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Ciccarone Articles

Ciccarone Center Research

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Discordance: Can we capitalize on it to better personalize atherosclerosis treatment?
By: Nasir K, Martin SS, Virani S.
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High-sensitivity C-reactive protein and cardiovascular disease: A resolute belief or an elusive link?
By: Yousuf O, Mohanty BD, Martin SS, Joshi PH, Blaha MJ, Nasir K, Blumenthal RS, Budoff MJ.
Although high-sensitivity C-reactive protein (hsCRP) is involved in the immunologic process that triggers vascular remodeling and plaque deposition and is associated with increased cardiovascular disease (CVD) risk, definitive randomized evidence for its role as a causative factor in atherothrombosis is lacking. This article reviews four distinct points from the literature to better understand the current state and application of hsCRP in clinical practice, and we highlight recommendations from societies and important considerations when using hsCRP to guide treatment decisions in the primary prevention setting.
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Pathways to quality inpatient management of hyperglycemia and diabetes: A call to action.
By: Draznin B, Gilden J, Golden SH, Inzucchi SE; PRIDE investigators.
This paper outlines eight aspects of inpatient glucose management (four as system-based issues and four as patient-based issues) in which randomized clinical trials are needed, and urges further progress in the science of inpatient diabetes management.
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Blood pressure and chronic kidney disease progression in a multi-racial cohort: the Multi-Ethnic Study of Atherosclerosis.
By: Bloomfield GS, Yi SS, Astor BC, Kramer H, Shea S, Shlipak MG, Post WS.
This study concluded that, with the inclusion of cystatin C in the estimated glomerular filtration rate assessment, hypertension was an important predictor of chronic kidney disease progression in a multi-ethnic cohort with stage 3 of the disease.
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Comparative effectiveness of risk markers for cardiovascular risk assessment in intermediate-risk individuals: coronary artery calcium versus “the rest”?
By: Barth AS, Abd TT, Blumenthal RS, Blaha MJ.
We evaluated four large population-based cohort studies regarding the net reclassification index (NRI) among intermediate risk patients. We concluded that the coronary artery calcium score was the strongest marker for clinical risk prediction and is the most likely to influence future clinical outcomes.
Relationship between the cortisol awakening response and other features of the diurnal cortisol rhythm: The Multi-Ethnic Study of Atherosclerosis.
By: Golden SH, Sanchez BN, Wu M, Champaneri S, Diez Roux AV, Seeman T, Wand GS.
Researchers for this study conclude that bedtime cortisol showed the strongest correlation with total cortisol area under the curve, suggesting it may be a marker of daily cortisol exposure.
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A clinician’s guide to the ABCs of cardiovascular disease prevention: The Johns Hopkins Ciccarone Center for the prevention of Heart Disease and American College of Cardiology Cardiosource approach to the Million Hearts Initiative.
By: Hsu S, Ton VK, Ashen MD, Martin SS, Gluckman TJ, Kohli P, Sisson SD, Blumenthal RS, Blaha MJ.
As part of an initiative that aims to prevent 1 million myocardial infarctions and strokes over the next 5 years, we present the simply organized “ABCDE” approach for guiding a consistent comprehensive approach to managing cardiovascular risk in daily clinical practice. We summarize recommendations related to each topic and reference landmark trials and data that support our approach.
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The role of echocardiography for cardiovascular risk assessment of the asymptomatic individual.
By: Michos ED, Abraham TP.
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Low-risk lifestyle, coronary calcium, cardiovascular events, and mortality: Results from MESA.
By: Ahmed HM, Blaha MJ, Nasir K, Jones SR, Rivera JJ, Agatston A, Blankstein R, Wong ND, Lakoski S, Budoff MJ, Burke GL, Sibley CT, Ouyang P, Blumenthal RS.
Unhealthy lifestyle habits are a major contributor to coronary artery disease (CAD). The purpose of the study was to investigate the associations of smoking, weight maintenance, physical activity, and Mediterranean-style diet with coronary calcium, cardiovascular events, and mortality. We discovered that, over the course of nearly 8 years, a combination of regular exercise, healthy diet, smoking avoidance, and weight maintenance contributed to lower coronary calcium incidence, slower calcium progression, and lower all-cause mortality.
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Disorders of lipid metabolism.
By: Martin SS, Blumenthal RS.
This chapter examines the evidence base for selective use of lipid-lowering agents in adults over the age of 65.
25-Hydroxyvitamin D and parathyroid hormone are not associated with carotid intima-media thickness or plaque in the Multi-Ethnic Study of Atherosclerosis.
By: Blondon M, Sachs M, Hoofnagle AN, Ix JH, Michos ED, Korcarz C, Gepner AD, Siscovick DS, Kaufman JD, Stein JH, Kestenbaum B, de Boer IH.
This study shows that the consistent lack of association of vitamin D and parathyroid hormone with carotid intima-media thickness and plaque suggests that these hormones may influence cardiovascular risk through pathways not reflected by carotid atherosclerosis.
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Sex steroid levels and response to weight loss interventions among postmenopausal women in the Diabetes Prevention Program.
By: Kim C, Barrett-Connor E, Randolph JF, Kong S, Nan B, Mather K, Golden SH and the Diabetes Prevention Program Research Group.

This study found that, among nonestrogen users, baseline sex steroids were not associated with reductions in weight or waistline circumference.

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Impaired left ventricular filling in COPD and emphysema: Is it the heart or the lungs?: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study.
By: Smith BM, Prince MR, Hoffman EA, Bluemke DA, Liu CY, Rabinowitz D, Hueper K, Parikh M, Gomes AS, Michos ED, Lima J, Barr RG.

These findings support a mechanism of upstream pulmonary causes of underfilling of the left ventricle in COPD and in patients with emphysema on computed tomography.

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Diagnosis and treatment of erectile dysfunction for reduction of cardiovascular risk.
By: Nehra A, Jackson G, Miner M, Billups KL, Burnett AL, et al.
Erectile dysfunction is a marker of increased cardiovascular risk in younger men and in men with diabetes. Lifestyle improvements and treatment of dyslipidemia and hypertension are very important to lower cardiovascular risk.
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Localization of myocardial scar in patients with cardiomyopathy and left bundle branch block using electrocardiographic Selvester QRS scoring.
By: Wieslander B, Wu KC, Loring Z, Andersson LG, Frank TF, Gerstenblith G, Tomaselli GF, Weiss RG, Wagner GS, Ugander M, Strauss DG.
This study describes the diagnostic performance of electrocardiographic criteria based on the Selvester QRS scoring system, first in localizing myocardial scar and second in screening for any non-septal scar in patients with strictly defined left bundle branch block.
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Family history of coronary heart disease (CHD) and markers of subclinical cardiovascular disease: Where do we stand?
By: Pandey AK, Pandey S, Blaha MJ, Agatston A, Feldman T, Ozner M, Santos RD, Budoff MJ, Blumenthal RS, Nasir K.
Family history of coronary artery disease is associated with markers of subclinical atherosclerosis, and this relationship remains statistically significant after adjusting for traditional risk factors. Our data suggest these individuals should be considered strongly as candidates for assessment of subclinical CVD to further refine risk and treatment goals.
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Left ventricular mechanical dyssynchrony by cardiac magnetic resonance is greater in patients with strict vs. nonstrict electrocardiogram criteria for left bundle-branch block.
By: Andersson LG, Wu KC, Wieslander B, Loring Z, Frank TF, Maynard C, Gerstenblith G, Tomaselli GF, Weiss RG, Wagner GS, Ugander M, Strauss DG.
This study found there was no significant difference between patients with nonstrict left bundle-branch block and non-left bundle-branch block. The greater observed LV dyssynchrony may explain why patients with strict left bundle-branch block have a better response to cardiac resynchronization therapy.
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Dynamic analysis of cardiac rhythms for discriminating atrial fibrillation from lethal ventricular arrhythmias.
By: DeMazumder D, Lake DE, Cheng A, Moss TJ, Guallar E, Weiss RG, Jones SR, Tomaselli GF, Moorman JR.

Implantable cardioverter-defibrillators (ICDs), the first line of therapy for preventing sudden cardiac death in high-risk patients, deliver appropriate shocks for termination of ventricular tachycardia (VT)/ventricular fibrillation. A common shortcoming of ICDs is imperfect rhythm discrimination, resulting in the delivery of inappropriate shocks for atrial fibrillation (AF). An underexplored area for rhythm discrimination is the difference in dynamic properties between AF and VT/ventricular fibrillation. We hypothesized that the higher entropy of rapid cardiac rhythms preceding ICD shocks distinguishes AF from VT/ventricular fibrillation. This new strategy for AF discrimination based on entropy estimation expands on simpler concepts of variability, performs well at fast heart rates, and has potential for broad clinical application.

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Which serum cholesterol markers should I use to lower my patient’s cardiovascular risk?
By: Makadia S, Harrington C, Blumenthal RS.
We reviewed the strengths and limitations of LDL-C, non-HDL-C, apolipoprotein B, and advanced lipoprotein testing in cardiovascular risk prediction.
The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician.
By: Jackson G, Nehra A, Miner M, Billups KL, Burnett AL, et al.
Endothelial dysfunction appears to be the physiologic link between erectile dysfunction and cardiovascular disease. Appropriate control of risk factors can lower the risk of both conditions.
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Nonfasting lipids: there is the population and then there is the patient.
By: Martin SS, Blaha MJ, Jones SR.

This article reviews the rationale for the measurements of lipids in the nonfasting state.

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Cardiac MRI scar patterns differ by sex in an implantable cardioverter-defibrillator and cardiac resynchronization therapy cohort.
By: Loring Z, Strauss DG, Gerstenblith G, Tomaselli GF, Weiss RG, Wu KC.
The findings from this study, which showed that the extent of myocardial scar is less in women than men, may have important implications for the future study of gender disparities in outcomes from implantable cardioverter-defibrillators and cardiac resynchronization therapy.
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Right, but not left, bundle branch block is associated with large anteroseptal scar.
By: Strauss DG, Loring Z, Selvester RH, Gerstenblith G, Tomaselli G, Weiss RG, Wagner GS, Wu KC.
This study concluded that right bundle branch block patients have significantly greater scar size than left bundle branch block patients.
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Computed tomography-derived cardiovascular risk markers, incident cardiovascular events, and all-cause mortality in nondiabetics: the Multi-Ethnic Study of Atherosclerosis.
By: Yeboah J, Carr JJ, Terry JG, Ding J, Zeb I, Liu S, Nasir K, Post W, Blumenthal RS, Budoff MJ.
This study reveals that the addition of coronary artery calcium to the Framingham risk score provides superior discrimination, especially in intermediate-risk individuals, compared with the addition of several computed tomography risk markers.
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Methods for estimation of disparities in medication use in an observational cohort study: results from the Multi-Ethnic Study of Atherosclerosis.
By: McClelland RL, Jorgensen NW, Post WS, Szklo M, Kronmal RA.
Evaluating disparities in health care is an important aspect of understanding differences in disease risk. The purpose of this study is to describe the methodology for estimating such disparities, to provide improved disparity estimation in a large multi-ethnic cohort study.
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Comparing the new European cardiovascular disease prevention guideline with prior American Heart Association guidelines: an editorial review.
By: Ton VK, Martin SS, Blumenthal RS, Blaha MJ.
Despite some minor disagreements on the weight of recommendations in certain areas, CVD prevention experts across two continents agree on one thing: prevention works in halting the progression of atherosclerosis and decreasing disease burden over a lifetime.
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Establishing a successful coronary CT angiography program in the emergency department: Official writing of the Fellow and Resident Leaders of the Society of Cardiovascular Computed Tomography (FiRST).
By: Maroules CD, Blaha MJ, El-Haddad MA, Ferencik M, Cury RC.
Recent multicenter trials have reported that coronary CT angiography is safe, reduces time to diagnosis, facilitates discharge, and may lower overall cost compared with routine care. This study provides a 10-step approach for establishing a successful coronary CT angiography program in the emergency department.
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Use of cardiac CT angiography imaging in an epidemiology study: the Methodology of the Multicenter AIDS Cohort Study cardiovascular disease substudy.
By: Hac?o?lu Y, Gupta M, Choi TY, George RT, Deible CR, Jacobson LP, Witt MD, Palella FJ, Post WS, Budoff MJ.
This study concluded that cardiac CT angiography may serve as a reference for use in future epidemiology studies aiming to assess coronary atherosclerosis and cardiac anatomy in low-risk populations while minimizing radiation exposure.
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The association of elective hormone therapy with changes in lipids among glucose intolerant postmenopausal women in the diabetes prevention program.
By: Golden SH, Kim C, Barrett-Connor E, Nan B, Kong S, Goldberg R; the Diabetes Prevention Program Research Group.

It is unclear how lipids change in response to lifestyle modification or metformin among postmenopausal glucose intolerant women using and not using hormone therapy (HT). We examined the one-year changes in lipids among postmenopausal, prediabetic women in the Diabetes Prevention Program (DPP), and whether changes were mediated by sex hormones. The beneficial effects of ILS and metformin on lowering LDL-C and raising HDL-C differ depending upon concurrent HT use.

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Thyroid hormones and electrocardiographic parameters: findings from the third national health and nutrition examination survey.
By: Zhang Y, Post WS, Cheng A, Blasco-Colmenares E, Tomaselli GF, Guallar E.
Variation in thyroid hormone levels in the general population, even within the normal range, was associated with various changes in electrocardiograms.
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Pulmonary hyperinflation and left ventricular mass: the Multi-Ethnic Study of Atherosclerosis COPD Study.
By: Smith BM, Kawut SM, Bluemke DA, Basner RC, Gomes AS, Hoffman E, Kalhan R, Lima JA, Liu CY, Michos ED, Prince MR, Rabbani L, Rabinowitz D, Shimbo D, Shea S, Barr RG.
Pulmonary hyperinflation, as measured by residual lung volume or residual lung volume to total lung capacity ratio, is associated with greater left ventricular mass, an important predictor of heart failure and cardiovascular mortality.
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Genetic variation in PEAR1 is associated with platelet aggregation and cardiovascular outcomes.
By: Lewis JP, Ryan K, O’Connell JR, Horenstein RB, Damcott CM, Gibson Q, Pollin TI, Mitchell BD, Beitelshees AL, Pakzy R, Tanner K, Parsa A, Tantry US, Bliden KP, Post WS, Faraday N, Herzog W, Gong Y, Pepine CJ, Johnson JA, Gurbel PA, Shuldiner AR.
Common genetic variation in platelet endothelial aggregation receptor-1 may be a determinant of platelet response and cardiovascular events in patients on aspirin alone or in combination with clopidogrel.
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Nonalcoholic fatty liver disease and serum lipoproteins: the Multi-Ethnic Study of Atherosclerosis.
By: DeFilippis AP, Blaha MJ, Martin SS, Reed RM, Jones SR, Nasir K, Blumenthal RS, Budoff MJ.
This study found that, after adjustment for multiple metabolic risk factors, adiposity, and measures of insulin resistance, there may be a link between nonalcoholic fatty liver disease and dyslipidemia.
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Genetic variants associated with VLDL, LDL and HDL particle size differ with race/ethnicity.
By: Frazier-Wood AC, Manichaikul A, Aslibekyan S, Borecki IB, Goff DC, Hopkins PN, Lai CQ, Ordovas JM, Post WS, Rich SS, Sale MM, Siscovick D, Straka RJ, Tiwari HK, Tsai MY, Rotter JI, Arnett DK.
Our findings suggest that the genetic underpinnings of mean lipoprotein diameter differ by race/ethnicity. As lipoprotein diameters are modifiable, this may lead new strategies to modify lipoprotein profiles during the reduction of insulin resistance that are sensitive to race/ethnicity.
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Impact of fitness versus obesity on routinely measured cardiometabolic risk in young, healthy adults.
By: Vranian MN, Keenan T, Blaha MJ, Silverman MG, Michos ED, Minder CM, Blumenthal RS, Nasir K, Meneghelo RS, Santos RD.
Although fitness and obesity are independently associated with cardiometabolic risk, and their effects are additive, obesity is more strongly associated with this risk when fitness and obesity are discordant. These findings underscore the need for weight loss in obese patients and suggest an unmeasured benefit of fitness.
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Cardiovascular disease prevention: Matching evidence-based algorithms with individualized care.
By: Madanieh R, Hasan RK, Anusionwu OF, Blumenthal RS, Blaha MJ.
Because appropriate use of statins in primary prevention remains a matter of debate, we reviewed several strategies for statin allocation, including strict “evidence-based” adherence to randomized controlled clinical trial entry criteria and more “personalized” risk assessments.
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Progression of coronary calcium and incident CHD events: MESA (Multi-Ethnic Study of Atherosclerosis).
By: Budoff MJ, Young R, Lopez VA, Kronmal RA, Nasir K, Blumenthal RS, Detrano RC, Bild DE, Guerci AD, Liu K, Shea S, Szklo M, Post W, Lima J, Bertoni A, Wong ND.
This study concluded that progression of coronary artery calcium (CAC) is associated with an increased risk for future heart disease events, even after controlling for other potentially confounding factors.
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Non-invasive detection of coronary endothelial response to sequential handgrip exercise in coronary artery disease patients and healthy adults.
By: Hays AG, Stuber M, Hirsch GA, Yu J, Schär M, Weiss RG, Gerstenblith G, Kelle S.
This study showed that coronary endothelial function does not change with repeated isometric handgrip stress in CAD patients or healthy subjects.
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Christopher Dyer Saudek, MD: diabetes expert and implantable insulin pump pioneer.
By: Golden SH, Kalyani RR, Donner T.
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Patient- and trial-specific barriers to participation in cardiovascular randomized clinical trials.
By: Martin SS, Ou FS, Newby LK, Sutton V, Adams P, Felker GM, Wang TY.
This study quantitatively examined the association of patient- and trial-specific factors with participation in cardiovascular randomized clinical trials.
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Endocrine and inflammatory profiles in type 2 diabetic patients with and without major depressive disorder.
By: Alvarez A, Faccioli J, Guinzbourg M, Castex MM, Bayón C, Masson W, Bluro I, Kozak A, Sorroche P, Capurro L, Grosembacher L, Proietti A, Finkelsztein C, Costa L, Day PF, Cagide A, Litwak LE, Golden SH.
This study found that diabetic patients with depression are more likely to have cardiovascular events, and different factors can determine this high association.
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Genetic associations with valvular calcification and aortic stenosis.
By: Thanassoulis G, Campbell CY, Owens DS, Smith JG, Smith AV, Peloso GM, Kerr KF, Pechlivanis S, Budoff MJ, Harris TB, Malhotra R, O’Brien KD, Kamstrup PR, Nordestgaard BG, Tybjaerg-Hansen A, Allison MA, Aspelund T, Criqui MH, Heckbert SR, Hwang SJ, Liu Y, Sjogren M, van der Pals J, Kälsch H, Mühleisen TW, Nöthen MM, Cupples LA, Caslake M, Di Angelantonio E, Danesh J, Rotter JI, Sigurdsson S, Wong Q, Erbel R, Kathiresan S, Melander O, Gudnason V, O’Donnell CJ, Post WS; CHARGE Extracoronary Calcium Working Group.
Genetic variation in the lipoprotein(a) locus, mediated by lipoprotein(a) levels, is associated with aortic valve calcification across multiple ethnic groups and with incident clinical aortic stenosis.
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Genome-wide association study of cardiac structure and systolic function in African Americans: the Candidate Gene Association Resource (CARe) study.
By: Fox ER, Musani SK, Barbalic M, Lin H, Yu B, Ogunyankin KO, Smith NL, Kutlar A, Glazer NL, Post WS, et al.
In the largest genome-wide association study of cardiac structure and function to date in African-Americans, researchers identified 4 genetic loci related to left ventricular mass, interventricular septal wall thickness, left ventricular internal diastolic diameter, and ejection fraction, which reached genome-wide significance.
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Metabolic syndrome risk profiles among African American adolescents: national health and nutrition examination survey, 2003-2010.
By: Fitzpatrick SL, Lai BS, Brancati FL, Golden SH, Hill-Briggs F.

Although African-American adolescents have the highest prevalence of obesity, they have the lowest prevalence of metabolic syndrome across all definitions used in previous research. To address this paradox, we sought to develop a model of the metabolic syndrome specific to African-American adolescents. Our findings provide a plausible model of the metabolic syndrome specific to African-American adolescents. Based on this model, approximately 19% and 16% of African-American boys and girls, respectively, are at high risk for having the metabolic syndrome.

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Hypoglycemia in non-critically ill, hospitalized patients with diabetes: evaluation, prevention, and management.
By: Rubin J, Golden SH.

Hypoglycemia among hospitalized patients with diabetes is a common problem. Of the > 8 million patients admitted to US hospitals annually with a diagnosis of diabetes, up to 25% may have a low blood glucose level during hospitalization. As a widely recognized cause of acute, potentially fatal events, hypoglycemia remains a significant barrier to optimal inpatient glycemic control. Although iatrogenic hypoglycemia is associated with adverse outcomes, it may be a marker for illness rather than causal in itself. Several factors, such as administration of exogenous insulin, mismatch of insulin administration with nutrition, and the loss of normal counterregulatory responses, place patients with diabetes at higher risk for hypoglycemia than patients without diabetes. Causes and predictors of hypoglycemia in hospitalized patients with diabetes are discussed. Careful attention to contributing factors, responsiveness to changes in clinical status, and specific institutional protocols and policies can reduce the risk of hypoglycemia. Use of subcutaneous basal-bolus insulin dosing consistent with national guidelines and correction rather than sliding-scale insulin may minimize both hyper- and hypoglycemia. A majority of the literature on inpatient hypoglycemia has been limited to the critical-care setting. This review therefore focuses on hypoglycemia among non-critically ill inpatients with diabetes.

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A systematic review and meta-analysis of the association between depression and insulin resistance.
By: Kan C, Silva N, Golden SH, Rajala U, Timonen M, Stahl D, Ismail K.
This study found that a small but significant cross-sectional association was observed between depression and insulin resistance, despite heterogeneity between studies.
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The ABCG8 G574R variant, serum plant sterol levels, and cardiovascular disease risk in the Old Order Amish.
By: Horenstein RB, Mitchell BD, Post WS, Lütjohann D, von Bergmann K, Ryan KA, Terrin M, Shuldiner AR, Steinle NI.

Although the G574R variant is associated with moderately elevated plant sterol levels, carriers of the 574R allele had modestly lower levels of carotid wall thickness compared with noncarriers.

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Gender differences in coronary plaque composition and burden detected in symptomatic patients referred for coronary computed tomographic angiography.
By: Qureshi W, Blaha MJ, Nasir K, Al-Mallah MH.
This study found that symptomatic women have a lower prevalence of obstructive coronary artery disease and are less likely to have mixed coronary plaque compared to symptomatic men. Future studies are needed to determine the prognostic implications of these findings.
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Metabolic syndrome risk profiles among African-American adolescents: national health and nutrition examination survey, 2003-2010.
By: Fitzpatrick SL, Lai BS, Brancati FL, Golden SH, Hill-Briggs F.

Although African American adolescents have the highest prevalence of obesity, they have the lowest prevalence of metabolic syndrome across all definitions used in previous research. To address this paradox, we sought to develop a model of the metabolic syndrome specific to African American adolescents. Our findings provide a plausible model of the metabolic syndrome specific to African American adolescents. Based on this model, approximately 19 and 16% of African American boys and girls, respectively, are at high risk for having the metabolic syndrome.

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Vitamin D, calcium, and atherosclerotic risk: evidence from serum levels and supplementation studies.
By: Lutsey PL, Michos ED.
This review summarizes evidence of the relationship between vitamin D, calcium supplements, and cardiovascular disease, and comments on the recent Institute of Medicine recommendations regarding use of these nutrients.
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