Overview

The American College of Cardiology’s 55th Annual Scientific Session was held in Atlanta, Georgia (March 11–14, 2006). The meeting encompassed 4 days of live and poster presentations on topics related to the most recent advances in the diagnosis, treatment, and prevention of cardiovascular disease.

This convention report highlights the live presentations that pertain to cardiovascular and metabolic risk factors. Topics range from novel considerations on the endocannabinoid system to controversial issues on the use of statins, as well as intervention considerations and strategies for the metabolic syndrome and dyslipidemia. The report ends with a summary of provocative new data from the RIO (Rimonabant in Obesity and Related Metabolic Disorders) program.

March 11, 2006

The answer to the question posed in the title is that each component of cardiovascular (CV) and metabolic risk can affect others. A clustering of risk factors-overweight, smoking, hypertension, hyperlipidemia, insulin resistance, glucose intolerance-increases risk geometrically. Tantalizing recent data suggest that treatment of global CV risk, and particularly hypertension, can diminish the risk of cognitive function. The link: angiotensin II, which causes potent vasoconstriction, aldosterone secretion and sympathetic activation. All of these actions contribute to the development of hypertension and cerebral insufficiency. Agents that reduce the actions of angiotensin II therefore appear to be a useful component of decreasing CV risk and cognitive disorders.

"Residual risk"-those were the key words at this symposium examining the gaps in progress in prevention of coronary and metabolic disorders. This refers to the nontraditional risk factors that often receive little attention from clinicians after hypertension and hyperlipidemia have been treated.

Intra-abdominal Adiposity: A Key Contributor to Cardiovascular Risk
Richard Nesto, MD, Associate Professor of Medicine, Harvard Medical School, Boston, Massachusetts; Chairman, Department of Cardiovascular Medicine, Lahey Clinic, Burlington, Massachusetts

Despite the progress in reducing morbidity and mortality from cardiovascular disease, most people still die from cardiovascular causes. Huge progress has been made in the prevention of myocardial infarction-in persons without diabetes. There has been little or no progress in those with diabetes. And Dr. Nesto pointed out that in New York City, as an example, the prevalence of diabetes more than doubled from 1994 to 2002, from 3.7% to 7.9%.

This symposium focused on current research of emerging markers, associated risk factors, and optimal patient management.

Update on the Metabolic Syndrome
Scott M. Grundy, MD, PhD, Professor of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

The metabolic syndrome is a specific clustering of metabolic and underlying risk factors: atherogenic dyslipidemia, insulin resistance, hypertension, abdominal obesity, a prothrombotic state, and a pro-inflammatory state. The pathogenesis is most importantly related to two important states: abdominal obesity and susceptibility factors. The susceptibility factors include primary insulin resistance, physical inactivity, advancing age, racial and ethnic factors, endocrine dysfunction, and genetic predisposition.

With regard to abdominal obesity, a body mass index (BMI) of ≥25 is desirable; but some obese people do not have abdominal obesity. This is a key difference in the metabolic syndrome because abdominal obesity, which contains excessive adipose tissue, produces nonesterified fatty acids, inflammatory cytokines, an increased inflammatory state, adiponectin, and angiotensinogen. Adipose tissue is insulin resistant. Muscle insulin resistance promotes hyperglycemia; liver insulin resistance results in increased triglyceride synthesis.

March 12, 2006

NCEP Guidelines: Are They Adequate?
Neil Stone, MD, Professor of Medicine, Northwestern University
Dr. Stone was a member of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP I and ATP III).

Yes, the NCEP/ATP III guidelines are aggressive enough. The intensity of low-density lipoprotein (LDL) reduction should be based on the absolute risk; the ATP III calculator is an easy method to determine absolute coronary risk.

Beyond coronary risk, ATP III does consider the metabolic syndrome. ATP III, based on the results of the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT), Incremental Decrease in Events through Aggressive Lipid Lowering (IDEAL), and Treating to New Targets (TNT) trials, recommends that a reasonable therapeutic option is an LDL <70 mg/dL. This option is particularly important in patients with cardiovascular disease (CVD) and acute coronary syndrome, multiple metabolic risk factors, or severe risk factors.

This symposium presented strategies for minimizing global risk through a series of case studies. After an introduction by Dr. Sidney Smith, two cases were presented that illustrated strategies for treatment of various risk factors for cardiovascular disease (CVD): atherosclerosis, hypertension, and heart failure.

Preventive Cardiology and Minimizing Cardiovascular Risk
Sidney C. Smith, Jr.,MD, Professor of Medicine and Director, Center for Cardiovascular Science and Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

The Framingham Study has revealed that about 40% of coronary heart disease (CHD) events occur in patients with below average total cholesterol (about 200 mg/dL). Therefore, proposes Dr. Smith, primary prevention is the most effective means of reducing the burden of CHD. Further, comprehensive early evaluation of at-risk patients is important in improving long-term outcomes.

March 13, 2006

Reverse Cholesterol Transport Made Simple
H. Bryan Brewer, Jr, MD, Director, Lipoprotein and Atherosclerosis Research, Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington, DC

The ATP-binding cassette, sub-family A, member 1 (ABCA1) transporter protein controls the rate-limiting step in high-density lipoprotein (HDL) particle assembly by mediating cholesterol efflux from cells. Oxysterol-induced RXR/LXR transcription factors induce the expression of the ABCA1 gene. Approximately 5% of plasma HDL is pre- b-HDL, which initiates cholesterol efflux from cells via ABCA1. About 95% of plasma HDL is mature α-HDL, which promotes cholesterol efflux via SR-B1 and ABCG1 transporters.

Welcoming Remarks: The Changing Approach to Patient Assessment
Antonio M. Gotto, MD, DPhil, Stephen and Suzanne Weiss Dean; Professor of Medicine, Cornell University Joan and Sanford I. Weill Medical College, New York, New York

The changing landscape of cardiovascular (CV) risk prevention suggests that a broader range of patients should be treated. In secondary prevention, the need for aggressive risk-factor management has long been accepted; now, its use in primary prevention is considered appropriate in high-risk patients.

The Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) study, discussed in more detail later in this report, shows that antihypertensive therapy is the most important step to lower risk of heart disease and stroke. Taking a combination of calcium-channel blockers (CCBs) and an angiotensin-converting enzyme (ACE) inhibitor together significantly reduces the risk of having a stroke or myocardial infarction (MI) and of developing diabetes compared with a beta blocker and a diuretic. By taking a combination of a CCB and an ACE inhibitor together with a statin, the risk of MI and stroke was decreased by more than half.

March 14, 2006

Waist Circumference and BMI Are Both Independently Associated with CVD: The International Day for the Evaluation of Abdominal Obesity (IDEA) Survey
Steven M. Haffner, MD, Professor of Medicine, University of Texas Health Science Center, Member, IDEA Study Executive Committee

The IDEA study confirms the importance of waist-circumference measures (in addition to body mass index (BMI), blood pressure, blood glucose, and lipid levels) in identifying patients in a primary-care setting who are at increased cardiometabolic risk.

Improvement of Metabolic Parameters with Rimonabant Beyond the Effect Attributable to Weight Loss Alone: Pooled One-Year Data from the RIO (Rimonabant in Obesity and Related Metabolic Disorders) Program
Xavier Pi-Sunyer, MD, MPH, Professor of Medicine at Columbia University College of Physicians and Surgeons; Chief of Endocrinology, Diabetes, and Nutrition, St. Luke's-Roosevelt Hospital Center

The endocannabinoid system (ECS) is an endogenous physiological system that plays a key role in food intake and energy balance as well as glucose and lipid metabolism. Preclinical data indicate that the ECS has a possible direct effect on peripheral tissues. Expression of CB1 receptors is widespread, including in many regions of the brain and peripheral tissues, such as adipose tissue, liver, skeletal muscle, and gastrointestinal tract. Over-activation transforms the ECS from a negative-feedback system to a self-reinforcing positive-feedback system, promoting positive caloric balance, lipogenesis, insulin resistance, and dyslipidemia. All of these effects are attenuated by CB1 blockade with rimonabant.