Coronary Artery Disease in Older Persons: New Views to Manage Risk

The Evolving View of the Older Patient With CAD: Identifying and Managing Risk Earlier

“The nonmodifiable risk factors for CAD (coronary artery disease) are those that are predisposing to the process of atherosclerosis and coronary disease, and the contributing factors include inactivity and obesity,” explained Alan B. Miller, MD, Professor of Medicine, University of Florida College of Medicine, Jacksonville. “Modifiable causative risk factors include hypertension, dyslipidemia, diabetes, and smoking. High systolic blood pressure is the predominant problem in hypertension in older patients. Other risk factors include HDL (high-density lipoprotein) cholesterol, diabetes, and ventricular hypertrophy on electro?cardiogram.” Dr. Miller explained that, as cholesterol levels increase, the risk for death increases. “If LDL (low-density lipoprotein) cholesterol is lowered with the intervention of various lipid-lowering agents, coronary risk is lowered substantially,” he stated. “The goal, based on current guidelines, is to get LDL to 100 mg/dL.”

The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study¹ looked at 3086 patients (mean age, approximately 65 years) who presented with unstable plaques and ruptured atheromas. Subjects were randomized to placebo or high-dose atorvastatin for 16 weeks. The researchers concluded that early and rapid lowering of cholesterol is effective in the acute setting. Other conclusions drawn were that the vulnerable plaques were stabilized; the number of foam cells in the cap was reduced; lipid from the core was depleted; the fibrous cap remaining in the ruptured atheroma was stabilized; endothelial function was improved; and the physiologic ability of nitric oxide was restored. Although lipid lowering is the keystone of CAD treatment, there are other factors of critical importance, according to Dr. Miller. “The incidence of diabetes is growing rapidly and is prevalent in the older population,” he added. “Those who are diabetic tend to have other risk factors, and those who are also hypertensive are particularly at risk.” With the elderly, blood pressure lowering should be done in a slow manner, using lower doses of antihypertensive agents. “Older African-Americans predominantly have low renin hypertension, and calcium antagonists work well in that particular group,” Dr. Miller explained. In older Caucasians, calcium antagonists and beta-blockers work fairly well, and angiotensin-converting enzyme (ACE) inhibitors work very well because a lot of these older Caucasians have high renin hypertension. However, ACE inhibitors do not work well as monotherapy in African-Americans. “Noninvasive coronary calcification assessment,” continued Dr. Miller, “has become an important medical and scientific breakthrough. A calcification score can show if a patient has atherosclerosis. This technology will be used more frequently.”

Reference

1. Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: The MIRACL study: A randomized controlled trial. JAMA 2001;285:1711-1718.

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The Role of IVUS in Identifying Patients at Risk for Coronary Syndromes

Steven E. Nissen, MD, Professor of Medicine, Cleveland Clinic Campus, Ohio State University, Columbus, OH, and Vice Chairman, Department of Cardiology, Cleveland Clinic Foundation, explained that, over the past 43 years, “cardiologists have focused an incredible amount of attention on identifying luminal narrowings in the coronary arteries as a means to detect the presence and to guide therapy of coronary disease. The problem with this is that CAD is not a disease of lumen size, but of the atheroma in the vessel wall.” It is the atheroma in the vessel wall that determines the natural history and pathophysiology of the disease, not the size of the lumen.

Intravascular ultrasound (IVUS) is a method by which to study CAD. This technique uses a catheter 1 mm in diameter with an ultrasound device built into the tip. The catheter is placed in the coronary arteries to look at plaque. “The pictures from this technology have taught cardiologists an incredible lesson about the true nature of coronary disease,” the speaker said. He explained that the catheter rotates in the artery at 1800 rotations per minute inside a sleeve, producing 30-frame-per-second pictures. “The way this disease works was first suggested by Dr. Seymour Glagoff, who said that a normal vessel develops atherosclerotic plaque, causing it to enlarge with no reduction in lumen size,” explained the speaker. “He called this compensatory expansion because he thought it would maintain the lumen and protect the patient against angina for years and was thereby an adaptive phenomenon. Only in the very end stage of the disease does the lumen narrow.” Dr. Nissen pointed out that searching for the stenosis is a misguided approach to diagnosing CAD. “We must treat it as a systemic disease. Waiting for the stenosis to appear is too late.” In 62% of men and in approximately 50% of women, the first symptom of coronary heart disease is sudden death or acute myocardial infarction (MI). “Every study shows that coronary intervention has no effect on the prognosis of CAD; it does not reduce the risk of death or MI. The only way to alter prognosis is by treating the underlying atherosclerotic risk factors.” “The real culprit is plaque rupture,” Dr. Nissen stated. “This causes a thrombus to form, leading to the catastrophic syndromes of acute CAD. The mission for cardiology in the next decade is to figure out whether patients have vulnerable plaques by identifying their characteristics.”

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Contemporary Views on Diagnosis and Treatment in Coronary Artery Disease: Applications in Clinical Practice

“What has been learned is that, like cancer, vascular disease is often metastatic,” began Anthony De Franco, MD, Assistant Professor of Medicine, Michigan State University, Lansing, and Medical Director, McLaren Heart and Vascular Center, McLaren Health Care Corporation, Flint, MI. “Two-thirds of those who present with ostensibly coronary disease actually have clear-cut evidence of peripheral vascular disease.” Dr. De Franco noted that he was taught the mistaken notion that disease in the carotid artery predicts only stroke. “Even mild carotid atherosclerosis is associated not only with stroke, but with MI and sudden cardiac death. The reason is simple: it is the same disease; it is the same risk factors predisposing to disease in the coronary arteries and in the cerebrovascular arteries. Thickness of the carotid intimal media boundary can now be measured in the submillimeter range using a noninvasive technique, and interventions to lower LDL cholesterol can profoundly reverse carotid intimal media thickness.” The speaker pointed out that telling patients that they have only  a small amount of plaque in their carotid artery should be accompanied by the news that they have a threefold higher risk of MI than age- and sex-matched controls. “In a 40-to-49-year-old age group studied at the Cleveland Clinic Foundation, 70% of hearts had atherosclerosis,”¹ continued Dr. De Franco. “The Bogalusa Heart Study² showed that 67% of persons in a 26-to-39-year age group had evidence of coronary atherosclerosis.” He explained that these data were not new because it was known that 10% of Korean War veterans who died at a young age had a coronary artery with a 75% stenosis. “The disease starts when people are still in school and slowly progresses over many years.”

Dr. De Franco also discussed the Prospective Randomized Evaluation of Vascular Effects of Norvasc Trial (PREVENT),³ which examined the calcium blocker amlodipine. “Amlodipine is profoundly different from the other calcium blockers,” he explained. It is a very potent antioxidant, an inhibitor of smooth muscle cell migration, and a membrane-stabilizing drug. In primate models on atherogenic diets, administration of amlodipine can actually prevent or retard atherosclerosis. The PREVENT study randomized patients to amlodipine 10 mg or placebo. The primary endpoint was the change in the angiogram, which did not occur. The secondary endpoints were a 30% reduction in documented events or procedures, a 33% reduction in documented angina, and no change in fatal or nonfatal MI. Progression of the carotid intimal media thickness occurred in the placebo group, but no change was seen in the amlodipine-treated group. “There would be no change in the angiogram because it is the disease in the wall that matters,” stated Dr. De Franco. He concluded by summarizing: “CAD is ubiquitous, begins in youth, and is strongly associated with risk factors from the youngest ages. The effect of these risk factors for major vascular events is continuous and extends into the range traditionally considered normal. Ultrasound demonstrates that remodeling causes angiography to underestimate the extent of disease,” he continued. Extraluminal and angiographically silent atheromas are responsible for most acute events and sudden death. Most patients, both young and elderly, progress to MI or sudden death before a diagnosis of CAD is considered. Because CAD is systemic and requires a systemic solution, the only reasonable approach is early and aggressive management, taking into account the patient’s global risk for vascular events. “Awaiting overt signs and symptoms before beginning treatment is perhaps no longer justified, because, in some aspects, symptoms may be regarded more properly as a medical failure rather than as the initial indication for treatment.”

References

1. Foody JM, Ferdinand FD,  Pearce GL, et al. HDL cholesterol level predicts survival in men after coronary artery bypass graft surgery: 20-year experience from The Cleveland Clinic Foundation. Circulation 2000;102(19 suppl 3): III90-III94.

2. Berenson GS, Srinivasan SR, Bao W, et al. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults: The Bogalusa Heart Study. N Engl J Med 1998;333(23): 1650-1656.

3. Pitt B, Byington RP, Furberg CD, et al. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events: PREVENT Investigators. Circulation 2000;102(13):1503-1510.