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Ciccarone Articles

Ciccarone Center Research



Landmark Articles

  • Baseline CAC accurately identifies coronary atherosclerosis and improves prediction of future cardiac events. However, whether knowledge of progression of CAC scores over time further improves risk prediction is unclear. We conducted a comprehensive review of published reports on CAC progression and found that CAC progression correlates with worsening atherosclerosis and may facilitate prediction of future cardiac events. These findings support the notion that slowing CAC progression with therapeutic interventions might provide prognostic benefit. However, despite promising early data, such interventions (most notably with statin therapy) have not been shown to slow the progression of CAC in any randomized controlled trial to date, outside of post hoc subgroup analyses. Thus, routine quantification of CAC progression cannot currently be recommended in clinical practice.
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  • It is important to note that the conclusion in the editorial that the Gottlieb et al. paper presents a “starkly contrasting picture” to a prior systematic review is based on a statistical error.Once again, Bayes’ theorem is critical. Although CAC = 0 may not definitively exclude important coronary artery disease (CAD) in patients referred for coronary angiography, there may be potential applications in lower-risk patients presenting with atypical chest pain features.
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  • In this observational study, we examined whether high baseline CACS were associated with the initiation as well continuation of new lipid-lowering medication (LLM), blood pressure-lowering medication (BPLM), and regular aspirin (ASA) use in a multi-ethnic population-based cohort. Findings indicate that CACS >400 was associated with a higher likelihood of initiation and continuation of LLM, BPLM, and ASA. The association was weaker for continuation than for initiation of these preventive therapies.
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  • We describe 6 risk algorithms (Framingham Risk Score for coronary heart disease events and for cardiovascular events, Adult Treatment Panel III, SCORE [Systematic Coronary Risk Evaluation] project, Reynolds Risk Score, ASSIGN [Assessing Cardiovascular Risk to Scottish Intercollegiate Guidelines Network/SIGN to Assign Preventative Treatment], and QRISK [QRESEARCH Cardiovascular Risk Algorithm]) for outcomes, population derived/validated, receiver-operating characteristic, variables included, and limitations. Areas of uncertainty include 10-year versus lifetime risk, prediction of CVD or coronary heart disease end points, nonlaboratory-based risk scores, age at which to start, race and sex differences, and whether a risk score should guide therapy. We believe that the best high-risk approach to CVD evaluation and prevention lies in routine testing for cardiovascular risk factors and risk score assessment. We recommend that health care providers discuss the global cardiovascular risk and lifetime cardiovascular risk score assessment with each patient.
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Variation in atherosclerotic plaque composition according to increasing coronary artery calcium scores on computed tomography angiography.
By: Nasir K, Rivera JJ, Yoon YE, Chang SA, Choi SI, Chun EJ, Budoff MJ, Blumenthal RS, Chang HJ.
This study examines the prognostic importance of noncalcified, partially calcified (mixed), and predominantly calcified plaques on CCTA and the effect of the absolute coronary calcium scores on the composition of the various plaques.
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Relationships of mitral annular calcification to cardiovascular risk factors: the Multi-Ethnic Study of Atherosclerosis (MESA).
By: Kanjanauthai S, Nasir K, Katz R, Rivera JJ, Takasu J, Blumenthal RS, Eng J, Budoff MJ.
The relationship between MAC, a fibrous, degenerative calcification of the mitral valve, and CVD risk factors is not well defined. Thus, we performed a cross-sectional study to determine which CVD risk factors are independently associated with MAC. We concluded that age, female gender, diabetes, and increased BMI were significantly associated with MAC. Prevalence of MAC was strongly associated with female gender and increasing age in all ethnicities.
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Clinical utility of statins for cardiovascular risk reduction in the among the elderly.
By: Long S, Blaha MJ, Blumenthal RS, Michos ED.
Age is one of the strongest predictors of cardiovascular disease (CVD) risk. Treatment with statins can significantly reduce CVD events and mortality in both primary and secondary prevention. Yet despite the high CVD risk among the elderly, there is underutilization of statins in this population (ie, the treatment-risk paradox). Few studies have investigated the use of statins in the elderly, particularly for primary prevention and, as a result, guidelines for treating the elderly are limited. This is likely due to: uncertainties of risk assessment in older individuals where the predictive value of individual risk factors is decreased; the need to balance the benefits of primary prevention with the risks of polypharmacy, health care costs, and adverse medication effects in a population with decreased life expectancy; the complexity of treating patients with many other comorbidities; and increasingly difficult social and economic concerns. As life expectancy increases and the total elderly population grows, these issues become increasingly important. JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) is the largest primary prevention statin trial to date and enrolled a substantial number of elderly adults. Among the 5695 JUPITER participants greater than or equal to 70 years of age, the absolute CVD risk reduction associated with rosuvastatin was actually greater than for younger participants. The implications of this JUPITER subanalysis and the broader role of statins among older adults is the subject of this review.
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Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification.
By: Shen H, Bielak LF, Ferguson JF, Streeten EA, Yerges-Armstrong LM, Liu J, Post W, O’Connell JR, Hixson JE, Kardia SL, Sun YV, Jhun MA, Wang X, Mehta NN, Li M, Koller DL, Hakonarson H, Keating BJ, Rader DJ, Shuldiner AR, Peyser PA, Reilly MP, Mitchell BD.
The vitamin D endocrine system is essential for calcium homeostasis, and low levels of vitamin D metabolites have been associated with CVD risk. We hypothesized that DNA sequence variation in genes regulating vitamin D metabolism and signaling pathways might influence variation in CAC. A common SNP in the CYP24A1 gene was associated with CAC quantity in 3 independent populations. This result suggests a role for vitamin D metabolism in the development of CAC quantity.
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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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Biological basis of depression in adults with diabetes.
By: Champaneri S, Wand GS, Malhotra SS, Casagrande SS, Golden SH.
Diabetes and depression are common comorbid conditions. Although certain health behaviors and risk factors partially explain the association of depression and diabetes, other potential mechanisms have yet to be elucidated. The objectives of this review were to summarize and review the recent evidence showing alterations of these three biological systems—HPA axis, SNS, and inflammatory cascade—in depression, diabetes, and diabetes-related risk factors.
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Cost-effective prevention of coronary heart disease.
By: Ashen MD.

Healthcare designed to prevent future illness and minimize progression of current illness is a powerful means to improve quality of life, minimize mortality, and decrease health care costs. Coronary heart disease (CHD) is the #1 killer of both men and women in the United States. Prevention of CHD involves early identification and management of risk factors through assessment and treatment. The goal in CHD prevention is to produce the largest relative risk reduction, the smallest number needed to treat, and the lowest cost per quality-adjusted life year saved. Evidence-based treatment strategies have been shown to cost-effectively minimize CHD risk and reduce morbidity and mortality. Approaches that encompass the lifespan, solidify assessment and treatment strategies in the primary care setting, and reach into the workplace, schools, churches, and homes to make small changes in risk factors across an entire population are important areas for improving CHD preventive care. Public health policies are also necessary to support implementation of preventive programs.

Risk factor differences for aortic versus coronary calcified atherosclerosis: the multi-ethnic study of atherosclerosis.
By: Criqui MH, Kamineni A, Allison MA, Ix JH, Carr JJ, Cushman M, Detrano R, Post W, Wong ND.
The goal of this study was to compare and contrast CAC with abdominal aortic calcium (AAC) in terms of their associations with traditional and novel CVD risk factors. AAC showed stronger correlations with most CVD risk factors than did CAC. The predictive value of AAC compared with CAC for incident CVD events remains to be evaluated.
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Coronary arterial calcium and outcomes.
By: Rubin J, Nasir K, Agatston AS, Blumenthal RS, Rivera JJ.
This is an excellent review of the strengths and limitations of coronary artery calcium measurements to improve CVD risk prediction.