background. Median (IQR) West African genetic ancestry was lowest in the first quintile of Lp(a) level and highest in the fifth quintile (5.5% [3.4%-12.9%] and 12.1% [5.0%-32.5%]; respectively; P P Conclusions and RelevanceResults of this cohort study suggest that differences in Lp(a) level distribution across the diverse US Hispanic or Latino population may carry important implications for the use of Lp(a) level in ASCVD risk assessment for this group. Cardiovascular outcomes data are needed to better understand the clinical impact of differences in Lp(a) levels by Hispanic or Latino background.

Background: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10 -11 . These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P =3.27×10 -30 ) and MMP-3 (β=-0.60±0.05, P =1.67×10 -32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P =1.34×10 -17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. Conclusions: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.

Introduction: Emerging evidence suggesting diabetes -protective effects of dietary fiber intake. However, the underlying mechanisms are not fully understood. Hypothesis: We hypothesize that higher dietary fiber intake can alter gut microbial composition /functional capacity and host circulating metabolomic profile, which may contribute to lower risk of diabetes. Methods: We evaluated the associations of dietary fiber intake with gut microbiome (measured by shotgun metagenomic sequencing, n=2959) and serum metabolome (639 metabolites measured by untargeted metabolomic approach, n=6198) in the HCHS/SOL cohort. We further examined prospective associations of baseline fiber/microbial-associated metabolites with incident diabetes over 6-years follow-up. Results: We identified 39 bacterial genera associated with fiber intake, after adjustment for sociodemographic, behavioral, and clinical factors. 12 of these fiber-associated genera were related with diabetes (e.g. the fiber-associated Roseburia was inversely associated with diabetes, Fig.1A ). We identified 83 fiber-associated metabolites which were clustered into 13 modules in network, 7 of which were significantly associated with risk of diabetes ( Fig.1B ). Some of these diabetes-associated metabolite modules were also associated with fiber/diabetes-associated bacterial taxa ( Fig.1C ). In particular, indolepropionate module, and another module comprised of the pro-vitamins such as beta-cryptoxanthin, were positively associated with fiber (all PButyrivibrio (P Conclusion: Among US Hispanics/Latinos, higher fiber intake was associated with favorable profiles of gut microbiota and circulating metabolites for diabetes, suggesting a potential role of gut microbiota and related metabolites in the link between dietary fiber intake and risk of diabetes.

Introduction: The relationship between milk intake and risk of diabetes is controversial with substantial ethnical difference. Whether such difference can be partially explained by LCT genotype that varies by ethnical background is unknown. Hypothesis: Higher milk intake is associated with lower risk of diabetes only in lactase non-persistent (LNP) individuals ( LCT rs4988235, GG) but not in LP individuals (AA/AG). Methods: We examined associations of milk intake with incident diabetes (n=7089, 768 incident cases over 6 years), 490 gut microbial species (n=1767) and 624 serum metabolites (n=3110), stratified by LCT genotype in US Hispanics from the HCHS/SOL. We related the identified microbial species and metabolites with metabolic traits and/or incident diabetes. Results: Higher milk intake was associated with lower risk of diabetes in LNP but not in LP individuals (Fig A). Milk intake was associated with different microbial species by LCT genotype, including 13 species specific to LNP individuals (Fig B), especially Bifidobacterium sp. (enriched), which were favorably associated with several metabolic traits (Fig C). In LNP individuals, milk intake was specifically associated with 20 metabolites (Fig D). Metabolites positively associated with milk, especially indolepropinate and β-cryptoxanthin, were favorably associated with metabolic traits and risk of diabetes (Fig E). Opposite patterns were found for metabolites negatively associated with milk, especially for several bile acids and branched chain amino acid metabolites (Fig E). Some of these metabolites are known microbiota related, were correlated with LNP specific milk-related bacteria, and partially mediated the milk-diabetes association in LNP individuals (Fig F). Such associations were not observed for LP specific milk-related bacteria or metabolites. Conclusion LCT genotype may modify the relationship between milk intake and diabetes, with a beneficial association in LNP individuals, partially explained by gut microbiota and serum metabolites.

Introduction: Hypertension (HTN) is a modifiable risk factor for heart failure (HF) and a common antecedent for pre-HF, but its effect on pre-HF is not well known. Hypothesis: Variations in blood pressure (BP) will be related to distinct patterns of pre-HF (prevalent and incident). Methods: Two echocardiograms were performed ∼4.3 years apart on 1643 adults in the Hispanic/Latino cohort ECHO SOL. Pre-HF was defined as systolic dysfunction (LVEF 15%) or diastolic dysfunction (≥ Grade 1) or left ventricular remodeling (left ventricular mass index >115 for men, >95 for women/ relative wall thickness >0.42). At visit 1 (V1), 953 were normotensives, and 690 hypertensives [controlled and uncontrolled]. Groups were subdivided at visit 2 (V2) based on maintenance or changes from V1 BP status. Logistic regression models were used to determine the association of BP with pre-HF. All analyses were weighted due to complex survey design. Results: Higher BP at baseline (linear and by tertiles) was significantly associated with prevalent pre HF (table 1). Higher pulse pressure was significantly associated with incident pre-HF (table 1). Normotensives at V1 who later developed HTN (≥ 130/80 mmHg) at V2 had higher odds of having prevalent (2.05 [95% CI, 1.24 - 3.39]) and incident (2.42 [95% CI, 1.07 - 5.51]) pre-HF than those who remained with BP Conclusion A significant association exists between BP and prevalent/incident pre-HF in the Hispanic/Latino population. Additionally, those who progress from normal BP to hypertension face an increased risk of developing prevalent/incident pre-HF compared to those who remain normotensives. Blood pressure control of

Obesity remains a global public health burden, with 4.7 million premature deaths globally attributed to obesity. Severe obesity (SevO: defined as body mass index (BMI)≥40) is a major risk factor for other comorbidities, including heart disease and Type 2 Diabetes, which disproportionately impact historically marginalized populations, including Hispanic/Latinos. Based on BRFSS data, 24.5% of US Hispanic/Latino adults are projected to have severe obesity by 2030. However, the etiology of the underlying metabolic dysfunction remains unknown. To address this gap, we identified metabolites associated with SevO in genotyped participants aged ≥20 with 25 < BMI ≥ 40 and metabolic data in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We investigated cross-sectional associations between Blom-transformed metabolites and baseline SevO, adjusting for age, study center, background group, smoking status, and principal components of ancestry, stratified by sex (SUGEN), and meta-analyzed (SAS 9.4). For the top 20 metabolites, we extracted publicly available HCHS/SOL metabolite GWAS (mGWAS) summary statistics to derive metaboQTLs, and summary statistics from a multi-population meta-analysis of SevO (N>70,000) and implemented forward MR analysis using the MendelianRandomization R package (v0.3.0), which provides various robust causal estimation methods for summary data. Anthropometry and data for 640 known Metabolon metabolites were available for 551 females (mean age: 43.3 years, 27% SevO) and 371 males (mean age 43.4 years, 15% SevO). We identified Bonferroni-corrected significant SevO associations (p Cytidine is a pyrimidine nucleoside consisting of D-ribose and cytosine, which is a precursor of cytidine triphosphate required in the one-carbon metabolism pathway to convert phosphatidylcholine (PC) to phosphatidylethanolamine (PE). PC biosynthesis is higher in adipose tissue macrophages in obese mice and humans. Indoleproprionate is a microbial metabolite of tryptophan produced by gut bacteria. Indoleproprionate levels have been shown to be associated with higher microbiome diversity and lower incidence of T2D. Our work points to future efforts to validate findings in other cohorts, including reverse MR to further elucidate the causal relationship between metabolites and severe obesity.

Introduction: Obesity is an epidemiologic challenge and a key risk factor for heart failure (HF). Pre-heart failure (pre-HF) has been recognized as an important entity to prevent progression to clinical HF. Defining the long-term effect of obesity on pre-HF is essential for understanding of HF risk and prevention. Purpose: To determine the prospective association of obesity on the incidence of pre-HF (defined as the presence of abnormal cardiac structure or function among persons without clinical HF). Methods: Data from 1580 individuals without HF and with anthropometric data from the population-based Echocardiographic-Study of Latinos were included. Pre-HF was defined as: 1) Systolic dysfunction - LV ejection fraction (LVEF) < 50% and global longitudinal strain (GLS) LV diastolic dysfunction - E/e’ >10 and left atrial volume index (LAVI) >34 mL/m 2 ; or 3) LV remodeling - LV mass index (LVMI)> 115gm/m 2 , >95gm/m 2 (male and female, respectively) and relative wall thickness (RWT) >0.42. Anthropometric data were: (body mass index {BMI}, waist circumference {WC}, waist-to-hip ratio {WHR}, fat mass {FM) and free fat mass {FFM}). Echocardiographic and anthropometric data were collected twice, on average 4.3 years apart, and analyzed using survey-weighted multivariable-adjusted regression models. Incident pre-HF was determined among participants Results: Mean age of 56 (42-74) years and 1048 (66%) were female. Baseline mean BMI was 29.9 kgm 2 , FM kg 28.3, FFM kg 50.1, WC 99.7cm, and WHR 0.94. Baseline BMI, FFM, FM, WC and WHR were significantly higher in individuals with prevalent pre-HF (all p

BACKGROUND AND AIMS: Peripheral artery disease (PAD) and lower levels of physical activity are both associated with higher mortality. Yet, their joint prognostic impact has not been systematically examined, especially in Hispanics/Latinos, and with objective measures. We aimed to examine the joint associations of PAD and physical activity with mortality in the Hispanic Community Health Study / Study of Latinos (HCHS/SOL). METHODS: We studied 7,620 Hispanic/Latino adults aged 45–74 years at baseline (2008–2011) who underwent assessment of PAD with ankle-brachial index (ABI) and physical activity with hip-worn accelerometry. We calculated four physical activity measures: sedentary time, light activity, moderate/vigorous activity, and total activity counts. We quantified the relationship between ABI and mortality overall, and by tertiles of activity measures in restricted cubic splines, using multivariable Cox models accounting for sampling weights. We also assessed cross-categories of ABI and activity measures with mortality. RESULTS: During a median follow up of 7.1 years, 314 participants died. We observed a U-shaped association of ABI with mortality overall (e.g., hazard ratio 1.80 [95%CI 1.20–2.80] at ABI 0.7 vs 1.2). This U-shaped association was generally consistent after stratifying by activity measures, but an elevated mortality risk for higher ABI was not evident in the most active tertile based on sedentary time, time in light activity, and total activity counts. In the cross-category analysis of ABI and physical activity, the highest mortality risk was consistently seen in abnormal ABI (≤0.9 or >1.4) plus the least active tertile (e.g., HR 5.61 [3.31–9.51] for light activity), compared to referent ABI (0.9–1.4) plus the other more active two tertiles, with no interactions between ABI and activity measure. CONCLUSIONS: Abnormal ABI and lower accelerometry-based physical activity were independently and jointly associated with mortality in Hispanics, suggesting the importance of simultaneously evaluating leg vascular condition and physical activity.

Introduction: In the U.S., Hispanic/Latino adults experience a higher incidence of stroke overall and at younger ages than non-Hispanic White adults. However, given the diversity of U.S. Hispanic/Latinos, understanding heterogeneity in stroke symptom recognition by background is critical to prevention. Methods: The primary outcome was self-reported stroke symptoms over the past year using the validated and telephone-administered Questionnaire for Verifying Stroke Free Status of 8,235 stroke free HCHS/SOL participants in 2017 (mean age=49 + 0.25). Stroke risk factors were collected at baseline (2008-2011) using standardized measurements and validated questionnaires. Stroke risk factors were defined as clinical factors (blood pressure, diabetes, anthropometrics, family history of cardiovascular disease [CVD], smoking, and alcohol consumption), medication use (aspirin, statin, and antihypertensive medication use), and self-reported sociodemographic factors (heritage, sex, education, and years in the mainland US). The prevalence of stroke symptoms and 95% confidence intervals (CI) were estimated overall, by heritage group and by stroke risk factors. Multivariable logistic regression models estimated associations (odds ratio [OR], 95% CI) between heritage group and stroke risk factors with stroke symptoms, accounting for the complex study design and adjusting for age, sex, and sociodemographic factors. Results: Overall, 15% (n=1,448) reported experiencing > 1 stroke symptom in the past year. The most common stroke symptoms reported were sudden numbness (8%) followed by sudden weakness (6%). The prevalence of > 1 stroke symptom among those aged > 50. The prevalence was also highest among those of mixed heritage (20%), followed by Puerto Rican heritage (19%), and was lowest among those of Dominican heritage (10%). In age and sex-adjusted models, reporting > 1 stroke symptom was significantly lower among those of Dominican heritage (OR=0.51, 95%CI: 0.40-0.67) and Cuban heritage (OR=0.64, 95%CI: 0.53-0.78) compared to Mexican heritage, while those of mixed heritage exhibited a higher odds (OR=1.58, 95%CI: 1.16-2.15); estimates were unchanged after adjusting for clinical factors and medication. History of diabetes (OR=1.40, 95%CI: 1.17-1.60), CVD (OR=1.94, CI: 1.67-2.26), and current smoking (OR=1.50, 95%CI: 1.28-1.75) were significantly associated with greater odds of reporting > 1 stroke symptom, while odds were lower for males than females (OR=0.78, 95%CI: 0.68-0.89). Conclusions: This is the first study to assess the prevalence of stroke symptoms among U.S. Hispanic/Latino adults and demonstrates a high burden of stroke symptoms in this relatively young population. The prevalence varied across heritage groups and stroke risk factors indicating a need for stroke recognition education and targeted screening.

Introduction: Multiple healthy eating patterns have been recommended by the Dietary Guidelines for Americans (2015-2020) for the prevention of cardiovascular disease (CVD). However, adherence to these dietary patterns and its relationship with risk of CVD remains unclear among US Hispanic/Latinos. Hypothesis: We aimed to evaluate three healthy eating patterns measured by three dietary quality indices (the Alternate Mediterranean diet (aMED), the Healthy Eating Index (HEI)-2015, and the healthful Plant-based Diet Index (hPDI)), and assessed the hypothesis that higher adherence to healthy eating patterns is associated with lower risk of CVD in US Hispanic/Latinos. Methods: We included 10,766 adult participants representing six Hispanic/Latino backgrounds (Mexican, Puerto Rican, Cuban, Dominican, Central American and South American), free of CVD or cancer at baseline, from the Hispanic Community Health Study/Study of Latinos. Dietary pattern scores were derived using information collected by two 24-hour dietary recalls at baseline (2008-11). The primary outcome was major incident CVD (n=248), comprised of coronary heart disease and stroke, during an average 6-year follow-up period. Relative risks for CVD were estimated using survey Poisson regression after adjustment for demographic, socioeconomic, and behavioral variables and sampling weights. Results: Mean scores of all three dietary quality indices were significantly different across six Hispanic/Latino background groups (all P P P -trend=0.002) for aMED, 0.64 (95% CI 0.39-1.05; P -trend=0.033) for HEI-2015, and 0.56 (95% CI, 0.35-0.88; P -trend=0.009) for hPDI when comparing highest to lowest tertiles in the overall sample. The associations between dietary quality scores and risk of CVD were not different across Hispanic/Latino backgrounds (all P for interaction ≥0.24) or not by US-born status (all P for interaction ≥0.25). Conclusions: Adherence to healthy eating patterns reflected by three diet quality indices varied by Hispanic/Latino background and immigrant generation, and higher compliance to healthy eating patterns was associated with lower risk of CVD risk in the US Hispanic/Latino population.

Introduction: Hypertension risk assessment is the first step towards primary prevention of hypertension. The pooled cohort equation (PCE) provides an atherosclerotic cardiovascular disease (ASCVD) risk score. We sought to examine whether incident hypertension varied across categories of ASCVD risk as defined by the PCE Methods: Data from the HCHS/SOL baseline and visit 2 exam were used. Hypertension (baseline and incident) was defined as SBP >140 mm Hg and DBP >90 mm Hg. We included participants 40-74 years of age free of hypertension and ASCVD at baseline (n=3,692). Participants were classified into one of four ASCVD risk categories based on the PCE: low (10%). Survey logistic regression models were used to determine the risk of hypertension overall, by age group and Hispanic/Latino background (Dominican, Central American, Cuban, Mexican, Puerto-Rican, South American) accounting for HCHS/SOL complex survey design. Results:: Overall, at baseline, the mean age was 51.2 ±0.23 years, 56% female, SBP: 119.7±0.26 and DBP: 72.6±0.20, ASCVD risk scores: low (65%); borderline (14.7%), intermediate (7.5%), and high (13.5%); 29.8% developed hypertension over 5.9 (range 4.1 – 9.6) years of follow-up. Intermediate (OR=2.2, CI: 1.5-3.2) and high (OR=2.5, CI: 1.9-3.5) baseline ASCVD risk categories were associated with increased odds of incident hypertension at follow-up compared to the low risk category. Age group and Hispanic/Latino background modified the relationship between increased baseline ASCVD score and incident hypertension, with strongest associations among those aged 50-59 years old (OR=2.3, CI: 1.7, 3.2) and Hispanics/Latinos of Dominican descent (OR=4.1, CI: 2.0, 8.4). Conclusions: Higher ASCVD risk was associated with an increased incidence of hypertension that varied by age and Hispanic/Latino background. The PCE ASCVD risk score can help guide public health measures to prevent hypertension.

Background: Life’s Simple 7 (LS7) include not smoking, having a healthy diet pattern, adequate physical activity, healthy body weight, and healthy blood pressure, cholesterol, and blood glucose. Better cardiovascular health metrics, measured by increasing LS7 scores, was associated with improved cognitive function. Purpose: Investigate the effect of LS7 on brain imaging outcomes in Hispanics/Latinos participating of the SOL-INCA sub-study. Methods: Hispanics/Latinos adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) who participated in the SOL - Investigation of Neurocognitive Aging Magnetic Resonance Imaging (SOL-INCA MRI) ancillary study underwent 3T brain MR imaging. LS7 scores and brain volumes were calculated. Volumes of interest included total brain, total and regional grey matter (frontal, temporal, parietal, and occipital), total white matter, total CSF, lateral ventricle, and white matter hyperintensity (WMH). WMH values were log-transformed. All MRI volumes were residualized for total cranial volume prior to analysis. The influence of LS7 scores on MRI outcomes was investigated using linear regression analysis adjusted by baseline characteristics. These included sex, height, immigrant status and years of residence in the US, age at MRI scan, Hispanic/Latino background, level of education, household income, insurance status, and language preference. Results: A total of 1,534 participants (males 33%) were included in the study. The average age (mean±SD) was 60±10 and the average LS7 score 7±2. In the adjusted model, increasing LS7 scores were associated with larger cerebral white (β=1.40; p≤0.001) and frontal grey volumes (β=0.33; p≤0.001) as well as smaller CSF (β=-1.26; p≤0.001) and WMH volumes (β=-0.01; p≤0.001). The association of higher LS7 scores and better brain MR outcomes was observed in both males and females. Conclusions: Higher LS7 scores are associated with improved biomarkers of brain health. Further studies are necessary to determine if the anatomic changes observed correlate with cognitive performance.

BACKGROUND: Asthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma. METHODS: WGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician’s diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes. RESULTS: A genome-wide significant association was identified between baseline FEV(1)/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10(−8) in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10(−6)). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV(1) (P = 3.3 × 10(−3)), postbronchodilator (PB) FEV(1) (7.3 × 10(−3)), and PB FEV(1)/FVC ratio (P = 2.7 × 10(−3)). The identified baseline FEV(1)/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR. CONCLUSIONS: These findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.

Introduction: Dietary macronutrient balance and reduced sodium intake are key modifiable risk factors for prevention of cardiovascular disease. Pre-heart failure (HF) (evidence of structural heart disease or abnormal cardiac function) is an independent risk factor for incident clinical HF development. We assessed associations of macronutrient and sodium intake with cardiac structure and function from the Echocardiographic Study of Latinos (Echo-SOL), an ancillary study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Hypothesis: We hypothesized that higher intake of protein and lower intake of fat, carbohydrate and sodium would be associated with healthier cardiac structure and function. Methods: Cross-sectional data from HCHS/SOL interviews were analyzed among 1818 adults (57% female, mean age 56 ± 0.17) with complete echo assessments. Intake of carbohydrates, proteins, fats, and sodium in relation to total caloric intake was derived from two 24-hour recalls. Associations between nutrients and pre-HF outcomes were estimated via simple linear regression as well as ANOVA across quintiles of each nutrient. All analyses were weighted and account for complex survey design. Results: Mean ± SE macronutrient intake for the overall target population was 52.3 ± 0.1% carbohydrates, 17.1 ± 0.05% protein, and 29.7 ± 0.1% fat. Mean dietary sodium intake was 3,107.2 ± 47.7mg. Higher percent of total daily calories from carbohydrates was associated with lower LV mass (-13.7g per 5%, p Conclusions: Our results suggest that a macronutrient balance favoring higher carbohydrate and lower fat consumption along with reduced sodium intake is associated with better cardiac structure and function. These findings have important implications for HF prevention. Future studies should explore the role of specific nutrient types.

After deep venous thrombosis (DVT), many patients have impaired quality of life (QOL). We aimed to assess whether pharmacomechanical catheter-directed thrombolysis (PCDT) improves short-term or long-term QOL in patients with proximal DVT and whether QOL is related to extent of DVT.The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial was an assessor-blinded randomized trial that compared PCDT with no PCDT in patients with DVT of the femoral, common femoral, or iliac veins. QOL was assessed at baseline and 1 month, 6 months, 12 months, 18 months, and 24 months using the Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms (VEINES-QOL/Sym) disease-specific QOL measure and the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary general QOL measures. Change in QOL scores from baseline to assessment time were compared in the PCDT and no PCDT treatment groups overall and in the iliofemoral DVT and femoral-popliteal DVT subgroups.Of 692 ATTRACT patients, 691 were analyzed (mean age, 53 years; 62% male; 57% iliofemoral DVT). VEINES-QOL change scores were greater (ie, better) in PCDT vs no PCDT from baseline to 1 month (difference, 5.7; P = .0006) and from baseline to 6 months (5.1; P = .0029) but not for other intervals. SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 2.4; P = .01) but not for other intervals. Among iliofemoral DVT patients, VEINES-QOL change scores from baseline to all assessments were greater in the PCDT vs no PCDT group; this was statistically significant in the intention-to-treat analysis at 1 month (difference, 10.0; P .0001) and 6 months (8.8; P .0001) and in the per-protocol analysis at 18 months (difference, 5.8; P = .0086) and 24 months (difference, 6.6; P = .0067). SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 3.2; P = .0010) but not for other intervals. In contrast, in femoral-popliteal DVT patients, change scores from baseline to all assessments were similar in the PCDT and no PCDT groups.Among patients with proximal DVT, PCDT leads to greater improvement in disease-specific QOL than no PCDT at 1 month and 6 months but not later. In patients with iliofemoral DVT, PCDT led to greater improvement in disease-specific QOL during 24 months.

Introduction: Altered acylcarnitine concentrations may reflect impaired mitochondrial metabolism and are implicated in cardiovascular disease (CVD). Disturbances in carnitine metabolism have been observed in HIV infection, but it is unknown whether this is related to CVD risk in HIV infected people. Methods: Twenty-six acylcarnitine species were profiled with ultrahigh-performance liquid chromatography/tandem mass spectrometry in 705 men and women with or at risk of HIV infection in the Multicenter AIDS Cohort Study and the Women’s Interagency HIV Study. Using a weighted score approach to define aggregate levels of plasma acylcarnitines, we assessed the associations of short-chain (C2-C7), medium-chain (C8-C14) and long-chain acylcarnitine (C16-C26) with incident carotid plaque, over 7-year follow-up, defined as a carotid artery region with focal intima-media thickness>1.5mm among those with no baseline carotid plaque. Results: The mean age was 45 years and 70% were non-white. The majority (70%) had HIV, and 68% of 394 participants on antiretroviral therapy (ART) had undetectable HIV viral load. Over 7 years, 108 participants developed carotid plaque. Comparing HIV-infected with HIV-uninfected participants, some individual acylcarnitines were higher (C3, C16, C20, C26) while others were lower (C8, C10, C20:4) (all P Conclusion: Plasma short-chain acylcarnitines were associated with increased risk of carotid plaque formation, independent of traditional CVD risk factors, especially in HIV-infected individuals and those with poor control of HIV viral load.

Background: HCHS/SOL showed that a sizeable proportion of Hispanics/Latinos (80% of men, 71% of women) had at least 1 major CVD risk factor (RF), with marked variations by ethnic background. Little is known about changes in CVD RF profiles over time in this population. Objective: To describe ~6-year changes in CVD RF profiles and examine associations with demographic and socioeconomic/ sociocultural factors. Methods: HCHS/SOL is a multi-center prospective community-based study of 16,415 Hispanic/Latino adults of Cuban, Dominican, Mexican, Puerto Rican, Central American, and South American backgrounds, aged 18-74 at Visit 1 (2008-11). Visit 2 (2014-17) is ongoing and 8,413 persons (~60% of the cohort to be studied) attended as of Sept. 2016. Analyses included 7,789 men and women with complete data. CVD RF profiles were defined as having 0 (0RF) or any 1 or more (1+RF) of the following: hypercholesterolemia, hypertension, obesity, diabetes, and smoking (see definitions in Table). Adjusted percent increases in number of RFs were computed. Multinomial logistic regression was used to examine associations of Visit 1 characteristics with change in RFs, adjusted for sociodemographic, sociocultural, and lifestyle factors. Results: After 5.8 years, 29% of men and 27% of women had increases in number of RFs; changes occurred more frequently in persons with 1+ RF at Visit 1 than in those with 0RF and varied by background ( Table ). Significantly higher odds of increase in number of RFs (vs. 0RF at both visits) were seen with older age (OR=1.07, 95% CI=1.06-1.08 per 1 yr) and male sex (1.74, 1.37-2.21); lower odds with higher education (0.60; 0.44-0.83 for > vs. < high school) and income (0.56, 0.38-0.81 for >$50,000 vs. Conclusions: In just a few years, a large percent of US Hispanic/Latino adults had an increase in number of adverse RFs, which varied by background; age, sex, education, and income were associated with RF increases. Greater efforts are needed to prevent CVD RFs in this population.

Background: Adult cardiorespiratory fitness (CRF) is associated with lower risk of cardiovascular disease and mortality. However, there is scarce information in youth about the role of CRF in subclinical measures of CVD, such as endothelial function. In this study we tested associations of cardiometabolic factors (CMF) and biomarkers of endothelial function (e-selectin; PAI-1). Methods: We included 1,380 participants (699 girls and 681 boys) aged 8-16 years from SOL Youth. CRF was assessed by a step test and VO2 max was estimated. CMF included fasting glucose, lipids, blood pressure. Inflammatory markers included hs-CRP and adiponectin. Associations of CRF with e-selectin and PAI-1 were assessed with multiple linear regression models, adjusting for potential confounders: actigraphy derived physical activity (PA) and sedentary time (SED), adiposity, and socio-demographic factors. Odds ratios were derived for the association of CRF and having ≥3 CVD risk factors (RF)(defined by elevated age/sex appropriate BP, lipids, glucose, and obesity), adjusted for confounders. Analyses accounted for complex survey design. Results: Boys and US-born youth were more likely to have higher CRF. CRF was positively correlated with PA (r=.23, p Conclusions: Among Latino youth, CRF appears to be a strong protective factor for endothelial dysfunction and CMF. Strategies to improve CRF may be a useful approach for improving cardiovascular health in youth.

Introduction: The HCHS/SOL demonstrated that diabetes mellitus (DM) was associated with elevated risk for CVD in a diverse Hispanic/Latino (H/L) cohort. However, the nature of these relationships as a function of H/L background, sex and other relevant variables is still unknown. Objective: We examined across approximately 6 years, the prevalence and incidence of DM and CVD and the CVD-DM relationship in diverse H/L. Methods: Participants at Visit 1:V1 (2008-2011) were 16,386 individuals with DM relevant data, whereas participants at Visit 2:V2 (2014-2016) were 8,401 individuals with similar data who attended the ongoing examination, constituting approximately 60% of the cohort to be studied. Descriptive characteristics were age-standardized to the 2010 U.S. population, and stratified by sex and H/L background. Prevalence estimates were weighted to the known population distribution, adjusting for sampling probability and nonresponse, and trimmed to handle extreme values of weights. Age-adjusted incidence rates /100 person years were estimated across Visit 1, based upon Poisson regression with robust variance taking into account the complex survey design. Both prevalence and incidence values are presented as % (95% CI). Prevalence and incidence of DM were examined by sex, age, H/L background, field center and BMI. We also examined the prevalence and incidence of CVD in those with and without DM by sex, H/L background, age and BMI. Results: Overall prevalence of DM was 17.8 (17.0, 18.6) at V1 and 19.4 (18.3, 20.5) at V2. The prevalence of DM at V2 was lowest, 11.2 (8.2, 15.3) for those of South American and highest for those of Puerto Rican, 22.5 (19.5, 25.8) background. While the prevalence of DM did not differ between women and men, the overall incidence rate for DM was significantly higher for men, 1.53 (1.32, 1.76) than for women, 1.06 (0.94, 1.18). The overall prevalence of CVD was significantly higher for DM than for non-DM individuals at V2: 9.2 (7.9, 10.7) vs. 4.5 (3.9, 5.2). The incidence rate across Visits, 0.71 (0.55, 0.92) vs. 0.20 (0.15, 0.27) was also higher for DM individuals. At V2 the CVD prevalence for DM men, 12.0 (9.7, 14.6) was greater than for DM women, 7.2 (5.6, 9.2). The relationship of CVD prevalence to DM status revealed different patterns among H/L background groups. At V2, for example, those of South American background showed relatively low CVD prevalence: 5.3 (2.6, 10.4) with DM vs. 4.2 (2.3, 7.5) without DM. In contrast, those of Puerto Rican background showed relatively high CVD prevalence: 15.6 (11.0, 21.6) with DM vs. 5.7 (4.1, 8.0) without DM. Conclusions: Overall prevalence and incidence of CVD was significantly higher for DM than for non-DM individuals and these CVD-DM relationships varied markedly across H/L background groups.

Background: Cardiovascular risk factor (RF) control is a cornerstone of diabetes management. Little is known about whether objectively-measured sedentary time and physical activity are associated with meeting RF goals in individuals with diabetes. Methods: We examined cross-sectional associations of sedentary behaviors and moderate-to-vigorous physical activity (MVPA) with meeting RF goals in 1,699 adults who self-reported diagnosed diabetes from the HCHS/SOL, a population-based cohort of US Hispanics/Latinos conducted between 2008 and 2011. Sedentary time and MVPA were assessed by Actical accelerometers for 7 days. Five RF goals were defined: HbA1c 40/50 mg/dL for men/women. Results: The mean time spent in sedentary behaviors and MVPA was 12.5 hrs/day and 17.2 mins/day, respectively. Adults with diabetes meeting greater number of RF goals spent, on average, less time in sedentary behaviors, and the odds of meeting ≥ 3 RF goals, relative to meeting zero RF goal, was 3.31 (95% CI 1.27, 7.68) times by comparing the lowest and highest tertiles of sedentary time (Figure 1). Specifically, after adjustment for potentially confounding variables and MVPA, less sedentary time was associated with increased odds of meeting HbA1c (OR for the lowest vs highest tertile of sedentary time =1.81 [1.20, 2.72]; P for trend =0.005) and triglyceride (OR =2.07 [1.34, 3.20]; P for trend =0.001) goals. MVPA was not associated with meeting any RF goals (all P for trend >0.21). Associations between sedentary time and meeting RF goals were consistent among adults meeting or not meeting MVPA recommendations. Conclusions: US Hispanics/Latino adults with diabetes who spend less sedentary time were more likely to meet RF goals, particularly HbA1c and triglyceride goals, regardless of MVPA. Our findings further emphasize the importance of reducing sedentary behaviors beyond increasing exercise in individuals with diabetes.

Left Ventricular Global Longitudinal Strain (LV-GLS) with speckle-tracking echocardiography carries incremental prognostic value to traditional cardiovascular risk factors (CVRF) and standard echocardiography. LV-GLS has not been described in a large representative population of US Hispanics/Latinos

Background: Extensive epidemiologic evidence suggests that greater acculturation levels are associated with higher risk of cardiovascular disease (CVD). However, there is little information on the reliability and validity of instruments to measure acculturation across Hispanic/Latino (H/L) groups who prefer to communicate in English or Spanish. Objective: To evaluate the psychometric properties of the Short Acculturation Scale (SASH) to determine whether it is a reliable measure in a large, diverse sample of H/Ls, and whether there is measurement invariance across language groups. Methods: Cross-sectional data were used from the multi-site HCHS/SOL (Bronx, Chicago, Miami and San Diego) and included Cuban, Dominican, Puerto Rican, Mexican, Central or South American background household resident adults (18 to 74 years old; n = 16,331). Households were selected using a stratified two-stage probability sampling design, and door-to-door recruitment with sampling weights calibrated to the 2010 US Population Census. A 10-item abbreviated version of the SASH was administered in English or Spanish per the participant’s preference. Standardized factor loadings were calculated for all item-level confirmatory factor analysis (CFA) and multi-group confirmatory factor analysis (MCFA) models. Results: The overall scale reliability was acceptable in the full sample (α =.90) and for both language versions (α =.78 for English, and α =.85 for Spanish). The Cronbach’s alphas were similar across H/L ethnic groups (ranging from α =.85 for South Americans to α =.89 for Mexicans). Data from the exploratory factor analysis suggested a 2 factor solution, with dimensions of language use and ethnic social relationships. In addition, CFA showed that the 2 factor solution was invariant across the Spanish and English groups. Conclusion: These preliminary findings suggest that the abbreviated SASH scale is reliable across language versions, and comparable (in terms of reliability and factors structure) across H/L ethnic groups.

Background: Prevalence and determinants of dyslipidemia among Hispanics/Latinos are not well known. Methods: Lipid and lipoprotein data from the HCHS/SOL -- a population-based cohort study of 16,415 US Hispanic/Latino participants, ages 18-74, from Cuban, Dominican, Mexican, Puerto Rican, and Central and South American backgrounds -- were used. Criteria for dyslipidemia are based on National Cholesterol Education Program Adult Treatment Panel III guidelines as low density lipoprotein-cholesterol (LDL-C) >130 mg/dl, triglycerides (TG) >200 mg/dl, non-high density lipoprotein (non-HDL-C) >160 mg/dl, or low HDL-C ( Results: Mean age was 40.7 years (SE 0.23) and 48.3% are male. The overall prevalence of any dyslipidemia was 65.1%; prevalence of elevated LDL-C was 35.5%, and highest among Cubans (44.5%; p Conclusion: Dyslipidemia is very common among Hispanics/Latinos; Cubans seem particularly at risk. Low HDL-C and elevated LDL-C are most commonly seen. Across all Hispanics, determinants of dyslipidemia varied depending on the type of dyslipidemia. To prevent dyslipidemias, effective public health measures among the Hispanic/Latino population are needed.

P75 The relationships of exercise and body mass index (BMI) to cardiovascular disease (CVD) risk are well established. While animal studies suggest that caloric restriction extend life, observational data in human has paradoxically equated longer life with higher energy intake. To further explore these relationships, we analyzed the NHANES I and 1992 follow-up study. Of 14,407 NHANES I participants, 9997 subjects with complete data, no heart disease, stroke and cancer, follow-up≥2 years were included. Mean age was 49±16 years. Mean caloric intake was 1760±851 Kcal/day. During an average of 17 years follow-up, of 3183 deaths, 1531 were CVD deaths (9.11/1000 person-years). From the highest to the lowest tertile of caloric intake, age- gender- race-adjusted CVD mortality rates were: 7.5, 9.1 and 10.9/1000 person-years respectively (p=0.02). In Cox regression analysis, adjusting for sociodemographic and CVD risk factors, lower caloric intake was associated with higher CVD mortality, as were lower exercise level and high BMI ( Table). Furthermore, subjects with history of diabetes, kidney disease or hypertension (n=5292) had lower caloric intake than those without these conditions. Excluding subjects with these diseases, after adjustment, no association was found between caloric intake and CVD mortality, while the associations of exercise and BMI with CVD persisted ( Table). In summary, the expected positive relationship of high BMI and low exercise to CVD mortality is again demonstrated in this national sample population. However, the surprising paradoxical association sometimes noted for caloric intake is found to be the result of confounding by chronic disease history. Table 1.