Atherosclerotic cardiovascular disease (ASCVD) events are the leading cause of death in the United States and globally. Traditional global risk algorithms may miss 50% of patients who experience ASCVD events. Noninvasive ultrasound evaluation of the carotid and femoral arteries can identify subjects at high risk for ASCVD events. We examined the ability of different global risk algorithms to identify subjects with femoral and/or carotid plaques found by ultrasound. The study population consisted of 1,464 asymptomatic adults (39.8% women) aged 23 to 87 years without previous evidence of ASCVD who had ultrasound evaluation of the carotid and femoral arteries. Three ASCVD risk algorithms (10-year Framingham Risk Score [FRS], 30-year FRS, and lifetime risk) were compared for the 939 subjects who met the algorithm age criteria. The frequency of femoral plaque as the only plaque was 18.3% in the total group and 14.8% in the risk algorithm groups (n = 939) without a significant difference between genders in frequency of femoral plaque as the only plaque. Those identified as high risk by the lifetime risk algorithm included the most men and women who had plaques either femoral or carotid (59% and 55%) but had lower specificity because the proportion of subjects who actually had plaques in the high-risk group was lower (50% and 35%) than in those at high risk defined by the FRS algorithms. In conclusion, ultrasound evaluation of the carotid and femoral arteries can identify subjects at risk of ASCVD events missed by traditional risk-predicting algorithms. The large proportion of subjects with femoral plaque only supports the use of including both femoral and carotid arteries in ultrasound evaluation.
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in the United States and globally. The identification of causes and the implementation of risk-predicting algorithms has greatly aided the treatment of patients at high risk. Nevertheless, there has been a failure to prospectively identify almost half of the patients who have an atherosclerotic cardiovascular event. Because of the deficiency of the traditional risk algorithms, there has been an interest in the use of noninvasive imaging techniques to better identify those at increased ASCVD risk. Coronary calcium score, intima-media thickness (IMT) of the carotid artery, and vascular plaque assessment of carotid and femoral arteries are among the methods undertaken. The accuracy, ease of data acquisition, and lack of radiation are advantages of ultrasound of the carotid and femoral arteries as a method of evaluation in asymptomatic adults. We have previously reported on the importance of evaluating the femoral arteries and compared the presence of plaque in carotid and femoral arteries in both men and women. In this article, we expanded those studies by evaluating the efficacy of 3 risk algorithms for identifying high-risk patients in our study population.
Methods
Our population consisted of 1,464 asymptomatic adults aged 23 to 87 years (39.8% women) within a multispecialty university-based group medical practice self-referred for screening vascular ultrasound evaluation at their annual preventive physical examination from July 2007 to December 2011. Exclusion criteria were previous myocardial infarction, angina, heart failure, angioplasty, stroke, or claudication. All subjects gave written informed consent, and the study was approved by the Western Institutional Review Board.
Systolic and diastolic blood pressures (BPs) were obtained by cuff sphygmomanometry in a seated position at the time of ultrasound evaluation. A fasting lipid profile was analyzed by a commercial laboratory, either LabCorp (New York, New York) or Quest (New York, New York). Current smoking was defined as smoking >5 cigarettes during the week preceding examination. Diabetes was defined as a fasting glucose ≥126 mg/dl, glycosylated hemoglobin ≥7.0%, or the use of hypoglycemic medication.
The 10- and 30-year Framingham CVD Risk Scores were calculated and subjects allocated to low-, intermediate-, and high-risk groups in accordance with the published recommendations (0% to 6%, 6% to 20%, >20% for 10-year Framingham Risk Score (FRS); 0% to 12%, 12% to 40%, and >40% for 30-year FRS). Subjects were allocated to lifetime risk categories by the following algorithm: low risk was BP <140/90 mm Hg and total cholesterol <200 mg/dl, with neither smoking nor diabetes present. Intermediate risk was defined as BP <160/100 mm Hg and total cholesterol <240 mg/dl, with neither smoking nor diabetes present. High risk was defined as having any of the following: BP 160/100 mm Hg or treated BP or total cholesterol 240 mg/dl or treated hyperlipidemia or either smoking or diabetes present (D. Lloyd-Jones, personal communication). To allocate those subjects who were receiving lipid-lowering therapy at the time of examination to the proper FRS or lifetime risk group, it was assumed for purposes of categorization that they all had a total cholesterol of 240 mg/dl.
Carotid and femoral ultrasound examinations were performed using a 7.5 MHz linear array transducer and a SonoSite MicroMaxx (Sonosite, Inc. Bothell, Washington) ultrasound machine by a single sonographer. The carotid and femoral arteries were interrogated in transverse and longitudinal planes. Carotid artery examination included evaluation of the common carotid artery within 2 cm of the origin of the carotid bulb, the carotid bulb itself, and the internal but not the external carotid artery. Both carotid arteries were examined and 2 measurements at 90° angles were obtained for each common carotid artery for intima-media thickness (IMT), a total of 4 measurements for each subject. Plaque was defined as a focal projection of ≥1.5 mm of the arterial wall into the lumen, as proposed in the Mannheim Consensus. SonoCalc (Sonosite) software was used for plaque and automated carotid IMT measurement. The reproducibility of the assessment of plaque presence has been previously described as 93%.
Initially, a Kolmogorov-Smirnov test was used to access the normality of distribution of continuous variables. Continuous variables were presented as median (interquartile range) as a result of non-normal distributions. Mann-Whitney U test (Wilcoxon signed-rank test) was performed to compare the risk distributions between men and women. Categorical variables were presented as frequency (percentage), and the chi-square test of proportion was performed to assess risk factors. All statistical analysis was performed using SAS software, version 9.4 (SAS Institute Inc., Cary, North Carolina), and significance level was set at p = 0.05 (2 sided).
Because the risk algorithm predictors had age-specific parameters, we included all 939 subjects who were between the ages of 23 and 60 in these analyses. When we analyzed plaque location by age and gender, the subjects <41 or >80 were excluded because there were insufficient numbers for analysis.
Results
Demographic characteristics of the complete study group and the Risk Algorithm Group are listed in Tables 1 and 2 . The frequency of femoral plaque as the only plaque was 18.3% in the total group and 14.8% in the risk algorithm group without a significant difference between genders in either group. The frequency of any plaque was 49.3% in the total group and 37.4% in the algorithm risk group with significantly more plaques in men than women for each group.
| Variable | Total (n= 1464, 100%) | Men (n= 881, 60.2%) | Women (n= 583, 39.8%) | P-value |
|---|---|---|---|---|
| Age (years) | 56 (49, 64) | 55 (47, 63) | 58 (52, 65) | <0.001 † |
| Age range (years) | 23 – 87 | 23 – 87 | 27 – 87 | – |
| White | 1381 (94.3%) | 837 (95.0%) | 544 (93.3%) | |
| Asian | 40 (2.7%) | 23 (2.6%) | 17 (2.9%) | |
| Black | 24 (1.6%) | 10 (1.1%) | 14 (2.4%) | |
| Hispanic | 19 (1.3%) | 11 (1.3%) | 8 (1.4%) | |
| Systolic BP (mmHg) | 120 (110, 130) | 120 (116, 134) | 120 (110, 130) | <0.001 † |
| Diastolic BP (mmHg) | 74 (70, 80) | 78 (70, 80) | 70 (70, 80) | <0.001 † |
| BP treated | 222 (15.2%) | 139 (15.8%) | 83 (14.2%) | 0.421 |
| Total Cholesterol (mg/dl) | 206.0 (181.0, 234.0) | 198.0 (174.0, 225.0) | 218.0 (192.0, 244.0) | <0.001 † |
| LDL Cholesterol (mg/dl) | 122.0 (100.0, 147.0) | 118.5 (98.0, 144.0) | 127.0 (104.0, 153.0) | <0.001 † |
| HDL Cholesterol (mg/dl) | 60.0 (48.0, 73.0) | 54.0 (45.0, 65.0) | 70.0 (59.0, 83.0) | <0.001 † |
| Tryglycerides (mg/dl) | 89.0 (66.0, 127.0) | 93.0 (69.0, 137.0) | 82.0 (62.0, 116.0) | <0.001 † |
| Lipid Treatment | 414 (28.3%) | 287 (32.6%) | 127 (21.8%) | <0.001 † |
| Diabetes mellitus | 37 (2.5%) | 24 (2.7%) | 13 (2.2%) | 0.555 |
| BMI (kg/m 2 ) | 25.0 (23.0, 28.0) | 26.0 (24.0, 28.0) | 23.0 (21.0, 27.0) | <0.001 † |
| Smoker | <0.001 † | |||
| Current | 61 (4.2%) | 38 (4.3%) | 23 (4.0%) | |
| Previous | 401 (27.4%) | 208 (23.6%) | 193 (33.2%) | |
| Never | 1001 (68.4%) | 635 (72.1%) | 366 (62.9%) | |
| CIMT (Average, mm) | 0.73 (0.66, 0.83) | 0.73 (0.66, 0.83) | 0.73 (0.66, 0.81) | 0.288 |
| CIMT (Maximum, mm) | 0.88 (0.79, 0.98) | 0.88 (0.80, 1.00) | 0.88 (0.79, 0.96) | 0.096 |
| Any Plaque | 722 (49.3%) | 466 (52.9%) | 256 (43.9%) | <0.001 † |
| Only Femoral Plaques | 268 (18.3%) | 167 (19.0%) | 101 (17.3%) | 0.429 |
| Only Carotid Plaques | 201 (13.7%) | 120 (13.6%) | 81 (13.9%) | 0.882 |
| Both Femoral and Carotid Plaques | 253 (17.3%) | 179 (20.3%) | 74 (12.7%) | <0.001 † |
| Variable | Total (n= 939, 100%) | Men (n= 603, 64.2%) | Women (n= 336, 35.8%) | P-value |
|---|---|---|---|---|
| Age (years) | 51 (45, 56) | 50 (44, 55) | 53 (48, 57) | <0.001 † |
| Age range (years) | 23 – 60 | 23 – 60 | 27 – 60 | – |
| White | 872 (92.9%) | 568 (94.2%) | 304 (90.5%) | |
| Asian | 33 (3.5%) | 21 (3.5%) | 12 (3.6%) | |
| Black | 17 (1.8%) | 5 (0.8%) | 12 (3.6%) | |
| Hispanic | 17 (1.8%) | 9 (1.5%) | 8 (2.4%) | |
| Systolic BP (mmHg) | 120 (110, 130) | 120 (114, 130) | 120 (110, 128) | <0.001 † |
| Diastolic BP (mmHg) | 74 (70, 80) | 78 (70, 80) | 70 (70, 80) | <0.001 † |
| BP treated | 103 (11.0%) | 66 (11.0%) | 37 (11.0%) | 0.975 |
| Total Cholesterol (mg/dl) | 208.0 (184.0, 235.0) | 205.0 (181.0, 229.0) | 217.0 (190.0, 242.0) | <0.001 † |
| LDL Cholesterol (mg/dl) | 125.0 (105.0, 151.0) | 124.0 (105.0, 148.0) | 126.0 (106.0, 154.0) | <0.001 † |
| HDL Cholesterol (mg/dl) | 58.0 (47.0, 70.0) | 53.0 (44.0, 63.0) | 69.0 (58.0, 80.0) | <0.001 † |
| Tryglycerides (mg/dl) | 89.0 (65.0, 130.0) | 97.0 (70.0, 142.0) | 80.0 (59.0, 111.0) | <0.001 † |
| Lipid Treatment | 195 (20.8%) | 143 (23.7%) | 52 (15.5%) | 0.003 ∗ |
| Diabetes mellitus | 23 (2.5%) | 16 (2.7%) | 7 (2.1%) | 0.588 |
| BMI (kg/m 2 ) | 26.0 (23.0, 28.0) | 26.0 (25.0, 29.0) | 23.0 (21.0, 27.0) | <0.001 † |
| Smoker | 0.004 ∗∗ | |||
| Current | 44 (4.7%) | 32 (5.3%) | 12 (3.6%) | |
| Previous | 220 (23.4%) | 121 (20.1%) | 99 (29.5%) | |
| Never | 675 (71.9%) | 450 (74.6%) | 225 (67.0%) | |
| CIMT (Average, mm) | 0.69 (0.63, 0.76) | 0.69 (0.63, 0.77) | 0.69 (0.63, 0.76) | 0.327 |
| CIMT (Maximum, mm) | 0.84 (0.77, 0.92) | 0.84 (0.77, 0.92) | 0.84 (0.76, 0.91) | 0.203 |
| Any Plaque | 351 (37.4%) | 248 (41.1%) | 104 (30.7%) | 0.002 ∗∗ |
| Only Femoral Plaques | 139 (14.8%) | 92 (15.3%) | 47 (14.0%) | 0.600 |
| Only Carotid Plaques | 121 (12.9%) | 78 (12.9%) | 43 (12.8%) | 0.952 |
| Both Femoral and Carotid Plaques | 91 (9.7%) | 78 (12.9%) | 13 (3.9%) | <0.001 † |
Figure 1 shows the distribution of subjects by age and gender. There is evidence of skewing of the population toward older subjects, which was taken into account in the statistical analysis.
Figure 2 shows the percentage of subjects with any plaque for each age group. We did not find any plaques in the few subjects <30 years. Thereafter, men showed a linear progression of plaque prevalence with advancing age. In women, there was a lower prevalence of plaque compared with men until menopause after which prevalence increased parallel to the increase in prevalence in men.
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