Peripheral arterial disease (PAD), similar to coronary artery disease (CAD), is a significant predictor of cardiovascular morbidity and mortality. Guidelines recommend a low-density lipoprotein (LDL) goal of <100 mg/dl for both groups. We assessed whether lipid control and statin use were as aggressively applied to PAD as to patients with CAD. This retrospective study of patients with the diagnosis of CAD, PAD, or both CAD and PAD compared lipid levels and statin use. For comparison of statins, we used a statin potency unit (1 potency unit = 10 mg of simvastatin). Among 11,134 subjects (CAD 9,563, PAD 596, and both CAD and PAD 975), mean LDL in the PAD group was higher than the CAD (92 vs 83 mg/dl, respectively, p <0.001) and the combined CAD and PAD groups (92 vs 80 mg/dl, respectively, p <0.001). Fewer patients with PAD achieved a target LDL of <100 mg/dl compared with CAD (62% vs 78%, respectively, p <0.001) and the combined group (62% vs 79%, respectively, p <0.001). Similar differences were noted for a target LDL of <70 mg/dl. Compared with the CAD group, a lesser number of patients with PAD received statin therapy (76% vs 100%, respectively, p <0.001) with lower mean potency unit (5.3 vs 8.1, respectively, p <0.001). In conclusion, our study demonstrated lower use and less aggressive application of statins in patients with PAD compared with patients with CAD, ensuing lower mean LDL in the CAD and combined PAD and CAD groups. Our study suggests that physicians are more aggressive with lipid control in patients with CAD compared with patients with PAD alone.
There is paucity of published reports that compare the treatment goals achieved among patients with peripheral arterial disease (PAD) compared with coronary artery disease (CAD). Furthermore, little is known if the target lipid control and use of lipid-lowering therapy are similar in patients with diagnosis of PAD alone versus patient with associated diagnosis of CAD with PAD. We hypothesize that compared with patients with CAD, a greater proportion of PAD-only patients continue to receive less aggressive lipid-lowering treatment in current clinical practice. Therefore our study aims to (1) compare lipid control between PAD versus CAD groups and PAD versus combined CAD and PAD groups and (2) compare statin use between PAD versus CAD groups and PAD versus combined CAD and PAD groups.
Methods
This is a retrospective observational study conducted in a large academic healthcare system. The Institutional Research Board of the University of Kansas Medical Center, where this study was conducted, approved the study. Electronic medical records from January 2009 to March 2012 were reviewed, and ambulatory patients who were 18 years of age or older and had International Classification of Disease codes for CAD, PAD, or both listed under the problem list were identified as the study population. Subjects were included in the study only if their lipid profile and medication lists were available in the electronic medical record system. Based on the diagnostic codes, patients were categorized into 3groups—CAD only, PAD only, or combined CAD and PAD. Demographic variables, last lipid profile available, co-morbidities, and statin therapy were compared among the 3 groups. The percentage of patients with low-density lipoprotein (LDL) levels <100 and <70 mg/dl was compared among the PAD, CAD, and combined CAD and PAD groups. Mean levels of total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, and triglycerides were also compared among the 3 groups. We identified the statins used and the mean doses utilized for each agent. To compare the various doses of statins used, we converted all statin doses to an equivalent potency unit, based on the comparative efficacy of the currently used statins on lipids levels, where 1 potency unit = 10 mg of simvastatin. For ezetimibe/statin combinations, the potency unit conversion was based on the strength of the statin considering the uniform dose of 10 mg of ezetimibe. For niacin/statin combinations, the potency unit conversion was also based on the strength of statin.
Statistical analysis was performed using the Statistical Program for Social Sciences (version 19.0; SPSS, Inc., Chicago, Illinois). Data were plotted (e.g., histograms and spaghetti plots linking variables) to examine for potential outliers and for the necessity of transformation before analysis. Summary statistics (e.g., mean, SD, minimum, maximum, and proportions) were calculated for all variables. Continuous variables are expressed as mean ± SD. For categorical variables, we used proportions for overall and subgroups. Chi-square test was used to find association between categorical variables. Fisher’s exact test was used where appropriate. One-way analysis of variance was used to compare all 3 groups, and independent sample t tests were used to compare PAD versus CAD groups and PAD versus combined CAD and PAD groups. A p value of <0.05 was accepted as indicating statistical significance.
Results
A total of 27,473 subjects comprised the population from which the study patients were obtained. Based on the diagnostic codes, 11,134 study patients were identified and categorized into 3 groups—9,563 (85.9%) had the diagnosis of CAD alone, 596 (5.4%) had the diagnosis of PAD alone, and 975 (8.7%) carried diagnoses of both CAD and PAD. A total of 1,571 patients had diagnosis of PAD (PAD only and combined CAD and PAD groups) with prevalence of 5.7%. The baseline characteristics of 3 different diagnostic groups are listed in Table 1 . Patients in the PAD group were significantly older, had higher percentage of women and black patients, and had lower body mass index compared with CAD group. PAD group had significantly higher number of smokers compared with CAD group. Diabetes, hypertension, and chronic/end-stage renal disease were more prevalent in the group with both CAD and PAD compared with the PAD-only group. Cerebrovascular diseases were significantly higher in the PAD group.
| Variables | CAD (n = 9,563) | PAD (n = 596) | p Value ∗ | CAD and PAD (n = 975) | p Value † |
|---|---|---|---|---|---|
| Age (yrs) | 69 ± 11 | 70 ± 12 | 0.007 | 72 ± 10 | 0.003 |
| Men | 6,281 (66) | 299 (51) | <0.001 | 661 (68) | <0.001 |
| White | 7,675 (80) | 435 (73) | <0.001 | 812 (83) | <0.001 |
| Black | 882 (9) | 103 (17) | 75 (8) | ||
| Others | 1,006 (11) | 58 (10) | 88 (9) | ||
| BMI (kg/m 2 ) | 30 ± 7 | 29 ± 8 | <0.001 | 29 ± 6 | 0.46 |
| Systolic blood pressure (mm Hg) | 128 ± 18 | 131 ± 20 | <0.001 | 130 ± 20 | 0.45 |
| Diastolic blood pressure (mm Hg) | 74 ± 11 | 73 ± 11 | 0.006 | 71 ± 12 | <0.001 |
| Smoker | 1,366 (14) | 137 (23) | <0.001 | 258 (26) | 0.12 |
| Diabetes mellitus | 3,098 (32) | 164 (28) | 0.013 | 401 (41) | <0.001 |
| Hypertension | 7,431 (78) | 458 (77) | 0.63 | 814 (84) | 0.001 |
| Chronic kidney disease | 1,158 (12) | 73 (12) | 0.92 | 211 (22) | <0.001 |
| End-stage renal disease | 147 (1.5) | 12 (2) | 0.36 | 43 (4) | 0.012 |
| Cerebrovascular disease | 216 (2) | 30 (5) | <0.001 | 26 (3) | 0.014 |
One-way analysis of variance showed that mean LDL level in the PAD group was significantly higher than the mean LDL level in the CAD and the combined CAD and PAD groups (92 vs 83 vs 80 mg/dl, respectively, p <0.001). The PAD group also had significantly higher mean total cholesterol compared with the other 2 groups (163 vs 151 vs 148 mg/dl, respectively, p <0.001) However, the mean high-density lipoprotein levels in PAD group were significantly higher than the other 2 groups (46 vs 45 vs 43 mg/dl, respectively, p <0.001), likely due to higher percentage of women in PAD group. Mean triglyceride levels were significantly different among 3 groups (134 vs 129 vs 136 mg/dl, respectively, p = 0.034). Comparative analyses were performed between PAD and CAD groups and PAD versus combined PAD and CAD groups as listed in Table 2 and Figure 1 . Significantly fewer number of patients with PAD achieved a target LDL of <100 mg/dl compared with CAD and the combined CAD and PAD groups. Similarly, significantly fewer patients in the PAD group achieved target LDL of <70 mg/dl ( Table 2 ; Figure 1 ).
| Lipids (mg/dl) | CAD (n = 9,563) | PAD (n = 596) | p Value ∗ | CAD and PAD (n = 975) | p Value † |
|---|---|---|---|---|---|
| Total cholesterol | 151 ± 40 | 163 ± 43 | <0.001 | 148 ± 42 | <0.001 |
| LDL cholesterol | 83 ± 33 | 92 ± 35 | <0.001 | 80 ± 31 | <0.00 |
| LDL cholesterol <100 | 7,420 (78) | 371 (62) | <0.001 | 768 (79) | <0.001 |
| LDL cholesterol <70 | 3,743 (39) | 178 (30) | <0.001 | 404 (41) | <0.001 |
| HDL cholesterol | 45 ± 15 | 46 ± 16 | 0.008 | 43 ± 15 | <0.001 |
| Triglycerides | 129 ± 91 | 134 ± 86 | 0.144 | 136 ± 113 | 0.78 |
In the CAD group, 100% of patients were on statin therapy compared with only 76% in the PAD group and 90% in the combined CAD and PAD groups (p <0.001). PAD group had significantly greater use of less potent statins (simvastatin, pravastatin, and lovastatin) and lesser use of high potent statins (rosuvastatin and atorvastatin). This was not compensated for by a higher mean dose of the lower potency statins in the PAD group ( Table 3 ). Patients with PAD were receiving significantly lower mean potency unit of statins compared with CAD and combined CAD and PAD groups (5.3 vs 8.1 vs 8.7, respectively, p <0.001). Comparative analysis confirmed these observations as listed in Table 4 and Figure 2 .
| Variables (Statin Type) | CAD (n = 9,563) | PAD (n = 596) | p Value ∗ | CAD and PAD (n = 975) | p Value † |
|---|---|---|---|---|---|
| Simvastatin | 3,604 (38) | 203 (34) | 326 (33) | ||
| Atorvastatin | 2,080 (22) | 90 (15) | 194 (20) | ||
| Rosuvastatin | 2,412 (25) | 77 (13) | 219 (23) | ||
| Pravastatin | 807 (8) | 44 (7) | 79 (8) | ||
| Lovastatin | 300 (3) | 25 (4) | 20 (2) | ||
| Fluvastatin | 22 (0.2) | 2 (0.3) | 3 (0.3) | ||
| Ezetimibe/simvastatin | 292 (3) | 10 (2) | 30 (3) | ||
| Niacin/simvastatin | 43 (0.4) | 2 (0.3) | 1 (0.1) | ||
| Niacin/lovastatin | 3 (0.03) | – | 1 (0.1) | ||
| Total | 9,563 (100) | 453 (76) | <0.001 | 873 (90) | <0.001 |
| Variables Mean Dose of Individual Statin (mg) | CAD (n = 9,563) | PAD (n = 596) | p Value ∗ | CAD and PAD (n = 975) | p Value † |
|---|---|---|---|---|---|
| Simvastatin | 36 ± 21 | 30 ± 17 | <0.001 | 37 ± 22 | <0.001 |
| Atorvastatin | 39 ± 24 | 30 ± 22 | <0.001 | 44 ± 25 | <0.001 |
| Rosuvastatin | 21 ± 12 | 15 ± 11 | <0.001 | 22 ± 13 | <0.001 |
| Pravastatin | 42 ± 22 | 38 ± 22 | 0.22 | 45 ± 25 | 0.12 |
| Lovastatin | 31 ± 12 | 28 ± 12 | 0.22 | 31 ± 12 | 0.40 |
| Fluvastatin | 59 ± 26 | 80 ± 0 | 0.29 | 67 ± 23 | 0.49 |
| Ezetimibe/simvastatin | 42 ± 21 | 40 ± 16 | 0.73 | 47 ± 23 | 0.36 |
| Niacin/simvastatin | 29 ± 10 | 30 ± 14 | 0.85 | 20 ± 0 | 0.67 |
| Niacin/lovastatin | 20 ± 0 | — | — | 20 ± 0 | — |
| Mean potency unit | 8.1 (8.2) | 5.3 (5.8) | <0.001 | 8.7 (8.8) | <0.001 |
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