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Ciccarone Articles

Ciccarone Center Research


American Journal of Cardiology

Landmark Articles

  • This study shifts the focus from prediction of events to detection of disease in the effort to improve personalized decision-making and outcomes. It also discusses innovative future strategies for risk estimation and treatment allocation in preventive cardiology.
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  • Much attention has been directed toward lifestyle modifications as effective means of reducing cardiovascular disease risk. We review recent observational and interventional trials investigating the effects of physical activity on markers of (or causal factors for) atherosclerotic burden and vascular disease. There is a strong correlation between physical activity and triglyceride reduction, apolipoprotein B reduction, HDL increase, change in LDL particle size, increase in tissue plasminogen activator activity, and decrease in CAC. Further research is needed to elucidate the effect on inflammatory markers and intima-media thickness.
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Emerging therapeutic approaches for the management of diabetes mellitus and macrovascular complications.
By: Golden SH.
Type 2 DM affects an estimated 26 million people in the U.S. and is the 7th leading cause of death. While effective therapy can prevent or delay the complications that are associated with diabetes, according to the Center for Disease Control, 35% of Americans with DM are undiagnosed, and another 79 million Americans have blood glucose levels that greatly increase their risk of developing DM in the next several years. This article reviews established and emerging therapeutic approaches for managing DM and prevention of macrovascular complications.
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Usefulness of baseline obesity to predict development of a high ankle brachial index (from the Multi-Ethnic Study of Atherosclerosis).
By: Tison GH, Ndumele CE, Gerstenblith G, Allison MA, Polak JF, Szklo M.
An abnormally high ABI is associated with increased all-cause and cardiovascular mortality. The relation of obesity to incident high ABI has not been characterized. The aim of this study was to investigate the hypothesis that increased obesity — quantified by body weight, body mass index, waist circumference, and waist-to-hip-ratio — is positively associated with a high ABI (?1.3) and with mean ABI increases over a 4-year follow-up. Independent, positive, and graded associations of increasing obesity with prevalent and incident high ABI and with mean increases in ABI values over time were found. Weight and body mass index seemed to be at least as strongly, if not more strongly, associated with a high ABI than were measures of abdominal obesity.
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Relation of mitral annular calcium and coronary calcium (from the Multi-Ethnic Study of Atherosclerosis [MESA]).
By: Hamirani YS, Nasir K, Blumenthal RS, Takasu J, Shavelle D, Kronmal R, Budoff M.
Atherosclerosis is a complex diffuse disorder. The close correlation between CAC score on computed tomography and extent and severity of coronary atherosclerosis is well established. It has been suggested that mitral annular calcification (MAC) may be a manifestation of generalized atherosclerosis. We observed a strong association between MAC and increasing burden of CAC. This association weakened but persisted after adjustment for age, gender, and other traditional risk factors. These findings suggest that presence of MAC is an indicator of atherosclerotic burden rather than just a degenerative change of the mitral valve.
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Mortality in individuals without known coronary artery disease but with discordance between the Framingham risk score and coronary artery calcium.
By: Ahmadi N, Hajsadeghi F, Blumenthal RS, Budoff MJ, Stone GW, Ebrahimi R.
A risk-management approach based on the Framingham risk score (FRS), although useful in preventing future CAD events, is unable to identify a considerable portion of patients with CAD who need aggressive medical management. CAC, an anatomic marker of atherosclerosis, correlates well with presence and extent of CAD. This study investigated mortality risk associated with CAC score and FRS in subjects classified as “low risk” versus “high risk” based on FRS. In conclusion, the prognostic value of CAC to predict future mortality is far superior to the FRS. Addition of CAC score to FRS significantly improves the identification and prognostication of patients without known CAD.
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Factors associated with presence and extent of coronary calcium in those predicted to be at low risk according to Framingham risk score (from the Multi-Ethnic Study of Atherosclerosis).
By: Okwuosa TM, Greenland P, Lakoski SG, Ning H, Kang J, Blumenthal RS, Szklo M, Crouse JR 3rd, Lima JA, Liu K, Lloyd-Jones DM.
Even among asymptomatic persons at low risk (<10% risk of an MI over the next decade) according to the Framingham risk score, high CAC scores signify a greater predicted risk of CHD events. We determined the noninvasive factors (without radiation exposure) significantly associated with CAC in low-risk, asymptomatic persons. In a cross-sectional analysis, we studied 3,046 individuals at a low 10-year predicted risk (Framingham risk score <10%) of CHD events. In low-risk persons, the traditional risk factors alone predicted advanced CAC with high discrimination and calibration. The biomarker combinations with and without cIMT were also significantly associated with advanced CAC; however, the improvement in the prediction and estimation of the clinical risk were modest compared to the traditional risk factors alone.
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Comparison of the racial/ethnic prevalence of regular aspirin use for the primary prevention of coronary heart disease from the multi-ethnic study of atherosclerosis.
By: Sanchez DR, Diez Roux AV, Michos ED, Blumenthal RS, Schreiner PJ, Burke GL, Watson K.
The regular use of aspirin (?3 days/week) was examined in a cohort of 6,452 White, Black, Hispanic, and Chinese patients without cardiovascular disease in 2000 to 2002 and 5,181 patients from the same cohort in 2005 to 2007. Framingham risk scores were stratified into low (<6% risk of MI over next decade), increased (6% to 9.9%), and high (?10%) risk. In 2000 to 2002 prevalences of aspirin use were 18% and 27% for those at increased and high risk, respectively. In conclusion, regular aspirin use in adults at increased and high risk for CHD remains suboptimal. Important racial/ethnic disparities exist for unclear reasons.
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Relation of aortic valve calcium detected by cardiac computed tomography to all-cause mortality.
By: Blaha MJ, Budoff MJ, Rivera JJ, Santos RD, Shaw LJ, Raggi P, Berman D, Rumberger JA, Blumenthal RS, Nasir K.
Aortic valve calcification was associated with increased all-cause mortality, independent of traditional risk factors and the presence of CAC.
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Relation of aortic valve calcium detected by cardiac computed tomography to all-cause mortality.
By: Blaha MJ, Budoff MJ, Rivera JJ, Khan AN, Santos RD, Shaw LJ, Raggi P, Berman D, Rumberger JA, Blumenthal RS, Nasir K.
Aortic valve calcium (AVC) can be quantified on the same computed tomographic scan as CAC. Although CAC is an established predictor of cardiovascular events, limited evidence is available for an independent predictive value for AVC. We studied a cohort of 8,401 asymptomatic subjects (mean age 53 ± 10 years, 69% men), who were free of known coronary heart disease and were undergoing computed tomography for assessment of subclinical atherosclerosis. The patients were followed for a median of 5 years (range 1 to 7) for the occurrence of mortality from any cause. In conclusion, AVC was associated with increased all-cause mortality, independent of the traditional risk factors and the presence of CAC.
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Statin therapy in primary prevention: New insights regarding women and the elderly.
By: Harrington C, Horne A Jr., Hasan R, Blumenthal RS.

Cardiovascular disease (CVD) remains the leading cause of death in men and women in the United States and is a leading cause of disability. Advances in pharmacotherapy and revascularization strategies have resulted in a decrease in mortality and an improvement of quality of life. The emphasis on primary and secondary prevention is imperative to provide high-quality and cost-effective medical care that will improve survival and quality of life.

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Should statin therapy be allocated on the basis of randomized trial evidence?
By: DeMazumder D, Hasan RK, Blumenthal RS, Michos ED, Jones S.
We questioned the utility of global risk assessment strategies based on the Framingham risk score for guiding statin therapy in light of current data that have become available from more recent and robust prospective randomized clinical trials since the publication of the National Cholesterol Education Program Adult Treatment Panel III guidelines. Moreover, the Adult Treatment Panel III guidelines do not support treatment of some patients who may benefit from statin therapy. In conclusion, we propose an alternative approach for incorporating more recent randomized trial data into future statin allocation algorithms and treatment guidelines.
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