Why carry out this study?
|
High Lp(a) have been identified as an independent risk factor for coronary artery disease (CAD). |
Lp(a) binds to platelets and ADP-P2Y12 -induced platelet reactivity is one of the main pathways involved in the occurrence of ischemic events in individuals with CAD. |
To the best of our knowledge, there are no studies addressing the association between the concentrations of Lp(a) and platelet reactivity in individuals on primary or secondary prevention of cardiovascular disease. |
What was learned from the study?
|
Lp(a) ≥ 50 mg/dL was not associated with higher ADP-induced platelet reactivity measured by VerifyNow™ P2Y12 point-of-care assay in individuals regardless of the presence or absence of CAD. |
This study suggests that platelet reactivity probably is not involved in the pathophysiological mechanisms underlying the atherothrombotic potential of Lp(a). |
Digital Features
Introduction
Methods
Study Population
Study Design
Lipoprotein (a)
Measurements of Platelet Reactivity
Statistical Analysis
Results
Distribution of Lp(a) Concentrations
Total | Lp(a) < 50 mg/dL | Lp(a) ≥ 50 mg/dL | P value | |
---|---|---|---|---|
(n = 396) | (n = 294) | (n = 102) | ||
Clinical characteristics | ||||
Age, years [median (IQR)] | 66.0 (61.0–72.0) | 66.0 (61.0–71.2) | 66.5 (60.7–73.0) | 0.687 |
Male sex [n (%)] | 266 (67.2) | 204 (69.4) | 62 (60.8) | 0.111 |
Non-Caucasian or non-Asian [n (%)] | 139 (35.1) | 85 (28.9) | 54 (52.9) | <0.001 |
Height (m) [median (IQR)] | 1.65 (1.59–1.71) | 1.65 (1.59–1.71) | 1.63 (1.58–1.72) | 0.241 |
Weight (kg) [median (IQR)] | 75.0 (66.5–83.9) | 76.0 (68.0–84.1) | 72.0 (62.0–80.0) | 0.003 |
BMI (kg/m2) [median (IQR)] | 27.4 (24.8–30.4) | 27.8 (25.2–30.8) | 26.5 (23.9–29.0) | 0.006 |
History of hypertension [n (%)] | 323 (81.6) | 234 (79.6) | 89 (87.3) | 0.085 |
History of diabetes [n (%)] | 161 (40.7) | 128 (43.5) | 33 (32.4) | 0.048 |
History of dyslipidemia [n (%)] | 290 (73.2) | 212 (72.1) | 78 (76.5) | 0.391 |
Previous MI [n (%)] | 269 (67.9) | 198 (67.3) | 71 (69.6) | 0.673 |
Previous PCI [n (%)] | 207 (52.3) | 155 (52.7) | 52 (51.0) | 0.762 |
Previous CABG [n (%)] | 98 (24.7) | 63 (21.4) | 35 (34.3) | 0.009 |
Previous stoke [n (%)] | 64 (16.2) | 38 (12.9) | 26 (25.5) | 0.003 |
Current smoker [n (%)] | 37 (9.3) | 33 (11.2) | 4 (3.9) | 0.029 |
Laboratory findings | ||||
Hemoglobin (g/dL) [mean (SD)] | 14.2 ± 1.5 | 14.2 ± 1.4 | 14.1 ± 1.6 | 0.397 |
Platelets count (103/μL) [median (IQR)] | 219.0 (185.0–261.0) | 215.5 (183.0–262.0) | 224.0 (195.7–254.5) | 0.255 |
WBC (103/μL) [median (IQR)] | 7.2 (6.0–8.5) | 7.2 (6.0–8.5) | 7.1 (5.6–8.2) | 0.115 |
hs-CRP (mg/L) [median (IQR)] | 1.6 (0.6–3.9) | 1.6 (0.6–3.8) | 1.7 (0.7–5.6) | 0.459 |
Fasting glucose (mg/dL) [median (IQR)] | 105.0 (96.0–121.0) | 106.0 (96.7–124.0) | 102.5 (95.0–117.7) | 0.045 |
HbA1c (%) [median (IQR)] | 6.0 (5.6–6.7) | 6.0 (5.7–6.7) | 5.9 (5.6–6.4) | 0.360 |
Creatinine (mg/dL) [median (IQR)] | 1.05 (0.89–1.29) | 1.03 (0.89–1.28) | 1.12 (0.88–1.31) | 0.204 |
MDRD (ml/min/1.73 m2) [median (IQR)] | 71.2 (54.9–85.9) | 71.7 (56.3–87.2) | 66.6 (49.9–83.2) | 0.054 |
TC (mg/dL) [median (IQR)] | 157.0 (134.2–188.7) | 156.0 (132.0–188.2) | 161.0 (140.7–189.2) | 0.284 |
HDL-C (mg/dL) [median (IQR)] | 43 (36–51) | 43 (36–50) | 45 (38–54) | 0.050 |
LDL-C (mg/dL) [median (IQR)] | 88.0 (69.0–116.0) | 87.0 (66.0–116.0) | 90.0 (77.7–118.5) | 0.053 |
TG (mg/dL) [median (IQR)] | 115.0 (81.0–161.0) | 119.5 (85.0–170.0) | 105.5 (75.0–138.2) | 0.013 |
Lp(a) (mg/dL) [median (IQR)] | 22.0 (7.9–52.2) | 13.2 (5.8–27.9) | 82.5 (67.6–114.5) | <0.001 |
Medications [n (%)] | ||||
Statin | 345 (87.1) | 249 (84.7) | 96 (94.1) | 0.014 |
Aspirin | 326 (82.3) | 234 (79.6) | 92 (90.2) | 0.016 |
ACEI/ARB | 299 (75.5) | 219 (74.5) | 80 (78.4) | 0.425 |
β-blocker | 333 (84.1) | 250 (85.0) | 83 (81.4) | 0.384 |
Anti-hyperglycemic drugs | ||||
Oral | 151 (38.1) | 120 (40.8) | 31 (30.4) | 0.062 |
Insulin | 47 (11.9) | 40 (13.6) | 7 (11.9) | 0.070 |
Study Groups
With CAD | Without CAD | P value | |
---|---|---|---|
(n = 326) | (n = 70) | ||
Clinical characteristics | |||
Age, years [median (IQR)] | 68.0 (62.0–73.0) | 60.5 (54.0–65.0) | < 0.001 |
Male sex [n (%)] | 233 (71.5) | 33 (47.1) | < 0.001 |
Non-Caucasian or non-Asian [n (%)] | 130 (39.9) | 9 (12.9) | < 0.001 |
Height (m) [median (IQR)] | 1.65 (1.59–1.71) | 1.65 (1.58–1.73) | 0.910 |
Weight (kg) [median (IQR)] | 74.7 (66.5–83.1) | 75.0 (68.5–86.2) | 0.537 |
BMI (kg/m2) [median (IQR)] | 27.4 (24.8–30.3) | 27.8 (25.3–30.6) | 0.381 |
History of hypertension [n (%)] | 279 (85.6) | 44 (62.9) | < 0.001 |
History of diabetes [n (%)] | 150 (46.0) | 11 (15.7) | < 0.001 |
History of dyslipidemia [n (%)] | 248 (76.1) | 42 (60.0) | 0.006 |
Prior MI [n (%)] | 269 (82.5) | 0 (0.0) | N/A |
Prior PCI [n (%)] | 207 (63.5) | 0 (0.0) | N/A |
Prior CABG [n (%)] | 98 (30.1) | 0 (0.0) | N/A |
Prior stoke [n (%)] | 64 (19.6) | 0 (0.0) | N/A |
Current smoker [n (%)] | 33 (10.1) | 4 (5.7) | 0.250 |
Laboratory findings | |||
Hemoglobin (g/dL) [mean (SD)] | 14.3 ± 1.5 | 13.6 ± 1.0 | < 0.001 |
Platelets count (103/μL) [median (IQR)] | 219.0 (185.0–266.5) | 219.5 (184.5–252.0) | 0.455 |
WBC (103/μL) [median (IQR)] | 7.4 (6.1–8.5) | 6.2 (5.2–7.5) | < 0.001 |
hs-CRP (mg/L) [median (IQR)] | 1.6 (0.6–4.3) | 1.7 (0.7–3.6) | 0.854 |
Fasting glucose (mg/dL) [median (IQR)] | 107.0 (98.0–125.7) | 98.0 (90.0–105.0) | < 0.001 |
HbA1c (%) [median (IQR)] | 6.1 (5.7–6.9) | 5.6 (5.4–6.0) | < 0.001 |
Creatinine (mg/dL) [median (IQR)] | 1.1 (0.9–1.3) | 0.9 (0.7–1.0) | < 0.001 |
MDRD (ml/min/1.73 m2) [mean (SD)] | 68.1 ± 22.0 | 82.6 ± 19.0 | < 0.001 |
TC (mg/dL) [median (IQR)] | 152.0 (132.0–181.0) | 185.0 (155.7–211.7) | < 0.001 |
HDL-C (mg/dL) [median (IQR)] | 42 (36–50) | 46 (40–56) | 0.001 |
LDL-C (mg/dL) [median (IQR)] | 85.0 (66.0–107.2) | 113.0 (88.7–133.2) | < 0.001 |
TG (mg/dL) [median (IQR)] | 115.5 (81.0–170.0) | 109.5 (83.5–130.2) | 0.046 |
Lp(a) (mg/dL) [median (IQR)] | 23.2 (8.1–59.4) | 14.9 (6.9–34.4) | 0.021 |
Medications [n (%)] | |||
Statin | 309 (94.8) | 36 (51.4) | < 0.001 |
Aspirin | 326 (100.0) | 0 (0.0) | N/A |
ACEI/ARB | 256 (78.5) | 43 (61.4) | 0.003 |
β-blocker | 292 (89.6) | 41 (58.6) | < 0.001 |
Anti-hyperglycemic drugs | |||
Oral | 143 (43.9) | 8 (11.4) | < 0.001 |
Insulin | 46 (14.1) | 1 (1.4) | 0.003 |
Association Between Lp(a) Concentrations and Platelet Reactivity
n | Lp(a) < 50 mg/dL | Lp(a) ≥ 50 mg/dL | P values | |
---|---|---|---|---|
C-EPI-induced platelet reactivity by PFA-100 (s) [median (IQR)]a | 156 | 102.0 (86.0–145.0) | 117 (97.0–165.5) | 0.235 |
Arachidonic acid-induced platelet reactivity by VerifyNow™ Aspirin (ARU) [mean (SD)]a | 130 | 530.0 ± 80.4 | 527.4 ± 83.7 | 0.819 |
ADP-induced platelet reactivity by Multiplate™ (AU min) [mean (SD)]a,b | 152 | 73.2 ± 23.4 | 73.2 ± 21.3 | 0.996 |
Arachidonic acid-induced platelet reactivity by Multiplate™ (AU min) [median (IQR)]b | 49 | 71.4 ± 24.3 | 76.1 ± 26.9 | 0.532 |
ADP-induced platelet reactivity by LTA (%) [median (IQR)]a | 130 | 80.6 (74.1–84.5) | 75.1 (70.5–82.8) | 0.112 |
Serum TxB2 (pg/mL) levels [mean (SD)]a | 59 | 208.6 ± 59.6 | 202.7 ± 58.5 | 0.770 |