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Ciccarone Center Research

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Race/ethnic difference in diabetes and diabetic complications.
By: Spanakis EK, Golden SH.

This study's data provide novel updates on race/ethnic differences in children and adults with type 1 diabetes, children with type 2 diabetes, and in Latino subpopulations.

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Metabolic rates of ATP transfer through creatine kinase (CK Flux) predict clinical heart failure events and death.
By: Bottomley PA, Panjrath GS, Lai S, Hirsch GA, Wu K, Najjar SS, Steinberg A, Gerstenblith G, Weiss RG.
Reduced CK flux may be a potential heart failure (HF) treatment target.
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Long-term predictive value of the Framingham Risk Score for Stroke in HIV-positive vs HIV-negative men.
By: Mateen FJ, Post WS, Sacktor N, Abraham AG, Becker JT, Smith BR, Detels R, Martin E, Phair JP, Shinohara RT; Multicenter AIDS Cohort Study (MACS) Investigators.

The Framingham Risk Score for Stroke prediction was systematically different in HIV+ vs. HIV- men with stroke events, while the score underestimates the long-term risk of stroke in HIV+ men.

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Measurement of arterial activity on routine FDG PET/CT images improves prediction of risk of future CV events.
By: Figueroa AL, Abdelbaky A, Truong QA, Corsini E, MacNabb MH, Lavender ZR, Lawler MA, Grinspoon SK, Brady TJ, Nasir K, Hoffmann U, Tawakol A.

Arterial fluorodeoxyglucose, measured from routinely obtained PET/CT images, substantially improved incident CVD prediction beyond Framingham risk score among individuals undergoing cancer surveillance.

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International ABI awareness as the next step in the PAD campaign.
By: Ratchford E.

Study investigates several issues related to peripheral artery disease (PAD) awareness among general practitioners (GPs) in Queensland. She contends that the study's response rate was low at 26%, however, it clearly highlights the importance of disseminating PAD guidelines and improving ankle-brachial index (ABI) awareness. She notes that the study distinguishes between PAD screening and PAD diagnosis.

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Response to comment on: Draznin et al. Pathways to quality inpatient management of hyperglycemia and diabetes: a call to action. Diabetes Care.
By: Draznin B, Gilden J, Golden SH, Inzucchi S; PRIDE Investigators.
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APOE modulates the correlation between triglycerides, cholesterol, and CHD through pleiotropy, and gene-by-gene interactions.
By: Maxwell TJ, Ballantyne CM, Cheverud JM, Guild CS, Ndumele CE, Boerwinkle E.
The relationship between total cholesterol and triglycerides varies by apolipoprotein E isoform genotype in African-American and European-American populations.
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Use of high sensitivity C-reactive protein for risk assessment.
By: Martin SS, Johnson AE, Blumenthal RS.
We present a state-of-the-art review of the use of blood-based biomarkers to refine cardiovascular risk prediction.
Association of depressive symptoms and anti-depressants with body mass index and waist circumference in elderly men and women: The ARIC Carotid MRI Study.
By: Golden SH, Hsu H, Astor BC, Malhotra S, Wand GS, Wasserman BA.

Depressive symptoms are associated with obesity, a precursor to type 2 diabetes and cardiovascular disease, and might in part explain the association of depressive symptoms with adverse metabolic outcomes. We determined the cross-sectional association between depressive symptoms and body mass index (BMI) and waist circumference (WC) in 1,314 elderly men and women age 60 to 83 years in the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study.

Vegetarian diets in cardiovascular prevention.
By: Ashen MD.

There is growing evidence that consumption of a vegetarian diet as well as specific components of a vegetarian diet lower the incidence of cardiovascular disease (CVD) and death. Vegetarian diets lower the probability of developing CVD, are effective in altering serum lipids, are beneficial in reducing blood pressure, improve glycemic control and insulin sensitivity, reduce weight, and lower mortality. Vascular effects of a vegetarian diet include a thinner carotid IMT and lower brachial artery resistance. Health care providers should be aware of the types of vegetarian diets and their risks and benefits in order to guide patients' dietary habits with the ultimate goal of reducing their CVD risk. While a patient does not have to become a complete vegetarian to reduce their CVD risk, they can make simple changes in their diet that are effective in risk reduction.

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Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile.
By: Martin SS, Blaha MJ, Elshazly MB, Toth PP, Kwiterovich PO, Blumenthal RS, Jones SR.
This study sought to develop a new method for calculating low-density lipoprotein cholesterol, the so-called “bad” form of blood fat that can lead to hardening of the arteries, that would be more accurate than the standard profile for measuring a person’s risk for heart attack and stroke.
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Non-high-density lipoprotein cholesterol, guideline targets, and population percentiles for secondary prevention in 1.3 million adults: the VLDL-2 study (very large database of lipids).
By: Elshazly MB, Martin SS, Blaha MJ, Joshi PH, Toth PP, McEvoy JW, Al-Hijji MA, Kulkarni KR, Kwiterovich PO, Blumenthal RS, Jones SR.
There is a significant patient-level discordance between non-HDL-C and LDL-C percentiles at lower LDL-C and higher triglyceride levels, which has implications for the treatment of high-risk patients.
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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, Buvat J, et al.
A question about erectile dysfunction should be included in assessment of cardiovascular disease (CVD) risk in all men and be added to CVD risk assessment guidelines.
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Creating a transdisciplinary research center to reduce cardiovascular health disparities in Baltimore, Maryland: Lessons learned.
By: Cooper LA, Boulware LE, Miller ER, Golden SH, Carson KA, Noronha G, Huizinga MM, Roter DL, Yeh HC, Bone LR, Levine DM, Hill-Briggs F, Charleston J, Kim MT, Wang NY, Aboumatar HJ, Halbert JP, Ephraim PL, Brancati FL.

Cardiovascular disease (CVD) disparities continue to have a negative impact on African Americans in the United States, largely because of uncontrolled hypertension. Despite the availability of evidence-based interventions, their use has not been translated into clinical and public health practice. The Johns Hopkins Center to Eliminate Cardiovascular Health Disparities is a new transdisciplinary research program with a stated goal to lower the impact of CVD disparities on vulnerable populations in Baltimore, Maryland. By targeting multiple levels of influence on the core problem of disparities in Baltimore, the center leverages academic, community, and national partnerships and a novel structure to support 3 research studies and to train the next generation of CVD researchers. We also share the early lessons learned in the center's design.

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Vitamin D deficiency is associated with development of subclinical coronary artery disease in HIV-infected African American cocaine users with low Framingham-defined cardiovascular risk.
By: Lai H, Fishman EK, Gerstenblith G, Moore R, Brinker JA, Keruly JC, Chen S, Detrick B, Lai S.

The incidence of subclinical CAD in HIV-infected African-American cocaine users with low CAD risk is high, especially in those with vitamin D deficiency.

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Relation of hepatic steatosis to atherogenic dyslipidemia.
By: Makadia SS, Blaha M, Keenan T, Ndumele C, Jones S, DeFilippis A, Martin S, Kohli P, Conceicao R, Carvalho J, Nasir K, Blumenthal R, Santos RD.
Hepatic steatosis may play a direct metabolic role in conferring increased cardiovascular risk.
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Is direct measure of LDL preferred over a calculated LDL?
By: Miller PE, Elshazly MB, Jones SR, Martin SS.
Ratio of dense to buoyant LDL subclass is associated with LDL density phenotype (VLDL-5).
By: Ahmed HM, Elshazly MB, Blaha MJ, Martin SS, Kulkarni K, Jones SR.

Dense LDL phenotypes are associated with increased atherogenicity, and are commonly evaluated for the purposes of atherosclerosis research and cardiovascular risk discrimination. In this study we examined the ability of LDL subclasses, expressed as a ratio of dense-to-buoyant subclass (LLDR), to predict LDL density phenotype. Further research is needed to investigate the relationship between lipoprotein density and size, and whether LLDR provides more cardiovascular risk discrimination than LDL density phenotype.

Statins and cognition: a systematic review and meta-analysis of short- and long-term cognitive effects.
By: Swiger KJ, Manalac RJ, Blumenthal RS, Blaha MJ, Martin SS.
In this study of patients without baseline cognitive dysfunction, short-term data are most compatible with no adverse effect of statins on cognition, and long-term data supports a beneficial role for statins in the prevention of dementia.
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How about a worldwide effort to collaborate on developing guidelines?
By: Martin SS.
Omega-3 fatty acid blood levels: clinical significance and controversy.
By: Superko HR, Superko SM, Nasir K, Agatston A, Garrett BC.
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Relationship between the cortisol awakening response and other features of the diurnal cortisol rhythm: the Multi-Ethnic Study of Atherosclerosis.
By: Golden SH, Sánchez BN, Wu M, Champaneri S, Diez Roux AV, Seeman T, Wand GS.
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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Niacin — a case study for the role of event-driven versus surrogate endpoint trials.
By: Blaha MJ, Michos ED.
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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.
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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Vegetarian diets in cardiovascular prevention.
By: Ashen MD, Blumenthal RS, Sperling L.
This article reviews the strengths and limitations of the various types of vegetarian diets and variations of them.
Very large database of lipids: rationale and design.
By: Martin SS, Blaha MJ, Toth PP, Joshi PH, McEvoy JW, Ahmed HM, Elshazly MB, Swiger KJ, Michos ED, Kwiterovich PO, Kulkarni KR, Chimera J, Cannon CP, Blumenthal RS, Jones SR.
The Very Large Database of Lipids database is an ongoing protocol that harnesses de-identified data from the daily operations of a commercial lipid laboratory and provides an opportunity for collaboration and new knowledge generation through careful examination of granular lipid data on a large scale.
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High-priority research needs for insulin delivery and glucose monitoring methods.
By: Yeh HC, Lau BD, Golden SH, Donner T, Brown TT, Bass EB.
This article summarizes future research needs in the area of technologies for insulin delivery and glucose monitoring methods.
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A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care?
By: Oni ET, Agatston AS, Blaha MJ, Fialkow J, Cury R, Sposito A, Erbel R, Blankstein R, Feldman T, Al-Mallah MH, Santos RD, Budoff MJ, Nasir K.

Considerable evidence supports the association of nonalcoholic fatty liver disease with subclinical atherosclerosis, independent of traditional risk factors and metabolic syndrome.

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Cardiovascular disease risk prediction and its integration into clinical practice.
By: Abd TT, Blaha MJ, Blumenthal RS, Joshi PH.
The authors highlighted measures of risk prediction and made suggestions on how to integrate these into a busy clinical practice.
No association of 9p21 with arterial elasticity and retinal microvascular findings.
By: Folsom AR, Pankow JS, Li X, Duprez DA, Jacobs DR Jr, Klein R, Klein B, Tang W, Wong TY, Cotch MF, Taylor KD, Rich SS, Hall JL, Post WS, Rotter JI.
This study does not support an association of 9p21 variation with arterial elasticity or retinal microvascular abnormalities.
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Validity of meta-analysis in diabetes: meta-analysis is an indispensable tool in evidence synthesis.
By: Golden SH, Bass EB.
This article presents supporting arguments to support the use for meta-analysis in diabetes clinical research in a pro-con debate.
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Statins and cognition; a systematic review and meta-analysis of short- and long-term cognitive effects.
By: Swiger KJ, Manolac RJ, Blumenthal RS, Blaha MJ, Martin SS.

In patients without baseline cognitive dysfunction, short-term data are most compatible with no adverse effect of statins on cognition, while long-term data appear to support a beneficial role in the prevention of dementia.

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Landmark lipid-lowering trials in the primary prevention of cardiovascular disease.
By: Chrispin J, Martin SS, Hasan RK, Joshi PH, Minder CM, McEvoy JW, Kohli P, Johnson AE, Wang L, Blaha MJ, Blumenthal RS.
Over the past 25?years, lipid-lowering therapies have been developed that are proven to not only lower cholesterol, but also to decrease adverse cardiovascular events and CVD mortality. This review highlights some key clinical trials encompassing several classes of lipid-lowering medications that have provided clinicians with an evidence-based framework for managing their patients’ cardiovascular risk.
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Statin therapy for hyperlipidemia.
By: McEvoy JW, Blumenthal RS, Blaha MJ.
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Statins for primary prevention of cardiovascular disease.
By: Minder CM, Blumenthal RS, Blaha MJ.
This article reviews the extensive evidence supporting the selective use of lipid-lowering therapy in intermediate to high-risk individuals.
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Association of resting heart rate with carotid and aortic arterial stiffness: Multi-Ethnic Study of Atherosclerosis.
By: Whelton SP, Blankstein R, Al-Mallah MH, Lima JA, Bluemke DA, Hundley WG, Polak JF, Blumenthal RS, Nasir K, Blaha MJ.

Results from this study suggest that a higher resting heart rate is associated with an increased arterial stiffness independent of atrioventricular nodal blocker use and physical activity level, with a stronger association for a peripheral (carotid) compared with a central (aorta) artery.

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Relation of hepatic steatosis to atherogenic dyslipidemia.
By: Makadia S, Blaha MJ, Keenan T, Ndumele C, Jones S, DeFilippis A, Martin SS, Kohli P, Conceicao RD, Carvalho JA, Nasir K, Blumenthal RS, Santos R.
This article looks at the relationship between fatty liver and atherogenic lipid profiles.
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Absolute coronary artery calcium score is the best predictor of non-calcified plaque involvement in patients with low calcium scores (1–100).
By: Tam LM, Joonseok K, Blumenthal RS, Nasir K, Al-Mallah MH, Blaha MJ.
This study looked at the predictors on non-calcified plaque in persons with mild coronary calcification.
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Lipid-modifying therapy.
By: Patel C, Blumenthal RS, Martin SS.
This comprehensive review goes over the evidence base for the upcoming National Cholesterol Education Program guidelines.
Effect of equivalent on-treatment apolipoprotein levels on outcomes (from the AIM-HIGH and HPS2-THRIVE).
By: Al-Hijji M, Martin SS, Joshi PH, Jones SR.

This viewpoint study seeks to explore the recent failures of the niacin trials through apolipoprotein lens.

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Cardiovascular disease risk prediction – integration into clinical practice.
By: Abd TT, Blaha MJ, Blumenthal RS, Joshi PH.
This study examined the strengths and limitation of various cardiovascular risk prediction algorithms.
Platelet COX-1-independent TxA2 generation in patients with acute coronary syndromes.
By: DeFilippis AP, Oloyede OS, Andrikopoulou E, Saenger AK, Palachuvattil JM, Fasoro YA, Guallar E, Blumenthal RS, Kickler TK, Jaffe AS, Gerstenblith G, Schulman SP, Rade JJ.

Aspirin's therapeutic action is via inhibition of platelet cyclooxygenase 1 (COX-1) thromboxane A2 (TxA2) production. The aim of this study was to evaluate TxA2 production, in the absence of platelet COX-1 activity, in coronary atherosclerotic heart disease patients with and without atherothrombotic myocardial infarction (MI). Differences in TxA2 production, in the absence of platelet COX-1 activity, between those with vs. without atherothrombotic MI were not observed when TxA2 generation was assessed on 11-dehydro-TxB2 production alone (polyclonal ELISA or LC-MS/MS), but differences were observed when TxA2 generation was assessed using 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2 (monoclonal ELISA). These findings highlight important differences between different commercially available assays for TxA2 generation and suggest that 11-dehydro-2,3-dinor-TxB2 may be critical to the biology of atherothrombosis. 

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Vitamin D deficiency is associated with coronary artery calcification in cardiovascularly asymptomatic African Americans with HIV infection.
By: Lai S, Fishman EK, Gerstenblith G, Brinker J, Tai H, Chen S, Li J, Tong W, Detrick B, Lai H.
These data suggest that, in order to reduce the risk for coronary artery disease in HIV-infected African-Americans, vitamin D levels should be closely monitored. These data also suggest that clinical trials should be conducted to examine whether vitamin D supplementations reduce the risk of CAD in this population.
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Friedewald estimated versus directly measured low-density lipoprotein cholesterol and treatment implications.
By: Martin SS, Blaha MJ, Elshazly MB, Brinton EA, Toth PP, McEvoy JW, Joshi PH, Kulkarni KR, Mize PD, Kwiterovich PO, Defilippis AP, Blumenthal RS, Jones SR.
This study discovered that, compared with direct measurement, the Friedewald equation tends to underestimate low-density lipoprotein cholesterol (LDL-C) and, therefore, warrants additional evaluation in high-risk patients. Achieving non-high-density lipoprotein cholesterol (HDL-C) targets are important to reach in the secondary prevention setting.
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ASK NOT what CRP can do for you.
By: Blumenthal RS, Ndumele CE, Martin SS.

This editorial examines the extent to which measurements of vascular inflammation can improve cardiovascular risk prediction.

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Prevalence and prognostic significance of exercise-induced non-sustained ventricular tachycardia in asymptomatic volunteers: The Baltimore Longitudinal Study of Aging.
By: Marine JE, Shetty V, Chow GV, Wright J, Gerstenblith G, Najjar SS, Lakatta EG, Fleg JL.
This longitudinal cohort analysis suggests that brief asymptomatic runs of exercise-induced non-sustained ventricular tachycardia, in the absence of clinical heart disease, are not uncommon in men, older adults, and those with hypertension, but are not associated with increased mortality after adjusting for baseline risk factors. These findings do not necessarily apply to patients with known structural heart disease.
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Non-HDL cholesterol, guideline targets, and population percentiles for secondary prevention in a clinical sample of 1.3 million adults: the very large database of lipids (VLDL-2 Study).
By: Elshazly MB, Martin SS, Blaha MJ, Joshi PH, Toth PP, McEvoy JW, Al-Hijji MA, Kulkarni KR, Kwiterovich PO, Blumenthal RS, Jones SR.
There is significant patient-level discordance between non-HDL-C and LDL-C percentiles at lower values of LDL-C and higher triglycerides. Current non-HDL-C cut-points for high-risk patients should be lowered to match percentiles of LDL-C cut-points. Relatively small absolute reductions in non-HDL-C cut-points result in substantial reclassification of patients to higher treatment categories with potential implications for risk assessment and treatment.
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The role of statins in diabetes mellitus.
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. The American Diabetes Association recommends that individuals with diabetes and a history of cardiovascular disease (CVD), as well as those > 40 years of age without CVD but with CVD risk factors, should be treated with a statin regardless of their baseline LDL cholesterol concentration. This review explains the rationale behind considering diabetes a CHD risk equivalent and summarizes the data for statin use in adults with diabetes without (primary prevention) and with (secondary prevention) established CVD. Although individuals with diabetes are at an increased risk for CVD and benefit from statin therapy, the risk of CVD in people with diabetes is heterogeneous. It therefore may be reasonable to match the intensity of statin therapy with patients' baseline CVD risk.

Obesity, adiposity, and dyslipidemia: A consensus statement from the National Lipid Association.
By: Bays HE, Toth PP, Kris-Etherton PM, Abate N, Aronne LJ, Brown WV, Gonzalez-Campoy JM, Jones SR, Kumar R, La Forge R, Samuel VT.
The goal of this statement is to better define the effect of adiposity on lipoproteins, how the pathos of excessive body fat (adiposopathy) contributes to dyslipidemia, and how therapies such as appropriate nutrition, increased physical activity, weight-management drugs, and bariatric surgery might be expected to impact dyslipidemia.
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Inflammation and CAD: Use of hs-C-Reactive protein as a diagnostic and prognostic tool.
By: Yousuf O, Martin SS, Whelton SP, Blumenthal RS.