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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Defining The Chronic Coronary Syndrome: A Spectrum Of Disease


GOAL
To provide cardiologists with up-to-date information on the diagnosis and treatment of patients with chronic coronary syndrome. 

TARGET AUDIENCE
This activity is designed for cardiologists. No prerequisites required.

LEARNING OBJECTIVES
The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, the participant should be able to:

  • Identify the scope of stable coronary syndrome (SCS).
  • Examine the current state of affairs in SCS.
  • Describe SCS in the refractory patient and complex patient.
  • Assess the benefits and limitations of current therapeutic options.
  • Examine the emerging evidence of new and evolving therapies.
  • Outline strategies for optimizing treatment of SCS.

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The estimated time to complete this educational activity: 2 hours.

Release date: October 15, 2006. Expiration date: October 15, 2008.

DISCLAIMER STATEMENT
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of The Johns Hopkins University School of Medicine name implies review of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from CV Therapeutics.

Full Disclosure Policy Affecting CME Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Director and Participating Faculty reported the following:

PROGRAM DIRECTORS

Prakash C. Deedwania, MD, FACC, FAHA, FCCP, FACP
Professor of Medicine
University of California, San Francisco School of Medicine
San Francisco, California
Chief, Cardiology Section
Director, Cardiovascular Research
VA Central California Healthcare System/UCSF Program
Fresno, California
Clinical Professor of Medicine
Stanford University
Palo Alto, California
Dr Deedwania reports serving as a consultant for and receiving honoraria from AstraZeneca, CV Therapeutics, and Pfizer Inc.

Gary Gerstenblith, MD
Professor of Medicine
Director of Clinical Research
Division of Cardiology
Johns Hopkins Hospital
Baltimore, Maryland
Dr Gerstenblith reports having no financial or advisory relationships with corporate organizations related to this activity.

PARTICIPATING FACULTY

Kanu Chatterjee, MD, FRCP, FCCP, FAHA, FACC, MACP
Ernest Gallo Distinguished Professor of Medicine
Director, Chatterjee Center for Cardiac Research
University of California, San Francisco School of Medicine
San Francisco, California
Dr Chatterjee reports receiving honoraria from CV Therapeutics, Merck and Company, Otsuka, Scios, and Yamanouchi.

Peter A. McCullough, MD, MPH, FACC, FACP, FAHA, FCCP
Consultant Cardiologist and Chief
Division of Preventive Medicine
William Beaumont Hospital
Royal Oak, Michigan
Dr McCullough reports having no financial or advisory relationships with corporate organizations related to this activity.

Karol E. Watson, MD, PhD
Assistant Professor of Medicine and  Co-Director
UCLA Program in Preventive Cardiology
Director, Center for Lipid and Hypertension
Co-Director, UCLA Center for Cholesterol and Lipid Management
Los Angeles, California
Dr Watson reports receiving grants/research support from Pfizer Inc; and receiving honoraria from AstraZeneca, Kos, Merck and Company, Pfizer Inc, and Schering-Plough.

Notice: All faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices. Johns Hopkins Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Johns Hopkins Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

 

Defining The Chronic Coronary Syndrome: A Spectrum Of Disease
Prakash C. Deedwania, MD, FACC, FAHA, FCCP, FACP, and Gary Gerstenblith, MD 

Angina is ultimately a supply-and-demand problem, resulting from a disproportionate increase in myocardial oxygen demand and/or decreased coronary blood flow reserve. The most frequent type of angina ("effort angina"; Table) is most commonly caused by atherosclerosis. In approximately 50% of patients with coronary artery disease (CAD), angina is the initial manifestation of ischemic heart disease. Prior to this cardiac event, extraluminal plaque burden has stealthily been increasing. It is only when the plaque encroaches into the lumen that the vascular remodeling becomes clinically apparent or even measurable by our current diagnostic measures.1 The type of obstruction also determines clinical outcomes and treatment choices. Severe obstruction by a fibrotic plaque would present as a positive exercise tolerance test and effort angina. Treatment would include antianginal medication, aggressive risk factor reduction, and possibly revascularization. Conversely, a vulnerable plaque may impose mild luminal obstruction, but it places the patient at much higher risk of plaque rupture and thus acute myocardial infarction, unstable angina, or sudden cardiac death. Medical management would be considered secondary prevention. If patients are lucky, they present with angina before sustaining a first cardiovascular event. How can we identify earlier patients with clinically silent, vulnerable plaques?

Not all angina is ischemia, and not all ischemic episodes result in a poor outcome. In this issue of Johns Hopkins Advanced Studies in Medicine, we describe a broader spectrum of CAD, which we have termed chronic coronary syndrome (CCS), a clinical state arising from diffuse atherosclerosis and sometimes coexisting with (or initially presenting as) acute coronary syndrome (Figure). Perhaps most importantly, CCS can be either symptomatic or asymptomatic, reflecting the systemic presence of atherosclerosis in the vascular bed; it is not a disease of focal stenosis or a singular lesion. In fact, the term CCS was selected carefully to reveal the endothelial instability, generally silent CAD, and pathophysiologic and clinical outcomes. With or without symptoms, patients with diffuse atherosclerosis (and thus CCS) are at risk for a coronary event.

Patients will move across the CAD continuum over time, and those who are asymptomatic should be considered high-risk patients that have as-yet undetected disease by our current diagnostic or screening methods. Asymptomatic patients benefit most from disease-modifying interventions, such as lifestyle modifications and lipid-lowering agents. Particular emphasis should be placed on exercise, as it is a useful treatment across the CAD disease spectrum. Symptomatic patients should undergo diagnostic testing and, depending on the results, might receive disease-modifying treatments along with other antianginal treatments.

The time horizon for CCS as a disease process extends far beyond the limited time frames of our current clinical trials. Therefore, screening for CCS should begin early in life, as atherosclerosis is a lifelong process. In this way, identification and modification of risk factors can delay or even interrupt the disease process rather than treating an established disease state.

Screening for CCS is a major challenge because risk factors play different roles in a major population versus an individual, partly due to factors that are not part of the global risk assessment, such as family history. Also, age is an important driver of the Framingham risk score; however, if disease-modifying treatments were implemented in patients in their 20s and 30s, the impact of age on the risk score would be reduced dramatically. Also, patients need to understand their own risk level, especially if they "feel fine" with cholesterol levels approaching 300 mg/dL.

To explore the concept of CCS, we convened a multidisciplinary panel of 19 cardiology thought leaders, including 17 cardiologists, a clinical pharmacist, and a cardiovascular nurse, for a 1-day "think tank" on CCS, from which this monograph was developed (synopsis of the presentations from our think tank).

Karol E. Watson, MD, PhD, and Peter A. McCullough, MD, MPH, FACC, FACP, FAHA, FCCP, begin this issue with a review of the epidemiology and clinical characteristics of CAD, and defining CCS. They also provide an important review of the differences—clinical and physiological—between men and women with regard to vascular disease and outcomes. As they point out, the changing epidemiology of CAD is causing a paradigm shift in our definition of at-risk patients. In broad terms, we are moving from a society of thin smokers with single risk factors for CAD to a population of older, obese, nonsmokers with multiple risk factors who experience a first infarction or symptomatic coronary disease at a younger age. Thus, the paradigm changes from identifying the risk of disease to identifying the anatomic presence of disease with new imaging technologies, and to implementing disease-modifying strategies in asymptomatic patients. In other words, the concept of "at risk" needs to be redefined: if a repairman noted that a household furnace had a 2% chance of exploding in the next 10 years, the homeowner would act immediately to repair it. Why do we not place the same sense of urgency on a patient with a 2% risk of myocardial infarction?

Prakash C. Deedwania, MD, FACC, FAHA, FCCP, FACP, and Kanu Chatterjee, MD, FRCP, FCCP, FAHA, FACC, MACP, continue this discussion with a review of the treatments currently available and under evaluation for CCS. On the committee for updating the American College of Cardiology/ American Heart Association guideline for chronic stable angina, they discuss the implications of this new paradigm and future treatments. The ideal treatments for CCS are those that modify systemic atherosclerotic processes and focus on established risk factors (ie, hypertension, hypercholesterolemia, dyslipidemia, diabetes, obesity, and lifetime risk). The challenge of treating CCS is to incorporate risk factor modification, diagnosis, and treatment into clinical practice; one aspect of CCS should not be focused on at the expense of the others. Furthermore, all CCS treatments are complementary: risk factor modification, medication, and revascularization.

During our discussions, highlights of which will be available on the Web site (www.jhasim.com/ccs), the panel members also noted that our traditional therapies are not yet optimally used, particularly for angina symptoms and disease-modifying treatment. Therefore, once CAD is detected, the next step is to define ischemic burden. Those patients with high ischemic burden need to be revascularized to improve outcomes; for those with low ischemic burden, the emphasis should be on symptom control with maximal antianginal therapies and risk factor modification to improve long-term outcomes. Lifestyle modifications (ie, disease-modifying therapies) are grossly underused and underemphasized. Patients for whom lifestyle modifications are recommended need to understand that these changes are not just to address cardiovascular disease but also to maintain function and independence, because these strategies cut across many other chronic diseases.

The goal of CCS treatment is to stabilize the atherosclerotic plaque and relieve symptoms to the extent possible using appropriate therapies. Some of the greatest obstacles to optimal use of drug treatments include optimal clinical application, cost, drug interactions, patient adherence, and determining treatment success. We now have several types of therapies at our disposal: statins, antihypertensive agents, and antiplatelet treatments. These should all be used in the appropriate patients to address all aspects of CCS. As a result, many patients will require multiple drug therapies, sometimes with a pill burden of 9 or more medications. This incurs a cost that some patients cannot absorb. Therefore, clinicians should familiarize themselves and make full use of pharmaceutical assistance programs to ensure that medical management is optimized.

Clinicians also need to be mindful of the pharmacokinetic and pharmacodynamic effects of these drugs, in addition to drug-drug interactions, particularly with so many drugs affecting many of the same cytochrome P450 pathways. Finally, it is well established that angina symptoms impact quality of life, and poor quality of life is associated with depression, which impacts clinical outcomes and functionality. Part of treatment individualization is determining what treatment success means to each patient. Although the clinician may be motivated by improvement in time ST-segment depression, patients ultimately care about quality of life and functionality.

We hope this issue of Johns Hopkins Advanced Studies in Medicine is a first step in what should be a long discussion of CCS and our deeper understanding of the spectrum of CAD.

REFERENCE

1. Abrams J. Chronic stable angina. N Engl J Med. 2005;352:2524-2728.

Professor of Medicine, UCSF School of Medicine, San Francisco, California; Chief, Cardiology Section, Director, Cardiovascular Research, VA Central California Healthcare System/UCSF Program, Fresno, California; Clinical Professor of Medicine, Stanford University, Palo Alto, California.

Professor of Medicine, Director of Clinical Research, Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland.

Address correspondence to: Gary Gerstenblith, MD, Professor of Medicine, Director of Clinical Research, Division of Cardiology, Johns Hopkins Hospital, 600 North Wolfe Street, Carnegie 591, Baltimore, MD 21287. E-mail: gblith@jhmi.edu.

The content in this monograph was developed with the assistance of a staff medical writer. Each author had final approval of his/her article and all its contents.





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.