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Ciccarone Articles

Ciccarone Center Research

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By: Subedi BH, Tota-Maharaj R, Silverman MG, Minder CM, Martin SS, Ashen MD, Blumenthal RS, Blaha MJ.
Diabetes is considered a risk equivalent for coronary heart disease (CHD). The use of statins for primary and secondary prevention in patients with diabetes is well established and supported by robust data from randomized, controlled trials and national guidelines. It is reasonable to match the intensity of statin therapy with patients’ baseline CVD risk.
By: Rosendorf C, Lackland DT, Allison M, Aronow WS, Black HR, Blumenthal RS, Cannon CP, de Lemos JA, Elliott WJ, Gersh BJ, Gore JH, Levy D, Long JB, O’Gara PT, Oparil S, White WB.
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By: McEvoy J, Nasir K, DeFilippis A, Lima J, Bluemke D, Hundley WG, Barr RG, Budoff M, Szklo M, Navas-Acien A, Polak J, Blumenthal R, Post W, Blaha M.

We sought to assess the impact of smoking status, cumulative pack-years, and time since cessation (the latter in former smokers only) on 3 important domains of cardiovascular disease: inflammation, vascular dynamics and function, and subclinical atherosclerosis. These findings expand our understanding of the harmful effects of smoking and help explain the cardiovascular benefits of smoking cessation.

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By: De Paula R, Aneni EC, Costa AR, Figueiredo VN, Moura FA, Freitas WM, Quaglia LA, Santos SN, Soares AA, Nadruz W, Blaha MJ, Blumenthal RS, Agatston A, Nasir K, Sposito AC.

Reduced zinc intake has been related to atherogenesis and arteriosclerosis. We verified this assumption in very old individuals, who are particularly prone to both zinc deficiency and structural and functional changes in the arterial wall. Although plasma zinc level is inversely related to systemic inflammatory activity, its plasma levels of daily intake are not associated to alterations in structure or function of the arterial wall. In the very elderly, plasma concentrations or daily intake of zinc is not related to endothelial dysfunction, arteriosclerosis, or atherosclerotic burden at coronary or carotid arteries.

By: Hung RK, Al-Mallah MH, McEvoy JW, Whelton SP, Blumenthal RS, Nasir K, Schairer JR, Brawner C, Alam M, Keteyian SJ, Blaha MJ.
Exercise capacity was a strong predictor of morbidity and mortality in patients with coronary artery disease. Patients with similar exercise capacities had equivalent mortality risk, irrespective of baseline revascularization status.
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By: Palta P, Golden SH, Teresi JA, Palmas W, Trief P, Weinstock RS, Shea A, Manly JJ, Luchsinger JA.
Mild cognitive impairment was not associated with metabolic control of diabetes among minority elderly individuals.
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By: Ndumele CE, Coresh J, Lazo ML, Hoogeveen RC, Blumenthal RS, Folsom AR, Selvin E, Ballantyne CM, Nambi V.
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By: Palta P, Golden SH, Teresi JA, Palmas W, Trief P, Weinstock RS, Shea A, Manly JJ, Luchsinger JA.
Elevated depressive symptoms were not associated with metabolic control of diabetes among minority elderly individuals.
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By: Rubin DJ, Donnell-Jackson K, Jhingan R, Golden SH, Paranjape A.
Findings from this qualitative study suggest several interventions that may reduce the risk of early readmission for patients with diabetes, including inpatient diabetes education, improving communication of discharge instructions, and involving patients more in medication reconciliation and post-discharge planning.
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By: Martin SS, Blumenthal RS.

Well-intentioned CV specialists often disagree, but we wholeheartedly support at least 90% of the new guidelines, which declare that primary prevention is here to stay. While many more adults will now qualify for statin therapy, heart-healthy dietary and exercise habits remain the foundation of primary prevention efforts. Following these new guidelines will allow clinicians to markedly reduce CVD events in their patients.

By: Salameh MJ, Ratchford EV.
By: Wang X, Sanchez BN, Golden SH, Shrager S, Kirschbaum C, Karlmangla AS, Seeman TE, Diez Roux AV.
All features of the daily cortisol curve changed significantly over the approximately six year follow-up period—the wakeup cortisol became higher; the cortisol awakening response became smaller; both the early and late decline became flatter and the area under the curve became larger.
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By: Tota-Maharaj R, Blaha MJ, Blankstein R, Silverman M, Eng J, Shaw LJ, Blumenthal RS, Budoff MJ, Nasir K.
The potent predictive value of coronary artery calcium burden applies to middle-aged as well as older adults.
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By: Pokharel Y, Nambi V, Martin SS, Hoogeveen RC, Nasir K, Khera A, Wong ND, Jones PH, Boone J, Roberts AJ, Ballantyne CM, Virani SS.

Retired National Football League (NFL) players were reported to have high prevalence of cardiovascular risk factors. Lipoprotein Associated Phospholipase A2 (LpPLA2) has shown to be associated with cardiovascular disease in the general population, but it is unknown whether such an association exists in retired NFL players. Our objective was to assess whether LpPLA2 mass was associated with coronary artery calcium (CAC) and carotid artery plaque (CAP) in retired NFL players. LpPLA2 mass was not associated with coronary or carotid subclinical atherosclerosis in retired NFL players.

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By: Stacy SR, Suarez-Cuervo C, Berger Z, Wilson LM, Yeh HC, Bass EB, Michos ED.
In chronic kidney disease patients suspected of having acute coronary syndromes, troponin levels can aid in identifying patients with a poor prognosis, but the diagnostic utility is limited by varying estimates of sensitivity and specificity.
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By: Michos ED, Wilson LM, Yeh HC, Berger Z, Suarez-Cuervo C, Stacy SR, Bass EB.
In chronic kidney disease patients without suspected acute coronary syndromes, troponin elevations were associated with worse prognosis.
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By: Cheng HG, Martin SS, Jones SR.
By: Golden SH, Purnell T, Halbert J, Matens R, Miller ER, Levine D, Nguyen TH, Gudzune KA, Crews DC, Mahlangu-Ngcobo M, Cooper LA.
This manuscript summarizes the key elements, implementation, and preliminary outcomes of the CVD Disparities Fellowship and Summer Internship Programs at the Johns Hopkins University Schools of Medicine, Nursing, and Bloomberg School of Public Health.
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By: Kohli P, Whelton SP, Hsu S, Yancy CW, Stone NJ, Chrispin J, Gilotra NA, Houston B, Ashen MD, Martin SS, Joshi PH, McEvoy JW, Gluckman TJ, Michos ED, Blaha MJ, Blumenthal RS.

To facilitate the guideline-based implementation of treatment recommendations in the ambulatory setting and to encourage participation in the multiple preventive health efforts that exist, we have organized several recent guideline updates into a simple ABCDEF approach. We would remind clinicians that evidence-based medicine is meant to inform recommendations but that synthesis of patient-specific data and use of appropriate clinical judgment in each individual situation is ultimately preferred.

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By: Ankam J, Feldman DI, Blaha MJ, Martin SS.

Following a myocardial infarction, lipid-lowering therapy is an established intervention to reduce the risk of recurrent cardiovascular events. Prior studies show a need to improve clinical practice in this area. Here, we review the latest research and perspectives on improving postmyocardial infarction lipid control. Optimizing lipid control could further enhance clinical outcomes after myocardial infarction.

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By: Remigio-Baker RA, Allison MA, Schreiner P, Szklo M, Crum RM, Leoutsakos J, Franco M, Carnethon MR, Nettleton J, Mujahid M, Diez Roux AV, Jensky N, Golden SH.
Sex, but not race/ethnicity, was found to modify the relationship between elevated depressive symptoms and visceral fat mass. Among men, a significant positive association was found between depressive symptoms and visceral adiposity, but no significant relationship was found among women.
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By: Al-Mallah MH, Keteyian SJ, Brawner CA, Whelton S, Blaha MJ.
The FIT Project, the largest study of physical fitness to date, uses electronic clinical epidemiologic techniques to answer many clinically relevant questions related to exercise capacity and prognosis.
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By: Freitas WM, Quaglia LA, Santos SN, de Paula RC, Santos RD, Blaha M, Rivera JJ, Cury R, Blumenthal R, Nadruz-Junior W, Agatston A, Figueiredo VN, Nasir K, Sposito AC; The Brazilian Study on Healthy Aging.

In a healthy cohort of individuals aged of 80 years or more the association between LDL-C and coronary atherosclerosis weakens with aging, while the opposite occurs with the levels of HDL-C.

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By: Holt RIG, deGroot M, Lucki I, Hunter CM, Sartorius N, Golden SH.
Comorbid diabetes and depression are a major clinical challenge as the outcomes of each condition are worsened by the other. This article summarizes the presentations and discussions during an international meeting on diabetes and depression convened by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in collaboration with the National Institute of Mental Health and the Dialogue on Diabetes and Depression.
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By: Miller PE, Budoff M, Zikusoka M, Li X, Palella F Jr, Kingsley LA, Witt MD, Sharrett AR, Jacobson LP, Post WS.
The lower prevalence of CAC in black men compared with white men appears to reflect less calcification of plaque and stenosis rather than a lower overall prevalence of plaque.
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By: Joshi PH, Toth PP, Lirette ST, Griswold ME, Massaro JM, Martin SS, Blaha MJ, Kulkarni KR, Khokhar AA, Correa A, D’Agostino Sr RB, Jones SR, on behalf of the Lipoprotein Investigators Collaborative (LIC) Study Group.
This study found that smaller, denser HDL3-C levels are primarily responsible for the inverse association between HDL-C and incident CHD in this diverse group of primary prevention subjects.
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By: Martin SS, Jones SR, Toth PP.
This report prioritizes higher-resolution HDL measurement techniques that capture better the biologically and clinically important characteristics of HDL.
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By: Korley FK, Schulman SP, Sokoll LJ, DeFilippis AP, Stolbach AI, Bayram JD, Saheed MO, Omron R, Fernandez C, Lwin A, Cai SS, Post WS, Jaffe AS.

With clinical use of high-sensitivity troponin I (hsTnI), more frequent troponin elevations will occur. However, the burden and implications of these elevations are not well understood. The authors quantified the prevalence of elevated hsTnI in patients presenting with possible acute coronary syndrome (ACS) who do not have elevated troponin with a current generation assay (cardiac troponin I [cTnI]) and determined the association of these newly detected elevations with a composite of all-cause mortality and subsequent cardiac hospitalization. On the initial sample, 9% to 11% of subjects without cTnI elevation had hsTnI elevation. Although the majority of the patients with these newly detected hsTnI elevations did not have ACS, they had a higher risk for all-cause mortality and subsequent cardiac hospitalization.

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By: Metkus Jr. TS, Blumenthal RS, Joshi PH.

An update to the 2005 Guidelines on the Role of Noninvastive Testing in the Clinical Evaluation of Women with Suspected Ischemic Heart Disease was authored in response to the documented gap in appropriate diagnosis and treatment of ischemic heart disease between women and men.

By: Desai CS, Martin SS, Blumenthal RS.
This is a state-of-art review on the possible effects of statin therapy on organs not in the cardiovascular system.
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By: Lutsey PL, Alonso A, Michos ED, Loehr LR, Astor BC, Coresh J, Folsom AR.
Low serum magnesium and high serum phosphorus and calcium were independently associated with greater risk of incident HF in this population-based cohort.
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By: Feldman DI, Martin SS.

LDL-C measurements and absolute risk assessments are important and provide complimentary information. More research is needed, but based on the best available evidence it appears that a balance of estimating risk (ARR) and measuring LDL-C (RRR) is appropriate. 

By: Sansbury BE, De Martino AM, Xie Z, Brooks AC, Brainard RE, Watson LJ, DeFilippis AP, Cummins TD, Harbeson MA, Brittian KR, Prabhu SD, Bhatnagar A, Jones SP, Hill BG.
These findings reveal extensive metabolic remodeling common to both hypertrophic and failing hearts that are indicative of extracellular matrix remodeling, insulin resistance and perturbations in amino acid, and lipid and nucleotide metabolism.
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By: Houston B, Martin SS.
This article reviewed the state-of-the-art research involving inhibition of phospholipid A2 to reduce subsequent cardiovascular events.
By: Jamal O, Aneni EC, Shaharyar S, Ali SS, Parris D, McEvoy JW, Veledar E, Blaha MJ, Blumenthal RS, Agatston AS, Coceicao RD, Feldman T, Carvalho JA, Santos RD, Nasir K.

Emerging data suggests that the combination of smoking and metabolic syndrome (MetS) markedly increases cardiovascular disease risk well beyond that of either condition. In this study we assess if this interaction can be explained by an additive increase in the risk of systemic inflammation by MetS and cigarette smoking. The study demonstrates an additive effect of cigarette smoking on the risk of systemic inflammation in MetS thus highlighting the need for determining smoking status among those with MetS and aggressively targeting smoking cessation in this population.

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By: Hulten E, Bittencourt MS, Singh A, O’Leary D, Christman MP, Osmani W, Abbara S, Steigner M, Truong QA, Nasir K, Rybicki F, Klein J, Hainer J, Brady TJ, Hoffmann U, Ghoshhajra B, Hachamovitch R, Di Carli MF, Blankstein R.
Coronary computed tomography angiography (CCTA) may lead to increased use of prognostically beneficial therapies in patients identified as having extensive, non-obstructive CAD.
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By: McEvoy JW.

Clinical informatics represents arguably the most significant advance in medicine since the deciphering of the human genome. In particular, as the “front end” of the clinical informatics revolution, the electronic health record has immense potential to transform modern healthcare. Demonstrated benefits of the electronic health record include decision support, adverse event tracking, and quality control.1 An additional strength of the electronic health record is an inherent capacity to augment research, including embedded, randomized, controlled clinical trials.

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By: Pokharel Y, Macedo FY, Nambi V, Martin SS, Nasir K, Wong ND, Boone J, Roberts AJ, Ballantyne CM, Virani SS.
In retired NFL players with a high prevalence of CAC and carotid artery plaque, neck circumference was not associated with coronary or carotid subclinical atherosclerosis.
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By: Michos ED, Carson KA, Schneider AL, Lutsey PL, Xing L, Sharrett AR, Alonso A, Coker LH, Gross M, Post W, Mosley TH, Gottesman RF.
single measure of 25-hydroxy vitamin D was not cross-sectionally associated with white matter hyper-intensities grade or prevalent subclinical infarcts and was not prospectively associated with their progression or subclinical brain infarcts seen on serial cerebral MRIs obtained approximately 10 years apart.
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By: Amin NP, Martin SS, Blaha MJ, Nasir K, Blumenthal RS, Michos ED.
The newly released 2013 ACC/AHA Guideline for Assessing Cardiovascular Risk was a major advance over prior guidelines, but the new risk equations do not appear to lead to significantly better discrimination than older models. Since the same risk factors are incorporated, using the new risk estimators may lead to inaccurate assessment of atherosclerotic cardiovascular risk in certain groups of patients. There also is likely an overestimation of risk when applied to modern populations. Future guidelines could provide clearer direction on which individuals would benefit from additional testing for more personalized preventive therapies.
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By: Martin SS, Khokhar AA, May HT, Kulkarni KR, Blaha MJ, Joshi PH, Toth PP, Muhlestein JB, Anderson JL, Knight S, Li Y, Spertus JA, Jones SR; on behalf of the Lipoprotein Investigators Collaborative (LIC).
In secondary prevention, increased risk for long-term hard clinical events is associated with low HDL3-C, but not HDL2-C or HDL-C, highlighting the potential value of subclassifying HDL-C.
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By: Zeb I, Abbas N, Nasir K, Budoff MJ.
CCTA may represent a cost-effective strategy and may be associated with less downstream testing for diagnosis of stable chest pain patients in low- to intermediate-risk patients; for low-risk acute chest pain patients; however, use of CCTA is associated with expedited patient management, less cost and safe exclusion of acute coronary syndrome.
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By: Martin SS, Abd TT, Jones SR, Michos ED, Blumenthal RS, Blaha MJ.
This article critically appraises the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol. The guideline succeeds in prioritizing statin therapy, expanding focus to atherosclerotic cardiovascular disease including stroke, and in emphasizing absolute cardiovascular risk to determine statin eligibility.
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By: Arking DE, Pulit SL, Crotti L, van der Harst P, Munroe PB, Koopmann TT, Sotoodehnia N, Rossin EJ, Morley M, Wang X, Johnson AD, Lundby A, Gudbjartsson DF, Noseworthy PA, Eijgelsheim M, Bradford Y, Tarasov KV, Dörr M, Müller-Nurasyid M, Lahtinen AM, Nolte IM, Smith AV, Bis JC, Isaacs A, Newhouse SJ, Evans DS, Post WS, et al.
This integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, long-QT syndrome, and sudden cardiac death.
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