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2015

Ciccarone Center Research

All Ciccarone Research Articles

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.
Abdominal obesity in rheumatoid arthritis: association with cardiometabolic risk factors and disease characteristics.
By: Giles JT, Allison M, Blumenthal RS, Post W, Gelber AC, Petri M, Tracy R, Szklo M, Bathon JM.
Abdominal adiposity, especially visceral adiposity, is emerging as a recognized cardiometabolic risk factor. This study was undertaken to investigate how abdominal fat is distributed in rheumatoid arthritis (RA), and its RA-related determinants. We compared men and women with RA with non-RA controls from MESA. The distribution of abdominal fat differs significantly by RA status. Higher VFA in men with RA, and the more potent association of VFA with cardiometabolic risk factors in men and women with RA, may contribute to cardiovascular risk in RA populations.
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Incidence of subclinical coronary atherosclerosis in patients with suspected embolic stroke using cardiac computed tomography.
By: Yoon YE, Chang HJ, Cho I, Jeon KH, Chun EJ, Choi SI, Bae HJ, Rivera JJ, Nasir K, Blumenthal RS, Lim TH.
The purpose of this study was to investigate the incidence of subclinical CAD in patients with suspected acute embolic stroke or transient ischemic attack (TIA) using 64-row multi-slice computed tomography (MSCT) and to examine its association with conventional risk stratification. In logistic regression analysis, only CACS independently predicted the presence ?50% occult CAD evidenced by CCTA. Subclinical CAD, including ?50% stenotic disease, is highly prevalent in patients who had suffered a suspected embolic stroke. The current guideline for further cardiac testing may have limited value to identify patients with ?50% CAD in this patient population, which can be improved by adopting CACS.
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Coronary artery calcium progression: an important clinical measurement? A review of published reports.
By: McEvoy JW, Blaha MJ, Defilippis AP, Budoff MJ, Nasir K, Blumenthal RS, Jones SR.
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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Coronary artery calcium progression — an important clinical measurement? (State of the Art Paper)
By: McEvoy JW, Blaha M, DeFilippis A, Budoff M, Nasir K, Blumenthal RS, Jones SR.

Baseline coronary artery calcification (CAC) accurately identifies coronary atherosclerosis and might improve prediction of future cardiac events. Serial assessment of CAC scores has been proposed for monitoring atherosclerosis progression and for assessing the effectiveness of medical therapies aimed at reducing cardiac risk. However, whether knowledge of progression of CAC scores over time further improves risk prediction is unclear. Several trials relating medical therapies to CAC progression have been performed without any formal guidelines on the definition of CAC progression and how it is best quantified. We conducted a comprehensive review of published reports on CAC progression. Increased CAC progression is associated with many known cardiac risk factors. We 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. First, standards of how CAC progression should be defined and assessed need to be developed. In addition, there remains a need for further studies analyzing the effect of other cardiac therapies on CAC progression and cardiac outcomes.

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Noninvasive visualization of coronary artery endothelial function in healthy subjects and in patients with coronary artery disease.
By: Hays AG, Hirsch GA, Kelle S, Gerstenblith G, Weiss RG, Stuber M.
The goal was to test 2 hypotheses: first, that coronary endothelial function can be measured non-invasively and abnormal function detected using clinical 3.0-T magnetic resonance imaging (MRI); and second, that the extent of local CAD, in a given patient, is related to the degree of local abnormal coronary endothelial function. We concluded that endothelial-dependent coronary artery dilation and increased blood flow in healthy subjects, and their absence in CAD patients, can now be directly visualized and quantified non-invasively. Local coronary endothelial function differs between severely and mildly diseased arteries in a given CAD patient. This novel, safe method may offer new insights regarding the importance of local coronary endothelial function and improved risk stratification in patients at risk for and with known CAD.
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Familial defective ApoB-100 is a major cause of increased LDL-cholesterol and coronary artery calcification in the old order Amish.
By: Shen H, Damcott CM, Rampersaud E, Pollin TI, Bielak LF, Post WS, Chang Y-PC, Rumberger JA, Shuldiner AR, Mitchell BD.

Elevated low-density lipoprotein cholesterol (LDL-C) levels are a major cardiovascular disease risk factor. Genetic factors are an important determinant of LDL-C levels. The R3500Q mutation in APOB is a major determinant of LDL-C levels and CAC in the Amish.

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Familial defective apolipoprotein B-100 and increased low-density lipoprotein cholesterol and coronary artery calcification in the old order amish.
By: Shen H, Damcott CM, Rampersaud E, Pollin TI, Horenstein RB, McArdle PF, Peyser PA, Bielak LF, Post WS, Chang YP, Ryan KA, Miller M, Rumberger JA, Sheedy PF 2nd, Shelton J, O’Connell JR, Shuldiner AR, Mitchell BD.
Elevated LDL-C levels are a major CVD risk factor. Genetic factors are an important determinant of LDL-C levels. To identify single nucleotide polymorphisms associated with LDL-C and subclinical coronary atherosclerosis, we performed a genome-wide association study of LDL-C in 841 asymptomatic Amish individuals aged 20 to 80 years, with replication in a second sample of 663 Amish individuals. We also performed scanning for CAC in 1,018 of these individuals. We concluded that the presence of R3500Q, the mutation responsible for familial defective apolipoprotein B-100, is a major determinant of LDL-C levels and CAC in the Amish.
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Risk factor differences for aortic vs. coronary calcified atherosclerosis: MESA.
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 coronary artery calcium (CAC) with abdominal aortic calcium (AAC) in terms of their associations with traditional and novel cardiovascular disease (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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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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Prevention strategies for coronary heart disease.
By: Blaha MJ, Ketlogetswe KS, Ndumele CE, Gluckman TJ, Blumenthal RS.
This state-of-the-art examination of comprehensive primary and secondary prevention strategies is a superb discussion of the impact of clinical trials and epidemiologic studies on our current national guidelines.
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.

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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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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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Zero coronary calcium and Bayes’ theorem.
By: Blaha MJ, Blumenthal RS, Nasir K.
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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What is the prognostic value of a zero calcium score? Ask Bayes!
By: McEvoy JW.
The role of calcium scoring (CS), if any, appears to be in the reclassification of asymptomatic patients at intermediate risk for CAD by traditional risk factor models. This has led to a Class IIb recommendation by the American Heart Association for the use of CS in these patients. Further research is ongoing to study the effect of such reclassification.
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Statistical modeling of Agatston score in multi-ethnic study of atherosclerosis (MESA).
By: Ma S, Liu A, Carr J, Post W, Kronmal R.
We show that, to fully describe the relationship between covariates and CAC development, the semiparametric model with nonproportional covariate effects is needed. In contrast, for the purpose of prediction, the parametric model with proportional covariate effects is sufficient. This study provides a statistical basis for describing the behaviors of CAC and insights into its biological mechanisms.
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Associations between genetic variants in the ACE, AGT, AGTR1 and AGTR2 genes and renal function in the multi-ethnic study of atherosclerosis.
By: Campbell CY, Fang BF, Guo X, Peralta CA, Psaty BM, Rich SS, Young JH, Coresh J, Kramer HJ, Rotter JI, Post WS.

These data suggest that genetic polymorphisms in the renin-angiotensin system are associated with renal phenotypes in the general population, but that many associations differ across racial/ethnic groups.

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Lipid disorders.
By: DeFilippis A, Blumenthal RS.
Use of nonsteroidal anti-inflammatory drugs in patients with cardiovascular disease: a cautionary tale.
By: Amer M, Bead VR, Bathon J, Blumenthal RS, Edwards DN.
Potentially, all nonsteroidal anti-inflammatory drugs (NSAIDs) possess a fair risk of adverse effects on gastrointestinal, cardiovascular, and renal systems. Until more evidence for safety via randomized trials is available, we recommend caution in prescribing COX-1 and 2 inhibitors for musculoskeletal disorders in patients with existing gastrointestinal or cardiovascular conditions.
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Preventing heart disease: Why our guidelines need to be modified.
By: Brooks GC, Blaha MJ, Blumenthal RS.

The authors comment on the need to change guidelines to prevent heart diseases among individuals in the U.S.

Relation of C-reactive protein to abdominal adiposity
By: Brooks GC, Blaha MJ, Blumenthal RS.
The association between high-sensitivity C-reactive protein (hsCRP) and abdominal adiposity persists when taking into account body mass index. Elevation of hsCRP might be reversible with weight loss and exercise. In conclusion, clinical measurements of abdominal adiposity readily provide data elucidating the systemic inflammatory state of patients and can help guide intensity of lifestyle modifications, thus leading to reduction of this inflammation.
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Abdominal adiposity in rheumatoid arthritis: Association with cardiometabolic risk factors and disease characteristics.
By: Giles JT, Allison M, Blumenthal RS, Post W, Gelber AC, Petri M, Tracy R, Szklo M, Bathon JM.
The distribution of abdominal fat differs significantly by rheumatoid arthritis (RA) status. Higher visceral fat area (VFA) in men with RA, and the more potent association of VFA with cardiometabolic risk factors in men and women with RA, may contribute to cardiovascular risk in RA populations.
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Atherosclerotic plaque composition among patients with stenotic coronary artery disease on noninvasive CT angiography.
By: Hamirani YS, Nasir K, Gopal A, Ahmadi N, Pal R, Flores F, Blumenthal RS, Budoff MJ.
Significant differences in plaque composition according to severity of CAD were observed in our study. Individuals with a higher likelihood of stenotic CAD were more likely to have higher underlying burden of exclusively calcified and mixed plaque. These findings should stimulate further investigations to assess the prognostic value of plaque according to their underlying composition.
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Statins and risk of incident diabetes.
By: McEvoy JW.

Reported limitations of a meta-analysis of whether statin therapy affects incident diabetes (13 statin trials with 91,140 participants) include the loss of statistical significance on exclusion of two trials in which incident diabetes was by physician report only. Post-hoc and subgroup analyses introduce analytical errors that can lead to misleading conclusions. Therefore, these capricious findings should be regarded as a hypothesis generating statistical anomaly, lest we fall foul of the logical fallacy, “Post hoc ergo propter hoc.”

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Rosuvastatin is similarly effective for primary prevention of cardiovascular disease in women as in men
By: Leventhal A, Michos ED.

Statins for the primary prevention of cardiovascular events in women with elevated high-sensitivity C-reactive protein or dyslipidemia: results from the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) and meta-analysis of women from primary prevention trials.

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