Primordial Prevention

The term primordial prevention, first coined by Strasser in 1978, describes efforts to prevent the development of CVD risk factors in a population. Primordial prevention occurs predominantly at the societal and community levels and includes policy decisions that influence dietary patterns, educational objectives, and the environment. One example of primordial prevention is policy-driven, population-wide reductions in intake of trans –fat and saturated fat in order to reduce total cholesterol levels.

The advantage of primordial prevention over other types of prevention is that intervention occurs before the onset of a given risk factor and its associated adverse effects. Primordial prevention also offers the possibility of sustainable gains in overall health and affordable care for a population, as the downstream need for subsequent acute CVD care is reduced or even eliminated. Also of importance is that primordial prevention can be applied to an entire population, without the need for screening to identify individuals at increased risk.

Primordial prevention measures usually produce only very small changes in risk factors at the individual patient level, inasmuch as these strategies are designed to reach larger numbers of individuals at a much earlier stage of life. As suggested by Rose, a leading epidemiologist, “A large number of people exposed to a small risk may generate many more cases than a small number exposed to a high risk.” In fact, according to some estimates, primordial prevention offers the possibility of much larger reductions in mortality rates than can be achieved with either primary or secondary prevention.

The principal disadvantage of primordial prevention is that it is difficult to implement. Encouraging change in the behavior of an apparently “healthy” individual is challenging, partly because the relative risk reduction that occurs in such an individual over the near term is often small. In many cases, it is also difficult to predict the exact effect of such population-wide interventions until they are implemented. Finally, the up-front cost of initiating primordial prevention strategies is commonly enormous.

Primordial prevention frequently takes the form of policy change, educational programs, and environmental policy. These prevention plans are commonly implemented by politicians and are shaped by epidemiologic research. Clinicians, however, are becoming increasingly active in this area. This is particularly true in pediatrics and adolescent medicine, in which primordial prevention efforts are likely to have the greatest long-term benefit.

Primary Prevention

Primary prevention consists of efforts to prevent adverse events, such as myocardial infarction and stroke, in individuals with known risk factors for CVD. Most frequently, such prevention takes the form of individualized lifestyle interventions, including diet and exercise, as well as pharmacotherapy aimed at risk factor improvement. Typically, primary prevention is initiated by primary care physicians and cardiologists in the outpatient setting and is guided by epidemiologic and clinical trial data. One example is the treatment of hypertensive patients with therapies to lower blood pressure in order to prevent subsequent CVD events.

The principal advantage of primary prevention is the ability to tailor therapy to individuals at higher risk before they develop clinically significant atherosclerotic disease. Because of this individualized approach, primary prevention strategies result in a larger relative risk reduction for the individual than does primordial prevention. Not surprisingly, patients receiving primary prevention are more receptive to risk factor modification, particularly if their individual CVD risk can be communicated appropriately.

In spite of this, there are several disadvantages to focusing solely on primary prevention. First, primary prevention requires screening of a large segment of the population to identify individuals with sufficient risk to warrant treatment. This can be an expensive process, and current risk prediction models are not perfect at identifying individuals for whom such therapy is appropriate. Second, primary prevention strategies probably delay rather than prevent the onset of overt disease. Finally, primary prevention strategies have been argued by some authorities to “medicalize” otherwise healthy people, potentially diverting attention away from persons who are acutely ill.

Despite these potential disadvantages, we believe that primary prevention strategies are crucial for lowering the burden of cardiovascular disease.

Secondary Prevention

Secondary prevention consists of efforts to prevent further CVD events and mortality among patients with clinically evident atherosclerotic CVD. Such efforts most commonly involve individualized lifestyle interventions, risk-reducing medications, and cardiac rehabilitation. Secondary prevention is usually guided by data from randomized clinical trials and is best initiated in the inpatient setting, with continuation in the outpatient setting to ensure long-term risk reduction. One example of secondary prevention is the use of aspirin, which reduces thrombotic events in patients with CVD.

The principal advantage of secondary prevention is the large relative risk reduction that can be achieved within a short period of time. In general, treatment of higher risk patients results in a smaller number-needed-to-treat (NNT) to prevent an adverse event. Such treatment is therefore usually more cost-effective for patients who qualify. Compliance with lifestyle changes and initiation of recommended therapies is also highest in patients who have experienced a previous CVD event, particularly if symptoms persist.

Focusing predominantly on secondary prevention, however, has several disadvantages. Even though a majority of adults in the United States eventually suffer a cardiovascular event, a proportionally smaller number are living with CVD at any one time. For example, in 2006, only 16.8 million individuals in the United States were living with CHD, and 6.5 million individuals in the United States were living with stroke; both groups represent only 7.8% of the total population. Despite numerous available therapies, rates of recurrent events in secondary prevention also remain high. In fact, as many as 1 per 6 individuals with CHD and 1 per 7 individuals with stroke experience an adverse cardiovascular event within 1 year of follow-up. Finally, isolated secondary prevention is costly. Without primordial and primary prevention to reduce the risk factor burden, the cost of secondary prevention in an increasingly obese, diabetic, and aging population is probably prohibitive. The financial burden is increased further when patients have become irreversibly disabled from an initial cardiovascular event.

Blurring of Prevention Types

Although each of the three levels of prevention is generally regarded as distinct, there can be variable degrees of overlap. This may be a source of potential confusion for patients, epidemiologists, and providers.

One such example is the case of a patient with a fasting blood glucose level of 132 mg/dL in the years 1996 and 1997. Between these two periods, the definition of diabetes mellitus was changed by the American Diabetes Association from a fasting blood glucose level of 140 mg/dL or higher to 126 mg/dL or higher. From the perspective of the patient, despite no change in glycemic control, he or she was free of diabetes one month and then was considered to have the disease the next month. From the perspective of the epidemiologist, who views risk factors as continuous variables, changing thresholds simply reflects changing understanding of disease. This can be a common problem in clinical cardiology, inasmuch as continuous risk factor variables are commonly dichotomized as normal or abnormal on the basis of specific cutoff points. For the clinician, redefining the cutoff point for a given risk factor reclassifies patients from those needing primordial prevention to those needing primary prevention, and therapy is thus changed. This was illustrated again in 2002, when the National Cholesterol Education Program (NCEP) declared diabetes (as well as peripheral arterial disease, abdominal aortic aneurysm, and moderate carotid atherosclerosis) CHD risk equivalents ; patients with these conditions became classified as those requiring secondary prevention.

Another example is the case of a patient in whom significant subclinical atherosclerosis (e.g., increased coronary artery calcium score or increased carotid intima-media thickness) was identified on an imaging study. Should such an individual receive lipid-modifying therapy to an intensity recommended by primary prevention guidelines, or are even more aggressive secondary prevention goals warranted? The current management of advanced subclinical atherosclerosis occupies an uncertain middle ground between primary and secondary prevention, and in fact such an approach has been termed “primary and a half prevention.”

These reclassifications may appear to be a matter of semantics to the individual, but the implications are far greater at the public health level. By definition, lowering the cutoff point to define a given risk factor will decrease the numbers of individuals who qualify for primordial prevention and increase the numbers of those who qualify for primary prevention. Similarly, as technology improves the identification of subclinical atherosclerosis, there is the potential to decrease the numbers of individuals who qualify for primary prevention and increase the numbers of those who qualify for secondary prevention. These “rightward shifts” in the level of prevention invite a more aggressive treatment approach that is unfortunately also accompanied by increased up-front cost. Such is expected to be the case if future cholesterol guidelines adopt the results of the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER). In fact, it is estimated that 20% of middle-aged adults would be newly eligible for lipid-lowering therapy ; thus, approximately 6.5 million additional middle-aged adults would be newly eligible for this therapy.

Population-Based Prevention

The basic premise of a population-based prevention approach is that many CVD events occur in patients who are not considered a priori to be at high risk. This premise is driven by the distribution of risk factors within the population, which most commonly resembles a rightward skewed bell curve. Although individuals with the least well-controlled risk factors suffer the highest event rates, they represent a small fraction of the entire population. In contrast, although those with suboptimal control of mild risk factors have lower event rates, they represent a larger percentage of the population and account for far greater numbers of adverse CVD events ( Figure 1-1 ).

A, Population distribution of risk factors. B, Risk factors and risk for cardiovascular disease (CVD). C, Risk factors and total number of deaths.

Proponents of a population-based strategy argue that small changes in the entire population can have a tremendous effect on CVD burden. One such example is a ban on trans –fats, which would be expected to result in a leftward-shift in the distribution of cholesterol levels and thus a substantial shift toward more optimal control of risk factors ( Figure 1-2 ). This approach would have differing effects within the population, but the net effect would still be significant reduction in the population-wide rate of adverse CVD events.

Population-based approach to control of risk factors.

Several advantages are associated with this approach. First, population-based strategies do not require broad screening efforts that rely on imperfect estimates of CVD risk. For example, taxing cigarettes or mandating reductions of salt in food affects broad numbers of individuals, even if not to the same degree. Second, like primordial prevention, population-based approaches have the potential to intervene early in the natural history of CVD, well before the development of CVD events. Third, population-based approaches to risk factor management produce numerous long-term benefits, not the least of which is a better quality of life. Last, this approach better accounts for behavioral and cultural differences between individual populations.

A population-based approach does, however, have several important drawbacks. Perhaps most important among these is the fact that such a strategy is likely to require broad-based governmental approval, which can be quite costly and whose implementation can be contentious. It is unlikely that financial support will come from pharmaceutical and device companies, whose general focus is on the development of therapeutics that are applicable to a select portion of the population. In addition, public support for policy that encourages lifestyle change within a population that considers itself “healthy” may be difficult to achieve. In fact, people may believe in the “prevention paradox,” a notion that broad-based interventions with large overall benefit produce modest, incremental benefits at the individual level. Finally, population-based approaches are extraordinarily hard to implement, and even harder to assess in terms of benefit. For example, it is unclear to what extent U.S. educational programs about diets low in saturated fats from the 1960s and 1970s contributed to increased consumption of carbohydrates, which may underlie the current epidemics of obesity and diabetes mellitus. In spite of these challenges, the Osaka Declaration serves as a good reference for population-based prevention by outlining economic and political barriers around the world.

Individual-Based Prevention

The basic premise of a targeted, patient-based strategy (commonly referred to as the individual-based or high-risk approach ) is that the largest reductions in relative risk are achieved in patients with the highest event rates ( Figure 1-3 ). These strategies are potentially cost saving, inasmuch as they can be applied to a smaller group of individuals guided by evidence from randomized-controlled trials. To be effective, however, an individual-based prevention strategy depends on effective risk-stratification tools to identify the portion of the population most likely to benefit. One such example is the cholesterol guidelines from the NCEP, in which the Framingham Risk Score is used.

Individual-based approach to control of risk factors.

First among the many advantages to this approach is its focused nature. Results of epidemiologic surveys suggest that as many as one third to half of all cardiovascular events occur in patients who have had a prior event, and nearly all of these patients have already sought medical attention. Second, individualized approaches offer individualized care in a population in which there is often significant heterogeneity in the distribution of risk factors. Third, it is easier to quantify the long-term effects by directly comparing the findings with those from clinical trials (e.g., efficacy vs. effectiveness). Finally, patients at higher risk are usually more easily motivated to achieve behavioral change and compliance with prescription medications.

The principal weakness of this approach is its reliance on currently imperfect risk assessment tools for screening and identification of patients at high risk. For example, although advanced age is a major factor that drives many risk prediction models, there is clear evidence that early prevention results in more favorable outcomes. Physicians’ noncompliance also plays a significant role. The benefits obtained in clinical trials are rarely reproduced in the real-world setting, partly because risk assessment tools and available evidence-based therapies are used incompletely. Simplification of the guidelines represents one means that may help with compliance, but personalized risk assessment and the appropriate steps to reducing risk still must be communicated effectively to the individual patient.