CSAC SPECIAL REPORT

Incorporating cardiovascular disease risk stratification into clinical decision making

Lawrence Herman, MPA, PA-C; Edward Blanchard, PhD, PA-C; Lyle Larson, PhD, PA-C; Marie-Michèle Léger, MPH, PA-C; Robert McNellis, MPH, PA-C; Tim Quigley, MPH, PA-C; Sarah Toth, MS, PA-C; Eileen Van Dyke, MPS, PA-C

The authors are members and staff of the Clinical and Scientific Affairs Council (CSAC) of the AAPA. This article was prepared for CSAC by Sarah F. Zarbock, PA-C.

Clinical decision making about patients who may be at risk for cardiovascular events is increasingly complicated by a growing body of conflicting data regarding the roles that hypertension, dyslipidemia, diabetes, obesity, smoking, family history, and other factors should play in estimating a patient's risk of a cardiovascular event. The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III), and other studies have all had a significant impact on risk factor assessment and treatment choices.^1,2

Primary care and patients at risk

ATP III suggests that clinicians consider multiple risk factors, especially related to short-term mortality. Patients can be stratified into three general categories according to the likelihood that a cardiovascular event will occur: extremely low risk, indeterminate risk, and high risk. Extremely low-risk patients are generally asymptomatic, young, and otherwise healthy and have no first-degree relative with a history of a cardiac event at a young age. These patients need counseling about healthy lifestyle practices to keep their risk low and education about warning signs for cardiovascular events.

Guidelines for specific testing interventions in all risk categories can be confusing and may even conflict. In general, all patients should be assessed for hypertension and dyslipidemia. A screening exam may be warranted in a preschool-age child when there is familial dyslipidemia. Typically, after a comprehensive history is obtained, including questions about a family history of dyslipidemia, a single screening exam may be warranted in someone as young as 20 years. Lipid profiles in men should be evaluated at age 35 years and in women at age 45 years. No further evaluation or treatment is required in these otherwise low-risk patients whose lipid levels are within a normal range.³

High-risk patients are those with known cardiac disease or equivalents (such as diabetes), multiple risk factors, or symptoms of cardiac disease. These patients require diagnostic intervention including laboratory, imaging, and cardiac function studies—along with appropriate and aggressive treatment, including referral when appropriate to prevent or reduce future events.

This article focuses on patients in the indeterminate-risk group, who pose the greatest challenge for the primary care clinician. This group includes healthy patients who have one or more underlying stable, chronic problems, such as hypertension or dyslipidemia, or a first-degree relative with a premature cardiovascular event (see "Risk assessment overview," and "Tools you can use to assess risk").

 

Risk assessment overview The assessment for cardiovascular risk should include a comprehensive history and physical examination, with identification of coronary heart disease (ie, clinically apparent coronary artery disease) and its risk equivalents and with complete lipid studies performed after a 9- to 12-hour fast (see "Tools you can use to assess risk"). Look for major risk factors other than elevated LDL cholesterol levels. If two or more of these other risk factors are present but the patient does not have coronary heart disease or equivalents, assess the short-term (10-year) risk and determine the risk category for therapy stratification. If LDL cholesterol is undesirably high, assess whether therapeutic lifestyle changes alone are warranted or pharmaceutical interventions should be initiated concurrently or subsequently, and determine what therapy, if any, should be used. Assess and treat elevated triglycerides.

The role of nonmodifiable risk factors

Age, gender, and family history are nonmodifiable risk factors. Because atherosclerosis is progressive, the risk of coronary artery disease (CAD) increases significantly with age in both men and women. Once developed, coronary plaques have the potential to rupture. CAD becomes significantly more common in older rather than younger people because of this characteristic age-related plaque progression, regardless of other factors such as cholesterol risk.⁴ As patients age, the rise in absolute risk reaches a clinical significance in men in their middle or late fifth decade and in women after menopause. In general, however, men are at greater risk for CAD than women. The reason is not completely understood, but elevations in LDL cholesterol and BP occur at earlier ages in men, and their overall lower levels of HDL cholesterol may play a role.²

Studies have shown that a family history of premature coronary heart disease (CHD) in a first-degree relative is an independent risk factor even when other risk factors are accounted for.^5,6 Premature CHD is clinical CHD or sudden death documented in a male relative younger than 55 years or a female relative younger than 65 years. The risk has been reported to be as much as a 12-fold increase compared to the general population.^7,8 This substantially elevated risk cannot be explained by a single inherited factor, suggesting that this increase in risk is both multifactorial and polygenic.^7,8

Modifiable risk factors

Even minimal cigarette smoking is associated with significant risk for CAD, yet many patients continue to smoke. Observational and randomized clinical trials have demonstrated risk reduction for those who quit smoking, with risk beginning to decline 6 months after smoking cessation.^9,10

An estimated 97 million Americans are either overweight or obese.¹¹ A patient whose body mass index (BMI) is between 25.0 and 29.9 kg/m² is considered overweight, and one whose BMI is 30.0 kg/m² or higher is considered obese. Overweight or obesity increases risk for all-cause mortality, especially from CAD and stroke. Overweight patients have a disproportionate incidence of hypertension, dyslipidemia, and type 2 diabetes compared to patients of normal weight. Additionally, the lifetime risk of developing these risk factors is increased in obese patients, particularly in those with abdominal obesity (defined as a waist circumference greater than 35 inches in women and 40 inches in men). Being overweight or obese is not currently considered an independent risk factor for CAD, but those who carry excess weight should be strongly urged to lose it.²

Physical inactivity is associated with increased risk for CAD and is a significant modifiable risk factor. Regular physical activity is a desirable goal in all patients, and the activity level of each patient should be considered when recommending lifestyle changes and prescribing medication.

Some modifiable risk factors, including hypertension and dyslipidemia, are influenced by genetics, but these factors account for only a small portion of the aggregate CAD seen in families. Although studies differ with regard to the degree to which CAD is influenced by genetics, patients with first-degree relatives with a premature cardiovascular event warrant aggressive investigation and modification of risk factors whenever possible.

Managing modifiable risk factors

A number of studies have demonstrated the role of diet in CAD.¹² Although some of the adverse effects of long-term atherogenic diets are related to established risk factors (eg, the effect of high salt intake on BP), diet also influences risk in other ways. For example, some populations who eat a Mediterranean diet high in vegetables, whole grains, and polyunsaturated fats are at a lower baseline risk for CAD than can be explained by assessing their standard risk factors.¹³ Baseline risk in such populations may be improved with increased intake of folic acid, B vitamins, omega-3 fatty acids, and other micronutrients. Use of vitamin E has not been shown to be beneficial.¹⁴

The results of the JNC 7 have changed the approach to the treatment of hypertension. Only BP less than 120/80 mm Hg is now considered normal. Pressures as low as 120/80 mm Hg with concomitant conditions, such as diabetes, now warrant aggressive treatment, and BP between 120/80 and 139/89 mm Hg is categorized as prehypertension. Studies over time and with varying definitions of hypertension have demonstrated a strong association between hypertension and an increased risk of CAD. Patients who have a BP that was previously categorized as high normal are at an increased risk of CAD compared to patients with optimal BPs.¹⁵ Significantly, clinical trials have established that reductions in BP in patients with hypertension reduce the risk for virtually all end points of CAD.¹⁶ The degree of BP reduction should be guided by the presence of concomitant risk factors.

Making sense of lipid levels

While many studies have established a relationship between elevated serum triglyceride levels and CAD, the 1998 publication of two large meta-analyses first identified elevated serum triglycerides as an independent marker of risk.^17,18 These data suggest that at least some triglyceride-rich lipoproteins are atherogenic. Confounding variables are so closely linked that patients whose serum triglyceride levels are less than 100 mg/dL usually are of normal weight; are physically active; do not smoke cigarettes, drink alcohol excessively, or consume a diet high in carbohydrates; do not have diabetes or renal disease; use no drugs such as corticosteroids, protease inhibitors, or estrogens long term; and have no first-degree relatives with documented hypertriglyceridemia.¹⁹ Obesity, physical inactivity, or both are almost always present when serum triglyceride levels are higher than 200 mg/dL.^20,21

The lipid and lipoprotein components of cholesterol have become a major focus of therapy. Four classes of lipoproteins are found in the serum of fasting persons: high-density (HDL), low-density (LDL), intermediate-density (IDL), and very low-density (VLDL). In clinical practice, IDL is included in LDL cholesterol measurements. LDL and VLDL are generally combined and labeled as non-HDL cholesterol.

Lowering LDL cholesterol levels is considered the gold standard therapy in the primary and secondary prevention of CAD. Despite current ATP III guidelines that in general call for total cholesterol levels to be less than 200 mg/dL, opinion is growing that "even lower is even better."^22,23

In epidemiologic studies, low levels of HDL cholesterol are strongly associated with increased CAD mortality and morbidity.^2,24 Whether low HDL levels or high LDL levels are more predictive of the progression of CAD is not yet clear, but very low HDL cholesterol is arguably the most predictive risk factor for CHD.^25,26

Understanding the roles of newer serum markers

Recently, three serum markers have drawn considerable attention: plasma total homocysteine (tHcy), an amino acid; the inflammatory marker C-reactive protein (CRP); and the leukocyte enzyme myeloperoxidase. Further research is needed to establish the roles of tHcy, CRP, and myeloperoxidase in CAD risk stratification. How to integrate these markers into clinical decision making and how to intervene when levels are abnormal have not been standardized. As a result, routine measurement of these markers cannot be recommended at this time.²⁷

REFERENCES

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AAPA CSAC. CSAC Special Report. JAAPA May 2004;17:48-51.

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