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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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Dyslipidemia management in women and men: exploring potential gender differences.
By: Sharma K, Nagy CD, Blumenthal RS.

This chapter first examines gender differences in CVD risk factors, then specifically focuses on dyslipidemia in women and the effects of estrogen on CVD risk, and finally addresses treatment guidelines for dyslipidemia.

Associations of SNPs in ADIPOQ and subclinical cardiovascular disease in MESA.
By: Wassel CL, Pankow JS, Rassmussen-Torvik LJ, Li N, Taylor KD, Guo X, Palmas WR, Post WS.

Circulating adiponectin is associated with both clinical and subclinical cardiovascular disease (CVD). Variants of the adiponectin gene (ADIPOQ) are associated with clinical CVD, but little is known about associations with subclinical CVD. We studied the association of 11 ADIPOQ single-nucleotide polymorphisms (SNPs) with common and internal carotid intima media thickness (cIMT), presence of coronary artery calcification (CAC), and CAC scores (in those with CAC) in 2,847 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were white (n = 712), African American (n = 712), Chinese (n = 718), and Hispanic (n = 705). All models were adjusted for age, sex, and field site, and stratified by race/ethnic group. African Americans with genotypes AG/GG of rs2241767 had 36% greater (95% confidence interval (CI; 16%, 59%), P = 0.0001) CAC prevalence; they also had a larger common cIMT (P = 0.0043). Also in African Americans, genotypes AG/AA of rs1063537 were associated with a 35% (95% CI (14%, 59%), P = 0.0005) greater CAC prevalence. Hispanics with the AA genotype of rs11711353 had a 37% (95% CI (14%, 66%), P = 0.0011), greater CAC prevalence compared to those with the GG genotype. Additional adjustment for ancestry in African-American and Hispanic participants did not change the results. No single SNP was associated with subclinical CVD phenotypes in Chinese or white participants. There appears to be an association between ADIPOQ SNPs and subclinical CVD in African Americans and Hispanics. Replication as well as assessment of other ADIPOQ SNPs is warranted.

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Risk factor differences for aortic versus coronary calcified atherosclerosis. The Multiethnic Study of Atherosclerosis.
By: Criqui MH, Kamineni A, Allison MA, Ix JH, Carr JJ, Cushman M, Detrano R, Post W, Wong ND.
Abdominal aortic calcium (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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Vitamin D in atherosclerosis, vascular disease, and endothelial function
By: Brewer LC, Michos ED, Reis JP
Large-scale, well-conducted, placebo-controlled clinical trials testing the efficacy of vitamin D supplementation in delaying, slowing, or reversing the atherosclerotic disease process have not yet been conducted. Until the results of these studies are available, we believe it is premature to recommend vitamin D as a therapeutic option in atherosclerosis.
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Cumulative exposure to ionizing radiation from diagnostic and therapeutic cardiac imaging procedures: a population-based analysis.
By: Chen J, Einstein AJ, Fazel R, Krumholz HM, Wang Y, Ross JS, Ting HH, Shah ND, Nasir K, Nallamothu BK.
Cardiac imaging procedures frequently expose patients to ionizing radiation, but their contribution to effective doses of radiation in the general population is unknown.
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Coronary artery calcium score and cardiovascular event prediction.
By: McEvoy JW.
In the study by Polonsky et al, the net reclassification index (NRI) for CHD (myocardial infarction, cardiac death, resuscitated arrest, and definite angina) was +25% overall. However, 24 of 209 patients who experienced events (11%) were reclassified to a lower risk group by calcium scoring. As the authors point out, a randomized controlled trial is needed to assess the use of coronary artery calcium score (CACS) reclassification on clinical outcomes. This current study is a compelling argument to provide support for such an endeavor.
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Thoracic aortic distensibility and thoracic aortic calcium (from the Multi-Ethnic Study of Atherosclerosis [MESA]).
By: Al-Mallah MH, Nasir K, Katz R, Takasu J, Lima JA, Bluemke DA, Hundley G, Blumenthal RS, Budoff MJ.
Using multivariate analysis, thoracic aortic calcification (TAC) was independently associated with aortic distensibility (AD) after adjusting for age, gender, ethnicity, and other covariates. Our analysis demonstrated that increased arterial stiffness is associated with increased TAC, independent of ethnicity and other atherosclerotic risk factors.
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Caveat emptor: the coronary calcium warranty.
By: McEvoy JW, Blaha MJ, Blumenthal RS.
It would be beneficial for clinicians to have the “warranty period” of a zero coronary calcium score stratified by baseline risk group (<10% and 10% to 20%). It may even be prudent to stratify further, as some have advocated for CAC testing in an expanded intermediate-risk group of 6% to 20% (e.g., <6%, 6% to 10%, and 10% to 20%). The investigators may have been overly prudent to suggest that “caution should be applied to interpreting our results among patients who are not receiving lipid-lowering therapy.” Although they express concern that the 756 patients on statin therapy (72%) may have had retarded CAC progression, randomized trials to date have not shown that statin therapy can achieve this. CAC = 0 has enormous potential for ruling out important coronary artery disease in asymptomatic patients. The duration and application of the “warranty period” remains an important topic for further research.
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Prevention of coronary heart disease: risk assessment, treatment strategies and the role of prevention in cost-effective health care.
By: Ashen, MD.
Omega-3’s for cardiovascular disease prevention.
By: DeFilippis AP, Blaha MJ, Jacobson T.


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