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Ciccarone Articles

Ciccarone Center Research

Year

2010

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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Association of single nucleotide polymorphisms on chromosome 9p21.3 with platelet reactivity: a potential mechanism for increased vascular disease.
By: Musunuru K, Post WS, Herzog W, Shen H, O’Connell JR, McArdle PF, Ryan KA, Gibson Q, Cheng YC, Clearfield E, Johnson AD, Tofler G, Yang Q, O’Donnell CJ, Becker DM, Yanek LR, Becker LC, Faraday N, Bielak LF, Peyser PA, Shuldiner AR, Mitchell BD.
Genome-wide association studies have identified a locus on chromosome 9p21.3 to be strongly associated with myocardial infarction/coronary artery disease and ischemic stroke. To gain insights into the mechanisms underlying these associations, we hypothesized that SNPs in this region would be associated with platelet reactivity across multiple populations. Subjects in the initial population included 1,402 asymptomatic Amish adults in whom we measured platelet reactivity and CAC. Our results suggest that risk alleles at 9p21.3 locus may have pleiotropic effects on myocardial infarction/coronary artery disease and stroke risk, possibly through their influence on platelet reactivity.
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The clinical utility of C-reactive protein in cardiovascular disease.
By: Musunuru K, Blumenthal RS, Mora S.

This review discusses the literature on hsCRP in asymptomatic populations, analyzes it according to CVD and diabetes, and provides summary recommendations for the use of hsCRP in clinical practice. In this context, we highlight recent data from the landmark JUPITER trial, which demonstrated that hsCRP can be used to target high-risk patients who have typical LDL-C concentrations and no known vascular disease or diabetes and who would benefit from statin use. We also summarize evidence that among patients treated with statin therapy, achieving low hsCRP concentrations may be a clinically relevant therapeutic goal along with achieving very low LDL-C concentrations.

The ankle-brachial index and incident cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis).
By: Criqui MH, McClelland RL, McDermott MM, Allison MA, Blumenthal RS, Aboyans V, Ix JH, Burke GL, Liu K, Shea S.
Abnormal ABIs, both low and high, are associated with elevated CVD risk. However, it is unknown whether this association is consistent across different ethnic groups, and whether it is independent of both newer biomarkers and other measures of subclinical atherosclerotic CVD. In this study, both a low and a high ABI were associated with elevated CVD risk in persons free of known CVD, independent of standard and novel risk factors, and independent of other measures of subclinical CVD. Further research should address the cost-effectiveness of measuring the ABI in targeted population groups.
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Appropriateness and utilization of cardiac CT: implications for development of future criteria.
By: Murphy MK, Brady TJ, Nasir K, Gazelle GS, Bamberg F, Truong QA, Mamuya WS, Abbara S, Lee TH, Blankstein R.
The cardiac CT (CCT) appropriateness criteria (AC) were jointly published by multiple societies to ensure effective utilization of CCT. We sought to determine how these criteria apply to CCT scans performed at a tertiary-care hospital.
 
In applying the AC to a large academic medical center, few CCT exams were inappropriate; however, many patients referred for CCT, particularly for evaluation of CAD, had an indication for which the level of appropriateness remained undetermined. Given the rapid adoption of CCT, these results emphasize the need to refine current criteria for appropriate utilization.
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Association of SNPs on chromosome 9p21.3 with platelet reactivity: A potential mechanism for increased vascular disease.
By: Musunuru K, Post WS, Herzog W, Shen H, O’Connell JR , Peyser PA, Faraday N, Shuldiner AR, Mitchell BD.

Genome-wide association studies have identified a locus on chromosome 9p21.3 to be strongly associated with myocardial infarction/coronary artery disease and ischemic stroke. To gain insights into the mechanisms underlying these associations, we hypothesized that single nucleotide polymorphisms (SNPs) in this region would be associated with platelet reactivity across multiple populations. Results suggest that risk alleles at 9p21.3 locus may have pleiotropic effects on myocardial infarction/coronary artery disease and stroke risk, possibly through their influence on platelet reactivity.

Read on Pubmed
elective use of coronary artery calcium screening: worth the cost?
By: Blumenthal RS, Hwang CW, Nasir K
Of all tests available for risk stratification, coronary artery calcium (CAC) superiorly divides patients into 2 clear subgroups of high and low future CHD risk, compared to carotid IMT testing. The results of the EISNER study alleviate the fear that such a strategy will inevitably lead to high downstream costs. The EISNER study provides further evidence for the urgency of a randomized trial that compares the current traditional risk factors-based approach with one supplemented by subclinical atherosclerotic screening to determine whether this approach can save lives in a manner that is at least moderately cost effective. This study does show that screening costs will beget more costs; testing produces more than the upfront cost of a procedure. In this regard, we applaud the recent efforts of the National Heart, Lung, and Blood Institute to initiate a dialogue on how to assess the societal utility of such screening tests and look forward to the outcome of these discussions.
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A practical approach to the metabolic syndrome: review of current concepts and management.
By: Tota-Maharaj R, DeFilippis AP, Blumenthal RS, Blaha MJ.

Recent evidence confirms that diet and exercise continue to be the cornerstone of any metabolic syndrome treatment strategy. The revised “ABCDE” approach incorporates the most recent influential studies into a simple yet thorough algorithm for management of the metabolic syndrome.

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Association of combinations of lipid parameters with carotid intima-media thickness and coronary artery calcium in MESA.
By: . Paramsothy P, Knopp RH, Bertoni AG, Blumenthal RS, Wasserman BA, Tsai MY, Wong ND, Heckbert SR.
The purpose of this study was to determine the association of combinations of lipid parameters with subclinical atherosclerosis.  Carotid intima-media thickness (CIMT) and coronary artery calcium (CAC) are significantly associated with incident cardiovascular disease (CVD). The association between common dyslipidemias (combined hyperlipidemia, [simple] hypercholesterolemia, dyslipidemia of metabolic syndrome, isolated low high-density lipoprotein cholesterol, and isolated hypertriglyceridemia) compared with normolipemia, and CIMT and CAC has not been previously examined.
 
Among 4,792 participants, only those with combined hyperlipidemia and hypercholesterolemia demonstrated both increased common CIMT (combined hyperlipidemia 0.048 mm thicker, 95% confidence interval [CI]: 0.016 to 0.080 mm; hypercholesterolemia 0.048 mm thicker, 95% CI: 0.029 to 0.067 mm) and internal CIMT (combined hyperlipidemia 0.120 mm thicker, 95% CI: 0.032 to 0.208 mm; and hypercholesterolemia 0.161 mm thicker, 95% CI: 0.098 to 0.223 mm) as well as increased risk for prevalent CAC (combined hyperlipidemia relative risk: 1.22, 95% CI: 1.08 to 1.38; hypercholesterolemia relative risk: 1.22, 95% CI: 1.11 to 1.34) compared with normolipemia. The interactions between lipid parameters and race, sex, or high-sensitivity C-reactive protein were not significant for any outcomes.
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Update on newer antihypertensive medicines and interventions.
By: Wu KC, Gerstenblith G.

The incidence and prevalence of systemic hypertension are reaching global epidemic proportions. Despite a diverse pharmacologic armamentarium of agents to treat high blood pressure, suboptimal control remains a significant problem in as many as 43% of patients and this rate has not significantly improved over the past 2 decades. There are a variety of factors contributing to this including patient nonadherence due to complex drug regimens and medication side effects, undertreatment, and treatment resistance. There, thus, remains a need to develop novel agents and approaches to antihypertensive therapy that facilitate attainment of optimal blood pressure levels. This monograph will review a number of new pharmacologic targets and interventions as well as a novel method of drug delivery to patients.

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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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