Categories of Risk Factors

CHD is a multifactorial disease with multilayered and overlapping “causes” (Box 70-1). More than 300 factors are described as “associated” with CHD. A National Heart, Lung and Blood Institute workshop on cardiovascular risk assessment classified factors implicated in the pathogenesis of a major coronary event into several levels: major atherogenic, plaque burden, conditional, underlying, susceptibility, undetermined, and protective. The multilayered, overlapping paradigm has a variety of mechanisms of action and interactions between levels.

Clinical Importance of Global Estimates for CHD Risk

Assessment of global cardiovascular risk based on major cardiovascular risk factors has three purposes of clinical interest: identification of high-risk patients who should have immediate attention and undergo immediate intervention, motivation of patients to adhere to risk-reduction therapies, and modification of the intensity of risk-reduction efforts on the basis of the total risk estimate (Fig. 70-1). Therapeutic decisions based on quantifiable measurements improve clinical decision making, increase motivation and compliance of patients, and can be evaluated for economic planning. Guidelines for management of individual risk factors recommend matching the intensity of preventive therapy to the absolute global cardiovascular risk. Cardiovascular epidemiologic research strives to quantify this global risk via predictive models.

Figure 70-1 Cardiovascular risk prediction.

BMI, body mass index; CHD, coronary heart disease; EBCT, electron beam CT; ECG, electrocardiogram; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; PAD, peripheral artery disease; PET, positron emission tomography.

The most common predicted event is the incidence of CHD, which can be defined as including angina pectoris, unstable angina, unrecognized myocardial infarction (MI), recognized MI, and CHD death. When risk cut points are defined to select patients for specific therapies, definitions of coronary end points have critical importance. However, of increased interest are symptomatic heart failure, hospital admission for unstable angina, need for revascularization procedures, and changes in functional capacity and quality of life.

Relative versus Absolute Risk

Absolute global risk is defined as the likelihood that CHD will develop in a person over a specified period, given the presence of cardiovascular risk factors. Absolute risk is considered the crucial determinant of whether and when to initiate pharmacologic therapy. Absolute risk can be calculated as short-term (usually 10 years) and long-term, or lifetime risk. Relative risk is the ratio of the likelihood of CHD developing in persons with and without given risk factors or at a given intensity of a risk factor. The difference between relative and absolute risk can be explained with an example of serum cholesterol concentration.

A young adult with a very high serum cholesterol concentration is at a low absolute risk for CHD but a high relative risk compared with a young adult with a low serum cholesterol concentration. CHD is unlikely to develop in the hypercholesterolemic young adult in the next 10 years, but the individual’s chances of experiencing premature CHD in the long term (e.g., before age 65) are high.

The goal for reducing elevated serum cholesterol concentration in young adults, therefore, is to retard atherogenesis throughout life, not only to prevent MI in the next decade.

Methods of Risk Assessment

Cardiovascular risk assessment uses two major approaches: simple counting and mathematical models.

Estimating Risk Using the Framingham Risk Scores

The Framingham Heart Study has generated prediction equations based on multivariate regression models to estimate CHD risk. The outcomes predicted are total CHD and “hard CHD.” In the Framingham Study, approaches based on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), whether as continuous or categorical variables, are similar in their ability to predict initial CHD events. However, extensive clinical data and clinical trial results suggest that LDL-C is the major atherogenic lipoprotein. Therefore, the use of LDL-C concentrations in the clinical setting is important whenever fasting samples are available. Despite studies advocating the use of the ratio of TC to high-density lipoprotein cholesterol (HDL-C), it was not used in Framingham predictions for two reasons. At the extremes of the TC or LDL-C distribution, equal ratios may not signify the same CHD risk, and, equally important, the use of a ratio may make it more difficult for physicians to focus on the separate values.

The blood pressure (BP) value used in the Framingham Risk Score is obtained at the time of assessment, whether the patient is taking antihypertensive drugs or not. The average of several BP measurements is needed for an accurate determination of the baseline concentration. Diabetes is defined as a fasting plasma glucose concentration greater than 126 mg/dL. The designation of “smoker” indicates any use of cigarettes within the past month.

Framingham Risk Scores provide two ways to estimate cardiovascular risk.

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