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Background Following the high morbidity and mortality due to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections in New Orleans, Louisiana, we sought to assess progress toward herd immunity. Methods Ochsner Health employees and patients who volunteered for Abbott SARS-CoV-2 immunoglobulin G (IgG) antibody test between March 1 and May 1, 2020 were included. We estimated IgG prevalence and used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for variables associated with IgG test status. Results Of the 13,343 participants with IgG test results, 78.6% were women, 70.6% were non-Hispanic White, 21.1% non-Hispanic Black, 2.9% Hispanic Americans and 5.4% belonged to other races. Overall, 7.99% (95% CI: 7.53-8.45%) of the participants tested IgG positive. In age-, sex- and body mass index (BMI)-adjusted analyses, non-Hispanic Blacks were 2.7-times more likely to test positive than non-Hispanic Whites (OR=2.72; 95% CI: 2.33-3.19). Corresponding ORs (95% CIs) were 1.29 (0.84-1.99) for Hispanic Americans and 1.22 (0.85-1.75) for Other race/ethnicities. Compared to participants in administrative occupations, physician assistants (OR=7.14; 95% CI: 1.72-29.6) and therapists (OR=4.74; 95% CI: 1.49-15.03) were significantly more likely to have IgG antibodies while the association among nurses was not significant (OR=2.35; 95% CI: 0.96-5.77). Relative to 1.40, the test threshold for positivity, our measurements indicate a strong immune response (5.38±1.69), especially among those with a higher BMI. Conclusions SARS-COV-2 IgG antibodies were prevalent only in 8% of the participants. IgG prevalence was highest among non-Hispanic Blacks and participants with higher BMI but was lower among older participants.

Introduction The Southern Community Cohort Study is a prospective study of low socioeconomic status (SES) blacks and whites from the southeastern US, where the burden of end-stage renal disease (ESRD) and its risk factors are high. We tested whether the 2.4-fold elevated risk of ESRD we previously observed in blacks compared to whites was explained by differences in baseline kidney function. Methods We conducted a case-cohort study of incident ESRD cases (n = 737) with stored blood and a probability sampled subcohort (n = 4238) and calculated estimated glomerular filtration rate (eGFR) from serum creatinine. 86% of participants were enrolled from community health centers in medically underserved areas and 14% from the general population in 12 states in the southeastern United States. Incident ESRD after entry into the cohort was ascertained by linkage of the cohort with the US Renal Data System (USRDS). Results Median (25th, 75th percentile) eGFR at baseline was 63.3 (36.0, 98.2) ml/min/1.73m2 for ESRD cases and 103.2 (86.0, 117.9) for subcohort. Black ESRD cases had higher median (25th, 75th) eGFR [63.3 (35.9, 95.9)] compared to whites [59.1 (39.4, 99.2)]. In multivariable Cox models accounting for sampling weights, baseline eGFR was a strong predictor of ESRD risk, and an interaction with race was detected (P = 0.029). The higher ESRD risk among blacks relative to whites persisted (hazard ratio: 2.58; 95% confidence interval: 1.65, 4.03) after adjustment for eGFR. Conclusion In this predominantly lower SES cohort, the racial disparity in ESRD risk is not explained by differences in baseline kidney function. Electronic supplementary material The online version of this article (10.1186/s12882-019-1502-z) contains supplementary material, which is available to authorized users.

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and hypercholesterolemia. In addition, total fat and folate intake have been associated with NAFLD. Aims: We investigated risk factors for NAFLD among individuals of largely low socioeconomic status, and whether these associations differed by race. Methods: A nested case-control study was conducted within the Southern Community Cohort Study. Through linkage of the cohort with Centers for Medicare and Medicaid Services, International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify incident NAFLD cases. Controls were matched 4:1 to cases on enrollment age, sex, and race. A logistic regression was used to estimate odds ratios for the associations of NAFLD with covariates of interest. Results: Neither total fat nor folate intake was significantly associated with NAFLD. Hypercholesterolemia (odds ratio 1.21) and body mass index (75th versus 25th percentile) for blacks (odds ratio 1.96) and whites (odds ratio 2.33) were associated with an increased risk of non-alcoholic fatty liver disease. No significant interaction with race for any of the studied variables was noted. Conclusions: Both hypercholesterolemia and increasing body mass index, but not total fat and folate intake, were risk factors for NAFLD in the Southern Community Cohort Study.

Background Copy number variation (CNV) in the salivary amylase gene (AMY1) modulates salivary α-amylase levels and is associated with postprandial glycemic traits. Whether AMY1-CNV plays a role in age-mediated change in insulin resistance (IR) is uncertain. Methods We measured AMY1-CNV using duplex quantitative real-time polymerase chain reaction in two studies, the Boston Puerto Rican Health Study (BPRHS, n = 749) and the Genetics of Lipid-Lowering Drug and Diet Network study (GOLDN, n = 980), and plasma metabolomic profiles in the BPRHS. We examined the interaction between AMY1-CNV and age by assessing the relationship between age with glycemic traits and type 2 diabetes (T2D) according to high or low copy numbers of the AMY1 gene. Furthermore, we investigated associations between metabolites and interacting effects of AMY1-CNV and age on T2D risk. Results We found positive associations of IR with age among subjects with low AMY1-copy-numbers in both studies. T2D was marginally correlated with age in participants with low AMY1-copy-numbers but not with high AMY1-copy-numbers in the BPRHS. Metabolic pathway enrichment analysis identified the pentose metabolic pathway based on metabolites that were associated with both IR and the interactions between AMY1-CNV and age. Moreover, in older participants, high AMY1-copy-numbers tended to be associated with lower levels of ribonic acid, erythronic acid, and arabinonic acid, all of which were positively associated with IR. Conclusions We found evidence supporting a role of AMY1-CNV in modifying the relationship between age and IR. Individuals with low AMY1-copy-numbers tend to have increased IR with advancing age.

OBJECTIVE To compare presenting characteristics of patients with adductor spasmodic dysphonia (ADSD), ADSD with laryngeal tremor (ADSD + LT), and laryngeal tremor without ADSD (LT). DESIGN Cross-sectional analysis. METHODS Patients treated for laryngeal movement disorders (1990-2016) were included. Analysis of variance and chi square tests measured differences in patient characteristics across the three disease groups. Using ADSD as the referent, multivariable logistic regression models were used to determine whether potential risk factors including patient demographics, family history, presence of potential inciting events prior to disease onset, and coprevalent movement disorders were associated with ADSD + LT or LT. RESULTS In all, 652 patients with ADSD (n = 377), ADSD + LT (n = 98), and LT (n = 177) were included. ADSD patients were significantly younger than those with ADSD + LT and LT (52.5 ± 13.4, 63.9 ± 11.3, and 69.3 ± 10.5 years, respectively; P

Objectives/hypothesis Intubation is an essential component of intensive care, yet it does have potential complications. Posterior glottic stenosis (PGS) is among the most severe sequela. Risk factors are poorly understood. One hypothesis is that large endotracheal tubes (ETTs) in smaller airways may increase risk. Because tracheal diameter is proportional to height, we designed a case-control study to evaluate the association between intensive care unit (ICU)-patient height (proxy for tracheal diameter) and their risk of postintubation PGS. Study design Retrospective case-control study METHODS: Among patients who underwent intubation in an ICU at a single tertiary care medical center between 2001 and 2015, a convenience sample of all patients with confirmed PGS (cases) were enrolled. Cases were matched 1:1 by age, sex, and race with intubated non-PGS controls chosen from the same population of ventilated patients. Data on height, weight, comorbidities, size of ETT, and duration of intubation were abstracted from the medical record. Multivariate models were used to test the association between patient height and risk of PGS development. Results In all, 106 PGS cases (mean age 48.9 years, 50.7% female, 79.2% Caucasian) were identified; 77 met inclusion criteria. Compared to matched controls, cases were significantly shorter (mean 166 cm vs. 173 cm, P = .001). Height and PGS showed an inverse relationship in multivariate models. Specifically, odds of PGS decreased 9% (95% confidence interval: 0.01%-16%) for each centimeter increase in height. Conclusions Shorter height is independently associated with increased odds of having PGS. Further work should consider whether height should be incorporated into ETT selection algorithms. Level of evidence 3b Laryngoscope, 128:2811-2814, 2018.

People with fatty liver disease are at high risk of magnesium deficiency. Meanwhile, low magnesium status is linked to both chronic inflammation and insulin resistance. However, no study has investigated the association between intake of magnesium and risk of mortality due to liver diseases. We evaluated the association between total magnesium intake and mortality due to liver diseases in the Third National Health and Nutrition Examination Study (NHANES III) cohort, which included 13,504 participants who completed liver ultrasound examination for hepatic steatosis. Overall magnesium intake was associated with a reduced risk of mortality due to liver disease at borderline significance (P = 0.05). In fully-adjusted analyses, every 100 mg increase in intake of magnesium was associated with a 49% reduction in the risk for mortality due to liver diseases. Although interactions between magnesium intake and alcohol use and hepatic steatosis at baseline were not significant (P > 0.05), inverse associations between magnesium intake and liver disease mortality were stronger among alcohol drinkers and those with hepatic steatosis. Our findings suggest higher intakes of magnesium may be associated with a reduced risk of mortality due to liver disease particularly among alcohol drinkers and those with hepatic steatosis. Further studies are warranted to confirm the findings.

Background and objectives Prognostic uncertainty is one barrier that impedes providers in engaging patients with CKD in shared decision making and advance care planning. The surprise question has been shown to identify patients at increased risk of dying. Design, setting, participants, & measurements In our prospective observational study, 488 patients ≥60 years of age with CKD stage 4 or 5 were enrolled. Binary surprise question (i.e., “Would you be surprised if this patient died in the next 12 months?”) responses were recorded, and dialysis planning preferences, presence of advance care planning documentation, and care preceding death were abstracted. Results The median patient age was 71 (65–77) years old. Providers responded no and yes to the surprise question for 171 (35%) and 317 (65%) patients, respectively. Median follow-up was 1.9 (1.5–2.1) years, during which 18% of patients died (33% of surprise question no, 10% of surprise question yes; P Conclusions Nephrologists’ prognostic perceptions were associated with modest changes in care, highlighting a critical gap in conservative management discussions, advance care planning, and end of life care among older adults with CKD stages 4 and 5 and high-risk clinical characteristics. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_09_18_CJASNPodcast_17_11.mp3

The SLC8A1 (solute carrier family 8, member 1) gene, encoding Na+/Ca2+ exchanger, is essential in regulating calcium reabsorption and homeostasis. Calcium homeostasis plays a key role in cell proliferation and apoptosis. We hypothesized that polymorphisms in five calcium-regulating genes (SLC8A1, ATP2B1, CALB1, CALB2, and CABP1) interact with calcium intake in relation to the risk of colorectal neoplasia. A two-phase (discovery and replication) study was conducted within the Tennessee Colorectal Polyp Study, including a total of 1275 cases and 2811 controls. In Phase I, we identified six out of 135 SNPs that significantly interacted with calcium intake in relation to adenoma risk. In Phase II, the calcium intake by rs4952490 (SLC8A1) interaction was replicated (P interaction = 0.048). We found an inverse association between calcium intake (1000-2000 mg/day) and colorectal adenomas, particularly for multiple/advanced adenomas, among the G-allele carriers but not among homozygous carriers of the common variant (A) in rs4952490. In the joint analysis of SLC8A1, KCNJ1 and SLC12A1 SNPs, carriers of variant alleles in at least two genes and with calcium intake above the DRI (1000 mg/day) were approximately 30-57% less likely to have adenomas than those whose calcium intake was below the DRI. The association was stronger for multiple/advanced adenomas. No association was found among those who did not carry any variant alleles in these genes when calcium intake was below 2500 mg per day. These findings, if confirmed, may provide a new avenue for the personalized prevention of colorectal adenoma and cancer. This article is protected by copyright. All rights reserved

Objectives This study sought to assess whether body mass index (BMI) was associated with subclinical left ventricular (LV) systolic dysfunction in African-American individuals. Background Higher BMI is a risk factor for cardiovascular disease, including heart failure. Obesity disproportionately affects African Americans; however, the association between higher BMI and LV function in African Americans is not well understood. Methods Peak systolic circumferential strain (ECC) was measured by tagged cardiac magnetic resonance in 1,652 adult African-American participants of the Jackson Heart Study between 2008 and 2012. We evaluated the association between BMI and ECC in multivariate linear regression and restricted cubic spline analyses adjusted for prevalent cardiovascular disease, conventional cardiovascular risk factors, LV mass, and ejection fraction. In exploratory analyses, we also examined whether inflammation, insulin resistance, or volume of visceral adipose tissue altered the association between BMI and ECC. Results The proportions of female, nonsmokers, diabetic, and hypertensive participants rose with increase in BMI. In multivariate-adjusted models, higher BMI was associated with worse ECC (β = 0.052; 95% confidence interval: 0.028 to 0.075), even in the setting of preserved LV ejection fraction. Higher BMI was also associated with worse ECC when accounting for markers of inflammation (C-reactive protein, E-selection, and P-selectin), insulin resistance, and volume of visceral adipose tissue. Conclusions Higher BMI is significantly associated with subclinical LV dysfunction in African Americans, even in the setting of preserved LV ejection fraction.

ObjectiveTo examine whether lifestyle factors, including sedentary time and physical activity, could independently contribute to risk of end-stage renal disease (ESRD).Study designCase-cohort study.SettingSouth-eastern USA.ParticipantsThe Southern Community Cohort Study recruited ~86 000 black and white participants from 2002 to 2009. We assembled a case cohort of 692 incident ESRD cases and a probability sample of 4113 participants.PredictorsSedentary time was calculated as hours/day from daily sitting activities. Physical activity was calculated as metabolic equivalent (MET)-hours/day from engagement in light, moderate and vigorous activities.OutcomesIncident ESRD.ResultsAt baseline, among the subcohort, mean (SD) age was 52 (8.6) years, and median (25th, 75th centile) estimated glomerular filtration rate (eGFR) was 102.8 (85.9–117.9) mL/min/1.73 m2. Medians (25th–75th centile) for sedentary time and physical activity were 8.0 (5.5–12.0) hours/day and 17.2 (8.7–31.9) MET-hours/day, respectively. Median follow-up was 9.4 years. We observed significant interactions between eGFR and both physical activity and sedentary behaviour (p2. The inverse association is most pronounced at physical activity levels >27 MET-hours/day. High levels of sitting time were associated with increased ESRD risk only among those with reduced kidney function (eGFR ≤30 mL/min/1.73 m2); this association was attenuated after excluding the first 2 years of follow-up.ConclusionsIn a population with a high prevalence of chronic kidney disease risk factors such as hypertension and diabetes, physical activity appears to be associated with reduced risk of ESRD among those with preserved kidney function. A positive association between sitting time and ESRD observed among those with advanced kidney disease is likely due to reverse causation.

Impaired hematologic status (IHS) was investigated as a determinant of immune function defined as cluster of differentiation 4 (CD4) T-helper cell count, quality of life (QOL) weight and hospitalization/mortality over 18-months among 398 adult persons living with HIV/AIDS (PLWHA) on anti-retroviral therapy. IHS was defined as having anemia at baseline (Hemoglobin: 200 μg/L for men and >150 μg/L for women) ferritin levels at baseline. Months-to-hospitalization/death or study-end (if no event) was calculated from enrollment. Multivariable linear-mixed models quantified associations between IHS and changes in CD4 cell-count, weight gain and QOL. Cox proportional hazards models calculated hazard ratios (HR) and corresponding 95% confidence intervals (CI) for IHS-related differences in time-to-hospitalization/death. The prevalences of anemia and high and low ferritin levels at baseline were 48.7% (n = 194), 40.5% (n = 161) and 17% (n = 68), respectively. Most patients (63.4%, n = 123) remained anemic during follow-up. Weight gained (ferritin-time interaction, p < 0.01) and QOL (anemia-time interaction, p = 0.05; ferritin-time interaction, p = 0.01) were lower for PLWHA with versus without IHS. Relative to anemia-free/normal ferritin, the risk of hospitalization/death was elevated for PLWHA with anemia (HR = 2.0; 95% CI: 1.2–3.6), low or high ferritin (HR: 1.8–1.9, 95% CI: 0.9–4.1) and those that developed new/persistent/progressive anemia (HR: 2.3–6.7, 95% CI: 1.0–12.7). Among PLWHA, IHS predicted deficits in QOL, low weight gain and a high risk of hospitalization/death. Intervention to mitigate persistent IHS may be warranted among PLWHA on long-term highly active antiretroviral therapy (HAART) to improve health outcomes.

Some studies suggest that the calcium to magnesium ratio intakes modify the associations of calcium or magnesium with risk of colorectal adenoma, adenoma recurrence, and cancer. Parathyroid hormone (PTH) plays a key role in the regulation of homeostasis for both calcium and magnesium. We hypothesized that polymorphisms in PTH and 13 other genes may modify the association between the calcium/magnesium intake ratio and colorectal neoplasia risk. We conducted a two-phase study including 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. In Phase I, we identified 19 SNPs that significantly interacted with the calcium/magnesium intake ratio in adenoma risk. In Phase II, rs11022858 in PTH was replicated. In combined analysis of phases I and II, we found high calcium/magnesium intake ratio tended to be associated with a reduced risk of colorectal adenoma (P for trend, 0.040) among those who carried the TT genotype in rs11022858. In stratified analyses, calcium intake (≥ 1000 mg/d) was significantly associated with 64% reduced adenoma risk (OR = 0.36 (95% CI : 0.18-0.74)) among those homozygous for the minor allele (TT genotype) (P for trend, 0.012), but not associated with risk in other genotypes (CC/TC). Conversely, we found that highest magnesium intake was significantly associated with 27% reduced risk (OR = 0.73 (95% CI : 0.54-0.97)) of colorectal adenoma (P for trend, 0.026) among those who possessed the CC/TC genotypes, particularly among those with the TC genotype, whereas magnesium intake was not linked to risk among those with the TT genotype. These findings, if confirmed, will help for the development of personalized prevention strategies for colorectal cancer. © 2015 Wiley Periodicals, Inc.

Background— Type 2 diabetes mellitus (T2D) and cardiovascular disease share risk factors and subclinical atherosclerosis (SCA) predicts events in those with and without diabetes mellitus. T2D genetic risk may predict both T2D and SCA. We hypothesized that greater T2D genetic risk is associated with higher extent of SCA. Methods and Results— In a cross-sectional analysis, including ≤9210 European Americans, 3773 African Americans, 1446 Hispanic Americans, and 773 Chinese Americans without known cardiovascular disease and enrolled in the Framingham Heart Study, Coronary Artery Risk Development in Young Adults, Multi-Ethnic Study of Atherosclerosis, and Genetic Epidemiology Network of Arteriopathy studies, we tested a 62 T2D-loci genetic risk score for association with measures of SCA, including coronary artery or abdominal aortic calcium score, common and internal carotid artery intima-media thickness, and ankle-brachial index. We used ancestry-stratified linear regression models, with random effects accounting for family relatedness when appropriate, applying a genetic-only (adjusted for sex) and a full SCA risk factors–adjusted model (significance, P P =0.004) and with common carotid artery intima-media thickness in the Framingham Heart Study ( P =0.009) was not confirmed in other study cohorts, either separately or in meta-analysis. Secondary analyses showed no consistent associations with β-cell and insulin resistance genetic risk sub-scores in the Framingham Heart Study and in the Coronary Artery Risk Development in Young Adults. Conclusions— SCA does not have a major genetic component linked to a burden of 62 T2D loci identified by large genome-wide association studies. A shared T2D-SCA genetic basis, if any, might become apparent from better functional information about both T2D and cardiovascular disease risk loci.

Objective. To determine whether 24 hr dietary recalls (DR) are a good measure of polyunsaturated fatty acid (PUFA) intake when compared to plasma levels, and whether plasma PUFA is associated with markers of HIV/AIDS progression and cardiovascular disease (CVD) risk.Methods. In a cross-sectional study among 210 antiretroviral therapy-naïve HIV-infected adults from Lusaka, Zambia, we collected data on medical history and dietary intake using 24 hr DR. We measured fatty acids and markers of AIDS progression and CVD risk in fasting plasma collected at baseline.Results. PUFA intakes showed modest correlations with corresponding plasma levels; Spearman correlations were 0.36(p<0.01)for eicosapentaenoic acid and 0.21(p=0.005)for docosahexaenoic acid. While there were no significant associations(p>0.05)between total plasma PUFA and C-reactive protein (CRP) or lipid levels, plasma arachidonic acid was inversely associated with CRP and triglycerides and positively associated with HDL-C, CD4+ T-cell count, and plasma albumin(p<0.05). Plasma saturated fatty acids (SFA) were positively associated with CRP (β= 0.24; 95% CI: 0.08 to 0.40,p=0.003) and triglycerides (β= 0.08; 95% CI: 0.03 to 0.12,p<0.01).Conclusions. Our data suggest that a single DR is inadequate for assessing PUFA intake and that plasma arachidonic acid levels may modulate HIV/AIDS progression and CVD risk.

Objective Dietary protein intake could have deleterious renal effects in populations at risk for chronic kidney disease. Here, we examined whether higher protein intake (≥80th percentile of energy from protein) is associated with decline in kidney function and whether this decline varies by diabetes status. Design Observational cohort study. Subjects and Settings Participants were African-Americans (n = 5,301), who enrolled in the Jackson Heart Study between 2000 and 2004. Methods Dietary intake was assessed using a validated food-frequency questionnaire at baseline, and serum creatinine was measured at baseline (visit 1) and 8 years later (visit 3). Estimated glomerular filtration rates (eGFRs) at baseline and follow-up were computed using the chronic kidney disease epidemiology collaboration equation. Main Outcome Measure The change in eGFR was computed by subtracting eGFR at visit 1 from that at visit 3. Results Of 3,165 participants with complete data, 64% were women, 57% had hypertension, and 19% had diabetes. The median (25th, 75th percentile) percent energy intake from protein was 14.3 (12.4, 16.4), comparable to that reported for the general US population (15% of energy). During a median (25th, 75th percentile) follow-up of 8.0 (7.4, 8.3) years, eGFR declined by 10.5% from a mean (SD) of 97.4 (17.5) to 86.9 (21.3) mL/min/1.73 m 2 . In the fully adjusted model, consumption of protein as percent of energy intake in lowest and highest quintiles was associated with decline in eGFR among diabetic subjects. The analysis of variance with a robust variance estimator was used to determine whether long-term change in eGFR significantly varies by protein intake. Conclusions Our results show that, among African-Americans with diabetes, higher protein intake as a percent of total energy intake is positively associated with greater decline in eGFR in analyses that accounted for risk factors for kidney disease.

Background: Glagov identified cross-sectional enlargement and maintenance of the lumen of the coronary artery (CA) in post-mortem studies as an early feature of atherosclerotic coronary heart disease (CHD) that precedes the development of stenosis, coronary artery calcium (CAC) and plaque rupture. This structural change in the CA wall has been termed positive remodeling. We hypothesized that larger CA cross-sectional areas, consistent with positively remodeled CA, is associated with prevalent or soon-to-be incident coronary heart disease (CHD) and cardiovascular disease (CVD) events. Methods: In 2946 black and white male and female CARDIA participants aged 42-56 years, who had thin-slice (CSA_all ). We performed logistic regression with medical-record adjudicated CVD prevalence (n=96) or incidence in the following 3 years (n=27) as the outcome, predicted from this estimate of positive remodeling adjusting for age, race, sex, presence of coronary artery calcium (CAC), and amount of pericardial fat as covariates. Results: CA CSA_all had a mean ± SD 21.2 ± 6.7 mm 2 . The adjusted odds ratio (OR) for having any CVD was 1.06 (95% CI 1.03-1.09, p2 (Table). ORs for CVD increased across quartiles of CA CSA_all . Corresponding OR for any coronary heart disease (n=66) was not significant, but was significant for stroke (n=42) and for heart failure (n=27). Further adjustment for traditional risk factors assessed in 2010-2011 did not alter these estimates substantially. Conclusion: Individuals with larger CA cross-sectional areas had increased odds of CVD, stroke, and heart failure, but not CHD, independent of CAC and pericardial fat. CA CSA_all may be an imaging biomarker of coronary positive remodeling and provide new insight into progression from subclinical to premature clinical CVD.

Background: Whether elevated intakes of trans fatty acids (TFAs) increase the risk of stroke remains unclear. Except for the Women's Health Initiative–Observational Study, most studies that directly assessed the association between TFA intake and stroke yielded null results. Objective: The aim of this study was to investigate the association between TFA intake and stroke incidence. Design: We prospectively investigated the association between TFA intake and stroke incidence in black and white men and women (n = 17,107) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Participants were recruited between 2003 and 2007 from the continental United States and followed for incident stroke. Diet was assessed by using the Block 1998 food-frequency questionnaire. Cox regression was used to test whether energy-adjusted TFA intake in 1-SD increments was associated with incident stroke. Results: During a median follow-up of 7 y, 479 strokes were identified, including 401 ischemic strokes. Sex modified the association between TFA intake and stroke (P-interaction = 0.06), and thus the results were stratified by sex. In fully adjusted models, a 1-SD (2-g/d) increase in TFA intake was associated with an increased risk of any stroke in men (HR: 1.14; 95% CI: 1.02, 1.28) but not in women (HR: 0.93; 95% CI: 0.79, 1.11). Similarly, our results showed an increased risk of ischemic stroke in men (HR: 1.13; 95% CI: 1.00, 1.28) but not in women (HR: 0.93; 95% CI: 0.77, 1.12). Conclusions: We show that sex modifies the association between TFA intake and stroke; for every 2-g/d increase in TFA intake, there was a 14% increase in the risk of stroke in men but not in women. Our findings provide further evidence to support the concerted effort to minimize TFAs in the diet.

Background and aims Adiponectin is an adipose-secreted protein that has been linked to changes in insulin sensitivity, high-density lipoprotein cholesterol levels, and inflammatory patterns. Although fenofibrate therapy can raise adiponectin levels, treatment response is heterogeneous and heritable, suggesting a role for genetic mediators. This is the first genome-wide association study of fenofibrate effects on circulating adiponectin. Methods and results Plasma adiponectin was measured in participants of the Genetics of Lipid Lowering Drugs and Diet Network ( n = 793) before and after a 3-week daily treatment with 160 mg of fenofibrate. Associations between variants on the Affymetrix Genome-Wide Human SNP Array 6.0 and adiponectin were assessed using mixed linear models, adjusted for age, sex, site, and family. We observed a statistically significant ( P = 5 × 10 −8 ) association between rs2384207 in 12q24, a region previously linked to several metabolic traits, and the fenofibrate-induced change in circulating adiponectin. Additionally, our genome-wide analysis of baseline adiponectin levels replicated the previously reported association with CDH13 and suggested novel associations with markers near the PCK1, ZBP1, TMEM18, and SCUBE1 genes. The findings from the single marker tests were corroborated in gene-based analyses. Biological pathway analyses suggested a borderline significant association between the EGF receptor signaling pathway and baseline adiponectin levels. Conclusions We present preliminary evidence linking several biologically relevant genetic variants to adiponectin levels at baseline and in response to fenofibrate therapy. Our findings provide support for fine-mapping of the 12q24 region to investigate the shared biological mechanisms underlying levels of circulating adiponectin and susceptibility to metabolic disease.

Cardiovascular disease (CVD) biomarkers were examined in a cohort of HIV-infected and HIV-uninfected adolescents who participated in Adolescent Trials Network study 083 utilizing samples from the Reaching for Excellence in Adolescent Care cohort, a longitudinal study of youth infected through adult risk behavior. Nonfasting blood samples from 97 HIV-infected and 81 HIV-uninfected adolescents infected by adult risk behaviors were analyzed for total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), triglycerides, apolipoprotein A-I, high-sensitivity C-reactive protein (hsCRP), soluble vascular adhesion molecule-1 (sVCAM-1), myeloperoxidase, and neopterin at baseline and 18 months later. Results were analyzed using ANOVA, Wilcoxon signed-rank, and paired t tests. Among infected subjects 67 received antiretroviral therapy and 30 were treatment naive. The HIV-infected and HIV-uninfected subjects were similar in gender, ethnicity, and cardiovascular risk factors such as smoking and obesity. In all groups lipid parameters were within accepted guidelines for cardiovascular risk. Among HIV-infected youth on antiretroviral therapy (ART), HDL and apoprotein A-I were significantly lower when compared to uninfected youth. hsCRP was not elevated and thus not predictive for risk in any group. sVCAM-1 levels were significantly elevated in both HIV-infected groups: 1,435 ng/ml and 1,492 ng/ml in untreated and treated subjects, respectively, and 1,064 ng/ml in the uninfected group (p

Background. Low body mass index (BMI) at antiretroviral therapy (ART) initiation is associated with early mortality, but the etiology is not well understood. We hypothesized that low pretreatment serum phosphate, a critical cellular metabolism intermediate primarily stored in skeletal muscle, may predict mortality within the first 12 weeks of ART. Methods. We prospectively studied 352 HIV-infected adults initiating ART in Lusaka, Zambia to estimate the odds of death for each 0.1 mmol/L decrease in baseline phosphate after adjusting for established predictors of mortality. Results. The distribution of phosphate values was similar across BMI categories (median value 1.2 mmol/L). Among the 145 participants with BMI 18.5 kg/m 2, 28 (19%) died within 12 weeks. Lower pretreatment serum phosphate was associated with increased mortality (odds ratio (OR) 1.24 per 0.1 mmol/L decrement, 95% CI: 1.05 to 1.47; ) after adjusting for sex, age, and CD4 + lymphocyte count. A similar relationship was not observed among participants with BMI ≥18.5 kg/m 2 (OR 0.96, 95% CI: 0.76 to 1.21; ). Conclusions. The association of low pretreatment serum phosphate level and early ART mortality among undernourished individuals may represent a variant of the refeeding syndrome. Further studies of cellular metabolism in this population are needed.

Background Fatty acids, including n-6 series, modulate immune function, but their effect on CD4 cell counts, death, or hospitalization in HIV-infected patients on antiretroviral therapy is unknown. Methods In a randomized trial for effects of multivitamins in HIV-infected patients in Uganda, we used gas chromatography to measure plasma n-6 fatty acids at baseline; determined CD4 counts at baseline, 3, 6, 12, and 18 months; and recorded hospitalization or death events. The associations of fatty acids with CD4 counts and events were analyzed using repeated-measures analysis of variance and Cox regression, respectively. Results Among 297 patients with fatty acids measurements, 16 patients died and 69 were hospitalized within 18 months. Except for linoleic acid, n-6 fatty acids levels were positively associated with CD4 counts at baseline but not during follow-up. In models that included all 5 major n-6 fatty acids, age; sex; body mass index; anemia status; use of antiretroviral therapy, multivitamin supplements, and alcohol; and the risk of death or hospitalization decreased significantly with an increase in linoleic acid and gamma-linolenic acid levels, whereas associations for dihomo-gamma-linolenic acid, arachidonic acid, and aolrenic acid were null. The hazard ratios (95% confidence intervals) per 1 SD increase in linoleic acid and gamma-linolenic acid were 0.73 (0.56-0.94) and 0.51 (0.36-0.72), respectively. Gamma-linolenic acid remained significant (hazard ratio = 0.51; 95% confidence interval: 0.35 to 0.68) after further adjustment for other plasma fatty acids. Conclusions Lower levels of gamma-linolenic acid are associated with lower CD4 counts and an increased risk of death or hospitalization. These results suggest a potential for using n-6 fatty acids to improve outcomes from antiretroviral therapy.

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and have been linked to acute kidney injury (AKI), chronic kidney disease (CKD) and cardiovascular disease (CVD). Patients who survive an AKI episode are at risk for future adverse kidney and cardiovascular outcomes. The objective of our study was to examine the prevalence and predictors of NSAID use among AKI survivors. Methods The Southern Community Cohort Study is a prospective study of low-income adults aged 40–79 in the southeastern US. Through linkage with Centers for Medicare and Medicaid Services, 826 participants with an AKI diagnosis (ICD-9 584.5-584.9) at any age prior to cohort enrollment were identified. At baseline, data were collected on regular use of prescription and over-the-counter NSAIDs, as well as demographic, medical and other characteristics. Additional comorbidities were ascertained via linkage with CMS or the US Renal Data System. Results One hundred fifty-four AKI survivors (19%) reported regular NSAID use at cohort enrollment (52 prescription, 81 OTC, 21 both) and the percentage of NSAID users did not vary by time since AKI event. Over 58% of users were taking NSAIDS regularly both before and after their AKI event. Hypertension (83%), arthritis (71%), heart failure (44%), CKD (36%) and diabetes (35%) were prevalent among NSAID users. In a multivariable model, history of arthritis (OR: 3.00; 95% CI: 1.92, 4.68) and acetaminophen use (OR: 2.43; 95% CI: 1.50, 3.93) were significantly associated with NSAID use, while prevalent CKD (OR: 0.63; 95% CI: 0.41, 0.98) and diabetes (OR: 0.44; 95% CI: 0.29, 0.69) were significantly inversely associated. Conclusions NSAID use among AKI survivors is common and highlights the need to understand physician and patient decision-making around NSAIDs and to develop effective strategies to reduce NSAID use in this vulnerable population. Electronic supplementary material The online version of this article (doi:10.1186/s12882-016-0411-7) contains supplementary material, which is available to authorized users.

Background Whether polyunsaturated fatty acids (PUFA) are associated with end-stage renal disease (ESRD) in populations with a high burden of risk factors for kidney disease is unknown. We sought to determine whether PUFA intake is associated with ESRD. Methods We conducted a nested case–control study of ESRD within the Southern Community Cohort Study (SCCS), a prospective cohort of low-income blacks and whites in the southeastern US (2002–2009). Through 2012, 1,074 incident ESRD cases were identified by linkage with the United States Renal Data System and matched to 3,230 controls by age, sex and race. Dietary intake of total, n-3 or n-6 PUFA was assessed from a validated food frequency questionnaire administered at baseline. Odds ratios (ORs) and 95 % confidence intervals (CIs) were computed from logistic regression models that included matching variables, body mass index, smoking, diabetes, hypertension, education, income, total energy intake and percent energy from protein and saturated fat. Results The mean (SD) age of participants was 55 (9) years. Most participants were women (55 %), black (87 %), with hypertension (67 %) and on average obtained 8 % of their energy from PUFA. Higher PUFA intake was marginally associated with a lower risk of ESRD in adjusted analyses. The adjusted odds ratios (95 % confidence intervals) for ESRD for the 5th vs. 1st quintile of PUFA were 0.79 (0.60–1.05; P trend = 0.06) for total PUFA, 0.81 (0.61–1.06; P trend = 0.04) for n-6 PUFA and 0.93 (0.71–1.21; P trend = 0.45) for n-3 PUFA. Conclusions We observed a marginally significant inverse trend between dietary PUFA intake and ESRD incidence, mainly driven by n-6 fatty acid intake. Our findings require replication but suggest that a diet rich in n-6 PUFA may prevent ESRD development in a population with a high burden of kidney disease risk factors.

Diabetes, a risk factor for end-stage renal disease (ESRD), is associated with impaired protein metabolism. We investigated whether protein intake is associated with ESRD and whether the risk is higher among blacks with diabetes.We conducted a nested case-control study of ESRD within the Southern Community Cohort Study, a prospective study of low-income blacks and whites in the southeastern US (2002-2009). Through 2012, 1057 incident ESRD cases were identified by linkage with the United States Renal Data System and matched to 3198 controls by age, sex, and race. Dietary intakes were assessed from a validated food frequency questionnaire at baseline. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models that included matching variables, BMI, education, income, hypertension, total energy intake, and percent energy from saturated and polyunsaturated fatty acids. Mean (±SD) daily energy intake from protein was higher among ESRD cases than controls (15.7 ± 3.3 vs. 15.1 ± 3.1%, P 0.0001). For a 1% increase in percent energy intake from protein, the adjusted ORs (95% CIs) for ESRD were 1.06 (1.02-1.10) for blacks with diabetes, 1.02 (0.98-1.06) for blacks without diabetes, 0.99 (0.90-1.09) for whites with diabetes and 0.94 (0.84-1.06) for whites without diabetes. Protein intake in g/kg/day was also associated with ESRD (4th vs. 1st quartile OR = 1.76; 95% CI: 1.17-2.65).Our results raise the possibility that among blacks with diabetes, increased dietary protein is associated with increased incidence of ESRD. Studies on how protein intake and metabolism affect ESRD are needed.

Alcohol intake has been shown to have a J-shaped association with blood pressure (BP). However, this association has not been examined in mixed race populations or in people with diabetes where tighter blood pressure control is recommended. Participants in the REGARDS study who were 45 years or older (n = 30,239) were included. Medical history (including self-reported alcohol intake) was collected by telephone while blood collection and clinical measurements were done during an in-home visit. We defined diabetes as use of medications and/or fasting glucose ≥ 126 mg/dL and hypertension as use of blood pressure lowering medications and/or BP ≥ 140/90 mmHg or BP ≥ 130/80 mmHg in people with diabetes. After adjustment for confounders, heavy drinking was associated with an increased odds of hypertension (OR = 1.59, 95% CI = 1.37, 1.87). Diabetes and gender significantly modified (interaction P < 0.05 for both) the association between alcohol use and hypertension, although heavy drinking remained associated with increased odds of hypertension in sub-group analyses. We did not observe the previously described J-shaped relationship in any sub-group except white females. These data suggest heavy alcohol consumption is associated with poor BP control and that heavy drinkers may want to consider limiting alcohol intake in order to manage hypertension.

Several clinical studies report increased risk of diabetes mellitus (DM) with pharmacologic treatment for hypertension (HTN). HTN genes may modify glycemic response to antihypertensive treatment. The current study examined the association of 24 single nucleotide polymorphisms (SNPs) in 11 HTN candidate genes with fasting glucose measured at 2, 4, and 6 years after treatment initiation. The study sample included participants free of diabetes at baseline in the Genetics of Hypertension Associated Treatment (GenHAT) study (N=9,309). GenHAT participants were randomized to receive treatment with a diuretic (chlorthalidone), calcium channel blocker (amlodipine), or ACE inhibitor (lisinopril). Mixed models for repeated measures were employed to test for gene and pharmacogenetic associations with fasting glucose during follow-up. Fasting glucose at year 2 increased on average 6.8 mg/dL, 4.8 mg/dL and 3.0 mg/dL from baseline in the chlorthalidone, amlodipine and lisinopril groups, respectively. Carrying the I allele (rs1799752) of the angiotensin-converting enzyme (ACE) I/D polymorphism was associated with lower fasting glucose levels (P=0.02). Additionally, an ACE promoter polymorphism (−262, rs4291) was associated with lower fasting glucose for the model AA/AT vs. TT which remained significant after correction for multiple testing (P=0.001). Finally, a SNP in the α-subunit of the amiloride-sensitive epithelial sodium channel (SCNN1A, rs2228576) modified the association of amlodipine versus chlorthalidone treatment with fasting glucose (P

People with fatty liver disease are at high risk of magnesium deficiency. Meanwhile, low magnesium status is linked to both chronic inflammation and insulin resistance. However, no study has investigated the association between intake of magnesium and risk of mortality due to liver cancer and other liver diseases. We evaluated the association between total magnesium intake and mortality due to liver cancer and other liver diseases in the Third National Health and Nutrition Examination Study (NHANES III) cohort, which included 13,504 participants who completed liver ultrasound examination for hepatic steatosis. Overall magnesium intake was associated with a reduced risk of mortality due to liver cancer and other liver disease at borderline significance (P=0.05). In multi-variable adjusted models, every 100 mg increase in intake of magnesium was associated with a 49% reduction in the risk for mortality due to liver cancer and other liver diseases. Although interactions between magnesium intake and alcohol use and hepatic steatosis at baseline were not significant (P>0.05), inverse associations between magnesium intake with liver cancer and other liver disease mortality were stronger among alcohol drinkers and those with hepatic steatosis. Our novel findings suggest higher intakes of magnesium may be associated with a reduced risk of mortality due to liver cancer and other liver disease particularly among alcohol drinkers and those with hepatic steatosis. Further studies are warranted to confirm the findings. Citation Format: Zhu Xiangzhu, Lijun Wu, Lei Fan, Edmond K Kabagambe, Yiqing Song, Menghua Tao, Xiaosong Zhong, Lifang Hou, Martha J. Shrubsole, Jie Liu, Qi Dai. Magnesium intake and mortality due to liver cancer and other liver diseases: Results from the Third National Health and Nutrition Examination Survey Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4258.

The fenofibrate effect on the subclass size distribution of lipoproteins before and after a high-fat challenge is not well studied.To characterize the baseline and post-prandial response (PPL) to a high-fat challenge following fenofibrate therapy, on changes in LDL, HDL, and VLDL particle subclasses, number, and size in 271 hypertriglyceridemic participants.Participants from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study who conducted PPL studies both before and after three weeks of fenofibrate (160 mg/d) treatment were analyzed. Particle size distributions were determined using nuclear magnetic resonance imaging, and lipid determinations were measured at fasting (0 hr), 3.5 hours, and 6 hours after ingestion of a standardized high-fat meal. Analyses were stratified by gender. Changes in particle subclass distributions were assessed using repeated measures analysis of variance adjusted for pedigree.Before PPL, fenofibrate in men (adjusted for age, field center, smoking status, diabetes, and weight circumference) lowered fasting and postprandial VLDL primarily due to reductions in postprandial levels of large and medium VLDL particles (9 SE +/-0.7 to 4 +/-0.4 and 78 / -4 to 36 / -3 nmol/L bothFenofibrate treatment resulted in a lower triglyceride excursion following a high-fat meal. This investigation provides new knowledge of the magnitude and time course of fenofibrate induced attenuation of Lipoprotein subclass size distribution following a postprandial lipid challenge.

The scaffolding protein PDZ domain containing 1 (PDZK1) regulates the HDL receptor scavenger receptor class B type I. However, the effect of PDZK1 genetic variants on lipids and metabolic syndrome (MetS) traits remains unknown. This study evaluated the association of 3 PDZK1 single nucleotide polymorphisms (SNP) (i33968C > T, i15371G > A, and i19738C > T) with lipids and risk of MetS and their potential interactions with diet. PDZK1 SNP were genotyped in 1000 participants (481 men, 519 women) included in the Genetics of Lipid Lowering Drugs and Diet Network study. Lipoprotein subfractions were measured by proton NMR spectroscopy and dietary intake was estimated using a validated questionnaire. The PDZK1_i33968C > T polymorphism was associated with MetS (P = 0.034), mainly driven by the association of the minor T allele with higher plasma triglycerides (P = 0.004) and VLDL (P = 0.021), and lower adiponectin concentrations (P = 0.022) than in participants homozygous for the major allele (C). We found a significant gene x BMI x diet interaction, in which the deleterious association of the i33968T allele with MetS was observed in obese participants with high PUFA and carbohydrate (P-values ranging from 0.004 to 0.020) intakes. Conversely, a there was a protective effect in nonobese participants with high PUFA intake (P T genetic variants may be associated with a higher risk of exhibiting MetS. This gene x BMI x diet interaction offers the potential to identify dietary and other lifestyle changes that may obviate the onset of MetS in individuals with a specific genetic background.

Background Smoking is associated with increased postprandial hypertriglyceridemia (PPT). Inflammation and insulin resistance are potential “drivers” for this phenomenon. We tested whether inflammatory patterns and/or insulin resistance explain the effect of smoking on PPT.

The transcription factor 7-like 2 (TCF7L2) has been recently associated with diabetes risk, and it may exert its effect through metabolic syndrome (MetS)-related traits and be subjected to modification by environmental factors. We investigated the effect of single nucleotide polymorphisms (SNP), rs7903146 and rs12255372, within the TCF7L2 locus on postprandial lipemia and other MetS-related traits and their modulation by dietary fat. Data were collected from 1083 European Americans participating in the Genetics of Lipid Lowering Drugs and Diet Network Study. Carriers of the minor T allele at the C/T rs7903146 SNP had higher fasting plasma glucose (P = 0.012), lower homeostasis model assessment of beta cell function (P = 0.041), higher plasma VLDL (P = 0.035), and lower large LDL particle (P = 0.007) concentrations and higher risk of MetS (P = 0.011) than CC individuals. Moreover, we identified significant interactions between this SNP and PUFA intake modulating fasting VLDL particle concentrations (P = 0.016) and postprandial triglycerides (TG) (P = 0.028), chylomicrons (P = 0.025), total VLDL (P = 0.026), and large VLDL (P = 0.018) concentrations. Thus, only T allele carriers with a PUFA intake > or = 7.36% of energy had elevated fasting plasma VLDL concentrations and postprandial TG-rich lipoproteins. These variables did not differ in T allele carriers and noncarriers in the low-PUFA intake group. Moreover, these significant interactions were due exclusively to (n-6) PUFA intake. In summary, high (n-6) PUFA intakes (> or = 6.62% of energy intake) were associated with atherogenic dyslipidemia in carriers of the minor T allele at the TCF7L2 rs7903146 SNP and may predispose them to MetS, diabetes, and cardiovascular disease.

Serum adiponectin levels have been positively associated with insulin sensitivity and are decreased in type 2 diabetes (T2D) and obesity. Genetic and environmental factors influence serum adiponectin and may contribute to risk of metabolic syndrome and T2D. Therefore, we investigated the effect of ADIPOQ single-nucleotide polymorphisms (SNPs), -11377CG and -11391GA, on metabolic-related traits, and their modulation by dietary fat in white Americans. Data were collected from 1,083 subjects participating in the Genetics of Lipid Lowering Drugs and Diet Network study. Mean serum adiponectin concentration was higher for carriers of the -11391A allele (P = 0.001) but lower for the -11377G allele carriers (P = 0.017). Moreover, we found a significant association with obesity traits for the -11391GA SNP. Carriers of the -11391A allele had significantly lower weight (P = 0.029), BMI (P = 0.019), waist (P = 0.003), and hip circumferences (P = 0.004) compared to noncarriers. Interestingly, the associations of the -11391GA with BMI and obesity risk were modified by monounsaturated fatty acids (MUFAs) intake (P-interaction = 0.021 and 0.034 for BMI and obesity risk, respectively). In subjects with MUFA intake above the median (or =13% of energy intake), -11391A carriers had lower BMI (27.1 kg/m(2) for GA+AA vs. 29.1 kg/m(2) for GG, P = 0.002) and decreased obesity risk (odds ratio for -11391A = 0.52, 95% confidence interval (CI); 0.28-0.96; P = 0.031). However, we did not detect genotype-related differences for BMI or obesity in subjects with MUFA intake13%. Our findings support a significant association between the -11391GA SNPs and obesity-related traits and the potential to moderate such effects using dietary modification.

Chronic inflammation has been identified as an important component of the metabolic syndrome (MetS). Therefore, environmental and genetic factors contributing to the variation of inflammatory responses could affect individuals' susceptibility to MetS. We investigated the association between common IL1beta genetic polymorphisms, inflammation, and the MetS, and the modulation of diet-related variables (i.e., erythrocyte membrane fatty acid composition) in a white U.S. population. IL1beta single nucleotide polymorphisms (SNP) (-1473G > C, -511G > A, -31T > C, 3966C > T, 6054G > A), clinical and biochemical measurements were characterized in a total of 1120 subjects (540 males and 580 females) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. The 6054 G > A SNP was significantly associated with plasma C-reactive protein (P = 0.054), adiponectin (P = 0.021), and the prevalence of MetS (P = 0.004). Moreover, there was a significant interaction between the 6054G > A SNP and erythrocyte membrane (n-3) PUFA (P = 0.019). Among subjects with low (n-3) PUFA content (below the median), the 6054 G allele was associated with increased risk of the MetS (OR = 3.29, 95%CI = 1.49-7.26 for GG and OR = 1.95, 95%CI = 0.85-4.46 for GA, P < 0.001) compared with the AA genotype, but there were no significant genotype associations among subjects with high (n-3) PUFA content (above the median). Further analyses supported a significant haplotype global effect on the MetS (P = 0.017) among subjects with low (n-3) PUFA content. These results suggested that IL1beta genetic variants were associated with measures of chronic inflammation and the MetS risk, and that genetic influences were more evident among subjects with low (n-3) PUFA intake.

Purpose There are no data for factors that could trigger myocardial infarction (MI) in the context of lifestyles in developing countries. Methods Using a case–crossover design, we assessed the effect of heavy physical exertion, sexual activity, acute respiratory tract infections, and gastroenteritis as triggers for MI in 530 survivors of a first MI from Costa Rica. Results Relative risks (RRs) for MI in the hour after heavy physical exertion and 2 hours after sexual activity were 4.94 (95% confidence interval [CI], 3.73–6.54) and 5.47 (95% CI, 2.71–11.02). Risk for MI after heavy physical exertion was greater for patients with poor physical fitness or elevated underlying cardiovascular risk (p < 0.0001 and p = 0.06, tests of homogeneity). RRs for acute respiratory tract infection and gastroenteritis were 1.48 (95% CI, 0.92–2.38) and 1.27 (95% CI, 0.95–1.69), respectively. Patients with three or more risk factors had an RR for MI for gastroenteritis of 2.08 (95% CI, 1.31–3.28). Conclusions Our results confirm previous studies in developed countries showing that heavy physical exertion and sexual activity are potential triggers for MI, and their effect is modified by physical fitness and underlying cardiovascular risk. Additional studies that explore the biologic effects of gastroenteritis as triggers of MI are warranted. UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Centro Centroamericano de Población (CCP)

Introduction: Heterozygous familial hypercholesterolemia (FH) is common but under-recognized, with an estimated prevalence of 1:200-1:500 and an associated high risk of premature cardiovascular disease (CVD). Little is known regarding the association between change in low-density lipoprotein cholesterol (LDL-C) and long-term CVD risk in FH patients. We hypothesized that FH patients who achieved LDL-C < 100 mg/dL or reduction ≥50% post-statin initiation would have reduced risk of non-fatal myocardial infarction (MI) or revascularization. Methods: Using Dutch Lipid Network criteria components, 174 “probable” and 125 “definite” FH patients with LDL-C measurements available before and after statin initiation were identified in the Vanderbilt de-identified electronic medical records (EMR) Synthetic Derivative database, 1996-2014. First non-fatal MI or revascularization was identified via validated EMR algorithm with positive predictive value=92%. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained from Cox regression models in relation to LDL-C levels (≥ vs. < vs. >100 mg/dL post-statin), adjusted for age, race, sex, blood pressure, smoking, and body mass index. Results: Mean (+/- SD) LDL-C levels prior to initiation of statin therapy were 207 (+/- 31) for probable and 304 (+/- 124) mg/dL for definite FH patients. Similar proportions of patients attained ≥50% reduction in LDL-C after statin initiation in both groups (24.1% and 26.4%), while 22.4% achieved LDL-C < 100 mg/dL in the probable group compared to only 4.8% in the definite group. Over median follow-up of 5.4 years, 34 probable and 19 definite FH patients experienced non-fatal MI or revascularization. The HR (95% CI) among those with post-statin LDL-C < 100 vs >100 mg/dL was 0.59 (0.23-1.52) overall, with no evidence of effect modification by probable/definite FH status (likelihood ratio test (LRT) p-value=0.58). A similar pattern was observed for LDL-C change ≥50% vs Conclusions: In this small sample of FH patients, lowering LDL-C to

Background DNA methylation is influenced by diet and single nucleotide polymorphisms (SNPs), and methylation modulates gene expression. Objective We aimed to explore whether the gene-by-diet interactions on blood lipids act through DNA methylation. Design We selected 7 SNPs on the basis of predicted relations in fatty acids, methylation, and lipids. We conducted a meta-analysis and a methylation and mediation analysis with the use of data from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium and the ENCODE (Encyclopedia of DNA Elements) consortium. Results On the basis of the meta-analysis of 7 cohorts in the CHARGE consortium, higher plasma HDL cholesterol was associated with fewer C alleles at ATP-binding cassette subfamily A member 1 (ABCA1) rs2246293 (β = -0.6 mg/dL, P = 0.015) and higher circulating eicosapentaenoic acid (EPA) (β = 3.87 mg/dL, P = 5.62 × 10(21)). The difference in HDL cholesterol associated with higher circulating EPA was dependent on genotypes at rs2246293, and it was greater for each additional C allele (β = 1.69 mg/dL, P = 0.006). In the GOLDN (Genetics of Lipid Lowering Drugs and Diet Network) study, higher ABCA1 promoter cg14019050 methylation was associated with more C alleles at rs2246293 (β = 8.84%, P = 3.51 × 10(18)) and lower circulating EPA (β = -1.46%, P = 0.009), and the mean difference in methylation of cg14019050 that was associated with higher EPA was smaller with each additional C allele of rs2246293 (β = -2.83%, P = 0.007). Higher ABCA1 cg14019050 methylation was correlated with lower ABCA1 expression (r = -0.61, P = 0.009) in the ENCODE consortium and lower plasma HDL cholesterol in the GOLDN study (r = -0.12, P = 0.0002). An additional mediation analysis was meta-analyzed across the GOLDN study, Cardiovascular Health Study, and the Multi-Ethnic Study of Atherosclerosis. Compared with the model without the adjustment of cg14019050 methylation, the model with such adjustment provided smaller estimates of the mean plasma HDL cholesterol concentration in association with both the rs2246293 C allele and EPA and a smaller difference by rs2246293 genotypes in the EPA-associated HDL cholesterol. However, the differences between 2 nested models were NS (P > 0.05). Conclusion We obtained little evidence that the gene-by-fatty acid interactions on blood lipids act through DNA methylation.

Background Low health literacy is associated with worse glycemic control among patients with diabetes; the relationship between health literacy and blood glucose among patients without diagnosed diabetes, particularly in resource-limited settings, is not known. Because emergency department patients are at risk for both low health literacy and undiagnosed diabetes, we examined their relationships among emergency department patients at the Georgetown Public Hospital Corporation in Guyana. Methods We conducted a cross-sectional study across random time blocks from May to August 2012 among Guyanese emergency department patients without a diagnosis of diabetes. Health literacy was assessed by the Single Item Literacy Screener (SILS, range 1-5); low health literacy was defined as SILS ≥ 3. We examined the relationships among health literacy, random blood glucose (RBG), and point-of-care glycated hemoglobin (HbA1c). Results Of the 228 enrolled patients, 125 (54%) were female, median age was 43 years (interquartile range 38 to 53), mean body mass index (BMI) was 25.6 kg/m2 (standard deviation 6.8 kg/m2), and 103 (45.2%) had low health literacy. The receiver operating characteristic area under the curve for RBG to detect elevated HbA1c (≥48mmol/mol) was 0.94 (95% CI: 0.91-0.97). After adjustment for age, sex, BMI, ethnicity, and education, the odds of having HbA1c ≥ 48 mmol/mol, consistent with undiagnosed diabetes, rose with decreasing health literacy (OR 2.2, 95% CI 1.2-3.8, p = 0.007, per point decrease in literacy). Conclusion This pilot study of Guyanese emergency department patients without diagnosed diabetes found that low health literacy was common and was associated with higher HbA1c and random blood glucose.

Antioxidants, particularly carotenoids and tocopherols, may protect against cardiovascular disease. The objective of this study was to determine whether dietary and adipose tissue carotenoids and tocopherols are associated with the risk of myocardial infarction (MI). Cases (n = 1456) of a first acute MI were identified and matched by age, sex, and residence to randomly selected population controls (n = 1456) living in Costa Rica. Carotenoids and tocopherols were measured in adipose tissue using HPLC. Dietary intake was assessed using a validated FFQ. Anthropometrical and lifestyle data were collected using an interviewer-administered questionnaire. Subjects were distributed into quintiles of intake or adipose tissue concentration of carotenoids or tocopherols. The lowest quintile was used as the referent in conditional logistic regression analyses. Adipose tissue beta-carotene showed a significant inverse relation with MI risk; the odds ratio (OR) comparing the highest to the lowest quintile was 0.70 (95% CI: 0.51-0.96, P for trend = 0.02). Intake of fruits and vegetables that are rich in beta-carotene was also inversely associated with the risk of MI (OR = 0.74; CI: 0.54-1.01, P for trend = 0.09). In contrast, lutein + zeaxanthin in adipose tissue (OR = 1.46; CI: 1.05-2.05, P for trend = 0.02) and diet (OR = 1.18; CI: 0.88-1.57, P for trend = 0.02) was positively associated with MI risk. MI risk was not associated with any of the other carotenoids or tocopherols in the diet or adipose tissue. Thus, the inverse association between beta-carotene and MI risk suggests that beta-carotene protects against MI or it is a marker of some protective factor in foods containing beta-carotene. The mechanism underlying the positive association between lutein + zeaxanthin and the risk of MI warrants investigation.

Trans-fatty acid intake is associated with coronary heart disease (CHD), but the atherogenic potential of individual trans-fatty acids (FA) from partially hydrogenated oils (18:1 and 18:2) or meat and dairy products (16:1 and 18:1) is unclear. Incident cases (n = 482) of a first nonfatal myocardial infarction (MI) were matched with population controls (n = 482) for age, gender and area of residence, all living in Costa Rica. Trans-FA in adipose tissue samples were assessed by gas chromatography. Odds ratios (OR) and 95% confidence intervals were calculated from conditional logistic regression models. Total adipose tissue trans-fat was positively associated with risk of MI. After adjusting for established risk factors and other confounders, the OR by quintiles of total trans-fat were 1.00, 1.34, 2.05, 2.22 and 2.94 (P-test for trend < 0.01). This association was attributed mainly to 18:2 trans-FA that were abundant in both adipose tissue and in partially hydrogenated soybean oil, margarines and baked products used by this population; OR = 1.00, 0.96, 2.09, 3.51 and 5.05 (P-test for trend < 0.001). Adipose tissue 16:1 trans-FA were also associated with MI; OR = 1.00, 1.57, 1.39, 1.34 and 2.58 (P-test for trend < 0.05). An association with 18:1 trans-FA was not detected. High 18:2 trans-FA in adipose tissue are associated with increased risk of MI. Because the use of hydrogenated oils is increasing worldwide, consumers should be aware of the harmful effects of products containing partially hydrogenated oils.

Known genetic susceptibility loci for type 2 diabetes (T2D) explain only a small proportion of heritable T2D risk. We hypothesize that DNA methylation patterns may contribute to variation in diabetes-related risk factors, and this epigenetic variation across the genome can contribute to the missing heritability in T2D and related metabolic traits. We conducted an epigenome-wide association study for fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) among 837 nondiabetic participants in the Genetics of Lipid Lowering Drugs and Diet Network study, divided into discovery (N = 544) and replication (N = 293) stages. Cytosine guanine dinucleotide (CpG) methylation at ∼470,000 CpG sites was assayed in CD4+ T cells using the Illumina Infinium HumanMethylation 450 Beadchip. We fit a mixed model with the methylation status of each CpG as the dependent variable, adjusting for age, sex, study site, and T-cell purity as fixed-effects and family structure as a random-effect. A Bonferroni corrected P value of 1.1 × 10−7 was considered significant in the discovery stage. Significant associations were tested in the replication stage using identical models. Methylation of a CpG site in ABCG1 on chromosome 21 was significantly associated with insulin (P = 1.83 × 10−7) and HOMA-IR (P = 1.60 × 10−9). Another site in the same gene was significant for HOMA-IR and of borderline significance for insulin (P = 1.29 × 10−7 and P = 3.36 × 10−6, respectively). Associations with the top two signals replicated for insulin and HOMA-IR (P = 5.75 × 10−3 and P = 3.35 × 10−2, respectively). Our findings suggest that methylation of a CpG site within ABCG1 is associated with fasting insulin and merits further evaluation as a novel disease risk marker.

Background and aims In vitro studies suggest that low density lipoprotein receptor-related protein 1 (LRP1) plays a role in the secondary uptake of chylomicrons. In addition, in vivo studies using LRP-1 knockout mice show these animals exhibit delayed chylomicron clearance. Whether this is true in humans is unknown. We aimed to determine whether genetic variants in LRP-1 are associated with postprandial chylomicron uptake in humans given an oral fat challenge. Methods and results As many as 817 men and women (mean age +/− standard deviation = 48.4 +/− 16.4 years) forming the study population for the Genetics of Lipid Lowering Drugs Network (GOLDN) study ingested an oral fat load of 700 kilocalories per m 2 of body surface area at 83% fat, after an 8-h fast. Chylomicrons were measured by nuclear resonance spectroscopy (NMR) at fasting, and 3.5 and 6 h after the meal. 26 Single nucleotide polymorphisms (SNPs) in the LRP-1 gene were genotyped on the Affymetrix 6.0 array. Chylomicrons were, as expected, zero at fasting. Mixed linear models adjusted for age, sex, study site and pedigree tested for associations between LRP-1 SNPs and changes in chylomicron concentrations 3.5–6 h. A gene-based test across all 26 SNPs was conducted which corrected for the linkage disequilibrium (LD) between SNPs. 11 LRP-1 SNPs were significantly associated with the change in chylomicron concentration correction for multiple testing ( Q P = 0.01). Conclusion These results require replication but strongly indicate the role of LRP1 in postprandial lipoprotein uptake and/or clearance. Clinical trial registration no NCT00083369.

Genotype does not change over the life course and may thus facilitate earlier identification of individuals at high risk for type 2 diabetes. We hypothesised that a genotype score predicts incident type 2 diabetes from young adulthood and improves diabetes prediction models based on clinical risk factors alone.The Coronary Artery Risk Development in Young Adults (CARDIA) study followed young adults (aged 18-30 years, mean age 25) serially into middle adulthood. We used Cox regression to build nested prediction models for incident type 2 diabetes based on clinical risk factors assessed in young adulthood (age, sex, race, parental history of diabetes, BMI, mean arterial pressure, fasting glucose, HDL-cholesterol and triacylglyercol), without and with a 38-variant genotype score. Models were compared with C statistics and continuous net reclassification improvement indices (NRI).Of 2,439 participants, 830 (34%) were black and 249 (10%) had a BMI ≥ 30 kg/m(2) at baseline. Over a mean 23.9 years of follow-up, 215 (8.8%) participants developed type 2 diabetes. The genotype score significantly predicted incident diabetes in all models, with an HR of 1.08 per risk allele (95% CI 1.04, 1.13) in the full model. The addition of the score to the full model modestly improved reclassification (continuous NRI 0.285; 95% CI 0.126, 0.433) but not discrimination (C statistics 0.824 and 0.829 in full models with and without score). Race-stratified analyses were similar.Knowledge of genotype predicts type 2 diabetes over 25 years in white and black young adults but may not improve prediction over routine clinical measurements.

Background Trans fatty acids (TFA) lower HDL and increase triglyceride concentrations while polyunsaturated fatty acids (PUFA) lower triglycerides and may decrease HDL concentrations. The effect of the interaction between trans fat and PUFA on lipids is uncertain. Methods Men and women (n = 1032) in the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) study were included. Fatty acids in erythrocyte membranes were measured with gas chromatography while data on potential confounders were obtained from questionnaires. To test the interaction between total erythrocyte PUFA (ePUFA) and TFA (eTFA) on lipid concentrations we distributed eTFA into tertiles and dichotomized ePUFA at the median concentration. Results For the 1st, 2nd and 3rd tertiles of eTFA, multivariate-adjusted means±s.e.m for HDL were 46.2±1.1, 46.3±1.1 and 45.5±1.0 mg/dL among those with low ePUFA, respectively, while they were 50.0±1.1, 46.9±1.1 and 44.7±1.1 mg/dL among those with high ePUFA, respectively (P for interaction = 0.01). For the 1st, 2nd and 3rd tertiles of eTFA, multivariate-adjusted means±s.e.m for triglycerides were 178.6±11.3, 144.7±10.9 and 140.8±10.6, respectively, among those with low ePUFA, while they were 133.8±11.3, 145.7±10.9 and 149.3±11.5, respectively, among those with high ePUFA (P for interaction = 0.005). Results for VLDL were similar to those for triglycerides. No significant interactions were observed for LDL or total cholesterol. Conclusions The relation between trans fat and HDL, VLDL and triglycerides may depend on PUFA. The benefit of avoiding trans fat may be greater among individuals with higher PUFA intake. Supplementation with PUFA among individuals with relatively high trans fat intake may have limited benefits on lipid profiles.

Evidence that physical activity (PA) modulates the association between the fat mass and obesity-associated gene (FTO) and BMI is emerging; however, information about dietary factors modulating this association is scarce. We investigated whether fat and carbohydrate intake modified the association of FTO gene variation with BMI in two populations, including participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n = 1069) and in the Boston Puerto Rican Health (BPRHS) study (n = 1094). We assessed energy, nutrient intake, and PA using validated questionnaires. Genetic variability at the FTO locus was characterized by polymorphisms rs9939609 (in the GOLDN) and rs1121980 (in the GOLDN and BPRHS). We found significant interactions between PA and FTO on BMI in the GOLDN but not in the BPRHS. We found a significant interaction between SFA intake and FTO on BMI, which was stronger than that of total fat and was present in both populations (P-interaction = 0.007 in the GOLDN and P-interaction = 0.014 in BPRHS for categorical; and P-interaction = 0.028 in the GOLDN and P-interaction = 0.041 in BPRHS for continuous SFA). Thus, homozygous participants for the FTO-risk allele had a higher mean BMI than the other genotypes only when they had a high-SFA intake (above the population mean: 29.7 ± 0.7 vs. 28.1 ± 0.5 kg/m²; P = 0.037 in the GOLDN and 33.6. ± 0.8 vs. 31.2 ± 0.4 kg/m²; P = 0.006 in BPRHS). No associations with BMI were found at lower SFA intakes. We found no significant interactions with carbohydrate intake. In conclusion, SFA intake modulates the association between FTO and BMI in American populations.

Background The presence of smaller low-density lipoproteins (LDL) has been associated with atherosclerosis risk, and the insulin resistance (IR) underlying the metabolic syndrome (MetS). In addition, some research has supported the association of very low-, low- and high-density lipoprotein (VLDL HDL) particle diameters with components of the metabolic syndrome (MetS), although this has been the focus of less research. We aimed to explore the relationship of VLDL, LDL and HDL diameters to MetS and its features, and by clustering individuals by their diameters of VLDL, LDL and HDL particles, to capture information across all three fractions of lipoprotein into a unified phenotype. Methods We used nuclear magnetic resonance spectroscopy measurements on fasting plasma samples from a general population sample of 1,036 adults (mean ± SD, 48.8 ± 16.2 y of age). Using latent class analysis, the sample was grouped by the diameter of their fasting lipoproteins, and mixed effects models tested whether the distribution of MetS components varied across the groups. Results Eight discrete groups were identified. Two groups (N = 251) were enriched with individuals meeting criteria for the MetS, and were characterized by the smallest LDL/HDL diameters. One of those two groups, one was additionally distinguished by large VLDL, and had significantly higher blood pressure, fasting glucose, triglycerides, and waist circumference (WC; P < .001). However, large VLDL, in the absence of small LDL and HDL particles, did not associate with MetS features. These associations held after additionally controlling for VLDL, LDL and HDL particle concentrations. Conclusions While small LDL diameters remain associated with IR and the MetS, the occurrence of these in conjunction with a shift to overall larger VLDL diameter may identify those with the highest fasting glucose, TG and WC within the MetS. If replicated, the association of this phenotype with more severe IR-features indicated that it may contribute to identifying of those most at risk for incident type II diabetes and cardiometabolic disease.

Background Postprandial lipemia (PPL) is likely a risk factor for cardiovascular disease but these changes have not been well described and characterized in a large cohort. We assessed acute changes in the size and concentration of total and subclasses of LDL, HDL, and VLDL particles in response to a high-fat meal. Participants (n = 1048) from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) Study who ingested a high-fat meal were included in this analysis. Lipids were measured at 0 hr (fasting), 3.5 hr, and 6 hr after a standardized fat meal. Particle size distributions were determined using nuclear magnetic resonance spectroscopy. Analyses were stratified by baseline triglycerides (normal vs. elevated) and gender. The effect of PPL on changes in lipoprotein subclasses was assessed using repeated measures ANOVA. Results Postprandially, LDL-C, HDL-C, VLDL-C, and triglycerides increased regardless of baseline triglyceride status, with the largest increases in VLDL-C and TG; however, those with elevated triglycerides demonstrated larger magnitude of response. Total LDL particle number decreased over the 6-hour time interval, mostly from a decrease in the number of small LDL particles. Similarly, total VLDL particle number decreased due to reductions in medium and small VLDL particles. Large VLDL particles and chylomicrons demonstrated the largest increase in concentration. HDL particles demonstrated minimal overall changes in total particle number. Conclusions We have characterized the changes in LDL and VLDL particle number, and their subclass patterns following a high-fat meal.

Background C-reactive protein (CRP) is positively associated with risk for cardiovascular disease and all-cause mortality. Some but not all randomized and non-randomized clinical trials found significant associations between fenofibrate therapy and CRP but the direction and magnitude of the association varied across studies. The duration of treatment, patient populations and sample sizes varied greatly, and most short-term studies (i.e., ≤ 12 weeks) had fewer than 50 patients. In this study we meta-analyzed randomized clinical trials to determine the short-term effect of fenofibrate on CRP. Methods Two reviewers independently searched PubMed and other online databases for short-term randomized clinical trials that reported CRP concentrations before and after fenofibrate treatment. Of the 81 studies examined, 14 studies with 540 patients were found eligible. Data for the change in CRP and corresponding measures of dispersion were extracted for use in the meta-analysis. Results The weighted mean CRP concentrations before and after fenofibrate therapy were 2.15 mg/L and 1.53 mg/L (-28.8% change), respectively. Inverse-variance weighted random effects meta-analysis revealed that short-term fenofibrate treatment significantly lowers CRP by 0.58 mg/L (95% CI: 0.36-0.80). There was significant heterogeneity between studies (Q statistic = 64.5, P< 0.0001, I2 = 79.8%). There was no evidence of publication bias and sensitivity analysis revealed that omitting any of the 14 studies did not lead to a different conclusion from the overall meta-analysis result. Conclusion Short-term treatment with fenofibrate significantly lowers CRP concentration. Randomized trials that will recruit patients based with high baseline CRP concentrations and with change in CRP as a primary outcome are needed.

We aimed to investigate the relationship between dietary saturated fat on fasting triglyceride (TG) and cholesterol levels, and any mediation of this relationship by dietary carbohydrate intake. Men and women in the NHLBI Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) study ( n = 1036, mean age ± SD = 49 ± 16 y) were included. Mixed linear models were run with saturated fat as a predictor variable and fasting TG, very low density lipoprotein cholesterol (VLDL-C), low density cholesterol (LDL-C) and high density cholesterol (HDL-C) as separate outcome variables. Subsequent models were run which included dietary carbohydrate as a predictor variable, and an interaction term between saturated fat and carbohydrate. All models controlled for age, sex, BMI, blood pressure and dietary covariates. In models that included only saturated fat as a predictor, saturated fat did not show significant associations with fasting lipids. When carbohydrate intake and an interaction term between carbohydrates and saturated fat intake was included, carbohydrate intake did not associate with lipids, but there was an inverse relationship between saturated fat intake and VLDL-C ( P = 0.01) with a significant interaction ( P = 0.01) between saturated fat and carbohydrate with regard to fasting VLDL-C concentrations. Similar results were observed for fasting TG levels. We conclude that, when controlling for carbohydrate intake, higher saturated fat was associated with lower VLDL-C and TGs. This was not the case at higher intakes of carbohydrate. This has important implications for dietary advice aimed at reducing TG and VLDL-C levels.