High Prevalence of Coronary Atherosclerosis in Asymptomatic Teenagers and Young Adults Evidence From Intravascular Ultrasound
TL;DR: This study demonstrates that coronary atherosclerosis begins at a young age and that lesions are present in 1 of 6 teenagers, and suggest the need for intensive efforts at coronary disease prevention in young adults.
Abstract: Background—Most of our knowledge about atherosclerosis at young ages is derived from necropsy studies, which have inherent limitations. Detailed, in vivo data on atherosclerosis in young individuals are limited. Intravascular ultrasonography provides a unique opportunity for in vivo characterization of early atherosclerosis in a clinically relevant context. Methods and Results—Intravascular ultrasound was performed in 262 heart transplant recipients 30.9±13.2 days after transplantation to investigate coronary arteries in young asymptomatic subjects. The donor population consisted of 146 men and 116 women (mean age of 33.4±13.2 years). Extensive imaging of all possible (including distal) coronary segments was performed. Sites with the greatest and least intimal thickness in each CASS segment were measured in multiple coronary arteries. Sites with intimal thickness ≥0.5 mm were defined as atherosclerotic. A total of 2014 sites within 1477 segments in 574 coronary arteries (2.2 arteries per person) were anal...
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Harvard University1, Aarhus University2, University of Texas at Austin3, Memorial Hermann Texas Medical Center4, National and Kapodistrian University of Athens5, University of Kentucky6, Utrecht University7, Icahn School of Medicine at Mount Sinai8, Tufts University9, Tulane University10, Armed Forces Institute of Pathology11, University of Washington12, Stanford University13, Erasmus University Rotterdam14, University of Turku15, University of Münster16, Mayo Clinic17, Emory University18, University of Bristol19, University of Ulm20, Veterans Health Administration21, University of Texas Health Science Center at Houston22, University of California, Los Angeles23, University of Pavia24, Pfizer25, University of Texas Southwestern Medical Center26, Lenox Hill Hospital27, Baylor College of Medicine28, University of Maryland, Baltimore29, Karolinska Institutet30, University of Chicago31, Cedars-Sinai Medical Center32, Northwestern University33, Indiana University34
TL;DR: The term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future and a quantitative method for cumulative risk assessment of vulnerable patients needs to be developed.
Abstract: Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.
2,719 citations
Cites background from "High Prevalence of Coronary Atheros..."
...Autopsy [84] and IVUS studies [85] have shown that atherosclerotic lesions are frequently found in young and asymptomatic individuals....
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TL;DR: Treatment of coronary atherosclerosis should involve 2 overlapping phases: first, addressing the culprit lesion, and second, aiming at rapid “stabilization” of other plaques that may produce recurrent events.
Abstract: During the past decade, our understanding of the pathophysiology of coronary artery disease (CAD) has undergone a remarkable evolution. We review here how these advances have altered our concepts of and clinical approaches to both the chronic and acute phases of CAD. Previously considered a cholesterol storage disease, we currently view atherosclerosis as an inflammatory disorder. The appreciation of arterial remodeling (compensatory enlargement) has expanded attention beyond stenoses evident by angiography to encompass the biology of nonstenotic plaques. Revascularization effectively relieves ischemia, but we now recognize the need to attend to nonobstructive lesions as well. Aggressive management of modifiable risk factors reduces cardiovascular events and should accompany appropriate revascularization. We now recognize that disruption of plaques that may not produce critical stenoses causes many acute coronary syndromes (ACS). The disrupted plaque represents a "solid-state" stimulus to thrombosis. Alterations in circulating prothrombotic or antifibrinolytic mediators in the "fluid phase" of the blood can also predispose toward ACS. Recent results have established the multiplicity of "high-risk" plaques and the widespread nature of inflammation in patients prone to develop ACS. These findings challenge our traditional view of coronary atherosclerosis as a segmental or localized disease. Thus, treatment of ACS should involve 2 overlapping phases: first, addressing the culprit lesion, and second, aiming at rapid "stabilization" of other plaques that may produce recurrent events. The concept of "interventional cardiology" must expand beyond mechanical revascularization to embrace preventive interventions that forestall future events.
1,547 citations
TL;DR: Investigators now appreciate that narrowing arteries do not necessarily presage myocardial infarction and that simply treating narrowed blood vessels does not prolong life.
1,020 citations
Cites background from "High Prevalence of Coronary Atheros..."
...Indeed, 1 in 6 American teenagers already has pathologic intimal thickening in their coronary arteries (19)....
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University of Miami1, University of California, Irvine2, Icahn School of Medicine at Mount Sinai3, Tulane University4, Baylor College of Medicine5, Oakland University6, University of California, San Diego7, University of Alabama8, The Ohio State University Wexner Medical Center9, Foundation for Biomedical Research10, Oregon Health & Science University11, University of Chicago12
TL;DR: This CPG is a practical tool that endocrinologists, other health care professionals, health-related organizations, and regulatory bodies can use to reduce the risks and consequences of dyslipidemia.
834 citations
TL;DR: Traditional risk factors like hypercholesterolemia are important for atherogenesis, but it is now apparent that the immune system also plays an important role and this could lead to novel therapeutic approaches that involve immune modulation.
Abstract: Traditional risk factors like hypercholesterolemia are important for atherogenesis, but it is now apparent that the immune system also plays an important role. Uncovering the mechanisms by which specific components of the immune system impact atherogenesis will not only provide new insights into the pathogenesis of lesion formation, but could also lead to novel therapeutic approaches that involve immune modulation.
652 citations
Cites background from "High Prevalence of Coronary Atheros..."
...Autopsy studies have confirmed the presence of advanced and obstructive lesions in young and clinically robust individuals, and intracoronary ultrasound studies have demonstrated the remarkable prevalence of coronary atherosclerosis in 37% of 'healthy' heart donors 20–29 years of age, 60% of those 30–39 years of age and 85% of those over 50 years of ag...
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References
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TL;DR: The survey shows significant interobserver and interlaboratory variation in measurement when examining the same echoes and indicates a need for ongoing education, quality control and standardization of measurement criteria.
Abstract: Four hundred M-mode echocardiographic surveys were distributed to determine interobserver variability in M-mode echocardiographic measurements. This was done with a view toward examining the need and determining the criteria for standardization of measurement. Each survey consisted of five M-mode echocardiograms with a calibration marker, measured by the survey participants anonymously. The echoes were judged of adequate quality for measurement of structures. Seventy-six of the 400 (19%) were returned, allowing comparison of interobserver variability as well as examination of the measurement criteria which were used. Mean measurements and percent uncertainty were derived for each structure for each criterion of measurement. For example, for the aorta, 33% of examiners measured the aorta as an outer/inner or leading edge dimension, and 20% measured it as an outer/outer dimension. The percent uncertainty for the measurement (1.97 SD divided by the mean) showed a mean of 13.8% for the 25 packets of five echoes measured using the former criteria and 24.2% using the latter criteria. For ventricular chamber and cavity measurements, almost one-half of the examiners used the peak of the QRS and one-half of the examiners used the onset of the QRS for determining end-diastole. Estimates of the percent of measurement uncertainty for the septum, posterior wall and left ventricular cavity dimension in this study were 10--25%. They were much higher (40--70%) for the right ventricular cavity and right ventricular anterior wall. The survey shows significant interobserver and interlaboratory variation in measurement when examining the same echoes and indicates a need for ongoing education, quality control and standardization of measurement criteria. Recommendations for new criteria for measurement of M-mode echocardiograms are offered.
7,649 citations
TL;DR: Findings indicate that as the number of cardiovascular risk factors increases, so does the severity of asymptomatic coronary and aortic atherosclerosis in young people.
Abstract: Background In adults, cardiovascular risk factors reinforce each other in their effect on cardiovascular events. However, information is scant on the relation of multiple risk factors to the extent of asymptomatic atherosclerosis in young people. Methods We performed autopsies on 204 young persons 2 to 39 years of age, who had died from various causes, principally trauma. Data on antemortem risk factors were available for 93 of these persons, who were the focus of this study. We correlated risk factors with the extent of atherosclerosis in the aorta and coronary arteries. Results The extent of fatty streaks and fibrous plaques in the aorta and coronary arteries increased with age. The association between fatty streaks and fibrous plaques was much stronger in the coronary arteries (r=0.60, P<0.001) than in the aorta (r=0.23, P=0.03). Among the cardiovascular risk factors, body-mass index, systolic and diastolic blood pressure, and serum concentrations of total cholesterol, triglycerides, low-density lipopr...
3,661 citations
TL;DR: It is concluded that human coronary arteries enlarge in relation to plaque area and that functionally important lumen stenosis may be delayed until the lesion occupies 40 percent of the internal elastic lamina area.
Abstract: Whether human coronary arteries undergo compensatory enlargement in the presence of coronary disease has not been clarified. We studied histologic sections of the left main coronary artery in 136 hearts obtained at autopsy to determine whether atherosclerotic human coronary arteries enlarge in relation to plaque (lesion) area and to assess whether such enlargement preserves the cross-sectional area of the lumen. The area circumscribed by the internal elastic lamina (internal elastic lamina area) was taken as a measure of the area of the arterial lumen if no plaque had been present. The internal elastic lamina area correlated directly with the area of the lesion (r = 0.44, P less than 0.001), suggesting that coronary arteries enlarge as lesion area increases. Regression analysis yielded the following equation: Internal elastic lamina area = 9.26 + 0.88 (lesion area) + 0.026 (age) + 0.005 (heart weight). The correlation coefficient for the lesion area was significant (P less than 0.001), whereas the correlation coefficients for age and heart weight were not. The lumen area did not decrease in relation to the percentage of stenosis (lesion area/internal elastic lamina area X 100) for values between zero and 40 percent but did diminish markedly and in close relation to the percentage of stenosis for values above 40 percent (r = -0.73, P less than 0.001). We conclude that human coronary arteries enlarge in relation to plaque area and that functionally important lumen stenosis may be delayed until the lesion occupies 40 percent of the internal elastic lamina area. The preservation of a nearly normal lumen cross-sectional area despite the presence of a large plaque should be taken into account in evaluating atherosclerotic disease with use of coronary angiography.
3,631 citations
01 Jan 1991
TL;DR: This document describes the collection and storage of specimens for analysis of blood pressure and other parameters of the autonomic nervous system in relation to disease progression.
Abstract: ABD active disease (abdomen) 1=normal, 2=suspicious, 3=abnormal, 4=unknown ACNE acne Grade 1-5 AD history of active disease 1=normal, 2=suspicious, 3=abnormal, 4=unknown AGE age (years) AMPM_B Time blood sample drawn 1=AM 2=PM AMPM_F Time of last food intake 1=AM 2=PM APO_A1 Apo A1 mg/100ml ARM_BP1 arm used for blood pressure 1=left, 2=right, 9=unknown ARM_BP2 arm used for blood pressure 1=left, 2=right, 9=unknown ARM_BP3 arm used for blood pressure 1=left, 2=right, 9=unknown ARM_SS arm used to measure skinfold, subscapular 1=right, 2=left, 9=unknown
1,607 citations
TL;DR: Aortic involvement with fatty streaks was greater in blacks than in whites, and the importance of risk-fa...
Abstract: We assessed the relation of risk factors for cardiovascular disease to early atherosclerotic lesions in the aorta and coronary arteries in 35 persons (mean age at death, 18 years). Aortic involvement with fatty streaks was greater in blacks than in whites (37 vs. 17 percent, P less than 0.01). However, aortic fatty streaks were strongly related to antemortem levels of both total and low-density lipoprotein cholesterol (r = 0.67, P less than 0.0001 for each association), independently of race, sex, and age, and were inversely correlated with the ratio of high-density lipoprotein cholesterol to low-density plus very-low-density lipoprotein cholesterol (r = -0.35, P = 0.06). Coronary-artery fatty streaks were correlated with very-low-density lipoprotein cholesterol (r = 0.41, P = 0.04). Mean systolic blood-pressure levels also tended to be higher in the four subjects with coronary-artery fibrous plaques than in those without them: 112 mm Hg as compared with 104 (P = 0.09). These results document the importance of risk-factor levels to early anatomical changes in the aorta and coronary arteries. The progression of fatty streaks to fibrous plaques is uncertain, but these data suggest that a rational approach to the prevention of cardiovascular disease should begin early in life.
1,027 citations