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Ciccarone Articles

Ciccarone Center Research



Landmark Articles

C-reactive protein modifies the association of plasma leptin with coronary calcium in asymptomatic overweight individuals.
By: Martin SS, Qasim AN, Rader DJ, Reilly MP.


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Combined cardiac magnetic resonance imaging and C-reactive protein levels identify a cohort at low risk for defibrillator firings and death.
By: Wu KC, Gerstenblith G, Guallar E, Marine JE, Dalal D, Cheng A, Marbán E, Lima JA, Tomaselli GF, Weiss RG.
Annually, ~80,000 Americans receive guideline-based primary prevention implantable cardioverter-defibrillators (ICDs), but appropriate firing rates are low. In a cohort of primary prevention ICD candidates, combining a myocardial heterogeneity index with an inflammatory biomarker identified a subgroup with a very low risk for adverse cardiac events, including ventricular arrhythmias. This novel approach warrants further investigation to confirm its value as a clinical risk stratification tool.
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Prevalence of traditional modifiable cardiovascular risk factors in patients with rheumatoid arthritis: comparison with control subjects from the multi-ethnic study of atherosclerosis.
By: Chung CP, Giles JT, Petri M, Szklo M, Post W, Blumenthal RS, Gelber AC, Ouyang P, Jenny NS, Bathon JM.
We tested the hypotheses that major modifiable cardiovascular risk factors were more frequent and rates of treatment, detection, and control were lower in patients with rheumatoid arthritis than in non-rheumatoid arthritis controls. Hypertension is more common in patients with rheumatoid arthritis, while other traditional CV risk factors are highly prevalent, under-diagnosed, and poorly controlled in patients with rheumatoid arthritis, as well as controls.
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Longitudinal predictors of progression of carotid atherosclerosis in rheumatoid arthritis.
By: Giles JT, Post WS, Blumenthal RS, Polak J, Petri M, Gelber AC, Szklo M, Bathon JM.
These prospective data provide evidence that inflammation is a contributor to the progression of subclinical atherosclerosis in rheumatoid arthritis and that it is potentially modified favorably by tumor necrosis factor inhibitors and detrimentally by glucocorticoids.
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Hepatic steatosis, obesity, and the metabolic syndrome are independently and additively associated with increased systemic inflammation.
By: Ndumele CE, Nasir K, Conceiçao RD, Carvalho JA, Blumenthal RS, Santos RD.
The goal of this study was to assess the independent and collective associations of hepatic steatosis, obesity, and the metabolic syndrome with elevated hsCRP levels. We evaluated 2,388 individuals without clinical cardiovascular disease between December 2004 and December 2006. Hepatic steatosis was diagnosed by ultrasound, and the metabolic syndrome was defined using National Heart, Lung, and Blood Institute criteria. We concluded that hepatic steatosis, obesity, and the metabolic syndrome are independently and additively associated with increased odds of high hsCRP levels.
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Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study.
By: Blaha MJ, Budoff MJ, DeFilippis AP, Blankstein R, Rivera JJ, Agatston A, O’Leary DH, Lima J, Blumenthal RS, Nasir K.
The landmark Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial showed that some patients with LDL-cholesterol (LDL-C) <130 mg/dL and high-sensitivity C-reactive protein (hsCRP) concentrations of >2 mg/L benefit from treatment with rosuvastatin, although the absolute rates of cardiovascular events were low. In a population eligible for JUPITER, we established whether coronary artery calcium (CAC) might further stratify risk; additionally we compared hsCRP with CAC for risk prediction across the range of low and high hsCRP values. CAC further stratifies risk in patients eligible for JUPITER, and could be used to target subgroups of patients who are expected to derive the most, and the least, absolute benefit from statin treatment. Focusing of treatment on the subset of individuals with normal LDL-C and at least moderate subclinical atherosclerosis should allow for more appropriate allocation of resources.
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Association between obesity, high-sensitivity C-reactive protein greater than or equal to 2 mg/L, and subclinical atherosclerosis: implications of JUPITER from the Multi-Ethnic Study of Atherosclerosis.
By: Blaha MJ, Rivera JJ, Budoff MJ, Blankstein R, Agatston A, O’Leary DH, Cushman M, Lakoski S, Criqui MH, Szklo M, Blumenthal RS, Nasir K.

Levels of hsCRP are closely associated with abdominal obesity, metabolic syndrome, and atherosclerotic cardiovascular disease. The JUPITER trial has encouraged using hsCRP greater than or equal to 2 mg/L to guide statin therapy; however, the association of hsCRP and atherosclerosis, independent of obesity, remains unknown. We concluded that high hsCRP, as defined by JUPITER, was not associated with CAC and was mildly associated with carotid intima-media thickness (cIMT) in the absence of obesity. In contrast, obesity was associated with both measures of subclinical atherosclerosis independently of hsCRP status.

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Lupus Atherosclerosis Prevention Study (LAPS).
By: Petri MA, Kiani AN, Post W, Christopher-Stine L, Magder LS.
CVD is one of the major causes of death in SLE. A study (200 patients with SLE without clinical CVD randomized to receive atorvastatin 40 mg daily or an identical placebo) was undertaken to investigate whether treatment with statins would reduce subclinical measures of atherosclerosis over a 2-year period. However, this study provided no evidence that atorvastatin reduces subclinical measures of atherosclerosis or disease activity over 2 years in patients with SLE. In fact, it does not reduce biochemical measures of inflammation. The anti-inflammatory effects of statins observed in the general population were not replicated in this SLE clinical trial.
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Association between high-sensitivity C-reactive protein and coronary plaque subtypes assessed by 64-slice coronary computed tomography angiography in an asymptomatic population.
By: Rubin J, Chang HJ, Nasir K, Blumenthal RS, Blaha MJ, Choi EK, Chang SA, Yoon YE, Chun EJ, Choi SI, Agatston AS, Rivera JJ.
We evaluated 1,004 asymptomatic South Korean subjects (mean age, 49±9 years) who underwent coronary computed tomography angiography (CCTA) as part of a health screening evaluation. We examined the association between increasing CRP levels and plaque subtypes using multivariable linear and logistic regression analysis. We concluded that elevated levels of CRP are associated with an increased prevalence of mixed coronary atherosclerotic plaque (MCAP) as assessed by CCTA. Longitudinal studies will determine if the excess risk observed in persons with elevated CRP may be mediated, at least in part, by an increased burden of MCAP.
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The relationship between inflammation, obesity and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA).
By: Lakoski SG, Cushman M, Siscovick DS, Blumenthal RS, Palmas W, Burke G, Herrington DM.
It has been suggested that inflammation is important in the etiology of hypertension and that this may be most relevant among obese persons. To study this, we examined the independent relationships between obesity, inflammation-related proteins (interleukin-6 (IL-6), CRP and fibrinogen) and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis. The relationship between inflammation-related proteins and hypertension risk was predominantly explained by other hypertension risk factors. Obesity, independent of inflammation, remained a potent risk factor for future hypertension.
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