Th2 cell clonal expansion at diagnosis in human type 1 diabetes.

Soon after diagnosis with type 1 diabetes (T1D), many patients experience a period of partial remission. A longer partial remission is associated with a better response to treatment, but the mechanism is not known. The frequency of CD4+CD25+CD127hi (127-hi) cells, a cell subset with an anti-inflammatory Th2 bias, correlates positively with length of partial remission. The purpose of this study was to further characterize the nature of the Th2 bias in 127-hi cells. Single cell RNA sequencing paired with TCR sequencing of sorted 127-hi memory cells identifies clonally expanded Th2 clusters in 127-hi cells from T1D, but not from healthy donors. The Th2 clusters express GATA3, GATA3-AS1, PTGDR2, IL17RB, IL4R and IL9R. The existence of 127-hi Th2 cell clonal expansion in T1D suggests that disease factors may induce clonal expansion of 127-hi Th2 cells that prolong partial remission and delay disease progression.

Endogenous Aß peptide promote Aß oligomerization tendency of spiked synthetic Aß in Alzheimer's disease plasma.

Alzheimer's disease (AD) is the most common form of age-associated dementia. Several studies have predicted that AD is caused by the production and deposition of the ß-amyloid peptide (Aß) in the brain, which is one of pathologic hallmarks of AD. In particular, Aß oligomers are reportedly the most toxic and pathogenic of other peptide forms. We previously developed Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß), a technique for measuring Aß oligomerization in plasma to diagnose AD. Here, we clarified the molecular sizes of oligomers that can be detected by the MDS and investigated differences in plasma spiking with a synthetic Aß peptide in the plasma of AD patients and individuals with non-AD neurological conditions. To determine Aß oligomer sizes detectable by MDS, size exclusion chromatography (SEC) was first performed on incubated samples of synthetic Aß42 peptides. As a result, no MDS signals were observed for the Aß42 monomer fractions, but strong signals were found for oligomers of 7-35-mers long. Also, an amplified luminescent proximity homogeneous assay-linked immunoassay (AlphaLISA) was used to confirm that synthetic Aß peptides not only recruited endogenous Aß in plasma but also induced significantly stronger seeding in AD plasma than in healthy control plasma. In addition, the absence of the MDS signals in Aß-depleted plasma confirmed that the increased oligomerization tendency in AD plasma is dependent on the presence of endogenous Aß in plasma. Therefore, the MDS-OAß measurement of oligomerization differences in plasma after incubation with spiked synthetic Aß peptides has significant potential in AD diagnosis.

A Novel Interdisciplinary Iterative Approach for Optimizing the Electronic Health Record to Improve Perioperative Efficiency.

OBJECTIVE: We present a holistic perioperative optimization approach led by a CI team with the goal to optimize the workflow within our EHR, improve operative room metrics and user satisfaction. SUMMARY OF BACKGROUND DATA: The EHR has become integral to perioperative care. Many approaches are utilized to improve performance including systems-based approaches, process redesign, lean methodology, checklists, root cause analysis, and parallel processing. Although most reports describe strategies improving day or surgery productivity, few include perioperative interventions to improve efficiencies. METHODS: An interdisciplinary CI team consisting of clinicians, informatics specialists, and analysts spent 6 weeks assessing users and optimizing all perioperative areas (scheduling, day of surgery, postop discharge/admission). Elbow-to-elbow retraining and simultaneous content development was performed utilizing an Agile workflow process optimization with the Scrum framework. This iterative approach averaged 1 week from build to change implementation. Pre/post optimization surveys were sent. RESULTS: Two hundred forty-two perioperative enhancements were completed. While most impacted documentation, all areas were enhanced including billing, reporting, registration, device integration, scheduling, central supply, and so on. FCOTS improved from <70% to >85% and total delay was halved. These parameters were consistently sustained for over 1 year after the 6-week optimization. While only 5% of pre-optimization users agreed to proficiency in the EHR system, this improved to 70% post-optimization. Furthermore, EHR confidence and acceptance improved from 40% to 90%. CONCLUSIONS: To improve workflow efficiency, all who contribute to the perioperative process must be assessed. This IT driven initiative resulted in improved FCOTS, perioperative workflows, and user satisfaction.

Teratomas of the cranial vault: a systematic analysis of clinical outcomes stratified by histopathological subtypes.

BACKGROUND: Teratomas of the cranial vault are divided into histopathological subtypes and grouped by prognoses: mature (good prognosis), mixed/malignant and immature teratomas (intermediate prognosis). This schema also includes non-teratomatous tumors. The authors of this study sought to elucidate histologically dependent predictors of survival and further clarify the classification system of intracranial teratomas. METHODS: We performed a systematic analysis of the published literature to identify studies describing patients with intracranial teratomas diagnosed with magnetic resonance imaging (MRI) and presenting definite information on histologies, therapies, and outcomes at a minimum follow-up of 2 years. Disease-free (DFS) and overall survival (OS) were evaluated. RESULTS: A total of 18 articles comprised of 134 patients were included. On univariate analysis, male sex and gross-total resection (GTR) were associated with high mean DFS (p = 0.0362 and p < 0.0001, respectively). On multivariate analysis, mature teratomas located in the pineal, and those having undergone subtotal resection (STR) demonstrated high mean OS (p = 0.0023 and p = 0.0044, respectively). Mature and mixed/malignant suprasellar teratomas had equally higher mean OS versus immature suprasellar teratomas (p < 0.0001). Mature and immature teratomas treated with adjuvant therapy had significantly higher mean OS compared to those managed with surgery alone (p = 0.0421 and p = 0.0423, respectively). Males with immature teratomas had the highest mean OS (p < 0.0001). Immature teratomas managed with surgery alone had higher mean DFS, but lower mean OS, compared to those treated with adjuvant therapy (p = 0.0176 and p = 0.0423, respectively). CONCLUSIONS: Our data highlight the divergent nature of the different histopathological subtypes of teratomas, and suggest that survival outcomes are multifactorial. Specifically, male sex, pineal, suprasellar, GTR, and STR were dependent predictors of OS, while histopathology was an independent predictor of OS.

Epigenetic regulation of COL15A1 in smooth muscle cell replicative aging and atherosclerosis.

Smooth muscle cell (SMC) proliferation is a hallmark of vascular injury and disease. Global hypomethylation occurs during SMC proliferation in culture and in vivo during neointimal formation. Regardless of the programmed or stochastic nature of hypomethylation, identifying these changes is important in understanding vascular disease, as maintenance of a cells' epigenetic profile is essential for maintaining cellular phenotype. Global hypomethylation of proliferating aortic SMCs and concomitant decrease of DNMT1 expression were identified in culture during passage. An epigenome screen identified regions of the genome that were hypomethylated during proliferation and a region containing Collagen, type XV, alpha 1 (COL15A1) was selected by 'genomic convergence' for characterization. COL15A1 transcript and protein levels increased with passage-dependent decreases in DNA methylation and the transcript was sensitive to treatment with 5-Aza-2'-deoxycytidine, suggesting DNA methylation-mediated gene expression. Phenotypically, knockdown of COL15A1 increased SMC migration and decreased proliferation and Col15a1 expression was induced in an atherosclerotic lesion and localized to the atherosclerotic cap. A sequence variant in COL15A1 that is significantly associated with atherosclerosis (rs4142986, P = 0.017, OR = 1.434) was methylated and methylation of the risk allele correlated with decreased gene expression and increased atherosclerosis in human aorta. In summary, hypomethylation of COL15A1 occurs during SMC proliferation and the consequent increased gene expression may impact SMC phenotype and atherosclerosis formation. Hypomethylated genes, such as COL15A1, provide evidence for concomitant epigenetic regulation and genetic susceptibility, and define a class of causal targets that sit at the intersection of genetic and epigenetic predisposition in the etiology of complex disease.

Whole-exome sequencing links a variant in DHDDS to retinitis pigmentosa.

Increasingly, mutations in genes causing Mendelian disease will be supported by individual and small families only; however, exome sequencing studies have thus far focused on syndromic phenotypes characterized by low locus heterogeneity. In contrast, retinitis pigmentosa (RP) is caused by >50 known genes, which still explain only half of the clinical cases. In a single, one-generation, nonsyndromic RP family, we have identified a gene, dehydrodolichol diphosphate synthase (DHDDS), demonstrating the power of combining whole-exome sequencing with rapid in vivo studies. DHDDS is a highly conserved essential enzyme for dolichol synthesis, permitting global N-linked glycosylation. Zebrafish studies showed virtually identical photoreceptor defects as observed with N-linked glycosylation-interfering mutations in the light-sensing protein rhodopsin. The identified Lys42Glu variant likely arose from an ancestral founder, because eight of the nine identified alleles in 27,174 control chromosomes were of confirmed Ashkenazi Jewish ethnicity. These findings demonstrate the power of exome sequencing linked to functional studies when faced with challenging study designs and, importantly, link RP to the pathways of N-linked glycosylation, which promise new avenues for therapeutic interventions.

Impact of CMS coverage decision on access to transcatheter aortic valve replacement.

OBJECTIVES: To assess the impact of the Centers for Medicare and Medicaid Services (CMS) national coverage determination (NCD) on access for patients with aortic stenosis (AS) with transcatheter aortic valve replacement (TAVR) in a tertiary care center. BACKGROUND: TAVR has given hope to patients with AS who are deemed inoperable. The effects of the NCD on access to patients with AS has not been evaluated. MATERIALS AND METHODS: A total of 94 inoperable AS patients were evaluated and treated from December 2011 through June of 2012 with TAVR. Patients who underwent transfemoral (TF) vs. non-TF access were compared. The CMS NCD was released on May 1, 2012 and on July 1, 2012, the nontransfemoral access program was put on hold due to lack of reimbursement. RESULTS: Patients in the TF (n = 33) and non-TF access (n = 61) groups were similar in age (85.2 ± 6.3 vs. 84.8 ± 6.6 P = 0.74) and STS mortality (9.38 ± 5.33 vs. 7.91 ± 3.69, P = 0.074). The iliofemoral arteries were larger diameter in the TF group (7.72 ± 1.49 vs. 6.21 ± 1.78, P < 0.001) and males (7.39 ± 1.81 vs. 6.1 ± 1.61 P < 0.001). More women underwent valve implantation via non-TF access (73 vs. 23%, P = 0.03). After the NCD, 21 patients who previously qualified for non-TF TAVR would not be reimbursed by CMS. Four died soon after. CONCLUSIONS: After the NCD, the proportion of inoperable patients with severe AS that can be treated with TAVR was greatly reduced due the lack of reimbursement for TAVR via non-TF access. This effect is particularly pronounced in women. © 2014 Wiley Periodicals, Inc.

Graphene for true Ohmic contact at metal-semiconductor junctions.

The rectifying Schottky characteristics of the metal-semiconductor junction with high contact resistance have been a serious issue in modern electronic devices. Herein, we demonstrated the conversion of the Schottky nature of the Ni-Si junction, one of the most commonly used metal-semiconductor junctions, into an Ohmic contact with low contact resistance by inserting a single layer of graphene. The contact resistance achieved from the junction incorporating graphene was about 10(-8) ~ 10(-9) Ω cm(2) at a Si doping concentration of 10(17) cm(-3).

Genomic signatures of a global fitness index in a multi-ethnic cohort of women.

The rates of obesity and sedentary lifestyle are on a dramatic incline, with associated detrimental health effects among women in particular. Although exercise prescriptions are useful for overcoming these problems, success can be hampered by differential responsiveness among individuals in cardiovascular fitness indices (i.e. improvements in strength, lipids, VO(2) max). Genomic factors appear to play an important role in determining this inter-individual variation. We performed microarray analyses on mRNA in whole blood from 60 sedentary women from a multi-ethnic cohort who underwent 12 weeks of exercise, to identify gene subsets that were differentially expressed between individuals who experienced the greatest and least improvements in fitness. We identified 43 transcripts in 39 unique genes (FDR<10%; FC>1.5) whose expression increased the most in "high" versus "low" pre-menopausal female responders. These 39 genes were enriched in six biological pathways, including oxidative phosphorylation (p = 8.08 × 10(-3)). Several of the 39 genes (i.e. TIGD7, UQCRH, PSMA6, WDR12, TFB2M, USP15) have previously reported associations with fitness-related phenotypes. In summary, we identified gene signatures based on mRNA analysis that define responsiveness to exercise in a largely minority-based female cohort. Importantly, this study validates several genes/pathways previously associated with exercise responsiveness and extends these findings with additional novel genes.

Synthesis and Biological Evaluation of a Library of Sulfonamide Analogs of Memantine to Target Glioblastoma.

A library of 34 lipophilic sulfonamides based upon the memantine core has been synthesized to identify potential drug candidates to cross the blood-brain barrier and target glioblastoma. The library was screened for in vitro activity against 4 mammalian cell lines, including U-87 (glioblastoma). Additional synthetic variation of the active compounds has validated the importance of specific regions of the pharmacophore, with the sulfonamide functionality and S-aryl unit displaying the most significant impact. In silico investigations suggest the active compounds might target DDR1 or RET proteins. The investigation has resulted in several compounds that warrant further development for lead optimization.

A fast, high-endurance and scalable non-volatile memory device made from asymmetric Ta2O(5-x)/TaO(2-x) bilayer structures.

Numerous candidates attempting to replace Si-based flash memory have failed for a variety of reasons over the years. Oxide-based resistance memory and the related memristor have succeeded in surpassing the specifications for a number of device requirements. However, a material or device structure that satisfies high-density, switching-speed, endurance, retention and most importantly power-consumption criteria has yet to be announced. In this work we demonstrate a TaO(x)-based asymmetric passive switching device with which we were able to localize resistance switching and satisfy all aforementioned requirements. In particular, the reduction of switching current drastically reduces power consumption and results in extreme cycling endurances of over 10(12). Along with the 10 ns switching times, this allows for possible applications to the working-memory space as well. Furthermore, by combining two such devices each with an intrinsic Schottky barrier we eliminate any need for a discrete transistor or diode in solving issues of stray leakage current paths in high-density crossbar arrays.

Atherosclerosis, inflammation, genetics, and stem cells: 2012 update.

Atherosclerosis is a peculiar form of inflammation triggered by cholesterol-rich lipoproteins and other noxious factors such as cigarette smoke, diabetes mellitus, and hypertension. Genetics also play an important role in the disease, accounting for about 40% of the risk. Of surprise in recent years of post-human genome sequencing, atherosclerosis-relevant genes discovered by non-biased techniques (ie, genome-wide association studies), did not rehash previously suspected pathways of lipid metabolism, diabetes, or hypertension. Instead these studies highlighted genes relevant to mechanisms of inflammation and stem cell biology. Only a minority of implicated genes were linked to lipid and other cardiac risk factor genes. Although such findings do not contradict the fact that atherosclerosis is triggered and exacerbated by elevated lipids, atherosclerosis "new genes" suggest that the mechanism responsible for the development of arterial lesions is more complex than a simple response to injury, where injury is necessary, but perhaps not sufficient, for disease progression.

Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5.

BACKGROUND: Coronary artery disease (CAD), and one of its intermediate risk factors, dyslipidemia, possess a demonstrable genetic component, although the genetic architecture is incompletely defined. We previously reported a linkage peak on chromosome 5q31-33 for early-onset CAD where the strength of evidence for linkage was increased in families with higher mean low density lipoprotein-cholesterol (LDL-C). Therefore, we sought to fine-map the peak using association mapping of LDL-C as an intermediate disease-related trait to further define the etiology of this linkage peak. The study populations consisted of 1908 individuals from the CATHGEN biorepository of patients undergoing cardiac catheterization; 254 families (N = 827 individuals) from the GENECARD familial study of early-onset CAD; and 162 aorta samples harvested from deceased donors. Linkage disequilibrium-tagged SNPs were selected with an average of one SNP per 20 kb for 126.6-160.2 MB (region of highest linkage) and less dense spacing (one SNP per 50 kb) for the flanking regions (117.7-126.6 and 160.2-167.5 MB) and genotyped on all samples using a custom Illumina array. Association analysis of each SNP with LDL-C was performed using multivariable linear regression (CATHGEN) and the quantitative trait transmission disequilibrium test (QTDT; GENECARD). SNPs associated with the intermediate quantitative trait, LDL-C, were then assessed for association with CAD (i.e., a qualitative phenotype) using linkage and association in the presence of linkage (APL; GENECARD) and logistic regression (CATHGEN and aortas). RESULTS: We identified four genes with SNPs that showed the strongest and most consistent associations with LDL-C and CAD: EBF1, PPP2R2B, SPOCK1, and PRELID2. The most significant results for association of SNPs with LDL-C were: EBF1, rs6865969, p = 0.01; PPP2R2B, rs2125443, p = 0.005; SPOCK1, rs17600115, p = 0.003; and PRELID2, rs10074645, p = 0.0002). The most significant results for CAD were EBF1, rs6865969, p = 0.007; PPP2R2B, rs7736604, p = 0.0003; SPOCK1, rs17170899, p = 0.004; and PRELID2, rs7713855, p = 0.003. CONCLUSION: Using an intermediate disease-related quantitative trait of LDL-C we have identified four novel CAD genes, EBF1, PRELID2, SPOCK1, and PPP2R2B. These four genes should be further examined in future functional studies as candidate susceptibility loci for cardiovascular disease mediated through LDL-cholesterol pathways.

Discovery of biomarker candidates for coronary artery disease from an APOE-knock out mouse model using iTRAQ-based multiplex quantitative proteomics.

Due to the lack of precise markers indicative of its occurrence and progression, coronary artery disease (CAD), the most common type of heart diseases, is currently associated with high mortality in the United States. To systemically identify novel protein biomarkers associated with CAD progression for early diagnosis and possible therapeutic intervention, we employed an iTRAQ-based quantitative proteomic approach to analyze the proteome changes in the plasma collected from a pair of wild-type versus apolipoprotein E knockout (APOE(-/-) ) mice which were fed with a high fat diet. In a multiplex manner, iTRAQ serves as the quantitative 'in-spectra' marker for 'cross-sample' comparisons to determine the differentially expressed/secreted proteins caused by APOE knock-out. To obtain the most comprehensive proteomic data sets from this CAD-associated mouse model, we applied both MALDI and ESI-based mass spectrometric (MS) platforms coupled with two different schemes of multidimensional liquid chromatography (2-D LC) separation. We then comparatively analyzed a series of the plasma samples collected at 6 and 12 wk of age after the mice were fed with fat diets, where the 6- or 12-wk time point represents the early or intermediate phase of the fat-induced CAD, respectively. We then categorized those proteins showing abundance changes in accordance with APOE depletion. Several proteins such as the γ and ß chains of fibrinogen, apolipoprotein B, apolipoprotein C-I, and thrombospondin-4 were among the previously known CAD markers identified by other methods. Our results suggested that these unbiased proteomic methods are both feasible and a practical means of discovering potential biomarkers associated with CAD progression.

Polymorphic variants in tenascin-C (TNC) are associated with atherosclerosis and coronary artery disease.

Tenascin-C (TNC) is an extracellular matrix protein implicated in biological processes important for atherosclerotic plaque development and progression, including smooth muscle cell migration and proliferation. Previously, we observed differential expression of TNC in atherosclerotic aortas compared with healthy aortas. The goal of this study was to investigate whether common genetic variation within TNC is associated with risk of atherosclerosis and coronary artery disease (CAD) in three independent datasets. We genotyped 35 single nucleotide polymorphisms (SNPs), including 21 haplotype tagging SNPs, in two of these datasets: human aorta tissue samples (n = 205) and the CATHGEN cardiovascular study (n = 1,325). Eleven of these 35 SNPs were then genotyped in a third dataset, the GENECARD family study of early-onset CAD (n = 879 families). Three SNPs representing a block of linkage disequilibrium, rs3789875, rs12347433, and rs4552883, were significantly associated with atherosclerosis in multiple datasets and demonstrated consistent, but suggestive, genetic effects in all analyses. In combined analysis rs3789875 and rs12347433 were statistically significant after Bonferroni correction for 35 comparisons, p = 2 × 10(-6) and 5 × 10(-6), respectively. The SNP rs12347433 is a synonymous coding SNP and may be biologically relevant to the mechanism by which tenascin-C influences the pathophysiology of CAD and atherosclerosis. This is the first report of genetic association between polymorphisms in TNC and atherosclerosis or CAD.

Metallic nanowire-graphene hybrid nanostructures for highly flexible field emission devices.

We report a simple but efficient method to prepare metallic nanowire-graphene (MN-G) hybrid nanostructures at a low temperature and show its application to the fabrication of flexible field emission devices. In this method, a graphene layer was transferred onto an anodic alumina oxide template, and vertically aligned Au nanowires were grown on the graphene surface via electrodeposition method. As a proof of concept, we demonstrated the fabrication of flexible field emission devices, where the MN-G hybrid nanostructures and another graphene layer on PDMS substrates were utilized as a cathode and an anode for highly flexible devices, respectively. Our field emission device exhibited stable and high field emission currents even when bent down to the radius of curvature of 25 mm. This MN-G hybrid nanostructure should prove tremendous flexibility for various applications such as bio-chemical sensors, field emission devices, pressure sensors and battery electrodes.

Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets.

Platelet-activating factor acetylhydrolase (PLA2G7) is a potent pro- and anti-inflammatory molecule that has been implicated in multiple inflammatory disease processes, including cardiovascular disease. The goal of this study was to investigate the genetic effects of PLA2G7 on coronary artery disease (CAD) risk in two large, independent datasets with CAD. Using a haplotype tagging (ht) approach, 19 ht single nucleotide polymorphisms (SNPs) were genotyped in CATHGEN case-control samples (cases = 806 and controls = 267) and in the GENECARD Family Study (n = 1101 families, 2954 individuals). Single SNP analysis using logistic regression revealed nine SNPs with significant association in all CATHGEN subjects (P = 0.0004-0.02). CATHGEN cases were further stratified into subgroups based on age of CAD onset (AOO) and severity of disease; 599 young affecteds (YA, AOO <56) and 207 old affected (OA, AOO >56). Significant genetic effects were observed in both OA and YA (P = 0.0001-0.02). The GENECARD probands demonstrated results similar to those seen in the YA CATHGEN cases (P = 0.002-0.05). Of the 19 SNPs genotyped, 3 SNPs result in nonsynonymous coding changes (I198T, A379V and R92H). Two of the coding SNPs, R92H and A379V, constitute two of the most significantly associated SNPs, even after Bonferroni correction and appear to represent independent associations (r(2) = 0.09). Multiple additional polymorphisms in low linkage disequilibrium with these coding SNPs were also strongly associated. In summary, PLA2G7 represents an important, potentially functional candidate in the pathophysiology of CAD based on replicated associations using two independent datasets and multiple statistical approaches. Further functional studies involving a combination of risk alleles are warranted.

Genomics of premature atherosclerotic vascular disease.

Atherosclerotic vascular disease is a systemic process with a common pathophysiology but with different disease manifestations depending on the vascular site. Over the past two decades, significant efforts have gone toward determining the genomic factors contributing to atherosclerotic vascular disease. Substantial information has been generated regarding the genomics of atherosclerotic coronary heart disease, and recently, several genomic analyses have looked at the cerebrovascular and peripheral vascular beds. This article reviews genomic investigations of atherosclerotic vascular disease in the coronary, cerebrovascular, and peripheral arteries. In this review, we have tried to restrict the discussion to studies of premature atherosclerosis, particularly those using non-biased genomic techniques.

Electrical manipulation of nanofilaments in transition-metal oxides for resistance-based memory.

The fabrication of controlled nanostructures such as quantum dots, nanotubes, nanowires, and nanopillars has progressed rapidly over the past 10 years. However, both bottom-up and top-down methods to integrate the nanostructures are met with several challenges. For practical applications with the high level of the integration, an approach that can fabricate the required structures locally is desirable. In addition, the electrical signal to construct and control the nanostructures can provide significant advantages toward the stability and ordering. Through experiments on the negative resistance switching phenomenon in Pt-NiO-Pt structures, we have fabricated nanofilament channels that can be electrically connected or disconnected. Various analyses indicate that the nanofilaments are made of nickel and are formed at the grain boundaries. The scaling behaviors of the nickel nanofilaments were closely examined, with respect to the switching time, power, and resistance. In particular, the 100 nm x 100 nm cell was switchable on the nanosecond scale, making them ideal for the basis for high-speed, high-density, nonvolatile memory applications.

Social determinants of health score: does it help identify those at higher cardiovascular risk?

OBJECTIVES: Cardiovascular disease (CVD) continues to disproportionately affect disadvantaged populations, leading to calls to address social determinants of health (SDOH) as a preventive strategy. Our aim is to create a weighed SDOH score and to test the impact of each SDOH factor on the Framingham risk score (FRS) and on individual traditional CVD risk factors. STUDY DESIGN: We conducted a retrospective cohort study. METHODS: We included patients seen at a primary care clinic at UHealth/University of Miami Health System who answered a SDOH survey between September 16, 2016, and September 10, 2017. The survey included SDOH domains recommended by the American Heart Association position statement and by the National Academy of Medicine. We selected the FRS as well as all traditional CVD risk factors as our outcome metrics. RESULTS: We included 2876 patients. The mean (SD) age of our cohort was 53.8 (15.8) years, 61% were female, 9% were Black, 38% were Hispanic, and 87% reported speaking English. The statistically significant ß coefficients in the FRS model corresponded to being born outside of the United States, being a racial minority, living alone, having a high social isolation score, and having a low geocoded median household income (P < .01). Increasing quartile of SDOH score was significantly associated with higher systolic blood pressure, FRS, glycated hemoglobin, and smoking pack-years (P < .05). It was also associated with fewer minutes spent exercising weekly (P < .01). CONCLUSIONS: The addition of self-reported SDOH data has a dose effect on CVD risk factors. Future studies should address how to intervene to address social factors.