Statin Assignment With 2013 Guideline vs 2001 Guideline
The computed tomographic angiograms of consecutive patients obtained at a private outpatient radiology practice were reviewed. Patients had presented for various reasons, including stable atypical chest pain, indeterminate stress test results, multiple risk factors, and a strong family history. Risk factors and patient histories were retrospectively collated from patient intake forms and medical records. Patients were included if they were 21 to 90 years of age and had readily available lipid data. Patients younger than 40 years or older than 75 years, without known atherosclerotic cardiovascular disease (ASCVD) or low-density lipoprotein (LDL) cholesterol ≥190 mg/dl, were not included in further analyses, because the GACR makes no recommendations for such patients. The study complied with Health Insurance Portability and Accountability Act guidelines and received a waiver from the local institutional review board.
The NCEP and GACR regression equations for risk estimation were developed using data from a time when few patients were on statins, and they do not specifically account for statin use. In the present study, the baseline total cholesterol and LDL cholesterol values of patients on statins at the time of imaging were estimated from the measured values. In one large study, the average decrease in LDL cholesterol with statin therapy was 34% and that of total cholesterol 25%. For patients on statins, this corresponds to increasing the measured values of LDL cholesterol by 52% and total cholesterol by 33%. Analyses were repeated in the subgroup of patients not on statins at the time of imaging to confirm conclusions based on all patients. In addition, a sensitivity analysis was performed by varying the LDL decrease between 10% and 70% with a proportional change in total cholesterol level.
Using the NCEP ATP III panel recommendations, the percent risk for coronary heart disease (CHD) at 10 years was calculated under its modified Framingham model. Then, risk factors were assessed: smoking (any in the past month), hypertension (history of hypertension or systolic pressure ≥140 mm Hg), high-density lipoprotein (counted as 1 if <40 mg/dl and as −1 if >60 mg/dl), age (men, ≥45 years; women, ≥55 years), and family history of premature CHD in a first-degree relative (men, <55 years; women, <65 years). Patients were categorized as low risk (0 or 1 risk factor), intermediate risk (≥2 risk factors and <10% risk for CHD at 10 years), moderately high risk (≥2 risk factors and 10% to 20% risk for CHD in 10 years), or high risk (≥2 risk factors and >20% risk for CHD in 10 years). Patients with known CHD, diabetes, or peripheral atherosclerosis were classified as high risk regardless of their risk factor count or Framingham estimate.
The decision to start statins was based on an LDL cholesterol target keyed to the risk category: low risk, <160 mg/dl; intermediate risk, <130 mg/dl; moderately high risk, <100 mg/dl; and high risk, <70 mg/dl.
Under the GACR, 4 groups benefit from statins:
Statins were assigned if a patient met any of these criteria. The heart failure and dialysis exclusions were not applied, because these data were unavailable.
Patients not already on beta-blockers received 100 mg of metoprolol by mouth about 1 h before CTA. If the heart rate remained higher than 72 beats/min, an additional 50 to 100 mg was administered. Heart rate, electrocardiogram, and blood pressure were monitored. Sublingual nitroglycerin spray 1/150 g was given 1 min before image acquisition. A 64-slice computed tomographic scanner was used (VCT 64, GE Healthcare, Waukesha, Wisconsin). An initial bolus-timing single-slice scan using 20 ml of contrast (iodine content 320 mg/ml) (Visipaque, GE Healthcare) was followed by a 20-ml saline bolus. Contrast injection of 80 ml at a flow rate of 5 ml/s was followed by a saline chaser, 50 ml at a flow rate of 5 ml/s. Collimation was 0.625 mm, rotation time 0.35 ms, scan pitch 0.16 to 0.24 depending on heart rate, field of view 25 cm, reconstruction matrix 512 × 512, table feed 20 mm/rotation, tube voltage 120 kVp, and tube current 450 to 800 mA. Electrocardiographic dose modulation was used when possible. Electrocardiographically gated datasets were reconstructed from 70%, 75%, and 80% of the R-R cycle length; additional reconstruction windows were used if motion artifacts were present. Cases after June 2006 mostly used prospective gating, while the rest were retrospectively gated. Overall, approximately two-thirds of the cases in this study were done with prospective gating.
Methods of scoring plaque burden have been discussed in detail previously. The coronary tree was analyzed using the AHA's 1975 16-segment definitions. Cases with image quality designated as "limited" for any reason were excluded. Heavy calcification was not an exclusion criterion.
Each coronary examination was scored using the following 3 methods:
In an earlier paper, we established reference values for the plaque-scoring methods using data from patients with known coronary artery disease. For the SPS, the category cutoff values were 0 (zero), 1 to 3 (mild), 4 to 7 (moderate), and ≥8 (heavy). A similar procedure was used to establish the values for the SSS method (0, 1 to 3, 4 to 8, and ≥9) and the SIS method (0, 1 or 2, 3 or 4, and >4).
SPS is an overall plaque burden score. However, SSS and SIS are better established in the published research. In particular, SSS is closely allied to the Duke prognostic score. Other investigators have shown outcome data for SIS and SSS All 3 have been included.
Certain findings may correlate with higher risk, in particular patterns of more proximal disease. Two prognostic assessments of this type were used:
Discrete variables are reported as proportions and continuous variables as mean ± SD, if approximately normally distributed, or as median (interquartile range) if not. Statistical significance was defined at the ≤0.05 level for all analyses (2-tailed). Spearman's rho was used for correlation because several important variables were substantially skewed; 95% confidence intervals (CI) for rho were calculated using Fisher's z transformation. Logistic regression was used, with the decision whether to start a statin as the dichotomous variable and various measures of disease severity as the continuous variable. Unit odds ratios with 95% CIs were calculated. McNemar's test was used to estimate the significance of the difference in proportions of patients assigned to statin therapy by the 2 risk methods. JMP Pro version 10.0.0 (SAS Institute Inc., Cary, North Carolina) was used to perform the analysis.
Methods
Study Population
The computed tomographic angiograms of consecutive patients obtained at a private outpatient radiology practice were reviewed. Patients had presented for various reasons, including stable atypical chest pain, indeterminate stress test results, multiple risk factors, and a strong family history. Risk factors and patient histories were retrospectively collated from patient intake forms and medical records. Patients were included if they were 21 to 90 years of age and had readily available lipid data. Patients younger than 40 years or older than 75 years, without known atherosclerotic cardiovascular disease (ASCVD) or low-density lipoprotein (LDL) cholesterol ≥190 mg/dl, were not included in further analyses, because the GACR makes no recommendations for such patients. The study complied with Health Insurance Portability and Accountability Act guidelines and received a waiver from the local institutional review board.
Baseline Cholesterol Estimation
The NCEP and GACR regression equations for risk estimation were developed using data from a time when few patients were on statins, and they do not specifically account for statin use. In the present study, the baseline total cholesterol and LDL cholesterol values of patients on statins at the time of imaging were estimated from the measured values. In one large study, the average decrease in LDL cholesterol with statin therapy was 34% and that of total cholesterol 25%. For patients on statins, this corresponds to increasing the measured values of LDL cholesterol by 52% and total cholesterol by 33%. Analyses were repeated in the subgroup of patients not on statins at the time of imaging to confirm conclusions based on all patients. In addition, a sensitivity analysis was performed by varying the LDL decrease between 10% and 70% with a proportional change in total cholesterol level.
NCEP Risk Estimation
Using the NCEP ATP III panel recommendations, the percent risk for coronary heart disease (CHD) at 10 years was calculated under its modified Framingham model. Then, risk factors were assessed: smoking (any in the past month), hypertension (history of hypertension or systolic pressure ≥140 mm Hg), high-density lipoprotein (counted as 1 if <40 mg/dl and as −1 if >60 mg/dl), age (men, ≥45 years; women, ≥55 years), and family history of premature CHD in a first-degree relative (men, <55 years; women, <65 years). Patients were categorized as low risk (0 or 1 risk factor), intermediate risk (≥2 risk factors and <10% risk for CHD at 10 years), moderately high risk (≥2 risk factors and 10% to 20% risk for CHD in 10 years), or high risk (≥2 risk factors and >20% risk for CHD in 10 years). Patients with known CHD, diabetes, or peripheral atherosclerosis were classified as high risk regardless of their risk factor count or Framingham estimate.
The decision to start statins was based on an LDL cholesterol target keyed to the risk category: low risk, <160 mg/dl; intermediate risk, <130 mg/dl; moderately high risk, <100 mg/dl; and high risk, <70 mg/dl.
GACR Risk Estimation
Under the GACR, 4 groups benefit from statins:
Known ASCVD with no New York Heart Association functional class II to IV heart failure or dialysis
LDL cholesterol ≥190 mg/dl
Age 40 to 75 years with diabetes and LDL >70 and <190 mg/dl without ASCVD
Age 40 to 75 without ASCVD or diabetes, LDL >70 and <190 mg/dl, and estimated 10-year risk of 7.5% or higher using new pooled cohort equations
Statins were assigned if a patient met any of these criteria. The heart failure and dialysis exclusions were not applied, because these data were unavailable.
CTA
Patients not already on beta-blockers received 100 mg of metoprolol by mouth about 1 h before CTA. If the heart rate remained higher than 72 beats/min, an additional 50 to 100 mg was administered. Heart rate, electrocardiogram, and blood pressure were monitored. Sublingual nitroglycerin spray 1/150 g was given 1 min before image acquisition. A 64-slice computed tomographic scanner was used (VCT 64, GE Healthcare, Waukesha, Wisconsin). An initial bolus-timing single-slice scan using 20 ml of contrast (iodine content 320 mg/ml) (Visipaque, GE Healthcare) was followed by a 20-ml saline bolus. Contrast injection of 80 ml at a flow rate of 5 ml/s was followed by a saline chaser, 50 ml at a flow rate of 5 ml/s. Collimation was 0.625 mm, rotation time 0.35 ms, scan pitch 0.16 to 0.24 depending on heart rate, field of view 25 cm, reconstruction matrix 512 × 512, table feed 20 mm/rotation, tube voltage 120 kVp, and tube current 450 to 800 mA. Electrocardiographic dose modulation was used when possible. Electrocardiographically gated datasets were reconstructed from 70%, 75%, and 80% of the R-R cycle length; additional reconstruction windows were used if motion artifacts were present. Cases after June 2006 mostly used prospective gating, while the rest were retrospectively gated. Overall, approximately two-thirds of the cases in this study were done with prospective gating.
Plaque Burden and Stenoses Scoring
Methods of scoring plaque burden have been discussed in detail previously. The coronary tree was analyzed using the AHA's 1975 16-segment definitions. Cases with image quality designated as "limited" for any reason were excluded. Heavy calcification was not an exclusion criterion.
Each coronary examination was scored using the following 3 methods:
Segmental plaque burden score (SPS): For each segment, plaque amount was scored as none or trace (0), mild, moderate, or heavy. These refer to the volume of plaque within a segment, whether calcified or not. In the case of multiple lesions, the score reflected the segment as a whole. The SPS was calculated as the sum of the individual segment scores.
Segmental stenosis score (SSS): Same as above, but using an estimate of worst diameter stenosis per segment rather than plaque volume, scored as very mild, <30% (0); mild, 30% to 49%; moderate, 50% to 69%; or severe, ≥70%. The SSS was calculated as the sum of the individual segment scores.
Segmental involvement score (SIS): For each segment, plaque amount was scored as absent or trace (0) or present, whether calcified or not. The SIS was calculated as the sum of the individual segment scores.
In an earlier paper, we established reference values for the plaque-scoring methods using data from patients with known coronary artery disease. For the SPS, the category cutoff values were 0 (zero), 1 to 3 (mild), 4 to 7 (moderate), and ≥8 (heavy). A similar procedure was used to establish the values for the SSS method (0, 1 to 3, 4 to 8, and ≥9) and the SIS method (0, 1 or 2, 3 or 4, and >4).
SPS is an overall plaque burden score. However, SSS and SIS are better established in the published research. In particular, SSS is closely allied to the Duke prognostic score. Other investigators have shown outcome data for SIS and SSS All 3 have been included.
Prognostic Features
Certain findings may correlate with higher risk, in particular patterns of more proximal disease. Two prognostic assessments of this type were used:
Modified Duke prognostic index: This index, derived from conventional angiographic data, correlates with cardiac morbidity and mortality. For each segment, stenosis is graded visually as very mild (<30% diameter), mild (30% to 49%), moderate (50% to 69%), or severe (≥70%). Then permutations of lesions carrying increasing risk for a coronary event are defined. The original scheme used 16 combinations, but we adopt the following modification. The categories are 0, no or trace plaque; 1, very mild or mild stenoses; 2, ≥2 mild stenoses with 1 proximal or 1 moderate stenosis; 3, 2 moderate stenoses or 1 severe stenosis; 4, 3 moderate stenoses or 2 severe stenoses or proximal left anterior descending coronary artery (LAD) severe stenosis; 5, 3 severe stenoses or 2 severe stenoses with proximal LAD involved; and 6, moderate or severe left main stenosis.
Criteria emphasized in a meta-analysis of 11 prognostic studies by Bamberg et al.: Left main stenosis ≥50%, any stenosis ≥50%, and any plaque. The number of proximal segments with stenosis ≥50% was also assessed, defined as proximal right coronary artery, middle right coronary artery, left main coronary artery, proximal LAD, middle LAD, proximal circumflex coronary artery, and obtuse marginal branch, following Hadamitzky et al..
Statistical Analysis
Discrete variables are reported as proportions and continuous variables as mean ± SD, if approximately normally distributed, or as median (interquartile range) if not. Statistical significance was defined at the ≤0.05 level for all analyses (2-tailed). Spearman's rho was used for correlation because several important variables were substantially skewed; 95% confidence intervals (CI) for rho were calculated using Fisher's z transformation. Logistic regression was used, with the decision whether to start a statin as the dichotomous variable and various measures of disease severity as the continuous variable. Unit odds ratios with 95% CIs were calculated. McNemar's test was used to estimate the significance of the difference in proportions of patients assigned to statin therapy by the 2 risk methods. JMP Pro version 10.0.0 (SAS Institute Inc., Cary, North Carolina) was used to perform the analysis.
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