The Changing Paradigm in Estimating the Risk of Cardiovascular Disease

Abstract & Commentary

By Rahul Gupta, MD, MPH, FACP, Clinical Assistant Professor, West Virginia University School of Medicine, Charleston, WV. Dr. Gupta reports no financial relationships relevant to this field of study.

Synopsis: The lifetime risk of cardiovascular disease is strongly influenced by risk factor burden and may be similar across race and birth cohorts.

Source: Berry JD, et al. Lifetime risks of cardiovascular disease. N Engl J Med 2012;366:321-329.

The framingham risk score (FRS) is often utilized in clinical practice to estimate an individual's 10-year absolute risk for developing coronary heart disease (CHD).1 Currently, the identification of risk status in persons without clinically manifest CHD or other forms of atherosclerotic disease is clinically determined by an overall two-step process. First, the number of risk factors, including measuring serum cholesterol, is counted. Second, for persons with multiple risk factors, a 10-year risk assessment is carried out with FRS to identify individuals whose short-term (10-year) risk warrants consideration of intensive treatment. By this method, appropriate persons can be targeted for drug therapy as primary prevention of CHD. However, by focusing on short-term risk, the FRS may inherently underestimate the lifetime cardiovascular risk in certain individuals, such as the younger population, who may feel otherwise falsely comforted in a good score and therefore may either not work to mitigate their existing risk factors or develop new ones. As a result, individuals categorized as low or intermediate 10-year risk for CHD may actually be at greater risk in the longer term.

Estimating lifetime risk rather than short-term risk may communicate the actual progressive cumulative risk of developing a disease during the remainder of an individual's life. In public health policy, lifetime risk estimates are often used to convey risk information about diseases such as cancers. This concept has also been used in the design of public health education campaigns for specific cancers in the general population, leading to early screening and diagnosis. Similar estimates of the lifetime risk of cardiovascular disease in individuals can provide a more comprehensive assessment of the overall burden of disease in population.

In their study, Berry et al utilized existing data from 18 cohort studies involving a total of 257,384 men and women (black and white) whose risk factors for cardiovascular disease were measured at the ages of 45, 55, 65, and 75 years. Their meta-analysis used blood pressure, cholesterol, diabetes, and smoking status to stratify participants according to risk factors into five mutually exclusive categories.

The researchers observed that among men and women who were 55 years of age, the higher burden of risk factors was associated with a much higher lifetime risk of death from cardiovascular disease. Those with an optimal risk-factor profile had a lower (4.7% in men; 6.4% in women) risk of death from cardiovascular disease through the age of 80 years compared to those with two or more major risk factors (29.6% in men; 20.5% in women). Those participants with an optimal risk-factor profile also had a lower (3.6% in men; < 1% in women) risk of fatal CHD or nonfatal myocardial infarction through the age of 80 years compared to those with two or more major risk factors (37.5% in men; 18.3% in women). Parallel trends were also observed for fatal or nonfatal stroke. Additionally, trends were similar among blacks and whites and across different birth cohorts. The authors found that a relatively low burden of these risk factors was associated with significant increases in the long-term risk of cardiovascular disease whereas the absence of such traditional risk factors was associated with a very low lifetime risk.


When describing the lifetime likelihood of developing cardiovascular disease in an individual, the presence or absence of traditional risk factors may be the most significant determinant. However, currently used tools for assessing such risk (FRS) may not adequately describe the lifetime cardiovascular disease burden in all individuals equitably. For example, individuals with multiple risk factors and an estimated 10-year CHD risk of > 20% are categorized as high risk and typically require drug therapy and therapeutic lifestyle changes to reach an LDL cholesterol goal of < 100 mg/dL.2 Similarly, individuals with an estimated 10-year CHD risk of 10-20% are categorized as moderately high risk and therapeutic lifestyle changes are recommended with an option for lipid-lowering therapy if LDL cholesterol is > 130 mg/dL. Individuals with an estimated 10-year CHD risk below 10% are considered moderate risk and therapeutic lifestyle changes are recommended with an option for lipid-lowering therapy only if LDL cholesterol is > 160 mg/dL. However, individuals with 0 to 1 risk factors are considered to be in the low-risk category and thus therapeutic lifestyle changes may be the only recommendation for many individuals. Such "low-risk" characterization may mislead such individuals to consider that it is not imperative to modify their risk factors. As a result, these individuals' persisting risk factors would significantly contribute to development of atherosclerosis over their lifetime. This increase in the overall burden of cardiovascular disease has significant clinical and public health implications. It is clear from existing studies that a decline in cardiovascular event rates in the general population is much more attributable to changes in the prevalence of risk factors rather than the effects of treatment.3,4 Therefore, the lifetime estimations of an individual's risk for cardiovascular disease may allow the development of suitable public health policies that would lead to lifestyle changes resulting in lowering of this burden by not only modification of the existing risk factors (such as cholesterol) but also prevention of the development of additional risk factors (diabetes, hypertension, smoking).


1. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Final report. Circulation 2002;106:3143-3421.

2. Grundy SM, et al. Circulation 2004;110:227-239.

3. Ford ES, et al. N Engl J Med 2007;356:2388-2998.

4. Bandosz P, et al. BMJ 2012;344:d8136.