Showing papers by "Barbara V. Howard published in 2022"

Biomarkers for Components of Dietary Protein and Carbohydrate with Application to Chronic Disease Risk Among Postmenopausal Women.

Abstract: BACKGROUND We recently developed protein and carbohydrate intake biomarkers using metabolomics profiles in serum and urine, and used them to correct self-reported dietary data for measurement error. Biomarker-calibrated carbohydrate density was inversely associated with chronic disease risk, while protein density associations were mixed. OBJECTIVE To elucidate and extend this earlier work through biomarker development for protein and carbohydrate components, including animal protein and fiber. METHODS Prospective disease association analyses in WHI cohorts of postmenopausal U.S. women, aged 50-79 when enrolled at 40 U.S. Clinical Centers. Biomarkers are developed using an embedded human feeding study (n = 153). Calibration equations for protein and carbohydrate components are developed using a WHI nutritional biomarker study (n = 436). Calibrated intakes are associated with chronic disease incidence in WHI cohorts (n = 81,954) over a 20-year (median) follow-up period, using hazard ratio regression methods. RESULTS Previously reported elevations in cardiovascular disease (CVD) with higher protein diets tended to be explained by animal protein density. For example, for coronary heart disease a 20% increment in animal protein density had hazard ratio (HR) and 95% confidence interval (CI) of 1.20 (1.02, 1.42) relative to the HR for total protein density. In comparison, cancer and diabetes risk showed little association with animal protein density beyond that attributable to total protein density. Inverse carbohydrate density associations with total CVD were mostly attributable to fiber density, with 20% increment HR (95% CI) factor of 0.89 (0.83, 0.94). Cancer risk showed little association with fiber density, while diabetes risk has 20% increment HR (95% CI) of 0.93 (0.88, 0.98) relative to the HRs for total carbohydrate density. CONCLUSIONS In a population of postmenopausal U.S. women, CVD risk is associated with high animal protein and low fiber diets, cancer risk is associated with low carbohydrate diets, and diabetes risk is associated with low fiber/low carbohydrate diets.This study is registered with clinicaltrials.gov identifier: NCT00000611.

APOE genotype, hippocampus, and cognitive markers of Alzheimer's disease in American Indians: Data from the Strong Heart Study

Abstract: The apolipoprotein E (APOE) ε4 allele confers higher risk of neurodegeneration and Alzheimer's disease (AD), but differs by race/ethnicity. We examined this association in American Indians.

Red blood cell fatty acid patterns from 7 countries: Focus on the Omega-3 index.

Abstract: Red blood cell (RBC) fatty acid (FA) patterns are becoming recognized as long-term biomarkers of tissue FA composition, but different analytical methods have complicated inter-study and international comparisons. Here we report RBC FA data, with a focus on the Omega-3 Index (EPA + DHA in% of total FAs in RBC), from samples of seven countries (USA, Canada, Italy, Spain, Germany, South Korea, and Japan) including 167,347 individuals (93% of all samples were from the US). FA data were generated by a uniform methodology from a variety of interventional and observational studies and from clinical laboratories. The cohorts differed in size, demographics, health status, and year of collection. Only the Canadian cohort was a formal, representative population-based survey. The mean Omega-3 Index of each country was categorized as desirable (>8%), moderate (>6% to 8%), low (>4% to 6%), or very low (≤4%). Only cohorts from Alaska (treated separately from the US), South Korea and Japan showed a desirable Omega-3 Index. The Spanish cohort had a moderate Omega-3 Index, while cohorts from the US, Canada, Italy, and Germany were all classified as low. This study is limited by the use of cohorts of convenience and small sample sizes in some countries. Countries undertaking national health status studies should utilize a uniform method to measure Omega-3 FA levels.

Circulating ceramides and sphingomyelins and the risk of incident cardiovascular disease among people with diabetes: the strong heart study

Abstract: Plasma ceramides and sphingomyelins have been independently linked to diabetes risk, glucose and insulin levels, and the risk of several cardiovascular (CVD) outcomes. However, whether individual ceramide and sphingomyelin species contribute to CVD risk among people with type 2 diabetes is uncertain. Our goal was to evaluate associations of 4 ceramide and 4 sphingomyelin species with incident CVD in a longitudinal population-based study among American Indians with diabetes.This analysis included participants with prevalent type 2 diabetes from two cohorts: a prospective cohort of 597 participants in the Strong Heart Family Study (116 incident CVD cases; mean age: 49 years; average length of follow-up: 14 years), and a nested case-control sample of 267 participants in the Strong Heart Study (78 cases of CVD and 189 controls; mean age: 61 years; average time until incident CVD in cases: 3.8 years). The average onset of diabetes was 7 years prior to sphingolipid measurement. Sphingolipid species were measured using liquid chromatography and mass spectrometry. Cox regression and logistic regression were used to assess associations of sphingolipid species with incident CVD; results were combined across cohorts using inverse-variance weighted meta-analysis.There were 194 cases of incident CVD in the two cohorts. In meta-analysis of the 2 cohort results, higher plasma levels of Cer-16 (ceramide with acylated palmitic acid) were associated with higher CVD risk (HR per two-fold higher Cer-16: 1.85; 95% CI 1.05-3.25), and higher plasma levels of sphingomyelin species with a very long chain saturated fatty acid were associated with lower CVD risk (HR per two-fold higher SM-22: 0.48; 95% CI 0.26-0.87), although none of the associations met our pre-specified threshold for statistical significance of p = 0.006.While replication of the findings from the SHS in other populations is warranted, our findings add to a growing body of research suggesting that ceramides, in particular Cer-16, not only are associated with higher diabetes risk, but may also be associated with higher CVD risk after diabetes onset. We also find support for the hypothesis that sphingomyelins with a very long chain saturated fatty acid are associated with lower CVD risk among adults with type 2 diabetes.

Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease

Abstract: Background: Epigenetic dysregulation has been proposed as a key mechanism for arsenic-related cardiovascular disease (CVD). We evaluated differentially methylated positions (DMPs) as potential mediators on the association between arsenic and CVD. Methods: Blood DNA methylation was measured in 2321 participants (mean age 56.2, 58.6% women) of the Strong Heart Study, a prospective cohort of American Indians. Urinary arsenic species were measured using high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry. We identified DMPs that are potential mediators between arsenic and CVD. In a cross-species analysis, we compared those DMPs with differential liver DNA methylation following early-life arsenic exposure in the apoE knockout (apoE−/−) mouse model of atherosclerosis. Results: A total of 20 and 13 DMPs were potential mediators for CVD incidence and mortality, respectively, several of them annotated to genes related to diabetes. Eleven of these DMPs were similarly associated with incident CVD in 3 diverse prospective cohorts (Framingham Heart Study, Women’s Health Initiative, and Multi-Ethnic Study of Atherosclerosis). In the mouse model, differentially methylated regions in 20 of those genes and DMPs in 10 genes were associated with arsenic. Conclusions: Differential DNA methylation might be part of the biological link between arsenic and CVD. The gene functions suggest that diabetes might represent a relevant mechanism for arsenic-related cardiovascular risk in populations with a high burden of diabetes.

The Portfolio Diet and Incident Type 2 Diabetes: Findings From the Women's Health Initiative Prospective Cohort Study.

Abstract: OBJECTIVE A plant-based dietary pattern, the Portfolio Diet, has been shown to lower LDL cholesterol and other cardiovascular disease risk factors. However, no study has evaluated the association of this diet with incident type 2 diabetes. RESEARCH DESIGN AND METHODS This analysis included 145,299 postmenopausal women free of diabetes at baseline in the Women's Health Initiative (WHI) Clinical Trials and Observational Study from 1993 to 2021. Adherence to the diet was assessed with a score based on six components (high in plant protein [soy and pulses], nuts, viscous fiber, plant sterols, and monounsaturated fat and low in saturated fat and cholesterol) determined from a validated food-frequency questionnaire. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs of the association of the Portfolio Diet, alongside the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets, with incident type 2 diabetes, with adjustment for potential confounders. RESULTS Over a mean follow-up of 16.0 years, 13,943 cases of incident type 2 diabetes were identified. In comparisons of the highest with the lowest quintiles of adherence, the HRs for risk of incident type 2 diabetes were 0.77 (95% CI 0.72, 0.82) for the Portfolio Diet, 0.69 (0.64, 0.73) for the DASH diet, and 0.78 (0.74, 0.83) for the Mediterranean diet. These findings were attenuated by 10% after additional adjustment for BMI. CONCLUSIONS Greater adherence to the plant-predominant Portfolio, DASH, and Mediterranean diets was prospectively associated with lower risk of type 2 diabetes in postmenopausal women.

Subclinical atherosclerosis in adolescents and young adults and the risk of cardiovascular disease: The Strong Heart Family Study (SHFS).

Abstract: Rates of cardiovascular disease (CVD) among American Indians (AI) have been increasing. Although we have observed an association between atherosclerosis and CVD in older adults, the potential association among young AI is unclear. Therefore, we aim to describe the prevalence of atherosclerosis among young AI and determine its association with CVD and all-cause mortality.We evaluated AI participants from the Strong Heart Family Study (SHFS), who were <40 years old and CVD free at the baseline examination, 2001-2003 (n = 1376). We used carotid ultrasound to detect baseline atherosclerotic plaque. We identified CVD events and all-cause mortality through 2019, with a median follow-up of 17.8 years. We used shared frailty Cox Proportional Hazards models to assess the association between atherosclerosis and time to CVD event or all-cause mortality, while controlling for covariates. Among 1376 participants, 71 (5.2%) had atherosclerosis at baseline. During follow-up, 120 (8.7%) had CVD events and 104 (7.6%) died from any cause. CVD incidence was higher in participants who had baseline atherosclerosis (13.51/1000 person-years) than in those who did not (4.95/1000 person-years, p = 0.0003). CVD risk and all-cause mortality were higher in participants with atherosclerosis, while controlling for covariates (CVD HR = 1.85, 95%CI = 1.02-3.37, p = 0.0420; all-cause mortality HR = 2.04, 95%CI = 1.07-3.89, p = 0.0291).Among young AI, atherosclerosis was independently associated with incident CVD and all-cause mortality later in life. Thus, atherosclerosis begins early in life and interventions in adolescents and young adults to slow the progression of disease could prevent or delay CVD events later in life.

Four-day food record macronutrient intake, with and without biomarker calibration, and chronic disease risk in postmenopausal women.

Abstract: We recently presented associations of biomarker-calibrated protein, protein density, carbohydrate, and carbohydrate density with the incidence of cardiovascular diseases, cancers, and diabetes in Women's Health Initiative cohorts (1993 to present, at 40 US clinical centers) of postmenopausal women. The biomarkers relied on serum and urine metabolomics profiles, and biomarker-calibration used regression of biomarkers on food frequency questionnaires. Here corresponding calibration equations are developed using food records and dietary recalls. Also, calibrated intakes based on food records are used in disease association estimation in a cohort subset (n=29,294) having food records. More biomarker variation was explained by food records than FFQs for absolute macronutrient intake, with 24-hour recalls intermediate. However, percent biomarker variation explained was similar for each assessment approach for macronutrient densities. Invasive breast cancer risk related inversely to carbohydrate and protein densities using food records, in analyses that included (calibrated) total energy intake and body mass index. Corresponding analyses for absolute intakes did not differ from the null, nor did absolute or relative intakes associate significantly with colorectal cancer or coronary heart disease. These analyses do not suggest major advantages for food records or dietary recalls compared to less costly and logistically simpler FFQs, for these nutritional variables.

Psychological and social support associations with mortality and cardiovascular disease in middle-aged American Indians: the Strong Heart Study

Abstract: Our study examined psychosocial risk and protective features affecting cardiovascular and mortality disparities in American Indians, including stress, anger, cynicism, trauma, depression, quality of life, and social support. The Strong Heart Family Study cohort recruited American Indian adults from 12 communities over 3 regions in 2001–2003 (N = 2786). Psychosocial measures included Cohen Perceived Stress, Spielberger Anger Expression, Cook-Medley cynicism subscale, symptoms of post-traumatic stress disorder, Centers for Epidemiologic Studies Depression scale, Short Form 12-a quality of life scale, and the Social Support and Social Undermining scale. Cardiovascular events and all-cause mortality were evaluated by surveillance and physician adjudication through 2017. Participants were middle-aged, 40% male, with mean 12 years formal education. Depression symptoms were correlated with anger, cynicism, poor quality of life, isolation, criticism; better social support was correlated with lower cynicism, anger, and trauma. Adjusted time-to-event regressions found that depression, (poor) quality of life, and social isolation scores formed higher risk for mortality and cardiovascular events, and social support was associated with lower risk. Social support partially explained risk associations in causal mediation analyses. Altogether, our findings suggest that social support is associated with better mood and quality of life; and lower cynicism, stress, and disease risk—even when said risk may be increased by comorbidities. Future research should examine whether enhancing social support can prospectively reduce risk, as an efficient, cost-effective intervention opportunity that may be enacted at the community level.

Lipidomics profiling of biological aging in American Indians: the Strong Heart Family Study

Abstract: Telomeres shorten with age and shorter leukocyte telomere length (LTL) has been associated with various age-related diseases. Thus, LTL has been considered a biomarker of biological aging. Dyslipidemia is an established risk factor for most age-related metabolic disorders. However, little is known about the relationship between LTL and dyslipidemia. Lipidomics is a new biochemical technique that can simultaneously identify and quantify hundreds to thousands of small molecular lipid species. In a large population comprising 1843 well-characterized American Indians in the Strong Heart Family Study, we examined the lipidomic profile of biological aging assessed by LTL. Briefly, LTL was quantified by qPCR. Fasting plasma lipids were quantified by untargeted liquid chromatography-mass spectrometry. Lipids associated with LTL were identified by elastic net modeling. Of 1542 molecular lipids identified (518 known, 1024 unknown), 174 lipids (36 knowns) were significantly associated with LTL, independent of chronological age, sex, BMI, hypertension, diabetes status, smoking status, bulk HDL-C, and LDL-C. These findings suggest that altered lipid metabolism is associated with biological aging and provide novel insights that may enhance our understanding of the relationship between dyslipidemia, biological aging, and age-related diseases in American Indians.

Behavioral determinants of arsenic-safe water use among Great Plains Indian Nation private well users: results from the Strong Heart Water Study

Abstract: Background and aim: Long-term arsenic exposure in potable water remains a serious public health challenge in the United States. Rural communities with a high reliance on private wells, including American Indian communities, are disproportionately impacted by arsenic contaminated water. However, efforts to decrease arsenic exposure are limited. The objective of this study is to evaluate the behavioral determinants associated with exclusive arsenic-safe water use in the Strong Heart Water Study (SHWS). Methods: The SHWS is a randomized control trial designed to reduce arsenic exposure in American Indian Great Plains communities. All households received point-of-use arsenic filters installed at baseline and were followed for up to two years. At each visit questionnaires were administered evaluating water use and behavioral determinants based on the RANAS (risks, attitudes, norms, abilities, and self-regulation) model of behavior change. Results: Among 75 participants, exclusive use of arsenic-safe water for drinking and cooking at follow-up was associated with higher baseline levels of perceived disapproval from friends and family for using arsenic-unsafe water for drinking (OR: 0.06, 95% CI: 0.01-0.34) and cooking (0.13, 0.02-0.72) (injunctive norms), greater concern for getting sick from arsenic exposure (0.17, 0.04-0.65) (perceived vulnerability), more self-efficacy to use the arsenic filter for drinking (10.5, 1.49-73.2) and cooking (12.5, 1.88-83.1), and higher arsenic knowledge (6.88, 1.07-44.4). Higher commitment to using the arsenic filter was also a significant predictor of exclusive arsenic-safe water use for drinking (11.7, 1.63-83.5) and cooking (8.43, 1.17-60.8) at follow-up. Exclusive arsenic-safe water use was not associated with sex, age, or education. From baseline to follow-up, the SHWS trial significantly increased perceived vulnerability, self-efficacy, and injunctive norms, and decreased concern about the cost of arsenic filters. Conclusion: Future arsenic interventions in our partner communities should target these behavioral determinants of use of arsenic safe water. Keywords: arsenic, health behavior, water treatment, water

Mid-Life Physical Activity and Late-Life Cognitive Performance among American Indians

Abstract: Introduction: Research on factors associated with late-life cognitive performance in diverse racial/ethnic groups is increasingly important due to the growing size and racial diversity of the elder population. Methods: Using data on American Indians (AIs) from the Strong Heart Study, we measured associations between mid-life physical activity (PA), assessed by a questionnaire or pedometer, and performance on tests of general cognitive function, phonemic fluency, verbal learning and memory, and processing speed. Cognitive tests were administered 7–21 years after PA measurements. To estimate associations, we used regression models with and without inverse-probability weights to account for potential attrition bias in the cohort. Results: Questionnaire and pedometer measures of PA were positively associated with cognitive function. Participants in the top quartile of questionnaire-based PA had Modified Mini-Mental State examination scores 3.2 (95% CI: 1.5–4.9) points higher than participants in the lowest quartile. Phonemic fluency scores also trended higher for participants in the top compared to the bottom categories for both PA measures: top questionnaire quartile = 2.7 (95% CI: 0.6–4.8) points higher and top pedometry tertile = 6.7 (95% CI: 2.7–10.7) points higher. We observed no associations between PA and tests assessing verbal learning and memory, or processing speed. Weighted model results were similar, but less precise. Conclusions: In this cohort of AIs with relatively low levels of PA, positive associations between mid-life PA and late-life cognitive performance were dose-dependent and of modest clinical significance.

Adapting a cooking, food budgeting and nutrition intervention for a rural community of American Indians with type 2 diabetes in the North-Central United States.

Abstract: American Indian (AI) communities experience persistent diabetes-related disparities, yet few nutrition interventions are designed for AI with type 2 diabetes or address socio-contextual barriers to healthy eating. We describe our process of adapting the evidence-based Cooking Matters® program for use by AI adults with type 2 diabetes in a rural and resource-limited setting in the North-Central United States. We conducted three focus groups with AI adults with diabetes to (i) identify Cooking Matters® adaptations and (ii) gather feedback on appropriateness of the adapted intervention using Barrera and Castro's cultural adaptation framework. Transcripts were coded using an inductive, constant comparison approach. Queries of codes were reviewed to identify themes. Contextual considerations included limited access to grocery stores and transportation barriers, reliance on government food assistance and the intergenerational burden of diabetes. Adaptations to content and delivery included incorporating traditional and locally available foods; appealing to children or others in multigenerational households and prioritizing visual over written content. Our use of Barrera and Castro's framework adds rigor and structure to the cultural adaptation process and increases the likelihood of future intervention success. Other researchers may benefit from using this framework to guide the adaptation of evidence-based interventions in AI communities.

Abstract EP35: Longitudinal Lipidomic Profiling Of Left Ventricular Mass In American Indians: The Strong Heart Study

Abstract: Background: Dyslipidemia is a major risk factor for CVD. Left ventricular mass (LVM) is an independent predictor of heart failure and other cardiovascular events. It is unclear whether and how altered plasma lipidome (all lipids in a plasma sample) affects LVM. The relationship between longitudinal change in plasma lipidome and change in LVM is also unstudied in any racial/ethnic group. Objective: To identify molecular lipid species associated with LVM, independent of traditional risk factors. Methods: Using an untargeted LC-MS, we repeatedly measured 1,542 lipids in 3,162 fasting plasma samples collected at two time points (2001-2003, 2006-2009, mean 5.5 years apart) from 1,581 American Indians in the Strong Heart Family Study. All participants were free of overt CVD at both time points. LVM was measured by M-mode echocardiography and LVM index (LVMI) was calculated as LVM/height 2.7 . Lipids associated with LVMI were identified by generalized estimating equation (GEE) models, adjusting for age, sex, center, BMI, smoking, blood pressure, renal function, LDL-c, and diabetes. We first conducted the analysis at each time point, separately, and then combined the results by meta-analysis. The longitudinal association between change in lipids and change in LVMI was examined by GEE, adjusting for the same covariates plus baseline lipids and LVMI. Multiple testing was controlled by false discovery rate at 0.05. Results: The mean age of participants was 39.8 years (62.5% women) at baseline and 45.1 years at follow-up. We identified 325 lipids (125 known), largely fatty acyls, sterol lipids, sphingolipids, glycerolipids, and glycerophospholipids, significantly associated with LVMI at both time points. Longitudinal changes in 17 lipids, including glycerolipids, glycerophospholipids, and sphingolipids, were either positively (ORs: 1.09 -1.95) or negatively (ORs: 0.50 - 0.69) associated with change in LVMI over 5 years of follow-up. Changes in lipids explain up to 1.58% of the variability in the change of LVMI during follow-up. Additional adjustments for use of anti-hypertensive and lipid-lowering drugs did not change the results. Conclusion: Altered fasting plasma lipidome and its longitudinal change over time were significantly associated with LVMI beyond clinical factors and baseline lipids. Our results shed light on the mechanisms through which dyslipidemia may affect LV remodeling, thereby contributing to heart failure or other cardiovascular events.

Abstract EP07: A Longitudinal Lipidomics Profiling For Risk Of Chronic Kidney Disease In American Indians: The Strong Heart Family Study

Abstract: Background: Dyslipidemia is associated with and often precedes the onset of chronic kidney disease (CKD). However, standard lipid panels fail to describe the full spectrum of blood lipidome. A longitudinal profiling of the full spectrum of blood lipidome associated with the risk of CKD is still lacking in any racial/ethnic group, including American Indians, a population that suffered a disproportionately high burden of CKD. Objective: To identify novel lipids and lipidomic signatures associated with risk of CKD in American Indians, independent of traditional risk factors. Methods: We included 1,910 American Indians who attended two examinations (~5.5 years apart) and were free of CKD and cardiovascular disease (CVD) at baseline. CKD was defined based on the estimated glomerular filtration rate (eGFR) calculated by the CKD-EPI formula. Fasting plasma levels of 1,542 lipids in 3,916 samples at two-time points were repeatedly measured by untargeted LC-MS. Machine learning (elastic net) was used to identify lipidomic predictors of CKD beyond traditional risk factors (age, sex, center, BMI, hypertension, diabetes, urinary albumin/creatinine ratio, HDL, triglyceride, and use of lipid-lowering medications). Mixed-effect linear models were used to examine the relationship between changes (baseline to 5-year follow-up) in lipidome and change in kidney function (eGFR), adjusting for traditional risk factors mentioned above, baseline lipid, and baseline eGFR. Multivariate analysis was conducted to identify discriminatory lipidomic signatures that can differentiate between high- and low-risk individuals. Results: Of 1,910 participants free of CKD and CVD (17.8% diabetic) at baseline, 55 (2.9%) developed incident CKD by the end of a 5-year follow-up. Elastic net identified 106 (24 known) lipids, largely glycerophospholipids (GPs), sphingomyelins (SMs), triacylglycerols (TAGs), fatty acids (FAs), and acylcarnitines (ACs), whose altered baseline levels were associated with the risk of CKD, independent of traditional risk factors. A composite lipid score composed of the 24 known lipids improved CKD risk prediction beyond traditional risk factors (AUROC improved from 0.944 to 0.963, P = 0.006). Longitudinal changes in 182 lipids (75 known) lipids, largely GPs, FAs, SMs, TAGs, ACs, and diacylglycerols (DAGs), explained up to 4.8% of the variation of the eGFR change. Multivariate analysis identified distinct lipidomic signatures that separated high- from low-risk participants. Conclusion: We identified novel molecular lipids that significantly predict CKD onset and progression among American Indians beyond traditional risk factors. Our findings shed light on the mechanisms by which dyslipidemia affects CKD and provide instrumental data for biomarker identification, risk prediction and stratification, prognosis, and potential therapeutics.

Association of Artificially Sweetened Beverage Consumption and Urinary Tract Cancers in the Women’s Health Initiative Observational Study

Abstract: Insufficient data exist to conclude whether consumption of artificially sweetened beverages is associated with a higher risk of urinary tract cancers.We sought to investigate whether urinary tract cancer incidence differed among women who consumed various amounts of artificially sweetened beverages.This was a secondary analysis of data from the Women's Health Initiative Observational Study, a multicenter longitudinal prospective study of the health of 93 676 postmenopausal women with a mean follow-up time of 13.5 yr. Women were identified at 40 clinical centers across the USA and enrolled from 1993 to 1998. Women between the ages of 50 and 79 yr were enrolled. We included women who answered questions about artificially sweetened beverage consumption and reported no prior urinary tract cancer diagnoses. The frequency of artificially sweetened beverage consumption was categorized as follows: rare artificially sweetened beverage consumption (never to fewer than one serving per week), frequent consumption (one to six servings per week), and daily consumption (more than one servings per day).The incidence of urinary tract cancer reported during subsequent visits until February 28, 2020 was recorded. Demographic characteristics were compared between those with varying levels of artificially sweetened beverage consumption. Descriptive statistics were used to report the rates of urinary tract cancer diagnosis, and Cox regression models were constructed to determine hazard ratios and adjust for potential confounders.We identified 80 388 participants who met the inclusion criteria. Most participants (64%) were infrequent consumers of artificially sweetened beverages, with 13% (n = 10 494) consuming more than one servings per day. The incidence of urinary tract cancers was low, with only 804 cases identified. Cox regression models showed that frequent artificially sweetened beverage consumption was associated with a higher risk of kidney cancer (adjusted hazard ratio 1.34, 95% confidence interval 1.03-1.75). There was no significant association between artificially sweetened beverage intake and bladder cancer.Frequent consumption of artificially sweetened beverages may be associated with a higher risk of kidney cancer among postmenopausal women.A secondary analysis of the Women's Health Initiative Observational Study showed that higher consumption of artificially sweetened beverages was associated with a higher risk of kidney cancer.

Artificially sweetened beverages and urinary incontinence—a secondary analysis of the Women's Health Initiative Observational Study

Abstract: In this secondary analysis of the Women’s Health Initiative Observational Study, women consuming artificially sweetened beverages daily had 10% greater odds of reporting mixed urinary incontinence after adjustments. Rare, frequent, or daily artifi cially sweetened beverage consumption was not associated with stress or urgency urinary incontinence symptoms. Abstract Objective The aim of this study was to determine if higher artificially sweetened beverage intake is associated with higher prevalence of urinary incontinence symptoms. Methods We conducted a secondary analysis of data from the Women's Health Initiative Observational Study. Our analytic cohort included 80,388 women. Participants who answered questions about beverage consumption and urinary incontinence symptoms at a 3-year follow-up visit were included. Demographic characteristics were compared between three groups of beverage consumers: never to less than one serving per week, one to six servings per week, and greater than or equal to one serving per day. Multivariable logistic regression models were constructed to estimate odds and type of urinary incontinence and adjust for potential confounders. Results Most participants (64%) were rare consumers of artificially sweetened beverages, with 13% (n = 10,494) consuming greater than or equal to 1 serving per day. The unadjusted odds of reporting urinary incontinence were 10% to 12% higher in women consuming one to six servings per week (odds ratio [OR], 1.10; 95% CI, 1.06-1.14) or greater than or equal to one serving per day (OR, 1.12; 95% CI, 1.07-1.18) versus never to less than one serving per week. In multivariable analyses, women consuming greater than or equal to one serving per day (ref: never to <1 serving/wk) had 10% higher odds of reporting mixed urinary incontinence (OR, 1.10; 95% CI, 1.02-1.19). There were no significant differences for stress or urgency urinary incontinence symptoms between groups. Conclusions When compared to never to less than one serving per week, women consuming greater than or equal to one serving per day of artificially sweetened beverages had 10% greater odds of reporting mixed urinary incontinence after adjustments. Amount of artificially sweetened beverage consumption was not associated with stress or urgency urinary incontinence symptoms.

Abstract P040: Dyslipidemia And The Incidence Of Subclinical And Clinical Cardiovascular Disease In Adolescents And Young Adults: The Strong Heart Family Study (SHFS)

Abstract: Introduction: Dyslipidemia is characterized by high levels of total cholesterol (TC), LDL cholesterol (LDL-C), triglycerides (TG), or low levels of HDL cholesterol (HDL-C) and is an established risk factor for subclinical and clinical cardiovascular disease (CVD) among adults. Although several investigations exist in older American Indian (AI) adults, the data on AI adolescents and young adults are scarce. Hypothesis: Dyslipidemia will be prevalent, and the incidence of subclinical and clinical CVD will be higher in young AI with than without baseline dyslipidemia. Methods: We evaluated AI participants from the SHFS, who were 14-39 years old at the baseline examination, 2001-2003 (n=1,436). To measure lipids, we drew blood after a 12-hour fast and defined dyslipidemia as any of the following: TC ≥ 200 mg/dL, LDL-C ≥ 100 mg/dL, TG ≥ 150 mg/dL, HDL-C < 40 mg/dL for men, HDL-C < 50mg/dL for women, non-HDL-C ≥ 130 mg/dL or taking lipid lowering medication. We used carotid ultrasound to detect atherosclerotic plaque at baseline and at the follow-up examination, 2006-2009. We identified CVD events through 2019 with a median follow-up of 17.8 years. We used log-rank tests to determine if the incidence of plaque or CVD events differed according to different categories of dyslipidemia. Results: Prevalence of dyslipidemia was 42%, 65%, and 73% for participants <20, 20-29, and 30-39 years old, respectively. During follow-up, 109 (9.9%) participants had incident plaque (of 1,107 plaque free participants) and 128 (9%) had a fatal or non-fatal CVD event (of 1,424 CVD free participants). Plaque incidence was higher in participants with high TC, LDL-C, TG, non-HDL-C, and dyslipidemia at baseline. CVD incidence was higher for participants with high TC, TG, and non-HDL-C (Table 1). Conclusions: AI adolescents and young adults have an unexpectedly high prevalence of dyslipidemia, which leads to higher incident plaque and CVD events later in life. These data provide evidence for the benefits of lipid screening and intervention among this population.

Abstract EP33: Plasma Lipidomic Signatures And Potential Biomarkers For Risk Of Depression: A Longitudinal Study In A Large Sample Of Community-dwelling American Indians In The Strong Heart Study

Abstract: Background: Depression is an independent risk factor for CVD. Dyslipidemia, an established risk factor for CVD, has also been associated with depression, but a full spectrum of plasma lipidome for risk of depression is still lacking in any racial/ethnic groups. Objective: To identify lipids associated with risk of depression, independent of known clinical factors. Methods: We studied 2,498 fasting plasma samples from 1,249 American Indians attending two exams (2001-2003, 2006-2009, average 5-year apart) in the Strong Heart Study. Plasma lipids were repeatedly measured by LC-MS. Depressive symptoms were assessed using the Center for Epidemiologic Studies for Depression Scale (CES-D). Depression was defined as total CES-D score ≥ 16. All participants were free of overt depression at baseline. Generalized estimating equation was used to identify lipids associated with risk of depression in a discovery sample (N=875), followed by replication in an independent sample (N=374). Results from discovery and replication samples were combined by meta-analysis. The model adjusted for age, sex, study center, BMI, and presence/absence of chronic diseases (e.g., diabetes, hypertension, CVD, CKD). Longitudinal analysis was conducted by regressing changes in lipids on changes in the CES-D score and related psychometric measures (e.g., quality of life, perceived stress, and social support), adjusting for clinical factors and baseline lipids. Network analysis was performed to identify differential lipid networks associated with risk of depression. Multiple testing was controlled at FDR<0.05. Results: Of 1,249 non-depressive participants at baseline (mean age 41, 66% women), 201 individuals (141 in discovery, 60 in replication) developed incident depression after 5-year follow-up. Our lipidomics detected 1,542 lipids (518 known) in 14 lipid classes. Of the 518 known lipids, baseline levels of 9 lipids (e.g., PI(18:1/18:2), SM(d39:1), SM(d41:2)) were associated with a 28-40% decreased risk of depression in both discovery and replication samples. Meta-analysis identified 7 glycerophospholipids (e.g., PC(40:6), PE(16:0/22:5), PI(18:1/18:2)) and 8 sphingomyelins (e.g., SM(d36:3), SM(d40:2), SM(d41:2)) associated with incident depression. Longitudinal changes in long-chain unsaturated fatty acids (e.g., FA(16:1), FA(18:1)) were inversely, while changes in saturated acylcarnitines (e.g., AC(24:0), AC(26:0)) were positively, associated with changes in CES-D score. Network analysis identified two differential lipid modules associated with risk of depression. Conclusion: Novel plasma lipids and lipidomic signatures significantly predict risk of depression beyond clinical factors. Our findings shed light on the mechanisms through which dyslipidemia contributes to depression and provide instrumental data for risk prediction, stratification, and potential therapeutics.