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  • 1
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    Online Resource
    Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Journal of the American Heart Association Vol. 6, No. 6 ( 2017-11-06)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 6 ( 2017-11-06)
    Abstract: Plasminogen activator inhibitor type 1 ( PAI ‐1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI ‐1 levels are associated with increased risk of coronary heart disease ( CHD ). However, it is unclear whether the association reflects a causal influence of PAI ‐1 on CHD risk. Methods and Results To evaluate the association between PAI ‐1 and CHD , we applied a 3‐step strategy. First, we investigated the observational association between PAI ‐1 and CHD incidence using a systematic review based on a literature search for PAI ‐1 and CHD studies. Second, we explored the causal association between PAI ‐1 and CHD using a Mendelian randomization approach using summary statistics from large genome‐wide association studies. Finally, we explored the causal effect of PAI ‐1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta‐analysis, the highest quantile of blood PAI ‐1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age‐ and sex‐adjusted model. The effect size was reduced in studies using a multivariable‐adjusted model (odds ratio=1.46; 95% CI : 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI ‐1 level on CHD risk (odds ratio=1.22 per unit increase of log‐transformed PAI ‐1; 95% CI : 1.01, 1.47). In addition, we also detected a causal effect of PAI ‐1 on elevating blood glucose and high‐density lipoprotein cholesterol. Conclusions Our study indicates a causal effect of elevated PAI ‐1 level on CHD risk, which may be mediated by glucose dysfunction.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.116.004918
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2653953-6
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  • 2
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    Admixture Mapping of Coronary Artery Calcified Plaque in African Americans With Type 2 Diabetes Mellitus
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Circulation: Cardiovascular Genetics Vol. 6, No. 1 ( 2013-02), p. 97-105
    Details
    In: Circulation: Cardiovascular Genetics, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 1 ( 2013-02), p. 97-105
    Abstract: The presence and severity of coronary artery calcified plaque (CAC) differs markedly between individuals of African and European descent, suggesting that admixture mapping may be informative for identifying genetic variants associated with subclinical cardiovascular disease. Methods and Results— Admixture mapping of CAC was performed in 1040 unrelated African Americans with type 2 diabetes mellitus from the African American-Diabetes Heart Study, Multi-Ethnic Study of Atherosclerosis and Family Heart Study using the Illumina custom ancestry informative marker panel. All cohorts obtained computed tomography scanning of the coronary arteries using identical protocols. For each ancestry informative marker, the probability of inheriting 0, 1, and 2 copies of a European-derived allele was determined. Linkage analysis was performed by testing for association between each ancestry informative marker using these probabilities and CAC, accounting for global ancestry, age, sex, and study. Markers on 1p32.3 in the GLIS1 gene (rs6663966, logarithm of odds [LOD]=3.7), 1q32.1 near CHIT1 (rs7530895, LOD=3.1), 4q21.2 near PRKG2 (rs1212373, LOD=3.0), and 11q25 in the OPCML gene (rs6590705, LOD=3.4) had statistically significant LOD scores, whereas markers on 8q22.2 (rs6994682, LOD=2.7), 9p21.2 (rs439314, LOD=2.7), and 13p32.1 (rs7492028, LOD=2.8) manifested suggestive evidence of linkage. These regions were uniformly characterized by higher levels of European ancestry associating with higher levels or odds of CAC. Findings were replicated in 1350 African Americans without diabetes mellitus and 2497 diabetic European Americans from Multi-Ethnic Study of Atherosclerosis and the Diabetes Heart Study. Conclusions— Fine mapping these regions will likely identify novel genetic variants that contribute to CAC and clarify racial differences in susceptibility to subclinical cardiovascular disease.
    Type of Medium: Online Resource
    ISSN: 1942-325X , 1942-3268
    URL: Article
    DOI: 10.1161/CIRCGENETICS.112.964114
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2927603-2
    detail.hit.zdb_id: 2457085-0
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  • 3
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    Occupation and the Prevalence of Respiratory Health Symptoms and Conditions : The Atherosclerosis Risk in Communities Study
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Journal of Occupational & Environmental Medicine Vol. 54, No. 2 ( 2012-02), p. 157-165
    Details
    In: Journal of Occupational & Environmental Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 2 ( 2012-02), p. 157-165
    Type of Medium: Online Resource
    ISSN: 1076-2752
    URL: Article
    DOI: 10.1097/JOM.0b013e31823e3a52
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 2070230-9
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  • 4
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    The Academic Learning Health System: A Framework for Integrating the Multiple Missions of Academic Medical Centers
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Academic Medicine Vol. 98, No. 9 ( 2023-09), p. 1002-1007
    Details
    In: Academic Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 98, No. 9 ( 2023-09), p. 1002-1007
    Abstract: The learning health system (LHS) has emerged over the past 15 years as a concept for improving health care delivery. Core aspects of the LHS concept include: promoting improved patient care through organizational learning, innovation, and continuous quality improvement; identifying, critically assessing, and translating knowledge and evidence into improved practices; building new knowledge and evidence around how to improve health care and health outcomes; analyzing clinical data to support learning, knowledge generation, and improved patient care; and engaging clinicians, patients, and other stakeholders in processes of learning, knowledge generation, and translation. However, the literature has paid less attention to how these LHS aspects may integrate with the multiple missions of academic medical centers (AMCs). The authors define an academic learning health system (aLHS) as an LHS built around a robust academic community and central academic mission, and they propose 6 features that emphasize how an aLHS differs from an LHS. An aLHS capitalizes on embedded academic expertise in health system sciences; engages the full spectrum of translational investigation from mechanistic basic sciences to population health; builds pipelines of experts in LHS sciences and clinicians with fluency in practicing in an LHS; applies core LHS principles to the development of curricula and clinical rotations for medical students, housestaff, and other learners; disseminates knowledge more broadly to advance the evidence for clinical practice and health systems science methods; and addresses social determinants of health, creating community partnerships to mitigate disparities and improve health equity. As AMCs evolve, the authors expect that additional differentiating features and ways to operationalize the aLHS will be identified and hope this article stimulates further discussion around the intersection of the LHS concept and AMCs.
    Type of Medium: Online Resource
    ISSN: 1040-2446
    URL: Article
    DOI: 10.1097/ACM.0000000000005259
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2025367-9
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  • 5
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    Abstract MP77: Associations Between Atrial Cardiopathy and Cerebral Amyloid: The Aric Pet Study
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 141, No. Suppl_1 ( 2020-03-03)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 141, No. Suppl_1 ( 2020-03-03)
    Abstract: Background: Atrial fibrillation (AF) is a risk factor for cognitive decline, perhaps due to silent cerebral infarction, but it is unknown if it also acts on Alzheimer’s Disease (AD)-specific mechanisms, such as deposition of β-amyloid (Aβ). Left atrial changes in structure or function, or atrial cardiopathy, can lead to AF but may cause infarcts independently, and thus might also impact cognition. We hypothesize that Aβ is associated with AF and atrial cardiopathy, independent of AF, when defined similarly to an ongoing clinical trial (ARCADIA). Methods: 321 participants without dementia from the Atherosclerosis Risk in Communities study underwent florbetapir (FBP) PET, electrocardiogram and 2D echocardiography. Atrial cardiopathy was defined as ≥1 of: 1) left atrial volume index (LAVI) 〉 34 ml/m2; 2) P-wave terminal force 〉 5000 uV x ms and 3) serum NT proBNP 〉 250 pg/mL. Cross-sectional associations between global cortical Aβ ( 〉 1.2 standardized uptake value ratio (SUVR)) and adjudicated history of atrial fibrillation and atrial cardiopathy, each, were evaluated using multivariable logistic regression. Results: Participants, with mean age 76 y, were 56% female and 42% black. Odds of elevated FBP SUVR was increased for those with atrial cardiopathy (Model 3) and nearly doubled among those with enlarged LAVI that remained significant after sequential adjustment, including AF (Table). There was no significant association between either P-wave terminal force or NT proBNP and elevated FBP SUVR (Table), nor between elevated SUVR and AF. Conclusions: In this cross-sectional analysis of a cohort of healthy, nondemented community-dwelling older individuals, we report a significant association between atrial cardiopathy as well as LAVI and elevated amyloid, by PET, without a similar association in individuals with AF. Potential limitations include reverse causation and survival bias. Ongoing work will help determine if changes in cardiac structure and function precede, or occur simultaneously with amyloid deposition.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.141.suppl_1.MP77
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1466401-X
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  • 6
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    Racial Differences in the Association of Insulin Resistance With Stroke Risk : The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Stroke Vol. 45, No. 8 ( 2014-08), p. 2257-2262
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 8 ( 2014-08), p. 2257-2262
    Abstract: Insulin resistance is associated with increased stroke risk, but the effect has not been adequately examined separately in white and black populations. Methods— The association of baseline insulin resistance with risk of cerebral infarction (CI) and intracerebral hemorrhage (ICH) was assessed in 12 366 white and 6782 black participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, recruited between 2003 and 2007 and followed for an average of 5.7 years. Insulin resistance was measured with the homeostasis model assessment-insulin resistance. Results— There were 364 incident CI and 41 incident ICH events. The risk for CI increased with the log of insulin resistance in whites (hazards ratio [HR] ln(IR) =1.17; 95% confidence interval [CI], 1.00–1.38) but was largely attenuated by adjustment for stroke risk factors (HR ln(IR) =1.05; 95% CI, 0.88–1.26). There was no association in blacks (HR ln(IR) =1.01; 95% CI, 0.81–1.25). After adjustment for demographic factors and risk factors, there was a significant difference by race in the association of insulin resistance with risk of ICH ( P =0.07), with a decrease in the risk of ICH in whites (HR ln(IR) =0.61; 95% CI, 0.35–1.04) but a nonsignificant increase in blacks (HR ln(IR) =1.20; 95% CI, 0.60–2.39). Conclusions— These data support the growing evidence that insulin resistance may play a more important role in stroke risk among white than black individuals and suggest a potentially discordant relationship of insulin resistance on CI and ICH among whites.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.114.005306
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1467823-8
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  • 7
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    Do Genetic Modifiers of High-Density Lipoprotein Cholesterol and Triglyceride Levels Also Modify Their Response to a Lifestyle Intervention in the Setting of Obesity and Type-2 Diabetes Mellitus? : The Action for Health in Diabetes (Look AHEAD) Study
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Circulation: Cardiovascular Genetics Vol. 6, No. 4 ( 2013-08), p. 391-399
    Details
    In: Circulation: Cardiovascular Genetics, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 4 ( 2013-08), p. 391-399
    Abstract: High-density lipoprotein cholesterol (HDL-C) and triglycerides are cardiovascular risk factors susceptible to lifestyle behavior modification and genetics. We hypothesized that genetic variants identified by genome-wide association studies as associated with HDL-C or triglyceride levels modify 1-year treatment response to an intensive lifestyle intervention, relative to a usual care of diabetes mellitus support and education. Methods and Results— We evaluated 82 single-nucleotide polymorphisms, which represent 31 loci demonstrated by genome-wide association studies to be associated with HDL-C and triglycerides, in 3561 participants who consented for genetic studies and met eligibility criteria. Variants associated with higher baseline HDL-C levels, cholesterol ester transfer protein ( CETP ) rs3764261 and hepatic lipase ( LIPC ) rs8034802, were found to be associated with HDL-C increases with intensive lifestyle intervention ( P =0.0038 and 0.013, respectively) and had nominally significant treatment interactions ( P =0.047 and 0.046, respectively). The fatty acid desaturase-2 rs1535 variant, associated with low baseline HDL-C ( P =0.017), was associated with HDL-C increases with intensive lifestyle intervention (0.0037) and had a nominal treatment interaction ( P =0.035). Apolipoprotein B (rs693) and LIPC (rs8034802) single-nucleotide polymorphisms showed nominally significant associations with HDL-C and triglyceride changes with intensive lifestyle intervention and a treatment interaction ( P 〈 0.05). Phosphatidylglycerophosphate synthase-1 single-nucleotide polymorphisms (rs4082919) showed the most significant triglyceride treatment interaction in the full cohort ( P =0.0009). Conclusions— This is the first study to identify genetic variants modifying lipid responses to a randomized lifestyle behavior intervention in overweight or obese individuals with diabetes mellitus. The effects of genetic factors on lipid changes may differ from the effects on baseline lipids and are modifiable by behavioral intervention.
    Type of Medium: Online Resource
    ISSN: 1942-325X , 1942-3268
    URL: Article
    DOI: 10.1161/CIRCGENETICS.113.000042
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2927603-2
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  • 8
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    Genetic Modifiers of Cardiorespiratory Fitness Response to Lifestyle Intervention
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Medicine & Science in Sports & Exercise Vol. 46, No. 2 ( 2014-02), p. 302-311
    Details
    In: Medicine & Science in Sports & Exercise, Ovid Technologies (Wolters Kluwer Health), Vol. 46, No. 2 ( 2014-02), p. 302-311
    Type of Medium: Online Resource
    ISSN: 0195-9131
    URL: Article
    DOI: 10.1249/MSS.0b013e3182a66155
    RVK:
    ZX 1000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 2031167-9
    SSG: 31
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  • 9
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    Abstract 043: Leisure-Time Physical Activity in Adulthood and Region of Interest (ROI) Brain Volumes: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Circulation Vol. 137, No. suppl_1 ( 2018-03-20)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 137, No. suppl_1 ( 2018-03-20)
    Abstract: Introduction: Several studies report late-life physical activity (PA) to be associated with less brain atrophy. Associations of PA and subclinical brain markers evaluated at older ages may be subject to reverse causality due to comorbidity, age-related changes in lifestyle, or incipient cognitive impairment. Therefore, we aimed to compare late-life cross-sectional estimates of PA and ROI brain volumes to those using prospective PA measures from mid- to late-life. Methods: Participants (n=1549, mean age: 75, 39% male, 20% Black) with repeat assessments of PA from visit 1 (1987-1989) and a brain magnetic resonance imaging (MRI) in 2011-2013 were included. Total volume of PA in metabolic equivalent-min/week was estimated using the Baecke Physical Activity Questionnaire and classified as no, low, middle or high at each visit. Based on visit 1 and 3 (1993-1995) PA assessments, a subset of participants (n=663) were further categorized as habitually inactive or having habitually low, middle, or high PA in mid-life. Brain MRI using 3D-1.5T equipment quantified ROI volumes following a standardized protocol. Weighted linear regression adjusted for intracranial volume, demographics, select cardiovascular risk factors and ApoE4 estimated the standardized difference in ROI volumes. Results: Compared to no PA, high PA was associated with larger ROI brain volumes cross-sectionally in late-life (Table). High mid-life PA was only modestly associated with larger frontal cortical and deep gray matter volumes in late-life (Table). Habitually high PA in mid-life was not associated with less atrophy across brain regions in late-life. Conclusions: Our results do not support a causal interpretation of the cross-sectional associations between PA and brain volumes reported in late-life. Drawing on long-term population-based data, this study provides novel information on the associations of PA across life epochs with brain health, which can inform translational and intervention efforts to reduce age-related cognitive impairment.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.137.suppl_1.043
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1466401-X
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  • 10
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    Heritability of Carotid Artery Intima-Medial Thickness in Type 2 Diabetes
    Ovid Technologies (Wolters Kluwer Health) ; 2002
    In:  Stroke Vol. 33, No. 7 ( 2002-07), p. 1876-1881
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 33, No. 7 ( 2002-07), p. 1876-1881
    Abstract: Background and Purpose — Carotid artery intima-medial thickness (IMT), a marker of subclinical atherosclerosis, is a strong predictor of subsequent cardiovascular morbidity. The role of genetic factors in thickening of the carotid wall remains largely unknown. We hypothesize that in families with multiple members having diabetes, carotid IMT is likely to be associated with both inherited and environmental factors. Methods — To determine the extent of the familial aggregation of carotid IMT in the presence of type 2 diabetes, we studied 252 individuals with type 2 diabetes (mean age 60.6 years) from 122 families. Common carotid artery IMT was measured by high-resolution B-mode ultrasonography. Other measured factors included lipid levels, body mass index, fasting glucose, hemoglobin A 1c , albumin/creatinine ratio, and self-reported medical history. Heritability estimates were obtained by using variance component methodology, as implemented in the SOLAR software package. Tests for association between carotid IMT and variables were performed by using mixed model analysis while accounting for the correlation due to family structure. Results — The age-, sex-, and race-adjusted heritability estimate for carotid IMT was 0.32 (SE 0.17, P =0.02). Further adjustment for total cholesterol, hypertension status, and current smoking status resulted in a heritability estimate of 0.41 (SE 0.16, P =0.004). The strongest predictors of carotid IMT, after adjusting for age and sex, were ethnicity (African American versus white), total cholesterol, and smoking status. Conclusions — These data provide empirical evidence that subclinical cardiovascular disease has a significant genetic component and merits a search for the genes involved in susceptibility to the atherosclerotic complications of diabetes.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/01.STR.0000019909.71547.AA
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2002
    detail.hit.zdb_id: 1467823-8
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