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School of Medicine
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Roger S. Blumenthal, MD
Ciccarone Center Research
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- Meet the Authors
The relationship of cigarette smoking with inflammation and subclinical vascular disease: The Multi-Ethnic Study of Atherosclerosis.
We sought to assess the impact of smoking status, cumulative pack-years, and time since cessation (the latter in former smokers only) on 3 important domains of cardiovascular disease: inflammation, vascular dynamics and function, and subclinical atherosclerosis. These findings expand our understanding of the harmful effects of smoking and help explain the cardiovascular benefits of smoking cessation.
- Read on Pubmed
Association of coronary artery calcium and coronary heart disease events in young and elderly participants in the Multi-Ethnic Study of Atherosclerosis: A secondary analysis of a prospective, population-based cohort.The potent predictive value of coronary artery calcium burden applies to middle-aged as well as older adults.Published in: Mayo Clinic ProceedingsRead on Pubmed
To facilitate the guideline-based implementation of treatment recommendations in the ambulatory setting and to encourage participation in the multiple preventive health efforts that exist, we have organized several recent guideline updates into a simple ABCDEF approach. We would remind clinicians that evidence-based medicine is meant to inform recommendations but that synthesis of patient-specific data and use of appropriate clinical judgment in each individual situation is ultimately preferred.Published in: Journal of the American Heart AssociationRead on Pubmed
This is a state-of-art review on the possible effects of statin therapy on organs not in the cardiovascular system.Published in: British Medical JournalRead on Pubmed
Headed in the right direction but at risk for miscalculation: a critical appraisal of the 2013 ACC/AHA risk assessment guideline.The newly released 2013 ACC/AHA Guideline for Assessing Cardiovascular Risk was a major advance over prior guidelines, but the new risk equations do not appear to lead to significantly better discrimination than older models. Since the same risk factors are incorporated, using the new risk estimators may lead to inaccurate assessment of atherosclerotic cardiovascular risk in certain groups of patients. There also is likely an overestimation of risk when applied to modern populations. Future guidelines could provide clearer direction on which individuals would benefit from additional testing for more personalized preventive therapies.Read on Pubmed
Nonfatal outcomes in the primary prevention of atherosclerotic cardiovascular disease: is all-cause mortality really all that matters?This article clearly shows that major nonfatal cardiovascular outcomes are very important to take into account when designing primary prevention guidelines.Read on Pubmed
Baseline subclinical atherosclerosis burden and distribution are associated with frequency and mode of future coronary revascularization: multi-ethnic study of atherosclerosis.There was a strong association between the baseline burden and regional distribution of CAC and the risk and type of future coronary revascularization among asymptomatic subjects.Read on Pubmed
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.Published in: American Journal of CardiologyRead on Pubmed
Critical review of high-sensitivity C-reactive protein and coronary artery calcium for the guidance of statin allocation: head-to-head comparison of the JUPITER and St. Francis Heart Trials.This analysis looks at the strengths and limitations of two large trials of statin therapy based on persons with an elevated hsCRP, CAC score, or both.Read on Pubmed
Concepts and controversies: the 2013 American College of Cardiology/American Heart Association risk assessment and cholesterol treatment guidelines.This editorial discusses the strengths and limitations of the new prevention guidelines.Published in: Annals of Internal MedicineRead on Pubmed
Dyslipidemia, coronary artery calcium, and incident atherosclerotic cardiovascular disease: implications for statin therapy from the multi-ethnic study of atherosclerosis.CAC scoring can help match statin therapy to absolute atherosclerotic CVD risk.Read on Pubmed
Impact of coronary artery calcium on coronary heart disease events in individuals at the extremes of traditional risk factor burden: the Multi-Ethnic Study of Atherosclerosis.The presence of a high CAC burden, even among individuals without risk factors, is associated with an elevated event rate, whereas the absence of CAC, even among those with many risk factors, is associated with a low event rate. CAC scoring can further risk-stratify asymptomatic individuals at the extremes of risk factor burden.Published in: European Heart JournalRead on Pubmed
Statins and cognition: a systematic review and meta-analysis of short- and long-term cognitive effects.In this study of patients without baseline cognitive dysfunction, short-term data are most compatible with no adverse effect of statins on cognition, and long-term data supports a beneficial role for statins in the prevention of dementia.Published in: Mayo Clinic ProceedingsRead on Pubmed
High-sensitivity C-reactive protein and cardiovascular disease: A resolute belief or an elusive link?Although high-sensitivity C-reactive protein (hsCRP) is involved in the immunologic process that triggers vascular remodeling and plaque deposition and is associated with increased cardiovascular disease (CVD) risk, definitive randomized evidence for its role as a causative factor in atherothrombosis is lacking. This article reviews four distinct points from the literature to better understand the current state and application of hsCRP in clinical practice, and we highlight recommendations from societies and important considerations when using hsCRP to guide treatment decisions in the primary prevention setting.Read on Pubmed
Unhealthy lifestyle habits are a major contributor to coronary artery disease (CAD). The purpose of the study was to investigate the associations of smoking, weight maintenance, physical activity, and Mediterranean-style diet with coronary calcium, cardiovascular events, and mortality. We discovered that, over the course of nearly 8 years, a combination of regular exercise, healthy diet, smoking avoidance, and weight maintenance contributed to lower coronary calcium incidence, slower calcium progression, and lower all-cause mortality.Published in: American Journal of EpidemiologyRead on Pubmed
Mortality rates in smokers and nonsmokers in the presence or absence of coronary artery calcification.
The aim of this study was to further explore the interplay between smoking status, coronary artery calcium (CAC), and all-cause mortality. Smoking is a risk factor for death across the entire spectrum of subclinical coronary atherosclerosis. Smokers with any CAC had significantly higher mortality than smokers without CAC, a finding with implications for smokers undergoing lung cancer CT-based screening. However, the absence of CAC might not be as useful a "negative risk factor" in active smokers, because this group has mortality rates similar to nonsmokers with mild-to-moderate atherosclerosis.
Coronary artery calcium for the prediction of mortality in young adults <45 years old and elderly adults >75 years old.The value of coronary artery calcium for predicting mortality extends to both elderly patients and those <45 years old. Elderly persons with no CAC have a lower mortality rate than younger persons with high CAC.Published in: European Heart JournalRead on Pubmed
Early in 2012, a debate over the merits of statin therapy in primary prevention was published in the Wall Street Journal. The statin opponent claimed that statins should only be used in secondary prevention and never in any primary-prevention patients at risk for cardiovascular events. In this evidence-based rebuttal to those claims, we review the evidence supporting the efficacy of statin therapy in primary prevention. Cardiovascular risk is a continuum in which those at an elevated risk of events stand to benefit from early initiation of therapy. Statins should not be reserved until after a patient suffers the catastrophic consequences of atherosclerosis. Contrary to the assertions of the statin opponent, this principle has been demonstrated through reductions in heart attacks, strokes, and mortality in numerous randomized controlled primary-prevention statin trials. In selected at-risk individuals, the combination of pharmacotherapy and lifestyle changes is more effective than either alone. Future investigation in prevention should focus on improving our ability to identify these at-risk individuals.Published in: Clinical CardiologyRead on Pubmed
Niacin and statin combination therapy for atherosclerosis regression and prevention of cardiovascular disease events: Reconciling the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global HealDespite substantial risk reductions targeting low-density lipoprotein cholesterol with statins, there remains significant residual risk as evidenced by incident and recurrent CVD events among statin-treated patients. Observational studies have shown that low levels of high-density lipoprotein cholesterol (HDL-C) are associated with increased CVD risk. It remains unclear whether strategies aimed at increasing HDL-C in addition to background statin therapy will further reduce risk.Read on Pubmed
In this featured debate in JAMA, we reviewed the extensive data from randomized clinical trials and observational studies supporting the selective use of lipid lowering therapy in a middle-aged man with hyperlipidemia.Published in: Journal of the American Medical AssociationRead on Pubmed
Potential implications of coronary artery calcium testing for guiding aspirin use among asymptomatic individuals with diabetes.We conclude that CAC can help risk stratify individuals with diabetes and may aid in selection of patients who may benefit from therapies such as low-dose aspirin for primary prevention of CVD.Published in: Diabetes CareRead on Pubmed
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.Published in: American Journal of CardiologyRead on Pubmed
The association of the Framingham and Reynolds risk scores with incidence and progression of coronary artery calcium in MESA.This innovative study found that the Reynolds Risk Score was modestly better than the traditional Framingham risk score in predicting the incidence of new coronary calcification and the progression of existing calcification. This observation also applied to clinical events.Read on Pubmed
Hepatic steatosis, obesity, and the metabolic syndrome are independently and additively associated with increased systemic inflammation.The goal of this study was to assess the independent and collective associations of hepatic steatosis, obesity, and the metabolic syndrome with elevated hsCRP levels. We evaluated 2,388 individuals without clinical cardiovascular disease between December 2004 and December 2006. Hepatic steatosis was diagnosed by ultrasound, and the metabolic syndrome was defined using National Heart, Lung, and Blood Institute criteria. We concluded that hepatic steatosis, obesity, and the metabolic syndrome are independently and additively associated with increased odds of high hsCRP levels.Read on Pubmed
Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study.The landmark Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial showed that some patients with LDL-cholesterol (LDL-C) <130 mg/dL and high-sensitivity C-reactive protein (hsCRP) concentrations of >2 mg/L benefit from treatment with rosuvastatin, although the absolute rates of cardiovascular events were low. In a population eligible for JUPITER, we established whether coronary artery calcium (CAC) might further stratify risk; additionally we compared hsCRP with CAC for risk prediction across the range of low and high hsCRP values. CAC further stratifies risk in patients eligible for JUPITER, and could be used to target subgroups of patients who are expected to derive the most, and the least, absolute benefit from statin treatment. Focusing of treatment on the subset of individuals with normal LDL-C and at least moderate subclinical atherosclerosis should allow for more appropriate allocation of resources.Read on Pubmed
Association between obesity, high-sensitivity C-reactive protein greater than or equal to 2 mg/L, and subclinical atherosclerosis: implications of JUPITER from the Multi-Ethnic Study of Atherosclerosis.
Levels of hsCRP are closely associated with abdominal obesity, metabolic syndrome, and atherosclerotic cardiovascular disease. The JUPITER trial has encouraged using hsCRP greater than or equal to 2 mg/L to guide statin therapy; however, the association of hsCRP and atherosclerosis, independent of obesity, remains unknown. We concluded that high hsCRP, as defined by JUPITER, was not associated with CAC and was mildly associated with carotid intima-media thickness (cIMT) in the absence of obesity. In contrast, obesity was associated with both measures of subclinical atherosclerosis independently of hsCRP status.
Coronary artery calcium progression: an important clinical measurement? A review of published reports.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.Read on Pubmed
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.Read on Pubmed
Coronary artery calcium in relation to initiation and continuation of cardiovascular preventive medications: The Multi-Ethnic Study of Atherosclerosis (MESA).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.Read on Pubmed
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.Read on Pubmed
The premature termination of the ARBITER 6–HALTS trial, the small number of patients studied, and the limited duration of follow-up preclude us from conclusively declaring niacin the adjunctive agent of choice on the basis of the evidence. A decrease of 0.014 mm in the carotid intima–media thickness (IMT) over 14 months does not necessarily merit changes in our lipid-lowering guidelines at this time. However, for now, we would support the use of niacin as the preferred adjunctive agent to be used in combination with the maximal dose of a potent statin in persons who have low levels of HDL cholesterol and established cardiovascular disease. In summary, the ARBITER 6–HALTS results are provocative and are an important contribution to preventive cardiology research. However, the secondary choices for optimizing cholesterol-lowering therapy, constituting part of the “C” component of the “ABCDEs” of secondary prevention of cardiovascular disease, should not overshadow the importance of the rest of the ABCDEs: assessment of risk, antiplatelet therapy, blood-pressure management, cholesterol modification and cigarette-smoking cessation, dietary and weight modification, and exercise habits.Published in: New England Journal of MedicineRead on Pubmed
Low HDL cholesterol but not high LDL cholesterol is independently associated with subclinical coronary atherosclerosis in healthy octogenarians.
In a healthy cohort of individuals aged of 80 years or more the association between LDL-C and coronary atherosclerosis weakens with aging, while the opposite occurs with the levels of HDL-C.
New insights into diagnostic testing guidelines in women.
An update to the 2005 Guidelines on the Role of Noninvastive Testing in the Clinical Evaluation of Women with Suspected Ischemic Heart Disease was authored in response to the documented gap in appropriate diagnosis and treatment of ischemic heart disease between women and men.
This is a state-of-art review on the possible effects of statin therapy on organs not in the cardiovascular system.
Cigarette smoking worsens systemic inflammation in persons with metabolic syndrome.
Emerging data suggests that the combination of smoking and metabolic syndrome (MetS) markedly increases cardiovascular disease risk well beyond that of either condition. In this study we assess if this interaction can be explained by an additive increase in the risk of systemic inflammation by MetS and cigarette smoking. The study demonstrates an additive effect of cigarette smoking on the risk of systemic inflammation in MetS thus highlighting the need for determining smoking status among those with MetS and aggressively targeting smoking cessation in this population.
Headed in the right direction but at risk for miscalculation: a critical appraisal of the 2013 ACC/AHA risk assessment guideline.
The newly released 2013 ACC/AHA Guideline for Assessing Cardiovascular Risk was a major advance over prior guidelines, but the new risk equations do not appear to lead to significantly better discrimination than older models. Since the same risk factors are incorporated, using the new risk estimators may lead to inaccurate assessment of atherosclerotic cardiovascular risk in certain groups of patients. There also is likely an overestimation of risk when applied to modern populations. Future guidelines could provide clearer direction on which individuals would benefit from additional testing for more personalized preventive therapies.
2013 American cholesterol treatment guideline: what was done well and what could be done better.
This article critically appraises the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol. The guideline succeeds in prioritizing statin therapy, expanding focus to atherosclerotic cardiovascular disease including stroke, and in emphasizing absolute cardiovascular risk to determine statin eligibility.
- Journal: Journal of the American College of Cardiology
- Year: 2014
- Topic: ASCVD (Atherosclerotic Cardiovascular Disease), Cholesterol / Lipids / Statins, Cardiovascular Risk Assessment
- Read more articles by: Roger S. Blumenthal, MD, Michael Blaha, MD, MPH, Erin Michos, MD, MHS, Seth Martin, MD, MHS, Steven Jones, MD
Associations of Pentraxin 3 with cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis.
In a study of apparently healthy adults, Pentraxin 3 was associated with CVD risk factors, subclinical CVD, CAC and incident coronary heart disease events independent of C-reactive protein (CRP) and CVD risk factors. These results support the hypothesis that PTX3 reflects different aspects of inflammation than CRP and may provide additional insight into the development and progression of atherosclerosis.
CPAP versus oxygen in obstructive sleep apnea.
In patients with cardiovascular disease or multiple CVD risk factors, the treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP), but not nocturnal supplemental oxygen, resulted in a significant reduction in blood pressure.
Letter regarding article, “Taking a longer term view of cardiovascular risk: the causal exposure paradigm.”
The fascinating story of PCSK9 Inhibition: Insights and perspective from ACC.14.
The development of PCSK9 inhibitors is coming along at a unique point in the realm of preventive cardiology from multiple perspectives.