Utility of Nontraditional Risk Markers in Individuals Ineligible for Statin Therapy According to the 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines

Abstract

Background In the general population, the majority of cardiovascular events occur in people at the low to moderate end of population risk distribution. The 2013 American College of Cardiology/ American Heart Association guideline on the treatment of blood cholesterol recommends consideration of statin therapy for adults with an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥7.5% based on traditional risk factors. Whether use of non-traditional risk markers can improve risk assessment in those below this threshold for statin therapy is unclear. Methods and Results Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), a population sample free of clinical CVD at baseline, we calibrated the Pooled Cohort Equations (cPCE). ASCVD was defined as myocardial infarction, coronary heart disease death, fatal or non-fatal stroke. Adults with initial cPCE <7.5% and elevated levels of additional risk markers (abnormal test) whose new calculated risk ≥ 7.5% were considered statin eligible: low-density lipoprotein cholesterol (LDL) ≥160 mg/dL, family history of ASCVD (FH), high-sensitivity C-reactive protein≥2 mg/dL, coronary artery calcium (CAC) score ≥300 Agatston units or ≥75th percentile for age, sex, and ethnicity, and ankle-brachial index<0.9. We compared the absolute (AR) and relative (RR) ASCVD risks among those with vs without elevated post-test estimated risk. We calculated the number needed to screen to identify one person with abnormal test (NNSI) for each risk marker, defined as the number of participants with baseline cPCE risk <7.5% ÷ number with abnormal test reclassified as statin eligible. Of 5,185 participants not taking statins with complete data (age 45-84), 4185 had a cPCE risk <7.5%. During 10 years of follow up, 57% of the ASCVD events occurred among adults with a cPCE risk <7.5% (183/320). Excluding people with diabetes, the CAC criterion reclassified 6.8% upward, with an event rate of 13.3%, AR of 10%, RR (95%CI) of 4.0(2.8-5.7) and NNSI of 14.7. The corresponding numbers for FH were 4.6%, 15.1%, 12%, 4.3(3.0-6.4) and 21.8 respectively; hs-CRP criterion were 2.6%, 10%, 6%, 2.6(1.4-4.8) and 39.2 respectively; ABI criterion were 0.6%, 9%, 5%, 2.3(0.6-8.6) and 176.5 respectively and LDLc criterion were 0.5%, 5%, 1%, 1.2(0.2-8.4) and 193.3 respectively. 431/3882(11.1%) of those with < 7.5% cPCE were reclassified to ≥ 7.5 %( statin eligible) by at least one of the additional risk marker criterion. Conclusions In this generally low-risk population sample, a large proportion of ASCVD events occurred among adults with a 10-yr. cPCE risk <7.5%. We found that the CAC, hsCRP, FH and ABI recommendations by the ACC/AHA cholesterol guidelines (Class IIB) identify small subgroups of asymptomatic population with <7.5% 10 yr. cPCE but with observed ASCVD event rates higher than 7.5% who may warrant statin therapy considerations.

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“…Currently, modalities such as the CAC and high sensitivity C-reactive protein (hsCRP) are suggested for evaluating “intermediate risk” individuals when there is uncertainty about the role for lipid-lowering agents. 6, 29 A CAC score ≥ 300 or ≥ the age, sex and ethnicity adjusted 75 th percentile, justifies upward risk revision and initiation of statin therapy. 30 …”

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“…Although this degree of CACS exceeds the volume utilized in most clinical practices nationwide, there is abundant data that CACS incrementally improves risk assessment alone and as an adjunctive test to global risk scores . Among a cohort of the MESA population deemed statin ineligible, CACS reclassified 6.8% of patients upward, with a calculated number needed to screen of 14.7 to prevent a ASCVD event . Conversely, among statin candidates, CACS identified 44% of individuals with a CACS of 0 AU in whom statins were recommended but had an observed event rate of <0.5% per year .…”