In this multi-ethnic urban population, adding stroke to the cardiovascular risk stratification outcome cluster resulted in a 55% relative increase in observed 10-year risk among those with predicted risk of 10-20%. Adding stroke to the outcomes of MI and CHD death also resulted in crossing of the threshold (>20% over 10 years) considered for preventive treatments, such as statins, for this intermediate risk group. Among the low-intermediate risk group of 5-10% predicted risk, there was a similar increase in observed 10-year risk (53%), and a crossing of the threshold (10% over 10 years) considered for treatments such as aspirin.13
Results were similar when analyses were limited to those of age ≤80 years, which is the upper age limit for which the FRS was intended.
The mainstays of current preventive approaches to cardiovascular disease, such as antiplatelet and statin medications, reduce risk of both stroke and cardiac disease, and the importance of considering both outcomes when predicting risk, instead of cardiac disease alone, is increasingly recognized.3
One implication of our findings is that including stroke in the risk prediction outcome cluster has a clinically significant impact on the absolute value of risk and results in crossing of clinically significant thresholds for treatment. These findings are particularly robust because of the large size of the cohort studied, the minimal loss to follow-up, the long duration of follow-up, the precision of outcome definitions, and the multi-ethnic composition of the source population.
We also found that the effect of adding stroke to the outcome cluster for risk prediction may have an even greater impact in African Americans, among whom prior research has shown an increased stroke incidence compared to whites.4, 14
For example, in the Atherosclerosis Risk in Communities study, the age-adjusted rate ratio for ischemic stroke comparing blacks to whites was 2.41.15
The causes of this increased incidence among blacks are not fully characterized,4
but our findings suggest that, by not accounting for the risk of stroke, the FRS may be drastically underestimating overall cardiovascular risk among blacks in the low-intermediate risk category.
We did not use population-specific calibrations of the Framingham equations, since none are available for the Northern Manhattan community. Furthermore, the FRS and FGS are generally used by practitioners without population-specific calibrations, and we wanted to reflect the general use of these risk prediction equations.11, 13, 16
In other publications, we have demonstrated that the addition of other anthropometric variables to the traditional Framingham Risk Score variables with coefficients that were optimized for our population have improved the prediction of stroke, MI, and vascular death.17
The aim of this analysis was not to evaluate the applicability of the FRS to our population, but rather to demonstrate the incremental cardiovascular risk that occurs when stroke is added to the outcome cluster.
Limitations of this study include the unique race-ethnic composition of the cohort, which may limit comparability of the findings to other populations. However, we believe that a strength of this population is the ability to detect differences in the performance of the Framingham risk prediction schemes by race-ethnic category, which is particularly relevant since the source population of the Framingham study is predominantly white, and the association between individual risk factors and outcome has been shown to differ by race-ethnicity.18
Further research is needed to clarify the optimal use of primary risk stratification schemes, particularly those that predict risk of a composite vascular outcome, and particularly among minority populations. Relevant questions are whether different clinical thresholds of risk should be employed with a composite vascular outcome, and which vascular events should be included in a composite vascular outcome. Ultimately, the addition of stroke to the outcome cluster of cardiovascular risk will improve the identification of those at moderate to high risk, particularly among minority populations, and expand the demand for more effective prevention programs for cardiovascular disease and stroke.