The 2013 ACC/AHA Guidelines for Assessing Cardiovascular Risk derived a new 10-year risk score for estimating hard atherosclerotic cardiovascular disease (ASCVD) events using pooled data from NHLBI-funded cohorts including ARIC, CHS, CARDIA, and Framingham.   When Drs. Ridker and Cook recently tested this new 10-year ASCVD risk calculator in 3 cohorts (WHS, PHS, and WHI), they found overall that the predicted risk was much greater than the observed risk.  A flurry of attention was immediately drawn to this “flawed” calculator and the implication that more patients would be above the 7.5% threshold and considered for statin therapy.  However most of the discordance was in those with >10% estimated 10-year risk, a group already recommended to be treated by prior guidelines, anda group that likely had a lower observed rate due to intensified preventive therapy). There was less discordance in the middle risk groups of 5-7.5% and 7.5-10%, but still over-estimation from observed event rates.  I would like to know how many patients were reclassified higher into the new 7.5%-10% group that would be newly “eligible” for statins.

Part of the discrepancy may be that these three cohorts tested were largely lower-risk, Caucasian cohorts.  Of note, Drs. Ridker and Cook have previously shown that the ATP-III version of the Framingham Risk Score for hard CHD events also overestimated risk¹, so there were problems with the old risk calculator too.

These risk calculators are largely driven by age.  Chronologic age is different from arterial age.   The 2013 guidelines only give a weak class IIb indication for optional screening tests when risk-based decisions to start pharmacologic therapy are “uncertain.”  Yet compared to traditional risk factors, coronary artery calcium (CAC) testing clearly out-performs.  Individuals without risk factors but elevated CAC have  substantially higher mortality event rates than those who have multiple risk factors but no CAC².   Individuals with CAC=0 scores have very low event rates³;  thus the number needed to treat to prevent one event with statins among those with CAC=0 would be prohibitively  high. These findings challenge the exclusive use of traditional risk assessment algorithms for guiding the intensity of primary prevention therapies.
 

When the new risk score was applied to the MESA (Multi-Ethnic Study of Atherosclerosis) and REGARDS studies, it performed sub-optimally with C-statistics of ~0.6-0.7.  For comparison, in MESA, the C-statistic for the prediction of CHD events ~0.8 with CAC⁴.   Thus, CAC may perform better than the ASCVD pooled risk score alone.  Nearly all men aged>65 would cross-over this 7.5% threshold. Yet elderly individuals with no CAC actually have a lower mortality than younger individuals with high CAC scores⁵.

I wholeheartedly support the concept of risk assessment and tailoring therapy to those at highest risk.  I agree that the new on-line risk calculator could use some fine-tuning. However, the absence of MESA in the pooled cohorts and the weak endorsement for incorporating the potent discriminator of CAC in patients without dyslipidemia are major limitations that still may be leading us off target.  Hopefully these limitations will be updated in the next version of the risk calculator.

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References

1. Cook NR, Paynter NP, Eaton CB, et al. Comparison of the Framingham and Reynolds Risk Scores for Global Cardiovascular Risk Prediction in the Multi-ethnic Women’s Health Initiative. Circulation 2012; 125(14):1748-56, S1-11.
2. Nasir K, Rubin J, Blaha MJ, et al. Interplay of coronary artery calcification and traditional risk factors for the prediction of all-cause mortality in asymptomatic individuals. Circ Cardiovasc Imaging. 2012;5(4):467-73.
3. Blaha MJ, Blumenthal RS, Budoff MJ, Nasir K. Understanding the utility of zero coronary calcium as a prognostic test: a Bayesian approach. Circ Cardiovasc Qual Outcomes. 2011;4(2):253-6.
4. Polonsky TS, McClelland RL, Jorgensen NW, et al. Coronary artery calcium score and risk classification for coronary heart disease prediction. JAMA 2010;303(16):1610-6.
5. Tota-Maharaj R, Blaha MJ, McEvoy JW, et al. Coronary artery calcium for the prediction of mortality in young adults <45 years old and elderly adults >75 years old. Eur Heart J. 2012;33(23):2955-62.

Keywords: Atherosclerosis, Cardiovascular Diseases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, National Heart, Lung, and Blood Institute (U.S.), Risk Assessment, Risk Factors

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