Sex-Based Differences in Clinical Characteristics and Outcomes among Patients with Peripheral Artery Disease: A Retrospective Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Study Variables
- Demographic data: age and sex.
- Clinical presentation at the ED admission including dyspnoea, fever, pain (defined as any degree and type of pain in the lower extremities), chest pain and neurological symptoms.
- Peripheral artery disease grade at ED presentation, according to Rutherford classification.
- Coexistent acute infections diagnosed at ED admission, categorized as bloodstream infections, lower limb and other infections not included in the previous categories.
- Laboratory findings including blood creatinine, eGFR (estimated Glomerular Filtration Rate calculated according to the CKD-EPI equation), urea, glucose, glycated haemoglobin (HbA1c), C-reactive protein (CRP), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, haemoglobin (Hb) and platelets (PLTs).
- Clinical history and comorbidities: CAD, congestive heart failure (CHF), cerebral vascular disease—previous stroke (CVD), type 2 diabetes mellitus (T2DM), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD) and dementia. Overall comorbidity severity was assessed by Charlson Comorbidity Index (CCI) [20].
2.3. Study Endpoints
2.4. Statistical Analysis
3. Results
3.1. Study Cohort and Baseline Characteristics
3.2. MALE Composite Outcome
3.3. MACE Composite Outcome
4. Discussion
5. Limitations
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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All Cases N 1640 | Male N 1103 | Female N 537 | p Value | |
---|---|---|---|---|
Age | 72 [64–81] | 71 [63–80] | 75 [69–84] | <0.001 |
Clinical presentation | ||||
Fever | 425 (25.9%) | 301 (27.3%) | 124 (23.1%) | 0.038 |
Pain | 704 (42.9%) | 463 (42%) | 241 (44.9%) | 0.144 |
Chest pain | 107 (6.5%) | 82 (7.4%) | 25 (23.4%) | 0.019 |
Dyspnoea | 184 (11.2%) | 136 (12.3%) | 48 (8.9%) | 0.024 |
Neurological symptoms | 67 (4.1%) | 48 (4.4%) | 19 (3.5%) | 0.261 |
PAD grade (according to Rutherford classification) | ||||
Rutherford Grade I-3 | 101 (6.2%) | 73 (6.6%) | 28 (5.2%) | |
Rutherford Grade II-4 | 171 (10.4%) | 106 (9.6%) | 65 (12.1%) | |
Rutherford Grade III-5 | 161 (9.8%) | 107 (9.7%) | 54 (10.1%) | 0.158 |
Rutherford Grade III-6 | 888 (54.1%) | 595 (53.9%) | 293 (54.6%) | |
Previous amputation | 265 (16.2%) | 197 (17.9%) | 68 (12.7%) | 0.004 |
Presence of infections | ||||
Bloodstream infection | 130 (7.9%) | 92 (8.3%) | 38 (7.1%) | 0.215 |
Lover limb infections | 888 (54.1%) | 595 (53.9%) | 293 (54.6%) | 0.813 |
Other infections | 1043 (63.6%) | 710 (64.4%) | 333 (62.0%) | 0.352 |
Laboratory findings | ||||
Creatinine (mg/dL) | 1.95 [0.83–2.07] | 2.1 [0.86–2.32] | 1.64 [0.74–1.71] | <0.001 |
eGFR (ml/min) | 54.3 [28.5–84.2] | 50.8 [29.4–76.7] | 55.6 [28.0–88.7] | 0.024 |
Urea (mg/dL) | 33.2 [18–40] | 33.6 [18–42] | 32.4 [18–39] | 0.186 |
Glucose (mg/dL) | 173 [107–207] | 172 [108–207] | 174 [104–208] | 0.443 |
HbA1c (mmol) | 61 [45–72] | 62 [44–74] | 61 [45–71] | 0.848 |
C-reactive protein (mg/L) | 95 [19–148] | 99 [25–152] | 88 [14–134] | 0.160 |
Total cholesterol (mg/dL) | 129 [102–150] | 124 [97–147] | 138 [110–161] | <0.001 |
HDL (mg/dL) | 32 [24–38] | 30 [23–36] | 36 [27–43] | <0.001 |
LDL (mg/dL) | 75 [53–90] | 72 [48–85] | 74 [53–90] | 0.077 |
Triglycerides (mg/dL) | 128 [86–154] | 122 [83–145] | 139 [93–173] | <0.001 |
Hb (gr/dL) | 11.3 [9.8–12.9] | 11.53 [9.8–13.2] | 11 [9.7–12.4] | <0.001 |
PLTs (×109/L) | 302 [204–369] | 292 [196–357] | 323 [218–400] | 0.001 |
Comorbidities | ||||
CCI | 4 [3–6] | 4 [3–6] | 4 [2–5] | 0.020 |
CAD | 699 (42.6%) | 497 (45.1%) | 202 (37.6%) | 0.002 |
Congestive heart failure | 447 (27.3%) | 314 (28.5%) | 133 (24.8%) | 0.064 |
Cerebrovascular disease | 149 (9.1%) | 98 (8.9%) | 51 (9.5%) | 0.374 |
Dementia | 109 (6.6%) | 67 (6.1%) | 42 (7.8%) | 0.111 |
COPD | 196 (12%) | 138 (12.5%) | 58 (10.8%) | 0.179 |
Diabetes | 1280 (78%) | 880 (79.8%) | 400 (74.5%) | 0.009 |
Chronic kidney disease | 565 (34.5%) | 391 (35.4%) | 174 (32.4%) | 0.122 |
Outcomes | ||||
Death (all causes) | 127 (7.7%) | 79 (7.2%) | 48 (8.9%) | 0.123 |
Length of stay (LOS) | 16 [7–20] | 16 [7–21] | 15 [7–19] | 0.148 |
Acute limb ischaemia (ALI) | 288 (17.6%) | 187 (17.0%) | 101 (18.8%) | 0.357 |
Overall revascularizations | 447 (27.3%) | 286 (25.9%) | 161 (30.1%) | 0.048 |
Angioplasty | 442 (27.0%) | 282 (25.6%) | 160 (29.8%) | 0.040 |
Stenting | 23 (1.4%) | 14 (1.3%) | 9 (1.7%) | 0.325 |
Urgent revascularizations | 267 (16.3%) | 168 (15.2%) | 99 (18.4%) | 0.058 |
Amputations | 302 (18.4%) | 220 (19.9%) | 82 (15.3%) | 0.012 |
MALE cumulative events | 660 (40.2%) | 454 (41.2%) | 206 (38.4%) | 0.151 |
Myocardial infarction | 60 (3.7%) | 40 (3.6%) | 20 (3.7%) | 0.510 |
Stroke | 28 (1.7%) | 18 (1.6%) | 10 (1.9%) | 0.438 |
MACE cumulative events | 123 (7.5%) | 78 (7.1%) | 45 (8.4%) | 0.199 |
Controls N 980 | MALE Cumulative Events N 660 | Unadjusted p Value | Adjusted Odds for MALE [95% Confidence Interval] | Multivariate p Value | |
---|---|---|---|---|---|
Age | 72 [65–81] | 71 [64–80] | 0.030 | 0.99 [0.98–1.01] | 0.484 |
Sex (male) | 649 (66.2%) | 454 (68.8%) | 0.151 | 1.27 [0.99–1.64] | 0.059 |
Clinical presentation | |||||
Fever | 265 (62.4%) | 160 (37.6%) | 0.110 | ||
Pain (any) | 333 (47.3%) | 371 (52.7%) | <0.001 | 3.65 [2.85–4.70] | <0.001 |
Chest pain | 91 (9.3%) | 16 (2.4%) | <0.001 | 0.25 [0.13–0.46] | 0.003 |
Dyspnoea | 166 (16.9%) | 18 (2.7%) | <0.001 | 0.28 [0.16–0.49] | 0.006 |
Neurological symptoms | 45 (4.6%) | 22 (3.3%) | 0.047 | ||
Laboratory findings | |||||
Creatinine (mg/dL) | 1.86 [0.84–2.02] | 2.08 [0.82–2.2] | 0.770 | ||
eGFR | 54.4 [29.3–82.3] | 53.8 [26.5–88.4] | 0.977 | ||
Urea (mg/dL) | 33.6 [18–41] | 32 [18–39] | 0.610 | ||
Glucose (mg/dL) | 174 [107–202] | 171 [107–215] | 0.780 | ||
HbA1C (mmol) | 57 [44–69] | 66 [51–78] | <0.001 | ||
C-reactive protein (mg/L) | 87 [16–128] | 107 [27–161] | <0.001 | ||
Total cholesterol (mg/dL) | 133 [104–157] | 123 [99–145] | <0.001 | ||
HDL (mg/dL) | 32 [25–39] | 33 [23–37] | 0.140 | ||
LDL (mg/dL) | 73 [50–88] | 73 [48–85] | 0.399 | ||
Triglycerides (mg/dL) | 131 [87–158] | 123 [86–151] | 0.315 | ||
Hb (gr/dL) | 11.4 [9.8–13] | 11.2 [9.7–12.9] | 0.054 | ||
PLT (×109/L) | 284 [194–344] | 328 [230–404] | <0.001 | ||
PAD grade (according to Rutherford classification) | |||||
Rutherford Grade I-3 | 67 (6.8%) | 34 (5.2%) | |||
Rutherford Grade II-4 | 125 (12.8%) | 46 (7.0%) | |||
Rutherford Grade III-5 | 123 (12.6%) | 38 (5.8%) | <0.001 | ||
Rutherford Grade III-6 | 359 (36.6%) | 529 (59.6%) | |||
Previous amputation | 141 (14.4%) | 124 (18.8%) | 0.011 | 0.91 [0.67–1.25] | 0.574 |
Presence of infections | |||||
Bloodstream infection | 62 (6.3%) | 68 (10.3%) | 0.004 | 1.75 [1.11–2.76] | 0.016 |
Lower limb infections | 359 (36.6%) | 529 (80.2%) | <0.001 | 18.9 [9.72–36.87] | 0.001 |
Other infections | 503 (51.3%) | 540 (81.8%) | <0.001 | 0.27 [0.13–0.55] | <0.001 |
Comorbidities | |||||
CCI | 4 [2–5] | 4 [3–6] | 0.003 | 1.03 [0.98–1.08] | 0.267 |
CAD | 412 (42%) | 287 (43.5%) | 0.576 | ||
Congestive heart failure | 282 (28.8%) | 165 (25%) | 0.101 | ||
Cerebrovascular disease | 99 (10.1%) | 50 (7.6%) | 0.015 | ||
Dementia | 70 (7.1%) | 39 (5.9%) | 0.360 | ||
COPD | 124 (12.7%) | 72 (10.9%) | 0.161 | ||
Diabetes | 749 (76.4%) | 531 (80.5%) | 0.008 | ||
Chronic kidney disease | 324 (57.3%) | 241 (42.7%) | 0.015 | ||
Outcomes | |||||
Length of stay (LOS) | 13.1 [7.1–16.5] | 19.3 [8.5–25.5] | <0.001 | ||
Death (all causes) | 76 (7.8%) | 51 (7.7%) | 0.075 |
Controls N 1517 | MACE Cumulative Events N 123 | Unadjusted p Value | Adjusted Odds for MACE [95% Confidence Interval] | Multivariate p Value | |
---|---|---|---|---|---|
Age | 72 [64–81] | 74 [68–83] | 0.093 | ||
Sex (male) | 1025 (63.4%) | 78 (67.8%) | 0.020 | 0.75 [0.50–1.11] | 0.153 |
Clinical presentation | |||||
Fever | 402 (26.5%) | 23 (18.7%) | 0.034 | ||
Pain | 658 (43.4%) | 46 (37.4%) | 0.030 | ||
Chest pain | 83 (5.5%) | 24 (19.5%) | <0.001 | 3.46 [1.82–6.56] | <0.001 |
Dyspnoea | 162 (10.7%) | 22 (17.9%) | 0.015 | 1.19 [0.69–2.04] | 0.520 |
Neurological symptoms | 55 (3.6%) | 12 (9.8%) | 0.002 | 2.96 [1.49–5.89] | <0.001 |
Laboratory findings | |||||
Creatinine (mg/dL) | 1.94 [0.82–2.02] | 2.09 [0.94–2.63] | 0.018 | ||
eGFR (ml/min) | 54.7 [29.2–85.2] | 45.2 [22.6–70.6] | 0.012 | ||
Urea (mg/dL) | 33 [18–40] | 36 [19.7–49] | 0.035 | ||
Glucose (mg/dL) | 174 [107–210] | 160 [107–184] | 0.160 | ||
HbA1c (mmol) | 61 [45–73] | 54 [43–62] | <0.001 | ||
C-reactive protein (mg/L) | 96 [19–148] | 88 [16–149] | 0.660 | ||
Total cholesterol (mg/dL) | 128 [101–150] | 135 [104–162] | 0.230 | ||
HDL (mg/dL) | 32 [24–38] | 31 [21–40] | 0.830 | ||
LDL (mg/dL) | 72 [50–86] | 84 [49–114] | 0.070 | ||
Triglycerides (mg/dL) | 127 [86–153] | 139 [98–177] | 0.048 | ||
Hb (gr/dL) | 11.3 [9.5–13] | 11.2 [9.6–13.1] | 0.430 | ||
PLT (×109/L) | 306 [210–373] | 249 [174–294] | <0.001 | ||
PAD grade (according to Rutherford classification) | |||||
Rutherford Grade I-3 | 88 (5.8%) | 13 (10.6%) | Reference | ||
Rutherford Grade II-4 | 147 (9.7%) | 24 (19.5%) | 0.71 [0.32–1.71] | 0.398 | |
Rutherford Grade III-5 | 152 (10%) | 9 (7.3%) | <0.001 | 0.44 [0.19–0.97] | 0.041 |
Rutherford Grade III-6 | 847 (55.8%) | 41 (33.3%) | 0.45 [0.21–0.90] | 0.026 | |
Previous amputation | 254 (16.7%) | 11 (8.9%) | 0.007 | 0.96 [0.37–2.50] | 0.012 |
Presence of infections | |||||
Bloodstream infection | 119 (7.8%) | 11 (8.9%) | 0.12 | ||
Lower limb infections | 847 (55.8%) | 41 (33.3%) | <0.001 | 0.61 [0.29–1.27] | 0.332 |
Other infections | 988 (65.1%) | 55 (44.7%) | <0.001 | 0.73 [0.38–1.38] | 0.336 |
Comorbidities | |||||
CCI | 4 [2–5] | 4 [3–6] | 0.003 | 1.08 [1.01–1.17] | 0.047 |
CAD | 626 (41.3%) | 73 (59.3%) | <0.001 | ||
Congestive heart failure | 405 (26.7%) | 42 (34.1%) | 0.017 | ||
Cerebrovascular disease | 130 (8.6%) | 19 (15.4%) | 0.021 | ||
Dementia | 101 (6.7%) | 8 (6.5%) | 0.57 | ||
COPD | 179 (11.8%) | 17 (13.8%) | 0.29 | ||
Diabetes | 1193 (78.6%) | 87 (70.7%) | 0.05 | ||
Chronic kidney disease | 521 (34.3%) | 44 (35.8%) | 0.41 | ||
Outcomes | |||||
Length of stay (LOS) | 15.73 [7.4–20.2] | 18.8 [7.5–26] | 0.011 | ||
Death (all causes) | 81 (5.3%) | 46 (37.4%) | <0.001 |
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De Matteis, G.; Biscetti, F.; Della Polla, D.A.; Serra, A.; Burzo, M.L.; Fuorlo, M.; Nicolazzi, M.A.; Novelli, A.; Santoliquido, A.; Gambassi, G.; et al. Sex-Based Differences in Clinical Characteristics and Outcomes among Patients with Peripheral Artery Disease: A Retrospective Analysis. J. Clin. Med. 2023, 12, 5094. https://doi.org/10.3390/jcm12155094
De Matteis G, Biscetti F, Della Polla DA, Serra A, Burzo ML, Fuorlo M, Nicolazzi MA, Novelli A, Santoliquido A, Gambassi G, et al. Sex-Based Differences in Clinical Characteristics and Outcomes among Patients with Peripheral Artery Disease: A Retrospective Analysis. Journal of Clinical Medicine. 2023; 12(15):5094. https://doi.org/10.3390/jcm12155094
Chicago/Turabian StyleDe Matteis, Giuseppe, Federico Biscetti, Davide Antonio Della Polla, Amato Serra, Maria Livia Burzo, Mariella Fuorlo, Maria Anna Nicolazzi, Angela Novelli, Angelo Santoliquido, Giovanni Gambassi, and et al. 2023. "Sex-Based Differences in Clinical Characteristics and Outcomes among Patients with Peripheral Artery Disease: A Retrospective Analysis" Journal of Clinical Medicine 12, no. 15: 5094. https://doi.org/10.3390/jcm12155094
APA StyleDe Matteis, G., Biscetti, F., Della Polla, D. A., Serra, A., Burzo, M. L., Fuorlo, M., Nicolazzi, M. A., Novelli, A., Santoliquido, A., Gambassi, G., Gasbarrini, A., Flex, A., Franceschi, F., & Covino, M. (2023). Sex-Based Differences in Clinical Characteristics and Outcomes among Patients with Peripheral Artery Disease: A Retrospective Analysis. Journal of Clinical Medicine, 12(15), 5094. https://doi.org/10.3390/jcm12155094