Synergistic Effects of Inflammation and Atherogenic Dyslipidemia on Subclinical Carotid Atherosclerosis Assessed by Ultrasound in Patients with Familial Hypercholesterolemia and Their Family Members
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Study Population
2.2. Laboratory Tests
2.3. Extracranial Carotid Artery Ultrasound Measurements
2.4. Statistical Analysis
3. Results
3.1. Description of Study Participants
3.2. Predictors of Carotid Atherosclerosis
3.3. Synergistic Effects of hsCRP with Atherogenic Dyslipidemia on Thicker CIMT
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Tabas, I.; Williams, K.J.; Borén, J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: Update and therapeutic implications. Circulation 2007, 116, 1832–1844. [Google Scholar] [CrossRef] [PubMed]
- Borén, J.; Chapman, M.J.; Krauss, R.M.; Packard, C.J.; Bentzon, J.F.; Binder, C.J.; Daemen, M.J.; Demer, L.L.; Hegele, R.A.; Nicholls, S.J.; et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: Pathophysiological, genetic, and therapeutic insights: A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J. 2020, 41, 2313–2330. [Google Scholar] [CrossRef]
- Wang, T.-D.; Chen, W.-J.; Chien, K.-L.; Su, S.S.-Y.; Hsu, H.-C.; Chen, M.-F.; Liau, C.-S.; Lee, Y.-T. Efficacy of cholesterol levels and ratios in predicting future coronary heart disease in a Chinese population. Am. J. Cardiol. 2001, 88, 737–743. [Google Scholar] [CrossRef]
- Kinosian, B.; Glick, H.; Garland, G. Cholesterol and Coronary Heart Disease: Predicting Risks by Levels and Ratios. Ann. Intern. Med. 1994, 121, 641–647. [Google Scholar] [CrossRef] [PubMed]
- Elshazly, M.B.; Nicholls, S.J.; Nissen, S.E.; John, J.S.; Martin, S.S.; Jones, S.R.; Quispe, R.; Stegman, B.; Kapadia, S.R.; Tuzcu, E.M.; et al. Implications of Total to High-Density Lipoprotein Cholesterol Ratio Discordance with Alternative Lipid Parameters for Coronary Atheroma Progression and Cardiovascular Events. Am. J. Cardiol. 2016, 118, 647–655. [Google Scholar] [CrossRef] [PubMed]
- Junyent, M.; Cofán, M.; Núñez, I.; Gilabert, R.; Zambón, D.; Ros, E. Influence of HDL Cholesterol on Preclinical Carotid Atherosclerosis in Familial Hypercholesterolemia. Arter. Thromb. Vasc. Biol. 2006, 26, 1107–1113. [Google Scholar] [CrossRef] [Green Version]
- März, W.; Scharnagl, H.; Winkler, K.; Tiran, A.; Nauck, M.; Boehm, B.O.; Winkelmann, B.R. Low-density lipoprotein triglycerides associated with low-grade systemic inflammation, adhesion molecules, and angiographic coronary artery disease: The Ludwigshafen Risk and Cardiovascular Health study. Circulation 2004, 110, 3068–3074. [Google Scholar] [CrossRef] [Green Version]
- Mora, S.; Rifai, N.; Buring, J.E.; Ridker, P.M. Additive Value of Immunoassay-Measured Fibrinogen and High-Sensitivity C-Reactive Protein Levels for Predicting Incident Cardiovascular Events. Circulation 2006, 114, 381–387. [Google Scholar] [CrossRef]
- Hackam, D.G.; Anand, S.S. Emerging risk factors for atherosclerotic vascular disease: A critical review of the evidence. JAMA 2003, 290, 932–940. [Google Scholar] [CrossRef]
- Verma, S.; Szmitko, P.E.; Ridker, P.M. C-reactive protein comes of age. Nat. Clin. Pract. Cardiovasc. Med. 2005, 2, 29–36. [Google Scholar] [CrossRef]
- Ridker, P.M.; Danielson, E.; Fonseca, F.A.; Genest, J.; Gotto, A.M., Jr.; Kastelein, J.J.; Koenig, W.; Libby, P.; Lorenzatti, A.J.; MacFadyen, J.G.; et al. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. N. Engl. J. Med. 2008, 359, 2195–2207. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rizzo, M.; Corrado, E.; Coppola, G.; Muratori, I.; Mezzani, A.; Novo, G.; Novo, S. The predictive role of C-reactive protein in patients with hypertension and subclinical atherosclerosis. Intern. Med. J. 2009, 39, 539–545. [Google Scholar] [CrossRef] [PubMed]
- Jacobson, T.A.; Ito, M.K.; Maki, K.C.; Orringer, C.E.; Bays, H.E.; Jones, P.H.; McKenney, J.M.; Grundy, S.M.; Gill, E.A.; Wild, R.A.; et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 1—Executive summary. J. Clin. Lipidol. 2014, 8, 473–488. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mookadam, F.; Moustafa, S.E.; Lester, S.J.; Warsame, T. Subclinical Atherosclerosis: Evolving Role of Carotid Intima-Media Thickness. Prev. Cardiol. 2010, 13, 186–197. [Google Scholar] [CrossRef] [PubMed]
- Pauciullo, P.; Giannino, A.; De Michele, M.; Gentile, M.; Liguori, R.; Argiriou, A.; Carlotto, A.; Faccenda, F.; Mancini, M.; Bond, M.; et al. Increased carotid artery intima-media thickness is associated with a novel mutation of low-density lipoprotein receptor independently of major cardiovascular risk factors. Metabolism 2003, 52, 1433–1438. [Google Scholar] [CrossRef]
- Chambless, L.E.; Heiss, G.; Folsom, A.R.; Rosamond, W.; Szklo, M.; Sharrett, A.R.; Clegg, L.X. Association of Coronary Heart Disease Incidence with Carotid Arterial Wall Thickness and Major Risk Factors: The Atherosclerosis Risk in Communities (ARIC) Study, 1987–1993. Am. J. Epidemiol. 1997, 146, 483–494. [Google Scholar] [CrossRef]
- O’leary, D.H.; Polak, J.F.; Kronmal, R.A.; Manolio, T.A.; Burke, G.L.; Wolfson, S.K., Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N. Engl. J. Med. 1999, 340, 14–22. [Google Scholar] [CrossRef]
- Chambless, L.E.; Folsom, A.R.; Clegg, L.X.; Sharrett, A.R.; Shahar, E.; Nieto, F.J.; Rosamond, W.D.; Evans, G. Carotid Wall Thickness is Predictive of Incident Clinical Stroke: The Atherosclerosis Risk in Communities (ARIC) Study. Am. J. Epidemiol. 2000, 151, 478–487. [Google Scholar] [CrossRef]
- Lorenz, M.W.; Von Kegler, S.; Steinmetz, H.; Markus, H.S.; Sitzer, M. Carotid intima-media thickening indicates a higher vascular risk across a wide age range: Prospective data from the Carotid Atherosclerosis Progression Study (CAPS). Stroke 2006, 37, 87–92. [Google Scholar] [CrossRef] [Green Version]
- Salonen, J.T.; Salonen, R. Ultrasound B-mode imaging in observational studies of atherosclerotic progression. Circulation 1993, 87 (Suppl. 3), II56–II65. [Google Scholar]
- Kitamura, A.; Iso, H.; Imano, H.; Ohira, T.; Okada, T.; Sato, S.; Kiyama, M.; Tanigawa, T.; Yamagishi, K.; Shimamoto, T. Carotid Intima-Media Thickness and Plaque Characteristics as a Risk Factor for Stroke in Japanese Elderly Men. Stroke 2004, 35, 2788–2794. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rosvall, M.; Janzon, L.; Berglund, G.; Engstrom, G.; Hedblad, B. Incident coronary events and case fatality in relation to common carotid intima-media thickness. J. Intern. Med. 2005, 257, 430–437. [Google Scholar] [CrossRef]
- Van der Meer, I.M.; Bots, M.I.; Hofman, A.; Iglesias del Sol, A.; van der Kuip, D.A.; Witteman, J.C. Predictive value of noninvasive measures of atherosclerosis for incident myocardial infarction: The Rotterdam Study. Circulation 2004, 109, 1089–1094. [Google Scholar] [CrossRef] [Green Version]
- Salonen, J.T.; Salonen, R. Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arter. Thromb. J. Vasc. Biol. 1991, 11, 1245–1249. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Belcaro, G.; Nicolaides, A.N.; Ramaswami, G.; Cesarone, M.R.; De Sanctis, M.; Incandela, L.; Ferrari, P.; Geroulakos, G.; Barsotti, A.; Griffin, M.; et al. Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects: A 10-year follow-up study (the CAFES-CAVE study). Atherosclerosis 2001, 156, 379–387. [Google Scholar] [CrossRef]
- Zouridakis, E.; Avanzas, P.; Arroyo-Espliguero, R.; Fredericks, S.; Kaski, J.C. Markers of Inflammation and Rapid Coronary Artery Disease Progression in Patients with Stable Angina Pectoris. Circulation 2004, 110, 1747–1753. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hashimoto, H.; Kitagawa, K.; Hougaku, H.; Etani, H.; Hori, M. C-reactive protein predicts carotid atherosclerosis progression in mild to moderate risk and middle-aged patients. Clin. Investig. Med. 2006, 29, 77–82. [Google Scholar]
- Kang, E.S.; Kim, H.J.; Kim, Y.M.; Lee, S.; Cha, B.S.; Kil Lim, S.; Kim, H.J.; Lee, H.C. Serum high sensitivity C-reactive protein is associated with carotid intima-media thickness in type 2 diabetes. Diabetes Res. Clin. Pract. 2004, 66, S115–S120. [Google Scholar] [CrossRef]
- Trinder, M.; Li, X.; DeCastro, M.L.; Cermakova, L.; Sadananda, S.; Jackson, L.M.; Azizi, H.; Mancini, G.J.; Francis, G.A.; Frohlich, J.; et al. Risk of Premature Atherosclerotic Disease in Patients with Monogenic Versus Polygenic Familial Hypercholesterolemia. J. Am. Coll. Cardiol. 2019, 74, 512–522. [Google Scholar] [CrossRef]
- Chang, N.-T.; Su, T.-C. Investigating the association between familial hypercholesterolemia and perceived depression. Atheroscler. Suppl. 2019, 36, 31–36. [Google Scholar] [CrossRef]
- Chien, K.-L.; Liau, C.-S.; Chen, M.-F.; Lee, Y.-T.; Jeng, J.-S.; Hwang, B.-S.; Su, T.-C. Primary Hypercholesterolemia, Carotid Atherosclerosis and Insulin Resistance Among Chinese. Lipids 2007, 43, 117–124. [Google Scholar] [CrossRef] [PubMed]
- Su, T.-C.; Jeng, J.-S.; Chien, K.-L.; Sung, F.C.; Hsu, H.C.; Lee, Y.T. Hypertension status is the major determinant of carotid atherosclerosis: A community-based study in Taiwan. Stroke 2001, 32, 2265–2271. [Google Scholar] [CrossRef] [PubMed]
- Su, T.-C.; Lee, Y.-T.; Chou, S.; Hwang, W.-T.; Chen, C.-F.; Wang, J.-D. Twenty-four-hour ambulatory blood pressure and duration of hypertension as major determinants for intima-media thickness and atherosclerosis of carotid arteries. Atherosclerosis 2006, 184, 151–156. [Google Scholar] [CrossRef]
- Su, T.C.; Jeng, J.S.; Wang, J.D.; Torng, P.L.; Chang, S.J.; Chen, C.F.; Liau, C.S. Homocysteine, circulating vascular cell adhesion molecule and carotid atherosclerosis in postmen-opausal vegetarian women and omnivores. Atherosclerosis 2006, 184, 356–362. [Google Scholar] [CrossRef] [PubMed]
- Su, T.C.; Jeng, J.S.; Chien, K.L.; Torng, P.L.; Sung, F.C.; Lee, Y.T. Measurement reliability of common carotid artery intima-media thickness by ultrasonographic assessment. J. Med. Ultrasound 1999, 7, 73–79. [Google Scholar]
- Knol, M.J.; VanderWeele, T.J.; Groenwold, R.H.H.; Klungel, O.H.; Rovers, M.M.; Grobbee, D.E. Estimating measures of interaction on an additive scale for preventive exposures. Eur. J. Epidemiol. 2011, 26, 433–438. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Richardson, D.B.; Kaufman, J.S. Estimation of the Relative Excess Risk Due to Interaction and Associated Confidence Bounds. Am. J. Epidemiol. 2009, 169, 756–760. [Google Scholar] [CrossRef] [Green Version]
- Ference, B.A.; Ginsberg, H.N.; Graham, I.; Ray, K.K.; Packard, C.J.; Bruckert, E.; Hegele, R.A.; Krauss, R.M.; Raal, F.J.; Schunkert, H.; et al. Low-density lipoproteins cause atherosclerotic cardi-ovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Ather-osclerosis Society Consensus Panel. Eur. Heart J. 2017, 38, 2459–2472. [Google Scholar] [CrossRef] [Green Version]
- Lien, W.-P.; Lai, L.-P.; Shyu, K.-G.; Hwang, J.-J.; Chen, J.-J.; Lei, M.-H.; Cheng, J.-J.; Huang, P.-J.; Tsai, K.-S. Low-serum, high-density lipoprotein cholesterol concentration is an important coronary risk factor in Chinese patients with low serum levels of total cholesterol and triglyceride. Am. J. Cardiol. 1996, 77, 1112–1115. [Google Scholar] [CrossRef]
- Chien, K.-L.; Hsu, H.-C.; Su, T.-C.; Chen, M.-F.; Lee, Y.-T.; Hu, F.B. Apolipoprotein B and non-high density lipoprotein cholesterol and the risk of coronary heart disease in Chinese. J. Lipid Res. 2007, 48, 2499–2505. [Google Scholar] [CrossRef] [Green Version]
- Fuster, V.; Badimon, L.; Badimon, J.J.; Chesebro, J.H. The pathogenesis of coronary artery disease and the acute coronary syndromes. N. Engl. J. Med. 1992, 326, 242–250. [Google Scholar] [PubMed]
- Hansson, G.K. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med. 2005, 352, 1685–1695. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Munro, J.M.; Cotran, R.S. The pathogenesis of atherosclerosis: Atherogenesis and inflammation. Laboratory investigation. J. Tech. Methods Pathol. 1988, 58, 249–261. [Google Scholar]
- Libby, P.; Ridker, P.M.; Hansson, G.K. Progress and challenges in translating the biology of atherosclerosis. Nature 2011, 473, 317–325. [Google Scholar] [CrossRef] [PubMed]
- Ross, R. Atherosclerosis is an inflammatory disease. N. Engl. J. Med. 1999, 340, 115–126. [Google Scholar] [CrossRef]
- Libby, P.; Loscalzo, J.; Ridker, P.M.; Farkouh, M.E.; Hsue, P.Y.; Fuster, V.; Hasan, A.A.; Amar, S. Inflammation, immunity, and infection in atherothrombosis: JACC review topic of the week. J. Am. Coll. Cardiol. 2018, 72, 2071–2081. [Google Scholar] [CrossRef]
- Ridker, P.M.; Cushman, M.; Stampfer, M.J.; Tracy, R.P.; Hennekens, C.H. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N. Engl. J. Med. 1997, 336, 973–979. [Google Scholar] [CrossRef]
- Buckley, D.I.; Fu, R.; Freeman, M.; Rogers, K.; Helfand, M. C-reactive protein as a risk factor for coronary heart disease: A systematic review and meta-analyses for the U.S. Preventive Services Task Force. Ann. Intern. Med. 2009, 151, 483–495. [Google Scholar] [CrossRef] [Green Version]
- Kaptoge, S.; Di Angelantonio, E.; Lowe, G.; Pepys, M.B.; Thompson, S.G.; Collins, R.; Danesh, J. Emerging Risk Factors Collaboration: C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: An individual participant meta-analysis. Lancet 2010, 375, 132–140. [Google Scholar]
- Ridker, P.M. Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) Investigators: C-reactive protein levels and outcomes after statin therapy. N. Engl. J. Med. 2005, 352, 20–28. [Google Scholar] [CrossRef]
- Ridker, P.M.; Everett, B.M.; Thuren, T.; MacFadyen, J.G.; Chang, W.H.; Ballantyne, C.; Fonseca, F.; Nicolau, J.; Koenig, W.; Anker, S.D.; et al. Anti-inflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 2017, 377, 1119–1131. [Google Scholar] [CrossRef] [PubMed]
- Ridker, P.M.; MacFadyen, J.G.; Everett, B.M.; Libby, P.; Thuren, T.; Glynn, R.J.; CANTOS Trial Group. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: A secondary analysis from the cantos ran-domised controlled trial. Lancet 2018, 391, 319–328. [Google Scholar] [CrossRef]
- Ridker, P.M.; Everett, B.M.; Pradhan, A.; MacFadyen, J.G.; Solomon, D.H.; Zaharris, E.; Mam, V.; Hasan, A.; Rosenberg, Y.; Iturriaga, E.; et al. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. N. Engl. J. Med. 2019, 380, 752–762. [Google Scholar] [CrossRef] [PubMed]
- Nidorf, S.M.; Eikelboom, J.; Budgeon, C.A.; Thompson, P.L. Low-Dose Colchicine for Secondary Prevention of Cardiovascular Disease. J. Am. Coll. Cardiol. 2013, 61, 404–410. [Google Scholar] [CrossRef] [Green Version]
- Tardif, J.-C.; Kouz, S.; Waters, D.D.; Bertrand, O.F.; Diaz, R.; Maggioni, A.P.; Pinto, F.J.; Ibrahim, R.; Gamra, H.; Kiwan, G.S.; et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N. Engl. J. Med. 2019, 381, 2497–2505. [Google Scholar] [CrossRef]
- Nidorf, S.M.; Fiolet, A.T.L.; Mosterd, A.; Eikelboom, J.W.; Schut, A.; Opstal, T.S.J.; The, S.H.K.; Xu, X.-F.; Ireland, M.A.; Lenderink, T.; et al. Colchicine in Patients with Chronic Coronary Disease. N. Engl. J. Med. 2020, 383, 1838–1847. [Google Scholar] [CrossRef]
- Spence, J.D. Measurement of Intima-Media Thickness vs. Carotid Plaque: Uses in Patient Care, Genetic Research and Evaluation of New Therapies. Int. J. Stroke 2006, 1, 216–221. [Google Scholar] [CrossRef]
Total | hsCRP (mg/L) | p Value for Trend | ||||
---|---|---|---|---|---|---|
Q1 (<0.4) n = 192 | Q2 (0.4–0.7) n = 190 | Q3 (0.7–1.6) n = 190 | Q4 (>1.6) n = 189 | |||
Male, % | 48.37 | 45.31 | 51.05 | 48.95 | 47.62 | 0.3810 |
Age, y/o | 42.38 ± 17.98 | 32.66 ± 17.29 | 44.98 ± 16.32 | 46.40 ± 16.94 | 45.74 ± 17.91 | <0.0001 |
Cholesterol, mg/dL | 236.57 ± 66.72 | 221.81 ± 69.16 | 235.71 ± 56.79 | 240.58 ± 67.98 | 246.86 ± 68.30 | 0.0019 |
Triglyceride, mg/dL | 131.05 ± 167.18 | 82.27 ± 39.09 | 114.59 ± 75.87 | 136.11 ± 94.17 | 152.63 ± 105.3 | <0.0001 |
HDL-C, mg/dL | 54.92 ± 16.67 | 58.73 ± 19.52 | 55.95 ± 14.85 | 54.29 ± 13.76 | 51.70 ± 16.23 | 0.0003 |
LDL-C, mg/dL | 155.57 ± 64.67 | 133.37 ± 65.17 | 147.81 ± 52.87 | 150.05 ± 63.39 | 156.87 ± 60.91 | 0.0018 |
CHO/HDL-C | 4.53 ± 1.62 | 3.96 ± 1.41 | 4.39 ± 1.21 | 4.65 ± 1.61 | 5.04 ± 1.73 | <0.0001 |
LDL/HDL-C | 2.99 ± 1.41 | 2.43 ± 1.32 | 2.79 ± 1.13 | 2.93 ± 1.43 | 3.24 ± 1.48 | <0.0001 |
Diabetes mellitus, % | 4.48 | 1.05 | 4.21 | 5.32 | 7.41 | 0.0014 |
Fasting glucose, mg/dL | 92.47 ± 16.65 | 87.05 ± 8.08 | 91.18 ± 15.83 | 95.02 ± 14.69 | 96.62 ± 23.13 | <0.0001 |
Hypertension, % | 21.23 | 8.90 | 22.99 | 23.40 | 29.79 | <0.0001 |
Systolic BP, mmHg | 111.86 ± 24.80 | 107.21 ± 14.47 | 115.60 ± 18.01 | 117.34 ± 16.42 | 118.70 ± 18.50 | <0.0001 |
Diastolic BP, mmHg | 70.48 ± 15.85 | 67.18 ± 10.32 | 72.69 ± 11.05 | 74.20 ± 10.85 | 74.99 ± 11.32 | <0.0001 |
Smoking habit, % | 17.35 | 10.94 | 18.95 | 20.53 | 19.05 | 0.0170 |
Alcohol habit, % | 16.01 | 12.63 | 17.65 | 17.02 | 16.76 | 0.1609 |
Carotid IMT, mm | 0.57 ± 0.19 | 0.53 ± 0.13 | 0.60 ± 0.15 | 0.63 ± 0.20 | 0.62 ± 0.16 | <0.0001 |
Plaque Score | 1.92 ± 3.33 | 0.87 ± 1.89 | 2.17 ± 3.46 | 2.73 ± 4.16 | 2.18 ± 3.32 | <0.0001 |
Statin use, % | 26.41 | 18.75 | 28.42 | 34.74 | 23.81 | 0.1283 |
LDL-C ≥ 160 mg/dL and hsCRP ≥ 2 mg/L (n = 36) | LDL-C ≥ 160 mg/dL and hsCRP < 2 mg/L (n = 162) | LDL-C < 160 mg/dL and hsCRP ≥ 2 mg/L (n = 112) | LDL-C < 160 mg/dL and hsCRP < 2 mg/L (n = 444) | p Value | |
---|---|---|---|---|---|
IMT | |||||
RCCA1, mm | 0.65 ± 0.17 | 0.63 ± 0.22 | 0.62 ± 0.20 | 0.57 ± 0.16 | 0.0005 |
RCCA2, mm | 0.62 ± 0.16 | 0.59 ± 0.18 | 0.60 ± 0.20 | 0.55 ± 0.15 | 0.0013 |
LCCA1, mm | 0.70 ± 0.21 | 0.66 ± 0.23 | 0.60 ± 0.19 | 0.57 ± 0.16 | <0.0001 |
LCCA2, mm | 0.72 ± 0.22 | 0.64 ± 0.27 | 0.61 ± 0.18 | 0.57 ± 0.16 | <0.0001 |
IMT mean, mm | 0.67 ± 0.16 | 0.63 ± 0.20 | 0.61 ± 0.17 | 0.57 ± 0.14 | <0.0001 |
Plaque Score | 3.92 ± 4.31 | 3.10 ± 4.09 | 1.92 ± 3.09 | 1.45 ± 2.90 | <0.0001 |
0% | 30.56 | 36.42 | 59.56 | 64.33 | <0.0001 |
1–2% | 16.67 | 22.84 | 11.71 | 15.35 | |
3–5% | 25.00 | 19.14 | 17.12 | 11.51 | |
≥6% | 27.78 | 21.60 | 12.61 | 8.80 |
TC/HDL ≥ 5 and hsCRP ≥ 2 mg/L (n = 70) | TC/HDL ≥ 5 and hsCRP < 2 mg/L (n = 172) | TC/HDL < 5 and hsCRP ≥ 2 mg/L (n = 78) | TC/HDL < 5 and hsCRP< 2 mg/L (n = 434) | p Value | |
---|---|---|---|---|---|
IMT | |||||
RCCA1, mm | 0.68 ± 0.22 | 0.64 ± 0.19 | 0.58 ± 0.15 | 0.57 ± 0.17 | <0.0001 |
RCCA2, mm | 0.67 ± 0.21 | 0.59 ± 0.15 | 0.55 ± 0.14 | 0.55 ± 0.17 | <0.0001 |
LCCA1, mm | 0.67 ± 0.19 | 0.65 ± 0.20 | 0.59 ± 0.19 | 0.57 ± 0.17 | <0.0001 |
LCCA2, mm | 0.69 ± 0.20 | 0.63 ± 0.19 | 0.58 ± 0.17 | 0.57 ± 0.20 | <0.0001 |
IMT mean, mm | 0.68 ± 0.18 | 0.63 ± 0.16 | 0.58 ± 0.15 | 0.57 ± 0.16 | <0.0001 |
Plaque Score | 2.78 ± 3.62 | 2.91 ± 4.14 | 2.08 ± 3.41 | 1.48 ± 2.86 | <0.0001 |
0% | 42.03 | 42.20 | 60.26 | 62.73 | <0.0001 |
1–2% | 17.39 | 21.97 | 8.97 | 15.51 | |
3–5% | 23.19 | 15.03 | 15.38 | 12.96 | |
≥6% | 17.39 | 20.81 | 15.38 | 8.80 |
Source | Partial SS | df | MS | F | p Value |
---|---|---|---|---|---|
LDL-C as predictor | |||||
Model | 5.64 | 3 | 1.88 | 10.35 | 0.000 |
LDL-C (≥160 vs. <160 mg/dL) | 4.21 | 1 | 4.21 | 23.20 | 0.000 |
hsCRP (≥2 vs. <2 mg/L) | 1.38 | 1 | 1.38 | 7.58 | 0.006 |
LDL-C*hsCRP | 0.73 | 1 | 0.73 | 4.02 | 0.045 |
Residual | 138.17 | 757 | 0.18 | ||
Total | 143.81 | 760 | |||
R-squared = 0.039; Adjusted R-squared = 0.036 | |||||
TC/HDL-C as predictor | |||||
Model | 5.59 | 3 | 1.86 | 10.26 | 0.000 |
TC/HDL-C (≥5 vs. < 5) | 3.52 | 1 | 3.52 | 19.37 | 0.000 |
hsCRP (≥2 mg/L vs. <2 mg/L) | 0.65 | 1 | 0.65 | 3.57 | 0.059 |
TC/HDL-C*hsCRP | 0.05 | 1 | 0.05 | 0.25 | 0.618 |
Residual | 138.22 | 757 | 0.18 | ||
Total | 143.81 | 760 | |||
R-squared = 0.039; Adjusted R-squared = 0.035 |
IMT ≥ 75th Percent | |||
---|---|---|---|
All Participants | FH Participants | Non-FH Participants | |
LDL-C as a predictor | |||
Model 1 LDL-C ≥ 160 mg/dL vs. LDL-C < 160 mg/dL | 2.42(1.53–3.82) ‡ | 1.25(0.47–3.29) | 1.86(1.04–3.31) * |
Model 2 LDL-C ≥ 160 mg/dL and hsCRP ≥ 2 mg/L vs. other 3 groups | 2.64(1.22–5.69) * | 2.17(0.85–5.54) | 1.38(0.48–3.97) |
Model 3 LDL-C ≥ 160 mg/dL and hsCRP ≥ 2 mg/L vs. LDL-C < 160 mg/dL and hsCRP < 2 mg/L | 3.56(1.56–8.16) ‡ | 1.55(0.35–6.92) | 1.60(0.51–5.01) |
TC/HDL-C as a predictor | |||
Model 1 TC/HDL-C ≥ 5 vs. TC/HDL-C < 5 | 2.68(1.67–4.30) ‡ | 1.35(0.60–3.06) | 2.15(1.12–4.12) * |
Model 2 TC/HDL-C ≥ 5 and hsCRP ≥ 2 mg/L vs. other 3 groups | 2.88(1.42–5.83) ‡ | 1.69(0.66–4.29) | 2.21(0.80–6.10) |
Model 3 TC/HDL-C ≥ 5 and hsCRP ≥ 2 mg/L vs. TC/HDL-C < 5 and CRP< 2 mg/L | 4.22(1.87–9.54) ‡ | 1.38(0.42–4.61) | 2.56(0.81–8.09) |
RERI | AP | SI | |
---|---|---|---|
LDL-C ≥ 160 mg/dL, hsCRP ≥ 2 mg/L | 1.020 (−0.992–3.032) | 0.366 (−0.165,0.898) | 2.333 (0.437–12.441) |
TC/HDL-C ≥ 5, hsCRP ≥ 2 mg/L | 1.148 (−0.880,3.175) | 0.402 (−0.101,0.905) | 2.629 (0.452,15.305) |
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Lin, P.-C.; Chen, C.-Y.; Wu, C.; Su, T.-C. Synergistic Effects of Inflammation and Atherogenic Dyslipidemia on Subclinical Carotid Atherosclerosis Assessed by Ultrasound in Patients with Familial Hypercholesterolemia and Their Family Members. Biomedicines 2022, 10, 367. https://doi.org/10.3390/biomedicines10020367
Lin P-C, Chen C-Y, Wu C, Su T-C. Synergistic Effects of Inflammation and Atherogenic Dyslipidemia on Subclinical Carotid Atherosclerosis Assessed by Ultrasound in Patients with Familial Hypercholesterolemia and Their Family Members. Biomedicines. 2022; 10(2):367. https://doi.org/10.3390/biomedicines10020367
Chicago/Turabian StyleLin, Po-Chih, Chung-Yen Chen, Charlene Wu, and Ta-Chen Su. 2022. "Synergistic Effects of Inflammation and Atherogenic Dyslipidemia on Subclinical Carotid Atherosclerosis Assessed by Ultrasound in Patients with Familial Hypercholesterolemia and Their Family Members" Biomedicines 10, no. 2: 367. https://doi.org/10.3390/biomedicines10020367
APA StyleLin, P.-C., Chen, C.-Y., Wu, C., & Su, T.-C. (2022). Synergistic Effects of Inflammation and Atherogenic Dyslipidemia on Subclinical Carotid Atherosclerosis Assessed by Ultrasound in Patients with Familial Hypercholesterolemia and Their Family Members. Biomedicines, 10(2), 367. https://doi.org/10.3390/biomedicines10020367