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2015

Ciccarone Center Research

All Ciccarone Research Articles

All men with vasculogenic erectile dysfunction require a cardiovascular workup.
By: Miner M, Nehra A, Jackson G, Bhasin S, Billups K, Burnett AL, et al.

This study supports the use of cardiovascular risk stratification and aggressive risk-factor management in all men with vasculogenic erectile dysfunction.

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Lower adiponectin is associated with subclinical cardiovascular disease among HIV-infected men.
By: Ketlogetswe KS, Post WS, Li X, Palella FJ Jr, Jacobson LP, Margolick JB, Kingsley LA, Witt MD, Dobs AS, Budoff MJ, Brown TT.
Adiponectin levels were lower in HIV-infected men and related to the severity of subclinical atherosclerosis, independent of traditional CVD risk factors.
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Determinants of intrathoracic adipose tissue volume and associations with cardiovascular disease risk factors in Amish.
By: Liu X, Post WS, McLenithan J, Terrin M, Magder L, Zeb I, Budoff M, Mitchell BD.
These data do not provide support for a significant role for intrathoracic fat in the development of CAC.
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Is there a role for coronary artery calcium scoring for management of asymptomatic patients at risk for coronary artery disease?: Clinical risk scores are not sufficient to define primary prevention treatment strategies among asymptomatic patients.
By: Blaha MJ, Silverman MG, Budoff MJ.
Subclinical atherosclerosis testing with CAC is currently superior to any combination of risk factors and serum biomarkers.
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Myocardial steatosis and its association with obesity and regional ventricular dysfunction: evaluated by magnetic resonance tagging and 1H spectroscopy in healthy African Americans.
By: Liu CY, Bluemke DA, Gerstenblith G, Zimmerman SL, Li J, Zhu H, Lai S, Lai H.
This study found no relationship between cardiac steatosis and left ventricular volumes or ejection fraction, though there is some evidence suggesting that cardiac steatosis may be associated with LV regional function in healthy African-American women.
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Risk factors: new risk-assessment guidelines— more or less personalized?
By: Blaha MJ, Blumenthal RS.
The new ACC/AHA cardiovascular-risk guidelines feature updated equations for women, distinct equations for African-Americans, and include stroke prediction. However, the equations rely on the same traditional risk factors as previous versions, are driven predominantly by age, and curtail the intermediate-risk group, in which personalized risk assessment is recommended.
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Current guidelines for high-density lipoprotein cholesterol in therapy and future directions.
By: Subedi BH, Joshi PH, Jones SR, Martin SS, Blaha MJ, Michos ED.
This review outlined current therapies and described future directions for potential new approaches for HDL therapeutics, including HDL infusions, delipidated HDL, liver X receptor agonists, Apo A-I upregulators, Apo A mimetics, and gene therapy.
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Critical review of high-sensitivity C-reactive protein and coronary artery calcium for the guidance of statin allocation: head-to-head comparison of the JUPITER and St. Francis Heart Trials.
By: Kim J, McEvoy JW, Nasir K, Budoff MJ, Arad Y, Blumenthal RS, Blaha MJ.
This analysis looks at the strengths and limitations of two large trials of statin therapy based on persons with an elevated hsCRP, CAC score, or both.
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Concepts and controversies: the 2013 American College of Cardiology/American Heart Association risk assessment and cholesterol treatment guidelines.
By: Martin SS, Blumenthal RS.
This editorial discusses the strengths and limitations of the new prevention guidelines.
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Prognostic value of nonobstructive and obstructive coronary artery disease detected by coronary computed tomography angiography to identify cardiovascular events.
By: Bittencourt MS, Hulten E, Ghoshhajra B, D, Christman MP, Montana P, Truong QA, Steigner M, Murthy VL, Rybicki FJ, Nasir K, Gowdak LH, Hainer J, Brady TJ, Di Carli MF, Hoffmann U, Abbara S, Blankstein R.
Regardless of whether obstructive or nonobstructive disease is present, the extent of plaque detected by CCTA enhances risk assessment.
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Incremental prognostic value of coronary artery calcium score versus CT angiography among symptomatic patients without known coronary artery disease.
By: Hulten E, Bittencourt MS, Ghoshhajra B, O’Leary D, Christman MP, Blaha MJ, Truong Q, Nelson K, Montana P, Steigner M, Rybicki F, Hainer J, Brady TJ, Hoffmann U, Di Carli MF, Nasir K, Abbara S, Blankstein R.
Among symptomatic patients with a CAC score of zero, a very low (1-2%) prevalence of potentially obstructive CAD can occur, although this finding was not associated with future coronary revascularization or adverse prognosis within two years.
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Modifiable lifestyle risks, cardiovascular disease, and all-cause mortality.
By: Ahmed HM, Blaha MJ, Blumenthal RS.
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C-reactive protein is independently associated with coronary atherosclerosis burden among octogenarians.
By: Quaglia LA, Freitas WM, Soares AA, Santos RD, Nadruz W, Blaha MJ, Coelho OR, Blumenthal R, Agatston A, Nasir K, Sposito AC.
We examined measures of inflammation and subclinical atherosclerosis in persons with successful cardiovascular aging.
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Cardiometabolic risk is associated with atherosclerotic burden and prognosis: results from the partners coronary computed tomography angiography registry.
By: Hulten E, Bittencourt MS, O’Leary D, Shah R, Ghoshhajra B, Christman MP, Montana P, Steigner M, Truong QA, Nasir K, Rybicki F, Hainer J, Brady TJ, Di Carli MF, Hoffmann U, Abbara S, Blankstein R.
Patients without diabetes who have multiple metabolic risk factors have a similar prognosis and burden of CAD as those with Type 2 diabetes not requiring insulin.
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Family history of coronary heart disease and the incidence and progression of coronary artery calcification: Multi-Ethnic Study of Atherosclerosis (MESA).
By: Pandey AK, Blaha MJ, Sharma K, Rivera J, Budoff MJ, Blankstein R, Al-Mallah M, Wong ND, Shaw L, Carr J, O’Leary D, Lima JA, Szklo M, Blumenthal RS, Nasir K.

A multiethnic, population-based study showed that a family history of premature CHD is associated with enhanced development and progression of subclinical disease, independent of other risk factors.

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Obstructive sleep apnea and diurnal non-dipping hemodynamic indices in patients at increased cardiovascular risk.
By: Seif F, Patel SR, Walia HK, Rueschman M, Bhatt DL, Blumenthal RS, Quan SF, Gottlieb DJ, Lewis EF, Patil SP, Punjabi NM, Babineau DC, Redline S, Mehra R.

We hypothesized increasing obstructive sleep apnea (OSA) severity would be associated with nondipping blood pressure (BP) in increased cardiovascular disease (CVD) risk. In patients at cardiovascular risk and moderate-to-severe OSA, increasing AHI and/or ODI were associated with increased odds of nondipping SBP and nondipping MAP. More severe levels of AHI and ODI also were associated with nondipping DBP. These results support progressive BP burden associated with increased OSA severity even in patients managed by cardiology specialty care.

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Impact of a pharmacy-based glucose management program on glycemic control in an inpatient general medicine population.
By: Efird LE, Golden SH, Visram K, Shermock K.
This study found no global benefit of the pharmacy-based glucose management program for improving blood glucose values compared with usual care.
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Short and lifetime cardiovascular risk estimates: same wine, different bottles. Do we have the COURAGE to abandon risk scores?
By: Nasir K, Blaha MJ.
This editorial examines the shortcomings of traditional cardiovascular risk assessment scores.
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Relation between self-reported physical activity level, fitness, and cardiometabolic risk.
By: Minder CM, Shaya GE, Michos ED, Keenan TE, Blumenthal RS, Nasir K, Carvalho JA, Conceição RD, Santos RD, Blaha MJ.
Self-reported physical activity level and directly measured fitness are moderately correlated, and the latter is more strongly associated with a protective cardiovascular risk profile.
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Association between resting heart rate and inflammatory biomarkers (high-sensitivity C-reactive protein, interleukin-6, and fibrinogen): from the Multi-Ethnic Study of Atherosclerosis.
By: Whelton SP, Narla V, Blaha MJ, Nasir K, Blumenthal RS, Jenny NS, Al-Mallah MH, Michos ED.
Heart rate (HR) at rest is associated with adverse cardiovascular events; however, the biologic mechanism for the relation is unclear. An increased HR at rest was associated with a higher level of inflammation among an ethnically diverse group of subjects without known cardiovascular disease.
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Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol.
By: Lange LA, Hu Y, Zhang H, Xue C, Schmidt EM, Tang ZZ, Bizon C, Lange EM, Smith JD... Turner O‘Donnell CJ, Post WS, et al.
This large, whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.
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Are we moving towards concordance on the principle that lipid discordance matters?
By: Martin SS, Michos ED.

The paper addresses the underappreciated concept of discordance between different lipid and lipoprotein measures in individual patients. The investigators address the prevalence of such discordance and its association with long-term incidence of coronary events.

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Exercise and physical activity for cardiovascular disease prevention.
By: Ahmed H, Ndumele CE.
Systematic review on noninvasive assessment of subclinical cardiovascular disease in obstructive sleep apnea: new kid on the block!
By: Ali SS, Oni ET, Warraich HJ, Blaha MJ, Blumenthal RS, Karim A, Shaharyar S, Jamal O, Fialkow J, Cury R, Budoff MJ, Agatston AS, Nasir K.
Patients with obstructive sleep apnea (OSA) have a high burden of CVD, but a causal relationship between the two remains unclear. This study shows OSA is an independent predictor of subclinical CVD, as CVD is more likely to occur in patients with long standing and severe OSA.
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Polypill therapy, subclinical atherosclerosis, and cardiovascular events — implications for the use of preventive pharmacotherapy: MESA (Multi-Ethnic Study of Atherosclerosis).
By: Bittencourt MS, Blaha MJ, Blankstein R, Budoff M, Vargas JD, Blumenthal RS, Agatston AS, Nasir K.
The authors conclude that avoidance of polypill therapy in individuals with subclinical atherosclerosis could allow for a more selective use of the treatment and, as a result, avoidance of treatment in those who are unlikely to benefit.
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Obstructive sleep apnea and diurnal nondipping hemodynamic indices in patients at increased cardiovascular risk.
By: Seif F, Patel SR, Walia HK, Rueschman M, Bhatt DL, Blumenthal RS, Quan SF, Gottlieb DJ, Lewis EF, Patil SP, Punjabi NM, Babineau DC, Redline S, Mehra R.
Progressive blood pressure burden is associated with increased obstructive sleep apnea severity, even in patients managed by cardiology specialty care.
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All-cause mortality in asymptomatic persons with extensive Agatston scores above 1000.
By: Patel J, Blaha MJ, McEvoy JW, Qadir S, Tota-Maharaj R, Shaw LJ, Rumberger JA, Callister TQ, Berman DS, Min JK, Raggi P, Agatston AA, Blumenthal RS, Budoff MJ, Nasir K.
Increasing calcified plaque in coronary arteries continues to predict a graded decrease in survival among patients with extensive Agatston score > 1000 with no apparent upper threshold.
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Reproducibility of measurements by multi-detector computed tomography: Intra- and inter-reader measures for epicardial and intra-thoracic adipose tissue.
By: Rezaeian P, Razipour A, Li D, Zeb I, Baskett M, Post WS, Budoff MJ.
Intracoronary cardiosphere-derived cells after myocardial infarction: evidence of therapeutic regeneration in the final 1-year results of the CADUCEUS trial (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction).
By: Malliaras K, Makkar RR, Smith RR, Cheng K, Wu E, Bonow RO, Marbán L, Mendizabal A, Cingolani E, Johnston PV, Gerstenblith G, Schuleri KH, Lardo AC, Marbán E.
Intracoronary administration of autologous cardiosphere-derived cells did not raise significant safety concerns.
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Heart disease and stroke statistics — 2014 update: a report from the American Heart Association.
By: Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee.
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Genetics and personalized medicine — a role in statin therapy?
By: Patel J, Abd T, Blumenthal RS, Nasir K, Superko HR.

The primary goal of this study was to feature the most important genes involved in lipid metabolism, clinical outcomes, and statin-induced side effects, highlighting genomewide association studies and the candidate gene approach.The primary goal of this study was to feature the most important genes involved in lipid metabolism, clinical outcomes, and statin-induced side effects, highlighting genome-wide association studies and the candidate gene approach.

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A systematic review of internet-based worksite wellness approaches for cardiovascular disease risk management: outcomes, challenges and opportunities.
By: Aneni EC, Roberson LL, Maziak W, Agatston AS, Feldman T, Rouseff M, Tran TH, Blumenthal RS, Blaha MJ, Blankstein R, Al-Mallah MH, Budoff MJ, Nasir K.
Internet-based programs hold promise for improving the cardiovascular wellness among employees. However, much work is required to fully understand its utility and long-term impact, especially in special/at-risk populations.
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Beyond BMI: the "metabolically healthy obese" phenotype and its association with clinical/subclinical cardiovascular disease and all-cause mortality: a systematic review.
By: Roberson LL, Aneni EC, Maziak W, Agatston A, Feldman T, Rouseff M, Tran T, Blaha MJ, Santos RD, Sposito A, Al-Mallah MH, Blankstein R, Budoff MJ, Nasir K.

This review analyzed the literature that has examined the burden of CVD and all-cause mortality in the metabolically healthy obese population.

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Dyslipidemia, coronary artery calcium, and incident atherosclerotic cardiovascular disease: implications for statin therapy from the multi-ethnic study of atherosclerosis.
By: Martin SS, Blaha MJ, Blankstein R, Agatston A, Rivera JJ, Virani SS, Ouyang P, Jones SR, Blumenthal RS, Budoff MJ, Nasir K.
CAC scoring can help match statin therapy to absolute atherosclerotic CVD risk.
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Statin use is not associated with presence of and severity of nonalcoholic fatty liver disease.
By: Oni ET, Sinha P, Karim A, Martin SS, Blaha MJ, Agatston AS, Blumenthal RS, Meneghelo RS, Conceiçao RD, Santos RD, Nasir K.
These results favor statin use in subjects with nonalcoholic fatty liver disease, since its use is not associated with the presence of the disease or increased fibrosis.
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The risk discussion: A key virtue of the 2013 ACC/AHA cholesterol treatment guidelines.
By: Martin SS, Stone NJ, Blumenthal RS.
Relation of thoracic aortic distensibility to left ventricular area (from the Multi-Ethnic Study of Atherosclerosis [MESA]).
By: Al-Mallah MH, Nasir K, Katz R, Lima JA, Bluemke DA, Blumenthal RS, Mao S, Hundley WG, Budoff MJ.
The aim of this study was to test the hypothesis that decreasing aortic compliance and increasing arterial stiffness are independently associated with increased left ventricular area.
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Subclinical cardiovascular disease in plaque psoriasis: association or causal link?
By: Shaharyar S, Warraich H, McEvoy JW, Oni E, Ali SS, Karim A, Jamal O, Blaha MJ, Blumenthal RS, Fialkow J, Cury R, Budoff MJ, Agatston AA, Nasir K.

Since patients with psoriasis have an increased burden of subclinical atherosclerosis and endothelial dysfunction, those with greater severity and/or disease duration should be targeted for primary screening for cardiovascular disease risk reduction.

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Peripheral Artery Disease.
By: Salameh MJ, Ratchford EV.
What role does genetics play in the variability in response to statin therapy?
By: Patel J, Abd T, Blumenthal RS, Nasir K, Superko R.
We examine the role of certain genetic polymorphisms in affecting the response to statin therapy.
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Discordance in lipid measurements: Can we capitalize to better personalize cardiovascular risk assessment and treatment?
By: Cruz D, Ahmed H, Jones S, Elshazly M, Martin S.

Lipid measurement is one of the cornerstones of cardiovascular risk assessment and treatment. It is widely accepted that reduction of atherogenic lipids reduces risk of atherosclerotic cardiovascular disease. As the study of lipids has yielded deeper understanding of the pathophysiology of lipid metabolism, it has become clear that different techniques to quantify atherogenic lipids and lipoproteins could be complementary. For example, low-density lipoprotein cholesterol can exist in a range of forms from small, dense to large, buoyant, and therefore, discordance may arise between measures of its cholesterol content and particle concentration. In this article, we review the most recent literature on discordance in lipid measurements. We emphasize interesting and important new findings, and aim to bring the reader up-to-date on the topic. We submit that lipid discordances create an opportunity to better personalize the risk assessed for atherogenic cardiovascular disease and the care we give patients with dyslipidemia. We note that while prior research has often examined one lipid measure vs another in their abilities to predict the average risk in a population, recent studies are increasingly asking what lipid discordance in individual patients can tell us about risk. We propose that this latter approach asks the more clinically important question. The message from these studies is consistent: discordance matters. As the field moves forward, we propose standardization of methods for discordance research. In our view, this will best enable us to further clarify the clinical implications of the principle of discordance and best inform personalized cardiovascular care.

Effect of tube voltage (100 vs. 120 kVp) on radiation dose and image quality using prospective gating 320 row multi-detector computed tomography angiography.
By: Khan AN, Khosa F, Shuaib W, Nasir K, Blankstein R, Clouse M.

Radiation dose may be lowered from 120 to 100 kVp with preservation of image quality in patients whose BMI is greater than or equal to 27.

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Cardiac complications of obesity.
By: Ashen MD, Blumenthal RS.
Development of a center for prevention of cardiovascular disease.
By: Ashen MD, Nell-Dybdahl CL, Sperling L, Blumenthal RS.
We discuss the key components of various types of preventive cardiology centers that can be put together in academic and private practice settings.
Response to importance of pressure pulse amplification in the association of resting heart rate and arterial stiffness.
By: Whelton SP, Blaha MJ.
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How do statins work?: Changing paradigms with implications for statin allocation.
By: Blaha MJ, Martin SS.
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Influence of image acquisition on radiation dose and image quality: full versus narrow phase window acquisition using 320 MDCT.
By: Khosa F, Khan A, Nasir K, Shuaib W, Budoff M, Blankstein R, Clouse ME.
Good heart rate control and predefined narrow window acquisition result in lower radiation dose, without compromising diagnostic image quality for coronary disease evaluation.
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Impact of coronary artery calcium on coronary heart disease events in individuals at the extremes of traditional risk factor burden: the Multi-Ethnic Study of Atherosclerosis.
By: Silverman MG, Blaha MJ, Krumholz HM, Budoff MJ, Blankstein R, Sibley CT, Agatston A, Blumenthal RS, Nasir K.
The presence of a high CAC burden, even among individuals without risk factors, is associated with an elevated event rate, whereas the absence of CAC, even among those with many risk factors, is associated with a low event rate. CAC scoring can further risk-stratify asymptomatic individuals at the extremes of risk factor burden.
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Derivation and validation of a novel method for more accurate estimation of LDL-C from the standard lipid profile.
By: Jones SR, Martin SS.

Low-density lipoprotein cholesterol (LDL-C) is of longstanding clinical and research interest and the primary target in national and international clinical practice guidelines. Conventionally, LDL-C is estimated by the Friedewald equation which assumes a fixed ratio of TG:VLDL-C of 5:1. Applying a factor of 5 to every individual patient is problematic given variance in the TG:VLDL-C ratio across the range of triglyceride and nonHDL-C levels. Rather than a fixed conversion factor, we have developed a method that uses a sliding scale factor to estimate VLDL-C with high precision from triglycerides and non-HDL cholesterol levels.

Effect of statin treatment on coronary plaque progression — a serial coronary CT angiography study.
By: Zeb I, Li D, Nasir K, Malpeso J, Batool A, Flores F, Dailing C, Karlsberg RP, Budoff M.

Statin therapy resulted in significantly lower progression of low attenuation plaque and noncalcified plaques compared to nonstatin users.

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