Association of Circulating Heme Oxygenase-1, Lipid Profile and Coronary Disease Phenotype in Patients with Chronic Coronary Syndrome
Abstract
:1. Introduction
2. Material and Methods
2.1. Study Design and Population
2.2. Clinical Definitions
2.3. HO-1 Measurements and Bio-Humoral Profile
2.4. Non-Invasive Imaging
2.4.1. Coronary CTA
2.4.2. Non-Invasive Stress Imaging Analysis
2.5. Statistical Analysis
3. Results
3.1. HO-1 Plasma Levels, Clinical and Bio-Humoral Profiles
3.2. Plasma HO-1, Coronary Atherosclerosis and Myocardial Ischemia
3.3. Plasma HO-1 Levels and Coronary Disease Phenotypes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statements
Acknowledgments
Conflicts of Interest
References
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Clinical Population n = 526 | Low HO-1 n = 263 | High HO-1 n = 263 | p Value | |
---|---|---|---|---|
Demographics | ||||
Age, years | 60 ± 9 | 61 ± 8 | 60 ± 9 | ns |
Males | 318 (60) | 145 (55) | 173 (66) | 0.0125 |
Clinical characteristics | ||||
Typical angina | 139 (26) | 76 (29) | 63 (24) | ns |
LVEF% | 60 ± 8 | 61 ± 8 | 59 ± 8 | 0.0110 |
CAD probability | 48 ± 19 | 48 ± 20 | 49 ± 18 | ns |
Cardiovascular risk factors | ||||
Family history of CAD | 186 (35) | 94 (36) | 92 (37) | ns |
Diabetes | 177 (34) | 83 (32) | 94 (36) | ns |
Hypercholesterolemia | 316 (60) | 157 (60) | 159 (60) | ns |
Hypertension | 349 (66) | 166 (63) | 163 (62) | ns |
Smoking | 129 (24) | 64 (24) | 65 (25) | ns |
BMI, kg/m2 | 27.7 ± 4.3 | 27.2 ± 4 | 28.2 ± 4.6 | 0.0076 |
Metabolic syndrome | 181 (34) | 80 (30) | 101 (38) | 0.0539 |
Pharmacological therapies | ||||
Beta-blockers | 212 (40) | 100 (38) | 112 (43) | ns |
Calcium channel blockers | 72 (14) | 30 (11) | 42 (16) | ns |
ACE Inhibitors | 157 (30) | 86 (33) | 71 (27) | ns |
ARBs | 89 (17) | 41 (16) | 48 (18) | ns |
Diuretics | 88 (17) | 44 (17) | 44 (17) | ns |
Anti-diabetic | 109 (21) | 45 (17) | 51 (19) | ns |
Statins | 274 (52) | 128 (49) | 146 (56) | ns |
Aspirin | 309 (59) | 155 (59) | 154 (59) | ns |
Nitrates | 58 (11) | 23 (9) | 35 (13) | ns |
Anti-coagulants | 11 (2) | 4 (1) | 7 (3) | ns |
Clinical Population n = 526 | Low HO-1 n = 263 | High HO-1 n = 263 | p Value | |
---|---|---|---|---|
Oxidative stress | ||||
HO-1, ng/mL | 5.65 ± 4.19 | 2.33 ± 1.43 | 8.97 ± 3.13 | <0.0001 |
GGT, IU/L | 40 ± 30 | 38 ± 27 | 42 ± 32 | 0.0074 |
Metabolic (glucose) | ||||
FPG, mg/dL | 112 ± 36 | 112 ± 34 | 113 ± 38 | ns |
Insulin, μUI/mL | 11.6 ± 11.0 | 12.7 ± 10.7 | 11.5 ± 11 | ns |
HOMA-IR index | 3.5 ± 4.2 | 3.4 ± 4.1 | 3.5 ± 4.1 | ns |
Metabolic (lipid) | ||||
Total-C, mg/dL | 183 ± 49 | 188 ± 50 | 178 ± 49 | 0.0166 |
LDL-C, mg/dL | 106 ± 40 | 110 ± 40 | 102 ± 40 | 0.0130 |
HDL-C, mg/dL | 52 ± 17 | 54 ± 16 | 51 ± 18 | 0.0054 |
Remnant-C, mg/dL | 24 ± 15 | 23 ± 14 | 25 ± 15 | ns |
Non-HDL-C, mg/dL | 130 ± 43 | 134 ± 43 | 126 ± 42 | 0.0528 |
Apo A1, mg/dL | 143 ± 32 | 145 ± 33 | 142 ± 32 | ns |
HDL-C/Apo A1 | 0.37 ± 0.12 | 0.38 ± 0.13 | 0.36 ± 0.1 | 0.0258 |
Apo B, mg/dL | 87 ± 28 | 90 ± 28 | 84 ± 28 | 0.0079 |
Apo A1/Apo B | 1.80 ± 0.85 | 1.71 ± 0.52 | 1.89 ± 1.07 | 0.0167 |
Lp (a) | 20 ± 22 | 23.6 ± 24.1 | 18.6 ± 21.8 | 0.0076 |
Triglycerides, mg/dL | 124 ± 81 | 120 ± 75 | 128 ± 86 | ns |
TG/HDL-C | 2.74 ± 2.45 | 2.55 ± 2.33 | 2.94 ± 2.55 | ns |
PCSK9, ng/mL | 213 ± 105 | 227 ± 110 | 199 ± 98 | 0.0024 |
Adipose tissue | ||||
Adiponectin, μg/mL | 9.8 ± 6.9 | 10.2 ± 6.4 | 9.2 ± 6.9 | 0.0030 |
Leptin, ng/mL | 9.9 ± 10.7 | 8.8 ± 8.3 | 11.2 ± 12.7 | ns |
Hepatic | ||||
AST, IU/L | 24 ± 10 | 24 ± 9 | 25 ± 11 | ns |
ALT, IU/L | 21 ± 13 | 20 ± 13 | 22 ± 14 | ns |
Remodeling | ||||
MMP-2, ng/mL | 159 ± 61 | 157 ± 63 | 161 ± 58 | ns |
MMP-9, ng/mL | 145 ± 206 | 162 ± 221 | 127 ± 187 | 0.0511 |
ALP, IU/L | 51 ± 18 | 53 ± 18 | 50 ± 18 | 0.0433 |
Inflammatory | ||||
hs-CRP, mg/dL | 0.40 ± 1.09 | 0.34 ± 0.56 | 0.47 ± 1.45 | ns |
IL-6, ng/L | 1.35 ± 2.35 | 1.12 ± 1.33 | 1.47 ± 2.83 | 0.0575 |
Cardiac | ||||
hs-cTnT, ng/L | 910 ± 21 | 10 ± 19 | 10 ± 22 | ns |
hs-cTnI, ng/L | 54 ± 240 | 41 ± 215 | 66 ± 262 | 0.0006 |
NT-proBNP, ng/L | 139 ± 291 | 119 ± 173 | 158 ± 374 | ns |
Renal | ||||
Creatinine, mg/dL | 0.96 ± 0.23 | 0.85 ± 0.23 | 0.91 ± 0.22 | 0.0014 |
Univariate | Multivariate | |||||
---|---|---|---|---|---|---|
Coefficient | SE | p Value | Coefficient | SE | p Value | |
Age | −0.010 | 0.004 | 0.0218 | −0.011 | 0.004 | 0.0128 |
Males | 0.243 | 0.079 | 0.0022 | |||
LVEF% | −0.010 | 0.005 | 0.0286 | |||
BMI | 0.025 | 0.009 | 0.0068 | |||
Beta-blockers | 0.141 | 0.079 | 0.0748 | |||
Statins | 0.198 | 0.078 | 0.0108 | |||
Nitrates | 0.249 | 0.124 | 0.0452 | 0.267 | 0.124 | 0.0317 |
GGT | 0.173 | 0.072 | 0.0159 | |||
Total-C | −0.466 | 0.143 | 0.0012 | |||
LDL-C | −0.289 | 0.095 | 0.0026 | |||
HDL-C | −0.394 | 0.122 | 0.0013 | |||
Non-HDL-C | −0.002 | 0.001 | 0.0065 | |||
HDL-C/Apo A1 | −1.214 | 0.332 | 0.0003 | −1.281 | 0.343 | 0.0002 |
Apo B | −0.369 | 0.117 | 0.0145 | −0.390 | 0.126 | 0.0017 |
Apo A1/Apo B | 0.111 | 0.046 | 0.0163 | |||
Lp (a) | −0.116 | 0.038 | 0.0024 | −0.101 | 0.038 | 0.0087 |
PCSK9 | −0.306 | 0.080 | 0.0002 | |||
Adiponectin | −0.186 | 0.061 | 0.0024 | |||
MMP-9 | −0.063 | 0.037 | 0.0876 | |||
ALP | −0.284 | 0.108 | 0.0088 | |||
IL-6 | 0.244 | 0.081 | 0.0027 | 0.180 | 0.081 | 0.0274 |
hs-cTnI | 0.093 | 0.027 | 0.0005 | 0.064 | 0.027 | 0.0189 |
Imaging Population n = 347 | Low HO-1 n = 174 | High HO-1 n = 173 | p Value | |
---|---|---|---|---|
Coronary Anatomy | ||||
Normals | 95 (27) | 52 (30) | 42 (24) | ns |
Patients with non-obstructive | 131 (38) | 59 (34) | 72 (42) | |
Patients with obstructive | 121 (35) | 62 (36) | 59 (34) | |
Coronary Plaques | ||||
Total No. of plaques | 4 ± 3.8 | 3.6 ± 3.5 | 4.5 ± 4 | 0.0265 |
No. of non-obstructive plaques | 3.1 ± 3 | 2.6 ± 2.6 | 3.6 ± 3.3 | 0.0018 |
No. of obstructive plaques | 0.9 ± 14.7 | 0.9 ± 1.8 | 0.8 ± 1.5 | ns |
No. of calcified plaques | 0.9 ± 1.7 | 0.5 ± 1 | 1.2 ± 2.1 | 0.0002 |
No. of non-calcified plaques | 0.5 ± 0.9 | 0.4 ± 0.9 | 0.5 ± 0.9 | ns |
No. of mixed plaques | 2.7 ± 3.2 | 2.6 ± 3.1 | 2.83 ± 3.4 | ns |
Risk Scores | ||||
CTA risk score | 11.9 ± 11 | 11 ± 10.6 | 12.8 ± 11.3 | ns |
CAC score (n = 286) | 292 ± 604 | 222 ± 414 | 361 ± 739 | 0.0497 |
Myocardial Ischemia | ||||
Patients with myocardial ischemia | 83 (24) | 34 (20) | 49 (28) | 0.0477 |
SDS at MPI (n = 274) | 3.41 ± 7.71 | 2.19 ± 5.12 | 4.14 ± 8.78 | 0.0272 |
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Caselli, C.; De Caterina, R.; Ragusa, R.; Liga, R.; Gimelli, A.; Scholte, A.J.H.A.; Clerico, A.; Knuuti, J.; Neglia, D. Association of Circulating Heme Oxygenase-1, Lipid Profile and Coronary Disease Phenotype in Patients with Chronic Coronary Syndrome. Antioxidants 2021, 10, 2002. https://doi.org/10.3390/antiox10122002
Caselli C, De Caterina R, Ragusa R, Liga R, Gimelli A, Scholte AJHA, Clerico A, Knuuti J, Neglia D. Association of Circulating Heme Oxygenase-1, Lipid Profile and Coronary Disease Phenotype in Patients with Chronic Coronary Syndrome. Antioxidants. 2021; 10(12):2002. https://doi.org/10.3390/antiox10122002
Chicago/Turabian StyleCaselli, Chiara, Raffaele De Caterina, Rosetta Ragusa, Riccardo Liga, Alessia Gimelli, Arthur J. H. A. Scholte, Aldo Clerico, Juhani Knuuti, and Danilo Neglia. 2021. "Association of Circulating Heme Oxygenase-1, Lipid Profile and Coronary Disease Phenotype in Patients with Chronic Coronary Syndrome" Antioxidants 10, no. 12: 2002. https://doi.org/10.3390/antiox10122002
APA StyleCaselli, C., De Caterina, R., Ragusa, R., Liga, R., Gimelli, A., Scholte, A. J. H. A., Clerico, A., Knuuti, J., & Neglia, D. (2021). Association of Circulating Heme Oxygenase-1, Lipid Profile and Coronary Disease Phenotype in Patients with Chronic Coronary Syndrome. Antioxidants, 10(12), 2002. https://doi.org/10.3390/antiox10122002