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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.

Findings from the The Multiple Risk Factor Intervention Trial (MRFIT) helped to shape thinking about global risk; it showed that risk with each additional risk factor is more than the sum of its parts. Elevated total cholesterol + glucose intolerance increased the risk of a CVD event 6-fold over those without these risk factors; add smoking to the picture and the risk increased 8-fold. Risk continued to increase even more with each additional risk factor such as left ventricular (LV) hypertrophy.

The recommendations from the American Heart Association Prevention Conference V Office Assessment Committee note that “Global risk should be a part of every patient’s medical record.” This reflects the National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III guidelines, which now focus on primary prevention in patients with multiple risk factors and recommend an assessment of global risk using the Framingham projections of 10-year absolute risk.

The ATP III guidelines consider metabolic syndrome a target for therapy—but a secondary target of risk reduction after lowering low-density lipoprotein (LDL) cholesterol. Intensity of therapy is determined by the number of risk factors present.

The Writing Group of the American Society for Hypertension also proposes a more comprehensive approach to reducing global cardiovascular (CV) risk: examining diabetes, LV hypertrophy, and other risk factors changes the goal for target blood pressure (BP). They encourage integrated CV risk management, eg, BP and lipid control. They also describe early markers and target organ damage.

Dr. Smith concludes that primary prevention is the goal for minimizing risk. Global risk assessment over the lifetime is important. Intensity of treatment is driven by overall risk.

Landmarks for Lipid-Lowering Therapies: Surveying Atherosclerotic Risk

Peter H. Jones, MD, Co-director, Lipid Metabolism and Atherosclerosis Clinic; Medical Director, Weight Management Center, The Methodist Hospital; Associate Professor Medicine, Section of Atherosclerosis and Lipid Research, Baylor College of Medicine, Houston, Texas

Case Presentation

A 48-year-old Hispanic woman presented to Dr. Jones’ office. She has no major medical issues, but it has been 3 years since her last visit. At the last visit, she was told she had borderline high BP but she can’t remember the numbers. She doesn’t smoke. She has gained weight over the past 3 years and she gets no regular exercise. She takes calcium for osteoporosis risk and a natural estrogen pill because she considers herself perimenopausal. She has two children and no history of gestational diabetes. This woman represents a very common presentation.

On physical examination, her BP is 141-2/80-84 mm Hg, and she weighs 174 pounds; body mass index (BMI) is 30 and she is 5’3” tall. Her waist circumference is 36 inches. Blood sugar is normal. Dual energy X-ray absortiometry scan reveals normal findings for her age and menopausal status.

According to Framingham data, this patient has a 2% CHD risk. However, this can be deceptive: she also possesses all five criteria for the metabolic syndrome. Dr. Jones urged lifestyle changes (weight loss and a regular exercise program) and follow-up in 6 months.

Specialized lipid tests might also be appropriate for this woman, as would measurement of C-reactive protein (CRP). Women with the metabolic syndrome generally have elevated CRP levels, especially with a higher BMI. In fact, the metabolic syndrome itself often portends a higher CRP level. However, elevated CRP does not change her CV risk according to the Framingham risk score. In the intermediate risk category, an elevated CRP would move men to the next level, but not women. The Air Force/Texas Coronary Atherosclerosis Prevention Study, a primary prevention study with lovastatin, showed the importance of CRP. Postmenopausal women tend to have higher CRP and triglyceride levels and, with this, a greater mortality risk for CVD. Further, the metabolic syndrome does have predictive risk for CVD and for future diabetes.

Lifestyle changes are the first step in reducing CV and diabetes risk in this patient. This strategy has been borne out in numerous studies, and the ATP III recommends reducing obesity and increasing exercise as very important factors and the foundation of reducing risk—in the presence or absence of the metabolic syndrome. These steps can reduce inflammation and increase insulin sensitivity.

The metabolic syndrome undoubtedly contributes importantly to global CV risk. But is it a CHD equivalent? Probably not yet, says Dr. Jones, particularly if the patient has a normal glucose level (<140 mg/dL).

LDL cholesterol has been the target of lipid-lowering therapy for 20 years. However, recent studies indicate that high-density lipoprotein (HDL) cholesterol deserves more importance as a target and may be the future of lipid treatment. Thus, if a patient is receiving a statin—which does not lower HDL to a great degree—addition of a fibrate or niacin to a statin may be indicated if the HDL cholesterol level is low.

One other intervention may be key: use of an insulin sensitizer may produce profound reductions in LDL oxidation and increases in HDL cholesterol. Dr. Jones’ Parting words: a woman who leaves your office with CV risk factors needs immediate intervention.

Interventions in Hypertension: Evidence that CVD Risk Is Closer than It Appears

Brent M. Egan, MD, Head, Hypertension Section, Division of General Internal Medicine, Medical University of South Carolina, Charleston, South Carolina

Dr. Egan picked up Dr. Jones’ case 7 years later. The patient, now a 55-year-old Hispanic woman, has moved to South Carolina and has received primary care. She had been started on hydrochlorothiazide (HCTZ) 12.5 mg 6 months earlier and was advised to intensify lifestyle efforts to lose weight and increase exercise, but has not followed this advice. She takes lovastatin 40 mg. She has noted dyspnea for past year during work as a hotel maid. She has no health insurance but has been unable to get Medicaid. Physical examination reveals a BP of 162/94 mm Hg. The patient has gained weight (178 pounds is current weight, up from 170). Her BMI has increased to 30.6 and her waist circumference is 37 inches. Fasting blood glucose is 122 mg/dL, potassium is 3.7 mEq/L, creatinine is 1.4 mg/dL, and estimated GFR is 41 mL/1.73 m2—an indication of stage 3 renal disease. Her electrocardiogram shows borderline LV hypertrophy. The Framingham risk score has increased to 5% with the presence of microalbuminuria and stage 3 kidney disease. She is almost certainly headed for development of diabetes.

The majority of hypertensive patients (61%) meet the criteria for the metabolic syndrome; half of obese women have it. But there is much overlap between chronic kidney disease and the metabolic syndrome. A combination doubles risk for ischemic heart disease. The risk of stage 3 kidney disease is underappreciated. While serum creatinine alone is not a good indicator for CV risk, it does put a patient at increased risk for LV hypertrophy.

The foundation of this patient’s treatment remains lifestyle changes; weight loss and exercise can lead to a 58% decrease in risk (Diabetes Prevention Study), but these measures likely will not be enough. Her patient profile is complicated by the fact that she is uninsured. While this patient’s hypertension should be treated, a diuretic may not be appropriate because of increased risk of diabetes (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]). An angiotensin-receptor blocker (ARB) or angiotensin-converting enzyme (ACE) inhibitor should be considered because of the presence of microalbuminuria. The Irbesartan Microalbuminuria Type 2 Diabetes Mellitus in Hypertensive Patients study (IRMA-2) showed that irbesartan 300 mg significantly reduces progression to nephropathy. A smaller dose—150 mg—reduced progression, but not significantly. The Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension study showed a significant reduction in LV mass with losartan.

Aspirin should be another component of this patient’s treatment. The Hypertension Optimal Treatment study revealed a 30% reduction in risk of myocardial infarction with low-dose aspirin for reduction of prothrombotic risk.

Because this patient is uninsured and does not qualify for Medicaid, Dr. Egan proposed ways of minimizing her cost, which could be as high as $453 to $3576 per year. Strategies for dealing with this include medical access programs. Generic ACE inhibitors, HCTZ, and nondihydropyridine calcium channel blockers are available. Aspirin is very inexpensive. Thus, in this patient, the cost of medications could be reduced to about $38 per month.

Using this expense-sparing strategy, the patient may be able to attain the objectives of treatment: prevention of CVD, no progression to type 2 diabetes or nephropathy, and maintenance of quality of life. The goals are 5-10% weight loss, 30 minutes of exercise daily, BP <130/80 mm Hg (with ARB or ACE inhibitor), LDL cholesterol lowering to <100 mg/dL, regression of LV hypertrophy, and, possibly, reversal of microalbuminuria.

Navigating Risk in Heart Failure: Strategies for Minimizing Risk Across the Stages of Heart Failure

Ileana Piña, MD, Professor of Medicine, Case Western Reserve University, Director, Section of Heart Failure and Cardiac Transplantation, Department of Medicine, Division of Cardiology, University Hospitals of Cleveland, Cleveland, Ohio

Case Presentation

Dr. Piña is called to see a 58-year-old woman in the coronary care unit, who had just been admitted with fatigue and shortness of breath progressing over the last 2-3 days. She has an abnormal electrocardiogram. She denies chest pain or discomfort, but admits to occasional jaw discomfort. Type 2 diabetes was diagnosed a year earlier, and she is receiving glyburide. She has never smoked. The patient cannot lie totally flat to sleep. She has a history of occasional BP elevation. She was taking ramipril but discontinued it because it was too expensive. She denies having known hyperlipidemia. However, she had been taking lovastatin but discontinued it due to gastrointestinal side effects.

Dr. Piña notes that, according to the Framingham risk score, this patient is at low CV risk, but this score does not tell the story for women. Sixty-four percent of women who die of sudden death have no previous symptoms. This is true for 50% of men.

The prevalence of diabetes has increased by a third between 1990 and 1998 and contributes dramatically to CHD risk. In women, the relative risk of CVD death with diabetes is higher in women than in men.

Continuing with the case, Dr. Piña found on an ECG that the patient had LV hypertrophy. Diabetic patients do not need a great dilation to develop heart failure. Dr. Piña further discovered that the patient had had a myocardial infarction in the past.

The structural abnormalities of her heart have the “makings” of many risk factors for CVD, but they are not manifest. The Survival and Ventricular Enlargement study revealed that increased LV area and volume are important predictors of CV events.

The Studies of Left Ventricular Function trial showed heart failure mortality is lower in men than women: 37.6% in men and 62.4% in women (NHANES III data). However, women are underrepresented in trials of heart failure, comprising only about 20% of the participants. Nevertheless, the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF) showed the benefit of beta blockers in women with heart failure.

This woman required changes in medication. An ACE inhibitor was added for treatment of heart failure and blood pressure. Hydrochlorothiazide was continued. A loop diuretic might be added if volume is high. If symptoms persist, addition of an ARB might be considered. Finally, aspirin should be added and the statin should be changed. 

In patients with CHF, physicians should aim to treat the LV dysfunction, not just the CHF symptoms. LV dysfunction is a chronic disease that is usually progressive, even when it seems compensated. The risk of sudden death or progressive CHF is very real. Adding a beta blocker to the treatment regimen while the disease is still compensated or after resolution of an acute exacerbation can stabilize or reverse the LV dysfunction and improve survival. Beta blockade is now a vital part of the standard of care for most patients with LV dysfunction.