Statin Eligibility, Coronary Artery Calcification, and Cardiovascular Events

Elizabeth Lai, Mercer University College of Pharmacy

The National Cholesterol Education Program’s 2004 Updated Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) guidelines and 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines have been used to determine statin eligibility over the last decade.  According to a review article, the 2013 ACC/AHA cholesterol guidelines group management of cholesterol by benefit from statin therapy.  It also includes improved risk assessment for the rest of the population by use of a global cardiovascular disease (CVD) risk calculator.1

A review of the 2013 ACC/AHA cholesterol guidelines suggests a new standard for treating cholesterol and focuses on using the appropriate intensity of statin therapy compared to the previous ATP III guideline which recommended treatment based on specific low-density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (HDL-C) treatment goals.2

Title: Guideline-Based Statin Eligibility, Coronary Artery Calcification, and Cardiovascular Events3
Design Longitudinal, community-based, cohort study; N = 2,435
Objective To determine whether the ACC/AHA guidelines improve identification of individuals who develop incident cardiovascular disease (CVD) and/or have coronary artery calcification (CAC) compared with the ATP III guidelines
Study Groups Incident cardiovascular disease and no incident cardiovascular disease
Methods Participants were from offspring and third-generation cohorts of the Framingham Heart Study and underwent multidetector computed tomography for CAC.  The 2004 ATP III guidelines were used to assess whether primary prevention of statin treatment was indicated if they met at least one of the following: (1) low-density lipoprotein cholesterol (LDL-C) level ≥100 mg/dL and diabetes mellitus or peripheral arterial disease or 10 year Framingham Risk Score (FRS) for coronary heart disease (CHD) of ≥20%; (2) LDL-C level 130 mg/dL and FRS > 10% but < 20% and two or more risk factors; (3) LDL-C level ≥160 mg/dL and FRS of < 10% and 2 or more risk factors; or (4) LDL-C level ≥190 mg/dL and < 2 risk factors.  The 2013 ACC/AHA guidelines identified those eligible for statin treatment based on: (1) clinical atherosclerotic cardiovascular disease (ASCVD); (2) LDL-C level ≥190 mg/dL; (3) diabetes diagnosis 40-75 years of age and LDL-C level of 70-189 mg/dL; or (4) no clinical ASCVD or diabetes, LDL-C level of 70-189 mg/dL, and estimated ASCVD risk of ≥7.5%.
Duration 2002-2005
Primary Outcome Measure Incident CVD (myocardial infarction, death due to coronary heart disease [CHD], or ischemic stroke)
Baseline Characteristics Abbreviations: standard deviation (SD), high-density lipoprotein cholesterol (HDL-C), coronary artery calcification (CAC), coronary heart disease (CHD)
Characteristics Total (N = 2435) No incident CVD (n = 2361) Incident CVD (n = 74)
Age, mean (SD) 51.3 (8.6) 51.1 (8.5) 57.7 (9.4)
Female, (%) 1355 (55.6) 1328 (56.2) 27 (36.5)
Traditional risk factors, (%)
Hypertension 616 (25.3) 588 (24.9) 28 (37.8)
Smoking 318 (13.1) 297 (12.6) 21 (28.4)
Diabetes mellitus 101 (4.1) 92 (3.9) 9 (12.2)
Family history of premature CHD 424 (22.1) 403 (21.7) 21 (35.6)
Lipid levels, mean (SD), mg/dL
Total cholesterol 199 (34) 199 (35) 204 (30)
LDL-C 121 (32) 120 (32) 128 (30)
HDL-C 56 (17) 56 (17) 48 (14)
Antihypertensive medications, (%) 353 (14.5) 336 (14.2) 17 (23.0)
Framingham risk score, mean (SD) 6.6 (5.7) 6.4 (5.5) 12.7 (8.9)
CAC score
Mean (SD) 93.3 (338) 84.3 (324) 380 (560)
Median (interquartile range) 0 (0-28.8) 0 (0-30.4) 170 (3-500)
Number (%) with score > 0 1015 (41.7) 957 (40.5) 58 (78.4)
Results Number of events/sample size (%) Hazard ratio (95% CI) P-value
Overall 74/2435 (3.0)
2004 ATP III guidelines
Statin eligible 24/348 (6.9) 3.1 (1.9-5.0) <0.001
Non statin eligible 50/2087 (2.4) 1 [reference]
2013 ACC/AHA guidelines
Statin eligible 59/941 (6.3) 6.8 (3.8-11.9) <0.001
Non statin eligible 15/1494 (1.0) 1 [reference]
P value for ATP III vs. ACC/AHA <0.001
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions In this community-based primary prevention cohort, the ACC/AHA guidelines for determining statin eligibility, compared with the ATP III, were associated with greater accuracy and efficiency in identifying increased risk of incident CVD and subclinical coronary artery disease, particularly in intermediate-risk participants.

The study revealed that the risk of CVD in statin eligible patients is significantly higher when the ACC/AHA guidelines are considered.  The population consisted mostly of white Americans and results cannot be generalized in different ethnic groups.  Significant differences were seen between risk factors, CAC, and outcomes in the study population.  Determination of statin eligibility considered no family history if complete family history was unavailable.  Following the 2013 ACC/AHA guidelines may help identify subclinical atherosclerosis and help prevent ASCVD with statin use.


  1. Virani SS. What is new in the 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic risk in adults?. Tex Heart Inst J. 2014;41(3):304-5.
  2. Virani SS. What is new in the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Risk in Adults?. Tex Heart Inst J. 2014;41(3):304-5.
  3. Pursnani A, Massaro JM, D’Agostino RB, Sr, O’Donnell CJ, Hoffmann U. Guideline-Based Statin Eligibility, Coronary Artery Calcification, and Cardiovascular Events. JAMA. 2015;314(2):134-141.



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