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Ciccarone Articles

Ciccarone Center Research



Landmark Article

  • The premature termination of the ARBITER 6–HALTS trial, the small number of patients studied, and the limited duration of follow-up preclude us from conclusively declaring niacin the adjunctive agent of choice on the basis of the evidence. A decrease of 0.014 mm in the carotid intima–media thickness (IMT) over 14 months does not necessarily merit changes in our lipid-lowering guidelines at this time. However, for now, we would support the use of niacin as the preferred adjunctive agent to be used in combination with the maximal dose of a potent statin in persons who have low levels of HDL cholesterol and established cardiovascular disease. In summary, the ARBITER 6–HALTS results are provocative and are an important contribution to preventive cardiology research. However, the secondary choices for optimizing cholesterol-lowering therapy, constituting part of the “C” component of the “ABCDEs” of secondary prevention of cardiovascular disease, should not overshadow the importance of the rest of the ABCDEs: assessment of risk, antiplatelet therapy, blood-pressure management, cholesterol modification and cigarette-smoking cessation, dietary and weight modification, and exercise habits.
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The JUPITER and AURORA clinical trials for rosuvastatin in special primary prevention populations: perspectives, outcomes, and consequences.
By: Narla V, Blaha MJ, Blumenthal RS, Michos ED.
This review outlines the JUPITER and AURORA trials — which examined the effect of statins in two specific patient populations who currently do not meet the guidelines for statin treatment but are nonetheless at high cardiovascular risk — interprets the data and significance of the results, analyzes the drawbacks and impact of both trials, and delineates the potential for further clinical trials.
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25-hydroxyvitamin D levels, race, and the progression of kidney disease.
By: Melamed ML, Astor B, Michos ED, Hostetter TH, Powe NR, Muntner P.
Low 25-hydroxyvitamin D, or 25(OH)D, levels are associated with development of end stage renal disease (ESRD), even after adjustment for multiple risk factors. Low 25(OH)D levels may account for a substantial proportion of the increased risk for ESRD experienced by black individuals.
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Gender differences in coronary plaque composition by coronary computed tomography angiography.
By: Blaha MJ, Nasir K, Rivera JJ, Choi EK, Chang SA, Yoon YE, Chun EJ, Choi SI, Agatston A, Blumenthal RS, Chang HJ.
In this population of asymptomatic middle-aged Korean individuals, males had a significantly greater burden of mixed coronary artery plaques (MCAP) and calcified arterial plaques (CAP). Future studies will determine whether these differences contribute to the accelerated cardiovascular risk observed in men.
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Life course socioeconomic conditions and metabolic syndrome in adults: the Atherosclerosis Risk in Communities (ARIC) Study.
By: Chichlowska KL, Rose KM, Diez-Roux AV, Golden SH, McNeill AM, Heiss G.
Black and white women with low childhood socioeconomic status (SES), early adult SES, mature adult SES or cumulative SES were more likely to have the metabolic syndrome (MetS) than those with high SES. These associations remained after adjustment for physical activity, smoking status, and drinking status. In contrast, there was no association of SES with MetS in men. Our findings suggest that socioeconomic disadvantage early in life and across the life course influences risk of the MetS in black and white women.
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Integrative predictive model of coronary artery calcification in atherosclerosis.
By: McGeachie M, Ramoni RL, Mychaleckyj JC, Furie KL, Dreyfuss JM, Liu Y, Herrington D, Guo X, Lima JA, Post W, Rotter JI, Rich S, Sale M, Ramoni MF.
Many different genetic and clinical factors have been identified as causes or contributors to atherosclerosis. We present a model of preclinical atherosclerosis based on genetic and clinical data that predicts the presence of coronary artery calcification in healthy Americans of European descent 45 to 84 years of age in the MESA study. Our investigation of joint genetic and clinical factors associated with atherosclerosis shows predictive results for both cases, as well as enhanced performance for their combination.
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Thirty-year multivariate risk assessment is a stronger predictor of cardiovascular disease than the 10-year model.
By: Ketlogetswe K, Blumenthal RS.
The 30-year prediction tool proposed by Pencina et al. now provides clinicians with a tool to assess longer-term risk of CVD and may lead to the introduction of earlier prevention strategies in asymptomatic individuals. The focus of the shorter-term prediction tools is a presumed direct benefit to individuals in the short run, whereas lifetime risk carries broader implications for public health and the need for the individual to adopt lifestyle changes to lower risk in the long run. It remains to be seen whether the use of the algorithm will translate into an increase in the number of younger individuals receiving aspirin and lipid-lowering therapies vs. a more aggressive lifestyle modification approach owing to clinician’s unease with prescribing medications to asymptomatic, seemingly healthy individuals.
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A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction.
By: Hare JM, Traverse JH, Henry TD, Dib N, Strumpf RK, Schulman SP, Gerstenblith G, DeMaria AN, Denktas AE, Gammon RS, Hermiller JB Jr, Reisman MA, Schaer GL, Sherman W.
Bone marrow-derived hMSCs may ameliorate consequences of MI, and have the advantages of preparation ease, allogeneic use due to immunoprivilege, capacity to home to injured tissue, and extensive pre-clinical support.
Intravenous allogeneic hMSCs are safe in patients after acute MI.  This trial provides pivotal safety and provisional efficacy data for an allogeneic bone marrow-derived stem cell in post-infarction patients. (Safety Study of Adult Mesenchymal Stem Cells [MSC] to Treat Acute Myocardial Infarction; NCT00114452). 
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Relationship of carotid distensibility and thoracic aorta calcification: multi-ethnic study of atherosclerosis.
By: Blaha MJ, Budoff M, Rivera JJ, Katz R, O’Leary DH, Polak JF, Takasu J, Blumenthal RS, Nasir K.
There is a strong independent association between carotid stiffness and thoracic aorta calcification. Carotid stiffness is more highly correlated with calcification of the aorta, a central elastic artery, than calcification of the coronary arteries. The prognostic significance of these findings requires longitudinal follow-up of the MESA cohort.
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Serum vitamin D, parathyroid hormone levels, and carotid atherosclerosis.
By: Reis JP, von Mühlen D, Michos ED, Miller ER 3rd, Appel LJ, Araneta MR, Barrett-Connor E.

In subgroup analyses, 1,25(OH)(2)D was inversely associated with internal carotid IMT among those with hypertension. These findings from a population-based cohort of older adults suggest a potential role for vitamin D in the development of subclinical atherosclerosis. Additional research is needed to determine whether vitamin D may influence the progression of atherosclerosis, including the effects of supplementation on the atherosclerotic process.

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Evidence-based guidelines for cardiovascular risk reduction: The safety and efficacy of high-dose statin therapy.
By: Ashen MD, Foody JM.
Suboptimal use of statins by patients who remain at an unnecessarily increased risk of CV disease may be explained by concerns over the safety and efficacy of high-dose statin regimens in certain populations. These issues are explored in the context of current, evidence-based clinical guidelines for low-density lipoprotein-cholesterol (LDL-C) management and, through 3 hypothetical case studies, selection of appropriate starting doses of statins, and titration to a higher dose or switching to a more potent statin, to ensure that patients reach their individual LDL-C goals and reduce their overall CV risk, is also examined.
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